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1 min ago


027, 95% CI 1.716-5.338; P < 0.001), CSS (HR 2.115, 95% CI 1.093-4.090; P = 0.026), DFS (HR 2.584, 95% CI 1.569-4.255; P < 0.001). Age, diabetes history, pathologic T stage, and lymph node status also were independent predictors of prognosis for BC patients.

Our results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.
Our results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.DNA damage repair (DDR) pathways play an essential role in maintaining genomic integrity. https://www.selleckchem.com/products/glutathione.html DDR dysfunction leads to accumulated DNA damage, predisposition to cancer, and high sensitivity to chemotherapy and radiotherapy. Recent studies have demonstrated that DDR status is associated with response to immune checkpoint inhibitors (ICIs). Among the DDR pathways, mismatch repair is one of the most recognized predictive biomarkers for ICIs. Furthermore, preclinical and early clinical studies suggest the rationale of combining agents targeting the DDR pathways, such as poly (ADP-ribose) polymerase (PARP) inhibitors, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, and ataxia telangiectasia and rad3-related (ATR) kinase inhibitors, with ICIs. In the present review, we describe the predictive role of DDR pathways in ICIs and summarize the advances in potential combination strategies of novel agents targeting DDR with ICIs for cancer treatment.Regulatory T cells (Tregs) are immunosuppressive cells involved in antitumor immunity. However, the regulation of Treg generation by inflammation in the tumor microenvironment has not been carefully investigated. Here, we demonstrated that IL-21-polarized inflammation was enriched in the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) and that IL-21 could promote PD-L1-induced Treg generation in a PD-1-dependent manner. Moreover, generated Tregs showed a greater ability to suppress the proliferation of tumor-associated antigen (TAA)-specific T cells than naturally occurring Tregs. Importantly, an anti-PD-1 antibody could inhibit only Treg expansion induced by clinical tumor explants with high expression of IL-21/PD-L1. In addition, neutralizing IL-21 could enhance the anti-PD-1 antibody-mediated inhibitory effect on Treg expansion. Furthermore, simultaneous high expression of IL-21 and PD-L1 was associated with more Treg infiltrates and predicted reduced overall and disease-free survival in patients with HNSCC. These findings indicate that IL-21 in the tumor microenvironment may promote PD-L1-induced, Treg-mediated immune escape in a PD-1-dependent manner and that an IL-21 neutralization strategy may enhance PD-1 blockade-based antitumor immunotherapy by targeting Treg-mediated immune evasion in patients with high expression of IL-21 and PD-L1.MYCN gene amplification and upregulated expression are major hallmarks in the progression of high-risk neuroblastoma. MYCN expression and function in modulating gene synthesis in neuroblastoma is controlled at virtually every level, including poorly understood regulation at the post-transcriptional level. MYCN modulates the expression of various microRNAs including the miR-17-92 cluster. MYCN mRNA expression itself is subjected to the control by miRNAs, most prominently the miR-17-92 cluster that balances MYCN expression by feed-back regulation. This homeostasis seems disturbed in neuroblastoma where MYCN upregulation coincides with severely increased expression of the miR-17-92 cluster. In the presented study, we applied high-throughput next generation sequencing to unravel the miRNome in a cohort of 97 neuroblastomas, representing all clinical stages. Aiming to reveal the MYCN-dependent miRNome, we evaluate miRNA expression in MYCN-amplified as well as none amplified tumor samples. In correlation with survival data analysis of differentially expressed miRNAs, we present various putative oncogenic as well as tumor suppressive miRNAs in neuroblastoma. Using microRNA trapping by RNA affinity purification, we provide a comprehensive view of MYCN-regulatory miRNAs in neuroblastoma-derived cells, confirming a pivotal role of the miR-17-92 cluster and moderate association by the let-7 miRNA family. Attempting to decipher how MYCN expression escapes elevated expression of inhibitory miRNAs, we present evidence that RNA-binding proteins like the IGF2 mRNA binding protein 1 reduce miRNA-directed downregulation of MYCN in neuroblastoma. Our findings emphasize the potency of post-transcriptional regulation of MYCN in neuroblastoma and unravel new avenues to pursue inhibition of this potent oncogene.Numerous colon cancer cases are resistant to chemotherapy based on oxaliplatin and suffer from relapse. A number of survival- and prognosis-related biomarkers have been identified based on database mining for patients who develop drug resistance, but the single individual gene biomarker cannot attain high specificity and sensitivity in prognosis prediction. This work was conducted aiming to establish a new gene signature using oxaliplatin resistance-related genes to predict the prognosis for colon cancer. To this end, we downloaded gene expression profile data of cell lines that are resistant and not resistant to oxaliplatin from the Gene Expression Omnibus (GEO) database. Altogether, 495 oxaliplatin resistance-related genes were searched by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. As suggested by functional analysis, the above genes were mostly enriched into cell adhesion and immune processes. Besides, a signature was built based on four oxaliplatin resistance-related genes selected from the training set to predict the overall survival (OS) by stepwise regression and least absolute shrinkage and selection operator (LASSO) Cox analysis. Relative to the low risk score group, the high risk score group had dismal OS (P 0.7). Additionally, multivariate Cox regression suggested that the signature constructed based on four oxaliplatin resistance-related genes predicted the prognosis for colon cancer cases [hazard ratio (HR), 2.77; 95% CI, 2.03-3.78; P less then 0.001]. Finally, external test sets were utilized to further validate the stability and accuracy of oxaliplatin resistance-related gene signature for prognosis of colon cancer patients. To sum up, this study establishes a signature based on four oxaliplatin resistance-related genes for predicting the survival of colon cancer patients, which sheds more light on the mechanisms of oxaliplatin resistance and helps identify colon cancer cases with a dismal prognostic outcome.

20 mins ago


The models were evaluated on a test set from an independent trial and achieved a Dice Similarity Coefficient (DSC) of 0.96 for heart segmentation and 0.95 for bladder segmentation, Average Surface Distance (ASD) of 0.44mm on heart and 0.90mm on bladder.

This methodology could be a valuable component to the FDG-PET/CT data processing chain by removing FDG physiological noise associated with heart and/or bladder accumulation prior to image analysis by manual, semi- or automated tumor analysis methods.
This methodology could be a valuable component to the FDG-PET/CT data processing chain by removing FDG physiological noise associated with heart and/or bladder accumulation prior to image analysis by manual, semi- or automated tumor analysis methods.Fungal pollution of indoor environments contributes to several allergic symptoms and represents a public health problem. It is well-established that 1-octen-3-ol, also known as mushroom alcohol, is a fungal volatile organic compound (VOC) commonly found in damp indoor spaces and responsible for the typical musty odor. Previously it was reported that exposure to 1-octen-3-ol induced inflammations and disrupted mitochondrial morphology and bioenergetic rate in Drosophila melanogaster. The aim of this study was to examine the influence of 1-octen-3-ol on dehydrogenase activity, apoptotic biomarkers, levels of nitric oxide (NO) and reactive oxygen species (ROS), as well as antioxidant enzymes activities. D. melanogaster flies were exposed to an atmosphere containing 1-octen-3-ol (2.5 or ∞l/L) for 24 hr. Data demonstrated that 1-octen-3-ol decreased dehydrogenases activity and NO levels but increased ROS levels accompanied by stimulation of glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities without altering caspase 3/7 activation. These findings indicate that adverse mitochondrial activity effects following exposure of D. melanogaster to 1-octen-3-ol, a fungal VOC, may be attributed to oxidant stress. The underlying mechanisms involved in adverse consequences of indoor fungal exposure appear to be related to necrotic but not apoptotic mechanisms. https://www.selleckchem.com/products/dcemm1.html The adverse consequences were sex-dependent with males displaying higher sensitivity to 1-octen-3-ol. Based upon on the fact that the fly genome shares nearly 75% of disease-related genes to human exposure to this fungus may explain the adverse human responses to mold especially for males.Primary liver cancer (PLC) significantly affects the health of patients globally owing to its high morbidity and low survival rate. Radiofrequency ablation (RFA) has recently been introduced for the clinical treatment of PLC. However, significant immunosuppressive effects are induced by RFA, which limits its application. This study aimed to explore the potential of combination therapy with RFA by investigating the effects of siRNAs against programmed death receptor 1 (PD-1) and transforming growth factor-β (TGF-β) on the antitumor effect induced by RFA. We observed that compared with si-NC, cell viability was reduced, apoptosis rate was elevated, release of inflammatory factors and percentage of CD3+CD8+ cells were increased, and the PI3K/AKT/mTOR pathway was repressed in the co-culture of RFA-treated H22 cells and CD8+ T cells by transfection with si-PD-1 and si-TGF-β; these effects were further enhanced by co-transfection with si-PD-1 and si-TGF-β. Additionally, in H22 cell xenograft-bearing mice treated with RFA, compared with the si-NC group, repressed tumor growth, prolonged survival, increased production of inflammatory factors and expression of CD3 and CD8 in tumor tissues, and downregulation of the PI3K/AKT/mTOR pathway were observed in the si-PD-1 and si-TGF-β groups; these effects were further enhanced in the si-PD-1 + si-TGF-β group. Taken together, our data revealed that suppression of the TGF-β signaling pathway produced a synergistic antitumor effect of combination therapy with PD-1 blockade and RFA against PLC. [Figure see text].Fungal infections of the orbit are infrequent. They typically affect immunocompromised individuals but, in some instances, can also affect an immunocompetent person. They mimic much orbital pathology clinically. Ours is a series of three patients eventually diagnosed with orbital aspergillosis but who, initially, were thought to have some other pathology.
Open trigger finger release (OTFR) and endoscopic trigger finger release (ETFR) are effective methods in treating stenosing tenosynovitis. However, a paucity of literature exists comparing the techniques. This study describes and compares postoperative complications following OTFR and ETFR at a single institution.

Patients undergoing trigger finger release between 2018 and 2020 within a single institution were identified. Electronic medical records were reviewed for patient demographics, surgical history, surgical characteristics, and clinical outcomes. Major and minor postoperative complications were assessed. Secondary outcome measures included tourniquet time and procedure time. Statistical analysis evaluated associations between postoperative complications, surgical technique, patient demographics, and surgical characteristics.

In total, 57 patients (80 digits) were included in the study 42 digits treated with OTFR and 38 digits treated with ETFR. Mean follow-up time was 57.6 ± 69.0 days (range, 7-3ed with OTFR and ETFR showed similar postoperative complication rates. Continued investigations into the benefits of ETFR are warranted.The Premack principle states that any Response A can reinforce any other Response B if the independent rate of A is greater than the independent rate of B. This theory demonstrates reinforcer relativity, where the relative probabilities of responses can be more impactful than preference. Applying the Premack principle involves arranging the environment to restrict access to certain responses based on relative probabilities of a set of given responses. Though the Premack principle is described in modern behavior analytic texts, Konarski et al. identified a lack of empirical evidence to support its application. The purpose of the current paper is to systematically review the extant literature using the Premack principle and evaluate how and if researchers have applied reinforcer relativity as described by Premack and the subsequent effectiveness of these procedures. Additionally, we make recommendations for practitioners and future researchers based on our findings.
Multiple sclerosis (MS) is more prevalent in women than in men. The sex of the patient, and pregnancy, are reported to be associated with the clinical features of MS. The mechanism of this is unclear.

This review summarizes data about sex differences in MS and the role of pregnancy. Possible mechanisms for the effects of sex and pregnancy are summarized, and practical suggestions for addressing these issues are provided.

There is considerable interdependence of the variables that are associated with MS. Men have a worse outcome of MS, and this could be due to the same factors that lead to greater incidence of neurodegenerative disease in men. The possible role of parity on the long-term outcome of MS is of interest. Future studies that look at the mechanisms of the effects of the sex of the patient on the outcome of MS are required. However, there are some actions that can be taken without further research. We can concentrate on public health measures that address the modifiable risk factors for MS and ensure that disease is controlled in women who intend to become pregnant and use appropriate disease modifying agents during pregnancy.
There is considerable interdependence of the variables that are associated with MS. Men have a worse outcome of MS, and this could be due to the same factors that lead to greater incidence of neurodegenerative disease in men. The possible role of parity on the long-term outcome of MS is of interest. Future studies that look at the mechanisms of the effects of the sex of the patient on the outcome of MS are required. However, there are some actions that can be taken without further research. We can concentrate on public health measures that address the modifiable risk factors for MS and ensure that disease is controlled in women who intend to become pregnant and use appropriate disease modifying agents during pregnancy.Neuropathic pain is a distressing medical condition with few effective treatments, and the role of VEGFA in inflammatory pain has been confirmed in many studies. However, the mechanism by which VEGFA affects neuropathic pain remains unclear. In this study, we demonstrated that VEGFA plays an important role in spare nerve injury (SNI)-induced neuropathic pain, which is mediated by enhanced expression and colocalization of VEGFA, p-AKT and TRPV1 in an SNI-induced neuropathic pain model. Soluble VEGFR1 (sFlt1) relieved mechanical hyperalgesia and the expression of inflammatory markers and also ameliorated the expression of VEGFA, VEGFR2, p-AKT, and TRPV1 in the spinal cord. However, these effects of sFlt1 could be blocked by rpVEGFA and 740 Y-P. Therefore, our study indicates that targeting VEGFA with sFlt1 reduces neuropathic pain development via the AKT/TRPV1 pathway in SNI-induced nerve injury. This study elucidates a new therapeutic target for neuropathic pain.
Melanoma is a highly heterogeneous and aggressive cutaneous malignancy. Ferroptosis, a new pathway of cell death depending on the intracellar iron, has been shown to be significantly associated with apoptosis of a number of tumors, including melanoma. Nevertheless, the relationship between ferroptosis-related genes (FRGs) and the melanoma patients' prognosis needs to be explored.

Download expression profiles of FRGs and clinical data from The Cancer Genome Atlas (TCGA) database. 70% data were randomly selected from the TCGA database and utilized the univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model to create a prognostic model, and the remaining 30% was used to validate the predictive power of the model. In addition, GSE65904 and GSE22153 date sets as the verification cohort to testify the predictive ability of the signature.

We identified nine FRGs relating with melanoma patients' overall survival (OS) and established a prognostic model based on their expression. During the research, patients were divided into group of high-risk and low-risk according to the results of LASSO regression analysis. Survival time was significantly longer in the low-risk group than that of in the high-risk group (P < 0.001). Enrichment analysis of different risk groups demonstrated that the reasons for the difference were related to immune-related pathways, and the degree of immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group.

The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.
The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.
Chemotherapy-related adverse events (AEs) can negatively impact the care of patients. The prevention and management of AEs often require additional medications. This study evaluated the percentages of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) undergoing second-line therapy with 5-fluorouracil (5-FU)-based regimens that experienced AEs during treatment and received medication to manage those AEs.

We conducted a retrospective observational analysis utilizing the Flatiron Health database of adult patients with mPDAC who started second-line therapy between January 2016 and August 2020. The occurrence of diarrhea, fatigue, nausea and vomiting, neuropathy, and hematologic AEs including G3/G4 anemia, neutropenia, and thrombocytopenia was assessed. The use of concomitant medications including atropine and granulocyte colony stimulating factor (G-CSF) was assessed.

Of the 825 eligible patients, 29.0% (
 = 239) received FOLFIRINOX, 24.0% (
 = 198) received FOLFOX, 6.8% (
 = 56) received FOLFIRI, and 40.

25 mins ago


Ghrelin is a stomach-derived hormone and a potent appetite stimulant. Ghrelin has recently harbored interest as a potential regulator of carbohydrate and lipid metabolism in skeletal muscle and adipose tissue; however, in vivo ghrelin administration is confounded by secondary effects. The assessment of the direct metabolic effects of acylated (AG) and unacylated (UnAG) ghrelin is a relatively new area of research. In isolated adipocytes and muscle, ghrelin has demonstrated antilipolytic effects. In muscle, ghrelin has been shown to acutely stimulate fat oxidation, which may protect the muscle from the insulin-desensitizing effects of high fatty acid concentrations. The effects of ghrelin directly on muscle glucose uptake are controversial. Whether ghrelin can be utilized therapeutically for conditions such as type 2 diabetes will depend on our better understanding of ghrelin's independent effects on muscle and adipose tissue metabolism, and whether this can predict ghrelin's effects when administered in vivo.Browning of white adipose tissue is a cold-induced phenomenon in rodents, constituted by the differentiation of a subset of thermogenic adipocytes among existing white adipocytes. Emerging evidence in the literature points at additional factors and environmental conditions stimulating browning in rodents, including physical exercise training. Exercise engages sympathetic activation which during cold activation promotes proliferation and differentiation of brown preadipocytes. Exercise also stimulates the release of multiple growth factors and cytokines. Importantly, there are clear discrepancies between human and rodents with regard to thermogenic capacity and browning potential. Here we provide a translational perspective on exercise-induced browning and review recent findings on the role of myokines and hepatokines in this process.In a large-scale survey in the UK, recruited veterinary practices were asked to inspect client-ownedcats and dogs, selected at random between April and June 2018, following a standardised flea inspection protocol. A total of 326 veterinary practices participated and 812 cats and 662 dogs were examined during the 3-month period. Fleas were collected, identified to species level and fleas of the same species collected from a single animal were pooled together and treated as a single sample. A total of 470 pooled flea samples were screened by PCR and DNA sequence analysis for a subset of Rickettsia species including R. felis and R. typhi. On analysis, 27 (5.7%) of the pooled flea samples were positive for R. felis DNA; these were predominantly in the cat flea, Ctenocephalides felis, but one dog flea, Ctenocephalides canis was also positive for this pathogen.Our main study objective was to determine the prevalence and trend of parasitic infection in client-owned dogs examined at the veterinary parasitology diagnostic laboratory of Oklahoma State University over the past 12 years. All results of centrifugal flotation, saline direct smear, sedimentation, Baermann, acid-fast staining for Cryptosporidium detection, and Giardia antigen examinations on fecal samples from client-owned dogs submitted to the Boren Veterinary Medical Hospital and Oklahoma Animal Disease Diagnostic Laboratory of Oklahoma State University from 2007 through 2018 were included. The impact of sex, age, and seasonality on the prevalence of parasitic infection was also statistically evaluated. A total of 7,409 cases were included for this study. Majority of cases (79.58%; 5,896/7,409) did not include any parasites, eggs, larva, oocysts, or cysts. Approximately 15.41% (1,142/7,409) of client-owned dogs were infected by at least one parasite, and 5.01% (371/7,409) of dogs were infected by multiple chus eggs (0.01%; 1/7,409), and Paragonimus kellicotti eggs (0.01%; 1/7,409). In addition to endoparasites, some ectoparasites, such as Demodex mites (0.22%; 16/7,409), Otodectes cynotis mites (0.01%; 1/7,409), Rhipicephalus sanguineus ticks (0.01%; 1/7,409), and Sarcoptes scabiei mites (0.01%; 1/7,409), were detected by fecal examinations. Pseudo/spurious parasites were identified in approximately 4.35% of cases (322/7,409). There was no statistically significant difference for parasite prevalence between sexes (p = 0.3231). However, statistically significant differences were observed with certain parasites when compared by age groups, and generally, prevalence of parasitism decreased as age of client-owned dogs increased (p less then 0.0001). Statistical analyses also revealed significant differences by months (p = 0.0013). Overall, the prevalence of parasitic infection in client-owned dogs decreased over the past 12 years (p less then 0.0001).In this work, pinewood and bamboo were pyrolyzed at 600 °C to prepare PBC and BBC-supported zerovalent iron (ZVI), respectively. Raman spectra suggested PBC was more intensively carbonized than BBC as indicated by higher ID/IG ratio. XRD and TEM confirmed nanoscaled ZVI was well dispersed in PBC but soldered in chain-structure in BBC. Maximal chromate (Cr(VI)) sorption capacity followed the order of PBC/ZVI (5.93 g kg-1)>BBC/ZVI (3.61 g kg-1)>BBC (3.55 g kg-1)>PBC (2.59 g kg-1). Desorption and XPS of four Cr-spent sorbents suggested reduction accounted for 79-88% of overall Cr(VI) detoxification. Greater Cr(VI) reduction of BBC than PBC indicated greater tendency of BBC to donate electrons. However, Cr(VI) reduction by PBC/ZVI was 1.7 times greater than BBC/ZVI, corresponding to greater electron transfer of PBC/ZVI (2.5 μA e-) than BBC/ZVI (0.5 μA e-). Thus, PBC is more conducible to transfer electrons as evidenced by Tafel and Amperometric analyses. Demineralization of pristine BC enhanced the difference between PBC/ZVI and BBC/ZVI regarding Cr(VI) reduction, suggesting the dominant role of biopolymers in biomass in terms of electron transfer capacity. Three model biopolymers were compared which indicated lignin-BC had lower electron transfer rates than cellulose-BC and hemicellulose-BC. BC prepared by lignin extracted from pinewood exhibited higher corrosion rate and lower electrical resistance than that from bamboo. Thus, unfavorable lignin in bamboo compromised electron transfer of BBC and Cr(VI) reduction by BBC/ZVI.Background The home environment is regarded as a safe, comfortable environment, however, home can also be a stressful place. Compared to staying in the indoor home environment, the effects of short visits to outdoor urban environments on short-term psychological, physiological and cognitive responses were not studied previously. Aim To evaluate whether visits to different urban and ethnic environments, in comparison to staying in the home indoor environment, leads to short-term changes in psychological, physiological and cognitive responses and whether these responses are independent of ethnicity. Methods The participants, 20-35 year-old healthy women (N = 72, 48 Arab and 24 Jewish), started the experiment at their home and visited six different outdoor urban environments in predominantly ethnic Arab or Jewish cities, in Israel. First they visited intra-ethnic city and afterward inter-ethnic city environments. In each city they first visited an urban park and afterward, in a random order, a residential neighbing the visits did not explain the observed changes between the outdoor environments and home. Conclusions Visits to urban parks compared to staying in the home environment had beneficial short-term changes in psychological, physiological, and cognitive responses, regardless of ethnicity. The changes could not be attributed to the investigated mediators. Women should be encouraged to go outdoors and specifically visit parks to improve their psychological and physiological health.Intentional or accidental release of copper nanoparticles (Cu-NPs) from consumer products during manufacturing, use, and end-of-life management could pose health and ecological risks. This paper presents a detailed study on the role of water chemistry on the fate of uncoated and carbon-coated Cu-NPs dispersed in aqueous cetyltrimethylammonium bromide (CTAB) surfactant in the presence and absence of humic acids (HAs). A range of water chemistry and HAs had minimum impact on hydrodynamic diameter and zeta-potential values of uncoated and carbon-coated Cu-NPs. The water pH significantly (p less then 0.001) affected the aggregation of uncoated Cu-NPs unlike that of carbon-coated Cu-NPs; however, the presence of HAs increased the stability of uncoated Cu-NPs. Although CTAB is considered as an efficient dispersant to stabilize Cu-NPs, the effect descended with time for uncoated Cu-NPs. The dissolution of Cu over time decreased with increasing pH for both uncoated (0.5-50% weight) and carbon-coated (0.5-40% weight) Cu-NPs. However, carbon-coated Cu-NPs exhibited significant dissolution (p less then 0.001) at neutral pH than uncoated Cu-NPs may be due to the additional carbon it acquired during coating. Increasing HAs concentration from 0 to 15 mg L-1 at pH 5.5 inhibited aggregations but enhanced dissolution of the uncoated and carbon-coated Cu-NPs. https://www.selleckchem.com/products/Trichostatin-A.html These findings inform risk analysis of Cu-NPs including how Cu-NPs fate, mobility and bioavailability are modulated by particles coating and dispersant, HAs presence, water chemistry and exposure time in dispersion media.Graphene oxides (GO) and layered double hydroxides (LDHs) were applied to produce alginate beads for the remove of 90Sr2+ and 79SeO42-. The Freundlich isotherm indicated that the Sr2+ sorptions were based on the energetically heterogeneous multilayer surfaces. In contrast, the sorption behavior of SeO42- fitted to the Langmuir adsorption isotherm models, indicating that the removal of SeO42- was caused by the ion-exchange of LDHs. The synthesized LDH/GO alginates beads were also applied for setting up small-bore adsorption columns with loading synthetic SeO42- and Sr2+ contaminated wastewater. Based on the water chemistry, the adsorbed amount of Sr2+ significantly increased after using alginates beads, which was attributed to the functional groups of either GO or alginic acid. The incorporated SeO42- was highly depended on the contents of fabricated LDHs in alginate beads. Specifically, the adsorption capacity of Sr2+ (0.85-0.91 mmol/g) on GO slightly increased after alginates fabrication. Therefore, it was deduced that this layered material was partially exfoliated during the manufacture and thus increased the sorption sites. Applications of LDH/GO alginates beads in the removal of both Sr2+ and SeO42- in water and soil treatment have a significant impact on the environmental remediation.Background Genetic variations in glutathione (GSH)-related and metallothionein (MT) genes, which are involved in producing enzymes in the methylmercury (MeHg) metabolism pathway, have been proposed as one of the reasons for the individual variability in MeHg toxicokinetics. Objective To investigate the impact of genetic variations in MT and GSH-related genes on the association of fish consumption with body burden of MeHg, as measured by hair Hg concentrations among young children and women of childbearing age. Methods A total of 179 unrelated children and 165 mothers with either high or low fish consumption were recruited from the community. Their hair total Hg (tHg) and MeHg levels and genotypes for SNPs located on the GCLC, GCLM, GPX1, GSTA1, GSTP1, MT1A, MT2A, and MT4 genes were determined. Based on their 14-day food records, the amounts of fish consumed and their MeHg intakes were estimated. The impact of genetic variations on hair Hg concentrations was examined by using Mann-Whitney tests and multivariable linear regression analyses.

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027, 95% CI 1.716-5.338; P < 0.001), CSS (HR 2.115, 95% CI 1.093-4.090; P = 0.026), DFS (HR 2.584, 95% CI 1.569-4.255; P < 0.001). Age, diabetes history, pathologic T stage, and lymph node status also were independent predictors of prognosis for BC patients.

Our results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.
Our results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.DNA damage repair (DDR) pathways play an essential role in maintaining genomic integrity. https://www.selleckchem.com/products/glutathione.html DDR dysfunction leads to accumulated DNA damage, predisposition to cancer, and high sensitivity to chemotherapy and radiotherapy. Recent studies have demonstrated that DDR status is associated with response to immune checkpoint inhibitors (ICIs). Among the DDR pathways, mismatch repair is one of the most recognized predictive biomarkers for ICIs. Furthermore, preclinical and early clinical studies suggest the rationale of combining agents targeting the DDR pathways, such as poly (ADP-ribose) polymerase (PARP) inhibitors, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, and ataxia telangiectasia and rad3-related (ATR) kinase inhibitors, with ICIs. In the present review, we describe the predictive role of DDR pathways in ICIs and summarize the advances in potential combination strategies of novel agents targeting DDR with ICIs for cancer treatment.Regulatory T cells (Tregs) are immunosuppressive cells involved in antitumor immunity. However, the regulation of Treg generation by inflammation in the tumor microenvironment has not been carefully investigated. Here, we demonstrated that IL-21-polarized inflammation was enriched in the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) and that IL-21 could promote PD-L1-induced Treg generation in a PD-1-dependent manner. Moreover, generated Tregs showed a greater ability to suppress the proliferation of tumor-associated antigen (TAA)-specific T cells than naturally occurring Tregs. Importantly, an anti-PD-1 antibody could inhibit only Treg expansion induced by clinical tumor explants with high expression of IL-21/PD-L1. In addition, neutralizing IL-21 could enhance the anti-PD-1 antibody-mediated inhibitory effect on Treg expansion. Furthermore, simultaneous high expression of IL-21 and PD-L1 was associated with more Treg infiltrates and predicted reduced overall and disease-free survival in patients with HNSCC. These findings indicate that IL-21 in the tumor microenvironment may promote PD-L1-induced, Treg-mediated immune escape in a PD-1-dependent manner and that an IL-21 neutralization strategy may enhance PD-1 blockade-based antitumor immunotherapy by targeting Treg-mediated immune evasion in patients with high expression of IL-21 and PD-L1.MYCN gene amplification and upregulated expression are major hallmarks in the progression of high-risk neuroblastoma. MYCN expression and function in modulating gene synthesis in neuroblastoma is controlled at virtually every level, including poorly understood regulation at the post-transcriptional level. MYCN modulates the expression of various microRNAs including the miR-17-92 cluster. MYCN mRNA expression itself is subjected to the control by miRNAs, most prominently the miR-17-92 cluster that balances MYCN expression by feed-back regulation. This homeostasis seems disturbed in neuroblastoma where MYCN upregulation coincides with severely increased expression of the miR-17-92 cluster. In the presented study, we applied high-throughput next generation sequencing to unravel the miRNome in a cohort of 97 neuroblastomas, representing all clinical stages. Aiming to reveal the MYCN-dependent miRNome, we evaluate miRNA expression in MYCN-amplified as well as none amplified tumor samples. In correlation with survival data analysis of differentially expressed miRNAs, we present various putative oncogenic as well as tumor suppressive miRNAs in neuroblastoma. Using microRNA trapping by RNA affinity purification, we provide a comprehensive view of MYCN-regulatory miRNAs in neuroblastoma-derived cells, confirming a pivotal role of the miR-17-92 cluster and moderate association by the let-7 miRNA family. Attempting to decipher how MYCN expression escapes elevated expression of inhibitory miRNAs, we present evidence that RNA-binding proteins like the IGF2 mRNA binding protein 1 reduce miRNA-directed downregulation of MYCN in neuroblastoma. Our findings emphasize the potency of post-transcriptional regulation of MYCN in neuroblastoma and unravel new avenues to pursue inhibition of this potent oncogene.Numerous colon cancer cases are resistant to chemotherapy based on oxaliplatin and suffer from relapse. A number of survival- and prognosis-related biomarkers have been identified based on database mining for patients who develop drug resistance, but the single individual gene biomarker cannot attain high specificity and sensitivity in prognosis prediction. This work was conducted aiming to establish a new gene signature using oxaliplatin resistance-related genes to predict the prognosis for colon cancer. To this end, we downloaded gene expression profile data of cell lines that are resistant and not resistant to oxaliplatin from the Gene Expression Omnibus (GEO) database. Altogether, 495 oxaliplatin resistance-related genes were searched by weighted gene co-expression network analysis (WGCNA) and differential expression analysis. As suggested by functional analysis, the above genes were mostly enriched into cell adhesion and immune processes. Besides, a signature was built based on four oxaliplatin resistance-related genes selected from the training set to predict the overall survival (OS) by stepwise regression and least absolute shrinkage and selection operator (LASSO) Cox analysis. Relative to the low risk score group, the high risk score group had dismal OS (P 0.7). Additionally, multivariate Cox regression suggested that the signature constructed based on four oxaliplatin resistance-related genes predicted the prognosis for colon cancer cases [hazard ratio (HR), 2.77; 95% CI, 2.03-3.78; P less then 0.001]. Finally, external test sets were utilized to further validate the stability and accuracy of oxaliplatin resistance-related gene signature for prognosis of colon cancer patients. To sum up, this study establishes a signature based on four oxaliplatin resistance-related genes for predicting the survival of colon cancer patients, which sheds more light on the mechanisms of oxaliplatin resistance and helps identify colon cancer cases with a dismal prognostic outcome.

20 mins ago


The models were evaluated on a test set from an independent trial and achieved a Dice Similarity Coefficient (DSC) of 0.96 for heart segmentation and 0.95 for bladder segmentation, Average Surface Distance (ASD) of 0.44mm on heart and 0.90mm on bladder.

This methodology could be a valuable component to the FDG-PET/CT data processing chain by removing FDG physiological noise associated with heart and/or bladder accumulation prior to image analysis by manual, semi- or automated tumor analysis methods.
This methodology could be a valuable component to the FDG-PET/CT data processing chain by removing FDG physiological noise associated with heart and/or bladder accumulation prior to image analysis by manual, semi- or automated tumor analysis methods.Fungal pollution of indoor environments contributes to several allergic symptoms and represents a public health problem. It is well-established that 1-octen-3-ol, also known as mushroom alcohol, is a fungal volatile organic compound (VOC) commonly found in damp indoor spaces and responsible for the typical musty odor. Previously it was reported that exposure to 1-octen-3-ol induced inflammations and disrupted mitochondrial morphology and bioenergetic rate in Drosophila melanogaster. The aim of this study was to examine the influence of 1-octen-3-ol on dehydrogenase activity, apoptotic biomarkers, levels of nitric oxide (NO) and reactive oxygen species (ROS), as well as antioxidant enzymes activities. D. melanogaster flies were exposed to an atmosphere containing 1-octen-3-ol (2.5 or ∞l/L) for 24 hr. Data demonstrated that 1-octen-3-ol decreased dehydrogenases activity and NO levels but increased ROS levels accompanied by stimulation of glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities without altering caspase 3/7 activation. These findings indicate that adverse mitochondrial activity effects following exposure of D. melanogaster to 1-octen-3-ol, a fungal VOC, may be attributed to oxidant stress. The underlying mechanisms involved in adverse consequences of indoor fungal exposure appear to be related to necrotic but not apoptotic mechanisms. https://www.selleckchem.com/products/dcemm1.html The adverse consequences were sex-dependent with males displaying higher sensitivity to 1-octen-3-ol. Based upon on the fact that the fly genome shares nearly 75% of disease-related genes to human exposure to this fungus may explain the adverse human responses to mold especially for males.Primary liver cancer (PLC) significantly affects the health of patients globally owing to its high morbidity and low survival rate. Radiofrequency ablation (RFA) has recently been introduced for the clinical treatment of PLC. However, significant immunosuppressive effects are induced by RFA, which limits its application. This study aimed to explore the potential of combination therapy with RFA by investigating the effects of siRNAs against programmed death receptor 1 (PD-1) and transforming growth factor-β (TGF-β) on the antitumor effect induced by RFA. We observed that compared with si-NC, cell viability was reduced, apoptosis rate was elevated, release of inflammatory factors and percentage of CD3+CD8+ cells were increased, and the PI3K/AKT/mTOR pathway was repressed in the co-culture of RFA-treated H22 cells and CD8+ T cells by transfection with si-PD-1 and si-TGF-β; these effects were further enhanced by co-transfection with si-PD-1 and si-TGF-β. Additionally, in H22 cell xenograft-bearing mice treated with RFA, compared with the si-NC group, repressed tumor growth, prolonged survival, increased production of inflammatory factors and expression of CD3 and CD8 in tumor tissues, and downregulation of the PI3K/AKT/mTOR pathway were observed in the si-PD-1 and si-TGF-β groups; these effects were further enhanced in the si-PD-1 + si-TGF-β group. Taken together, our data revealed that suppression of the TGF-β signaling pathway produced a synergistic antitumor effect of combination therapy with PD-1 blockade and RFA against PLC. [Figure see text].Fungal infections of the orbit are infrequent. They typically affect immunocompromised individuals but, in some instances, can also affect an immunocompetent person. They mimic much orbital pathology clinically. Ours is a series of three patients eventually diagnosed with orbital aspergillosis but who, initially, were thought to have some other pathology.
Open trigger finger release (OTFR) and endoscopic trigger finger release (ETFR) are effective methods in treating stenosing tenosynovitis. However, a paucity of literature exists comparing the techniques. This study describes and compares postoperative complications following OTFR and ETFR at a single institution.

Patients undergoing trigger finger release between 2018 and 2020 within a single institution were identified. Electronic medical records were reviewed for patient demographics, surgical history, surgical characteristics, and clinical outcomes. Major and minor postoperative complications were assessed. Secondary outcome measures included tourniquet time and procedure time. Statistical analysis evaluated associations between postoperative complications, surgical technique, patient demographics, and surgical characteristics.

In total, 57 patients (80 digits) were included in the study 42 digits treated with OTFR and 38 digits treated with ETFR. Mean follow-up time was 57.6 ± 69.0 days (range, 7-3ed with OTFR and ETFR showed similar postoperative complication rates. Continued investigations into the benefits of ETFR are warranted.The Premack principle states that any Response A can reinforce any other Response B if the independent rate of A is greater than the independent rate of B. This theory demonstrates reinforcer relativity, where the relative probabilities of responses can be more impactful than preference. Applying the Premack principle involves arranging the environment to restrict access to certain responses based on relative probabilities of a set of given responses. Though the Premack principle is described in modern behavior analytic texts, Konarski et al. identified a lack of empirical evidence to support its application. The purpose of the current paper is to systematically review the extant literature using the Premack principle and evaluate how and if researchers have applied reinforcer relativity as described by Premack and the subsequent effectiveness of these procedures. Additionally, we make recommendations for practitioners and future researchers based on our findings.
Multiple sclerosis (MS) is more prevalent in women than in men. The sex of the patient, and pregnancy, are reported to be associated with the clinical features of MS. The mechanism of this is unclear.

This review summarizes data about sex differences in MS and the role of pregnancy. Possible mechanisms for the effects of sex and pregnancy are summarized, and practical suggestions for addressing these issues are provided.

There is considerable interdependence of the variables that are associated with MS. Men have a worse outcome of MS, and this could be due to the same factors that lead to greater incidence of neurodegenerative disease in men. The possible role of parity on the long-term outcome of MS is of interest. Future studies that look at the mechanisms of the effects of the sex of the patient on the outcome of MS are required. However, there are some actions that can be taken without further research. We can concentrate on public health measures that address the modifiable risk factors for MS and ensure that disease is controlled in women who intend to become pregnant and use appropriate disease modifying agents during pregnancy.
There is considerable interdependence of the variables that are associated with MS. Men have a worse outcome of MS, and this could be due to the same factors that lead to greater incidence of neurodegenerative disease in men. The possible role of parity on the long-term outcome of MS is of interest. Future studies that look at the mechanisms of the effects of the sex of the patient on the outcome of MS are required. However, there are some actions that can be taken without further research. We can concentrate on public health measures that address the modifiable risk factors for MS and ensure that disease is controlled in women who intend to become pregnant and use appropriate disease modifying agents during pregnancy.Neuropathic pain is a distressing medical condition with few effective treatments, and the role of VEGFA in inflammatory pain has been confirmed in many studies. However, the mechanism by which VEGFA affects neuropathic pain remains unclear. In this study, we demonstrated that VEGFA plays an important role in spare nerve injury (SNI)-induced neuropathic pain, which is mediated by enhanced expression and colocalization of VEGFA, p-AKT and TRPV1 in an SNI-induced neuropathic pain model. Soluble VEGFR1 (sFlt1) relieved mechanical hyperalgesia and the expression of inflammatory markers and also ameliorated the expression of VEGFA, VEGFR2, p-AKT, and TRPV1 in the spinal cord. However, these effects of sFlt1 could be blocked by rpVEGFA and 740 Y-P. Therefore, our study indicates that targeting VEGFA with sFlt1 reduces neuropathic pain development via the AKT/TRPV1 pathway in SNI-induced nerve injury. This study elucidates a new therapeutic target for neuropathic pain.
Melanoma is a highly heterogeneous and aggressive cutaneous malignancy. Ferroptosis, a new pathway of cell death depending on the intracellar iron, has been shown to be significantly associated with apoptosis of a number of tumors, including melanoma. Nevertheless, the relationship between ferroptosis-related genes (FRGs) and the melanoma patients' prognosis needs to be explored.

Download expression profiles of FRGs and clinical data from The Cancer Genome Atlas (TCGA) database. 70% data were randomly selected from the TCGA database and utilized the univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model to create a prognostic model, and the remaining 30% was used to validate the predictive power of the model. In addition, GSE65904 and GSE22153 date sets as the verification cohort to testify the predictive ability of the signature.

We identified nine FRGs relating with melanoma patients' overall survival (OS) and established a prognostic model based on their expression. During the research, patients were divided into group of high-risk and low-risk according to the results of LASSO regression analysis. Survival time was significantly longer in the low-risk group than that of in the high-risk group (P < 0.001). Enrichment analysis of different risk groups demonstrated that the reasons for the difference were related to immune-related pathways, and the degree of immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group.

The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.
The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.
Chemotherapy-related adverse events (AEs) can negatively impact the care of patients. The prevention and management of AEs often require additional medications. This study evaluated the percentages of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) undergoing second-line therapy with 5-fluorouracil (5-FU)-based regimens that experienced AEs during treatment and received medication to manage those AEs.

We conducted a retrospective observational analysis utilizing the Flatiron Health database of adult patients with mPDAC who started second-line therapy between January 2016 and August 2020. The occurrence of diarrhea, fatigue, nausea and vomiting, neuropathy, and hematologic AEs including G3/G4 anemia, neutropenia, and thrombocytopenia was assessed. The use of concomitant medications including atropine and granulocyte colony stimulating factor (G-CSF) was assessed.

Of the 825 eligible patients, 29.0% (
 = 239) received FOLFIRINOX, 24.0% (
 = 198) received FOLFOX, 6.8% (
 = 56) received FOLFIRI, and 40.

25 mins ago


Ghrelin is a stomach-derived hormone and a potent appetite stimulant. Ghrelin has recently harbored interest as a potential regulator of carbohydrate and lipid metabolism in skeletal muscle and adipose tissue; however, in vivo ghrelin administration is confounded by secondary effects. The assessment of the direct metabolic effects of acylated (AG) and unacylated (UnAG) ghrelin is a relatively new area of research. In isolated adipocytes and muscle, ghrelin has demonstrated antilipolytic effects. In muscle, ghrelin has been shown to acutely stimulate fat oxidation, which may protect the muscle from the insulin-desensitizing effects of high fatty acid concentrations. The effects of ghrelin directly on muscle glucose uptake are controversial. Whether ghrelin can be utilized therapeutically for conditions such as type 2 diabetes will depend on our better understanding of ghrelin's independent effects on muscle and adipose tissue metabolism, and whether this can predict ghrelin's effects when administered in vivo.Browning of white adipose tissue is a cold-induced phenomenon in rodents, constituted by the differentiation of a subset of thermogenic adipocytes among existing white adipocytes. Emerging evidence in the literature points at additional factors and environmental conditions stimulating browning in rodents, including physical exercise training. Exercise engages sympathetic activation which during cold activation promotes proliferation and differentiation of brown preadipocytes. Exercise also stimulates the release of multiple growth factors and cytokines. Importantly, there are clear discrepancies between human and rodents with regard to thermogenic capacity and browning potential. Here we provide a translational perspective on exercise-induced browning and review recent findings on the role of myokines and hepatokines in this process.In a large-scale survey in the UK, recruited veterinary practices were asked to inspect client-ownedcats and dogs, selected at random between April and June 2018, following a standardised flea inspection protocol. A total of 326 veterinary practices participated and 812 cats and 662 dogs were examined during the 3-month period. Fleas were collected, identified to species level and fleas of the same species collected from a single animal were pooled together and treated as a single sample. A total of 470 pooled flea samples were screened by PCR and DNA sequence analysis for a subset of Rickettsia species including R. felis and R. typhi. On analysis, 27 (5.7%) of the pooled flea samples were positive for R. felis DNA; these were predominantly in the cat flea, Ctenocephalides felis, but one dog flea, Ctenocephalides canis was also positive for this pathogen.Our main study objective was to determine the prevalence and trend of parasitic infection in client-owned dogs examined at the veterinary parasitology diagnostic laboratory of Oklahoma State University over the past 12 years. All results of centrifugal flotation, saline direct smear, sedimentation, Baermann, acid-fast staining for Cryptosporidium detection, and Giardia antigen examinations on fecal samples from client-owned dogs submitted to the Boren Veterinary Medical Hospital and Oklahoma Animal Disease Diagnostic Laboratory of Oklahoma State University from 2007 through 2018 were included. The impact of sex, age, and seasonality on the prevalence of parasitic infection was also statistically evaluated. A total of 7,409 cases were included for this study. Majority of cases (79.58%; 5,896/7,409) did not include any parasites, eggs, larva, oocysts, or cysts. Approximately 15.41% (1,142/7,409) of client-owned dogs were infected by at least one parasite, and 5.01% (371/7,409) of dogs were infected by multiple chus eggs (0.01%; 1/7,409), and Paragonimus kellicotti eggs (0.01%; 1/7,409). In addition to endoparasites, some ectoparasites, such as Demodex mites (0.22%; 16/7,409), Otodectes cynotis mites (0.01%; 1/7,409), Rhipicephalus sanguineus ticks (0.01%; 1/7,409), and Sarcoptes scabiei mites (0.01%; 1/7,409), were detected by fecal examinations. Pseudo/spurious parasites were identified in approximately 4.35% of cases (322/7,409). There was no statistically significant difference for parasite prevalence between sexes (p = 0.3231). However, statistically significant differences were observed with certain parasites when compared by age groups, and generally, prevalence of parasitism decreased as age of client-owned dogs increased (p less then 0.0001). Statistical analyses also revealed significant differences by months (p = 0.0013). Overall, the prevalence of parasitic infection in client-owned dogs decreased over the past 12 years (p less then 0.0001).In this work, pinewood and bamboo were pyrolyzed at 600 °C to prepare PBC and BBC-supported zerovalent iron (ZVI), respectively. Raman spectra suggested PBC was more intensively carbonized than BBC as indicated by higher ID/IG ratio. XRD and TEM confirmed nanoscaled ZVI was well dispersed in PBC but soldered in chain-structure in BBC. Maximal chromate (Cr(VI)) sorption capacity followed the order of PBC/ZVI (5.93 g kg-1)>BBC/ZVI (3.61 g kg-1)>BBC (3.55 g kg-1)>PBC (2.59 g kg-1). Desorption and XPS of four Cr-spent sorbents suggested reduction accounted for 79-88% of overall Cr(VI) detoxification. Greater Cr(VI) reduction of BBC than PBC indicated greater tendency of BBC to donate electrons. However, Cr(VI) reduction by PBC/ZVI was 1.7 times greater than BBC/ZVI, corresponding to greater electron transfer of PBC/ZVI (2.5 μA e-) than BBC/ZVI (0.5 μA e-). Thus, PBC is more conducible to transfer electrons as evidenced by Tafel and Amperometric analyses. Demineralization of pristine BC enhanced the difference between PBC/ZVI and BBC/ZVI regarding Cr(VI) reduction, suggesting the dominant role of biopolymers in biomass in terms of electron transfer capacity. Three model biopolymers were compared which indicated lignin-BC had lower electron transfer rates than cellulose-BC and hemicellulose-BC. BC prepared by lignin extracted from pinewood exhibited higher corrosion rate and lower electrical resistance than that from bamboo. Thus, unfavorable lignin in bamboo compromised electron transfer of BBC and Cr(VI) reduction by BBC/ZVI.Background The home environment is regarded as a safe, comfortable environment, however, home can also be a stressful place. Compared to staying in the indoor home environment, the effects of short visits to outdoor urban environments on short-term psychological, physiological and cognitive responses were not studied previously. Aim To evaluate whether visits to different urban and ethnic environments, in comparison to staying in the home indoor environment, leads to short-term changes in psychological, physiological and cognitive responses and whether these responses are independent of ethnicity. Methods The participants, 20-35 year-old healthy women (N = 72, 48 Arab and 24 Jewish), started the experiment at their home and visited six different outdoor urban environments in predominantly ethnic Arab or Jewish cities, in Israel. First they visited intra-ethnic city and afterward inter-ethnic city environments. In each city they first visited an urban park and afterward, in a random order, a residential neighbing the visits did not explain the observed changes between the outdoor environments and home. Conclusions Visits to urban parks compared to staying in the home environment had beneficial short-term changes in psychological, physiological, and cognitive responses, regardless of ethnicity. The changes could not be attributed to the investigated mediators. Women should be encouraged to go outdoors and specifically visit parks to improve their psychological and physiological health.Intentional or accidental release of copper nanoparticles (Cu-NPs) from consumer products during manufacturing, use, and end-of-life management could pose health and ecological risks. This paper presents a detailed study on the role of water chemistry on the fate of uncoated and carbon-coated Cu-NPs dispersed in aqueous cetyltrimethylammonium bromide (CTAB) surfactant in the presence and absence of humic acids (HAs). A range of water chemistry and HAs had minimum impact on hydrodynamic diameter and zeta-potential values of uncoated and carbon-coated Cu-NPs. The water pH significantly (p less then 0.001) affected the aggregation of uncoated Cu-NPs unlike that of carbon-coated Cu-NPs; however, the presence of HAs increased the stability of uncoated Cu-NPs. Although CTAB is considered as an efficient dispersant to stabilize Cu-NPs, the effect descended with time for uncoated Cu-NPs. The dissolution of Cu over time decreased with increasing pH for both uncoated (0.5-50% weight) and carbon-coated (0.5-40% weight) Cu-NPs. However, carbon-coated Cu-NPs exhibited significant dissolution (p less then 0.001) at neutral pH than uncoated Cu-NPs may be due to the additional carbon it acquired during coating. Increasing HAs concentration from 0 to 15 mg L-1 at pH 5.5 inhibited aggregations but enhanced dissolution of the uncoated and carbon-coated Cu-NPs. https://www.selleckchem.com/products/Trichostatin-A.html These findings inform risk analysis of Cu-NPs including how Cu-NPs fate, mobility and bioavailability are modulated by particles coating and dispersant, HAs presence, water chemistry and exposure time in dispersion media.Graphene oxides (GO) and layered double hydroxides (LDHs) were applied to produce alginate beads for the remove of 90Sr2+ and 79SeO42-. The Freundlich isotherm indicated that the Sr2+ sorptions were based on the energetically heterogeneous multilayer surfaces. In contrast, the sorption behavior of SeO42- fitted to the Langmuir adsorption isotherm models, indicating that the removal of SeO42- was caused by the ion-exchange of LDHs. The synthesized LDH/GO alginates beads were also applied for setting up small-bore adsorption columns with loading synthetic SeO42- and Sr2+ contaminated wastewater. Based on the water chemistry, the adsorbed amount of Sr2+ significantly increased after using alginates beads, which was attributed to the functional groups of either GO or alginic acid. The incorporated SeO42- was highly depended on the contents of fabricated LDHs in alginate beads. Specifically, the adsorption capacity of Sr2+ (0.85-0.91 mmol/g) on GO slightly increased after alginates fabrication. Therefore, it was deduced that this layered material was partially exfoliated during the manufacture and thus increased the sorption sites. Applications of LDH/GO alginates beads in the removal of both Sr2+ and SeO42- in water and soil treatment have a significant impact on the environmental remediation.Background Genetic variations in glutathione (GSH)-related and metallothionein (MT) genes, which are involved in producing enzymes in the methylmercury (MeHg) metabolism pathway, have been proposed as one of the reasons for the individual variability in MeHg toxicokinetics. Objective To investigate the impact of genetic variations in MT and GSH-related genes on the association of fish consumption with body burden of MeHg, as measured by hair Hg concentrations among young children and women of childbearing age. Methods A total of 179 unrelated children and 165 mothers with either high or low fish consumption were recruited from the community. Their hair total Hg (tHg) and MeHg levels and genotypes for SNPs located on the GCLC, GCLM, GPX1, GSTA1, GSTP1, MT1A, MT2A, and MT4 genes were determined. Based on their 14-day food records, the amounts of fish consumed and their MeHg intakes were estimated. The impact of genetic variations on hair Hg concentrations was examined by using Mann-Whitney tests and multivariable linear regression analyses.

30 mins ago


This case involved a 63-year-old man. He underwent robot-assisted radical prostatectomy (RARP) for prostate cancer. One year after the operation, he consulted our hospital about left inguinal swelling. Under a diagnosis of a left external inguinal hernia, transabdominal preperitoneal repair (TAPP) was performed under general anesthesia. The inside of the hernia orifice had been damaged by the RARP, and the resultant fibrosis was so marked that it was difficult to dissect the preperitoneal space. Furthermore, an external iliac vein injury occurred during the operation. The bleeding was controlled, and we used laparoscopic continuous non-absorbable sutures to repair the external iliac vein injury. The number of TAPP procedures performed after radical prostatectomy has been increasing in recent years, but dissecting the preperitoneal space inside a hernia orifice is difficult. Although external iliac vein injuries are rare complications of TAPP procedures, they can be laparoscopically repaired.
Labels are the first source of information for the safe use of pesticides, but farmers rarely read labels before pesticide use. Using data from a sample of 300 orchard farmers in Meshginshar County, Iran, this study examined farmers' intention and behavior in reading and using risk information displayed on pesticide labels, using the theory of planned behavior (TPB).

Only 26% of the respondents mentioned that they read pesticide labels. Most farmers showed a low tendency towards reading pesticide labels due to low education, advanced age, and label-related problems, i.e., use of too technical language and unclear texts with small and illegible fonts. From the three basic variables of the TPB, subjective norms and perceived behavioral control (PBC) showed a significant impact on intention, while attitudes showed no significant impact. The three main variables of the TPB explained 90.2% of the variance in farmers' intention to read and use the labels. Furthermore, PBC and intention significantly affected fae labels. © 2021 Society of Chemical Industry.
To externally validate and compare Resorlu-Unsal stone score (RUSS), modified Seoul National University Renal Stone Complexity Score(S-ReSC), Ito's nomogram, and Retrograde Intra-Renal Surgery (R.I.R.S.) scoring systems for predicting capabilities of both the stone-free status and complications in a multi-institutional study.

We performed a retrospective analysis of 949 patients who underwent flexible ureterorenoscopy (f-URS) and laser lithotripsy for renal stones in two institutions between March-2015 and June-2020. The RUSS, modified S-ReSC, Ito's nomogram, and R.I.R.S. scores were calculated for each patient by the same surgeon on imaging methods. Results were compared for their predictive capability of stone-free status and complications.

Of 949 patients 603 were male and 346 were female with a mean age of 47.2±14.3 (range 2-84 years). Mean stone burden was 102.6±42.2 (48-270mm
). All nomograms predicted stone-free status (Area Under Curve (AUC) were 0.689, 0.657, 0.303, and 0.690, respectively). dicting post-operative complications, they were associated with complications in our study. However, these four scoring systems have some significant limitations. https://www.selleckchem.com/products/go-6983.html The ideal scoring system is yet to be developed.
To explore the concept of assertiveness in the patients with thalassaemia major.

It was a qualitative study with a conventional content analysis design.

Data were collected using a semi-structured interview. The research sample included 16 patients with thalassaemia major who were selected using purposeful sampling method from among such patients at educational and therapeutic centres. Then, they were analysed using MAXQDA10 software.

During the analysis of data for the concept of assertiveness, three sub-concepts of "courage to self-presentation," "demonstrating the abilities" and "attendance in groups" were developed.
During the analysis of data for the concept of assertiveness, three sub-concepts of "courage to self-presentation," "demonstrating the abilities" and "attendance in groups" were developed.
To systematically review the status of self-care in patients with heart failure through the Self-Care of Heart Failure Index scale.

A systematic review and meta-analysis.

Following national and international databases were searched to retrieve eligible studies PubMed, Web of Science, Embase, Google Scholar, Scientific Information Database and Magiran. The studies were screened and selected by two researchers. Data analysed through the random-effects model, and the I
index was used to assess heterogeneity. Stata software version 12.0 was used for analysis. The PRISMA statement was used to report systematic review and meta-analysis.

Of the 5,953 articles initially identified, 39 studies were included. The average score was estimated at 58.16 (CI 54.39-61.94) for self-care maintenance, 53.11 (CI 49.17-57.05) for self-care management and 58.66 (CI 54.32-63.00) for self-care confidence. Despite the high heterogeneity of the studies, the results indicated that self-care practice is inadequate in all the three dimensions of self-care (maintenance, management and confidence).
Of the 5,953 articles initially identified, 39 studies were included. The average score was estimated at 58.16 (CI 54.39-61.94) for self-care maintenance, 53.11 (CI 49.17-57.05) for self-care management and 58.66 (CI 54.32-63.00) for self-care confidence. Despite the high heterogeneity of the studies, the results indicated that self-care practice is inadequate in all the three dimensions of self-care (maintenance, management and confidence).
The aim of the present study was to evaluate the potential protective mechanism of icariin against oxidative damage caused by hydrogen peroxide in MC3T3-E1 cells.

MC3T3-E1 cells were treated with different concentrations of icariin to explore the optimal dose of icariin. MC3T3-E1 cells were divided into groups treated with various concentrations of hydrogen peroxide (H
O
; 0, 0.1, 0.2, 0.5, 1, and 2 mM) for 24 h to induce oxidative damage and cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Then, cells were divided into five groups control, H
O
(0.2 mM), icariin (0.1 μM) and H
O
(0.2 mM), + icariin (0.1 μM). Cell viability was detected by CCK-8 assay. In addition, the content of glutathione and superoxide dismutase and the activity level of malondialdehyde in these treatment groups were determined. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining were also performed to measure the early and late osteogenesis, respectively. Protein expression of β-catenin and cyclin D1 was measured by western blot assay.

35 mins ago


Sorcin (SOluble Resistance-related Calcium bInding proteiN) is a calcium binding protein that plays a key role in multidrug resistance (MDR) in human cancers. This study aimed at understanding the binding mechanism and structural basis for the interaction of structurally and functionally unrelated chemotherapeutic agent, namely doxorubicin, etoposide, omacetaxine mepesuccinate and paclitaxel with Sorcin by utilizing docking and molecular dynamic simulation approaches. The docking evaluation of etoposide, omacetaxine mepesuccinate and paclitaxel have shown a high affinity binding with Sorcin at the Ca2+-binding C-terminal domain (SCBD) in a comparable mode and affinity of binding to doxorubicin. Moreover, all of the docked compounds were shown to interact both hydrophilically and hydrophobically with the same residues within the active pocket which is located at interface of the Sorcin and collectively formed by EF5 loop, G helix and EF4 loop. However, the MD simulations revealed that the dynamics of Sorcin structure is different in the presence of the compounds when compared and contrasted to the Apo Sorcin, particularly in the first 25 ns, after which each system gained considerable structure stability. The difference in dynamics might be the outcome of high N and C-terminal flexibility that seem not to disturb compounds binding conformation but more likely is affecting chemical interaction network by breaking and establishing old and new hydrogen bonds, respectively. https://www.selleckchem.com/products/AZD0530.html This detailed mechanistic understanding of different chemotherapeutic agents binding to Sorcin might be useful to open windows for designing and developing new inhibitors that are potentially capable of reversing the MDR in human cancers.Chemodynamic therapy (CDT) is an emerging tumour-specific therapeutic technology. However, the relatively insufficient catalytic activity of CDT agents in the tumour microenvironment (TME) limits their biomedical application. In addition, severe hypoxia and glutathione (GSH) overexpression in the TME greatly limit the antitumour efficiency of monotherapy. Herein, a cancer cell membrane-camouflaged and ultrasmall CeO2-decorated MnO2 (mMC) composite is developed for amplified CDT, photodynamic therapy (PDT) and photothermal therapy (PTT). Due to the homotypic targeting ability of cancer cell membranes, mMC nanoparticles preferentially accumulate in tumour tissue. In the TME, CeO2 acts as a highly efficient CDT agent to convert endogenous H2O2 to toxic reactive oxygen species (ROS) for killing cancer cells. Meanwhile, MnO2 irradiated with near-infrared (NIR) light displays prominent hyperthermia and ROS generation performance to perform PTT and PDT. Moreover, MnO2 can produce oxygen to ameliorate hypoxia and deplete GSH to relieve the antioxidant capability of tumours, which is beneficial to the simultaneous augmentation of PDT and CDT. Most importantly, the catalytic activity of CeO2 was greatly improved by hyperthermia. Consequently, a significantly enhanced therapeutic efficiency was obtained by the above multiple synergistic effects. This work provides a proof of concept for amplified tumour therapy by synchronously self-supplying oxygen, consuming GSH, and enhancing catalytic activity.The protozoan Plasmodium falciparum is the main aetiological agent of tropical malaria. Characteristic of the phylum is the presence of a plastid-like organelle which hosts several homologs of plant proteins, including a ferredoxin (PfFd) and its NADPH-dependent reductase (PfFNR). The PfFNR/PfFd redox system is essential for the parasite, while mammals share no homologous proteins, making the enzyme an attractive target for novel and much needed antimalarial drugs. Based on previous findings, three chemically reactive residues important for PfFNR activity were identified namely, the active-site Cys99, responsible for hydride transfer; Cys284, whose oxidation leads to an inactive dimeric form of the protein; and His286, which is involved in NADPH binding. These amino acid residues were probed by several residue-specific reagents and the two cysteines were shown to be promising targets for covalent inhibition. The quantitative and qualitative description of the reactivity of few compounds, including a repurposed drug, set the bases for the development of more potent and specific antimalarial leads.Atherosclerosis still remains the leading cause of morbidity and mortality worldwide, and deeper understanding of target signaling that protect from the atherosclerosis progression may provide novel therapeutic strategies. CDGSH iron-sulfur domain-containing protein 1 (CISD1) is a protein localized on the outer membrane of mitochondria, and plays key roles in regulating cell death and oxidative stress. However, its potential on atherosclerosis development and the underlying mechanisms are largely unknown. Here, in our study, we found markedly decreased CISD1 expression in lipid-laden THP1 macrophages. Notably, lentivirus (LV)-mediated CISD1 over-expression remarkably ameliorated lipid deposition in macrophages stimulated by ox-LDL. Furthermore, cellular total ROS and mitochondrial ROS generation, and impairment of mitochondrial membrane potential (MMP) were highly induced by ox-LDL in THP1 cells, while being considerably reversed upon CISD1 over-expression. Inflammatory response caused by ox-LDL was also significantly restrained in macrophages with CISD1 over-expression. Mechanistically, we found that CISD1 could interact with dynamin-related protein 1 (Drp1). Intriguingly, CISD1-improved mitochondrial dysfunction and inflammation in ox-LDL-treated macrophages were strongly abolished by Drp1 over-expression, indicating that Drp1 suppression might be necessary for CISD1 to perform its protective effects in vitro. In high fat diet (HFD)-fed apolipoprotein E-deficient (ApoE-/-) mice, tail vein injection of lentiviral vector expressing CISD1 remarkably decreased atherosclerotic lesion area, serum LDL cholesterol levels and triglyceride contents. Inflammatory response, cellular total and mitochondrial ROS production, and Drp1 expression levels in aorta tissues were also dramatically ameliorated in HFD-fed ApoE-/- mice, contributing to the inhibition of atherosclerosis in vivo. Therefore, improving CISD1 expression may be a novel therapeutic strategy for atherosclerosis treatment.
This study aimed to compare the efficacy between neoadjuvant chemotherapy (NACT) plus intensity-modulated radiotherapy (IMRT) and NACT plus concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC).

Data from 603 patients with ascending (T4 and N0-1) or descending (T1-2&N3) NPC who were treated at Sun Yat-sen University Cancer Center between October 2009 and February 2012 were retrospectively analyzed. These patients were divided into two groups NACT+IMRT (n=302) and NACT+CCRT (n=301). The primary endpoint was overall survival (OS), which was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards model, and landmark analysis.

In univariate analysis, there was no significant difference in 5-year OS between the NACT+IMRT and NACT+CCRT groups (hazard ration [HR] 0.69; 95% confidence interval [CI] 0.47-1.01; P=0.057). However, after adjustment for age (<45years, ≥45years), gender, histological stage (I/II, III), T stage (1/2, 3, 4), and N stage (0/1,ng-term survival outcomes than those treated with NACT+CCRT, especially the patients younger than 45 years old or in stage T3/N2/N3. Additionally, NACT+IMRT may be a better option than NACT+CCRT in patients within the first 24 months.
Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection.

Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported.

75 patients with median follow-up time of 47months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed reastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.
Cochlear implantation (CI) has been shown to reduce vestibular function postoperatively in the implanted ear. The objective of this study was to identify the prevalence of preoperative vestibular weakness in CI candidates and identify any risk factors for postoperative dizziness.

Retrospective cohort study.

Patients who underwent CI and had preoperative videonystagmography (VNG) at the Silverstein Institute from January 1, 2017 to May 31, 2020 were evaluated. The primary endpoint was dizziness lasting more than one month postoperatively.

One hundred and forty nine patients were evaluated. Preoperative VNG revealed that 46 (30.9%) had reduced vestibular response (RVR) on one side and 32 (21.5%) had bilateral vestibular hypofunction (BVH). Postoperative dizziness occurred in 14 (9.4%) patients. Patients with postoperative dizziness were more likely to have abnormal preoperative VNG (RVR or BVH), compared to patients without postoperative dizziness (78.6% versus 49.6%, p = 0.0497). In cases of RVR, implantation of the weaker or stronger vestibular ear did not affect the postoperative dizziness (16.1% versus 6.7%, p=0.38). Postoperative VNG in patients with dizziness showed decreased caloric responses in the implanted ear (28.4 to 6.4 degrees/s, p=0.02).

Preoperative caloric weakness is prevalent in CI candidates and abnormal preoperative vestibular testing may be a predictor of postoperative dizziness. CI has the potential to cause vestibular injury and preoperative testing may aid in both counseling and decision-making.
Preoperative caloric weakness is prevalent in CI candidates and abnormal preoperative vestibular testing may be a predictor of postoperative dizziness. CI has the potential to cause vestibular injury and preoperative testing may aid in both counseling and decision-making.
Mothers from middle-income countries (MIC) are estimated to have higher rates of adverse childhood experiences (ACEs) and depression during pregnancy compared to mothers from high income countries. Prenatal depression can adversely impact on a mother's feelings towards her foetus and thus may be partially responsible for intergenerational transmission of risk associated with maternal ACEs. However, the extent to which prenatal depressive symptoms mediate the association between maternal ACEs and foetal attachment is unknown.

Data on foetal attachment, ACEs, and prenatal depression came from mothers in their third trimester of pregnancy (n=1,185) located across eight MICs, participating in the prospective birth cohort Evidence for Better Lives Study - Foundational Research (EBLS-FR). Data were from the baseline measurement.

Full-sample path mediation analyses, adjusting for relevant covariates, suggested a full mediating effect of prenatal depression. However, at the individual-country level, both positive and negative effects of ACEs on foetal attachment were observed after the inclusion of depressive symptoms as a mediator, suggesting cultural and geographical factors may influence a mother's empathic development after ACE exposure.