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01/06/2025


Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.
It was shown, that Connective Tissue Grafts (CTG) retrieved from the tuberosity tends to determine hyperplastic responses and may induce a beneficial over-keratinization of non-keratinized mucosa. Clinically evaluate and compare CTG from tuberosity ability to increase soft tissue thickness and the keratinization potential after recipient area is either prepared using split or full thickness flap in edentulous mandible.

Fourty implants were placed in 10 edentulous patients with atrophied mandible (Class IV of Misch) presenting less than 1.0 mm of keratinized tissue using a flapless approach and immediately restored with acrylic temporary bridge on multi-unit abutments. The surgical sites were split-mouth randomized and prepared as CTG recipients by a tunneling procedure. https://www.selleckchem.com/products/a-438079-hcl.html Twenty benefited of a partial thickness approach and 20 of a full thickness one. The CTG was placed buccally using partial thickness or full thickness flap according to the randomization schedule. The width of keratinized tissue (KT), the .
Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re-excision practices.

To evaluate the impact of this consensus guideline on our institutional practices.

We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectively-maintained institutional database. A retrospective chart review was performed to determine margin status and re-excision rates during the 2 years before and the 2 years after the guideline was published in order to determine the effect on our re-excision rates. Close margins were defined as <2 mm.

In the 2 years before the consensus guideline was published, 184 patients with DCIS underwent BCS. Twenty-six patients had positive margins and 24 underwent re-excision, including three who hional practices slightly, but not dramatically as many of our surgeons' practices were comparable to the guideline recommendations prior to 2016. We continue to use clinical judgment based on patient and tumor characteristics in deciding which patients will benefit from margin re-excision.
With the rapid influx of novel anti-cancer agents, phase I clinical trials in oncology are evolving. Historically, response rates on early phase trials have been modest with the clinical benefit and ethics of enrolment debated. However, there is a paucity of real-world data in this setting.

To better understand the changing landscape of phase I oncology trials, we performed a retrospective review at our institution to examine patient and trial characteristics, screening outcomes, and treatment outcomes.

We analyzed all consecutive adult patients with advanced solid organ malignancies who were screened across phase I trials from January 2013 to December 2018 at a single institution. During this period, 242 patients were assessed for 28 different trials. Median age was 64 years (range 30-89) with an equal sex distribution. Among 257 screening visits, the overall screen failure rate was 18%, resulting in 212 patients being enrolled onto a study. Twenty-six trials (93%) involved immunotherapeutic agents or urvival in our cohort are superior to historically reported rates and comparable to contemporaneous studies. Severe treatment-related toxicity was relatively uncommon, and treatment-related mortality was rare.Bedside diagnosis of skin cancer remains a challenging task. The real-time noninvasive technology of optical coherence tomography (OCT) masters a high diagnostic accuracy in basal cell carcinoma (BCC) but a lower specificity in recognizing imitators and other carcinomas. We investigate the delicate signal of papillary dermis using an in-house developed ultrahigh resolution OCT (UHR-OCT) system with shadow compensation and a commercial multi-focus high resolution OCT (HR-OCT) system for clinical BCC imaging. We find that the HR-OCT system struggled to resolve the dark band signal of papillary dermis where the UHR-OCT located this in all cases and detected changes in signal width. UHR-OCT is able to monitor extension and position of papillary dermis suggesting a novel feature for delineating superficial BCCs in pursuit of a fast accurate diagnosis. Comprehensive studies involving more patients are imperative in order to corroborate results.
Although aging is strongly associated with both heart failure and a decline in gait speed, a definition of slowness incorporating an age-related decline has yet to be developed. We aimed to define an event-driven cut-off for the relative decline in gait speed against age-adjusted reference values derived from the general population and evaluate its prognostic implications.

Standardized gait speed (SGS) was defined as the median gait speed stratified by age, sex, and height in 3777 elderly (age≥65years) individuals without a history of cardiovascular diseases (Tokyo Metropolitan Institute of Gerontology-Longitudinal Interdisciplinary Study on Aging general population cohort). The mortality event-driven optimal cut-off of the SGS ratio (actual gait speed divided by the respective SGS) was defined using FRAGILE-HF cohort data and externally validated using Kitasato cohort data, comprising 1301 and 1247 hospitalized elderly patients with heart failure, respectively. Using FRAGILE-HF data, the optimal SGS ratio cut-off was determined as 0.

01/04/2025


The ability of the ANN models to discriminate 8 month survival with higher accuracy than the respective LR models was further confirmed in 53 consecutive patients. Conclusion We developed ANN models predicting the 8 month survival of unresectable pancreatic cancer patients. These models may help to optimize personalized patient management. Copyright © 2020 Tong, Liu, Ma, Zhang, Lin, Bao, Xu, Gu, Zheng, Liu, Fang, Deng and Zhao.Existing mathematical models for the glucose-insulin (G-I) dynamics often involve variables that are not susceptible to direct measurement. Standard clinical tests for measuring G-I levels for diagnosing potential diseases are simple and relatively cheap, but seldom give enough information to allow the identification of model parameters within the range in which they have a biological meaning, thus generating a gap between mathematical modeling and any possible physiological explanation or clinical interpretation. In the present work, we present a synthetic mathematical model to represent the G-I dynamics in an Oral Glucose Tolerance Test (OGTT), which involves for the first time for OGTT-related models, Delay Differential Equations. Our model can represent the radically different behaviors observed in a studied cohort of 407 normoglycemic patients (the largest analyzed so far in parameter fitting experiments), all masked under the current threshold-based normality criteria. We also propose a novel approach td to better define new health criteria. Copyright © 2020 Contreras, Medina-Ortiz, Conca and Olivera-Nappa.High-rate anaerobic digestion (AD) is a reliable, efficient process to treat wastewaters and is often operated at temperatures exceeding 30°C, involving energy consumption of biogas in temperate regions, where wastewaters are often discharged at variable temperatures generally below 20°C. High-rate ambient temperature AD, without temperature control, is an economically attractive alternative that has been proven to be feasible at laboratory-scale. In this study, an ambient temperature pilot scale anaerobic reactor (2 m3) was employed to treat real dairy wastewater in situ at a milk processing plant, at organic loading rates of 1.3 ± 0.6 to 10.6 ± 3.7 kg COD/m3/day and hydraulic retention times (HRT) ranging from 36 to 6 h. Consistent high levels of COD removal efficiencies, ranging from 50 to 70% for total COD removal and 70 to 84% for soluble COD removal, were achieved during the trial. Within the reactor biomass, stable active archaeal populations were observed, consisting mainly of Methanothrix (previouslyahony, Murray, Wilmes and O'Flaherty.Placenta-derived amniotic cells have prominent features for application in regenerative medicine. However, there are still discrepancies in the characterization of human amniotic epithelial and mesenchymal stromal cells. It seems crucial that the characterization of human amniotic membrane cells be investigated to determine whether there are currently discrepancies in their characterization reports. In addition, possible causes for the witnessed discrepancies need to be addressed toward paving the way for further clinical application and safer practices. The objective of this review is to investigate the marker characterization as well as the potential causes of the discrepancies in the previous reports on placenta-derived amniotic epithelial and mesenchymal stromal cells. The current discrepancies could be potentially due to reasons including passage number and epithelial to mesenchymal transition (EMT), cell heterogeneity, isolation protocols and cross-contamination, the region of cell isolation on placental disk, measuring methods, and gestational age. Copyright © 2020 Ghamari, Abbasi-Kangevari, Tayebi, Bahrami and Niknejad.The high yield mutants require a high-throughput screening method to obtain them quickly. Here, we developed an L-arginine biosensor (ARG-Select) to obtain increased L-arginine producers among a large number of mutant strains. This biosensor was constructed by ArgR protein and argC promoter, and could provide the strain with the output of bacterial growth via the reporter gene sacB; strains with high L-arginine production could survive in 10% sucrose screening. To extend the screening limitation of 10% sucrose, the sensitivity of ArgR protein to L-arginine was decreased. Corynebacterium crenatum SYPA5-5 and its systems pathway engineered strain Cc6 were chosen as the original strains. This biosensor was employed, and L-arginine hyperproducing mutants were screened. Finally, the HArg1 and DArg36 mutants of C. crenatum SYPA5-5 and Cc6 could produce 56.7 and 95.5 g L-1 of L-arginine, respectively, which represent increases of 35.0 and 13.5%. These results demonstrate that the transcription factor-based biosensor could be applied in high yield strains selection as an effective high-throughput screening method. https://www.selleckchem.com/products/turi.html Copyright © 2020 Xu, Liu, Chen, Peng, Yang, Zhang, Xu and Rao.The dissemination of DNA and xenogenic elements across waterways is under scientific and public spotlight due to new gene-editing tools, such as do-it-yourself (DIY) CRISPR-Cas kits deployable at kitchen table. Over decades, prevention of spread of genetically modified organisms (GMOs), antimicrobial resistances (AMR), and pathogens from transgenic systems has focused on microbial inactivation. However, sterilization methods have not been assessed for DNA release and integrity. Here, we investigated the fate of intracellular DNA from cultures of model prokaryotic (Escherichia coli) and eukaryotic (Saccharomyces cerevisiae) cells that are traditionally used as microbial chassis for genetic modifications. DNA release was tracked during exposure of these cultures to conventional sterilization methods. Autoclaving, disinfection with glutaraldehyde, and microwaving are used to inactivate broths, healthcare equipment, and GMOs produced at kitchen table. DNA fragmentation and PCR-ability were measured on top of cell severe DNA-affecting method. Reappraisal of sterilization methods is required along with risk assessment on the emission of DNA fragments in urban systems and nature. Copyright © 2020 Calderón-Franco, Lin, van Loosdrecht, Abbas and Weissbrodt.

12/30/2024


Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) regulate glucose and energy homeostasis. Targeting both pathways with GIP receptor (GIPR) antagonist antibody (GIPR-Ab) and GLP-1 receptor (GLP-1R) agonist, by generating GIPR-Ab/GLP-1 bispecific molecules, is an approach for treating obesity and its comorbidities. In mice and monkeys, these molecules reduce body weight (BW) and improve many metabolic parameters. BW loss is greater with GIPR-Ab/GLP-1 than with GIPR-Ab or a control antibody conjugate, suggesting synergistic effects. GIPR-Ab/GLP-1 also reduces the respiratory exchange ratio in DIO mice. https://www.selleckchem.com/products/all-trans-retinal.html Simultaneous receptor binding and rapid receptor internalization by GIPR-Ab/GLP-1 amplify endosomal cAMP production in recombinant cells expressing both receptors. This may explain the efficacy of the bispecific molecules. Overall, our GIPR-Ab/GLP-1 molecules promote BW loss, and they may be used for treating obesity.Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective humoral immunity. We performed transcriptional profiling and cellular analysis on circulating Tfh before and after influenza vaccination in young and elderly adults. First, whole-blood transcriptional profiling shows that ICOS+CD38+ cTfh following vaccination preferentially enriches in gene sets associated with youth versus aging compared to other circulating T cell types. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly had increased the expression of genes associated with inflammation, including tumor necrosis factor-nuclear factor κB (TNF-NF-κB) pathway activation. Finally, vaccine-induced ICOS+CD38+ cTfh display strong enrichment for signatures of underlying age-associated biological changes. These data highlight the ability to use vaccine-induced cTfh as cellular "biosensors" of underlying inflammatory and/or overall immune health.Aortic rupture and dissection are life-threatening complications of ascending thoracic aortic aneurysms (aTAAs), and risk assessment has been largely based on the monitoring of lumen size enlargement. Temporal changes in the extracellular matrix (ECM), which has a critical impact on aortic remodeling, are not routinely evaluated, and cardiovascular biomarkers do not exist to predict aTAA formation. Here, Raman microspectroscopy and Raman imaging are used to identify spectral biomarkers specific for aTAAs in mice and humans by multivariate data analysis (MVA). Multivariate curve resolution-alternating least-squares (MCR-ALS) combined with Lasso regression reveals elastic fiber-derived (Ce1) and collagen fiber-derived (Cc6) components that are significantly increased in aTAA lesions of murine and human aortic tissues. In particular, Cc6 detects changes in amino acid residues, including phenylalanine, tyrosine, tryptophan, cysteine, aspartate, and glutamate. Ce1 and Cc6 may serve as diagnostic Raman biomarkers that detect alterations of amino acids derived from aneurysm lesions.Microbiota maturation and immune development occur in parallel with, and are implicated in, allergic diseases, and research has begun to demonstrate the importance of prenatal influencers on both. Here, we investigate the meconium metabolome, a critical link between prenatal exposures and both early microbiota and immune development, to identify components of the neonatal gut niche that contribute to allergic sensitization. Our analysis reveals that newborns who develop immunoglobulin E (IgE)-mediated allergic sensitization (atopy) by 1 year of age have a less-diverse gut metabolome at birth, and specific metabolic clusters are associated with both protection against atopy and the abundance of key taxa driving microbiota maturation. These metabolic signatures, when coupled with early-life microbiota and clinical factors, increase our ability to accurately predict whether or not infants will develop atopy. Thus, the trajectory of both microbiota colonization and immune development are significantly affected by metabolites present in the neonatal gut at birth.Although the knee joint and temporomandibular joint (TMJ) experience similar incidence of cartilage ailments, the knee orthopedics field has greater funding and more effective end-stage treatment options. Translational research has resulted in the development of tissue-engineered products for knee cartilage repair, but the same is not true for TMJ cartilages. Here, we examine the anatomy and pathology of the joints, compare current treatments and products for cartilage afflictions, and explore ways to accelerate the TMJ field. We examine disparities, such as a 6-fold higher article count and 2,000-fold higher total joint replacement frequency in the knee compared to the TMJ, despite similarities in osteoarthritis incidence. Using knee orthopedics as a template, basic and translational research will drive the development and implementation of clinical products for the TMJ. With more funding opportunities, training programs, and federal guidance, millions of people afflicted with TMJ disorders could benefit from novel, life-changing therapeutics.Concern has arisen that the purported similarity between syncytin-1 and the SARS-CoV-2 spike protein may induce immune cross reactivity resulting in female sterility. We used frozen embryo transfer as a model to compare implantation rates between SARS-CoV-2 vaccine seropositive, infection seropositive and seronegative women. We found no difference in serum hCG documented implantation rates or sustained implantation rates between the three groups. The concern regarding Covid vaccines or illness causing female sterility are unfounded.Here, we describe a protocol combining functional metrics with genomic data to elucidate drivers of within-cell-type heterogeneity via the phenotype-to-genotype link. This technique involves using fluorescence tagging to label and isolate cells grown in 3D culture, enabling high-throughput enrichment of phenotypically defined cell subpopulations by fluorescence-activated cell sorting. We then perform a validated phenotypically supervised single-cell analysis pipeline to reveal unique functional cell states, including genes and pathways that contribute to cellular heterogeneity and were undetectable by unsupervised analysis. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020).

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01/06/2025


Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.
It was shown, that Connective Tissue Grafts (CTG) retrieved from the tuberosity tends to determine hyperplastic responses and may induce a beneficial over-keratinization of non-keratinized mucosa. Clinically evaluate and compare CTG from tuberosity ability to increase soft tissue thickness and the keratinization potential after recipient area is either prepared using split or full thickness flap in edentulous mandible.

Fourty implants were placed in 10 edentulous patients with atrophied mandible (Class IV of Misch) presenting less than 1.0 mm of keratinized tissue using a flapless approach and immediately restored with acrylic temporary bridge on multi-unit abutments. The surgical sites were split-mouth randomized and prepared as CTG recipients by a tunneling procedure. https://www.selleckchem.com/products/a-438079-hcl.html Twenty benefited of a partial thickness approach and 20 of a full thickness one. The CTG was placed buccally using partial thickness or full thickness flap according to the randomization schedule. The width of keratinized tissue (KT), the .
Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re-excision practices.

To evaluate the impact of this consensus guideline on our institutional practices.

We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectively-maintained institutional database. A retrospective chart review was performed to determine margin status and re-excision rates during the 2 years before and the 2 years after the guideline was published in order to determine the effect on our re-excision rates. Close margins were defined as <2 mm.

In the 2 years before the consensus guideline was published, 184 patients with DCIS underwent BCS. Twenty-six patients had positive margins and 24 underwent re-excision, including three who hional practices slightly, but not dramatically as many of our surgeons' practices were comparable to the guideline recommendations prior to 2016. We continue to use clinical judgment based on patient and tumor characteristics in deciding which patients will benefit from margin re-excision.
With the rapid influx of novel anti-cancer agents, phase I clinical trials in oncology are evolving. Historically, response rates on early phase trials have been modest with the clinical benefit and ethics of enrolment debated. However, there is a paucity of real-world data in this setting.

To better understand the changing landscape of phase I oncology trials, we performed a retrospective review at our institution to examine patient and trial characteristics, screening outcomes, and treatment outcomes.

We analyzed all consecutive adult patients with advanced solid organ malignancies who were screened across phase I trials from January 2013 to December 2018 at a single institution. During this period, 242 patients were assessed for 28 different trials. Median age was 64 years (range 30-89) with an equal sex distribution. Among 257 screening visits, the overall screen failure rate was 18%, resulting in 212 patients being enrolled onto a study. Twenty-six trials (93%) involved immunotherapeutic agents or urvival in our cohort are superior to historically reported rates and comparable to contemporaneous studies. Severe treatment-related toxicity was relatively uncommon, and treatment-related mortality was rare.Bedside diagnosis of skin cancer remains a challenging task. The real-time noninvasive technology of optical coherence tomography (OCT) masters a high diagnostic accuracy in basal cell carcinoma (BCC) but a lower specificity in recognizing imitators and other carcinomas. We investigate the delicate signal of papillary dermis using an in-house developed ultrahigh resolution OCT (UHR-OCT) system with shadow compensation and a commercial multi-focus high resolution OCT (HR-OCT) system for clinical BCC imaging. We find that the HR-OCT system struggled to resolve the dark band signal of papillary dermis where the UHR-OCT located this in all cases and detected changes in signal width. UHR-OCT is able to monitor extension and position of papillary dermis suggesting a novel feature for delineating superficial BCCs in pursuit of a fast accurate diagnosis. Comprehensive studies involving more patients are imperative in order to corroborate results.
Although aging is strongly associated with both heart failure and a decline in gait speed, a definition of slowness incorporating an age-related decline has yet to be developed. We aimed to define an event-driven cut-off for the relative decline in gait speed against age-adjusted reference values derived from the general population and evaluate its prognostic implications.

Standardized gait speed (SGS) was defined as the median gait speed stratified by age, sex, and height in 3777 elderly (age≥65years) individuals without a history of cardiovascular diseases (Tokyo Metropolitan Institute of Gerontology-Longitudinal Interdisciplinary Study on Aging general population cohort). The mortality event-driven optimal cut-off of the SGS ratio (actual gait speed divided by the respective SGS) was defined using FRAGILE-HF cohort data and externally validated using Kitasato cohort data, comprising 1301 and 1247 hospitalized elderly patients with heart failure, respectively. Using FRAGILE-HF data, the optimal SGS ratio cut-off was determined as 0.

01/04/2025


The ability of the ANN models to discriminate 8 month survival with higher accuracy than the respective LR models was further confirmed in 53 consecutive patients. Conclusion We developed ANN models predicting the 8 month survival of unresectable pancreatic cancer patients. These models may help to optimize personalized patient management. Copyright © 2020 Tong, Liu, Ma, Zhang, Lin, Bao, Xu, Gu, Zheng, Liu, Fang, Deng and Zhao.Existing mathematical models for the glucose-insulin (G-I) dynamics often involve variables that are not susceptible to direct measurement. Standard clinical tests for measuring G-I levels for diagnosing potential diseases are simple and relatively cheap, but seldom give enough information to allow the identification of model parameters within the range in which they have a biological meaning, thus generating a gap between mathematical modeling and any possible physiological explanation or clinical interpretation. In the present work, we present a synthetic mathematical model to represent the G-I dynamics in an Oral Glucose Tolerance Test (OGTT), which involves for the first time for OGTT-related models, Delay Differential Equations. Our model can represent the radically different behaviors observed in a studied cohort of 407 normoglycemic patients (the largest analyzed so far in parameter fitting experiments), all masked under the current threshold-based normality criteria. We also propose a novel approach td to better define new health criteria. Copyright © 2020 Contreras, Medina-Ortiz, Conca and Olivera-Nappa.High-rate anaerobic digestion (AD) is a reliable, efficient process to treat wastewaters and is often operated at temperatures exceeding 30°C, involving energy consumption of biogas in temperate regions, where wastewaters are often discharged at variable temperatures generally below 20°C. High-rate ambient temperature AD, without temperature control, is an economically attractive alternative that has been proven to be feasible at laboratory-scale. In this study, an ambient temperature pilot scale anaerobic reactor (2 m3) was employed to treat real dairy wastewater in situ at a milk processing plant, at organic loading rates of 1.3 ± 0.6 to 10.6 ± 3.7 kg COD/m3/day and hydraulic retention times (HRT) ranging from 36 to 6 h. Consistent high levels of COD removal efficiencies, ranging from 50 to 70% for total COD removal and 70 to 84% for soluble COD removal, were achieved during the trial. Within the reactor biomass, stable active archaeal populations were observed, consisting mainly of Methanothrix (previouslyahony, Murray, Wilmes and O'Flaherty.Placenta-derived amniotic cells have prominent features for application in regenerative medicine. However, there are still discrepancies in the characterization of human amniotic epithelial and mesenchymal stromal cells. It seems crucial that the characterization of human amniotic membrane cells be investigated to determine whether there are currently discrepancies in their characterization reports. In addition, possible causes for the witnessed discrepancies need to be addressed toward paving the way for further clinical application and safer practices. The objective of this review is to investigate the marker characterization as well as the potential causes of the discrepancies in the previous reports on placenta-derived amniotic epithelial and mesenchymal stromal cells. The current discrepancies could be potentially due to reasons including passage number and epithelial to mesenchymal transition (EMT), cell heterogeneity, isolation protocols and cross-contamination, the region of cell isolation on placental disk, measuring methods, and gestational age. Copyright © 2020 Ghamari, Abbasi-Kangevari, Tayebi, Bahrami and Niknejad.The high yield mutants require a high-throughput screening method to obtain them quickly. Here, we developed an L-arginine biosensor (ARG-Select) to obtain increased L-arginine producers among a large number of mutant strains. This biosensor was constructed by ArgR protein and argC promoter, and could provide the strain with the output of bacterial growth via the reporter gene sacB; strains with high L-arginine production could survive in 10% sucrose screening. To extend the screening limitation of 10% sucrose, the sensitivity of ArgR protein to L-arginine was decreased. Corynebacterium crenatum SYPA5-5 and its systems pathway engineered strain Cc6 were chosen as the original strains. This biosensor was employed, and L-arginine hyperproducing mutants were screened. Finally, the HArg1 and DArg36 mutants of C. crenatum SYPA5-5 and Cc6 could produce 56.7 and 95.5 g L-1 of L-arginine, respectively, which represent increases of 35.0 and 13.5%. These results demonstrate that the transcription factor-based biosensor could be applied in high yield strains selection as an effective high-throughput screening method. https://www.selleckchem.com/products/turi.html Copyright © 2020 Xu, Liu, Chen, Peng, Yang, Zhang, Xu and Rao.The dissemination of DNA and xenogenic elements across waterways is under scientific and public spotlight due to new gene-editing tools, such as do-it-yourself (DIY) CRISPR-Cas kits deployable at kitchen table. Over decades, prevention of spread of genetically modified organisms (GMOs), antimicrobial resistances (AMR), and pathogens from transgenic systems has focused on microbial inactivation. However, sterilization methods have not been assessed for DNA release and integrity. Here, we investigated the fate of intracellular DNA from cultures of model prokaryotic (Escherichia coli) and eukaryotic (Saccharomyces cerevisiae) cells that are traditionally used as microbial chassis for genetic modifications. DNA release was tracked during exposure of these cultures to conventional sterilization methods. Autoclaving, disinfection with glutaraldehyde, and microwaving are used to inactivate broths, healthcare equipment, and GMOs produced at kitchen table. DNA fragmentation and PCR-ability were measured on top of cell severe DNA-affecting method. Reappraisal of sterilization methods is required along with risk assessment on the emission of DNA fragments in urban systems and nature. Copyright © 2020 Calderón-Franco, Lin, van Loosdrecht, Abbas and Weissbrodt.

12/30/2024


Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) regulate glucose and energy homeostasis. Targeting both pathways with GIP receptor (GIPR) antagonist antibody (GIPR-Ab) and GLP-1 receptor (GLP-1R) agonist, by generating GIPR-Ab/GLP-1 bispecific molecules, is an approach for treating obesity and its comorbidities. In mice and monkeys, these molecules reduce body weight (BW) and improve many metabolic parameters. BW loss is greater with GIPR-Ab/GLP-1 than with GIPR-Ab or a control antibody conjugate, suggesting synergistic effects. GIPR-Ab/GLP-1 also reduces the respiratory exchange ratio in DIO mice. https://www.selleckchem.com/products/all-trans-retinal.html Simultaneous receptor binding and rapid receptor internalization by GIPR-Ab/GLP-1 amplify endosomal cAMP production in recombinant cells expressing both receptors. This may explain the efficacy of the bispecific molecules. Overall, our GIPR-Ab/GLP-1 molecules promote BW loss, and they may be used for treating obesity.Humoral immune responses are dysregulated with aging, but the cellular and molecular pathways involved remain incompletely understood. In particular, little is known about the effects of aging on T follicular helper (Tfh) CD4 cells, the key cells that provide help to B cells for effective humoral immunity. We performed transcriptional profiling and cellular analysis on circulating Tfh before and after influenza vaccination in young and elderly adults. First, whole-blood transcriptional profiling shows that ICOS+CD38+ cTfh following vaccination preferentially enriches in gene sets associated with youth versus aging compared to other circulating T cell types. Second, vaccine-induced ICOS+CD38+ cTfh from the elderly had increased the expression of genes associated with inflammation, including tumor necrosis factor-nuclear factor κB (TNF-NF-κB) pathway activation. Finally, vaccine-induced ICOS+CD38+ cTfh display strong enrichment for signatures of underlying age-associated biological changes. These data highlight the ability to use vaccine-induced cTfh as cellular "biosensors" of underlying inflammatory and/or overall immune health.Aortic rupture and dissection are life-threatening complications of ascending thoracic aortic aneurysms (aTAAs), and risk assessment has been largely based on the monitoring of lumen size enlargement. Temporal changes in the extracellular matrix (ECM), which has a critical impact on aortic remodeling, are not routinely evaluated, and cardiovascular biomarkers do not exist to predict aTAA formation. Here, Raman microspectroscopy and Raman imaging are used to identify spectral biomarkers specific for aTAAs in mice and humans by multivariate data analysis (MVA). Multivariate curve resolution-alternating least-squares (MCR-ALS) combined with Lasso regression reveals elastic fiber-derived (Ce1) and collagen fiber-derived (Cc6) components that are significantly increased in aTAA lesions of murine and human aortic tissues. In particular, Cc6 detects changes in amino acid residues, including phenylalanine, tyrosine, tryptophan, cysteine, aspartate, and glutamate. Ce1 and Cc6 may serve as diagnostic Raman biomarkers that detect alterations of amino acids derived from aneurysm lesions.Microbiota maturation and immune development occur in parallel with, and are implicated in, allergic diseases, and research has begun to demonstrate the importance of prenatal influencers on both. Here, we investigate the meconium metabolome, a critical link between prenatal exposures and both early microbiota and immune development, to identify components of the neonatal gut niche that contribute to allergic sensitization. Our analysis reveals that newborns who develop immunoglobulin E (IgE)-mediated allergic sensitization (atopy) by 1 year of age have a less-diverse gut metabolome at birth, and specific metabolic clusters are associated with both protection against atopy and the abundance of key taxa driving microbiota maturation. These metabolic signatures, when coupled with early-life microbiota and clinical factors, increase our ability to accurately predict whether or not infants will develop atopy. Thus, the trajectory of both microbiota colonization and immune development are significantly affected by metabolites present in the neonatal gut at birth.Although the knee joint and temporomandibular joint (TMJ) experience similar incidence of cartilage ailments, the knee orthopedics field has greater funding and more effective end-stage treatment options. Translational research has resulted in the development of tissue-engineered products for knee cartilage repair, but the same is not true for TMJ cartilages. Here, we examine the anatomy and pathology of the joints, compare current treatments and products for cartilage afflictions, and explore ways to accelerate the TMJ field. We examine disparities, such as a 6-fold higher article count and 2,000-fold higher total joint replacement frequency in the knee compared to the TMJ, despite similarities in osteoarthritis incidence. Using knee orthopedics as a template, basic and translational research will drive the development and implementation of clinical products for the TMJ. With more funding opportunities, training programs, and federal guidance, millions of people afflicted with TMJ disorders could benefit from novel, life-changing therapeutics.Concern has arisen that the purported similarity between syncytin-1 and the SARS-CoV-2 spike protein may induce immune cross reactivity resulting in female sterility. We used frozen embryo transfer as a model to compare implantation rates between SARS-CoV-2 vaccine seropositive, infection seropositive and seronegative women. We found no difference in serum hCG documented implantation rates or sustained implantation rates between the three groups. The concern regarding Covid vaccines or illness causing female sterility are unfounded.Here, we describe a protocol combining functional metrics with genomic data to elucidate drivers of within-cell-type heterogeneity via the phenotype-to-genotype link. This technique involves using fluorescence tagging to label and isolate cells grown in 3D culture, enabling high-throughput enrichment of phenotypically defined cell subpopulations by fluorescence-activated cell sorting. We then perform a validated phenotypically supervised single-cell analysis pipeline to reveal unique functional cell states, including genes and pathways that contribute to cellular heterogeneity and were undetectable by unsupervised analysis. For complete details on the use and execution of this protocol, please refer to Chen et al. (2020).

12/18/2024


Herein, an exact and efficient analytic solution for an unperturbed satellite relative motion was developed using a direct geometrical approach. The derivation of the relative motion geometrically interpreted the projected Keplerian orbits of the satellites on a sphere (Earth and celestial spheres) using the solutions of full-sky spherical triangles. The results were basic and computationally faster than the vector and plane geometry solutions owing to the advantages of the full-sky spherical geometry. Accordingly, the validity of the proposed solution was evaluated by comparing it with other analytic relative motion theories in terms of modeling accuracy and efficiency. The modeling accuracy showed an equivalent performance with Vadali's nonlinear unit sphere approach, which is essentially equal to the Yan-Alfriend nonlinear theory. Moreover, the efficiency was demonstrated by the lowest computational cost compared with other models. In conclusion, the proposed modeling approach illustrates a compact and efficient closed-form solution for satellite relative motion dynamics.There is still no consensus on how to determine the dose of spinal anaesthesia with adequate sensory block for a planned surgery. This retrospective study aimed to explore the associations of miscellaneous factors with peak sensory block level after spinal anaesthesia with hyperbaric bupivacaine, and to construct a predictive model for single-shot spinal anaesthesia. We collected the records of 401 non-pregnant adults who underwent spinal anaesthesia with 0.5% hyperbaric bupivacaine at the L3-4 or L4-5 intervertebral space for lower body surgeries. Multiple linear regression analysis was used to investigate predictors of the block level and build up the predictive model. https://www.selleckchem.com/products/Pemetrexed-disodium.html Five variables were identified as independent predictors of the peak sensory block level, including bupivacaine dose, height, weight, gender and age. The predictive model for peak block level after spinal anaesthesia could be expressed as a formula with these five variables and the estimated predictive power was 0.72. Based on this model, it is possible to determine a reasonable dose of hyperbaric bupivacaine for spinal anaesthesia, which gives adequate sensory block required for diverse surgical procedures in various patients and could be considered as a dose reference for sensory block height in spinal anaesthesia.Urbanization and natural disasters can disrupt landscape connectivity, effectively isolating populations and increasing the risk of local extirpation particularly in island systems. To understand how fragmentation affects corridors among forested areas, we used circuit theory to model the landscape connectivity of the endemic bat Stenoderma rufum within Puerto Rico. Our models combined species occurrences, land use, habitat suitability, and vegetation cover data that were used either as resistance (land use) or conductance layers (habitat suitability and vegetation cover). Urbanization affected connectivity overall from east to west and underscored protected and rustic areas for the maintenance of forest corridors. Suitable habitat provided a reliable measure of connectivity among potential movement corridors that connected more isolated areas. We found that intense hurricanes that disrupt forest integrity can affect connectivity of suitable habitat. Some of the largest protected areas in the east of Puerto Rico are at an increasing risk of becoming disconnected from more continuous forest patches. Given the increasing rate of urbanization, this pattern could also apply to other vertebrates. Our findings show the importance of maintaining forest integrity, emphasizing the considerable conservation value of rustic areas for the preservation of local biodiversity.Theileria equi, an intraerythrocytic protozoan parasite, causes equine piroplasmosis, a disease which negatively impacts the global horse industry. Genetic manipulation is one of the research tools under development as a control method for protozoan parasites, but this technique needs to be established for T. equi. Herein, we report on the first development of a stable transgenic T. equi line expressing enhanced green fluorescent protein/blasticidin S deaminase (eGFP/BSD). To express the exogenous fusion gene in T. equi, regulatory regions of the elongation factor-1 alpha (ef-1α) gene were identified in T. equi. An eGFP/BSD-expression cassette containing the ef-1α gene promoter and terminator regions was constructed and integrated into the T. equi genome. On day 9 post-transfection, blasticidin-resistant T. equi emerged. In the clonal line of T. equi obtained by limiting dilution, integration of the eGFP/BSD-expression cassette was confirmed in the designated B-locus of the ef-1α gene via PCR and Southern blot analyses. Parasitaemia dynamics between the transgenic and parental T. equi lines were comparable in vitro. The eGFP/BSD-expressing transgenic T. equi and the methodology used to generate it offer new opportunities for better understanding of T. equi biology, with the add-on possibility of discovering effective control methods against equine piroplasmosis.Listeria monocytogenes is an opportunistic pathogen that is widely distributed in the environment. The aquatic environment may represent a potential source for the transmission of L. monocytogenes to animals and the food chain. The present study assessed the occurrence of L. monocytogenes in 191 surface water samples from rivers, streams and inland canals throughout Switzerland. Twenty-five (13%) of the surface water samples contained L. monocytogenes. Whole genome sequence (WGS) data were used to characterize the 25 isolates. The isolates belonged to major lineages I and II, with the majority assigned to either serotype 1/2a (48%), or 4b (44%). The predominant CCs identified were the hypervirulent serotype 4b clones CC1 and CC4, and the serotype CC412; all three have been implicated in listeriosis outbreaks and sporadic cases of human and animal infection worldwide. Two (8%) of the isolates belonged to CC6 which is an emerging hypervirulent clone. All isolates contained intact genes associated with invasion and infection, including inlA/B and prfA.

12/11/2024


Reports from Arabian Gulf countries have demonstrated emergence of novel methicillin resistant Staphylococcus aureus (MRSA) strains. To address the lack of data from the United Arab Emirates (UAE), genetic characterisation of MRSA identified between December 2017 and August 2019 was conducted using DNA microarray-based assays. The 625 MRSA isolates studied were grouped into 23 clonal complexes (CCs) and assigned to 103 strains. CC5, CC6, CC22 and CC30 represented 54.2% (n/N = 339/625) of isolates with other common CCs being CC1, CC8, CC772, CC361, CC80, CC88. Emergence of CC398 MRSA, CC5-MRSA-IV Sri Lanka Clone and ST5/ST225-MRSA-II, Rhine-Hesse EMRSA/New York-Japan Clone in our setting was detected. Variants of pandemic CC8-MRSA-[IVa + ACME I] (PVL+) USA300 were detected and majority of CC772 strains were CC772-MRSA-V (PVL+), "Bengal- Bay Clone". Novel MRSA strains identified include CC5-MRSA-V (edinA+), CC5-MRSA-[VT + fusC], CC5-MRSA-IVa (tst1+), CC5-MRSA-[V/VT + cas + fusC + ccrA/B-1], CC8-MRSA-V/VT, CC22-MRSA-[IV + fusC + ccrAA/(C)], CC45-MRSA-[IV + fusC + tir], CC80-MRSA-IVa, CC121-MRSA-V/VT, CC152-MRSA-[V + fusC] (PVL+). Although several strains harboured SCC-borne fusidic acid resistance (fusC) (n = 181), erythromycin/clindamycin resistance (ermC) (n = 132) and gentamicin resistance (aacA-aphD) (n = 179) genes, none harboured vancomycin resistance genes while mupirocin resistance gene mupR (n = 2) and cfr gene (n = 1) were rare. An extensive MRSA repertoire including CCs previously unreported in the region and novel strains which probably arose locally suggest an evolving MRSA landscape.Immiscible semiconductors are of premier importance since the source of lighting has been replaced by white light-emitting-diodes (LEDs) composed of thermodynamically immiscible InxGa1-xN blue LEDs and yellow phosphors. For realizing versatile deep-ultraviolet to near-infrared light-emitters, Al1-xInxN alloys are one of the desirable candidates. Here we exemplify the appearance and self-formation sequence of compositional superlattices in compressively strained m-plane Al1-xInxN films. On each terrace of atomically-flat m-plane GaN, In- and Al-species diffuse toward a monolayer (ML) step edge, and the first and second uppermost -rows are alternately formed, which grow into respective 0001-planes. Simultaneously, approximately 5-nm-period Al0.70In0.30N/Al0.74In0.26N ordering is formed to mitigate the lattice mismatch along [0001], which grow into approximately 5-nm-period Al0.70In0.30N/Al0.74In0.26N [Formula see text] superlattices as step-flow growth progresses. Spatially resolved cathodoluminescence spectra identify the emissions from particular structures.Epithelial cells of the conducting airways are a pivotal first line of defense against airborne pathogens and allergens that orchestrate inflammatory responses and mucociliary clearance. https://www.selleckchem.com/products/glutathione.html Nonetheless, the molecular mechanisms responsible for epithelial hyperreactivity associated with allergic asthma are not completely understood. Transcriptomic analysis of human airway epithelial cells (HAECs), differentiated in-vitro at air-liquid interface (ALI), showed 725 differentially expressed immediate-early transcripts, including putative long noncoding RNAs (lncRNAs). A novel lncRNA on the antisense strand of ICAM-1 or LASI was identified, which was induced in LPS-primed HAECs along with mucin MUC5AC and its transcriptional regulator SPDEF. LPS-primed expression of LASI, MUC5AC, and SPDEF transcripts were higher in ex-vivo cultured asthmatic HAECs that were further augmented by LPS treatment. Airway sections from asthmatics with increased mucus load showed higher LASI expression in MUC5AC+ goblet cells following multi-fluorescent in-situ hybridization and immunostaining. LPS- or IL-13-induced LASI transcripts were mostly enriched in the nuclear/perinuclear region and were associated with increased ICAM-1, IL-6, and CXCL-8 expression. Blocking LASI expression reduced the LPS or IL-13-induced epithelial inflammatory factors and MUC5AC expression, suggesting that the novel lncRNA LASI could play a key role in LPS-primed trained airway epithelial responses that are dysregulated in allergic asthma.Visceral fat is associated with cardiovascular and kidney disease. However, the relationship between body composition and anthropometric measures in type 1 diabetes is unknown. Using z-statistics, we ranked the ability of body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR) and a body shape index (ABSI) to capture measures of body composition from 603 Dual-energy-X-Ray-Absorptiometry scans of adults with type 1 diabetes. Albuminuria was defined as urinary albumin excretion rate of at least 30 mg/24 h. Women with albuminuria had higher visceral fat mass % (VFM%) (0.9 vs. 0.5%, p = 0.0017) and lower appendicular lean mass % (AppLM%) (25.4 vs 26.4%, p = 0.03) than those without. Men with albuminuria had higher VFM% (1.5 vs. 1.0%, p = 0.0013) and lower AppLM% (30.0 vs 32.3, p  less then  0.0001) than those without. In men, WHtR estimated VFM% best (z-statistics = 21.1), followed by WC (z = 19.6), BMI (z = 15.1), WHR (z = 14.6) and ABSI (z = 10.1). In women, the ranking was WC (z = 28.9), WHtR (z = 27.3), BMI (z = 20.5), WHR (z = 12.7) and ABSI (z = 10.5). Overall, the ranking was independent of albuminuria. Adults with type 1 diabetes and albuminuria have greater VFM% and lower AppLM% than those without. WHtR and WC best estimate the VFM% in this population, independently of albuminuria and sex.Combining the advantages of structured random measurement matrix and chaotic structure, this paper introduces a color image encryption algorithm based on a structural chaotic measurement matrix and random phase mask. The Chebyshev chaotic sequence is used in the algorithm to generate the flip permutation matrix, the sampling subset and the chaotic cyclic matrix for constructing the structure perceptual matrix and the random phase mask. The original image is compressed and encrypted simultaneously by compressed sensing, and re-encrypted by two-dimensional fractional Fourier transform. Simulation experiments show the effectiveness and reliability of the algorithm.