TGFβ2 significantly increased YAP/TAZ nuclear localization in HSC cells, which was prevented by either filamentous-actin relaxation or depolymerization. Pharmacological YAP/TAZ inhibition using verteporfin without light stimulation decreased fibronectin expression and actomyosin cytoskeletal rearrangement in HSC cells induced by TGFβ2. Similarly, verteporfin significantly attenuated TGFβ2-induced HSC cell-encapsulated hydrogel contraction.
Our data provide evidence for a pathologic role of aberrant YAP/TAZ signaling in HSC cells under simulated glaucomatous conditions and suggest that pharmacological YAP/TAZ inhibition has promising potential to improve outflow tissue dysfunction.
Our data provide evidence for a pathologic role of aberrant YAP/TAZ signaling in HSC cells under simulated glaucomatous conditions and suggest that pharmacological YAP/TAZ inhibition has promising potential to improve outflow tissue dysfunction.
Many health care systems publish hospital-level quality measures as a driver of hospital performance and to support patient choice, but it is not known if patients with cancer respond to them.
To investigate hospital quality and patient factors associated with treatment location.
This choice modeling study used national administrative hospital data. Patients with colon and rectal cancer treated in all 163 English National Health Service (NHS) hospitals delivering colorectal cancer surgery between April 2016 and March 2019 were included. The extent to which patients chose to bypass their nearest surgery center was investigated, and conditional logistic regression was used to estimate the association of additional travel time, hospital quality measures, and patient characteristics with treatment location.
Additional travel time in minutes, hospital characteristics, and patient characteristics age, sex, cancer T stage, socioeconomic status, comorbidity, and rural or urban residence.
Treatment location.spital characteristics that reflect overall hospital quality and the availability of robotic surgery but not to specific disease-related outcome measures. Policies allowing patients to choose where they have colorectal cancer surgery may not result in better outcomes but could drive inequities in the health care system.
Patients appear responsive to hospital characteristics that reflect overall hospital quality and the availability of robotic surgery but not to specific disease-related outcome measures. Policies allowing patients to choose where they have colorectal cancer surgery may not result in better outcomes but could drive inequities in the health care system.RNA G-quadruplexes (rG4s) are RNA secondary structures, which are formed by guanine-rich sequences and have important cellular functions. Existing computational tools for rG4 prediction rely on specific sequence features and/or were trained on small datasets, without considering rG4 stability information, and are therefore sub-optimal. Here, we developed rG4detector, a convolutional neural network to identify potential rG4s in transcriptomics data. rG4detector outperforms existing methods in both predicting rG4 stability and in detecting rG4-forming sequences. To demonstrate the biological-relevance of rG4detector, we employed it to study RNAs that are bound by the RNA-binding protein G3BP1. G3BP1 is central to the induction of stress granules (SGs), which are cytoplasmic biomolecular condensates that form in response to a variety of cellular stresses. Unexpectedly, rG4detector revealed a dynamic enrichment of rG4s bound by G3BP1 in response to cellular stress. In addition, we experimentally characterized G3BP1 cross-talk with rG4s, demonstrating that G3BP1 is a bona fide rG4-binding protein and that endogenous rG4s are enriched within SGs. Furthermore, we found that reduced rG4 availability impairs SG formation. Hence, we conclude that rG4s play a direct role in SG biology via their interactions with RNA-binding proteins and that rG4detector is a novel useful tool for rG4 transcriptomics data analyses.LitCovid (https//www.ncbi.nlm.nih.gov/research/coronavirus/)-first launched in February 2020-is a first-of-its-kind literature hub for tracking up-to-date published research on COVID-19. The number of articles in LitCovid has increased from 55 000 to ∼300 000 over the past 2.5 years, with a consistent growth rate of ∼10 000 articles per month. In addition to the rapid literature growth, the COVID-19 pandemic has evolved dramatically. For instance, the Omicron variant has now accounted for over 98% of new infections in the United States. In response to the continuing evolution of the COVID-19 pandemic, this article describes significant updates to LitCovid over the last 2 years. First, we introduced the long Covid collection consisting of the articles on COVID-19 survivors experiencing ongoing multisystemic symptoms, including respiratory issues, cardiovascular disease, cognitive impairment, and profound fatigue. Second, we provided new annotations on the latest COVID-19 strains and vaccines mentioned in the literature. Third, we improved several existing features with more accurate machine learning algorithms for annotating topics and classifying articles relevant to COVID-19. LitCovid has been widely used with millions of accesses by users worldwide on various information needs and continues to play a critical role in collecting, curating and standardizing the latest knowledge on the COVID-19 literature.
Blood pressure (BP) and cholesterol control remain challenging. Remote care can deliver more effective care outside of traditional clinician-patient settings but scaling and ensuring access to care among diverse populations remains elusive.
To implement and evaluate a remote hypertension and cholesterol management program across a diverse health care network.
Between January 2018 and July 2021, 20 454 patients in a large integrated health network were screened; 18 444 were approached, and 10 803 were enrolled in a comprehensive remote hypertension and cholesterol program (3658 patients with hypertension, 8103 patients with cholesterol, and 958 patients with both). A total of 1266 patients requested education only without medication titration. Enrolled patients received education, home BP device integration, and medication titration. https://www.selleckchem.com/products/CHIR-258.html Nonlicensed navigators and pharmacists, supported by cardiovascular clinicians, coordinated care using standardized algorithms, task management and automation software, and ine-directed therapy at scale, reduce cardiovascular risk, and minimize the need for in-person visits among diverse populations.YEASTRACT+ (http//yeastract-plus.org/) is a tool for the analysis, prediction and modelling of transcription regulatory data at the gene and genomic levels in yeasts. It incorporates three integrated databases YEASTRACT (http//yeastract-plus.org/yeastract/), PathoYeastract (http//yeastract-plus.org/pathoyeastract/) and NCYeastract (http//yeastract-plus.org/ncyeastract/), focused on Saccharomyces cerevisiae, pathogenic yeasts of the Candida genus, and non-conventional yeasts of biotechnological relevance. In this release, YEASTRACT+ offers upgraded information on transcription regulation for the ten previously incorporated yeast species, while extending the database to another pathogenic yeast, Candida auris. Since the last release of YEASTRACT+ (January 2020), a fourth database has been integrated. CommunityYeastract (http//yeastract-plus.org/community/) offers a platform for the creation, use, and future update of YEASTRACT-like databases for any yeast of the users' choice. CommunityYeastract currently provides information for two Saccharomyces boulardii strains, Rhodotorula toruloides NP11 oleaginous yeast, and Schizosaccharomyces pombe 972h-. In addition, YEASTRACT+ portal currently gathers 304 547 documented regulatory associations between transcription factors (TF) and target genes and 480 DNA binding sites, considering 2771 TFs from 11 yeast species. A new set of tools, currently implemented for S. cerevisiae and C. albicans, is further offered, combining regulatory information with genome-scale metabolic models to provide predictions on the most promising transcription factors to be exploited in cell factory optimisation or to be used as novel drug targets. The expansion of these new tools to the remaining YEASTRACT+ species is ongoing.CRISPR-Cas base editing (BE) system is a powerful tool to expand the scope and efficiency of genome editing with single-nucleotide resolution. The editing efficiency, product purity, and off-target effect differ among various BE systems. Herein, we developed CRISPRbase (http//crisprbase.maolab.org), by integrating 1 252 935 records of base editing outcomes in more than 50 cell types from 17 species. CRISPRbase helps to evaluate the putative editing precision of different BE systems by integrating multiple annotations, functional predictions and a blasting system for single-guide RNA sequences. We systematically assessed the editing window, editing efficiency and product purity of various BE systems. Intensive efforts were focused on increasing the editing efficiency and product purity of base editors since the byproduct could be detrimental in certain applications. Remarkably, more than half of cancer-related off-target mutations were non-synonymous and extremely damaging to protein functions in most common tumor types. Luckily, most of these cancer-related mutations were passenger mutations (4840/5703, 84.87%) rather than cancer driver mutations (863/5703, 15.13%), indicating a weak effect of off-target mutations on carcinogenesis. In summary, CRISPRbase is a powerful and convenient tool to study the outcomes of different base editors and help researchers choose appropriate BE designs for functional studies.Electrochemical sensors for the dissolved CO2 (dCO2) measurement have attracted great interest because of their simple setup and the resulting low costs. However, the developed sensors suffer from the requirement of the external electrical power supply throughout the sensing. Here, the fabrication and evaluation of a self-powered biosensor based on biofuel cells (BFCs) for dCO2 measurements are described. In this device, AuNPs-multiwalled carbon nanotubes/GOx-modified carbon paper (CP) served as a bioanode for the oxidation of glucose, while imine-linked covalent triazine framework (I-CTF)-modified CP was employed as the cathode for the reduction of Fe(CN)63-. I-CTF is a porous organic polymer with a high CO2 capture capacity. Voltammetry and electrochemical impedance spectroscopy confirmed that the electron transfer of Fe(CN)63- on the I-CTF-modified electrode decreases after contacting I-CTF with dCO2. In the designed BFC, by capturing CO2 by the I-CTF-modified cathode, a significant decrease in open-circuit voltage (EOCV) of the BFC was observed, which can be used for the sensitive measurement of dCO2. In addition to the self-powering feature, the EOCV of the BFC sensor can be restored when the captured CO2 is desorbed from the I-CTF-modified cathode by increasing the temperature of the cathode. Finally, the BFC is integrated into a circuit containing a matching capacitor; the charges generated by the BFC are accumulated on the capacitor, and then the instantaneous current is quickly detected using a switching regulator and a digital multimeter. Under optimal conditions, the instantaneous current of the BFC sensor was found to sensitively respond to dCO2 in a wide concentration range from 1.3 × 10-5 to 0.252 atm with a low detection limit of 5 × 10-6 atm.