Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China.

INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.

Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306).

Background & Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvedilol-treating cohort. Results: In the meta-analysis with six studies (n = 819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new "CSPH risk" model. In the HVPG cohort (n = 151), the new model accurately predicted CSPH with cutoff values of 0 and -0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n = 1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <-0.68 (low-risk), -0.68 to 0 (medium-risk), and >0 (high-risk). In the carvedilol-treated cohort, patients with high-risk CSPH treated with carvedilol (n = 81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n = 613 before propensity score matching [PSM], n = 162 after PSM). Conclusions: Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

The impact of the stress hyperglycemia ratio on the risk of contrast-associated acute kidney injury in patients undergoing coronary angiography: a large real-world cohort study.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is an important complication in the perioperative period of coronary angiography (CAG). Dysglycemia is closely associated with the occurrence of CA-AKI. However, the association between stress hyperglycemia and CA-AKI in patients undergoing CAG remains unclear. The study aims to investigate the association of the stress hyperglycemia ratio (SHR) and CA-AKI under CAG in a large real-world cohort. METHODS: This was a retrospective observational study, and patients undergoing CAG were enrolled. SHR is calculated by dividing the random blood glucose with the estimated average glucose derived from the glycosylated hemoglobin (HbA1c), and subjects were divided into five groups according to SHR. The outcome was CA-AKI defined as an increase in serum creatinine of ≥ 0.3 mg/dL (26.5 µmol/L) or 1.5-fold higher than normal levels in 48 h. The association was assessed with logistic regression and restricted cubic spline analysis. RESULTS: In 19,965 participants (men: 73.3%, mean age: 63.1 ± 10.8 years) undergoing CAG, a total of 1,621 CA-AKI cases occurred. There were reverse J-shaped associations between the SHR and CA-AKI after adjustment for other confounding factors. Moreover, SHR improved the predictive effectiveness of the traditional Mehran score (AUC 0.65 vs 0.63, P < 0.001), a predictive model of CA-AKI in patients undergoing percutaneous coronary intervention. CONCLUSIONS: There were reverse J-shaped associations of SHR with CA-AKI risk among patients undergoing CAG, and the assessment of SHR before CAG may assist clinicians in identifying patients at higher risk of CA-AKI.

Correlation between novel inflammatory markers and carotid atherosclerosis: A retrospective case-control study.

OBJECTIVE: Carotid atherosclerosis is a chronic inflammatory disease, which is a major cause of ischemic stroke. The purpose of this study was to analyze the relationship between carotid atherosclerosis and novel inflammatory markers, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to neutrophil ratio (PNR), neutrophil to lymphocyte platelet ratio (NLPR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), in order to find the best inflammatory predictor of carotid atherosclerosis. METHOD: We included 10015 patients who underwent routine physical examinations at the physical examination center of our hospital from January 2016 to December 2019, among whom 1910 were diagnosed with carotid atherosclerosis. The relationship between novel inflammatory markers and carotid atherosclerosis was analyzed by logistic regression, and the effectiveness of each factor in predicting carotid atherosclerosis was evaluated by receiver operating characteristic (ROC) curve and area under the curve (AUC). RESULT: The level of PLR, LMR and PNR in the carotid atherosclerosis group were lower than those in the non-carotid atherosclerosis group, while NLR, NLPR, SII, SIRI and AISI in the carotid atherosclerosis group were significantly higher than those in the non-carotid atherosclerosis group. Logistic regression analysis showed that PLR, NLR, LMR, PNR, NLPR, SII, SIRI, AISI were all correlated with carotid atherosclerosis. The AUC value of NLPR was the highest, which was 0.67, the cut-off value was 0.78, the sensitivity was 65.8%, and the specificity was 57.3%. The prevalence rate of carotid atherosclerosis was 12.4% below the cut-off, 26.6% higher than the cut-off, and the prevalence rate increased by 114.5%. CONCLUSION: New inflammatory markers were significantly correlated with carotid atherosclerosis, among which NLPR was the optimum inflammatory marker to predict the risk of carotid atherosclerosis.

Phenotypic, genomic, and transcriptomic heterogeneity in a pancreatic cancer cell line.

OBJECTIVES: To evaluate the suitability of the MIA PaCa-2 cell line for studying pancreatic cancer intratumor heterogeneity, we aim to further characterize the nature of MIA PaCa-2 cells' phenotypic, genomic, and transcriptomic heterogeneity. METHODS: MIA PaCa-2 single-cell clones were established through flow cytometry. For the phenotypic study, we quantified the cellular morphology, proliferation rate, migration potential, and drug sensitivity of the clones. The chromosome copy number and transcriptomic profiles were quantified using SNPa and RNA-seq, respectively. RESULTS: Four MIA PaCa-2 clones showed distinctive phenotypes, with differences in cellular morphology, proliferation rate, migration potential, and drug sensitivity. We also observed a degree of genomic variations between these clones in form of chromosome copy number alterations and single nucleotide variations, suggesting the genomic heterogeneity of the population, and the intrinsic genomic instability of MIA PaCa-2 cells. Lastly, transcriptomic analysis of the clones also revealed gene expression profile differences between the clones, including the uniquely regulated ITGAV, which dictates the morphology of MIA PaCa-2 clones. CONCLUSIONS: MIA PaCa-2 is comprised of cells with distinctive phenotypes, heterogeneous genomes, and differential transcriptomic profiles, suggesting its suitability as a model to study the underlying mechanisms behind pancreatic cancer heterogeneity.

Stabilization of Lattice Oxygen Evolution Reactions in Oxophilic Ce-Mediated Bi/BiCeO1.8H Electrocatalysts for Efficient Anion Exchange Membrane Water Electrolyzers.

The lattice oxygen mechanism (LOM) offers an efficient reaction pathway for oxygen evolution reactions (OERs) in energy storage and conversion systems. Owing to the involvement of active lattice oxygen enhancing electrochemical activity, addressing the structural and electrochemical stabilities of LOM materials is crucial. Herein, a heterostructure (Bi/BiCeO1.8H) containing abundant under-coordinated oxygen atoms having oxygen nonbonding states is synthesized by a simple electrochemical deposition method. Given the difference in reduction potentials between Bi and Ce, partially reduced Bi nanoparticles and surrounding under-coordinated oxygen atoms are generated in BiCeO1.8H. It is found that the lattice oxygen can be activated as a reactant of the OER when the valence state of Bi increases to Bi5+, leading to increased metal-oxygen covalency and that the oxophilic Ce3+/4+ redox couple can maintain the Bi nanoparticles and surrounding under-coordinated oxygen atoms by preventing over-oxidation of Bi. The anion exchange membrane water electrolyzer with Bi/BiCeO1.8H exhibits a low cell voltage of 1.79 V even at a high practical current density of 1.0 A cm-2. Furthermore, the cell performance remains significantly stable over 100 h with only a 2.2% increase in the initial cell voltage, demonstrating sustainable lattice oxygen redox.

RNF31 alleviates liver steatosis by promoting p53/BNIP3-related mitophagy in hepatocytes.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the liver illnesses that may be affected by mitophagy, which is the selective removal of damaged mitochondria. RNF31, an E3 ubiquitin ligase, is carcinogenic in many malignancies. However, the influence of RNF31 on mitochondrial homeostasis and NAFLD development remains unknown. METHODS: Oleic-palmitic acid treated hepatocytes and high-fat diet (HFD)-fed mice were established to observe the effect of RNF31 on hepatocyte mitophagy and steatosis. Mitophagy processes were comprehensively assessed by mt-Keima fluorescence imaging, while global changes in hepatic gene expression were measured by RNA-seq. RESULTS: The present study discovered a reduction in RNF31 expression in lipotoxic hepatocytes with mitochondrial dysfunction. The observed decrease in RNF31 expression was associated with reduced mitochondrial membrane potential, disturbed mitophagy, and increased steatosis. Additionally, the findings indicated that RNF31 is a pivotal factor in the initiation of mitophagy and the facilitation of mitochondrial homeostasis, resulting in a decrease in steatosis in lipotoxic hepatocytes. Mechanistically, RNF31 enhanced p53 ubiquitination and subsequent proteasomal degradation. Down-regulation of p53 led to increased expression of the mitophagy receptor protein BCL2 and adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), thereby promoting mitophagy in hepatocytes. Furthermore, it was demonstrated that the transportation of RNF31 via small extracellular vesicles derived from mesenchymal stem cells (referred to as sEV) had a substantial influence on reducing hepatic steatosis and restoring liver function in HFD-fed mice. CONCLUSIONS: The findings highlight RNF31's essential role in the regulation of mitochondrial homeostasis in hepatocytes, emphasizing its potential as a therapeutic target for NAFLD.

Tumor­suppressive effects of Smad­ubiquitination regulator 2 in papillary thyroid carcinoma.

Smad-ubiquitination regulator 2 (SMURF2) functions as a homolog of E6AP carboxyl terminus-type E3 ubiquitin ligase to regulate cell cycle progression and tumor growth factor expression. SMURF2 has been revealed to function as a tumor suppressor in a number of cancers; however, its function in papillary thyroid carcinoma (PTC) remains largely unknown. Therefore, the aim of the present study was to investigate the function of SMURF2 in PTC. Reverse transcription-quantitative PCR and western blotting were used to detect cellular expression of SMURF2 in vitro. After increasing or inhibiting the expression of SMURF2, MTT was used to detect the effect on tumor cell proliferation and Transwell assays were used to detect the effect on tumor cell migration and invasion. Finally, ELISA was used to detect the effects on glucose and glutamine metabolism in tumor cells and the findings revealed that SMURF2 was downregulated in PTC tissues. Moreover, SMURF2 inhibited the proliferation, invasion and migration of PTC cells, and promoted their apoptosis. Finally, SMURF2 inhibited cell glycolysis and glutaminolysis and affected metabolism in the PTC cell line, TPC-1. Thus, the findings of the present study suggest that SMURF2 may be a potential target in the treatment of PTC.

A comparative study of 11 non-linear regression models highlighting autoencoder, DBN, and SVR, enhanced by SHAP importance analysis in soybean branching prediction.

To explore a robust tool for advancing digital breeding practices through an artificial intelligence-driven phenotype prediction expert system, we undertook a thorough analysis of 11 non-linear regression models. Our investigation specifically emphasized the significance of Support Vector Regression (SVR) and SHapley Additive exPlanations (SHAP) in predicting soybean branching. By using branching data (phenotype) of 1918 soybean accessions and 42 k SNP (Single Nucleotide Polymorphism) polymorphic data (genotype), this study systematically compared 11 non-linear regression AI models, including four deep learning models (DBN (deep belief network) regression, ANN (artificial neural network) regression, Autoencoders regression, and MLP (multilayer perceptron) regression) and seven machine learning models (e.g., SVR (support vector regression), XGBoost (eXtreme Gradient Boosting) regression, Random Forest regression, LightGBM regression, GPs (Gaussian processes) regression, Decision Tree regression, and Polynomial regression). After being evaluated by four valuation metrics: R2 (R-squared), MAE (Mean Absolute Error), MSE (Mean Squared Error), and MAPE (Mean Absolute Percentage Error), it was found that the SVR, Polynomial Regression, DBN, and Autoencoder outperformed other models and could obtain a better prediction accuracy when they were used for phenotype prediction. In the assessment of deep learning approaches, we exemplified the SVR model, conducting analyses on feature importance and gene ontology (GO) enrichment to provide comprehensive support. After comprehensively comparing four feature importance algorithms, no notable distinction was observed in the feature importance ranking scores across the four algorithms, namely Variable Ranking, Permutation, SHAP, and Correlation Matrix, but the SHAP value could provide rich information on genes with negative contributions, and SHAP importance was chosen for feature selection. The results of this study offer valuable insights into AI-mediated plant breeding, addressing challenges faced by traditional breeding programs. The method developed has broad applicability in phenotype prediction, minor QTL (quantitative trait loci) mining, and plant smart-breeding systems, contributing significantly to the advancement of AI-based breeding practices and transitioning from experience-based to data-based breeding.

Hierarchically Interconnected 3D Catalyst Structure of Porous Multi-Metal Oxide Nanofibers for High-Performance Li-O2 Batteries.

Non-aqueous lithium-oxygen batteries (LOBs) have emerged as a promising candidate due to their high theoretical energy density and eco-friendly cathode reaction materials. However, LOBs still suffer from high overpotential and poor cycling stability resulting from difficulties in the decomposition of discharge reaction Li2 O2 products. Here, a 3D open network catalyst structure is proposed based on highly-thin and porous multi-metal oxide nanofibers (MMONFs) developed by a facile electrospinning approach coupled with a heat treatment process. The developed hierarchically interconnected 3D porous MMONFs catalyst structure with high specific surface area and porosity shows the enhanced electrochemical reaction kinetics associated with Li2 O2 formation and decomposition on the cathode surface during the charge and discharge processes. The uniquely assembled cathode materials with MMONFs exhibit excellent electrochemical performance with energy efficiency of 82% at a current density of 50 mA g-1 and a long-term cycling stability over 100 cycles at 200 mA g-1 with a cut-off capacity of 500 mAh g-1 . Moreover, the optimized cathode materials exhibit a remarkable energy density of 1013 Wh kg-1 at the 100th discharge and charge cycle, which is nearly four times higher than that of C/NMC721, which has the highest energy density among the cathode materials currently used in electric vehicles.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy Is Associated with HLA-A*3303 and HLA-DPB1*0501.

We determined the genetic association between specific human leucocyte antigen (HLA) loci and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Our results showed that autoimmune GFAP astrocytopathy was associated with HLA-A*3303 (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.32-3.06, p = 0.00072, padj. = 0.046) and HLA-DBP1*0501 (OR = 0.51, 95% CI = 0.36-0.71, p = 0.000048, padj. = 0.0062). Moreover, HLA-A*3303 carriers with the disease had a longer hospital stay (p = 0.0005) than non-carriers. This study for the first time provides evidence for a role of genetic factor in the development of autoimmune GFAP astrocytopathy. ANN NEUROL 2024;95:901-906.

Association of plasma homocysteine with peripheral arterial disease in the hypertensive adults: A cross-sectional study.

Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross-sectional study. The outcome was PAD, which defined as an ankle-brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60-17.80) µmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06-1.19). Patients in the upper plasma Hcy tertile (≥16.16 µmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (<12.33 µmol/L) after adjustment for multiple potential confounders. Subgroup analyses showed the association between Hcy and PAD was robust among various strata. Among Chinese adults with hypertension, plasma Hcy is an independent risk factor for PAD. This finding may improve the risk stratification of PAD.

Elimination of Random Mixed Noise in ECG Using Convolutional Denoising Autoencoder With Transformer Encoder.

Electrocardiogram (ECG) signals frequently encounter diverse types of noise, such as baseline wander (BW), electrode motion (EM) artifacts, muscle artifact (MA), and others. These noises often occur in combination during the actual data acquisition process, resulting in erroneous or perplexing interpretations for cardiologists. To suppress random mixed noise (RMN) in ECG with less distortion, we propose a Transformer-based Convolutional Denoising AutoEncoder model (TCDAE) in this study. The encoder of TCDAE is composed of three stacked gated convolutional layers and a Transformer encoder block with a point-wise multi-head self-attention module. To obtain minimal distortion in both time and frequency domains, we also propose a frequency weighted Huber loss function in training phase to better approximate the original signals. The TCDAE model is trained and tested on the QT Database (QTDB) and MIT-BIH Noise Stress Test Database (NSTDB), with the training data and testing data coming from different records. All the metrics perform the most robust in overall noise and separate noise intervals for RMN removal compared with the baseline methods. We also conduct generalization tests on the Icentia11k database where the TCDAE outperforms the state-of-the-art models, with a 55% reduction of the false positives in R peak detection after denoising. The TCDAE model approximates the short-term and long-term characteristics of ECG signals and has higher stability even under extreme RMN corruption. The memory consumption and inference speed of TCDAE are also feasible for its deployment in clinical applications.

From Hit to Lead: Structure-Based Optimization of Novel Selective Inhibitors of Receptor-Interacting Protein Kinase 1 (RIPK1) for the Treatment of Inflammatory Diseases.

Receptor-interacting protein kinase 1 (RIPK1) is a key regulator of cellular necroptosis, which is considered as an important therapeutic target for necroptosis-related indications. Herein, we report the structural optimization and structure-activity relationship investigations of a series of eutectic 5-substituted-indole-3-carboxamide derivatives. The prioritized compound 10b exhibited low nanomolar IC50 values against RIPK1 and showed good kinase selectivity. Based on its eutectic structure, 10b occupied both the allosteric and ATP binding pockets of RIPK1, making it a potent dual-mode inhibitor of RIPK1. In vitro, 10b had a potent protective effect against necroptosis in cells. Compound 10b also provided robust protection in a TNFα-induced systemic inflammatory response syndrome (SIRS) model and imiquimod (IMQ)-induced psoriasis model. It also showed good pharmacokinetic properties and low toxicity. Overall, 10b is a promising lead compound for drug discovery targeting RIPK1 and warrants further study.

Integrating SNVs and CNAs on a phylogenetic tree from single-cell DNA sequencing data.

Single-cell DNA sequencing enables the construction of evolutionary trees that can reveal how tumors gain mutations and grow. Different whole-genome amplification procedures render genomic materials of different characteristics, often suitable for the detection of either single-nucleotide variation or copy number aberration, but not ideally for both. Consequently, this hinders the inference of a comprehensive phylogenetic tree and limits opportunities to investigate the interplay of SNVs and CNAs. Existing methods such as SCARLET and COMPASS require that the SNVs and CNAs are detected from the same sets of cells, which is technically challenging. Here we present a novel computational tool, SCsnvcna, that places SNVs on a tree inferred from CNA signals, whereas the sets of cells rendering the SNVs and CNAs are independent, offering a more practical solution in terms of the technical challenges. SCsnvcna is a Bayesian probabilistic model using both the genotype constraints on the tree and the cellular prevalence to search the optimal solution. Comprehensive simulations and comparison with seven state-of-the-art methods show that SCsnvcna is robust and accurate in a variety of circumstances. Particularly, SCsnvcna most frequently produces the lowest error rates, with ability to scale to a wide range of numerical values for leaf nodes in the tree, SNVs, and SNV cells. The application of SCsnvcna to two published colorectal cancer data sets shows highly consistent placement of SNV cells and SNVs with the original study while also supporting a refined placement of ATP7B, illustrating SCsnvcna's value in analyzing complex multitumor samples.

Association between metabolic syndrome and early-stage colorectal cancer.

BACKGROUND: Accumulating studies have suggested metabolic syndrome (MetS) contributed to colorectal cancer (CRC) development. However, advanced CRC might decrease the detection proportion of MetS due to chronic malnutrition, we included patients with early-stage CRC to examine the associations among MetS, onset age, and different tumorigenesis pathways of CRC. METHODS: We conducted a retrospective study that included 638 patients with early-stage CRC from January 2014 to December 2018. Patient information was collected from the medical record system and further refined during the follow-up. Stratified analyses of the associations between MetS and different stratification factors were determined by the Cochran‒Mantel‒Haenszel test. RESULTS: There were 16 (13.3%) and 111 (21.4%) cases suffering from MetS in the early-onset and late-onset CRC groups, respectively. MetS coexisted in early-stage CRC patients ≥ 50 years of age more frequently than patients < 50 years of age (OR 1.77; 95% CI 1.01 to 3.12), but not for women patients (OR 0.84; 95% CI 0.79 to 0.90). MetS patients were associated with a higher risk of advanced serrated lesions than that of conventional adenomas (OR 1.585; 95% CI 1.02 to 2.45), especially in patients ≥ 50 years (OR 1.78; 95% CI 1.11 to 2.85). CONCLUSIONS: Metabolic dysregulation might partly contribute to the incidence of colorectal serrated lesions. Prevention of MetS should be highly appreciated in the early diagnosis and early treatment of the colorectal cancer system, especially in patients ≥ 50 years.

Association of prothrombin complexe concentrate with venous thrombosis after cardiac surgery: a case-control study.

Background: Prothrombin complex concentrate (PCC) enhances coagulation and controls bleeding. We aimed to assess whether perioperative infusion of PCC is associated with venous thrombosis after cardiac surgery. Methods: We conducted a case-control study of patients undergoing cardiac surgery at our hospital in 2021. Multivariate logistic regression was used to assess the correlation between perioperative PCC infusion and postoperative venous thrombosis in cardiac surgery. Stratified analysis was also performed by age, hospitalization days, and whether warfarin, warfarin combined with heparin, warfarin combined with antiplatelet drugs were used postoperatively. Results: Data from 161 patients undergoing cardiac surgery were included in the analysis. Of these, 37 (23.0%) patients in the case group developed venous thrombosis, and 124 (77.0%) patients in the control group did not develop venous thrombosis. In the analysis without adjustment for confounders (model 1), perioperative PCC infusion significantly increased the risk of postoperative venous thrombosis (OR: 3.10, 95% CI: 1.26-7.59, P = 0.0135). In the model analysis adjusted for sex, age, and hospitalization days (model 2), perioperative PCC infusion was no longer significantly associated with the risk of postoperative venous thrombosis (OR: 1.76, 95% CI: 0.56-7.59, P = 0.3317). In the fully adjusted model (model 3), there was a marginally significant association between perioperative infusion of PCC and the risk of postoperative venous thrombosis (OR: 0.03, 95% CI: 0.00-1.23, P = 0.0637). Conclusions: Our findings show no significant association between perioperative PCC infusion in cardiac surgery and the development of postoperative venous thrombosis. Randomized controlled trials are needed to determine the causal relationship between perioperative PCC infusion and venous thrombosis in cardiac surgery.

Engineered Escherichia coli Consortia Function in a Programmable Pattern for Multiple Enzymatic Biosynthesis.

Coordinating microbial consortia to realize complex synthetic pathways is an area of great interest in the rapidly growing field of biomanufacturing. This work presents a programmable method for assembling living cells based on the surface display of affinity groups, enabling whole-cell catalysis with optimized catalytic efficiency through the rational arrangement of cell assemblies and enzymes. In the context of d-phenyllactic acid (d-PLA) synthesis, four enzymes were rationally arranged considering substrate channeling and protein expression levels. The production efficiencies of d-PLA catalyzed by engineered microbial consortia were 1.31- and 2.55-fold higher than those of biofilm and whole-cell catalysts, respectively. Notably, substrate channeling was identified between the coimmobilized rate-limiting enzymes, resulting in a 3.67-fold improvement in catalytic efficiency compared with hybrid catalysts (free enzymes coupled with whole-cell catalysts). The highest yield of d-PLA catalyzed by microbial consortia was 102.85 ± 3.39 mM with 140 mM benzaldehyde as the substrate. This study proposes a novel approach to cell enzyme assembly for coordinating microbial consortia in multiple enzymatic biosynthesis processes.

Upregulation of ubiquitin carboxy­terminal hydrolase 47 (USP47) in papillary thyroid carcinoma ex vivo and reduction of tumor cell malignant behaviors after USP47 knockdown by stabilizing SATB1 expression in vitro.

Aberrant ubiquitination contributes to cancer development, including thyroid carcinoma. The present study assessed the expression of ubiquitin carboxy-terminal hydrolase 47 (USP47) and underlying molecular events in the development of papillary thyroid carcinoma (PTC). The effects of USP47 on PTC cell invasion and migration were analyzed by Transwell assays, while. the effects of USP47 and SATB1on PTC cell gene expression and changes in tumor cell metabolism were assayed by reverse transcription-quantitative PCR, western bolt, or ELISA, respectively. The expression of USP47 mRNA and protein was upregulated in PTC tissue and associated with the PTC tumor size. Knockdown of USP47 expression in PTC cell lines (TPC-1 and K1), decreased the cell proliferation mobility and invasion capacities, whereas USP47 overexpression in these cell lines showed an inverse effect and promoted cell glycolysis and glutamine metabolism. Moreover, expression of special AT-rich sequence-binding protein-1 (SATB1) was high in PTC tissue and was associated with USP47 expression. SATB1 expression promoted tumor cell glycolysis and glutamine metabolism, while USP47 protein bound to and deubiquitinated SATB1 to increase its intracellular levels, thus promoting glycolysis and glutamine metabolism. USP47 promotion of PTC development may be due to its stabilization of SATB1 protein, suggesting that targeting the USP47/SATB1 signaling axis may serve as a therapeutic intervention for PTC.

Fused-Ring Electron-Acceptor Single Crystals with Chiral 2D Supramolecular Organization for Anisotropic Chiral Optoelectronic Devices.

Supramolecular chiral organization gives π-conjugated molecules access to fascinating specific interactions with circularly polarized light (CPL). Such a feature enables the fabrication of high-performance chiral organic electronic devices that detect or emit CPL directly. Herein, it is shown that chiral fused-ring electron-acceptor BTP-4F single-crystal-based phototransistors demonstrate distinguished CPL discrimination capability with current dissymmetry factor exceeding 1.4, one of the highest values among state-of-the-art direct CPL detectors. Theoretical calculations prove that the chirality at the supramolecular level in these enantiomeric single crystals originates from chiral exciton coupling of a unique quasi-2D supramolecular organization consisting of interlaced molecules with opposite helical conformation. Impressively, such supramolecular organization produces a higher dissymmetry factor along the preferred growth direction of the chiral single crystals in comparison to that of the short axis direction. Furthermore, the amplified, inverted, and also anisotropic current dissymmetry compared to optical dissymmetry is studied by finite element simulations. Therefore, a unique chiral supramolecular organization that is responsible for the excellent chiroptical response and anisotropic electronic properties is developed, which not only enables the construction of high-performance CPL detection devices but also allows a better understanding of the structure-property relationships in chiral organic optoelectronics.