The potential adverse effects of hypodermic glucagon-like peptide -1 receptor agonist on patients with type 2 diabetes: A population-based study.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a class of injectable antidiabetic drugs, have shown significant efficacies in improving glycemic and weight control in patients with type 2 diabetes (T2D). However, the long-term safety of GLP-1 RAs remains insufficiently studied. This study aimed to provide real-world evidence on potential adverse outcomes associated with GLP-1 RAs use in T2D patients without major chronic diseases including impaired cardiac or renal function. METHODS: We conducted a retrospective cohort study involving 7746 T2D patients on GLP-1 RAs in Shenzhen, China. They were compared with 124 371 metformin-only users and 36 146 insulin-only users, forming two therapy control groups. GLP-1 RAs users were also further 1:2 paired with the control groups. Competing risk survival analyses were conducted to assess the incidence risks, presenting subdistributional hazard ratios (sHRs) with 95% confidence intervals (CIs) for various adverse outcomes associated with GLP-1 RAs use. RESULTS: Compared with metformin-only users, GLP-1 RAs use was associated with increased risks of various adverse outcomes (sHRs with 95% CIs), including pancreatitis (2.01, 1.24-3.24), acute nephritis (3.20, 2.17-4.70), kidney failure (3.73, 2.74-5.08), thyroid cancer (2.25, 1.23-4.10), and thyroid dysfunction (1.27, 1.00-1.63), respectively; Similar results were also found when compared with insulin-only users. Importantly, long-term (≥12 months) GLP-1 RAs use may further elevate the incidence risks of pancreatitis, acute nephritis, thyroid cancer, and thyroid dysfunction. CONCLUSION: Compared with traditional T2D treatments, GLP-1 RAs use may be associated with increased risks of various adverse outcomes in a Chinese population. Cautions were strongly warranted in the use of GLP-1 RAs. Further validation is crucial across diverse populations.

MURDA: Multisource Unsupervised Raman Spectroscopy Domain Adaptation Model with Reconstructed Target Domains for Medical Diagnosis Assistance.

Artificial intelligence combined with Raman spectroscopy for disease diagnosis is on the rise. However, these methods require a large amount of annotated spectral data for modeling to achieve high diagnostic accuracy. Annotating labels consumes significant medical resources and time. To reduce dependence on labeled medical data resources, we propose a method called Multisource Unsupervised Raman Spectroscopy Domain Adaptation Model with Reconstructed Target Domains (MURDA). It transfers knowledge learned from source domain data sets of different diseases to an unlabeled target domain data set. Compared to knowledge transfer from a single source domain, knowledge from multiple disease source domains provides more generalized knowledge. Considering the diversity of autoimmune diseases and the limited sample size, we apply MURDA to assist in the medical diagnosis of autoimmune diseases. Additionally, we propose a Double-Branch Multiscale Convolutional Self-Attention (DMCS) feature extractor that is more suitable for spectral data feature extraction. On three sets of serum Raman spectroscopy data sets for autoimmune diseases, the multisource domain adaptation diagnostic accuracy of MURDA was superior to traditional single source and multisource models, with accuracy rates of 73.6%, 83.4%, and 82.9%, respectively. Compared with pure source tasks without domain adaptation, it improved by 15.1%, 36%, and 21.6%, respectively. This demonstrates the effectiveness of Raman spectroscopy combined with MURDA in diagnosing autoimmune diseases. We investigated the important decision dependency peaks in migration tasks, providing assistance for future research on artificial intelligence combined with Raman spectroscopy for diagnosing autoimmune diseases. Furthermore, to validate the effectiveness and generalization performance of MURDA, we conducted experiments on the publicly available RRUFF data set, exploring the application of multisource unsupervised domain adaptation in more Raman spectroscopy scenarios.

Time-dependent cardiovascular risks following pneumonia in inpatient and outpatient settings: A register-based cohort study.

Background: The elevated long-term cardiovascular disease (CVD) risks associated with pneumonia have been observed among inpatients, yet the risks associated with outpatients are less understood. Methods: We used register-based data and a matched cohort design, including 98,354 pneumonia inpatients and 44,486 outpatients, as well as a 5-fold number of matched healthy controls. Associations between pneumonia presentation (in inpatient and outpatient settings) and long-term CVD risks were measured by rate difference and hazard ratio (HR) using Poisson and Cox regressions in a time-dependent manner. Results: During a maximum follow-up period of 5.7 years of ischemic heart disease (IHD), heart failure (HF), and stroke were documented among pneumonia inpatients.Relative to healthy controls, pneumonia patients showed increased risks of IHD, HF, and stroke. Women and young inpatients demonstrated stronger associations of CVD with pneumonia; inpatients aged 60 years or older showed the highest excessive CVD risks. Conclusions: Pneumonia demanding outpatient and inpatient cares are intermediate-term and long-term risk factors of incident CVDs respectively, underscoring the need to plan setting-specific and time-dependent CVD-preventive cares following pneumonia presentation.

Perfluoroalkyl substances exposure and the risk of breast cancer: A nested case-control study in Jinchang Cohort.

BACKGROUND: As persistent organic pollutants (POPs), perfluoroalkyl substances (PFAS) may potentially impact human health. Our study aimed to investigate the prospective association between PFAS exposure and the incidence risk of breast cancer in females. METHODS: By fully following the Jinchang Cohort after a decade, we conducted this nested case-control study with 135 incidence cases of breast cancer (BC) and 540 bias-paired controls. The PFAS levels were tested by baseline serum samples. Conditional logistic regression and a restricted cubic spline model were employed to investigate the BC incidence risks and the dose-response associated with single PFAS component exposure. Furthermore, the Quantile g-computation model (Qgc), random forest model (RFM), and bayesian kernel machine regression models (BKMR) were integrated to estimate the mixed effects of PFAS exposure on the incidence risk of BC. RESULTS: Exposures to specific PFAS components were positively associated with an increased incidence risk of breast cancer. By grouping the study population into different baseline menopausal statuses, PFHxS, PFNA, PFBA, PFUdA, PFOS, and PFDA demonstrated a similarly positive correlation with BC incidence risks. However, the increased incidence risks of BC associated with PFOA, PFOS, PFUdA, and 9CL-PF3ONS exposure were exclusively found in the premenopausal population. Both BKMR and Qgc revealed that exposure to mixed PFAS was associated with an increased risk of breast cancer, with Qgc specifically indicating an odds ratio (OR) of 2.21 (95% CI: 1.53, 3.19). Random forests showed that PFBA, PFOS, PFHxS, and PFDA emerged as predominant factors potentially influencing breast cancer incidence. CONCLUSION: Our findings suggest a strong association between PFAS exposure and the incidence of breast cancer. Premenopausal women should exercise more caution regarding PFAS exposure.

Burden of digestive system diseases in China and its provinces during 1990-2019: Results of the 2019 Global Disease Burden Study.

BACKGROUND: Evaluating the impact of digestive system diseases is vital for devising effective prevention strategies. However, comprehensive reports on the burden of digestive system diseases in China are lacking. Our study aimed to provide an overview of the burden and trends of digestive system diseases from 1990 to 2019 in China and its provinces. METHODS: This cross-sectional study utilized the Global Disease Burden Study 2019 to estimate the incidence, mortality rate, disability-adjusted life years (DALYs), years of life disability, years of life lost, and changes in the burden of digestive diseases across 31 Chinese provinces from 1990 to 2019. The analysis of disease burden primarily examines the characteristics of sub-disease distribution, time trends, age distribution, and sex distribution. Additionally, we compared provincial age-standardized DALYs for digestive diseases with the expected rates based on the socio-demographic index (SDI). RESULTS: In 2019, there were 499.2 million cases of digestive system diseases in China, resulting in 1,557,310 deaths. Stomach cancer, colon and rectal cancer, and esophageal cancer are the top three diseases associated with mortality and DALY related to digestive system diseases. Meanwhile, cirrhosis and other chronic liver diseases, gastroesophageal reflux disease, and gallbladder and biliary diseases are the top three kinds of diseases with the highest prevalence among digestive system diseases. The risk of gastric cancer sharply increases among men after the age of 40 years, leading to a significant disparity in burden between men and women. As the SDI increased, the DALYs associated with digestive system diseases in China and its provinces showed a downward trend. CONCLUSION: Our study highlights the inverse correlation between DALYs associated with digestive system diseases and the SDI, providing valuable insights that can assist public health officials in the estimation of the disease burden in this area.

Peroxisome proliferator­activated receptor γ alleviates human umbilical vein endothelial cell injury in deep vein thrombosis by blocking endoplasmic reticulum stress.

The present study aimed to explore the role of peroxisome proliferator-activated receptor γ (PPARγ) in the development of deep vein thrombosis (DVT), as well as to discover the potential regulatory mechanism of PPARγ. Human umbilical vein endothelial cells (HUVECs) were treated with modified glycated human serum albumin (M-HSA) to mimic DVT. PPARγ expression and activity were detected using western blot analysis and the corresponding activity detection kit, respectively. Cell Counting Kit-8 and the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays were employed to detect cell viability and apoptosis, respectively. The levels of thrombosis-related factors and inflammatory cytokines were detected by ELISA. The levels of oxidative stress-related factors were determined by the corresponding commercial kits. In addition, tunicamycin (TM), the agonist of endoplasmic reticulum stress (ERS), was applied to investigate the potential mechanism. The results indicated that M-HSA caused reduced expression and activity of PPARγ in HUVECs; these effects were reversed by PPARγ overexpression, which significantly inhibited M-HSA-induced cell viability loss, cell apoptosis, inflammation and oxidative stress in HUVECs. In addition, ERS was activated following M-HSA stimulation in HUVECs, but was suppressed by PPARγ overexpression. Furthermore, TM partly abolished the protective role of PPARγ overexpression against cell viability loss, cell apoptosis, inflammation and oxidative stress in M-HSA-induced HUVECs. In summary, PPARγ antagonized M-HSA-induced HUVEC injury by suppressing the activation of ERS, which provides a novel strategy for the treatment of DVT.

Effective surface passivation of GaAs nanowire photodetectors by a thin ZnO capping.

The III-V nanowire (NW) structure is a good candidate for developing photodetectors. However, high-density surface states caused by the large surface-to-volume ratio severely limit their performance, which is difficult to solve in conventional ways. Here, a robust surface passivation method, using a thin layer of ZnO capping, is developed for promoting NW photodetector performance. 11 cycles of ZnO, grown on pure zinc blende high-quality GaAs NWs by atomic layer deposition, significantly alleviates the undesirable effect of the surface states, without noticeable degradation in NW morphology. An average 20-fold increase in micro-photoluminescence intensity is observed for passivated NWs, which leads to the development of detectors with high responsivity, specific detectivity, and optical gain of 9.46 × 105 A W-1, 3.93 × 1014 Jones, and 2.2 × 108 %, respectively, under low-intensity 532 nm illumination. Passivated NW detectors outperform their counterparts treated by conventional methods, so far as we know, which shows the potential and effectiveness of thin ZnO surface passivation on NW devices.

Development of esophagogastroduodenoscopy in China: results from the national census in 2013 and 2020.

Background: Given the significant burden of upper digestive diseases, there has been a substantial increase in the utilization of esophagogastroduodenoscopy (EGD) in China from 2012 to 2019. The objective of this study is to investigate the development, practice, and factors influencing the widespread use of EGD during this period. Methods: Two national censuses were conducted among all hospitals in mainland China that perform gastrointestinal endoscopy. These censuses aimed to extract information on the infrastructure, volume, and quality of EGD. The analysis of potential factors influencing EGD practice was based on real-world data from open access sources. Results: From 2012 to 2019, the number of hospitals performing EGD in mainland China increased from 1,518 to 2,265 (1.49-fold) in tertiary hospitals and from 3,633 to 4,097 (1.12-fold) in secondary hospitals, respectively. The national utilization rate of EGD also increased from 1,643.53 to 2,018.06 per 100,000 inhabitants, indicating a 1.23-fold increase. Regions with more endoscopists per 100,000 inhabitants (OR 9.61, P<0.001), more tertiary hospitals performing EGD per million inhabitants (OR 2.43, P<0.001), higher incidence of esophageal and gastric cancer (OR 2.09, P=0 016), and higher number of hospitals performing EGD per million inhabitants (OR 1.77, P=0.01) tended to provided more numerous and qualitied EGD. And hospital grading, regional GDP, incidence of esophageal and gastric cancer and the volume of EGD were observed as the significantly relevant factors of malignant dictation rate (MDR) (P<0.05), but not the number and educational background of endoscopists. Conclusion: Over the past seven years, China has made significant progress in EGD. However, challenges persist in terms of quality and inequality.

Self-supervised Adversarial Training of Monocular Depth Estimation against Physical-World Attacks.

Monocular Depth Estimation (MDE) plays a vital role in applications such as autonomous driving. However, various attacks target MDE models, with physical attacks posing significant threats to system security. Traditional adversarial training methods, which require ground-truth labels, are not directly applicable to MDE models that lack ground-truth depth. Some self-supervised model hardening techniques (e.g., contrastive learning) overlook the domain knowledge of MDE, resulting in suboptimal performance. In this work, we introduce a novel self-supervised adversarial training approach for MDE models, leveraging view synthesis without the need for ground-truth depth. We enhance adversarial robustness against real-world attacks by incorporating L0-norm-bounded perturbation during training. We evaluate our method against supervised learning-based and contrastive learning-based approaches specifically designed for MDE. Our experiments with two representative MDE networks demonstrate improved robustness against various adversarial attacks, with minimal impact on benign performance. Our code: https://github.com/Bob-cheng/DepthModelHardening.

Development and status quo of digestive endoscopy in China: An analysis based on the national census in 2013 and 2020.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

Porous Ruthenium-Tungsten-Zinc Nanocages for Efficient Electrocatalytic Hydrogen Oxidation Reaction in Alkali.

With the rapid development of anion exchange membrane technology and the availability of high-performance non-noble metal cathode catalysts in alkaline media, the commercialization of anion exchange membrane fuel cells has become feasible. Currently, anode materials for alkaline anion-exchange membrane fuel cells still rely on platinum-based catalysts, posing a challenge to the development of efficient low-Pt or Pt-free catalysts. Low-cost ruthenium-based anodes are being considered as alternatives to platinum. However, they still suffer from stability issues and strong oxophilicity. Here, we employ a metal-organic framework compound as a template to construct three-dimensional porous ruthenium-tungsten-zinc nanocages via solvothermal and high-temperature pyrolysis methods. The experimental results demonstrate that this porous ruthenium-tungsten-zinc nanocage with an electrochemical surface area of 116 m2 g-1 exhibits excellent catalytic activity for hydrogen oxidation reaction in alkali, with a kinetic density 1.82 times and a mass activity 8.18 times higher than that of commercial Pt/C, and a good catalytic stability, showing no obvious degradation of the current density after continuous operation for 10,000 s. These findings suggest that the developed catalyst holds promise for use in alkaline anion-exchange membrane fuel cells.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China.

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.

Structural heterogeneity in tetra-armed gels revealed by computer simulation: Evidence from a graph theory assisted characterization.

Designing homogeneous networks is considered one typical strategy for solving the problem of strength and toughness conflict of polymer network materials. Experimentalists have proposed the hypothesis of obtaining a structurally homogeneous hydrogel by crosslinking tetra-armed polymers, whose homogeneity was claimed to be verified by scattering characterization and other methods. Nevertheless, it is highly desirable to further evaluate this issue from other perspectives. In this study, a coarse-grained molecular dynamics simulation coupled with a stochastic reaction model is applied to reveal the topological structure of a polymer network synthesized by tetra-armed monomers as precursors. Two different scenarios, distinguished by whether internal cross-linking is allowed, are considered. We introduce the Dijkstra algorithm from graph theory to precisely characterize the network structure. The microscopic features of the network structure, e.g., loop size, dispersity, and size distribution, are obtained via the Dijkstra algorithm. By comparing the two reaction scenarios, Scenario II exhibits an overall more idealized structure. Our results demonstrate the feasibility of the Dijkstra algorithm for precisely characterizing the polymer network structure. We expect this work will provide a new insight for the evaluation and description of gel networks and further help to reveal the dynamic process of network formation.

SLE diagnosis research based on SERS combined with a multi-modal fusion method.

As artificial intelligence technology gains widespread adoption in biomedicine, the exploration of integrating biofluidic Raman spectroscopy for enhanced disease diagnosis opens up new prospects for the practical application of Raman spectroscopy in clinical settings. However, for systemic lupus erythematosus (SLE), origin Raman spectral data (ORS) have relatively weak signals, making it challenging to obtain ideal classification results. Although the surface enhancement technique can enhance the scattering signal of Raman spectroscopic data, the sensitivity of the SERS substrate to airborne impurities and the inhomogeneous distribution of hotspots degrade part of the signal. To fully utilize both kinds of data, this paper proposes a two-branch residual-attention network (DBRAN) fusion technique, which allows the ORS to complement the degraded portion and thus improve the model's classification accuracy. The features are extracted using the residual module, which retains the original features while extracting the deep features. At the same time, the study incorporates the attention module in both the upper and lower branches to handle the weight allocation of the two modal features more efficiently. The experimental results demonstrate that both the low-level fusion method and the intermediate-level fusion method can significantly improve the diagnostic accuracy of SLE disease classification compared with a single modality, in which the intermediate-level fusion of DBRAN achieves 100% classification accuracy, sensitivity, and specificity. The accuracy is improved by 10% and 7% compared with the ORS unimodal and the SERS unimodal modalities, respectively. The experiment, by fusing the multimodal spectral, realized rapid diagnosis of SLE disease by fusing multimodal spectral data, which provides a reference idea in the field of Raman spectroscopy and can be further promoted to clinical practical applications in the future.

Multimorbidity and mortality among older patients with coronary heart disease in Shenzhen, China.

BACKGROUND: The current understanding of the magnitude and consequences of multimorbidity in Chinese older adults with coronary heart disease (CHD) is insufficient. We aimed to assess the association and population-attributable fractions (PAFs) between multimorbidity and mortality among hospitalized older patients who were diagnosed with CHD in Shenzhen, China. METHODS: We conducted a retrospective cohort study of older Chinese patients (aged ≥ 65 years) who were diagnosed with CHD. Cox proportional hazards models were used to estimate the associations between multimorbidity and all-cause and cardiovascular disease (CVD) mortality. We also calculated the PAFs. RESULTS: The study comprised 76,455 older hospitalized patients who were diagnosed with CHD between January 1, 2016, and August 31, 2022. Among them, 70,217 (91.9%) had multimorbidity, defined as the presence of at least one of the predefined 14 chronic conditions. Those with cancer, hemorrhagic stroke and chronic liver disease had the worst overall death risk, with adjusted HRs (95% CIs) of 4.05 (3.77, 4.38), 2.22 (1.94, 2.53), and 1.85 (1.63, 2.11), respectively. For CVD mortality, the highest risk was observed for hemorrhagic stroke, ischemic stroke, and chronic kidney disease; the corresponding adjusted HRs (95% CIs) were 3.24 (2.77, 3.79), 1.91 (1.79, 2.04), and 1.81 (1.64, 1.99), respectively. All-cause mortality was mostly attributable to cancer, heart failure and ischemic stroke, with PAFs of 11.8, 10.2, and 9.1, respectively. As for CVD mortality, the leading PAFs were heart failure, ischemic stroke and diabetes; the corresponding PAFs were 18.0, 15.7, and 6.1, respectively. CONCLUSIONS: Multimorbidity was common and had a significant impact on mortality among older patients with CHD in Shenzhen, China. Cancer, heart failure, ischemic stroke and diabetes are the primary contributors to PAFs. Therefore, prioritizing improved treatment and management of these comorbidities is essential for the survival prognosis of CHD patients from a holistic public health perspective.

Liquid biopsy of oesophageal squamous cell carcinoma: implications in diagnosis, prognosis, and treatment monitoring.

Oesophageal squamous cell carcinoma (ESCC) is a common malignant tumour of the gastrointestinal tract. Early detection and access to appropriate treatment are crucial for the long-term survival of patients. However, limited diagnostic and monitoring methods are available for identifying early stage ESCC. Endoscopic screening and surgical resection are commonly used to diagnose and treat early ESCC. However, these methods have disadvantages, such as high recurrence, lethality, and mortality rates. Therefore, methods to improve early diagnosis of ESCC and reduce its mortality rate are urgently required. In 1961, Gary et al. proposed a novel liquid biopsy approach for clinical diagnosis. This involved examining exosomes, circulating tumour cells, circulating free DNA, and circulating free RNA in body fluids. The ability of liquid biopsy to obtain samples repeatedly, wide detection range, and fast detection speed make it a feasible option for non-invasive tumour detection. In clinical practice, liquid biopsy technology has gained popularity for early screening, diagnosis, treatment efficacy monitoring, and prognosis assessment. Thus, this is a highly promising examination method. However, there have been no comprehensive reviews on the four factors of liquid biopsy in the context of ESCC. This review aimed to analyse the progress of liquid biopsy research for ESCC, including its classification, components, and potential future applications.

Olympic gels formed through catenation of dsDNA rings regulated by topoisomerase II: A coarse-grained model.

Topological regulation of DNA by topoisomerases in cells is very crucial for life. We propose a coarse-grained model to study the catenation process of double-stranded DNA (dsDNA) rings regulated by topoisomerase II (TOP2) and provide a computational method to characterize the topological structures of the Olympic gels obtained. The function of TOP2 in the catenation of dsDNA rings is implicitly fulfilled by operating the length of a stretchable catch bond in the dsDNA ring. After the catenation reaction of initially noncatenated dsDNA rings in the solution, the Olympic gel is obtained and the interlocked topology of the dsDNA rings can be characterized by a computational method derived from the HOMFLY polynomial, based on which the catenation degree and the complexity of catenation are quantified. Detailed dependence of the catenation degree and the complexity of the catenated topology on key parameters, including the size of the transient broken gap and the duration time of the break on the dsDNA ring during operation by TOP2, the initial molar ratio of TOP2 to the dsDNA rings, and the reaction temperature, has been investigated.

The nuclear pore Y-complex functions as a platform for transcriptional regulation of FLOWERING LOCUS C in Arabidopsis.

The nuclear pore complex (NPC) has multiple functions beyond the nucleo-cytoplasmic transport of large molecules. Subnuclear compartmentalization of chromatin is critical for gene expression in animals and yeast. However, the mechanism by which the NPC regulates gene expression is poorly understood in plants. Here we report that the Y-complex (Nup107-160 complex, a subcomplex of the NPC) self-maintains its nucleoporin homeostasis and modulates FLOWERING LOCUS C (FLC) transcription via changing histone modifications at this locus. We show that Y-complex nucleoporins are intimately associated with FLC chromatin through their interactions with histone H2A at the nuclear membrane. Fluorescence in situ hybridization assays revealed that Nup96, a Y-complex nucleoporin, enhances FLC positioning at the nuclear periphery. Nup96 interacted with HISTONE DEACETYLASE 6 (HDA6), a key repressor of FLC expression via histone modification, at the nuclear membrane to attenuate HDA6-catalyzed deposition at the FLC locus and change histone modifications. Moreover, we demonstrate that Y-complex nucleoporins interact with RNA polymerase II to increase its occupancy at the FLC locus, facilitating transcription. Collectively, our findings identify an attractive mechanism for the Y-complex in regulating FLC expression via tethering the locus at the nuclear periphery and altering its histone modification.

Development, quality, and influencing factors of colonoscopy in China: results from the national census in 2013 and 2020.

Background and Aim: With the increasing burden of colorectal cancer (CRC), the practice of colonoscopy is gaining attention worldwide. However, it exhibits distinct trends between developing and developed countries. This study aims to explore its development and identify influencing factors in China. Methods: The Chinese Digestive Endoscopy Censuses were conducted twice in mainland China under the supervision of health authorities. Information regarding the practice of colonoscopy was collected through a structured online questionnaire. The authenticity of the data was evaluated through logical tests, and a random selection of endoscopic reports underwent manual validation by Quality Control Centers. Potential factors associated with colonoscopy were analyzed using real-world information. Results: From 2012 to 2019, the number of hospitals that performed colonoscopy increased from 3,210 to 6,325 (1.97-fold), and the volume increased from 5.83 to 12.92 million (2.21-fold). The utilization rate rose from 436.0 to 914.8 per 100,000 inhabitants (2.10-fold). However, there was an exacerbation of regional inequality in the adequacy of colonoscopy. Regions with higher incidence of CRC, higher gross domestic product per capita, more average numbers of endoscopists and tertiary hospitals tended to provide more accessible colonoscopy (P<0.001). Nationwide, the cecal intubation rate improved from 83.9% to 94.4% and the unadjusted adenoma detection rate (ADR) improved from 16.3% to 18.1%. Overall, hospital grading, educational background of endoscopists, economic income, and colonoscopy volume were observed as the significantly positive factors affecting ADR (P<0.05), but not the incidence of CRC or the number of endoscopists. Conclusions: Tremendous progress in colonoscopy has been made in China, but some issues needed timely reflection. Our findings provide timely evidence for better colonoscopy strategies and measures, such as quality control and medical education of endoscopists.

Nickel chloride promotes lung cancer invasion and metastasis by up-regulating the expression of E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis.

Nickel compounds are widely used in industries and daily life as important industrial products. Long-term exposure to nickel compounds has been associated with increased incidence and poor prognosis of lung cancer. However, the molecular mechanism by which exposure to nickel compounds induces the malignant phenotype of lung cancer cells remains unclear. In this study, we confirmed that nickel chloride (NiCl2) exposure promotes invasion and metastasis through IL-6/STAT3 both in vitro and vivo. Mechanistically, we found that NiCl2 mediated the transcriptional regulation of E3 ubiquitin ligase TRIM31 by SATAT3 phosphorylation, and promoted its up-regulation. Overexpression TRIM31 is an independent risk factor for lung cancer patients, and it promotes the invasion and metastasis of lung cancer cells. In addition, E3 ubiquitination ligase TRIM31 binds to its substrate TP53 protein in the RING region and accelerates TP53 protein ubiquitination and degradation. Functional recovery experiments showed that NiCl2 exposure promotes the invasion and metastasis ability of lung cancer and ubiquitination-mediated degradation of TP53 protein through the STAT3/TRIM31 axis. These findings reveal the role and mechanism of NiCl2 in lung cancer progression, indicating that STAT3 and TRIM31 may be promising targets for the treatment of lung cancer.