Analysing a Group of Homologous BAHD Enzymes Provides Insights into the Evolutionary Transition of Rosmarinic Acid Synthases from Hydroxycinnamoyl-CoA:Shikimate/Quinate Hydroxycinnamoyl Transferases.

The interplay of various enzymes and compounds gives rise to the intricate secondary metabolic networks observed today. However, the current understanding of their formation and expansion remains limited. BAHD acyltransferases play important roles in the biosynthesis of numerous significant secondary metabolites. In plants, they are widely distributed and exhibit a diverse range of activities. Among them, rosmarinic acid synthase (RAS) and hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT) have gained significant recognition and have been extensively investigated as prominent members of the BAHD acyltransferase family. Here, we conducted a comprehensive study on a unique group of RAS homologous enzymes in Mentha longifolia that display both catalytic activities and molecular features similar to HCT and Lamiaceae RAS. Subsequent phylogenetic and comparative genome analyses revealed their derivation from expansion events within the HCT gene family, indicating their potential as collateral branches along the evolutionary trajectory, leading to Lamiaceae RAS while still retaining certain ancestral vestiges. This discovery provides more detailed insights into the evolution from HCT to RAS. Our collective findings indicate that gene duplication is the driving force behind the observed evolutionary pattern in plant-specialized enzymes, which probably originated from ancestral enzyme promiscuity and were subsequently shaped by principles of biological adaptation.

A Light Multi-View Stereo Method with Patch-Uncertainty Awareness.

Multi-view stereo methods utilize image sequences from different views to generate a 3D point cloud model of the scene. However, existing approaches often overlook coarse-stage features, impacting the final reconstruction accuracy. Moreover, using a fixed range for all the pixels during inverse depth sampling can adversely affect depth estimation. To address these challenges, we present a novel learning-based multi-view stereo method incorporating attention mechanisms and an adaptive depth sampling strategy. Firstly, we propose a lightweight, coarse-feature-enhanced feature pyramid network in the feature extraction stage, augmented by a coarse-feature-enhanced module. This module integrates features with channel and spatial attention, enriching the contextual features that are crucial for the initial depth estimation. Secondly, we introduce a novel patch-uncertainty-based depth sampling strategy for depth refinement, dynamically configuring depth sampling ranges within the GRU-based optimization process. Furthermore, we incorporate an edge detection operator to extract edge features from the reference image's feature map. These edge features are additionally integrated into the iterative cost volume construction, enhancing the reconstruction accuracy. Lastly, our method is rigorously evaluated on the DTU and Tanks and Temples benchmark datasets, revealing its low GPU memory consumption and competitive reconstruction quality compared to other learning-based MVS methods.

Modified Sijunzi Granules Exhibit Hemostatic Effect by Activating Akt and Erk Signal Pathways via Regulating 5-HT and Its Receptors Levels.

OBJECTIVE: To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism. METHODS: AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis. RESULTS: The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05). CONCLUSIONS: MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP.

Meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among Chinese children and adolescents: Prevalence, associations, and the population impacts.

OBJECTIVES: To examine the association between meeting the Canadian 24-Hour Movement Guidelines and physical-mental comorbidity among children and adolescents in a cross-sectional study. METHODS: A total of 21,061 students aged 11-17 years from Zhejiang Province, China was recruited in the study. We examined the coexistence of five specific physical illnesses - hypertension, high myopia, dental caries, scoliosis, and obesity - with mental illness, specifically depressive symptoms. Generalized linear mixed models were performed to assess the association between overall and specific combinations of movement guidelines and physical-mental comorbidity, presented by odds ratio (OR) and 95% confidence interval (CI). Population attributable fraction (PAF) was calculated to estimate the preventable proportion of comorbid cases via meeting all three movement recommendations. RESULTS: Of the included participants, 19.3% had physical-mental comorbidity. There were 3.8% and 17.0% meeting all three and none of the recommendations, respectively. Meeting at least one recommendation, except for moderate-to-vigorous physical activity recommendation only, was associated with a lower risk of physical-mental comorbidity, with ORs (95% CIs) ranging from 0.72 (0.66-0.79) to 0.40 (0.31-0.51). Meeting more recommendations was associated with decreased comorbid risks, and the association was stronger in 4th-6th graders. The association between specific combinations of recommendations and comorbid risks showed differences by gender and grade. Of the comorbid cases, 42.1% were attributed to not adhering to all three recommendations, and the PAFs varied from 27.4% to 55.7% across different genders and grades. CONCLUSION: Adherence to the 24-h movement guidelines was associated with lower risks of physical-mental comorbidity among children and adolescents.

Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990-2050: a bayesian age-period-cohort modeling study.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Competitive effects of the macroalga Caulerpa taxifolia on key physiological processes in the scleractinian coral Turbinaria peltata under thermal stress.

An increased abundance of macroalgae has been observed in coral reefs damaged by climate change and local environmental stressors. Macroalgae have a sublethal effect on corals that includes the inhibition of their growth, development, and reproduction. Thus, this study explored the effects of the macroalga, Caulerpa taxifolia, on the massive coral, Turbinaria peltata, under thermal stress. We compared the responses of the corals' water-meditated interaction with algae (the co-occurrence group) and those in direct contact with algae at two temperatures. The results show that after co-culturing with C. taxifolia for 28 days, the density content of the dinoflagellate endosymbionts was significantly influenced by the presence of C. taxifolia at ambient temperature (27 °C), from 1.3 × 106 cells cm-2 in control group to 0.95 × 106 cells cm-2 in the co-occurrence group and to 0.89 × 106 cells cm-2 in the direct contact group. The chlorophyll a concentration only differed significantly between the control and the direct contact group at 27 °C. The protein content of T. peltata decreased by 37.2% in the co-occurrence group and 49.0% in the direct contact group compared to the control group. Meanwhile, the growth rate of T. peltata decreased by 57.7% in the co-occurrence group and 65.5% in the direct contact group compared to the control group. The activity of the antioxidant enzymes significantly increased, and there was a stronger effect of direct coral contact with C. taxifolia than the co-occurrence group. At 30 °C, the endosymbiont density, chlorophyll a content, and growth rate of T. peltata significantly decreased compared to the control temperature; the same pattern was seen in the increase in antioxidant enzyme activity. Additionally, when the coral was co-cultured with macroalgae at 30 °C, there was no significant decrease in the density or chlorophyll a content of the endosymbiont compared to the control. However, the interaction of macroalgae and elevated temperature was evident in the feeding rate, protein content, superoxide dismutase (SOD), and catalase (CAT) activity compared to the control group. The direct contact of the coral with macroalga had a greater impact than water-meditated interactions. Hence, the competition between coral and macroalga may be more intense under thermal stress.

The Study of COVID-19's Perceptions as a Motivation to Exercise and Keep Fit Among Older Adults.

Since the end of 2019, a novel coronavirus pandemic (COVID-19), characterized by solid infectivity, rapid communication and diverse communication routes, has become widespread worldwide. This study investigates the motivations of older adults to exercise and keep fit due to the COVID-19 pandemic. The research is based on a survey of older adults in Chengdu, Sichuan Province, China. It adopts the event strength system theory as a conceptual framework and the stimulus-organism-response (S-O-R) theory for causal inferences. (1) the perception of COVID-19's novelty had a significant negative impact on older adults" intention to exercise and stay fit, and the perception of COVID-19's disruptiveness and criticality had a significant positive impact on older adults" intention to exercise and fitness; (2) The perception of COVID-19's novelty had a significant negative effect on risk cognition, and the disruptive and critical cognitions had a significant positive effect on risk perceptions; (3) risk perceptions had a prominent positive effect on older adults" intention to exercise and fitness; and (4) risk communication played an important moderating role between COVID-19 event strength cognition and older adults' intention to exercise and fitness. The study revealed that the perception of COVID-19's seriousness significantly impacted older adults" intentions to exercise and keep fit and that risk perception and communication acted as mediating factors.

Combined associations of general obesity and central obesity with hypertension stages and phenotypes among children and adolescents in Zhejiang, China.

General and central obesity are suggested to be associated with elevated blood pressure (BP), whereas few studies have investigated their combined associations with hypertension in children. This study aimed to assess the associations of combinations of general obesity and central obesity with hypertension in Chinese children, including its stages and phenotypes. A total of 5430 children aged 7-17 years in Zhejiang Province were enrolled. General obesity was evaluated by body mass index (BMI), while central obesity was by waist circumference (WC). Then all children were sorted into three mutually exclusive groups: normal weight with or with no central obesity (NW), abnormal weight with no central obesity (AWNCO), and abnormal weight with central obesity (AWCO). Hypertension was defined as either a systolic or diastolic BP ≥ 95th percentile, and further classified into stage 1 hypertension, stage 2 hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic diastolic hypertension (SDH). Logistic regression was used. AWNCO and AWCO were associated with stage 1 hypertension (AWNCO, odds ratio [OR] = 1.94, 95% confidence interval [CI]: 1.59-2.37; AWCO, 2.67, 2.20-3.25), stage 2 hypertension (AWNCO, 2.35, 1.33-4.13; AWCO, 4.53, 2.79-7.37), ISH (AWNCO, 2.50, 1.96-3.18; AWCO, 3.95, 3.15-4.95), and SDH (AWNCO, 2.48, 1.75-3.52; AWCO, 2.78, 1.94-3.99). Children with AWCO were more likely to have stage 1 and stage 2 hypertension, as well as ISH and SDH. The combined measurement of general and central obesity is suggested as an appropriate screening tool for hypertension among children and adolescents.

"We are in the forgotten corner!" a qualitative study of experiences and challenges among Chinese older women at the onset of acute myocardial infarction.

Background: Acute myocardial infarction (AMI) is a common and serious cardiovascular disease (CVD) that is one of the leading causes of death among women globally and in China. However, there are sex-associated differences and inequalities in the detection and management of AMI, especially in older people. There is little research demonstrating how challenges and barriers affect older women's help-seeking behavior and health-related procedures in China. Purpose: The objective of this study was to explore the experiences of older women with AMI, focusing on their perception, challenges, and coping strategies at the onset of AMI in Wuhan, China. Methods: This study utilized a qualitative research design approach and conducted semi-structured, in-depth, and audio-recorded interviews with 18 women aged 65-84 years, purposively selected from two tertiary hospitals in Wuhan City from November 2021 to April 2022. Results: Interpretative Phenomenological Analysis (IPA) was used in this study to analyze the data on 18 participants and three major themes were generated: disease perception disorder, negative coping strategies, and barriers due to social-environmental contexts. Conclusion: To reduce older women's delay in seeking help, healthcare professionals should provide public health education that emphasizes sex-related disparities, and age-specific knowledge-attitude aspects to high-risk groups. Policy-based and health administration recommendations, including e-health information support, access to care, and social-environmental factors, should be highlighted to promote women's health behavior.

A deep learning method for foot-type classification using plantar pressure images.

Background: Flat foot deformity is a prevalent and challenging condition often leading to various clinical complications. Accurate identification of abnormal foot types is essential for appropriate interventions. Method: A dataset consisting of 1573 plantar pressure images from 125 individuals was collected. The performance of the You Only Look Once v5 (YOLO-v5) model, improved YOLO-v5 model, and multi-label classification model was evaluated for foot type identification using the collected images. A new dataset was also collected to verify and compare the models. Results: The multi-label classification algorithm based on ResNet-50 outperformed other algorithms. The improved YOLO-v5 model with Squeeze-and-Excitation (SE), the improved YOLO-v5 model with Convolutional Block Attention Module (CBAM), and the multilabel classification model based on ResNet-50 achieved an accuracy of 0.652, 0.717, and 0.826, respectively, which is significantly higher than those obtained using the ordinary plantar-pressure system and the standard YOLO-v5 model. Conclusion: These results indicate that the proposed DL-based multilabel classification model based on ResNet-50 is superior in flat foot type detection and can be used to evaluate the clinical rehabilitation status of patients with abnormal foot types and various foot pathologies when more data on patients with various diseases are available for training.

A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia.

BACKGROUND: Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. METHODS: In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. FINDINGS: We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98). INTERPRETATION: In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. FUNDING: National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

Health-related quality of life and its influencing factors in patients with breast cancer based on the scale QLICP-BR.

Breast cancer is the most common cancer and the leading cause of cancer death among females worldwide. During the past 15 years, quality of life (QOL) has become an important aspect of breast cancer treatment. The purpose of this study was to evaluate QOL of breast cancer patients in China, and investigate its associations with sociodemographic and clinical variables. A cross-sectional study was conducted in 246 breast cancer patients in China. Recruited patients were surveyed for QOL using the QOL instruments for cancer patients-breast cancer QLICP-BR (V2.0). We assessed the associations between potential influencing factors and QOL using multiple linear regression models. The general mean QOL score for our population was 70.24 with SD = 8.70. Results indicated that medical insurance, drinking history, alkaline phosphatase, serum chloride ion level, serum calcium ion level, serum phosphorus ion level, mean corpuscular volume, mean corpuscular hemoglobin, red cell volume distribution width and platelet had significant associations with QOL of breast cancer patients. Our results emphasized that many factors are affecting QOL of breast cancer patients, which may provide a reference for targeted management or intervention strategies of breast cancer patients to improve their QOL.

Spatial structure of the non-integrable discrete defocusing Hirota equation.

In this paper, we investigate the spatial property of the non-integrable discrete defocusing Hirota equation utilizing a planar nonlinear discrete dynamical map method. We construct the periodic orbit solutions of the stationary discrete defocusing Hirota equation. The behavior of the orbits in the vicinity of the special periodic solution is analyzed by taking advantage of the named residue. We characterize the effects of the parameters on the aperiodic orbits with the aid of numerical simulations. A comparison with the non-integrable discrete defocusing nonlinear Schrödinger equation case reveals that the non-integrable discrete defocusing Hirota equation has more abundant spatial properties. Rather an interesting and novel thing is that for any initial value, there exists triperiodic solutions for a reduced map.

Enhanced photodegradation of p-arsanilic acid by oxalate in goethite heterogeneous system under UVA irradiation.

The widespread used organoarsenicals have drawn attention for decades due to their potential environment risks. In this study, a heterogeneous system of goethite/oxalate irradiated using UVA light (λ = 365 nm) was applied for the removal of ASA, a kind of organoarsenicals used in animal feeding operations as additives, from the aqueous phase through photodegradation. Results showed that the presence of 5 mM of oxalate significantly enhanced the photodegradation efficiency of ASA in the 0.1 g/L of goethite suspended system from 28 to ~100% within 180 min reaction at pH 5. Acid conditions favored the photoreaction rate, compared with neutral and basic conditions. This reaction process was also influenced by the initial concentration of oxalate and ASA. Furthermore, the mechanism study was conducted by quenching experiments and revealed the important roles of ·OH in the degradation of ASA in the goethite/oxalate/UVA system. By analyzing the reaction products, both inorganic arsenic (As(III) and As(V)) and ammonia were detected during the photodegradation of ASA. These findings help to gain a better understanding of the geochemical behavior of ASA in surface water and can also provide a potential treatment method for the organoarsenicals contaminated water.

Cadmium and lead removal by Mg/Fe bimetallic oxide-loaded sludge-derived biochar: batch adsorption, kinetics, and mechanism.

Biochar is a valuable adsorbent for the removal of heavy metals from water, and it is important to explore ways to increase its heavy metal adsorption capacity. In this study, Mg/Fe bimetallic oxide was loaded onto sewage sludge-derived biochar to enhance its heavy metal adsorption capacity. Batch adsorption experiments for the removal of Pb(II) and Cd(II) were performed to evaluate the removal efficiency of Mg/Fe layer bimetallic oxide-loaded sludge-derived biochar ((Mg/Fe)LDO-ASB). The physicochemical properties of (Mg/Fe)LDO-ASB and corresponding adsorption mechanisms were studied. The maximum adsorption capacities of (Mg/Fe)LDO-ASB for Pb(II) and Cd(II), which were calculated by isotherm model, were 408.31 and 270.41 mg/g, respectively. Adsorption kinetics and isotherms analysis showed that the dominant adsorption process of Pb(II) and Cd(II) uptake by (Mg/Fe)LDO-ASB was spontaneous chemisorption and heterogeneous multilayer adsorption, and film diffusion was the rate-limiting step. SEM-EDS, FTIR, XRD, and XPS analyses revealed that the Pb and Cd adsorption processes of (Mg/Fe)LDO-ASB involved oxygen-containing functional group complexation, mineral precipitation, electron-π-metal interactions, and ion exchange. The order of their contribution was as follows: mineral precipitation (Pb: 87.92% and Cd: 79.91%) > ion exchange (Pb: 9.84% and Cd: 16.45%) > metal-π interaction (Pb: 0.85% and Cd: 0.73%) > oxygen-containing functional group complexation (Pb: 1.39% and Cd: 2.91%). Mineral precipitation was the main adsorption mechanism, and ion exchange played a crucial role in Pb and Cd adsorption.

Potential Global Invasion Risk of Scale Insect Pests Based on a Self-Organizing Map.

In the present study, a global presence/absence dataset including 2486 scale insect species in 157 countries was extracted to assess the establishment risk of potential invasive species based on a self-organizing map (SOM). According to the similarities in species assemblages, a risk list of scale insects for each country was generated. Meanwhile, all countries in the dataset were divided into five clusters, each of which has high similarities of species assemblages. For those countries in the same neuron of the SOM output, they may pose the greatest threats to each other as the sources of potential invasive scale insect species, and therefore, require more attention from quarantine departments. In addition, normalized ζi values were used to measure the uncertainty of the SOM output. In total, 9 out of 63 neurons obtained high uncertainty with very low species counts, indicating that more investigation of scale insects should be undertaken in some parts of Africa, Asia and Northern Europe.

Epidemiological and clinical features of hypertrophic scar and keloid in Chinese college students: A university-based cross-sectional survey.

Background: Hypertrophic scar (HS) and keloid (KD) are common dermal fibroproliferative growth caused by pathological wound healing. HS's prevalence is currently undetermined in China. Though it primarily occurs in dark-skinned individuals, KD can develop in all races, and its prevalence among Chinese people is poorly documented. Objective: To explore the present epidemiological status of them in Chinese college students. Methods: We conducted a university-based cross-sectional study at one university in Fujian, China. A total of 1785 participants aged 16-34 years (mean age, 20.0 ± 2.0; 58.7% female) were enrolled and statistical analyses were performed. Results: HS and KD were observed in 5.2% (95% confidence interval [CI]: 4.2-6.2) and 0.6% (95% CI: 0.3-1.0) of the population respectively. There was a significant difference by sex in HS (P < 0.05), but not in KD. The prevalence of HS and KD both showed a significant difference by age (P < 0.05), but not in ethnic and native place distribution. The occurrence of HS and KD were both concentrated in individuals 9-20 years old (HS: 77.2%; KD: 81.8%). They were mainly distributed in the upper limbs (52.1%; 64.3%), and the main cause was trauma (51.0%; 35.7%). In addition, male sex was a risk factor for HS (adjusted P < 0.001), and KD was associated with age ≥22 years and family history (adjusted P < 0.050). Conclusion: HS and KD are common in Chinese college students, and more attention and research is warranted.

Berberine attenuates liver fibrosis by autophagy inhibition triggering apoptosis via the miR-30a-5p/ATG5 axis.

Berberine (BBR) is an effective drug against liver fibrosis (LF). Autophagy is involved in the pathogenesis of LF; however, the mechanism linking BBR to autophagy in LF remains unresolved. To explore the underlying mechanism, we assessed the effects of BBR on autophagy and apoptosis of activated hepatic stellate cells (HSCs) in vitro and in a murine model of fibrosis. The decreased expression of the autophagy activation marker ATG5, autophagosome formation, and autophagy flux in the HSC model confirmed that BBR inhibited autophagy in activated HSCs and in mice with liver fibrosis. Moreover, ATG5 was necessary for inducing autophagy and HSC activation. BBR suppressed ATG5 expression by upregulating miR-30a-5p expression, which affected the stability of ATG5 mRNA by binding to its 3'-untranslated region, an effect that was attenuated by treatment with a miR-30a-5p inhibitor. BBR also markedly induced HSC apoptosis, as indicated by the upregulated expression of the pro-apoptosis markers p53, BAX, and cleaved PARP and the downregulated expression of the anti-apoptosis marker BCL-2, effects that were reversed by ATG5 overexpression. In vivo, BBR improved mouse LF by decreasing collagen deposition, inflammatory cell infiltration, and expression of fibrosis markers hydroxyproline, α-smooth muscle actin, and collagen type 1-A1 and the autophagy marker LC3. BBR had a protective effect on mouse fibrotic livers and reduced serum aspartate aminotransferase and alanine aminotransferase levels. Collectively, these results reveal a novel mechanism of BBR-induced autophagy inhibition triggering apoptosis in HSCs, providing a reliable experimental and theoretical basis for developing BBR-based candidate drugs for LF.

Associations of the Triglyceride and Glucose Index With Hypertension Stages, Phenotypes, and Their Progressions Among Middle-Aged and Older Chinese.

Objectives: To assess the associations of the triglyceride and glucose (TyG) index with hypertension stages, phenotypes, and their progressions. Methods: The data originated from the China Health and Retirement Longitudinal Study. Multinomial logistic regression investigated the associations of the TyG index with hypertension stages (stage 1, stage 2), phenotypes (isolated systolic hypertension [ISH], isolated diastolic hypertension [IDH], systolic diastolic hypertension [SDH]), their progressions. Results: Compared with the lowest quartile of TyG index, the highest quartile was associated with increased risks of stage 1 hypertension (OR 1.71, 95% CI 1.38-2.13), stage 2 (1.74, 1.27-2.38), ISH (1.66, 1.31-2.11), IDH (2.52, 1.26-5.05), and SDH (1.65, 1.23-2.23). Similar results were found when TyG index was a continuous variable. From 2011 to 2015, a higher baseline TyG index was associated with normotension to stage 1 (per-unit: 1.39, 1.16-1.65), normotension to ISH (per-unit: 1.28, 1.04-1.56), and normotension to IDH (per-unit: 1.94, 1.27-2.97). Conclusion: The TyG index was associated with different hypertension stages, phenotypes, their progressions, and could be served as a surrogate indicator for early hypertension management.

Investigating the change in gene expression profile of blood mononuclear cells post-laparoscopic sleeve gastrectomy in Chinese obese patients.

Background: Laparoscopic sleeve gastrectomy (LSG) is a sustainable technique that effectively treats morbid obesity. However, the molecular mechanisms underlying the improvement of metabolic health following this process warrants more investigation. This study investigates LSG-related molecules and uses bulk RNA-sequencing high-throughput analysis to unravel their regulatory mechanisms. Methods: Peripheral blood mononuclear cells (PBMC) were collected from ten obese patients with BMI ≥ 32.5 kg/m2 in the Department of General Surgery of Kunming First People's Hospital. After LSG, patients were followed up for one month, and blood samples were retaken. Blood samples from ten patients before and after LSG and bulk RNA-Seq data were analyzed in this study. LSG-associated gene expression was detected by weighted gene coexpression network analysis (WGCNA) and differential analysis. Subsequently, essential signature genes were identified using logistic least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) were utilized to reveal the potential functions of the target genes. Furthermore, the Pearson correlation of signature genes with leptin and lipocalin was also explored. Finally, we constructed a robust endogenous RNA (ceRNA) network based on miRWalk and starBase databases. Results: We identified 18 overlapping genes from 91 hub genes, and 165 differentially expressed mRNAs (DE-mRNA), which were revealed to be significantly associated with immune cells, immune response, inflammatory response, lipid storage, and localization upon functional enrichment analysis. Three signature genes, IRF1, NFKBIA, and YRDC, were identified from the 18 overlapping genes by LASSO and SVM-REF algorithms. The logistic regression model based on the three signature genes highlighted how robustly they discriminated between samples. ssGSEA indicated these genes to be involved in lipid metabolism and degradation pathways. Moreover, leptin levels were significantly reduced in patients undergoing LSG, and NFKBIA significantly negatively correlated with leptin. Finally, we identified how the long non-coding RNA (lncRNA) ATP2B1-AS1 regulated the expression of the signature genes by competitively binding to six microRNAs (miRNAs), which were hsa-miR-6509-5p, hsa-miR-330-5P, hsa-miR-154-5P, hsa-miR-145-5P, hsa-miR4726-5P and hsa-miR-134-5P. Conclusion: This study identified three critical regulatory genes significantly differentiated between patients before and after LSG treatment and highlighted their potentially crucial role after bariatric surgery. This provides novel insights to increase our understanding of the underlying mechanisms of weight loss and associated metabolic improvement after bariatric surgery.