The study of honokiol as a natural product-based antimicrobial agent and its potential interaction with FtsZ protein.

Multidrug resistant bacteria have been a global health threat currently and frontline clinical treatments for these infections are very limited. To develop potent antibacterial agents with new bactericidal mechanisms is thus needed urgently to address this critical antibiotic resistance challenge. Natural products are a treasure of small molecules with high bioactive and low toxicity. In the present study, we demonstrated that a natural compound, honokiol, showed potent antibacterial activity against a number of Gram-positive bacteria including MRSA and VRE. Moreover, honokiol in combination with clinically used ß-lactam antibiotics exhibits strong synergistic antimicrobial effects against drug-resistant S. aureus strains. Biochemical studies further reveal that honokiol may disrupt the GTPase activity, FtsZ polymerization, cell division. These biological impacts induced by honokiol may ultimately cause bacterial cell death. The in vivo antibacterial activity of honokiol against S. aureus infection was also verified with a biological model of G. mellonella larvae. The in vivo results support that honokiol is low toxic against the larvae and effectively increases the survival rate of the larvae infected with S. aureus. These findings demonstrate the potential of honokiol for further structural advancement as a new class of antibacterial agents with high potency against multidrug-resistant bacteria.

Machine learning to predict the relationship between Vibrio spp. concentrations in seawater and oysters and prevalent environmental conditions.

Vibrio parahaemolyticus and Vibrio vulnificus are bacteria with a significant public health impact. Identifying factors impacting their presence and concentrations in food sources could enable the identification of significant risk factors and prevent incidences of foodborne illness. In recent years, machine learning has shown promise in modeling microbial presence based on prevalent external and internal variables, such as environmental variables and gene presence/absence, respectively, particularly with the generation and availability of large amounts and diverse sources of data. Such analyses can prove useful in predicting microbial behavior in food systems, particularly under the influence of the constant changes in environmental variables. In this study, we tested the efficacy of six machine learning regression models (random forest, support vector machine, elastic net, neural network, k-nearest neighbors, and extreme gradient boosting) in predicting the relationship between environmental variables and total and pathogenic V. parahaemolyticus and V. vulnificus concentrations in seawater and oysters. In general, environmental variables were found to be reliable predictors of total and pathogenic V. parahaemolyticus and V. vulnificus concentrations in seawater, and pathogenic V. parahaemolyticus in oysters (Acceptable Prediction Zone >70 %) when analyzed using our machine learning models. SHapley Additive exPlanations, which was used to identify variables influencing Vibrio concentrations, identified chlorophyll a content, seawater salinity, seawater temperature, and turbidity as influential variables. It is important to note that different strains were differentially impacted by the same environmental variable, indicating the need for further research to study the causes and potential mechanisms of these variations. In conclusion, environmental variables could be important predictors of Vibrio growth and behavior in seafood. Moreover, the models developed in this study could prove invaluable in assessing and managing the risks associated with V. parahaemolyticus and V. vulnificus, particularly in the face of a changing environment.

Outcomes of Transcatheter Closure of Congenital Left Circumflex Coronary Artery Fistula.

BACKGROUND: Congenital left circumflex coronary artery fistula (LCX-CAF) is a relatively rare type of coronary artery fistula (CAF); little is known about the outcomes of transcatheter closure (TCC) of LCX-CAF. METHODS AND RESULTS: All consecutive patients admitted to Fuwai Hospital and scheduled for TCC of LCX-CAF between January 2012 and December 2022 were reviewed retrospectively. Of the 25 consecutive patients (mean [±SD] age 34±20 years; 48% male) admitted and scheduled for TCC of congenital LCX-CAF, the procedure was feasible in 22 (77.3%). The mean (±SD) diameter of the fistulas was 6.99±2.04 mm; 21 (84%) patients had a large fistula (i.e., diameter >2-fold greater than non-feeding coronary artery). Occluders were deployed via a transarterial approach and arteriovenous loop in 6 (27.3%) and 16 (72.7%) patients, respectively. No procedural complications were recorded. Although the procedural success rates are similar for single LCX-CAF and left anterior descending CAF (81.25% vs. 92.86%; P=0.602), the mean time from initial angiography to first occluder deployment is significantly longer for LCX-CAF (83.06±36.07 vs. 36.00±9.49 min; P<0.001). The mean (±SD) follow-up time was 62.2±45.5 months. The incidence of myocardial infarction and recanalization of the fistula was 4.5% (1/22) and 9.1% (2/22), respectively. CONCLUSIONS: TCC of LCX-CAF is a feasible and effective alternative to surgical repair, with comparable outcomes in selected patients. Optimal medical therapy to prevent post-closure myocardial infarction requires further investigation.

Biodegradable Cardiac Occluder with Surface Modification by Gelatin-Peptide Conjugate to Promote Endogenous Tissue Regeneration.

Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long-term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l-lactic acid)-gelatin-A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein-derived peptides (A5G81) to the surface of polydioxanone and poly (l-lactic acid) fibers. The polymer microfiber-biomacromolecule-peptide frame with biophysical and biochemical cues could orchestrate the biomaterial-host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti-inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell-biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell-material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.

[Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma].

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

A Mobile Health-Based Management for Patients with Limited Lung Function to Improve Treatment Outcomes and Quality of Life After Minimally Invasive Thoracoscopic Lobectomy.

Objective: Limited lung function is an independent risk factor for postoperative respiratory failure in non-small cell lung cancer (NSCLC) patients. In this study, we developed a mobile health-based management for NSCLC patients with limited lung function who were scheduled to receive lobectomy and evaluated its effects on the patient's pulmonary function and quality of life. Methods: A total of 60 NSCLC patients scheduled to receive minimally invasive thoracoscopic lobectomy were enrolled and then randomized into the traditional management group and the program management group, with 30 patients per group. Based on the WeChat mini program, a management software for patients with limited lung function was established, including two portals: the patient portal and the nurse one. The pain assessment was performed using the Visual Analog Scale (VAS) scores, the cough assessment using the Leicester Cough Questionnaire, and the quality-of-life assessment using the EORTC QLQ-30 at 1 day before surgery, 1 week, 2 weeks, 1 month, 6 months, or 12 months after surgery. Results: The program management group exhibited an increased PaO2 (96.68 ± 7.92 vs. 87.69 vs. 5.50; P = .018) concomitant with a declined PaCO2 (38.55 ± 2.79 vs. 40.65 ± 2.17; p = 0.034) at 12 months after surgery compared with the traditional management group. The VAS scores showed significant differences at 2 weeks after surgery between the traditional management (median: 2; range: 2-3) and program management (median: 2; range: 1-2) groups (P = .012). The scores of Leicester Cough Questionnaire showed remarkable differences at 12 months after surgery between the traditional management (20.00 ± 1.54) and program management (18.99 ± 2.08) groups (P = .036). The total scores of EORTC QLQ-30 showed notable differences at 12 months after surgery between the traditional management (83.05 ± 14.09) and program management (90.55 ± 11.32) groups (P = .027). Conclusion: The study demonstrated improved pulmonary function and a better quality of life conferred by the mobile health-based management based on WeChat mini program for NSCLC patients with limited lung function and undergoing thoracoscopic lobectomy in a long follow up.

Linking microbial contamination to food spoilage and food waste: the role of smart packaging, spoilage risk assessments, and date labeling.

Ensuring a safe and adequate food supply is a cornerstone of human health and food security. However, a significant portion of the food produced for human consumption is wasted annually on a global scale. Reducing harvest and postharvest food waste, waste during food processing, as well as food waste at the consumer level, have been key objectives of improving and maintaining sustainability. These issues can range from damage during processing, handling, and transport, to the use of inappropriate or outdated systems, and storage and packaging-related issues. Microbial growth and (cross)contamination during harvest, processing, and packaging, which causes spoilage and safety issues in both fresh and packaged foods, is an overarching issue contributing to food waste. Microbial causes of food spoilage are typically bacterial or fungal in nature and can impact fresh, processed, and packaged foods. Moreover, spoilage can be influenced by the intrinsic factors of the food (water activity, pH), initial load of the microorganism and its interaction with the surrounding microflora, and external factors such as temperature abuse and food acidity, among others. Considering this multifaceted nature of the food system and the factors driving microbial spoilage, there is an immediate need for the use of novel approaches to predict and potentially prevent the occurrence of such spoilage to minimize food waste at the harvest, post-harvest, processing, and consumer levels. Quantitative microbial spoilage risk assessment (QMSRA) is a predictive framework that analyzes information on microbial behavior under the various conditions encountered within the food ecosystem, while employing a probabilistic approach to account for uncertainty and variability. Widespread adoption of the QMSRA approach could help in predicting and preventing the occurrence of spoilage along the food chain. Alternatively, the use of advanced packaging technologies would serve as a direct prevention strategy, potentially minimizing (cross)contamination and assuring the safe handling of foods, in order to reduce food waste at the post-harvest and retail stages. Finally, increasing transparency and consumer knowledge regarding food date labels, which typically are indicators of food quality rather than food safety, could also contribute to reduced food waste at the consumer level. The objective of this review is to highlight the impact of microbial spoilage and (cross)contamination events on food loss and waste. The review also discusses some novel methods to mitigate food spoilage and food loss and waste, and ensure the quality and safety of our food supply.

[Component identification and analysis in vivo of Sanhan Huashi formula].

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Extracellular Matrix/Glycopeptide Hybrid Hydrogel as an Immunomodulatory Niche for Endogenous Cardiac Repair after Myocardial Infarction.

The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage-endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.

The effect of agricultural subsidies on chemical fertilizer use: Evidence from a new policy in China.

This study uses a nationally representative rural household survey from China, the difference-in-difference, three-step approach, and Seemingly Unrelated Regression methods to assess the impacts of China's new agricultural subsidy on chemical fertilizer use, heterogeneity effect, and mechanism. The results show that, first, the new agriculture subsidy reduces the use of chemical fertilizer by about 7.2 percent. A series of robustness tests confirm the finding. Second, the heterogeneity analysis shows that the subsidy's negative impact on fertilizer use is substantially greater among younger farmers than among older farmers. The negative effect also is significantly more in the main grain-producing areas than in non-grain-producing regions in China. Third, the mediating effect analysis shows that farmland scale mediates 8.3 percent of fertilizer use, and the adoption of agricultural machinery mediates 48.6 percent of fertilizer use. Our findings underscore the positive role that reforming the agrarian subsidy policy plays in sustainable development.

Genome-wide identification of Coptotermes formosanus immune genes and their potential roles in termite control.

In recent years, the use of microbes to control termites has attracted increasing attention. It was found that pathogenic bacteria, nematodes, and fungi effectively control termites under laboratory conditions. However, their effects have not been replicated in the field, and one reason for this is the complex immune defense mechanisms of termites, which are mainly regulated by immune genes. Therefore, altering the expression of immune genes may have a positive influence on the biocontrol efficacy of termites. Coptotermes formosanus Shiraki is one of the most economically important termite pests worldwide. Currently, the large-scale identification of immune genes in C. formosanus is primarily based on cDNA library or transcriptome data rather than at the genomic level. In this study, we identified the immune genes of C. formosanus according to genome-wide analysis. In addition, our transcriptome analysis showed that immune genes were significantly downregulated when C. formosanus was exposed to the fungus Metarhizium anisopliae or nematodes. Finally, we found that injecting dsRNA to inhibit three immune genes (CfPGRP-SC1, CfSCRB3, and CfHemocytin), which recognize infectious microbes, significantly increased the lethal effect of M. anisopliae on termites. These immune genes show great potential for C. formosanus management based on RNAi. These results also increase the number of known immune genes in C. formosanus which will provide a more comprehensive insight into the molecular basis of immunity in termites.

Salt Restriction and Angiotensin-Converting Enzyme Inhibitor Improve the Responsiveness of the Small Artery in Salt-Sensitive Hypertension.

For salt-sensitive hypertension (SSH), salt restriction and angiotensin-converting enzyme (ACE) inhibitors are essential treatments, but their effect on the function of resistance arteries is unclear. Here, we present an intravital study to detect the effect of salt restriction and ACE inhibitors on the function of the mesenteric small artery (MSA) in SSH. Dahl salt-sensitive rats were randomized into the following groups: ACE inhibitor gavage, salt restriction, ACE inhibitor combined with salt restriction, and high-salt diet. After a 12-week intervention, the mesenteric vessels maintained their perfusion in vivo, and the changes in the diameter and blood perfusion of the MSAs to norepinephrine (NE) and acetylcholine (ACh) were detected. Switching from a high-salt diet to a low-salt diet (i.e., salt restriction) attenuated the vasoconstriction of the MSAs to NE and promoted the vasodilatation to ACh, while ACE inhibitor improved the vasodilatation more obviously. Pathologically, changes in local ACE, AT1R, and eNOS expression were involved in these processes induced by a high-salt diet. Our study suggests that salt restriction and ACE inhibitor treatment improve high salt intake-induced MSA dysfunction in SSH, and salt restriction is a feasible and effective treatment. Our findings may provide a scientific basis for the treatment of hypertension.

The bacterial communities in vagina of different Candida species-associated vulvovaginal candidiasis.

The incidence of vaginal infection caused by Candida species has considerably increased over the past two decades. Candida albicans is the main cause of vulvovaginal candidiasis (VVC); however, non-albicans Candida (NAC) species, such as Candida glabrata and Candida tropicalis, are now frequently identified in VVC patients. Although the vaginal microbiome (VMB) was well studied in Candida albicans-associated VVC patients, the fungal influence on bacterial communities of NAC species-associated VVC and potential microbial interplay contributing to VVC pathology remain elusive. We characterized VMB via Candida albicans and NAC species-associated VVC patients, as Candida albicans (CA, n = 16), Candida glabrata (CG, n = 16), Candida tropicalis (CT, n = 4), and recruiting healthy (CON, n = 20) women as references of dysbiosis and eubiosis. The bacterial diversity of the vagina in the CG group significantly declined. Further, all VVC patients have a higher abundance of Lactobacillus iners, especially for the CG group. Meanwhile, the predicted functions in all VVC are toned which may be associated with a disruption in the bacterial network. In conclusion, according to the taxonomic analysis, we found that the vaginal microbiome in C. glabrata-associated VVC women is different from that of other Candida species-associated VVC women, implying a different pathogenesis.

A fully biodegradable polydioxanone occluder for ventricle septal defect closure.

Ventricular septal defect (VSD) is one of the commonest congenital heart diseases (CHDs). Current occluders for VSD treatment are mainly made of nitinol, which has the risk of nickel allergy, persistent myocardial abrasion and fatal arrythmia. Herein, a fully biodegradable polydioxanone (PDO) occluder equipped with a shape line and poly-l-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker. PDO occluder showed great mechanical strength, fatigue resistance, geometry fitness, biocompatibility and degradability. In a rat subcutaneous implantation model, PDO filaments significantly alleviated inflammation response, mitigated fibrosis and promoted endothelialization compared with nitinol. The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up, demonstrating the biodegradable PDO occluder could not only effectively repair VSD, induce cardiac remodeling but also address the complications associated with metal occluders. Furthermore, a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up. Collectively, the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.

Feasibility of a Percutaneous and Non-Fluoroscopic Procedure for Transcatheter Mitral Valve Edge-to-Edge Repair.

Background: Transcatheter edge-to-edge repair (TEER) of the mitral valve has emerged as an alternative treatment for mitral regurgitation (MR). However, the high radiation exposure during the process has been associated with multiple adverse effects for medical staff. In this study, we assessed the feasibility and safety of TEER performed solely under the echocardiographic (echo) guidance. Methods: Between April 2021 to August 2021, we retrospectively collected characteristics of 23 patients with MR who underwent TEER under echocardiographic guidance exclusively. Follow-up evaluations were performed at 1- , 3-months and 1-year post procedure. Results: All 23 patients (mean age, 66.1 ± 12.1 years; 65.2% males) successfully underwent echo-guided TEER, with 22 patients under transesophageal echo (TEE) guidance and 1 patient under transthoracic echo (TTE) guidance for severe esophageal stenosis. Of the patients, 60.9% received 1 implant and 39.1% received 2 implants. The median total procedural time was 130 (interquartile range, IQR: 90-150) min and the device procedure time was 73 (IQR: 58-100) min. The median length of stay was 6 (IQR: 5-9) days. At 3-months follow-up, 63.6% of patients had an MR ≤ 1+ and 90.9% had an MR ≤ 2+ (p < 0.001 vs. baseline). Improvement in functional status was observed, with 40.9% of patients classified as New York Heart Association (NYHA) functional class I and 45.5% as NYHA functional class II (p < 0.001 compared to baseline) at 3-months. At 1-year follow-up, 90.4% maintained MR reduction with MR ≤ 2+ (p < 0.001 vs. baseline). Single leaflet device attachment (SLDA) occurred in one patient (4.3%) 1-week post procedure. Conclusions: This retrospective, single-center, and pilot study demonstrates the feasibility, safety, and low complication rates of TEER guided solely by echocardiography. Our findings support the systematic use of echocardiography as the sole guidance modality for TEER, highlighting its potential as an alternative to fluoroscopy-guided procedures. Further multicenter and comparative studies are warranted to confirm these results and provide a more comprehensive evaluation of this approach.

The role of fiscal expenditure on science and technology in carbon reduction: Evidence from provincial data in China.

Environmental problems caused by carbon emissions have negative impacts on human life and society. It is therefore important to identify potential approaches to carbon emission reduction. In this study, we analyze the impact fiscal expenditure on science and technology has on carbon emissions using a panel dataset from 2007 to 2016 at Chinese provincial levels. An instrumental variable approach is employed to address the potential endogeneity of fiscal expenditure. Our results show that fiscal expenditure on science and technology has a significant and negative effect on carbon emissions by improving green innovation, economic structure upgrade, energy consumption structure, and energy efficiency. A one hundred RMB yuan increase in fiscal expenditure on science and technology would lower carbon emissions by 0.654 tons. Heterogeneity analysis reveals that the carbon reduction effects of fiscal expenditure on science and technology are larger in regions where internet coverage and the share of industry in the economy are high. Our results highlight the significant role of fiscal expenditure on science and technology in carbon reduction.

VX765 alleviates dextran sulfate sodium-induced colitis in mice by suppressing caspase-1-mediated pyroptosis.

Inflammatory bowel disease (IBD) is an autoimmune disease involving intestinal tissue. IBD activates a series of cell death pathways. Pyroptosis is recently identified as a critical cell death pathway in IBD associated with the activation of caspase-1. VX765 is a caspase-1 inhibitor that can be converted to VRT-043198 in vivo. This study was designed to explore the therapeutic effect of VX765 on colitis using a dextran sulfate sodium (DSS)-induced colitis model in mice. In this research, the caspase-1 inhibitor on inflammatory, pyroptosis, apoptosis, macrophage activation, and intestinal barrier were investigated. We found that administration of VX765 attenuated body weight loss, colonic shortening, and colonic pathological injury in mice. Our study also revealed a therapeutic effect of VX765 on colitis in a dose-dependent manner. VX765 inhibited pyroptosis by curbing the Caspase-1/GSDMD pathway and its downstream key inflammatory cytokines--IL-1ß and IL-18. These results indicated that VX765 might have a dose-dependent therapeutic effect on DSS-induced colitis in mice.

The temperature of internet: Internet use and depression of the elderly in China.

Introduction: Depression has become one of the most prevalent mental illnesses affecting the elderly in aging countries, i. e., in countries of the world whose population is slowly aging. It has become an important topic for scientists and policymakers to analyze how best to improve the elderly's mental health and save them from depression. The aim of this paper was to investigate whether and to what extent internet use may affect depression in the elderly. The heterogeneous effects of internet use on the elderly's depression across age, gender, and occupation were also investigated. Methods: The data used in the present study were gathered from the China Health and Retirement Longitudinal Study that was conducted in 2018. The propensity score matching technique and the endogenous switch regression model were employed in this study to address potential endogeneity caused by both observed and unobserved factors. Results: The results of the present study show that the elderly who are relatively young, male, well educated, live in an urban area, or have a small family are more likely to use the internet. The elderly who have healthy eyes or good eyesight, those who are not employed in the agricultural sector, or those who are retired, and those who are not eligible to receive any subsistence allowance or drink wine have a higher probability of using the internet. We also find that internet use significantly reduces the elderly's depression status by 3.370 points, which is roughly equivalent to a reduction of 37.19%. Heterogeneity analysis on internet use reveals that the health effect is particularly effective for agricultural workers, female, or the older elderly. Conclusion: The results of the present study highlight the significant welfare effects brought about by the development of internet infrastructure. To improve the mental health of the elderly, the government should encourage them to adopt the internet. In particular, the needs of the elderly who are older, female, or have agricultural work should be paid more attention to motivate them to use the internet more to alleviate depression.