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This study aims to document the implementation of sign bilingualism and co-enrollment education in a kindergarten in Quzhou, Zhejiang Province, China, to identify the major characteristics of the programme, and to report findings of children's language in terms of vocabulary and surveys on the views and attitudes of the stakeholders of the programme, including deaf and hard-of-hearing (DHH) as well as hearing children and teachers. The results indicate that (a) both deaf and hearing teachers enjoy working in the Sign Bilingualism and Co-enrollment (SLCO) class and believe it is beneficial for their professional development; (b) parents of both DHH children and hearing children are happy to send their children to the SLCO class; (c) the teachers and parents agree that the SLCO programme is helpful for the overall development of not only the DHH children but also the hearing children. They believe that such an environment benefits the children's language and communication skills and the development of self-confidence and social cognition; (d) both the teachers and parents believe that the DHH children and their hearing peers get along well with each other in the SLCO class and also enjoy learning sign language. Furthermore, they all agree that the SLCO programme is promising and should be continued in the current school and implemented in more schools.

Abstract Background The establishment of microbial communities in neonatal mammals plays a pivotal role in shaping their immune responses to infections and other immune-related conditions. This process is influenced by a combination of endogenous and exogenous factors. Previously, we reported that depletion of CD71 + erythroid cells (CECs) results in an inflammatory response to microbial communities in newborn mice. Results Here, we systemically tested this hypothesis and observed that the small intestinal lamina propria of neonatal mice had the highest frequency of CECs during the early days of life. This high abundance of CECs was attributed to erythropoiesis niches within the small intestinal tissues. Notably, the removal of CECs from the intestinal tissues by the anti-CD71 antibody disrupted immune homeostasis. This disruption was evident by alteration in the expression of antimicrobial peptides (AMPs), toll-like receptors (TLRs), inflammatory cytokines/chemokines, and resulting in microbial dysbiosis. Intriguingly, these alterations in microbial communities persisted when tested 5 weeks post-treatment, with a more notable effect observed in female mice. This illustrates a sex-dependent association between CECs and neonatal microbiome modulation. Moreover, we extended our studies on pregnant mice, observing that modulating CECs substantially alters the frequency and diversity of their microbial communities. Finally, we found a significantly lower proportion of CECs in the cord blood of pre-term human newborns, suggesting a potential role in dysregulated immune responses to microbial communities in the gut. Conclusions Our findings provide novel insights into pivotal role of CECs in immune homeostasis and swift adaptation of microbial communities in newborns. Despite the complexity of the cellular biology of the gut, our findings shed light on the previously unappreciated role of CECs in the dialogue between the microbiota and immune system. These findings have significant implications for human health. Video Abstract

Abstract Hepatitis E virus (HEV) is a positive-sense, single-stranded RNA virus and causes primarily acute self-limiting infections. The ORF1 of the HEV genome encodes a polyprotein around 190 kDa, which contains several putative domains, including helicase and RNA-dependent RNA polymerase. The HEV-encoded helicase is a member of the superfamily 1 helicase family and possesses multiple enzymatic functions, such as RNA 5′-triphosphatase, RNA unwinding, and NTPase, which are thought to contribute to viral RNA synthesis. However, the helicase interaction with cellular proteins remains less known. Oxysterol binding protein (OSBP) is a lipid regulator that shuffles between the Golgi apparatus and the endoplasmic reticulum for cholesterol and phosphatidylinositol-4-phosphate exchange and controls the efflux of cholesterol from cells. In this study, the RNAi-mediated silencing of OSBP significantly reduced HEV replication. Further studies indicate that the HEV helicase interacted with OSBP, shown by co-immunoprecipitation and co-localization in co-transfected cells. The presence of helicase blocked OSBP preferential translocation to the Golgi apparatus. These results demonstrate that OSBP contributes to HEV replication and enrich our understanding of the HEV-cell interactions.

Abstract Deep shale has the characteristics of large burial depth, rapid changes in reservoir properties, complex pore types and structures, and unstable production. The whole-rock X-ray diffraction (XRD) analysis, reservoir physical property parameter testing, scanning electron microscopy (SEM) analysis, high-pressure mercury intrusion testing, CO2 adsorption experimentation, and low-temperature nitrogen adsorption–desorption testing were performed to study the pore structure characteristics of marine shale reservoirs in the southern Sichuan Basin. The results show that the deep shale of the Wufeng Formation Longyi1 sub-member in the Luzhou area is superior to that of the Weiyuan area in terms of factors controlling shale gas enrichment, such as organic matter abundance, physical properties, gas-bearing properties, and shale reservoir thickness. SEM is utilized to identify six types of pores (mainly organic matter pores). The porosities of the pyrobitumen pores reach 21.04–31.65%, while the porosities of the solid kerogen pores, siliceous mineral dissolution pores, and carbonate dissolution pores are low at 0.48–1.80%. The pores of shale reservoirs are mainly micropores and mesopores, with a small amount of macropores. The total pore volume ranges from 22.0 to 36.40 μL/g, with an average of 27.46 μL/g, the total pore specific surface area ranges from 34.27 to 50.39 m2/g, with an average of 41.12 m2/g. The pore volume and specific surface area of deep shale gas are positively correlated with TOC content, siliceous minerals, and clay minerals. The key period for shale gas enrichment, which matches the evolution process of shale hydrocarbon generation, reservoir capacity, and direct and indirect cap rocks, is from the Middle to Late Triassic to the present. Areas with late structural uplift, small uplift amplitude, and high formation pressure coefficient characteristics favor preserving shale gas with high gas content and production levels.

Abstract Background The relationship between the triglyceride-glucose (TyG) index and its derived index, the triglyceride glucose-waist height ratio (TyG-WHtR), with mortality and cardiovascular diseases (CVDs) in patients with non-alcoholic fatty liver disease (NAFLD) remains unclear. Methods This study enrolled 6627 adults aged 18 and above diagnosed NAFLD from the National Health and Nutrition Examination Survey (NHANES, 1999–2018). Binary weighted logistic regression analyses, cox proportional hazards model and restricted cubic spline (RCS) were used to analyze the relationship between TyG and TyG-WHtR with all-cause mortality, CVD mortality and CVDs. Mediation analysis explored the mediating role of glycohemoglobin, insulin and hypertension in the above relationships. Meanwhile, the incremental predictive value of the TyG index and TyG-WHtR was further assessed. Results Except for no significant association between the TyG index and both all-cause mortality and chronic heart failure (CHF), both TyG and TyG-WHtR exhibited significant positive correlations or trends of positive correlation with all-cause mortality, CVD mortality, total-CVD, CHF, coronary heart disease (CHD) and angina pectoris. For all-cause mortality, CVD mortality and CHF, TyG-WHtR was a better predictor than TyG (TyG-WHtR: HR 1.31, 95%CI 1.03–1.66; HR 2.22, 95%CI 1.42–3.47; OR 3.99, 95%CI 1.79–8.93). In contrast, TyG index demonstrated a stronger association with total-CVD, CHD and angina pectoris (TyG index: OR 2.00, 95%CI 1.26–3.18; OR 1.85, 95%CI 1.19–2.91; OR 2.93, 95%CI 1.23-7.00). RCS analysis showed that after adjusting for covariates, most of the aforementioned relationships were linear(P overall 0.05), while the associations of the TyG index and TyG-WHtR with all-cause mortality and CHF were non-linear(P overall

There are many instances of intellectual property rights violations due to the common usage of digital data on the Internet, including unauthorised use, copying, and theft of digital content. Intellectual property rights of digital photos must be upheld, as they are very valuable materials. Digital watermarking is a more modern method to do this. By using a watermark (WM), the owner's information is included into the content, which may then be shared or saved. When required, this technology will retrieve the encoded WM information to prove ownership. Different technologies have been investigated and created on the basis of existing technologies, fields of use, etc. This paper proposes a novel approach to digital watermarking based on a neural network. First, the trigger data set and noise data set are generated from the binary encoding and random cutting of the original training samples. Then, the pattern with higher watermark trigger accuracy is obtained from the trigger set. Simulation results show that the proposed algorithm performs better in terms of accuracy and computing time cost compared to existing algorithms

Introduction Withdrawal symptoms lead to smoking relapse and reduce the intention to quit. The present pilot RCT examined the effect of simple and very brief handgrip and isometric exercises on reducing withdrawal symptoms, measured by the strength of tobacco craving, Questionnaire of Smoking Urges-Brief (QSU-B), Mood and Physical Symptoms Scale (MPSS), and Positive and Negative Affect Schedule (PANAS). Methods In this 2-arm, open-labeled pilot RCT, 30 current smokers who had abstained from tobacco for at least 9 hours were randomly assigned (allocation ratio 1:1) to either the intervention group that watched a 5-minute video and did 5-minute handgrip and isometric exercises (pulling and pushing) or control group that watched 10-minute healthy-diet videos. Measurements were taken before, immediately after, and 10 minutes post-intervention. Outcomes were selfreported strength of tobacco craving, QSU-B, MPSS, and PANAS scores. The effect size for group-by-time interaction was assessed using Cohen’s f2 (small=0.02, medium=0.15, large=0.35). Results Group-by-time interactions showed that the intervention group showed larger reductions than the control group in the strength of tobacco craving (Cohen’s f2=0.54, 95% CI: 0.52–0.57), QSU-B (Cohen’s f2=0.77; 95% CI: 0.74–0.80), and MPSS (Cohen’s f2=0.51; 95% CI: 0.46–0.56) over the three measurement points. Conclusions This RCT showed that simple and brief handgrip and isometric exercises could immediately reduce withdrawal symptoms and up to 10 minutes. CLINICAL TRIAL REGISTRATION: in https://clinicaltrials.gov/ IDENTIFIER: NCT04059497

Abstract Purpose To use artificial intelligence to establish an automatic diagnosis system for corneal endothelium diseases (CEDs). Methods We develop an automatic system for detecting multiple common CEDs involving an enhanced compact convolutional transformer (ECCT). Specifically, we introduce a cross-head relative position encoding scheme into a standard self-attention module to capture contextual information among different regions and employ a token-attention feed-forward network to place greater focus on valuable abnormal regions. Results A total of 2723 images from CED patients are used to train our system. It achieves an accuracy of 89.53%, and the area under the receiver operating characteristic curve (AUC) is 0.958 (95% CI 0.943–0.971) on images from multiple centres. Conclusions Our system is the first artificial intelligence-based system for diagnosing CEDs worldwide. Images can be uploaded to a specified website, and automatic diagnoses can be obtained; this system can be particularly helpful under pandemic conditions, such as those seen during the recent COVID-19 pandemic.

Abstract Background Myocardial ischemia/reperfusion injury (MIRI) is an important complication of reperfusion therapy, and has a lack of effective prevention and treatment methods. Oleuropein (OP) is a natural strong antioxidant with many protective effects on cardiovascular diseases, but its protective effect on MIRI has not yet been studied in depth. Methods Tert-Butyl hydroperoxide (tBHP) was used to establish an in vitro oxidative stress model. Cell viability was detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH). Flow cytometry and fluorescence assays were performed for evaluating the ROS levels and mitochondrial membrane potential (MMP). Immunofluorescence analysis detected the NRF2 nuclear translocation and autophagy indicators. Further, Western blotting and quantitative real-time PCR were performed to evaluate the expression levels of proteins and mRNAs. Molecular docking, CETSA, and molecular interaction analysis explored the binding between OP and TLR4. The protective effects of OP in vivo were determined using a preclinical MIRI rat model. Results OP protected against tBHP-treated injury, reduced ROS levels and reversed the damaged MMP. Mechanistically, OP activated NRF2-related antioxidant pathways, inhibited autophagy and attenuated the TLR4/MAPK signaling pathway in tBHP-treated H9C2 cells with a high binding affinity to TLR4 (K D = 37.5 µM). The TLR4 inhibitor TAK242 showed a similar effect as OP. In vivo, OP could alleviate cardiac ischemia/reperfusion injury and it ameliorated adverse cardiac remodeling. Consistent with in vitro studies, OP inhibited TLR4/MAPK and autophagy pathway and activated NRF2-dependent antioxidant pathways in vivo. Conclusion This study shows that OP binds to TLR4 to regulate oxidative stress and autophagy for protecting damaged cardiomyocytes, supporting that OP can be a potential therapeutic agent for MIRI.

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Abstract This study (ISRCTN17174559) aimed to explore the efficacy and safety of a kind of herbal porridge (Hou Gu Mi Xi) on the clinical symptoms of functional dyspepsia (FD). This was a single‐center, single‐dose, prospective, double‐blind, randomized controlled trial involving 64 participants with FD (35 cases and 29 controls) for 2 months of intervention and 1 month of follow‐up. The 7‐point Global Overall Symptom Scale (GOSS), 36‐Item Short Form Survey (SF‐36), and other indicators were assessed at baseline (day 0), at days 15, 30, and 60 of treatment, and at follow‐up 1 month after the end of the intervention. Many participants with FD achieved remission of their epigastric symptoms at follow‐up on the 90th day after treatment with herbal porridge compared to the placebo group (45.71% vs. 20.69%, p = .036). Furthermore, herbal porridge appeared to be effective in improving the quality of life of participants with FD, which was reflected in the rising SF‐36 scores for physical role, bodily pain, emotional role, and mental health. Although adverse events were reported, there was no overall difference in the number of adverse events between the two groups (p = .578). Herbal porridge is another effective and safe method for improving the symptoms and quality of life in patients with FD.

BackgroundThe relationship between epilepsy and risk of acute myocardial infarction (AMI) is not fully understood. Evidence from the Stockholm Heart Study indicates that the risk of AMI is increased in people with epilepsy. This study aims to analyze the temporal trends in prevalence, adverse clinical outcomes, and risk factors of AMI in patients with epilepsy (PWE).MethodsPatients aged 18 years or older, diagnosed with epilepsy with or without AMI and hospitalized from January 1, 2008, to December 31, 2017, were identified from the National Inpatient Sample (NIS) database. The Cochran–Armitage trend test and logistic regressions were conducted using SAS 9.4. Odds ratios (ORs) were generated for multiple variables.ResultsA total of 8,456,098 inpatients were eligible for our analysis, including 181,826 comorbid with AMI (2.15%). The prevalence of AMI diagnosis in PWE significantly increased from 1,911.7 per 100,000 hospitalizations in 2008 to 2,529.5 per 100,000 hospitalizations in 2017 (Ptrend

Graveoline exhibits various biological activities. However, only limited studies have focused on its hepatoprotective properties. This study evaluated the anti-inflammatory and hepatoprotective activities of graveoline, a minor 2-phenylquinolin-4-one alkaloid isolated from Ruta graveolens L., in a liver injury model in vitro and in vivo. A network pharmacology approach was used to investigate the potential signaling pathway associated with the hepatoprotective activity of graveoline. Subsequently, biological experiments were conducted to validate the findings. Topological analysis of the KEGG pathway enrichment revealed that graveoline mediates its hepatoprotective activity through genes associated with the hepatitis B viral infection pathway. Biological experiments demonstrated that graveoline effectively reduced the levels of alanine transaminase and aspartate transaminase in lipopolysaccharide (LPS)-induced HepG2 cells. Graveoline exerted antihepatitic activity by inhibiting the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and elevated the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) in vitro and in vivo. Additionally, graveoline exerted its hepatoprotective activity by inhibiting JAK1 and STAT3 phosphorylation both in vitro and in vivo. In summary, graveoline can attenuate acute liver injury by inhibiting the TNF-α inflammasome, activating IL-4 and IL-10, and suppressing the JAK1/STAT3 signaling pathway. This study sheds light on the potential of graveoline as a promising therapeutic agent for treating liver injury.

Coupled drugs, especially antibody-coupled drugs (ADCs), are a hot topic in oncology. As the development of ADCs has progressed, different coupling modes have emerged, inspired by their structural design have emerged. Technological advances have led to interweaving and collision of old and new concepts of coupled drugs, and have even challenged the concepts and techniques of coupled drugs at this stage. For example, antibody-oligonucleotide conjugates are a new class of chimeric biomolecules synthesized by coupling oligonucleotides with monoclonal antibodies through linkers, offering precise targeting and improved pharmacokinetic properties. This study aimed to elucidate the mechanism of action of coupled drugs and their current development status in antitumor therapy to provide better strategies for antitumor therapy.

In recent decades, there has been ongoing development in the application of computer vision (CV) in the medical field. As conventional contact-based physiological measurement techniques often restrict a patient’s mobility in the clinical environment, the ability to achieve continuous, comfortable and convenient monitoring is thus a topic of interest to researchers. One type of CV application is remote imaging photoplethysmography (rPPG), which can predict vital signs using a video or image. While contactless physiological measurement techniques have an excellent application prospect, the lack of uniformity or standardization of contactless vital monitoring methods limits their application in remote healthcare/telehealth settings. Several methods have been developed to improve this limitation and solve the heterogeneity of video signals caused by movement, lighting, and equipment. The fundamental algorithms include traditional algorithms with optimization and developing deep learning (DL) algorithms. This article aims to provide an in-depth review of current Artificial Intelligence (AI) methods using CV and DL in contactless physiological measurement and a comprehensive summary of the latest development of contactless measurement techniques for skin perfusion, respiratory rate, blood oxygen saturation, heart rate, heart rate variability, and blood pressure.

Background Systematic reviews (SRs) are being published at an accelerated rate. Decision-makers may struggle with comparing and choosing between multiple SRs on the same topic. We aimed to understand how healthcare decision-makers (eg, practitioners, policymakers, researchers) use SRs to inform decision-making and to explore the potential role of a proposed artificial intelligence (AI) tool to assist in critical appraisal and choosing among SRs.Methods We developed a survey with 21 open and closed questions. We followed a knowledge translation plan to disseminate the survey through social media and professional networks.Results Our survey response rate was lower than expected (7.9% of distributed emails). Of the 684 respondents, 58.2% identified as researchers, 37.1% as practitioners, 19.2% as students and 13.5% as policymakers. Respondents frequently sought out SRs (97.1%) as a source of evidence to inform decision-making. They frequently (97.9%) found more than one SR on a given topic of interest to them. Just over half (50.8%) struggled to choose the most trustworthy SR among multiple. These difficulties related to lack of time (55.2%), or difficulties comparing due to varying methodological quality of SRs (54.2%), differences in results and conclusions (49.7%) or variation in the included studies (44.6%). Respondents compared SRs based on the relevance to their question of interest, methodological quality, and recency of the SR search. Most respondents (87.0%) were interested in an AI tool to help appraise and compare SRs.Conclusions Given the identified barriers of using SR evidence, an AI tool to facilitate comparison of the relevance of SRs, the search and methodological quality, could help users efficiently choose among SRs and make healthcare decisions.

BackgroundType 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research.ObjectiveThis study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers.MethodsWe used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package “bibliometrix” were used to conduct this bibliometric analysis.ResultsEventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research.ConclusionIn the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.

IntroductionPopulation-level competition and spatial patterns may explain the role of competitive exclusion in communities, which is important for vegetation restoration and biodiversity conservation.MethodsWe analyzed the competitive intensity, spatial patterns, and renewal of Populus euphratica Oliv. forests in the Tarim River Basin using the Hegyi competition index and spatial point pattern analysis in a completely random model with different habitats and different forest ages. ResultsThe greatest competitive distance for P. euphratica was 10 m, and the intensity of competition steadily decreased as the diameter increased. The intensity of intraspecific and interspecific competition in young, mature, and old P. euphratica forests was as follows: riverside habitat > transitional habitat > desert margin habitat. The Simpson index values for the three habitats decreased as follows: transitional > riverside > desert margin, and the Shannon-Wiener index and Pielou index values decreased as follows: riverside > transitional > desert margin. In the riverside habitat, the young P. euphratica forest experienced the greatest competitive intensity, the mature forest in the transitional habitat was the largest, and the forest in the desert margin habitat was the oldest. Competitive intensity was greatest in the young riverside P. euphratica forest, mature P. euphratica forest in the transitional habitat, and old forest in the desert margin. Riverside P. euphratica experienced strong competition from Populus pruinosa. Competitive exclusion caused P. pruinosa to disappear from the transitional and desert margin habitats. Young, mature, and old P. euphratica forests were randomly distributed along the riverside and in the transitional habitat, while mature and old P. euphratica forests were randomly distributed in the desert margin. Populus pruinosa, Tamarix ramosissima, and Tamarix hispida were mainly randomly distributed, and T. ramosissima and T. hispida were clustered at small scales. In the riverside habitat, young, mature, and old P. euphratica had no spatial correlation, and there was a significant negative correlation at small scales in the transitional habitat. The density of P. euphratica seedlings in the riverside habitat was greater than that in the transitional habitat, and greater competitive pressures on P. euphratica tree seedlings caused a lower renewal density.ConclusionsWhen planting P. euphratica forests, spacing greater than 10 m can effectively reduce stand competition and thus promote seedling regeneration.

To investigate the effects of steel fibers on the macroscopic mechanical properties, fracture properties and microstructure of the interfacial transition zones (ITZs) in concrete, composite spilt tensile and three-point bending specimens with three different volume fractions of steel fibers (0.5%, 1.0%, and 1.5%) and two types of rock aggregates (Limestone, Granite) were tested, and the fiber- cement paste and reinforced cement paste-aggregate interfacial transition zone microstructure by scanning electron microscopy (SEM). The results show that SF affects the mechanical properties of ITZ on different rock surfaces by different mechanisms, and the high volume content of steel fibers (≥1.5%) significantly reduces the tensile strength, fracture energy and fracture toughness in the transition zone.

To investigate the flexural behaviors of Fiber-reinforced polymer (FRP) and steel bars hybrid reinforced concrete (Hybrid-RC) beams, twelve beams were designed and manufactured, including one steel bars reinforced concrete (Steel-RC) beam, one GFRP reinforced concrete (GFRP-RC) beam, and ten Hybrid-RC beams. The effects of FRP bars type, concrete strength, and effective reinforcement ratio on the flexural behaviors of Hybrid-RC beams were studied through experiments and compared with the predicted results of theoretical models. The research results indicated that when the reinforcement area and service load were the same, the crack width, deflection, ultimate bearing capacity, and ductility of Hybrid-RC beams were between Steel-RC and GFRP-RC beam. The flexural bearing capacity of Hybrid-RC beams might also be increased by using FRP bars with a higher elastic modulus or by increasing the effective reinforcement ratio; however, it would reduce the ductility of the beams. In contrast, increasing the concrete strength could simultaneously increase the Hybrid-RC beams’ flexural bearing capacity and ductility. The equation for calculating the stress of FRP bars in the ultimate state of Hybrid-RC beams was obtained by fitting regression based on the test results, and the equation’s predicted results and test results showed good agreement. In addition, the predicted results of the flexural behaviors of Hybrid-RC beams using the theoretical model agreed with the experimental results.

Background Epstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential.Methods Flow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors.Results EBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice.Conclusions MMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors.

Liquid crystal monomers (LCMs) are the raw material for liquid crystal displays, and their use is steadily increasing in electronic products. Recently, LCMs have been reported to be novel endocrine disrupting chemicals, however, the mechanisms underlying their potential for thyroid hormone disruption and visual toxicity are not well understood. In this study, six widely used fluorinated LCMs (FLCMs) were selected to determine putative mechanisms underlying FLCM-induced toxicity to the zebrafish thyroid and visual systems. Exposure to FLCMs caused damage to retinal structures and reduced cell density of ganglion cell layer, inner nuclear layer, and photoreceptor layer approximately 12.6–46.1%. Exposure to FLCMs also disrupted thyroid hormone levels and perturbed the hypothalamic-pituitary-thyroid axis by affecting key enzymes and protein in zebrafish larvae. A thyroid hormone-dependent GH3 cell viability assay supported the hypothesis that FLCMs act as thyroid hormone disrupting chemicals. It was also determined that FLCMs containing aliphatic ring structures may have a higher potential for T3 antagonism compared to FLCMs without an aliphatic ring. Molecular docking in silico suggested that FLCMs may affect biological functions of thyroxine binding globulin, membrane receptor integrin, and thyroid receptor beta. Lastly, the visual motor response of zebrafish in red- and green-light was significantly inhibited following exposure to FLCMs. Taken together, we demonstrate that FLCMs can act as thyroid hormone disruptors to induce visual dysfunction in zebrafish via several molecular mechanisms.

Although food waste is an urgent issue with widespread economic, societal, and environmental impacts, it remains understudied in the marketing discipline. This is surprising, since most food waste occurs at the retail and consumption stages of the food life cycle. This research fills this gap by examining how resource mindset and self-construal jointly shape consumer food waste. Specifically, inducing a scarcity mindset signals that there is no resource to waste, mitigating consumer food waste regardless of self-construal. In contrast, under an abundance mindset, where there is resource to waste, activating an interdependent (vs. independent) self-construal can effectively reduce consumer food waste. The authors identify sharing obligation, the tendency to share valuable resources with in-groups, as a key mechanism behind the effect. In support of this mechanism, enhancing sharing obligation (e.g., highlighting the sharing concept, highlighting others' food needs) or diminishing it (e.g., highlighting family resource abundance) attenuates the effect of self-construal on consumer food waste under an abundance mindset. The results from one large-scale field study, four controlled experiments, and a country-level secondary data analysis provide convergent support for the proposed framework. This research not only contributes to the related literature but also provides actionable strategies for mitigating consumer food waste. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring’s PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

Abstract Disaster information content is an objective mapping of disaster situations, social response, and public opinions. Social response to emergency is an important mechanism for implementing and guaranteeing emergency management of major natural hazard-related disasters. Understanding how disaster information content affects social response to emergencies is helpful for managing risk communication and efficient disaster response. Based on the 2008 freezing-rain and snowstorm disasters in southern China, this study used Python to extract 7,857 case-related media reports and applied natural language processing for text analysis. It used three typical cases to identify and analyze disaster media report content and the relationship between these reports and the social response to the emergency. Eight categories of disaster response—such as prewarning and forecasting, announcements by the authorities, and social mobilization—appeared in the disaster information in the media, along with disaster impact information, that is, real-time disaster status. Disaster response information and an appropriate amount of disaster impact information played important roles in prewarning, disaster relief, public opinion guidance, and social stability maintenance and can serve important functions in communicating with all stakeholders of emergency management, assisting or influencing emergency departments or individuals in decision making, and eliminating “information islands.” Empathy caused the general public to become “disaster responders” through receiving information. Rumors and an excess of negative information may have a perverse amplification effect on public opinion and increase the unpredictability of the disaster situation and the risk of social crisis.

Abstract Objective The study aimed to explore the mechanism of artemisinin in treating primary Sjögren’s syndrome (pSS) based on network pharmacology and experimental validation. Methods Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. Results Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. Conclusion The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.

Abstract Background Missing data is frequently an inevitable issue in cohort studies and it can adversely affect the study's findings. We assess the effectiveness of eight frequently utilized statistical and machine learning (ML) imputation methods for dealing with missing data in predictive modelling of cohort study datasets. This evaluation is based on real data and predictive models for cardiovascular disease (CVD) risk. Methods The data is from a real-world cohort study in Xinjiang, China. It includes personal information, physical examination data, questionnaires, and laboratory biochemical results from 10,164 subjects with a total of 37 variables. Simple imputation (Simple), regression imputation (Regression), expectation-maximization(EM), multiple imputation (MICE) , K nearest neighbor classification (KNN), clustering imputation (Cluster), random forest (RF), and decision tree (Cart) were the chosen imputation methods. Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) are utilised to assess the performance of different methods for missing data imputation at a missing rate of 20%. The datasets processed with different missing data imputation methods were employed to construct a CVD risk prediction model utilizing the support vector machine (SVM). The predictive performance was then compared using the area under the curve (AUC). Results The most effective imputation results were attained by KNN (MAE: 0.2032, RMSE: 0.7438, AUC: 0.730, CI: 0.719-0.741) and RF (MAE: 0.3944, RMSE: 1.4866, AUC: 0.777, CI: 0.769-0.785). The subsequent best performances were achieved by EM, Cart, and MICE, while Simple, Regression, and Cluster attained the worst performances. The CVD risk prediction model was constructed using the complete data (AUC:0.804, CI:0.796-0.812) in comparison with all other models with p

AbstractThe genome-level features are crucial genetic resources for species identification and phylogenetic analysis. Here, the complete mitochondrial genome of Aphidius colemani Viereck 1912 (Hymenoptera: Braconidae: Aphidiinae) was sequenced, determined and analyzed. The circular genome is 16,372 bp in length with an overall base composition of 38.9% for A, 46.2% for T, 6.7% for C, and 8.2% for G. The mitochondrial genome of A. colemani contained 13 protein-coding genes that initiated by the ATN codon, 22 transfer RNA genes, two ribosomal RNA genes (rRNAs), and a control region (CR). It shared the same gene arrangement patterns that occurred in two tRNA clusters of trnI-trnQ-trnM and trnW-trnC-trnY with Aphidius gifuensis. Phylogenetic analyses using Bayesian inference and Maximum-likelihood methods supported that the two species of Aphidiinae formed a clade and sister to other subfamilies of Braconidae.

Abstract Background Skeletal muscle atrophy, particularly ageing‐related muscular atrophy such as sarcopenia, is a significant health concern. Despite its prevalence, the underlying mechanisms remain poorly understood, and specific approved medications are currently unavailable. Deleted in breast cancer 1 (DBC1) is a well‐known regulator of senescence, metabolism or apoptosis. Recent reports suggest that DBC1 may also potentially regulate muscle function, as mice lacking DBC1 exhibit weakness and limpness. However, the function of DBC1 in skeletal muscle and its associated molecular mechanisms remain unknown, thus prompting the focus of this study. Methods Tibialis anterior (TA) muscle‐specific DBC1 knockdown C57BL/6J male mice were generated through a single injection of 2.00 E + 11 vg of adeno‐associated virus 9 delivering single‐guide RNA for DBC1. Grip strength and endurance were assessed 2 months later, followed by skeletal muscle harvest. Muscle atrophy model was generated by cast immobilization of the mouse hindlimb for 2 weeks. Molecular markers of atrophy were probed in muscles upon termination. Cardiotoxin (CTX) was injected in TA muscles of DBC1 knockdown mice, and muscle regeneration was assessed by immunohistochemistry, quantitative PCR and western blotting. DBC1 knockdown C2C12 cells and myotubes were investigated using immunofluorescence staining, Seahorse, immunohistology, fluorescence‐activated cell sorting and RNA‐sequencing analyses. Results DBC1 knockdown in skeletal muscle of young mice led to signatures of muscle atrophy, including a 28% reduction in muscle grip force (P = 0.023), a 54.4% reduction in running distance (P = 0.002), a 14.3% reduction in muscle mass (P = 0.007) and significantly smaller myofibre cross‐sectional areas (P