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Isoorientin (Iso) is a natural flavonoid present in the human diet, known for its anti-inflammatory, antioxidant, and antiviral properties. The purpose of this research was to illustrate the anti-inflammatory potential of Iso in ulcerative colitis (UC) mice and elucidate potential mechanisms. The mice model of UC was induced by cyclic intervention with Dextran Sulfate Sodium (DSS). We evaluated the efficacy of Iso in the treatment of UC, detected the expression of proteins related to the Galectin-3/NLRP3/IL-1β signaling pathway, and assessed the intestinal mucosa barrier function of colon tissue. Our findings demonstrated that Iso could improve colon length, the index of colonic weight, pathological damage to the colon, and serum cytokine secretion of UC mice. Most importantly, Iso could competitively bind Galectin-3, inhibit the interaction of Galectin-3 with NLRP3 and the expression of Galectin-3, NLRP3, ASC, caspase-1, IL-1β, and IL-18, increase the expression of MUC2, Occludin, and ZO-1. In summary, Iso had a therapeutic effect on UC mice, and its mechanism may be to inhibit the inflammatory response and improve the intestinal mucosa barrier by binding Galectin-3 and inhibiting the Galectin-3/NLRP3/IL-1β signaling pathway.

To fully utilize the voltage regulation capacity of flexible load and distributed generations (DGs), we propose a novel Approximatively Completed Observed Markov Decision Process-based (ACOMDP-based) Reinforcement Learning (RL) (namely, ACMRL) scheme for a multi-objective Automatic Voltage Control (AVC) problem considering Differential Increment Incentive Mechanism (DIIM)-based Incentive-Based Demand Response (IBDR). Firstly, we propose a DIIM to motivate high-flexibility consumers to achieve maximum potential in real-time voltage control while ensuring the best economy. Secondly, we characterize the multi-objective AVC problem as an ACOMDP model, transformed from the Partially Observable Markov Decision Process (POMDP) model, by introducing a novel hidden system state vector that incorporates the belief state, and the high confidence probability vector. The belief state and the high-confidence probability vector describe the probability distribution extracted from the historical observed state, portraying the precise state and the uncertainty existing in the state update process. Then, the ACOMDP block is inputted into the RL block, which adopts a modified underlying network architecture with the Asynchronous Advantage Actor-Critic (MA3C) algorithm embedded with the Shared Modular Policies(SMP) module. The MA3C-based RL block, characterized by enhanced communication efficiency, enables expedited generation of optimal decision-making actions even in the face of substantial uncertainty. Case studies are conducted in a practical district in Suzhou, China, and simulation results validate the superior performance of the proposed methodology.

Abstract To fully utilize the voltage regulation capacity and interaction characteristics of the Transmission and Distribution (T&D) system, a novel Modified Partially Observed Markov Decision Process (MPOMDP)‐based Reinforcement Learning (RL) scheme for Autonomous Voltage Control is proposed, which incorporates Demand Response (DR) and cooperation with the Transmission Network . The proposed scheme consists of two vital components: an MPOMDP block and a Modified Asynchronous Advantage Actor‐Critic‐based RL block. The MPOMDP block innovatively exploits the confidence interval of the observed state to make a better perception of the precise system state by introducing two new probability vectors. Then the MPOMDP block is fed into the underlying architecture of the RL block for asynchronously capturing features and optimal decision‐making, where the solving framework additionally brings in a public data buffer to realize boundary information sharing. Case studies are conducted on a modified T&D system considering N‐1 contingencies, with a training dataset from a district in Suzhou, China. Simulation results demonstrate that the proposed scheme can achieve significant voltage optimization while ensuring fast convergence speed.

Abstract Background Therapeutic options for ulcerative colitis (UC) have increased since the introduction of biologics a few decades ago. Due to the wide range of biologics available, physicians have difficulty in selecting biologics and do not know how to balance the best drug between clinical efficacy and safety. This study aimed to compare the efficacy and safety of biologics in treating ulcerative colitis. Methods In this study, eight electronic databases (PubMed, Web of Science, Cochrane, Embase, Sinomed, China National Knowledge Infrastructure, Chongqing VIP Information, and WanFang Data) were searched to collect eligible studies without language restrictions. Retrieved 1 June 2023, from inception. All articles included in the mesh analysis are randomised controlled trials (RCTs). The inclusion of drugs for each outcome was ranked using a curved surface under cumulative ranking (SUCRA). Higher SUCRA scores were associated with better outcomes, whereas lower SUCRA scores were associated with better safety. This study has registered with PROSPERO, CRD42023389483. Results Induction Therapy: Among the biologic therapies evaluated for induction therapy, vedolizumab demonstrated the highest efficacy in achieving clinical remission (OR vs daclizumab, 9.09; 95% CI, 1.01–81.61; SUCRA 94.1) and clinical response. Guselkumab showed the lowest risk of recurrence of UC (SUCRA 94.9%), adverse events resulting in treatment discontinuation (SUCRA 94.8%), and serious infections (SUCRA 78.0%). Maintenance Therapy: For maintenance therapy, vedolizumab ranked highest in maintaining clinical remission (OR vs mesalazine 4.36; 95% CI, 1.65–11.49; SUCRA 89.7) and endoscopic improvement (SUCRA 92.6). Infliximab demonstrated the highest efficacy in endoscopic improvement (SUCRA 92.6%). Ustekinumab had the lowest risk of infections (SUCRA 92.9%), serious adverse events (SUCRA 91.3%), and serious infections (SUCRA 67.6%). Conclusion Our network meta-analysis suggests that vedolizumab is the most effective biologic therapy for inducing and maintaining clinical remission in UC patients. Guselkumab shows promise in reducing the risk of recurrence and adverse events during induction therapy. Infliximab is effective in improving endoscopic outcomes during maintenance therapy. Ustekinumab appears to have a favorable safety profile. These findings provide valuable insights for clinicians in selecting the most appropriate biologic therapy for UC patients.

Abstract Tropical disturbances play an important role in the formation of tropical cyclones (TCs), but their climate characteristics are still poorly understood. The present study investigated the characteristics of tropical disturbances over the western North Pacific (WNP) for the period 1965–2020 using the reanalysis datasets. An algorithm based on the threshold of synoptic-scale vorticity and convection was developed to identify and track tropical disturbances. Approximately 116 tropical disturbances were detected primitively in the WNP from June to November each year, and about 13.1% of them subsequently developed into TCs. These developing disturbances contributed to the formation of 80.9% TCs in the WNP. Compared with nondeveloping disturbances, the position of developing disturbances is more eastward and southward, whereas the majority of their lifetimes and propagation speeds are similar. The annual numbers of developing disturbances exhibit significant interannual (interdecadal) variability. The percentage of TCs associated with disturbances also experiences a significant inverse interdecadal relationship with the number of TC genesis in the WNP, indicating that the formation probability of TCs is inconsistent with the transition probability from disturbances to TCs. In addition, the long-term trends of developing and nondeveloping disturbances suggest that global warming might be responsible for more tropical disturbances in the WNP instead of higher transition probability from disturbances to TCs.

Bursaphelenchus xylophilus causes pine wilt disease, which poses a serious threat to forestry ecology around the world. Microorganisms are environmentally friendly alternatives to the use of chemical nematicides to control B. xylophilus in a sustainable way. In this study, we isolated a nematophagous fungus—Arthrobotrys robusta—from the xylem of diseased Pinus massoniana. The nematophagous activity of A. robusta against the PWNs was observed after just 6 h. We found that B. xylophilus entered the trap of A. robusta at 24 h, and the nervous system and immunological response of B. xylophilus were stimulated by metabolites that A. robusta produced. At 30 h of exposure to A. robusta, B. xylophilus exhibited significant constriction, and we were able to identify xenobiotics. Bursaphelenchus xylophilus activated xenobiotic metabolism, which expelled the xenobiotics from their bodies, by providing energy through lipid metabolism. When PWNs were exposed to A. robusta for 36 h, lysosomal and autophagy-related genes were activated, and the bodies of the nematodes underwent disintegration. Moreover, a gene co-expression pattern network was constructed by WGCNA and Cytoscape. The gene co-expression pattern network suggested that metabolic processes, developmental processes, detoxification, biological regulation, and signaling were influential when the B. xylophilus specimens were exposed to A. robusta. Additionally, bZIP transcription factors, ankyrin, ATPases, innexin, major facilitator, and cytochrome P450 played critical roles in the network. This study proposes a model in which mobility improved whenever B. xylophilus entered the traps of A. robusta. The model will provide a solid foundation with which to understand the molecular and evolutionary mechanisms underlying interactions between nematodes and nematophagous fungi. Taken together, these findings contribute in several ways to our understanding of B. xylophilus exposed to microorganisms and provide a basis for establishing an environmentally friendly prevention and control strategy.

Abstract SET is a multifunctional oncoprotein which is ubiquitously expressed in all kinds of cells. The SET protein participates in many cellular processes including cell cycle, cell migration, apoptosis, transcription, and DNA repair. Accumulating evidence demonstrates that the expression and activity of SET correlate with cancer occurrence, metastasis, and prognosis. Therefore, the SET protein is regarded as a potential target for cancer therapy and several inhibitors are being developed for clinical use. Herein, we comprehensively review the physiological and pathological functions of SET as well as its structure‐function relationship. Additionally, the regulatory mechanisms of SET at both transcriptional and posttranslational levels are also discussed.

The study aims to investigate the effects of (-)-Linarinic acid (LA) and one of its derivatives (LAd) on brain injury induced by ischemia. Malonaldehyde (MDA) is determined as an index for lipid peroxidation both in vitro and vivo. Mice were pre-treated with LA and LAd for 3 d. Thereafter, they were induced to have incomplete cerebral ischemia with both bilateral carotid artery occlusion and hypotension (BCAOH). In the first part of the in vivo experiment, mice were divided into four groups: sham (control), ischemia, ischemia + LA (200 mg/kg, i.g.) and ischemia + LAd (200 mg/kg, i.g.). In the second part, the dose-response of LAd was investigated at 100, 200 and 400 mg/kg i.g., respectively. A modified neurological severity score was developed for evaluating behavioral deficits of the mice with ischemia. Brains of the mice were excised in order to determinate MDA after ischemia for 6 h. Survival time, survival rate, neurological injury score and MDA level in brains were observed. Results were: 1) The data in vitro showed that both LA and LAd could inhibit the generation of MDA. IC50 values obtained by Probit analysis were 2.9 mM for LAd and 4.88 mM for LA; 2) BCAOH could significantly shorten the survival span, reduce the survival rate and cause neurological deficits, which were associated with high level of lipid hydroperoxide production in cerebral tissues; 3) LAd decreased lipid peroxidation and improved the neurological outcome more than LA. It is concluded that LAd offers a better neuroprotection than LA against brain damage caused by cerebral ischemia.

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin β1 expression. Subsequently, integrin β1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

BackgroundThe objective of this study was to explore the relationship between sedentary behavior and non-suicidal self-injury (NSSI), and to provide a theoretical basis for preventing and reducing the occurrence of NSSI behavior and the development of intervention measures.MethodsBetween September and December 2021, a sedentary behavior and NSSI survey was administered to 10327 Chinese adolescents aged 12–17 who had been randomly selected using the stratified cluster random sampling method. The results were analyzed using the chi-square test and logistic regression analysis to explore the relationship between sedentary behavior and NSSI in this population.ResultsThe study found an overall NSSI detection rate among the participants of 25.1%, with occasional NSSI and frequent NSSI detection rates of 11.0% and 14.1%, respectively. The NSSI detection rate is higher in girls than in boys. After controlling for related influencing factors, the NSSI detection rates among adolescents with sedentary behavior duration ≥8 hours and screen time ≥2 hours were 1.393(β= 0.332, P

An ideal biomaterial should create a customized tissue-specific microenvironment that can facilitate and guide the tissue repair process. Due to its good biocompatibility and similar biochemical properties to native tissues, decellularized extracellular matrix (dECM) generally yields enhanced regenerative outcomes, with improved morphological and functional recovery. By utilizing various decellularization techniques and post-processing protocols, dECM can be flexibly prepared in different states from various sources, with specifically customized physicochemical properties for different tissues. To initiate a well-orchestrated tissue-regenerative response, dECM exerts multiple effects at the wound site by activating various overlapping signaling pathways to promote cell adhesion, proliferation, and differentiation, as well as suppressing inflammation via modulation of various immune cells, including macrophages, T cells, and mastocytes. Functional tissue repair is likely the main aim when employing the optimized dECM biomaterials. Here, we review the current applications of different kinds of dECMs in an attempt to improve the efficiency of tissue regeneration, highlighting key considerations on developing dECM for specific tissue engineering applications.

Coronavirus nonstructural protein 2 (Nsp2) is regarded as a virulence determinant and plays a critical role in virus replication, and innate immunity. Screening and identifying host cell proteins that interact with viral proteins is an effective way to reveal the functions of viral proteins. In this study, the host proteins that interacted with transmissible gastroenteritis virus (TGEV) Nsp2 were identified using immunoprecipitation combined with LC-MS/MS. 77 host cell proteins were identified as putative Nsp2 interaction host cell proteins and a protein-protein interaction (PPI) was constructed. The identified proteins were found to be associated with various subcellular locations and functional categories through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. It is hypothesized that the host cell proteins interacting with TGEV Nsp2 are mainly involved in the formation of the cytoplasmic translation initiation complex, mRNA binding, ribosomes, and proteasomes. Among these, the ATP5B, a core subunit of the mitochondrial ATP synthase was further studied. The Coimmunoprecipitation (Co-IP) and indirect immunofluorescence (IFA) results confirmed that TGEV Nsp2 interacted with ATP5B. Furthermore, the downregulation of ATP5B expression was found to promote TGEV replication, suggesting that ATP5B might function as a negative regulator of TGEV replication. Collectively, our results offer additional insights into the functions of Nsp2 and provide a novel antiviral target against TGEV.

Abstract Background Pulmonary function is very important for the healthy development of children and adolescents. However, fewer studies have been conducted on pulmonary function trends in children and adolescents in remote areas. The aim of this study was to estimate the forced vital capacity (FVC) trend and its relationship with body mass index (BMI) among young people in Xinjiang during 1985–2014 using data from seven successive national surveys. Methods A total of 19,449 Xinjiang children and adolescents aged 7–18 years were extracted from the Chinese National Survey on Students’ Constitution and Health. Height, weight, and FVC were measured repeatedly in each survey. FVC comparisons between adjacent surveys by age and sex were conducted by nonparametric Kruskal-Wallis after Kolmogorov-Smirnov of normality. One-way ANOVA and least significant difference(LSD) method was used to compare differences in FVC levels of Xinjiang children and adolescents with different BMI. The relationship between BMI and FVC was investigated using a nonlinear regression model. Results The FVC levels of Xinjiang children and adolescents peaked in 2000, with overall FVC levels being 8.7% higher in 2000 than in 1985. Since then, a substantial decline occurred, contrasting to 2000, with FVC levels decreasing by 27% in 2014, which was still lower than that in 1985 by 20.73%. The proportion of overnutrition boys increased from 0.2% in 1985 to 22.1% in 2014, and girls from 0.5% in 1985 to 14.5% in 2014. An inverted U-shape association between FVC and BMI values was obtained for Xinjiang children and adolescents. Conclusions Targeted measures should be carried out in schools to control BMI levels to ensure good lung function in children and adolescents in Xinjiang. Future studies should pay more attention to other factors affecting FVC, such as dietary behaviour, physical activity, and racial differences among children and adolescents.

Abstract Angiogenesis is crucial for successful bone defect repair. Co‐transplanting Bone Marrow Stromal Cells (BMSCs) and Endothelial Cells (ECs) has shown promise for vascular augmentation, but it face challenges in hostile tissue microenvironments, including poor cell survival and limited efficacy. In this study, the mitochondria of human BMSCs are isolated and transplanted to BMSCs from the same batch and passage number (BMSCsmito). The transplanted mitochondria significantly boosted the ability of BMSCsmito‐ECs to promote angiogenesis, as assessed by in vitro tube formation and spheroid sprouting assays, as well as in vivo transplantation experiments in balb/c mouse and SD rat models. The Dll4‐Notch1 signaling pathway is found to play a key role in BMSCsmito‐induced endothelial tube formation. Co‐transplanting BMSCsmito with ECs in a rat cranial bone defect significantly improves functional vascular network formation, and improve bone repair outcomes. These findings thus highlight that mitochondrial transplantation, by acting through the DLL4‐Notch1 signaling pathway, represents a promising therapeutic strategy for enhancing angiogenesis and improving bone repair. Hence, mitochondrial transplantation to BMSCS as a therapeutic approach for promoting angiogenesis offers valuable insights and holds much promise for innovative regenerative medicine therapies.

Abstract Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Highlights Aligned graphene building blocks take full advantages of the outstanding properties of graphene. Comprehensive review of recent advancements in the utilization of highly aligned graphene aerogels for multifunctional applications. By systematically summarizing the controlled assembly, aligned structural attributes, quantitative characterization methods, anisotropic properties, and multifunctional applications of graphene aerogels, this review enhances understanding of the material's potential for diverse applications, offering tailored properties and novel functionalities.

Abstract Angiogenesis is a complex, highly-coordinated and multi-step process of new blood vessel formation from pre-existing blood vessels. When initiated, the sprouting process is spearheaded by the specialized endothelial cells (ECs) known as tip cells, which guide the organization of accompanying stalk cells and determine the function and morphology of the finally-formed blood vessels. Recent studies indicate that the orchestration and coordination of angiogenesis involve dynamic tip cell selection, which is the competitive selection of cells to lead the angiogenic sprouts. Therefore, this review attempt to summarize the underlying mechanisms involved in tip cell specification in a dynamic manner to enable readers to gain a systemic and overall understanding of tip cell formation, involving cooperative interaction of cell rearrangement with Notch and YAP/TAZ signaling. Various mechanical and chemical signaling cues are integrated to ensure the right number of cells at the right place during angiogenesis, thereby precisely orchestrating morphogenic functions that ensure correct patterning of blood vessels. Video Abstract

ObjectiveThis sought to explore the association between soybean product consumption and executive function (EF) in Chinese Tibetan adolescents in high-altitude areas.MethodsA total of 1,184 Tibetan children and adolescents were tested on demographic variables, soybean product consumption, and executive function in Lhasa and Nagchu regions of Tibet, China, using stratified whole population sampling. One-way ANOVA, linear regression analysis, and logistic regression analysis were used to analyze the associations existing between soybean product consumption and executive function.ResultsThe proportions of Hardly ever, Occasionally, and Often in Soy Consumption among Tibetan children and adolescents in high altitude areas of Tibet, China were 21.7, 50.3, and 28.0%, respectively. The difference in 2 back reaction time among Tibetan children and adolescents with different soybean product consumption was statistically significant (F = 6.374, p = 0.002). The difference in conversion function reaction time was also statistically significant (F = 8.129, p

BackgroundIn recent years, the addition of immune checkpoint inhibitors (ICI) to chemotherapy (CT) has become a research hotspot in the therapy of metastatic triple-negative breast cancer. Nevertheless, controversial results have been revealed among the published randomized controlled trials. Hence, a meta-analysis was performed to assess the therapeutic effect of this treatment regimen.MethodsFive English databases (PubMed, WOS, CENTRAL, Scopus, and Embase), and four Chinese databases (CBM, CNKI, VIP, and Wanfang), as well as oncological meetings, were systematically searched to identify eligible studies that assessed the addition of ICI to CT versus CT alone in metastatic triple-negative breast cancer. The pooled hazard ratios (HR) of progression-free survival (PFS) and overall survival (OS) were estimated using fixed- or random-effect model. Subgroup analyses were also performed in the intention-to-treat (ITT) and PD-L1-positive individuals.ResultsAll told there are five eligible randomized controlled trials involving 3,000 patients were enrolled in this meta-analysis. Compared with CT alone, the ICI plus CT regimen significantly increased PFS in the ITT (HR = 0.80, 95% CI: 0.73–0.88) and PD-L1-positive (HR = 0.70, 95% CI: 0.62–0.79) populations, as well as OS in the ITT (HR = 0.89, 95% CI: 0.81–0.97) and PD-L1-positive populations (HR = 0.80, 95% CI: 0.71–0.91). Moreover, the PFS of sufferers treated with the combination strategy of ICI with CT increased alongside PD-L1 enrichment. A clinical benefit in terms of objective response rate was also distinctly observed in both populations treated with ICI plus CT. In the subgroup analysis, patients in the no prior CT subgroup experienced a striking increase in PFS in both populations; however, a difference was not observed in other subgroups.ConclusionsThe combination strategy striking improves PFS and OS in both ITT and PD-L1-positive populations, and PFS is prolonged with PD-L1 enrichment. Patients who do not receive CT prior to this treatment are associated with longer PFS in both populations.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42021289817.

Thermoultrasound (USB) as a promising alternative to traditional hot water (HWB) blanching was employed to blanch sweet potatoes and its influence on enzyme activity, drying behavior, energy consumption and physiochemical properties of sweet potatoes were investigated. Results showed that successive increases in blanching temperature and time resulted in significant (p

The Lombok Strait (LS), Ombai Strait (OS), and Timor Passage (TP) are three major outlets of the Indonesian Throughflow to the Indian Ocean. Here, sources and pathways of the LS, OS, and TP outflows are explored by a Lagrangian particle tracking analysis based on a ~3 km regional ocean model simulation. The Makassar Strait transport contributes to ~80%, ~75%, and ~45% of the LS, OS, and TP outflows, respectively. However, ~41% and ~19% of the TP and OS outflows stem from the Lifamatola Passage, which largely feeds the upper and intermediate layers of the outflows. The role of Karimata Strait is quite limited and restricted to the upper layer. It takes 1-2 years and 2-6 years for the Makassar Strait water to reach the OS and TP, respectively, whereas the Lifamatola Passage water passes through the OS (2-6 years) and TP (3-9 years) on a prolonged transit time. In the Banda Sea, the western boundary current is the main pathway toward the OS, while the waters to the TP tend to take a basin interior route.

Abstract While the pivotal role of the Indonesian Throughflow (ITF) in the global ocean circulation and climate has been widely recognized, accurate estimation of its volume transport based on observational data remains challenging. This work provides an updated estimate of the monthly ITF geostrophic transport (ITFG) in the upper 700 m at the IX1 section between Indonesia and Australia. The ITFG estimate is better constrained by improved data correction and new salinity data products. The mean ITFG of 1993–2018 is 8.2 ± 0.2 Sv, in which contributions of the temperature and salinity components (ITFT and ITFS) are 5.5 ± 0.2 and 2.8 ± 0.1 Sv, respectively. The interannual variability (∼4.4 Sv in standard deviation) is dominated by ITFT, as the result of wind‐driven thermocline dynamics, and slightly attenuated in amplitude by ITFS. The strengthening trend of 1.33 Sv decade−1 during 1993–2018 primarily arises from ITFS and secondarily from ITFT.

BackgroundAssociations between body composition and execution function (EF) were currently studied in low altitude (LA) areas. However, the research on the correlation between waist circumference (WC) and EF among adolescents living at high altitude (HA) was limited.ObjectiveWe sought to explore the association between WC and EF in Chinese Tibetan adolescents aged 13–18 years in HA areas.MethodsAfter excluding invalid data and extreme values, 1,228 participants (583 boys and 645 girls) were eventually included. The areas of Lhasa (average elevation of 3650 m), Nagqu (4500 m), Qamdo (3500 m), and Nyingchi (3100 m) in China were chosen as study sites. Participants completed tasks to measure inhibitory control, working memory, and cognitive flexibility. The predictive association between WC and EF was explored by One-way ANOVA, Pearson correlation, and linear regression analysis.ResultsAfter controlling for concomitant variables, the reaction time (RT) of responding to inhibitory control (difference incongruent and congruent), working memory (1-back, 2-back), and cognitive flexibility (heterogeneous, difference in heterogeneous and homogeneous) stimuli in subjects with WC ≥ 85th percentile was longer than that in those with WC of the 15th percentile or below [by 1.785 ms (95% CI: 0.078, 3.491), 208.734 ms (95% CI: 96.886, 320.582), 106.679 ms (95% CI: 16.485, 196.873), 82.307 ms (95% CI: 19.171, 145.442), and 58.397 ms (95% CI: 0.343,116.452), respectively], (P < 0.05).ConclusionAfter adjustment for concomitant variables, WC was significantly positively associated with the RT of inhibitory control, working memory, and cognitive flexibility among Chinese Tibetan adolescents in HA areas.

Endothelial tip cell outgrowth of blood-vessel sprouts marks the initiation of angiogenesis which is critical in physiological and pathophysiological procedures. However, how mechanical characteristics of extracellular matrix (ECM) modulates tip cell formation has been largely neglected. In this study, we found enhanced CD31 expression in the stiffening outer layer of hepatocellular carcinoma than in surrounding soft tissues. Stiffened matrix promoted sprouting from endothelial cell (EC) spheroids and upregulated expressions of tip cell-enriched genes in vitro. Moreover, tip cells showed increased cellular stiffness, more actin cytoskeleton organization and enhanced YAP nuclear transfer than stalk and phalanx ECs. We further uncovered that substrate stiffness regulates FAK and Paxillin phosphorylation in focal adhesion of ECs promoting Rac1 transition from inactive to active state. YAP is subsequently activated and translocated into nucleus, leading to increased tip cell specification. p-Paxillin can also loosen the intercellular connection which also facilitates tip cell specification. Collectively our present study shows that matrix stiffness modulates tip cell formation through p-PXN-Rac1-YAP signaling axis, shedding light on the role of mechanotransduction in tip cell formation. This is of special significance in biomaterial design and treatment of some pathological situations.

The southeastern Indian Ocean (SEIO) exhibits prominent decadal variability in sea surface salinity (SSS), showing salinity decreases during 1995-2000 and 2005-2011 and increases during 2000-2005 and after 2011. These salinity changes are linked to the Indo-Pacific climate and have impacts on the regional marine environment. Yet, the underlying mechanism has not been firmly established. In this study, decadal SSS variability of the SEIO is successfully simulated by a high-resolution regional ocean model, and the mechanism is explored through a series of sensitivity experiments. The results suggest that freshwater transport of the Indonesian throughflow (ITF) and local precipitation are two major drivers for the SSS decadal variability. They mutually cause most of the variability, with a generally larger contribution of precipitation. Other processes, such as evaporation and advection driven by local winds, play a minor role. Further analysis shows that the decadal precipitation in the SEIO is mainly associated with the decadal variability of Ningaloo Niño. Ocean dynamic processes significantly modify the relationship between SSS and precipitation, greatly shortening their lag time. The changes in both volume transport and salinity of the ITF water can cause large salinity changes in the SEIO region. Although local wind forcing gives rise to considerable changes in evaporation rate and ocean current advection, its overall contribution to decadal SSS variability is small compared to local precipitation and the ITF.

Abstract Background Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABAA receptors (α5GABAARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABAARs are involved in the function of MD2. Methods Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABAARs. Electrophysiology was employed to measure tonic currents. For α5GABAARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABAARs, respectively. Results Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABAARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABAARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABAARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits. Conclusions MD2 contributes to the occurrence of PND by regulating α5GABAARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.

ObjectivesTo assess the clinical efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy or chemoradiotherapy alone in the treatment of cervical cancer.MethodsThe PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, and VIP databases were systematically searched for relevant literature. Ultimately, six randomised controlled trials (n=393) were included in our meta-analysis.ResultsA total of 393 patients were included, of which 197 were in the nimotuzumab combined with chemoradiotherapy group and 196 were in the chemoradiotherapy group. The results of our meta-analysis showed that the complete remission rate (risk ratio [RR] = 1.34, 95% confidence interval [CI]: 1.08-1.65, P = 0.007), objective response rate (RR = 1.30, 95% CI: 1.16-1.44, P < 0.05), and three-year survival rate (RR = 1.27, 95% CI: 1.06-1.51, P = 0.008) in the nimotuzumab combined with chemoradiotherapy group were significantly improved compared with the chemoradiotherapy group. This difference was not statistically significant when comparing the incidence of adverse reactions (such as leukocytopenia, gastrointestinal reaction, radiocystitis, and radioproctitis) between the two groups.ConclusionsNimotuzumab in combination with chemoradiotherapy has some advantages over chemoradiotherapy alone in the treatment of cervical cancer and does not increase toxicity. Therefore, nimotuzumab has the potential to be an effective treatment for cervical cancer; however, further evidence from large-scale randomised controlled trials is needed.

ObjectivesTo evaluate the clinical curative effects and toxicity of neoadjuvant chemoradiotherapy for resectable gastric cancer compared to those of neoadjuvant chemotherapy.MethodsA systematic review and meta-analysis of the randomized controlled trials (RCTs) of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy were performed in patients with resectable gastric cancer.ResultsSeven RCTs were included (601 patients; 302 in the neoadjuvant chemoradiotherapy group and 299 in the neoadjuvant chemotherapy group). The neoadjuvant chemoradiotherapy group had an increased number of patients with a complete response [odds ratio (OR) = 3.79, 95% confidence interval (CI): 1.68–8.54, p = 0.001] and improved objective response rate (OR = 2.78, 95% CI: 1.69–4.57, p < 0.0001), 1-year (OR = 3.51, 95% CI: 1.40–8.81, p = 0.007) and 3-year (OR = 2.14, 95% CI: 1.30–3.50, p = 0.003) survival rates, R0 resection rate (OR = 2.21, 95% CI: 1.39–3.50, p = 0.0008), and complete pathologic response (OR = 4.39, 95% CI: 1.59–12.14, p = 0.004). Regarding the incidence of adverse effects after neoadjuvant therapy, only the occurrence rate of gastrointestinal reaction in the neoadjuvant chemoradiotherapy group was higher than that in the neoadjuvant chemotherapy group (OR = 1.76, 95% CI: 1.09–2.85, p = 0.02), and there was no significant difference in other adverse effects. There was no difference in the incidence of postoperative complications between the two groups.ConclusionNeoadjuvant chemoradiotherapy for resectable gastric cancer has several advantages in terms of efficacy and safety compared to neoadjuvant chemotherapy. Therefore, neoadjuvant chemoradiotherapy has great potential as an effective therapy for resectable gastric cancers.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-3-0164, registration number INPLASY202230164.

ObjectivesTo compare the survival and complications of neoadjuvant chemoradiation (NCRT) versus neoadjuvant chemotherapy (NCT) for esophageal squamous cell carcinoma (ESCC).MethodsWe conducted a systematic literature search of the PubMed, Web of Science, Cochrane Library, EMBASE, CNKI, Wanfang Data, CBM, and VIP databases from inception to November 2021. Meta-analyses were performed using RevMan (version 5.3) and Stata version 15.0.ResultsA total of 18 studies were included, which involved 3137 patients, The results of the metaanalysis showed that the pathological complete remission rate (odds ratio [OR] = 5.21, 95% confidence interval [CI]: 2.85-9.50, pConclusionThe use of NCRT in the treatment of patients with ESCC patients showed significant advantages in terms of survival and safety relative to the use of NCT.

Soil salinization is an important factor contributing to the deterioration of soil environment and low crop yield in arable land. In this study, the effects of five fulvic acid applications (0 (CK), 150 (T1), 300 (T2), 450 (T3), and 600 (T4) kg·ha−1) on soil physicochemical properties, humus content of each component, and cotton (Xinluzao No. 82) growth were investigated. It was confirmed that fulvic acid improved soil water-stable macroaggregates, moisture distribution, and desalinization. 0–20 cm soil relative desalinization rate was significantly increased by 2–11.75%. The pH value decreased by 0.09–0.21. The soil organic matter content was significantly increased compared to CK (p < 0.05), with 7.5–26.93% increase in organic matter content in 0–20 cm soil layer. Soil humification was increased to different degrees, with the most significant increase in humic carbon content in T3 treatment (p < 0.05). There was a significant increase in leaf area index (LAI), stem diameter, and plant height of cotton (p < 0.05). Cotton yield increased by 3.64–8.36% compared to CK (p < 0.05). Correlation analysis showed that cotton yield was significantly correlated with the soil textures of saline soils. The best improvement was achieved with 450 kg·ha−1 fulvic acid. The results of this study can provide a theoretical basis for the improvement of saline soils in arid zones to enhance crop growth and yield.

Background: Previous studies had shown that poor quality of early parental attachment is a risk factor for suicide, but few have focus on the mechanism between suicidal ideation and parental attachment. The aim of this study was to explore how parental attachment, anhedonia, and peer attachment were associated with suicidal ideation in adolescents.Method: Participants were enrolled in middle schools, in Hefei, Anhui, China. All participants completed socio-demographic characteristic and standard assessments on parental attachment, peer attachment, anhedonia, and suicidal ideation by paper surveys. The effect of parental attachment on suicidal ideation mediated by anhedonia and peer attachment was analyzed by a structural equation model (SEM) using SPSS AMOS 23.0.Results: The SEM analysis revealed that the standard total effect of parental attachment on suicidal ideation was −0.137 (Z=−27.00, 95% confidence interval [CI; −0.147, −0.127], p

ObjectivesTo evaluate the clinical curative effects and toxicity of recombinant human adenovirus-p53 injection (rAd-p53) plus chemotherapy (CT), radiotherapy (RT), or concurrent chemoradiotherapy (CRT) for the treatment of cervical cancer.MethodsWe identified 14 eligible studies in the PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wangfangdate, CBM, and VIP databases from their inception to May 2021 and performed meta-analyses using RevMan version 5.3.ResultsThis analysis included 14 studies involving 737 patients. The results of the meta-analysis results showed significantly improved complete remission (odds ratio [OR] = 2.54, 95% confidence interval [CI]: 1.74–3.70, p < 0.00001), partial remission (OR = 1.56, 95% CI: 1.14–2.14, p = 0.006), and object response (OR = 4.47, 95% CI: 3.02–6.60, p < 0.00001) rates in the rAd-p53 combination therapy group compared to those in the CT/RT/CRT group. The results of subgroup analyses of CT/RT/CRT were consistent with the overall results. Regarding the incidence of adverse reactions, only the occurrence rate of fever (OR = 18.21, 95% CI: 10.54–31.47, p < 0.00001) in the rAd-p53 combination group was higher than that in the CT/RT/CRT group. No other significant differences were observed in other adverse reactions.ConclusionRAd-p53 combined with CT/RT/CRT for the treatment of cervical cancer showed significant advantages in efficacy and safety compared to those in the CT/RT/CRT group. Therefore, rAd-p53 has great potential as an effective therapy for cervical cancer.Systematic Review Registrationhttps://inplasy.com/inplasy-2021-5-0058/.

The increase in sedentary behavior in children and adolescents has become a worldwide public health problem. This study aimed to explore the associations between sedentary time (ST) and sedentary patterns (SP) and the cardiorespiratory fitness (CRF) of Chinese children and adolescents. The CRF of 535 participants was determined using a 20-m shuttle run test. ST and SP were measured with accelerometers. Questionnaires were used to investigate the different types of ST. Multiple linear regression models were used to test the associations between ST and SP and CRF. In this study, only some ST and SP indicators were found to be significantly associated with CRF in girls. With each additional 10 min of screen time or passive traffic time, VO2max decreases by 0.06 mL/kg/min (B = −0.006, 95% CI: −0.010~−0.001) and 0.31 mL/kg/min (B = −0.031, 95% CI: −0.061~−0.002), respectively, with MVPA control. With each additional 10 min of breaks in ST or duration of breaks in ST, VO2max increases by 0.41 mL/kg/min (B = 0.041, 95% CI: 0.007~0.076) and 0.21 mL/kg/min (B = 0.021, 95% CI: 0.007~0.035), respectively, with control total ST. Breaks in ST (B = 0.075, 95% CI: 0.027~0.123) and the duration of breaks in ST (B = 0.021, 95% CI: 0.012~0.146) were positively correlated with CRF when controlling for LPA, but these associations were not significant when controlling for MVPA (B = 0.003, 95% CI: −0.042~0.048; B = 0.001, 95% CI: −0.024~0.025). The total ST of children and adolescents was found to not be correlated with CRF, but when ST was divided into different types, the screen time and passive traffic time of girls were negatively correlated with CRF. More breaks in ST and the duration of breaks in ST were positively associated with higher CRF in girls. MVPA performed during breaks in ST may be the key factor affecting CRF. Schools and public health departments should take all feasible means to actively intervene with CRF in children and adolescents.

This paper is to investigate the existence and uniqueness of solutions for an integral boundary value problem of new fractional differential equations with a sign-changed parameter in Banach spaces. The main used approach is a recent fixed point theorem of increasing Ψ−h,r-concave operators defined on ordered sets. In addition, we can present a monotone iterative scheme to approximate the unique solution. In the end, two simple examples are given to illustrate our main results.

With the increase in depth of coal mining, the hydrogeological complexity largely increases and water inrush accidents happen more frequently. For the safety of coal mining, horizontal directional drilling and grouting techniques have been implemented to detect and plug the fractures and conduits that deliver high-pressure groundwater to coal mine. Taking the grouting engineering performed at Xingdong coal mine at 980 m below sea level as an example, we collected the data of grouting quantity, the loss of drilling fluid, gamma value, water temperature, average water absorption, distance between grouting loss points, water pressure on coal seam floor, and aquifuge thickness at 90 boreholes in the mine to conduct grey relational analysis, first. The analysis showed that the grouting quantity was highly correlated with all other factors. Subsequently, grey system evaluation was used to evaluate the risk of water inrush from the coal seam floor. The results of risk analysis illustrated that three water inrushes from Ordovician limestone occurred in mining face 2127, 2125, and 2222 in the study area were all located in the area with a risk score higher than 65. Through grouting, the identified cracks were effectively blocked and waterproof layers beneath the coal seam floors were constructed to reduce the threat of water inrush. By comparing the risk assessment results with three water inrush cases before grouting operation, we found that water inrush areas were consistent with the area of higher risk.

Component factories are experiencing the problems associated with lean production, especially the accuracy of production time prediction and the unnecessary waste in terms of time and resource utilization. In order to solve these problems, a discrete event simulation- (DES-) based lean planning and optimization method for precast component production is proposed by integrating the complexity assessment (CS), discrete event simulation (DES), and lean management (LM). The method includes three submodels: improved production planning, DES, and lean analysis and optimization. In the submodel of improved production planning, a complexity evaluation index system for precast components is established through investigating five component factories, consulting seven domain experts and analysing relevant literature. In the submodel of DES, the DES technique is adopted to simulate and analyse the production activities of precast components. The submodel of lean analysis and optimization provides multidimensional analysis, comparative analysis, and suggestions. Finally, a detailed production case is selected to simulate and test the proposed method. The important findings are as follows: (1) this method can minimize the difference between the processing time of each workstation to avoid bottleneck stations as much as possible; (2) this method can capture the uncertainty during precast component production, and the most likely production time calculated by the method is 12.05 hours instead of the 11.50 hours originally estimated by the component factory; (3) this method can identify some unnecessary waste in the production process of precast components, including less than 50% utilization of workstations and unnecessary equipment purchases; (4) this method also provides some suggestions regarding production optimization. Due to the particularity of precast component production, it further expands the boundary of lean production methodology from the perspective of the construction industry rather than the manufacturing industry. The proposed method assists component factories in planning and optimizing the precast component production when they make detailed production plans.

MYB transcription factors have been demonstrated to play key regulatory roles in plant growth, development and abiotic stress response. However, knowledge concerning the involvement of rice MYB genes in salinity and drought stress resistance are largely unknown. In the present study, we cloned and characterized the OsMYB6 gene, which was induced by drought and salinity stress. Subcellular localization of OsMYB6-YFP fusion protein in protoplast cells indicated that OsMYB6 was localized in the nucleus. Overexpression of OsMYB6 in rice did not suggest a negative effect on the growth and development of transgenic plants, but OsMYB6-overexpressing plants showed increased tolerance to drought and salt stress compared with wild-type plants, as are evaluated by higher proline content, higher CAT and SOD activities, lower REL and MDA content in transgenic plants under drought and salt stress conditions. In addition, the expression of abiotic stress-responsive genes were significantly higher in OsMYB6 transgenic plants than that in wild-type plants under drought and salt stress conditions. These results indicate that OsMYB6 gene functions as a stress-responsive transcription factor which plays a positive regulatory role in response to drought and salt stress resistance, and may be used as a candidate gene for molecular breeding of salt-tolerant and drought-tolerant crop varieties.