Analysis of factors influencing hospitalization cost of patients with distal radius fractures: an empirical study based on public traditional Chinese medicine hospitals in two cities, China.

BACKGROUND: Distal radius fractures (DRFs) have become a public health problem for all countries, bringing a heavier economic burden of disease globally, with China's disease economic burden being even more acute due to the trend of an aging population. This study aimed to explore the influencing factors of hospitalization cost of patients with DRFs in traditional Chinese medicine (TCMa) hospitals to provide a scientific basis for controlling hospitalization cost. METHODS: With 1306 cases of DRFs patients hospitalized in 15 public TCMa hospitals in two cities of Gansu Province in China from January 2017 to 2022 as the study object, the influencing factors of hospitalization cost were studied in depth gradually through univariate analysis, multiple linear regression, and path model. RESULTS: Hospitalization cost of patients with DRFs is mainly affected by the length of stay, surgery and operation, hospital levels, payment methods of medical insurance, use of TCMa preparations, complications and comorbidities, and clinical pathways. The length of stay is the most critical factor influencing the hospitalization cost, and the longer the length of stay, the higher the hospitalization cost. CONCLUSIONS: TCMa hospitals should actively take advantage of TCMb diagnostic modalities and therapeutic methods to ensure the efficacy of treatment and effectively reduce the length of stay at the same time, to lower hospitalization cost. It is also necessary to further deepen the reform of the medical insurance payment methods and strengthen the construction of the hierarchical diagnosis and treatment system, to make the patients receive reasonable reimbursement for medical expenses, thus effectively alleviating the economic burden of the disease in the patients with DRFs.

Multi-omics explores the potential regulatory role of acetylation modification in flavonoid biosynthesis of Ginkgo biloba.

Flavonoids are crucial medicinal active ingredients in Ginkgo biloba. However, the effect of protein post-translational modifications (PTMs) on flavonoid biosynthesis remains poorly explored. Lysine acetylation, a reversible PTM, plays a crucial role in metabolic regulation. This study aims to investigate the potential role of acetylation in G. biloba flavonoid biosynthesis. Through comprehensive analysis of transcriptomes, metabolomes, proteomes, and acetylated proteins in different tissues, a total of 11,788 lysine acetylation sites were identified on 4324 acetylated proteins, including 89 acetylation sites on 23 proteins. Additionally, 128 types of differentially accumulated flavonoids were identified among tissues, and a dataset of differentially expressed genes related to the flavonoid biosynthesis pathway was constructed. Twelve (CHI, C3H1, ANR, DFR, CCoAOMT1, F3H1, F3H2, CCoAOMT2, C3H2, HCT, F3'5'H, and FG2) acetylated proteins that might be involved in flavonoid biosynthesis were identified. Specifically, we found that the modification levels of CCoAOMT1 and F3'5'H sites correlated with the catalytic production of homoeriodictyol and dihydromyricetin, respectively. Inhibitors of lysine deacetylase (trichostatin A, TSA) impacted total flavonoid content in different tissues and increased flavonoid levels in G. biloba roots. Treatment with TSA revealed that expression levels of GbF3'5'H and GbCCoAOMT1 in stems and leaves aligned with total flavonoid content variations, while in roots, expression levels of GbC3H2 and GbFG2 corresponded to total flavonoid content changes. Collectively, these findings reveal for the first time the important role of acetylation in flavonoid biosynthesis.

Potential effects of soil petroleum contamination on decomposition of Artemisia annua plant litter.

The accumulation of petroleum contaminants in phytoremediating plants can significantly impact the decomposition of their litter. However, the mechanisms underlying these effects and the potential influence of the contaminant concentration remain unclear. In this study, litter from Artemisia annua plants grown in soil with varying concentrations of petroleum (0, 15, 30, and 45 g kg-1) was collected. The litter samples were then inoculated with soil microorganisms and subjected to an indoor simulation of decomposition under controlled temperature and humidity conditions. Changes in the chemical properties, activities of decomposition-related enzymes in the litter, and decomposition rates were measured. Additionally, structural equation modeling was employed to analyze the mechanism through which soil petroleum contamination affects litter decomposition. The findings revealed several key points: (1) increasing soil petroleum contamination tended to reduce the concentration of carbon and nitrogen in litter while increasing those of lignin and total petroleum hydrocarbons (TPH). (2) Soil petroleum contamination tended to increase the activities of both total lignocellulases and total nutrient cycling-related enzymes in litter. (3) Soil petroleum contamination might indirectly inhibit the activity of lignocellulases by increasing the concentration of lignin and TPH in litter. However, it might also directly accelerate the activity of these enzymes, resulting in contradictory effects on litter decomposition. (4) Finally, A. annua litter produced in soil contaminated with 15 and 30 g kg-1 of petroleum exhibited significantly lower decomposition rates than that from uncontaminated soil.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Differential effect of China's Zero Markup Drug Policy on provider-induced demand in secondary and tertiary hospitals.

Following the marketization of China's health system in the 1980's, the government allowed public hospitals to markup the price of certain medications by 15% to compensate for reduced revenue from government subsidies. This incentivized clinicians to induce patient demand for drugs which resulted in higher patient out-of-pocket payments, higher overall medical expenditure, and poor health outcomes. In 2009, China introduced the Zero Markup Drug Policy (ZMDP) which eliminated the 15% markup. Using Shanghai as a case study, this paper analyzes emerging and existing evidence about the impact of ZMDP on hospital expenditure and revenue across secondary and tertiary public hospitals. We use data from 150 public hospitals across Shanghai to examine changes in hospital expenditure and revenue for various health services following the implementation of ZMDP. Our analysis suggests that, across both secondary and tertiary hospitals, the implementation of ZMDP reduced expenditure on drugs but increased expenditure on medical services, exams, and tests thereby increasing hospital revenue and keeping inpatient and outpatient costs unchanged. Moreover, our analysis suggests that tertiary facilities increased their revenue at a faster rate than secondary facilities, likely due to their ability to prescribe more advanced and, therefore, more costly procedures. While rigorous experimental designs are needed to confirm these findings, it appears that ZMDP has not reduced instances of medical expenditure provoked by provider-induced demand (PID) but rather shifted the effect of PID from one revenue source to another with differential effects in secondary vs. tertiary hospitals. Supplemental policies are likely needed to address PID and reduce patient costs.

Large-scale lexical and genetic alignment supports a hybrid model of Han Chinese demic and cultural diffusions.

The Han Chinese history is shaped by substantial demographic activities and sociocultural transmissions. However, it remains challenging to assess the contributions of demic and cultural diffusion to Han culture and language, primarily due to the lack of rigorous examination of genetic-linguistic congruence. Here we digitized a large-scale linguistic inventory comprising 1,018 lexical traits across 926 dialect varieties. Using phylogenetic analysis and admixture inference, we revealed a north-south gradient of lexical differences that probably resulted from historical migrations. Furthermore, we quantified extensive horizontal language transfers and pinpointed central China as a dialectal melting pot. Integrating genetic data from 30,408 Han Chinese individuals, we compared the lexical and genetic landscapes across 26 provinces. Our results support a hybrid model where demic diffusion predominantly impacts central China, while cultural diffusion and language assimilation occur in southwestern and coastal regions, respectively. This interdisciplinary study sheds light on the complex social-genetic history of the Han Chinese.

Gene structure, expression and function analysis of the MyoD gene in the Pacific white shrimp Litopenaeus vannamei.

The Pacific white shrimp Litopenaeus vannamei is a representative species of decapod crustacean and an economically important marine aquaculture species worldwide. However, research on the genes involved in muscle growth and development in shrimp is still lacking. MyoD is recognized as a crucial regulator of myogenesis and plays an essential role in muscle growth and differentiation in various animals. Nonetheless, little information is available concerning the function of this gene among crustaceans. In this study, we identified a sequence of the MyoD gene (LvMyoD) with a conserved bHLH domain in the L. vannamei genome. Phylogenetic analysis revealed that both the overall protein sequence and specific functional sites of LvMyoD are highly conserved with those of other crustacean species and that they are evolutionarily closely related to vertebrate MyoD and Myf5. LvMyoD expression is initially high during early muscle development in shrimp and gradually decreases after 40 days post-larval development. In adults, the muscle-specific expression of LvMyoD was confirmed through RT-qPCR analysis. Knockdown of LvMyoD inhibited the growth of the shrimp in body length and weight. Histological observation and transcriptome sequencing of muscle samples after RNA interference (RNAi) revealed nuclear agglutination and looseness in muscle fibers. Additionally, we observed significant effects on the expression of genes involved in heat shock proteins, myosins, actins, protein synthesis, and glucose metabolism. These findings suggest that LvMyoD plays a critical role in regulating muscle protein synthesis and muscle cell differentiation. Overall, this study highlights the involvement of LvMyoD in myogenesis and muscle growth, suggesting that it is a potentially important regulatory target for shrimp breeding efforts.

Towards an actionable One Health approach.

BACKGROUND: Despite the increasing focus on strengthening One Health capacity building on global level, challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region. Recognizing these gaps, the One Health Action Commission (OHAC) was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact. MAIN TEXT: This viewpoint describes the agenda of, and motivation for, the recently formed OHAC. Recognizing the urgent need for evidence to support the formulation of necessary action plans, OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses, antimicrobial resistance, addressing food safety, and to enhance capacity building for context-sensitive One Health implementation. CONCLUSIONS: By promoting broader engagement and connection of multidisciplinary stakeholders, OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge, distilled practical experience and actionable policy advice, guided by strong ethical principles of One Health.

Comparative Transcriptomic Analysis Revealing the Potential Mechanisms of Erythritol-Caused Mortality and Oviposition Inhibition in Drosophila melanogaster.

Erythritol has shown excellent insecticidal performance against a wide range of insect species, but the molecular mechanism by which it causes insect mortality and sterility is not fully understood. The mortality and sterility of Drosophila melanogaster were assessed after feeding with 1M erythritol for 72 h and 96 h, and gene expression profiles were further compared through RNA sequencing. Enrichment analysis of GO and KEGG revealed that expressions of the adipokinetic hormone gene (Akh), amylase gene (Amyrel), α-glucosidase gene (Mal-B1/2, Mal-A1-4, Mal-A7/8), and triglyceride lipase gene (Bmm) were significantly up-regulated, while insulin-like peptide genes (Dilp2, Dilp3 and Dilp5) were dramatically down-regulated. Seventeen genes associated with eggshell assembly, including Dec-1 (down 315-fold), Vm26Ab (down 2014-fold) and Vm34Ca (down 6034-fold), were significantly down-regulated or even showed no expression. However, there were no significant differences in the expression of three diuretic hormone genes (DH44, DH31, CAPA) and eight aquaporin genes (Drip, Big brain, AQP, Eglp1, Eglp2, Eglp3, Eglp4 and Prip) involved in osmolality regulation (all p value > 0.05). We concluded that erythritol, a competitive inhibitor of α-glucosidase, severely reduced substrates and enzyme binding, inhibiting effective carbohydrate hydrolysis in the midgut and eventually causing death due to energy deprivation. It was clear that Drosophila melanogaster did not die from the osmolality of the hemolymph. Our findings elucidate the molecular mechanism underlying the mortality and sterility in Drosophila melanogaster induced by erythritol feeding. It also provides an important theoretical basis for the application of erythritol as an environmentally friendly pesticide.

Optimal decision-making in relieving global high temperature-related disease burden by data-driven simulation.

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019. The burdens of five categories of disease causes - cardiovascular diseases, infectious respiratory diseases, injuries, metabolic diseases, and non-infectious respiratory diseases - were designated as intermediate outcome variables. The cumulative burden of these five categories, referred to as the total HTD burden, was the final outcome variable. We evaluated the predictive performance of eight models and subsequently introduced twelve intervention measures, allowing us to explore optimal decision-making strategies and assess their corresponding contributions. Our model selection results demonstrated the superior performance of the Graph Neural Network (GNN) model across various metrics. Utilizing simulations driven by the GNN model, we identified a set of optimal intervention strategies for reducing disease burden, specifically tailored to the seven major regions: East Asia and Pacific, Europe and Central Asia, Latin America and the Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa. Sectoral mitigation and adaptation measures, acting upon our categories of Infrastructure & Community, Ecosystem Resilience, and Health System Capacity, exhibited particularly strong performance for various regions and diseases. Seven out of twelve interventions were included in the optimal intervention package for each region, including raising low-carbon energy use, increasing energy intensity, improving livestock feed, expanding basic health care delivery coverage, enhancing health financing, addressing air pollution, and improving road infrastructure. The outcome of this study is a global decision-making tool, offering a systematic methodology for policymakers to develop targeted intervention strategies to address the increasingly severe challenge of HTDs in the context of global warming.

Dietary kaempferol exerts anti-obesity effects by inducing the browing of white adipocytes via the AMPK/SIRT1/PGC-1α signaling pathway.

Browning of white adipose tissue is a novel approach for the management of obesity and obesity-related metabolic disorders. Kaempferol (KPF) is a common dietary nutrient found abundantly in many fruits and vegetables and has been shown to have the potential to regulate lipid metabolism. However, the detailed mechanism by which it affects the browning of white adipose tissue remains unclear. In the present study, we sought to determine how KPF induces adipocytes to undergo a browning transformation by establishing a primary adipocyte model and an obese mouse model. Our results showed that KPF-treated mice were rescued from diet-induced obesity, glucose tolerance and insulin resistance, associated with increased expression of adaptive thermogenesis-related proteins. KPF-promoted white adipose browning correlated with the AMPK/SIRT1/PGC-1α pathway, as the use of an AMPK inhibitor in preadipocytes partially reversed the observed browning phenotype of KPF-treated cells. Taken together, these data suggest that KPF promotes browning of white adipose tissue through activation of the AMPK/SIRT1/PGC-1α pathway. This study demonstrates that KPF is a promising natural product for the treatment of obesity by promoting white fat browning.

Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential.

Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases - have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA.

Regional anaesthesia education for consultants and specialists in the UK: a mixed-methods analysis.

BACKGROUND: Regional anaesthesia plays an important role in perioperative care, but gaps in proficiency persist among consultants and specialists. This study aimed to assess confidence levels in performing Plan A blocks among this cohort and to examine the barriers and facilitators influencing regional anaesthesia education. METHODS: Utilising a mixed-methods design, we performed a quantitative survey to gauge self-reported confidence in performing Plan A blocks, coupled with qualitative interviews to explore the complexities of educational barriers and facilitators. UK consultant and specialist anaesthetists were included in the study. RESULTS: A total of 369 survey responses were analysed. Only 22% of survey respondents expressed confidence in performing all Plan A blocks. Specialists (odds ratio [OR] 0.391, 95% confidence interval [CI] 0.179-0.855, P=0.016) and those in their roles for >10 yr (OR 0.551, 95% CI 0.327-0.927, P = 0.024) reported lower confidence levels. A purposive sample was selected for interviews, and data saturation was reached at 31 interviews. Peer-led learning emerged as the most effective learning modality for consultants and specialists. Barriers to regional anaesthesia education included apprehensions regarding complications, self-perceived incompetence, lack of continuing professional development time, insufficient support from the multidisciplinary team, and a lack of inclusivity within the regional anaesthesia community. Organisational culture had a substantial impact, with the presence of local regional anaesthesia champions emerging as a key facilitator. CONCLUSIONS: This study highlights persistent perceived deficiencies in regional anaesthesia skills among consultants and specialists. We identified multiple barriers and facilitators, providing insights for targeted interventions aimed at improving regional anaesthesia education in this group.

Reconstructing the ancestral gene pool to uncover the origins and genetic links of Hmong-Mien speakers.

BACKGROUND: Hmong-Mien (HM) speakers are linguistically related and live primarily in China, but little is known about their ancestral origins or the evolutionary mechanism shaping their genomic diversity. In particular, the lack of whole-genome sequencing data on the Yao population has prevented a full investigation of the origins and evolutionary history of HM speakers. As such, their origins are debatable. RESULTS: Here, we made a deep sequencing effort of 80 Yao genomes, and our analysis together with 28 East Asian populations and 968 ancient Asian genomes suggested that there is a strong genetic basis for the formation of the HM language family. We estimated that the most recent common ancestor dates to 5800 years ago, while the genetic divergence between the HM and Tai-Kadai speakers was estimated to be 8200 years ago. We proposed that HM speakers originated from the Yangtze River Basin and spread with agricultural civilization. We identified highly differentiated variants between HM and Han Chinese, in particular, a deafness-related missense variant (rs72474224) in the GJB2 gene is in a higher frequency in HM speakers than in others. CONCLUSIONS: Our results indicated complex gene flow and medically relevant variants involved in the HM speakers' evolution history.

Exploring the causal associations of micronutrients on urate levels and the risk of gout: A Mendelian randomization study.

BACKGROUND & AIMS: Growing evidence has indicated a potential association between micronutrient levels, urate levels, and the risk of gout. However, the causal association underlying these associations still remains uncertain. Previous observational studies and randomized controlled trials investigating the association between micronutrients, urate levels, and the risk of gout have been limited in their scope and depth. The aim of this study was to utilize Mendelian randomization (MR) to investigate the causal associations between genetically predicted micronutrient levels, urate levels, and the risk of gout. METHODS: In this study, we conducted a comprehensive examination of 10 specific micronutrients (vitamin B6, vitamin B12, vitamin C, vitamin D, folate, calcium, iron, copper, zinc, and selenium) as potential exposures. Two-sample MR analyses were performed to explore their causal associations with urate levels and the risk of gout. In these analyses, gout data were collected from the Global Biobank Meta-Analysis Initiative (N = 1,069,839, N cases = 30,549) and urate levels data from CKDGen Consortium (N = 288,649) by utilizing publicly available summary statistics from independent cohorts of European ancestry. We performed inverse-variance weighted MR analyses as main analyses, along with a range of sensitivity analyses, such as MR-Egger, weighted median, simple mode, weighted mode, Steiger filtering, MR-PRESSO, and Radial MR analysis, to ensure the robustness of our findings. RESULTS: The results of our study indicate that there were negative associations between serum vitamin B12 and urate levels, as well as serum folate and the risk of gout. Specifically, we found a negative association between vitamin B12 levels and urate levels, with a ß coefficient of -0.324 (95% CI -0.0581 to -0.0066, P = 0.0137) per one standard deviation (SD) increase. Similarly, a negative association was observed between folate levels and gout risk, with an odds ratio of 0.8044 (95% CI 0.6637 to 0.9750, P = 0.0265) per one SD increase. On the other hand, we identified positive associations between serum calcium levels and both urate levels and the risk of gout. Specifically, there was a positive association between serum calcium levels and urate levels (ß coefficient: 0.0994, 95% CI 0.0519 to 0.1468, P = 4.11E-05) per one SD increase. Furthermore, a positive association was found between serum calcium levels and the risk of gout, with an odds ratio of 1.1479 (95% CI 1.0460 to 1.2598, P = 0.0036) per one SD increase. These findings were robust in extensive sensitivity analyses. By employing MR-PRESSO and Radial MR to eliminate outliers, the observed associations have been reinforced. No clear associations were found between the other micronutrients and the urate levels, as well as the risk of gout. CONCLUSION: Our findings provided evidence that there were negative associations between serum vitamin B12 and urate levels, as well as serum folate and the risk of gout, while positive associations existed between the serum calcium levels and urate levels, as well as the risk of gout.

Mass spectrometry study on SARS-CoV-2 recombinant vaccine with comprehensive separation techniques to characterize complex heterogeneity.

SARS-CoV-2, the causative agent of COVID-19, has imposed a major public health threat, which needs effective therapeutics and vaccination strategies. Several potential candidate vaccines being rapidly developed are in clinical evaluation and recombinant vaccine has gained much attention thanks to its potential for greater response predictability, improved efficacy, rapid development and reduced side effects. Recombinant vaccines are designed and manufactured using bacterial, yeast cells or mammalian cells. A small piece of DNA is taken from the virus or bacterium against which we want to protect and inserted into the manufacturing cells. Due to the extremely complex heterogeneity of SARS-CoV-2 recombinant vaccine, single technology platform cannot achieve thorough and accurate characterization of such difficult proteins so integrating comprehensive technologies is essential. This study illustrates an innovative workflow employing multiple separation techniques tandem high-resolution mass spectrometry for comprehensive and in-depth characterization of SARS-CoV-2 recombinant vaccine, including ultra-high performance liquid chromatography (UHPLC), ion exchange chromatography (IEX) and imaged capillary isoelectric focusing (icIEF). The integrated methodology focuses on the importance of cutting-edge icIEF-MS online coupling and icIEF fractionation applied to revealing the heterogeneity secret of SARS-CoV-2 recombinant vaccine.

Ferroptosis mediated by TNFSF9 interferes in acute ischaemic stroke reperfusion injury with the progression of acute ischaemic stroke.

In this study, we investigated the potential involvement of TNFSF9 in reperfusion injury associated with ferroptosis in acute ischaemic stroke patients, mouse models and BV2 microglia. We first examined TNFSF9 changes in peripheral blood from stroke patients with successful reperfusion, and constructed oxygen-glucose deprivation-reperfusion (OGD-R) on BV2 microglia, oxygen-glucose deprivation for 6 h followed by reoxygenation and re-glucose for 24 h, and appropriate over-expression or knockdown of TNFSF9 manipulation on BV2 cells and found that in the case of BV2 cells encountering OGD-R over-expression of TNFSF9 resulted in increased BV2 apoptosis. Still, the knockdown of TNFSF9 ameliorated apoptosis and ferroptosis. In an in vivo experiment, we constructed TNFSF9 over-expression or knockout mice by intracerebral injection of TNFSF9-OE or sh-TNFSF9 adenovirus. We performed the middle cerebral artery occlusion (MCAO) model on day four, 24 h after ligation of the proximal artery, for half an hour to recanalize. As luck would have it, over-expression of TNFSF9 resulted in increased brain infarct volumes, neurological function scores and abnormalities in TNFSF9-related TRAF1 and ferroptosis-related pathways, but knockdown of TNFSF9 improved brain infarcts in mice as well as reversing TNFSF9-related signalling pathways. In conclusion, our data provide the first evidence that TNFSF9 triggers microglia activation by activating the ferroptosis signalling pathway following ischaemic stroke, leading to brain injury and neurological deficits.

Structure and function analyses of the SRC gene in Pacific white shrimp Litopenaeus vannamei.

SRC gene encodes scavenger receptor class C, a member of the scavenger receptor family, and has only been identified and investigated in invertebrates. Our previous studies have revealed that SRC is a novel candidate gene associated with body weight in Pacific white shrimp (Litopenaeus vannamei). In order to comprehend the underlying mechanism by which LvSRC affects shrimp growth, we analyzed the structure, phylogeny, expression profiles and RNA interference (RNAi) of this gene in L. vannamei. We found that LvSRC contains two CCP domains and one MAM domain, with the highest expression level in the heart and relatively low expression level in other tissues. Notably, LvSRC exhibited significantly higher expression levels in the fast-growing group among groups with different growth rates, suggesting its potential involvement as a gene contributing to the growth of L. vannamei. RNAi of LvSRC inhibited body length and body weight gain compared to the control groups. Moreover, through RNA-seq analysis, we identified 598 differentially expressed genes (DEGs), including genes associated with growth, immunity, protein processing and modification, signal transduction, lipid synthesis and metabolism. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant changes in the signaling pathways related to growth, lipid metabolism and immune response, suggesting that LvSRC exhibits the potential to participate in diverse physiological processes and immune regulation. These findings deepen our understanding of the structure and function of the SRC in shrimp and lay the foundation for further research into the regulatory mechanism of LvSRC. Additionally, they provide potential applications in shrimp genetics and breeding.

Effect of Clot Burden Score on Safety and Efficacy of Intravenous Alteplase Prior to Mechanical Thrombectomy in Acute Ischemic Stroke: A Subgroup Analysis of a Randomized Phase 3 Trial.

BACKGROUND AND PURPOSE: Whether thrombus burden in acute ischemic stroke modify the effect of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remains uncertain. We aim to investigate the treatment effect of stratified clot burden score (CBS) on the efficacy and safety of direct versus bridging MT. MATERIALS AND METHODS: This is an exploratory subgroup analysis of a randomized trial evaluating the effect of CBS on clinical outcome in the DIRECT-MT trial. CBS was divided into 3 groups (0-3, 4-6, and 7-10) based on preoperative CTA, where higher scores indicated a lower clot burden. We report the adjusted common odds ratio for a shift toward better outcomes on the mRS after thrombectomy alone compared with combination treatment by stratified CBS groups. RESULTS: No modification effect of mRS distribution was observed by CBS subgroups (CBS 0-3: adjusted common ratio odds 1.519 [95% CI, 0.928-2.486]; 4-6: 0.924 [0.635-1.345]; 7-10: 1.040 [0.481-2.247]). Patients with CBS 4-6 had a higher rate of early reperfusion (adjusted OR (aOR), 0.3 [95% CI, 0.1-0.9]), final reperfusion (aOR 0.5 [95% CI, 0.3-0.9]), and fewer thrombectomy attempts (aOR 0.4 [95% CI, 0.1-0.7]). Patients with CBS 7-10 had a higher rate of asymptomatic intracranial hemorrhage (14.9% versus 36.8%, P = .0197) for bridging MT. No significant difference was observed in other safety outcomes by trichotomized CBS. CONCLUSIONS: The subgroup analysis of DIRECT-MT suggested that thrombus burden did not alter the treatment effect of IVT before MT on functional outcomes in CBS subgroups.

Self-Enhancement of Perfluorinated Sulfonic Acid Proton Exchange Membrane with Its Own Nanofibers.

High-performance proton exchange membrane (PEM) is crucial for the proton exchange membrane fuel cell (PEMFC). Herein, a novel "self-enhanced" PEM is fabricated for the first time, which is composed of perfluorinated sulfonic acid (PFSA) resin and its own nanofibers as reinforcement. With this strategy, the interfacial compatibility issue of conventional fiber-reinforced membranes is fully addressed and up to 80 wt% loading of PFSA nanofibers can be incorporated. Furthermore, on account of chain orientation within the PFSA nanofiber, single fiber exhibits super-high conductivity of 1.45 S cm-1, leading to state-of-the-art proton conductivity (1.1 S cm-1) of the as-prepared "self-enhanced" PEM so far, which is an order of magnitude increase compared with the bulk PFSA membrane (0.29 S cm-1). It surpasses any commercial PEM including the popular GORE-SELECT and Nafion HP membranes and is the only PEM with conductivity at 100 S cm-1 level. In addition, the mechanical strength and swelling ratio of membranes are both substantially improved simultaneously. Based on the high-performance "self-enhanced" PEM, high peak power densities of up to 3.6 W cm-2 and 1.7 W cm-2 are achieved in H2-O2 and H2-Air fuel cells, respectively. This strategy can be applied in any polymeric electrolyte membrane.