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Background: Coronary atherosclerosis (CAS) is a complex chronic inflammatory disease with significant genetic and environmental contributions. While genome-wide association studies (GWAS) have pinpointed many risk loci, over 75 % are in non-coding regions, complicating functional analysis and understanding gene-disease mechanisms. Methods: We conducted a cross-tissue transcriptome-wide association study (TWAS) using data from the GWAS Catalog (16,041 cases, 440,307 controls) and the Genotype-Tissue Expression (GTEx) v8 eQTL dataset. Initially, we used the Unified Test for Molecular Signatures (UTMOST) for analysis, followed by validation with Functional Summary-based Imputation (FUSION) and conditional and joint (COJO) analyses. Candidate genes were further refined using Multi-marker Analysis of Genomic Annotation (MAGMA). Causal relationships were assessed through Summary Data-Based Mendelian Randomization (SMR), colocalization analysis (COLOC), and Mendelian Randomization (MR). GeneMANIA was used to identify interacting genes, and Phenome-Wide Association Study (PheWAS) was employed to enhance the results. Results: UTMOST identified 33 susceptibility genes for CAS. Out of these, 17 met stringent criteria in both UTMOST and FUSION analyses. Combining results from UTMOST, FUSION, and MAGMA, we identified four critical candidate genes. WDPCP was the only gene to pass SMR, COLOC, and MR analyses, confirming its causal role in CAS. GeneMANIA revealed additional interacting genes, and PheWAS validated WDPCP's role as a susceptibility gene. Conclusion: WDPCP is a potential novel susceptibility gene for CAS, influencing endothelial function, lipid metabolism, and coronary artery development. This study extends GWAS findings, highlighting WDPCP's potential as a therapeutic target and its consistent expression across different tissues. Further validation studies are warranted.

High nitrogen austenitic stainless steels (HNASSs) have received widespread attention owing to their outstanding corrosion resistance, excellent weldability and workability. However, these materials usually exhibit insufficient yield strength to satisfy the requirement in service because of their face-centered cubic (fcc) structure. Here, we report a novel material design strategy of constructing both grain-scaled and atomic-scaled heterostructure through applying appropriate thermo-mechanical treatment to improve the comprehensive mechanical properties of HNASS. The optimal comprehensive mechanical properties with a yield strength of 1361 MPa and a uniform elongation of 10.6% are achieved. The results show that the ultrahigh yield strength mainly originates from the lath structure consisting of local chemical order domains (∼490 MPa), and the satisfactory ductility benefits from both deformation twinning and dislocation slip. This work proposes for the first time the strategy to improve mechanical properties of HNASS by introducing the multi-scaled heterostructure, and guides the development of high-performance steels and many other advanced fcc materials.

Background: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials. Methods: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was “(romosozumab) AND (osteoporosis OR safety)”. Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale. Results: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51–12.57; p

Background: The interaction between muscle and bone is shown to be clinically important but the underlying mechanisms are largely unknown. The canonical Wnt/β-catenin signaling pathway is reported to be involved in muscle-bone crosstalk, but its detailed function remains unclear. This systematic review aims to investigate and elucidate the role of the Wnt/β-catenin signaling pathways in muscle-bone crosstalk. Methods: We conducted a literature search on the Web of Science, PubMed, EBSCO and Embase with keywords “Wnt*”, “bone*” and “muscle*”. A systematic review was completed according to the guideline of preferred reporting items of systematic reviews and meta-analyses (PRISMA). Data synthesis included species (human, animal or cell type used), treatments involved, outcome measures and key findings with respect to Wnts. Results: Seventeen papers were published from 2007 to 2021 and were extracted from a total of 1529 search results in the databases of Web of Science (468 papers), PubMed (457 papers), EBSCO (371) and Embase (233). 12 Wnt family members were investigated in the papers, including Wnt1, Wnt2, Wnt2b, Wnt3a, Wnt4, Wnt5a, Wnt8a, Wnt8b, Wnt9a, Wnt10a, Wnt10b and Wnt16. Many studies showed that muscles were able to increase or decrease osteogenesis of bone, while bone increased myogenesis of muscle through Wnt/β-catenin signaling pathways. Wnt3a, Wnt4 and Wnt10b were shown to play important roles in the crosstalk between muscle and bone. Conclusions: Wnt3a, Wnt4 and Wnt10b are found to play important mediatory roles in muscle-bone crosstalk. The role of Wnt4 was mostly found to regulate muscle from the bone side. Whilst the role of Wnt10b during muscle ageing was proposed, current evidence is insufficient to clarify the specific role of Wnt/β-catenin signaling in the interplay between sarcopenia and osteoporosis. More future studies are required to investigate the exact regulatory roles of Wnts in muscle-bone crosstalk in musculoskeletal disease models such as sarcopenia and osteoporosis. Translational potential of this article: The systematic review provides an extensive overview to reveal the roles of Wnt/β-catenin signaling pathways in muscle-bone crosstalk. These results provide novel research directions to further understand the underlying mechanism of sarcopenia, osteoporosis, and their crosstalk, finally helping the future development of new therapeutic interventions.

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.The Translational Potential of this Article.Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

Background: Homeostatic dysregulation (HD), the measure of aging-related physiological dysregulation, serves as an essential intervenable indicator of aging. Objective: To explore the associations of three healthy dietary patterns with HD, investigate the most recommended dietary patterns, and identify the significant beneficial and harmful food groups Methods: This prospective cohort study included 8,288 participants aged 30–79 years from the China Multi-Ethnic Cohort (CMEC), with a female majority (61.6%). Dietary information was obtained through the baseline food frequency questionnaire (FFQ). Three dietary patterns were constructed: Dietary Approaches to Stop Hypertension (DASH), alternative Mediterranean diets (aMED), and Healthy Diet Score (HDS). HD was constructed based on clinical biomarkers and anthropometric measurements. Follow-up analyses adjusted for baseline data were employed to assess the longitudinal associations of three dietary patterns at baseline with HD at follow-up. Additionally, quantile G-computation was utilized to evaluate the relative contribution of each food group to the association with HD. Results: Over a follow-up period of 2.0 years, all healthy dietary patterns exhibited negative associations with HD, with βQ5/Q1 = −0.112, 95%CI (−0.172, −0.051) for HDS, with βQ5/Q1 = −0.073, 95%CI (−0.134, −0.012) for aMED, with βQ5/Q1 = −0.047, 95%CI (−0.107,0.014) for DASH. The results of the component analyses revealed that soybean products were the most significant beneficial food group (relative contribution of 24.0%), while alcohol was identified as the major harmful food group (relative contribution of 76.9%). Conclusion: Healthy dietary patterns, especially HDS, are negatively associated with HD. Additionally, soybean products and alcohol are the most significant beneficial and detrimental food groups respectively. Developing appropriate nutritional strategies may help reduce the burden of disease and promote healthy aging.

Increasing evidence indicates that 2-hydroxyglutarate (2HG) is an oncometabolite that drives tumour formation and progression. Due to mutations in isocitrate dehydrogenase (IDH) and the dysregulation of other enzymes, 2HG accumulates significantly in tumour cells. Due to its structural similarity to α-ketoglutarate (αKG), accumulated 2HG leads to the competitive inhibition of αKG-dependent dioxygenases (αKGDs), such as KDMs, TETs, and EGLNs. This inhibition results in epigenetic alterations in both tumour cells and the tumour microenvironment. This review comprehensively discusses the metabolic pathways of 2HG and the subsequent pathways influenced by elevated 2HG levels. We will delve into the molecular mechanisms by which 2HG exerts its oncogenic effects, particularly focusing on epigenetic modifications. This review will also explore the various methods available for the detection of 2HG, emphasising both current techniques and emerging technologies. Furthermore, 2HG shows promise as a biomarker for clinical diagnosis and treatment. By integrating these perspectives, this review aims to provide a comprehensive overview of the current understanding of 2HG in cancer biology, highlight the importance of ongoing research, and discuss future directions for translating these findings into clinical applications.

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Biochar has been recognised as an efficacious amendment for the remediation of compound heavy metal contamination in soil. However, the molecular mechanism of biochar-mediated tolerance to compound heavy metal toxicity in cotton is unknown. The objective of this research was to investigate the positive impact of biochar (10 g·kg−1) on reducing damage caused by compound heavy metals (Cd, Pb, and As) in cotton (Gossypium hirsutum L.). The results revealed that biochar reduced Cd concentrations by 24.9 % (roots), and decreased Pb concentrations by 37.1 % (roots) and 59.53 % (stems). Biochar maintained ionic homoeostasis by regulating the expression of metal transporter proteins such as ABC, HIPP, NRAMP3, PCR, and ZIP, and genes related to the carbon skeleton and plasma membrane. Biochar also downregulated genes related to photosynthesis, thereby increasing photosynthesis. Biochar re-established redox homoeostasis in cotton by activating signal transduction, which regulated the activity of the enzymes POD, SOD, and CAT activity; and the expression of related genes. This research revealed the molecular mechanism by which biochar confers resistance to the harmful effects of compound heavy metal toxicity in cotton. The application of biochar as a soil amendment to neutralise the toxicity of compound heavy metals is recommended for cash crop production.

Sensory analysis is an interdisciplinary field that combines multiple disciplines to analyze food qualitatively and quantitatively. At present, this analysis method has been widely used in product development, quality control, marketing, flavor analysis, safety supervision and inspection of alcoholic beverages. Due to the changing needs of analysis, new and more optimized methods are still emerging. Thereinto, intelligent and biometric technologies with growing attention have also been applied to sensory analysis. This work summarized the sensory analysis methods from three aspects, including traditional artificial sensory analysis, intelligent sensory technology, and innovative technologies. Meanwhile, the application sensory analysis in alcoholic beverages and its industrial production was scientifically emphasized. Moreover, the future tendency of sensory analysis in the alcoholic beverage industry is also highlights.

The neuromuscular junction (NMJ) is a specialized chemical synapse that converts neural impulses into muscle action. Age-associated NMJ degeneration, which involves nerve terminal and postsynaptic decline, denervation, and loss of motor units, significantly contributes to muscle weakness and dysfunction. Although physical training has been shown to make substantial modifications in NMJ of both young and aged animals, the results are often influenced by methodological variables in existing studies. Moreover, there is still lack of strong consensus on the specific effects of exercise on improving the morphology and function of the ageing NMJ. Consequently, the purpose of this study was to conduct a systematic review to elucidate the effects of exercise training on NMJ compartments in the elderly.We conducted a systematic review using PubMed, Embase, and Web of Science databases, employing relevant keywords. Two independent reviewers selected studies that detailed NMJ changes during exercise in ageing, written in English, and available in full text.In total, 20 papers were included. We examined the altered adaptation of the NMJ to exercise, focusing on presynaptic and postsynaptic structures and myofibers in older animals or humans. Our findings indicated that aged NMJs exhibited different adaptive responses to physical exercise compared to younger counterparts. Endurance training, compared with resistance and voluntary exercise regimens, was found to have a more pronounced effect on NMJ structural remodeling, particularly in fast twitch muscle fibers. Physical exercise was observed to promote the formation and maintenance of acetylcholine receptor (AChR) clusters by increasing the recombinant docking protein 7 (Dok7) expression and stabilizing Agrin and lipoprotein receptor-related protein 4 (LRP4). These insights suggest that research on exercise-related therapies could potentially attenuate the progression of neuromuscular degeneration.Translational potential of this article: This systematic review provides a detailed overview of the effects of different types of physical exercise on improving NMJ in the elderly, providing scientific support for the timely intervention of muscle degeneration in the elderly by physical exercise, and providing help for the development of new therapeutic interventions in the future.

The purpose of this paper is to evaluate the effect of different exercise therapy on patients with chronic neck pain. By searching PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, WanFang Data and other databases, we screened the literatures that met the inclusion criteria until June 2022. RCT bias risk assessment tool recommended in Cochrane manual was used to evaluate the literature quality, and Stata16.0 software was used for mesh meta-analysis. A total of 76 studies, 12 exercise therapies and 5219 participants were included. In terms of pain, Pilates [MD ​= ​−2.71,95%CI (−3.87, −1.55), P ​= ​0.000] had the most significant effect. Second training for the stability of [MD ​= ​-2.39, 95 ​% CI (−3.14, −1.64), P ​= ​0.000) and VR [MD ​= ​−2.35, 95 ​% CI (−3.6, −1.11), P ​= ​0.000). In terms of functional indexes, respiratory training [MD ​= ​−16.31,95%CI (−28.52, −4.1), P ​= ​0.009] had the most significant effect. Secondly for muscle energy technology [MD ​= ​−7.47, 95 ​% CI (−12.37, −2.58), P ​= ​0.003) and aerobic training [MD ​= ​−7.36, 95 ​% CI (−12.56, −2.16), P ​= ​0.006]. Current evidence shows that Pilates, stability training and virtual reality training are the most effective in pain intervention, muscle energy technology and comprehensive exercise training are outstanding in helping functional recovery, suggesting that appropriate exercise therapy should be implemented according to the symptoms of patients to achieve the best treatment effect.

The response to climate change and air pollution control demonstrates strong synergy across scientific mechanisms, targets, strategies, and governance systems. This report, based on a monitoring indicator system for coordinated governance of air pollution and climate change, employs an interdisciplinary approach combining natural and social sciences. It establishes 20 indicators across five key areas: air pollution and climate change, governance systems and practices, structural transformation and technologies, atmospheric components and emission reduction pathways, and health impacts and co-benefits. This report tries to provide actionable insights into the interconnectedness of air pollution and climate governance. It highlights key policy gaps, presents updated indicators, and offers a refined monitoring framework to track progress toward China's dual goals of reducing emissions and improving air quality. Compared to previous editions, this year's report has updated four key indicators: meteorological impacts on air quality, climate change and its effects, governance policies, and low-carbon building energy systems. The aim is to further refine the monitoring framework, track progress, and establish a comprehensive theory for collaborative governance while identifying challenges and proposing solutions for China's pathway to carbon neutrality and clean air. The report comprises six chapters. The executive summary chapter is followed by analyzing air pollution and climate change interactions. Governance systems and practices are discussed in the third chapter, focusing on policy implementation and local experiences. The fourth chapter addresses structural transformations and emission reduction technologies, including energy and industrial shifts, transportation, low-carbon buildings, carbon capture and storage, and power systems. The fifth chapter outlines atmospheric component dynamics and emission pathways, presenting insights into emission drivers and future strategies. The sixth chapter assesses health impacts and the benefits of coordinated actions. Since 2019, China Clean Air Policy Partnership has produced annual reports on China's progress in climate and air pollution governance, receiving positive feedback. In 2023, the report was co-developed with Tsinghua University's Carbon Neutrality Research Institute, involving over 100 experts and multiple academic forums. The collaboration aims to continuously improve the indicator system and establish the report as a key resource supporting China's efforts in pollution reduction, carbon mitigation, greening, and sustainable growth.

Efforts to enhance the performance of thermoelectric generators (TEGs) in engine waste heat recovery have primarily focused on directly increasing energy conversion efficiency. Heat leakage can occur in many parts of a TEG. It is needed to develop a model to help researchers study this phenomenon and propose measures to reduce heat leakage. To address this gap, this study establishes and validates a computational fluid dynamic (CFD) and finite element (FE) coupled model based on a TEG prototype and its engine test bench. Unlike other models, this approach captures the intricate dynamics of heat propagation from the TEG via air gaps, encompassing conduction, convection, and radiation. Comprehensive analysis reveals that heat leakage accounts for approximately 11% of TEG power output loss. Ignoring the impact of heat leakage can lead to an overestimation of TEG power output. Key areas of heat leakage are identified, and numerical factors influencing this phenomenon are explored. Vertical TEG placement and optimal spacing between thermoelectric modules emerge as effective strategies for mitigating the impact of heat leakage on power output. Leveraging these insights, strategic thermoelectric module placement, vertical TEG orientation, and the application of thermal insulation materials to the heat exchanger are proposed as measures to enhance TEG power output by approximately 5%. The experimental and numerical results underscore the feasibility of optimizing TEGs from the perspective of heat leakage, a crucial aspect previously overlooked. These findings provide valuable insights for future TEG optimization endeavors, highlighting the importance of addressing heat leakage to maximize TEG performance.

Background: Ferroptosis and disulfidptosis are regulatory forms of cell death that play an important role in tumorigenesis and progression. However, few biomarkers about disulfidptosis and ferroptosis related genes (DFRGs) have been developed to predict the prognosis of bladder cancer (BC). Methods: We conducted a bioinformatics analysis using public BC datasets to examine the prognostic significance of differentially expressed DFRGs. A Lasso regression was employed to create a prognostic prediction model from these DFRGs. Hub DFRGs that play a role in immunotherapy response and immunoregulation were pinpointed. Immunohistochemistry (IHC) experiment was performed to assess NUBPL and c-MYC expression in BC patients who underwent surgery or received immune checkpoint inhibitor (ICI) immunotherapy at Peking University Cancer Hospital. Results: We constructed a valid model to predict the prognosis of BC based on DFRGs and performed relevant validation, the results demonstrated that the model was an independent prognostic factor for BC. Further analysis indicated that the model score, combined with the expression of various immune factors and tumor mutation burden (TMB), could predict the prognosis for BC. In addition, we also found that NUBPL was strongly associated with prognosis and response to ICI treatment, and NUBPL may influence BC malignant progression through the c-MYC pathway. Conclusions: Our research findings highlight the satisfactory predictive value of DFRGs in the immune microenvironment and suggest that NUBPL may be a highly promising biomarker for predicting the prognosis and efficacy of ICI treatment in BC patients.

Extremely high temperatures have become a major hurdle to tourists' experiences in various destinations. In this study, we present the first nationwide estimation of the temperature-tourism response function using a fine-grained panel dataset constructed by matching tourism data and daily meteorological datasets for 280 cities from 2005 to 2019 in China. Results show a non-linear relationship between temperature and tourism employing the temperature bins method, which is not sensitive to response equations. In addition, we conduct a rich heterogeneity analysis in the article to further analyse the effects of other external conditions on the temperature-tourism relationship, including the destination's level of tourism economic development, population, infrastructure development, and tourism resource endowment. We also observed that increasing summer temperatures result in decreased tourism arrivals and revenue, while rising autumn temperatures lead to increased tourism arrivals and revenue. This research contributes to a deeper understanding of the complex relationship between temperature dynamics and tourism patterns, offering insights into destination management and adaptation strategies.

Summary: Injury is common in the life of organisms. Because the extent of damage cannot be predicted, injured organisms must determine how much tissue needs to be restored. Although it is known that amputation position affects the regeneration speed of appendages, mechanisms conveying positional information remain unclear. We investigated tissue dynamics in regenerating caudal fins of the African killifish (Nothobranchius furzeri) and found position-specific, differential spatial distribution modulation, persistence, and magnitude of proliferation. Single-cell RNA sequencing revealed a transient regeneration-activated cell state (TRACS) in the basal epidermis that is amplified to match a given amputation position and expresses components and modifiers of the extracellular matrix (ECM). Notably, CRISPR-Cas9-mediated deletion of the ECM modifier sequestosome 1 (sqstm1) increased the regenerative capacity of distal injuries, suggesting that regeneration growth rate can be uncoupled from amputation position. We propose that basal epidermis TRACS transduce positional information to the regenerating blastema by remodeling the ECM.

Summary: Increasing air pollution could undermine human health, but the causal link between air pollution and eye and ear health has not been well-studied. Based on four-week-level records of eye and ear health over 1991–2015 provided by the China Health and Nutrition Survey, we estimate the causal effect of air pollution on eye and ear health. Using two-stage least squares estimation, we find that eye or ear disease possibility rises 1.48% for a 10 μg/m3 increase in four-week average PM2.5 concentration. The impacts can last about 28 weeks and will be insignificant afterward. Females, individuals aged 60 years and over, with high exposure environments, relatively poor economic foundations, and low knowledge levels are more vulnerable to such negative influences. Behavioral channels like more smoking activities and less sleeping activities could partly explain this detrimental effect. Our findings enlighten how to minimize the impact of air pollution and protect public health.

Influenced by the water design principle of Chinese classical garden, the design of urban waterbodies (lakes, ponds and wetlands) in China typically exhibits natural-like morphological characteristics, but what similarities and differences among these characteristics remain unclear. Also, the morphology of urban waterbodies is mostly designed with beauty and lacks quantitative research and methodological support, which is not favourable to the exploration of the correlation between waterbody morphology and ecology. In this study, 11 quantifiable morphological indicators are selected from water surface, shoreline complexity and water-land spatial morphology. A Grasshopper-based model for waterbody morphology quantification and analysis was constructed and applied to 42 cases in China. Combined with frequency, correlation and PCA analysis, the cases and indicators with higher composite scores generally showed more natural water surface morphology, island distribution, and diversified land and water spaces. The thresholds for the more representative indicators are 0.10–0.60 for the circularity ratio (C), 1.01–1.15 for the shoreline fractal dimension (D0), 1.58–29.42 for the island nearest-neighbour index (NN), 1.20–2.50 for the shoreline development index (SDI), 0.20–0.55 for the compactness ratio (Rc) and 0.30–0.85 for the unit water surface morphological difference ratio (ΔB). Focusing on these indicators, along with ΔB and I which describe spatial inclusiveness and island distribution, their regression equations and threshold ranges provide a primary basis for developing waterbody morphology designs and generative algorithms. This methodology has been experimentally applied in the design of a case waterbody in Suqian City Park. Overall, this study constructs and validates the feasibility of a Grasshopper-based algorithm for the quantitative analysis and morphogenetic design of waterbody morphology. It demonstrates the potential of this method for understanding complex waterbody morphology and water-land spaces, and supports a new digital methodology for the optimisation of waterscape design.

The aim of this study was to investigate the global epidemiological trends in the incidence and deaths of acute respiratory infections (ARIs), encompassing both upper respiratory infections (URIs) and lower respiratory infections (LRIs), from 1990 to 2021. Using data from the Global Burden of Disease study 2021 (GBD 2021), we utilized the average annual percentage change (AAPC) to examine the trends in the age-standardized incidence rate and deaths rate (ASIR and ASDRs) of URIs and LRIs. In 2021, the global ASIR of URIs and LRIs were 166,770.73 (95 % UI: 148,098.16–189,487.93) per 100,000 and 4283.61 (95 % UI: 4057.03–4524.89) per 100,000, respectively. The highest ASIR of URIs occurred in high-sociodemographic index (SDI) regions (232744.64, 95 % UI: 206887.07–261694.81) per 100,000, whereas LRIs occurred in low-SDI regions (9261.1, 95 % UI: 8741.61–9820.86) per 100,000. In 2021, the global ASDRs of URIs and LRIs were 0.28 (95 % UI: 0.09–0.61) per 100,000 and 28.67 (95 % UI: 25.92–31.07) per 100,000, respectively. The highest ASDRs of both URIs and LRIs were observed in low-SDI regions, with 1.1 (95 % UI: 0.08–2.78) per 100,000 and 70.68 (95 % UI: 62.56–78.62) per 100,000, respectively. From 1990 to 2021, the global ASIR for URIs and LRIs decreased, with AAPCs of −0.17 % (95 % CI: 0.17 % to −0.16 %) and −1.28 % (95 % CI: −1.37 % to −1.22 %), respectively. The global ASDRs also decreased (−3.39 % for URIs; −2.46 % for LRIs). However, during the COVID-19 pandemic, the ASIR of URIs increased in many countries, especially in high-SDI regions (rate difference before and during the COVID-19 pandemic in ASIR was 2210.19 per 100,000.) and low-SDI regions (rate difference in ASIR: 111.26 per 100,000). The global incidence and deaths related to ARIs have decreased over the past 32 years. However, it remains a significant public health concern, particularly due to the notable incidence of URIs in high SDI regions and the deaths associated with both URIs and LRIs in low SDI regions. Furthermore, an increase in the incidence of URIs was observed in both high- and low-SDI regions during the COVID-19 pandemic, highlighting the need for increased attention.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes, and its pathogenesis remains elusive. Ferroptosis, a process dependent on iron-mediated cell death, plays a crucial role in DCM via disrupted iron metabolism, lipid peroxidation, and weakened antioxidant defenses. Hyperglycemia, oxidative stress, and inflammation may exacerbate ferroptosis in diabetes. This review emphasizes the interaction between cardiac fibroblasts and cardiomyocytes in DCM, influencing ferroptosis occurrence. By exploring ferroptosis modulation for potential therapeutic targets, this article offers a fresh perspective on DCM treatment. The study systematically covers the interplay, mechanisms, and targeted drugs linked to ferroptosis in DCM development.

Desert grassland is an essential component of the northern grasslands of China, representing an ecosystem that transitions from grassland to desert. However, it is a fragile ecological environment. Evaluating degraded grassland ecosystems is a prerequisite for degradation prevention and management. However, a systematic and standardized evaluation system for the fragile ecosystems of desert grassland ecological regions in China is lacking. Therefore, to accurately identify the degree of desert grassland degradation, this study selected 66 sample plots in Otog Banner and, using the analytic hierarchy process-entropy method, established a comprehensive evaluation system for desert grasslands. Using nine vegetation indices extracted from unmanned aerial vehicle multispectral imagery, we employed machine learning regression algorithms to develop a model for assessing grassland degradation features. The results indicated that the primary factor influencing grassland degradation was the land condition layer, followed by the resilience layer. The regression model constructed using the random forest algorithm demonstrated optimal performance in grassland degradation evaluation, with correlation coefficients of 0.981 and 0.942. Finally, we established a high-precision grassland degradation assessment model with an average relative error of 9.49%, offering a novel approach for the rapid diagnosis of grassland degradation through remote sensing macroscopic evaluation.

Background: Colorectal cancer (CRC) is a prevalent cause of death from malignant tumors. This study aimed to develop a nicotinamide adenine dinucleotide (NAD+) metabolism and immune-related prognostic signature, providing a theoretical foundation for prognosis and therapy in CRC patients. Methods: NAD + metabolism-related and immune-related subtypes of CRC patients were identified by consistent clustering. Differentially expressed genes (DEGs) between the two subtypes of CRC were identified by overlapping. A risk signature was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Independent prognostic predictors were authenticated by Cox analysis. Gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) were applied to investigate the connection between the prognostic signature and the immune microenvironment. Chemotherapy drug sensitivity and immunotherapy responsiveness were projected using the ‘pRRophetic’ package and Tumor Immune Dysfunction and Exclusion (TIDE) website. The Human Protein Atlas (HPA) database was used to assess the protein expression of prognostic genes in CRC and normal tissues. Results: Using bioinformatics methods, three prognostic genes related to immune-related NAD + metabolism were identified, and the results were used to establish and verify a prognostic signature related to immune-related NAD + metabolism in CRC patients. Cox regression analysis confirmed that the risk score was a reliable independent prognostic predictor. GSVA and ssGSEA indicated that the prognostic signature was associated with the immune microenvironment. TIDE analysis suggested that the signature might act as an immunotherapy predictor. Chemotherapy sensitivity analysis revealed that COMP was correlated with chemotherapy sensitivity in CRC patients and might be a potential therapeutic target. Conclusion: This study identified NAD + metabolism-immune-related prognostic genes (MOGAT2, COMP, and DNASE1L3) and developed a prognostic signature for CRC prognosis, which is significant for clinical prognosis prediction and treatment strategy decisions for CRC patients.

Wind power exhibits low controllability and is situated in dispersed geographical locations, presenting complex coupling and aggregation characteristics in both temporal and spatial dimensions. When large-scale wind power is integrated into the power grid, it will bring a significant technical challenge: the highly variable nature of wind power poses a threat to the safe and stable control of the power, frequency, and voltage in the power system. Simultaneously, the model predictive control (MPC) technology provides more opportunities for investigating control issues related to large-scale wind power integration in power systems. This paper provides a timely and systematic overview of the applications of MPC in the field of wind power for the first time, innovatively embedding MPC technology into multi-level (e.g., wind turbines, wind farms, wind power cluster, and power grids) and multi-objective (e.g., power, frequency, and voltage) control. Firstly, the basic concept and classification criteria of MPC are developed, and the available modeling methods in wind power are carefully compared. Secondly, the application scenarios of MPC in multi-level and multi-objective wind power control are summarized. Finally, how to use a variety of optimization algorithms to solve these models is discussed. Based on the broad review above, we summarize several key scientific issues related to predictive control and discuss the challenges and future development directions in detail. This paper details the role of MPC technology in multi-level and multi-objective control within the wind power sector, aiming to help engineers and scientists understand its substantial potential in wind power integration in power systems.

Studies have demonstrated that donkey milk (DM) displays anti-tumor activity. In this study, we investigated the role and underlying mechanism of DM in the progression of 4T1 breast tumors in mice. We found that DM significantly reduced tumor volumes and tumor weights in 4T1-treated mice. Simultaneously, DM ameliorated the pathological changes in spleen, liver and lung tissues of 4T1 tumor-bearing mice. WB results showed that DM inducing the expression of Bax and pyroptosis-related proteins, and inhibiting the expression of Bcl-2 in tumors. Besides, DM up-regulation of Th1 cytokines and down-regulation of Th2/Treg cytokines in the tumors and spleen. Moreover, DM significantly decreased the ratios of p-JAK2/JAK2, p-STAT3/STAT3, p-STAT5/STAT5, as well as up-regulation the ratio of p-STAT4/STAT4 in tumors and spleen. Our data suggest that DM inhibit the growth of mouse 4T1 tumors by inducing apoptosis and pyroptosis, as well as promoting Th1 cell activation and quelling immunosuppression from Tregs.

Objective: Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models. Methods: A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included. Results: A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag+ and Cu2+; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation. Conclusion: Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing in vivo. Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy. The translational potential of this paper: The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.

High-efficiency and low-cost knowledge sharing can improve the decision-making ability of autonomous vehicles by mining knowledge from the Internet of Vehicles (IoVs). However, it is challenging to ensure high efficiency of local data learning models while preventing privacy leakage in a high mobility environment. In order to protect data privacy and improve data learning efficiency in knowledge sharing, we propose an asynchronous federated broad learning (FBL) framework that integrates broad learning (BL) into federated learning (FL). In FBL, we design a broad fully connected model (BFCM) as a local model for training client data. To enhance the wireless channel quality for knowledge sharing and reduce the communication and computation cost of participating clients, we construct a joint resource allocation and reconfigurable intelligent surface (RIS) configuration optimization framework for FBL. The problem is decoupled into two convex subproblems. Aiming to improve the resource scheduling efficiency in FBL, a double Davidon–Fletcher–Powell (DDFP) algorithm is presented to solve the time slot allocation and RIS configuration problem. Based on the results of resource scheduling, we design a reward-allocation algorithm based on federated incentive learning (FIL) in FBL to compensate clients for their costs. The simulation results show that the proposed FBL framework achieves better performance than the comparison models in terms of efficiency, accuracy, and cost for knowledge sharing in the IoV.

The greenhouse environment represents a dynamic, nonlinear system characterized by hysteresis and is influenced by a myriad of interacting environmental parameters, posing a complex multi-variable optimization challenge. This study proposes a multi-objective adaptive annealing genetic algorithm to optimize above-ground environmental factors in greenhouses, addressing the challenges of variable environmental conditions and extensive heating and humidity infrastructure. Initially, after analyzing the multi-objective model of greenhouse above-ground environmental factors, including temperature, relative humidity, and CO2 concentration, a comprehensive multi-objective, multi-constraint model was developed to encapsulate these factors in greenhouse environments. Subsequently, the model optimization incorporated multi-parameter coding of decision variables, a fitness function, and an annealing dynamic penalty factor. Validation conducted at Yangling Agricultural Demonstration Park revealed that the application of multi-objective adaptive annealing genetic algorithms (schemes 1 and 2) significantly outperformed the single-objective genetic algorithm (scheme 3) and the traditional genetic algorithm (scheme 4). Specifically, the improvements included a reduction in average temperature rise by 2.64 °C and 5.29 °C for schemes 1 and 2, respectively, equating to 20 % and 34 % decreases. Additionally, average humidification reductions of 2.39 % and 3.9 % were observed, alongside decreases in the total lengths of heating and humidification pipes by up to 2.99 km and 0.443 km, respectively, with a maximum reduction of 14 % in heating pipes. The integration of an annealing dynamic penalty factor enhanced the adaptive climbing ability of schemes 1 and 2, improving static stability and robustness. Furthermore, the number of iterations required to achieve convergence was reduced by approximately 170–240 times compared to schemes 3 and 4. This reduction in iterations also resulted in a significant decrease in running time by 5–13 min, corresponding to time savings of 31 %–56 %, thereby achieving further optimization.

High-polarity iridoids from Radix Scrophulariae (R. Scrophulariae) offer a range of benefits, including anti-inflammatory, antioxidant, antitumour, antibacterial, antiviral, and antiallergic effects. Although previous studies have indicated the potential of R. Scrophulariae for hyperthyroidism prevention and treatment, the specific active compounds involved and their mechanisms of action are not fully understood. This study explored the effects of high-polarity iridoid glycosides from R. Scrophulariae on hyperthyroidism induced in rats by levothyroxine sodium. The experimental design included a control group, a hyperthyroidism model group, and a group treated with iridoid glycosides. Serum triiodothyronine (T3) and thyroxine (T4) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Transcriptomic and proteomic analyses were applied to liver samples to identify differentially expressed genes and proteins. These analyses were complemented by trend analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The effectiveness of key factors was further examined through molecular biology techniques. ELISA results indicated a notable increase in T3 and T4 in the hyperthyroid rats, which was significantly mitigated by treatment with iridoid glycosides. Transcriptomic analysis revealed 6 upregulated and 6 downregulated genes in the model group, showing marked improvement following treatment. Proteomic analysis revealed changes in 30 upregulated and 50 downregulated proteins, with improvements observed upon treatment. The PI3K-Akt signalling pathway was investigated through KEGG enrichment analysis. Molecular biology methods verified the upregulation of Spp1, Thbs1, PI3K, and Akt in the model group, which was reversed in the treatment group. This study revealed that highly polar iridoids from R. Scrophulariae can modulate the Spp1 gene and Thbs1 protein via the PI3K-Akt signalling pathway, suggesting a therapeutic benefit for hyperthyroidism and providing a basis for drug development targeting this condition.

Fungal biofilm is a microbial community composed of fungal cells and extracellular polymeric substances (EPS). In recent years, fungal biofilms have played an increasingly important role in many fields. However, there are few studies on fungal biofilms and their related applications and development are still far from enough. Therefore, this review summarizes the composition and function of EPS in fungal biofilms, and improves and refines the formation process of fungal biofilms according to the latest viewpoints. Moreover, based on the study of Saccharomyces cerevisiae and Candida albicans, this review summarizes the gene regulation network of fungal biofilm synthesis, which is crucial for systematically understanding the molecular mechanism of fungal biofilm formation. It is of great significance to further develop effective methods at the molecular level to control harmful biofilms or enhance and regulate the formation of beneficial biofilms. Finally, the quorum sensing factors and mixed biofilms formed by fungi in the current research of fungal biofilms are summarized. These results will help to deepen the understanding of the formation process and internal regulation mechanism of fungal biofilm, provide reference for the study of EPS composition and structure, formation, regulation, group behavior and mixed biofilm formation of other fungal biofilms, and provide strategies and theoretical basis for the control, development and utilization of fungal biofilms.

Carrots as a representative type of delicious and healthy vegetables has become increasingly popular due to its unique flavors and nutritional value. Vast amount of research has been completed on chemical composition and aroma profile of fresh carrot. However, the knowledge of fresh carrot is only scattered. Therefore, a more comprehensive review to fresh carrot is requisite to be reported. This review first describes the botany of carrots; then, the chemical ingredients and their various functions are discussed. The volatile constituents and the effects of terpenoids on aroma profiles of fresh carrot are also discussed. Finally, sources of variation in the formation and development of carrot aroma through heat processing and dehydration are analyzed. This information will further help researchers to solve the problem of insufficient aroma of carrot products and standardize for each type of carrot through improving the production process.

As a local specialty of Tibet, Qingke baijiu (QB) is made from highland barley, and is referred to as the manufacturing process of light-aroma baijiu. Using highland barley in the Qu-making and the high-temperature stacking process of sauce-aroma baijiu results in a novel Qingke baijiu (NQB). This study analyzed two kinds of NQBs by GC-MS, GC×GC-MS, and GC-O-MS, and compared them with QB, light-aroma, strong-aroma, and sauce-aroma baijiu. A total of 346 volatile compounds and 60 aroma-active compounds were detected in NQB. There were 14 compounds with FD≥27 and OAVs ≥1. Although NQB and QB shared 39 volatile compounds, NQB has more than three times the overall concentration of volatile compounds than QB. In contrast to QB, NQB exhibited a richer flavor profile and a more intense fruity, floral, and acidic aroma. Meanwhile, the distilled grains and sorghum aroma were comparatively diminished.

Sinomenine (SIN), an alkaloid derived from the traditional Chinese medicine, Caulis Sinomenii, has been used as an anti-inflammatory drug in China for over 30 years. With the continuous increase in research on the pharmacological mechanism of SIN, it has been found that, in addition to the typical rheumatoid arthritis (RA) treatment, SIN can be used as a potentially effective therapeutic drug for anti-tumour, anti-renal, and anti-nervous system diseases. By reviewing a large amount of literature and conducting a summary analysis of the literature pertaining to the pharmacological mechanism of SIN, we completed a review that focused on SIN, found that the current research is insufficient, and offered an outlook for future SIN development. We hope that this review will increase the public understanding of the pharmacological mechanisms of SIN, discover SIN research trial shortcomings, and promote the effective treatment of immune diseases, inflammation, and other related diseases.

Objective: To explore the preventive effect of electroacupuncture pretreatment on stroke in rats by inhibiting ferroptosis and oxidative stress. Methods: Rats were randomly assigned to the sham, middle cerebral artery occlusion/reperfusion (MCAO/R), MCAO/R + EP, MCAO/R + EP + erastin, and MCAO/R + EP + ferrostatin 1 groups. Daily electroacupuncture was performed 2 weeks before establishing the MCAO/R model utilizing the modified Zea Longa suture method. Rats were sacrificed 1 day after reperfusion, and brain tissues were collected. They were prepared for hematoxylin and eosin staining, prussian blue staining, transmission electron microscope. Measurement of total iron levels using a commercial kit, detection of malondialdehyde (MDA) and superoxide dismutase (SOD) levels by ELISA, and examination of 15-lox2, GPX4, SLC7A11, ACSL4, and TFR1 by western blotting. Results: Compared with sham rats, cerebral infarction size was dramatically larger in MCAO/R rats. Moreover, the MCAO/R group displayed damaged mitochondria with a disarranged structure of cristae; free iron, total iron levels, and oxidative stress were significantly higher. Cerebral pathological lesions, oxidative stress, total iron levels, and protein levels of ACSL4, TFR1, and 15-lox2 were significantly reduced in the MCAO/R + EP and MCAO/R + EP + ferrostatin 1 groups, while the protective effect of electroacupuncture pretreatment on cerebral ischemia-reperfusion injury was inhibited by treatment with the ferroptosis activator erastin. Conclusion: Electroacupuncture pretreatment can protect rats from cerebral ischemia-reperfusion injury by reducing the area of cerebral infarction and inhibiting ferroptosis and oxidative stress.

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly, the exact pathogenesis of which remains incompletely understood, and effective preventive and therapeutic drugs are currently lacking. Cholesterol plays a vital role in cell membrane formation and neurotransmitter synthesis, and its abnormal metabolism is associated with the onset of AD. With the continuous advancement of imaging techniques and molecular biology methods, researchers can more accurately explore the relationship between cholesterol metabolism and AD. Elevated cholesterol levels may lead to vascular dysfunction, thereby affecting neuronal function. Additionally, abnormal cholesterol metabolism may affect the metabolism of β-amyloid protein, thereby promoting the onset of AD. Brain cholesterol levels are regulated by multiple factors. This review aims to deepen the understanding of the subtle relationship between cholesterol homeostasis and AD, and to introduce the latest advances in cholesterol-regulating AD treatment strategies, thereby inspiring readers to contemplate deeply on this complex relationship. Although there are still many unresolved important issues regarding the risk of brain cholesterol and AD, and some studies may have opposite conclusions, further research is needed to enrich our understanding. However, these findings are expected to deepen our understanding of the pathogenesis of AD and provide important insights for the future development of AD treatment strategies targeting brain cholesterol homeostasis.

Background: Lung adenocarcinoma (LUAD) is a pulmonary malignant disease that poses a high risk of mortality and morbidity. Previous study indicated that ORC1 plays an oncogenic function. However, the precise regulatory function that ORC1 serves in the progression of LUAD is still not clearly known. Methods: Bioinformatics analyses were performed using TCGA and GEO datasets. The human LUAD cell line NCIH1355, NCIH1568 as well as BEAS-2B cell line (human normal lung epithelial cell) were utilized for in vitro study. LUAD cell proliferation were determined via CCK-8 assays and RT-qPCR for ki-67. The relation of ORC1 and SLC7A11 was detected by Western blot and qPCR with or without sh-RNA. The expression level ACSL4, the biomarker of ferroptosis, were detected using RT-qPCR. Results: ORC1 and SLC7A11 exhibit high expression levels in both LUAD patients and cell lines, and are strongly associated with poor prognosis. In vitro experiments demonstrate that ORC1 and SLC7A11 promote proliferation of LUAD cell lines while inhibiting gefitinib-induced ferroptosis. Additionally, the function of ORC1 in LUAD cells is dependent on SLC7A11. Conclusion: ORC1 promotes LUAD cell proliferation and inhibits ferroptosis in a SLC7A11-dependent manner. This implies that ORC1 could potentially serve as a useful diagnosis biomarker and treatment target.

China is now confronting the intertwined challenges of air pollution and climate change. Given the high synergies between air pollution abatement and climate change mitigation, the Chinese government is actively promoting synergetic control of these two issues. The Synergetic Roadmap project was launched in 2021 to track and analyze the progress of synergetic control in China by developing and monitoring key indicators. The Synergetic Roadmap 2022 report is the first annual update, featuring 20 indicators across five aspects: synergetic governance system and practices, progress in structural transition, air pollution and associated weather-climate interactions, sources, sinks, and mitigation pathway of atmospheric composition, and health impacts and benefits of coordinated control. Compared to the comprehensive review presented in the 2021 report, the Synergetic Roadmap 2022 report places particular emphasis on progress in 2021 with highlights on actions in key sectors and the relevant milestones. These milestones include the proportion of non-fossil power generation capacity surpassing coal-fired capacity for the first time, a decline in the production of crude steel and cement after years of growth, and the surging penetration of electric vehicles. Additionally, in 2022, China issued the first national policy that synergizes abatements of pollution and carbon emissions, marking a new era for China's pollution-carbon co-control. These changes highlight China's efforts to reshape its energy, economic, and transportation structures to meet the demand for synergetic control and sustainable development. Consequently, the country has witnessed a slowdown in carbon emission growth, improved air quality, and increased health benefits in recent years.

This study investigates the utilization of polyethylene fiber (PEF) and microsilica for the production of high-strength and high-toughness geopolymer concrete (HSHTGC). The influence of the PEF factor or microsilica content on fracture parameters and strength is evaluated, while acoustic emission (AE) response and crack morphologies are employed to validate the fracture performance results. By combing PEF with microsilica, this study successfully prepared HSHTGC with compressive strength exceeding 90 MPa, significant multi-cracking characteristics, as well as high toughness and ductility. The optimal microsilica content and fiber volume fraction are determined to be 32 wt% and 1.5 vol%, respectively. It is observed that when the fiber factor exceeds 800, there is a decline in compressive strength, initiation, and unstable fracture toughness, however, the fracture energy and ductility index consistently increase monotonically. These findings indicate that fiber toughening has a more pronounced effect than fiber strengthening. Moreover, microsilica plays a crucial role in filling voids and improving bonding between fibers and matrix under both tensile and compressive loads throughout the entire process. HSHTGCs with high fiber factors and increased microsilica contents exhibit a multi-cracking mode along with elevated RA values but reduced AF values during failure process, which correspondingly reflect their enhanced toughness.

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Introduction: The COVID-19 pandemic has caused high mortality rates in hip fracture patients, but data for Asian patients are lacking. Whilst Cycle threshold (Ct) values and D-dimer have been reported as predictors of mortality in COVID-19 patients, their prognostic roles in those with concomitant hip fracture remain unknown. The objectives of this study were to i) assess the clinical outcomes of COVID-19 hip fractures patients in the Chinese population, ii) identify risk factors of mortality and complications, and iii) determine the prognostic roles of Ct values and D-dimer levels. Methodology: This cohort study was conducted during the 5th wave of the COVID-19 pandemic. Inclusion criteria were 1) hip fracture 2) ​≥ ​60 years old 3) low-energy trauma. Outcomes were 90-day all-cause mortality, complications, length of stay, discharge destination and mobility status. Logistic regression analysis was performed to identify risk factors for mortality and complications. Subgroup analysis was performed for patients with Ct ​ ​30, comparing their outcomes of operations performed within 48 ​h vs beyond 48 ​h. Results: 159 hip fracture patients were included, 42 patients were COVID-19 positive. COVID-19 group had significantly higher 90-day mortality rates (21.4% vs 9.4%), complication rates (45.2% vs 28.2%) and longer length of stay (17.06 vs 10.84 nights). COVID-19 was an independent risk factor for mortality and complications. Amongst the COVID-19 group, risk factors for poor outcomes were advanced age, steroids use, conservative treatment and American Society of Anaesthesiologists (ASA) score ≥ 3. Conservative treatment was associated with higher mortality (OR ​= ​16.00; p ​= ​0.025) in COVID-19 hip fracture patients. There was no significant difference between Ct values ​30 regarding mortality and complication rate. D-dimer and timing to operation did not affect outcomes. Conclusions: Patients with concomitant COVID-19 and hip fracture are at high risk of mortality and complications. Ct values and D-dimer levels have no prognostic roles for hip fracture outcomes. Early operative treatment is recommended as soon as patients are medically fit.

The effect of grain boundaries on the strength and electrical conductivity of annealed copper wires was studied. After annealing at 100 °C for 30 min, the copper wires retained a fiber-like structure. The increase in electrical conductivity is believed to stem from the decrease of crystallographic defects introduced by drawing. Recrystallization occurred when the annealing temperature reached 150 °C. The formation of small recrystallized grains led to the introduction of additional grain boundaries perpendicular to the drawing direction, resulting in a slight decrease in electrical conductivity. When the annealing temperature rose up to 200 °C, complete recrystallization took place in the copper wires. The grain boundaries parallel to the drawing direction play an important role in boundary strengthening, while the grain boundaries perpendicular to the drawing direction play an important role in both boundary strengthening and electron scattering. The electrical resistivity of grain boundaries in fully recrystallized copper wires at room temperature was determined experimentally, and an empirical relation is proposed to quickly determine the electric conductivity of copper wires at room temperature based on the boundary spacing along the drawing direction.

Osteogenesis imperfecta (OI) is a rare genetic disease characterized by bone fragility and bone formation. Sclerostin could negatively regulate bone formation by antagonizing the Wnt signal pathway, whereas it imposes severe cardiac ischemic events in clinic. Our team has screened an aptamer that could promote bone anabolic potential without cardiovascular risk. However, the affinity of the aptamer is lower and needs to be improved. In the study, hydrophobic quinoline molecule with unique orientations (seven subtypes) were incorporated into key sites of a bone anabolic aptamer against sclerostin to form a modified aptamer library. Among all the quinoline modifications, 5-quinoline modification could shape the molecular recognition of modified aptamers to sclerostin to facilitate enhancing its binding to sclerostin toward the highest affinity by interacting with newly participated binding sites in sclerostin. Further, 5-quinoline modification could facilitate the modified aptamer attenuating the suppressed effect of the transfected sclerostin on both Wnt signaling and bone formation marker expression levels in vitro, promoting bone anabolism in OI mice (Col1a2+/G610C). The proposed quinoline-oriented modification strategy could shape the molecular recognition of modified aptamers to proteins to facilitate enhancing its binding affinity and therapeutic potency.

With the target of achieving carbon peaking and neutrality in the power sector in China, both State Grid and China Southern Power Grid have made plans of a rapid increase of renewables in future years towards 2060. However, considering the interactions between the power system and meteorological, society factors, whether those plans would lead to CO2 emission peak in 2030 and carbon neutrality in 2060 is still questionable and needs further analysis. Therefore, a Power-Meteorology-Society System is formulated and interactions between these factors will impact the CO2 emission of the power system is studied. Case study shows that these environmental, social factors as well as their interactions will have significant negative impact to the CO2 emission reduction in China's power grid; With current trend of generation and transmission development and higher-than-expected CO2 emission, while the grid could still reach its target of carbon peak in 2030, there will be some challenge for the grid to reach carbon neutrality in the year 2060. Based on that, the authors analyze some potential solutions such as transmission construction, energy storage and the Carbon Capture, Utilization and Storage (CCUS), and try to find a relatively cost-benefit path to reach carbon-neutrality for the grid in 2060.

Mangrove wetlands are hotspots of the global nitrogen (N) cycle and important sinks of microplastics (MPs) due to their ecotone location between terrestrial and marine ecosystems. However, the effects of MPs on N cycle processes in mangrove ecosystems are still poorly understood. Thus, the present study assessed the impacts by adding MPs to mangrove sediments in a microcosm incubation experiment. The results showed that MPs increased dissolved organic carbon and nitrate but reduced ammonium contents in the sediments. MPs increased C:N stoichiometric and N:C-acquiring enzymatic ratios, indicating an intensified N limitation in mangrove sediments following exposure of MPs. MPs decreased microbial community diversity and shifted sediment microbial communities from r- to K-strategists, consistent with the intensified N limitation. In response, dissimilatory nitrate reduction to ammonium (DNRA) rates increased while nitrous oxide (N2O) production reduced suggesting more efficient N utilization in MPs treatments. The MPs with heteroatoms such as PLA- and PVC-MPs, increased DNRA rates by 67.5–78.7%, exhibiting a stronger impact than PE-MPs. The variation partitioning analysis revealed that the variances of DNRA rates and N2O production could be attributed to synergistic effects of physicochemical properties, nutrient limitation, and microbial community in mangrove sediments. Overall, this study provides pertinent insights into the impacts of MPs as a new carbon source on nutrient limitation and N turnover in mangrove ecosystems.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a widely used diagnostic and therapeutic procedure. Effective sedation is crucial to enhance patient comfort and optimize endoscopist performance. Various sedation protocols, including Propofol and Dexmedetomidine (Pro-Dex), Ketamine and Propofol (Keto-Fol), Propofol and Midazolam (Pro-Mid), and Propofol alone, have been utilized during ERCP. This retrospective study aims to compare the safety and efficacy of these four sedation protocols. Methods: A retrospective analysis was conducted on data from 600 patients who underwent ERCP between 2018 and 2021, with each patient receiving one of the four sedation protocols. Protocol assignment was based on the endoscopist's preference. Data on hemodynamic parameters, sedation level, recovery time, and procedure-related complications were collected. Results: Baseline data showed no significant differences among the groups pre-procedure. The Pro-Dex group exhibited significantly lower mean total propofol dose, shorter recovery time, and faster achievement of Ramsay Sedation Scale (RSS) score 3–4 compared to the other groups. The Pro-group demonstrated significantly longer hospital stay than the other three groups (median, 4.19 ± 1.1 vs. 3.48 ± 1.2 days in the KP groups, p = 0.042). There were no significant variations in the incidence of respiratory depression, hypotension, or bradycardia among the four groups. Additionally, notable trends were found for hemodynamic measures, total propofol dosage, time to reach the desired level of sedation (as measured by the Ramsay Sedation Scale), and hospital stay based on BMI categories, indicating that higher BMI is linked to more serious outcomes. Conclusion: Our retrospective study demonstrates that the Pro-Dex protocol offers superior sedation quality, faster recovery, and fewer complications compared to the other protocols during ERCP. However, the incidence of ERCP-related adverse events did not significantly differ among the four sedation protocols. These findings can aid clinicians in selecting the most appropriate sedation protocol for ERCP, considering patient and endoscopist preferences.

Background and objective: Cerebral edema (CED) is a serious complication of acute ischemic stroke (AIS), especially in patients with large hemispheric infarction (LHI). Herein, a deep learning-based approach is implemented to extract CSF from T2-Weighted Imaging (T2WI) and evaluate the relationship between quantified cerebrospinal fluid and outcomes. Methods: Patients with acute LHI who underwent magnetic resonance imaging (MRI) were included. We used a deep learning algorithm to segment the CSF from T2WI. The hemispheric CSF ratio was calculated to evaluate its relationship with the degree of brain edema and prognosis in patients with LHI. Results: For the 93 included patients, the left and right cerebrospinal fluid regions were automatically extracted with a mean Dice similarity coefficient of 0.830. Receiver operating characteristic analysis indicated that hemispheric CSF ratio was an accurate marker for qualitative severe cerebral edema (area under receiver-operating-characteristic curve 0.867 [95% CI, 0.781–0.929]). Multivariate logistic regression analysis of functional prognosis showed that previous stroke (OR = 5.229, 95% CI 1.013–26.984), ASPECT≤6 (OR = 13.208, 95% CI 1.136–153.540) and low hemispheric CSF ratio (OR = 0.966, 95% CI 0.937–0.997) were significantly associated with higher chances for unfavorable functional outcome in patients with LHI. Conclusions: Automated assessment of CSF volume provides an objective biomarker of cerebral edema that can be leveraged to quantify the degree of cerebral edema and confirm its predictive effect on outcomes after LHI.

Background & Aims: Thrombospondin-2 (THBS2) expression is associated with liver fibrosis regardless of etiology. However, the role of THBS2 in the pathogenesis of liver fibrosis has yet to be elucidated. Methods: The in vivo effects of silencing Thbs2 in hepatic stellate cells (HSCs) were examined using an adeno-associated virus vector (serotype 6, AAV6) containing short-hairpin RNAs targeting Thbs2, under the regulatory control of cytomegalovirus, U6 or the α-smooth muscle promoter, in mouse models of carbon tetrachloride or methionine-choline deficient (MCD) diet-induced liver fibrosis. Crosstalk between THBS2 and toll-like receptor 4 (TLR4), as well as the cascaded signaling, was systematically investigated using mouse models, primary HSCs, and human HSC cell lines. Results: THBS2 was predominantly expressed in activated HSCs and dynamically increased with liver fibrosis progression and decreased with regression. Selective interference of Thbs2 in HSCs retarded intrahepatic inflammatory infiltration, steatosis accumulation, and fibrosis progression following carbon tetrachloride challenge or in a dietary model of metabolic dysfunction-associated steatohepatitis. Mechanically, extracellular THBS2, as a dimer, specifically recognized and directly bound to TLR4, activating HSCs by stimulating downstream profibrotic focal adhesion kinase (FAK)/transforming growth factor beta (TGF-β) pathways. Disruption of the THBS2-TLR4-FAK/TGF-β signaling axis notably alleviated HSC activation and liver fibrosis aggravation. Conclusions: THBS2 plays a crucial role in HSC activation and liver fibrosis progression through TLR4-FAK/TGF-β signaling in an autocrine manner, representing an attractive potential therapeutic target for liver fibrosis. Impact and implications: Thrombospondin-2 (THBS2) is emerging as a factor closely associated with liver fibrosis regardless of etiology. However, the mechanisms by which THBS2 is involved in liver fibrosis remain unclear. Here, we showed that THBS2 plays a prominent role in the pathogenesis of liver fibrosis by activating the TLR4-TGF-β/FAK signaling axis and hepatic stellate cells in an autocrine manner, providing a potential therapeutic target for the treatment of liver fibrosis.