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Introduction Antithrombin (AT) deficiency, often caused by mutations in the SERPINC1 gene, is a well-established risk factor for venous thromboembolism (VTE), which can lead to serious complications such as deep vein thrombosis (DVT), pulmonary embolism (PE), and cerebral venous sinus thrombosis (CVST). Syndecan-4 (SDC4), an endothelial cell membrane protein, enhances AT’s anticoagulant function by facilitating its interaction with the vascular endothelium, thereby supporting hemostatic balance. Methods Our team enrolled a patient diagnosed with CVST, and subsequent genetic testing identified the SERPINC1 p.Phe155del variant. This study sought to elucidate the interaction between AT mutations and SDC4 in VTE pathogenesis using clinical case analyses, molecular docking, co-immunoprecipitation (Co-IP), and immunofluorescence assays. Results The patient was diagnosed with Type I hereditary AT deficiency, with a five-generation family pedigree constructed. Molecular docking simulations showed the SERPINC1 p.Phe155del variant weakened the protein’s interaction with SDC4. Cell-level co-immunoprecipitation and immunofluorescence results were consistent with molecular docking findings, confirming that the SERPINC1 p.Phe155del mutant binds less strongly to SDC4 than the wild-type. Conclusion This reduced binding may underlie hereditary AT deficiency and increased venous thrombosis risk. The findings from this research deepen understanding of the connection between hereditary hypercoagulable states and VTE —with CVST as one possible clinical manifestation—offering new insights to inform clinical diagnosis and treatment.

The COVID-19 pandemic has profoundly changed our lives. While healthcare resources were redistributed and mobilized to focus on dealing with the COVID-19 crisis, there have been unmet medical needs of patients with other diseases such as syphilis, weaving an integral but neglected component of the pandemic story. In different countries, the epidemiology of newly reported syphilis underwent diverse changes during the COVID-19 pandemic. Asymptomatic cases experienced the largest decline in number. From the perspective of transmission, on one hand, the implementation of lockdown measures led to a higher degree of abstinence and sex distancing in many countries, thereby reducing the transmission of syphilis. On the other hand, vertical transmission was reported to have increased significantly during COVID-19. Meanwhile, the volume of STI clinic capacity declined, and STI staff were redeployed to facilitate the contact tracing of COVID-19. As a result, many STI centers converted traditional in-person clinical services to telemedicine and self-testing. However, syphilis testing and clinical treatment cannot fully adapt to this conversion. In syphilis diagnosis, COVID-19 infection and vaccination were reported to cause false positivity in syphilis serological tests. Diverse cutaneous manifestations of COVID-19 could resemble the skin lesions in syphilis patients, requiring differential diagnosis from clinicians. As for the post-pandemic years, consequent to service interruptions and diagnosis delays, a surge in the number of confirmed cases of syphilis is expected. The COVID-19 pandemic has also been a meaningful lesson for the control and prevention of infectious diseases. The experience in combating COVID-19 has underscored the importance of maintaining a robust and well-supported medical system for the provision of sexual health services and better healthcare equality even during eras of crisis, not least for syphilis patients.The COVID-19 pandemic has profoundly changed our lives. While healthcare resources were redistributed and mobilized to focus on dealing with the COVID-19 crisis, there have been unmet medical needs of patients with other diseases such as syphilis, weaving an integral but neglected component of the pandemic story. In different countries, the epidemiology of newly reported syphilis underwent diverse changes during the COVID-19 pandemic. Asymptomatic cases experienced the largest decline in number. From the perspective of transmission, on one hand, the implementation of lockdown measures led to a higher degree of abstinence and sex distancing in many countries, thereby reducing the transmission of syphilis. On the other hand, vertical transmission was reported to have increased significantly during COVID-19. Meanwhile, the volume of STI clinic capacity declined, and STI staff were redeployed to facilitate the contact tracing of COVID-19. As a result, many STI centers converted traditional in-person clinical services to telemedicine and self-testing. However, syphilis testing and clinical treatment cannot fully adapt to this conversion. In syphilis diagnosis, COVID-19 infection and vaccination were reported to cause false positivity in syphilis serological tests. Diverse cutaneous manifestations of COVID-19 could resemble the skin lesions in syphilis patients, requiring differential diagnosis from clinicians. As for the post-pandemic years, consequent to service interruptions and diagnosis delays, a surge in the number of confirmed cases of syphilis is expected. The COVID-19 pandemic has also been a meaningful lesson for the control and prevention of infectious diseases. The experience in combating COVID-19 has underscored the importance of maintaining a robust and well-supported medical system for the provision of sexual health services and better healthcare equality even during eras of crisis, not least for syphilis patients.

Ischemic stroke is an important public health problem. However, comprehensive data on its burden in aging populations is limited. The aim of this study is to provide an up-to-date assessment of the prevalence, incidence, mortality, disability-adjusted life years, and risk factors for ischemic stroke globally in adults aged 60 years and older from 1990 to 2021 based on population changes. The Global Burden of Diseases, Injuries, and Risk Factors Study 2021 served as the data source for this study. Average annual percentage changes were estimated over the study period to quantify temporal patterns and assess trends in age-standardized rates of the prevalence, incidence, mortality, and disability-adjusted life-years of ischemic stroke. The significant increase in the prevalence and incidence of ischemic stroke is mainly related to population ageing and the significant increase in the number of people over 60 years of age, with the significant increase in the population over 60 years of age being the main driving force, while epidemiological changes have had the opposite effect. Critically, using the entire age population for calculations will prompt us to underestimate the burden of ischemic stroke. The burden of ischemic stroke disease is highest in older men than in older women, and the age-standardized prevalence rates, incidence rates, mortality rates, and disability-adjusted life-years rates are 26-35% higher in men than in women. High-middle sociodemographic index and Sub-Saharan Africa regions suffer the heaviest burden. Ischemic stroke health inequities widen, with less developed regions bearing a heavier ischemic stroke burden and the disparity in that burden becoming more pronounced over time. Population aging is the primary driver of the growing burden of ischemic stroke. Our findings indicate that prevention and control of this disease remain critical public health challenges. Targeted interventions addressing modifiable risk factors could significantly reduce the global burden of ischemic stroke.

Malignant melanoma (MM) is a highly aggressive form of skin cancer with increasing global incidence rates, particularly in developed countries. Variations in the prevalence and quality of care provided to patients with melanoma exist across different regions and across different sex and age. Assessing the global burden of melanoma and evaluating the quality of care can provide valuable insights for developing targeted interventions in certain underperforming regions and improving patient outcomes. This study aimed to systematically analyze the Global Burden of Disease Study from 1990 to 2019 to assess the quality of care for skin malignant melanoma on a global scale. We conducted a comprehensive literature review and extracted data on melanoma incidence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Disease Study. We incorporated these variables using principal component analysis (PCA) to form an informative single variable of quality of care index (QCI) and analyzed its spatial–temporal variations as well as disparities across age, sex and socio-demographic index (SDI). The overall Quality of Care Index (QCI) for melanoma improved from 82.81 in 1990 to 91.29 in 2019. The QCI score showed a positive correlation with socioeconomic status across regions. Australia ranked highest in QCI (99.96), while Central African Republic, and Kiribati had the lowest scores. China and Saudi Arabia showed significant QCI improvement, while the QCI of the Democratic People's Republic of Korea, Zimbabwe, and Guam decreased from 1990 to 2019. The highest QCI scores were observed in the age groups of 20–39 years old (93.40–94.65). Gender disparities narrowed globally in these three decades, but lower Socio-demographic Index (SDI) regions showed increased gender inequities. Our findings highlighted the spatial–temporal variations in the quality of care of MM as well as its disparities across different SDI levels, age groups and sex. These findings offer valuable insights and guidance for implementing focused interventions and resource allocation to enhance the quality of care and overall outcomes for MM worldwide, especially for underperforming regions.

Purpose: General paresis is a common type of neurosyphilis featuring progressive cognitive deterioration. The lack of a golden standard of diagnosis and its nonspecific clinical manifestations resulted in a high rate of misdiagnoses. This study aims to investigate the clinical, laboratory and radiological presentations of general paresis and enrich its knowledge for timely diagnoses. Patients and methods: The study collected hospitalized patients admitted for general paresis from September 2002 to November 2022. Their socio-demographical and medical status, clinical presentations, cognitive assessments, laboratory and radiographical manifestations and treatment information were collected retrospectively. Results: A total of 20 males and 5 females were included. Patients' ages ranged from 30 to 66 years (average 50.3 years). The average and median time for diagnosing general paresis was 14.1 months and 10.0 months respectively. The most frequent initial symptom is memory deterioration (68.0%). Impaired calculative ability and memory deterioration were the most frequent cognitive anomalies, as found in 50% and 45.4% of subjects during examination. The mean and median scores of MoCA was 16.7 and 17 respectively. Serological tests revealed positive TPPA for all patients and a median RPR titer at 1:64 positive. All CSF samples with TPPA and FTA-ABS results reported positivity. The MRI manifestations of general paresis include patchy or speckled hyperintensities (70.8%) and cerebral atrophy (45.8%). The most common lesioned sites in MRI were the ventricular and paraventricular area (50.0%) and temporal lobes (45.8%). For treatment, penicillin-based anti-syphilitic plans were adopted in 17 patients (68.0%). Conclusion: The clinical features and radiological alternations of general paresis patients often exhibited diverse and nonspecific alternations. However, some specific clinical manifestations and auxiliary examinations can provide meaningful clues for the identification and differential diagnosis of this disease. Keywords: neurosyphilis, general paresis, syphilis, neuropsychiatric symptoms

Agriculture contributes to a decline in local species diversity and to above- and below-ground biotic homogenization. Here, we conduct a continental survey using 1185 soil samples and compare microbial communities from natural ecosystems (forest, grassland, and wetland) with converted agricultural land. We combine our continental survey results with a global meta-analysis of available sequencing data that cover more than 2400 samples across six continents. Our combined results demonstrate that land conversion to agricultural land results in taxonomic and functional homogenization of soil bacteria, mainly driven by the increase in the geographic ranges of taxa in croplands. We find that 20% of phylotypes are decreased and 23% are increased by land conversion, with croplands enriched in Chloroflexi, Gemmatimonadota, Planctomycetota, Myxcoccota and Latescibacterota . Although there is no significant difference in functional composition between natural ecosystems and agricultural land, functional genes involved in nitrogen fixation, phosphorus mineralization and transportation are depleted in cropland. Our results provide a global insight into the consequences of land-use change on soil microbial taxonomic and functional diversity. Agricultural land-use change affects belowground biodiversity. Here, the authors compare soil microbial communities from natural ecosystems and agricultural systems, finding that agricultural conversion leads to taxonomic and functional homogenisation.

Displacement monitoring data is essential for assessing the structural safety of high-arch dams. Existing models, predominantly based on single-model architectures, often lack the ability to effectively integrate multiple algorithms, leading to limited predictive performance and poor interpretability. This study proposes an ensemble learning framework for dam displacement prediction, combining Hydraulic–Seasonal–Temporal model (HST), Random Forest (RF), and Bidirectional Gated Recurrent Unit (BiGRU) models as base learners. A stacking strategy is employed to enhance predictive accuracy, and the Grey Wolf Optimizer (GWO) is used for hyperparameter optimization. To improve model transparency, the Shapley Additive Explanations (SHAP) algorithm is applied for interpretability analysis. Extensive experiments demonstrate that the proposed ensemble model outperforms individual models, achieving a Root Mean Squared Error (RMSE) of 0.2241 and a Coefficient of Determination (R2) of 0.9993 on the test set. The SHAP analysis further elucidates the contribution of key variables, providing valuable insights into the displacement prediction process and offering a robust technical foundation for arch dam safety monitoring and early risk warning.

Under the backdrop of global climate warming, both forest vegetation greening and resilience decline coexist, and the consistency of these trends at the regional scale remains controversial. This study uses the kNDVI (Kernel Normalized Difference Vegetation Index) and TAC (Temporal Autocorrelation) index framework, combined with BEAST and Random Forest methods, to quantify and analyze the spatiotemporal evolution of forest resilience and its driving factors in Southwest China from 2000 to 2022. The results show the following: (1) Forest resilience exhibits a “high in the northwest and low in the southeast” spatial distribution, with a temporal pattern of “increase-decrease-increase.” The years 2010 and 2015 are key turning points. Trend shift analysis divides resilience into six types. (2) Although forest vegetation shows a clear greening trend, resilience does not necessarily increase with greening, and in some areas, an “increase in greening—decline in resilience” asynchronous pattern appears. (3) The annual average temperature, precipitation, and solar radiation are the main climate factors and their influence on resilience follows a nonlinear relationship. Higher temperatures and increased radiation may suppress resilience, while increased precipitation can enhance it. This study suggests incorporating the TAC indicator into ecological monitoring and early warning systems, along with applying trend classification results for region-specific management to improve the scientific basis and adaptability of forest governance under climate change.

The development of effective and broad-spectrum antiviral therapies remains an unmet need. Current virus-targeted antiviral strategies are often limited by narrow spectrum of activity and the rapid emergence of resistance. As a result, there is increasing interest in alternative approaches that target host cell factors critical for viral replication. One promising strategy is the targeting of deubiquitinases (DUBs), enzymes that regulate key host and viral proteins involved in viral reactivation and replication. In this study, we explore the potential of targeting a DUB complex for antiviral therapy based on our previous study. Our previous work revealed that the OTUD4-USP7 DUB complex plays a crucial role in KSHV lytic reactivation. Here, we developed a peptide, p8, which effectively disrupts the interaction between OTUD4 and USP7, leading to decreased abundance of the key viral transcription factor, RTA, and suppression of murine herpesvirus replication in vivo . These findings underscore the OTUD4-USP7 DUB complex as a promising host-targeting antiviral therapeutic target for the treatment of KSHV-associated malignancies. Moreover, our study highlights the potential of DUB-targeting therapies as a novel and effective strategy for the development of broad-spectrum antiviral agents.