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Abstract Background Patients with liver cirrhosis face high infection risks due to immune dysfunction and hospital-related factors, increasing mortality rates when sepsis occurs. While various biomarkers predict outcomes in cirrhosis, few are accessible and reliable. This study addresses the gap by evaluating the prognostic potential of the lactate-to-albumin ratio (LAR). Methods We retrospectively analyzed data from patients with cirrhosis and sepsis who were admitted to the intensive care unit at Beth Israel Deaconess Medical Center between 2008 and 2022. LAR was calculated from the ratio obtained from the first measurement taken within 24 h of admission. The optimal LAR threshold was determined using R statistical software. Kaplan-Meier analysis was used to compare mortality risks between two patient groups, while multivariate Cox proportional hazards regression models were used to assess the association between LAR and mortality risk in patients with cirrhosis and concomitant sepsis. A restricted cubic spline (RCS) was used to explore potential dose-response relationships between LAR and mortality. Receiver operating characteristic (ROC) analyses were used to assess the predictive ability, sensitivity, and specificity of LAR for all-cause mortality in patients with cirrhosis and combined sepsis, and the area under the curve (AUC) was calculated. Finally, subgroup analyses were performed to assess the relationship between LAR and prognosis across different populations. Results A total of 1731 patients were included in the study. The optimal LAR threshold was identified as 1.0 using R statistical software. Kaplan-Meier analysis indicated that patients with higher LAR levels had a higher risk of 14-day, 28-day, and 90-day all-cause mortality (all log-rank P

Abstract Objective This study aims to investigate the factors contributing to kinesiophobia in patients following percutaneous coronary intervention (PCI). Methods Purposive sampling was employed to conduct semi-structured interviews with 14 patients and 4 healthcare professionals who satisfied the inclusion and exclusion criteria, from May 2023 to June 2023. Data were coded, categorized, and thematically analyzed using the Colaizzi seven-step analysis method. Results The factors contributing to kinesiophobia in patients post-PCI were classified into four primary themes: heightened psychological stress, increased uncertainty regarding exercise, reduced self-efficacy, and inadequate support systems. Conclusion Kinesiophobia in patients post-PCI hinders adherence to cardiac rehabilitation protocols. Early identification and analysis of the factors contributing to kinesiophobia can guide the development and implementation of effective intervention strategies. Clinical registration number Not applicable.

Abstract HIV acquisition has been found to be associated with increased risk of cardiometabolic syndrome in the past. In this study, we attempt to delineate the associated factors of metabolic syndrome among persons living with HIV in a single medical center in Taiwan using mostly integrase inhibitors-based regimen as HAART. A cross-sectional study involving all people living with HIV (PLWH) aged ≥ 18 years who visited MacKay Memorial Hospital, Taipei, Taiwan between September 7, 2022 to January 31, 2023 was performed. A modified National Cholesterol Education Program ATP III definition of metabolic syndrome was used to define metabolic syndrome and body mass index was used as surrogate for waist circumference. 809 PLWH participated in the study, in which 81.3% of patients were on integrase inhibitor-based HAART regimen. The prevalence of metabolic syndrome was 10.0%, which is markedly lower than those reported in the literature. Age was a significant risk factor for metabolic syndrome. HIV-related factors (CD4, viral load, HAART regimen) did not affect the presence of metabolic syndrome. Prevalence rate of metabolic syndrome appeared to have declined among PLWH compared to previous reports, possibly secondary to widespread use of integrase inhibitors. Age remains a strong risk factor for the development of metabolic syndrome among PLWH.

Abstract Inverse design via topology optimization has led to innovations in integrated photonics and offers a promising way for designing high-efficiency on-chip couplers with a minimal footprint. In this work, we exploit topology optimization to design a compact vertical coupler incorporating a bottom reflector, which achieves sub-decibel coupling efficiency on the 220-nm silicon-on-insulator platform. The final design of the vertical coupler yields a predicted coupling efficiency of −0.35 dB at the wavelength of 1550 nm with a footprint of 14 µm $$\times$$ × 14 µm, which is considerably smaller than conventional grating couplers. Its topology-optimized geometry can be realized by applying one full-etch and one 70-nm shallow-etch process and the fabricability is also guaranteed by a minimum feature size around 150 nm. Analysis of the potential fabrication imperfections indicates that the topology-optimized coupler is more resilient to in-plane variations, as the deviation of approximately ±100 nm in the misalignment of the topology-optimized features, ±20 nm in the size of the topology-optimized features, and ±10 nm in shallow etch depth yields an additional 1-dB loss as a penalty at the wavelength of 1550 nm. The proposed vertical coupler can further miniaturize photonic integrated circuits and enable highly-efficient networks between optical fibers and other photonic devices.

Abstract Background Primary pulmonary lymphoepithelial carcinoma (pLEC) is a subtype of non-small cell lung cancer (NSCLC) characterized by Epstein-Barr virus (EBV) infection. However, the molecular pathogenesis of pLEC remains poorly understood. Methods In this study, we explored pLEC using whole-exome sequencing (WES) and RNA-whole-transcriptome sequencing (RNA-seq) technologies. Datasets of normal lung tissue, other types of NSCLC, and EBV-positive nasopharyngeal carcinoma (EBV+-NPC) were obtained from public databases. Furthermore, we described the gene signatures, viral integration, cell quantification, cell death and immune infiltration of pLEC. Results Compared with other types of NSCLC and EBV+-NPC, pLEC patients exhibited a lower somatic mutation burden and extensive copy number deletions, including 1p36.23, 3p21.1, 7q11.23, and 11q23.3. Integration of EBV associated dysregulation of gene expression, with CNV-altered regions coinciding with EBV integration sites. Specifically, ZBTB16 and ERRFI1 were downregulated by CNV loss, and the FOXD family genes were overexpressed with CNV gain. Decreased expression of the FOXD family might be associated with a favorable prognosis in pLEC patients, and these patients exhibited enhanced cytotoxicity. Conclusion Compared with other types of NSCLC and NPC, pLEC has distinct molecular characteristics. EBV integration, the aberrant expression of genes, as well as the loss of CNVs, may play a crucial role in the pathogenesis of pLEC. However, further research is needed to assess the potential role of the FOXD gene family as a biomarker.

Abstract Porcine deltacoronavirus (PDCoV), also known as HKU15, is a swine enteropathogenic virus that is believed to have originated in birds. PDCoV belongs to the genus Deltacoronavirus (DCoV), the members of which have mostly been identified in diverse avian species. We recently reported that chicken or porcine aminopeptidase N (APN), the major cellular receptor for PDCoV, can mediate cellular entry via three pseudotyped retroviruses displaying spike proteins from three avian DCoVs (HKU11, HKU13, and HKU17). In the present work, to better understand how avian-origin CoVs may be transmitted to pigs, we investigated the unknown DCoV entry pathway in avian cells. We show that clathrin-mediated endocytosis is involved in the entry of these DCoV pseudoviruses into chicken-origin DF-1 cells. Pseudovirus entry was suppressed by means of pharmacological inhibitors, dominant-negative mutants, and siRNAs targeting various cellular proteins and signalling molecules, suggesting that PDCoV and avian DCoV pseudovirus entry into DF-1 cells depends on clathrin, dynamin-2, cathepsins and a low-pH environment but is independent of caveolae and macropinocytosis. Furthermore, we found that DCoV pseudovirus entry was linked to Rab5- and Rab7-dependent pathways. This is the first report demonstrating that these DCoVs utilize clathrin-mediated endocytosis pathways to enter avian-origin cells, providing new insights into interspecies transmission of DCoVs.

Indium is a promising joining material for low-temperature soldering and thermal interface applications. Copper is a common metal pad used to join indium to form solder joints. Interfacial reactions and thermomigration are two important research subjects for the reliability assessment of solder joints. In this study, the interfacial reactions of copper/indium joints annealed at 210 °C are investigated with a focus on the growth kinetics of intermetallic compounds (IMCs) formed at the joints. Sandwiched copper/indium/copper joints are prepared via thermocompression to study the thermomigration across the joint driven by a temperature gradient of 794 °C cm−1. The results show that the Cu11In9 phase forms at the copper/indium joints, whereas its growth rate is influenced by the impurity content and grain size of the electroplated copper substrates. The thermomigration effect is significant in copper/indium/copper joints, wherein the Cu11In9 phase at the cold end grows at a much faster rate than does that at the hot end. The average product of the diffusivity and molar heat of transport (D × Q∗) for copper in molten indium is calculated to be (3.09 ± 0.21) × 10−2 J cm2 mol−1 s−1.

Abstract Tris (2‐chloroisopropyl) phosphate (TCPP) is an emerging environmental pollutant associated with liver diseases. However, its effects on hepatocellular carcinoma (HCC) remain unknown. Choline, a necessary dietary nutrient, has previously demonstrated inhibitory effects on HCC. Therefore, elucidating the underlying mechanism of TCPP exposure on HCC development and investigating whether choline could mitigate these effects may improve the prognosis of HCC patients. In this study, we examined the tumor‐promoting effects of TCPP on HCC and explored the protective effects of choline. Our findings revealed that choline treatment attenuated the tumor‐promoting effects of TCPP exposure on HCC cells’ epithelial‐mesenchymal transition (EMT) and lung metastasis. Further investigation showed that TCPP exposure induced ROS production via NOX4 upregulation, while choline inhibited ROS generation, thereby mitigating the effects of TCPP on EMT and metastasis in HCC cells. Mechanistic analysis demonstrated that excessive ROS inhibited levels of Keap1, leading to upregulation and nuclear translocation of Nrf2, which promoted autophagy flux and accelerated EMT and metastasis of HCC cells. However, choline treatment significantly impaired TCPP‐induced autophagy by attenuating the ROS/Nrf2/Keap1 pathway. Overall, our data illustrate the adverse effects of TCPP on the malignant progression of HCC and suggest that choline may serve as a potential nutrient to counteract the tumor‐promoting effects of TCPP on HCC.

Abstract Background Evidence indicates that cognitive function is influenced by potential environmental factors. We aimed to determine the variables influencing cognitive function. Methods Our study included 164,463 non-demented adults (89,644 [54.51%] female; mean [SD] age, 56.69 [8.14] years) from the UK Biobank who completed four cognitive assessments at baseline. 364 variables were finally extracted for analysis through a rigorous screening process. We performed univariate analyses to identify variables significantly associated with each cognitive function in two equal-sized split discovery and replication datasets. Subsequently, the identified variables in univariate analyses were further assessed in a multivariable model. Additionally, for the variables identified in multivariable model, we explored the associations with longitudinal cognitive decline. Moreover, one- and two- sample Mendelian randomization (MR) analyses were conducted to confirm the genetic associations. Finally, the quality of the pooled evidence for the associations between variables and cognitive function was evaluated. Results 252 variables (69%) exhibited significant associations with at least one cognitive function in the discovery dataset. Of these, 231 (92%) were successfully replicated. Subsequently, our multivariable analyses identified 41 variables that were significantly associated with at least one cognitive function, spanning categories such as education, socioeconomic status, lifestyle factors, body measurements, mental health, medical conditions, early life factors, and household characteristics. Among these 41 variables, 12 were associated with more than one cognitive domain, and were further identified in all subgroup analyses. And LASSO, rigde, and principal component analysis indicated the robustness of the primary results. Moreover, among these 41 variables, 12 were significantly associated with a longitudinal cognitive decline. Furthermore, 22 were supported by one-sample MR analysis, and 5 were further confirmed by two-sample MR analysis. Additionally, the quality of the pooled evidence for the associations between 10 variables and cognitive function was rated as high. Based on these 10 identified variables, adopting a more favorable lifestyle was significantly associated with 38% and 34% decreased risks of dementia and Alzheimer’s disease (AD). Conclusion Overall, our study constructed an evidence database of variables associated with cognitive function, which could contribute to the prevention of cognitive impairment and dementia.

Abstract In the previous study, discarded oyster farming bamboo scaffolding (BS) demonstrated the potential for application in pulping and papermaking through the soda pulping process. However, soda pulping involves high temperatures and chemical dosages. Therefore, this study develops an alternative pulping process to lower temperature and chemical demands by utilizing a high-consistency kneader (HCK), simultaneously promoting the utilization of BS in pulping and papermaking. This study applies a factorial experimental design to assess the impact of thermo-alkali pretreating conditions (temperature and NaOH dosage) by analyzing pulping yield, freeness, fiber appearance, and handsheet properties. The factorial analysis shows that the temperature and NaOH dosage of thermo-alkali pretreatment significantly affect the pulp properties. The optimal condition of 125℃ and 7.5% NaOH dosage has the highest accepts ratio, the best refining capacity, and the highest handsheet strength. Further compared with previous soda pulping research, utilizing HCK can produce similar pulp properties while increasing the pulping yield and reducing the temperature (-26.5%) and chemical demands (-46.4%). In summary, HCK demonstrates feasibility and potential for application in the pulping process, offering a new perspective on mechanical pulping as presented in this study, while also creating an opportunity to promote BS utilization.

Dynamic management of virtual machines (VMs) in cloud data centers is essential for achieving flexibility, efficiency, and high productivity in cloud systems. With the rapid growth of cloud technologies and increasing demand for cloud-based services, effective resource management has become a critical factor for ensuring quality service delivery while minimizing operational costs. This is particularly important for organizations seeking to optimize their resource utilization and adapt dynamically to fluctuating workloads. This paper introduces a novel model designed to address these challenges by enhancing existing algorithms and employing advanced techniques. The approach integrates genetic algorithms and refrigeration simulation into the migration replacement process, leveraging absorbing Markov chains for predictive analysis. By continuously monitoring resource status, analyzing incoming data, and forecasting critical server conditions, the model effectively reduces unnecessary VM migrations. Simulations conducted using the Clodsim environment demonstrate the model’s efficiency in reducing energy consumption across low, medium, and high-load scenarios. The proposed method achieves an average reduction in energy consumption of 17% compared to state-of-the-art methods, while also minimizing violations of service-level agreements (SLA). This research highlights the importance of combining predictive analytics with robust optimization techniques to improve cloud resource management. By achieving significant energy savings and enhancing system reliability, the proposed model offers a practical, sustainable framework for dynamic VM management, addressing the challenges posed by growing user demands and resource constraints in modern cloud data centers.

Abstract Cardiac regenerative therapy has recently progressed by reprogramming somatic cells into induced pluripotent stem cells (iPSCs) and advanced by large-scale differentiation-derived cardiomyocytes (hiPSC-CMs). However, repairing damaged cardiac tissues with hiPSC-CMs remains limited due to immune rejection, cardiac arrhythmias, and concerns over tumor formation after hiPSC-CM transplantation. Despite efforts in profiling epigenomic changes during cardiac differentiation, regulatory mechanisms underlying 5-methylcytosine (m5C) deposition in RNA m5C epitranscriptomic landscape during hiPSC-to-cardiomyocyte differentiation remain unclear. Herein, bisulfite RNA-sequencing analysis was conducted in human pluripotent stem cells (hPSCs) from three independent cellular origins, and their derived cardiomyocytes (hPSC-CM), metabolic-maturation of derived cardiomyocytes (hPSC-CM-lac) and biochemical-enhanced derived cardiomyocytes (hPSC-CM-TDI). Integrated analysis of differentially methylated RNA m5C profiles and transcriptome-wide expression facilitated the identification of m5C sites coupled to the cardiomyocyte differentiation and RNA-dependent regulatory mechanisms of stem cell pluripotency. The RNA m5C profiles in this dataset allow the evaluations of the m5C level and distribution of specific m5C loci and facilitate understanding of the m5C epitranscriptomic landscape in biological functions of hPSC-CM beyond in vivo transplantation barriers.

Abstract Background Duck circovirus (DuCV) infections commonly induce immunosuppression and secondary infections in ducks, resulting in significant economic losses in the duck breeding industry. Currently, effective vaccines and treatments for DuCV have been lacking. Therefore, rapid, specific, and sensitive detection methods are crucial for preventing and controlling DuCV. Methods A lateral flow strip (LFS) detection method was developed using recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 12a (Cas12a). The RPA-CRISPR/Cas12a-LFS targeted the DuCV replication protein (Rep) and was operated at 37 ℃ and allowed for visual interpretation without requiring sophisticated equipment. Results The results revealed that the reaction time of RPA-CRISPR/Cas12a-LFS is only 45 min. This method achieved a low detection limit of 2.6 gene copies. Importantly, this method demonstrated high specificity and no cross-reactivity with six other avian viruses. In a study involving 97 waterfowl samples, the Rep RPA-CRISPR/Cas12a-LFS showed 100% consistency and agreement with real-time quantitative polymerase chain reaction. Conclusion These findings underscored the potential of this user-friendly, rapid, sensitive, and accurate detection method for on-site DuCV detection.

Abstract Background Preeclampsia (PE) is a serious pregnancy complication associated with impaired trophoblast function. Integrin β3 (ITGB3) is a cell adhesion molecule that plays a role in cell movement. The objective of this study was to identify the biological function and expression level of ITGB3 in PE. Methods Cell proliferation, migration, invasion, adhesion, and apoptosis were estimated by CCK8 assay, transwell, scratch assays, and flow cytometry, respectively. The expression levels of ITGB3 were determined by qRT-PCR, western blot, and immunohistochemistry (IHC). Co-immunoprecipitation and Alphafold-Multimer protein complex structure prediction software were employed to identify the molecules that interact with ITGB3. Results Cell functional experiments conducted on HTR8/SVneo cells demonstrated that ITGB3 significantly enhanced proliferation, migration, invasion, and adhesion, while simultaneously inhibiting apoptosis. Relative ITGB3 expression levels were observed to be lower in PE placental tissue than in normal tissue and similarly reduced in hypoxic HTR8/SVneo cells. RNA-sequencing data from PE placental samples in the GEO database were analyzed to identify differentially expressed genes associated with the disease. We identified a total of 1460 mRNAs that were significantly differentially expressed in PE patients. Specifically, 798 mRNAs were significantly upregulated, and 662 mRNAs were significantly downregulated. Notably, the ITGB3 exhibited a pronounced down-regulation among the differential expression mRNA. Conclusions This study suggested that ITGB3 plays an important role in promoting the proliferative, migratory, invasive, and adhesive capabilities of trophoblast cells. These findings may facilitate a more in-depth understanding of the molecular mechanisms that promote PE progression.

Abstract Background The functional aspects of non-suicidal self-injury (NSSI) among adolescents represent a complex phenomenon requiring deeper understanding. While research has identified various NSSI functions, including emotional regulation, attention-seeking, and social avoidance, the field lacks comprehensive analysis of how these functions cluster into distinct profiles. Understanding these functional profiles is crucial for developing targeted interventions. Method A cross-sectional study of 1,783 adolescents (1,464 girls, 318 boys) aged 12–18 years was conducted across 14 psychiatric or general hospitals in nine Chinese provinces. Participants completed the Functional Assessment of Self-Mutilation (FASM), which assesses 22 distinct NSSI functions across three primary dimensions: emotional regulation, attention-seeking, and social avoidance. Additional measures included the Patient Health Questionnaire (PHQ-9) for depression and Generalized Anxiety Disorder Scale (GAD-7) for anxiety symptoms. Latent profile analysis was employed to identify distinct patterns in NSSI functions, with model selection based on fit indices including AIC, BIC, entropy, and LMRT. Results Latent profile analysis revealed four distinct functional profiles: low attention-seeking-high social avoidance (LA-HS, 19.7%), high attention-seeking-high social avoidance (HA-HS, 9.5%), low attention-seeking and social avoidance (LA-LS, 57.8%), and high attention-seeking-low social avoidance (HA-LS, 13.0%). The HA-HS profile demonstrated the most severe clinical presentation, showing significantly elevated scores in NSSI frequency (M = 26.160, SD = 9.771), anxiety (GAD-7: M = 16.265, SD = 4.951), and depression (PHQ-9: M = 20.612, SD = 6.003). The LA-HS profile showed the second-highest severity (NSSI: M = 25.800, SD = 10.058; GAD-7: M = 14.775, SD = 5.376; PHQ-9: M = 19.966, SD = 5.938). Both profiles also demonstrated significantly higher rates of suicidal ideation (HA-HS: 77.6%; LA-HS: 79.2%) compared to other profiles. Conclusions Our findings reveal distinct patterns in how adolescents utilize NSSI functionally, particularly regarding attention-seeking and social avoidance dimensions. These functional profiles show meaningful associations with psychological outcomes, suggesting that understanding NSSI functions, rather than just behaviors, may be crucial for assessment and intervention. The identification of these distinct functional profiles among Chinese adolescents highlights the importance of function-specific approaches in clinical assessment and treatment planning.

Abstract Background Breast milk is a natural treasure for infants, and its microbiota contains a rich array of bacterial species. When breastfeeding is not possible, infant formula with probiotics can be used as a sole source or as a breast milk supplement. The main aim of this study was to evaluate the growth outcomes and tolerance of infants consuming an infant formula containing Bifidobacterium animalis ssp. lactis CP-9 (B. animalis CP-9) or Lactobacillus salivarius AP-32 (L. salivarius AP-32), which were isolated from breast milk and the guts of healthy infants. The safety of these strains in terms of antibiotic resistance and their ability to modulate the gut microbiota were also evaluated. Methods One hundred eighty healthy infants were included in this study and separated into three groups: the control group, the L. salivarius AP-32 group, and the B. animalis CP-9 group. In this clinical study, adverse events, growth effects, and the incidence of allergies and gastrointestinal disorders in infants consuming infant formula containing B. animalis CP-9 or L. salivarius AP-32 were evaluated. Finally, the impact of the probiotic infant formula on the gut microbiota was elucidated via next-generation sequencing (NGS) analysis. Results The 4-month interventional study revealed that body weight, recumbent length, and head circumference were similar among the three groups. No adverse events related to the intervention were observed. The microbiota composition was more diverse on day 0 and became more uniform by month 4. B. animalis CP-9 and L. salivarius AP-32 were found to be susceptible to streptomycin, tetracycline, erythromycin, clindamycin, chloramphenicol, and ampicillin. Conclusions The use of infant formula containing B. animalis CP-9 and L. salivarius AP-32 was considered safe and well tolerated, with no adverse events observed during the study. While these strains showed low antibiotic resistance and no immediate concerns related to antibiotic resistance genes, further research is needed to comprehensively assess their long-term safety and efficacy and the potential risk of horizontal gene transfer in broader contexts. Trial registration The trial was registered with the US Library of Medicine (clinicaltrials.gov) with the number NCT03993301 on 20/06/2019.

Abstract Background Pure partial trisomy 16q12.1q22.1 is a rare chromosome copy number variant (CNV). The primary clinical phenotypes associated with this syndrome include abnormal facial morphology, global developmental delay (GDD), short stature, and reported predisposing factors for atypical behavior, autism, the development of learning disabilities, and neuropsychiatric disorders. The dosage-sensitive genes associated with partial trisomy are not disclosed preventing to establish a genotype-phenotype correlation. Methods We report a case of a Chinese patient diagnosed with GDD and an abnormal facial shape, who was found to have partial trisomy 16 through karyotyping and high-throughput sequencing analysis. Karyotype and CNV tracing analyses were also conducted on the biological parents of the patient to assess for any chromosomal structural abnormalities. Additionally, we included 29 patients with pure partial trisomy 16q, reported in the DECIPHER database and the literature. We and performed a genotype-phenotype correlation analysis. Results The proband, a 2-year-old female, was found to have a de novo 21.96 Mb duplication located between 16q12.1q22.1, with no other deletions observed on other chromosomes, indicating a pure partial trisomy of 16q. Through genotype and phenotype analysis of 29 individuals, we found that patients with the duplicated region located at the distal region of 16q may exhibit more severe symptoms than those with duplication at the proximal region; however, no relationship was identified between phenotype and the size of the duplicated segment. Conclusion We report, for the first time, a patient with partial trisomy 16q validated by multiple genetic tests, including CNV-seq, whole exome sequencing (WES), and karyotyping. It is speculated that partial trisomy of 16q may be associated with continuous gene duplication. However, functional studies are necessary to identify the causative gene or critical region linked to duplication syndrome of chromosome 16q.

Abstract Highly efficient perovskite solar cells (PSCs) in the n-i-p structure have demonstrated limited operational lifetimes, primarily due to the layer-to-layer ion diffusion in the perovskite/doped hole-transport layer (HTL) heterojunction, leading to conductivity drop in HTL and component loss in perovskite. Herein, we introduce an ultrathin (~7 nm) p-type polymeric interlayer (D18) with excellent ion-blocking ability between perovskite and HTL to address these issues. The ultrathin D18 interlayer effectively inhibits the layer-to-layer diffusion of lithium, methylammonium, formamidium, and iodide ions. Additionally, D18 improves the energy-level alignment at the perovskite/HTL interface and facilitates efficient hole extraction. The resulting PSCs achieve efficiencies of 26.39 (certified 26.17) and 25.02% with aperture areas of 0.12 and 1.00 square centimeters, respectively. Remarkably, the devices retain 95.4% of the initial efficiency after 1100 hours of operation in maximum power point tracking, representing significant stability advancements for high-efficiency n-i-p PSCs.

Abstract Background and objective The neutrophil percentage to albumin ratio (NPAR) is an emerging, costimulatory indicator of inflammation that is associated with a variety of diseases, such as non-alcoholic fatty liver disease, liver fibrosis, stroke, and cardiovascular disease. However, the relationship between NPAR and gallstones (GS) has not yet been explored. Therefore, this study aimed to evaluate the association of the NPAR with the odds of GS and the age of patients at the time of their first GS surgery. Methods Participants were selected from the National Health and Nutrition Examination Survey (NHANES) in the United States, a nationally representative survey. Logistic regression analysis and dose-response curve were performed to analyze the relationship between NPAR and the prevalence of GS. Multiple linear regression analysis and dose-response curve were used to analyze the association between NPAR and the age of patients at the time of their first GS surgery. Subgroup analyses further explored the relationships between NPAR and age, sex, race, body mass index, hypertension, and diabetes. Results In total, 7805 adults aged > 20 years were included in this study, of whom 838 had a history of GS. After adjusting for all potential confounders, each 1-unit increase in NPAR was found to be associated with a 4% increase in the prevalence of GS (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02, 1.07) and an advancement in the age of the patient at the time of the first GS surgery by 0.35 years (β = − 0.35, 95% CI: − 0.68, − 0.02). Dose-response curves further confirmed that NPAR was positively associated with the prevalence of GS and negatively associated with the age of patients at the time of their first GS surgery. The results of the subgroup analyses suggested that after adjusting for all potential confounders, the positive association of NPAR with the prevalence of GS was more pronounced in the 40–59-year-old (OR: 1.07, 95% CI: 1.02, 1.12), male (OR: 1.07, 95% CI: 1.02, 1.12), non-Hispanic Black (OR: 1.06, 95% CI: 1.01, 1.12), non-hypertensive (OR: 1.06, 95% CI: 1.02, 1.10), and non-diabetic populations (OR=: 1.05, 95% CI: 1.02, 1.08). Conclusions The higher the NPAR, the higher the prevalence of GS, and the earlier the age of the patient at the time of the first GS surgery. Due to the nature of cross-sectional study, it is not possible to determine a causal relationship between them.

Abstract This paper presents a novel architecture utilizing blockchain technology to enhance educational systems. A method is proposed that empowers non‐fungible tokens by updating their metadata through an API layer, making blockchain technology more accessible to K‐12 students. Leveraging Google Blockly, a visual programming language, the aim is to engage students in computational thinking and foster their understanding of blockchain concepts. The approach promotes student engagement, facilitates the comprehension of digital ownership and value, and develops essential skills for the digital age. Through the method, the contribution is in the advancing of blockchain in education. The demo video can be seen using the following link, https://youtu.be/ZPVKgWtSb6U.

Abstract Fibrosis, an excessive self-repair response, is an age-related pathological process that universally affects various major organs such as the heart, liver, kidney, and lungs. Continuous accumulation of pathological tissue fibrosis destroys structural integrity and causes loss of function, with consequent organ failure and increased mortality. Although some differences exist in the triggering mechanisms and pathophysiologic manifestations of organ-specific fibrosis, they usually share similar cascading responses and features, including chronic inflammatory stimulation, parenchymal cell injury, and macrophage recruitment. Macrophages, due to their high plasticity, can polarize into different phenotypes in response to varied microenvironments and play a crucial role in the development of organ fibrosis. This review examined the relationship between macrophages and the pathogenesis of organ fibrosis. Moreover, it analyzed how fibrosis can be modulated by targeting macrophages, which may become a novel and promising therapeutic strategy for fibrosis.

Abstract Ecotourism is rooted in nature, sustainability, and education. Multiple external factors influence the development of ecotourism, yet our comprehension of these influences remains limited. The study thoroughly investigates the factors contributing to their interest in ecotourism by analysing Chinese ecotourism participants’ personal stories and reflections. The study’s findings identify ten categories of external factors that influence the formation of ecotourists, including organisation, education, and exposure to nature, which impact ecotourists at different stages of life. Out of these, the influence of organisations is the most crucial element for forming ecotourists, although other factors also hold significant importance. The study emphasises the challenging and complex process of becoming an ecotourist. This process involves the interplay between various external influences and individual internal systems at different life stages. External factors affect individuals’ cognitive processes, capacity for empathy, and belief systems, which are essential in altering their motivations for travel, leading to a shift towards embracing more environmentally responsible and sustainable behaviours, ultimately turning them into ecotourists. This exploratory study delves into the complex relationship between external influences and their significant impact on ecotourists’ development. It offers fresh insights into ecotourism participation in China, enriching the existing knowledge in the field. It suggests that future research should focus on exploring the role of informal education factors and how to provide more support for the development of ecotourists.

Abstract The vibration caused by the existing operating metro has a negative impact on the construction of new metro lines and the nearby surroundings. The focus of this study is the confined interchange area between Beijing Metro Line 17 and Shilihe Station of Line 10. In the study area, the interchange between Shilihe Station of Line 10 and Line 17 has a confined frame structure that is already in operation without any overburden between the existing line and the new line; therefore, the vibration of the operating subway interferes with the construction. The measured and numerical simulation results show that the vibration response has an attenuating effect in the frame structure from top to bottom, and these studies are related to the train operating speeds of 20 km/h, 40 km/h, 60 km/h and 80 km/h. The type and spacing of the I-beams also have an effect, and the higher the train speed, the greater the vibration response. The principle of equivalent stiffness of I-beam is proposed, and the functional relationship between equivalent stiffness and I-beam parameters is deduced. The models of no vibration amplification effect, weak vibration amplification effect and strong vibration amplification effect are established, and it is obtained that when the I-beam is I20b and the spacing is 0.8 m, the equivalent stiffness is maximum, the vibration response of the frame structure is minimum, the vibration load is attenuated in the frame structure, and the vibration amplification effect of the soil on both sides is smaller. The study of the vibration amplification effect provides some theoretical guidance for the construction of similar projects.

Abstract Background It is unclear regarding the association between metabolomic state/genetic risk score(GRS) and brain volumes and how much of variance of brain volumes is attributable to metabolomic state or GRS. Methods Our analysis included 8635 participants (52.5% females) aged 40–70 years at baseline from the UK Biobank. Metabolomic profiles were assessed using nuclear magnetic resonance at baseline (between 2006 and 2010). Brain volumes were measured using magnetic resonance imaging between 2014 and 2019. Machine learning was used to generate metabolomic state and GRS for each of 21 brain phenotypes. Results Individuals in the top 20% of metabolomic state had 2.4–35.7% larger volumes of 21 individual brain phenotypes compared to those in the bottom 20% while the corresponding number for GRS ranged from 1.5 to 32.8%. The proportion of variance of brain volumes (R [2]) explained by the corresponding metabolomic state ranged from 2.2 to 19.4%, and the corresponding number for GRS ranged from 0.8 to 8.7%. Metabolomic state provided no or minimal additional prediction values of brain volumes to age and sex while GRS provided moderate additional prediction values (ranging from 0.8 to 8.8%). No significant interplay between metabolomic state and GRS was observed, but the association between metabolomic state and some regional brain volumes was stronger in men or younger individuals. Individual metabolomic profiles including lipids and fatty acids were strong predictors of brain volumes. Conclusions In conclusion, metabolomic state is strongly associated with multiple brain volumes but provides minimal additional prediction value of brain volumes to age + sex. Although GRS is a weaker contributor to brain volumes than metabolomic state, it provides moderate additional prediction value of brain volumes to age + sex. Our findings suggest metabolomic state and GRS are important predictors for multiple brain phenotypes.

The evaluation of urban underground space (UUS) suitability involves multiple indicators. Assigning weight to these indicators is crucial for accurate assessment. This paper presents a method for spatially variable weight assignment of indicators using the order relation analysis method (G1-method), the entropy weight method, an improved grey relational analysis (GRA) and a set of spatial weight adjustment coefficients. First, the subjective and objective weights of indicators for engineering geological and hydrogeological conditions were determined by the G1-method and entropy weight method, respectively, and their combined weights were then obtained using the principle of minimum discriminatory information. This study highlighted the impact of surface restrictions, such as buildings, on UUS, and the degree of the influence of these buildings gradually decreased with the increase in depth of the rock and soil mass in UUS, which resulted in changes in weights of indicators with depth. To address this issue, a coefficient was defined as the standardized value of the ratio of additional stress applied by restrictions to the self-weight stress of soil at the same depth to modify the combined weights so that all weights of indicators could vary in space. Finally, an improved GRA was used to determine the suitability level of each evaluation cell using the maximum correlation criterion. This method was applied to the 3D suitability evaluation of UUS in Sanlong Bay, Foshan City, Guangdong Province, China, including 16 evaluation indexes. This study comprehensively considered the influence of multiple factors, thereby providing reference for evaluating the suitability of UUS in big cities.

This article introduces the use of Internet-mediated joint construction (JC) to engage second language (L2) writers to participate in virtual classroom activities in an online teaching environment. Affected by the ongoing COVID-19 pandemic, schools and universities in the People's Republic of China were required to rapidly transit to remote teaching. The switch from the traditional classroom-based scenarios to the online environment was challenging for teachers. One of the extreme difficulties is to engage students in virtual-class activities. To address this issue, the authors designed an Internet-mediated JC teaching practice and implemented it on ClassIn, an online teaching platform for one semester. Analysis of students' after-class online surveys and interviews suggested that the Internet-mediated JC practice helped students to build a connected network and thus engaged them in actively interacting with both the teacher and peers in the online environment. Pedagogical implications are discussed to contribute to the teaching practice of L2 online writing instruction.

Vaporizers have a wide range of applications in industry, and the welding of finned tubes is an important step in the manufacturing of vaporizers. The obstruction of U-shaped tubes poses a huge challenge to the detection of weld seams by visual sensors and robot welding, making it difficult to achieve automatic welding of finned tubes. Therefore, this paper designed an automatic robot welding system for finned tubes based on laser vision sensors, and innovatively proposed a point cloud construction method for dissimilar complex weld seams, which can achieve fast and high-precision collection of finned tube point clouds. Furthermore, a finned tube point cloud processing method was proposed, which can complete the calculation of circular weld seam parameters by extracting the fin end face and tubes. Finally, precise positioning of finned tube weld seams was achieved. Experimental results showed that the welding seam positioning accuracy of the method proposed in this paper is better than 0.22 mm, which meets the welding requirements of finned tubes.

Abstract Abundant residual heat from industrial emissions may provide energy resource for CO2 conversion, which relies on H2 gas and cannot be accomplished at low temperatures. Here, we report an approach to store electrons and hydrogen atoms in catalysts using sunlight and water, which can be released for CO2 reduction in dark at relatively low temperatures (150−300 °C), enabling on-demand CO2 conversion. As a proof of concept, a model catalyst is developed by loading single Cu sites on hexagonal tungsten trioxide (Cu/WO3). Under light illumination, hydrogen atoms are generated through photocatalytic water splitting and stored together with electrons in Cu/WO3, forming a metastable intermediate (Cu/HxWO3). Subsequent activation of Cu/HxWO3 through low-temperature heating releases the stored electrons and hydrogen atoms, reducing CO2 into valuable products. Furthermore, we demonstrate the practical feasibility of utilizing natural sunlight to drive the process, opening an avenue for harnessing intermittent solar energy for CO2 utilization.

Abstract Background In recent years, the hypervirulent and carbapenem-resistant Klebsiella pneumoniae has been increasingly reported worldwide. The objective of this study was to compare the antibiotic resistance and virulence profiles of carbapenem-resistant hypervirulent K.pneumoniae (CR-hvKP) and hypervirulent carbapenem-resistant K.pneumoniae (hv-CRKP) and identify the prevailing strain in clinical settings. Methods In this study, hv-CRKP or CR-hvKP were identified based on the results of whole-genome analysis (WGS), multilocus sequence typing (MLST) and the antimicrobial susceptibility testing. We then compared antibiotic resistance and virulence profiles between CR-hvKP and hv-CRKP through the antimicrobial susceptibility testing and a series of virulence experiments including biofilm formation ability detection method, the resistance test against human serum, siderophore production test, neutrophil phagocytosis assay and Galleria mellonella infection model. Additionally, pathway enrichment analysis was conducted to assess the effect of SNPs on the phenotype. Results In this study, we categorized 17.4% of hypervirulent and carbapenem-resistant K. pneumoniae strains as CR-hvKP and 82.6% as hv-CRKP. Among them, 84.2% (16/19) of CR-hvKP strains harboring carbapenemase genes exhibited lower imipenem and meropenem MIC values compared to hv-CRKP strains. The virulence potential of hv-CRKP and CR-hvKP was confirmed by using virulence experiments in vitro and in vivo, showing that virulence of the CR-hvKP strains was comparable to that of hv-CRKP strains. Notably, the 90 hv-CRKP strains were classified into 3 different ST types and 8 capsule types, each showing varying degrees of resistance and virulence. We observed that subclonal replacement was within the predominant hv-CRKP clone, with the ST11-KL64 strain, characterized by high-level resistance and virulence emerging as the currently prevailing subclone, replacing ST11-KL47. KEGG enrichment analysis showed that pathways associated with the citrate cycle (TCA cycle), glycolysis/gluconeogenesis, glutathione metabolism, two-component regulatory system, and folate metabolism were significantly enriched among the group expressing different levels of capsular polysaccharides. Conclusions The hv-CRKP strains exhibited a greater survival advantage in the hospital environment than CR-hvKP strains. Notably, the ST11-KL64 hv-CRKP strain which displayed a high level of resistance and hypervirulence, warrants the most clinical vigilance. Clinical trial number Not applicable.

Abstract NK cells and macrophages constitute the predominant immune cell subsets in the decidua during the first trimester of pregnancy, with macrophages typically adopting an anti-inflammatory phenotype. Conversely, in the third trimester, macrophages undergo a shift towards a pro-inflammatory phenotype concurrent with a reduction in NK cell numbers. The direct regulatory impact of NK cells on macrophage phenotype remains poorly explored. In our investigation, we observed that ICAM1+ macrophages stimulate the expression of intracellular C3 in LFA1+ decidual NK cells. Notably, Cathepsin W within NK cells exhibit the potential to generate active C3b fragments, effectively inhibit the proinflammatory phenotype of macrophages by binding to VSIG4. Our study unveils a direct regulatory mechanism orchestrated by decidual NK cells over macrophages, providing a potential pathogenic explanation for recurrent spontaneous abortion.

Abstract Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.

Abstract Obstructed atomic insulator is recently proposed as an unconventional material, in which electric charge centers localized at sites away from the atoms. A half-filling surface state would emerge at specific interfaces cutting through these charge centers and avoid intersecting any atoms. In this article, we utilized photoemission spectroscopy and density functional theory calculations to study one of the obstructed atomic insulator candidates, NiP2. A floating surface state with large effective mass that is close to the Fermi level and isolated from all bulk states is resolved on the (100) cleavage plane, implying better catalytic activity in this plane than the previously studied surfaces. Density functional theory calculation results elucidate that this floating surface state is originated from the obstructed Wannier charge centers, albeit underwent surface reconstruction. Our findings not only shed lights on the study of obstructed atomic insulators, but also provide possible route for development of new catalysts.

Abstract Objective The selection of appropriate materials and techniques for reconstructing skull base defects is crucial for restoring function, minimizing complications, and enhancing aesthetics. Dermal fat grafts (DFGs) have been established in many surgeries for contour correction. However, there is little literature describing the application of free dermal fat grafts for reconstruction of lateral skull base surgery defects. Therefore, the aim of this study was to evaluate the clinical effect of using free dermal fat grafts in the reconstruction of lateral skull base defects. Methods In this study, 32 patients who underwent primary autologous free dermal fat graft reconstruction for lateral skull base defects were enrolled. Postoperative complications both in the donor and recipient area were evaluated. Three-dimensional (3D) reconstruction techniques were applied to visualize the fat graft shape and volume variations for the assessment of postoperative restoring function. A telephone questionnaire was used for the assessment of postoperative facial aesthetics and patient satisfaction. Results A total of 32 patients who met the inclusion criteria were included in the study, showing satisfying results in safety and aesthetics. Participants’ ages averaged at 42.03 years, with the youngest being 18 and the oldest at 75 years old. No patient had postoperative complications of abdominal wounds in the donor area, only two patients had postoperative infections and one patient had a postoperative effusion in the recipient area. The volume of the grafts ranged from a minimum of 24.4 cm³ to a maximum of 131 cm³, with the highest recorded resorption volume being 33.63 cm³. The average resorption rate of the dermal fat graft was 24.36%, ranging from a minimum of 11% to a maximum of 43%. 3D reconstruction based on MRI imaging data indicated that DFGs have a lower resorption rate than traditional free fat grafts. The telephone questionnaire revealed high patient satisfaction with facial aesthetics, with the majority rating their outcomes positively. Conclusions Dermal fat grafts have fewer complication and can provide better resistance to infection and radiation aspect. Based on 3D reconstruction techniques via MRI imaging data, we found that dermal fat grafts have lower resorption rate than traditional free fat grafts, which can be a suitable material for reconstruction of lateral skull base defects.

Abstract Higher sensitivity with specific recognition of a sensor could ease the burden of sample purification or labelling procedure for specific testing and detection and there appear two methods including surface enhanced infrared absorption (SEIRA) and surface enhanced Raman scattering (SERS), promising better sensitivity and specificity, simultaneously, via detection of molecular footprints. Furthermore, researchers employ Fano resonance to further boost the detection limit of SEIRA by coupling between two absorption bands from molecules and metamaterials. Still, the current metamaterial absorbers are almost narrow band and require a specific design, only suitable for limited chemicals. Thus, in this work, we would like to design a broadband oblique-wire-bundle (OWB) metamaterial absorber (MA) which could interact with multiple functional groups’ absorption from a sample, thus easing the burden of custom-made resonators. In experiments, indeed, our designed OWB MA developed four Fano resonance responses with three PMMAs’ functional groups and one function group from carbon dioxide. The counterpart planar MA also performed SEIRA yet without occurrence of Fano resonance as a comparison. We believe this proposed OWB MA could facilitate the development of rapid detection in the field of food safety and chemical detection.

Tefluthrin (Tef) is categorized as a type-I pyrethroid insecticide, telmisartan (Tel) functions as an angiotensin II receptor blocker, and KB-R7943 has been identified as an inhibitor of the Na+-Ca2+ exchange process. However, the influence of these compounds on the amplitude and gating properties of voltage-gated Na+ current (INa) in neurons associated with pain signaling remains unclear. In cultured dorsal root ganglion (DRG) neurons, whole-cell current recordings revealed that Tef or Tel increased the peak amplitude of INa, concomitant with an elevation in the time constant of INa inactivation, particularly in the slow component. Conversely, exposure to KB-R7943 resulted in a depression in INa, coupled with a decrease in the slow component of the inactivation time constant of INa. Theoretical simulations and bifurcation analyses were performed on a modeled interneuron in the spinal dorsal horn. The occurrence of INa inactivation accentuated the subthreshold oscillations (SO) in the membrane potential. With an increase in applied current, SO became more pronounced, accompanied by the emergence of high-frequency spiking (HS) with a frequency of approximately 150 Hz. Moreover, an elevation in INa conductance further intensified both SO and HF. Consequently, through experimental and in silico studies, this work reflects that Tef, Tel, or KB-R7943 significantly impacts the magnitude and gating properties of INa in neurons associated with pain signaling. The alterations in INa magnitude and gating in these neurons suggest a close relationship with pain transmission.

Abstract Introduction This study investigated the effects of automatic dual rotational Risley prisms (ADRRPs), a mobile phone application-operated device, on vergence abilities in young adults. Methods Fifty-six participants aged 20–24 performed vergence exercises. The test group used prisms with power changes from 30Δ base-out to 10Δ base-in, while the control group used plano lenses for 10 min. Ophthalmic examinations included lateral heterophoria, near point of convergence (NPC), vergence facility (VF), negative fusional vergence (NFV), and positive fusional vergence (PFV), all measured before and after the vergence exercises. Pre- and post-test results were analyzed using a paired sample t test. Additionally, three cases with convergence insufficiency (CI) performed similar exercises for 12 weeks. Results Participants were divided into the test group (n = 39; age 21.82 ± 1.10 years) and control group (n = 17; age 20.53 ± 0.51 years). In the test group, NPC improved from 6.11 ± 2.52 cm to 5.77 ± 2.30 cm (p = 0.023). VF increased from 13.75 ± 4.10 cpm to 16.50 ± 4.42 cpm (p = 0.007). PFV at 6 m and 0.4 m increased from 19.49 ± 6.77∆ to 22.19 ± 6.64∆ (p

Background/purpose: Challenges exist regarding the bonding efficiency of polyaryletherketone (PAEK), a high-performance thermoplastic, attributed to its chemical inertness and hydrophobic surface, hindering effective bonding with resin-matrix cement. This research explored the impact of handheld nonthermal plasma (HNP), under varying operational parameters, on PAEK surface wettability and changes in bonding performance with cement. Materials and methods: Three types of disc-shaped PEAK specimens were prepared, with surface treatments categorized as grinding, airborne-particle abrasion (APB), and HNP. Surface wettability was analyzed using a contact angle analyzer (n = 10). Specimens were bonded with resin cement and subjected to artificial aging tests: distilled water bath (NA), thermocycling, and highly accelerated stress tests (n = 10 for each test). Shear bond strength (SBS) was measured, failure modes were analyzed, and statistical analyses were conducted. Results: The HNP markedly improved PAEK surface wettability, achieving superhydrophilicity (P

Abstract Racial and ethnic minorities bear a disproportionate burden of type 2 diabetes (T2D) and its complications, with social determinants of health (SDoH) recognized as key drivers of these disparities. Implementing efficient and effective social needs management strategies is crucial. We propose a machine learning analytic pipeline to calculate the individualized polysocial risk score (iPsRS), which can identify T2D patients at high social risk for hospitalization, incorporating explainable AI techniques and algorithmic fairness optimization. We use electronic health records (EHR) data from T2D patients in the University of Florida Health Integrated Data Repository, incorporating both contextual SDoH (e.g., neighborhood deprivation) and person-level SDoH (e.g., housing instability). After fairness optimization across racial and ethnic groups, the iPsRS achieved a C statistic of 0.71 in predicting 1-year hospitalization. Our iPsRS can fairly and accurately screen patients with T2D who are at increased social risk for hospitalization.

Abstract Background The co-occurrence of Lemierre’s syndrome, primarily triggered by Fusobacterium necrophorum following oropharyngeal infection, with diabetic ketoacidosis (DKA) in diabetes mellitus (DM) patients, underscores a rare but life-threatening clinical scenario. Lemierre’s syndrome induced DKA is extremely rare, with only one case report in adult and no case yet reported in elderly. Case Presentation We reported a case of a 69-year-old female who presented with DKA triggered by deep neck space infection (DNSI), leading to rapid clinical deterioration within 6 h that necessitated high flow nasal cannula (HFNC) and antibiotic administration. Laboratory findings included leukocytosis, elevated serum C-reactive protein, hyperglycemia, ketonemia, and severe metabolic acidosis. Culture of the fluid from a neck mass puncture drainage and blood were positive for Klebsiella pneumoniae. The patient was further complicated by thrombosis of the left internal jugular vein with extension to the sigmoid and a neck abscess surrounding the carotid artery sheath, consistent with Lemierre’s syndrome. This condition was managed aggressively with fluid resuscitation, insulin therapy, surgical drainage, antibiotics, and anticoagulation led to a significant improvement in her condition. Following a 13-day hospitalization, there was significant clinical improvement, culminating in the patient’s discharge. Conclusions The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of DKA and Lemierre’s syndrome among clinicians. Early recognition and treatment are crucial to prevent mortality in such complex cases.

Abstract Source‐to‐sink analysis examines the effects of source areas and basin (sink) dynamics on the generation, transport, composition, distribution and deposition of sediment in modern and ancient sedimentary systems. Detrital zircon, as one of the most stable detrital minerals, its U–Pb geochronology and geochemistry is pivotal for sedimentary provenance analysis and reconstructing palaeogeography. The South China Sea (SCS), as the largest marginal sea in the Southeast Asia, is closely related to the uplift of the Tibetan Plateau and the evolution of Chinese rivers. In this study, we mainly collect published detrital zircon of Cenozoic sediments in the SCS (include Hainan and Taiwan Islands). These detrital zircon were concentrated on Cenozoic multiple episodic rift basins in the northern part of the SCS. A total of 21,760 detrital zircon U–Pb data from 293 samples and 995 detrital zircon Lu‐Hf isotope data from 22 samples were collected in this dataset, with the main study epochs being the Palaeogene and Neogene. Best ages of these grains are range from 4,691 to 10 Ma and more than half of them within age less than 500 Ma. The 176Hf/177Hf ratios of the SCS samples ranging from 0.280509 to 0.28306 and the εHf(t) values from −63.8 to 24.6. The main age group of the SCS Cenozoic sediments were at 130–95 Ma, 175–130 Ma and 265–230 Ma. The detrital zircon U–Pb age and Lu–Hf isotope data contained in this dataset is an important geological record of the sedimentary and tectonic evolution of the SCS and the evolution of rivers such as the ancient Pearl River and the ancient Red River, which can provide a basis and important clues or exploring the source of sediments in the SCS, the dynamical processes of basin evolution, the evolution of the coastal drainage system and the tectonic uplift of the Tibetan Plateau.

Abstract Complications of detrital zircons databases provide a means for statistically analysing a variety of significant geological problems. In this work, we tried to collect a database about the South China Phanerozoic detrital zircon geochronology data. The data statistics of this paper rely on the OneSediment Working Group of The Deep‐time Digital Earth program (DDE). By November 2022, the database contains a total of 699 samples with 55,532 U–Pb ages and 3,770 effective Hf isotope data, from 130 papers. Abundant information including reference title, sample ID, locality, rock type, research institution, GPS coordinates, U–Pb ages, εHf(t) values, etc., have been involved in our database, and all data can be downloaded from DDE Data Publish & Repository website, https://repository.deep‐time.org/. Through the integrated data, we can improve the previous studies and avoid the waste of resources caused by a large number of repeated studies.

Abstract The etiology of primary open angle glaucoma is constituted by both intraocular pressure-dependent and intraocular pressure-independent mechanisms. However, GWASs of traits affecting primary open angle glaucoma through mechanisms independent of intraocular pressure remains limited. Here, we address this gap by subtracting the genetic effects of a GWAS for intraocular pressure from a GWAS for primary open angle glaucoma to reveal the genetic contribution to primary open angle glaucoma via intraocular pressure-independent mechanisms. Seventeen independent genome-wide significant SNPs were associated with the intraocular pressure-independent component of primary open angle glaucoma. Of these, 7 are located outside known normal tension glaucoma loci, 11 are located outside known intraocular pressure loci, and 2 are novel primary open angle glaucoma loci. The intraocular pressure-independent genetic component of primary open angle glaucoma is associated with glaucoma endophenotypes, while the intraocular pressure-dependent component is associated with blood pressure and vascular permeability. A genetic risk score for the intraocular pressure-independent component of primary open angle glaucoma is associated with 26 different retinal micro-vascular features, which contrasts with the genetic risk score for the intraocular pressure-dependent component. Increased understanding of these intraocular pressure-dependent and intraocular pressure-independent components provides insights into the pathogenesis of glaucoma.

Abstract Background Metabolic dysfunction-associated steatohepatitis (MASH) is a growing global health concern with no effective pharmacological treatments. SNP-630, a newly developed synthetic molecule with multiple mechanisms of action, and a mixture of two of its active metabolites (SNP-630-MS) inhibit CYP2E1 expression to prevent reactive oxygen species generation, thereby reducing the accumulation of hepatic triglycerides and lowering chemokine levels. This study investigated the SNP-630’s potential to alleviate the liver injury in MASH and its efficacy in both a mouse model and patients with MASH to identify a drug candidate that targets multiple pathways implicated in MASH. Methods SNP-630 and SNP-630-MS were separately administered to the MASH mouse model. The tolerability, safety, and efficacy of SNP-630-MS were also evaluated in 35 patients with MASH. The primary endpoint of the study was assessment of the changes in serum alanine aminotransferase (ALT) levels from baseline to week 12, while the secondary endpoints included the evaluation of liver inflammation, steatosis, and fibrosis parameters and markers. Results SNP-630 treatment in mice improved inflammation, liver steatosis, and fibrosis compared with that in the MASH control group. Both SNP-630 and SNP-630-MS treatments markedly reduced ALT levels, hepatic triglyceride content, and the expression of inflammatory cytokines monocyte chemoattractant protein 1 and fibrotic collagen (i.e., Col1a1, Col3a1, and Timp1) in mice. In the clinical trial, patients treated with SNP-630-MS exhibited significant improvement in ALT levels at week 12 compared with baseline levels, with no reports of severe adverse events. This improvement in ALT levels surpassed that achieved with most other MASH candidates. SNP-630-MS demonstrated potential antifibrotic effects, as evidenced by a significant decrease in the levels of fibrogenesis-related biomarkers such as CCL4, CCL5, and caspase 3. Subgroup analysis using FibroScan measurements further indicated the efficacy of SNP-630-MS in ameliorating liver fibrosis. Conclusions SNP-630 and SNP-630-MS demonstrated favorable results in mice. SNP-630-MS showed excellent tolerability in mice and patients with MASH. Efficacy analyses indicated that SNP-630-MS improved liver steatosis and injury in patients with MASH, suggesting that SNP-630 and 630-MS are promising therapeutic options for MASH. Larger scale clinical trials remain warranted to assess the efficacy and safety of SNP-630 in MASH. Trial registration: ClinicalTrials.gov NCT03868566. Registered 06 March 2019-Retrospectively registered, https://clinicaltrials.gov/study/NCT03868566

Abstract Knee osteoarthritis (KOA) has a high incidence among the elderly, significantly impacting their quality of life and overall health. Medial unicompartmental knee arthroplasty (UKA) is an excellent choice for treating knee single-compartment lesions, and lower limb alignment has a profound impact on medial UKA. To explore the influence of different lower limb alignments on medial UKA. In this study, we selected MR and CT data of healthy adult male knee joints to establish a complete finite element analysis (FEA) model of the knee joint. After validation, we established a finite element model of medial UKA. Subsequently, we created 60 sets of FEA models with different lower limb alignments to analyze the impact of different lower limb alignments on medial UKA. A vertical load of 1000 N was applied to the FEA models with different lower limb alignments. During the process of shifting the Mikulicz line from the midpoint of the knee joint towards the medial side, the lower limb load was primarily concentrated on the medial compartment. The stress values of the lateral meniscus, tibial cartilage, and femoral cartilage gradually decreased. ROI (region of interest) 1 and ROI 2 showed the maximum principal strain changes, while ROI 3 and ROI 4 exhibited less pronounced fluctuations, with the maximum principal strain roughly proportionally increased. During the process of shifting the Mikulicz line towards the lateral side from the midpoint of the knee joint, the stress on the lateral compartment increased observably. ROI 1, ROI 2, ROI 3, and ROI 4 showed decreased maximum principal strains, approximately inversely proportional changes, but the overall reduction was relatively small. Different lower limb alignments have a profound impact on the short- and long-term joint function after UKA. When the Mikulicz line is 10 mm inside the midpoint of the knee joint or slightly outside, there is a relatively lower risk of tibial component fractures, lower stress on the lateral compartment, and lower load on the prosthesis. During medial UKA, measures such as bone resection and prosthesis selection should be taken to ensure that the Mikulicz line is in the ideal position.

Abstract Biocatalysis is an attractive approach for the synthesis of chiral pharmaceuticals and fine chemicals, but assessing and/or improving the enantioselectivity of biocatalyst towards target substrates is often time and resource intensive. Although machine learning has been used to reveal the underlying relationship between protein sequences and biocatalytic enantioselectivity, the establishment of substrate fitness space is usually disregarded by chemists and is still a challenge. Using 240 datasets collected in our previous works, we adopt chemistry and geometry descriptors and build random forest classification models for predicting the enantioselectivity of amidase towards new substrates. We further propose a heuristic strategy based on these models, by which the rational protein engineering can be efficiently performed to synthesize chiral compounds with higher ee values, and the optimized variant results in a 53-fold higher E-value comparing to the wild-type amidase. This data-driven methodology is expected to broaden the application of machine learning in biocatalysis research.