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Abstract Recent development of artificial intelligence (AI) technology has resulted in the fruition of machine learning-based weather prediction (MLWP) systems. Five prominent global MLWP model, Pangu-Weather, FourCastNet v2 (FCN2), GraphCast, FuXi, and FengWu, emerged. This study conducts a homogeneous comparison of these models utilizing identical initial conditions from ERA5. The performance is evaluated in the Eastern Asia and Western Pacific from June to November 2023. The evaluation comprises Root Mean Square Error and Anomaly Correlation Coefficients within the designated region, typhoon track and intensity predictions, and a case study for Typhoon Haikui. Results indicate that FengWu emerges as the best-performing model, followed by FuXi and GraphCast, with FCN2 and Pangu-Weather ranking lower. A multi-model ensemble, constructed by averaging predictions from the five models, demonstrates superior performance, rivaling that of FengWu. For the 11 typhoons in 2023, FengWu demonstrates the most accurate track prediction; however, it also has the largest intensity errors.

Abstract The Taihangshan-Yanshan region (TYR) is an important ecological barrier area for Beijing-Tianjin-Hebei, and the effectiveness of its ecological restoration and protection is of great significance to the ecological security pattern of North China. Based on the FVC data from 2000 to 2021, residual analysis, parametric optimal geodetector technique (OPGD) and multi-scale geographically weighted regression analysis (MGWR) were used to clarify the the multivariate driving mechanism of the evolution of FVC in the TYR. Results show that: (1) FVC changes in the TYR show a slowly fluctuating upward trend, with an average growth rate of 0.02/10a, and a spatial pattern of "high in the northwest and low in the southeast"; more than half of the FVC increased during the 22-year period. (2) The results of residual analysis showed that the effects of temperature and precipitation on FVC were very limited, and a considerable proportion (80.80% and 76.78%) of the improved and degraded areas were influenced by other factors. (3) The results of OPGD showed that the main influencing factors of the spatial differentiation of FVC included evapotranspiration, surface temperature, land use type, nighttime light intensity, soil type, and vegetation type (q > 0.2); The explanatory rates of the two-factor interactions were greater than those of the single factor, which showed either nonlinear enhancement or bifactorial enhancement, among which, the interaction of evapotranspiration with mean air and surface temperature has the strongest effect on the spatial and temporal evolution of FVC (q = 0.75). Surface temperature between 4.98 and 10.4 °C, evapotranspiration between 638 and 762 mm/a, and nighttime light between 1.96 and 7.78 lm/m2 favoured an increase in vegetation cover, and vegetation developed on lysimetric soils was more inclined to be of high cover. (4) The correlation between each variable and FVC showed different performance, GDP, elevation, slope and FVC showed significant positive correlation in most regions, while population size, urban population proportion, GDP proportion of primary and secondary industries, and nighttime light intensity all showed negative correlation with FVC to different degrees. The results can provide data for formulating regional environmental protection and restoration policies.

Abstract Lung cancer stands as the leading cause of mortality among all types of tumors, with over 40% of cases being lung adenocarcinoma (LUAD). Family with sequence similarity 83 member A (FAM83A) emerges as a notable focus due to its frequent overexpression in LUAD. Despite this, the precise role of FAM83A remains elusive. This study addresses this gap by unveiling the crucial involvement of FAM83A in maintaining the cancer stem cell-like (CSC-like) phenotype of LUAD. Through a global proteomics analysis, the study identifies human epidermal growth factor receptor 2 (HER2 or ErbB2) as a crucial target of FAM83A. Mechanistically, FAM83A facilitated ErbB2 expression at the posttranslational modification level via the E3 ubiquitin ligase STUB1 (STIP1-homologous U-Box containing protein 1). More importantly, the interaction between FAM83A and ErbB2 at Arg241 promotes calcineurin (CALN)-mediated dephosphorylation of ErbB2, followed by inhibition of STUB1-mediated ubiquitin-proteasomal ErbB2 degradation. The maintenance of the CSC-like phenotype by FAM83A, achieved through the posttranslational regulation of ErbB2, offers valuable insights for identifying potential therapeutic targets for LUAD.

BackgroundSenescence-accelerated mouse prone 8 (SAMP8) and age-matched SAMR1 mice are used to study the pathogenesis and therapeutics of Alzheimer’s disease (AD); however, the molecular mechanisms are not completely understood.ObjectiveThis study aimed to examine the effects of the 5-month administration of formononetin in SAMP8 mice and used RNA-seq to explore the molecular targets.MethodsSAMP8 mice were orally administered formononetin (0, 8, and 16 mg/kg) from 4 months of age, and age-matched SAMR1 mice were used as controls. Behavioral tests were performed in 9-month-old mice, followed by histopathologic analysis. Total RNA from the hippocampus was isolated and subjected to RNA-seq, RT-qPCR, and bioinformatics analysis.ResultsThe 9-month-old SAMP8 mice exhibited cognition deficits, evidenced by novel object recognition, open-field test, elevated plus maze, and passive avoidance. Nissl bodies in the cortex and hippocampus were decreased. Formononetin treatments ameliorated behavioral deficits and improved morphological changes, which were evidenced by Nissl and H&E staining. RNA-seq revealed distinct gene expression patterns between SAMP8 and SAMR1 mice. Differentially expressed genes in SAMP8 mice were attenuated or normalized by formononetin. Ingenuity pathway analysis (IPA) of canonical pathway and upstream regulators revealed increases in proinflammatory factors and immune dysfunction and decreases in NRF2 and SIRT-1 signaling pathways, leading to neuroinflammation. Formononetin treatment attenuated or reversed these molecular changes. The transcriptome of SAMP8 mice was correlated with transcriptomic profiles of other AD mouse models in the GEO database.ConclusionNeuroinflammation and decreased antioxidant and SIRT-1 signaling contributed to cognitive deficits in aged SAMP8 mice, which are potential therapeutic targets of formononetin in combination with other therapies.

Abstract Background There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. Methods A total of 226 COVID-19 patients admitted to Beijing Youan Hospital’s emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. Results A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p

Purpose: This umbrella review summarized the factors influencing parents’ hesitancy to vaccinate their children against COVID-19 and the evidence to reduce it. Methods: The analysis included PubMed, Embase, Cochrane Library, Web of Science, and Scopus articles published before March 22, 2024. It considered all meta-analyses that investigated parental COVID-19 vaccine hesitancy. Results: Eight studies were included. Hesitancy rate of parents from five continents to vaccinate their children against COVID-19 was between 0.69 % and 95.0 %. The comprehensive synthesis in this review shows that the influencing factors originate from four aspects: Parents’ attitudes, including their trust in the scientific community, concerns about COVID-19 complications, perceptions of children's susceptibility, and support from the social environment, including government incentives, low vaccination costs, and specific sociodemographic characteristics, were positive factors that reduced parental vaccine hesitancy in children. Conversely, negative aspects, including vaccine distrust, the spread of misinformation, poor economic status, and concern about unprecedentedly short development time, were associated with increased hesitancy. Conclusion: Our study identified positive and negative factors for parental COVID-19 vaccine hesitancy in children and highlighted that parental attitude was the most important determinant.

Purpose: This study aimed to examine the impact of a history of SARS-CoV-2 infection on the hesitancy of college students to receive additional COVID-19 vaccine booster doses. Methods: A population-based self-administered online survey was conducted in July 2024 in Taizhou, China. A total of 792 respondents were included in this study. Logistic regression was conducted to identify factors associated with college students’ hesitation to receive booster doses of the COVID-19 vaccine. Results: Of 792 respondents, 32.2 % hesitated to receive additional doses of the COVID-19 vaccine booster. Furthermore, 23.5 % of the respondents reported an increase in hesitancy to receiving additional COVID-19 vaccine booster doses compared to before they were infected with SARS-CoV-2. In the regression analyses, college students who had a secondary infection were more hesitant to receive additional COVID-19 vaccine booster doses (OR = 0.481, 95 % CI: (0.299–0.774), P = 0.003). Moreover, students with secondary infections who were male (OR = 0.417, 95 % CI: 0.221–0.784, P = 0.007), with lower than a bachelor’s degree (OR = 0.471, 95 % CI: 0.272–0.815, P = 0.007), in non-medical majors (OR = 0.460, 95 % CI: 0.248–0.856, P = 0.014), and sophomores or below (OR = 0.483, 95 % CI: 0.286–0.817, P = 0.007) were more hesitant to receive additional COVID-19 vaccine booster doses. Conclusion: A history of SARS-CoV-2 infection affects college students’ hesitation to receive additional COVID-19 vaccine booster doses, which was higher in those who experienced secondary infections.

Abstract Background Whether body mass index (BMI) is a risk factor for poor bowel preparation is controversial, and the optimal bowel preparation regimen for people with a high BMI is unclear. Methods We prospectively included 710 individuals with high BMIs (≥ 24 kg/m2) who were scheduled to undergo colonoscopy from January to November 2021 at 7 hospitals. Participants were randomly allocated into 3 L split-dose polyethylene glycol (PEG) group (n=353) and 2 L PEG group (n=357). The primary outcome was the rate of adequate bowel preparation, and the secondary outcomes included Boston Bowel Preparation Scale (BBPS) score, polyp detection rate, cecal intubation rate, and adverse reactions during bowel preparation. Furthermore, we did exploratory subgroup analyses for adequate bowel preparation. Results After enrollment, 15 individuals didn’t undergo colonoscopy, finally 345 participants took 3 L split-dose PEG regimen, and 350 participants took 2 L PEG regimen for colonoscopic bowel preparation. 3 L split-dose PEG regimen was superior to 2 L PEG regimen in the rate of adequate bowel preparation (81.2% vs. 74.9%, P = 0.045), BBPS score (6.71±1.15 vs. 6.37±1.31, P < 0.001), and the rate of polyp detection (62.0% vs. 52.9%, P = 0.015). The cecal intubation rate was similar in both groups (99.7%). Regarding adverse reactions, individuals were more likely to feel nausea in the 3 L PEG group (30.9% vs. 19.3%; P = 0.001); however, the degree was mild. In the subgroup analysis for adequate bowel preparation, 3 L split-dose PEG regimen performed better than 2 L PEG regimen in the overweight (BMI 25-29.9 kg/m2 ) (P = 0.006) and individuals with constipation (P = 0.044), while no significant differences were observed in relatively normal (BMI 24-24.9 kg/m2) (P = 0.593) and obese individuals (BMI ≥ 30 kg/m2) (P = 0.715). Conclusions 3 L split-dose PEG regimen is superior to 2 L PEG regimen for colonoscopic Bowel Preparation in relatively high-BMI individuals, especially overweight individuals (BMI 25-29.9 kg/m2 ). Trial Registration This trial was registered in the Chinese Clinical Trials Registry (ChiCTR2000039068). The date of first registration, 15/10/2020, http://www.chictr.org.cn

This paper proposes a kinetostatic approach for analyzing the joint torques of a redundant snake robot. The method is suitable for weightless space environments. With the high degree of freedom and flexible cable actuation, the redundant snake robot is well-suited for utilization in space-weightless environments. This method reduces computational cost by using the multiplication of matrices and vectors instead of inverse matrices. Taking advantage of the velocity screw (twist) and force screw (wrench), this strategy provides an idea for redundant serial robots to achieve the calculation of joint torques. This methodology is straightforward for programming and has good computational efficiency. The instantaneous work performed by the actuation is expressed with the force screw. According to the principle of virtual work, the kinetostatic equation of the robot can be obtained and the torque required for each joint can be determined. Meanwhile, to solve the inertia force generated by joint acceleration, D’Alembert’s principle is adopted to transform the dynamic problem into a static problem. Through kinetostatic analysis of a redundant snake robot, this paper shows the approach of establishing the kinetostatic model to calculate the torque in screw form. At the same time, the actuation distribution of the redundant snake robot is also cracked effectively for practical purposes. Due to the difficulty of achieving weightless space environments, this paper validates the method by using ADAMS simulation without gravity in the simulation.

The Notch pathway is a conserved cell-cell communication pathway that controls cell fate decisions. Here we sought to determine how Notch pathway activation inhibits the neuroendocrine cell fate in the lungs, an archetypal process for cell fate decisions orchestrated by Notch signaling that has remained poorly understood at the molecular level. Using intratumoral heterogeneity in small-cell lung cancer as a tractable model system, we uncovered a role for the transcriptional regulators REST and YAP as promoters of the neuroendocrine to non-neuroendocrine transition. We further identified the specific neuroendocrine gene programs repressed by REST downstream of Notch in this process. Importantly, we validated the importance of REST and YAP in neuroendocrine to non-neuroendocrine cell fate switches in both developmental and tissue repair processes in the lungs. Altogether, these experiments identify conserved roles for REST and YAP in Notch-driven inhibition of the neuroendocrine cell fate in embryonic lungs, adult lungs, and lung cancer.

Abstract Direct-current triboelectric nanogenerators arising from electrostatic breakdown can eliminate the bottleneck problem of air breakdown in conventional triboelectric nanogenerators, offering critical benefits of constant-current output, resistance to electromagnetic interference, and high output power density. Previous understanding is that its output characteristics are described by a capacitor-breakdown model or dictated by one or two discharge domains in direct-current triboelectric nanogenerators. Here, we demonstrate that the former holds only for ideal conditions and the latter cannot fully explain the dynamic process and output performance. We systematically image, define, and regulate three discharge domains in direct-current triboelectric nanogenerators, then a “cask model” is developed to bridge the cascaded-capacitor-breakdown dynamic model in ideal conditions and real outputs. Under its guidance, the output power is increased by an order of magnitude within a wide range of resistive loads. These unexplored discharge domains and optimization methods revolutionize the output performance and potential applications of direct-current triboelectric nanogenerators.

Background: Endometriosis (EMs) is a common chronic inflammatory disease which is characterized by multiple clinical symptoms and high recurrence rate due to the absence of effective therapies. Huayu Jiedu Formula (HYJDF), is a traditional Chinese medicine prescription with five major herbs. It has been used as traditional medicine to treat EMs for more than twenty years and exerted a good therapeutic effect. However, the underlying mechanism is unclear. Here we aim to observe the effects of HYJDF on EMs and investigate the therapeutic mechanism. Methods: The extract components of HYJDF were identified and quantified by an UHPLC-QE-MS method. Network pharmacology was used to obtain the core targets of HYJDF for the treatment of EMs and the specific biologic processes involved. A total of 68 EMs cases were randomly divided into control (gestrinone) and observation (HYJDF) groups. The overall effectiveness, pain scores, cyst-size changes, serum CA125 levels, quality-of-life scores, safety, and adverse events were evaluated before and after treatment. For the mechanism research, DNA methylation-chip analysis was performed to determine the differential genes. EMs mice models and human ectopic stromal cells (ESCs) were treated with HYJDF and its pharmaceutical serum, respectively. The ectopic foci was measured via H&E staining while the expressions of the target genes were verified by real-time PCR and Western blot analysis. The inflammatory cytokine levels in the peritoneal fluid of mice were detected by ELISA. The proliferative potential of cells was analyzed by MTS whereas the apoptosis and cell cycle were determined through flow analysis. Results: The total number of components detected in positive and negative ion modes was 839 and 597, respectively. Network pharmacology suggested that HYJDF treated EMs through DNA methylation. We found that HYJDF and gestrinone exerted good therapeutic effect with no obvious difference, but the HYJDF treatment group had fewer side effects. GATA 6, which was hypomethylated and abundant in endometriotic cells, potently induced inflammatory response. This finding indicated the important role of GATA 6 in EMs development. Moreover, HYJDF ameliorated inflammatory response (i.e., reduced the levels of IL-1β and PGE2 in peritoneal fluid), suppressed ESCs proliferation, and increased cell apoptosis by down-regulating GATA 6 expression. Conclusion: We demonstrated that HYJDF has anti-inflammation activity and increased cell apoptosis through the reduction of GATA 6 expression in ectopic tissues, which showed good therapeutic effect without any obvious side effects. These findings suggest that HYJDF may be a new and efficient traditional Chinese medicine for the treatment of EMs.

Background: Vaccination is the most effective means of preventing outbreaks of infectious diseases, and family ;decision makers play an important role in decision-making regarding family matters and may influence other family members to take an active role in vaccinating children against COVID-19. Purpose: This study examined the influence of family decision makers on the hesitation of other family members to vaccinate their children against COVID-19. Methods: A population-based, self-administered online questionnaire was administered in Taizhou, China, from September 1, 2021, to September 15, 2021. The questionnaire included demographic information, knowledge, attitudes, and perceptions about the COVID-19 vaccine as well as hesitation regarding the use of the COVID-19 vaccination in children. In total, 490 respondents were included in this study. Logistic regression was used to assess the factors associated with vaccine hesitancy. Results: In total, 490 respondents from 190 households were interviewed. Of the 190 family decision makers, 43.7% (83/190) were hesitant to vaccinate their children against COVID-19. When family decision makers were hesitant to vaccinate children against COVID-19, 65.1% (82/126) of the other family members expressed similar hesitancy regarding vaccination. When family decision makers were not hesitant to vaccinate children, only 21.3% (37/174) of other family members were hesitant to do so. In the regression analysis, family decision makers' hesitation to vaccinate their children was associated with other family members' hesitation (OR=6.264, 95% CI:3.132–12.526). In addition, decision makers’ perceptions of the safety of the vaccine (OR=0.422, 95% CI:0.215–0.826) and hesitation to vaccinate themselves (OR=8.967, 95% CI:4.745–16.948) influenced their hesitation to vaccinate their children. Conclusion: The present study found that family decision makers' hesitation to vaccinate children against COVID-19 influenced other family members' hesitation to vaccinate children. In addition, family decision makers' perceptions of the safety of the vaccine and their hesitation to vaccinate themselves influenced other family members’ hesitation to vaccinate their children.