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Abstract Background Mothers play a crucial role in influencing their daughters’ HPV vaccination decisions. Addressing barriers to receiving HPV vaccination among mothers of girls may achieve two goals in one strike: increasing vaccination coverage among both mothers and their daughters. This study aims to examine the HPV vaccination uptake and its determinants among mothers of girls in China at both the individual and interpersonal levels. Methods From July to October 2023, a cross-sectional online study was conducted to investigate HPV vaccine refusal for daughters aged 9–17 years among 11,678 mothers in Shenzhen, China. A randomized selection method was employed, targeting 11 primary schools and 13 secondary schools in Shenzhen. The research team invited mothers of girls to participate in an anonymous online survey. Multilevel logistic regression models (level 1: schools; level 2: individual participants) were employed to analyze the data. Results Among 11,678 mothers, 41.1% self-reported receiving at least one dose of HPV vaccination. Through multilevel logistic regression analysis, eight items measuring illness representations of HPV, which refers to how people think about HPV, were associated with higher HPV vaccination uptake (AOR: 1.02–1.14). These items included identity (identifying symptoms of HPV), timeline (whether HPV is acute/chronic), negative consequences, personal and treatment control (whether HPV is under volitional control), concern, negative emotions, and coherence (overall understanding of HPV). In addition, participants refusing HPV vaccines for the index daughters (AOR: 0.82, 95%CI: 0.76, 0.89) had lower vaccine uptake. Perceived more difficulties in accessing the 9-valent vaccines (AOR: 1.06, 95%CI: 1.04, 1.08) and more satisfaction with vaccine-related promotional materials (AOR: 1.50, 95%CI: 1.46, 1.54) at the individual level were associated with higher vaccine uptake. At the interpersonal factors, higher frequency of exposure to testimonials given by others about HPV vaccination on social media (AOR: 1.19, 95%CI: 1.14, 1.25) and thoughtful consideration of the veracity of the information (AOR: 1.11, 95%CI: 1.07, 1.16) were correlated with higher HPV vaccination uptake. Conclusions These findings offer essential implications for modifying HPV disease perceptions, addressing difficulties in accessing the 9-valent HPV vaccines, and enhancing health communication needs to improve HPV vaccine uptake among mothers of girls.

Abstract Background Although immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer treatment, only a minority of colorectal cancer (CRC) patients respond to them. Enhancing tumor immunogenicity by increasing major histocompatibility complex I (MHC-I) surface expression is a promising strategy to boost the antitumor efficacy of ICIs. Methods Dual luciferase reporter assays were performed to find drug candidates that can increase MHC-I expression. The effect of nilotinib on MHC-I expression was verified by dual luciferase reporter assays, qRT-PCR, flow cytometry and western blotting. The biological functions of nilotinib were evaluated through a series of in vitro and in vivo experiments. Using RNA-seq analysis, immunofluorescence assays, western blotting, flow cytometry, rescue experiments and microarray chip assays, the underlying molecular mechanisms were investigated. Results Nilotinib induces MHC-I expression in CRC cells, enhances CD8+ T-cell cytotoxicity and subsequently enhances the antitumor effects of anti-PDL1 in both microsatellite instability and microsatellite stable models. Mechanistically, nilotinib promotes MHC-I mRNA expression via the cGAS-STING-NF-κB pathway and reduces MHC-I degradation by suppressing PCSK9 expression in CRC cells. PCSK9 may serve as a potential therapeutic target for CRC, with nilotinib potentially targeting PCSK9 to exert anti-CRC effects. Conclusion This study reveals a previously unknown role of nilotinib in antitumor immunity by inducing MHC-I expression in CRC cells. Our findings suggest that combining nilotinib with anti-PDL1 therapy may be an effective strategy for the treatment of CRC.

Abstract Radar High‐Resolution Range Profile (HRRP) has great potential for target recognition because it can provide target structural information. Existing work commonly applies deep learning to extract deep features from HRRPs and achieve impressive recognition performance. However, most approaches are unable to distinguish between the target and non‐target regions in the feature extraction process and do not fully consider the impact of background noise, which is harmful to recognition, especially at low signal‐to‐noise ratios (SNR). To tackle these problems, the authors propose a radar HRRP target recognition framework termed Adaptive Soft Threshold Transformer (ASTT), which is composed of a patch embedding (PE) layer, ASTT blocks, and Discrete Wavelet Patch Merging (DWPM) layers. Given the limited semantic information of individual range cells, the PE layer integrates nearby isolated range cells into semantically explicit target structure patches. Thanks to its convolutional layer and attention mechanism, the ASTT blocks assign a weight to each patch to locate the target areas in the HRRP while capturing local features and constructing sequence correlations. Moreover, the ASTT block efficiently filters noise features in combination with a soft threshold function to further enhance the recognition performance at low SNR, where the threshold is adaptively determined. Utilising the reversibility of the discrete wavelet transform, the DWPM layer efficiently eliminates the loss of valuable information during the pooling process. Experiments based on simulated and measured datasets show that the proposed method has excellent target recognition performance, noise robustness, and small‐scale range shift robustness.

ABSTRACT Aim New‐onset diabetes mellitus is a frequent and severe complication arising after liver transplantation (LT). We aimed to identify the risk factors for new‐onset diabetes mellitus after liver transplantation (NODALT) and to develop a risk prediction score system for relevant risks. Methods We collected and analyzed data from all recipients who underwent liver transplantation at the First Affiliated Hospital of Xi'an Jiaotong University. The OR derived from a multiple logistic regression predicting the presence of NODALT was used to calculate the risk prediction score. The performance of the risk prediction score was externally validated in patients who were from the CLTR (China Liver Transplant Registry) database. Results A total of 468 patients met the outlined criteria and finished the follow‐up. Overall, NODALT was diagnosed in 115 (24.6%) patients. Age, preoperative impaired fasting glucose (IFG), postoperative fasting plasma glucose (FPG), and the length of hospital stay were significantly associated with the presence of NODALT. The risk prediction score includes age, preoperative IFG, postoperative FPG, and the length of hospital stay. The risk prediction score of the area under the receiver operating curve was 0.785 (95% CI: 0.724–0.846) in the experimental population and 0.782 (95% CI: 0.708–0.856) in the validation population. Conclusions Age at the time of transplantation, preoperative IFG, postoperative FPG, and length of hospital stay were independent predictive factors of NODALT. The use of a simple risk prediction score can identify the patients who have the highest risk of NODALT and interventions may start early.

Highlights Novel laser-induced transfer method for fabricating glucose sensors from recycled e-waste copper, offering a sustainable and cost-effective solution. Unique heterogeneous Cu x O nano-skeletons derived from discarded printed circuit boards exhibiting exceptional glucose-sensing performance (sensitivity: 9.893 mA mM−1 cm−2, detection limit: 0.34 μM). Miniaturized glucose detection device, optimized for scalability and portability, revolutionizing diabetes management and patient care.

ABSTRACTTransgene silencing is a common phenomenon observed in Caenorhabditis elegans, particularly in the germline, but the precise mechanisms underlying this process remain elusive. Through an analysis of the transcription factors profile of C. elegans, we discovered that the expression of several transgenic reporter lines exhibited tissue-specific silencing, specifically in the intestine of C. elegans. Notably, this silencing could be reversed in mutants defective in endogenous RNA interference (RNAi). Further investigation using knock-in strains revealed that these intestine-silent genes were indeed expressed in vivo, indicating that the organism itself regulates the intestine-specific silencing. This tissue-specific silencing appears to be mediated through the endo-RNAi pathway, with the main factors of this pathway, mut-2 and mut-16, are significantly enriched in the intestine. Additionally, histone modification factors, such as met-2, are involved in this silencing mechanism. Given the crucial role of the intestine in reproduction alongside the germline, the transgene silencing observed in the intestine reflects the self-protective mechanisms employed by the organisms. In summary, our study proposed that compared to other tissues, the transgenic silencing of intestine is specifically regulated by the endo-RNAi pathway.

Ceftazidime-avibactam (CZA) is a recently approved combination synthetic β-lactamase inhibitor used in human clinical medicine. Cases of CZA resistance in humans have already been reported, but limited research has investigated CZA resistance in pets. This study explored the prevalence and transmission of CZA-resistant Escherichia coli (CZAREC) among pets, their owners, veterinarians, and the environment in animal hospitals. A total of 5,419 clinical samples were collected from dogs and cats, along with samples from the environment (n = 5,843), veterinarians (n = 557), and pet owners (n = 368) in animal hospitals. From these samples, 760 Escherichia coli (E. coli) isolates were obtained, out of which 60 were identified as CZAREC. These included 34 isolates from the environment (9.14 %, n = 372), three from veterinarians (8.11 %, n = 37), and 23 from animals (6.82 %, n = 337). No CZAREC isolates were found in pet owners. The predominant sequence types of CZARECs were ST156 (n = 20), ST410 (n = 19) and ST101 (n = 7). Bayesian analysis revealed six clusters comprising 47 isolates from the hospital environment, pets, and veterinaries, displaying genetic relatedness of less than 100 core genome single nucleotide polymorphisms (cgSNPs) between any two isolates in each cluster. Some CZAREC isolates with high genetic similarity persisted in the same animal hospital for four to six months. Moreover, discriminant analysis of principal components indicated that most isolates from different hosts shared a genetic source in the human/dog/cat merged cluster. Overall, evidence of CZARECs transmission was found among pets, the environment, and veterinarians in animal hospitals. The findings emphasize the importance of monitoring CZARECs in the veterinary clinical setting to ensure the health of both pets and humans.

Abstract Background Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24’s role in peripheral nociception remain unclear. Methods Using patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca2+ channels (T-type channels). Results IL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2. Conclusion Our findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.

Abstract Modulation of the cervix by steroid hormones and commensal microbiome play a central role in the health of the female reproductive tract. Here we describe organ-on-a-chip (Organ Chip) models that recreate the human cervical epithelial-stromal interface with a functional epithelial barrier and production of mucus with biochemical and hormone-responsive properties similar to living cervix. When Cervix Chips are populated with optimal healthy versus dysbiotic microbial communities (dominated by Lactobacillus crispatus and Gardnerella vaginalis, respectively), significant differences in tissue innate immune responses, barrier function, cell viability, proteome, and mucus composition are observed that are similar to those seen in vivo. Thus, human Cervix Organ Chips represent physiologically relevant in vitro models to study cervix physiology and host-microbiome interactions, and hence may be used as a preclinical testbed for development of therapeutic interventions to enhance women’s health.

Coronavirus disease 2019 (COVID-19) is a severe global public health emergency that has caused a major crisis in the safety of human life, health, global economy, and social order. Moreover, COVID-19 poses significant challenges to healthcare systems worldwide. The prediction and early warning of infectious diseases on a global scale are the premise and basis for countries to jointly fight epidemics. However, because of the complexity of epidemics, predicting infectious diseases on a global scale faces significant challenges. In this study, we developed the second version of Global Prediction System for Epidemiological Pandemic (GPEP-2), which combines statistical methods with a modified epidemiological model. The GPEP-2 introduces various parameterization schemes for both impacts of natural factors (seasonal variations in weather and environmental impacts) and human social behaviors (government control and isolation, personnel gathered, indoor propagation, virus mutation, and vaccination). The GPEP-2 successfully predicted the COVID-19 pandemic in over 180 countries with an average accuracy rate of 82.7%. It also provided prediction and decision-making bases for several regional-scale COVID-19 pandemic outbreaks in China, with an average accuracy rate of 89.3%. Results showed that both anthropogenic and natural factors can affect virus spread and control measures in the early stages of an epidemic can effectively control the spread. The predicted results could serve as a reference for public health planning and policymaking.

Corona virus disease 2019 (COVID-19) has exerted a profound adverse impact on human health. Studies have demonstrated that aerosol transmission is one of the major transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenic microorganisms such as SARS-CoV-2 can survive in the air and cause widespread infection among people. Early monitoring of pathogenic microorganism transmission in the atmosphere and accurate epidemic prediction are the frontier guarantee for preventing large-scale epidemic outbreaks. Monitoring of pathogenic microorganisms in the air, especially in densely populated areas, may raise the possibility to detect viruses before people are widely infected and contain the epidemic at an earlier stage. The multi-scale coupled accurate epidemic prediction system can provide support for governments to analyze the epidemic situation, allocate health resources, and formulate epidemic response policies. This review first elaborates on the effects of the atmospheric environment on pathogenic microorganism transmission, which lays a theoretical foundation for the monitoring and prediction of epidemic development. Secondly, the monitoring technique development and the necessity of monitoring pathogenic microorganisms in the atmosphere are summarized and emphasized. Subsequently, this review introduces the major epidemic prediction methods and highlights the significance to realize a multi-scale coupled epidemic prediction system by strengthening the multidisciplinary cooperation of epidemiology, atmospheric sciences, environmental sciences, sociology, demography, etc. By summarizing the achievements and challenges in monitoring and prediction of pathogenic microorganism transmission in the atmosphere, this review proposes suggestions for epidemic response, namely, the establishment of an integrated monitoring and prediction platform for pathogenic microorganism transmission in the atmosphere.

Abstract Purpose To understand the ocular biometric parameters characteristics and refractive errors in 3-to 6-year-old preschool children in Chengdu, China, and to investigate the prevalence of refractive errors. Method A school-based cross-sectional study was conducted in Chengdu from 2020 to2022 with a total of 666 kindergartens. All children were measured by non-cycloplegic autorefraction and uncorrected visual acuity (UCVA) and ocular biometric parameters. Finally, univariate linear regression models were used to analyze the relationship between ocular biometric parameters and refraction. Results A total of 108,578 preschool children aged 3–6 underwent examinations, revealing a myopia prevalence of 6.1%. The mean axial length (AL), keratometry (K), corneal radius (CR), axial length/corneal radius (AL/CR) Ratio, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), and vitreous chamber depth (VCD) were 22.35 ± 0.69 mm, 43.35 ± 1.58 D, 7.80 ± 0.28 mm, 2.87 ± 0.08, 533.31 ± 32.51 μm, 2.70 ± 0.28 mm, 3.91 ± 0.27 mm, and 15.20 ± 0.68 mm, respectively. With increasing age, AL, CR, AL/CR ratio, CCT, ACD, LT, and VCD also increased. Regardless of age, males consistently exhibited longer AL, flatter corneal curvature, shallower ACD, thicker CCT, thinner LT, and longer VCD compared to females. AL, K, CR, LT, and VCD all showed significant linear relationships with SE (all P

Abstract Background Sedentary behavior has been demonstrated to be a modifiable factor for several chronic diseases, while coffee consumption is believed to be beneficial for health. However, the joint associations of daily sitting time and coffee consumption with mortality remains poorly understood. This study aimed to evaluate the independent and joint associations of daily sitting time and coffee intakes with mortality from all-cause and cardiovascular disease (CVD) among US adults. Methods An analysis of a prospective cohort from the 2007–2018 National Health and Nutrition Examination Survey of US adults (n = 10,639). Data on mortality were compiled from interview and physical examination data until December 31, 2019. Daily sitting time was self-reported. Coffee beverages were from the 24-hour diet recall interview. The main outcomes of the study were all-cause and cardiovascular disease mortality. The adjusted hazard ratios [HRs] and 95% confidence intervals [CI] were imputed by Cox proportional hazards regression. Results Among 10,639 participants in the study cohort, there were 945 deaths, 284 of whom died of CVD during the follow-up period of up to 13 years. Multivariable models showed that sitting more than 8 h/d was associated with higher risks of all-cause (HR, 1.46; 95% CI, 1.17–1.81) and CVD (HR, 1.79; 95% CI, 1.21–2.66) mortality, compared with those sitting for less than 4 h/d. People with the highest quartile of coffee consumption were observed for the reduced risks of both all-cause (HR, 0.67; 95% CI, 0.54–0.84) and CVD (HR, 0.46; 95% CI, 0.30–0.69) mortality compared with non-coffee consumers. Notably, joint analyses firstly showed that non-coffee drinkers who sat six hours or more per day were 1.58 (95% CI, 1.25–1.99) times more likely to die of all causes than coffee drinkers sitting for less than six hours per day, indicating that the association of sedentary with increased mortality was only observed among adults with no coffee consumption but not among those who had coffee intake. Conclusions This study identified that sedentary behavior for more than 6 h/d accompanied with non-coffee consumption, were strongly associated with the increased risk of mortality from all-cause and CVD.

Abstract High-throughput sequencing has ushered in a paradigm shift in gastric microbiota, breaking the stereotype that the stomach is hostile to microorganisms beyond H. pylori. Recent attention directed toward the composition and functionality of this 'community' has shed light on its potential relevance in cancer. The microbial composition in the stomach of health displays host specificity which changes throughout a person's lifespan and is subject to both external and internal factors. Distinctive alterations in gastric microbiome signature are discernible at different stages of gastric precancerous lesions and malignancy. The robust microbes that dominate in gastric malignant tissue are intricately implicated in gastric cancer susceptibility, carcinogenesis, and the modulation of immunosurveillance and immune escape. These revelations offer fresh avenues for utilizing gastric microbiota as predictive biomarkers in clinical settings. Furthermore, inter-individual microbiota variations partially account for differential responses to cancer immunotherapy. In this review, we summarize current literature on the influence of the gastric microbiota on gastric carcinogenesis, anti-tumor immunity and immunotherapy, providing insights into potential clinical applications.

ABSTRACT: The circadian misalignment (CM) disordered circadian rhythms exert adverse effects on animals. Poultry as one of animals suffers health and welfare problems due to long-term lighting photoperiods caused by CM. However, the roles of CM on organ development, cell growth, metabolism and immune are still unclear in chickens. In this study, a Chinese dual-purpose native breed, was used to explore the effects of CM on transcriptomic pattern of brain and cell energy biogenesis, and further fecal microbiota transplantation (FMT) was applied to investigate its “therapy” effect from CM suffering. Our results showed that the CM led to stunting in brain and small intestine of chicken. CM decreased of cell proliferation, and energy production, mtDNA copies and expression of genes related to cell cycle or mitochondrial biogenetics, while it upregulated the reactive oxygen species (ROS) level and the sensitivity to inflammation. Interestingly, FMT rescued the organ developmental defects and cell dysfunctions induced by CM. Circadian misalignment brought about abnormal tissue and cell developments, energy biogenesis, and immune response in birds. This study provided a comprehensive perspective on understanding the regulation of CM and FMT on bird development and welfare.

IntroductionNanofibrous spheres, with their injectable format and biomimetic three-dimensional topologies that emulate the complexity of natural extracellular environments, have become increasingly attractive for applications in biomedical and regenerative medicine. Our research contributes to this growing field by detailing the design and fabrication of a novel series of polylactic acid/nano-hydroxyapatite (PLA/nHA) hybrid nanofibrous spheres.MethodsThese advanced structures were created by integrating electrospinning and electrospray techniques, which allowed for precise control over the nanofibrous spheres, especially in size. We have conducted a comprehensive investigation into the nanofibrous spheres’ capacity to deliver stem cells efficiently and maintain their viability post-implantation, as well as their potential to induce osteogenic differentiation.Results and DiscussionThe results show that these nanofibrous spheres are biocompatible and injectable, effectively supporting the attachment, growth, and differentiation of bone marrow-derived mesenchymal stem cells while aiding in their targeted transportation to bone defect areas to execute their regenerative functions. The findings of this study could significantly impact the future development of biocompatible materials for a range of therapeutic applications, including bone tissue engineering and regenerative therapy.

Background: China started to implement the HPV vaccination program for females in 2016. This study investigated associations between mothers’ decisional conflicts, satisfaction with governmental health promotion materials, and their daughters’ HPV vaccination uptake. Methods: A cross-sectional online survey was conducted between July and October 2023 among mothers of girls aged 9–17 years in Shenzhen, China. Participants were mothers having a daughter aged 9–17 years at the survey date and a smartphone with internet access. About 3 % of all primary and secondary schools in Shenzhen were randomly selected by the research team (11 primary schools and 13 secondary schools). Teachers at the selected schools invited mothers of female students aged 9–17 years to complete an anonymous online questionnaire. Multivariate logistic regression was fitted. Results: Among 11,728 mothers who completed the survey, 18.9% of their index daughters received at least one dose of HPV vaccination. In multivariate analysis, less decisional conflict about the choice of HPV vaccines for their daughters (AOR: 1.07, 95%CI: 1.05, 1.10), more satisfaction with the government’s health promotional materials related to HPV vaccines (AOR: 1.15, 95%CI: 1.12, 1.19), receiving more cue to action from significant others (AOR: 1.23, 95%CI: 1.19, 1.27), and perceived higher self-efficacy related to HPV vaccines (AOR: 1.79, 95%CI: 1.67, 1.92) were associated with a higher uptake of HPV vaccines. Perceived susceptibility to HPV (AOR: 0.79, 95%CI: 0.74, 0.85), perceived barriers to having the index daughter receive HPV vaccines (AOR: 0.82, 95%CI: 0.80, 0.84), and mothers who were hesitant to receive HPV vaccination (AOR: 0.75, 95%CI: 0.68, 0.84) were associated with a lower uptake. Conclusion: HPV vaccination uptake was low among girls in China. Future health promotion should address mothers’ decisional conflicts about the choice of HPV vaccines for their daughters and improve the health promotional materials. School-based HPV vaccination programs might be useful.

Abstract Wood‐decay macrofungi play a vital role in forest ecosystems by promoting nutrient cycling and soil structure, and their evolution is closely related to their host plants. This study investigates the potential evolutionary adaptation of wood‐decay macrofungi to their host plants, focusing on whether these relationships differ between gymnosperms and angiosperms. While previous research has suggested non‐random associations between specific fungi and plant deadwood, direct evidence of evolutionary adaptation has been lacking. Our study, conducted in a subtropical region, utilized metabarcoding techniques to identify deadwood species and associated fungi. We found significant evidence of evolutionary adaptation when considering all sampled species collectively. However, distinct patterns emerged when comparing angiosperms and gymnosperms: a significant evolutionary adaptation was observed of wood‐decay macrofungi to angiosperms, but not to gymnosperms. This variation may be due to the longer evolutionary history and more stable species interactions of gymnosperms, as indicated by a higher modularity coefficient (r = .452), suggesting greater specialization. In contrast, angiosperms, being evolutionarily younger, displayed less stable and more coevolving interactions with fungi, reflected in a lower modularity coefficient (r = .387). Our findings provide the first direct evidence of differential evolutionary adaptation dynamics of these fungi to angiosperms versus gymnosperms, enhancing our understanding of forest ecosystem carbon cycling and resource management.

Ficus carica is an economically important horticultural plant. Due to its abundant secondary metabolites, F. carica has gained interest for its applications in medicine and as a nutritional supplement. Both external and internal factors affect the accumulation of secondary metabolites in F. carica. The assembly of the F. carica genome has facilitated functional analysis of key genes and transcription factors associated with the biosynthesis of secondary metabolites, particularly anthocyanin. In this review, we summarize the various types and functions of secondary metabolites, with a particular focus on flavonoids, coumarins, and terpenes. We also explore the factors influencing their biosynthesis and accumulation, including varieties, tissue, environmental factors (e.g., light), stresses (e.g., high temperature, low temperature, drought, nutrient deficiencies, salinity), hormonal treatments, and developmental factors. Furthermore, we discuss the involvement of structural genes and transcription factors in the biosynthesis of secondary metabolites, specifically anthocyanin and furanocoumarins, knowledge of which will promote the breeding and genetic engineering of novel F. carica varieties.

B-cell acute lymphoblastic leukemia (B-ALL) is a malignant blood disorder, particularly detrimental to children and adolescents, with recurrent or unresponsive cases contributing significantly to cancer-associated fatalities. IKBKE, associated with innate immunity, tumor promotion, and drug resistance, remains poorly understood in the context of B-ALL. Thus, this research aimed to explore the impact of the IKBKE inhibitor MCCK1 on B-ALL cells. The study encompassed diverse experiments, including clinical samples, in vitro and in vivo investigations. Quantitative real-time fluorescence PCR and protein blotting revealed heightened IKBKE mRNA and protein expression in B-ALL patients. Subsequent in vitro experiments with B-ALL cell lines demonstrated that MCCK1 treatment resulted in reduced cell viability and survival rates, with flow cytometry indicating cell cycle arrest. In vivo experiments using B-ALL mouse tumor models substantiated MCCK1's efficacy in impeding tumor proliferation. These findings collectively suggest that IKBKE, found to be elevated in B-ALL patients, may serve as a promising drug target, with MCCK1 demonstrating potential for inducing apoptosis in B-ALL cells both in vitro and in vivo.

Abstract Extracting maximal information from experimental data requires access to the likelihood function, which however is never directly available for complex experiments like those performed at high energy colliders. Theoretical predictions are obtained in this context by Monte Carlo events, which do furnish an accurate but abstract and implicit representation of the likelihood. Strategies based on statistical learning are currently being developed to infer the likelihood function explicitly by training a continuous-output classifier on Monte Carlo events. In this paper, we investigate the usage of Monte Carlo events that incorporate the dependence on the parameters of interest by reweighting. This enables more accurate likelihood learning with less training data and a more robust learning scheme that is more suited for automation and extensive deployment. We illustrate these advantages in the context of LHC precision probes of new Effective Field Theory interactions.

Abstract Herpes simplex virus 1 (HSV-1) latent infection entails repression of viral lytic genes in neurons. By functional screening using luciferase-expressing HSV-1, we identify ten neuron-specific microRNAs potentially repressing HSV-1 neuronal replication. Transfection of miR-9, the most active candidate from the screen, decreases HSV-1 replication and gene expression in Neuro-2a cells. Ectopic expression of miR-9 from lentivirus or recombinant HSV-1 suppresses HSV-1 replication in male primary mouse neurons in culture and mouse trigeminal ganglia in vivo, and reactivation from latency in the primary neurons. Target prediction and validation identify transcription factors Oct-1, a known co-activator of HSV transcription, and all three Onecut family members as miR-9 targets. Knockdown of ONECUT2 decreases HSV-1 yields in Neuro-2a cells. Overexpression of each ONECUT protein increases HSV-1 replication in Neuro-2a cells, human induced pluripotent stem cell-derived neurons, and primary mouse neurons, and accelerates reactivation from latency in the mouse neurons. Mutagenesis, ChIP-seq, RNA-seq, ChIP-qPCR and ATAC-seq results suggest that ONECUT2 can nonspecifically bind to viral genes via its CUT domain, globally stimulate viral gene transcription, reduce viral heterochromatin and enhance the accessibility of viral chromatin. Thus, neuronal miR-9 promotes viral epigenetic silencing and latency by targeting multiple host transcription factors important for lytic gene activation.

Objective: To optimize the extraction method of total flavonoids from Peony purpurea seeds with microwave-assisted deep eutectic solvent, and to investigate its antioxidant activity in vitro. Methods: Microwave-assisted technology using deep eutectic solvent as extraction solvent was used to extract total flavonoids from Paeonia rockii seeds. Single factorial experiments and response surface methodology optimized the extraction process. The in vitro antioxidant activity of the total flavonoids was evaluated in terms of the rate of scavenging of DPPH radicals and the rate of scavenging of hydroxyl radicals. Results: Under the deep eutectic solvent system with chloride as hydrogen bond acceptor and urea as hydrogen bond donor, the deep eutectic solvent system with a molar ratio of 1:3 and a water content of 41.80% (V/V) was optimal. The ratio of material to liquid was 1:19 g/mL, the power of the microwave was 110 W and the time of the microwave was 3.00 min. The total flavonoid yield from Paeonia rockii seeds was 1.76 mg/g. When the total flavonoid concentration of the extract was 80 μg/mL, the scavenging rate of DPPH reached 82.00%. And the scavenging rate of hydroxyl radicals was 42.10% when the total flavonoid concentration of the extract was up to 80 μg/mL. Conclusion: Microwave-assisted deep eutectic solvent extraction of total flavonoids from Paeonia rockii seeds has high content, antioxidant activity and DPPH free radical scavenging rate of more than 80%.

Abstract The athlete's paradox phenomenon involves the accumulation of intramuscular triglycerides (IMTG) in both insulin-resistant and insulin-sensitive endurance athletes. Nevertheless, a complete understanding of this phenomenon is yet to be achieved. Recent research indicates that lactate, a common byproduct of physical activity, may increase the accumulation of IMTG in skeletal muscle. This is achieved through the activation of G protein-coupled receptor 81 (GPR81) leads to the suppression of the cyclic adenosine monophosphate–protein kinase A (cAMP–PKA) pathway. The mechanism accountable for the increase in mitochondrial content in skeletal muscle triggered by lactate remains incomprehensible. Based on current research, our objective is to explore the role of the GPR81-inhibited cAMP–PKA pathway in the aggregation of IMTG and the increase in mitochondrial content as a result of prolonged exercise. The GPR81–cAMP–PKA-signaling pathway regulates the buildup of IMTG caused by extended periods of endurance training (ET). This is likely due to a decrease in proteins related to fat breakdown and an increase in proteins responsible for fat production. It is possible that the GPR81–cAMP–PKA pathway does not contribute to the long-term increase in mitochondrial biogenesis and content, which is induced by chronic ET. Additional investigation is required to explore the possible hindrance of the mitochondrial biogenesis and content process during physical activity by the GPR81–cAMP–PKA signal.

Abstract Background This study examined the association between social support and the severity of positive symptoms in rural community-dwelling schizophrenia patients during the COVID-19 pandemic. Method The cross-sectional study included 665 rural community-dwelling schizophrenia patients investigated during the COVID-19 pandemic. Social support was measured using the Social Support Rating Scale, and positive symptoms were assessed using the Positive Scale extracted from the Positive and Negative Syndrome Scale. Multiple linear regression was adopted to examine the association of social support with positive symptoms. Result The scores for total social support, subjective support, objective support and the use of social support were 28.3 ± 5.9, 16.4 ± 5.2, 6.5 ± 1.4 and 5.4 ± 2.8, respectively. Total social support (β = −0.08, 95%CI: −0.13 to −0.02, P

Terahertz synthetic aperture radar (THz SAR) imaging has gradually become one of the hotspots with the development of THz technology. The wide bandwidth can provide satisfactory resolution in the SAR imaging, whereas the small wavelength makes the imaging system more sensitive to the platform vibration error (VE), which may seriously affect its image quality. In this article, a novel parameters estimation method of motion error in the THz SAR imaging based on the Viterbi algorithm (VA) and random sample consensus (RANSAC) algorithm is proposed. First, the VA is employed to extract the instantaneous frequency (IF) introduced by the platform VE. The VA is defined based on the generalization of IF characteristics, and it further considers the relationship between the frequency points at adjacent time points based on the maximum value search in the time–frequency representation, which makes it perform well in the IF extraction. Second, the RANSAC algorithm in conjunction with the nonlinear least square (NLS) algorithm and the minimum-entropy principle is proposed to perform the VE parameters estimation. Due to the noise or the platform velocity variation, there will exist the points that deviate from the high-frequency VE, which can be mitigated via the combination of the RANSAC algorithm and the NLS technique. Simultaneously, the well-focused THz SAR imaging results can be acquired after compensating via the best parameter estimation results selected by the minimum-entropy principle. Finally, the validity of the proposed method has been demonstrated through the simulation and real-measured experiments.

Implementing the model-based control strategies for Series Elastic Actuators (SEAs) is not an easy task due to the unknown system dynamics in their force models such as modeling uncertainties and external disturbances. In this paper, an enhanced unknown system dynamics estimator (EUSDE) is presented for the SEAs to online estimate the lumped unknown system dynamics in real time with guaranteed convergence and noise rejection response. The proposed approach is an extension of our previously developed unknown system dynamics estimator (USDE). The key idea is to further address the sensitivity of the USDE to measurement noise to further enhance the estimation performance. In this line, a high-order filter is introduced to the design and analysis of USDE. Moreover, this study also provides a comparative analysis of USDE and EUSDE from both the time-domain and frequency-domain perspectives. Finally, comparative simulation and experimental results are provided to demonstrate the effectiveness of the proposed methods.

Abstract Background To construct and validate a prediction model of the risk of citrate accumulation in patients with hepatic dysfunction receiving continuous renal replacement therapy with regional citrate anticoagulation (RCA-CRRT), which reduces the risk of citrate accumulation. Methods All patients who received RCA-CRRT from 2021 to 2022 and were hospitalized in the First Affiliated Hospital of Zhejiang University were considered for study participation. Logistic regression analysis was used to identify the risk factors for citrate accumulation, based on which a nomogram model was constructed and validated in the validation group. Results Six factors were finally identified, from which a nomogram was created to predict the risk of citrate accumulation. The area under the curve of the prediction model was 0.814 in the training group and 0.819 in the validation group, and the model showed acceptable agreement between the actual and predicted probabilities. Decision curve analysis also demonstrated that the model was clinically useful. Conclusions The model constructed from six factors reliably predicted the risk of citrate accumulation in patients with hepatic insufficiency who received RCA-CRRT.

Abstract To explore the research status on mechanism of the skid-resistance for asphalt pavement, the related achievements of the rubber friction, the tire–road contact, and the influence factors were reviewed. The rubber friction was reviewed from the mechanism and rubber friction model. The tire-road contact was studied from the modeling methods, the evaluation methods, and the skid-resistance mechanisms at different conditions. The influence factors of skid-resistance were summarized from different designing processes. This review showed that the appropriate contact or evaluation model should be selected according to the required parameters. Although the finite element method is widely used, the accuracy of the model, the boundary conditions, and the load cases need to be further improved. The optimized aggregates and asphalt binders, reasonable gradation, reasonable geometric design, and strict construction quality control are necessary for good initial skid-resistance. Pavement texture as an important factor affecting skid-resistance should be considered in pavement gradation design, especially for wearing layer technology.

In complex environments, mobile robots performing tasks with different hazard levels need to consider different road factors, this paper proposes a functional model correlating task hazard levels with road factors, proposing an innovative Hybrid Adaptive Genetic Algorithm (HAGA). The HAGA integrates an optimized two-optimization (2-opt) operator* with an enhanced Adaptive Genetic Algorithm (AGA) for efficient path planning in diverse tasks and complex road conditions. Firstly, pre-optimize the initial paths is performed by introducing a new domain knowledge-based operator that duplicates paths in the path are deleted to avoid the redundant paths, and then they are divided into the TOP layer and the ordinary layer, the TOP layer is optimized by using the adaptive 2-opt* operator that satisfies the hyperbolic tangent function (TANH), and the crossover and variability of the ordinary layer are optimized by using the S-type function (Sigmoid function, Sigmoid) and TANH AGA for the optimization treatment for the crossover and variance of the ordinary layer, respectively, to establish a robot path planning algorithm suitable for multitasking in complex environments. The experiment proves that the improved HAGA has strong global search ability and also improves the local search ability, has good generality and robustness, and reduces the optimal path distance by a minimum of 2.74% and a maximum of 10.86% compared with the comparison algorithm in the experiment. The experimental results showed that the method enables mobile robots to perform tasks with different hazard levels in complex environments with good generalization and robustness, and the coefficient of variation (CV) of repeated experiments at five safety levels was kept within 2 %. which had good universality and versatility. This research has the potential to enhance the safety and efficiency of mobile robot operations in challenging environments.

Objective: This study aimed to evaluate the effect of case-based learning (CBL) method with virtual reality (VR) simulation technology (CBL-VR) on midwifery laboratory courses. Methods: A quasi-experimental design was employed. A total of 135 midwifery students were recruited from Nursing College of Guilin Medical University in China from September 2020 to January 2022. Intervention group recruited students from the Class of 2019 (n = 59) and control group recruited students from the Class of 2018 (n = 76). The intervention group students received the CBL-VR method based on traditional laboratory teaching, the contents of course included four sections: eutocia (6 class hours), dystocia (6 class hours), umbilical cord prolapse (2 class hours), and neonatal asphyxia and resuscitation (4 class hours), 40 min per class hour. The control group students received the traditional laboratory teaching. Students’ academic performance, Self-Directed Learning (SDL) Ability Questionnaire, and the education satisfaction questionnaire were used to evaluate the teaching efficacy between two groups. Results: After intervention, the intervention group students achieved higher scores than the control group in individual operation ability (90.88 ± 2.14 vs. 89.24 ± 3.15), team operation ability (90.97 ± 2.33 vs. 81.28 ± 5.45), and midwifery case analysis ability (88.64 ± 3.19 vs. 86.70 ± 2.56) (P ＜0.01). Prior to the implementation of the course, there was no difference in the SDL ability scores between the two groups of students (P ＞ 0.05). However, following the course intervention, the SDL ability scores of the intervention group were higher than those of the control group (94.78 ± 6.59 vs. 88.12 ± 8.36), and the scores in all dimensions of the intervention group were also higher (P

Abstract The recent claim of room temperature superconductivity in a copper-doped lead apatite compound, called LK-99, has sparked remarkable interest and controversy. Subsequent experiments have largely failed to reproduce the claimed superconductivity, while theoretical works have identified multiple key features including strong electronic correlation, structural instabilities, and dopability constraints. A puzzling claim of several recent theoretical studies is that both parent and copper-doped lead apatite structures are dynamically unstable at the harmonic level, questioning decades of experimental reports of the parent compound structures and the recently proposed copper-doped structures. In this work, we demonstrate that both parent and copper-doped lead apatite structures are dynamically stable at room temperature. Anharmonic phonon–phonon interactions play a key role in stabilizing some copper-doped phases, while most phases are largely stable even at the harmonic level. We also show that dynamical stability depends on both volume and correlation strength, suggesting controllable ways of exploring the copper-doped lead apatite structural phase diagram. Our results fully reconcile the theoretical description of the structures of both parent and copper-doped lead apatite with the experiment.

Abstract The circadian-controlled DNA repair exhibits a strong diurnal rhythm. Disruption in circadian clock and DNA repair is closely linked with hepatocellular carcinoma (HCC) progression, but the mechanism remains unknown. Here, we show that polymerase beta (POLB), a critical enzyme in the DNA base excision repair pathway, is rhythmically expressed at the translational level in mouse livers. Hepatic POLB dysfunction dampens clock homeostasis, whereas retards HCC progression, by mediating the methylation of the 4th CpG island on the 5′UTR of clock gene Per1. Clinically, POLB is overexpressed in human HCC samples and positively associated with poor prognosis. Furthermore, the hepatic rhythmicity of POLB protein expression is orchestrated by Calreticulin (CALR). Our findings provide important insights into the molecular mechanism underlying the synergy between clock and food signals on the POLB-driven BER system and reveal new clock-dependent carcinogenetic effects of POLB. Therefore, chronobiological modulation of POLB may help to promote precise interventions for HCC.

Abstract Invariant cell lineage in C. elegans enables spatiotemporal resolution of transcriptional regulatory mechanisms controlling the fate of each cell. Here, we develop RAPCAT (Robust-point-matching- And Piecewise-affine-based Cell Annotation Tool) to automate cell identity assignment in three-dimensional image stacks of L1 larvae and profile reporter expression of 620 transcription factors in every cell. Transcription factor profile-based clustering analysis defines 80 cell types distinct from conventional phenotypic cell types and identifies three general phenotypic modalities related to these classifications. First, transcription factors are broadly downregulated in quiescent stage Hermaphrodite Specific Neurons, suggesting stage- and cell type-specific variation in transcriptome size. Second, transcription factor expression is more closely associated with morphology than other phenotypic modalities in different pre- and post-differentiation developmental stages. Finally, embryonic cell lineages can be associated with specific transcription factor expression patterns and functions that persist throughout postembryonic life. This study presents a comprehensive transcription factor atlas for investigation of intra-cell type heterogeneity.

Background Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients’ condition.Methods An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided.Results A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP.Conslusions Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.

ABSTRACTThis study investigated the influences of mother-daughter communication and social media on mothers’ HPV vaccine refusal for their daughters aged 9–17. A cross-sectional online survey among 11,728 mothers of girls aged 9–17 in Shenzhen, China was implemented between July and October 2023. Multi-level logistic regression models were fitted. Among 11,728 participants, 43.2% refused to have their daughters receive an HPV vaccination. In multivariate analysis, more openness in the mother-daughter communication (AOR: 0.99, 95%CI: 0.98, 0.99), perceived more positive outcomes of mother-daughter communication (AOR: 0.77, 95%CI: 0.75, 0.79), higher frequency of exposure to testimonials about daughters’ HPV vaccination (AOR: 0.81, 95%CI: 0.78, 0.85) and information encouraging parents to vaccinate their daughters against HPV on social media (AOR: 0.76, 95%CI: 0.73, 0.79), and thoughtful consideration of the veracity of the information specific to HPV vaccines (AOR: 0.80, 95%CI: 0.77, 0.83) were associated with lower vaccine refusal. Mothers who were not the main decision-makers of daughters’ HPV vaccination (AOR: 1.28 to 1.46), negative outcome expectancies of mother-daughter communication (AOR: 1.06, 95%CI: 1.04, 1.08), and mothers’ HPV vaccine refusal (AOR: 2.81, 95%CI: 2.58, 3.06) were associated with higher vaccine refusal for their daughters. The level of mothers’ HPV vaccine refusal for their daughters was high in China. Openness and outcome expectancies of mother-daughter communication and information exposure on social media were considered key determinants of HPV vaccine refusal for daughters. Future HPV vaccination programs should consider these interpersonal factors.

AbstractRainfall is an excitation factor for rainfall-type debris flows, and high-frequency rainfall commonly does not directly trigger large-scale catastrophic debris flows. A low-frequency, large-scale catastrophic debris flow occurred in Heishui Gully (HSG), Pingwu County, Sichuan Province, southwestern China on 12 July 2022. In this study, the HSG debris flow was used as a case study to reveal the formation mechanisms of low-frequency and large-scale catastrophic debris flow triggered by high-frequency gentle rainfall by calculating and analysing a total of five indicators, including the Standard Precipitation Index (SPI), the Freeze-Thaw Index (FTI), the empirical relationship between earthquakes and landslides, the hypsometric integral (HI) and human activities. The study results indicate that high-frequency gentle rainfall is a direct factor in the debris flow outbreak in HSG. Long-duration extreme drought conditions and extreme freeze-thaw erosion provided sufficient soil conditions for debris flow formation. Frequent earthquakes and mature erosional geomorphologic evolution have indirectly contributed to the debris flow formation. Simultaneously, human activities downstream of HSG amplified the risk of debris flow disaster. The results reveal the contribution of extreme climates and human activities to low-frequency, large-scale catastrophic debris flows initiated by high-frequency gentle rainfall, which is significant for accurately assessing and predicting debris flow occurrence.

Abnormal serum Na (SNa) levels are common in patients with chronic kidney disease (CKD) which is associated with increased morbidity and mortality. There are relatively few studies on the effect of SNa indicators on the prognosis of patients undergoing maintenance hemodialysis (MHD). We aim to investigate the effect of long-term SNa levels on the survival and prognosis of patients undergoing hemodialysis (HD). Newly entered HD patients in the registration system of Zhejiang Provincial Dialysis Quality Control Center between January 1, 2010 and December 31, 2019 were included and followed up until December 31, 2020. Multiple sodium levels were collected from patients, defining long-term SNa as the mean of multiple SNa, according to which patients were grouped, with the prognostic differences between subgroups compared by Kaplan-Meier modeling and multifactorial Cox regression modeling. Finally, a total of 21,701 patients were included in this study and Cox regression showed that decreased SNa levels (Na < 135 mmol/L, HR = 1.704, 95% CI 1.408–2.063, p 145mmol/L, HR = 2.150, 95% CI 1.615–2.863, p

PURPOSEGenetic variants of ovarian cancer (OV) show ethnic differences, but data from the Chinese population are still insufficient. Here, we elucidate the inheritance landscape in Chinese patients with OV and examine the functional implications of a Chinese-enriched RAD51D variant.METHODSBetween 2015 and 2018, 373 consecutive patients with OV were prospectively enrolled. Variants of BRCA1/2, other homologous recombination repair (HRR) genes, and DNA mismatch repair (MMR) genes were analyzed using next-generation sequencing. An enriched RAD51D variant was identified, and its functional effects were examined using Cell Counting Kit-8, colony formation, transwell migration, and drug sensitivity assays.RESULTSOverall, 31.1% (116/373) of patients had at least one pathogenic or likely pathogenic germline variant. BRCA1 and BRCA2 accounted for 16.09% and 5.36%, respectively, with one patient having both variants. In addition, 32 (8.58%) patients carried other HRR gene variants, whereas three (0.8%) patients had MMR gene variants. The RAD51D variant ranked third (8/373, 2.1%), and its rate was much higher than that in other populations. Remarkably, all eight patients harbored the RAD51D K91fs variant (c.270_271dup, p.Lys91Ilefs*13) and demonstrated satisfactory platinum response and favorable prognosis. This variant confers enhanced sensitivity to poly (ADP-ribose) polymerase inhibitors in OV cells. However, the effects on platinum sensitivity were inconsistent across different cell lines. Against the background of the TP53 variant, RAD51D K91fs variant showed increased sensitivity to cisplatin.CONCLUSIONOur study revealed the inheritance landscape of OV and identified an enriched RAD51D variant in Chinese patients with OV. This can serve as an important reference for OV management and a potential therapeutic target.

Summary: Amygdala serves as a highly cellular, heterogeneous brain region containing excitatory and inhibitory neurons and is involved in the dopamine and serotoninergic neuron systems. An increasing number of studies have revealed the underpinned mechanism mediating social hierarchy in mammal and vertebrate, however, there are rare studies conducted on how amygdala on social hierarchy in poultry. In this study, we conducted food competition tests and determined the social hierarchy of the rooster. We performed cross-species analysis with mammalian amygdala, and found that cell types of human and rhesus monkeys were more closely related and that of chickens were more distant. We identified 26 clusters and divided them into 10 main clusters, of which GABAergic and glutamatergic neurons were associated with social behaviors. In conclusion, our results provide to serve the developmental studies of the amygdala neuron system and new insights into the underpinned mechanism of social hierarchy in roosters.

Background: Anterior shoulder dislocation is the most common type of shoulder dislocation and is easy to develop into recurrent type, causing economic burden to society. This study uses the bibliometric method to analyze the global research status, hotspots and trends of anterior shoulder dislocation, aiming to promote the exploration of anterior shoulder dislocation. Methods: The literature on anterior shoulder dislocation in the past two decades were retrieved and downloaded from the Web of Science Core Collection (WOSCC) database. CiteSpace, VOSviewer and bibliometrix package of R software were used to conduct scientific bibliometric analysis of the literature. Finally, some statistical graphics were performed in Graphpad Prism. Results: A total of 3914 publications related to anterior shoulder dislocation from 2003 to 2022 were retrieved and screened from the WOSCC database. The ranking of the analysis results showed that Provencher MT was the author with the highest frequency of occurrence. Rush University was the most notable contributor. The American Journal of Sports Medicine was the most comprehensive journal. The United States was the most prominent country. Keywords related to surgical treatment were more significant than others. Conclusion: In the past two decades, the research output on anterior shoulder dislocation have been increasing year by year. The focus has gradually shifted to surgical treatment. Surgical treatment may continue to be the research hotspots in this field in the future.

Abstract Since ancient times, humans have learned to use fire and other heating methods to fight against dangerous pathogens, like cooking raw food, sterilizing surgical tools, and disinfecting other pathogen transmission media. However, it remains difficult for current heating methods to achieve extremely fast and highly efficient sterilization simultaneously. Herein, an ultrafast and uniform heating‐based strategy with outstanding bactericidal performance is proposed. Ultra‐precise laser manufacturing is used to fabricate the Joule heater which can be rapidly heated to 90 °C in 5 s with less than 1 °C fluctuation in a large area by real‐time temperature feedback control. An over 98% bactericidal efficiency on S. aureus for 30 s and on E. coli for merely 5 s is shown. The heating strategy shows a 360 times faster acceleration compared to the commonly used steam sterilization from the suggested guidelines by the Centers for Disease Control and Prevention (CDC), indicating that high temperatures with short duration can effectively disinfect microorganisms. As a proof of concept, this heating strategy can be widely applied to sterilizing cash and various objects to help protect the public from bacteria in daily life.

In this work, a dynamic model considering time-varying mesh stiffness and backlash was proposed and a test rig was built to investigate the vibration behavior of the idle gear set in a gerotor pump. The effects of input shaft speed, torque fluctuation, and gear tooth backlash on the dynamic performance of gerotor pump were analyzed according to the numerical and experimental results. Results demonstrate that when the torque fluctuation is neglected, the dynamic transmission error of drive gear is dominated by the first three mesh harmonic components; however, the RMS values of vibration acceleration have high frequency characteristics. When the torque fluctuation is considered, the dynamic responses of gerotor pump are modulated by the torque fluctuation. The effect of tooth backlash on the dynamic performance of gerotor pump is limited and mostly depended on the torque fluctuation condition. The gerotor pump noise is dominated by the low frequency component around the mesh frequency. The vibration energy can be divided into two parts in the frequency domain. In the low frequency band, the vibration energy is caused by the mechanical vibration. However, in the high frequency band, the cavitation phenomena may cause the concentration of the vibration energy and resonant of pump structure.

Reasonable zoning is essential for maintaining the integrity and stability of natural ecosystems and achieving multi-goal management of national parks, and can facilitate efficient management and protection of various resources. Biocultural diversity is an important result and outstanding representation of human-land relationships, directly affecting the resilience of socio-ecological systems. Taking Kunlun Mountains National Park in Qinghai Province (KMNP) as an example, we transformed the dualistic conservation model of biology and culture, and the Coupling Coordination Degree Model (CCDM) was used to establish a technical framework for the functional zoning of national parks based on the collaborative protection of biological diversity and cultural diversity. The research results indicated that biocultural diversity and its coupling relationship of KMNP are relatively good, with high coupling areas mainly dominated by cultural diversity and low coupling areas mainly by biological diversity. The research suggests that KMNP should be divided into 4 functional zones: strict protection area, ecological conservation area, traditional utilization area, and comprehensive development area. These findings provide references for the planning and construction of national parks and reserves around the world, to unleash their transformative potential in addressing global biodiversity loss.

To realize large-scale hydrogen production by electrolysis of water, it is essential to develop non-precious metal catalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Here, we fabricate Sn-, Fe-, and Co-based sulfide/oxyhydroxide heterostructural catalyst on nickel foam (FeSnCo0.2SxOy/NF) by solvothermal method. The FeSnCo0.2SxOy/NF requires low overpotentials of 48 and 186 mV at 10 mA·cm–2, respectively, for HER and OER. When it is assembled into an electrolytic cell as a bifunctional electrocatalyst, it only needs 1.54 V to reach 10 mA·cm–2, far better than IrO2||Pt/C electrolyzer. The formation of sulfide/hydroxide heterostructural interfaces improves the electron transfer and reduces the reaction energy barrier, thus promoting the electrocatalytic processes.

ObjectivesTo explore the population-wide impacts of an evidence-based high-risk strategy for prevention of cardiovascular diseases in resource-poor populations.MethodsA cluster randomized controlled trial was conducted among 120 villages in rural China, with 60 on intervention and 60 on usual care as controls, for 2 years. The intervention emphasized training village doctors to identify high-risk individuals and administering standardized treatments focusing on hypertension management. A random sample of 20 men aged ≥50 years and 20 women aged ≥60 years was drawn from each village before randomization for the baseline survey, and another independent random sample with the same age and sex distribution was drawn at 2 years for the post-intervention survey. The primary outcome was the population mean systolic blood pressure (SBP). Secondary outcomes included the proportions of patients who received regular primary care, antihypertensive medications, aspirin, or lifestyle advice.ResultsA total of 5,654 high cardiovascular risk individuals were identified and managed by village doctors in intervention villages for 15 months on average, with mean SBP lowered by 19.8 mmHg and the proportion with blood pressure under control increased from 22.1% to 72.7%. The primary analysis of the two independent samples (5,050 and 4,887 participants each) showed that population-wide mean SBP in intervention villages did not differ from that in control villages at 2 years (mean difference = 1.0 mmHg, 95% CI: −2.19, 4.26; P = 0.528), though almost all secondary outcomes concerning primary care indicators significantly increased in intervention villages.ConclusionsIn our study, the pragmatic cardiovascular risk management program targeting on high-risk individuals significantly improved the quality of primary care. However, its impact on population blood pressure level and the burden of hypertension-related diseases appeared very limited. Clinical Trial RegistrationClinicalTrial.gov identifier, NCT01259700.

The use of collaborative robots (Cobots) for materials development in chemical laboratories is currently of high priority. Herein, the Cobot is used for autonomous continued analysis and synthesis of graphene oxide–polyethyleneimine‐based membrane to unify a method and prospects for big data collection are shown. Membranes have already demonstrated a selective affinity to potassium cations and promised to adjust permeability for other cations by changing pH. The Cobot allows a variation of membrane properties by its composition modification. The present strategy combines a novel perspective of material production by Cobots and the application of machine learning. Moreover, the current approach can be adapted for different modern chemical laboratories for various scientific research, and the proper workflow is provided.