Search

Abstract G protein alpha q subunit (Gαq) can binds to the G protein-coupled receptor (GPCR) for signaling and is closely related to lipid metabolism. Endurance exercise is an effective means of combating acquired obesity and its complications, but the mechanisms by which endurance exercise modulates hereditary obesity and its complications are unknown. In this study, we achieved knockdown of Gαq in drosophila adipose tissue and skeletal muscle by constructing the Gαq-UAS-RNAi/Ppl-Gal4 and Gαq-UAS-RNAi/Mef2-GAl4 systems. Drosophila were subjected a three-week endurance exercise intervention, and changes in relevant indicators were detected and observed by RT-PCR, ELISA, oil red staining, immunofluorescence staining, and transmission electron microscopy. The results showed that knockdown of Gαq in both adipose tissue and skeletal muscle induced a significant increase in triglycerides accompanied by a decrease in rapid climbing ability, a decrease in Superoxide Dismutase (SOD) activity level, and a decrease in Mitochondrial respiratory chain complexI (MRCC I) content in Drosophila whole body and skeletal muscle, and down-regulated the expression of the G protein alpha q subunit (Gαq), the skeletal muscle myosin heavy chain expression gene (Mhc), mitochondrial biogenesis gene Spargal(the PGC-1alpha homologue in Drosophila). Endurance exercise significantly improved the triglyceride levels in the whole body and skeletal muscle of drosophila with Gαq knockdown in adipose tissue and skeletal muscle, as well as their ability to climb, increased SOD activity level and MRCCI content level, and up-regulated the expression of Gαq, Mhc, and Spargal(Srl). Thus, the present findings suggest that genetic defects in the Gαq gene in adipose and skeletal muscle tissues induce hereditary obesity and skeletal muscle dysfunction, and that endurance exercise attenuates this hereditary obesity and concomitant skeletal muscle dysfunction in drosophila by improving skeletal muscle fiber contractile proteins, mitochondrial function and function, and antioxidant capacity via mediating the Gαq/Mhc, Gαq/Srl/MRCC-I, and Gαq/SOD pathways.

Abstract This study aimed to investigate the structural properties of tobacco polysaccharide (TP) and its mechanism of modulating hyperlipidemia in high-fat diet-induced mice. The structural properties of TP were characterized by FT-IR, 1HNMR, SEM, AFM and thermogravimetric analysis. And the regulatory mechanism of TP on lipid metabolism was investigated in hyperlipidemia mice. These results showed that TP had a high composition of reducing monosaccharide and the glycosidic bond type was α-glycosidic bond. The intervention by TP resulted in a significant reduction of body weight and improvement in lipid accumulation. And the modulation mechanism by which TP ameliorated the abnormalities of lipid metabolism was associated with the expression levels of lipid metabolism-related genes and serum exosomes miRNA-128-3p, as well as the modulation of structure and abundance of the gut microbiota in mice. In addition, TP treatment significantly increased the content of short-chain fatty acids (SCFAs) in mice feces. The results of molecular docking and dual-luciferase assay exhibited a good interaction between propionic acid and PPAR-α, and it was hypothesized that the interaction might further ameliorate the hyperlipidemia. Therefore, TP can regulate the expression levels of lipid metabolism-related genes through miRNAs from serum exosomes and SCFAs from gut microbiota.

Abstract The electrocatalytic reduction of nitrate toward ammonia under mild conditions addresses many challenges of the Haber-Bosch reaction, providing a sustainable method for ammonia synthesis, yet it is limited by sluggish reduction kinetics and multiple competing reactions. Here, the titanium hydride electrocatalyst is synthesized by electrochemical hydrogenation reconstruction of titanium fiber paper, which achieves a large ammonia yield rate of 83.64 mg h−1 cm−2 and a high Faradaic efficiency of 99.11% with an ampere-level current density of 1.05 A cm−2 at −0.7 V versus the reversible hydrogen electrode. Electrochemical evaluation and kinetic studies indicate that the lattice hydrogen transfer from titanium hydride promotes the electrocatalytic performance of nitrate reduction reaction and the reversible equilibrium reaction between lattice hydrogen and activate hydrogen not only improves the electrocatalytic activity of nitrate reduction reaction but also demonstrates notable catalytic stability. These finding offers a universal design principle for metal hydrides as catalysts for effectively electrochemical ammonia production, highlighting their potential for sustainable ammonia synthesis.

Abstract Background Bipolar disorder may begin as depression or mania, which can affect the treatment and prognosis. The physiological and pathological differences among pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The aims of the present study were to investigate subcortical structural alterations in PBD patients with first-episode depressive (PBD-FED) and first-episode manic (PBD-FEM). Methods A total of 59 individuals including 28 PBD-FED, 13 PBD-FEM, and 18 healthy controls (HCs) underwent high-resolution structural magnetic resonance scans. FreeSurfer 7.2 was used to detect changes in subcortical volumes. Simultaneously, thalamic, hippocampal, and amygdala subregion volumes were compared between the three groups. Results Analysis of covariance controlling for age, sex, education, and estimated intracranial volume shows third and fourth ventricle enlargement in patients with PBD. Compared with the PBD-FED and HCs, the PBD-FEM group had reduced gray matter volume in the left thalamus, bilateral hippocampus, and right amygdala. Subsequent subregion analyses showed right cortico-amygdaloid transient, bilateral accessory-basal nucleus, left hippocampal tail, right hippocampal head, and body volume reduction in the PBD-FEM group. Conclusions The present findings provided evidence of decreased subcortical structure in PBD-FEM patients, which might present its trait feature.

Reservoir heterogeneity, water-oil mobility ratio, cementation degree, and strong injection and production significantly influence long-term waterflooding and polymer flooding processes in oil reservoir development, leading to the formation of low-resistance dominant seepage channels in the lower part of thick oil layers without internal laminations. Understanding the spatial distribution and evolution of dominant seepage channels in oil reservoirs during waterflooding and polymer flooding is crucial for improving reservoir development and recovery rates. It uses a streamlined numerical simulation method to quantitatively show the spatial and temporal distribution of dominant seepage channels in the oil reservoir. A model and chart were created to demonstrate the relationship between permeability and throat radius, capturing changes in reservoir permeabilities over time. The study developed a comprehensive mathematical model to identify dominant seepage channels, considering parameters such as inter-well flow ratio, injection efficiency, permeability change value, and water saturation. Research findings indicate a 14.8 % increase in reservoir permeability after polymer flooding, with slight changes in porosity and a 20.3 % decrease in clay content. The established mathematical model and identification criteria were used to comprehensively quantitatively evaluate flow channels, describing the distribution characteristics and evolution process of dominant seepage channels in the experimental area over four periods: pre-polymer flooding, low water-saturation period during polymer flooding, post-polymer injection, and subsequent 10 years of water flooding. Both polymer flooding and subsequent water flooding have significantly altered the distribution pattern of predominant fluid pathways: 254 well layers now demonstrate robust predominant fluid pathways (19 %); another 272 well layers feature moderately predominant fluid pathways (22 %); while an additional 440 well layers display weaker predominant fluid pathways (approximately 35 %). There has been a noticeable increase in both weak and moderate predominant fluid pathways, which are now more widespread in the area. However, localized occurrences of strong predominant fluid pathways persist with no significant change in their distribution characteristics. Analysis at four different time points shows a clear trend of increasing intensity as we move from polymer to subsequent water flooding in this decade. Additionally, examination along an axis from upper left to lower right reveals a linear progression that indicates clear connections among different categories of dominant seepage channel. The verification results show a strong correlation between the calculated dominant seepage channel distribution and actual water-injection profile test results, indicating that the method effectively identifies dominant seepage channels in oil reservoirs after polymer flooding and has the potential to enhance oil recovery further.

In this paper, we analyze the outage performance of Unmanned Aerial Vehicles (UAVs)-enabled downlink Non-Orthogonal Multiple Access (NOMA) communication systems with the Semi-Grant-Free (SGF) transmission scheme. A UAV provides coverage services for a Grant-Based (GB) user and one Grant-Free (GF) user is allowed to utilize the same channel resource opportunistically. The analytical expressions for the exact and asymptotic Outage Probability (OP) of the GF user are derived. The results demonstrate that no-zero diversity order can be achieved only under stringent conditions on users' quality of service requirements. Subsequently, an efficient Dynamic Power Allocation (DPA) scheme is proposed to relax such data rate constraints. The analytical expressions for the exact and asymptotic OP of the GF user with the DPA scheme are derived. Finally, Monte Carlo simulation results are presented to validate the correctness of the derived analytical expressions and demonstrate the effects of the UAV's location and altitude on the OP of the GF user.

Abstract The ancient Yi script has been used for over 8000 years, which can be ranked with Oracle,Sumerian,Egyptian,Mayan and Harappan,and is one of the six ancient scripts in the world. In this article, we collected 2922 handwritten single word samples of commonly used ancient Yi characters. Each character was written by 310 people respectively, with a total of 427,939 valid characters. We completed continuous handwritten text sampling, written by 250 people, with 5 texts per person, covering topics such as Yi astronomy, geography, rituals, and agriculture. In the process of data collection, we proposed an automatic sampling method for ancient Yi script, and completed the automatic cutting and labeling of handwritten samples. Furthermore, we tested the recognition performance of the sorted data set under different deep learning network models. The results show that ancient Yi script has diverse shape structures and rich writing styles, which can be used as a benchmark data set in related fields such as handwritten text recognition and handwritten text generation.

Abstract The abrasive water-jet (AWJ) erosion process involves the complex interaction between fluid medium, abrasive particles and solid material, which brings great challenges to the establishment of numerical model. Because traditional grid-based methods are not suitable for the problems of local deformation and material removal, the meshfree method smoothed particle hydrodynamics (SPH), based on the unresolved coupling and the discrete element method (DEM), is adopted to establish the model for AWJ study. The fluid medium is treated as a weakly compressible viscous liquid, the solid material is treated as an elastic-plastic material, and the abrasives are treated as rigid bodies. The fluid and solid phases are discretized with SPH particles, and the abrasives are described with DEM particles. The Johnson-Cook (J-C) and Johnson-Holmquist-II (JH-2) constitutive models are used to describe the stress-strain behavior of ductile and brittle materials, respectively. The effectiveness of the numerical model is further verified by AWJ impact experiments. The plastic deformation and cumulative failure characteristics of ductile materials, and the crack formation and propagation characteristics of brittle materials are systematically analyzed. The results provide insight for the AWJ research and lay a foundation for investigation of other complex fluid-particle flow in a numerical way.

Abstract Background Immune checkpoint inhibitors (ICIs) have emerged as a novel and effective treatment strategy, yet their effectiveness is limited to a subset of patients. The gut microbiota, recognized as a promising anticancer adjuvant, is being increasingly suggested to augment the efficacy of ICIs. Despite this, the causal link between the gut microbiota and the success of immunotherapy is not well understood. This gap in knowledge has driven us to identify beneficial microbiota and explore the underlying molecular mechanisms. Methods Through 16S rDNA sequencing, we identified distinct gut microbiota in patients undergoing treatment with ICIs. Following this, we assessed the impact of probiotics on anti-PD-1 therapy in bladder cancer using mouse models, employing a multi-omics strategy. Subsequently, we uncovered the mechanisms through which Blautia-produced metabolites enhance antitumor immunity, utilizing untargeted metabolomics and a range of molecular biology techniques. Results In our research, the LEfSe analysis revealed a significant enrichment of the Blautia genus in the gut microbiota of patients who responded to immunotherapy. We discovered that the external addition of Blautia coccoides hampers tumor growth in a bladder cancer mouse model by enhancing the infiltration of CD8+ T cells within the tumor microenvironment (TME). Further investigations through untargeted metabolomics and molecular biology experiments showed that oral administration of Blautia coccoides elevated trigonelline levels. This, in turn, suppresses the β-catenin expression both in vitro and in vivo, thereby augmenting the cancer-killing activity of CD8+ T cells. Conclusions This research provided valuable insights into enhancing the efficacy of PD-1 inhibitors in clinical settings. It was suggested that applying Blautia coccoides and its metabolic product, trigonelline, could serve as a synergistic treatment method with PD-1 inhibitors in clinical applications. Graphical Abstract

Abstract Unmanned Aerial Vehicle (UAV) oblique photogrammetry has been extensively employed in mining, albeit predominantly for reconstructing three-dimensional scenes and detecting changes within mining sites, lacking predictive capabilities. Leveraging 3D real scene model data, this study presents a two-stage prediction model, merging the probabilistic integral method with recurrent neural network (PIMF-RNN), to mitigate the impact of internal and external factors on surface subsidence, thereby enhancing predictive accuracy. Building upon this framework, a methodology was developed to forecast the maximum surface subsidence height and affected area under the block caving method, offering crucial data support for mitigating hazards associated with this mining technique. Analysis of surface data from Pulang copper mine during 2018–2020 demonstrates a prediction accuracy of 91.47% for maximum surface subsidence height and 87.52% for subsidence area. This research expands the potential applications of UAV oblique photogrammetry techniques within mining contexts. Furthermore, it establishes a cost-effective and efficient operational procedure for predicting mine surface subsidence.

The Sichuan Basin is one of the most severely air-polluted regions in China. To study the scavenging effect of precipitation on PM2.5 and PM10 in Sichuan Basin, the PM2.5 and PM10 mass concentration data from 90 environmental monitoring stations and observation data from 17 ground meteorological stations in Sichuan Basin from 2016 to 2021 were used. First, the effects of precipitation on the spatial distribution of PM2.5 and PM10 in the Sichuan Basin were analyzed. Then, the influence of precipitation intensity and duration on PM2.5 and PM10 removal effects was revealed based on the removal rates of aerosol particle mass concentration changes before and after precipitation. Finally, by calculating the removal coefficients using the raindrop spectral distribution, raindrop sizes, and end-of-fall velocities, the removal effects of precipitation on four PM2.5 and PM10 pollution events in the Sichuan Basin were investigated. The results are as follows: (1) In the Sichuan Basin, precipitation affects the spatial distribution of PM2.5 and PM10. The greater the precipitation amounts and the longer the duration of precipitation, the greater the removal rates and the more significant the scavenging effect. (2) In cases of heavy rainfall, removal rates are not sensitive to increases in precipitation duration when it exceeds 6 hours. (3) When the raindrop diameter, the total number of raindrops, and the minute rain intensity peak, and the raindrop spectra broaden and intensify, rapid decreases of PM2.5 and PM10 mass concentrations occur. (4) The removal coefficients are indicative of variations in PM2.5 and PM10 mass concentrations. When the peak removal coefficients are above 10 h-1, the scavenging effect of precipitation on PM2.5 and PM10 is significant.

Abstract The human thermal stress indices and datasets are vital for promoting public health and reducing negative environmental impacts as global climate change and extreme meteorological events increase. The current thermal indices generally use an instantaneous or average value to describe thermal stress which cannot reflect the distribution of thermal comfort conditions over time, and there are no global-scale thermal stress datasets with both 0.1° or higher spatial resolution and hourly temporal resolution available yet. A novel human thermal metric, Thermal Stress Duration (TSD), is proposed to represent the accumulative time of different thermal stress levels within a certain period. A high temporal resolution global gridded dataset of human thermal stress metrics (HiGTS) is presented, which consists of hourly gridded maps of Universal Thermal Climate Index (UTCI), Universal Thermal Stress (UTS), and daily TSD at 0.1° × 0.1° spatial resolution over the global land surface, spanning from January 1, 2000, to December 31, 2023.

Abstract Muscle stem cells (MuSCs) are effective in treating inflammatory diseases driven by overactive innate immune responses, such as colitis and acute lung injury, due to their immunomodulatory properties. However, their potential in treating diseases driven by adaptive immune responses is still uncertain. When primed with inflammatory cytokines, MuSCs strongly suppressed T cell activation and proliferation in vitro in co-culture with activated splenocytes or peripheral blood mononuclear cells. Systemic administration of MuSCs from both mice and humans alleviated pathologies in mice with concanavalin A-induced acute liver injury, characterized by hyperactivated T lymphocytes. Importantly, MuSCs showed significant species-specific differences in their immunoregulatory functions. In mouse MuSCs (mMuSCs), deletion or inhibition of inducible nitric oxide synthase (iNOS) reduced their immunosuppressive activity, and absence of iNOS negated their therapeutic effects in liver injury. Conversely, in human MuSCs (hMuSCs), knockdown or inhibition of indoleamine 2,3-dioxygenase (IDO) eliminated their immunosuppressive effects, and loss of IDO function rendered hMuSCs ineffective in treating liver injury in mice. These results reveal significant species-specific differences in the mechanisms by which MuSCs mediate T cell immunosuppression. Mouse MuSCs rely on iNOS, while human MuSCs depend on IDO expression. This highlights the need to consider species-specific responses when evaluating MuSCs’ therapeutic potential in immune-related disorders.

Abstract Retained fetal membranes (RFM) is an important reproductive disease in dairy cows, caused by maternal and fetal placental tissue adhesion. The main collagen in maternal and fetal placenta tissues is collagen type IV (COL-IV) and its breakdown is the key to placental expulsion. Focal adhesion kinase (FAK) has been shown to regulate the hydrolysis of Col-IV by affecting the activity of MMP-2 and MMP-9 activity, but the regulation of the mechanisms involved in placenta expulsion in dairy cows after postpartum are still unclear. The aim of this study was to investigate the pathogenic mechanism of RFM by studying the relationship between the FAK signaling pathway and COL-IV regulation. Maternal placental tissues were collected from six healthy and six cows with RFM of similar age, parity, body condition and milk yield at 12 h postpartum. In vitro experiments were performed on bovine endometrial epithelial cells from three groups including a FAK inhibitor group, a FAK activator group and a control group without FAK inhibitor and activator. The abundance of molecules involved in the FAK signaling pathway and COL-IV was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The immunohistochemical results showed that the key molecules of FAK signaling pathway FAK, Src, MMP-2 and MMP-9 and Col-IV were expressed in placental tissues. The expression level of FAK, Src, MMP-2, and MMP-9 were significantly down-regulated (P

Abstract Objectives Preterm delivery rates have increased obviously worldwide over the past decade, yet reliable epidemiological studies on the incidence of preterm birth and temporal trends are not available in Hainan, The Free Trade Port in China. We aimed to describe the rate of preterm birth and trends between 2010 and 2021 and to primarily explore risk factors associated with preterm birth in Hainan, China. Methods This was an observational study was based on data from the Hainan Provincial Birth Certificate System (HPBCS) for live births between 1 January 2010 and 31 December 2021. We included pregnancies resulting in at least one live birth, with newborns born at a gestational age of 28 weeks or greater, or with a birth weight of 1000 g or more. The outcome were preterm birth rates and their trends over time. Potential risk factors were collected, including infant gender, maternal age, paternal age, maternal ethnicity, paternal ethnicity, home address, and single or multiple pregnancies. The logistic regression model was used to assess the relationship between preterm birth and potential risk factors. Results A total of 1,537,239 live births and 86,328 preterm births were investigated, giving a total preterm birth rate of 5.62%. The overall preterm birth rate increased from 4.47% in 2010 to 7.12% in 2021 (compound annual growth rate [CAGR] 4.32). The CAGR of late preterm birth is consistent with the overall preterm birth rate (4.32%). The fastest growth is observed in the rate of very preterm births (5.53%), while the rate of moderate preterm births exhibits the slowest growth (3.87%). Infant gender, multiple pregnancy, home address, parental age, and ethnicity had significant effects on preterm birth. Conclusion The preterm birth rate was increasing year by year from 2010 to 2021 in Hainan, The Free Trade Port in China. Incidence of preterm births in Hainan Province in relation to multiple pregnancies, infant sex, parental age, parental race and residential address.

Abstract The accumulation of α-synuclein induces neuronal loss in midbrain nuclei and leads to the disruption of motor circuits, while the pathology of α-synuclein in cortical regions remains elusive. To better characterize cortical synucleinopathy, here we generate a mouse model with the overexpression of human α-synuclein in the primary motor cortex (M1) of mice. A combination of molecular, in vivo recording, and behavioral approaches reveal that cortical expression of human α-synuclein results in the overexcitation of cortical pyramidal neurons (PNs), which are regulated by the decreased inhibitory inputs from parvalbumin-interneurons (PV-INs) to impair complex motor skill learning. Further mechanistic dissections reveal that human α-synuclein aggregation activates ferroptosis, contributing to PV-IN degeneration and motor circuit dysfunction. Taken together, the current study adds more knowledge to the emerging role and pathogenic mechanism of ferroptosis in neurodegenerative diseases.

Abstract Background The global rise in developmental delays underscores the critical need for a thorough understanding and timely interventions during early childhood. Addressing this issue, the Chinese Baby Connectome Project (CBCP)’s behavior branch is dedicated to examining language acquisition, social-emotional development, and environmental factors affecting Chinese children. The research framework is built around three primary objectives: developing a 0–6 Child Development Assessment Toolkit, implementing an Intelligent Coding System, and investigating environmental influence. Methods Utilizing an accelerated longitudinal design, the CBCP aims to enlist a minimum of 1000 typically developing Chinese children aged 0–6. The data collected in this branch constitutes parental questionnaires, behavioral assessments, and observational experiments to capture their developmental milestones and environmental influences holistically. The parental questionnaires will gauge children’s developmental levels in language and social-emotional domains, alongside parental mental well-being, life events, parenting stress, parenting styles, and family relationships. Behavioral assessments will involve neurofunctional developmental evaluations using tools such as the Griffiths Development Scales and Wechsler Preschool and Primary Scale of Intelligence. Additionally, the assessments will encompass measuring children’s executive functions (e.g., Head-Toe-Knee-Shoulder), social cognitive abilities (e.g., theory of mind), and language development (e.g., Early Chinese Vocabulary Test). A series of behavior observation. experiments will be conducted targeting children of different age groups, focusing primarily on aspects such as behavioral inhibition, compliance, self-control, and social-emotional regulation. To achieve the objectives, established international questionnaires will be adapted to suit local contexts and devise customized metrics for evaluating children’s language and social-emotional development; deep learning algorithms will be developed in the observational experiments to enable automated behavioral analysis; and statistical models will be built to factor in various environmental variables to comprehensively outline developmental trajectories and relationships. Discussion This study’s integration of diverse assessments and AI technology will offer a detailed analysis of early childhood development in China, particularly in the realms of language acquisition and social-emotional skills. The development of a comprehensive assessment toolkit and coding system will enhance our ability to understand and support the development of Chinese children, contributing significantly to the field of early childhood development research. Trial registration This study was registered with clinicaltrials.gov NCT05040542 on September 10, 2021.

ObjectiveTo understand the composition of the respiratory virus pathogen spectrum of influenza-like cases in Guizhou province from 2022 to 2023, and to further analyze the genetic characteristics and variation patterns of influenza A (H1N1) pdm subtype viruses. MethodsA total of 519 influenza-like cases were collected in Guizhou province from 2022 to 2023. Multiplex fluorescent quantitative PCR was used to detect common respiratory pathogens, including influenza viruses (IFV), parainfluenza viruses (HPIV), coronaviruses (HCoV), respiratory syncytial virus (RSV), adenovirus (ADV), human metapneumovirus (HMPV), rhinovirus (HRV), and bocavirus (HBoV), as well as their subtypes. SPSS 22.0 was used for data analysis of the detection results. High-throughput sequencing technology was used to determine the whole genome sequences of influenza A (H1N1) pdm subtype viruses. Nextclade and MEGA7 were used to analyze the hemagglutinin (HA) gene sequences and the mutations in glycosylation sites, antigenic determinants, and receptor-binding sites. ResultsA total of 363 positive samples were detected, with an overall positive rate of 61.42%. The top three detection rates were IFV-A (H1N1) pdm subtype viruses (positive rate 15.06%, 89 cases), IFV-A (H3N2) subtype viruses (positive rate 13.71%, 81 cases), and SARS-CoV-2 (positive rate 13.37%, 79 cases). The P-values for the detection rates of respiratory pathogens in different genders and age groups were 0.119 and 0.078, respectively, with P > 0.05, indicating no statistically significant differences. The detection rate of respiratory pathogens in different seasons was P < 0.001, showing a statistically significant difference. A total of 36 cases of mixed infections were detected, with a detection rate of 6.09%. Rhinovirus mixed infections were the most common (17 cases, accounting for 47.22%). A total of 16 whole genome sequences of influenza A(H1N1)pdm09 subtype viruses from Guizhou province were obtained, all belonging to the 6B.1A.5a.2a evolutionary branch. The Sb antigenic determinant underwent A186T and Q189E amino acid substitutions. The receptor-binding site underwent mutations in the 190-helix (184-191): A186T, Q189E, and the 220-loop E224A. No changes in glycosylation sites were found. ConclusionRespiratory viruses are important pathogens in influenza-like cases, with influenza viruses being the most common. The proportion of mixed infections is relatively high. IFV and HMPV detection rates show significant seasonal differences. The molecular structure and function of influenza A(H1N1)pdm09 subtype viruses in Guizhou province from 2022 to 2023 have not undergone major changes, and they match well with the vaccine strains, indicating good antibody protection from influenza vaccines.

Abstract Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0]; HR 0.63 [95% CI 0.48–0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

Abstract Background Cell and gene therapy products (CGTPs) often receive accelerated approvals, lacking comprehensive long-term safety and efficacy data, which can raise significant safety concerns. This research aims to study the post-marketing surveillance (PMS) of CGTPs in the European Union (EU), the United States (US), Japan, South Korea, and China, to offer insights for the development of a secure and standardized post-marketing regulatory framework for CGTPs. Methods Related regulations and the implementation effect of PMS for approved CGTPs were studied searching PubMed, CNKI, and the official websites of the European Medicines Agency, the US Food and Drug Administration, Japan’s Pharmaceuticals and Medical Device Agency, South Korea’s Ministry of Food and Drug Safety, and the National Medical Products Administration of China. Results Compared to those in China, the guidelines of PMS for CGTPs in the EU, the US, Japan, and South Korea was more comprehensive. Notably, the EU had dedicated regulations and supporting guidelines of PMS. Of the 26 CGTPs approved in the EU, 88% were under additional monitoring, 38% received conditional marketing authorization, and 12% were authorized under exceptional circumstances, with 77% designated as orphan drugs. The US had released 34 guidelines specifically for CGTPs which, forming the foundation of post-marketing risk management. Among the 27 CGTPs approved in the US, 22% were required to perform risk evaluation and mitigation strategies, 37% added black box warnings in the package inserts, 63% mandated to post-marketing requirements, and 15% subject to post-marketing commitments. In Japan, stringent supervision measures encompassing all-case surveillance (79%) and re-examination (53%) were applied to the 19 approved CGTPs, with 21% approved through conditional and time-limited approval. The PMS for CGTPs in South Korea, mainly included PSUR, re-examination, and re-evaluation. China had introduced several relevant regulations, which consisted of general statements and lacked detailed guidance. Conclusions This study demonstrates that the regulatory policies of PMS for CGTPs in the EU, the US, Japan, and South Korea were comprehensive. The implementation of PMS for CGTPs in the EU, the US, and Japan was well developed. This knowledge holds valuable insights for China’s future learning and development in this field.

Abstract Tibetan Buddhist monasteries constitute significant cultural heritages of ethnic minorities, evolving into the Principal-Subordinate Monastery System (PSMS) with profound historical and cultural significance. This system exhibits an integrated hierarchical structure in terms of religious dominance, political administration, and cultural diffusion. Existing research primarily focuses on internal humanistic factors such as governance patterns, while there is not any research focused on its patterns and manifestations in spatial distribution. This study aims to elucidate the spatial distribution characteristics of the PSMS in Hehuang region, including the Tibetan Buddhist monasteries from all sects in the Hehuang region since the Song Dynasty It establishes a hierarchical PSMS database based on the affiliation relationships, aimed at storing spatial and property information related to PSMS. The database standardizes the naming and coding of monasteries, and classifies them through hierarchical relationships to ensure data consistency and usability. Finally, the classified and coded monastery data were analyzed by GIS tools to form the PSMS spatial distribution characterisation framework. Results reveal that (1) Monasteries demonstrate notable spatial clustering patterns from both holistic and sectarian perspectives, with density being influenced by the principal monastery’s position. (2) Almost every PSMS exhibits a spatial pattern centered around the principal monastery, with subordinate monasteries clustering within a defined range correlated with the administrative region of the principal monastery. (3) PSMS scale variations are controlled by principal monasteries, exhibiting positive correlations in hierarchical structure, control quantity, and distribution range. (4) The spatial orientation of PSMS correlates with river distribution, while the relationships among mountain ranges require further investigation. These findings provide initial insights into the spatial distribution characteristics of PSMS, confirming the spatial influence of the principal monastery. Besides, this study established an innovative spatial research framework for heritage clusters with multiple types and hierarchies. Thus, this study offers new insights into the spatial distribution of Tibetan Buddhist monastery heritage and presents a framework for further examining the spatial distribution of the Tibetan Buddhist monastery heritage in other regions, as well as other heritage clusters where connected and clustered through religious and cultural ties.

Abstract The impact of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) traits on suicidal thoughts and behaviors (STBs) remains inadequately explored. Hence, the present study aims to delve deeper into these intricate issues, contributing to a better understanding of these complex challenges among Chinese youth. The data of 90,882 participants was collected from 63 Chinese universities and colleges in Jilin, China. We aim to explore the risks of STBs on ASD, ADHD, and co-occurrence of ASD + ADHD by using the Autism Spectrum Quotient-10 items (AQ-10) and Adult ADHD Self Report Scale (ASRS). Propensity score matching (PSM) was implemented to balance demographical variables across the four groups. Binary logistic regression was then conducted to further analyze and compare suicide risk across the four groups, also accounting for sex differences. Suicide risks were significantly higher in the ADHD (OR = 1.24, p

Abstract The question of whether artificial intelligence (AI) can surpass human capabilities is crucial in the application of AI in clinical medicine. To explore this, an interpretable deep learning (DL) model was developed to assess myopia status using retinal refraction maps obtained with a novel peripheral refractor. The DL model demonstrated promising performance, achieving an AUC of 0.9074 (95% CI 0.83–0.97), an accuracy of 0.8140 (95% CI 0.70–0.93), a sensitivity of 0.7500 (95% CI 0.51–0.90), and a specificity of 0.8519 (95% CI 0.68–0.94). Grad-CAM analysis provided interpretable visualization of the attention of DL model and revealed that the DL model utilized information from the central retina, similar to human readers. Additionally, the model considered information from vertical regions across the central retina, which human readers had overlooked. This finding suggests that AI can indeed surpass human capabilities, bolstering our confidence in the use of AI in clinical practice, especially in new scenarios where prior human knowledge is limited.

Abstract Background Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. Methods This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. Results (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (β = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010–0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. Conclusions In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. Trial registration NCT, NCT03158246. Registered 18/05/2017.

Abstract Most current Data Center Interconnects (DCI) use intensity modulation direct detection (IMDD) configurations due to their low complexity and cost. However, significant scaling challenges allow coherent solutions to become contenders in these short reach applications. We present an O-band coherent optical fiber transmission system based on Quantum Dot—Mode Locked Lasers (QD-MLLs) using two independent free-running comb lasers, one each for the carrier and the Local Oscillator (LO). Using a comb-to-comb configuration, we demonstrate a 10 km single mode fiber, O-band, coherent, heterodyne, 12.1 Tbps system operating at 0.47 Tbps/λ using 26 λs. We used fewer comb lines (26 λs), faster symbol rate (56 GBaud) and higher constellation cardinality (32 QAM) relative to the highest capacity C-band systems reported to date. Through design, analysis, and experimentation, we quantify the optimum comb line spacing for this use case. We compare potential configurations for increasing data center interconnect capacities whilst reducing power consumption, complexity, and cost.

ObjectiveTo understand the impaired self-care ability after stroke and its influencing factors among urban and rural elderly people in Henan province, and provide a reference for taking corresponding intervention measures. MethodsFrom July to December 2022, a multi-stage random sampling method was used to select 3 193 elderly people aged ≥ 65 years old who had lived in the local area for ≥ 2.5 years after stroke in 15 districts (counties) of five major regions of eastern Henan, western Henan, southern Henan, northern Henan, and central Henan for a questionnaire survey, and the impaired self-care ability after stroke and its influencing factors of urban and rural elderly people in the region were analyzed. ResultsAmong the 3 067 elderly people after stroke in Henan province finally included in the analysis, 554 had impaired self-care ability, with an impairment rate of 18.06% after stroke; the impairment rates of self-care ability after stroke among urban and rural elderly people in Henan province were 10.96% and 20.00%, respectively, and the impairment rate of self-care ability after stroke among urban elderly people was lower than that among rural elderly people (χ2 = 28.513, P < 0.001); the results of multivariate unconditional logistic regression analysis showed that smoking, kidney disease, heart disease, eye disease, and liver disease were risk factors for impaired self-care ability after stroke among urban elderly people in Henan province, while exercise habits were a protective factor for impaired self-care ability after stroke among urban elderly people in Henan province. Smoking, hearing impairment, kidney disease, heart disease, eye disease, and liver disease were risk factors for impaired self-care ability after stroke among rural elderly people in Henan province, while improved toilet environment, exercise habits, and healthy eating habits were protective factors for impaired self-care ability after stroke among rural elderly people in Henan province. ConclusionThe impairment rate of self-care ability after stroke among rural elderly people in Henan province was higher than that among urban elderly people, and smoking status, presence or absence of exercise habits, kidney disease, heart disease, eye disease, and liver disease were common influencing factors for impaired self-care ability after stroke among urban and rural elderly people in the region.

In the upcoming 6-generation (6G) revolution, the achievement of low power consumption has become a key objective in research concerning terahertz devices. As an important component of passive devices, there are very few low-loss dielectric ceramics in the terahertz range. To elucidate the mechanism of loss and promote the application of microwave dielectric ceramics for future 6G technology (covering microwave and terahertz frequencies), the terahertz responses of ANb2O6 (A = Zn, Co, Mn, and Ni) columbite niobates were studied. The influences of magnetic loss on the Q×f values in the microwave range with different transition metal ions in the A-site were reasonably analyzed. Moreover, due to the weakened magnetic relaxation properties in the terahertz range, the samples all exhibited low loss and approximate transparency, especially for MnNb2O6 and NiNb2O6 (tanδ < 0.01 and absorption coefficient < 10 cm−1 below 1.2 THz), which subverted the definition of traditional low-loss microwave dielectric ceramics. Ultimately, based on Mie theory, we designed a prototypical broadband metamaterial reflector to validate the applicability of the ANb2O6 system in the terahertz band, which is highly important for the development of terahertz ceramic-based passive devices.

Abstract Background The treatment strategy for patients with severe tooth wear associated with Class II Division 2 malocclusion remains a major challenge for dental practitioners. Objectives To systematically review and summarize the literature on treatment strategies, restoration procedures and clinical outcomes for Class II Division 2 malocclusion patients with severe tooth wear. Methods A literature review was conducted using Pubmed, Embase, the Cochrane Library, and Web of Science to identify eligible articles. Publications until October 16th, 2023 were searched independently and cross-checked by two researchers. Results Of 1513 articles screened, 10 reports detailed treatment processes, including six males and four females aged 34–68 years old. Four articles recorded pre-treatment freeway space (FWS) values ranging from 5 to 9 mm. All ten cases had significant occlusal vertical dimension (OVD) loss and the increase in OVD after treatment ranged from 1 to 7 mm. Pre-prosthetic orthodontic treatment was performed in two cases, in one of which only the maxillary region was orthodontically treated. The most common restorations provided were full coverage restorations. In most cases, temporary restorations were applied before the permanent restorations for eight weeks to six months. Four different sequences of final restoration were proposed. Follow-up ranged from four months to six years and included seven patients, one of them showed symptoms of temporomandibular disorder (TMD). Conclusions A multidisciplinary team (MDT) approach to treatment is recommended. Consideration of pre-prosthetic orthodontic treatment is essential. Commonly used cephalometric measurements for anterior teeth include the interincisal angle and collum angle. The increases in OVD ranging from 1 to 7 mm can be effectively accommodated. Temporary restorations are recommended to accommodate the OVD, and the transition periods of 8 weeks to 6 months help the patients adapted well. Four different sequences for final rehabilitation have demonstrated positive clinical outcomes. Full crown restorations have emerged as the preferred choice for the ultimate restoration of these patients.

Abstract Background Pectus carinatum (PC) mainly present at the growth spurt time of the early teenage years or the puberty. Poor outer appearance is a major reason for seeking help for surgeons to increase self-confidence and self-esteem. At present, minimally invasive repair (MIR) is one of effective ways to correct the chest wall deformity. Therefore, there is great practical significance to conduct clinical research on MIR about the adolescent PC. Methods We applied Abramson procedure in PC group or we applied Abramson procedure and Nuss procedure in PC/PE group. We retrospectively reviewed the results of 41 cases who underwent the surgical correction at our department from January 2020 to April 2023. Results All the procedures were successfully done without severe complications. The median operation Time was 80 min in PC group while was 130 min in PC/PE group. The median LOS were 4 days in PC group while 5 days in PC/PE group. The median compression depth was 32 mm in PC group while 12 mm in PC/PE group. Postoperatively, there are some complications. All Pneumothorax patients being treated conservatively were found in 9 patients in two groups. One patient suffered overcorrection after operation. There were 3 patients suffered steel wires breakage in two groups. One patient reoperation postoperatively for the dislocation of the bar secondary to steel wires breakage. Conclusions The Abramson procedure or Abramson procedure and Nuss procedure have good short-term results in repair PC and PC/PE. Select one or two procedures should be done individually based on whether the lower plane over depressed after Abramson procedure.

Abstract UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.

Metalenses with achromatic performance offer a new opportunity for high-quality imaging with an ultra-compact configuration; however, they suffer from complex fabrication processes and low focusing efficiency. In this study, we propose an efficient design method for achromatic microlenses on a wavelength scale using materials with low dispersion, an adequately designed convex surface, and a thickness profile distribution. By taking into account the absolute chromatic aberration, relative focal length shift (FLS), and numerical aperture (NA), microlens with a certain focal length can be realized through our realized map of geometric features. Accordingly, the designed achromatic microlenses with low-dispersion fused silica were fabricated using a focused ion beam, and precise surface profiles were obtained. The fabricated microlenses exhibited a high average focusing efficiency of 65% at visible wavelengths of 410–680 nm and excellent achromatic capability via white light imaging. Moreover, the design exhibited the advantages of being polarization-insensitive and near-diffraction-limited. These results demonstrate the effectiveness of our proposed achromatic microlens design approach, which expands the prospects of miniaturized optics such as virtual and augmented reality, ultracompact microscopes, and biological endoscopy.

Abstract Pumped storage plants (PSPs) play an important role in renewable energy consumption in power systems. Variable‐speed technology is a new and critical direction for the development of PSPs. In pump mode, variable‐speed pumped storage units (VSPSUs) have wider power regulation ranges and more flexible power responses than fixed‐speed pumped storage units (FSPSUs); however, the corresponding quantification study of VSPSUs is rare. Therefore, this study aims to quantify the static and dynamic power regulation characteristics of VSPSU in pump mode. First, the modeling of the fast speed control strategy of VSPSU in pump mode is improved. Then, the power regulation range of the VSPSU is explored. The factors (i.e., power command, governor, and converter) affecting the power response rapidity are quantified through the engineering case of a variable‐speed PSP adopting the doubly fed induction machine. Accordingly, suggestions on the settings of the parameters are provided. Quantification results show that parameter tuning based on this study effectively solves the problem of low regulation rate caused by great power fluctuations under typical power regulation cases in pump mode. This VSPSU has the fastest regulation rate of 13.75%/s when adjusting 40% power. This study could provide technical support to the practical operation of VSPSU.

Abstract Spinal diseases and frozen shoulder are prevalent health problems in Asian populations. Early assessment and treatment are very important to prevent the disease from getting worse and reduce pain. In the field of computer vision, it is a challenging problem to assess the range of motion. In order to realize efficient, real-time and accurate assessment of the range of motion, an assessment system combining MediaPipe and YOLOv5 technologies was proposed in this study. On this basis, Convolutional Block Attention Module (CBAM) is introduced into the YOLOv5 target detection model, which can enhance the extraction of feature information, suppress background interference, and improve the generalization ability of the model. In order to meet the requirements of large-scale computing, a client/server (C/S) framework structure is adopted. The evaluation results can be obtained quickly after the client uploads the image data, providing a convenient and practical solution. In addition, a game of "Picking Bayberries" was developed as an auxiliary treatment method to provide patients with interesting rehabilitation training.

Abstract Objective Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. Methods We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. Results The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. Conclusion P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Abstract The wearable contact lens that continuously monitors intraocular pressure (IOP) facilitates prompt and early-state medical treatments of oculopathies such as glaucoma, postoperative myopia, etc. However, either taking drugs for pre-treatment or delaying the treatment process in the absence of a neural feedback component cannot realize accurate diagnosis or effective treatment. Herein, a neuroprosthetic contact lens enabled sensorimotor system is reported, which consists of a smart contact lens with Ti3C2T x Wheatstone bridge structured IOP strain sensor, a Ti3C2T x temperature sensor and an IOP point-of-care monitoring/display system. The point-of-care IOP monitoring and warning can be realized due to the high sensitivity of 12.52 mV mmHg−1 of the neuroprosthetic contact lens. In vivo experiments on rabbit eyes demonstrate the excellent wearability and biocompatibility of the neuroprosthetic contact lens. Further experiments on a living rate in vitro successfully mimic the biological sensorimotor loop. The leg twitching (larger or smaller angles) of the living rat was demonstrated under the command of motor cortex controlled by somatosensory cortex when the IOP is away from the normal range (higher or lower).

Abstract Objective We aimed to investigate the impact of sarcopenia and sarcopenic obesity (SO) on the clinical outcome in older patients with COVID-19 infection and chronic disease. Methods We prospectively collected data from patients admitted to Huadong Hospital for COVID-19 infection between November 1, 2022, and January 31, 2023. These patients were included from a previously established comprehensive geriatric assessment (CGA) cohort. We collected information on their pre-admission condition regarding sarcopenia, SO, and malnutrition, as well as their medical treatment. The primary endpoint was the incidence of intubation, while secondary endpoints included in-hospital mortality rates. We then utilized Kaplan-Meier (K-M) survival curves and the log-rank tests to compare the clinical outcomes related to intubation or death, assessing the impact of sarcopenia and SO on patient clinical outcomes. Results A total of 113 patients (age 89.6 ± 7.0 years) were included in the study. Among them, 51 patients had sarcopenia and 39 had SO prior to hospitalization. Intubation was required for 6 patients without sarcopenia (9.7%) and for 18 sarcopenia patients (35.3%), with 16 of these being SO patients (41%). Mortality occurred in 2 patients without sarcopenia (3.3%) and in 13 sarcopenia patients (25.5%), of which 11 were SO patients (28%). Upon further analysis, patients with SO exhibited significantly elevated risks for both intubation (Hazard Ratio [HR] 7.43, 95% Confidence Interval [CI] 1.26–43.90, P

With the increasing demand for high power density, and to meet extreme working conditions, research has been focused on investigating the performance of power electronics devices at cryogenic temperatures. The aim of this paper is to review the performance of power semiconductor devices, passive components, gate drivers, sensors, and eventually power electronics converters at cryogenic temperatures. By comparing the physical properties of semiconductor materials and the electrical performance of commercial power semiconductor devices, silicon carbide switches show obvious disadvantages due to the increased on-resistance and switching time at cryogenic temperature. In contrast, silicon and gallium nitride devices exhibit improved performance when temperature is decreased. The performance ceiling of power semiconductor devices can be influenced by gate drivers, within which the commercial alternatives show deteriorated performance at cryogenic temperature compared to room temperature. Moreover, options for voltage and current sense in cryogenic environments are justified. Based on the cryogenic performance of the various components afore-discussed, this paper ends by presenting an overview of the published converter, which are either partially or fully tested in a cryogenic environment.

ObjectivesIn order to meet the practical requirements for simulating ship motion in adverse sea conditions on land, the development of a high-speed heavy-load and large-travel lifting platform is necessary.MethodsAiming at the characteristics of moving platforms such as heavy-load high-speed and variable parameters, the dynamic simulation analysis of a high-speed lifting platform with a weight-balanced structure and four-steel-cable synchronous servo drive is carried out on the basis of Adams simulation software. Based on the principle of the similarity of control characteristics, a 1∶14 reduced ratio high-speed lifting platform is developed. ResultsThrough the response characteristic testing of the platform, its advantages such as strong synchronization and highly accurate control system are verified. The moving platform can accurately simulate the heave motion of ships in adverse sea conditions.ConclusionsThe high-speed lifting platform with a weight balance and four-steel-cable synchronous servo drive designed herein will fill in the blank for the large-scale heave motion simulation of ships and provide references for the R&D of similar motion simulators.

Abstract Artificial intelligence (AI) decision support systems in pediatric healthcare have a complex application background. As an AI decision support system (AI-DSS) can be costly, once applied, it is crucial to focus on its performance, interpret its success, and then monitor and update it to ensure ongoing success consistently. Therefore, a set of evaluation indicators was explicitly developed for AI-DSS in pediatric healthcare, enabling continuous and systematic performance monitoring. The study unfolded in two stages. The first stage encompassed establishing the evaluation indicator set through a literature review, a focus group interview, and expert consultation using the Delphi method. In the second stage, weight analysis was conducted. Subjective weights were calculated based on expert opinions through analytic hierarchy process, while objective weights were determined using the entropy weight method. Subsequently, subject and object weights were synthesized to form the combined weight. In the two rounds of expert consultation, the authority coefficients were 0.834 and 0.846, Kendall's coordination coefficient was 0.135 in Round 1 and 0.312 in Round 2. The final evaluation indicator set has three first-class indicators, fifteen second-class indicators, and forty-seven third-class indicators. Indicator I-1(Organizational performance) carries the highest weight, followed by Indicator I-2(Societal performance) and Indicator I-3(User experience performance) in the objective and combined weights. Conversely, 'Societal performance' holds the most weight among the subjective weights, followed by 'Organizational performance' and 'User experience performance'. In this study, a comprehensive and specialized set of evaluation indicators for the AI-DSS in the pediatric outpatient clinic was established, and then implemented. Continuous evaluation still requires long-term data collection to optimize the weight proportions of the established indicators.

Abstract Dry reforming of methane (DRM) is a highly endothermic process, with its development hindered by the harsh thermocatalytic conditions required. We propose an innovative DRM approach utilizing a 16 W pulsed laser in combination with a cost-effective Mo2C catalyst, enabling DRM under milder conditions. The pulsed laser serves a dual function by inducing localized high temperatures and generating *CH plasma on the Mo2C surface. This activates CH4 and CO2, significantly accelerating the DRM reaction. Notably, the laser directly generates *CH plasma from CH4 through thermionic emission and cascade ionization, bypassing the traditional step-by-step dehydrogenation process and eliminating the rate-limiting step of methane cracking. This method maintains a carbon-oxygen balanced environment, thus preventing the deactivation of the Mo2C catalyst due to CO2 oxidation. The laser-catalytic DRM achieves high yields of H2 (14300.8 mmol h−1 g−1) and CO (14949.9 mmol h−1 g−1) with satisfactory energy efficiency (0.98 mmol kJ−1), providing a promising alternative for high-energy-consuming catalytic systems.

Abstract Background About 1/3 of primary biliary cholangitis (PBC) patients suffered from poor response worldwide. And these patients present intestinal disturbances. We aimed to identify signatures of microbiota and metabolites in PBC patients with poor response, comparing to patients with response. Methods This study enrolled 25 subjects (14 PBC patients with response and 11 PBC patients with poor response). Metatranscriptomics and metabolomics analysis were carried out on their fecal. Results PBC patients with poor response had significant differences in the composition of bacteria, characterized by decreased Gemmiger etc. and increased Ruminococcus etc. The differential microbiota functions characterized by decreased abundance of elongation factor Tu and elongation factor G base on the KO database, as well as decreased abundance of Replicase large subunit etc. based on the SWISS-PROT database. PBC with poor response also had significant differences in 17 kinds of bacterial metabolites, characterized by decreased level of metabolites vital in bile acids metabolism pathway (L-Cysteine etc.) and the all-trans-Retinoic acid, a kind of immune related metabolite. The altered microbiota was associated with the differential expressed metabolites and clinical liver function indicators. 1 bacterial genera, 2 bacterial species and 9 metabolites simultaneously discriminated PBC with poor response from PBC with response with high accuracy. Conclusion PBC patients with poor response exhibit unique changes in microbiota and metabolite. Gut microbiota and metabolite-based algorithms could be used as additional tools for differential prediction of PBC with poor prognosis.

Abstract Background Although radical surgical resection is the most effective treatment for hepatocellular carcinoma (HCC), the high rate of postoperative recurrence remains a major challenge, especially in patients with alpha-fetoprotein (AFP)-negative HCC who lack effective biomarkers for postoperative recurrence surveillance. Emerging radiomics can reveal subtle structural changes in tumors by analyzing preoperative contrast-enhanced computer tomography (CECT) imaging data and may provide new ways to predict early recurrence (recurrence within 2 years) in AFP-negative HCC. In this study, we propose to develop a radiomics model based on preoperative CECT to predict the risk of early recurrence after surgery in AFP-negative HCC. Patients and methods Patients with AFP-negative HCC who underwent radical resection were included in this study. A computerized tool was used to extract radiomic features from the tumor region of interest (ROI), select the best radiographic features associated with patient’s postoperative recurrence, and use them to construct the radiomics score (RadScore), which was then combined with clinical and follow-up information to comprehensively evaluate the reliability of the model. Results A total of 148 patients with AFP-negative HCC were enrolled in this study, and 1,977 radiographic features were extracted from CECT, 2 of which were the features most associated with recurrence in AFP-negative HCC. They had good predictive ability in both the training and validation cohorts, with an area under the ROC curve (AUC) of 0.709 and 0.764, respectively. Tumor number, microvascular invasion (MVI), AGPR and radiomic features were independent risk factors for early postoperative recurrence in patients with AFP-negative HCC. The AUCs of the integrated model in the training and validation cohorts were 0.793 and 0.791, respectively. The integrated model possessed the clinical value of predicting early postoperative recurrence in patients with AFP-negative HCC according to decision curve analysis, which allowed the classification of patients into subgroups of high-risk and low-risk for early recurrence. Conclusion The nomogram constructed by combining clinical and imaging features has favorable performance in predicting the probability of early postoperative recurrence in AFP-negative HCC patients, which can help optimize the therapeutic decision-making and prognostic assessment of AFP-negative HCC patients.

Abstract Background Colorectal cancer (CRC) arises from complex interactions between host and environment, which include the gut and tissue microbiome. It is hypothesized that epigenetic regulation by gut microbiota is a fundamental interface by which commensal microbes dynamically influence intestinal biology. The aim of this study is to explore the interplay between gut and tissue microbiota and host DNA methylation in CRC. Methods Metagenomic sequencing of fecal samples was performed on matched CRC patients (n = 18) and healthy controls (n = 18). Additionally, tissue microbiome was profiled with 16S rRNA gene sequencing on tumor (n = 24) and tumor-adjacent normal (n = 24) tissues of CRC patients, while host DNA methylation was assessed through whole-genome bisulfite sequencing (WGBS) in a subset of 13 individuals. Results Our analysis revealed substantial alterations in the DNA methylome of CRC tissues compared to adjacent normal tissues. An extensive meta-analysis, incorporating publicly available and in-house data, identified significant shifts in microbial-derived methyl donor-related pathways between tumor and adjacent normal tissues. Of note, we observed a pronounced enrichment of microbial-associated CpGs within the promoter regions of genes in adjacent normal tissues, a phenomenon notably absent in tumor tissues. Furthermore, we established consistent and recurring associations between methylation patterns of tumor-related genes and specific bacterial taxa. Conclusions This study emphasizes the pivotal role of the gut microbiota and pathogenic bacteria in dynamically shaping DNA methylation patterns, impacting physiological homeostasis, and contributing to CRC tumorigenesis. These findings provide valuable insights into the intricate host-environment interactions in CRC development and offer potential avenues for therapeutic interventions in this disease.

BackgroundAbnormal eye movements occur at the early stages of Alzheimer’s disease (AD). However, the characteristics of abnormal eye movements of patients with AD and their relationship with clinical symptoms remain inconsistent, and their predictive value for diagnosing and monitoring the progression of AD remains unclear.MethodsA total of 42 normal controls, 63 patients with mild cognitive impairment due to AD (AD-MCI), and 49 patients with dementia due to AD (AD-D) were recruited. Eye movements were assessed using the EyeKnow eye-tracking and analysis system. Cognitive function, neuropsychiatric symptoms, and activities of daily living were evaluated using various rating scales, and correlation analyses and receiver operating characteristic curves were performed.ResultsPatients with AD exhibited increased number of offsets and offset degrees, prolonged offset duration, and decreased accuracy in lateral fixation; reduced accuracy, prolonged saccadic duration, and decreased velocity in prosaccade; decreased accuracy and corrected rate, prolonged corrected antisaccadic duration, and reduced velocity in antisaccade; and reduced accuracy and increased inhibition failures in memory saccade. Eye movement parameters were correlated with global cognition and the cognitive domains of memory, language, attention, visuospatial ability, execution function, and activities of daily living. Subgroup analysis indicated that the associations between eye movements and clinical symptoms in patients with AD were influenced by disease severity and history of diabetes. In the AD-D and AD with diabetes groups, these associations diminished. Nevertheless, the associations persisted in the AD-MCI and AD without diabetes groups. The areas under the curves for predicting AD, AD-MCI, and AD-D were 0.835, 0.737, and 0.899, respectively (all p

Abstract Fine particulate matter (PM2.5) is suggested to pose a severe risk to the kidneys by inducing functional degradation and chronic kidney diseases (CKD). This study aims to explore the nephrotoxicity of PM2.5 exposure and the underlying mechanism. Herein, based on the UK Biobank, it is found that per interquartile range (IQR) increase in PM2.5 is associated with a 6% (95% CI: 1%–11%), 7% (95% CI: 3%–11%), 9% (95% CI: 4%–13%), 11% (95% CI: 9%–13%), and 10% (95% CI: 8%–12%) increase in the risk of nephritis, hydronephrosis, kidney stone, acute renal failure, and CKD, respectively. In experimental study, noticeable kidney injury, which is the initiation of kidney diseases, is observed with PM2.5 exposure in C57BL/6N mice (n = 8), accompanied with oxidative stress, autophagy and pyroptosis. In vitro, HK‐2 cells with PM2.5‐stimulation exhibit tubulopathy, increased reactive oxygen species (ROS) generation and activated pyroptosis and autophagy. All changes are abolished by ROS scavenger of N‐acetyl‐L‐cysteine (NAC) both in vivo and in vitro. In conclusion, the study provides evidence showing that PM2.5 exposure is associated with 5 kinds of kidney diseases by directly inducing nephrotoxicity, in which ROS may be the potential target by triggering autophagy and pyroptosis.

Sediment plays a pivotal role in deep-sea ecosystems by providing habitats for a diverse range of microorganisms and facilitates the cycling processes of carbon, sulfur and nitrogen. Beyond the normal seafloor (NS), distinctive geographical features such as cold seeps (CS) and hydrothermal vent (HV) are recognized as life oases harboring highly diverse microbial communities. A global atlas of microorganisms can reveal the notable association between geological processes and microbial colonization. However, a comprehensive understanding of the systematic comparison of microbial communities in sediments across various deep-sea regions worldwide and their contributions to Earth's elemental cycles remains limited. Analyzing metagenomic data from 163 deep-sea sediment samples across 73 locations worldwide revealed that microbial communities in CS sediments exhibited the highest richness and diversity, followed by HV sediments, with NS sediments showing the lowest diversity. The NS sediments were predominantly inhabited by Nitrosopumilaceae, a type of ammonia-oxidizing archaea (AOA). In contrast, CSs and HVs were dominated by ANME-1, a family of anaerobic methane-oxidizing archaea (ANME), and Desulfofervidaceae, a family of sulfate-reducing bacteria (SRB), respectively. Microbial networks were established for each ecosystem to analyze the relationships and interactions among different microorganisms. Additionally, we analyzed the metabolic patterns of microbial communities in different deep-sea sediments. Despite variations in carbon fixation pathways in ecosystems with different oxygen concentrations, carbon metabolism remains the predominant biogeochemical cycle in deep-sea sediments. Benthic ecosystems exhibit distinct microbial potentials for sulfate reduction, both assimilatory and dissimilatory sulfate reduction (ASR and DSR), in response to different environmental conditions. The presence of nitrogen-fixing microorganisms in CS sediments may influence the global nitrogen balance. In this study, the significant differences in the taxonomic composition and functional potential of microbial communities inhabiting various deep-sea environments were investigated. Our findings emphasize the importance of conducting comparative studies on ecosystems to reveal the complex interrelationships between marine sediments and global biogeochemical cycles.

Abstract Acute anterior uveitis (AAU) is a common extra‐articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)‐B27 genetic marker. To explore the underlying mechanisms of HLA‐B27+ AS‐associated AAU, we employed single‐cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA‐B27+ AS‐associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune‐associated proteins, Th17‐related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X‐inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA‐B27+ AS‐associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential.

Abstract Settling the structure stacking of graphene (G) nanosheets to maintain the high dispersity has been an intense issue to facilitate their practical application in the microelectronics‐related devices. Herein, the co‐doping of the highest electronegative fluorine (F) and large atomic radius chlorine (Cl) into G via a one‐step electrochemical exfoliation protocol is engineered to actualize the ultralong cycling stability for flexible micro‐supercapacitors (MSCs). Density functional theoretical calculations unveiled that the F into G can form the “ionic” C─F bond to increase the repulsive force between nanosheets, and the introduction of Cl can enlarge the layer spacing of G as well as increase active sites by accumulating the charge on pore defects. The co‐doping of F and Cl generates the strong synergy to achieve high reversible capacitance and sturdy structure stability for G. The as‐constructed aqueous gel‐based MSC exhibited the superb cycling stability for 500,000 cycles with no capacitance loss and structure stacking. Furthermore, the ionic liquid gel‐based MSC demonstrated a high energy density of 113.9 mW h cm−3 under high voltage of up to 3.5 V. The current work enlightens deep insights into the design and scalable preparation of high‐performance co‐doped G electrode candidate in the field of flexible microelectronics.

Abstract During the past few decades, pyroelectric sensors have attracted extensive attention due to their prominent features. However, their effectiveness is hindered by low electric output. In this study, the laser processed lithium niobate (LPLN) wafers are fabricated to improve the temperature–voltage response. These processed wafers are utilized to construct pyroelectric sensors as well as human–machine interfaces. The laser induces escape of oxygen and the formation of oxygen vacancies, which enhance the charge transport capability on the surface of lithium niobate (LN). Therefore, the electrodes gather an increased quantity of charges, increasing the pyroelectric voltage on the LPLN wafers to a 1.3 times higher voltage than that of LN wafers. For the human–machine interfaces, tactile information in various modes can be recognized by a sensor array and the temperature warning system operates well. Therefore, the laser modification approach is promising to enhance the performance of pyroelectric devices for applications in human–machine interfaces.