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Apocynum pictum (A. pictum) honey is rich in effective ingredients including flavonoids, terpenes, and alkaloids that are beneficial to human health. In this study, widely targeted metabolomics were used to detect the plant-derived secondary metabolites of the same batch of A. pictum honey from 2022 to 2024, in order to explore whether storage time changes the quality of A. pictum honey, especially the content of plant-derived secondary metabolites with important health benefits. The results showed that storage time had no significant effect on the content of sugars, proteins, and other major components in A. pictum honey. At the same time, we also found that although storage time had an impact on the content of some secondary metabolites such as flavonoids in A. pictum honey, the changes in the content of the characteristic active ingredient, hyperoside, in A. pictum honey were not significant. These findings suggest that storage time has a minimal impact on the quality of A. pictum honey. This study provides a theoretical basis for the rational storage of A. pictum honey.

The removal of back armor marks the first stage in the comprehensive processing of river crabs. However, the current low level of mechanization undermines the effectiveness of this process. By integrating robotic systems with image recognition technology, the efficient removal of dorsal armor from river crabs is anticipated. This approach relies on the rapid identification and precise positioning of the processing location at the crab’s tail, both of which are essential for optimal results. In this paper, we propose a lightweight deep learning model called YOLOv7-SPSD for detecting river crab tails. The goal is to accurately determine the processing location for the robotic removal of river crab back armor. We start by constructing a crab tail dataset and completing the data labeling process. To enhance the lightweight nature of the YOLOv7-tiny model, we incorporate the Slimneck module, PConv, and the SimAM attention mechanism. These additions help achieve an initial reduction in model size while preserving detection accuracy. Furthermore, we optimize the model by removing redundant parameters using the DepGraph pruning algorithm, which facilitates its application on edge devices. Experimental results show that the lightweight YOLOv7-SPSD model achieves a mean Average Precision (mAP) of 99.6% at a threshold of 0.5, an F1-score of 99.6%, and processes frames at a rate of 7.1 frames per second (FPS) on a CPU. Compared to YOLOv7-tiny, the improved model increases FPS by 2.7, reduces GFLOPS by 74.6%, decreases the number of parameters by 71.6%, and lowers its size by 8.1 MB. This study enhances the deployment of models in river crab processing equipment and introduces innovative concepts and methodologies for advancing intelligent river crab deep processing technology.

Rare-earth-metal-based materials have emerged as frontrunners in the quest for high-performance hydrogen storage solutions, offering a paradigm shift in clean energy technologies. This comprehensive review delves into the cutting-edge advancements, challenges, and future prospects of these materials, providing a roadmap for their development and implementation. By elucidating the fundamental principles, synthesis methods, characterization techniques, and performance enhancement strategies, we unveil the immense potential of rare-earth metals in revolutionizing hydrogen storage. The unique electronic structure and hydrogen affinity of these elements enable diverse storage mechanisms, including chemisorption, physisorption, and hydride formation. Through rational design, nanostructuring, surface modification, and catalytic doping, the hydrogen storage capacity, kinetics, and thermodynamics of rare-earth-metal-based materials can be significantly enhanced. However, challenges such as cost, scalability, and long-term stability need to be addressed for their widespread adoption. This review not only presents a critical analysis of the state-of-the-art but also highlights the opportunities for multidisciplinary research and innovation. By harnessing the synergies between materials science, nanotechnology, and computational modeling, rare-earth-metal-based hydrogen storage materials are poised to accelerate the transition towards a sustainable hydrogen economy, ushering in a new era of clean energy solutions.

In recent years, the Swept-Source Phase Microscope (SS-PM) has gained more attention due to its greater robustness to sample motion and lower signal decay with depth. However, the mechanical wavelength tuning of the swept source creates small variations in the wavenumber sampling of spectra that introduce serious phase noise. We present a software post-processing method to eliminate phase noise in SS-PM. This method does not require high-quality swept light sources or high-precision synchronization devices and achieves ~72 pm displacement sensitivity using a conventional SS-PM system. We compare the performance of this method with traditional software-based methods by measuring phase fluctuations. The phase fluctuations in the traditional software-based method are five times those of the proposed method, which means the proposed method has better sensitivity. Using this method, we reconstructed phase images of air wedges and resolution plates to demonstrate the SS-PM’s potential for high-sensitivity surface profiling measurement. Finally, we discuss the advantages of SS-PM over traditional Spectral-Domain PM techniques.

Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides a comprehensive overview of the latest advancements in LNP research, focusing on preclinical safety assessments encompassing toxicity, reactogenicity, and immunogenicity. Summary and Outlook: Additionally, it outlines potential strategies for addressing these challenges and offers insights into future research directions for enhancing the application of LNPs in mRNA therapeutics.

Oil and natural gas resources are crucial energy sources formed during the geological and biological evolution of the Earth [...]

Suspension bridges are the most common type of bridge used to cross the ocean. The cable clamps in suspension bridges clamp the main cables by bolt preload, but the elastic interaction of the bolts reduces the preload, which is detrimental to the force in suspension bridges. However, research on the factors influencing the elastic interaction of cable clamp bolts in suspension bridges is currently limited. This paper aims to explore the law of influence of external factors on the elastic interaction of bolts through a combined approach of theoretical analysis, full-scale experiment, and finite element simulation. The results indicate that the average preload loss was reduced by about 27% when the elastic modulus was increased by about 110%. The average preload loss was reduced by about 45% when the bolt center distance was increased by 75%. The number of bolts has a small effect on the elastic interaction, which can be ignored. When the preload of bolt installation was increased by 133%, the average preload loss was reduced by approximately 125%, which was almost a linear relationship. Tightening the bolt from the center bolt creates greater elastic interaction. The conclusions can provide suggestions for reducing the elastic interaction of bolts in the design and construction of suspension bridge cable clamps.

Surface downward longwave radiation (SDLR) is crucial for maintaining the global radiative budget balance. Due to their ease of practicality, SDLR parameterization models are widely used, making their objective evaluation essential. In this study, against comprehensive ground measurements collected from more than 300 globally distributed sites, four SDLR parameterization models, including three popular existing ones and a newly proposed model, were evaluated under clear- and cloudy-sky conditions at hourly (daytime and nighttime) and daily scales, respectively. The validation results indicated that the new model, namely the Peng model, originally proposed for SDLR estimation at the sea surface and applied for the first time to the land surface, outperformed all three existing models in nearly all cases, especially under cloudy-sky conditions. Moreover, the Peng model demonstrated robustness across various land cover types, elevation zones, and seasons. All four SDLR models outperformed the Global Land Surface Satellite product from Advanced Very High-Resolution Radiometer Data (GLASS-AVHRR), ERA5, and CERES_SYN1de-g_Ed4A products. The Peng model achieved the highest accuracy, with validated RMSE values of 13.552 and 14.055 W/m2 and biases of −0.25 and −0.025 W/m2 under clear- and cloudy-sky conditions at daily scale, respectively. Its superior performance can be attributed to the inclusion of two cloud parameters, total column cloud liquid water and ice water, besides the cloud fraction. However, the optimal combination of these three parameters may vary depending on specific cases. In addition, all SDLR models require improvements for wetlands, bare soil, ice-covered surfaces, and high-elevation regions. Overall, the Peng model demonstrates significant potential for widespread use in SDLR estimation for both land and sea surfaces.

In this paper, Panax ginseng cyclophilin (PgCyP) was successfully obtained through a genetic engineering technique. A bioinformatics method was used to analyze the physicochemical properties and structure of PgCyP. The results showed that PgCyP belongs to the cyclophilin gene family. The protein encoded by the PgCyP gene contains the active site of PPIase (R62, F67, and H133) and a binding site for cyclosporine A (W128). The relative molecular weight of PgCyP is 187.11 bp; its theoretical isoelectric point is 7.67, and it encodes 174 amino acids. The promoter region of PgCyP mainly contains the low-temperature environmental stress response (LTR) element, abscisic acid-responsive cis-acting element (ABRE), and light-responsive cis-acting element (G-Box). PgCyP includes a total of nine phosphorylation sites, comprising four serine phosphorylation sites, three threonine phosphorylation sites, and two tyrosine phosphorylation sites. PgCyP was recombined and expressed in vitro, and its recombinant expression was investigated. Furthermore, it was found that the recombinant PgCyP protein could effectively inhibit the germination of Phytophthora cactorum spores and the normal growth of Phytophthora cactorum mycelia in vitro. Further experiments on the roots of susceptible Arabidopsis thaliana showed that the PgCyP protein could improve the resistance of arabidopsis to Phytophthora cactorum. The findings of this study provide a basis for the use of the PgCyP protein as a new type of green biopesticide.

Foxtail millet is an important cereal crop in the North China Plain. However, excessive nitrogen fertilizer application over the years has led to declining yield and soil quality. This study investigated nutrient management strategies for foxtail millet based on crop yield levels and soil nutrient availability. In a field where targeted fertilization was conducted over six seasons, nitrogen fertilization effects and the dynamics of soil-available nitrogen were monitored continuously for two consecutive years (2022–2023) across five different foxtail millet varieties with varying yield levels. The study aimed to determine the optimal nitrogen application rate for achieving a high yield of foxtail millet, the minimum soil nitrate threshold required to maintain soil fertility, and the effective nitrogen application rate range for sustaining soil-available nitrate levels. Results showed that fertilization significantly affected dry matter weight during flowering, while variety affected dry matter weight at maturity. The average nitrogen application rate for achieving high yield across all five millet varieties was 141.3 kg·ha−1. Specifically, the average nitrogen application rate of nitrogen-efficient varieties achieving high yield (5607.32–5637.19 kg·ha−1) was 151.5 kg·ha−1, while the average nitrogen application rate of nitrogen-inefficient varieties achieving high yield (4749.77–4847.74 kg·ha−1) was 134.5 kg·ha−1. Soil NH4+-N and NO3−-N content increased when nitrogen application rate exceeded 360 kg·ha−1, posing environmental risks. To achieve high yield, soil nitrate levels would be maintained at an average of 17.23 mg·kg−1 (before sowing) and 9.75 mg·kg−1 (at maturity). A relationship between soil nitrate and nitrogen application rate was established: y = 867.5 − 50z (where y represents the optimal nitrogen application rate for high yield (kg·ha−1), and z represents soil NO3−-N content in the 0–20 cm layer before sowing, ranging from 10.0 to 17.35 mg·kg−1), which provided a practical method for nitrogen fertilization to achieve high yield of foxtail millet. In this study, the fertilization strategy was optimized according to soil nutrient level and yield targets, and the nitrogen application rate was controlled within 360 kg·ha−1 based on the soil nitrate nitrogen content, which will be instructive for reducing fertilizer use, maximizing fertilizer efficiency, and increasing yield.

Abstract Background The entomogenous fungus Beauveria bassiana is used as a biological insecticide worldwide, wild B. bassiana strains with high pathogenicity in the field play an important role in controlling insect pests via not only screening of highly virulent strains but also natural infection, but the pathogenicity degeneration of wild strains severely affected aforementioned effects. Previous studies have showed that multiple factors contributed to this phenomenon. It has been extensively proved that the mycovirus infection caused hypovirulence of phytopathogenic fungi, which has been used for plant disease biocontrol. However, it remains unknown whether the mycovirus epidemics is a key factor causing hypovirulence of B. bassiana naturally in the field. Methods Wild strains of B. bassiana were collected from different geographic locations in Jilin Province, China, to clarify the epidemic and diversity of the mycoviruses. A mycovirus Beauveria bassiana chrysovirus 2 (BbCV2) we have previously identified was employed to clarify its impact on the pathogenicity of host fungi B. bassiana against the larvae of insect pest Ostrinia furnacalis. The serological analysis was conducted by preparing polyclonal antibody against a BbCV2 coat protein, to determine whether it can dissociate outside the host fungal cells and subsequently infect new hosts. Transcriptome analysis was used to reveal the interactions between viruses and hosts. Results We surprisingly found that the mycovirus BbCV2 was prevalent in the field as a core virus in wild B. bassiana strains, without obvious genetic differentiation, this virus possessed efficient and stable horizontal and vertical transmission capabilities. The serological results showed that the virus could not only replicate within but also dissociate outside the host cells, and the purified virions could infect B. bassiana by co-incubation. The virus infection causes B. bassiana hypovirulence. Transcriptome analysis revealed decreased expression of genes related to insect epidermis penetration, hypha growth and toxin metabolism in B. bassiana caused by mycovirus infection. Conclusion Beauveria bassiana infected by hypovirulence-associated mycovirus can spread the virus to new host strains after infecting insects, and cause the virus epidemics in the field. The findings confirmed that mycovirus infection may be an important factor affecting the pathogenicity degradation of B. bassiana in the field.

Abstract Objective The persistence of HPV infection is a significant etiological factor in the development of cervical cancer. The present study investigated the prevalence and genotype distribution of human papillomavirus (HPV) in a cohort of 164,137 unvaccinated women from Wenzhou, aiming to provide guidance for clinics in the cervical cancer screening and HPV vaccination strategies. Methods The present retrospective study included a total of 164,137 women, comprising 118,484 outpatients and 45,653 healthy female subjects recruited from 2015 to 2020. Cervical exfoliated cells were collected from these participants for subsequent DNA extraction. The extracted DNA samples were underwent analysis using a fluorescence in situ hybridization method, encompassing the detection of 27 HPV genotypes. Results The overall prevalence of HPV was 17.35%; this corresponded to a prevalence of 19.10% in the outpatient group and 12.82% in the healthy female group. Among the outpatient group, the five most prevalent HPV genotypes were identified as HPV 52, 58, 16, 53, and 61. In the healthy female group, the five most common HPV genotypes were found to be HPV 52, 53, 58, 61, and 81. Additionally, it was estimated that the highest rate of HPV infection occurred among individuals aged between 10 and 19 years old (44.65%) and those aged between 60 and 69 years old (27.35%). Conclusions The prevalence of HPV in this region is substantial; therefore, it is imperative to implement scientifically sound and rational clinical interventions such as vaccination. Routine cervical screening should be performed to prevent the development of cervical intraepithelial neoplasia resulting from persistent infection with high-risk HPV, particularly in women with gynecological diseases and those over 60 years old.

Abstract An ever-growing portion of the economy is dedicated to the field of education, intensifying the urgency of identifying strategies to secure the sector’s enduring prosperity and elevate educational standards universally. This study introduces a model for enhancing games and optimizing data analysis within the context of early childhood education (ECE) majors, hinging on deep learning (DL). This approach aims to enhance the quality of instruction provided to ECE majors and refine the effectiveness of their professional pursuits. This study commences by examining the incorporation of DL technologies within the domain of ECE and delving into their fundamental underpinnings. Subsequently, it expounds upon the design philosophy underpinning ECE games operating within the framework of DL. Finally, it outlines the game improvement and data analysis (GIADA) model tailored to ECE majors. This model is constructed upon DL technology and further refined through the integration of convolutional neural networks (CNN). Empirical findings corroborate that the DL-CNN GIADA model achieves data analysis accuracy ranging from 83 to 93% across four datasets, underscoring the pronounced optimization prowess bestowed by CNN within the DL-based GIADA model. This study stands as an invaluable reference for the application and evolution of artificial intelligence technology within the realm of education, thereby contributing substantively to the broader landscape of educational advancement.

Dendritic bridging plays a key role in hot tearing formation and crack propagation, but it has yet to be clearly understood. This article describes the formation process of interdendritic bridging and its effect on the propagation of hot tearing. Two types of interdendritic bridging are proposed: mechanical bridging where dendrites are in contact with each other but are connected only by the surface tension of liquid film and metallurgical bridging where dendrites are metallurgically bonded at their contact points. Mechanical bridging cannot effectively impede crack propagation, thus exhibiting a brittle fracture characteristic, while metallurgical bridging can hinder crack propagation, resulting in a ductile fracture characteristic. Experiments on a high manganese steel were carried out to provide evidence of these two types of bridging and illustrate unique features on fractured surface that are associated with these two types of bridging. In this paper, the process of dendritic bridge formation is clearly described and its effect on hot tearing propagation is discussed.

Abstract A single type of signal processing means that it is difficult to analyze vibration signals comprehensively and effectively. By comprehensively using wavelet analysis techniques, a comprehensive and in-depth study of aero-engine vibration conditions is realized as a way to carry out health management. By introducing various types of wavelet analysis techniques and using Labview2022 programming, corresponding signal processing tools are developed for the analysis of the collected vibration signals. The comprehensive analysis of aero-engine vibration signals based on the wavelet transform method is realized, and the corresponding products are successfully applied in engineering practice.

Modern planetary gear transmissions are often made with flexible components and operated at high or varying speed. Despite advances in understanding their dynamic performance, they remain vulnerable to problems leading—in some cases—to subsequent system failure. In this study, using angular and translational displacements as generalized coordinates, we establish lumped-parameter dynamic sub-models of the sun and planet gears that accurately consider gear-tooth dynamic behavior; we also develop reduced-order finite-element sub-models that fully consider the flexibility of the housing and carrier. Investigating the coupling between these sub-models in depth enables us to construct a complete hybrid dynamic model that can be used for coupling-dynamics analysis of flexible planetary gears under high- and variable-speed conditions. The accuracy of our planetary-gear-dynamics model is verified by comparing simulation data in the time and frequency domains to the results of experiments conducted on a planetary gear transmission system test bench specially built for this purpose. Finally, the dynamic characteristics of high-speed flexible planetary gears are studied at low speed, high speed, and high acceleration.

Abstract. Background:. Atherosclerosis-related diseases represent significant health issues among adults globally. Despite their widespread impact, comprehensive data concerning the global and national burden and trends of these diseases remain sparse. Our objective is to examine the trends in the burden of atherosclerosis among adults from 1990 to 2019 at both global and national levels. Methods:. We reported the average annual percentage changes (AAPCs) in prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of atherosclerosis-related diseases (ischemic heart disease [IHD], ischemic stroke, and peripheral arterial disease [PAD]) at the global and national levels among individuals based on a trend analysis of the Global Burden of Diseases Study (GBD) 2019. We further analyzed these global trends as a function of age, gender, and the social development index. We also used joinpoint regression analysis to identify the year with the most substantial changes in global trends. Results:. Globally, the AAPC of IHD incidence rose from 1990 to 2019 (0.20; 95% confidence interval [CI], 0.12-0.28), with substantial surges in 1995, 2001, 2005, 2010, and 2017. Conversely, AAPC of IHD mortality rates exhibited a different trend until a rise in 2014. The AAPC of incidence rates of ischemic stroke and PAD also escalated during the same period, with respective 0.43 (95% CI, 0.39-0.48) and 0.13 (95% CI, 0.06-0.21). For ischemic stroke, both incidence and mortality soared in 2014, while PAD incidence declined in 1994 and 1998, then sharply climbed in 2016. Nationally, the Northern Mariana Islands experienced the steepest increase in IHD and PAD incidence and mortality between 1990 and 2019. China saw a significant rise in ischemic stroke incidence, whereas the highest mortality rate increase occurred in Timor-Leste. By sociodemographic index (SDI) quintile, low-middle-, middle-, and high-middle-SDI countries all showed upward trends in IHD, ischemic stroke, and PAD incidence. Simultaneously, IHD and ischemic stroke mortality rates, as well as DALYs, dropped in the low-, high-middle-, and high-SDI nations. However, PAD mortality rates and DALYs saw an uptick across all SDI quintiles. Regarding age demographics, a global decrease in the AAPC IHD incidence as noted in individuals above 55 years old, in contrast to an increase in the 20-55 age group during this period. AAPC of mortality rates for IHD, ischemic stroke, and PAD decreased across all ages. The AAPC showed an increase in IHD incidence in both genders. Conversely, IHD's DALYs saw a reduction in both males and females. Ischemic stroke patterns mirrored these trends, whereas all measures for PAD exhibited growth for both sexes. Conclusions:. From 1990 to 2019, there was an overall increasing trend in the global incidence of all three clinical manifestations of atherosclerosis. Between 1990 and 2019, both the mortality rate and DALYs for IHD and ischemic stroke declined across all age groups. Overall, the burden of atherosclerosis-related diseases has not significantly decreased and even shows signs of trending upward. These findings strongly suggest that despite some progress made, efforts to control atherosclerosis diseases globally need to be intensified.

Abstract Dynamic ageing process of cross‐linked polyethylene (XLPE) cable insulation under combined electro‐thermal effect is investigated by the construction of theoretical analysis model and the practice of operation‐simulated ageing test. Firstly, theoretical analysis model is constructed from time and spatial dimensions. From the time dimension, in the light of the impeding trend of internal stress to external stress, the XLPE ageing process of Steady state ‐Transition state ‐Steady state (STS) is proposed to illustrate the dynamic ageing process of XLPE. From the spatial dimension, the insulation is divided into three scales to quantify the ageing. Secondly, to practice the theoretical analysis model, an operation‐simulated ageing test was conducted on two high voltage alternating current cables with service years of 15 and 30 for 540 days. Subsequently, relevant diagnostic measurements were applied to analyse the influence of physicochemical characteristics on the dielectric and heat transfer performances of the cables. The results show that the degradation of the actual operating cable is an extremely slow process. On the one hand, the response in physical changes of morphology counterbalances the external stress, maintaining the stability. On the other hand, once the chemical changes occur, negative feedback mechanism tends to impede the occurrence of further degradation by regulating fields distribution.

Abstract Seasonal variations have long been observed in various aspects of human life. While there is an abundance of research that has characterized seasonality effects in, for example, cognition, mood, and behavior, including studies of underlying biophysical mechanisms, direct measurements of seasonal variations of brain functional activities have not gained wide attention. We have quantified seasonal effects on functional connectivity as derived from MRI scans. A cohort of healthy human subjects was divided into four groups based on the seasons of their scanning dates as documented in the image database of the Human Connectome Project. Sinusoidal functions were used as regressors to determine whether there were significant seasonal variations in measures of brain activities. We began with the analysis of seasonal variations of the fractional amplitudes of low frequency fluctuations of regional functional signals, followed by the seasonal variations of functional connectivity in both global- and network-level. Furthermore, relevant environmental factors, including average temperature and daylength, were found to be significantly associated with brain functional activities, which may explain how the observed seasonal fluctuations arise. Finally, topological properties of the brain functional network also showed significant variations across seasons. All the observations accumulated revealed seasonality effects of human brain activities in a resting-state, which may have important practical implications for neuroimaging research.

Abstract Epigenetic reprogramming occurs during reproduction to reset the genome for early development. In flowering plants, mechanistic details of parental methylation remodeling in zygote remain elusive. Here we analyze allele-specific DNA methylation in rice hybrid zygotes and during early embryo development and show that paternal DNA methylation is predominantly remodeled to match maternal allelic levels upon fertilization, which persists after the first zygotic division. The DNA methylation remodeling pattern supports the predominantly maternal-biased gene expression during zygotic genome activation (ZGA) in rice. However, parental allelic-specific methylations are reestablished at the globular embryo stage and associate with allelic-specific histone modification patterns in hybrids. These results reveal that paternal DNA methylation is remodeled to match the maternal pattern during zygotic genome reprogramming and suggest existence of a chromatin memory allowing parental allelic-specific methylation to be maintained in the hybrid.

Abstract Endo-lysosomal escape is a highly inefficient process, which is a bottleneck for intracellular delivery of biologics, including proteins and nucleic acids. Herein, we demonstrate the design of a lipid-based nanoscale molecular machine, which achieves efficient cytosolic transport of biologics by destabilizing endo-lysosomal compartments through nanomechanical action upon light irradiation. We fabricate lipid-based nanoscale molecular machines, which are designed to perform mechanical movement by consuming photons, by co-assembling azobenzene lipidoids with helper lipids. We show that lipid-based nanoscale molecular machines adhere onto the endo-lysosomal membrane after entering cells. We demonstrate that continuous rotation-inversion movement of Azo lipidoids triggered by ultraviolet/visible irradiation results in the destabilization of the membranes, thereby transporting cargoes, such as mRNAs and Cre proteins, to the cytoplasm. We find that the efficiency of cytosolic transport is improved about 2.1-fold, compared to conventional intracellular delivery systems. Finally, we show that lipid-based nanoscale molecular machines are competent for cytosolic transport of tumour antigens into dendritic cells, which induce robust antitumour activity in a melanoma mouse model.

Abstract Macrophage filopodia, which are dynamic nanotube-like protrusions, have mainly been studied in the context of pathogen clearance. The mechanisms by which they facilitate intercellular communication and mediate tissue inflammation remain poorly understood. Here, we show that macrophage filopodia produce a unique membrane structure called “filopodial tip vesicle” (FTV) that originate from the tip of macrophages filopodia. Filopodia tip-derived particles contain numerous internal-vesicles and function as cargo storage depots via nanotubular transport. Functional studies indicate that the shedding of FTV from filopodia tip allows the delivery of many molecular signalling molecules to fibroblasts. We observed that FTV derived from M1 macrophages and high glucose (HG)-stimulated macrophages (HG/M1-ftv) exhibit an enrichment of the chemokine IL11, which is critical for fibroblast transdifferentiation. HG/M1-ftv induce renal interstitial fibrosis in diabetic mice, while FTV inhibition or targeting FTV IL11- alleviates renal interstitial fibrosis, suggesting that the HG/M1-ftv IL11 pathway may be a novel mechanism underlying renal fibrosis in diabetic nephropathy. Collectively, FTV release could represent a novel function by which filopodia contribute to cell biological processes, and FTV is potentially associated with macrophage filopodia-related fibrotic diseases. Video Abstract

Abstract Background Serum uric acid levels are higher in patients with type 2 diabetes and prediabetes compared to healthy individuals, and hyperuricemia causes a significant rate of complications and mortality through heart and kidney diseases. Accordingly, the present systematic review and meta-analysis aimed to investigate the effect of empagliflozin on serum uric acid levels. Materials and methods Electronic databases, including PubMed, Scopus, Web of Science, Cochrane, and Google Scholar, were used to search papers until May 22, 2023. Data analysis was conducted by STATA Version 14, and P-value

Abstract Background Immense attention has been given to the outcome of COVID-19 infection. However, comprehensive studies based on large populational cohort with long-term follow-up are still lacking. This study aimed to investigate the risk of various short-term comorbidities (within one month) and long-term sequelae (above one month) after COVID-19 infection. Methods In this large prospective cohort study with 14 months follow-up information based on UK biobank, we included 16,776 COVID-19-positive participants and 58,281 COVID-19-negative participants matched for comparison. The risk of each comorbidity and sequela was evaluated by multivariable logistic regression analysis and presented as hazard ratio (HR) and 95% confidence interval (95% CI). Results COVID-19-positive individuals had a higher risk of 47 types of comorbidities within one month following COVID-19 infection, especially those who were older, male, overweight/obese, ever-smoked, with more pre-existing comorbidities and hospitalized. About 70.37% of COVID-19 patients with comorbidities had more than one co-occurring comorbidities. Additionally, only 6 high-risk sequelae were observed after one month of COVID-19 infection, and the incidence was relatively low (

The role of warm conveyor belts （WCBs） on the development of cyclones and precipitation and their relationship to occluded fronts are investigated for extratropical cyclones causing snowstorms in northeastern China during 2006 -2021， using ERA5 reanalysis data and Lagrangian Analysis Tool （LAGRANTO）.Main results show that： （1） The correlation coefficient of 0.63 which could pass significance test of α=0.01 implies strong correlation between cyclone intensification and WCB strength.Most of cyclones have occluded in the 24 h period of strongest deepening， and these occluded fronts are mainly warm-type occlusions.（2） Rapidly intensifying occluded cyclones typically have strong WCBs， which low-level inflow mainly locates in the center and warm sector of cyclones， while the outflow has two branches： some trajectories rise to the high levels northwest of the cyclone， and others ascend to the downstream of cyclone following the upper westerly winds； the interaction between low-level potential vorticity （PV） and upper-level PV in cyclone occluding stage eventually forms a PV tower throughout the troposphere.（3） Non-occluded cyclones also have strong WCBs and positive low-level PV anomalies， but lack of significant upper-level PV forcing.The development of these cyclones is weak.Weakly intensifying occluded cyclones have a PV tower， but their WCBs and precipitation are weak.（4） Cyclones with strong （weak） warm conveyor belts cause more （less） precipitation， and the distribution of rainfall is closely related to the location of warm conveyor belts.The WCB trajectories moving towards to cyclone center play an important role for cyclone development.The warm advection and low-level diabatic PV production generated by these trajectories both enhance the low-level circulation and contribute to the cyclone intensification.

Objectives: To evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). Methods: This phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. Results: A total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. Conclusion: ormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. Clinical trials registration: ChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization).

Burning rate catalysts (BRCs) are usually utilized to adjust the burning rates of solid rocket propellants (SRPs). Carbon nanotubes (CNTs), for their unique structure and properties, have been studied by several researchers worldwide with a wide range of applications. In this paper, several worthy CNTs-based materials and effects are described. Specifically, the influence of CNTs on the thermal behavior of energetic materials (EMs) are discussed, and we investigated the impact of CNTs/metal (metal oxide, MO) composites on the thermal degradation of EMs. Applications for SRPs and solid rocket nozzle motors might benefit from a focus on the examination of the burning rate, pressure exponent characteristics, and hazardous aspects. It was discovered that CNTs, as opposed to the comparable micro-sized additives, can modify the combustion behavior and speed up the burning of SRPs. Lastly, the difficulties encountered in implementing some of these applications are also examined in terms of manufacturing, processing, pricing, and potential future uses.

In this paper, konjac powde were hydrolyzed by Bacillus licheniformis to prepare oligosaccharides. The effects of concentration of konjac powder, inoculum amount of strain, bacteriolysis temperature and hydrolysis time on hydrolysis rate of konjac powder were determined by single factor tests. The antioxidant activity of konjac powder oligosaccharides was evaluated with the scavenging ability of ·OH, ·O2−· and DPPH· as indexes. The prebiotic activity of konjac powder oligosaccharides was investigated by in vitro fermentation test. The results showed that the optimal hydrolysis process parameters was as follows: concentration of konjac powder 20 g/L, inoculation capacity 1×107 CFU/g, hydrolysis temperature 43.6 ℃, hydrolysis time 10.2 h. Under the optimal conditions, the hydrolysis rate of konjac powder was 39.06%±0.12%, and the yield of KGOS was 66.72%. With the prolongation of hydrolysis time, the viscosity of solution decreased from 2430.33 mPa·s to 18.06 mPa·s. When the concentration of konjac powder was 10 mg/mL, the clearance rates of ·OH, ·O2− and DPPH· were 61.47%, 34.60% and 81.43%, respectively. The OD600 of KGOS, glucose and konjac powder on the proliferation of Lactobacillus plantarum, Lactobacillus brevity and Lactobacillus casei in vitro were 0.775, 1.371, 0.236, 0.791, 1.339, 0.224 and 0.916, 1.336, 0.243, respectively. The results provide a theoretical basis for the further processing and utilization of oligosaccharides in konjac powder.

Abstract Background To develop and validate a multivariable risk prediction model for ketosis‐prone type 2 diabetes mellitus (T2DM) based on clinical characteristics. Methods A total of 964 participants newly diagnosed with T2DM were enrolled in the modeling and validation cohort. Baseline clinical data were collected and analyzed. Multivariable logistic regression analysis was performed to select independent risk factors, develop the prediction model, and construct the nomogram. The model's reliability and validity were checked using the receiver operating characteristic curve and the calibration curve. Results A high morbidity of ketosis‐prone T2DM was observed (20.2%), who presented as lower age and fasting C‐peptide, and higher free fatty acids, glycated hemoglobin A1c and urinary protein. Based on these five independent influence factors, we developed a risk prediction model for ketosis‐prone T2DM and constructed the nomogram. Areas under the curve of the modeling and validation cohorts were 0.806 (95% confidence interval [CI]: 0.760–0.851) and 0.856 (95% CI: 0.803–0.908). The calibration curves that were both internally and externally checked indicated that the projected results were reasonably close to the actual values. Conclusions Our study provided an effective clinical risk prediction model for ketosis‐prone T2DM, which could help for precise classification and management.

Abstract Smart sensors with excellent performance are accelerating the development of biomedicine and the Internet of Energy. Nanodielectrics exhibit unique electrical and mechanical properties. As the predominant materials in optical magnetic field sensor (MFS), they can not only exert the anti‐interference of optical sensing, but improve the measuring characteristics of optical sensors. For instance, the optical fibre quantum probe for the magnetic field can obtain a higher sensitivity of 0.57 nT/Hz1/2, while the measurement range of the sensor that uses Co‐doped ZnO nanorods as cladding is 17–180 mT. Here, these exciting recent achievements in the realm of optical sensing methods for magnetic field detection are reviewed, with a focus on nanodielectrics, which provide an emerging opportunity to achieve higher sensitivity and a wider measurement range of MFS.

In present work, tensile behaviors of cold-rolled 304L stainless steel were investigated at both room temperature (RT) and liquid nitrogen temperature (LNT). After cold-rolling with a thickness reduction of ∼92%, the 304L stainless steel exhibits an ultrahigh yield strength of 1787 MPa at the expense of ductility (1.06% of uniform elongation) at RT. At LNT, the yield strength (upper yield point of σyu = 2308.4 MPa and lower yield point of σyl = 1894.2 MPa) and uniform elongation (23%) increase greatly. Detailed microstructural investigation reveals that the cold-rolled 304L stainless steel comprises mainly of deformation induced martensite and high density of dislocations (9.06 ×1014 m−2), leading to a lack of dislocation storage capacity and thus brittle fracture at RT. While interrupt tests at LNT reveal a first increase and then decline in dislocation density with tensile strain, accompanied with phase transformation from austenite to martensite. The delamination events also occur, characterized by the multiple separated laminated ligaments observed at fracture surface. Therefore, the high dense dislocations and transformation-induced plasticity (TRIP) effect as well as delamination toughening mechanism contributes to the excellent combination of strength and ductility at LNT. Our work provides experimental and microstructural insights into the deformation mechanisms of the ∼92%-cold-rolled 304L stainless steel during tensile deformation at RT and LNT.

Hot isostatic pressed Ti2AlNb alloys with trapezoid-shaped sections were hot rolled at 1000 °C to obtain the specimens with the gradient of deformation. The effect of the rolling reduction on the microstructure of the Ti2AlNb alloys was investigated by this high throughput method, and the mechanical properties of the gradient alloys were studied. With the increasing rolling reduction, the morphology of the orthorhombic (O) phase changed from well-arranged herringbone and palisade structures to a randomly distributed lamellar structure. By the electron backscatter diffraction characterization, the textures of the B2 and O phases changed with the increasing rolling reduction, and the texture of the O phase was depressed. The elevated-temperature tensile properties of the Ti2AlNb and Mo-modified Ti2AlNb gradient specimens were measured, and the deformation gradient was 36.0–43.0% and 43.0–50.0%, respectively. The heavily deformed gradient specimens exhibited higher strength and ductility than the lightly deformed ones, due to the increasing low-angle grain boundary and uniform distribution of local strain.

Abstract Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8+ T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8+ T cells, as well as differentially drove the functional commitment of CD8+ T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8+ T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC.

Abstract Nonalcoholic fatty liver disease (NAFLD) is usually characterized with disrupted bile acid (BA) homeostasis. However, the exact role of certain BA in NAFLD is poorly understood. Here we show levels of serum hyodeoxycholic acid (HDCA) decrease in both NAFLD patients and mice, as well as in liver and intestinal contents of NAFLD mice compared to their healthy counterparts. Serum HDCA is also inversely correlated with NAFLD severity. Dietary HDCA supplementation ameliorates diet-induced NAFLD in male wild type mice by activating fatty acid oxidation in hepatic peroxisome proliferator-activated receptor α (PPARα)-dependent way because the anti-NAFLD effect of HDCA is abolished in hepatocyte-specific Pparα knockout mice. Mechanistically, HDCA facilitates nuclear localization of PPARα by directly interacting with RAN protein. This interaction disrupts the formation of RAN/CRM1/PPARα nucleus-cytoplasm shuttling heterotrimer. Our results demonstrate the therapeutic potential of HDCA for NAFLD and provide new insights of BAs on regulating fatty acid metabolism.

Abstract Objectives The purpose of this study was to survey the prevalence of C-shaped root canal system in mandibular first premolar in Chinese population by reading Cone-beam computed tomography (CBCT) images and to analyze its anatomical characteristics by CBCT and Micro–computed tomography (Micro-CT). Methods and materials The prevalence and the morphologic features of C-shaped root canal system were evaluated by observing CBCT images of 760 patients (1520 mandibular first premolars). 66 mandibular first premolars with C-shaped root canal system were scanned by Micro-CT. The morphologic features including radicular groove, C-shaped root canal categories in the cross-sections and in the 3D models, accessory and connecting canals, apical foramina and accessory foramina, were analyzed using image software. Results C-shaped root canal system was identified in 16.9% of mandibular first premolars. The minimum mesial wall thickness most commonly occurred at the lingual site (69.7%). Regarding to the cross-sectional classification, the maximum was C2 (41.5%). In the 3D classification, the most common was S (34.8%). Accessory canals were observed in 36.4% of the samples and occurred mostly in the middle and apical regions. 42.4% samples had 1–3 variable connecting canals, and 40.9% samples had only one apical foramen. Conclusions The incidence of C-shaped root canal system in mandibular first premolars was 16.9% in the Chinese population. The anatomy was very complex and variable, mostly distributed in the middle and apical regions of the root canal. The mesial wall of C-shaped canal was extremely thin on the lingual side.

Abstract Transcription factors (TFs) play key roles in regulating differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment of Sox11 mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data, Sox11 levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate that Sox11 expression is reduced in aged MuSCs. Age-related decline of Sox11 expression is associated with reduced chromatin contacts within the topologically associating domains. Unexpectedly, Myod1Cre-driven deletion of Sox11 in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreER- or Rosa26CreER- driven (MuSC-specific or global) deletion of Sox11 in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remains to be elucidated.

Abstract To investigate the effect of initial cracks on the fatigue performance of high-strength bolts for high-speed train brake discs, the fatigue crack propagation behavior of high-strength bolts under the coupling action of preload and dynamic fatigue load was investigated experimentally and numerically based on the theory of linear elastic fracture mechanics. Firstly, fatigue tests of high-strength bolts with initial crack defects were carried out, and then a three-dimensional accurate numerical model with the hexahedral mesh for a bolt-nut was established by MATLAB, and the fatigue crack propagation behaviors were investigated using ABAQUS-FRANC3D interactive technology. In this paper, the effects of the initial crack state, the bolt preload, the axial excitation load, and the friction coefficient of the screw pair on crack propagation life were emphatically studied, and the simulated crack propagation trajectory and crack propagation life agreed well with the experimental results. The findings indicated that 0°-oriented cracks beginning at the maximum principal stress were predicted to have the shortest fatigue life. The crack propagation life was sensitive to the initial crack size, the coefficient of initial crack geometry, and the bolt preload, but not to the friction coefficient of the screw pair. Furthermore, when evaluating the effect of fatigue load on crack propagation, the load ratio, the mean load, and the load range should all be considered.

Summary: Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

ABSTRACT: This experiment aimed to study the effect of 1% Artemisia annua added to the diet on growth performance, antioxidant capacity, immunity and intestinal morphology, and gut microbiota of geese. Seventy-two 35-day-old male geese (Zi goose) with similar body weight were selected and randomly divided into 2 groups. Each treatment group of 36 geese was divided into 6 subgroups, each having 6 male geese. The experiment lasted for 21 d. Control group (CON) was fed a basal diet and the experimental group (AAL) was fed a basal diet + 1% Artemisia annua. BW, ADG, and ADFI of the AAL group increased (p < 0.05) and the FCR decreased (p < 0.05) compared with the CON group. The addition of Artemisia annua to the diet increased catalase (CAT), glutathione peroxidase (GSH-px), and superoxide dismutase (SOD) enzyme activities, increased total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) content in serum and jejunum of geese (p < 0.05). Meanwhile, serum IgA, IgG, IgM, and lysozyme (LZM), increased at different time points in the AAL group compared to the CON group (p < 0.05), and decrease in the content of interferon-γ (IFN-γ) , IL-6 (p < 0.05), but no effect on complement C3 and C4. Morphological observation of the small intestine showed that the jejunal crypt depth was decreased in the AAL group (p < 0.05) while elevating the jejunal villus height/crypt depth (p < 0.05). 16S rRNA sequencing results showed the Artemisia annua increased the diversity of cecum microbiota, increasing the relative abundance of Bacteroides, Fecalibacterium, and Paraprevotella. In conclusion, the addition of 1% Artemisia annua to the diet could improve the growth performance, antioxidant and immune ability of geese, as well as improve the development of the jejunum intestinal tract of geese, and change the structure of the cecum microbiota, which had a positive effect on the growth and development of geese. Artemisia annua can be further developed as a feed additive.

Introduction: MYC transcription factors are the basic regulators of the jasmonic acid signaling pathway and play important roles in plant growth and development and the response to adverse stress. In recent years, severe winter freezing and late spring frost in the main planting area of walnut in Xinjiang have affected the growth and development of walnut, which has become a prominent problem restricting walnut production. Xinjiang wild walnut is the only remaining wild species of walnuts in China, which contains a lot of genes with excellent traits, and is important for the cultivation and breeding.Methods: In this paper, the physicochemical properties and bioinformatics of MYC transcription factor members in walnut were analyzed, and the nine MYC were screened from the transcriptome data under low temperature stress. At last, we study the subcellular localizations and the expression patterns of the nine MYC members in Xinjiang wild walnut.Results: The results revealed that 30 MYC members were identified from published walnut whole-genome data, and their evolutionary relationships with Arabidopsis and poplar were divided into six groups according to clustering analysis, among which JrMYC22 and JrMYC23 had high homology with PtrMYC2b, which is induced by jasmonic acid in response to low-temperature stress. Walnut MYC members are unevenly distributed on 12 chromosomes. The prediction of promoter cis-acting elements of walnut MYC transcription factor family members revealed that cis-acting elements related to jasmonic acid and lowtemperature stress were the ones with the greatest number of members, with 12. In addition, all nine MYC family members in Xinjiang wild walnut plants responding to low-temperature stress exhibited strong fluorescence responses in the nucleus. The expression levels of these members in response to low-temperature stress revealed that JrMYC28, JrMYC31, JrMYC33, JrMYC34, and JrMYC35 were highly expressed, and it was hypothesized that JrMYC28, JrMYC31, JrMYC33, JrMYC34, and JrMYC35 might play a key role in the response to lowtemperature stress.Discussion: The results of this study provide a theoretical basis for further research on the functional mechanisms of the MYC transcription factor family members in walnut.

IntroductionSound waves are refracted along the direction of their propagation owing to spatial and temporal fluctuations in the speed of sound in seawater. Errors are compounded when sound speed profiles (SSPs) with low precision are used to detect and locate distant underwater targets because an accurate SSP is critical for the identification of underwater objects based on acoustic data. Only sparse historical spatiotemporal data on the SSP of the South China Sea are available owing to political issues, its complex atmospheric system, and the unique topography of its seabed, because of which frequent oceanic movements at the mesoscale affect the accuracy of inversion of its SSP.MethodIn this study, we propose a method for the inversion of the SSP of the South China Sea based on a long short-term memory model. We use continuous-time data on the SSP of the South China Sea as well as satellite observations of the height and temperature of the sea surface to make use of the long-term and short-term memory-related capacities of the proposed model.ResultIt can achieve highly accurate results while using a small number of samples by virtue of the unique structure of its memory. Compared with the single empirical orthogonal function regression method, the inversion accuracy of this model is improved by 24.5%, and it performed exceptionally well in regions with frequent mesoscale movements.DiscussionThis enables it to effectively address the challenges posed by the sparse sample distribution and the frequent mesoscale movements of the South China Sea.

Abstract BackgroundPredicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. ObjectiveThe aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. MethodsWe assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose

Background: The prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. Methods: HPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan–Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). Results: A total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p

IntroductionThe potential role of the endometrial microbiota in the pathogenesis of endometrial polyps (EPs) warrants further investigation, given the current landscape of limited and inconclusive research findings. We aimed to explore the microecological characteristics of the uterine cavity in patients with EPs and investigate the potential of endometrial microbiota species as novel biomarkers for identifying EPs.MethodsEndometrial samples were collected from 225 patients who underwent hysteroscopies, of whom 167 had EPs, whereas 58 had non- hyperproliferative endometrium status. The endometrial microbiota was assessed using 16S rRNA gene sequencing. We characterized the endometrial microbiota and identified microbial biomarkers for predicting EPs.ResultsThe endometrial microbial diversity and composition were significantly different between the EP and control groups. Predictive functional analyses of the endometrial microbiota demonstrated significant alterations in pathways involved in sphingolipid metabolism, steroid hormone biosynthesis, and apoptosis between the two groups. Moreover, a classification model based on endometrial microbial ASV-based biomarkers along with the presence of abnormal uterine bleeding symptoms achieved powerful classification potential in identifying EPs in both the discovery and validation cohorts.ConclusionOur study indicates a potential association between altered endometrial microbiota and EPs. Endometrial microbiota-based biomarkers may prove valuable for the diagnosis of EPs.Clinical trial registrationChinese Clinical Trial Registry (ChiCTR2100052746).

BackgroundArtificial intelligence (AI) has emerged as a transformative force across the health sector and has garnered significant attention within sexual and reproductive health and rights (SRHR) due to polarizing views on its opportunities to advance care and the heightened risks and implications it brings to people’s well-being and bodily autonomy. As the fields of AI and SRHR evolve, clarity is needed to bridge our understanding of how AI is being used within this historically politicized health area and raise visibility on the critical issues that can facilitate its responsible and meaningful use. ObjectiveThis paper presents the protocol for a scoping review to synthesize empirical studies that focus on the intersection of AI and SRHR. The review aims to identify the characteristics of AI systems and tools applied within SRHR, regarding health domains, intended purpose, target users, AI data life cycle, and evidence on benefits and harms. MethodsThe scoping review follows the standard methodology developed by Arksey and O’Malley. We will search the following electronic databases: MEDLINE (PubMed), Scopus, Web of Science, and CINAHL. Inclusion criteria comprise the use of AI systems and tools in sexual and reproductive health and clear methodology describing either quantitative or qualitative approaches, including program descriptions. Studies will be excluded if they focus entirely on digital interventions that do not explicitly use AI systems and tools, are about robotics or nonhuman subjects, or are commentaries. We will not exclude articles based on geographic location, language, or publication date. The study will present the uses of AI across sexual and reproductive health domains, the intended purpose of the AI system and tools, and maturity within the AI life cycle. Outcome measures will be reported on the effect, accuracy, acceptability, resource use, and feasibility of studies that have deployed and evaluated AI systems and tools. Ethical and legal considerations, as well as findings from qualitative studies, will be synthesized through a narrative thematic analysis. We will use the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) format for the publication of the findings. ResultsThe database searches resulted in 12,793 records when the searches were conducted in October 2023. Screening is underway, and the analysis is expected to be completed by July 2024. ConclusionsThe findings will provide key insights on usage patterns and evidence on the use of AI in SRHR, as well as convey key ethical, safety, and legal considerations. The outcomes of this scoping review are contributing to a technical brief developed by the World Health Organization and will guide future research and practice in this highly charged area of work. Trial RegistrationOSF Registries osf.io/ma4d9; https://osf.io/ma4d9 International Registered Report Identifier (IRRID)PRR1-10.2196/53888

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Two new species of the genus Macrothele Ausserer, 1871 are described from Yunnan Province, China: Macrothele nullispine sp. nov. and M. auriculata sp. nov. Detailed descriptions, photos of morphological characteristics, DNA barcode sequences and genetic distances of the new species are provided.

Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers.Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10–300 mg [single dose]; 20–100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers.Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100–300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25–0.5 h post-dose and was maintained 48–168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20–100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups.Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development.