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Abstract Background Regenerating family member 3A (REG3A) is involved in the development of multiple malignant tumors, including pancreatic ductal adenocarcinoma (PDAC). However, any role of REG3A in PDAC remains controversial due to its unclear tissue localization or direct receptors, and complex downstream signal transductions. Methods Morphological analysis and public multi-omics data retrieval were was utilized to elucidate the tissue localization of REG3A in PDAC. To ascertain the pro-oncogenic role of secreted REG3A, experiments were conducted using in vitro PDAC cell lines and in vivo tumor formation assays in nude mice. A battery of investigative techniques, including RNA sequencing, phospho-kinase arrays, western blot analyses, in silico docking simulations, gene truncation strategies, and co-immunoprecipitation, were employed to delve into the downstream signaling transduction pathways induced by REG3A. Results In this study, we confirmed an association between increased serum levels of REG3A and poor prognosis in patients with PDAC. Morphological staining and bioinformatic analysis showed that REG3A was mainly expressed in peritumoral acinar cells that were spatially close to tumor region, while it was almost negative in PDAC tumor cells. Peritumoral REG3A expression levels, but not tumoral REG3A, were highly correlated with PDAC progression. Further in vitro experiments including RNA sequencing and molecular biological assays revealed that secreted REG3A could directly bind to the epidermal growth factor receptor (EGFR), an important pro-oncogene involved in cellular proliferation, and subsequently activate the downstream mitogen-activated protein kinase (MAPK) signals to promote PDAC tumor cell growth. Conclusion Taken together, our data indicated that increased expression of REG3A in peritumoral acinar cells acts as a specific event to indicate PDAC progression, and verified EGFR as a possible target of REG3A, providing mechanistic insights into the role of REG3A, the diagnostic method and therapeutic strategy of PDAC.

Abstract Mesenchymal stem/stromal cells (MSCs) have garnered attention for their potential in cancer therapy due to their ability to home to tumor sites. Engineered MSCs have been developed to deliver therapeutic proteins, microRNAs, prodrugs, chemotherapy drugs, and oncolytic viruses directly to the tumor microenvironment, with the goal of enhancing therapeutic efficacy while minimizing off-target effects. Despite promising results in preclinical studies and clinical trials, challenges such as variability in delivery efficiency and safety concerns persist. Ongoing research aims to optimize MSC-based cancer eradication and immunotherapy, enhancing their specificity and efficacy in cancer treatment. This review focuses on advancements in engineering MSCs for tumor-targeted therapy.

Highlights Alkaline earth cations are successfully incorporated into perovskite lattice with the aid of sulfonic acid anions, while alkaline earth metal halides are lack of doping capacity. The sulfonic acid anions effectively regulate the crystallization of perovskite and passivate the metallic Pb0 defect states, thereby improving the power conversion efficiency of perovskite solar cells. By comparing the property of FACF3SO3 and Ca(CF3SO3)2-doped perovskite films, the impact of suppressing halide migration with an activation energy of 1.246 eV is attributed to Ca2+ cations, thus providing methodology for decoupling the effects of cations and anions.

Abstract Cancer development is associated with adaptation to various stressful conditions, such as extracellular acidosis. The adverse tumor microenvironment also selects for increased malignancy. Mitochondria are integral in stress sensing to allow for tumor cells to adapt to stressful conditions. Here, we show that colorectal cancer cells adapted to acidic microenvironment (CRC-AA) are more reliant on oxidative phosphorylation than their parental cells, and the acetyl-CoA in CRC-AA cells are generated from fatty acids and glutamine, but not from glucose. Consistently, CRC-AA cells exhibit increased mitochondrial mass and fitness that depends on an upregulated autophagic flux-lipid droplet axis. Lipid droplets (LDs) function as a buffering system to store the fatty acids derived from autophagy and to protect mitochondria from lipotoxicity in CRC-AA cells. Blockade of LD biogenesis causes mitochondrial dysfunction that can be rescued by inhibiting carnitine palmitoyltransferase 1 α (CPT1α). High level of mitochondrial superoxide is essential for the AMPK activation, resistance to apoptosis, high autophagic flux and mitochondrial function in CRC-AA cells. Thus, our results demonstrate that the cascade of autophagic flux and LD formation plays an essential role in sustaining mitochondrial fitness to promote cancer cell survival under chronic acidosis. Our findings provide insight into the pro-survival metabolic plasticity in cancer cells under microenvironmental or therapeutic stress and imply that this pro-survival cascade may potentially be targeted in cancer therapy.

Abstract The same cumulative carbon emission reduction target can correspond to multiple emission reduction pathways. This study explores how different coal power transition pathways with the same cumulative emissions reductions impact the transition costs, by assessing the dynamic transition processes for coal plants adopting multiple mitigation technologies concurrently or sequentially, such as flexibility operation, biomass and coal co-firing, carbon capture and storage, and compulsory retirement. We develop a plant-level dynamic optimization model and apply it to China’s 4200+ coal plants. We find that under deep decarbonization, the majority of Chinese coal plants retrofit with multiple technologies to reduce emissions and retire naturally at lower costs while contributing to grid stability. Optimizing the pathway can potentially save over 700 billion U.S. Dollars for achieving the same target or increase cumulative emissions reduction from 30% to 50% at no additional cost. This analysis can help inform a cost-effective coal phase-out under China’s carbon neutrality.

Abstract Background Keratoconus (KC) is a prevalent corneal condition with a modest genetic basis. Recent studies have reported significant genetic associations in multi-ethnic cohorts. However, the situation in the Chinese population remains unknown. This study was conducted to identify novel genetic variants linked to KC and to evaluate the potential applicability of a polygenic risk model in the Han Chinese population. Methods A total of 830 individuals diagnosed with KC and 779 controls from a Chinese cohort were enrolled and genotyped by whole-genome sequencing (WGS). Common and rare variants were respectively subjected to single variant association analysis and gene-based burden analysis. Polygenic risk score (PRS) models were developed using top single-nucleotide polymorphisms (SNPs) identified from a multi-ethnic meta-analysis and then evaluated in the Chinese cohort. Results The characterization of germline variants entailed correction for population stratification and validation of the East Asian ancestry of the included samples via principal component analysis. For rare protein-truncating variants (PTVs) with minor allele frequency (MAF)

Abstract EH (Euphorbia Humifusa) is commonly known as ground spurge, contains various compounds such as flavonoids, triterpenes, coumarins, sterols, tannins, and phenolic acids. It exerts a wide spectrum of properties including anti-bacterial, anti-inflammatory, Antioxidant, anti-viral, hypoglycemic, and anti-tumor. In this article, we focus on the antitumor effects of EH and its active constituents, providing evidence for further research on this medicinal herb.

ABSTRACT Population aging presents a major challenge to China's economic and social development. While some research has addressed the relationship between population aging and energy consumption or generalized carbon emissions, its impact on living carbon emissions has been less explored. This study uses provincial panel data from the Yellow River Basin (2006–2020) and employs a threshold regression model to analyze the relationship between population aging and living carbon emissions. A Multiple Mediation Effect Model is also applied to explore the mechanisms behind this relationship, with a comparative analysis between urban and rural areas. The results indicate a U‐shaped nonlinear effect of population aging on living carbon emissions, which are initially inhibited and then promoted, with different “turning points” for rural and urban regions. As income levels rise, population aging has a marginally increasing effect on living carbon emissions. However, upgrading the consumption expenditure structure, expanding family size, and increasing clean energy consumption can help mitigate the promoting effect of aging on emissions. The mediation model identifies four pathways through which population aging influences living carbon emissions, with income level and consumption expenditure structure playing key roles. This study offers policy insights for addressing urban‐rural disparities and fostering sustainable regional development.

The acoustic wave transmission of MWD data is an important means to realize the high-speed and accurate transmission of borehole data in coal mine, which is conducive to changing the situation that most of the underground gas extraction in coal mine is in “blind drilling”. In order to verify the reliability of acoustic wave transmission in drill pipe, the acoustic wave propagation characteristics of drill pipe pillar composed of mining drill pipe are investigated. According to the basic theory of sound wave transmission in solid, the sound wave transmission channel is equivalent to a periodic structure composed of drill pipe and its joint, and the transmission characteristics of sound wave in drill pipe are analyzed by using the propagation equation of sound wave in periodic structure. Through numerical simulation, the propagation of sound waves in drill pipe is analyzed, and the effects of different drill pipe diameters, knock positions and sand injection conditions on the propagation characteristics and attenuation law of sound waves are compared. The results show that the larger outer diameter of drill pipe and the lower knock point are beneficial to signal transmission. The water injection signal inside the drill pipe attenuates obviously, and the amplitude of the signal attenuates exponentially, while the influence of the external sand environment on the signal intensity can be ignored. The excitation signal, acoustic output and attenuation characteristics obtained by the test platform agree with the basic trend of the simulation results.

Abstract Objective The association between gait speed and adverse outcomes after stroke has not been fully illustrated. This study aimed to explore the association of gait speed on long‐term outcomes in minor stroke or transient ischemic attack (TIA). Methods We performed a longitudinal study with acute minor stroke or TIA based on a subgroup of the Third China National Stroke Registry data. The gait speed was evaluated using a 10‐meter walking test at discharge and 3 months after the stroke onset. The primary outcomes were poor functional outcomes at 1 year, defined by a modified Rankin Score (mRS) of 2–6. Additional outcomes included all‐cause death, ambulate dependency (mRS score 4–6), cognitive impairment (Montreal Cognitive Assessment

In traditional wire arc additive manufacturing process, it is difficult to control the chemical composition of deposition layer. A double filler wire with alternating current was proposed to fabricate the NiTi alloy. In this process, Ni filling wire and Ti filling wire were connected to alternating current. The macrographic, phase evolution, and mechanical properties of the as-printed sample at various wire feed speed ratios were studied. The results show that the deposition layers were consistently uniform in the deposition process. The coarse dendritic grain structure gradually changed with decreasing Ni wire feed speed. Columnar and equiaxed microstructures were observed in the deposition sample at different wire feed speed ratios. Different wire feeding speed ratios lead to variations in Ni concentration in the molten pool. The content of Ni might affect the formation of martensite and austenite during solidification. The average microhardness increases with increasing Ni wire feed speed. When the wire feeding ratio of Ni/Ti was 1.2, the compressive strength reached 1664 MPa. This study introduces an innovative method in arc additive manufacturing of NiTi alloy by utilizing an AC power source into the double filler wires.

Abstract Objective To investigate the efficacy of physical activity as a crucial intervention for Autism spectrum disorder (ASD) in clinical settings, we conducted a network meta-analysis to evaluate the effect of various exercise interventions on sociability and communication in individuals with ASD. Our aim was to identify the exercise modalities most conducive to enhancing these essential skills. Methods We searched Web of Science, PubMed, Cochrane Library, Scopus, Embase, and searched Chinese databases from inception to April 2024. We included randomized controlled trials that assessed the effects of different exercise types on sociability and communication in individuals with ASD. Network meta-analysis (NMA) was performed using a frequentist approach, and the node-splitting method was applied to assess inconsistency. Results We included 38 original studies published between 2009 and 2024, with a total of 1,382 participants analyzed for sociability outcomes. Results indicated that sports games [SMD = 1.12, 95%CI (0.51, 1.73)], combination therapy [SMD = 1.11, 95%CI (0.13, 2.09)], group ball sports [SMD = 1.06, 95%CI (0.37, 1.75)], and outdoor exercise [SMD = 1.02, 95%CI (0.50, 1.55)] were more effective than passive controls. A total of 25 original literatures were included in the analysis of communication ability, involving 904 subjects, and the results showed that combination therapy [SMD = 1.57, 95% CI (0.74, 2.40)], sports games [SMD = 1.01, 95% CI (0.45, 1.56)], group ball games [SMD = 0.85, 95% CI (0.45, 1.26)], outdoor exercise [SMD = 0.79, 95% CI (0.48, 1.11)], and mind-body exercise [SMD = 0.79, 95% CI (0.29, 1.30)], all of which were more effective than passive controls. Conclusion Physical exercise plays a significant role in alleviating symptoms and enhancing sociability and communication in individuals with ASD. Our findings highlight that sports games, combination therapy, team ball sports, and outdoor exercise are particularly effective in improving sociability. In terms of communication skills, combination therapy, sports games, team ball sports, outdoor exercise, and mind-body exercise demonstrated the most substantial benefits. These results provide a robust foundation for future interventions aimed at improving the quality of life for individuals with ASD.

Abstract Ghd7 is a central regulator to multiple growth and development processes in rice. While it is not clear how Ghd7 is regulated by upstream factors. To identify its upstream regulator, the truncated Ghd7 promoter fragments were used to screen cis elements binding to rice total nuclear proteins. Electrophoretic mobility shift assays screened one truncated fragment f3 binding to the proteins. Subsequently, the fragment f3 was employed to screen a yeast one-hybrid library, and a transcription factor OsIAA23 was screened as a direct upstream regulator of Ghd7. Dual-luciferase transient assay demonstrated the transcriptional repression effect of OsIAA23 on the activity of Ghd7, and the location of the cis elements binding to OsIAA23 in the region 1264 to 1255 bp upstream of ATG. Genetic analysis between the wild type Ghd7-OsIAA23 and single/double mutants further verified that OsIAA23 downregulated Ghd7 expression and led to a delayed heading under long day conditions. Moreover, natural variations in fragment f3 were associated with heading and geographic distribution in rice. This study sheds light on the direct regulatory mechanism of OsIAA23 on Ghd7, which enriches the understanding of the Ghd7 involved flowering regulatory network in rice.

Abstract Objective To investigate the diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis (IM). Methods A total of 135 children with IM as the IM group and 100 healthy volunteers as the healthy group were included in this retrospective study. Peripheral blood lymphocyte subsets marked as CD3+, CD4+, CD8+, CD16 + CD56+, and CD19 + in the peripheral blood were quantified using flow cytometry. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, AUROC curve, and Kappa consistency test to assess the diagnostic value of these markers in IM. Results The AUROC curve for CD8 + cells and for CD4+/CD8 + ratios both achieved a value of 1 with the sensitivity and specificity of 100% (P

Abstract Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers. Furthermore, we investigated to what extent the PGS effect was influenced by direct and indirect genetic effects (i.e., shared familial effects). We derived ADHD-PGS in 50,768 individuals aged 18–90 years from the Dutch Lifelines Cohort study. Using generalised estimating equations, we estimated the association of PGS with cardiometabolic diseases, derived from self-report and several biomarkers measured during a physical examination. We additionally ran within-sibling PGS analyses, using fixed effects models, to disentangle direct effects of individuals’ own ADHD genetic risk from confounding due to indirect genetic effects of relatives, as well as population stratification. We found that higher ADHD-PGS were statistically significantly associated with several cardiometabolic diseases (R-squared [R2] range = 0.03–0.50%) and biomarkers (related to inflammation, blood pressure, lipid metabolism, amongst others) (R2 range = 0.01–0.16%) (P

Abstract This study employs the photo-elicitation (PE) interview method to explore the social construction of contemporary Chinese lesbian identity. It examines how individuals use visual symbols in their daily lives to construct and express their sexual orientation. The research highlights the diversity and creativity in Chinese lesbian identity expression, while addressing challenges from traditional family values, gender norms, and evolving social attitudes. Introducing the “Visual Narratives of Identity” (VNI) framework, this study bridges the gap between academic research and lived experiences, offering insights into identity expression under social and cultural constraints. The findings emphasize the complex strategies participants use to navigate social expectations and maintain personal authenticity. This study enriches the theoretical landscape of sexual orientation identity in visual culture studies, advocates for methodological diversity, and deepens our understanding of the complexities within Chinese lesbian subcultures.

Abstract Classifying emission reduction zones on different scales has important implications for the ecological protection and high‐quality development of the Yellow River Basin. Based on remote sensing data and a light‐carbon conversion model, carbon footprints at provincial, municipal, and county scales in the Yellow River Basin are measured. The spatiotemporal evolution critical paths of carbon footprints at the three spatial scales are compared and classified into different zones using spatiotemporal evolution analysis methods. The conclusions are as follows: (1) The carbon footprint increased over the years. The spatial distributions of carbon footprints at the three scales are not only consistent but also different. The study of carbon footprints at the county scale is more conducive to the summary of the spatiotemporal evolution and the formulation of detailed emission reduction schemes. (2) Four provinces, 48 cities, and 373 counties are designated as a “core protected zone”; three provinces, 29 cities, and 177 counties are designated as a “strictly governed zone”; one province, 12 cities, and 47 counties are designated as a “key restricted zone”; four cities and 39 counties are designated as an “alert diffusion zone.” (3) The agglomeration expansion trend and the spillover effect of high‐carbon footprint units at the county scale are more obvious. Further enhancement of the path‐locking characteristics of the carbon footprints of counties will make governance more difficult. Effective governance of carbon footprint at the county scale is of urgent concern. These results provide scientific evidence for multiscale carbon emission control and zoning policy formulation in the Yellow River Basin.

Abstract Short‐chain fatty acids (SCFAs) are major metabolites produced by the gut microbiota through the fermentation of dietary fiber, and they have garnered significant attention due to their close association with host health. As important mediators between the gut microbiota and the host, SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics, activating G protein‐coupled receptors, and inhibiting pathogenic microbial infections. This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health, enhancing energy metabolism, mitigating diseases such as cancer, obesity, and diabetes, modulating the gut‐brain axis and gut‐lung axis, and promoting bone health.

This paper evaluates the integrated benefits of photovoltaic (PV) building systems in terms of energy, economy, and environment, providing a scientific basis for low-carbon sustainable buildings. Using the renovation project of a hospital in Ordos, Inner Mongolia, as a case study, we simulated energy consumption and power generation of PV-integrated buildings with EnergyPlus and JEPlus. The study considers three retrofit scenarios: installing PV panels on the exterior walls and roofs; replacing external windows with PV windows; combining both PV panels and windows. The impact on building energy consumption, carbon emissions, and economic costs was examined under various window-to-wall ratios (WWR) and PV power capacities. A multi-objective optimization analysis was performed using the TOPSIS method to identify the most balanced solutions. The results indicate that optimal PV system configurations should balance energy consumption, carbon emissions, and costs. For scenario 1, a WWR of 0.4 and 100 W power yield the best performance. For scenario 2, a WWR of 0.2 with type 3 PV windows is optimal. For scenario 3, a WWR of 0.2, 300 W power, and type 1 PV windows effectively reduce energy consumption and carbon emissions while maximizing economic benefits.

Accurately estimating and forecasting short-term daily reference crop evapotranspiration (ETo) is crucial for real-time irrigation decision-making and regional agricultural water management. Although the Penman-Monteith formula shows high accuracy, the requirement for excessive meteorological factors by this formula restricts its practical application. Previous studies have developed many ETo estimation models using deep learning (DL) algorithm, which only require temperature data as input. Subsequently, temperature forecast data is used to drive these models for ETo forecasting. However, these models are often limited to the specific locations of their training sets due to significant climatic variations across regions. Besides, weather forecasts at different lead days typically exhibit different biases. It remains unclear whether train ETo forecasting models for different lead times will enhance the overall forecasting accuracy. Hence, in this study, we innovatively utilized an extensive array of weather forecast data to develop customized ETo forecasting models for each day of the next 15 days, while incorporating both location and seasonal features into the model training procedure. Five deep learning (DL) models were employed in this study, namely Long Short-Term Memory (LSTM), Bidirectional LSTM (Bi-LSTM), Gated Recurrent Unit (GRU), Convolutional Neural Networks Bi-LSTM (CNN-BiLSTM), and CNN-BiLSTM-Attention. The results revealed that the differences in the performance of estimating ETo among the DL models were less pronounced compared to the variations that existed between diverse training strategies. By integrating location and seasonality information into the training set, we found a notable improvement in the accuracy of ETo estimating, with the average Root Mean Square Error (RMSE) of the five DL models decreasing from 0.55 mm d−1 to 0.48 mm d−1. Furthermore, when we directly employed a larger volume of weather forecast data to train the models, the forecasting accuracy of ETo was significantly improved, and among the five DL models, GRU performs the best. Specifically, the RMSE values for the ETo forecasts made by GRU model for the 1st, 4th, 7th, and 15th days in the future have decreased from 0.70, 0.87, 1.00 and 1.33 mm d−1 to 0.51, 0.56, 0.61 and 0.67 mm d−1, respectively. Additionally, compared to previous studies, we have successfully extended the lead time of ETo forecasts from 7 days to 15 days. These results indicate that the ETo estimating and forecasting models developed in this study demonstrate strong applicability across the entire country, which can provide effective support for irrigation water resource management.

Ovarian cancer, a formidable gynaecological malignancy, poses a significant global health challenge, and it is characterised by late-stage diagnosis and a high mortality rate. Even in its early stages, when treatment choices are scarce, ovarian cancer is still a complicated cancer to treat. In this work, we used computational approaches to find putative Traditional Chinese Medicine (TCM) inhibitors that target Phosphoserine Aminotransferase 1 (PSAT1), a crucial enzyme linked to the development of early-stage ovarian cancer. Using a methodical screening approach, we chose a panel of TCM compounds and prepared them, expected to interact with PSAT1. We next evaluated the binding affinities using molecular docking, which helped to identify Coniferin and Tetrahydrocurcumin compounds as potent inhibitors with the docking score of -8.8 kcal/mol and -8.9 Kcal/mol, respectively, and compared to the native ligand. The inhibitory effects of Coniferin and Tetrahydrocurcumin compounds were evaluated with the Pharmacokinetic studies and compared with the standard values, which resulted in an utter performance against each descriptor of the QikProp and performed the Molecular Interaction Fingerprints that resulted in the most interaction residues with counts were 4GLY, 4ASN, 4HIE, 4SER, 4THR, 3ARG and many more. Further, 100ns MD Simulation was performed in neutralised water, resulting in entirely stable deviations, fluctuations, and many intermolecular interactions, and the MM\GBSA studies on all 1000 trajectories have supported the complex's stability. The computational studies have shown a completely stable performance that supports Coniferin, and Tetrahydrocurcumin can be a potent inhibitor of PSAT1. However, further experimental works are needed to confirm this study.

BackgroundThis study aims to investigate the connection between serum lipids, per- and polyfluoroalkyl substances (PFAS), and age-related macular degeneration (AMD) risk and assess whether serum lipids mediate the association between PFAS and AMD.Methods1605 participants were enrolled from NHANES 2005-2008. Four serum PFAS levels with high detective rates, including perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) were examined. Restricted cubic spline analysis (RCS) and weighted quantile sum (WQS) analysis were employed to detect nonlinear and mixed exposure effects.ResultsPFOS level was associated with any AMD (OR, 1.54; 95% CI, 1.12 to 2.11; P = 0.011), early AMD (OR, 1.43; 95% CI, 1.06 to 1.95; P = 0.024), and late AMD (OR, 3.35; 95% CI, 1.55 to 7.23; P = 0.004) risk. PFHxS (OR, 1.72; 95% CI, 1.01 to 2.93; P = 0.045) and PFOA (OR, 2.10; 95% CI, 1.21 to 3.63; P = 0.011) levels were associated with late AMD risk. The RCS showed a nonlinear connection between PFOS exposure and AMD risk (P nonlinear = 0.006). WQS analysis indicated a positive relationship between mixed PFAS exposure and AMD risk (OR, 1.34; 95% CI, 1.03 to 1.75; P = 0.030). Serum total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were associated with AMD risk (ORTC, 1.005; 95% CI, 1.001 to 1.009; P = 0.026. ORHDL, 1.028; 95% CI, 1.014 to 1.042; PConclusionsPFOS exposure was connected with AMD risk and serum TC and HDL mediated this relationship.

Olmsted syndrome (OS) is a rare disorder characterized by a mutilating palmoplantar keratoderma and periorificial keratotic plaques, but which shows considerable clinical heterogeneity. Recently, transient receptor potential vanilloid 3 (TRPV3) mutations associated with autosomal dominant or recessive OS have been reported. Here we describe a classically OS case with definitive diagnosis of OS based on clinical features and a genetic assay. Genetic analysis revealed heterozygous variants in the TRPV3 gene using whole-exome sequencing of case-parents’ trios. This mutation was not identified in his mother. Notably, a previously unreported heterozygous frameshift mutation, c.1964 T > C (p.L655P), was identified in exon 15 of the TRPV3 gene in this patient and his father. Additionally, the patient was effectively managed with oral erlotinib at a daily dose of 75 mg. After 3 months of treatment, most plantar lesions resolved, and the pain experienced was mildly alleviated. No significant adverse effects were observed in this case during treatment. In addition, we review the OS literature regarding TRPV3 gene mutations.

Abstract Obesity and nonalcoholic fatty liver disease (NAFLD) are established risk factors for drug‐induced liver injury (DILI). The previous study demonstrates that benzbromarone (BBR), a commonly prescribed pharmaceutical agent for managing gout and hyperuricemia, exacerbates hepatic steatosis and liver injury specifically in obese individuals. However, the precise mechanism underpinning this adverse effect remains incompletely elucidated. Given the significance of BBR and its analogs in anti‐gout/hyperuricemia drug discovery, elucidating the mechanism by which BBR exacerbates obesity‐specific DILI warrants further investigation. In this study, through a combined multi‐omics, pharmacological, and pharmacokinetic approaches, it is found that BBR‐induced obesity‐specific DILI is primarily through the potentiation of peroxisome proliferator‐activated receptor gamma (PPARγ) signaling pathways. Further in vivo and in vitro pharmacokinetic analyses reveal that obese db/db mice exhibited a diminished capacity to metabolize BBR in their livers. This reduction leads to prolonged retention of BBR, subsequently resulting in chronic and sustained hepatic PPARγ agonism. This study demonstrates that a slow metabolism‐driven amplification of hepatic PPARγ agonism mediates BBR‐induced obesity‐specific hepatic steatosis and subsequent DILI, which also emphasizes the importance of the reduced hepatic drug metabolism capacity in patients with obesity or pre‐existing NAFLD in both clinical practice and drug discovery processes.

Abstract Lasing in the bad-cavity regime has promising applications in quantum precision measurement and frequency metrology due to the reduced sensitivity of the laser frequency to cavity-length fluctuations. Thus far, relevant studies have been mainly focused on conventional cavities whose finesse is high enough that the resonance linewidth is sufficiently narrow compared to the cavity’s free spectral range, though still in the bad-cavity regime. However, lasing output from the cavity whose finesse is close to the limit of 2 has never been experimentally accessed. Here, we demonstrate an extremely bad-cavity laser, analyze the physical mechanisms limiting cavity finesse, and report on the worst-ever laser cavity with finesse reaching 2.01. The optical cavity has a reflectance close to zero and only provides weak optical feedback. The laser power can be as high as tens of μW and the spectral linewidth reaches a few kHz, over one thousand times narrower than the gain bandwidth. In addition, the measurement of cavity pulling reveals a pulling coefficient of 0.0148, the lowest value ever achieved for a continuous-wave laser. Our findings open up an unprecedentedly innovative perspective for future new ultra-stable lasers, which could possibly trigger future discoveries in optical clocks, cavity QED, continuous-wave superradiant laser, and explorations of quantum many-body physics.

Abstract Chemodynamic therapy represents a novel tumor therapeutic modality via triggering catalytic reactions in tumors to yield highly toxic reactive oxygen species (ROS). Nevertheless, low efficiency catalytic ability, potential systemic toxicity and inefficient tumor targeting, have hindered the efficacy of chemodynamic therapy. Herein, a rationally designed catalytic nanoplatform, composed of folate acid conjugated liposomes loaded with copper peroxide (CP) and chloroquine (CQ; a clinical drug) (denoted as CC@LPF), could power maximal tumor cytotoxicity, mechanistically via maneuvering endogenous and exogenous copper for a highly efficient catalytic reaction. Despite a massive autophagosome accumulation elicited by CP-powered autophagic initiation and CQ-induced autolysosomal blockage, the robust ROS, but not aberrant autophagy, underlies the synergistic tumor inhibition. Otherwise, this combined mode also elicits an early onset, above all, long-term high-level existence of immunogenic cell death markers, associated with ROS and aberrant autophagy -triggered endoplasmic reticulum stress. Besides, CC@LPF, with tumor targeting capability and selective tumor cytotoxicity, could elicit intratumor dendritic cells (mainly attributed to CQ) and tumor infiltrating CD8+ T cells, upon combining with PD-L1 therapeutic antibody, further induce significant anti-tumor effect. Collectively, the rationally designed nanoplatform, CC@LPF, could enhance tumor chemoimmunotherapy via deploying endogenous plus exogenous copper and remodeling tumor microenvironment. Graphical abstract

Abstract Background Information on the influences of daily eating frequency (DEF) and nighttime fasting duration (NFD) on biological aging is minimal. Our study investigated the potential associations of DEF and NFD with accelerated aging. Methods Out of 24212 participants in NHANES 2003–2010 and 2015–2018, 4 predicted age metrics [homeostatic dysregulation (HD), Klemera–Doubal method (KDM), phenoAge (PA), and allostatic load (AL)] were computed based on 12 blood chemistry parameters. Utilizing 24-h dietary recall, DEF was measured by the frequency of eating occurrences, while NFD was determined by assessing the timing of the initial and final meals throughout the day. Weighted multivariate linear regression models and restricted cubic spline (RCS) were utilized to examine the associations. Results Compared to DEF of ≤ 3.0 times, subjects with DEF ≥ 4.6 times demonstrated lower KDM residual [β: -0.57, 95% confidence-interval (CI): (-0.97, -0.17)] and PA residual [β: -0.47, 95% CI: (-0.69, -0.25)]. In comparison to NFD between 10.1 and 12.0 h, individuals with NFD ≤ 10.0 h were at higher HD [β: 0.03, 95% CI: (0.01, 0.04)], KDM residual [β: 0.34, 95% CI: (0.05, 0.63)], and PA residual [β: 0.38, 95% CI: (0.18, 0.57)]. Likewise, those with NFD ≥ 14.1 h also had higher HD [β: 0.02, 95% CI: (0.01, 0.04)] and KDM residual [β: 0.33, 95% CI: (0.03, 0.62)]. The results were confirmed by the dose–response relationships of DEF and NFD with predicted age metrics. Lactate dehydrogenase (LDH) and globulin (Glo) were acknowledged as implicated in and mediating the relationships. Conclusions DEF below 3.0 times and NFD less than 10.0 or more than 14.1 h were independently associated with higher predicted age metrics.

Abstract Background Healthy dietary patterns have been negatively associated with methylation-based measures of biological age, yet previous investigations have been unable to establish the relationship between them and biological aging assessed through blood chemistry-based clinical biomarkers. We sought to assess the associations of 4 dietary metrics with 4 measures of biological age. Methods Among 16,666 participants in NHANES 1999–2018, 4 dietary metrics [Dietary inflammatory index (DII), Dietary approaches to stop hypertension index (DASH), Alternate mediterranean diet score (aMED), and Healthy eating index-2015 (HEI-2015)] were calculated through the ‘dietaryindex’ R package. Twelve blood chemistry parameters were utilized to compute 4 indicators of biological age [homeostatic dysregulation (HD), allostatic load (AL), Klemera–Doubal method (KDM), and phenotypic age (PA)]. Binomial logistic regression models and restricted cubic spline (RCS) regression were employed to evaluate the associations. Results All 4 dietary metrics were significantly associated with biological age acceleration or deceleration. In comparison to the lowest DII, the odds ratios (ORs) for accelerated HD, AL, KDM, and PA were 1.25 (1.08,1.45), 1.29 (1.11,1.50), 1.34 (1.08,1.65), and 1.61 (1.39,1.87) for the highest. The multivariable-adjusted ORs of the highest quartile of DASH, aMED, and HEI-2015 were 0.85 (0.73,0.97), 0.88 (0.74,1.04), and 0.84 (0.74,0.96) for HD, 0.64 (0.54,0.75), 0.61 (0.52,0.72), and 0.70 (0.59,0.82) for AL, 0.68 (0.54,0.85), 0.62 (0.50,0.76), and 0.71 (0.58,0.87) for KDM, and 0.50 (0.42,0.59), 0.64 (0.54,0.76), and 0.51 (0.44,0.58) for PA when compared with the lowest level. The findings were validated by the best-fitting dose-response curves for the associations. Among participants consuming dietary supplements (P interaction < 0.05), the positive effects of a healthy dietary pattern on biological aging were more pronounced. Systemic immune inflammation index (SII) and atherogenic index of plasma (AIP) were identified as being involved in and mediating the associations. Conclusions Biological aging assessed through blood chemistry-based clinical biomarkers is negatively associated with diet quality. The anti-aging benefits of improving the diet may be due to its ability to reduce inflammation and lower blood lipids.

Abstract The outbreak of the COVID-19 pandemic catalysed the rapid uptake of telemedicine as a vital tool for physicians to provide healthcare services to patients. However, despite the potential advantages of telemedicine, there remains a paucity of research examining physicians’ attitudes and utilisation patterns towards this mode of healthcare delivery. Therefore, this study investigated the factors impacting physicians’ telemedicine utilisation during the COVID-19 pandemic. Based on the unified theory of acceptance and use of technology and protection motivation theory, a cross-sectional survey was conducted between June 3rd and October 26th, 2022. A structural equation model was subsequently developed to validate the response-based research model. Of the 296 physicians surveyed, 134 reported an increase in the frequency of telemedicine use following the COVID-19 pandemic, and 88.9% of respondents supported the implementation of telemedicine services at their hospitals. The analysis revealed that perceived vulnerability, perceived severity, performance expectations, effort expectations, and facilitating conditions were significant factors influencing physicians’ willingness to adopt telemedicine. Importantly, the results suggest that strategies to enhance the usefulness and convenience of telemedicine systems are imperative for fostering adoption. Such efforts will be instrumental in expediting the promotion and implementation of internet-based healthcare services to enhance the accessibility of healthcare services in China.

Abstract Background Lung cancer is a heterogeneous disease and the primary cause of cancer-related mortality worldwide. Somatic mutations, including large structural variants, are important biomarkers in lung cancer for selecting targeted therapy. Genomic studies in lung cancer have been conducted using short-read sequencing. Emerging long-read sequencing technologies are a promising alternative to study somatic structural variants, however there is no current consensus on how to process data and call somatic events. In this study, we preformed whole genome sequencing of lung cancer and matched non-tumour samples using long and short read sequencing to comprehensively benchmark three sequence aligners and seven structural variant callers comprised of generic callers (SVIM, Sniffles2, DELLY in generic mode and cuteSV) and somatic callers (Severus, SAVANA, nanomonsv and DELLY in somatic modes). Results Different combinations of aligners and variant callers influenced somatic structural variant detection. The choice of caller had a significant influence on somatic structural variant detection in terms of variant type, size, sensitivity, and accuracy. The performance of each variant caller was assessed by comparing to somatic structural variants identified by short-read sequencing. When compared to somatic structural variants detected with short-read sequencing, more events were detected with long-read sequencing. The mean recall of somatic variant events identified by long-read sequencing was higher for the somatic callers (72%) than generic callers (53%). Among the somatic callers when using the minimap2 aligner, SAVANA and Severus achieved the highest recall at 79.5% and 79.25% respectively, followed by nanomonsv with a recall of 72.5%. Conclusion Long-read sequencing can identify somatic structural variants in clincal samples. The longer reads have the potential to improve our understanding of cancer development and inform personalized cancer treatment.

Abstract Anthocidaris crassispina is a very popular edible sea urchin distributed along the coast of the South China Sea. In this study, we performed whole-genome sequencing and generated a chromosome-level assembly of this species. The total length of the genomic contig sequence was 891.02 Mb, and contig N50 was 808.15 kb when Hifiasm was used for assembly. The Hi-C library was constructed and sequenced, yielding approximately 68.61 Gb of data. After Hi-C assembly, approximately 886.72 Mb of sequence was able to be mapped onto 21 chromosomes, accounting for 99.52% of the total genome length. Among the sequences located on the chromosomes, those for which the order and direction could be determined accounted for approximately 826.82 Mb, or 93.24% of the total length. These results provide valuable resources for further study of A. crassispina at the genetic level.

Abstract Mechanochemistry studies the effect of mechanical force on chemical bonds, bringing opportunities for synthesizing alloys, ceramics, organics, polymers, and biomaterials. A vital issue of applying macro-scale mechanical force to manipulate crystal structures is finding ways to precisely adjust the force directions to break micro-scale target chemical bonds. Inspired by a common technique of driving a wedge into the wood to make wood chopping much easier, a wedging strategy of splitting three-dimensional structured crystalline frameworks and then converting them to nanosheets was proposed, where specific molecules were wedged into crystalline frameworks to drive the directional transmission of mechanical force to break chemical bonds. As a result, various crystalline framework nanosheets including metal−organic framework nanosheets, covalent organic framework nanosheets, and coordination polymer nanosheets were fabricated. This wedging crystal strategy exhibits advantages of operability, flexibility and designability, and furthermore, it is expected to expand mechanochemistry applications in material preparation.

Abstract Whenever the elastic energy of a solid depends on magnetic field, there is a magnetostrictive response. Field-linear magnetostriction implies piezomagnetism and vice versa. Here, we show that Mn3Sn, a non-collinear antiferromanget with Weyl nodes, hosts a large and almost perfectly linear magnetostriction even at room temperature. The longitudinal and transverse magnetostriction, with opposite signs and similar amplitude are restricted to the kagome planes and the out-of-plane response is negligibly small. By studying four different samples with different Mn:Sn ratios, we find a clear correlation between the linear magnetostriction, the spontaneous magnetization and the concentration of Sn vacancies. The recently reported piezomagnetic data fits in our picture. We show that linear magnetostriction and piezomagnetism are both driven by the field-induced in-plane twist of spins. A quantitative account of the experimental data requires the distortion of the spin texture by Sn vacancies. We find that the field-induced domain nucleation within the hysteresis loop corresponds to a phase transition. Within the hysteresis loop, a concomitant mesoscopic modulation of local strain and spin twist angles, leading to twisto-magnetic stripes, arises as a result of the competition between elastic and magnetic energies.

Abstract Macrophages play a pivotal role in orchestrating the immune response against pathogens. While the intricate interplay between macrophage activation and metabolism remains a subject of intense investigation, the role of glutamate oxaloacetate transaminase 1 (Got1) in this context has not been extensively assessed. Here, we investigate the impact of Got1 on macrophage polarization and function, shedding light on its role in reactive oxygen species (ROS) production, pathogen defense, and immune paralysis. Using genetically modified mouse models, including both myeloid specific knockout and overexpression, we comprehensively demonstrate that Got1 depletion leads to reduced ROS production in macrophages. Intriguingly, this impairment in ROS generation does not affect the resistance of Got1 KO mice to pathogenic challenges. Furthermore, Got1 is dispensable for M2 macrophage differentiation and does not influence the onset of LPS-induced immune paralysis. Our findings underscore the intricate facets of macrophage responses, suggesting that Got1 is dispensable in discrete immunological processes.

Abstract The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment.

In this work, two kinds of primary batteries, both of which included a Zn anode, C rod cathode, copper wire and electrolyte composed of Cd2+-contaminated water or soil, were constructed in the first attempt to both remove Cd2+ and generate electricity. Unlike traditional technologies such as electrokinetic remediation with high energy consumption, this technology could realize Cd2+ migration to aggregation and solidification and generate energy at the same time through simultaneous galvanic reactions. The passive surface of Zn and C was proven via electrochemical measurements to be porous to maintain the relatively active galvanic reactions for continuous Cd2+ precipitation. Cd2+ RE (removal efficiency) and electricity generation were investigated under different conditions, based on which two empirical models were established to predict them successfully. In soil, KCl was added to desorb Cd2+ from soil colloids to promote Cd2+ removal. These systems were also proven to remove Cd2+ efficiently when their effects on plants, zebrafish, and the soil bacterial community were tested. LEDs could be lit for days by utilizing the electricity produced herein. This work provides a novel, green, and low-cost route to remediate Cd2+ contamination and generate electricity simultaneously, which is of extensive practical significance in the environmental and energy fields.

Abstract Emulsion gels with specific rheological properties have widespread applications in foods, cosmetics, and biomedicines. However, the constructions of water‐in‐oil emulsion gels are still challenging, due to the limited interactions available in the continuous oil phase. Here, a versatile strategy is developed to prepare a new type of emulsion gels, called Jammed Pickering emulsion gels (JPEGs). In the JPEG system, SiO2 NPs in the oil phase serve as colloidal surfactants to stabilize water‐in‐oil Pickering emulsions, while positively‐charged NH2‐PEG‐NH2 molecules in the water phase cross‐link negatively‐charged SiO2 NPs at the water/oil interface, making NP‐stabilized water droplets hard to deform and thus jamming the emulsion system to form emulsion gels. The strategy to prepare JPEGs is versatile and applicable to diverse oil phases. The designed JPEGs possess many advantages, including good biocompatibility for widespread applications, shear‐thinning rheological properties for easy processing, good stability Over a wide temperature range and Against centrifugation, good adhesion to wet tissues for tissue engineering, and well‐controlled sustained release Under intestinal conditions. The developed JPEGs are demonstrated to be a promising delivery platform and the strategy to achieve JPEGs will trigger more innovations of material design.

Accurately and efficiently predicting the permeability of porous media is essential for addressing a wide range of hydrogeological issues. However, the complexity of porous media often limits the effectiveness of individual prediction methods. This study introduces a novel Particle Swarm Optimization-based Permeability Integrated Prediction model (PSO-PIP), which incorporates a particle swarm optimization algorithm enhanced with dynamic clustering and adaptive parameter tuning (KGPSO). The model integrates multi-source data from the Lattice Boltzmann Method (LBM), Pore Network Modeling (PNM), and Finite Difference Method (FDM). By assigning optimal weight coefficients to the outputs of these methods, the model minimizes deviations from actual values and enhances permeability prediction performance. Initially, the computational performances of the LBM, PNM, and FDM are comparatively analyzed on datasets consisting of sphere packings and real rock samples. It is observed that these methods exhibit computational biases in certain permeability ranges. The PSO-PIP model is proposed to combine the strengths of each computational approach and mitigate their limitations. The PSO-PIP model consistently produces predictions that are highly congruent with actual permeability values across all prediction intervals, significantly enhancing prediction accuracy. The outcomes of this study provide a new tool and perspective for the comprehensive, rapid, and accurate prediction of permeability in porous media.

The university property management department has been facing a challenge with the strategic management of campus spaces due to the need for informal learning spaces (ILSs) to facilitate students’ independent studies. However, there’s limited research on how these ILSs perform, particularly concerning human-made sounds. This study delves into the impact of human-made sounds on students, considering their individual differences and positive experiences in various types of ILSs within an Australian university campus. The investigation includes open-ended questions to delve deeper into students’ positive experiences with human-made sounds across different ILSs. The research findings demonstrate that the impact of human-made sounds on students is influenced by certain individual characteristics. Additionally, the study identifies three types of positive experiences regarding human-made sounds in ILSs for students: a sense of relaxation induced by human-made sounds, the sound-masking effect, and increased motivation for learning. This study could assist university property managers in understanding students’ perceptions of human-made sounds and aid in strategic management of campus space that aligns with students’ needs and preferences for ILSs, improving the overall learning environment and support student success.

Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body.

Background: Regulated cell death (RCD) has considerable impact on tumor progress and sensitivity of treatment. Lung adenocarcinoma (LUAD) show a high resistance for conventional radiotherapies and chemotherapies. Currently, regulation of cancer cell death has been emerging as a new promising therapeutic avenue for LUAD patients. However, the crosstalk in each pattern RCD is unclear. Methods: We integrated collected the hub-genes of 12 RCD subroutines and compressively analyzed these hub-genes synergistic effect in LUAD. The characters of RCD genes expression and prognosis were developed in The Cancer Genome Atlas (TCGA)-LUAD data. We developed and validated an RCD risk model based on TCGA and GSE70294 data set, respectively. Functional annotation and tumor immunotherapy based on the risk model were also investigated. Results: 28 RCD-related genes and two LUAD molecular cluster were identified. Survival analysis revealed that the prognosis in high-risk group was worser than those in low-risk group. Functional enrichment analysis indicated that the RCD risk model correlated with immune responses. Further analysis indicated that the high-risk group in RCD risk model exhibited an immunosuppressive microenvironment and a lowly immunotherapy responder ratio. Conclusions: We present an RCD risk model which have a promising ability in predicting LUAD prognosis and immunotherapy response.

BackgroundNumerous experimental studies have shown that exercise can serve as an intervention with beneficial effects on children and adolescents with autism. However, a systematic review on the specific areas affected has not been conducted.MethodsPreliminary research sources were obtained by searching four databases, and two researchers independently screened the literature that met the study criteria. The study was conducted under the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.Results37 studies were included in the final analysis, of which 9 studies were quantitatively synthesized and 28 studies were qualitatively analyzed. Exercise interventions have positive effects on motor performance, cognitive function, individual and social relationships, behavioral problems, physical health, and brain function in children and adolescents with autism. The results of the meta-analysis indicate that exercise can effectively improve social skills [SMD=-0.53, 95%CI (-0.76, -0.3), P=0.000].ConclusionsLong-term, regular, chronic exercise is beneficial for children and adolescents with autism, particularly in the area of social skills.Systematic review registrationhttps://www.crd.york.ac.uk/prospero PROSPERO, identifier CRD42024554530.

Abstract To address the current problems of low accuracy and poor reliability of the discrete element model of cotton stalks, as well as the difficulty of guiding the design and optimization of the equipment through simulations, the discrete element modeling and physical-mechanical tests of cotton stalks in machine harvested film-stalk mixtures are carried out. The peak tensile force $$F_{\rm j}^{\max }$$ F j max , the peak pressure $$F_{\rm y}^{\max }$$ F y max , the peak bending force $$F_{\rm w}^{\max }$$ F w max , the peak shear force $$F_{\rm j}^{\max }$$ F j max , and the force-displacement (F–x) curves of cotton stalks are obtained from the physical tests. The discrete element model of double-layer cotton stalks based on the flat-joint model is established with the PFC $$^{\rm 3D}$$ 3 D software. The $$F_{\rm y}^{\max }$$ F y max is taken as the response value, and the microscopic parameters of the cotton stalk model are used as the test factors, then the Plackett–Burman test, the steepest climb test, and the Box–Behnken test are sequentially designed using Design-Expert software. The second-order regression model describing the relationship between the $$F_{\rm y}^{\max }$$ F y max and the microscopic parameters is established. The optimal parameter combinations of the microscopic parameters are obtained, and then they are utilized to construct the compression, bending, and shear models of cotton stalks and to carry out the validation tests. The results confirm that the established discrete element model could accurately characterize the biomechanical properties of cotton stalks and that the parameter calibration method is reasonable, which could provide a reference for the discrete element modeling of cotton stalks and other stalks, and also offer a theoretical basis for the research of the crushing and separation mechanism of the film-stalk mixtures and the development of the equipment.

Abstract Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011–2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.

Abstract Objective To compare the effect of different indicators on stress‐induced hyperglycemia for predicting in‐hospital outcomes of acute intracerebral hemorrhage. Methods Using data from the Chinese Stroke Center Alliance database, which is a national, multicenter, prospective, and consecutive program. Stress‐induced hyperglycemia was described as glycemic gap (GG, defined as fasting blood glucose [FBG] minus estimated average blood glucose) and stress hyperglycemia ratio (SHR, defined as FBG‐to‐estimated average blood glucose ratio [SHR 1] or FBG‐to‐HbA1c ratio [SHR 2]). The primary outcome was in‐hospital mortality, and the second outcome was hematoma expansion. Results A total of 71,333 patients with acute intracerebral hemorrhage were included. In multivariate analyses, the highest levels of GG (OR 1.68, 95% CI 1.12–2.51), SHR 1 (OR 1.73, 95% CI 1.15–2.60), and SHR 2 (OR 2.07, 95% CI 1.33–3.23) were associated with in‐hospital death (all the p trends 0.05) was related to hematoma expansion. No association between GG or SHR 1 and hematoma expansion was observed. The areas under the ROC curve of GG, SHR 1, and SHR 2 for in‐hospital mortality were 0.8808 (95% CI 0.8603–0.9014), 0.8796 (95% CI 0.8589–0.9002), and 0.8806 (95% CI 0.8600–0.9012). The areas under the ROC curve of SHR 2 for hematoma expansion were 0.7133 (95% CI 0.6964–0.7302). Interpretation SHR (FBG‐to‐HbA1c ratio) was associated with both in‐hospital death and hematoma expansion in intracerebral hemorrhage, and might serve as an accessory indicator for the in‐hospital prognosis of intracerebral hemorrhage.

Abstract Background Guillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias. Case presentation The child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement. Conclusions Anti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.

Abstract Background Changes in economy and dietary guidelines brought a great shock to diet quality and meal behaviors, but if these transformations have extended to minerals intake and their sources was still poorly understood. It is essential to evaluate time trends in minerals intake and their sources to inform policy makers. Objective To investigate trends in minerals intake and their sources among U.S. adults. Methods This analysis used dietary data collected by 24-h recalls from U.S. adults (≥ 20 years) in NHANES (1999-March 2020). Minerals intake, age-adjusted percentage of participants meeting recommendations, and minerals sources were calculated among all participants and by population subgroups in each NHANES survey cycle. Weighted linear or logistic regression models were used to examine the statistical significance of time trends. Results A total of 48223 U.S. adults were included in this analysis. From 1999 to March 2020, intake of calcium (from 0.94 to 1.02 g/day), magnesium (from 308.07 to 321.85 mg/day), phosphorus (from 1.24 to 1.30 g/day), and sodium (from 3.24 to 3.26 mg/day) from food and beverages (FB) and dietary supplements (DSs) significantly increased, and intake of iron (from 19.17 to 16.38 mg/day), zinc (from 16.45 to 14.19 mg/day), copper (from 1.79 to 1.38 mg/day), and potassium (from 2.65 to 2.50 g/day) from FB + DSs decreased (all FDR

BackgroundIt is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. ObjectiveTo observe the effects of combined exposure to PM2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. MethodsA total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (TN-FA), a normal temperature-concentrated PM2.5 group (TN-PM), a heat-filter air group (TH-FA), a heat-concentrated PM2.5 group (TH-PM), a cold-filter air group (TC-FA), and a cold-concentrated PM2.5 group (TC-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. ResultsThe transcriptomics results indicated that the PM2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the TN-PM mice compared to the TN-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P

A long noncoding RNA (lncRNA) is longer than 200 bp. It regulates various biological processes mainly by interacting with DNA, RNA, or protein in multiple kinds of biological processes. Adenosine monophosphate-activated protein kinase (AMPK) is activated during nutrient starvation, especially glucose starvation and oxygen deficiency (hypoxia), and exposure to toxins that inhibit mitochondrial respiratory chain complex function. AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes, including lipid and glucose metabolism, thereby maintaining intracellular energy homeostasis by activating catabolism and inhibiting anabolism. The AMPK signalling pathway consists of AMPK and its upstream and downstream targets. AMPK upstream targets include proteins such as the transforming growth factor β-activated kinase 1 (TAK1), liver kinase B1 (LKB1), and calcium/calmodulin-dependent protein kinase β (CaMKKβ), and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1), hepatocyte nuclear factor 4α (HNF4α), and silencing information regulatory 1 (SIRT1). In general, proteins function relatively independently and cooperate. In this article, a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the regulatory mechanisms involved in human ageing and age-related diseases are provided.

Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV1 and FVC by 35.26 mL (95 % CI: −60.75, −9.78) and 38.56 mL (95 % CI: −66.60, −10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.