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Abstract This study aims to identify colorectal cancer (CRC)-related proteomic profiles and develop a prediction model for CRC onset by integrating proteomic profiles with genetic and non-genetic factors (QCancer-15) to improve the risk stratification and estimate of personalized initial screening age. Here, using a two-stage strategy, we prioritize 15 protein biomarkers as predictors to construct a protein risk score (ProS). The risk prediction model integrating proteomic profiles with polygenic risk score (PRS) and QCancer-15 risk score (QCancer-S) shows improved performance (C-statistic: 0.79 vs. 0.71, P = 4.94E–03 in training cohort; 0.75 vs 0.69, P = 5.49E–04 in validation cohort) and net benefit than QCancer-S alone. The combined model markedly stratifies the risk of CRC onset. Participants with high ProS, PRS, or combined risk score are proposed to start screening at age 46, 41, or before 40 years old. In this work, the integration of blood proteomics with PRS and QCancer-15 demonstrates improved performance for risk stratification and clinical implication for the derivation of risk-adapted starting ages of CRC screening, which may contribute to the decision-making process for CRC screening.

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). Methods: A total of 155 patients with CHB-related HCC who received ICI–based therapy (in the Department of Hepatology, Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute & Hospital) between April 2021 and December 2023 were evaluated. Patients were divided into two groups: MASLD concurrent with CHB [MASLD-CHB] (n = 38), and CHB (n = 117). Results: The median progression-free survival (PFS, 6.9 months vs. 9.3 months; P = 0.001), progressive disease (57.89% vs. 37.61%; P = 0.028), and disease control rate (42.11% vs. 62.39%; P = 0. 028) in the MASLD-CHB group were significantly worse than the CHB group. The median overall survival was not attained. The percentage of CD4+PD1+ (17. 56% vs. 8.89%; P < 0.001) and CD8+PD1+ T cells (10.50% vs. 7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB group. Concurrent MASLD [hazard ratio (HR) = 1.921; 95% CI, 1.138–3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment (HR = 2.412; 95% CI, 1.360–4.279; P = 0.003) were independent risk factors for PFS in all patients. Conclusions: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

Abstract Background To investigate the mechanism of Golgi matrix protein 130(GM130) regulating the antiviral immune response of TLR3 after herpes simplex virus type 1(HSV-1) infection of microglia cells. We explored the regulatory effects of berberine on the immune response mediated by GM130 and TLR3. Methods An in vitro model of HSV-1 infection was established by infecting BV2 cells with HSV-1. Results Compared to the uninfected group, the Golgi apparatus (GA) fragmentation and GM130 decreased after HSV-1 infection; TLR3 increased at 6 h and began to decrease at 12 h after HSV-1 infection; the secretion of interferon-beta(IFN-β), tumour necrosis factor alpha(TNF-α), and interleukin-6(IL-6) increased after infection. Knockdown of GM130 aggravated fragmentation of the GA and caused TLR3 to further decrease, and the virus titer also increased significantly. GM130 knockdown inhibits the increase in TLR3 and inflammatory factors induced by TLR3 agonists and increases the viral titer. Overexpression of GM130 alleviated fragmentation of the GA induced by HSV-1, partially restored the levels of TLR3, and reduced viral titers. GM130 overexpression reversed the reduction in TLR3 and inflammatory cytokine levels induced by TLR3 inhibitors. Therefore, the decrease in GM130 levels caused by HSV-1 infection leads to increased viral replication by inhibiting TLR3-mediated innate immunity. Berberine can protect the GA and reverse the downregulation of GM130, as well as the downregulation of TLR3 and its downstream factors after HSV-1 infection, reducing the virus titer. Conclusions In microglia, one mechanism of HSV-1 immune escape is disruption of the GM130/TLR3 pathway. Berberine protects the GA and enhances TLR3-mediated antiviral immune responses.

Abstract Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality.

Abstract Background Assessing dietary phenylalanine (Phe) tolerance is crucial for managing hyperphenylalaninemia (HPA) in children. However, traditionally, adjusting the diet requires significant time from clinicians and parents. This study aims to investigate the development of a machine-learning model that predicts a range of dietary Phe intake tolerance for children with HPA over 10 years following diagnosis. Methods In this multicenter retrospective observational study, we collected the genotypes of phenylalanine hydroxylase (PAH), metabolic profiles at screening and diagnosis, and blood Phe concentrations corresponding to dietary Phe intake from over 10 years of follow-up data for 204 children with HPA. To incorporate genetic information, allelic phenotype value (APV) was input for 2965 missense variants in the PAH gene using a predicted APV (pAPV) model. This model was trained on known pheno-genotype relationships from the BioPKU database, utilizing 31 features. Subsequently, a multiclass classification model was constructed and trained on a dataset featuring metabolic data, genetic data, and follow-up data from 3177 events. The final model was fine-tuned using tenfold validation and validated against three independent datasets. Results The pAPV model achieved a good predictive performance with root mean squared error (RMSE) of 1.53 and 2.38 on the training and test datasets, respectively. The variants that cause amino acid changes in the region of 200–300 of PAH tend to exhibit lower pAPV. The final model achieved a sensitivity range of 0.77 to 0.91 and a specificity range of 0.8 to 1 across all validation datasets. Additional assessment metrics including positive predictive value (0.68–1), negative predictive values (0.8–0.98), F1 score (0.71–0.92), and balanced accuracy (0.8–0.92) demonstrated the robust performance of our model. Conclusions Our model integrates metabolic and genetic information to accurately predict age-specific Phe tolerance, aiding in the precision management of patients with HPA. This study provides a potential framework that could be applied to other inborn errors of metabolism.

Abstract Soybean seeds are susceptible to damage from the Riptortus pedestris, which is a significant factor affecting the quality of soybean seeds. Currently, manual screening methods for soybean seeds are limited to visual inspection, making it difficult to identify seeds that are phenotypically defect-free but have been punctured by stink bugs on the sub-surface. To facilitate the convenient and efficient identification of healthy soybean seeds, this paper proposes a soybean seed pest detection method based on spatial frequency domain imaging combined with RL-SVM. Firstly, soybean optical data is obtained using single integration sphere technique, and the vigor index of soybean seeds is obtained through germination experiments. Then, based on the above two data items using feature extraction algorithms (the successive projections algorithm and the competitive adaptive reweighted sampling algorithm), the characteristic wavelengths of soybeans are identified. Subsequently, the spatial frequency domain imaging technique is used to obtain the sub-surface images of soybean seeds in a forward manner, and the optical coefficients such as the reduced scattering coefficient $${{\mu }{\prime}}_{s}$$ μ ′ s and absorption coefficient $${\mu }_{a}$$ μ a of soybean seeds are inverted. Finally, RL-MLR, RL-GRNN, and RL-SVM prediction models are established based on the ratio of the area of insect-damaged sub-surface to the entire seed, soybean varieties, and $${\mu }_{a}$$ μ a at three wavelengths (502 nm, 813 nm, and 712 nm) for predicting and identifying soybean the stinging and sucking pest damage levels of soybean seeds. The experimental results show that the spatial frequency domain imaging technique yields small errors in the optical coefficients of soybean seeds, with errors of less than 15% for $${\mu }_{a}$$ μ a and less than 10% for $${{\mu }{\prime}}_{s}$$ μ ′ s . After parameter adjustment through reinforcement learning, the Macro-Recall metrics of each model have improved by 10%-15%, and the RL-SVM model achieves a high Macro-Recall value of 0.9635 for classifying the pest damage levels of soybean seeds.

Abstract The rumen microbiome plays an important role in providing energy and protein to the host. Manipulation of rumen microbiome during early life may have a long-term beneficial effect on the health, growth performance, and feed efficiency of ruminants. To better understand the profiles and functional potentials of rumen microbiome in young ruminants, metagenomic binning was performed to investigate the rumen microbiome of goat kids from one to 84 days of age. A total of 797 metagenome-assembled genomes (MAGs) were recovered from the rumen of 42 Laiwu black goat kids. Our findings provide fundamental knowledge of the rumen microbiome during early life based on metagenomic binning, which may provide insights into effective strategies to achieve long-term beneficial effects on animal health and production.

Abstract Purpose Glial fibrillary acidic protein astrocytopathy (GFAP-A) pathogenesis remains uncertain, with potential viral involvement. More clinical cases are needed to deepen our understanding of this disease, along with the exploration of more effective treatment options to provide clinicians with additional choices. Methods We report a severe case of GFAP-A secondary to EBV infection, characterized predominantly by central respiratory failure. Additionally, we conducted a literature review summarizing the characteristics of GFAP-IgG-positive patients associated with EBV infection. Results Among the 13 patients identified, fever (92.3%) and headache (84.6%) were the most common initial symptoms, while urinary dysfunction was universally present in all patients. Over half of the patients with altered consciousness required endotracheal intubation (7/11, 63.6%), with only one individual experiencing complete resolution without any residual sequela. Only two patients (16.7%) displayed the classic feature of periventricular enhancement on neuroimaging, whereas T2-FLAIR hyperintensities were more prevalent. All patients tested positive for GFAP-IgG in CSF, and 91.7% (11/12) had detectable serum GFAP-IgG antibodies. Three patients (23.1%) achieved full recovery solely through antiviral therapy. In patients receiving various immunotherapies, 60% (6/10) still had residual sequelae. Conclusion EBV infection may contribute to the pathogenesis of GFAP-A. GFAP antibody testing is recommended for diagnostic evaluation in cases of central nervous system viral infections presenting with respiratory insufficiency. For severe GFAP-A patients, Protein A immunoadsorption (Protein A IA).

Abstract Background In China, community rehabilitation workers are facing a growing challenge related to heavy occupational stress, which is having an impact on employment turnover. Previous studies have explored the effect of the public service motivation of workers in “helping” jobs on occupational stress or turnover intention, but there is a lack of clarification of the impact of altruism on turnover intention in the case of complex pathways involving various factors. Methods A stratified sampling method was used, and a total of 82 community rehabilitation workers who assist disabled people from 34 community health centres in Jiangmen city were included in the study from August to October 2022. The turnover intention, occupational stress, burnout, quality of life, altruism, and certain sociodemographic information of community rehabilitation workers were measured using a structured questionnaire. The partial least squares method was employed to construct and test the structural equation model. Results Although altruism had no direct impact on occupational stress or turnover intention, altruism moderated the effect of occupational stress on burnout (β Mod = −0.208) and quality of life (β Mod = 0.230) and weakened the mediation of burnout and quality of life between occupational stress and turnover intention. Conclusions This study proposes to address the dilemma of “strong function” and “weak specialty” in community rehabilitation services and to conduct positive psychological interventions for community rehabilitation workers through the guidance of altruistic values.

Abstract Background The prevalence of sarcopenia is increasing in worldwide with accelerated aging process. The high dietary protein intakes are associated with improved muscle mass and strength especially in Asian countries. However, there are few researches on amino acid levels or mechanism exploration. We conducted a case-control study to explore the amino acid metabolic characteristics and potential mechanism of elderly women with sarcopenia using targeted amino acid metabolomics approach combined with an analysis of dietary intake. Methods For our case-control study, we recruited women (65–75 y) from a Shanghai community with 50 patients with sarcopenia and 50 healthy controls. The consensus updated by the Asian Working Group on Sarcopenia in 2019 was used to screening for sarcopenia and control groups. We collected fasting blood samples and evaluated dietary intake. We used the amino acid-targeted metabolomics by ultra performance liquid chromatography tandem mass spectrometry to identify metabolic differentials between the case and control groups and significantly enriched metabolic pathways. Results The case (sarcopenia) group had a lower intake of energy, protein, and high-quality protein (P

Abstract Contemporary studies in polarization multiplexing are hindered by the intrinsic orthogonality constraints of polarization states, which restrict the scope of multiplexing channels and their practical applications. This research transcends these barriers by introducing an innovative nonorthogonal polarization-basis multiplexing approach. Utilizing spatially varied eigen-polarization states within metaatoms, we successfully reconstruct globally nonorthogonal channels that exhibit minimal crosstalk. This method not only facilitates the generation of free-vector holograms, achieving complete degrees-of-freedom in three nonorthogonal channels with ultra-low energy leakage, but it also significantly enhances the dimensions of the Jones matrix, expanding it to a groundbreaking 10 × 10 scale. The fusion of a controllable eigen-polarization engineering mechanism with a vectorial diffraction neural network culminates in the experimental creation of 55 intricate holographic patterns across these expanded channels. This advancement represents a profound shift in the field of polarization multiplexing, unlocking opportunities in advanced holography and quantum encryption, among other applications.

Abstract Objectives This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). Methods This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. Result The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. Conclusions CSVDs are associated with increased exposure to elevated BP later in life.

Abstract Integration of functional fillers into liquid metals (LM) induces rheology modification, enabling the free-form shaping of LM at the micrometer scale. However, integrating non-chemically modified low-dimensional materials with LM to form stable and uniform dispersions remain a great challenge. Herein, we propose a solvent-assisted dispersion (SAD) method that utilizes the fragmentation and reintegration of LM in volatile solvents to engulf and disperse fillers. This method successfully integrates MXene uniformly into LM, achieving better internal connectivity than the conventional dry powder mixing (DPM) method. Consequently, the MXene/LM (MLM) coating exhibits high electromagnetic interference (EMI) shielding performance (105 dB at 20 μm, which is 1.6 times that of coatings prepared by DPM). Moreover, the rheological characteristic of MLM render it malleable and facilitates direct printing and adaptation to diverse structures. This study offers a convenient method for assembling LM with low-dimensional materials, paving the way for the development of multifunctional soft devices.

Abstract Background To assess the improvement of image quality and diagnostic acceptance of thinner slice iodine maps enabled by deep learning image reconstruction (DLIR) in abdominal dual-energy CT (DECT). Methods This study prospectively included 104 participants with 136 lesions. Four series of iodine maps were generated based on portal-venous scans of contrast-enhanced abdominal DECT: 5-mm and 1.25-mm using adaptive statistical iterative reconstruction-V (Asir-V) with 50% blending (AV-50), and 1.25-mm using DLIR with medium (DLIR-M), and high strength (DLIR-H). The iodine concentrations (IC) and their standard deviations of nine anatomical sites were measured, and the corresponding coefficient of variations (CV) were calculated. Noise-power-spectrum (NPS) and edge-rise-slope (ERS) were measured. Five radiologists rated image quality in terms of image noise, contrast, sharpness, texture, and small structure visibility, and evaluated overall diagnostic acceptability of images and lesion conspicuity. Results The four reconstructions maintained the IC values unchanged in nine anatomical sites (all p > 0.999). Compared to 1.25-mm AV-50, 1.25-mm DLIR-M and DLIR-H significantly reduced CV values (all p

Abstract Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.

Abstract This study aimed to develop a machine learning (ML)-based tool for early and accurate prediction of in-hospital mortality risk in patients with spontaneous intracerebral hemorrhage (sICH) in the intensive care unit (ICU). We did a retrospective study in our study and identified cases of sICH from the MIMIC IV (n = 1486) and Zhejiang Hospital databases (n = 110). The model was constructed using features selected through LASSO regression. Among five well-known models, the selection of the best model was based on the area under the curve (AUC) in the validation cohort. We further analyzed calibration and decision curves to assess prediction results and visualized the impact of each variable on the model through SHapley Additive exPlanations. To facilitate accessibility, we also created a visual online calculation page for the model. The XGBoost exhibited high accuracy in both internal validation (AUC = 0.907) and external validation (AUC = 0.787) sets. Calibration curve and decision curve analyses showed that the model had no significant bias as well as being useful for supporting clinical decisions. XGBoost is an effective algorithm for predicting in-hospital mortality in patients with sICH, indicating its potential significance in the development of early warning systems.

Abstract Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The “Atyp.C” parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case–control study identified clinical primary or newly recurrent BC (study period, 2022–2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman’s rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P

The high metabolic requirements of cancer cells result in excess accumulation of H+ in the tumor microenvironment. Therefore, the extracellular pH of solid tumors is acidic, whereas the pH of normal tissues is more alkaline. The acidic tumor environment is correlated with tumor metastasis, immune escape, and chemoresistance, but the underlying mechanisms remain elusive. Herein, we demonstrate that sodium bicarbonate, a weakly alkaline compound, induces cytotoxicity in ovarian cancer cells and hinders cancer migration and invasion in vitro. The anti-cancer efficacy of Olaparib can be significantly augmented when combined with sodium bicarbonate. In vivo experiments suggest that the combinatorial treatment of sodium bicarbonate and Olaparib is biocompatible and more effective at inhibiting ovarian cancer growth than either treatment alone. Additionally, RNA-sequencing results reveal that the differentially expressed genes are enriched in pathways related to reactive oxygen species (ROS) generation, such as the cGMP/PKG pathway. The combined treatment increases M1 macrophage composition in tumors and reduces the accumulation of excessive ROS. These findings strongly suggest that sodium bicarbonate holds great potential as an adjuvant treatment by scavenging ROS accumulation and promoting M1 macrophage composition, thereby enhancing Olaparib’s anti-cancer activity.

AimsTo investigate the epidemiological and clinical characteristics of children with Mycoplasma pneumoniae pneumonia (MPP) in Hubei, China.MethodsWe retrospectively analyzed inpatients with MPP from 20 hospitals in Hubei, China from January 2021 to December 2022. The co-detected pathogens of Mycoplasma pneumoniae (M. pneumoniae) were investigated using targeted next-generation sequencing (tNGS), and 23S rRNA gene mutations were analyzed to assess the macrolide resistance.ResultsM. pneumoniae infected 20.7% of patients with CAP, with cough (96.59%) and fever (80.28%) being the most prevalent symptoms. The infection rates in children younger than 1, 1–2, 3–6, 7–12, and older than 12 years were 6.17%, 19.98%, 26.97%, 43.93%, and 2.95%, respectively. Among 1,349 patients undergoing tNGS, the overall co-detection rate was 59.45%, with Streptococcus pneumoniae (29.30%), Haemophilus influenzae (23.57%), and Human rhinovirus (17.21%) being the most commonly co-detected pathogens. In 635 patients undergoing the 23S rRNA gene mutation test, 86.30% exhibited positive mutations (A2063G, 98.00%; A2064G, 1.50%; A2067G, 0.50%). Despite a significant age difference (P = 0.037) between macrolide-resistant M. pneumoniae and macrolide-sensitive M. pneumoniae groups, there were no significant differences in symptoms, lab data, or disease severity.ConclusionsIn Hubei Province, the prevalence of exhibited consistent changes during the COVID-19 pandemic. MPP was prevalent year-round, particularly in summer and autumn, with school-age children being more susceptible. Co-detections of viruses and bacteria were frequent in MPP cases, and macrolide resistance exceeded 85%. Ongoing surveillance of M. pneumoniae in children is crucial for understanding the healthcare impact of MPP.

Nasopharyngeal carcinoma (NPC) is a neoplasm related to inflammation; the expression of cytokines, such as CCL3, CCL4, CCL20, IL-1α, IL-1β, IL-6, IL-8, and IL-10, among others, is presumed to be associated with NPC occurrence and development. Therefore, the circulating levels of these cytokines may be potential biomarkers for assessing tumor aggressiveness, exploring cellular interactions, and monitoring tumor therapeutic responses. Numerous scholars have comprehensively explored the putative mechanisms through which these inflammatory factors affect NPC progression and therapeutic responses. Moreover, investigations have focused on elucidating the correlation between the systemic levels of these cytokines and the incidence and prognosis of NPC. This comprehensive review aims to delineate the advancements in research concerning the relationship between inflammatory factors and NPC while considering their prospective roles as novel prognostic and predictive biomarkers in the context of NPC.

3D superstructures (3DSs) have attracted increasing interest because of the collective synergistic effects of individual building units, but their customization relies on tedious multistep strategy or high‐end nanofabrication technology. Herein, for the first time, a facile block copolymer micelle‐mediated anisotropic growth approach is reported to fabricate gold 3DSs consisting of tunable and intersecting lamellae with sawtooth‐like edges. The preparation of the 3DSs depends on the mediation of reduction kinetics of gold precursors and adsorption of block copolymer micelles on gold crystal surfaces using disulfiram as ligands. The thickness of lamellae in the 3DSs is controllable from ≈21 to 102 nm by adjusting the weight fraction of the micellar hydrophobicity blocks and the composed lamellar number is regulated from ≈3 to ≈30. Additional morphologies, such as a dendritic mesoporous structure and meatball‐like shapes, are obtained through controlling the extent of micelle swelling. Finite‐difference time‐domain simulations demonstrate that the unique 3DSs of gold lamellae with sawtooth‐like edges form abundant hotspots giving rise to surface‐enhanced Raman scattering (SERS). The 3DSs exhibit strong electromagnetic field enhancement and excellent performance as SERS substrates for detecting 4‐mercaptobenzoic acid.

BackgroundInvestigation into the immune heterogeneity linked with atherosclerosis remains understudied. This knowledge gap hinders the creation of a robust theoretical framework essential for devising personalized immunotherapies aimed at combating this disease.MethodsSingle-cell RNA sequencing (scRNA-seq) analysis was employed to delineate the immune cell-type landscape within atherosclerotic plaques, followed by assessments of cell-cell interactions and phenotype characteristics using scRNA-seq datasets. Subsequently, pseudotime trajectory analysis was utilized to elucidate the heterogeneity in cell fate and differentiation among macrophages. Through integrated approaches, including single-cell sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning techniques, we identified hallmark genes. A risk score model and a corresponding nomogram were developed and validated using these genes, confirmed through Receiver Operating Characteristic (ROC) curve analysis. Additionally, enrichment and immune characteristic analyses were conducted based on the risk score model. The model’s applicability was further corroborated by in vitro and in vivo validation of specific genes implicated in atherosclerosis.ResultThis comprehensive scRNA-seq analysis has shed new light on the intricate immune landscape and the role of macrophages in atherosclerotic plaques. The presence of diverse immune cell populations, with a particularly enriched macrophage population, was highlighted by the results. Macrophage heterogeneity was intricately characterized, revealing four distinct subtypes with varying functional attributes that underscore their complex roles in atherosclerotic pathology. Intercellular communication analysis revealed robust macrophage interactions with multiple cell types and detailed pathways differing between proximal adjacent and atherosclerotic core groups. Furthermore, pseudotime trajectories charted the developmental course of macrophage subpopulations, offering insights into their differentiation fates within the plaque microenvironment. The use of machine learning identified potential diagnostic markers, culminating in the identification of RNASE1 and CD14. The risk score model based on these biomarkers exhibited high accuracy in diagnosing atherosclerosis. Immune characteristic analysis validated the risk score model’s efficacy in defining patient profiles, distinguishing high-risk individuals with pronounced immune cell activities. Finally, experimental validation affirmed RNASE1’s involvement in atherosclerotic progression, suggesting its potential as a therapeutic target.ConclusionOur findings have advanced our understanding of atherosclerosis immunopathology and paved the way for novel diagnostic and therapeutic strategies.

The development and quality of tea plants (Camellia sinensis (L.) O. Ktze.) are greatly hampered by drought stress (DS), which affects them in a number of ways, including by interfering with their metabolism of nitrogen (N). Arbuscular mycorrhizal fungi (AMF) are known to enhance water and nutrient absorption in plants, but their specific effects on tea plant N metabolism under DS and the associated regulatory mechanisms remain unclear. This study aimed to evaluate the impact of Claroideoglomus etunicatum inoculation on N assimilation in tea plants (C. sinensis cv. Fuding Dabaicha) under well-watered (WW) and DS conditions, and to explore potential molecular mechanisms. After 8 weeks of DS treatment, root mycorrhizal colonization was significantly inhibited, and the biomass of tea shoots and roots, as well as the contents of various amino acids (AAs) were reduced. However, AMF inoculation significantly increased the contents of tea polyphenols and catechins in leaves by 13.74%-36.90% under both WW and DS conditions. Additionally, mycorrhizal colonization notably increased N content by 12.65%-35.70%, various AAs by 11.88%-325.42%, and enzymatic activities associated with N metabolism by 3.80%-147.62% in both leaves and roots. Gene expression analysis revealed a universal upregulation of N assimilation-related genes (CsAMT1;2, CsAMT3;1, CsGS1, CsNADH-GOGAT, CsTS2, CsGGT1, and CsADC) in AMF-colonized tea roots, regardless of water status. Under DS condition, AMF inoculation significantly upregulated the expressions of CsNRT1;2, CsNRT1;5, CsNRT2;5, CsNR, CsGS1, CsGDH1, CsGDH2, CsTS2, CsGGT1, CsGGT3, and CsSAMDC in tea leaves. These findings suggest that AMF improved tea plant adaptability to DS by enhancing N absorption and assimilation, accompanied by the synthesis and accumulation of various AAs, such as Glu, Gln, Asp, Lys, Arg, GABA and Pro. This is achieved through the upregulation of N metabolism-related genes and the activation of related enzymes in tea plants under DS condition. These findings provide valuable insights into the role of AMF in regulating tea plant N metabolism and enhancing stress tolerance.

Environmental chemicals and pollutants are increasingly recognized for their potential transgenerational effects. Acetyl tributyl citrate (ATBC), a widely used plasticizer substituting di-(2-ethylhexyl) phthalate (DEHP), was identified as an inducer of lipogenesis in male mice by our previous research. This study aimed to investigate the impact of ATBC exposure on the metabolic homeostasis of female mice and simultaneously evaluate its intergenerational effects.Female C57BL/6J mice were orally exposed to ATBC (0.01 or 1 μg/kg/day) for 10 weeks before mating with unexposed male mice. The resulting F1 female mice were bred with unexposed males to generate F2 offspring. Our results indicated that 10-week ATBC exposure disrupted glucose metabolism homeostasis and the reproductive system in F0 female mice. In F1 female mice, elevated liver lipid levels and mild insulin resistance were observed. In the F2 generation, maternal ATBC exposure resulted in increased weight gain, elevated liver triglycerides, and higher fasting blood glucose levels, primarily in F2 male mice. These findings suggest that maternal ATBC exposure may exert intergenerational disturbing effects on glucose metabolism across generations of mice. Further investigation is needed to evaluate the health risks associated with ATBC exposure.

The oxidation of coal at room temperature provides the initial heat source for spontaneous coal combustion (CSC). In the CSC theoretical study, exploring the active substances in coal that can be oxidized at room temperature is a complex problem. Previous thermal decomposition experiments have found that coal after pyrolysis contains active sites that can exist stably in inert gases and be oxidized at room temperature. Thus it is speculated that there may also be primary active sites that are forced to be stored under inert media in coal. In order to explore the primary active sites of coal, the vacuum drying technology is applied. Based on that, the water in the raw coal can reach the boiling point under the low-temperature environment of negative vacuum pressure to complete the removal of water and gas. Under different experimental conditions (coal, desorption temperature, oxidation temperature, particle size), the cyclic oxidation online monitoring technology is used to design and implement the room temperature oxidation experiment of the desorbed coal samples. At the same time, the reaction mechanism is analyzed by the corresponding low-temperature nitrogen adsorption, XPS, ESR experiments. After vacuum desorbed, the oxidation experiments under cyclic conditions show that the massive gaseous oxidation products such as CO and CO2 will be formed in the process of raw oxidation at room temperature, and the gases appear and accumulate soon after oxygen is introduced, which proves that coal oxidation can occur at room temperature. The room temperature oxidation experiment after the desorption of raw coal indicates that there are a large number of active sites affected by water-gas masking in the raw coal. They are unable to undergo the oxidation exothermic processes, while the coal after the desorption of water and gas under negative pressure exposes massive active sites and forms a channel conducive to oxygen transport and reaction, which rapidly occur oxidation exothermic phenomenon and lead to the rise of coal temperature. Therefore, the active structure leading to the spontaneous warming of the raw coal is found, and the experiments extend the view of room temperature oxidation of the active sites from the particular case state of the pyrolysis to the general state. From the comparison of gas product generation, it can be seen that CO, which is not easy to be adsorbed by pores, is produced quickly at the moment of contact between the primary active site and oxygen. Therefore, it can be concluded that CO is more suitable as an intuitive gas evaluation index of the concentration of the active sites compared with CO2. The room temperature oxidation of the primary active sites of coal helps reveal the mechanism of coal spontaneous combustion and provides a solution to the problem of spontaneous combustion during gas extraction in high-gas mines and the problem of CO over-limit in low-rank coal mines.

The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser Facility (EuXFEL) is equipped with a multipurpose diagnostic end-station (DES) at the end of the instrument. The imager unit in DES is a key tool for aligning the beam to a standard trajectory and for adjusting optical elements such as focusing lenses or the split-and-delay line. Furthermore, the DES features a bent-diamond-crystal spectrometer to disperse the spectrum of the direct beam to a line detector. This enables pulse-resolved characterization of the EuXFEL spectrum to provide X-ray energy calibration, and the spectrometer is particularly useful in commissioning special modes of the accelerator. Together with diamond-based intensity monitors, the imager and spectrometer form the DES unit which also contains a heavy-duty beamstop at the end of the MID instrument. Here, we describe the setup in detail and provide exemplary beam diagnostic results.

Abstract Avalanche or carrier-multiplication effect, based on impact ionization processes in semiconductors, has a great potential for enhancing the performance of photodetector and solar cells. However, in practical applications, it suffers from high threshold energy, reducing the advantages of carrier multiplication. Here, we report on a low-threshold avalanche effect in a stepwise WSe2 structure, in which the combination of weak electron-phonon scattering and high electric fields leads to a low-loss carrier acceleration and multiplication. Owing to this effect, the room-temperature threshold energy approaches the fundamental limit, E thre ≈ E g, where E g is the bandgap of the semiconductor. Our findings offer an alternative perspective on the design and fabrication of future avalanche and hot-carrier photovoltaic devices.

Abstract Background We explored the clinical significance of miR-28-5p pre- and post-endovascular abdominal aortic aneurysm repair (EVAR) in abdominal aortic aneurysm (AAA) patients. Methods Subjects included AAA patients receiving EVAR and non-AAA people without statistical differences from AAA patient in comorbidities/Framingham risk score. Fasting elbow venous blood (4 mL) was collected in the morning of the day of EVAR surgery and in the morning of 3 months post-EVAR. Pre-/post-EVAR serum miR-28-5p expression, AAA maximum diameter alterations, CD3+/CD4+/CD8+/TC/TG pre-/post-EVAR, and the correlations between miR-28-5p and AAA maximum diameter were investigated. Prediction of miR-28-5p on post-EVAR mortality, prognosis, and independent factors of post-EVAR death were analyzed using receiver operating characteristic curve (ROC)/Kaplan-Meier curve/univariable and multivariable Cox regression. According to the cut-off value of ROC curve for postoperative miR-28-5p was the cut-off value, and the patients were classified into the miR-28-5p high- and low-expression groups. The survival or death of both groups were compared after 48-month follow-up. Results Serum miR-28-5p levels in AAA patients dropped post-EVAR. AAA patients showed notable differences in CD3+/CD4+/CD8+/TC/TG levels pre-/post-EVAR. The miR-28-5p low-expression group exhibited higher CD3+/CD4+ and lower CD8+/TC/TG levels. We observed a positive correlation between post-EVAR miR-28-5p and AAA maximum diameter and between the pre-/post-EVAR miR-28-5p fold change and the AAA maximum diameter change. Postoperative miR-28-5p demonstrated good predictive value for postoperative death. Hypertension, Framingham risk score, TC, TG, and miR-28-5p were independent influencing factors of post-EVAR death. Conclusion EVAR decreased serum miR-28-5p expression in AAA patients. Post-operative miR-28-5p level and pre-/post-operative fold change level are positively-correlated with AAA diameter.

Abstract Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of β-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and β-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

Abstract Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.

Abstract Artificial Intelligence (AI) is currently experiencing a bloom driven by deep learning (DL) techniques, which rely on networks of connected simple computing units operating in parallel. The low communication bandwidth between memory and processing units in conventional von Neumann machines does not support the requirements of emerging applications that rely extensively on large sets of data. More recent computing paradigms, such as high parallelization and near-memory computing, help alleviate the data communication bottleneck to some extent, but paradigm- shifting concepts are required. Memristors, a novel beyond-complementary metal-oxide-semiconductor (CMOS) technology, are a promising choice for memory devices due to their unique intrinsic device-level properties, enabling both storing and computing with a small, massively-parallel footprint at low power. Theoretically, this directly translates to a major boost in energy efficiency and computational throughput, but various practical challenges remain. In this work we review the latest efforts for achieving hardware-based memristive artificial neural networks (ANNs), describing with detail the working principia of each block and the different design alternatives with their own advantages and disadvantages, as well as the tools required for accurate estimation of performance metrics. Ultimately, we aim to provide a comprehensive protocol of the materials and methods involved in memristive neural networks to those aiming to start working in this field and the experts looking for a holistic approach.

Predicting computational intensity (CI) is essential for domain decomposition and load balance in parallel geoprocessing. However, traditional CI prediction is limited in capturing the heterogeneity of spatial domain, leading to poor accuracy and load imbalance. Leveraging recent advancements in deep learning from Artificial Intelligence (AI), this paper proposes a deep learning-based approach for predicting CI and enhancing domain decomposition, which reduces the dependency on expert knowledge through automatic feature learning. In the approach, Convolutional Neural Networks are employed to capture the heterogeneity of spatial domain, encompassing structural, distribution, and topological characteristics. A fully connected layer is then utilized for CI prediction and optimized domain decomposition. Comparative experiments were implemented between the proposed approach and three traditional methods, using two cases: spatial intersection on vector data and peak perilousness assessment. The results demonstrate that the proposed approach achieves a speedup ratio of 19.8 and a parallel efficiency of 0.82. The findings highlight the advantages of the proposed approach in terms of parallel performance and usability. This study serves as a valuable reference for illustrating how deep learning can enhance parallel geoprocessing, providing a roadmap for applying deep learning techniques to geocomputations and fostering further advancements of AI GIS.

Published studies on outdoor air pollution and tuberculosis risk have shown heterogeneous results. Discrepancies in prior studies may be partially explained by the limited geographic scope, diverse exposure times, and heterogeneous statistical methods. Thus, we conducted a multi-province, multi-city time-series study to comprehensively investigate this issue. We selected 67 districts or counties from all geographic regions of China as study sites. We extracted data on newly diagnosed pulmonary tuberculosis (PTB) cases, outdoor air pollutant concentrations, and meteorological factors in 67 sites from January 1, 2014 to December 31, 2019. We utilized a generalized additive model to evaluate the relationship between ambient air pollutants and PTB risk. Between 2014 and 2019, there were 172,160 newly diagnosed PTB cases reported in 67 sites. With every 10-μg/m3 increase in SO2, NO2, PM10, PM2.5, and 1-mg/m3 in CO, the PTB risk increased by 1.97% [lag 0 week, 95% confidence interval (CI): 1.26, 2.68], 1.30% (lag 0 week, 95% CI: 0.43, 2.19), 0.55% (lag 8 weeks, 95% CI: 0.24, 0.85), 0.59% (lag 10 weeks, 95% CI: 0.16, 1.03), and 5.80% (lag 15 weeks, 95% CI: 2.96, 8.72), respectively. Our results indicated that ambient air pollutants were positively correlated with PTB risk, suggesting that decreasing outdoor air pollutant concentrations may help to reduce the burden of tuberculosis in countries with a high burden of tuberculosis and air pollution.

ABSTRACTDeep learning (DL) models have been widely used for remote sensing-based landslide mapping due to their impressive capabilities for automatic information extraction. However, the large volumes of parameters and calculations have compromised the efficiency of DL models in extracting landslides from a large set of RS images. Lightweight convolutional neural networks (CNNs) exhibit promising feature representation abilities with fewer parameters. This study aims to introduce a new lightweight CNN called MS2LandsNet, designed to detect landslides with both high efficiency and accuracy. The MS2LandsNet consists of three down-sampling stages embedded with multi-scale feature fusion (MFF), aiming to decrease parameters while aggregating contextual features. Additionally, we incorporate multi-scale channel attention (MSCA) into MFF to improve performance. According to experimental results on three landslip datasets, MS2LandsNet obtains the highest F1 score of 85.90% and the highest IoU of 75.28%. Notably, MS2LandsNet accomplishes the resuts with the fewest parameters and the fastest inference speed, outperforming seven classical semantic segmentation models and three lightweight CNNs. The proposed lightweight model holds potential for application on a cloud computing platform for larger-scale landslide mapping tasks in future work.

Organoids, characterized by their high physiological attributes, effectively preserve the genetic characteristics, physiological structure, and function of the simulated organs. Since the inception of small intestine organoids, other organoids for organs including the liver, lungs, stomach, and pancreas have subsequently been developed. However, a comprehensive summary and discussion of research findings on gastrointestinal tract (GIT) organoids as disease models and drug screening platforms is currently lacking. Herein, in this review, we address diseases related to GIT organoid simulation and highlight the notable advancements that have been made in drug screening and pharmacokinetics, as well as in disease research and treatment using GIT organoids. Organoids of GIT diseases, including inflammatory bowel disease, irritable bowel syndrome, necrotizing enterocolitis, and Helicobacter pylori infection, have been successfully constructed. These models have facilitated the study of the mechanisms and effects of various drugs, such as metformin, Schisandrin C, and prednisolone, in these diseases. Furthermore, GIT organoids have been used to investigate viruses that elicit GIT reactions, including Norovirus, SARS-CoV-2, and rotavirus. Previous studies by using GIT organoids have shown that dasabuvir, gemcitabine, and imatinib possess the capability to inhibit viral replication. Notably, GIT organoids can mimic GIT responses to therapeutic drugs at the onset of disease. The GIT toxicities of compounds like gefitinib, doxorubicin, and sunset yellow have also been evaluated. Additionally, these organoids are instrumental for the study of immune regulation, post-radiation intestinal epithelial repair, treatment for cystic fibrosis and diabetes, the development of novel drug delivery systems, and research into the GIT microbiome. The recent use of conditioned media as a culture method for replacing recombinant hepatocyte growth factor has significantly reduced the cost associated with human GIT organoid culture. This advancement paves the way for large-scale culture and compound screening of GIT organoids. Despite the ongoing challenges in GIT organoid development (e.g., their inability to exist in pairs, limited cell types, and singular drug exposure mode), these organoids hold considerable potential for drug screening. The use of GIT organoids in this context holds great promises to enhance the precision of medical treatments for patients living with GIT diseases.

Abstract Constructing discriminative representations of molecules lies at the core of a number of domains such as drug discovery, chemistry, and medicine. State‐of‐the‐art methods employ graph neural networks and self‐supervised learning (SSL) to learn unlabeled data for structural representations, which can then be fine‐tuned for downstream tasks. Albeit powerful, these methods are pre‐trained solely on molecular structures and thus often struggle with tasks involved in intricate biological processes. Here, it is proposed to assist the learning of molecular representation by using the perturbed high‐content cell microscopy images at the phenotypic level. To incorporate the cross‐modal pre‐training, a unified framework is constructed to align them through multiple types of contrastive loss functions, which is proven effective in the formulated novel tasks to retrieve the molecules and corresponding images mutually. More importantly, the model can infer functional molecules according to cellular images generated by genetic perturbations. In parallel, the proposed model can transfer non‐trivially to molecular property predictions, and has shown great improvement over clinical outcome predictions. These results suggest that such cross‐modality learning can bridge molecules and phenotype to play important roles in drug discovery.

BackgroundLower urinary tract symptoms (LUTS) are clinically frequent and seriously affect the psychological and mental health of children and adolescents. However, most studies on LUTS and its influence on the psychological behavior and mental health have focused on adults. This study aimed to investigate LUTS prevalence and associated factors in children and adolescents and explore its impact on psychological behavior.Materials and methodsFrom October 2019 to November 2021, an epidemiological LUTS survey was carried out on 6,077 children aged 6–15 years old in 12 primary and secondary schools in China by using anonymous questionnaires.ResultsA total of 5,500 valid questionnaires were collected, and the total prevalence of four representative symptoms of LUTS: urgency, frequency, daytime urinary incontinence, and nocturnal enuresis was 19.46%, 14.55%, 9.75%, and 8.4%, respectively. The prevalence decreased with age, which decreased rapidly in children aged 6–12 years old. The incidence of LUTS in those who did not continue to use disposable diapers (DD) and began to perform elimination communication (EC) after the age of 1 was significantly higher than that of those who stopped using DD and started EC before 1 year of age (P

This study investigated the potential of gamma-aminobutyric acid (GABA), a potent bioactive compound and inhibitory neurotransmitter, in mitigating chronic ammonia stress-induced liver toxicity in crucian carp (Carassius carassius). GABA is known for its role in alleviating stress responses and enhancing antioxidant defense. In this study, experimental fishes (weighing 20.51 ± 0.39 g) underwent 56 days of chronic ammonia stress (10 ± 0.053 mg/L), with or without supplemented with GABA (100 mg/kg) in the diet. Serum ammonia (152.14 ± 2.94, CK-95.82 ± 0.81 μmol/L), serum MDA content (3.41 ± 1.24, CK-1.25 ± 0.08 μmol/L), and liver MDA content (1.98 ± 1.72, CK-0.84 ± 0.02 μmol/g prot) were significantly increased in the ammonia exposure group compared with the CK group. GABA supplementation effectively alleviates the detrimental effects of chronic ammonia stress, specifically on growth parameters, serum ammonia levels, and malondialdehyde content. GABA supplementation elevated the expressions of antioxidant genes (zu/cu sod, cat), promoted the expressions of nrf2, and reduced the expression of keap1. Moreover, GABA significantly alleviated liver injury and reduced gene expression of three types of transmembrane proteins (perk, ire1, and atf6). GABA further regulated the expression of downstream apoptotic target genes (upregulation of bcl2; downregulation of bax, caspase3, and caspase9) through endoplasmic reticulum stress (ERS) pathways. This finding indicated the multifaceted benefits of GABA in combating chronic ammonia stress in crucian carp, providing valuable insights for the development of sustainable aquaculture practices.

In this study, the process of catalytic oxidation of methane considering radiative heat transfer was simulated using FLUENT computational software to study the effect of thermal radiation on the oxidation performance of the simulated device, and to investigate the extent to which radiative heat transfer affects the oxidation performance of the device under different operating conditions. The results show that the extent to which thermal radiation affects the oxidative performance of the equipment increases with increasing inlet temperature. When the intake temperature reaches 900K, its proportion is close to 45 %. At the same time, as the inlet gas temperature increases, the maximum reaction temperature of the oxidation unit is 1154 K, and the methane conversion rate reaches up to 89 %. The main factor affecting the oxidation performance of the unit at this time is radiation heat transfer. The extent to which thermal radiation affects the oxidative performance of the device diminishes with increasing inlet velocity. When the wind speed reaches 2 m/s, the proportion of radiative heat transfer is only 10 %, the maximum reaction temperature of the plant falls to 993 K, and the methane conversion rate drops to 68 %. At this time, the main factor affecting the oxidation performance of the plant is convective heat transfer. The influence of thermal radiation on oxidation performance gradually diminishes with an increase in intake velocity, and the proportion of radiative heat transfer decreases continuously. At methane concentrations above 1 %, the proportion of radiative heat transfer is less than 25 per cent, the maximum reaction temperature of the unit increases to 1087 K, and the methane conversion rises to 88 %. At this point, the main factor affecting the oxidation performance of the plant is convective heat transfer.

BackgroundTo investigate the correlation between retinal vascular changes and ICA stenosis by measuring retinal vessels using full-width-at-half-maximum (FWHM) and intelligent image recognition.MethodsThis research selected patients who were admitted to the Vascular Surgery Department of Quzhou People’s Hospital from January 2018 to December 2020 and were preparing for Carotid Artery Stenting (CAS). Participants were divided into two groups: without ICA stenosis (Group 0) and with ICA stenosis (Group 1). A total of 109 cases were included in the study, with 50 cases in Group 1 and 59 cases in Group 0. Vascular images of superior temporal zone B of the retina were obtained by spectral domain optical coherence tomography (SD-OCT). The edges of retinal vessels were identified by FWHM. Each vessel of all subjects was measured three times with the FWHM, and the average value was taken to obtain the retinal arteriolar lumen diameter (RALD), retinal arteriolar outer diameter (RAOD), retinal venular lumen diameter (RVLD), and retinal venular outer diameter (RVOD),Arterial Wall Thickness (AWT),Venular Wall Thickness (VWT)=(RVOD-RVLD)/2,Arteriovenous Ratio (AVR) = RAOD/RVOD.ResultsWe found that compared to Group 0, Group 1 had smaller RALD (P < 0.001) and RAOD (P < 0.001), and wider RVOD (P < 0.001), with thicker VWT (P < 0.001). When compared with the contralateral eye in Group 1, the ipsilateral eye exhibited even smaller RALD,RAOD and AVR (P < 0.001, P < 0.001, P < 0.001). After CAS, the RALD,RAOD and AVR in Group 1 increased (P < 0.001, P < 0.001, P < 0.001),while the RVLD and RVOD decreased (P < 0.05, P < 0.001). Our research reveals a significant correlation between retinal vascular changes and internal ICA stenosis.ConclusionUtilizing SD-OCT in conjunction with the FWHM,we achieved a non-invasive, intelligent, stable, and precise acquisition of data pertaining to retinal vessels. These findings underscore a significant correlation between alterations in retinal vascular structure and the presence of ICA stenosis, as demonstrated by our research.

Climate change and water shortage have brought great challenges to agricultural production in the North China Plain, and it’s crucial to find the suitable method to address these challenges. Climate model projections were used to drive the Agro-Hydrological & chemical and Crop systems simulator (AHC) that considering the impact of irrigation on field microclimate. Yield, evapotranspiration (ET), water productivity (WP), and the impact on groundwater level of 6 wheat varieties under 6 sprinkler irrigation scheduling (IS1: no irrigation; IS6: full irrigation without water deficit; IS2–5: deficit irrigation with 0.2, 0.4, 0.6, and 0.8 times water of IS6 after wheat greening) were estimated in Xingtai under current and two shared social economic paths scenarios (SSP2–4.5 and SSP5–8.5). The optimal combination of irrigation and variety (OC) was selected by Topsis method. The results indicated that AHC had a high accuracy in simulating the growth of six varieties (R2>0.80, NRMSE

Due to their ecological sensitivity and limited resource availability, grasslands are exceptionally vulnerable to environmental changes and human activities. However, comprehensive and in-depth analyses of the interplay between grasslands and human activities remain scarce. This study employed bibliometrics and critical paper analysis to scrutinize 4738 publications from 2000 to 2023. The findings reveal that: (1) Since 2000, research on grassland-human activity interactions has evolved and intensified, spanning diverse disciplines including environmental ecology, plant science, agricultural science, and biodiversity conservation. A notable trend is the relative clustering of scholars and research institutions within Eastern and Western countries and within national boundaries. China leads in publication volume, whereas the United States exerts greater influence in the international collaborative network. (2) Approximately 80% of the highly co-citation literature concentrates on elucidating scientific knowledge, particularly the impact of human activities on vegetation characteristics, grassland communities, and ecosystems. Research hotspots predominantly encompass European grasslands, North America’s Great Plains, and the Tibetan Plateau grasslands in China. The remaining 20% focuses on methodological advancements and tools, with frequent utilization of R language, PC-ORD, and Google Earth Engine (GEE). (3) Initial studies (2000–2005) primarily investigated the effects of specific anthropogenic activities on grassland biomes at a community level through experimental observations. Subsequent research (2006–2013) shifted towards exploring the overarching characteristics and transformations of grassland rangelands at regional scales, heavily relying on remote sensing technologies. More recent studies (2014–2023) have emphasized a comprehensive, quantitative appraisal of the multifaceted impacts of internal and external stressors on grassland ecosystems. This study enhances the understanding of the historical trajectory of grassland-anthropogenic relationship research, highlighting pivotal knowledge and collaborative tools.

Background: Previous studies have suggested that the Pro-Kin visual feedback balance system can promote the recovery of balance function in stroke patients. Objectives: However, this system has not been used effectively in the early stages of stroke rehabilitation. This study aimed to investigate the effect of Pro-Kin system combined with weight loss system for the early recovery of balance and walking ability following a stroke. Methods: A total of 62 patients who underwent radiological diagnosis of stroke were randomly divided into two groups: a control group ( n = 31) and a treatment group ( n = 31). Both groups received conventional balance training. The treatment group also received training on the Pro-Kin system in conjunction with a weight loss system. Balance was measured using the Berg Balance Scale (BBS), Timed ‘Up & Go’ (TUG) test and Pro-Kin system. Walking ability was assessed using the Functional Ambulation Classification (FAC). The tests were performed before the start of treatment and on the 4th week following the training. There was no statistically significant difference between the groups before training. Results: After 4 weeks of training in both groups, there were significant improvements in balance and walking ability. BBS values and FAC were significantly higher ( p

Summary: Background: The use of real-time continuous glucose monitoring (rtCGM) technology remains largely investigational in the hospital setting. The current study aimed to evaluate the effectiveness of rtCGM in inpatients with diabetes who were treated with short-term continuous subcutaneous insulin infusion (CSII). Methods: In this randomized, parallel controlled trial conducted on the endocrinology wards in a tertiary hospital located in Shanghai, adults with type 1 and type 2 diabetes who required short-term CSII during hospitalization were randomly assigned (1:1) to receive either rtCGM-based glucose monitoring and management program or point-of-care (POC) standard of care (8 times/day) with blinded CGM. Primary outcome measure was the difference in the percentage of time within the target glucose range of 3.9–10 mmol/L (TIR, %). This study was registered at www.chictr.org.cn (ChiCTR2300068933). Findings: Among the 475 randomized participants (237 in the rtCGM group and 238 in the POC group), the mean age of was 60 ± 13 years, and the mean baseline glycated hemoglobin level was 9.4 ± 1.8%. The CGM-recorded mean TIR was 71.1 ± 15.8% in the rtCGM group and 62.9 ± 18.9% in the POC group, with a mean difference of 8.2% (95% confidence interval [CI]: 5.1–11.4%, P 10 mmol/L was significantly lower in the rtCGM group than in the POC group (28.3 ± 15.8% vs. 36.6 ± 19.0%, P

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (PSA), poses a grave threat to the global kiwifruit industry. In this study, we examined the role of microRNAs (miRNAs) in kiwifruit’s response to PSA. Kiwifruit seedlings subjected to PSA treatment showed significant changes in both miRNA and gene expression compared to the control group. We identified 364 differentially expressed miRNAs (DEMs) and 7170 differentially expressed genes (DEGs). Further analysis revealed 180 miRNAs negatively regulating 641 mRNAs. Notably, two miRNAs from the miRNA482 family, miRNA-215-3p and miRNA-29-3p, were found to increase kiwifruit’s sensitivity to PSA when overexpressed. These miRNAs were linked to the regulation of NBS-LRR target genes, shedding light on their role in kiwifruit’s defence against PSA. This study offers insights into the miRNA482-NBS-LRR network as a crucial component in enhancing kiwifruit bioresistance to PSA infestation and provides promising candidate genes for further research.

Scrophularia ningpoensis Hemsl. (SN) is an herbal medicine used as a functional food in China. SN has traditionally been used to treat diabetes mellitus (DM), but its mechanism of action is not well understood. Our previous study indicated that the aqueous extract of SN can reduce hepatic insulin resistance and correct the irregular shape of pancreatic islets in diabetic mice. This study aims to investigate whether the aqueous extract of SN can regulate pyroptosis in pancreatic β-cells and explore its underlying mechanisms. Db/db mice were orally given an aqueous extract of SN for eight weeks. Subsequently, their pancreatic tissues were collected for histopathological analysis and immunoblotting. Rat insulinoma (INS-1) cells were cultured either alone or with the aqueous extract of SN and evaluated for cell viability, pyroptotic body formation, AMP-activated protein kinase (AMPK) activity, the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome and gasdermin D (GSDMD) activation, and reactive oxygen species (ROS) production under high glucose (HG) exposure conditions. The aqueous extract of SN reduced insulitis and pancreatic β-cell death in db/db mice. Increased AMPK phosphorylation and decreased NLRP3 inflammasome and GSDMD activation were observed in pancreatic tissues after administration of the aqueous extract of SN. In vitro, the aqueous extract of SN increased cell viability and AMPK phosphorylation in a concentration-dependent manner. Additionally, the aqueous extract of SN corrected excessive ROS generation, NLRP3 inflammasome and GSDMD activation, and pyroptotic body formation. Inhibition of AMPK negated these beneficial effects of the aqueous extract of SN on INS-1 cells. The study concluded that the aqueous extract of SN alleviates β-cell pyroptosis by inhibiting NLRP3/GSDMD activation in an AMPK-dependent manner.

In order to investigate the effect of different water filling times on the compression deformation of filled gangue, a large-scale crushed gangue deformation testing system was utilized, and two sets of gradient loading experiments were designed. Through rigorous experimental analysis, distinct patterns of deformation during loading and constant load stages are elucidated, with a particular focus on the influence of water filling timing. Quantitative assessment reveals that early water filling induces rapid gangue deformation, primarily during loading stages, while later water filling stages exhibit a heightened impact on constant load stages. Moreover, the study identifies a stepped deformation phenomenon attributed to the irregularities in crushed gangue particles, shedding light on the underlying mechanisms governing gangue behavior under varying water filling conditions. Notably, an in-depth analysis of energy consumption patterns underscores the dominant role of strain, especially in later water filling stages, significantly influencing deformation characteristics. The study further explores the implications of water filling timing on mining subsidence effects, offering quantitative insights into the stability of gangue backfilling. Under the action of the cumulative deformation and concentrated filling effect, the equivalent filling height is slightly higher than that of the early water filling state, but this trend weakens with the increase of mining height. The conclusions of this study can provide experimental data for stability analysis of crushed gangue filling the abandoned mines with different water filling timing.

To tackle the challenge of extracting residual coal resources in Zhangzhao Coal Mine while preventing floor water inrush, a strip filling mining method has been proposed. A two-step mining approach was designed to ensure roof stability and avoid floor water inrush. The first step involves mining and filling at 15 m intervals, leaving a 20 m strip coal pillar. In the second step, a 20 m strip coal pillar is mined and filled at intervals. To meet the filling mining requirements, tailings and industrial slag are used to create the filling body, designed using a paste ratio test. The optimal ratio for silt has been determined to be 1:5, with a mass concentration of 70 %. Simulation tests were conducted to determine the dynamic failure development of the floor under different advancing footage. The self-designed pressurized water sac was used in the simulation experiment, and the results showed that maximum floor damage occurred at 130 m. Additionally, monitoring stations were installed during mining to track the failure depth of the floor. The research revealed that filling mining significantly reduces the failure depth of the floor and prevents water bursting passages, demonstrating the potential of this method for use under similar conditions. This study provides useful references and recommendations for future mining efforts.