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To investigate the functional effects of superfine grinding treatment on Polygonatum cyrtonema Hua powder, in this study, the sample was ground and sieved by pharmacopoeia test sieves (50, 100, 200 and 325 mesh) to prepare P. cyrtonema Hua powder with different particle sizes. Its physical properties were studied using scanning electron microscopy and Fourier transform infrared spectroscopy, while the in vitro gastrointestinal digestion process was simulated. The results showed that the particle size of P. cyrtonema Hua powder exhibited a significant difference (P

Abstract We present SpliceTransformer (SpTransformer), a deep-learning framework that predicts tissue-specific RNA splicing alterations linked to human diseases based on genomic sequence. SpTransformer outperforms all previous methods on splicing prediction. Application to approximately 1.3 million genetic variants in the ClinVar database reveals that splicing alterations account for 60% of intronic and synonymous pathogenic mutations, and occur at different frequencies across tissue types. Importantly, tissue-specific splicing alterations match their clinical manifestations independent of gene expression variation. We validate the enrichment in three brain disease datasets involving over 164,000 individuals. Additionally, we identify single nucleotide variations that cause brain-specific splicing alterations, and find disease-associated genes harboring these single nucleotide variations with distinct expression patterns involved in diverse biological processes. Finally, SpTransformer analysis of whole exon sequencing data from blood samples of patients with diabetic nephropathy predicts kidney-specific RNA splicing alterations with 83% accuracy, demonstrating the potential to infer disease-causing tissue-specific splicing events. SpTransformer provides a powerful tool to guide biological and clinical interpretations of human diseases.

Abstract Resilience, the ability to maintain fundamental functionality amidst failures and errors, is crucial for complex networked systems. Most analytical approaches rely on predefined equations for node activity dynamics and simplifying assumptions on network topology, limiting their applicability to real-world systems. Here, we propose ResInf, a deep learning framework integrating transformers and graph neural networks to infer resilience directly from observational data. ResInf learns representations of node activity dynamics and network topology without simplifying assumptions, enabling accurate resilience inference and low-dimensional visualization. Experimental results show that ResInf significantly outperforms analytical methods, with an F1-score improvement of up to 41.59% over Gao-Barzel-Barabási framework and 14.32% over spectral dimension reduction. It also generalizes to unseen topologies and dynamics and maintains robust performance despite observational disturbances. Our findings suggest that ResInf addresses an important gap in resilience inference for real-world systems, offering a fresh perspective on incorporating data-driven approaches to complex network modeling.

Abstract Background Pulmonary fibrosis is a serious interstitial lung disease with no viable treatment except for lung transplantation. Glucagon-like peptide-1 receptor (GLP-1R), commonly regarded as an antidiabetic target, exerts antifibrotic effects on various types of organ fibrosis. However, whether GLP-1R modulates the development and progression of pulmonary fibrosis remains unclear. In this study, we investigated the antifibrotic effect of GLP-1R using in vitro and in vivo models of pulmonary fibrosis. Methods A silica-induced pulmonary fibrosis mouse model was established to evaluate the protective effects of activating GLP-1R with liraglutide in vivo. Primary cultured lung fibroblasts treated with TGF-β1 combined with IL-1β (TGF-β1 + IL-1β) were used to explore the specific effects of liraglutide, MCC950, and 3PO on fibroblast activation in vitro. Cell metabolism assay was performed to determine the glycolytic rate and mitochondrial respiration. RNA sequencing was utilized to analyse the underlying molecular mechanisms by which liraglutide affects fibroblast activation. ChIP‒qPCR was used to evaluate histone lactylation at the promoters of profibrotic genes in TGF-β1 + IL-1β- or exogenous lactate-stimulated lung fibroblasts. Results Activating GLP-1R with liraglutide attenuated pulmonary inflammation and fibrosis in mice exposed to silica. Pharmacological inhibition of the NLRP3 inflammasome suppressed PFKFB3-driven glycolysis and vice versa, resulting in decreased lactate production in TGF-β1 + IL-1β-stimulated lung fibroblasts. Activating GLP-1R inhibited TGF-β1 + IL-1β-induced fibroblast activation by disrupting the interaction between the NLRP3 inflammasome and PFKFB3-driven glycolysis and subsequently prevented lactate-mediated histone lactylation to reduce pro-fibrotic gene expression. In addition, activating GLP-1R protected mitochondria against the TGF-β1 + IL-1β-induced increase in oxidative phosphorylation in fibroblasts. In exogenous lactate-treated lung fibroblasts, activating GLP-1R not only repressed NLRP3 inflammasome activation but also alleviated p300-mediated histone lactylation. Finally, GLP-1R activation blocked silica-treated macrophage-conditioned media-induced lung fibroblast activation. Conclusions The antifibrotic effects of GLP-1R activation on pulmonary fibrosis could be attributed to the inhibition of the interaction between NLRP3 inflammasome and PFKFB3-driven glycolysis, and histone lactylation in lung fibroblasts. Thus, GLP-1R is a specific therapeutic target for the treatment of pulmonary fibrosis.

Abstract Background Females with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the “high-risk DOR” group. Objective The primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs). Methods A total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson’s chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02). Results According to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM. Conclusion(s) Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.

Objective: Rhythmic physical activity holds promise for positively influencing the gross motor development of 4-5-year-old children, yet empirical research in this domain remains limited. This study aimed to investigate the effects of rhythmic physical activity on the gross motor development in children aged 4–5 years. Methods: Fifty children aged 4–5 years were recruited and randomly assigned to either the intervention or control group. Both groups participated in a 10-week intervention program facilitated by a professional trainer, with support from numerous dedicated volunteers from reputable sports universities. This program comprised a one-week baseline assessment followed by 8 weeks of rhythmic physical activity training conducted three times per week. Gross motor performance was assessed using the PGMQ scale before and one week after the intervention. Results: Following the 8-week intervention, the intervention group demonstrated significant enhancements in displacement ability, with notable improvements observed in. Specifically, the scores for running, sliding lateral transfer, leaping step, two-footed back-and-forth jump, and total displacement ability showed significant increases (P 0.05). The two-way repeated measures ANOVA of intervention × time revealed significant differences in scores for running, sliding lateral movement, leaping step, jumping back and forth with both feet, leading ability, kicking, manipulation ability, single-leg stand, double-leg stand, balance ability, and gross motor scores (P

Abstract Nonlinear charge transport, such as nonreciprocal longitudinal resistance and nonlinear Hall effect, has attracted considerable interest in probing the symmetries and topological properties of new materials. Recent research has revealed significant nonreciprocal longitudinal resistance and nonlinear Hall effect in MnBi2Te4, an intrinsic magnetic topological insulator, induced by the quantum metric dipole. However, the inconsistent response with charge density and conflicting C3z symmetry requirement necessitate a thorough understanding of factors affecting the nonlinear transport measurement. This study uncovers an experimental factor leading to significant nonlinear transport signals in MnBi2Te4, attributed to gate voltage oscillation from the application of large alternating current. Additionally, a methodology is proposed to suppress this effect by individually grounding the voltage electrodes during second-harmonic measurements. The investigation underscores the critical importance of assessing gate voltage oscillation’s impact before determining the intrinsic nature of nonlinear transport in 2D material devices with an electrically connected operative gate electrode.

Abstract Background Trachelospermum jasminoides has medicinal and ornamental value and is widely distributed in China. Although the chloroplast genome has been documented, the mitochondrial genome has not yet been studied. Results The mitochondrial genome of T. jasminoides was assembled and functionally annotated using Illumina and nanopore reads. The mitochondrial genome comprises a master circular molecular structure of 605,764 bp and encodes 65 genes: 39 protein-coding genes, 23 transfer RNA (tRNA) genes and 3 ribosomal RNA genes. In addition to the single circular conformation, we found many alternative conformations of the T. jasminoides mitochondrial genome mediated by 42 repetitive sequences. Six repetitive sequences (DRS01–DRS06) were supported by nanopore long reads, polymerase chain reaction (PCR) amplifications, and Sanger sequencing of the PCR products. Eleven homologous fragments were identified by comparing the mitochondrial and chloroplast genome sequences, including three complete tRNA genes. Moreover, 531 edited RNA sites were identified in the protein-coding sequences based on RNA sequencing data, with nad4 having the highest number of sites (54). Conclusion To our knowledge, this is the first description of the mitochondrial genome of T. jasminoides. Our results demonstrate the existence of multiple conformations. These findings lay a foundation for understanding the genetics and evolutionary dynamics of Apocynaceae.

Abstract Background Heatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer’s solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke. Methods Fifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins. Results Compared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived. Conclusions NS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.

Abstract Excessive peripheral microvascular constriction during acute psychological stress reflects similar changes in coronary blood flow and is a predictor of adverse cardiovascular outcomes. Among individuals with coronary artery disease (CAD), we sought to determine if genetic factors contribute to the degree of microvascular constriction during mental stress. A total of 580 stable CAD individuals from two prospective cohort studies underwent mental stress testing. Digital pulse wave amplitude was continuously measured and the stress/rest (sPAT) ratio of pulse wave amplitude was calculated. Race stratified genome-wide association studies (GWAS) of sPAT-ratio were conducted using linear regression of additive genetic models. A trans-ethnic meta-analysis integrated the four sets of GWAS results. Participants were followed for the outcome of recurrent cardiovascular events (myocardial infarction, heart failure, revascularization, and CV death) for a median of 5 years. We used Wei-Lin-Weissfeld (WLW) model to assess the association between sPAT-ratio with recurrent events. Mean age was 63 ± 9. We identified three SNPs in linkage disequilibrium, closely related to chr7:111,666,943 T > C (rs6466396) that were associated with sPAT-ratio (p = 6.68E-09). Participants homozygous for the T allele had 80% higher risk of incident adverse events (HR 1.8, 95% CI, 1.4–2.2). Also, participants with a lower sPAT-ratio (

Abstract Urolithiasis is a leading urological disorder where accurate preoperative identification of stone types is critical for effective treatment. Deep learning has shown promise in classifying urolithiasis from CT images, yet faces challenges with model size and computational efficiency in real clinical settings. To address these challenges, we developed a non-invasive prediction approach for determining urinary stone types based on CT images. Through the refinement and improvement of the self-distillation architecture, coupled with the incorporation of feature fusion and the Coordinate Attention Module (CAM), we facilitated a more effective and thorough knowledge transfer. This method circumvents the extra computational expenses and performance reduction linked with model compression and removes the reliance on external teacher models, markedly enhancing the efficacy of lightweight models. achieved a classification accuracy of 74.96% on a proprietary dataset, outperforming current techniques. Furthermore, our method demonstrated superior performance and generalizability on two public datasets. This not only validates the effectiveness of our approach in classifying urinary stones but also showcases its potential in other medical image processing tasks. These results further reinforce the feasibility of our model for actual clinical deployment, potentially assisting healthcare professionals in devising more precise treatment plans and reducing patient discomfort.

Abstract Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-COV-2, Influenza A, B, and respiratory syncytial virus with a sensitivity of 10 copies/mL. When integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single-copy spatial resolution of 0.83 copies/m3 for airborne virus surveillance with an air flow rate of 400 L/min and a sampling time of 30 minutes. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.

Abstract Background With the increasing prevalence of obesity, there is growing awareness of the impact of overweight and obesity on total hip arthroplasty (THA). Research exploring the accuracy of acetabular component orientation in THA between robotic-assisted and manual techniques across different BMI categories is insufficient. Methods This prospective study evaluated 221 patients who underwent THA with a Robotic Interactive Orthopaedic Arm system and 252 patients who underwent manual THA between March 2022 and January 2024. The patients were divided into four groups according to their BMI. We analysed whether there were differences in the accuracy of acetabular component positioning between robotic-assisted THA and manual THA across different BMI categories. Results In the overweight group, robotic-assisted THA achieved a significantly higher rate of abductions within the target range (73/6) than manual THA (62/28) (p = 0.000). Both abductions and anteversions within the target range were also significantly more frequent in the robotic-assisted THA group (69/10) than in the manual THA group (56/34) (p = 0.000). Among the obese patients, robotic-assisted THA showed a perfect record for anteversions within the target range (29/0), markedly outperforming manual THA (39/6) (p = 0.040). Conclusion In the overweight (24 kg/m² ≤ BMI

Abstract Epigenetic reprogramming plays a critical role in cancer progression of cancer, and N6-methyladenosine (m6A) is the most common RNA modification in eukaryotes. The purpose of this study was to explore the related modification mode of m6A regulator construction and evaluate the invasion and migration of thyroid cancer. Our results showed that m6A levels were significantly increased in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) samples, which may have been induced by the down-regulation of demethylase fat mass and obesity-associated gene (FTO). Moreover, FTO inhibited PTC and ATC invasion and metastasis through the epithelial-to-mesenchymal transition (EMT) pathway in vivo and in vitro. Mechanistically, an m6A-mRNA epitranscriptomic microarray showed that Cadherin 12 (CDH12) is the key target gene mediated by FTO in an m6A-dependent manner. CDH12 promotes invasion and metastasis through the EMT pathway in thyroid cancer, both in vivo and in vitro. Furthermore, we found that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an important m6A reading protein, that regulates the stability of CDH12 mRNA and mediates EMT progression, thereby promoting the invasion and metastasis of PTC and ATC. Thus, FTO, IGF2BP2 and CDH12 may be effective therapeutic targets for PTC and ATC with significant invasion or distant metastasis. Schematic summary of FTO-IGF2BP2 axis in modulation of CDH12 mRNA m6A and upregulation of CDH12 expression in the invasion and metastasis of thyroid carcinoma.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa−1, as well as cyclic stability (over 500 cycles), a wide detection range of 0–150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

Abstract Background Fibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids. Method We isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20–22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo. Results ADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments. Conclusions Adipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars. Graphical Abstract

Abstract Background The mandibular retromolar space (RMS) has not been extensively studied in relation to various sagittal skeletal classes and patterns of third-molar eruption. The objective of this study was to test the null hypothesis that there is no difference in the mandibular RMS among normodivergent subjects with different skeletal classes and patterns of mandibular third-molar eruption, using cone-beam computed tomography (CBCT). Method A total of 105 normodivergent patients (20–40 years) were included in this study. Participants were categorized into Class I, II and III groups based on ANB and further impacted and erupted groups based on the eruption patterns of the mandibular third molars. Measurements of the mandibular RMS were taken at four planes parallel to the occlusal plane, along the cusp line. Comparative analyses were conducted among the three sagittal groups and between the impacted and erupted groups. Results The Class II group exhibited a statistically smaller RMS (P

Abstract Background There is a serious public health concern regarding the emergence of carbapenem-resistant Escherichia coli (CREC). The purpose of this study is to identify the molecular characterization and risk factors of CREC in Fujian province, China. Methods A total of 48 CREC isolates were collected from various clinical samples. The strains were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Susceptibility to antibiotics was determined by the standard broth microdilution method. Polymerase chain reaction (PCR) was used to screen common drug resistance genes. Multilocus sequence typing (MLST) was used to type isolates. RT-qPCR was used to detect gene expression of acrA, acrB, and tolC. Conjugation assays were used to analyze the transferability of plasmids carrying mcr-1 or bla NDM. Risk factors for CREC infection were identified by logistic regression analysis. Results 48 CREC strains were collected, with 81.25% producing carbapenemase (CP-CREC), and 18.75% were not producing carbapenemase (no-CP-CREC). They belonged to 21 sequence type (STs) and five unknown STs. Perianal swabs were the main sample type, with 25 patients found to have hematological malignancies. All isolates of CP-CREC were found to contain bla NDM (bla NDM−5 (n = 32), bla NDM−1 (n = 5), bla NDM−4 (n = 1), and bla NDM−13 (n = 1)), among which one isolate co-existence bla NDM−5 and bla OXA−48. Two bla NDM-positive strains, specifically bla NDM−5 and bla NDM−4, were found to co-habor mcr-1 with ST617. Conjugation assays confirmed that bla NDM−1, bla NDM−13, and most bla NDM−5(68.75%, 22/32) could be transferred between E. coli strains. Four of the 9 non-CP-CREC isolates had deletions in ompC and ompF with bla CTX−M production, while the other five showed high expression of acrA, acrB, and tolC. Antibiotics usage, antifungal treatment, detection of other pathogens (prior to CREC infection), and respiratory disease were identified as independent risk factors for CREC infection. The area under the receiver operating characteristic curve for the scoring system was 0.937. Youden’s index, with sensitivity and specificity of 0.96 and 0.78, was maximal when 2 points were scored. Conclusions In CP-CREC, carbapenem resistance is caused primarily by multiple types of bla NDM, while non-CP-CREC is caused by loss of porin protein or high expression of efflux pumps coupled with carrying bla CTX−M. CREC isolates were highly diverse in terms of ST, with a total of 21 STs identified. Here, we first describe a clinical strain of CREC from China both mcr-1 and bla NDM −4 with ST617. An easy-to-use scoring system was developed to diagnose CREC infections.

Abstract Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

Highlights The developmental history of high-entropy materials and the conceptual origin of “high entropy” is comprehensively reviewed. The preparation methods of various high-entropy electrode materials are comprehensively reviewed. The application properties of various high-entropy electrode materials in electrocatalysis and energy storage are comprehensively reviewed, with a prospective outlook on the future development of such materials.

Abstract Background Premarital sexual behavior (PSB) is a controversial topic in China. However, in recent times, changes in attitudes have led to PSB being more common among college students. This study investigated the attitudes of Chinese undergraduates toward PSB to identify whether a typological classification exists among them. Methods A total of 278 undergraduate students from two public universities in Mainland China completed a 17-item survey that included five dimensions( emotions, responsiveness, sexual health, sexual freedom, and condemnation) on attitudes toward PSB. Data were collected online from April 2023 to July 2023. Results The PSB questionnaire demonstrated good reliability and construct validity in this study, with a Cronbach’s α of 0.759 and a KMO value of 0.769. Meanwhile, a series of models were estimated specifying one through five latent classes and three typologies on the attitude were identified: “Affective,”“Avoidant,” and “Open.” After the best fitting model was determined, multiple analysis of variance testing of different factors such as gender, year of study and where one came from were found to have significant effects on attitude complexity (p

Sorghum faces significant production challenges due to drought stress. Melatonin has been demonstrated to play a crucial role in coping with stresses in plants. This study investigated the effect of exogenous melatonin on the sorghum seedling growth, photosynthetic capacity, and antioxidant system under drought stress. The results indicated that drought stress inhibited the growth of sorghum seedlings by a marked reduction in leaf relative water content, along with a significant increase in both malondialdehyde and hydrogen peroxide content. The drought stress also led to a significant diminution in chlorophyll contents, thereby curtailing the capacity for light energy capture. Furthermore, the efficiency of the photosynthetic electron transport chain was adversely impacted. However, the application of exogenous melatonin notably mitigated the adverse effects on sorghum seedlings under the drought stress. Additionally, it stimulated an elevation in the photosynthetic rate and a decrease in non-photochemical quenching. The exogenous melatonin also facilitated the preservation of the chloroplast ultra-structure and boosted the activity of antioxidant enzymes and the content of non-enzymatic antioxidants. Cluster heat maps and principal component analysis further revealed significant correlations among various parameters under different treatment conditions. These results highlight melatonin’s role in improving sorghum’s drought tolerance, which is beneficial for agricultural management.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix (ECM) deposition. However, current treatments are not satisfactory. Therefore, more effective therapies need to be explored. Cepharanthine (CEP) is a naturally occurring alkaloid that has recently been reported to have multiple pharmacological effects, particularly in chronic inflammation. Methods For in vivo experiments, first, a pulmonary fibrosis murine model was generated via tracheal injection of bleomycin (BLM). Second, the clinical manifestations and histopathological changes of the mice were used to verify that treatment with CEP might significantly reduce BLM-induced fibrosis. Furthermore, flow cytometric analysis was used to analyze the changes in the number of M2 macrophages in the lung tissues before and after treatment with CEP to explore the relationship between macrophage M2 polarization and pulmonary fibrosis. In vitro, we constructed two co-culture systems (THP-1 and MRC5 cells, RAW264.7 and NIH 3T3 cells), and measured the expression of fibrosis-related proteins to explore whether CEP could reduce pulmonary fibrosis by regulating macrophage M2 polarization and fibroblast activation. Results The results showed that the intranasal treatment of CEP significantly attenuated the symptoms of pulmonary fibrosis induced by BLM in a murine model. Our findings also indicated that CEP treatment markedly reduced the expression of fibrosis markers, including TGF-β1, collagen I, fibronectin and α-SMA, in the mouse lung. Furthermore, in vitro studies demonstrated that CEP attenuated pulmonary fibrosis by inhibiting fibroblast activation through modulating macrophage M2 polarization and reducing TGF-β1 expression. Conclusions This study demonstrated the potential and efficacy of CEP in the treatment of pulmonary fibrosis. In particular, this study revealed a novel mechanism of CEP in inhibiting fibroblast activation by regulating macrophage M2 polarization and reducing the expression of fibrosis-associated factors. Our findings open a new direction for future research into the treatment of pulmonary fibrosis.

Abstract Non-alcoholic Fatty Liver Disease (NAFLD), noted for its widespread prevalence among adults, has become the leading chronic liver condition globally. Simultaneously, the annual disease burden, particularly liver cirrhosis caused by NAFLD, has increased significantly. Neutrophil Extracellular Traps (NETs) play a crucial role in the progression of this disease and are key to the pathogenesis of NAFLD. However, research into the specific roles of NETs-related genes in NAFLD is still a field requiring thorough investigation. Utilizing techniques like AddModuleScore, ssGSEA, and WGCNA, our team conducted gene screening to identify the genes linked to NETs in both single-cell and bulk transcriptomics. Using algorithms including Random Forest, Support Vector Machine, Least Absolute Shrinkage, and Selection Operator, we identified ZFP36L2 and PHLDA1 as key hub genes. The pivotal role of these genes in NAFLD diagnosis was confirmed using the training dataset GSE164760. This study identified 116 genes linked to NETs across single-cell and bulk transcriptomic analyses. These genes demonstrated enrichment in immune and metabolic pathways. Additionally, two NETs-related hub genes, PHLDA1 and ZFP36L2, were selected through machine learning for integration into a prognostic model. These hub genes play roles in inflammatory and metabolic processes. scRNA-seq results showed variations in cellular communication among cells with different expression patterns of these key genes. In conclusion, this study explored the molecular characteristics of NETs-associated genes in NAFLD. It identified two potential biomarkers and analyzed their roles in the hepatic microenvironment. These discoveries could aid in NAFLD diagnosis and management, with the ultimate goal of enhancing patient outcomes.

Abstract Background Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy. Methods Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI. Results By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections. Conclusions Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts. Graphical Abstract

Abstract Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m−1 K−1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V−1 s−1. Such carrier-phonon decoupling behaviors enable the greatly enhanced μ W/κ L of ~5.2 × 103 cm3 K J−1 V−1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

Abstract Seed vigor is a complex trait encompassing seed germination, seedling emergence, growth, seed longevity, and stress tolerance, all are crucial for direct seeding in rice. Here, we report that the AP2/ERF transcription factor OsRAV1 (RELATED TO ABI3 AND VP1) positively regulates seed germination, vigor, and salt tolerance. Additionally, OsRAV1 was differently expressed in embryo and endosperm, with the OsRAV1 localized in the nucleus. Transcriptomic analysis revealed that OsRAV1 modulates seed vigor through plant hormone signal transduction and phenylpropanoid biosynthesis during germination. Haplotype analysis showed that rice varieties carrying Hap3 displayed enhanced salt tolerance during seed germination. These findings suggest that OsRAV1 is a potential target in breeding rice varieties with high seed vigor suitable for direct seeding cultivation.

Abstract Background Benzyl acetate is an aromatic ester with a jasmine scent. It was discovered in plants and has broad applications in food, cosmetic, and pharmaceutical industries. Its current production predominantly relies on chemical synthesis. In this study, Escherichia coli was engineered to produce benzyl acetate. Results Two biosynthetic routes based on the CoA-dependent β-oxidation pathway were constructed in E. coli for benzyl acetate production. In route I, benzoic acid pathway was extended to produce benzyl alcohol by combining carboxylic acid reductase and endogenous dehydrogenases and/or aldo-keto reductases in E. coli. Benzyl alcohol was then condensed with acetyl-CoA by the alcohol acetyltransferase ATF1 from yeast to form benzyl acetate. In route II, a plant CoA-dependent β-oxidation pathway via benzoyl-CoA was assessed for benzyl alcohol and benzyl acetate production in E. coli. The overexpression of the phosphotransacetylase from Clostridium kluyveri (CkPta) further improved benzyl acetate production in E. coli. Two-phase extractive fermentation in situ was adopted and optimized for benzyl acetate production in a shake flask. The most optimal strain produced 3.0 ± 0.2 g/L benzyl acetate in 48 h by shake-flask fermentation. Conclusions We were able to establish the whole pathway for benzyl acetate based on the CoA-dependent β-oxidation in single strain for the first time. The highest titer for benzyl acetate produced from glucose by E. coli is reported. Moreover, cinnamyl acetate production as an unwanted by-product was very low. Results provided novel information regarding the engineering benzyl acetate production in microorganisms. Graphical abstract

Abstract. Background:. Accurately and efficiently extracting microbial genomic sequences from complex metagenomic data is crucial for advancing our understanding in fields such as clinical diagnostics, environmental microbiology, and biodiversity. As sequencing technologies evolve, this task becomes increasingly challenging due to the intricate nature of microbial communities and the vast amount of data generated. Especially in intensive care units (ICUs), infections caused by antibiotic-resistant bacteria are increasingly prevalent among critically ill patients, significantly impacting the effectiveness of treatments and patient prognoses. Therefore, obtaining timely and accurate information about infectious pathogens is of paramount importance for the treatment of patients with severe infections, which enables precisely targeted anti-infection therapies, and a tool that can extract microbial genomic sequences from metagenomic dataset would be of help. Methods:. We developed MetaGeneMiner to help with retrieving specific microbial genomic sequences from metagenomes using a k-mer-based approach. It facilitates the rapid and accurate identification and analysis of pathogens. The tool is designed to be user-friendly and efficient on standard personal computers, allowing its use across a wide variety of settings. We validated MetaGeneMiner using eight metagenomic samples from ICU patients, which demonstrated its efficiency and accuracy. Results:. The software extensively retrieved coding sequences of pathogens Acinetobacter baumannii and herpes simplex virus type 1 and detected a variety of resistance genes. All documentation and source codes for MetaGeneMiner are freely available at https://gitee.com/sculab/MetaGeneMiner. Conclusions:. It is foreseeable that MetaGeneMiner possesses the potential for applications across multiple domains, including clinical diagnostics, environmental microbiology, gut microbiome research, as well as biodiversity and conservation biology. Particularly in ICU settings, MetaGeneMiner introduces a novel, rapid, and precise method for diagnosing and treating infections in critically ill patients. This tool is capable of efficiently identifying infectious pathogens, guiding personalized and precise treatment strategies, and monitoring the development of antibiotic resistance, significantly impacting the diagnosis and treatment of severe infections.

High-entropy alloys (HEAs) provides a new way to develop new materials with adjustable performance due to their unique cocktail effect. Inspired by HEAs, a ceramic material with high-entropy effect has been developed, which was named high-entropy ceramics (HECs). With the introduction of the concept of entropy stability, research on HECs has developed rapidly. At present, research on the performance of HECs has extended to traditional performance such as thermomechanical performance, oxidation resistance, and magnetic properties, as well as emerging performance such as catalytic performance, optical properties, and radiation resistance. Based on the definition of HECs, this paper reviews the crystal structure and preparation methods of HECs and supplements the simulation calculation methods and descriptors which is suitable for HECs. In this paper, the performance of HECs at this stage is divided into traditional fields and emerging fields according to the application fields. A variety of performance regulation methods are reviewed, and the development and research directions of HECs are prospected.

Honeycomb structures have been widely used in aerospace and automotive applications due to their high efficiency, high strength and high specific stiffness. However, most of the reported publications have focused on the surface shape variations of honeycomb structures, and there is a lack of studies on the variations of honeycomb structures with respect to the internal cell walls (Z-direction). To address these issues, this study proposes to combine the torsional design of honeycomb and Bouligand structures to fabricate twisted honeycomb structures (THS) with cell wall (z-direction) variations using powder bed fusion technology. The THS (30°) exhibits excellent specific energy absorption (SEA) performance, and the SEA of THS (0°), THS (60°), and THS (90°) are reduced by 8.5%, 19.7%, and 37.3%, respectively, compared with that of THS (30°) structure, and the THS (30°) has better repeatability. The effects of structural parameters on the energy absorption performance were analyzed. At THS (30°), changing the number of unit cells, wall length and wall thickness has a large effect on the compression performance. The results show that the specific energy absorption performance of THS reaches a maximum value of 74.6 kJ/kg for the number unit cells n = 3, wall length l = 5 mm and wall thickness t = 1 mm.

Artificial Intelligence (AI) Machine Learning (ML) technologies, particularly Deep Learning (DL), have demonstrated significant potential in the interpretation of Remote Sensing (RS) imagery, covering tasks such as scene classification, object detection, land-cover/land-use classification, change detection, and multi-view stereo reconstruction. Large-scale training samples are essential for ML/DL models to achieve optimal performance. However, the current organization of training samples is ad-hoc and vendor-specific, lacking an integrated approach that can effectively manage training samples from different vendors to meet the demands of various RS AI tasks. This article proposes a solution to address these challenges by designing and implementing LuoJiaSET, a large-scale training sample database system for intelligent interpretation of RS imagery. LuoJiaSET accommodates over five million training samples, providing support for cross-dataset queries and serving as a comprehensive training data store for RS AI model training and calibration. It overcomes challenges related to label semantic categories, structural heterogeneity in label representation, and interoperable data access.

Studies addressing the anatomical values of the supraspinatus outlet area (SOA) and the available supraspinatus outlet area (ASOA) are insufficient. This study focused on precisely measuring the SOA and ASOA values in a sample from the Chinese population using 3D CT (computed tomography) reconstruction. We analyzed CT imaging of 96 normal patients (59 males and 37 females) who underwent shoulder examinations in a hospital between 2011 and 2021. The SOA, ASOA, acromiohumeral distance (AHD), coracohumeral distance (CHD), coracoacromial arch radius (CAR), and humeral head radius (HHR) were estimated, and statistical correlation analyses were performed. There were significant sex differences observed in SOA (men: 957.62 ± 158.66 mm2; women: 735.87 ± 95.86 mm2) and ASOA (men: 661.35 ± 104.88 mm2; women: 511.49 ± 69.26 mm2), CHD (men: 11.22 ± 2.24 mm; women: 9.23 ± 1.35 mm), CAR (men: 37.18 ± 2.70 mm; women: 33.04 ± 3.15 mm), and HHR (men: 22.65 ± 1.44 mm; women: 20.53 ± 0.95 mm). Additionally, both SOA and ASOA showed positive and linear correlations with AHD, CHD, CAR, and HHR (R: 0.304–0.494, all p < 0.05). This study provides physiologic reference values of SOA and ASOA in the Chinese population, highlighting the sex differences and the correlations with shoulder anatomical parameters.

Objectives: With the development of the manufacturing industry, precision grinding has become an indispensable part of the high-end manufacturing field. As a key tool for precision grinding, the surface reshaping technology of diamond rollers is one of the critical technologies for making diamond rollers. Currently, the diamond grinding wheel grinding method is commonly used for diamond roller precision reshaping. In the process of precision reshaping, the surface profile of the diamond roller is an important indicator for assessing its reshaping quality. However, in the current reshaping detection, the workers often stop the machine to remove the rollers and place them on the profiler, which greatly increases the time and the cost of roller reshaping. Therefore, to improve the efficiency of diamond roller reshaping, a method based on sensors to monitor the state of contour reshaping during the process of diamond roller reshaping is explored. Methods: To realize online monitoring and discrimination of the diamond roller contour reshaping state, the diamond roller grinding monitoring platform was first built according to the structure of the GC-X3 machine tool, and LabVIEW was used to read and save the signals collected by the acquisition card. Secondly, the diamond rollers with different contour reshaping states were processed by the GC-X3 machine tool, and the signals with different reshaping states collected by the computer were analyzed in time and frequency domains. The wavelet packet decomposition method was used to decompose the signals according to the characteristics of time and frequency domains, and the signals of different nodes obtained after decomposition were calculated and compared to identify and determine the characteristic values of the signals. Finally, the machine learning method was used to establish the recognition model of the diamond roller contour reshaping state. The model is based on the mapping relationship between the characteristic values of the vibration signals and the contour reshaping state to realize the intelligent recognition of the contour reshaping state of the diamond roller. Results: After preprocessing the signal, it can be observed through the time and the frequency domains that the maximum amplitudes of the X and Y axis vibration signals decrease with the improvement of the roller profile accuracy. The amplitudes of the X and Y axis vibration signals during rough trimming are 1.00 and 0.50 V, respectively. The amplitudes of the X and Y axis vibration signals during fine trimming are 0.50 and 0.40 V, respectively. The amplitudes of X and Y axis vibration signals at the completion of trimming are 0.29 and 0.27 V respectively, and the main frequencies of signals at the completion of rough, fine, and finishing are all distributed within 1 000 Hz. The root mean square and the variance of wavelet packet coefficients mainly occur at nodes (3,0) to (3,3), and as the grinding accuracy increases, the root mean square and the variance of wavelet packet coefficients decrease gradually. When rough trimming diamond rollers with diamond grinding wheels, the roundness error value of the roller profile is larger than that after fine trimming and the completion of trimming, resulting in a larger local grinding allowance. A large number of abrasive particles from the diamond grinding wheel come into contact with the roller, which increases the material removal amount of the diamond roller, the grinding force also increases, and the resulting vibration also increases accordingly. During the fine trimming process, the roundness error of the roller contour is reduced, so that the diamond wheel cutting the diamond roller allowance is reduced, the removal amount is also reduced, the grinding force is reduced, and the vibration generated is also reduced. At the same time, the root mean square and the variance of the wavelet packet coefficients in the completion of trimming decrease correspondingly as the roundness error value of the roller profile decreases. As the trend and fluctuation of the root mean square and the variance of the wavelet packet coefficients in the X and Y axes are generally consistent, the root mean square and the variance of the wavelet packet coefficients in the direction of the X-axis are selected as the feature vectors for the classification of experimental data. The wavelet packet is used to decompose the X-axis signal, and the variance and the root mean square of each node are calculated to obtain 16 characteristic values of the vibration signal. There is a mapping relationship between these characteristic values and the reshaping state of the roller, and the random forest algorithm is used to classify the vibration signals based on these 16 characteristic values, and the recognition accuracy reaches 93.3%. Conclusions: The contour reshaping of the diamond roller is the key to the production of diamond rollers. In the process of roller machining, the method combining sensor monitoring and machine learning models is used to judge the reshaping state of the diamond roller. The method can be used to identify the modified state of the diamond roller profile, reduce the number of roller disassemblies and roller profile detections, and improve the processing efficiency.

Abstract Recent studies have suggested that mRNA internal m7G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m7G. Such interactions, especially IGF2BP3 with m7G, could promote the degradation of m7G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m7G modification, while IGF2BP1 prefers m6A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53, is m7G-modified at its 3’UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m7G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.

Abstract The marine ecological red lines (MERLs) is an institutional innovation of the Chinese government to seek a balance between ecological protection and social development. China’s MERLs was designated in 2017, but there are problems such as insufficient consideration of areas of high ecological importance and lack of convergence with marine functional zoning. This paper carries out the adjustment of the MERLs in China by constructing the methods of marine ecological importance assessment and human activities disposal assessment, and the results show that after the adjustment, the type and distribution pattern of China’s MERLs is more reasonable, the areas of high ecological importance in the MERLs increases significantly, the intensity of human activities in the MERLs declines significantly, and the unification with the use of marine space is realized. China’s adjustment of the MERLs is based on scientific assessment and realizes the coordination of development and protection, which can provide a reference for global marine ecological protection.

Abstract Background The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet. Methods 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017–2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram. Results In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11–2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04–3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745–0.819), which was assessed by DCA to be clinically important. Conclusion In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

Abstract Accurate fluorescence imaging of nanocarriers in vivo remains a challenge owing to interference derived mainly from biological tissues and free probes. To address both issues, the current study explored fluorophores in the near-infrared (NIR)-II window with aggregation-caused quenching (ACQ) properties to improve imaging accuracy. Candidate fluorophores with NIR-II emission, ACQ984 (λ em = 984 nm) and IR-1060 (λ em = 1060 nm), from the aza-BODIPY and cyanine families, respectively, were compared with the commercial fluorophore ICG with NIR-II tail emission and the NIR-I fluorophore P2 from the aza-BODIPY family. ACQ984 demonstrates high water sensitivity with complete fluorescence quenching at a water fraction greater than 50%. Physically embedding the fluorophores illuminates various nanocarriers, while free fluorophores cause negligible interference owing to the ACQ effect. Imaging based on ACQ984 revealed fine structures in the vascular system at high resolution. Moreover, good in vivo and ex vivo correlations in the monitoring of blood nanocarriers can be established, enabling real-time noninvasive in situ investigation of blood pharmacokinetics and dynamic distribution in various tissues. IR-1060 also has a good ACQ effect, but the lack of sufficient photostability and steady post-labeling fluorescence undermines its potential for nanocarrier bioimaging. P2 has an excellent ACQ effect, but its NIR-I emission only provides nondiscriminative ambiguous images. The failure of the non-ACQ probe ICG to display the biodistribution details serves as counterevidence for the improved imaging accuracy by NIR-II ACQ probes. Taken together, it is concluded that fluorescence imaging of nanocarriers based on NIR-II ACQ probes enables accurate in vivo bioimaging and real-time in situ pharmacokinetic analysis.

Abstract Derived from enteroendocrine cells (EECs), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are pivotal incretin hormones crucial for blood glucose regulation. Medications of GLP-1 analogs and GLP-1 receptor activators are extensively used in the treatment of type 2 diabetes (T2D) and obesity. However, there are currently no agents to stimulate endogenous incretin secretion. Here, we find the pivotal role of KCNH2 potassium channels in the regulation of incretin secretion. Co-localization of KCNH2 with incretin-secreting EECs in the intestinal epithelium of rodents highlights its significance. Gut epithelial cell-specific KCNH2 knockout in mice improves glucose tolerance and increases oral glucose-triggered GLP-1 and GIP secretion, particularly GIP. Furthermore, KCNH2-deficient primary intestinal epithelial cells exhibit heightened incretin, especially GIP secretion upon nutrient stimulation. Mechanistically, KCNH2 knockdown in EECs leads to reduced K+ currents, prolonged action potential duration, and elevated intracellular calcium levels. Finally, we found that dofetilide, a KCNH2-specific inhibitor, could promote incretin secretion in enteroendocrine STC-1 cells in vitro and in hyperglycemic mice in vivo. These findings elucidate, for the first time, the mechanism and application of KCNH2 in regulating incretin secretion by EECs. Given the therapeutic promise of GLP-1 and GIP in diabetes and obesity management, this study advances our understanding of incretin regulation, paving the way for potential incretin secretagogue therapies in the treatment of diabetes and obesity.

Abstract Timely and effective diagnosis of fungal keratitis (FK) is necessary for suitable treatment and avoiding irreversible vision loss for patients. In vivo confocal microscopy (IVCM) has been widely adopted to guide the FK diagnosis. We present a deep learning framework for diagnosing fungal keratitis using IVCM images to assist ophthalmologists. Inspired by the real diagnostic process, our method employs a two-stage deep architecture for diagnostic predictions based on both image-level and sequence-level information. To the best of our knowledge, we collected the largest dataset with 96,632 IVCM images in total with expert labeling to train and evaluate our method. The specificity and sensitivity of our method in diagnosing FK on the unseen test set achieved 96.65% and 97.57%, comparable or better than experienced ophthalmologists. The network can provide image-level, sequence-level and patient-level diagnostic suggestions to physicians. The results show great promise for assisting ophthalmologists in FK diagnosis.

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

Abstract Objective The present study aimed to identify various distinguishing features for use in the accurate classification of stereoelectroencephalography (SEEG) channels based on high‐frequency oscillations (HFOs) inside and outside the epileptogenic zone (EZ). Methods HFOs were detected in patients with focal epilepsy who underwent SEEG. Subsequently, HFOs within the seizure‐onset and early spread zones were defined as pathological HFOs, whereas others were defined as physiological. Three features of HFOs were identified at the channel level, namely, morphological repetition, rhythmicity, and phase–amplitude coupling (PAC). A machine‐learning (ML) classifier was then built to distinguish two HFO types at the channel level by application of the above‐mentioned features, and the contributions were quantified. Further verification of the characteristics and classifier performance was performed in relation to various conscious states, imaging results, EZ location, and surgical outcomes. Results Thirty‐five patients were included in this study, from whom 166 104 pathological HFOs in 255 channels and 53 374 physiological HFOs in 282 channels were entered into the analysis pipeline. The results revealed that the morphological repetitions of pathological HFOs were markedly higher than those of the physiological HFOs; this was also observed for rhythmicity and PAC. The classifier exhibited high accuracy in differentiating between the two forms of HFOs, as indicated by an area under the curve (AUC) of 0.89. Both PAC and rhythmicity contributed significantly to this distinction. The subgroup analyses supported these findings. Significance The suggested HFO features can accurately distinguish between pathological and physiological channels substantially improving its usefulness in clinical localization. Plain Language Summary In this study, we computed three quantitative features associated with HFOs in each SEEG channel and then constructed a machine learning‐based classifier for the classification of pathological and physiological channels. The classifier performed well in distinguishing the two channel types under different levels of consciousness as well as in terms of imaging results, EZ location, and patient surgical outcomes.

Abstract Background Atherosclerosis and metabolic syndrome are the main causes of cardiovascular events, but their underlying mechanisms are not clear. In this study, we focused on identifying genes associated with diagnostic biomarkers and effective therapeutic targets associated with these two diseases. Methods Transcriptional data sets of atherosclerosis and metabolic syndrome were obtained from GEO database. The differentially expressed genes were analyzed by RStudio software, and the function-rich and protein-protein interactions of the common differentially expressed genes were analyzed.Furthermore, the hub gene was screened by Cytoscape software, and the immune infiltration of hub gens was analyzed. Finally, relevant clinical blood samples were collected for qRT-PCR verification of the three most important hub genes. Results A total of 1242 differential genes (778 up-regulated genes and 464 down-regulated genes) were screened from GSE28829 data set. A total of 1021 differential genes (492 up-regulated genes and 529 down-regulated genes) were screened from the data set GSE98895. Then 23 up-regulated genes and 11 down-regulated genes were screened by venn diagram. Functional enrichment analysis showed that cytokines and immune activation were involved in the occurrence and development of these two diseases. Through the construction of the Protein–Protein Interaction(PPI) network and Cytoscape software analysis, we finally screened 10 hub genes. The immune infiltration analysis was further improved. The results showed that the infiltration scores of 7 kinds of immune cells in GSE28829 were significantly different among groups (Wilcoxon Test 0.3 & P 0.3 & P

Abstract Aims Both hypercapnia and hypocapnia are common in patients with acute heart failure (AHF), but the association between partial pressure of arterial carbon dioxide (PaCO2) and AHF prognosis remains unclear. The objective of this study was to investigate the connection between PaCO2 within 24 h after admission to the intensive care unit (ICU) and mortality during hospitalization and at 1 year in AHF patients. Methods and results AHF patients were enrolled from the Medical Information Mart for Intensive Care IV database. The patients were divided into three groups by PaCO2 values of 45 mmHg. The primary outcome was to investigate the connection between PaCO2 and in‐hospital mortality and 1 year mortality in AHF patients. The secondary outcome was to assess the prediction value of PaCO2 in predicting in‐hospital mortality and 1 year mortality in AHF patients. A total of 2374 patients were included in this study, including 457 patients in the PaCO2 45 mmHg group. The in‐hospital mortality was 19.5%, and the 1 year mortality was 23.9% in the PaCO2 45 mmHg group was associated with an increased risk of in‐hospital mortality (HR 1.387, 95% CI 1.050–1.832, P = 0.021); the 1 year mortality showed no significant difference (HR 1.286, 95% CI 0.995–1.662, P = 0.055) compared with the PaCO2 = 35–45 mmHg group. The Kaplan–Meier survival curves showed that the PaCO2

Background: Cereal crops are a primary energy source for humans. Grain size and weight affect both evolutionary fitness and grain yield of cereals. Although studies on gene mining and molecular mechanisms controlling grain size and weight are constantly emerging in cereal crops, only a few systematic reviews on the underlying molecular mechanisms and their breeding applications are available so far. Aim of review: This review provides a general state-of-the-art overview of molecular mechanisms and targeted strategies for improving grain size and weight of cereals as well as insights for future yield-improving biotechnology-assisted breeding. Key scientific concepts of review: In this review, the evolution of research on grain size and weight over the last 20 years is traced based on a bibliometric analysis of 1158 publications and the main signaling pathways and transcriptional factors involved are summarized. In addition, the roles of post-transcriptional regulation and photosynthetic product accumulation affecting grain size and weight in maize and rice are outlined. State-of-the-art strategies for discovering novel genes related to grain size and weight in maize and other cereal crops as well as advanced breeding biotechnology strategies being used for improving yield including marker-assisted selection, genomic selection, transgenic breeding, and genome editing are also discussed.

Reducing fertilizer-N rate, applying a nitrification inhibitor (NI), and incorporating straw are widely recommended to improve N use efficiency of crops and decrease N losses. A field 15N tracer study was conducted to compare their effectiveness on fertilizer-N fates during the maize growing season in Northeast China. The following six treatments were used: (1) no N fertilization (control); (2) 200 kg urea-N ha−1 (100%N); (3) 200 kg urea-N ha−1 and straw (100%N + S); (4) 160 kg urea-N ha−1 (80%N); (5) 160 kg urea-N ha−1 and NI (Nitrapyrin in this study) (80%N + NI); and (6) 160 kg urea-N ha−1, NI, and straw (80%N + NI + S). The results showed that the five N fertilization treatments yielded 16–25% more grain and 39–60% more crop N uptake than the control, but the differences among the five treatments were not statistically significant. Compared with the 100%N, 20% fertilizer-N reduction (80%N) decreased the 15N concentration in topsoil and plant pools but increased the proportion of plant 15N recovery at harvesting (NUE15N, 60% vs. 50%). Compared with the 80%N, NI co-application (80%N + NI) delayed soil nitrification and increased soil 15N retention at harvesting (52% vs. 36%), thereby decreasing NUE15N significantly. Straw incorporation decreased fertilizer-N retention in soil compared with NI co-application because it promoted NUE15N significantly. In conclusion, the results demonstrate that NI and straw additions are efficient strategies for stabilizing fertilizer-N in soils and potentially minimizing N loss; however, their effects on NUE15N vary and the related mechanism must be further clarified in long-term trials.

Abstract Background Healthcare-associated infections (HAIs) are important indicators of healthcare quality. The aseptic non touch technique (ANTT), a standardised aseptic technique, is a crucial preventative measure against HAIs. However, there is insufficient evidence currently available regarding ANTT awareness and proficiency among nurses. This study aimed to investigate the status of ANTT proficiency in a cohort of nurses and analyse the associated risk factors, with the ultimate goal of providing a reference for promoting the application of ANTT in clinical practice. Methods The study population was sampled from nurses working in a tertiary hospital in Zhejiang Province, China, in January 2024. A cross-sectional survey was conducted using a self-designed questionnaire to assess ANTT knowledge. Multivariate linear regression analysis was used to analyse the risk factors influencing ANTT knowledge in nurses. Results A total of 458 nurses were included in this study. The cohort had an overall score of 49.7% correct responses on the ANTT knowledge questionnaire, with a mean score of 12.4 ± 2.4 out of 25, and 30.1% of the nurses felt that they did not need training related to ANTT. Multivariate linear regression analysis indicated that professional title, educational level, and the need for ANTT training were independently associated with ANTT knowledge in nurses. Nurses with Master’s degrees and associated chief nurses were observed to have higher levels of ANTT knowledge compared to the rest. Conclusions ANTT knowledge is insufficient among nurses in China, and its importance is not widely recognised. Continuous efforts are required to strengthen this knowledge. Constructing sustained, multiform, and stratified training programmes may represent an effective method to strengthen ANTT knowledge among nurses and promote its clinical use.

Abstract Background Herpes zoster is an infectious skin disease caused by the reactivation of the varicella zoster virus (VZV), which has been latent in the posterior root ganglia of the spinal cord or cranial ganglia for an extended period. Neurological complications caused by herpes zoster include aseptic meningitis, white matter disease, peripheral motor neuropathy, and Guillain-Barré syndrome. However, reduced unilateral sweating caused by the VZV is very rare. Case Presentation This article reports the case of a 34-year-old woman who was admitted to our hospital with sore throat, dizziness, and reduced sweating on the left side of her body. Physical examination found herpes lesions on the left upper lip and left external ear canal (scabbed) and reduced sweating on the left side of the body. Head magnetic resonance imaging (MRI) with contrast showed no abnormalities. After a lumbar puncture, the patient was diagnosed with viral meningitis by VZV infection. The electromyographic skin sympathetic reflex indicated damage to the left sympathetic nerve. Conclusions Secondary unilateral sweating reduction is a rare neurological complication of herpes zoster, caused by damage to the autonomic nervous system. Literature review and comprehensive examination indicated that the reduced unilateral sweating was due to the activation of latent herpes zoster virus in the autonomic ganglia which has damaged the autonomic nervous system. For patients who exhibit acute hemibody sweat reduction, doctors should consider the possibility of secondary autonomic nervous system damage caused by herpes zoster.

The purpose of this research was to determine wheat quality characteristics of individual flour flow in low-temperature flour system, which could provide reference and basis for the production of different special wheat flour. In this study, 12 flour flows samples and channel flour (the market product of this batch) in the low-temperature milling system were taken as the research object, their quality characteristics and dough rheological properties were measured to compare and analyze the quality differences between different flour flows. 12 flour flows include 4 break flour flow, 6 reduction flour flows, 1 slag- grinding flour flow and 1 tail-grinding flour flow. The results showed that the brightness of 1M、2M、3M of reduction flour flows and slag- grinding flour flow were brighter than those of other flour flows; the protein content, wet gluten content and gluten index of reduction flour flow were generally lower than those of break flour flow; the ash and damaged starch of head flour flow in the reduction and break system were lower than those of final flour flow, and the peak viscosity was higher than that of final flour flow. The water absorption of 500 FU of final flour flow in the reduction and break system were higher than those of head flour flow; the P value, W value, L value, G value, energy and maximum resistance of break flour flows were generally higher than those of the reduction flour flows, but the extensibility of wheat flour was generally lower than those of the reduction flour flows.

Abstract The purpose of this study was to compare the effects of High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) on weight, body composition, blood lipid indicators, and metabolic status in college students living with obesity. The study focused on a sample of 40 college students living with obesity, including 20 males and 20 females, aged between 18 and 25. Participants were randomly assigned to either the HIIT group or the MICT group. Both groups underwent an 8-week intervention, consisting of three sessions per week with alternate-day training. The MICT group's training consisted of continuous aerobic exercise for 35 min at 60–70% of maximum heart rate. The HIIT group engaged in 28 min of alternating high-intensity and low-intensity exercise, where the high-intensity phase was at 85–90% of maximum heart rate for 4 min, followed by a 3-min recovery period at 50–60% of maximum heart rate, repeated four times. Both groups underwent heart rate monitoring before and after the training sessions to ensure the accuracy of the training intensity. Within each group, further distinctions were made based on gender, resulting in the following subgroups: Male HIIT group (n = 10), Female HIIT group (n = 10), Male MICT group (n = 10), and Female MICT group (n = 10). Differences in anthropometric and biochemical indicators among the groups were analyzed, and the different effects of the two intervention strategies on the obese college student population were comprehensively evaluated. Compared to the baseline assessment, the HIIT group showed a more favorable declining trend than the MICT group in terms of body morphology and body composition, particularly in the aspect of body fat percentage (BF%). The male HIIT group, female HIIT group, male MICT group, and female MICT group respectively reduced by − 23.71%, − 26.76%, − 9.81%, − 7.16%. Male and female HIIT group experienced a more pronounced decrease compared to the MICT group, with the female HIIT group reducing an additional 3.75% more than the male HIIT group. Regarding intergroup differences, BF% significant differences were shown between male MICT group and the HIIT group (P