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Abstract Glycosylation, a key mode of protein modification in living organisms, is critical in regulating various biological functions by influencing protein folding, transportation, and localization. Changes in glycosylation patterns are a significant feature of cancer, are associated with a range of pathological activities in cancer‐related processes, and serve as critical biomarkers providing new targets for cancer diagnosis and treatment. Glycoproteins like human epidermal growth factor receptor 2 (HER2) for breast cancer, alpha‐fetoprotein (AFP) for liver cancer, carcinoembryonic antigen (CEA) for colon cancer, and prostate‐specific antigen (PSA) for prostate cancer are all tumor biomarkers approved for clinical use. Here, we introduce the diversity of glycosylation structures and newly discovered glycosylation substrate—glycosylated RNA (glycoRNA). This article focuses primarily on tumor metastasis, immune evasion, metabolic reprogramming, aberrant ferroptosis responses, and cellular senescence to illustrate the role of glycosylation in cancer. Additionally, we summarize the clinical applications of protein glycosylation in cancer diagnostics, treatment, and multidrug resistance. We envision a promising future for the clinical applications of protein glycosylation.

Abstract Rapid urbanization has significantly altered landscape environments in both urban and rural regions, and these landscapes have been demonstrated to play a pivotal role in human well-being. This study develops a coherent framework that integrates landscape change, landscape ecological indicators, and landscape preferences within the context of the evolving landscape environments of rural communities in Taiwan. Four distinct types of rural communities were selected, and a quantitative methodology was employed to investigate the variations and transformations in landscape preferences among rural residents in the context of landscape change. A qualitative methodology was employed to investigate the relationship between landscape ecological indicators and landscape preferences. The study’s findings indicate significant temporal variations in residents’ landscape preferences, with landscape beauty, stewardship, and coherence emerging as key determinants in the evaluation of these preferences. Landscape ecological indicators were found to be significantly correlated with variables such as landscape complexity, landscape beauty, openness, naturalness, and comprehensive landscape assessment. The findings of this study indicate that design planners, land managers, and public sector organizations can employ multidimensional thinking in the management of rural landscapes to align with the visual aesthetic preferences of rural residents.

Abstract Background Atypical squamous cells of undetermined significance (ASC-US) often present diagnostic challenges with cytology-based results, leading to potential underdiagnosis or overdiagnosis. An effective triage method is essential for managing these cases to reduce unnecessary referrals and treatment. Methods A total of 322 women diagnosed with ASC-US were tested for HPV-DNA and the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test in the study. Results Methylation levels of PAX1 and JAM3 were significantly elevated in cervical lesions classified as CIN2 or more severe lesions (CIN2+). The methylation assay demonstrated a sensitivity of 83.8% and a specificity of 95.8%, outperforming HPV-DNA testing in differentiating high-grade cervical lesions among women with ASC-US. Moreover, PAX1 m /JAM3 m testing significantly reduced the colposcopy referral rate for further diagnostic procedures in high-risk HPV-positive women by 79.5%. Conclusions PAX1 m /JAM3 m testing shows promise as a reliable supplemental method to HPV-DNA testing for the triage of women with cytologic ASC-US. In addition, the molecular triage based on the CISCER assay or single PAX1 or JAM3 methylation, had better effects in the women with non-HPV16/18 group. This approach could potentially minimize overtreatment and unnecessary referrals in clinical practice, enhancing patient management and resource utilization.

Abstract Background Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The purpose of the present study is to evaluate the role of melatonin in alleviating HS-induced spermatogenesis dysfunction in male dairy goats and further explore its mechanism. Results HS impaired spermatogenesis, sperm formation in the testes, and sperm maturation in the epididymis of dairy goats, resulting in decreased sperm quality. Melatonin rescued the decrease of sperm quality induced by HS via decreasing inflammatory and oxidative stress levels in testicular tissue and enhancing intercellular barrier function within the testes. Amplicon-based microbiota analysis revealed that despite gut microbiota differences between melatonin-treated dairy goats and NC dairy goats to some extent, melatonin administration tends to return the gut microbiota of male dairy goats under HS to the levels of natural control dairy goats. To explore whether the protective role of melatonin in sperm quality is mediated by regulating gut microbiota, fecal microbiota of HS dairy goats with or without melatonin treatment were transferred to HS mice, respectively. We found HS mice that had received fecal bacteria of HS dairy goats experienced serious testicular injury and dyszoospermia, while this phenomenon was ameliorated in HS mice that had received fecal bacteria of dairy goats treated with melatonin, indicating melatonin alleviates HS-induced spermatogenic damage in a microbiota dependent manner. We further found that the testicular tissue of both HS dairy goats and mice transplanted with HS dairy goat feces produced large amounts of arachidonic acid (AA)-related metabolites, which were closely associated with semen quality. Consistently, supplementation with AA has been shown to elevate the levels of inflammation and oxidative stress in the testicular tissue of mice, disrupting intercellular connections and ultimately leading to spermatogenic disorders. Conclusion This study has revealed that melatonin can effectively alleviate spermatogenic disorders in dairy goats caused by HS. This beneficial effect was primarily achieved through the modulation of gut microbiota, which subsequently inhibited the excessive synthesis of AA in testicular tissue. These discoveries are of great significance for preventing or improving the decline in male livestock reproductive performance caused by HS, enhancing the reproductive efficiency of elite male breeds, and ultimately improving the production efficiency of animal husbandry. Video Abstract

Abstract Background This study aimed to examine the association between the American Heart Association’s (AHA) newly revised Life’s Essential 8 (LE8) algorithm, designed for assessing cardiovascular health (CVH), and cognitive impairment among older adults in the United States. Methods This study employed a cross-sectional design, utilizing data from the 2011–2014 National Health and Nutrition Examination Survey to explore the relationship between CVH and cognitive impairment in older adults. CVH scores are assessed based on the AHA definition of the LE8, categorized into three tiers: low (0–49), medium (50–79), and high (80–100). Cognitive impairment is evaluated using three distinct scoring systems: the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The lowest quartile as the cut-off point; below or equal to the lower quartile was considered as low cognitive population, and above the lower quartile was normal population. To analyze the association, multivariable logistic regression and restricted cubic spline (RCS) models were employed. Results A significant negative correlation exists between the LE8 and cognitive impairment. After adjusting for multiple variables, the odds ratios (OR) for cognitive impairment, as measured by the CERAD, AFT, and DSST, were compared between patients with high and low CVH. The results indicated OR values of 0.60 (95% CI: 0.36–0.98), 0.72 (95% CI: 0.52–0.97), and 0.29 (95% CI: 0.16–0.53) for the CERAD, AFT, and DSST, respectively. Additionally, the RCS curve demonstrated a significant linear relationship between lifestyle factors encapsulated by the LE8 and cognitive impairment. Conclusions The findings indicate higher adherence to LE8 was associated with lower odds of cognitive impairment. Furthermore, maintaining optimal CVH is crucial in preventing cognitive impairment.

Abstract Background Many studies have indicated that abnormal bone mineral density (BMD) is related to abnormal liver and kidney function, but the effect of serum albumin level on abnormal BMD and osteoporotic fracture is still controversial. The aim of this retrospective study was to investigate the effects of serum albumin levels on abnormal BMD and osteoporotic fractures. Methods The study included 538 patients through the electronic medical records of inpatients and outpatients stored at Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology. A multivariate logistic regression model was employed to test the relationship between serum albumin levels and abnormal BMD, and the effect of serum albumin levels on osteoporotic fractures was verified through the U test. Correlation between age, sex, kidney stones, coronary heart disease, hypertension, diabetes, fatty liver disease, haemoglobin (HB), mean corpuscular haemoglobin concentration (MCHC), platelets (PLT), platelet distribution width (PDW), lymphocytes (LYMP), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), uric acid (UA), total bilirubin (TBIL), total cholesterol (TC), high-density lipoprotein (HDL) and abnormal BMD were analysed by logistic regression modelling after excluding confounding factors. Results The ALB level in osteoporotic patients was 41.70 (36.40–45.00) g/L, which was significantly lower than those in the normal BMD and reduced BMD groups. The odds ratio (OR) (95% confidence interval [CI]) between the osteoporosis and normal BMD groups was 0.445 (0.394–0.502); the OR (95% CI) between the osteoporosis and reduced BMD groups was 0.395 (0.341–0.459). In the subgroup analysis by whether or not a fracture was present, the OR (95% CI) was 0.073 (0.045–0.119). Conclusions ALB is a protective factor against osteoporosis and osteoporotic fractures, suggesting that it may have the potential to predict osteoporosis onset and fractures.

Abstract Nasopharyngeal carcinoma (NPC) is the most common cancer originating in nasopharynx. Metabolic reprogramming plays a critical role in tumor progression. Exploring mechanisms underlying metabolic reprogramming contributes to deeper understanding of NPC pathogenesis. Here, we found downregulation of RORA and SPLUNC1 in NPC, and RORA downregulation indicates poor prognosis. RORA binds to SPLUNC1 promoter to induce its transcription, and RORA overexpression inhibits cell proliferation and glycolysis by directly upregulating SPLUNC1. UBR5 inhibits RORA via promoting RORA ubiquitination and degradation, and UBR5 silencing represses proliferation and glycolysis in NPC. Additionally, METTL14, which is highly expressed in NPC, facilitates UBR5 mRNA stability by promoting its m6A modification through IGF2BP2. UBR5/RORA/SPLUNC1 axis facilitates M2 polarization by activating the GPR132 signaling. UBR5 silencing inhibits tumor growth, glycolysis and M2 polarization through RORA/SPLUNC1 signaling in mice. In conclusion, UBR5 promotes proliferation, glycolysis and M2 polarization by metabolically reprograming NPC cells through suppression of the RORA/SPLUNC1 signaling.

Abstract Background Sequencing-based genetic testing is widely used in biomedical research, including pathogenic microorganism detection with metagenomic next-generation sequencing (mNGS). The application of sequencing results to clinical diagnosis and treatment relies on various interpretation knowledge bases. Currently, the existing knowledge bases are primarily built through manual knowledge extraction. This method requires professionals to read extensive literature and extract relevant knowledge from it, which is time-consuming and costly. Furthermore, manual extraction unavoidably introduces subjective biases. In this study, we aimed to automatically extract knowledge for interpreting mNGS results. Method We propose a novel approach to automatically extract pathogenic microorganism knowledge based on the question-answer (QA) model. First, we construct a MicrobeDB dataset since there is no available pathogenic microorganism QA dataset for training the model. The created dataset contains 3,161 samples from 618 published papers covering 224 pathogenic microorganisms. Then, we fine-tune the selected baseline model based on MicrobeDB. Finally, we utilize ChatGPT to enhance the diversity of training data, and employ data expansion to increase training data volume. Results Our method achieves an Exact Match (EM) and F1 score of 88.39% and 93.18%, respectively, on the MicrobeDB test set. We also conduct ablation studies on the proposed data augmentation method. In addition, we perform comparative experiments with the ChatPDF tool based on the ChatGPT API to demonstrate the effectiveness of the proposed method. Conclusions Our method is effective and valuable for extracting pathogenic microorganism knowledge.

Objective Clarifying paraspinal muscle (PM) change in degenerative lumbar scoliosis (DLS) is positive to evaluate the progression of scoliosis. This research compares the characteristic of PM change among different coronal sub‐types of DLS and explores its potential clinical significance. Methods A total of 84 DLS patients between June 2019 to December 2021 were retrospectively analyzed. Patients were classified into three types based on the coronal balance distance (CBD): Type A, CBD 3 cm; Type C: C7PL shifted to the convex side of the curve, and CBD >3 cm. Fat infiltration rates in the multifidus (MS) and erector spinae (ES) at the apex of the main and fractional curves, and spinopelvic parameters were analyzed statistically. Pearson's or Spearman's correlation was applied to analyze the correlation between asymmetric degree of PM change and these parameters in three types. Results There were 62 cases with coronal sub‐Type A, 6 cases with Type B, and 16 cases with Type C. Patients in Type B and C demonstrated higher fat infiltration in MS on the concave side of both the main and fractional curves when compared to those in Type A. The asymmetric degree of ES change was positively correlated with CBD at the apex of the main curve in Type B and at the apex of the fractional curve in Type C respectively, and that of MS was positively correlated with apical vertebral rotation, while negatively strong‐correlated with pelvic incidence and sacral slope in Type C. Conclusion PM fatty infiltration presented difference among varied coronal sub‐types of DLS patients. The CBD in Type B and C patients was correlated with the asymmetric degree of ES change.

Abstract In this paper, an electro-hydraulic exciter controlled by an alternating current distribution valve is proposed, and a systematic analysis of the influence of pipe effect on the vibration characteristics of the electro-hydraulic exciter is investigated by simulation and experiments. The vibration characteristics curves for different pipe parameters are obtained, and the relative errors between simulation and experiment are evaluated. Moreover, a significant regression model of pipe parameters and vibration characteristics of the electro-hydraulic exciter is established by using the quadratic regression analysis method and the Box-Behnken experiment design method. Significant differences in the influence of pipe parameters on vibration characteristics are obtained by ANOVA (Analysis of Variance), and the influence of pipe parameter interaction on vibration characteristics is discussed. The results show that the relative importance of pipe parameters on the vibration characteristics of electro-hydraulic exciter, from high to low, is as follows: pipe diameter, elastic modulus, and pipe length. Notably, there is also an interaction between the pipe parameters, and the significance of these interactions is ranked from high to low as the interaction between the layers of steel wire and diameter, the interaction between diameter and length, and the interaction between the layers of steel wire and length.

In order to investigate the key nodes affecting the changes of Yixian dark tea flavor and quality during the Pile fermentation, in this study, the sensory quality and non-volatile profiles of Yixian dark tea samples at different pile fermentation periods (0, 3, 6, 9, 12, 15, 18 h) were investigated by sensory evaluation, amino acids analyzer, liquid chromatography and liquid chromatography mass spectrometry. The results showed that the intensity of bitterness in dark tea infusions declined after 9 h of pile fermentation, along with the increasing intensities of astringency, thickness and stale-mellow. Total catechins showed a significant decrease in concentrations during pile fermentation. In contrast, the concentration of gallic acid increased. Concentration of caffeine reduced by 14.7% compared to the original concentration after 18 h of pile fermentation. Total amino acids concentration showed an increasing tendency in the later period of pile fermentation. Concentrations of flavonoids and its mono-glycosides increased after 9~12 hours, while its di-glycosides showed an increasing tendency after 12 hours of pile fermentation. The analysis of key taste substances (VIP>1, DOT>1) showed that myricetin-3-O-galactoside, astragalin, isoquercitrin, quercetin-3-O-rutinose, epigallocatechin, epicatechin, epigallocatechin gallate, and caffeine were the most important flavor presenting substances affecting the quality changes of Yixian dark tea. Among them, the content of the first three glycosides increased significantly from 9~12 hours of stacking; The contents of epigallocatechin and epicatechin were significantly reduced during 9~12 hours. Epigallocatechin gallate and caffeine showed a significant decrease after pile fermentation; Quercetin-3-O-rutinoside decreased significantly in the middle stage (9~12 hours) and increased significantly after 15 hours. It was an important factor in the increase of astringency of tea broth in the late stage of pile fermentation. This study give a theoretical basis for improving the tea processing of Yixian dark tea and understanding the formation mechanism of its key flavor.

Abstract Benign prostatic hyperplasia (BPH) is a condition commonly observed in aging males. Inflammatory and metabolic factors are pivotal in the development and progression of BPH. The degree to which the effects of 91 inflammation-related proteins on BPH are mediated by 1400 plasma metabolites remains ambiguous. Our research analyzed the impact of these traits utilizing genetic evidence.Two-sample Mendelian randomization (MR) and multivariable MR (MVMR) were utilized in our study to infer the genetic causal effect of inflammation-related proteins on BPH, with metabolites serving as mediators. Increased levels of IL-2 were linked to a heightened incidence of BPH (β = 0.071, OR:1.074, 95% CI [1.002–1.152], p = 0.045), whereas lower concentrations of N6,N6-dimethyllysine were associated with decreased risk (β1=-0.127, p = 0.02; β2=-0.039, p = 0.008). The mediation effect was 0.005 (95% CI [0.0004, 0.012], OR: 1.005, 95% CI [1.000, 1.012]), accounting for 7.04% of the total effect. subsequently, we examined the phenotypic co-localization of the two pairings independently, revealing that the posterior probability of rs145516501 associated with IL-2 and BPH was 80.7%, whereas the posterior likelihood of rs4917820 linked to N6,N6-dimethyllysine levels and BPH was 95.9%. The research indicated that N6,N6-dimethyllysine levels seem to influence the causative relationship between IL-2 and BPH. These results elucidate the complex interplay between inflammation-related proteins and metabolism in the context of BPH, offering novel diagnostic and therapeutic avenues and enhancing our comprehension of the disease’s etiology for prospective research.

Abstract As the proliferation of video content continues, and many video archives lack suitable metadata, therefore, video retrieval, particularly through example‐based search, has become increasingly crucial. Existing metadata often fails to meet the needs of specific types of searches, especially when videos contain elements from different modalities, such as visual and audio. Consequently, developing video retrieval methods that can handle multi‐modal content is essential. An innovative Multi‐modal Video Search by Examples (MVSE) framework is introduced, employing state‐of‐the‐art techniques in its various components. In designing MVSE, the authors focused on accuracy, efficiency, interactivity, and extensibility, with key components including advanced data processing and a user‐friendly interface aimed at enhancing search effectiveness and user experience. Furthermore, the framework was comprehensively evaluated, assessing individual components, data quality issues, and overall retrieval performance using high‐quality and low‐quality BBC archive videos. The evaluation reveals that: (1) multi‐modal search yields better results than single‐modal search; (2) the quality of video, both visual and audio, has an impact on the query precision. Compared with image query results, audio quality has a greater impact on the query precision (3) a two‐stage search process (i.e. searching by Hamming distance based on hashing, followed by searching by Cosine similarity based on embedding); is effective but increases time overhead; (4) large‐scale video retrieval is not only feasible but also expected to emerge shortly.

177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Abstract Background Micrococcus antarcticus (M. antarcticus) is an aerobic Gram-positive spherical actinobacterium that was initially isolated from Chinese Great-Wall station in Antarctica in 2000. M. antarcticus was considered to be of low pathogenicity, no previous cases of human infection by this organism have been reported. Here we describe the first report with community-acquired pneumonia (CAP) caused by M. antarcticus. Case presentation An 87-year-old female was presented to the Central Hospital of Wuhan in November 2023 with a chief complaint of cough, sputum production, and chest tightness for 2 weeks. Microbial culture of the patient’s bronchoalveolar lavage fluid (BALF) and identification of the isolates using Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing revealed M. antarcticus infection. Combined with clinical symptoms, laboratory and imaging examination, the patient was diagnosed with CAP. Then cefoperazone/sulbactam and levofloxacin was administrated, the patient’s condition was improved and she was discharged after a week after admission, no abnormalities were detected during a 5-month follow-up. Conclusions This case highlights that M. antarcticus, first identified from a patient with CAP, is an extremely rare pathogenic microorganism. Clinicians should be aware of its potential as a pathogen in the diagnosis and treatment of CAP.

Abstract Cervical cancer (CC) was considered to be the most common gynaecological cancer, with an estimated 342,000 deaths worldwide each year, as the majority of patients were diagnosed at an advanced stage of the disease. The purpose of this study was to evaluate the predictive value of multi-locus methylation assay for the early detection of CC. The cervical exfoliated cell samples from 492 HPV-positive females with cervical lesions were collected and subjected to methylation detection of gene FAM19A4, EPB41L3 and PAX1 after bisulfite conversion. The levels of gene methylation in patients with different severity of cervical lesions were evaluated and compared. The receiver-operating characteristic (ROC) curve was established and efficacy indexes such as sensitivity, specificity and area under the curve (AUC) were calculated to assess the diagnostic value of DNA methylation detection at multiple gene loci for CC. The methylation levels of FAM19A4, EPB41L3 and PAX1 were significantly increased with the grade of cervical squamous intraepithelial lesions. The sensitivities of FAM19A4, EPB41L3 and PAX1 alone for high-grade squamous intraepithelial lesion (HSIL) and CC diagnosis were 84.6%, 86.3% and 88.0%, respectively; when three markers were combined by a logistic regression model, the sensitivity was 88.0%, with a high specificity of 97.7% and AUC of 0.957 (95% CI 0.937–0.977). Methylation status of FAM19A4, EPB41L3 and PAX1 were highly specific and effective for monitoring the progression of cervical lesions and the tri-gene methylation assay could be used as a triage tool for CC early screening.

Abstract Presenilin-associated protein (PSAP) is a mitochondrial proapoptotic protein as established in cell biology studies. It remains unknown whether it involves in neurodegenerative diseases. Here, we explored PASP expression in adult and aged human brains and its alteration relative to Alzheimer-disease (AD)-type neuropathology. In pathology-free brains, light PASP immunoreactivity (IR) occurred among largely principal neurons in the cerebrum and subcortical structures. In the brains with AD pathology, enhanced PSAP IR occurred in neuronal and neuritic profiles with a tangle-like appearance, with PSAP and pTau protein levels elevated in neocortical lysates relative to control. Neuronal/neuritic profiles with enhanced PSAP IR partially colocalized with pTau, but invariably with Amylo-Glo labelled tangles. The neuronal somata with enhanced PASP IR also showed diminished IR for casein kinase 1 delta (Ck1δ), a marker of granulovacuolar degeneration; and diminished IR for sortilin, which is normally expressed in membrane and intracellular protein sorting/trafficking organelles. In old 3xTg-AD mice with β-amyloid and pTau pathologies developed in the brain, PSAP IR in the cerebral sections exhibited no difference relative to wildtype mice. These findings indicate that PSAP upregulation is involved in the course of tangle formation especially in the human brain during aging and in AD pathogenesis.

Abstract Of the hitherto over 60 taxonomically identified species in the genus of Pseudo-nitzschia, 26 have been confirmed to be toxigenic. Nevertheless, the acquisition and evolution of the toxin biosynthesis (dab) genes by this extensive group of Pseudo-nitzschia species remains unclear. Through constructing chromosome-level genomes of three Pseudo-nitzschia species and draft genomes of ten additional Pseudo-nitzschia species, putative genomic integration sites for the dab genes in Pseudo-nitzschia species were explored. A putative breakpoint was observed in syntenic regions in the dab gene cluster-lacking Pseudo-nitzschia species, suggesting potential independent losses of dab genes. The breakpoints between this pair of conserved genes were also identified in some dab genes-possessing Pseudo-nitzschia species, suggesting that the dab gene clusters transposed to other loci after the initial integration. A “single acquisition, multiple independent losses (SAMIL)” model is proposed to explain the acquisition and evolution of the dab gene cluster in Pseudo-nitzschia species.

Abstract Background Gestational diabetes mellitus (GDM) is a common complication of mid–to-late pregnancy. Here, we constructed a predictive model for GDM based on a combination of clinical characteristics and relevant serum markers. Methods Data from full-term singleton vaginal deliveries from January 2022 to January 2023 were retrospectively collected from the obstetrics department. The data collected were segregated and assigned to training, validation, and external test sets. Maternal demographic characteristics, living and working habits, and haematological indicators, such as liver function and lipids were collected using a questionnaire designed for the study. The “rms” package in R was used to explore GDM-associated factors through stepwise regression at P 0.05. The ROC curve AUCs for the three groups were 0.93 (95% CI: 0.89–0.97), 0.72 (95% CI: 0.62–0.81), and 0.68 (95% CI: 0.53–0.83), respectively. Conclusion In this study, a GDM prediction model was constructed to achieve high performance in GDM risk prediction based on routine obstetric tests and information.

We prepared biocompatible and environment-friendly zinc oxide nanoparticles (ZnO NPs) with upconversion properties and catalase-like nanozyme activity. Photodynamic therapy (PDT) application is severely limited by the poor penetration of UV–Visible light and a hypoxic tumor environment. Here, we used ZnO NPs as a carrier for the photosensitizer chlorin e6 (Ce6) to construct zinc oxide–chlorin e6 nanoparticles (ZnO-Ce6 NPs), simultaneously addressing both problems. In terms of penetration, ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6, achieving deep-penetrating photodynamic therapy under long-wavelength light. Interestingly, the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles. As nanozymes, ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors, providing oxygen for photodynamic action and relieving hypoxia. The enhanced photodynamic action produces a large amount of reactive oxygen species, which overactivate autophagy and trigger immunogenic cell death (ICD), leading to antitumor immunotherapy. In addition, even in the absence of light, ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.

Abstract Introduction Mesenchymal stromal cell (MSC)-based cell therapy is a promising approach for various inflammatory disorders based on their immunosuppressive capacity. Osteopontin (OPN) regulates several cellular functions including tissue repair, bone metabolism and immune reaction. However, the biological function of OPN in regulating the immunosuppressive capacity of MSCs remains elusive. Objectives This study aims to highlight the underlying mechanism of the proinflammatory cytokines affect the therapeutic ability of MSCs through OPN. Methods MSCs in response to the proinflammatory cytokines were collected to determine the expression profile of OPN. In vitro T-cell proliferation assays and gene editing were performed to check the role and mechanisms of OPN in regulating the immunosuppressive capacity of MSCs. Inflammatory disease mouse models were established to evaluate the effect of OPN on improving MSC-based immunotherapy. Results We observed that OPN, including its two isoforms iOPN and sOPN, was downregulated in MSCs upon proinflammatory cytokine stimulation. Interestingly, iOPN, but not sOPN, greatly enhanced the immunosuppressive activity of MSCs on T-cell proliferation and thus alleviated the inflammatory pathologies of hepatitis and colitis. Mechanistically, iOPN interacted with STAT1 and mediated its deubiquitination, thereby inducing the master immunosuppressive mediator inducible nitric oxide synthase (iNOS) in MSCs. In addition, iOPN expression was directly downregulated by activated STAT1, which formed a negative feedback loop to restrain MSC immunosuppressive capacity. Conclusion Our findings demonstrated that iOPN expression modulation in MSCs is a novel strategy to improve MSC-based immunotherapy.

Abstract Pressure dynamics can reflect the basic characteristics of fluid flow through underground porous formation. In this research, the oil–gas two-phase flow model for a double-porosity media formation with permeability-stress sensitivity was first established for three kinds of outer boundaries. The unified governing equation was deduced by utilizing the H function. The nonlinear mathematical model in consideration of permeability-stress sensitivity was linearized by implementing the canonical perturbation transformation and then solved by using the Laplace transformation. After that, a sequence of typical log–log curves of pressure dynamics influenced by various model parameters were plotted and analyzed. These curves reflect the typical characteristic of a V shape caused by the inter-porosity fluid flow from matrix toward natural fractures. Oil saturation and permeability-stress sensitivity coefficient have much influence on the pressure dynamics. Ultimately, the established model of oil–gas two-phase flow was validated through a well-test fitting interpretation for a real condensate gas well in a sandstone formation. This research can offer insights into the pressure dynamics dominated by the oil–gas two-phase flow in naturally fractured formations and the permeability-stress sensitivity effect.

Abstract Background Physical activity and sleep are established modifiable lifestyle factors, but the optimal time of the day of these behaviours for health is unknown. This study examined the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality. Methods This prospective cohort study included 6,673 participants who have attended the accelerometer assessment in the 2011–2014 National Health and Nutrition Examination Surveys (NHANES). Diurnal patterns of accelerometer-measured physical activity and sleep were identified using K-means clustering analysis. All-cause mortality was ascertained from the accelerometer measurement to December 31, 2019 (median follow-up 6.8 years). Survey-weighted Cox proportional hazard models were performed to estimate the independent and joint associations of diurnal patterns of physical activity and sleep with all-cause mortality. Results Diurnal patterns identified were: early-morning (32.4%), midday (42.5%), and late-afternoon (25.1%) for physical activity; and irregular sleep (37.4%), morning lark (33.6%), and night owl (29.0%) for sleep. After adjusting for volume of physical activity, sleep duration and other potential covariates, the early-morning physical activity pattern (hazard ratio 1.36, 95% confidence interval 1.13–1.64) and irregular sleep pattern (1.42, 1.01–1.99) were independently associated with higher risk of all-cause mortality, compared with midday physical activity and morning lark sleep patterns, respectively. In addition, participants with the combined pattern of early-morning physical activity and irregular sleep had higher risk of all-cause mortality compared to those with midday physical activity combined with a morning lark sleep pattern (1.92, 1.33–2.78). Several sociodemographic differences were observed in the strength of these associations. Conclusions Wearable activity-rest monitoring data showed that peak physical activity in the early morning and irregular sleep diurnal patterns are associated with increased mortality risk, and the combination of these patterns further exaggerated the risk. Public health program should acknowledge that the diurnal patterns of physical activity and sleep, in addition to their duration and frequency, may play a crucial role in lifestyle-based health promotion and management strategies.

Abstract The preoperative diagnosis and management of Peutz–Jeghers syndrome (PJS) patients with cervical lesions remain problematic. This study analysed the associations between pathological types of cervical lesions in PJS patients and their MRI features. A total of 34 PJS patients were included and two experienced radiologists reviewed the MRIs independently. Based on the pathological diagnosis, the patients were categorized into four groups: normal (n = 4), lobular endocervical glandular hyperplasia (LEGH, n = 11), atypical LEGH (aLEGH, n = 8), and gastric-type endocervical adenocarcinoma (G-EAC, n = 11). By observing the MRI features, we found statistically significant differences in the extent of lesions (P = 0 .001), distribution of microcysts (P = 0 .001), proportion of microcysts (P

Abstract Understanding the relationship between various socioeconomic factors and urban forest structure is essential for directing resources to ensure equitable distribution of green space. Through a case study of a desert city, i.e., Phoenix, AZ, this study provides a novel application of Multiscale Geographically Weighted Regression (MGWR) in which we explore the spatially variable relationships between a wide array of socioeconomic indicators and urban forest attributes. Through the computation of various scales of influence for different explanatory variables, MGWR enhances our analysis’s precision and stresses the association between socioeconomic status and urban forest structure at local and regional scales. Our results indicate that although there has been a pattern of green inequality where minority and low-income communities have less access to urban forests, education levels were mostly insignificant based on the MGWR results. In some instances, higher incomes are negatively correlated with tree canopy coverage. Additionally, the stem density model outperformed the canopy coverage model in terms of prediction accuracy. This research adds a new dimension to urban forestry literature and emphasizes the value of customized urban planning strategies and the environmental justice implications of urban forestry, particularly in arid environments.

Abstract In surgical medicine, suturing is the standard treatment for large incisions, yet traditional sutures are limited in functionality. Electrical stimulation is a non-pharmacological therapy that promotes wound healing. In this context, we designed a passive and biodegradable mechanoelectric suture. The suture consists of multi-layer coaxial structure composed of (poly(lactic-co-glycolic acid), polycaprolactone) and magnesium to allow safe degradation. In addition to the excellent mechanical properties, the mechanoelectrical nature of the suture grants the generation of electric fields in response to movement and stretching. This is shown to speed up wound healing by 50% and reduce the risk of infection. This work presents an evolution of the conventional wound closure procedures, using a safe and degradable device ready to be translated into clinical practice.

Abstract The crosstalk between adipose tissue and the liver is finely controlled to maintain metabolic health. Yet, how adipose tissue controls toxic free fatty acid overflow into the liver remains incompletely understood. Here, we show that adipocyte activating transcription factor 3 (ATF3) was induced in human or mouse obesity. Adipocyte Atf3 −/− (Atf3 Adi−/− ) mice developed obesity, glucose intolerance, and metabolic dysfunction-associated steatohepatitis (MASH) in chow diet, high-fat diet, or Western diet-fed mice. Blocking fatty acid flux by inhibiting hepatocyte CD36, but not the restoration of hepatic AMPK signaling, prevented the aggravation of MASH in Atf3 Adi−/− mice. Further studies show that the loss of adipocyte ATF3 increased lipolysis via inducing adipose triglyceride lipase, which in turn induced lipogenesis and inflammation in hepatocytes. Moreover, Atf3 Adi−/− mice had reduced energy expenditure and increased adipose lipogenesis and inflammation. Our data demonstrate that adipocyte ATF3 is a gatekeeper in counteracting MASH development under physiological and pathological conditions.

Abstract Otitis media (OM), a condition stemming from the proliferation of various bacteria within the tympanic cavity (TC), is commonly addressed through the administration of ofloxacin (OFL), a fluoroquinolone antibiotic. Nevertheless, the escalating issue of antibiotic resistance and the challenge of drug leakage underscore the exploration of an alternative, more effective treatment modality in clinical practice. Here, we introduce a simple and easily implementable fluid-regulated strategy aimed at delivering immunomodulatory hydrogels into the TC, ensuring conformal contact with the irregular anatomical surfaces of the middle ear cavity to more effectively eliminate bacteria and treat OM. This innovative strategy exhibits expedited therapeutic process of antibiotic-resistant, acute and chronic OM rats, and significant reductions in the severity of tympanic membrane (TM) inflammation, residual bacteria within the TC (0.12 *105 CFU), and the thickness of TM/TC mucosa (17.63/32.43 μm), as compared to conventional OFL treatment (3.6, 0.76 *105 CFU, 48.70/151.26 μm). The broad-spectrum antibacterial and antibiofilm properties of this strategy against a spectrum of OM pathogens are demonstrated. The strategy is validated to bolster the host’s innate immune response through the stimulation of antibacterial protein synthesis, macrophage proliferation and activation, thereby accelerating bacterial eradication and inflammation resolution within the TC. This facile, cost-effective and in vivo degradable technology exhibits promising prospects for future clinical implementation.

Abstract Background Stutzerimonas nitrititolerans (S. nitrititolerans) is a rare human pathogenic bacterium and has been inadequately explored at the genomic level. Here, we report the first case of carbapenem-resistant S. nitrititolerans isolated from the peritoneal dialysis fluid of a patient with chronic renal failure. This study analyzed the genomic features, antimicrobial resistance, and virulence factors of the isolated strain through whole genome sequencing (WGS). Methods The bacterial isolate from the peritoneal dialysis fluid was named PDI170223, and preliminary identification was conducted through Matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS). WGS of the strain PDI170223 was performed using the Illumina platform, and a phylogenetic tree was constructed based on the 16S rRNA gene sequences. Antimicrobial susceptibility test (AST) was conducted using the TDR-200B2 automatic bacteria identification/drug sensitivity tester. Results S. nitrititolerans may emerge as a human pathogen due to its numerous virulence genes, including those encoding toxins, and those involved in flagellum and biofilm formation. The AST results revealed that the strain is multidrug- and carbapenem-resistant. The antimicrobial resistance genes of S. nitrititolerans are complex and diverse, including efflux pump genes and β⁃lactam resistance genes. Conclusion The analysis of virulence factors and antimicrobial resistance of S. nitrititolerans provides clinical insight into the pathogenicity and potential risks of this bacterium. It is crucial to explore the mechanisms through which S. nitrititolerans causes diseases and maintains its antimicrobial resistance, thereby contributing to development of effective treatment and prevention strategies.

Abstract Network is an essential tool today, and the Intrusion Detection System (IDS) can ensure the safe operation. However, with the explosive growth of data, current methods are increasingly struggling as they often detect based on a single scale, leading to the oversight of potential features in the extensive traffic data, which may result in degraded performance. In this work, we propose a novel detection model utilizing multi-scale transformer namely IDS-MTran. In essence, the collaboration of multi-scale traffic features broads the pattern coverage of intrusion detection. Firstly, we employ convolution operators with various kernels to generate multi-scale features. Secondly, to enhance the representation of features and the interaction between branches, we propose Patching with Pooling (PwP) to serve as a bridge. Next, we design multi-scale transformer-based backbone to model the features at diverse scales, extracting potential intrusion trails. Finally, to fully capitalize these multi-scale branches, we propose the Cross Feature Enrichment (CFE) to integrate and enrich features, and then output the results. Sufficient experiments show that compared with other models, the proposed method can distinguish different attack types more effectively. Specifically, the accuracy on three common datasets NSL-KDD, CIC-DDoS 2019 and UNSW-NB15 has all exceeded 99%, which is more accurate and stable.

Abstract PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

Abstract Maintaining stillness is essential for accurate bioelectrical signal acquisition, but dynamic noise from breathing remains unavoidable. Isotropic adhesives are often used as bioelectronic interfaces to ensure signal fidelity, but they can leave irreversible residues, compromising device accuracy. We propose a hydrogel with selective frequency damping and asymmetric adhesion as a bioelectronic interface. This hydrogel mitigates dynamic noise from breathing, with a damping effect in the breathing frequency range 60 times greater than at other frequencies. It also exhibits an asymmetric adhesion difference of up to 537 times, preventing residues. By homogenizing ion distribution, extending Debye length, and densifying the electric field, the hydrogel ensures stable signal transmission over 10,000 cycles. Additionally, it can non-invasively diagnose otitis media with higher sensitivity than invasive probes and has been effective in clinical polysomnography monitoring, aiding in the diagnosis of obstructive sleep apnea.

Abstract The characterization of protein complex is vital for unraveling biological mechanisms in various life processes. Despite advancements in biophysical tools, the capture of non-covalent complexes and deciphering of their biochemical composition continue to present challenges for low-input samples. Here we introduce SNAP-MS, a Stationary-phase-dissolvable Native Affinity Purification and Mass Spectrometric characterization strategy. It allows for highly efficient purification and characterization from inputs at the pico-mole level. SNAP-MS replaces traditional elution with matrix dissolving during the recovery of captured targets, enabling the use of high-affinity bait-target pairs and eliminates interstitial voids. The purified intact protein complexes are compatible with native MS, which provides structural information including stoichiometry, topology, and distribution of proteoforms, size variants and interaction states. An algorithm utilizes the bait as a charge remover and mass corrector significantly enhances the accuracy of analyzing heterogeneously glycosylated complexes. With a sample-to-data time as brief as 2 hours, SNAP-MS demonstrates considerable versatility in characterizing native complexes from biological samples, including blood samples.

Abstract Background Cereal diseases caused by insect-transmitted viruses are challenging to forecast and control because of their intermittent outbreak patterns, which are usually attributed to increased population densities of vector insects due to cereal crop rotations and indiscriminate use of pesticides, and lack of resistance in commercial varieties. Root microbiomes are known to significantly affect plant health, but there are significant knowledge gaps concerning epidemics of cereal virus diseases at the microbiome-wide scale under a variety of environmental and biological factors. Results Here, we characterize the diversity and composition of rice (Oryza sativa) root-associated bacterial communities after infection by an insect-transmitted reovirus, rice black-streaked dwarf virus (RBSDV, genus Fijivirus, family Spinareoviridae), by sequencing the bacterial 16S rRNA gene amplified fragments from 1240 samples collected at a consecutive 3-year field experiment. The disease incidences gradually decreased from 2017 to 2019 in both Langfang (LF) and Kaifeng (KF). BRSDV infection significantly impacted the bacterial community in the rice rhizosphere, but this effect was highly susceptible to both the rice-intrinsic and external conditions. A greater correlation between the bacterial community in the rice rhizosphere and those in the root endosphere was found after virus infection, implying a potential relationship between the rice-intrinsic conditions and the rhizosphere bacterial community. The discrepant metabolites in rhizosphere soil were strongly and significantly correlated with the variation of rhizosphere bacterial communities. Glycerophosphates, amino acids, steroid esters, and triterpenoids were the metabolites most closely associated with the bacterial communities, and they mainly linked to the taxa of Proteobacteria, especially Rhodocyclaceae, Burkholderiaceae, and Xanthomonadales. In addition, the greenhouse pot experiments demonstrated that bulk soil microbiota significantly influenced the rhizosphere and endosphere communities and also regulated the RBSDV-mediated variation of rhizosphere bacterial communities. Conclusions Overall, this study reveals unprecedented spatiotemporal dynamics in rhizosphere bacterial communities triggered by RBSDV infection with potential implications for disease intermittent outbreaks. The finding has promising implications for future studies exploring virus-mediated plant-microbiome interactions. Video Abstract

This study aimed to study the effects of three current popular high-temperature treatments (electric roasting, air frying and superheated steam) on the physicochemical properties and taste quality of grass carp meat. Physicochemical properties were analyzed by measuring pH, water holding capacity, color value, thiobarbituric acid reactive substance and protein carbonyl content of fish meat. Taste quality was characterized by measuring the free amino acids content and flavor nucleotides content of fish meat. The results showed that compared with the raw grass carp meat in the control group, the indexes of physicochemical properties of grass carp meat processed by different high-temperature treatments were significantly increased in different degrees (P

In the event of severe accidents in pressurized water reactor (PWR) nuclear power plants, the potential leakage of radioactive aerosols through containment cracks poses a considerable radioactive hazard to the public. Understanding aerosol transport and retention in cracks helps reduce the conservatism and uncertainty of radioactive hazard assessment. Concrete cracks are recognized as a pivotal pathway for the leakage of radioactive aerosols, and several researchers have undertaken experimental investigations concerning the aerosol transport and retention in concrete cracks. However, the majority of these studies have rather low gas flow Reynolds numbers. In this work, an experimental setup is built to study aerosol transport and retention in concrete cracks under high Reynolds number flow. The TiO2 aerosol with a mass median diameter of 1 μm and two concrete crack specimens are used in experiments. The results of gas flow experiments indicate that the Reynolds number is capable of reaching 10547. Combining the flow experimental data and Suzuki's formula, the equivalent heights of these two crack specimens are approximated as 303.67 μm and 231.48 μm. The experimental results indicate a notably high retention rate of aerosols, exceeding 0.8. Furthermore, under high Reynolds number flow, the retention rate varies over a relatively narrow range, with the larger the equivalent height of the crack resulting in a lower retention rate. The experimental results match well with the mechanistic analysis based on inertial deposition theory, demonstrating the rationality of the inertial deposition theory.

Abstract Background and Objective Tinengotinib, a novel multi-target small molecule kinase inhibitor, is currently undergoing phase II clinical trial in the USA and China. The purpose of this open-label study was to investigate the absorption, metabolism, and excretion of [14C]tinengotinib following a single oral dose in healthy subjects. Methods Six healthy male subjects received a single oral dose of [14C]tinengotinib capsules at 10 mg/100 µCi, and blood, urine, and feces samples were collected. Phenotyping experiments were further conducted to confirm the enzymes involved in its metabolism. Results Tinengotinib was rapidly absorbed in plasma with a time to peak drug concentration (T max) of 1.0–4.0 h post-dose and a long terminal half-life (t ½) of 23.7 h. Blood-to-plasma radioactivity concentration ratios across timepoints ranged from 0.780 to 0.827, which indicated minimal association of radioactivity with blood cells. The mean cumulative excreted radioactivity was 99.57% of the dose, including 92.46% (68.65% as unchanged) in feces and 7.11% (0.28% as unchanged) in urine. In addition to unchanged tinengotinib, a total of 11 radioactive metabolites were identified in plasma, urine, and feces. The most abundant circulating radioactivity was the parent drug in plasma, which comprised 88.23% of the total radioactivity area under the concentration–time curve (AUC). Metabolite M410-3 was a major circulating metabolite, accounting for 5.38% of the parent drug exposure and 4.75% of the total drug-related exposure, respectively. All excreted metabolites accounted for less than 5.10% and 1.82% of the dose in feces and urine, respectively. In addition, no unique metabolites were observed in humans. Tinengotinib was metabolized mainly via CYP3A4. Conclusions Overall, tinengotinib demonstrated a complete mass balance with limited renal excretion, no disproportionate blood metabolism, and slow elimination, primarily through the fecal route. The results of this study provide evidence to support the rational use of tinengotinib as a pharmacotherapeutic agent. Registration ChinadrugTrials.org.cn identifier: CTR20212852.

ObjectiveTo comprehensively and objectively describe the development history, research hotspots, and trends of digital public health, providing a reference for future digital public health research. MethodsBy searching the Chinese National Knowledge Infrastructure (CNKI) and Web of Science (WOS) core databases for digital public health-related research literature from January 1990 to June 2023, 6 437 articles from CNKI and 5 344 articles from WOS were included. Using the bibliometric analysis software CiteSpace, visual analysis, keyword co-occurrence, cluster analysis, timeline analysis, and burst analysis were conducted on all retrieved literature. ResultsSince 2013, the discipline of public health has entered a rapid development stage. Domestic and international research jointly focuses on infectious and chronic disease monitoring and prediction, as well as the extensive application of emerging technologies such as big data and artificial intelligence in the field of public health. The Chinese keyword co-occurrence knowledge map contains 728 nodes and 2 286 connections, with 56 clusters formed among Chinese keywords. Domestic research focuses on healthcare system construction, with research hotspots including informatization and electronic medical record management. The English keyword co-occurrence knowledge map contains 980 nodes and 3 824 connections, with 67 clusters formed among English keywords. International research emphasizes disease intervention methods, with research hotspots including social media and digital mental health. ConclusionThe discipline of digital public health is currently in a period of rapid development, with research contents and trends closely related to the development and innovation of digital technology and major public health events. In the future, personalized digital health services will become a research hotspot, and the discipline of digital public health has broad prospects.

Abstract Apoptosis is a genetically programmed form of cell death that is substantially conserved across the evolutionary tree. Apoptotic cell elimination includes recognition, phagocytosis, and degradation. Failure to clear apoptotic cells can ultimately cause a series of human diseases, such as systemic lupus erythematosus, Alzheimer's disease, atherosclerosis, and cancer. Consequently, the timely and effective removal of apoptotic cells is crucial to maintaining the body's homeostasis. GPCRs belong to the largest membrane receptor family. Its intracellular domain exerts an effect on the trimer G protein. By combining with a variety of ligands, the extracellular domain of G protein initiates the dissociation of G protein trimers and progressively transmits signals downstream. Presently, numerous G protein‐coupled receptors (GPCRs) have been identified as participants in the apoptosis signal transduction pathway and the apoptotic cell clearance pathway. Therefore, studies on the mechanism of GPCRs in the clearance of apoptotic cells is important for the development of GPCRs therapeutics.

Abstract Background The ectoparasite Psoroptes ovis var. cuniculi causes substantial economic losses to the global rabbit industry. Currently, microscopy for identifying Psoroptes mite in skin scrapings, as the “diagnosis gold standard,” remains a challenge owing to its poor sensitivity in detecting low-level and/or early stage mite infestations. Additionally, Psoroptes infestations rapidly trigger cutaneous inflammation, thus the mites might produce some molecules to deal with the harmful effects of inflammation for their long-time survival on the host skin, but these molecules are still mostly unknown. Methods To seek a sensitive diagnostic method and illuminate the new antiinflammatory molecules, we characterized a novel cystatin of P. ovis var. cuniculi (PsoCys) using bioinformatics and molecular biology methods. Results The results showed that PsoCys comprised the classical features of the type II cystatin superfamily including an N-terminal glycine residue, a central QXVXG motif, and a C-terminal LW motif. In mixed stages of mites, the transcription level of PsoCys was significantly higher in “fed” mites than in “starved” mites (P

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA), a rare but life-threatening systemic vasculitis, is distinguished by marked eosinophilia and presents with diverse symptoms, including asthma, cutaneous purpura, ecchymosis, skin necrosis, cardiac lesions, peripheral neuropathy, and necrotizing vasculitis. The etiology of EGPA involves a complex interaction among humoral, adaptive, innate, and allergic immune responses. Standard treatment employs prolonged high-dose glucocorticoid therapy, which is critical for survival; however, some patients’ symptoms cannot be relieved. Case report This case report details the medical management of an 11-year-old patient with EGPA, who was at risk of bilateral lower limb amputation due to differential arterial occlusion and severe, necrotizing vasculitis-induced gangrene in both feet. Treatment modalities administered included systemic infusion of Umbilical Cord Mesenchymal Stem Cells (UC-MSCs), targeted gastrocnemius muscle injections, and application of a Placenta-Derived Mesenchymal Stem Cells (PD-MSCs) hydrogel. Results After receiving a four-month regimen of allogeneic mesenchymal stem cell therapy via intravenous and local administration, the patient showed normalized eosinophil counts, reestablished blood flow in the dorsal arteries, and marked improvement in foot ulcerations. Conclusion Mesenchymal stem cell therapy is a promising option for severe EGPA cases refractory to glucocorticoids.

Abstract Weeds are undesired plants competing with crops for light, nutrients, and water, negatively impacting crop growth. Identifying weeds in wheat fields accurately is important for precise pesticide spraying and targeted weed control. Grass weeds in their early growth stages look very similar to wheat seedlings, making them difficult to identify. In this study, we focused on wheat fields with varying levels of grass weed infestation and used unmanned aerial vehicles (UAVs) to obtain images. By utilizing deep learning algorithms and spectral analysis technology, the weeds were identified and extracted accurately from wheat fields. Our results showed that the precision of weed detection in scattered wheat fields was 91.27% and 87.51% in drilled wheat fields. Compared to areas without weeds, the increase in weed density led to a decrease in wheat biomass, with the maximum biomass decreasing by 71%. The effect of weed density on yield was similar, with the maximum yield decreasing by 4320 kg·ha− 1, a drop of 60%. In this study, a method for monitoring weed occurrence in wheat fields was established, and the effects of weeds on wheat growth in different growth periods and weed densities were studied by accurately extracting weeds from wheat fields. The results can provide a reference for weed control and hazard assessment research.

Abstract Neutrophil extracellular traps (NETs), crucial in immune defense mechanisms, are renowned for their propensity to expel decondensed chromatin embedded with inflammatory proteins. Our comprehension of NETs in pathogen clearance, immune regulation and disease pathogenesis, has grown significantly in recent years. NETs are not only pivotal in the context of infections but also exhibit significant involvement in sterile inflammation. Evidence suggests that excessive accumulation of NETs can result in vessel occlusion, tissue damage, and prolonged inflammatory responses, thereby contributing to the progression and exacerbation of various pathological states. Nevertheless, NETs exhibit dual functionalities in certain pathological contexts. While NETs may act as autoantigens, aggregated NET complexes can function as inflammatory mediators by degrading proinflammatory cytokines and chemokines. The delineation of molecules and signaling pathways governing NET formation aids in refining our appreciation of NETs’ role in immune homeostasis, inflammation, autoimmune diseases, metabolic dysregulation, and cancer. In this comprehensive review, we delve into the multifaceted roles of NETs in both homeostasis and disease, whilst discussing their potential as therapeutic targets. Our aim is to enhance the understanding of the intricate functions of NETs across the spectrum from physiology to pathology.

Abstract Pyroptosis is a type of programmed cell death characterized by cell swelling and osmotic lysis, resulting in cytomembrane rupture and release of immunostimulatory components, which play a role in several pathological processes. Significant cellular responses to various stimuli involve the formation of inflammasomes, maturation of inflammatory caspases, and caspase-mediated cleavage of gasdermin. The function of pyroptosis in disease is complex but not a simple angelic or demonic role. While inflammatory diseases such as sepsis are associated with uncontrollable pyroptosis, the potent immune response induced by pyroptosis can be exploited as a therapeutic target for anti-tumor therapy. Thus, a comprehensive review of the role of pyroptosis in disease is crucial for further research and clinical translation from bench to bedside. In this review, we summarize the recent advancements in understanding the role of pyroptosis in disease, covering the related development history, molecular mechanisms including canonical, non-canonical, caspase 3/8, and granzyme-mediated pathways, and its regulatory function in health and multiple diseases. Moreover, this review also provides updates on promising therapeutic strategies by applying novel small molecule inhibitors and traditional medicines to regulate pyroptosis. The present dilemmas and future directions in the landscape of pyroptosis are also discussed from a clinical perspective, providing clues for scientists to develop novel drugs targeting pyroptosis.

Deterministically achieving on-chip photon storage and retrieval is a fundamental challenge for integrated photonics. Moreover, this requirement is increasingly urgent as photon storage and retrieval is crucial to realize truly scalable room-temperature quantum computing. However, most of existing quantum memories integrated on chips must either work at cryogenic temperature or else are strongly coupled with the environment, which hugely reduces the efficiency. Here, we propose an on-chip room-temperature quantum memory comprising three coupled microcavities, which presents an ideal dark state decoupled by a waveguide, thereby allowing on-demand photon storage and retrieval with high efficiency and high fidelity simultaneously. Furthermore, we demonstrate that the single-photon temporal duration can be increased or decreased by a factor of 103, thereby enabling many crucial quantum applications. Our error-robust approach highlights the potential for a solid-state photonic molecule for use as on-chip quantum memory and for optical quantum computing.

Fly ash grouting is a common method for mine fire prevention and control. Aiming at the problems of fly ash slurry which is prone to water-loss cracking, poor stability and low fire prevention efficiency, fly ash colloids were prepared by adding high molecular polymer xanthan gum (XG) and hydroxypropyl methyl cellulose (HPMC) to fly ash slurry, and the gel formation time, water-retaining property and thermal stability of fly ash colloids with different water-cement ratios were tested. The effect of colloid on the inhibition of coal spontaneous combustion was studied by programmed temperature. The results showed that when the water-cement ratio of fly ash slurry was 10∶1, the glue formation time was 9.52 min, and the water-retaining property and static stability were good. The fly ash colloid exhibited the shear dilution phenomenon of non-Newtonian fluid, and the energy storage modulus G′ was higher than the loss modulus G″. It was a pseudo-plastic fluid conforming to the power law model, and exhibited the properties of elastic solid. The weight loss process of fly ash colloidal heating can be divided into three stages (30-100 ℃, 218-380 ℃ and 380-800 ℃), and the total mass loss was about 6.17%. Fly ash colloid had the function of high moisture content, oxygen isolation and fissure sealing. The inhibition rate of coal sample after inhibition was 75.86%, and the corresponding temperature point of CO and C2H4 gas generation were 30 ℃ and 20 ℃ later than that of raw coal. The spontaneous combustion process of coal had been effectively inhibited.

Abstract Objective We explored the preliminary value of abnormal spindle-like microcephaly- associated (ASPM) protein in aiding precise risk sub-stratification, prediction of metabolic heterogeneity, and prognosis of neuroblastoma (NB). Methods This retrospective study enrolled newly diagnosed patients with NB who underwent positron emission tomography/computed tomography (PET/CT) before therapy, and tumor tissue was collected after surgery. Regression analysis was used to evaluate ASPM expression and risk stratification in patients with NB. The expression levels of ASPM, clinical information, and PET/CT text features were analyzed using univariate and multivariate survival analyses. Finally, a correlation analysis was used to explore the relationship between ASPM and tumor metabolic heterogeneity. Results There were 48 patients with NB in this study (35 boys and 13 girls); 22 patients progressed and 16 died. We found that the level of ASPM was highly associated with risk stratification (OR = 5.295, 95%IC: 1.348–41.722, p = 0.021). Patients with NB and high-risk stratification with high ASPM level had a lower 3-year progression-free survival (PFS) rate (14.28%) and 1-year PFS rate (57.14%) than those with low ASPM level (57.14% and 93.75%, respectively). Using univariate and multivariate survival analyses, this study revealed that ASPM and LDH were independent risk factors for both PFS and overall survival (OS), whales GLZLM_ZLNU was only a risk factor for PFS. Conclusion ASPM holds promise as a novel biomarker for refining current risk stratification and predicting prognosis in neuroblastoma. Elevated levels of ASPM, LDH, and GLZLM_ZLNU may be associated with poorer survival outcomes in neuroblastoma patients.

Abstract Background Different hormone receptor (HR) expression patterns have significant biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the distinction between HR-positive /HER2-positive (HR+/HER2+) and HR-negative/HER2-positive (HR-/HER2+) subtypes remains unclear. Methods This retrospective study analyzed 828 patients with HER2-positive breast cancer at the First Affiliated Hospital of Xi’an Jiaotong University from 2012 to 2022. Baseline characteristics were compared by chi-square test. Survival outcomes were estimated by Kaplan-Meier method. Results In total, 56.3% (n = 466) had HR-positive and 43.7% (n = 362) had HR-negative disease. Comparatively, HR+/HER2 + breast cancers presented favorable clinicopathological features. At a median follow-up of 49 months, 199 disease-free survival (DFS) events and 99 deaths were observed. HR+/HER2 + patients had significantly better survival outcomes than HR-/HER2 + patients. HR-positive status was an independent protective factor for overall survival (OS) [P = 0.032; hazard ratio, 0.61; 95% confidence interval (CI), 0.39–0.96] and DFS (P = 0.001; hazard ratio, 0.61; 95% CI, 0.46–0.81). HR+/HER2 + patients were significantly less sensitive to neoadjuvant therapy than HR-/HER2 + patients. In the first-line treatment for HR+/HER2 + advanced breast cancer, receiving endocrine therapy significantly improved advanced-OS (P

Abstract Objective This study aims to assess the performance of various scoring systems in predicting the 28-day mortality of patients with aortic aneurysms (AA) admitted to the intensive care unit (ICU). Methods We utilized data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) to perform a comparative analysis of various predictive systems, including the Glasgow Aneurysm Score (GAS), Simplified Acute Physiology Score (SAPS) III, SAPS II, Logical Organ Dysfunction System (LODS), Sequential Organ Failure Assessment (SOFA), Systemic Inflammatory Response Syndrome (SIRS), and The Oxford Acute Illness Severity Score (OASIS). The discrimination abilities of these systems were compared using the area under the receiver operating characteristic curve (AUROC). Additionally, a 4-knotted restricted cubic spline regression was employed to evaluate the association between the different scoring systems and the risk of 28-day mortality. Finally, we conducted a subgroup analysis focusing on patients with abdominal aortic aneurysms (AAA). Results This study enrolled 586 patients with AA (68.39% male). Among them, 26 patients (4.4%) died within 28 days. Comparative analysis revealed higher SAPS II, SAPS III, SOFA, LODS, OASIS, and SIRS scores in the deceased group, while no statistically significant difference was observed in GAS scores between the survivor and deceased groups (P = 0.148). The SAPS III system exhibited superior predictive value for the 28-day mortality rate (AUROC 0.805) compared to the LODS system (AUROC 0.771), SOFA (AUROC 0.757), SAPS II (AUROC 0.759), OASIS (AUROC 0.742), SIRS (AUROC 0.638), and GAS (AUROC 0.586) systems. The results of the univariate and multivariate logistic analyses showed that SAPS III was statistically significant for both 28-day and 1-year mortality. Subgroup analyses yielded results consistent with the overall findings. No nonlinear relationship was identified between these scoring systems and 28-day all-cause mortality (P for nonlinear > 0.05). Conclusion The SAPS III system demonstrated superior discriminatory ability for both 28-day and 1-year mortality compared to the GAS, SAPS II SIRS, SOFA, and OASIS systems among patients with AA.

Abstract Normal veins could develop to varicose vein (VV) by some risk factors, and might further progress to shallow vein thrombosis (SVT). However, the molecular mechanism of key genes associated with the progression and regression of VV are still not thorough enough. In this study, the healthy control (HC), VV, and SVT vascular samples were collected for transcriptome sequencing. The differentially expressed genes (DEGs) were screened by “DESeq2”, including DEGs1 (HC vs. VV), DEGs2 (HC vs. SVT) and DEGs3 (VV vs. SVT). And their functional enrichment analyses were conducted by “ClusterProfiler”. The receiver operating characteristic (ROC) curve was used to obtain the key genes (KGs) of the pathogenesis of VV and SVT. The qRT-PCR assay was performed to validate the expressions of KGs. Immune cell infiltration analyses were conducted based on ssGSEA method. The competitive endogenous RNAs (ceRNAs) regulatory network was constructed. The target drugs of KGs were predicted using DrugBank database. The biofunctions of DACT3 were further investigated through a series of experiments in vitro. All of these DEGs were associated with inflammation and immunity related functions. Immune cell infiltration was significantly different between VV and SVT. Six key genes including PLP2, DACT3, LRRC25, PILRA, MSX1 and APOD that were associated with the progression and regression of VV were screened. The expression of LRRC25 and PILRA was significantly negatively associated with central memory T cell, and significantly positively associated with B cell. Besides, XIST was the critical regulator of multiple KGs. Cimetidine was potential drug for VV and SVT therapy. Overexpression of DACT3 significantly inhibited the proliferation and migration of vascular smooth muscle cells (VSMCs), and affected their cell cycle and phenotypic transition. This study identified six key genes associated with the progression and regression of VV. Among them, DACT3 was proved to hinder VV progression. These findings may help to deepen understanding its underlying mechanisms.