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Abstract In this paper, we investigate the localization of matter fields on a flat fermion thick brane. To localize scalar and fermion fields within a five-dimensional spacetime, we introduce the Yukawa coupling mechanism. Based on this framework, we study the localization and evolution of the scalar field, as well as the localization of the fermion field on the brane. For scalar fields, various effective potentials can be derived from the variation of the scalar field function $$F(\varPhi )$$ F ( Φ ) in the coupling function. The flat brane can exhibit an effective potential resembling either a volcano or an infinitely deep potential well. By choosing the appropriate coupling parameters, we can find the localized zero mode and some resonance states. This result is similar to the localization of the fermion field on a background scalar field. Additionally, we employ various resonance states as initial values to further explore the evolution on the brane. For the fermion field, we find that the fermion zero mode cannot be localized on the brane. However, by varying the coupling parameters, we obtain an asymmetric infinitely deep potential well. As the coupling parameters increase, the asymmetry become more pronounced.

Abstract Since the spontaneously broken of the Lorentz symmetry in the gravity theory with the non-minimally coupling between the Kalb–Ramond (KR) field (that acquires a nonzero vacuum expectation value) and the Einstein gravity, there exists the exactly static and spherically symmetric black holes solutions related with the Lorentz violating parameter. Based on this, we consider the corresponding black hole solution in the de-Sitter (dS) spacetime with the KR field and investigate the thermodynamic properties in the expanded phase space through introducing the interplay entropy between the black hole and cosmological horizons. Especially we analyze the effect of the Lorentz-violating parameter on the thermodynamic properties. Furthermore, the Lyapunov exponent and the shadow of these static and spherically symmetric black holes in this Lorentz-violating gravity theory are also investigated. These study will open a new perspective to probe the thermodynamics of black holes.

During a survey of saprobic fungi on medicinal plants in Southwestern China, thirty-nine hyphomycetous collections belonging to Dictyosporiaceae, Melanommataceae, and Stachybotryaceae were identified, representing nineteen distinct species. These taxa were characterised and identified based on morphological and culture characteristics, coupled with phylogenetic analyses of combined sequences of calmodulin (cmdA), the internal transcribed spacer region of ribosomal DNA (ITS), nuclear large subunit ribosomal DNA (LSU), RNA polymerase second-largest subunit (rpb2), the translation elongation factor 1-alpha (tef1-α), and β-tubulin (tub2). Twelve novel species are described, including Camposporium alangii, C. polygoni, Dendryphiella verrucosispora, Jalapriya cheirospora, Memnoniella cnidiicola, M. guttulatispora, M. reniformis, M. reynoutriae, M. verrucosispora, Sirastachys aspidistrae, Sir. ellipsoidispora, and Striatibotrys biguttulatispora. Additionally, three new host records, M. alishanensis, Sir. castanedae, and Stachybotrys chartarum, and four new hosts and geographical records of M. ellipsoidea, M. pseudonilagirica, Str. rhabdospora, and Virgatospora echinofibrosa are reported. Memnoniella nilagirica is revised and synonymised under M. pseudonilagirica. Key morphological characteristics, hosts specificity, and distributional data of Memnoniella, Sirastachys, and Striatibotrys were summarised. This study provides comprehensive illustrations, descriptions, and notes for each new taxon and record, marking the first report of these species from medicinal plants.

Abstract Diagnosing neurosyphilis in clinical settings poses significant challenges due to the absence of highly efficient diagnostic criteria. Our objective was to enhance the existing diagnostic criteria and assess their sensitivity and specificity for identifying neurosyphilis in HIV-negative patients. We conducted a retrospective review of patient records from a cross-sectional study carried out between December 2019 and May 2023. This study was designed to explore clinical practices in the diagnosis and treatment of neurosyphilis. We proposed and validated a new set of diagnostic criteria across 782 cases, comparing three different NS criteria for diagnostic efficiency. Among the 782 patients analyzed, 410 were diagnosed with neurosyphilis, while 372 were not. The newly developed NS criteria demonstrated a sensitivity of 99.5% and a specificity of 94.6%, with the added benefit of being user-friendly. In subgroups categorized by neurological symptoms and syphilis stages, the new NS criteria also exhibited high sensitivity and specificity. Statistical analyses confirmed that the novel NS criteria performed comparably well to the expanded NS criteria. The novel NS criteria for HIV-negative patients exhibited high sensitivity and specificity, proving to be both effective and convenient for physicians to implement.

Abstract Critical-sized bone defects are usually accompanied by bacterial infection leading to inflammation and bone nonunion. However, existing biodegradable materials lack long-term therapeutical effect because of their gradual degradation. Here, a degradable material with continuous ROS modulation is proposed, defined as a sonozyme due to its functions as a sonosensitizer and a nanoenzyme. Before degradation, the sonozyme can exert an effective sonodynamic antimicrobial effect through the dual active sites of MnN4 and Cu2O8. Furthermore, it can promote anti-inflammation by superoxide dismutase- and catalase-like activities. Following degradation, quercetin-metal chelation exhibits a sustaining antioxidant effect through ligand-metal charge transfer, while the released ions and quercetin also have great self-antimicrobial, osteogenic, and angiogenic effects. A rat model of infected cranial defects demonstrates the sonozyme can rapidly eliminate bacteria and promote bone regeneration. This work presents a promising approach to engineer biodegradable materials with long-time effects for infectious bone defects.

Abstract As we know, the horizon area of a black hole will increase when it absorbs matter. Based on Barrow’s concept of a fractal black hole horizon, it has been proposed (Phys Lett B 831:137181, 2022) that for a spherically fractal structure, the minimum increase in the horizon area is the area of the smallest bubble sphere. The corresponding black hole entropy is of a logarithmic form, which is similar to that of Boltzmann entropy under a certain condition. Based on this, we re-derive the entropy of Barrow’s Einstein–power-Yang–Mills (EPYM) anti-de Sitter (AdS) black hole, and calculate its temperature and heat capacity. There exists an interesting phenomenon wherein the ratio between Barrow’s temperature and the Hawking temperature of the EPYM AdS black hole is fully consistent with that of other Schwarzschild-like black holes. The Barrow and Hawking temperatures within a certain range of $$\Lambda $$ Λ are found to increase monotonically, and the corresponding heat capacities are all positive, which means that these black holes are thermodynamically stable. In addition, for Barrow’s EPYM AdS black hole, its heat capacity has a Schottky anomaly-like behavior, which may reflect the existence of a discrete energy level and microscopic degrees of freedom.

During a survey of saprobic fungal niches in Southwestern China, eighteen ascomycetous collections of Nigrograna (Nigrogranaceae, Pleosporales, Dothideomycetes) were found on dead branches of medicinal plants. These taxa were characterized and identified based on morphological and culture characteristics, and phylogenetic analyses of a combined the internal transcribed spacer region of rDNA (ITS), nuclear large subunit rDNA (28S, LSU), RNA polymerase second-largest subunit (rpb2), nuclear small subunit rDNA (18S, SSU), and translation elongation factor 1-alpha (tef1-α) sequence dataset also confirmed their placement. As a result, four novel species, namely Nigrograna camelliae, N. guttulata, N. longiorostiolata and N. neriicola were described. Additionally, four new host records of N. acericola, N. magnoliae, N. oleae and N. thymi were introduced. Furthermore, this study addresses the taxonomic status of N. trachycarpi, proposing its synonymy under N. oleae. Detailed illustrations, descriptions and informative notes for each newly identified taxon and novel host record are provided in this study.

Abstract The epidermal growth factor receptor (EGFR) is a validated therapeutic target for RAS/RAF wild‐type colorectal cancer (CRC). However, monoclonal antibody‐based anti‐EGFR therapies such as cetuximab have limited effectiveness. Herein, it is identified that EGFR internalization is associated with poor treatment response and prognosis in patients with CRC, based on a retrospective analysis of patients treated with cetuximab. It is further demonstrated that the endocytosis inhibitor prochlorperazine (PCZ) can move EGFR, which is hidden inside the cell, to the cell surface to improve therapeutic antibody binding. Thus, a thermosensitive hydrogel co‐loaded with cetuximab and PCZ (Gel@Cmab/PCZ) is constructed for sustained inhibition of endocytosis and effective cetuximab delivery. Peritumoral injection of Gel@Cmab/PCZ shows strong antitumor efficacy in subcutaneous and orthotopic CRC tumor models and completely abrogated liver metastasis when combined with chemotherapy. In a humanized patient‐derived xenograft model, a single injection of Gel@Cmab/PCZ with one‐third of the conventional cetuximab dose achieved 91% tumor growth inhibition, which promoted NK cell infiltration into tumor tissues and their antibody‐dependent cell‐mediated cytotoxicity effect. This study represents a novel strategy to boost the monoclonal antibody‐mediated anti‐tumor response in CRC.

Abstract In this paper, the higher-dimensional topological dS black hole with a nonlinear source (HDTNS) is considered. First, we obtain the thermodynamic quantities of the ( $$n+1$$ n + 1 )-dimensional topological dS black hole, which satisfy the first law of thermodynamics. Second, based on the effective thermodynamic quantities and Maxwell’s equal-area law method, we explore the phase equilibrium for the HDTNS. The boundary of the two-phase coexistence region in the $$P_\textrm{eff}^{0}-T_\textrm{eff}^{0}$$ P eff 0 - T eff 0 diagram is obtained. The critical thermodynamic quantities as well as the horizon potential are also investigated. Furthermore, we analyze the effect of parameters (the spacetime dimension n and the ratio of two horizon radii $$x= {r_{+}}$$ x = r + / $$ {r_{c}}$$ r c ) on the boundary of the two-phase coexistence region and study the latent heat of phase transition for this system, which corresponds to the Clapeyron equation. The results indicate that the phase transition in HDTNS spacetime is analogous to that in a van der Waals (vdW) fluid system, which is determined by electrical potential at the horizon. These results help to understand the fundamental properties of black holes. A more intuitive and profound understanding of gravity is gained by studying the thermodynamic properties of different spacetimes. They provide a theoretical basis for an in-depth study of the classical and quantum properties of de Sitter spacetime and its evolution.

Childhood obesity presents a serious health concern associated with gut microbiota alterations. Dietary interventions targeting the gut microbiota have emerged as promising strategies for managing obesity in children. This study aimed to elucidate the impact of stachyose (STS) supplementation on the gut microbiota composition and metabolic processes in obese children. Fecal samples were collected from 40 obese children (20 boys and 20 girls) aged between 6 and 15 and in vitro fermentation was conducted with or without the addition of STS, respectively, followed by 16S rRNA amplicon sequencing and analysis of short-chain fatty acids (SCFAs) and gases. Notably, our results revealed that STS supplementation led to significant alterations in gut microbiota composition, including an increase in the abundance of beneficial bacteria such as Bifidobacterium and Faecalibacterium, and a decrease in harmful bacteria including Escherichia-Shigella, Parabacteroides, Eggerthella, and Flavonifractor. Moreover, STS supplementation resulted in changes in SCFAs production, with significant increases in acetate levels and reductions in propionate and propionate, while simultaneously reducing the generation of gases such as H2S, H2, and NH3. The Area Under the Curve (AUC)-Random Forest algorithm and PICRUSt 2 were employed to identify valuable biomarkers and predict associations between the gut microbiota, metabolites, and metabolic pathways. The results not only contribute to the elucidation of STS’s modulatory effects on gut microbiota but also underscore its potential in shaping metabolic activities within the gastrointestinal environment. Furthermore, our study underscores the significance of personalized nutrition interventions, particularly utilizing STS supplementation, in the management of childhood obesity through targeted modulation of gut microbial ecology and metabolic function.

Background Percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported to be safe and effective at midterm follow‐up to treat drug‐refractory hypertrophic obstructive cardiomyopathy in a single center. However, data from other centers are lacking. This retrospective cohort study aimed to investigate the efficacy and safety of PIMSRA from another independent center. Methods and Results PIMSRA was performed in 76 patients with hypertrophic obstructive cardiomyopathy in our center from April 2020 to June 2023. The primary outcome was the reduction of left ventricular outflow tract gradient after 6 months or more post‐PIMSRA. Secondary outcomes were periprocedural major adverse clinical events. Sixty‐one patients returned to the hospital for follow‐up 6 to 30 (median, 14) months after the procedure. At the last follow‐up of the 61 patients, the maximum septal thickness decreased from a median of 23.6 (interquartile range, 20.5–26.4) to 19.1 (interquartile range, 16.0–22.1) mm (P

In this study, a dynamic headspace (DHS) combined with thermal desorption/gas chromatography-mass spectrometry (TD/GC-MS) method was established to analyze the volatile composition of baked green tea. Extraction parameters including tea amount, trapping temperature, incubation temperature, total purge volume, purge rate, and drying rate were optimized. Furthermore, the key odorants of baked green tea made from different tea cultivars were identified by gas chromatography-olfactometry-mass spectrometry (GC-O-MS). The results indicated that the optimal extraction conditions were as follows: tea amount of 200 mg, trapping temperature of 70 ℃, incubation temperature of 70 ℃, total purge volume of 350 mL, purge rate of 10 mL/min, and drying rate of 10 mL/min. A total of 74 volatile components were identified in green tea made from three representative varieties. Multivariate statistical analysis showed that the aroma compounds of the three green teas varied greatly, and 18 key differential volatile aroma components were identified. The contents of isopropylidesneacetone and linalool in LongJing 43 (LJ 43) baked green tea were the highest among these three teas. Fuding Dabaicha (FDDB) baked green tea contained the highest levels of 6-methyl-5-heptene-2-one, octanal, cyclohexanone, acetophenone, copaene and epicubenol. A total of 28 odorants were identified by GC-O-MS analysis. The odorants were mainly responsible for odor attributes such as green, refreshing, floral, fruity, herbal, woody and sweet aromas. The total aroma intensity of floral and fruity attributes was the highest, followed by the green and refreshing attributes. Taken collectively, linalool, calamenene, δ-cadinene, 6-methyl-5-heptene-2-one and octanal were the key differential odorants among the three green teas. Linalool contributed significantly to LJ 43 baked green tea, and the other four odorants contributed significantly to the formation of the aroma quality of FDDB baked green tea.

Freshwater fungi are highly diverse in China and frequently reported from submerged wood, freshwater insects, herbaceous substrates, sediments, leaves, foams, and living plants. In this study, we investigated two freshwater species that were collected from Yunnan and Guizhou provinces in China. Detailed morphological analysis complemented by multi-gene phylogenetic analyses based on LSU, SSU, ITS, RPB2 and TEF1-α sequences data revealed them to be two new saprobic species, namely Acrogenospora alangii sp. nov. and Conioscypha yunnanensis sp. nov. in their asexual morphs. Additionally, Acrogenospora alangii sp. nov. is reported for the first time as a freshwater ascomycete associated with the medicinal plant Alangium chinense (Alangiaceae). Detailed morphological descriptions, illustrations and updated phylogenetic relationships of the new taxa are provided herein.

Medicinal plants serve as vital resources for preventing and treating diseases, with their flowers, fruits, leaves, roots, or entire plants being utilized in the pharmaceutical industry or as direct therapeutic agents. During our investigation of microfungi associated with medicinal plants in Guizhou and Sichuan Provinces, China, several asexual and sexual fungal morphs were collected. Multi-locus phylogenetic analysis based on combined ITS, LSU, SSU and TEF1-α datasets revealed that these taxa are related to the family Dictyosporiaceae. Morphological characteristics, along with multi-locus phylogenetic analysis, supported the establishment of Dictyocheirospora alangii sp. nov. and Pseudocoleophoma rosae sp. nov., as well as the introduction of a novel genus Neoxylochrysis, which accommodates Neoxylochrysis typhicola comb. nov. (≡Pseudocoleophoma typhicola). In addition, four new host records are introduced for Aquadictyospora lignicola from Periploca forrestii, Dendryphiella eucalyptorum from Leonurus japonicus, Ophiopogon japonicus and Sambucus javanica, D. vinosa from Phytolacca americana, and Dictyocheirospora rotunda from Euonymus japonicus and Prinsepia utilis. Detailed descriptions, micrographs of the new taxa and a phylogenetic tree are provided.

Objective To systematically assess the diagnostic accuracy of CXCL13 testing of cerebrospinal fluid (CSF) for neurosyphilis diagnosing.Design Systematic review and meta-analysis.Data sources PubMed, Embase, Cochrane Library and Web of Science databases from their inception until 1 May 2023.Eligibility criteria Both cross-sectional and case–control diagnostic test studies evaluating the diagnostic value of CSF CXCL13 in diagnosing neurosyphilis were included, with no language restrictions.Data extraction and synthesis Two researchers extracted data independently from all finally included articles. The updated Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. Quantitative synthesis was done using a bivariate random-effects model.Results This meta-analysis included seven eligible studies involving a total of 1152 patients with syphilis and 430 patients with neurosyphilis. The pooled sensitivity, specificity and summary area under the curve (AUC) of CSF CXCL13 testing for the diagnosis of neurosyphilis were 0.76 (95% CI 0.64 to 0.85; I2=82%), 0.83 (95% CI 0.80 to 0.85; I2=32.29%) and 0.84 (95% CI 0.81 to 0.87), respectively. Sensitivity analysis confirmed the stability of the combined results. Meta-regression analysis revealed that the heterogeneity of pooled sensitivity was related to different study regions; subgroup analysis indicated that the diagnostic value of CSF CXCL13 testing reported in studies from China was superior to that reported in non-Chinese studies (pooled sensitivity, specificity and summary AUC values were 0.84 (I2=0) vs 0.64 (I2=79.53%), 0.83 (I2=42.03%) vs 0.83 (I2=32.87%) and 0.87 vs 0.83, respectively). The diagnostic value reported in studies with a sample size ≥200, unclassified neurosyphilis and HIV-negative subgroups was superior to the total combined value.Conclusions This meta-analysis has demonstrated a reasonable level of accuracy for diagnosis of neurosyphilis with CSF CXCL13 testing. Further multicentre, prospective diagnostic studies, especially in asymptomatic neurosyphilis and HIV-infected patients, are needed to provide more evidence for evaluation before clinical application.PROSPERO registration number CRD42023414212.

Abstract Background The aim of this study was to determine the underlying potential mechanisms and function of DIO3OS, a lincRNA in osteosarcoma and clarify that DIO3OS can be used as a potential diagnostic biomarker and immunotherapeutic target. Methods The expression matrix data and clinical information were obtained from XENA platform of UCSC and GEO database as the test cohorts. The external validation cohort was collected from our hospital. Bioinformatics analysis was used to annotate the biological function of DIO3OS. Immune infiltration and immune checkpoint analysis were applied to evaluate whether DIO3OS can be used as an immunotherapeutic target. ROC curves and AUC were established to assess the diagnostic value of DIO3OS for differentiating patients from other subtypes sarcoma. The expression analysis was detected by qRT-PCR, western blot, and immunohistochemical. Wound healing assay and Transwell assay were applied to determine the migration and invasion function of DIO3OS in osteosarcoma cell lines. The tail vein injection osteosarcoma cells metastases model was used in this research. Results High expression of DIO3OS was identified as a risk lincRNA for predicting overall survival of osteosarcoma in test cohort. The outcomes of experiments in vitro and in vivo showed that low expression of DIO3OS limited osteosarcoma tumor metastasis with inhibiting TGF-β signaling pathway. Immune checkpoint genes (CD200 and TNFRSF25) expressions were inhibited in the low DIO3OS expression group. The DIO3OS expression can be applied to reliably distinguish osteosarcoma from lipomatous neoplasms, myomatous neoplasms, nerve sheath tumors, and synovial-like neoplasms. This result was further validated in the validation cohort. Conclusions In conclusion, our outcomes indicated that DIO3OS is a potential diagnostic and prognostic biomarker of osteosarcoma, emphasizing its potential as a target of immunotherapy to improve the treatment of osteosarcoma through TGF-β signaling pathway. Trial registration number: The present retrospectively study was approved by the Ethics Committee of The Second Affiliated Hospital of Nanchang University [Review (2020) No. (115)].

Abstract Background Accurately predicting the risk of atherosclerotic cardiovascular disease (ASCVD) is crucial for implementing individualized prevention strategies and improving patient outcomes. Our objective is to develop machine learning (ML)-based models for predicting ASCVD risk in a prospective Chinese population and compare their performance with conventional regression models. Methods A hybrid dataset consisting of 551 features was used, including 98 demographic, behavioral, and psychological features, 444 Electrocardiograph (ECG) features, and 9 Echocardiography (Echo) features. Seven machine learning (ML)-based models were trained, validated, and tested after selecting the 30 most informative features. We compared the discrimination, calibration, net benefit, and net reclassification improvement (NRI) of the ML models with those of conventional ASCVD risk calculators, such as the Pooled Cohort Equations (PCE) and Prediction for ASCVD Risk in China (China-PAR). Results The study included 9,609 participants (mean age 53.4 ± 10.4 years, 53.7% female), and during a median follow-up of 4.7 years, 431 (4.5%) participants developed ASCVD. In the testing set, the final ML-based ANN model outperformed PCE, China-PAR, recalibrated PCE, and recalibrated China-PAR in predicting ASCVD. This was demonstrated by the model's higher area under the curve (AUC) of 0.800, compared to 0.777, 0.780, 0.779, and 0.779 for the other models, respectively. Additionally, the model had a lower Hosmer–Lemeshow χ2 of 9.1, compared to 37.3, 67.6, 126.6, and 18.6 for the other models. The net benefit at a threshold of 5% was also higher for the ML-based ANN model at 0.017, compared to 0.016, 0.013, 0.017, and 0.016 for the other models, respectively. Furthermore, the NRI was 0.089 for the ML-based ANN model, while it was 0.355, 0.098, and 0.088 for PCE, China-PAR, and recalibrated PCE, respectively. Conclusions Compared to conventional regression ASCVD risk calculators, such as PCE and China-PAR, the ANN prediction model may help optimize identification of individuals at heightened cardiovascular risk by flexibly incorporating a wider range of potential predictors. The findings may help guide clinical decision-making and ultimately contribute to ASCVD prevention and management.

Poor dietary habits have been associated with dysbiosis and microbial imbalance in pregnant women. Such imbalances can pose health risks during pregnancy. This study aimed to explore the impact of Polygonati Rhizoma on the gut microbiota of pregnant women through In vitro simulated fermentation. Interestingly, significant differences in microbial community richness and structure were found between the control and the treatment with Polygonati Rhizoma. Analysis of composition and variability indicated that the treatment with Polygonati Rhizoma group showed higher levels of Lactobacillus and Bifidobacterium, but lower levels of Parabacteroides and Lachnoclostridium. The study also investigated specific genera differences between groups using the co-occurrence network analysis and their correlations with microbial metabolites by the redundancy analysis (RDA), Mantel-test network heatmap, and heatmap highlighting the relationships among gut microbiota, short-chain fatty acids (SCFAs), and gases in the absence or presence of Polygonati Rhizoma supplementation. Functional predictions from BugBase phenotype prediction indicated changes in potentially pathogenic and aerobic bacteria in Polygonati Rhizoma supplementation. Overall, the findings provide valuable insights into the influence of Polygonati Rhizoma on the gut microbiota in pregnant women associated with poor dietary habits.

Abstract Hydrogels are prevailing drug delivery depots to improve antitumor efficacy and reduce systemic toxicity. However, the application of conventional free drug‐loaded hydrogel is hindered by poor drug penetration in solid tumors. Here, an injectable ferritin‐based nanocomposite hydrogel is constructed to facilitate tumor penetration and improve cancer chemoimmunotherapy. Specifically, doxorubicin‐loaded human ferritin (Dox@HFn) and oxidized dextran (Dex‐CHO) are used to construct the injectable hydrogel (Dox@HFn Gel) through the formation of pH‐sensitive Schiff‐base bonds. After peritumoral injection, the Dox@HFn Gel is retained locally for up to three weeks, and released intact Dox@HFn gradually, which can not only facilitate tumor penetration through active transcytosis but also induce immunogenic cell death (ICD) to tumor cells to generate an antitumor immune response. Combining with anti‐programmed death‐1 antibody (αPD‐1), Dox@HFn Gel induces remarkable regression of orthotopic 4T1 breast tumors, further elicits a strong systemic anti‐tumor immune response to effectively suppress tumor recurrence and lung metastasis of 4T1 tumors after surgical resection. Besides, the combination of Dox@HFn GelL with anti‐CD47 antibody (αCD47) inhibits postsurgical tumor recurrence of aggressive orthotopic glioblastoma tumor model and significantly extends mice survival. This work sheds light on the construction of local hydrogels to potentiate antitumor immune response for improved cancer therapy.

Intervertebral disc degeneration (IVDD) is a prevalent cause of low back pain and a leading contributor to disability. IVDD progression involves pathological shifts marked by low-grade inflammation, extracellular matrix remodeling, and metabolic disruptions characterized by heightened glycolytic pathways, mitochondrial dysfunction, and cellular senescence. Extensive posttranslational modifications of proteins within nucleus pulposus cells and chondrocytes play crucial roles in reshaping the intervertebral disc phenotype and orchestrating metabolism and inflammation in diverse contexts. This review focuses on the pivotal roles of phosphorylation, ubiquitination, acetylation, glycosylation, methylation, and lactylation in IVDD pathogenesis. It integrates the latest insights into various posttranslational modification-mediated metabolic and inflammatory signaling networks, laying the groundwork for targeted proteomics and metabolomics for IVDD treatment. The discussion also highlights unexplored territories, emphasizing the need for future research, particularly in understanding the role of lactylation in intervertebral disc health, an area currently shrouded in mystery.

Abstract Considering the nonlinearity of the Yang Mills charge, we investigate the Joule–Thomson expansion for the Einstein–Power–Yang–Mills AdS black holes in the context of the gauge-gravity duality. Under this framework, we calculate the Joule–Thomson coefficient, describe all relevant inversion and isenthalpic curves in the temperature-pressure plane that determining in this manner the corresponding cooling and heating regions. Finally we analyze the effect of the charge nonlinearity on the Joule–Thomson expansion.

Abstract Identifying risk factors for atrial fibrillation (AF) and evaluating their impact are essential to avoid the occurrence of adverse events. However, few studies to date have explored the prevalence, risk factors, and prognosis of AF in hypertensive patients. The objective of this study was to investigate the epidemiology of AF in a hypertensive population and determine the relationship between AF and all‐cause mortality. At baseline, a total of 8541 Chinese patients with hypertension were enrolled from the Northeast Rural Cardiovascular Health Study. A logistic regression model was established to assess the relationship between blood pressure and AF, and Kaplan–Meier survival curve analysis and multivariate Cox regression were used to explore the relationship between AF and all‐cause mortality. Meanwhile, subgroup analyses illustrated the robustness of results. This study found that the overall prevalence rate of AF was 1.4% in its Chinese hypertensive population. After adjusting for the confounding factors, every standard deviation increase in diastolic blood pressure (DBP) was associated with a 37% increase in the prevalence of AF (95% confidence interval: 1.152–1.627, p

Scene text images have very complex and changeable features.Using region proposal network(RPN) to extract text rectangle position candidate boxes is an indispensable step,which can greatly improve the accuracy of text detection.However,recent studies show that the methods of regressing the center point,width and height of the text rectangular candidate boxes by minimizing the smooth L1 loss function would easily cause problems such as missing boundary information and inaccurate regression.Therefore,this paper proposes a scene text detection model based on improved region proposal network.First,the backbone network composed of the residual network and the feature pyramid network is used to generate a shared feature map.Then,an improved regression method and vertex-based loss function(Vertex-IOU) are used to generate a series of text rectangular candidate boxes on the shared feature map.Finally,ROI Align is used to convert these candidate boxes into fixed-size feature maps for bounding box regression in the fully connected layer.Through comparative experiments on ICDAR2015 dataset,the results show that the test effect is improved compared with other models,which proves the effectiveness of our model.

Abstract In this work, we investigate the relation between the photon sphere radius and the first-order phase transition for the charged Einstein-power-Yang-Mills AdS black hole. Through the analysis, we find with a certain condition there exist the non-monotonic behaviors between the photon sphere radius, the impact parameter, the non-linear Yang-Mills charge parameter, temperature, and pressure. And both the changes of photon sphere radius and impact parameter before and after phase transition can be regarded as the order parameter, their critical exponents near the critical point are equal to the same value 1/2, just like the ordinary thermal systems. These indicate that there maybe exists a universal relation of gravity nearby the critical point for a black hole thermodynamical system. Furthermore, the effect of impact parameter on the deflect angle is also investigated.

BackgroundOsteosarcoma is a highly aggressive type of bone cancer with a poor prognosis. In the tumor immune microenvironment, T-cell exhaustion can occur due to various factors, leading to reduced tumor-killing ability. The purpose of this study was to construct a prognostic model based on T-cell exhaustion-associated genes in osteosarcoma.MethodsPatient data for osteosarcoma were retrieved from the TARGET and GEO databases. Consensus clustering was employed to identify two novel molecular subgroups. The dissimilarities in the tumor immune microenvironment between these subgroups were evaluated using the “xCell” algorithm. GO and KEGG analyses were conducted to elucidate the underlying mechanisms of gene expression. Predictive risk models were constructed using the least absolute shrinkage and selection operator algorithm and Cox regression analysis. To validate the prognostic significance of the risk gene expression model at the protein level, immunohistochemistry assays were performed on osteosarcoma patient samples. Subsequently, functional analysis of the key risk gene was carried out through in vitro experimentation.ResultsFour gene expression signatures (PLEKHO2, GBP2, MPP1, and VSIG4) linked to osteosarcoma prognosis were identified within the TARGET-osteosarcoma cohort, categorizing patients into two subgroups. The resulting prognostic model showed strong predictive capability, with area under the receiver operating characteristic curve (AUC) values of 0.728/0.740, 0.781/0.658, and 0.788/0.642 for 1, 3, and 5-year survival in both training and validation datasets. Notably, patients in the low-risk group had significantly higher stromal, immune, and ESTIMATE scores compared to high-risk counterparts. Additionally, a nomogram was developed, exhibiting high accuracy in predicting the survival outcome of osteosarcoma patients. Immunohistochemistry, Kaplan-Meier, and time-dependent AUC analyses consistently supported the prognostic value of the risk model within our osteosarcoma patient cohort. In vitro experiments provided additional validation by demonstrating that the downregulation of GBP2 promoted the proliferation, migration, and invasion of osteosarcoma cells while inhibiting apoptosis.ConclusionThe current study established a prognostic signature associated with TEX-related genes and elucidated the impact of the pivotal gene GBP2 on osteosarcoma cells via in vitro experiments. Consequently, it introduces a fresh outlook for clinical prognosis prediction and sets the groundwork for targeted therapy investigations in osteosarcoma.

Abstract Objective As disc fragment completely loses contact with the parent disc and can migrate in all directions of the epidural space, making it appear similar to schwannoma, it is fairly difficult to make a definitive diagnosis for mimicking tumor discs. The aim of this research is to differentially diagnose mimicking tumor discs and schwannomas using coronal magnetic resonance imaging (MRI) of three‐dimensional fast‐field echo with water‐selective excitation (CMRI). Methods Among 76 patients (38 men and 38 women; mean age, 52.88 ± 15.80 [range, 18–78 years]) who were retrospectively examined in this study, 38 were primarily diagnosed with schwannomas and pathologically diagnosed with mimicking tumor discs after surgery, and 38 were primarily diagnosed with neurogenic tumors and pathologically diagnosed with schwannomas after surgery. Open surgery was performed in all the patients between March 2016 and April 2020. The preliminary diagnosis of all patients was considered an intraspinal tumor based on conventional two‐dimensional MRI sequences. After open surgery, the final diagnosis was confirmed to mimic a tumor disc or schwannoma based on postoperative pathology reports. The sensitivity, specificity, and reliability of CMRI and conventional MRI for identifying mimicking tumor discs and schwannomas were compared. Chi‐square and McNemar tests were used for statistical analyses. Results Symptoms were considerably relieved in all the patients after surgery. Seven patients had grade 1 extensor digitorum longus, triceps surae, or quadriceps femoris muscle strength prior to surgery. No nerve root injury was observed in any of the patients. CMRI showed significantly higher sensitivity (94.74%) and specificity (94.74%) than conventional MRI (71.05% and 92.11%, respectively; p = 0.012 0.05, respectively) for differential identification between mimicking tumor discs and schwannomas. Moreover, CMRI showed a higher reliability (kappa value = 0.787) than conventional MRI (kappa value = 0.374). Conclusions CMRI is a better non‐invasive technology for the identification of intraspinal lesions, especially for differentiating between mimicking tumor discs and schwannomas.

Abstract Background Neurosyphilis may cause irreversible neurological sequelae. First-line treatment consists of penicillin G, with ceftriaxone being an alternative treatment in patients allergic to penicillin. The lack of clinical data comparing the efficacy of these two drugs indicated the need for comparative clinical trials to improve national treatment guidelines in China. Methods/design In this multicenter randomized controlled clinical trial, 290 patients newly diagnosed with neurosyphilis will be randomized 1:1 to treatment with aqueous crystalline penicillin G (ACPG) or ceftriaxone. Patients will be treated with standard regimens of ACPG or ceftriaxone according to Chinese National Guidelines and will be followed up for 12 months. All clinical parameters will be assessed at baseline and at follow-up 3, 6, 9, and 12 months later. The primary outcomes will include cerebrospinal fluid (CSF) white blood cell (WBC) count, serological efficacy, and clinical efficacy. The secondary outcomes will include CSF protein concentrations, Mini-Mental State Examination (MMSE) scores, imaging results, recurrence, and time to recovery from neurosyphilis. Adverse events will be monitored and recorded during the trial. Discussion This trial will provide clinical data to determine whether ceftriaxone is non inferior to ACPG in treating neurosyphilis and will provide evidence for the improvement of treatment guidelines. Trial registration Chinese Clinical Trial Registry ChiCTR2100047164. Registered on 9 June 2021 and updated on 23 November 2021.

Abstract Background The awareness and willingness to use doxycycline-based syphilis chemoprophylaxis among men who have sex with men (MSM) in China remain largely unknown. Methods We recruited MSM online from Nanjing, Wuhan and Changsha between August and October of 2021, collected data from online survey, analyzed their data using descriptive statistics, and constructed binary logistic regression for factors associated with awareness and willingness to use chemoprophylaxis for syphilis and HIV. Results Of 725 participants (44.0% of which resided in Nanjing, 37.7% in Changsha, and 18.3% in Wuhan), a majority were under 25 years of age; 62.2% had college degrees; 11.3% were HIV positive; and 5.10% had prior syphilis infection. Only 28.83% of participants had heard of syphilis chemoprophylaxis before. Odds of knowing syphilis chemoprophylaxis were higher in those who think it is necessary to have syphilis chemoprophylaxis versus those who think it is unnecessary (P = 0.002), and were higher in those whose acquaintance had chemoprophylaxis experience before (P

PurposeDiarrhea is among the top five causes of morbidity and mortality in children. Dysbiosis of the gut microbiota is considered the most important risk factor for diarrhea. Prebiotics have shown efficacy in treating diarrhea by regulating the balance of the gut microbiota in vivo.MethodsIn this study, we used an in vitro fermentation system to prevent the interference of host-gut microbe interactions during in vivo examination and investigated the effect of fructo-oligosaccharides (FOS) on gut microbiota composition and metabolism in 39 pediatric patients with functional diarrhea.Results16S rRNA sequencing revealed that FOS significantly improved α- and β-diversity in volunteers with pediatric diarrhea (p 2, p 2, p 0.8). Functional prediction using PICRUSt 2 revealed that the FOS-induced alteration of gut microbiota was most likely mediated by effects on starch and sucrose metabolism.ConclusionThis study is the first to evince that FOS can modulate gut microbial disorders in children with functional diarrhea. Our findings provide a framework for the application of FOS to alleviate functional diarrhea in children and reduce the use of antibiotics for managing functional diarrhea-induced disturbances in the gut microbiota.

Abstract Since the black hole and cosmological horizons in the de Sitter (dS) spacetime with the Reissner–Nordström (RN) black hole are not independent with each other, which is caused by the gravitational effect, the interplay between two horizons should be considered. Based on this, by introducing the interactive entropy the RN–dS spacetime is analogous to a thermodynamic system with various thermodynamic quantities, in which the laws of thermodynamics still hold on. In our work, the thermodynamic properties of the RN–dS spacetime are mapped out in the induced phase space, which are similar to that in AdS black holes. The phase transition of the RN–dS spacetime between the high-potential and the low-potential black hole phases is observed. Compared with an ordinary thermodynamic system, the similar behaviors about the Joule–Thomson expansion and the critical exponents are also checked out. Finally, the scalar curvatures of two existent phases are presented to reveal the underlying microstructure and nature of phase transition in the RN–dS spacetime, which opens a new window to investigate the dS spacetime with black holes from an observational perspective.

Abstract For Anti-de Sitte (AdS) black holes, the isochoric heat capacity of system is vanished, while the isobaric heat capacity is not. However, this situation does not hold on for de Sitter (dS) black holes. In this work, by introducing the interaction between the black hole horizon and the cosmological horizon of the Reissner–Nordström-de Sitter (RNdS) spacetime with quintessence, we discuss the phase transition of this system. The results show that the spacetime not only has the similar phase transition behavior to that of Van der Waals (VdW) system, and the non-vanishing isochoric heat capacity fulfills the whole thermodynamics system. Through the discussion of the entropic force between two horizons, we find out the role of entropic force in the evolution of spacetime. In addition, we also study the influence of various parameters on the phase transition and entropic force, which will provide a new method for exploring the interaction among black hole molecules from a micro perspective.

Abstract Background Cardiovascular disease (CVD) brings high mortality and economic burden to patients, especially in rural areas. Simple, low-cost abdominal adiposity measures may help identify individuals with increased CVD risk. It is unclear that which obesity indices is the best to predict CVD in hypertensive people. Methods Northeast China Rural Cardiovascular Health Study (NCRCHS) is a prospective cohort study in a general population in Northeast China. The study examined the cardiovascular health from 2013 to 2015, and follow-up captured the CVD incidence in 2018. Baseline waist-to-height ratio (WHtR), waist circumference (WC), waist-to-hip (WHR)and body mass index (BMI) were calculated and analyzed in relation to the CVD incidence. Results A total of 4244 hypertensive adults without pre-existing CVD at baseline were included in this analysis (age 35–92 years; 2108 men). Over a median follow-up of 4.66 years, a total of 290 CVD cases (6.83%) were documented during the follow-up. Baseline WHtR showed a significant positive association with CVD incidence, even after adjusting for age, sex, diabetes, drinking, smoking, SBP, DBP, Triglyceride, HDL-C, LDL-C, and TC (Hazard Ratios per SD of WHtR ranging from 1.03 to 1.31, p = 0.017). Reclassification and discrimination analyses indicated WHtR addition could improve the conventional model for predicting adverse outcomes within 4 years. Moreover, WHtR predicted the CVD incidence better than other obesity indices (BMI, WC, WHR). Conclusion These findings support a positive association between WHtR and CVD incidence in CVD-free hypertensive adults. WHtR can be used to predict CVD incidence in hypertensive adults.

Abstract For the higher-dimensional dS spacetime embedded with black holes with non-linear charges, there are two horizons with different radiation temperatures. By introducing the interplay between two horizons this system can be regarded as an ordinary thermodynamic system in the thermodynamic equilibrium described by the thermodynamic quantities ( $$T_{eff},~P_{eff},~V,~S,~\Phi _{eff}$$ T eff , P eff , V , S , Φ eff ). In this work, our focus is on the thermodynamic properties of phase transition for the four-dimensional dS spacetime with different values of the charge correction $${\bar{\phi }}$$ ϕ ¯ . We find that with the increasing of the non-linear charge correction the two horizons get closer and closer, and the correction entropy is negative which indicates the interaction between the two horizons stronger and stronger. Furthermore, the heat capacity at constant pressure, isobaric expansion coefficient, and the isothermal compression coefficient have the Schottky peak at the critical point. However, the heat capacity as constant volume for the dS spacetime is nonzero. Finally, the dynamical properties of phase transition for this system have investigated based on Gibbs free energy, where exists the different behavior with that for AdS black holes.

Long-term hypercaloric diets may adversely affect the development of ovarian follicles. We investigated the effects of high sugar (HS), high fat low sugar (HFLS), and high fat normal sugar (HFNS) diets on the ovarian follicle development in mice fed with these diets as compared to those fed with normal diet (control) for 180 days. Body weight, gonadal fat, glucose, lipid, insulin, estrous cycle, sex hormones and ovarian tissues were examined, and metabolism-related protein expression in the ovaries was evaluated by immunoblotting. The mice fed with hypercaloric diets showed hyperinsulinemia and hyperlipidemia, and exhibited heavier body and gonadal fat weights, longer estrous cycles, and fewer preantral and antral follicles than mice fed with normal diet. The sex hormone levels in the blood were similar to those in controls, except for significantly elevated estradiol levels in the HS diet group. The AMPKα phosphorylation was reduced, while AKT phosphorylation and caspase-3 levels were increased in the ovarian tissues of mice in all three hypercaloric diet groups than those in control. Taken together, the results suggest hyperinsulinemia and hyperlipidemia as possible mechanisms that impair the development of ovarian follicles in response to long-term exposure to unhealthy hypercaloric diets.

Abstract Background Hyperlipidemia (HLP) and hypertension (HTN) are both independent risk factors for ischemic stroke. This study aimed to assess whether HTN and HLP have a synergistic effect on the risk of ischemic stroke. Methods Between January and August 2013, 11,695 subjects in rural areas of northeastern China were enrolled. The additive and multiplicative scales were used to evaluate the interaction. Results The prevalence of ischemic stroke was 5.7%. Using the healthy group (without HTN or HLP) as the reference group, subjects with both HTN and HLP had a higher risk of ischemic stroke (odds ratio [OR]: 3.369, 95% confidence interval [CI]: 2.579–4.402), and this OR was greater than that of subjects with only HTN (OR: 1.995, 95% CI 1.526–2.610) or HLP (OR: 1.321, 95% CI 0.937–1.862) (adjusting for age, sex, race, education level, family income, current smoking and drinking status, physical activity, body mass index, diabetes, family history of stroke, and atrial fibrillation). Regarding the additive scale, the relative excess risk due to interaction (OR: 1.053, 95% CI 0.458–1.648) was positive after adjusting for confounders. Moreover, the attributable proportion was 31.3%, which means that 31.3% of the total risk of ischemic stroke was due to the synergistic interaction between HTN and HLP. Furthermore, the synergistic index (S) of ischemic stroke was 1.8 (95% CI 1.157–2.801), which also indicates a synergistic interaction between HTN and HLP. Regarding the multiplicative scale, the interaction effect was also significant after adjusting for confounders (OR: 2.163, 95% CI 1.817–2.575). Conclusion The results suggest that the synergistic effect of HTN and HLP on ischemic stroke is significantly higher than the sum of their independent effects. The quantification of the combined effect should help to promote healthy blood pressure and blood lipid levels among the general population.

Neurosyphilis is a major clinical manifestation of syphilis. In recent years, an increase in neurosyphilis cases has been reported in many countries. The overall incidence of neurosyphilis remains unknown, and there is a lack of understanding of the disease pathogenesis, which hampers clinical management, development of prevention strategies, and control. This article proposes the CARE-NS research strategy to enhance the clinical management of neurosyphilis, which consists of six key features: comprehensive management including multidisciplinary treatment (C), alleviating neurological impairment and sequelae (A), risk factors and clinical epidemiology (R), etiology and pathogenesis (E), new diagnostic indicators and strategies (N), and social impact and cost-effectiveness analysis (S).

In this paper, we study the localization of the five-dimensional U(1) gauge field coupled with a background scalar potential on symmetric and asymmetric degenerate Bloch branes. By decomposing the U(1) gauge field AM into its vector part (A^M) and scalar components, we found that the Lagrangian of the five-dimensional U(1) gauge field can be rewritten as two independent parts: one for the vector field and the other for two scalar fields. Regarding the vector part, the effective potential exhibits a volcano-like shape with finite depth. We obtain a massless vector field on both types of Bloch branes and a set of massive KK resonances. For the scalar part, their massless modes are coupled with each other, while two sets of massive scalar KK modes are independent. Similar to the vector effective potential, the scalar potentials create infinite wells for both types of degenerate Bloch brane solutions. Therefore, there is only one independent massless scalar mode and two sets of massive scalar Kaluza–Klein resonances. Furthermore, we also observed that, for the two types of Bloch brane solutions, the asymmetric parameter c0 has different effects on the localization of scalar modes.

Species in the Botryosphaeriaceae are common plant pathogens, endophytes, and saprobes found on a variety of mainly woody hosts. Botryosphaeriaceae is a high-profile fungal family whose genera have been subjected to continuous revisions in recent years. Surveys conducted during 2019 and 2020 on several decaying woody hosts (from dead arial twigs, branches, stems, bark, and seed pods) in China and Thailand revealed a high diversity of Botryosphaeriaceae fungi. Identification of 16 Botryosphaeriaceae isolates was carried out based on both morphological characteristics and phylogenetic analyses of combined ITS, LSU, tef1-α, and tub2 sequence data. Four novel species (Dothiorella ovata, Do. rosacearum, Do. septata, and Lasiodiplodia delonicis) and seven previously known species (Botryosphaeria fujianensis, Diplodia mutila, Di. seriata, L. crassispora, L. mahajangana, Macrophomina euphorbiicola and Sphaeropsis eucalypticola) were identified while new hosts and geographical records were reported. This study indicates that the fungal family Botryosphaeriaceae seems to be common and widespread on a broad range of hosts in China and Thailand.

Idiopathic short stature (ISS) is the most common clinical cause of the short stature with an unclear aetiology and a lack of effective treatment. Circular RNAs have been shown to play a significant regulatory role through various signal transduction pathways in a variety of diseases in recent years. However, the role of circular RNAs on ISS is not yet well-understood and requires a special attention. The differentially expressed circular RNAs were screened by microarray chip analysis, and RT-qPCR was used to verify the expression of hsa_circ_0008870 in ISS patients. Subsequently, in vitro and in vivo experiments were conducted to determine the biological functions of hsa_circ_0008870 in ISS. The authors first confirmed that hsa_ circ_0008870 was downregulated in ISS children. Meanwhile, we also observed that the downregulated hsa_circ _0008870 significantly inhibited chondrocyte proliferation and endochondral ossification in vivo and in vitro. Mechanistically, hsa_circ_0008870 regulates MAPK1 expression by sponge miR-185-3p. This mechanism of action was further verified through rescue experiments. Finally, the authors revealed that the silencing of hsa_circ_0008870 induces low expression of MAPK1 by impairing the sponge action of miR-185-3p, thereby inhibiting chondrocyte proliferation, hypertrophy, and endochondral ossification, which results in a short stature phenotype. In addition to these, we also observed an interesting phenomenon that upregulated of miR-185-3p can in turn inhibit the expression of hsa_circ_0008870 in chondrocytes. This suggests that hsa_circ_0008870 could potentially serve as a therapeutic target for the treatment of ISS.

Zingiber cassumunar is an important plant used in traditional medicine and as a natural mosquito repellent. However, the compounds responsible for the repellent activity of the plant are still unknown. The aim of the study is to identify the components of Z. cassumunar essential oil that show repellent activity against Aedes albopictus. We also evaluated the larvicidal and adulticidal activities of Z. cassumunar essential oil against Ae. albopictus. In-cage mosquito repellent experiments showed that Z. cassumunar essential oil possessed moderate repellent activity with a minimum effective dose (MED) of 0.16 ± 0.01 mg/cm2, compared to reference standard N,N-diethyl-3-methylbenzamide (DEET, 0.03 ± 0.01 mg/cm2). Bioassay-guided fractionation identified the major active compound of Z. cassumunar essential oil as (−)-terpinen-4-ol (1) (MED: 0.19 ± 0 mg/cm2). We also found that Z. cassumunar essential oil showed moderate larvicidal activity against first instar larvae of Ae. albopictus with a LC50 (50% lethal concentration) of 44.9 μg/L after 24 h. Fumigation bioassays showed that Z. cassumunar essential oil exhibits moderate adulticidal activity against Ae. albopictus with a LC50 of 5.44%, while (−)-terpinen-4-ol showed significant adulticidal activity with a LC50 of 2.10% after 24 h. This study verifies that the Z. cassumunar essential oil has mosquito repellent activity, and that (−)-terpinen-4-ol is mainly responsible for this activity. Furthermore, this study provides scientific support for the folk usage of Z. cassumunar essential oil as mosquito repellent and indicates that Z. cassumunar essential oil and (−)-terpinen-4-ol can be used as plant-derived repellents and insecticides for mosquito control.

Abstract Background Patients with connective tissue disease, such as dermatomyositis (DM), and positive anti-TIF1γ self-antibodies are commonly diagnosed with malignant tumors as a comorbidity. The relationship between anti-TIF1γ self-antibodies and existing malignant tumors has been confirmed by several reports. However, interstitial pneumonia with autoimmune features (IPAF) cases with a positive anti-TIF1γ self-antibody developing to solid malignant tumors are rarely reported now. Case presentation Herein, we presented an IPAF patient with anti-TIF1γ self-antibodies. No evidence of malignant tumors was found at the initial visit. However, the patient had developed stage IVB lung squamous cell carcinoma at the 1-year follow-up review. Conclusions Altogether, this report described a rare case of IPAF patient with anti-TIF1γ self-antibodies developed to advanced lung squamous cell carcinoma in 1 year. The present case highlights more frequent imaging examinations to identify the occurrence of malignant tumors as early as possible in IPAF patients with positive anti-TIF1γ self-antibodies.

Most existing risk assessments of Android applications directly assign weights to factors according to experience, and calculate security risks by counting the frequency statistics of few factors. A new method for risk assessment of Android applications is proposed, which can provide both quantitative and qualitative assessment. This method integrates multiple risk factors such as system permissions, API calls, the action properties of Intent Filter, and data flow. The risks of factors are assigned based on their risk classification and addition, and the weights of factor subsets are distributed based on hierarchical clustering. Experiments show that the assessment results can effectively reflect the real security risks of Android applications.

In this study, the effects of zymosan (HG, hydrolyzed glucan) on the structure and metabolism of fecal microbiota in Chinese healthy people was investigated by an in vitro simulated intestinal microecology fermentation model. We found that HG significantly regulated fecal microbiota composition, including the increase of Bifidobacterium, Faecalibacterium, Prevotella and the decrease of Escherichia-Shigella. Moreover, HG significantly increased the total production of short chain fatty acids (SCFAs) and gases, in which the production of Acetic acid, Propionic acid, CO2, and H2 significantly increased while the production of Isovaleric acid and NH3 significantly decreased. Additionally, the supplement of HG showed certain differences in the regulation of microbiota from four groups. HG significantly increased the relative abundance of Bifidobacterium and significantly decreased the relative abundance of Escherichia-Shigella excluding the older men group. Meanwhile, and the relative abundance of Lactobacillus was significantly increased in young populations. And the relative abundance of Bacteroides was significantly decreased only in the young women. Furthermore, HG significantly increased H2 concentration only in older men. These findings suggest that HG, as a new generation of prebiotics, could regulate the structure of fecal microbiota and its metabolites in a better direction, but when HG participates in precision nutrition formula, it may be necessary to consider the differences in the utilization of different populations.

BackgroundDetermining risk factors of cardiovascular disease (CVD)-related mortality and evaluating their influence are important for effectively reducing corresponding mortality. However, few research findings have estimated the relationship between atrial fibrillation (AF) and CVD-related mortality among hypertension individuals.ObjectiveThe objective of this study was to investigate the epidemiology of AF in a hypertension population and determine the relationship between AF and CVD-related mortality.MethodsUsing a multistage, stratified, and cluster random sampling method, the prospective cohort study with a median follow-up of 3.51 years enrolled 10,678 hypertensive participants at baseline. The prevalence, awareness, and anticoagulation data of AF in this focal population were carefully assessed. Stepwise logistic regression and Cox regression analysis were respectively performed to evaluate the determinants of AF and the association between AF and CVD-related mortality.ResultsThe overall prevalence of AF was 1.3% (95% CI, 1.1%−1.6%) in the hypertensive population, and it was higher in men than in women (1.8% vs. 1.0%, respectively; p=0.001). The awareness of AF was 53.1%, and the rate of oral anticoagulant (OAC) therapy was only 4.2%, although all AF participants should have required according to the European Society of Cardiology guidelines. The determinants of AF included elder, male, and history of coronary heart disease in the hypertensive population. Besides, compared with individuals without AF, the risk of CVD-related mortality significantly increased in the hypertensive population with AF (HR 3.37, 95% CI 2.10–5.40).ConclusionOur results indicated a huge burden of AF and underuse of OAC therapy for them in a community-based hypertensive population. Considering that most of the risk factors of AF were unmodifiable in hypertensive individuals, as well as its high risk of mortality, long-term interventions including AF education, timely screening, and widespread use of OACs should be emphasized in the focal populations.

Current strategies to boost anti-tumor immune response include the use of immune checkpoint inhibitors and bispecific T cell-engaging antibodies. Here the authors describe a versatile antibody immobilization nanoplatform that can be used to deliver different combinations of immunotherapeutics, showing therapeutic superiority in pre-clinical models.

Background and Aims: TRIM21 is a ubiquitin E3 ligase that is implicated in numerous biological processes including immune response, cell metabolism, redox homeostasis, and cancer development. We recently reported that TRIM21 can negatively regulate the p62-Keap1-Nrf2 antioxidant pathway by ubiquitylating p62 and prevents its oligomerization and protein sequestration function. As redox homeostasis plays a pivotal role in many cancers including liver cancer, we sought to determine the role of TRIM21 in hepatocarcinogenesis. Methods: We examined the correlation between TRIM21 expression and the disease using publicly available data sets and 49 cases of HCC clinical samples. We used TRIM21 genetic knockout mice to determine how TRIM21 ablation impact HCC induced by the carcinogen DEN plus phenobarbital (PB). We explored the mechanism that loss of TRIM21 protects cells from DEN-induced oxidative damage and cell death. Results: There is a positive correlation between TRIM21 expression and HCC. Consistently, TRIM21-knockout mice are resistant to DEN-induced hepatocarcinogenesis. This is accompanied by decreased cell death and tissue damage upon DEN treatment, hence reduced hepatic tissue repair response and compensatory proliferation. Cells deficient in TRIM21 display enhanced p62 sequestration of Keap1 and are protected from DEN-induced ROS induction and cell death. Reconstitution of wild-type but not the E3 ligase-dead and the p62 binding-deficient mutant TRIM21 impedes the protection from DEN-induced oxidative damage and cell death in TRIM21-deficient cells. Conclusions: Increased TRIM21 expression is associated with human HCC. Genetic ablation of TRIM21 leads to protection against oxidative hepatic damage and decreased hepatocarcinogenesis, suggesting TRIM21 as a preventive and therapeutic target.

Abstract Background To investigate the relationship between triglyceride glucose-body mass index (TyG-BMI) and ischemic stroke. Methods Leveraging two Chinese general population surveys, the Northeast China Rural Cardiovascular Health Study (NCRCHS, N = 11,097) and the National Stroke Screening and Intervention Program in Liaoning (NSSIPL, N = 10,862), we evaluated the relationship between TyG-BMI and ischemic stroke by a restricted cubic spline and multivariate logistic regression after adjusting age, sex, level of education, exercise regularly, current smoking, current drinking, atrial fibrillation, hypertension, coronary artery disease, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. The category-free analysis was used to determine whether TyG-BMI enhanced the capacity of estimating ischemic stroke. Results A total of 596 and 347 subjects, respectively, from NSSIPL and NCRCHS were survivors of ischemic stroke. In NSSIPL, the relationship between TyG-BMI and ischemic stroke was linear and did not have a threshold or saturation effect according to the results of the restricted cubic spline. The regression analysis indicated that the risk of ischemic stroke increased 20% for per SD increase of TyG-BMI after multivariate adjustment [odds ratio (OR): 1.20, 95% confidence interval (CI): 1.10–1.32]. Compared with those in the lowest tertile, the risk of ischemic stroke in subjects with intermediate and high TyG-BMI was significantly higher [OR (95% CI): 1.39 (1.10–1.74); OR (95% CI) 1.72 (1.37–2.17), respectively]. Category-free analysis indicated that TyG-BMI had a remarkable improvement in the ability to estimate prevalent ischemic stroke [NRI (95% CI): 0.188 (0.105–0.270)]. These abovementioned relationships were confirmed in NCRCHS. Conclusions The present study found the robust correlation between TyG-BMI and ischemic stroke, independently of a host of conventional risk factors. Meanwhile, our findings also suggested the potential usefulness of TyG-BMI to improve the risk stratification of ischemic stroke.

Android is increasingly facing the threat of malware attacks. It is difficult to effectively detect large-sample and multi-class malware for traditional machine learning methods such as support vector machine, method for Android malware detection and family classification based on deep neural network was proposed. Based on the comprehensive extraction of application components, Intent Filter, permissions, and data flow, the method performed an effective feature selection to reduce dimensions, and conducted a large-sample detection and multi-class classification for malware based on deep neural network. The experimental results show that the method can conduct an effective detection and classification. The accuracy of binary classification between benign and malicious Apps is 97.73%, and the accuracy of family multi-class classification can reach 93.54%, which is higher than other machine learning algorithms.