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Abstract Person Re-identification (Re-ID) technology aims to solve the matching problem of the same pedestrians at different times and places, which has important application value in the field of public safety. At present, most scholars focus on designing complex models to improve the accuracy of Re-ID, but the high complexity of the model further restricts the practical application of Re-ID algorithm. To solve the above problems, this paper designs a lightweight Self-selective Receptive Field (SRF) block instead of directly designing complex models. Specifically, the module can be plug-and-play on the general backbone network, so as to significantly improve the performance of Re-ID while effectively controlling the amount of its own parameter and calculation: (1) the SRF block encodes pedestrian targets and image contexts at different scales by constructing pyramidal convolution group and allows the module to independently select the size of the receptive field through training by means of self-adaptive weighting; (2) in order to reduce the complexity of SRF block, we introduce a "channel scaling factor" and design a "grouped convolution operation" by constraining the channels of the feature map and changing the structure of the convolution kernel respectively. Experiments on multiple datasets show that SRF Network (SRFNet) for Re-ID can achieve a good balance between performance and complexity, which fully demonstrates the effectiveness of SRF block.

Four new N-acylated aminoalkanoic acids, namely clonoroseins E−H (1−4), together with three previously identified analogs, clonoroseins A, B, and D (5−7), were identified from the endophytic fungus Clonostachys rosea strain 15020 (CR15020), using Feature-based Molecular Networking (FBMN). The elucidation of their chemical structures, including their absolute configurations, was achieved through spectroscopic analysis combined with quantum chemical calculations. Bioinformatics analyses suggested that an iterative type I HR-PKS (CrsE) generates the polyketide side chain of these clonoroseins. Furthermore, a downstream adenylate-forming enzyme of the PKS (CrsD) was suspected to function as an amide synthetase. CrsD potentially facilitates the transformation of the polyketide moiety into an acyl-AMP intermediate, followed by nucleophilic substitution with either β-alanine or γ-aminobutyric acid to produce amide derivatives. These findings significantly expand our understanding of PKS-related products originating from C. rosea and also underscore the powerful application of FBMN analytical methods in characterization of new compounds.

AbstractContext The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use.Objective The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases.Methods We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence.Results Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment.Conclusions Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.

Abstract Visual adaptive devices have potential to simplify circuits and algorithms in machine vision systems to adapt and perceive images with varying brightness levels, which is however limited by sluggish adaptation process. Here, the avalanche tuning as feedforward inhibition in bionic two-dimensional (2D) transistor is proposed for fast and high-frequency visual adaptation behavior with microsecond-level accurate perception, the adaptation speed is over 104 times faster than that of human retina and reported bionic sensors. As light intensity changes, the bionic transistor spontaneously switches between avalanche and photoconductive effect, varying responsivity in both magnitude and sign (from 7.6 × 104 to −1 × 103 A/W), thereby achieving ultra-fast scotopic and photopic adaptation process of 108 and 268 μs, respectively. By further combining convolutional neural networks with avalanche-tuned bionic transistor, an adaptative machine vision is achieved with remarkable microsecond-level rapid adaptation capabilities and robust image recognition with over 98% precision in both dim and bright conditions.

Abstract Background An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy. Methods This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord’ test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations. Results A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low. Conclusions This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.

Abstract Endoplasmic reticulum stress (ERS) and oxidative stress (OS) are adaptive responses of the body to stressor stimulation. Although it has been verified that Trichinella spiralis (T. spiralis) can induce ERS and OS in the host, their association is still unclear. Therefore, this study explored whether T. spiralis-secreted serpin-type serine protease inhibitor (TsAdSPI) is involved in regulating the relationship between ERS and OS in the host intestine. In this study, mice jejunum and porcine small intestinal epithelial cells (IECs) were detected using qPCR, western blotting, immunohistochemistry (IHC), immunofluorescence (IF), and detection kits. The results showed that ERS- and OS-related indexes changed significantly after TsAdSPI stimulation, and Bip was located in IECs, indicating that TsAdSPI could induce ERS and OS in IECs. After the use of an ERS inhibitor, OS-related indexes were inhibited, suggesting that TsAdSPI-induced OS depends on ERS. When the three ERS signalling pathways, ATF6, IRE1, and PERK, were sequentially suppressed, OS was only regulated by the PERK pathway, and the PERK-eif2α-CHOP-ERO1α axis played a key role. Similarly, the expression of ERS-related indexes and the level of intracellular Ca2+ were inhibited after adding the OS inhibitor, and the expression of ERS-related indexes decreased significantly after inhibiting calcium transfer. This finding indicated that TsAdSPI-induced OS could affect ERS by promoting Ca2+ efflux from the endoplasmic reticulum. The detection of the ERS and OS sequences revealed that OS occurred before ERS. Finally, changes in apoptosis-related indexes were detected, and the results indicated that TsAdSPI-induced ERS and OS could regulate IEC apoptosis. In conclusion, TsAdSPI induced OS after entering IECs, OS promoted ERS by enhancing Ca2+ efflux, and ERS subsequently strengthened OS by activating the PERK-eif2α-CHOP-ERO1α axis. ERS and OS induced by TsAdSPI synergistically promoted IEC apoptosis. This study provides a foundation for exploring the invasion mechanism of T. spiralis and the pathogenesis of host intestinal dysfunction after invasion.

Fungal bifunctional terpene synthases (BFTSs) catalyze the formation of numerous di-/sester-/tri-terpenes skeletons. However, the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space. In this study, we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase (FoFS) by a single mutation at L89, leading to the production of three new sesterterpenes. Further computational analysis revealed that the reconstitution of the hydrogen-bond (H-bond) network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket. Thus, the dynamic orientation of W69 alters the carbocation transport, leading to the production of diverse ring system skeletons. These findings enhance our knowledge on understanding the molecular mechanisms, which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.

Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer with limited therapeutic options, and enhancing radiosensitivity remains a key challenge in improving treatment outcomes. Quercetin (Que) can inhibit the progression of hepatocellular carcinoma (HCC); however, its effect on HCC radiosensitivity remains unclear. This research investigates the role of Que in regulating HCC growth and radiosensitivity, aiming to provide a scientific foundation for enhancing the clinical efficacy of radiation therapy in HCC. The CCK-8 assay was used to determine the optimal treatment conditions for Que and X-rays. Changes in cell growth, cycle arrest, invasion, migration, the relative proportion of JC-1 red and green fluorescence (mitochondrial membrane potential), and the levels of ROS, MDA, SOD, and GSH-Px (oxidative stress) were assessed using flow cytometry, Transwell assays, JC-1 staining, Western blot, and ELISA, respectively, under Que, X-ray, and co-treatment conditions. The effect of miR-216a-3p knockdown on the action of Que was also explored, and the potential pathways by which Que regulates HCC growth and radiosensitivity were investigated in conjunction with in vivo subcutaneous transplantation tumor experiments. The in vitro treatment parameters for Que and X-rays were 100 µM and 4 Gy. Que combined with X-ray therapy enhanced HCC cell radiosensitivity, reduced proliferation, invasion, and migration, and promoted oxidative stress and apoptosis. Que was found to upregulate miR-216a-3p in HCC cells. Rescue experiments with miR-216a-3p knockdowns demonstrated that Que regulates HCC cell radiosensitivity via miR-216a-3p. In vivo research further showed that Que increased tumor sensitivity to X-rays by upregulating miR-216a-3p, thereby inhibiting HCC growth. In conclusion, Que has been shown to enhance HCC radiosensitization by upregulating miR-216a-3p and inhibiting HCC progression. Que may be a promising agent for increasing the radiosensitivity of HCC.

BackgroundOlder adults with cognitive impairment can experience poor oral health due to reduced self-care ability, yet the impact of various oral health indicators on the cognitive ability remains unclear. We investigated the relationship between oral health indicators and mild cognitive impairment (MCI) in older adults.MethodsA cross-sectional study of 234 older adults aged 65 years or over was performed form January to March 2023 at health screening departments of hospitals. This study used the Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL), Clinical Dementia Rating (CDR), and Hachinski Ischemic Score (HIS) to measure MCI. Two qualified dentists performed clinical oral examinations (number of teeth lost, dental caries, removable dentures, periodontitis). The other oral health status was measured by subjective assessment questionnaires, and the oral health-related quality of life (OHRQoL) was assessed by Geriatric Oral Health Assessment Index (GOHAI).ResultsOf the 234 older adults, 166 had MCI and 68 had normal cognitive ability. The univariate analyses revealed that older adults with poor oral health indicators of dental caries, mastication ability, oral and maxillofacial pain, self-perceived oral health status and OHRQoL had lower cognitive levels. The stepwise logistic regression analysis observed that higher education level (OR = 0.06, 95%CI = 0.007, 0.567) and OHRQoL score (OR = 0.92, 95%CI = 0.878, 0.963) were negatively associated with the presence of MCI. The area under the ROC curve (AUC) of MCI was 0.675 (95% CI: 0.600, 0.749) with a low sensitivity of 41.6% and a moderate specificity of 86.8%.ConclusionOHRQoL was found to be associated with MCI, implying that OHRQoL may be important in cognitive decline. The GOHAI scale can be used to more easily assess the oral health of older adults, which is important for the timely detection of poor oral status to delay cognitive decline.

Abstract Resistive switching memories have garnered significant attention due to their high‐density integration and rapid in‐memory computing beyond von Neumann's architecture. However, significant challenges are posed in practical applications with respect to their manufacturing process complexity, a leakage current of high resistance state (HRS), and the sneak‐path current problem that limits their scalability. Here, a mild‐temperature thermal oxidation technique for the fabrication of low‐power and ultra‐steep memristor based on Ag/TiOx/SnOx/SnSe2/Au architecture is developed. Benefiting from a self‐assembled oxidation layer and the formation/rupture of oxygen vacancy conductive filaments, the device exhibits an exceptional threshold switching behavior with high switch ratio exceeding 106, low threshold voltage of ≈1 V, long‐term retention of >104 s, an ultra‐small subthreshold swing of 2.5 mV decade−1 and high air‐stability surpassing 4 months. By decreasing temperature, the device undergoes a transition from unipolar volatile to bipolar nonvolatile characteristics, elucidating the role of oxygen vacancies migration on the resistive switching process. Further, the 1T1R structure is established between a memristor and a 2H‐MoTe2 transistor by the van der Waals (vdW) stacking approach, achieving the functionality of selector and multi‐value memory with lower power consumption. This work provides a mild‐thermal oxidation technology for the low‐cost production of high‐performance memristors toward future in‐memory computing applications.

Abstract Asthma is a common allergic disease characterized by airway hypersensitivity and airway remodeling. Ferroptosis is a regulated death marked by iron accumulation and lipid peroxidation. Several environmental pollutants and allergens have been shown to cause ferroptosis in epithelial cells, but the relationship between birch pollinosis and ferroptosis in asthma is poorly defined. Here, for the first time, we have identified ferroptosis of type II alveolar epithelial cells in mice with Bet v 1-induced asthma. Further analysis revealed that treatment with ferrostatin-1 reduced TH2/TH17-related inflammation and alleviated epithelial damage in mice with Bet v 1-induced asthma. In addition, ACSL4-knocked-down A549 cells are more resistant to Bet v 1-induced ferroptosis. Analysis of clinical samples verified higher serum MDA and 4-HNE concentrations compared to healthy individuals. We demonstrate that birch pollen allergen Bet v 1 induces ferroptosis underlaid TH2 and TH17 hybrid asthma. Lipid peroxidation levels can be considered as a biomarker of asthma severity, and treatment with a specific ferroptosis inhibitor could be a novel therapeutic strategy.

Abstract This study aimed to assess the therapeutic effect of immune checkpoint inhibitors (ICIs) in patients with unresectable hepatocellular carcinoma (uHCC) and investigate the correlation between surrogate endpoints and overall survival (OS). A systematic literature search included phase I, II, and III clinical trials comparing ICIs to placebo or other therapies for uHCC treatment. Correlations between OS and surrogate endpoints were evaluated using meta-regression analyses and calculating the surrogate threshold effect (STE). The correlation analysis showed a weak association between OS and progression-free survival (PFS), with an R2 value of 0.352 (95% CI: 0.000–0.967). However, complete response (CR) exhibited a strong correlation with OS (R2 = 0.905, 95% CI: 0.728–1.000). Subgroup analyses revealed high correlations between OS and PFS, CR, stable disease (SD), and DC in phase III trials (R2: 0.827–0.922). For the ICI + IA group, significant correlations were observed between OS and SD, progressive disease (PD), and grade 3–5 immune-related adverse events (irAEs) (R2: 0.713–0.969). Analyses of the correlation between survival benefit and risk of mortality across various time points showed a strong association within the first year (R2: 0.724–0.868) but a weak association beyond one year (R2: 0.406–0.499). In ICI trials for uHCC, PFS has limited utility as a surrogate endpoint for OS, while CR exhibits a strong correlation with OS. Subgroup analyses highlight high correlations between OS and PFS, SD, and DC in phase III trials. Notably, the ICI + IA group shows significant associations between OS and SD, PD, and grade 3–5 irAEs. These findings offer valuable insights for interpreting trial outcomes and selecting appropriate endpoints in future clinical studies involving ICIs for uHCC patients.

Daocai is a traditional salted pickle in the southeastern region of Guizhou with a unique aroma, color, and taste. The quality of Daocai is greatly influenced by the fermentation temperature. In this study, high-throughput sequencing and headspace-gas chromatography-ion mobility spectrometry were used to investigate the changes in microbial community succession and volatile flavor compounds during Daocai fermentation under temperature-controlled (D group) and non-temperature-controlled (C group).We found that the predominant genera in the C group samples were Latilactobacillus(40.57 %), Leuconostoc(21.25 %), Cystofilobasidium(22.12 %), Vishniacozyma(23.89 %), and Leucosporidium(24.95 %), whereas Weissella(29.39 %), Lactiplantibacillus(45.61 %), Mucor(68.26 %), and Saccharomyces(23.94 %) were the predominant genera in the D group. A total of 92 VFCs were detected in Daocai samples, including 5 isothiocyanates, 16 esters, 14 alcohols, 24 aldehydes, 17 ketones, 3 acids, 2 pyrazines, 1 pyridines, 1 thiazoles, 3 furans, 4 alkenes, and 2 nitriles. Further analysis revealed Latilactobacillus, Leuconostoc, Lactococcus, Cystofilobasidium, Leucosporidium, Holtermanniella, and Dioszegia as key bacteria involved in flavor formation. They are closely related to the formation of flavors such as aldehydes, furans, pyridines, and alkenes. This study contributes to our understanding of the relationship between bacterial communities and the flavor formation during Daocai fermentation.

Background Renal microcirculation plays a pivotal role in kidney function by maintaining structural and functional integrity, facilitating oxygen and nutrient delivery, and waste removal. However, a thorough bibliometric analysis in this area remains lacking. Therefore, we aim to provide valuable insights through a bibliometric analysis of renal microcirculation literature using the Web of Science database.Methods We collected renal microcirculation-related publications from the Web of Science database from January 01, 1990, to December 31, 2022. The co-authorship of authors, organizations, and countries/regions was analyzed with VOSviewer1.6.18. The co-occurrence of keywords and co-cited references were analyzed using CiteSpace6.1.R6 software to generate visualization maps. Additionally, burst detection was applied to keywords and cited references to forecast research hotspots and future trends.Results Our search yielded 7462 publications, with the American Journal of Physiology-Renal Physiology contributing the most articles. The United States, Mayo Clinic, and Lerman Lilach O emerged with the highest publication count, indicating their active collaborations. ‘Type 2 diabetes’ was the most significant keyword cluster, and ‘diabetic kidney disease’ was the largest cluster of cited references. ‘Cardiovascular outcome’ and ‘diabetic kidney diseases’ were identified as keywords in their burst period over the past three years.Conclusion Our bibliometric analysis illuminates the contours of nephrology and microcirculation research, revealing a landscape ripe for challenges and the seeds of future scientific innovation. While the trends discerned from the literature emerging opportunities in diagnostic innovation, renal microcirculation research, and precision medicine interventions, their translation to clinical practice is anticipated to be a deliberate process.

Meaning in life, which has two possible sources: self-acceptance and social support, is essential to the mental health and development of college students. The current study aims to further clarify the symptom-level relations between meaning in life, self-acceptance, and social support, finding possible ways to improve meaning in the life of college students. Thousand three hundred and forty-eight Chinese college students completed the online questionnaire, including Self-acceptance Questionnaire, Social Support Rating Scale, and Meaning in Life Questionnaire and the data from 1,263 participants was used. Cross-sectional network analysis was used to examine the relation between self-acceptance and social support. We also explored the relation between dimensions of self-acceptance and social support and meaning in life using the flow network. The results show symptom “SlA” (self-acceptance) is the bridge symptom linking self-acceptance and social support. In the flow diagrams, “SlA” is directly and positively associated with the presence of meaning. Objective Support shares the strongest positive association with the search for meaning. The symptom “SIA” may be an important targeting symptom when trying to improve the meaning in life of college students. Additionally, social support is essential for college students to develop meaning in life.

Abstract The adjustable structures and remarkable physicochemical properties of 2D monoelemental materials, such as silicene and germanene, have attracted significant attention in recent years. They can be transformed into silicane (SiH) and germanane (GeH) through covalent functionalization via hydrogen atom termination. However, synthesizing these materials with a scalable and low‐cost fabrication process to achieve high‐quality 2D SiH and GeH poses challenges. Herein, groundbreaking 2D SiH and GeH materials with varying compositions, specifically Si0.25Ge0.75H, Si0.50Ge0.50H, and Si0.75Ge0.25H, are prepared through a simple and efficient chemical exfoliation of their Zintl phases. These 2D materials offer significant advantages, including their large surface area, high mechanical flexibility, rapid electron mobility, and defect‐rich loose‐layered structures. Among these compositions, the Si0.50Ge0.50H electrode demonstrates the highest discharge capacity, reaching up to 1059 mAh g−1 after 60 cycles at a current density of 75 mA g−1. A comprehensive ex‐situ electrochemical analysis is conducted to investigate the reaction mechanisms of lithiation/delithiation in Si0.50Ge0.50H. Subsequently, an initial assessment of the c‐Li15(SixGe1‐x)4 phase after lithiation and the a‐Si0.50Ge0.50 phase after delithiation is presented. Hence, this study contributes crucial insights into the (de)lithiation reaction mechanisms within germanane‐silicane alloys. Such understanding is pivotal for mastering promising materials that amalgamate the finest properties of silicon and germanium.

BackgroundChronic kidney disease (CKD)-related secondary hyperparathyroidism (SHPT) is associated with higher morbidity and death. The goal of this study was to mine the SHPT data already available to do a meta-analysis on the global prevalence of SHPT caused by CKD.MethodsEmbase, Medline, Web of Science, Cochrane Central Databases, and Google Scholar were searched to identify studies on the prevalence of SHPT due to CKD from inception to November 2023. Pooled prevalence was calculated using the DerSimonian-Laird random effects model with a logit transformation.ResultsTwenty-one eligible studies involving 110977 patients were included. Our results revealed that the estimated global prevalence of SHPT due to CKD was 49.5% (95% CI 30.20–68.18), regardless of the diagnostic criteria. For subgroup analysis, Southern Asia (84.36%, 95% CI 79.35–88.34) had a significantly higher SHPT prevalence than other geographic regions. SHPT due to CKD was most prevalent in China (85.14%, 95% CI 81.74–88.00).ConclusionsSHPT due to CKD is highly prevalent. This necessitates awareness and therapeutic approaches from primary care physicians, medical professionals, and health strategy authorities.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024514007.

Background and aimsCervical cancer, a prevalent gynecological malignant tumor, poses a significant threat to women’s health and lives. Immune checkpoint inhibitor (ICI) therapy has emerged as a promising avenue for treating cervical cancer. For patients with persistent or recurrent metastatic cervical cancer, If the sequence of dead receptor ligand-1 (PD-L1) is positive, ICI show significant clinical efficacy. PD-L1 expression serves as a valuable biomarker for assessing ICI therapeutic efficacy. However, the complex tumor immune microenvironment (TIME), encompassing immune cell composition and tumor-infiltrating lymphocyte (TIL) status, also exerts a profound influence on tumor immunity and prognosis. Given the remarkable strides made by ICI treatments in improving the survival rates of cervical cancer patients, it becomes essential to identify a comprehensive biomarker that integrates various TIME aspects to enhance the effectiveness of ICI treatment. Therefore, the quest for biomarkers linked to multiple facets of TIME in cervical cancer is a vital pursuit.MethodsIn this study, we have developed an Immune-Associated Gene Prognostic Index (IRGPI) with remarkable prognostic value specifically for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The Cancer Genome Atlas CESC dataset (n = 305) was meticulously analyzed to pinpoint key immune-related genes via weighted gene co-expression network analysis and differential gene expression assays. Subsequently, we employed Cox regression analysis to construct the IRGPI. Furthermore, the composition of immune cells and TIL status were examined using CIBERSORT and TIDE. Tumor expression of Epigen, LCN10, and P73 were determined with immunohistochemistry.ResultsThe resulting IRGPI, composed of EPGN, LCN10, and TP73 genes, displayed a strong negative correlation with patient survival. The discovery was validated with a patient cohort from our hospital. The IRGPI not only predicts the composition of immune cell subtypes such as Macrophages M1, NK cells, Mast cells, Plasma cells, Neutrophils, Dendritic cells, T cells CD8, and T cells CD4 within CESC, but also indicates TIL exclusion, dysfunction, and PD-1 and PD-L1 expression. Therefore, the IRGPI emerges as a promising biomarker not only for prognostic assessment but also for characterizing multiple immune features in CESC. Additionally, our results underscored the significant associations between the IRGPI and immune cell composition, TIL exclusion, and dysfunction, along with PD-1 and PD-L1 expression in the TIME.ConclusionConsequently, the IRGPI stands out as a biomarker intimately connected to both the survival and TIME status of CESC patients, offering potential insights into immunotherapy strategies for CESC.

Abstract Background One factor that influences nursing students' decision to engage in volunteer activities is volunteer motivation. It is important to understand the motivations of nursing students to volunteer. However, the majority of current studies have concentrated on the present level of nursing students' motivation to volunteer. Objectives To identify subgroups of nursing students' volunteer motivation and its influential factors. Methods From January to February 2022, a cross-sectional online study was conducted, and 2569 nursing students from 10 provinces in China were recruited. Participants completed the General Information Questionnaire, Volunteer Functional Inventory (VFI), Perceived Stress Scale (PSS) and Perceived Social Support Scale (PSSS). We explore the categories and characteristics of volunteer motivation using latent profile analysis. Then, we determined factors that affect undergraduate nursing students' volunteer motivation using multinomial logistic regression. Results The volunteer motivation score of the nursing students was 77.65 (15.22). The study found that volunteer motivation could be divided into three categories: low-low protective volunteer motivation group (9.3%), general-high career values volunteer motivation group (37.5%), and high volunteer motivation group (53.2%). Perceived social support scale score, perceived stress scale score, gender, and grade significantly influenced the volunteer motivation of nursing students in different categories (both P

Abstract Previous studies examining the association between hemoglobin concentration and hypertension have yielded inconsistent results. There is still a lack of evidence regarding the association between hemoglobin concentration and hypertension risk in native Tibetans at high altitude. We performed this cross‐sectional study in Luhuo County of Ganzi Tibetan Autonomous Prefecture (average altitude of 3500 m). In this study, we enrolled 1547 native Tibetans. The association between hemoglobin concentration and hypertension risk was examined by multivariate binary logistic regression and smooth curve fitting. Native Tibetans with hypertension had significantly higher hemoglobin concentrations than those without hypertension (165.9 ± 21.5 g/L vs. 157.7 ± 19.2 g/L, P

AbstractObjective Diabetes mellitus complicated with heart failure has high mortality and morbidity, but no reliable diagnoses and treatments are available. This study aimed to develop and verify a new model nomogram based on clinical parameters to predict diastolic cardiac dysfunction in patients with Type 2 diabetes mellitus (T2DM).Methods 3030 patients with T2DM underwent Doppler echocardiography at the First Affiliated Hospital of Shenzhen University between January 2014 and December 2021. The patients were divided into the training dataset (n = 1701) and the verification dataset (n = 1329). In this study, a predictive diastolic cardiac dysfunction nomogram is developed using multivariable logical regression analysis, which contains the candidates selected in a minor absolute shrinkage and selection operator regression model. Discrimination in the prediction model was assessed using the area under the receiver operating characteristic curve (AUC-ROC). The calibration curve was applied to evaluate the calibration of the alignment nomogram, and the clinical decision curve was used to determine the clinical practicability of the alignment map. The verification dataset was used to evaluate the prediction model’s performance.Results A multivariable model that included age, body mass index (BMI), triglyceride (TG), creatine phosphokinase isoenzyme (CK-MB), serum sodium (Na), and urinary albumin/creatinine ratio (UACR) was presented as the nomogram. We obtained the model for estimating diastolic cardiac dysfunction in patients with T2DM. The AUC-ROC of the training dataset in our model was 0.8307, with 95% CI of 0.8109–0.8505. Similar to the results obtained with the training dataset, the AUC-ROC of the verification dataset in our model was 0.8083, with 95% CI of 0.7843–0.8324, thus demonstrating robust. The function of the predictive model was as follows: Diastolic Dysfunction = −4.41303 + 0.14100*Age(year)+0.10491*BMI (kg/m2) +0.12902*TG (mmol/L) +0.03970*CK-MB (ng/mL) −0.03988*Na(mmol/L) +0.65395 * (UACR > 30 mg/g) + 1.10837 * (UACR > 300 mg/g). The calibration plot diagram of predicted probabilities against observed DCM rates indicated excellent concordance. Decision curve analysis demonstrated that the novel nomogram was clinically useful.Conclusion Diastolic cardiac dysfunction in patients with T2DM can be predicted by clinical parameters. Our prediction model may represent an effective tool for large-scale epidemiological study of diastolic cardiac dysfunction in T2DM patients and provide a reliable method for early screening of T2DM patients with cardiac complications.KEY MESSAGESThis study used clinical parameters to predict diastolic cardiac dysfunction in patients with T2DM. This study established a nomogram for predicting diastolic cardiac dysfunction by multivariate logical regression analysis. Our predictive model can be used as an effective tool for large-scale epidemiological study of diastolic cardiac dysfunction in patients with T2DM and provides a reliable method for early screening of cardiac complications in patients with T2DM.

Abstract Introduction Hypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30–60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension. Methods and analysis This study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6–10 am) or a bedtime (6–10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12. Discussion Antihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice. Trial registration ChiCTR2200059719. Registered on 10 May 2022 ( http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4 ) {2a,2b}

Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the microcirculation that impair myocardial perfusion. CMD plays a pivotal role in numerous cardiovascular diseases, including myocardial ischemia with non-obstructive coronary arteries, heart failure, and acute coronary syndromes. This review summarizes recent advances in CMD pathophysiology, assessment, and treatment strategies, as well as ongoing challenges and future research directions. Signaling pathways implicated in CMD pathogenesis include adenosine monophosphate-activated protein kinase/Krüppel-like factor 2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang II), endothelin-1 (ET-1), RhoA/Rho kinase, and insulin signaling. Dysregulation of these pathways leads to endothelial dysfunction, the hallmark of CMD. Treatment strategies aim to reduce myocardial oxygen demand, improve microcirculatory function, and restore endothelial homeostasis through mechanisms including vasodilation, anti-inflammation, and antioxidant effects. Traditional Chinese medicine (TCM) compounds exhibit therapeutic potential through multi-targeted actions. Small molecules and regenerative approaches offer precision therapies. However, challenges remain in translating findings to clinical practice and developing effective pharmacotherapies. Integration of engineering with medicine through microfabrication, tissue engineering and AI presents opportunities to advance the diagnosis, prediction, and treatment of CMD.

In this study, “Honghu White Lotus”, “Red Lotus (HH)”, “Hunan Cunshan Lotus (CS)”, “Wuyi Xuanlian”, “Space Lotus 36”, “Fujian Jianning White Lotus (JB)”, “Jiangsu Yangzhou Lotus (JY)”, and “Suzhou Dongshan Lotus” were selected as experimental subjects. The lotus seed flesh and lotus plumule of each cultivar were selected for nutritional quality and functional active substance analyses. Comparing different cultivars of lotus seeds, the protein and crude fat contents of JY flesh were the highest at 65.59 mg/g and 13%, respectively. The VC content of JB flesh and lotus plumule is the highest at 41.56 mg/g and 204.29 mg/g, respectively. JB flesh has the lowest soluble sugar content, at 17.87 mg/g, while HB’s lotus plumule and flesh have the highest content, at 33.67 mg/g and 29.62 mg/g, respectively. There was no significant difference in the crude fat content of the flesh and lotus plumule among the eight cultivars. TK flesh and lotus plumule have the highest amylose content, at 23.67 mg/g and 76.81 mg/g, respectively. Among them, the total starch content of JB (476.17 mg/g) was relatively high, whereas its amylose content was only 26.09 mg/g. Lower amylose content makes it less prone to aging. The total phenolic and flavonoid contents of the JY lotus plumule were the highest, at 18.64 and 21.04 mg/g, respectively. The alkaloid content of CS, HH, and JY was relatively high at 20.01, 19.29, and 18.68 mg/g, respectively. These can provide a consultation for the estimation and processing of the nutritional quality of different lotus seeds.

This study investigated the impact of variety and harvest time on the visual appearance, nutritional quality, and functional active substances of six lotus root cultivars: “Xinsanwu”, “Wuzhi No. 2”, “Baiyuzhan”, “Huaqilian”, “Elian No. 6”, and “Elian No. 5”. Samples were collected monthly from December 2023 to April 2024. A nutrient analysis revealed a decrease in the water content with a delayed harvest. The total soluble solids and soluble sugar content peaked towards the end and middle-to-late harvest periods, respectively. Starch levels initially increased before declining, while the soluble protein exhibited a triphasic trend with an initial rise, a dip, and a final increase. The vitamin C (Vc) content varied across cultivars. Functional active substances displayed dynamic changes. The total phenolics initially decreased, then increased, before ultimately declining again. The total flavonoid content varied by both cultivar and harvest time. The phenolic acid and flavonoid content mirrored the trends observed for total phenolics and total flavonoids. Gastrodin was the most abundant non-flavonoid compound across all varieties. “Wuzhi No. 2” and “Baiyuzhan” displayed higher levels of functional active substances and starch, while the Elian series and “Xinsanwu” cultivar exhibited a greater content of Vc, soluble sugar, and soluble protein. Specific harvest periods yielded optimal results: “Wuzhi No. 2” (H1 and H5), “Huaqilian” (H2), and “Baiyuzhan” (H3 and H4) demonstrated a high nutrient and functional active substance content. Overall, the lotus roots harvested in period H4 achieved the highest score. Overall, this study provides the foothold for the rapid identification of superior lotus root cultivars and the valorization of lotus root by-products via advanced processing methods. Additionally, it offers valuable insights for market participants and consumers to select optimal varieties and harvest times based on their specific needs.

Fragment-based drug discovery (FBDD) focuses on small compounds, known as fragments, typically with a molecular weight of less than 300 Da. This study highlights the benefits of employing a pure natural product library for FBDD, contrasting with the predominant use of synthetic libraries. Practical methods for rapidly constructing such libraries from crude extracts were demonstrated across various plant and microbial samples. Twenty-nine (29) natural product fragments, including a new compound (20), were identified. Antimicrobial activities were assessed for a subset of the isolated compounds, revealing potent fragments (MICs 4–8 μg/mL) against Mycobacterium bovis bacille Calmette-Guérin (BCG), Staphylococcus aureus (SA), and methicillin-resistant S. aureus (MRSA). Furthermore, a native mass spectrometry technique was introduced to rapidly identify non-competitive fragments against malarial proteins. As a result, two pairs of non-competitive fragments, lepiotin C (31) and 7-amino deacetoxy cephalosporanic acid (32) binding to dynein light chain 1, methyl gallate (33) and β-santanin (34) binding to dUTPase, were identified, serving as promising starting points for developing potent malarial protein inhibitors.

Sesquiterpenoids served as an important source for natural product drug discovery. Although genome mining approaches have revealed numerous novel sesquiterpenoids and biosynthetic enzymes, the comprehensive landscape of fungal sesquiterpene synthases (STSs) remains elusive. In this study, 123 previously reported fungal STSs were subjected to phylogenetic analysis, resulting in the identification of a fungi-specific STS family known as trichodiene synthase-like sesquiterpene synthases (TDTSs). Subsequently, the application of hidden Markov models allowed the discovery of 517 TDTSs from our in-house fungi genome library of over 400 sequenced genomes, and these TDTSs were defined into 79 families based on a sequence similarity network. Based on the novelty of protein sequences and the completeness of their biosynthetic gene clusters, 23 TDTS genes were selected for heterologous expression in Aspergillus oryzae. In total, 10 TDTSs were active and collectively produced 12 mono- and sesquiterpenes, resulting in the identification of the first chamipinene synthase, as well as the first fungi-derived cedrene, sabinene, and camphene synthases. Additionally, with the guidance of functionally characterized TDTSs, we found that TDTSs in Family 1 could produce bridged-cyclic sesquiterpenes, while those in Family 2 could synthesize spiro- and bridged-cyclic sesquiterpenes. Our research presents a new avenue for the genome mining of fungal sesquiterpenoids.

Wheat (Triticum aestivum L.) is one of the most important cereal crops worldwide, and its production is challenged by global climate change and a shortage of resources. The root system plays a vital role in uptaking water and nutrients and sensing soil environmental signals, and it has great potential to improve the final yield and stress tolerance of wheat. In order to further explore the genes regulating root development, this study focused on qRS-6D, located on chromosome 6D and spanning from 462,701,391 to 465,068,943, which was significantly associated with the total root length, root volume, root surface, and root fresh weight in our previous GWAS analysis. Firstly, its genetic effects were validated using an F6 segregating population by comparing the root-related traits of homologous lines harboring the alternative haplotypes of this QTL. Then, the number of causal genes of this QTL was narrowed down to four with a transcriptome-wide association study. Additionally, qRS-6D has been demonstrated to have genetic effects on several yield- (kernel length, kernel width, and thousand-kernel weight) and plant structure-related traits (plant height, peduncle length, total tiller number, productive tiller number, flag leaf length, and flag leaf angle). Relatively, the frequency of the favorable haplotype increased with the wheat breeding practice. This study provides a reliable genetic locus to improve root development and structure and evaluate its application potential in wheat breeding improvement.

Preparing submicron and nanoscale phosphors with good optical properties for practical applications is a challenging task for current inorganic long afterglow luminescent materials. This study utilized commercialized SrAl2O4:Eu2+, Dy3+ phosphors (SAOED) as raw materials and employed solvents with lower polarity or non-polar solvents for dynamic solvothermal treatment. The commercialized phosphor’s overall average particle size was reduced from 42.3 μm to 23.6 μm while maintaining the fluorescence intensity at 91.39% of the original sample. Additionally, the study demonstrated the applicability of the dynamic solvothermal method to most other commercialized inorganic phosphors. The experiment produced a high-brightness nano-sized phosphor with a yield of 5.64%. The average diameter of the phosphor was 85 nm, with an average thickness of 16 nm. The quantum efficiency of the phosphor was 74.46% of the original sample. The fingerprint imaging results suggest that the nano-sized phosphors have potential for practical applications.

This study aimed to verify the biogenic amines degradation performance and potential application value of Lactobacillus casei on biogenic amines. In this study, high performance liquid chromatography (HPLC) was used to study the biogenic amines degradation performance of this strain under liquid culture conditions and its biogenic amines degradation effect in 6 kinds of commercially available fermented foods in Guizhou. The results showed that in the liquid culture experiment, the biogenic amines degradation rates of this strain to histamine, spermidine, phenylethylamine, putrescine, cadaverine, tyramine, and tryptamine was 9.44%, 23.39%, 16.27%, 13.68%, 19.14%, 18.16%, and 12.45%, respectively. In addition, it was found that its degradation rates of tryptamine in Zhenyuan Daocai was 56.68%, the degradation rates of cadaverine, histamine and spermidine in bean paste were 68.06%, 74.52% and 85.82%, the degradation rates of tryptamine and cadaverine in soy sauce were 66.75% and 81.53%, the degradation rates of tryptamine in paocai was 45.74%, the degradation rates of tryptamine, cadaverine, histamine and spermidine in canned fish were 55.66%, 63.92%, 45.96% and 52.62%, the degradation rates of tryptamine, histamine and spermidine in sausage were 71.15%, 56.26% and 75.54%, respectively. The study also found that this strain had the ability to produce and degrade biogenic amines, and the degradation of the same biogenic amine in different foods was different. This study would provide a theoretical basis for the application of Lactobacillus casei in low-amine fermented food.

Abstract Aims To investigate the relationship between stroke survivors' perceptions of recurrence risk, coping styles and depression state, and the role coping styles play in mediating that relationship. Design A cross‐sectional descriptive study. Methods From one hospital in Huaxian, China, 320 stroke survivors were randomly selected as a convenience sample. In this research, the Simplified Coping Style Questionnaire, the Patient Health Questionnaire‐9 and the Stroke Recurrence Risk Perception Scale were all used. Structural equation modelling and correlation analysis were used to analyse the data. This research followed the EQUATOR and STROBE checklists. Results There were 278 valid survey responses. There were mild to severe depressive symptoms in 84.8% of stroke survivors. In stroke survivors, there was a significant negative relationship (p

Nucleic acid detection plays a key role in diverse diagnosis and disease control. Currently available nucleic acid detection techniques are challenged by trade-offs among speed, simplicity, precision and cost. Here, we described a novel method, designated SENSOR (Sulfur DNA mediated nucleic acid sensing platform), for rapid nucleic acid detection. SENSOR was developed from phosphorothioate (PT)-DNA and sulfur binding domain (SBD) which specifically binds double-stranded PT-modified DNA. SENSOR utilizes PT-DNA oligo and SBD as targeting module, which is linked with split luciferase reporter to generate luminescence signal within 10 min. We tested detection on synthesized nucleic acid and COVID-19 pseudovirus, achieving attomolar sensitivity combined with an amplification procedure. Single nucleotide polymorphisms (SNP) could also be discriminated. Indicating SENSOR a new promising nucleic acid detection technique.

Abstract Radiotherapy benefits patients with advanced esophageal squamous cell carcinoma (ESCC) in terms of symptom relief and long-term survival. In contrast, a substantial proportion of ESCC patients have not benefited from radiotherapy. This study aimed to establish and validate an artificial neural network-based radiomics model for the pretreatment prediction of the radiotherapy response of advanced ESCC by using integrated data combined with feasible baseline characteristics of computed tomography. A total of 248 patients with advanced ESCC who underwent baseline CT and received radiotherapy were enrolled in this study and were analyzed by two types of radiomics models, machine learning and deep learning. As a result, the Att. Resnet50 pretrained network model indicated superior performance, with AUCs of 0.876, 0.802 and 0.732 in the training, internal validation, and external validation cohorts, respectively. Similarly, our Att. Resnet50 pretrained network model showed excellent calibration and significant clinical benefit according to the C index and decision curve analysis. Herein, a novel pretreatment radiomics model was established based on deep learning methods and could be used for radiotherapy response prediction in advanced ESCC patients, thus providing reliable evidence for therapeutic decision-making.

ObjectiveMercury sphygmomanometer (MS) has now been less and less used and no new devices have been manufactured (according to Minamata convention 2013). The application of the electronic sphygmomanometer (ES) in clinical practice has become increasingly common. However, reliable evidence for the use of the ES in high-altitude areas remains scarce. The purpose of this study was to validate the applicability of the ES in high altitude areas.MethodsIn Luhuo County, Sichuan Province, China, 3,400 m above the sea level, two trained physicians measured the blood pressure (BP) of participants using both the mercury sphygmomanometer and the ES. Pearson correlation analysis and paired T-test, respectively, were used to compare the correlation and the difference between the BP values measured by the two devices. The applicability of the ES in high-altitude areas was evaluated according to the validation standards of the 2018 Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Collaboration Statement.ResultsIn this study, 257 participants were included. There was a strong correlation between BP values measured by the two devices, with correlation coefficients for systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 0.97 and 0.93, respectively. Compared with the MS, the ES tended to measure the subjects' DBP (76.21 ± 13.29 mmHg vs. 76.53 ± 14.07 mmHg; P = 0.557) accurately, but overestimate the SBP of the subjects (123.32 ± 22.25 mmHg vs. 121.34 ± 22.88 mmHg; P

Abstract We previously reported that sodium pentobarbital inhibited the growth of the breast cancer associated with the normalization of microcirculatory hemodynamics and oxygenation. Here, we aimed to screen the key regulatory proteins involved in pentobarbital‐induced normalization of microcirculatory hemodynamics in the breast cancer tissues. A nude mice model of xenograft was established using triple negative breast cancer cell line MDA‐MB‐231. After tumor cell implantation, the mice were subcutaneously injected with 50 mg/kg/day of sodium pentobarbital or an equal volume of solvent adjacent to the tumor for 14 days. Liquid chromatography linked to tandem mass spectrometry (LC–MS/MS) was used to analyze the difference in protein expression profile between the two groups. Ingenuity pathway analysis (IPA) was used to perform the canonical pathway analysis, upstream regulators analysis, and protein–protein interaction networks analysis. Screened proteins were confirmed by real‐time quantitative polymerase chain reaction (RT–qPCR) and Western blot analysis. A total of 101 differentially expressed proteins were revealed between groups. Canonical pathway analysis suggested that acute phase response signaling (z = 1, p = .00208), dilated cardiomyopathy signaling pathway (z = −2, p = .00671), and ILK signaling (z = 1, p = .0172) were key pathways with highlight associations. The mRNA and protein expressions of SMTNL1 were found significantly decreased in pentobarbital‐treated tumor tissues compared with those in controls (both p

ObjectTo explore the potential association between dietary live microbe intake and abdominal aortic calcification (AAC).MethodsWe conducted a cross-section study based on the National Health and Nutrition Examination Survey (NHANES). We categorized the participants into three groups (low, medium, and high dietary intake of live microbes) according to Sanders’s dietary live microbe classification system and participants’ 24-h dietary recall data. AAC was quantified by using dual-energy X-ray absorptiometry (DXA) and diagnosed by using the Kauppila AAC-24 score system. The analyses utilized weighted logistic regression and weighted linear regression.ResultsA total of 2,586 participants were included. After the full adjustment for covariates, compared to participants with a low dietary live microbe intake, participants with a high dietary live microbe intake had a significantly lower risk of severe AAC (OR: 0.39, 95% CI: 0.22, 0.68, p = 0.003), and the AAC score was also significantly decreased (β:−0.53, 95% CI: −0.83, −0.23, p = 0.002).ConclusionIn this study, more dietary live microbial intake was associated with lower AAC scores and a lower risk of severe AAC. However, more research is needed to verify this.

Abstract Background: Recently, novel anthropometric indices (AHIs), including the body roundness index (BRI) and a body shape index (ABSI), were proposed to evaluate a subject’s nutritional status and metabolic disorders. In the present study, we mainly analyzed the relationship between AHIs and the incidence of hypertension and preliminarily compared their abilities to discriminate hypertension incidence in the Chinese population from the China Health and Nutrition Survey (CHNS). Methods: A total of 12,154 participants were included in this longitudinal study. The age range of this cohort was 18–94 years old (mean age: 40.73 ± 13.85 years old). 4511 participants developed hypertension during a median of 7.00 years of follow-up. Cox regression analysis, stratified analysis, and interaction tests were used to analyze the relationship between AHIs and the incidence of hypertension. Time-dependent receiver operating characteristic (ROC) curves, integrated discrimination improvement (IDI) and net reclassification index (NRI) were calculated to appraise the AHIs’ discrimination value of new-onset hypertension. Results: Kaplan‒Meier curves demonstrated that the participants in higher quartiles of AHIs (ABSI or BRI) at baseline were at greater risk of hypertension incidence during the follow-up. After adjusting for confounding factors, multivariate Cox regression models showed that the quartiles of BRI were significantly associated with an increased risk of hypertension in the whole cohort but were relatively weak for ABSI quartiles (P for trend = 0.387). In addition, ABSI z score (HR = 1.08, 95% CI: 1.04–1.11) and BRI z score (HR = 1.27, 95% CI: 1.23–1.30) were positively associated with increased incident hypertension in the total population. Stratified analysis and interaction tests showed a greater risk of new-onset hypertension in those

The COVID-19 pandemic has caused severe health problems worldwide and unprecedented decimation of the global economy. Moreover, after more than 2 years, many populations are still under pressure of infection. Thus, a broader perspective in developing antiviral strategies is still of great importance. Inspired by the observed multiple benefits of heparin in the treatment of thrombosis, the potential of low molecular weight heparin (LMWH) for the treatment of COVID-19 have been explored. Clinical applications found that LMWH decreased the level of inflammatory cytokines in COVID-19 patients, accordingly reducing lethality. Furthermore, several in vitro studies have demonstrated the important roles of heparan sulfate in SARS-CoV-2 infection and the inhibitory effects of heparin and heparin mimetics in viral infection. These clinical observations and designed studies argue for the potential to develop heparin mimetics as anti-SARS-CoV-2 drug candidates. In this review, we summarize the properties of heparin as an anticoagulant and the pharmaceutical possibilities for the treatment of virus infection, focusing on the perspectives of developing heparin mimetics via chemical synthesis, chemoenzymatic synthesis, and bioengineered production by microbial cell factories. The ultimate goal is to pave the eminent need for exploring novel compounds to treat coronavirus infection-caused diseases.

Abstract Background Referring to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2018 pathological classification, we aim to reveal the significance of cellular/fibrocellular crescents in lupus nephritis (LN) patients. Methods Patients with LN proven by renal biopsy at the First Affiliated Hospital of Wenzhou Medical University from December 2001 to November 2017 were identified, and eligible cases were divided into two groups according to the presence or absence of cellular/fibrocellular crescents in renal biopsy tissues. Results A total of 401 LN patients were identified from our follow-up database, and 296 eligible LN patients were enrolled in the study. Of these patients, 146 patients in the group without cellular/fibrocellular crescents (non-crescent group) and 150 patients in the group with cellular/fibrocellular crescents (Crescent group). The median follow-up time of patients was 47 months, and a total of 54 patients progressed to the composite endpoint. Crescent group had higher serum creatinine, lower serum albumin, higher systemic lupus erythematosus (SLE) disease activity index, and higher activity index of renal tissue. The interaction between cellular/fibrocellular crescents and proteinuria at baseline was associated with the prognostic risk of LN (P = 0.006). In the group with proteinuria

Mare basalts on the lunar surface are tangible expressions of the complex thermal evolution and geological processes that have occurred within the lunar interior. These basaltic manifestations are highly important because they provide invaluable insights into lunar geological evolution. Notably, the Oceanus Procellarum region, which is renowned for its extensive and long-lasting basaltic volcanism, is a premier location to investigate late-stage lunar thermal evolution. The primary aim of this research is to elucidate the geomorphological, compositional, and temporal attributes that define the mare basalts within the Oceanus Procellarum region. To achieve this aim, we comprehensively analyzed the geomorphological features present within the region, leveraging Kaguya/SELENE TC images and digital elevation models. Specifically, these geomorphological features encompass impact craters, wrinkle ridges, sinuous rilles, and volcanic domes. Subsequently, we thoroughly examined the mineralogical attributes of basalts in the Oceanus Procellarum region, leveraging Kaguya/SELENE MI data and compositional map products. To more accurately reflect the actual ages of the mare basalts in the Oceanus Procellarum region, we carefully delineated the geological units within the area and employed the latest crater size-frequency distribution (CSFD) technique to precisely determine their ages. This refined approach allowed for a more comprehensive and accurate understanding of the basaltic rocks in the study area. Overall, our comprehensive study included an in-depth analysis of the volcanic activity and evolution of the Oceanus Procellarum region, along with an examination of the correlation between the mineralogical composition and ages of mare basalts. The findings from this exhaustive investigation reveal a definitive age range for basalt units within the Oceanus Procellarum region from approximately 3.69 Ga to 1.17 Ga. Moreover, the latest mare basalts that formed were pinpointed north of the Aristarchus crater. Significantly, the region has experienced at least five distinct volcanic events, occurring approximately 3.40 Ga, 2.92 Ga, 2.39 Ga, 2.07 Ga, and 1.43 Ga, leading to the formation of multiple basalt units characterized by their unique mineral compositions and elemental abundances. Through the application of remote sensing mineralogical analysis, three primary basalt types were identified: low-titanium, very-low-titanium, and intermediate-titanium basalt. Notably, the younger basalt units exhibit an elevated titanium proportion, indicative of progressive olivine enrichment. Consequently, these younger basalt units exhibit more intricate and complex mineral compositions, offering valuable insights into the dynamic geological processes shaping the lunar surface.

Summary: Tianhe Zhuifeng Gao (TZG) shows a satisfying therapeutic efficacy in treating arthromyodynia, which shares similar etiology to myofascial pain syndrome (MPS). We herein aim to explore whether TZG could be a potential prescription for MPS therapy. An MPS rat model was successfully established presenting with reduced pain thresholds, abnormal local switch responses, etc., which was effectively reversed by TZG treatment externally. A transcriptome sequencing based on the active MTrPs samples of rats, combined with network analysis revealed that TZG might ameliorate the progression of MPS by impairing neutrophil extracellular traps (NETs) release through inhibiting PI3K-RAC2 signaling to reduce NADPH oxidase-originated ROS. Experimentally, the expression levels of inducers, biomarkers of NETs formation and vessel injury, and p-PI3K, p-P47, and RAC2 proteins were all significantly up-regulated in affected tissues, which were markedly reversed by TZG. Our results not only shed light into broadening the clinical indications of TZG, but benefit MPS therapy.

BackgroundMachine learning radiomics models are increasingly being used to predict gastric cancer prognoses. However, the methodological quality of these models has not been evaluated. Therefore, this study aimed to evaluate the methodological quality of radiomics studies in predicting the prognosis of gastric cancer, summarize their methodological characteristics and performance.MethodsThe PubMed and Embase databases were searched for radiomics studies used to predict the prognosis of gastric cancer published in last 5 years. The characteristics of the studies and the performance of the models were extracted from the eligible full texts. The methodological quality, reporting completeness and risk of bias of the included studies were evaluated using the RQS, TRIPOD and PROBAST. The discrimination ability scores of the models were also compared.ResultsOut of 283 identified records, 22 studies met the inclusion criteria. The study endpoints included survival time, treatment response, and recurrence, with reported discriminations ranging between 0.610 and 0.878 in the validation dataset. The mean overall RQS value was 15.32 ± 3.20 (range: 9 to 21). The mean adhered items of the 35 item of TRIPOD checklist was 20.45 ± 1.83. The PROBAST showed all included studies were at high risk of bias.ConclusionThe current methodological quality of gastric cancer radiomics studies is insufficient. Large and reasonable sample, prospective, multicenter and rigorously designed studies are required to improve the quality of radiomics models for gastric cancer prediction.Study registrationThis protocol was prospectively registered in the Open Science Framework Registry (https://osf.io/ja52b).

The chemical diversity of terpenoids is typically established by terpene synthase-catalyzed cyclization and diversified by post-tailoring modifications. Fungal bifunctional terpene synthase (BFTS) associated P450 enzymes have shown significant catalytic potentials through the development of various new terpenoids with different biological activities. This study discovered the BFTS and its related gene cluster from the plant endophytic fungus Didymosphaeria variabile 17020. Heterologous expression of the BFTS in Saccharomyces cerevisiae resulted in the characterization of a major product diterpene variediene (1), along with two new minor products neovariediene and neoflexibilene. Further heterologous expression of the BFTS and one cytochrome P450 enzyme VndE (CYP6138B1) in Aspergillus oryzae NSAR1 led to the identification of seven norditerpenoids (19 carbons) with a structurally unique 5/5 bicyclic ring system. Interestingly, in vivo experiments suggested that the cyclized terpene variediene (1) was modified by VndE along with the endogenous enzymes from the host cell A. oryzae through serial chemical conversions, followed by multi-site hydroxylation via A. oryzae endogenous enzymes. Our work revealed that the two-enzymes biosynthetic system and host cell machinery could produce structurally unique terpenoids.

Abstract Prelithiation technology is widely considered a feasible route to raise the energy density and elongate the cycle life of lithium‐ion batteries. The principle of prelithiation is to introduce extra active Li ions in the battery so that the lithium loss during the first charge and long‐term cycling can be compensated. Such an effect does not need to change the major electrode material or battery structure and is compatible with the majority of current lithium‐ion battery production lines. At this stage, various prelithiation methods have been reported, some of which are already in the pilot‐scale production stage. But there is still no definitive development roadmap for prelithiation. In this review, we first introduce the influence of prelithiation on electrochemical performance from a theoretical point of view and then compare the pros and cons of different prelithiation methods in different battery manufacturing stages. Finally, we discuss the challenges and future development trends of prelithiation. We aim to build up a bridge between academic research and industrial application. Some engineering problems in the promotion of prelithiation technique are extensively discussed, including not only the implementation of prelithiation but also some collateral issues on battery designing and management.

Epigenetics modification is a process that does not change the sequence of deoxyribonucleic acid (DNA) in disease progression but can alter the genetic expression of the brain in Alzheimer’s disease (AD). In this study, we deployed the weighted gene co-expression network analysis (WGCNA) to explore the role of Class I histone deacetylases (HDACs) in AD, which included HDAC1, HDAC2, HDAC3, and HDAC8. The aim of the study was to find how Class I HDACs affected AD pathology by analyzing the Gene Expression Omnibus (GEO) microarray datasets GSE33000. We found that HDAC1 and HDAC8 were more highly expressed in the cortex of AD patients than in Controls, while HDAC2 and HDAC3 were lower expressed. By WGCNA analysis, we found the blue module was associated with HDAC1 and HDAC8, and the turquoise module was related to HDAC2 and HDAC3. Functional enrichment analysis revealed that the Wnt signaling pathway and synaptic plasticity played an important role in the modification of HDAC1 and HDAC8 while gap junction and cell-cell junction were involved in the regulation of HDAC2 and HDAC3 in the disease progression of AD. By Receiver Operating Characteristics (ROC) analysis, we concluded that HDAC1 might be the most probable diagnostic biomarker of Class I HDACs for AD. Our study provided a comprehensive understanding of Class I HDACs and provided new insight into the function of HDAC1 in AD disease progression.

BackgroundIn recent years, with the continuous development of treatments for hematological malignancies (HMs), the remission and survival rates of patients with HMs have been significantly improved. However, because of severe immunosuppression and long-term recurrent neutropenia during treatment, the incidence and mortality of bloodstream infection (BSI) were all high in patients with HMs. Therefore, we analyzed pathogens’ distribution and drug-resistance patterns and developed a nomogram for predicting 30-day mortality in patients with BSIs among HMs.MethodsIn this retrospective study, 362 patients with positive blood cultures in HMs were included from June 2015 to June 2020 at West China Hospital of Sichuan University. They were randomly divided into the training cohort (n = 253) and the validation cohort (n = 109) by 7:3. A nomogram for predicting 30-day mortality after BSIs in patients with HMs was established based on the results of univariate and multivariate logistic regression. C-index, calibration plots, and decision curve analysis were used to evaluate the nomogram.ResultsAmong 362 patients with BSIs in HMs, the most common HM was acute myeloid leukemia (48.1%), and the most common pathogen of BSI was gram-negative bacteria (70.4%). The final nomogram included the septic shock, relapsed/refractory HM, albumin

ABSTRACT Since the outbreak caused by a porcine epidemic diarrhea virus (PEDV) variant in 2010, the current epidemic of PEDV genotype 2 (G2) has caused huge economic losses to the pig industry in China. In order to better understand the biological characteristics and pathogenicity of the current PEDV field strains, 12 PEDV isolates were collected and plaque purified during 2017 to 2018 in Guangxi, China. The neutralizing epitopes of the spike proteins and the ORF3 proteins were analyzed to evaluate genetic variations, and they were compared with the reported G2a and G2b strains. Phylogenetic analysis of the S protein showed that the 12 isolates were clustered into the G2 subgroup (with 5 and 7 strains in G2a and G2b, respectively) and that they shared 97.4 to 99.9% amino acid identities. Among them, one of the G2a strains, CH/GXNN-1/2018, which had a titer of 106.15 PFU/mL, was selected for pathogenicity analysis. Although piglets infected with the CH/GXNN-1/2018 strain exhibited severe clinical signs and the highest level of virus shedding within 24 h postinfection (hpi), recovery and decreased virus shedding were seen after 48 hpi, and no piglets died during the whole process. Thus, the CH/GXNN-1/2018 strain had low virulence in suckling piglets. Virus neutralizing antibody analysis showed that the CH/GXNN-1/2018 strain induced cross-protection against both homologous G2a and heterologous G2b PEDV strains as early as 72 hpi. These results are of great significance for understanding PEDV in Guangxi, China, and they provide a promising naturally occurring low-virulent vaccine candidate for further study. IMPORTANCE The current epidemic of porcine epidemic diarrhea virus (PEDV) G2 has caused huge economic losses to the pig industry. Evaluation for low virulence of the PEDV strains of subgroup G2a would be useful for the future development of effective vaccines. In this study, 12 field strains of PEDV were obtained successfully, and they were characterized from Guangxi, China. The neutralizing epitopes of the spike proteins and the ORF3 proteins were analyzed to evaluate antigenic variations. One of the G2a strains, CH/GXNN-1/2018, was selected for pathogenicity analysis, and it showed that the CH/GXNN-1/2018 strain had low virulence in suckling piglets. These results provide a promising naturally occurring low-virulent vaccine candidate for further study.

IntroductionTransversus abdominis plane block (TAPB) is now commonly administered for postoperative pain control and reduced opioid consumption in patients undergoing major colorectal surgeries, such as colorectal cancer, diverticular disease, and inflammatory bowel disease resection. However, there remain several controversies about the effectiveness and safety of laparoscopic TAPB compared to ultrasound-guided TAPB. Therefore, the aim of this study is to integrate both direct and indirect comparisons to identify a more effective and safer TAPB approach.Materials and methodsSystematic electronic literature surveillance will be performed in the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases for eligible studies through July 31, 2023. The Cochrane Risk of Bias version 2 (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tools will be applied to scrutinize the methodological quality of the selected studies. The primary outcomes will include (1) opioid consumption at 24 hours postoperatively and (2) pain scores at 24 hours postoperatively both at rest and at coughing and movement according to the numerical rating scale (NRS). Additionally, the probability of TAPB-related adverse events, overall postoperative 30-day complications, postoperative 30-day ileus, postoperative 30-day surgical site infection, postoperative 7-day nausea and vomiting, and length of stay will be analyzed as secondary outcome measures. The findings will be assessed for robustness through subgroup analyses and sensitivity analyses. Data analyses will be performed using RevMan 5.4.1 and Stata 17.0. P value of less than 0.05 will be defined as statistically significant. The certainty of evidence will be examined via the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) working group approach.Ethics and disseminationOwing to the nature of the secondary analysis of existing data, no ethical approval will be required. Our meta-analysis will summarize all the available evidence for the effectiveness and safety of TAPB approaches for minimally invasive colorectal surgery. High-quality peer-reviewed publications and presentations at international conferences will facilitate disseminating the results of this study, which are expected to inform future clinical trials and help anesthesiologists and surgeons determine the optimal tailored clinical practice for perioperative pain management.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281720, identifier (CRD42021281720).

Owing to its high ornamental, medicinal and horticultural values, herbaceous peony (Paeonia lactiflora Pall.) has been widely used as a landscaping and economical plant around the world. However, the lack of an efficient and stable regeneration system in P. lactiflora restricts its rapid propagation and large-scale production. By testing the key factors affecting callus formation, proliferation, adventitious bud induction and rooting, here, we developed an in vitro system for callus induction and regeneration in P. lactiflora. Our results show that callus formation was affected by explant types, culture environment, basal medium and plant growth regulators. Using cotyledons as explants, we established good conditions for P. lactiflora callus induction and callus proliferation. We effectively obtained adventitious buds differentiated from callus in Murashige and Skoog (MS) medium containing kinetin (KT) and thidiazuron (TDZ). Adventitious bud growth can be further promoted by adding gibberellin 3 (GA3), 1-naphthaleneacetic acid (NAA) and 6-benzyleaminopurine (6-BA) into the MS medium. A high percentage of rooting can be achieved by adding indolebutyric acid (IBA) and activated carbon (AC) to ½ MS medium. Overall, our system promotes callus induction and adventitious bud regeneration for P. lactiflora through improved culture conditions and plant growth regulators in the culture media, and lays a foundation for subsequent genetic engineering research.

One new aromadendrane-type sesquiterpenoid, namely ximaocavernosin P [(+)-1], and three new cadinane-type sesquiterpenoids, namely (+)-maninsigin D [(+)-4], (+)- and (−)-ximaocavernosin Q [(+)- and (−)-5], together with five related known ones [2, 3, (−)-4, 6, and 7], were isolated from the Hainan sponge Acanthella cavernosa. Compounds 4 and 5 were isolated as racemic forms, which were further separated to the corresponding enantiomers [(+)-4/(−)-4 and (+)-5/(−)-5], respectively, by using chiral-phase HPLC. The structures of new compounds were elucidated by extensive spectroscopic analysis and comparison with the reported data. In addition, the absolute configuration of optically pure (+)-1 and 2 were determined by time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations or X-ray diffraction analysis. A plausible biosynthetic pathway of these sesquiterpenoids and their internal correlation were proposed and discussed. In an in vitro bioassay, (+)-aristolone (3) exhibited promising anti-inflammatory activity by the inhibition of LPS-induced TNF-α and CCL2 release in RAW 264.7 macrophages.