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Abstract Aims Nutrition and inflammation status play a vital role in the prognosis of patients with heart failure (HF). This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a novel composite indicator of inflammation and nutrition, and short‐term mortality among critically ill patients with HF. Methods This retrospective study included 548 critically ill patients with HF from the MIMIC‐IV database. ALI was computed using body mass index, serum albumin and neutrophil–lymphocyte ratio. The primary endpoint was all‐cause in‐hospital mortality, and the secondary endpoint was 90 day mortality. Kaplan–Meier survival curve analysis with long‐rank test and Cox proportional hazards regression models were employed to assess the relationship between baseline ALI and short‐term mortality risk. The incremental predictive ability of ALI was evaluated by C‐statistic, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results The average age of 548 patients was 72.2 (61.9, 82.1) years, with 60% being male. Sixty‐three patients (11.5%) died in the hospital, and 114 patients (20.8%) died within 90 days of intensive care unit admission. The Kaplan–Meier analysis revealed that the cumulative incidences of both in‐hospital and 90 day mortality were significantly higher in patients with lower ALI (log‐rank test, in‐hospital mortality: P

In this work, a foam composed of helical carbon nanofiber arrays was successfully synthesized via chemical vapor deposition. By controlling synthesis parameters including the synthesising temperature and gas flow rate, carbon nanofibers with straight, kinked, and spring-like morphologies were obtained. Adjusting the precursor feed led to the formation of foams with well-ordered carbon nanofiber structures. The nanofibers exhibit diameters ranging from 98 to 175 nm and lengths extending to the centimetre scale. Experimental results confirm that these fibers are organic carbon nanofibers, attributed to low-temperature catalytic synthesis. Structural characterization reveals that the catalyst assumes a regular polyhedral shape and becomes embedded within the fibers, which symmetrically grow from both faces of the catalyst. Structural analysis indicate that the carbon nanofibers are hollow, multi-walled structures with numerous defects. The resulting foam demonstrates porous, along with excellent elasticity and high mechanical strength.

There are critical transition phenomena during the progression of many diseases. Such critical transitions are usually accompanied by catastrophic disease deterioration, and their prediction is of significant importance for disease prevention and treatment. However, predicting disease deterioration solely based on a single sample is a difficult problem. In this study, we presented the network information gain (NIG) method, for predicting the critical transitions or disease state based on network flow entropy from omics data of each individual. NIG can not only efficiently predict disease deteriorations but also detect their dynamic network biomarkers on an individual basis and further identify potential therapeutic targets. The numerical simulation demonstrates the effectiveness of NIG. Moreover, our method was validated by successfully predicting disease deteriorations and identifying their potential therapeutic targets from four real omics datasets, i.e., an influenza dataset and three cancer datasets.

Abstract Background Endogenous sex hormones in postmenopausal women have been associated with risk of cardiovascular diseases. The aim of this study was to determine the association between endogenous sex hormones and the revised Framingham Stroke Risk Profile (rFSRP) in postmenopausal women. Methods This is an observational cross-sectional study on the Vara-Skövde cohort, a Swedish population-based study for longitudinal surveillance of the development and progress of type 2 diabetes and hypertension. The participants were physically examined in 2002–2005 and sex hormones were analysed with liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Women who were ≥55 years old, with estradiol levels below 20 pg/mL, not using hormonal therapy, and with no self-reported history of stroke, were included (N = 133). The outcome variable was rFSRP. Regression analyses of log-transformed rFSRP were fitted against levels of sex hormones (17-α-OH-progesterone, estrone, estradiol, progesterone, dihydrotestosterone, dehydroepiandrosterone, testosterone and androstenedione), adjusting for body mass index (BMI) or waist-to-hip ratio (WHR), C-reactive protein (CRP) and cholesterol level. Results Levels of estrone and estradiol were positively associated with rFSRP in the crude model (estrone β = 0.208, 95% CI = 0.081;0.336, P = 0.002; estradiol β = 0.170, CI = 0.034;0.305, P = 0.015). Adjustments for BMI revealed significant positive associations between progesterone (β = 0.155 95% CI = 0.025;0.285, P = 0.020), estrone (β = 0.167, 95% CI = 0.037;0.297, P = 0.013) and 17-α-OH-progesterone (β = 0.146, 95% CI = 0.014; 0.277, P = 0.030) and rFSRP, and adjustments for WHR revealed a significant positive association between testosterone and rFSRP (β = 0.152, CI = 0.026;0.278, p = 0.018). Conclusions Increase of estrone was associated with higher rFSRP, also in the fully adjusted model, whereas progesterone, 17-α-OH-progesterone and testosterone were significant only in the models adjusting for BMI and WHR respectively. Larger studies studying stroke events are warranted to confirm these findings. Clinical trial number Not applicable.

Abstract Background To explore the effect of non-pharmacological interventions (NPIs) on respiratory pathogen profiles among hospitalized infants aged 0–3 months in Beijing during the coronavirus disease 2019 (COVID-19) pandemic. Methods Respiratory specimens were collected from 1,184 infants aged 0–3 months who were hospitalized for acute respiratory infection at the Children’s Hospital affiliated with the Capital Institute of Pediatrics from January 2018 to December 2023. The data were divided into three groups—the pre-epidemic (January 2018 to December 2019), epidemic prevention and control (January 2020 to December 2022), and post-epidemic (January 2023 to December 2023) groups—based on the outbreak of COVID-19 and the implementation and termination of NPIs. The specimens were tested for 14 respiratory pathogens, including influenza virus A (Flu A), influenza virus B, respiratory syncytial virus, parainfluenza virus (PIV), adenovirus (ADV), human metapneumovirus (HMPV), human bocavirus, human rhinovirus (HRV), coronavirus, Chlamydia trachomatis, Chlamydia pneumoniae (C.pn), Mycoplasma pneumoniae, Bordetella pertussis, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results A total of 1,184 infants, including 649 males and 535 females, with acute respiratory infections were admitted. The positive detection rate for respiratory pathogens was 51.77% (n = 613). In 2023, the proportion of infants with respiratory infections after the epidemic was 19.4% (319/1646), the positive detection rate of respiratory pathogens was 68.3% (218/319), and the mixed infection detection rate of respiratory pathogens was 16.1% (35/218). Prior to the epidemic, these rates were 11.9% (431/3611), 37.1% (160/431), and 5.0% (8/160), respectively. During the epidemic prevention and control period, these rates significantly increased to 12.4% (434/3486), 54.1% (235/434), and 11.1% (26/235) (P

Abstract Background Primary healthcare (PHC) plays a key role in hyperlipidemia (HL) management yet lacks adequate monitoring and feedback. This study aims at identifying pragmatic measures out from routinely collected electronic records to enable automatic monitoring and inform continuous optimization of HL-management at PHC settings. Methods The study used randomly selected electronic records of PHC (from the province-wide data center of Anhui-province, China) as the main data source and generated both procedure-based and encounter-based measures for assessing HL-management. The procedure-based measures were derived from specific quality-facts of 21 stages/procedures (e.g., lipid lowering medication prescription) using self-designed algorithms. While the encounter-based measures included number or rate of visits for HL, currently-noticed hyperlipidemia (CNHL, or HL noticed during the current consultation), and ever-diagnosed hyperlipidemia (EDHL). Analysis of these measures employed mainly simple descriptives and linear regression modeling. Results The study revealed interesting findings including: low and varied rates of visits for HL(from 0.01 to 1.43%) and visits by patients with EDHL/CNHL(from 0.13 to 20.54% or from 0.02 to 2.99%) between regions; large differences (5.14 to 22.20 times) between the mean or cumulative proportions of visits by patients with EDHL versus CNHL among clinician groups; consistent increase in the ratio of visits for HL in all cause visits over the study period (from 0.087 to 1.000%) accompanied with relatively stable proportions of patients with CNHL/EDHL; Relatively low scores in the procedure-based measures (ranged from 0.00 to 36.08% for specific procedures by seasons). Conclusions The measures identified are not only feasible from real-world PHC records but also give some useful metrics about how well current HL-management is going and what future actions are needed.

Abstract Differentiating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) without a kidney biopsy remains a major challenge, often leading to missed opportunities for targeted treatments that could greatly improve NDRD outcomes. To reform the traditional biopsy-all diagnostic paradigm and avoid unnecessary biopsy, we developed a transformer-based deep learning (DL) system for detecting DN and NDRD upon non-invasive multi-modal data of fundus images and clinical characteristics. Our Trans-MUF achieved an AUC of 0.980 (95% CI: 0.979 to 0.980) over the internal retrospective set and also had superior generalizability over a prospective dataset (AUC: 0.989, 95% CI: 0.987 to 0.990) and a multicenter, cross-machine and multi-operator dataset (AUC: 0.932, 95% CI: 0.931 to 0.939). Moreover, the nephrologists‘ diagnosis accuracy can be improved by 21%, through visualization assistance of the DL system. This paper lays a foundation for automatically differentiating DN and NDRD without biopsy. (Registry name: Correlation Study Between Clinical Phenotype and Pathology of Type 2 Diabetic Nephropathy. ID: NCT03865914. Date: 2017-11-30).

Abstract Background Exosomes, as extracellular membrane vesicles, play important roles in intercellular communication and can influence tumour progression. Circular RNAs (circRNAs) have been reported in various malignancies and are also important components of exosomes. However, the role of exosomal circRNAs in gastric cancer (GC) progression has not been completely clarified. Methods The exosomal circRNAs enriched in GC were identified using exosomal circRNA sequencing. The biological function of circMAN1A2 in GC was investigated using a series of in vitro and in vivo experiments. PKH-67 staining was used to label the exosomes. The molecular mechanism of exosomal circMAN1A2 was investigated via mass spectrometry, immunoprecipitation, Western blot, and single-cell RNA-sequencing data analyses. Results In our study, we determined that circMAN1A2 (hsa_circ_0000118) was enriched in GC-derived exosomes. Higher circMAN1A2 expression was related to poor survival in GC patients (HR = 2.917, p = 0.0120). Exosomal circMAN1A2 promoted GC progression in vitro and in vivo and suppressed the antitumour activity of T cells. Moreover, circMAN1A2 bound to SFPQ in GC cells and T cells, promoting the G1/S phase transition of the cell cycle in GC cells while inhibiting the activation of the T cell receptor signalling pathway in T cells to decrease antitumour activity. Mechanistically, circMAN1A2 competed with FBXW11 for binding to SFPQ, preventing FBXW11-mediated k48-linked ubiquitination and SFPQ protein degradation, thereby stabilizing SFPQ expression. Conclusions Our work confirms the critical role of exosomal circMAN1A2 in the progression and immunosuppression of GC. This novel axis of circMAN1A2-SFPQ provides new insights into exosomal circRNA-based GC diagnostic and therapeutic strategies.

[Objective] To investigate the effect of empowerment guidance on readiness for discharge and self-management ability in elderly patients at high risk of falls. [Methods] A total of 80 elderly patients with high risk of falls admitted to the Geriatrics Department of the First Hospital of Jilin University from March to December 2023 were selected as the study subjects and divided into the conventional group and the empowerment group according to the random number table method, with 40 cases in each group.Routine falls prevention health education was given to the conventional group, and empowerment guidance was given to the empowerment group.The scores of Discharge Readiness Scale and Adult Health Self-management Ability Scale were compared between the two groups.Results After the intervention, the empowerment group was significantly higher than the conventional group in the discharge readiness scores and self-management ability scores, and the difference was statistically significant (P

Abstract Objective To determine the efficacy and safety of combined low‐dose rituximab with conventional therapy for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) treatment. Methods Total 73 patients with CIDP were enrolled for the retrospective cohort study, and divided into conventional first‐line therapy cohort (n = 40) and combined low‐dose rituximab (100 mg per infusion) cohort (n = 33). The outcome measures include scores of I‐RODS, mRS, INCAT, ONLS, TSS, and COMPASS 31 scale at baseline and regular four visits (4, 16, 28, and 52 weeks), as well as proportion of favorable response and outcome, corticosteroids dosage, and deterioration occurrence during follow‐up. Results Compared to conventional therapy cohort, combined rituximab cohort presented better improvements and higher proportion of favorable response in scales assessments at each visit, as well as significantly reduced corticosteroids dosage and deterioration occurrence during the follow‐up. Analyses of subgroups showed better improvements in both typical CIDP and CIDP variants in combined rituximab cohort than those in conventional therapy cohort, but had no differences between each other. Early initiating combined rituximab regimen (

Abstract Background Carotenoids have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. The data for the effect of dietary specific carotenoids on biological aging is limited. Our study aims to examine the association between dietary carotenoid intake levels and biological aging. Methods This cross-sectional study was performed among 27,338 adults from NHANES 1999–2018. Dietary intake was assessed through two 24-hour dietary recall interviews. Biological aging indices included allostatic load (AL), homeostatic dysregulation (HD), Klemera-Doubal method (KDM), and phenoAge (PA). Multiple linear regression, weighted quantile sum (WQS) regression and quantile g-computation (QG-comp) were used to explore the associations of single carotenoid and mixed carotenoids with biological aging. Results Associations between dietary carotenoid intake levels and biological aging indices were significant among adults across the United States. Multiple linear regression showed that most carotenoids were significantly negatively correlated with AL (β = -0.017 - -0.011), HD (β = -0.045 - -0.032), KDM (β = -0.984 - -0.471), and PA (β = -0.975 - -0.539). Subgroup analysis indicated that male, older individuals, smokers, alcohol drinkers, and less physically active individuals are particularly sensitive populations. Meanwhile, WQS regression and QG-comp analyses consistently indicated a negative association between mixed carotenoids exposure and four biological aging indices, highlighting that lutein/zeaxanthin and β-carotene were responsible for the outcomes. Conclusions Increased dietary intakes of various carotenoids were associated with lower biological aging indices, which was possibly and mainly driven by lutein/zeaxanthin and β-carotene.

Abstract Bacterial blight (BB) of rice caused by Xanthomonas oryzae pv. oryzae (Xoo), is an important disease in rice-growing countries, including Pakistan, where it was first reported in the mid-1970s. Transcription activator-like effectors (TALEs) play vital roles in many plant diseases caused by Xanthomonas spp.; however, Pakistani Xoo TALome diversity and their contribution to pathogenicity is largely unknown. In this study, 101 Xoo strains were screened using specific PCR primers. The genomic DNA from these strains underwent BamHI digestion and hybridized with the internal SphI fragment of PthXo1. Southern blot analysis revealed 16 to 20 putative tale fragments among the tested strains. These strains were further classified into 11 genotypes based on the number and size of the hybridizing bands. Genotypes 1, 2, 3, and 4 represented 24, 2, 51, and 17 strains, respectively. Pathogenicity assays on near-isogenic lines (NILs) containing different resistance (R) genes exhibited that CBB23 was incompatible with all tested Pakistani-Xoo genotypes, whereas IRBB5 and IRBB4 showed resistance against specific genotypes. In contrast, paddy trails on NILs containing single, double, and triple mutants of OsSWEET11a, OsSWEET13, and OsSWEET14 in the effector binding elements (EBEs) of cv. Kitaake revealed that KP-22 and LD-5 harbor novel virulent TAL effector/s. Interestingly, the expression analysis of six clade-III OsSWEET genes suggests that novel TALE/s targeting unidentified susceptibility gene/s. Altogether, this study highlights gene-for-gene relationships between tested rice lines and Pakistani-Xoo strains. This is the first report providing the diversity of TALEs and their relationship to R and S (susceptibility) genes. Further identification of novel virulent TALE/s and their cognate target/s is warranted to precisely elucidate their role in BB.

Abstract As a novel experiential approach, live streaming at tourist destinations has garnered significant attention and profoundly impacts tourists’ travel decisions. This study aims to validate the effects of usefulness, authenticity, and interactivity of destination live streams on the decision-making process of tourists. Grounded in stimulus–organism–response (S-O-R) theory, this research identifies the usefulness, authenticity, and interactivity of destination live streams as the “stimulus,” while telepresence and trust as the “organism,” with tourists’ travel decisions as the “response.” Utilizing survey questionnaires, 274 valid data were collected and analyzed through structural equation modeling in SPSS 26.0 and Amos 28.0 software to assess the impact of destination live streams on tourists’ travel decisions. The findings reveal that both interactivity and authenticity positively influence tourists’ telepresence. Additionally, the usefulness, interactivity, and authenticity of these live streams also positively affect perceived trust among viewers, which subsequently enhances their travel decisions. This study highlights the usefulness, authenticity, and interactivity as external stimuli in destination live streams, elucidating their influence on tourists’ travel decisions and contributing to the understanding of the live streaming phenomenon within the tourism sector.

Abstract Background Recent studies suggest that neutrophil elastase inhibitor (Sivelestat) may improve pulmonary function and reduce mortality in patients with acute respiratory distress syndrome. We examined the association between receipt of sivelestat and improvement in oxygenation among patients with acute respiratory distress syndrome (ARDS) induced by COVID-19. Methods A large multicentre cohort study of patients with ARDS induced by COVID-19 who had been admitted to intensive care units (ICUs). We used propensity score matching to compare the outcomes of patients treated with sivelestat to those who were not. The differences in continuous outcomes were assessed with the Wilcoxon signed-rank test. Kaplan–Meier method was used to show the 28-day survival curves in the matched cohorts. A log-rank P-test stratified on the matched pairs was used to test the equality of the estimated survival curves. A Cox proportional hazards model that incorporated a robust sandwich-type variance estimator to account for the matched nature of the data was used to estimate hazard ratios (HR). All statistical analyses were performed with SPSS 26.0 and R 4.2.3. A two-sided p-value of

Abstract Biofilms are ubiquitous surface-associated bacterial communities embedded in an extracellular matrix. It is commonly assumed that biofilm cells are glued together by the matrix; however, how the specific biochemistry of matrix components affects the cell-matrix interactions and how these interactions vary during biofilm growth remain unclear. Here, we investigate cell-matrix interactions in Vibrio cholerae, the causative agent of cholera. We combine genetics, microscopy, simulations, and biochemical analyses to show that V. cholerae cells are not attracted to the main matrix component (Vibrio polysaccharide, VPS), but can be attached to each other and to the VPS network through surface-associated VPS and crosslinks formed by the protein Bap1. Downregulation of VPS production and surface trimming by the polysaccharide lyase RbmB cause surface remodeling as biofilms age, shifting the nature of cell-matrix interactions from attractive to repulsive and facilitating cell dispersal as aggregated groups. Our results shed light on the dynamics of diverse cell-matrix interactions as drivers of biofilm development.

With changes in modern lifestyles, weakened immunity becomes a health problem for an increasing number of people. The development of natural active products with immunomodulatory activity becomes a popular research topic. Marine sulfated polysaccharides are natural active products that are rich in sulfate groups and are extracted and isolated from marine organisms. They have a unique structure and multiple biological activities and have shown great potential with regard to having immune regulatory activity. To better understand the effects of marine sulfated polysaccharides on immune regulatory activity and the associated underlying mechanisms, this article was designed to analyse and summarize the current research literature on marine sulfated polysaccharides. The types of marine sulfated polysaccharides are summarized based on their structure and source, with a focus on functions involving regulating macrophages, natural killer cells, T/B lymphocytes, complement systems, and gut microbiota. The immune regulatory activity of marine sulfated polysaccharides and the underlying mechanisms are summarized. This article provides a theoretical basis for subsequent research on the immunomodulatory activity and structure-activity relationships of marine sulfated polysaccharides and provides novel ideas for the development of new marine sulfated polysaccharide immunoenhancers. In the future, functional foods or special medical foods based on marine sulfated polysaccharides designed to treat immune deficiency, tumours, and autoimmune diseases may be developed, and these foods will play a positive role in promoting the development of the food industry and human health.

The mode selection of a low guiding magnetic field relativistic Cherenkov generator based on coaxial combined periodic double-corrugation slow-wave structure (CPD-SWS) is studied. Owing to the flexible combination of different double-corrugation periods of the CPD-SWS, the electric field distribution can be modified and the coupling impedance of the specific mode can be enhanced, and thus the expected mode can be selected. The research results indicate that the quasi-TEM mode can be selected by adjusting the depth of the outer and inner corrugations of CPD-SWS. Moreover, the TM01 mode can be selected by adjusting the length of the corrugation and the depth of the outer corrugations of CPD-SWS. Furthermore, the TM02 mode can be selected by adjusting the depth of the outer corrugations and increasing the blade thickness. In addition, the particle in cell (PIC) simulation results show that the output microwave spectrum is pure for each case, which demonstrates that the quasi-TEM mode, TM01 mode and TM02 mode was selected successfully by using the CPD-SWS, respectively.

Abstract The tubers of Curcuma kwangsiensis are regarded as an important medicinal material in China. In C. kwangsiensis cultivation, tuber expansion is key to yield and quality, but the regulatory mechanisms are not well understood. In this study, metabolomic and transcriptomic analyses were conducted to elucidate the mechanism underlying tuber expansion development. The results showed that auxin (IAA), jasmonic acid (JA), gibberellin (GA3), ethylene (ETH), and brassinolide (BR) levels increased during tuber expansion development. Metabolomic analysis showed that 197 differentially accumulated metabolites (DAMs) accumulated during tuber expansion development and these also play important roles in the accumulation of carbohydrates and secondary metabolites. 6962 differentially expressed genes (DEGs) were enriched in plant hormone signal transduction, starch and sucrose metabolism, linoleic acid metabolism, MAPK signaling pathway as well as sesquiterpenoid and triterpenoid biosynthesis. Comprehensive analysis revealed that DEGs and DAMs of plant hormone signal transduction, ABC transporters and biosynthesis of phenylpropanoids and terpenoids are critical pathways in regulating tuber expansion. In addition, some transcription factors (ARF, C2H2, C3H, NAC, bHLH, GRAS and WRKY) as well as hub genes (HDS, HMGR, ARF7, PP2CA, PAL and CCOMT) are also involved in this process. This study lays a theoretical basis for the molecular mechanism of tuber expansion in C. kwangsiensis.

Abstract Objective Ondansetron orally soluble pellicle can serve as an alternative option for preventing nausea and vomiting in patients who receive chemotherapy. However, there is a lack of clinical evidence regarding ondansetron. This study aimed to explore the efficacy and safety of ondansetron in patients with malignant tumours who received chemotherapy drugs with a moderate-to-high emetic risk. Methods In total, 163 patients with malignant tumours received 24 mg of ondansetron via orally soluble pellicles at 30 min before chemotherapy (8 mg each time for three consecutive administrations). The incidence rates of nausea and vomiting in the three days after chemotherapy were recorded. Results Regarding the effect of ondansetron on vomiting, the complete response (zero episodes of vomiting), major response (1–2 episodes of vomiting), minor response (3–5 episodes of vomiting), and failure (> 5 episodes of vomiting) rates were 96.9%, 1.2%, 1.2%, and 0%, respectively. The major efficacy rate for vomiting (complete response + major response rates) was 98.1%. Moreover, 96.3% of patients did not experience nausea, 2.5% of patients experienced mild nausea, 1.2% of patients experienced moderate nausea, and 0.0% of patients experienced severe nausea. The major efficacy rate for nausea (no nausea) was 96.3%. Age > 65 years was negatively associated with major efficacy for vomiting, and a chemotherapy regimen involving cisplatin was negatively associated with major efficacy for nausea. A total of 42 (25.8%) patients experienced adverse events. The most common adverse events were elevated levels of alanine transaminase (6.7%), elevated levels of aspartate transaminase (3.7%), fatigue (3.7%), and cough (2.5%). Conclusion Ondansetron orally soluble pellicle shows good antiemetic efficacy and high safety in patients with malignant tumours who receive chemotherapy drugs with a moderate-to-high emetic risk.

Understanding the patterns of financial activities and predicting their evolution and changes has always been a significant challenge in the field of behavioral finance. Stock price prediction is particularly difficult due to the inherent complexity and stochastic nature of the stock market. Deep learning models offer a more robust solution to nonlinear problems compared to traditional algorithms. In this paper, we propose a simple yet effective fusion model that leverages the strengths of both transformers and convolutional neural networks (CNNs). The CNN component is employed to extract local features, while the Transformer component captures temporal dependencies. To validate the effectiveness of the proposed approach, we conducted experiments on four stocks representing different sectors, including finance, technology, industry, and agriculture. We performed both single-step and multi-step predictions. The experimental results demonstrate that our method significantly improves prediction accuracy, reducing error rates by 45%, 32%, and 36.8% compared to long short-term memory(LSTM), attention-based LSTM, and transformer models.

ObjectiveTo evaluate the prognostic value of radiation-induced lymphocytopenia in the survival of patients with primary hepatocellular carcinoma receiving radiation therapy. MethodsThe clinical data of 98 patients with unresectable primary hepatocellular carcinoma who received radiotherapy were retrospectively analyzed. The minimum absolute lymphocyte count (min ALC) was graded in accordance with CTCAE V4.0. The optimal threshold of min ALC for prognosis was calculated by using the receiver operating characteristic curve, and the correlation of min ALC with clinical characteristics and dosimetry parameters was analyzed. The Kaplan-Meier method was employed to analyze the survival of patients with different levels of min ALC. Univariate and multivariate Cox proportional regression models were applied to analyze prognostic factors. ResultsThe baseline and min ALC of 98 patients during radiotherapy were 1.52×109/L and 0.45×109/L, respectively(P

Abstract Background Limited epidemiological evidence exists regarding the role of healthy eating patterns in reducing the risk of Crohn’s disease (CD) and ulcerative colitis (UC). This study aimed to investigate the association between adherence to four established healthy eating patterns and subsequent CD or UC risk, and further examined whether these associations are linked to anti-inflammatory mechanisms. Methods We conducted a prospective cohort study of 197,391 participants from the UK Biobank who completed at least one dietary questionnaire and were free from inflammatory bowel disease or cancer at baseline. Four dietary patterns were assessed, including Alternate Mediterranean Diet (AMED), Healthy Eating Index 2015 (HEI-2015), Healthful Plant-based Diet Index (HPDI), and EAT-Lancet. Cox proportional models with restricted cubic splines were applied to explore the associations. The potential role of low-grade inflammation in these associations was examined through mediation analysis. Results During 2,193,436 person-years follow-up, 260 CD and 601 UC cases were identified. Higher AMED and HEI-2015 scores were associated with a reduced risk of CD but no UC, with no evidence against nonlinearity. These associations remained consistent across multiple sensitive and subgroup analyses. For dietary components, the fruits and monounsaturated fatty acids: saturated fatty acids ratio in AMED, and total fruits, total protein foods and fatty acid in HEI-2015 were linked to a decreased CD risk. Both diets were also associated with lower plasma inflammation biomarkers. Mediation analysis indicated that 7.66% and 13.40% of the reductions in CD risk attributed to AMED and HEI-2015 diets, respectively, were mediated by low-grade inflammation scores. Conclusions Higher adherence to AMED and HEI-2015 might significantly reduce CD risk, partly due to their anti-inflammatory properties.

Abstract Objective Cervical squamous cell carcinoma (CSCC) has a poor prognosis due to persistent HPV infection. LncRNA TPRG1-AS1 is linked to regulating the development of many cancers, so the regulatory mechanism and prognostic value of TPRG1-AS1 in CSCC were explored. Methods 138 patients with cervical cancer were included. TPRG1-AS1 expression and miR-590-3p were analyzed by qRT-PCR. The association between TPRG1-AS1 and clinicopathological features was investigated. Independent prognostic factors of CSCC were analyzed by multifactorial Cox regression. Patient survival was analyzed using Kaplan–Meier plotter curves. CCK-8 was employed to evaluate the proliferative capacity of the cells. Transwell assays were performed to evaluate the effects of TPRG1-AS1 and miR-590-3p on cell migration and invasion performance, and the target of both was reported by DLR assay. Results TPRG1-AS1 levels were ascended in CSCC, and miR-590-3p levels were reduced. TPRG1-AS1 and miR-590-3p target binding and expression correlated negatively. Knockdown of TPRG1-AS1 expression could facilitate high miR-590-3p expression, which reduced cell proliferation, migration, and invasion ability. TPRG1-AS1 is an independent prognostic factor. Conclusion TPRG1-AS1 has potential as a prognostic marker for CSCC. Silencing the expression of TPRG1-AS1 could contribute to the high miR-590-3p expression thereby slowing down the progression of CSCC.

Abstract Background Planetary plastic pollution poses a major threat to ecosystems and human health in the Anthropocene, yet its impact on biogeochemical cycling remains poorly understood. Waterlogged rice paddies are globally important sources of CH4. Given the widespread use of plastic mulching in soils, it is urgent to unravel whether low-density polyethylene (LDPE) will affect the methanogenic community in flooded paddy soils. Here, we employed a combination of process measurements, short-chain and long-chain fatty acid (SCFAs and LCFAs) profiling, Fourier-transform ion cyclotron resonance mass spectrometry, quantitative PCR, metagenomics, and mRNA profiling to investigate the impact of LDPE nanoplastics (NPs) on dissolved organic carbon (DOC) and CH4 production in both black and red paddy soils under anoxic incubation over a 160-day period. Results Despite significant differences in microbiome composition between the two soil types, both exhibited similar results to NPs exposure. NPs induced a change in DOC content and CH4 production up to 1.8-fold and 10.1-fold, respectively. The proportion of labile dissolved organic matter decreased, while its recalcitrance increased. Genes associated with the degradation of complex carbohydrates and aromatic carbon were significantly enriched. The elevated CH4 production was significantly correlated to increases in both the PCR-quantified mcrA gene copy numbers and the metagenomic methanogen-to-bacteria abundance ratio. Notably, the latter was linked to an enrichment of the hydrogenotrophic methanogenesis pathway. Among 391 metagenome-assembled genomes (MAGs), the abundance of several Syntrophomonas and Methanocella MAGs increased concomitantly, suggesting that the NPs treatments stimulated the syntrophic oxidation of fatty acids. mRNA profiling further identified Methanosarcinaceae and Methanocellaceae to be the key players in the NPs-induced CH4 production. Conclusions The specific enrichment of Syntrophomonas and Methanocella indicates that LDPE NPs stimulate the syntrophic oxidation of LCFAs and SCFAs, with Methanocella acting as the hydrogenotrophic methanogen partner. Our findings enhance the understanding of how LDPE NPs affect the methanogenic community in waterlogged paddy soils. Given the importance of this ecosystem, our results are crucial for elucidating the mechanisms that govern carbon fluxes, which are highly relevant to global climate change. Video Abstract

Abstract Encapsulin nanocompartments loaded with dedicated cargo proteins via unique targeting peptides, play a key role in stress resistance, iron storage and natural product biosynthesis. Mmp1 and cysteine desulfurase (Enc-CD) have been identified as the most abundant representatives of family 2 encapsulin systems. However, the molecular assembly, catalytic mechanism, and physiological functions of the Mmp1 encapsulin system have not been studied in detail. Here we isolate and characterize an Enc-CD-loaded Mmp1 encapsulin system from Mycobacterium smegmatis mc2155. The cryo-EM structure of the Mmp1 encapsulin and the crystal structure of the naked cargo Enc-CD have been determined. The structure shows that the Mmp1 protomer assembles two conformation models, the icosahedron (T = 1) and homodecamer, with the resolution of 2.60 Å and 2.69 Å. The Enc-CD at 2.10 Å resolution is dimeric and loaded into the Mmp1 (T = 1) encapsulin through the N-terminal long disordered region. Mmp1 encapsulin protects Enc-CD against oxidation as well as to maintain structural stability. These studies provide new insights into the mechanism by which Enc-CD-loaded encapsulin stores sulfur and provides a framework for discovery of new anti-mycobacterial therapeutics.

Abstract Background Blood–brain barrier (BBB) integrity disruption is a key pathological link of diabetes-induced cognitive impairment (DCI), but the detailed mechanism of how the diabetic environment induces BBB integrity disruption is not fully understood. Our previous study found that Zi Shen Wan Fang (ZSWF), an optimized prescription consisting of Anemarrhenae Rhizoma (Anemarrhena asphodeloides Bge.), Phellodendri Chinensis Cortex (Phellodendron chinense Schneid.) and Cistanches Herba (Cistanche deserticola Y.C.Ma) has excellent efficacy in alleviating DCI, however, whether its mechanism is related to repairing BBB integrity remains unclear. This study aims to reveal the mechanism of BBB integrity destruction in DCI mice, and to elucidate the mechanism by which ZSWF repairs BBB integrity and improves cognitive function in DCI mice. Methods Diabetic mouse model was established by feeding a 60% high-fat diet combined with a single intraperitoneal injection of 120 mg/kg streptozotocin (STZ). DCI mice were screened with morris water maze (MWM) after 8 weeks of sustained hyperglycemic stimulation. ZSWF was administered daily at doses of 9.36 and 18.72 g/kg for 8 weeks. Cognitive function was evaluated using MWM, blood–brain-barrier (BBB) integrity was tested using immunostaining and western blot, the underlying mechanisms were explored using single-cell RNA sequencing (scRNA-seq), validation experiments were performed with immunofluorescence analysis, and the potential active ingredients of ZSWF against cerebrovascular senescence were predicted using molecular docking. Moreover, cerebral microvascular endothelial cells were cultured, and the effects of mangiferin on the expression of p21 and Vcam1 were investigated by immunofluorescence staining and RT-qPCR. Results ZSWF treatment significantly ameliorated cognitive function and repaired BBB integrity in DCI mice. Using scRNA-seq, we identified 14 brain cell types. In BBB constituent cells (endothelial cells and pericytes), we found that Cdkn1a and senescence-associated secretory phenotype (SASP) genes were significantly overexpressed in DCI mice, while ZSWF intervention significantly inhibited the expression of Cdkn1a and SASP genes in cerebrovascular cells of DCI mice. Moreover, we also found that the communication between brain endothelial cells and pericytes was decreased in DCI mice, while ZSWF significantly increased the communication between them, especially the expression of PDGFRβ in pericytes. Molecular docking results showed that mangiferin, the blood component of ZSWF, had a stronger affinity with the upstream proteins of p21. In vitro experiments showed that high glucose significantly increased the expression of p21 and Vcam1 in bEnd.3 cells, while mangiferin significantly inhibited the expression of p21 and Vcam1 induced by high glucose. Conclusion Our study reveals that ZSWF can ameliorate cognitive function in DCI mice by repairing BBB integrity, and the specific mechanism of which may be related to preventing cerebrovascular cells senescence, and mangiferin is its key active ingredient. Graphical Abstract

Abstract Radiation-induced lung injury is a common complication of chest tumor radiotherapy; however, effective clinical treatments are still lacking. Stem cell-derived exosomes, which contain various signaling molecules such as proteins, lipids, and miRNAs, not only retain the tissue repair and reconstruction properties of stem cells but also offer improved stability and safety. This presents significant potential for treating radiation-induced lung injury. Nonetheless, the clinical adoption of stem cell-derived exosomes for this purpose remains limited due to scientific, practical, and regulatory challenges. In this review, we highlight the current pathology and therapies for radiation-induced lung injury, focusing on the potential applications and therapeutic mechanisms of stem cell-derived exosomes. We also discuss the limitations of existing stem cell-derived exosomes and outline future directions for exosome-based treatments for radiation-induced lung injury.

Abstract Objectives This study aims to identify predictors of knee osteoarthritis (KOA) risk in middle-aged population, construct and validate a nomogram for KOA in this demographic. Methods From June to December 2020, we conducted a cross-sectional survey on 5,527 middle-aged individuals from Changsha and Zhangjiajie cities in Hunan Province, selected using a stratified multi-stage random sampling method. Data collection involved a structured questionnaire encompassing general demographic, physical condition, and lifestyle behaviors dimensions. The dataset was randomly split into a training set (n = 3868) and a validation set (n = 1659) at a 7:3 ratio via computerized randomization. We analyzed the prevalence of self-reported KOA and identified its influencing factors using logistic regression. A nomogram was constructed based on these "three-dimensional" factors. Subsequent validation was conducted, and the nomogram's performance was further evaluated through ROC curves, C-index, Hosmer–Lemeshow test, and calibration curves. Results The self-reported prevalence of KOA in the middle-aged population was 11.4% (632/5527). The risk factor with the greatest impact is: diagnosed with osteoporosis(95% CI 2.269–3.568, OR = 2.845), followed by age between 51 to 60 years (95% CI 2.176–3.151, OR = 2.619), diagnosed with hypertension(95% CI 1.633–2.499, OR = 2.02), diagnosed with diabetes (OR = 1.689), ethnic Han Chinese (OR = 1.673), exercise according to physical condition (OR = 1.643), pay attention to keeping the knee joint warm (OR = 1.535), eating habits are mainly light vegetables (OR = 1.374), male gender (OR = 1.343), drink occasionally in small amounts (OR = 1.286); a higher level of education (OR = 0.477) and frequently or always apply an external or plaster to relieve symptoms after knee discomfort (OR = 0.377; OR = 0.385) are protective factors. The C-index of the training set model was 0.8107 (95% CI: 0.8102–0.8111), with a statistically significant area under the ROC curve (AUC = 0.818), and the calibration curve showed a good fit. The C-index for the validation set was 0.8124 (95% CI: 0.8109–0.8140), with an AUC of 0.812. The Hosmer–Lemeshow test resulted in a P-value of 0.46 (P ≥ 0.05)indicating good calibration of the model. Conclusion The three dimensions nomogram generated in this study was a valid and easy-to-use tool for assessing the risk of KOA in middle-aged population, and helped healthcare professionals to screen the high-risk population.

Abstract Anthracycline doxorubicin (DOX) remains the first-line chemotherapeutic drug for the efficient treatment of breast cancer, but its severe cardiotoxicity limits its long-term application in clinical tumor chemotherapy. Until now, the pathogenesis mechanism of DOX-induced cardiotoxicity (DIC) is still not fully understood. According to current studies, the oxidative stress caused by the imbalance of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and mitochondrial dysfunction in myocardial cells are closely related to DIC. Presently, the usual technology to solve the DIC problem is to use a multifunctional nanoplatform to load DOX and obtain a new medicinal agent, thereby enhancing the efficacy of chemotherapeutic drugs and reducing toxic side effects. Herein, the present investigation employed the Mannich condensation reaction, initiated by L-cysteine and (-)-epigallocatechin-3-gallocarboxylate (EGCG), to synthesize EGCG&Cys nanoformulation with both anti-tumor and anti-oxidant properties. The EGCG&Cys were then employed as the DOX carrier to construct a novel chemotherapeutic drug, EGCG&Cys(DOX), for high-efficiency breast cancer treatment. The tumor growth inhibition index of EGCG&Cys(DOX) in tumor-bearing mice was 12.56% superior to the DOX group with the same concentration. Meanwhile, the anti-oxidant properties of EGCG can effectively eliminate a large amount of free radicals produced by DOX and significantly alleviate DIC by improving mitochondrial functional pathways. Ultrasound echocardiography (UCG) showed that the mean LVEF and LEFS values in the 5 mg/kg DOX treatment group were significantly reduced by 54.4% and 63.4%, and the EGCG&Cys(DOX) group mice were consistent with those of the non-chemotherapy group. Moreover, electrocardiogram, serum biochemical indicators, and histopathological analysis results also demonstrate that the cardiotoxicity of EGCG&Cys(DOX) novel chemotherapy drugs is significantly reduced. Consequently, this study presents a new technology for preparing highly efficient and safe nano-chemotherapeutic drugs and an in-depth evaluation of the antitumor efficacy and safety of the synthesized novel drugs, which gave fresh life to the development of nanomedicine in the clinical treatment of breast cancer. Graphical Abstract

Abstract Baryonic two-body B mesons decays have been measured experimentally for some time, which provides an excellent ground for studying the QCD of baryonic B decays. In this work, we investigate the two-body doubly-charmed baryonic B decays in the perturbative QCD (PQCD) approach including higher twist contributions to the light-cone distribution amplitudes (LCDAs). The charmed baryon LCDAs are included up to the twist four and the effect of the subleading component of the B meson LCDAs is studied for details. With the inclusion of these higher-power contributions, the PQCD results on rates can explain the current experimental data well. Moreover, we note that the SU(3) symmetry breaking is important in the concerned processes and play an essential role in understanding the measurements of B B ¯ 0 → Λ c + Λ ¯ c − $$ \mathcal{B}\left({\overline{B}}^0\to {\Lambda}_c^{+}{\overline{\Lambda}}_c^{-}\right) $$ and B B − → Ξ c 0 Λ ¯ c − $$ \mathcal{B}\left({B}^{-}\to {\Xi}_c^0{\overline{\Lambda}}_c^{-}\right) $$ . We also evaluate the angular asymmetries for the first time, which have neither been measured experimentally nor calculated theoretically. All these predictions can be tested in future.

Abstract Background In China, investigations into the efficacy of neurological clinical teaching try to ascertain the impacts of various teaching methods on intervention outcomes. However, these studies often suffer from limited sample sizes, single-center studies and low quality, compounded by the lack of direct comparative analyses between teaching methods, thereby leaving the identification of the most effective method unresolved. This study aims to compare the effectiveness of various teaching methods in the standardized training of Chinese neurology clinicians to inform an optimal teaching model utilizing a Bayesian network meta-analysis (NMA) approach. Methods A comprehensive computer search was conducted to identify randomized controlled trials (RCTs) assessing the efficacy of 7 teaching methods: problem-based learning (PBL), case-based learning (CBL), flipped classroom model (FCM), evidence-based medicine (EBM), clinical practice (CP), team-based learning (TBL), and lecture-based learning (LBL). The search, which spanned databases including the China National Knowledge Infrastructure (CNKI), Chinese Citation Database (CDD), China Science Periodical Database (CSPD), Chinese BioMedical Literature Database (CBM), PubMed, Web of Science, and the Cochrane Library, covered the period from the inception of these databases to April 1, 2023. The quality of the included studies was evaluated, and the data were analyzed in R 4.3.2 and Stata 17.0 software. Results From the 31 studies included, comprising 2124 subjects, significant findings emerged. In theoretical examinations, a statistically significant difference was noted among the teaching methods, with CBL, PBL, TBL, FCM, and EBM showing superior performance over the LBL method. The effectiveness ranking of these methods was as follows: CBL > PBL > TBL > FCM > EBM > CP > LBL. In terms of practical skills examinations, a similar pattern of effectiveness was observed. Here, the order of effectiveness was CBL > EBM > PBL > TBL > FCM > CP > LBL. Conclusions This NMA indicated that the modern teaching pedagogies, particularly CBL, could be effective in neurology education, and might help improve the theoretical examinations and practical skills of neurology clinicians. Fully tapping into the strengths of modern teaching methods in neurology teaching will require additional work and advancing research.

Abstract Per- and polyfluoroalkyl substances (PFASs) have recently garnered considerable concerns regarding their impacts on human and ecological health. Despite the important roles of polyamide membranes in remediating PFASs-contaminated water, the governing factors influencing PFAS transport across these membranes remain elusive. In this study, we investigate PFAS rejection by polyamide membranes using two machine learning (ML) models, namely XGBoost and multimodal transformer models. Utilizing the Shapley additive explanation method for XGBoost model interpretation unveils the impacts of both PFAS characteristics and membrane properties on model predictions. The examination of the impacts of chemical structure involves interpreting the multimodal transformer model incorporated with simplified molecular input line entry system strings through heat maps, providing a visual representation of the attention score assigned to each atom of PFAS molecules. Both ML interpretation methods highlight the dominance of electrostatic interaction in governing PFAS transport across polyamide membranes. The roles of functional groups in altering PFAS transport across membranes are further revealed by molecular simulations. The combination of ML with computer simulations not only advances our knowledge of PFAS removal by polyamide membranes, but also provides an innovative approach to facilitate data-driven feature selection for the development of high-performance membranes with improved PFAS removal efficiency.

Abstract Background Gasdermin D (GSDMD) is a key effector molecule that activates pyroptosis through its N terminal domain (GSDMD-NT). However, the roles of GSDMD in colorectal cancer (CRC) have not been fully explored. The role of the full-length GSDMD (GSDMD-FL) is also not clear. In this study, we observed that GSDMD modulates CRC progression through other mechanisms in addition to activating GSDMD-NT. Methods Clinical CRC samples and human-derived CRC cell lines were used in this study. GSDMD expression was evaluated by RT-qPCR, Western blot and immunohistochemical (IHC) analysis. GSDMD knockdown and overexpression stable cell lines were established by Lentiviral transduction. CCK-8 assay, flow cytometry analysis for cell cycle, Transwell assay, and cell scratch assay were performed in vitro to explore the impact of GSDMD on CRC progression. Mouse subcutaneous transplantation tumor models were constructed to assess the role of GSDMD in vivo. Intestinal epithelial cell (IEC)-specific knockout of Gsdmd mice (Gsdmd ΔIEC) was used to evaluate the effect of GSDMD on intestinal adenoma formation in AOM-DSS and Apc min/+ mouse models. RNA sequencing was performed to explore the regulatory pathways associated with the role of GSDMD in CRC cells. Co-Immunoprecipitation (CO-IP), Western blot and immunofluorescence (IF) were conducted to investigate the interactions between GSDMD and EGFR. Exogenous addition of Gefitinib was used to evaluate the effect of GSDMD on autophosphorylation of EGFR at the Tyr1068 site. Results GSDMD was highly expressed in clinical CRC tissues and human-derived CRC cell lines. GSDMD knockdown inhibited the viability, cell cycle changes, invasion ability and migration ability of CRC cell lines in vitro and vivo, whereas GSDMD overexpression had the opposite effects. Intestinal adenoma development was reduced in Gsdmd ΔIEC mice in both AOM-DSS and Apc min/+ mouse models. GSDMD-FL interacted with EGFR and promoted CRC progression by inducing autophosphorylation of EGFR at the Tyr1068 site, subsequently activating ERK1/2. Exogenous Gefitinib abrogated the tumorigenic properties of GSDMD. Conclusions GSDMD-FL promotes CRC progression by inducing EGFR autophosphorylation at the Tyr1068 site, subsequently activating the downstream ERK1/2. Inhibition of GSDMD is a potential strategy for the treatment of colorectal cancer.

Abstract In dynamic systems like the circulatory system, establishing localized cytokine gradients is challenging. Upon lipopolysaccharide (LPS) stimulation, we observed that monocytes release numerous migrasomes enriched with inflammatory cytokines, such as TNF-α and IL-6. These cytokines are transported into migrasomes via secretory carriers, leading to their immediate exocytosis or eventual release from detached migrasomes. We successfully isolated TNF-α and IL-6-enriched, monocyte-derived migrasomes from the blood of LPS-treated mice. Total secretion analysis revealed a substantial amount of TNF-α and IL-6 released in a migrasome-packaged form. Thus, detached, monocyte-derived migrasomes represent a type of extracellular vesicle highly enriched with cytokines. Physiologically, these cytokine-laden migrasomes rapidly accumulate at local sites of inflammation, effectively creating a concentrated source of cytokines. Our research uncovers novel mechanisms for cytokine release and delivery, providing new insights into immune response modulation.

Abstract Aims The morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) continue to increase with the accelerating global aging process. During the past decade, the pathophysiology, diagnostic methods, and prognostic prediction of HFpEF have been revolutionized, resulting in new and effective management strategies. Dynamic prognostic assessment facilitates systematic clinical management of patients, and the aim of this study was to investigate the risk factors for mortality in patients with HFpEF and to develop a risk prediction assessment model. Methods and reults Data for the derivation cohort were obtained from three databases, PubMed, Embase, and Cochrane. The validation cohort was obtained from the Chinese Heart Failure Center database. The β‐coefficient was calculated based on the risk ratio (RR) and 95% confidence intervals (CI) corresponding to each risk factor to construct a mortality risk assessment model. A total of 30 studies were included in the meta‐analysis: 22 prospective cohort studies and 8 retrospective cohort studies, including 34 196 HFpEF patients. Seven predictors of all‐cause mortality in HFpEF patients were derived. Considering the need for feasibility in clinical practice, we performed subgroup and sensitivity analyses and determined the following cutoff values: age > 75 years (RR: 2.07, 95% CI: 1.83–2.35; P

The Tropical Cyclone (TC) Rainfall Climatology and Persistence Model (R-CLIPER) is a statistical parametric model for TC precipitation based on observations of North Atlantic TCs or global TCs. It boasts simple inputs and quick calculations, enabling climate-scale TC precipitation simulations, thus providing technical support for TC precipitation forecasting and risk assessments. This study focuses on TCs in the Western North Pacific region and performs localization of the R-CLIPER model. Firstly, based on precipitation data from Tropical Rainfall Measuring Mission (TRMM) satellite and Fengyun satellite (FY2C/2E) precipitation data, the radial average profiles of precipitation from TCs of 6 different intensity levels (i.e., super typhoon, strong typhoon, typhoon, severe tropical storm, tropical storm, tropical depression) are extracted. Secondly, combined with the R-CLIPER model framework, a globally optimal parameterization fitting method for TC precipitation profiles is developed. Two models are constructed, including the R-CLIPER for the Western North Pacific Ocean based on TRMM data/FY data, namely TRMM-R-CLIPER-WNP (Model 1) and FY-R-CLIPER-WNP (Model 2). Finally, based on the 62 tropical cyclones in the Northwest Pacific from 2012 to 2013 and the 26 cyclones that affected Zhejiang from 2009 to 2021 the models are evaluated in terms of fitting error and precipitation falling area. The results are as follows. (1) The TC rainfall profiles derived from TRMM data are relatively sharp near the maximum rainfall, while those from FY2C/2E satellite data are smoother and more detailed due to its higher spatial resolution. (2) The RMSE of TRMM parameterized profiles is 0.28 mm·h-1, and that of FY2C/2E profiles is 0.51 mm·h-1. (3) Based on the ground-based station data evaluation, when the rainfall threshold is less than 3 mm·h-1, the ETS score of Model 1 is better than that of Model 2. But when the threshold is greater than 3 mm·h-1, Model 2 is better. Both models perform better when the TC is centered over the sea than over land, indicating higher accuracy of TC central rainfall intensity prediction over the ocean than over land. In conclusion, using the parameterized fitting method, the accuracy of the R-CLIPER model in simulating TC precipitation in the Northwest Pacific region can be improved by 5.5%. Additionally, it was revealed that the error in TC precipitation simulations is influenced by factors such as model data sources, model framework, and parameterization schemes.

Abstract Objective To explore the clinical efficacy of modified limbal stem cell transplantation(Modified LSC transplantation) and bandage contact lens(BCL) implantation in pterygium surgery. Methods A total of 479 patients with primary pterygium who were admitted to our hospital from March 2019 to March 2023 were randomly divided into three groups: the normal group (Group A: 89 patients), the control group (Group B: 195 patients), and the modified group (Group C: 195 patients). Each group received different intervention measures. Group A did not undergo surgical treatment and were required to follow up as outpatients. Group B received LSC transplantation combined with interrupted suturing plus BCL, whereas Group C received modified LSC transplantation combined with BCL. The degree of corneal irritation symptoms, wound healing and graft status under slit lamp, incidence and recurrence rate of complications, tear film rupture time, tear secretion test, intraocular pressure, ocular surface inflammation response(IL-1β, PGE2, TNF-α, VEGF), and visual quality were compared and analyzed at various time points after surgery. Results Compared with those in the Group B, patients in the Group C experienced faster normalization of corneal epithelium recovery, fewer corneal irritation symptoms, and better wound healing. The break-up time (BUT) of the tear film at 1 week to 1 year postoperatively was significantly greater in the Group C than Group B, with values approaching those of Group A by 3 months (P 0.05). The ELISA results indicated that the expression levels of the ocular surface inflammatory factors IL-1β, TNF-α, PEG2, and VEGF in the Group C were lower than those in Group B from 1 week to 1 year post surgery. Under both natural light and low-light conditions (spatial frequency/6 cd), Group C had better best-corrected visual acuity and contrast sensitivity than Group B at 1 week to 1 year postoperatively. Additionally, Group C had lower corneal higher-order aberrations (including astigmatism, spherical aberrations, and total higher-order aberrations) and superior vision-related quality of life scores at 1 year postoperatively than Group B, with statistically significant differences (P

Abstract Southwest Primorye hosts approximately 9% of the remaining wild Amur tiger population and represents hope for the revival of tigers in Northeast China and the Korean peninsula. Decades of conservation efforts have led to a significant increase in population size, from less than 10 individuals surviving in the region in 1996 to multiple folds today. However, while the population size has recovered since the mid-1900s, the effects of genetic depletion on evolutionary potential are not easily reversed. In this study, a non-invasive genetic analysis of the Amur tiger subpopulation in Southwest Primorye was conducted using microsatellite loci and mitochondrial genes to estimate genetic diversity, relatedness, and determine the impact of historical demographic dynamics. A total of 32 individuals (16 males, 15 females, and 1 unidentified sex) were identified, and signs of bottlenecks were detected, reflecting past demographic events. Low genetic variation observed in mitochondrial DNA also revealed genetic depletion within the population. Most individuals were found to be closely related to each other, raising concerns about inbreeding given the small population size and somewhat isolated environment from the main population in Sikhote-Alin. These findings emphasize the urgent need to establish ecological corridors to neighboring areas to restore genetic diversity and ensure the conservation of the Amur tiger population in Southwest Primorye.

Abstract While hydrogel-based flexible sensors find extensive applications in fields such as medicine and robotics, their performance can be hindered by the rapid evaporation of water, leading to diminished sensitivity and mechanical durability. Despite the exploration of some effective solutions, such as introducing organic solvents, electrolytes, and elastomer composites, these approaches still suffer from problems including diminished conductivity, interface misalignment, and insufficient protection under dynamic conditions. Inspired by cell membrane structures, we developed an adaptive lipid-integrated bilayer coating (ALIBC) to enhance water retention in hydrogel-based sensors. Lipid layers and long-chain amphiphilic molecules are used as compact coating and anchoring agents on the hydrogel surface, mimicking the roles of lipids and membrane proteins in cell membranes, while spare lipids from aggregates within hydrogels can migrate to the surface to combat dehydration under deformation. This lipid-integrated bilayer coating prevents the water evaporation of hydrogels at both static and dynamic states without affecting the inherent flexibility, conductivity, and no cytotoxicity. Hydrogel-based sensors with ALIBC exhibited significantly enhanced performance in conditions of body temperature, extensive deformation, and long-term dynamic sensing. This work presents a general approach for precisely controlling the water-retaining capacity of hydrogels and hydrogel-based sensors without compromising their intrinsic physical properties.

Abstract Background Chronic pain poses a clinical challenge due to its associated costly disability and treatment needs. Determining how pain transitions from acute to chronic is crucial for effective management. Upregulation of the chemokine C-X-C motif ligand 12 (CXCL12) in nociceptive pathway is associated with chronic pain. Our previous study has reported that elevated plasma CXCL12 mediates intracerebral neuroinflammation and the comorbidity of cognitive impairment in neuropathic pain, but whether it is also involved in the pathogenesis of pathologic pain has not been investigated. Methods Intravenous or intrathecal injection (i.v. or i.t.) of recombinant mouse CXCL12, neutralizing antibody (anti-CXCL12) or AMD3100 [an antagonist of its receptor C-X-C chemokine receptor type 4 (CXCR4)] was used to investigate the role of CXCL12 signaling pathway in pain chronicity. Two behavioral tests were used to examine pain changes. ELISA, immunofluorescence staining, Western blot, quantitative Real Time-PCR and Cytokine array were applied to detect the expressions of different molecules. Results We found that increased plasma CXCL12 was positively correlated with pain severity in both chronic pain patients and neuropathic pain model in mice with spared nerve injury (SNI). Neutralizing plasma CXCL12 mitigated SNI-induced hyperalgesia. A single i.v. injection of CXCL12 induced prolonged mechanical hyperalgesia and activation of the nociceptive pathway. Multiple intravenous CXCL12 caused persistent hypersensitivity, enhanced structural plasticity of nociceptors and up-regulation of the CXCL12/CXCR4 axis in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH). However, intrathecal blocking of CXCL12/CXCR4 pathway by CXCL12 antibody or CXCR4 antagonist AMD3100 significantly alleviated CXCL12-induced pain hypersensitivity and pathological changes. Conclusions Our study provides strong evidence that a sustained increase in plasma CXCL12 contributes to neuropathic pain through a positive feedback loop that enhances nociceptor plasticity, and suggests that targeting CXCL12/CXCR4 axis in plasma or nociceptive pathways has potential value in regulating pain chronicity.

Abstract Aims Non-suicidal self-injury (NSSI) is a serious issue that is increasingly prevalent among children and adolescents, especially in rural areas. Developing a suitable predictive model for NSSI is crucial for early identification and intervention. Methods This study included 2090 Chinese rural children and adolescents. Participants’ sociodemographic information, symptoms of anxiety as well as depression, personality traits, family environment and NSSI behaviors were collected through a questionnaire survey. Gender, age, grade, and all survey results except sociodemographic information were used as relevant factors for prediction. Support vector machines, decision tree and random forest models were trained and validated by the train set and valid set, respectively. The metrics of each model were tested and compared to select the most suitable one. Furthermore, the mean decrease Gini index was calculated to measure the importance of relevant factors. Results The prevalence of NSSI was 38.3%. Out of the 6 models assessed, the random forest model demonstrated the highest suitability in predicting the prevalence of NSSI. It achieved sensitivity, specificity, AUC, accuracy, precision, and F1 scores of 0.65, 0.72, 0.76, 0.70, 0.57, and 0.61, respectively. Anxiety and depression were the top two contributing factors in the prediction model. Neuroticism and conflict were the factors that contributed the most to personality traits and family environment, respectively, in terms of prediction. In addition, demographic factors contributed little to the prediction in this study. Conclusion This study focused on Chinese children and adolescents in rural areas and demonstrated the potential of using machine learning approaches in predicting NSSI. Our research complements the application of machine learning methods to psychiatric and psychological problems.

Abstract The development of negative photoconductivity (NPC)-related devices is of great significance for numerous applications, such as optoelectronic detection, neuromorphic computing, and optoelectronic synapses. Here, an unusual but interesting NPC phenomenon in the novel cesium cobalt chlorine (Cs2CoCl4) single crystal-based optoelectronic devices is reported, which simultaneously possess volatile resistive switching (RS) memory behavior. Joint experiment−theory characterizations reveal that the NPC behavior is derived from the intrinsic vacancy defects of Cs2CoCl4, which could trap photogenerated charge carriers and produce an internal electric field opposite to the applied electric field. Such NPC effect enables an abnormal photodetection performance with a decrease in electrical conductivity to illumination. Also, a large specific detectivity of 2.7 × 1012 Jones and broadband NPC detection wavelength from 265 to 780 nm were achieved. In addition to the NPC response, the resulting devices demonstrate a volatile RS performance with a record-low electric field of 5 × 104 V m−1. By integrating the characteristics of electric-pulse enhancement from RS and light-pulse depression from NPC, an artificial optoelectronic synapse was successfully demonstrated, and based on the simulation of artificial neural network algorithm, the recognition application of handwritten digital images was realized. These pioneer findings are anticipated to contribute significantly to the practical advancement of metal halides in the fields of in-memory technologies and artificial intelligence.

Utilizing standardized artificial regulatory sequences to fine-tuning the expression of multiple metabolic pathways/genes is a key strategy in the creation of efficient microbial cell factories. However, when regulatory sequence expression strengths are characterized using only a few reporter genes, they may not be applicable across diverse genes. This introduces great uncertainty into the precise regulation of multiple genes at multiple expression levels. To address this, our study adopted a fluorescent protein fusion strategy for a more accurate assessment of target protein expression levels. We combined 41 commonly-used metabolic genes with 15 regulatory sequences, yielding an expression dataset encompassing 520 unique combinations. This dataset highlighted substantial variation in protein expression level under identical regulatory sequences, with relative expression levels ranging from 2.8 to 176-fold. It also demonstrated that improving the strength of regulatory sequences does not necessarily lead to significant improvements in the expression levels of target proteins. Utilizing this dataset, we have developed various machine learning models and discovered that the integration of promoter regions, ribosome binding sites, and coding sequences significantly improves the accuracy of predicting protein expression levels, with a Spearman correlation coefficient of 0.72, where the promoter sequence exerts a predominant influence. Our study aims not only to provide a detailed guide for fine-tuning gene expression in the metabolic engineering of Escherichia coli but also to deepen our understanding of the compatibility issues between regulatory sequences and target genes.

The 8-Syndrome structure of the Child Behavior Checklist (CBCL) has been well supported globally, but its validity in the Chinese sample remains untested. A total of 67,257 school students aged 6–16 were included. The Chinese version of the CBCL consists of 118 specific behavioral and emotional items, with two open-ended screening items. Confirmatory factor analysis (CFA), cluster analysis, and network analysis were employed to test the 8-Syndrome structure in the Chinese CBCL. The Chinese CBCL showed a comparative fit index (CFI) of 0.734, indicating poor fit in the Chinese sample. Cluster and network analyses suggested that Anxious/Depressed (AD), Withdrawn/Depressed (WD), and Thought Problems (TP) might form internalizing factors (representing emotional or thought problems), whereas Aggressive Behavior (AB), Rule-Breaking Behavior (RBB), and Attention Problems (AP) might comprise externalizing factors (representing behavioral problems). Age emerged as a significant factor influencing emotional and behavioral problems in the Chinese sample (p

Contemporary society is confronted with multifaceted challenges, and the intricate interplay of interconnected factors significantly complicates emergency response efforts. Current practices rely on quick decisions by domain experts; however, the limitations of individual expertise and the urgency of crises hinder both precision and standardization. To address these issues, we propose a novel approach: an intelligent method for emergency decision-making grounded in a standardized digital knowledge graph. First, our study examined the underlying theory of standardized digital transformation and event-chain evolution. This led to the construction of a knowledge graph encompassing standard emergency knowledge, as well as supplementary derivative data pertinent to event response. Second, through the application of semantic analysis and intention recognition of the decision target, coherent and interpretable query sentences for the decision system were crafted. These query sentences then served as a conduit for retrieving standard emergency knowledge relevant to the current emergency situation, as well as potential secondary disasters. The overarching goal is to provide emergency decision makers with effective support mechanisms that are both well informed and tailored to the specific demands of each situation.

Adenosine triphosphate (ATP)-activated prodrug approaches demonstrate potential in antibacterial uses. However, their efficacy frequently faces obstacles due to uncontrolled premature activation and spatiotemporal distribution differences under physiological circumstances. Herein, we present an endogenous ATP-activated prodrug system (termed ISD3) consisting of nanoparticles (indole-3-acetic acid/zeolitic imidazolate framework-8@polydopamine@platinum, IZPP) embedded in a silk fibroin-based hydrogel, aimed at treating multidrug-resistant (MDR) bacteria-infected pressure ulcers. Initially, an ultraviolet-triggered adhesive ISD3 barrier is formed over the pressure ulcer wound by a simple local injection. Subsequently, the bacteria-secreted ATP prompts the degradation of IZPP, allowing the loaded IAA prodrug and nanozyme to encounter spatiotemporally on a single carrier, thereby efficiently generating reactive oxygen species (ROS). Exposure to 808 nm near-infrared light enhances the catalytic reaction speed, boosting ROS levels for stronger antibacterial action. Once optimal antibacterial action is reached, ISD3 switches to a dormant state, halting any further ROS production. Moreover, the bioactive components in ISD3 can exert anti-inflammatory functions, aiding in pressure ulcer recovery. Overall, our research introduces a hydrogel prodrug strategy activated by bacterial endogenous ATP, which precisely manages ROS generation and accelerates the recovery of MDR bacteria-infected pressure ulcers.

In this paper, the Cu-10.8Al-8.3Mn-0.37Si alloy containing Mn5Si3 phase was obtained by adding Si element to the Cu-10.8Al-8.3Mn alloy. The two alloys were printed by laser powder bed fusion. The changes in the organization and tensile properties of the alloys and the mechanism were investigated. After Si addition, the Mn5Si3 nano phase precipitated in the alloy in addition to the β1 austenite phase. The Mn5Si3 phase was co-lattice with the β1 phase with an average size of 10 nm and was diffusely distributed. Standard tensile experiments showed that the yield strength of the Cu-10.8Al-8.3Mn-0.37Si alloy decreased by 57.7% and the elongation increased by 266% compared to the Cu-10.8Al-8.3Mn alloy, while the tensile strength remained essentially unchanged. The presence of Mn5Si3 phase provided nucleation points for martensite and promoted the generation of stress-induced martensite. Hence the yield strength was reduced. TEM results showed that the β1 phase in the Cu-10.8Al-8.3Mn-0.37Si alloy was fully transformed into stress-induced martensite after deformation, which displayed the transformation induced plasticity effect and hindered the slip of dislocations. Meanwhile, the Mn5Si3 phase was sheared by the stacking faults, which promoted the accumulation of hetero-deformation-induced stress. Therefore, the hardening capacity and plasticity of the Cu-10.8Al-8.3Mn-0.37Si alloy were enhanced. This work provides a new idea for the plasticity enhancement of Cu–Al–Mn-based shape memory alloys achieved by co-lattice nano-precipitated phase strengthening.

Abstract Perovskite-based materials have become a new direction for peroxymonosulfate (PMS) activation in pollutants degradation. However, the mechanism towards PMS activation remains insufficient. In this paper, a series of LaM x Mn 1−x O3 materials with B-site doping were developed by sol-gel self-propagating combustion method. The prepared LaFe0.3Mn0.7O3/PMS system exhibited the desired catalytic activity, almost 100% removal efficiency of TC can be achieved within 50 min and 98% initial catalytic activity could be maintained after 5 cycles. Quenching experiments and EPR tests together certified the vital roles of •O2 − and 1O2 during the TC degradation procedure. Simultaneously, the catalytic performance of the LaFe0.3Mn0.7O3/PMS system was examined in relation to varying pH values, coexisting chemicals, and water conditions. DFT calculations demonstrated an increased electron concentration in the reactive sites after Fe doping. In addition, LaFe x Mn 1−x O3 at the electron-rich state increased the bond strength with O atoms and encouraged the adsorption/desorption of intermediates in the PMS activation process. The aforementioned outcomes showed the possibility for application in intricate, realistic aquatic environments.

Abstract Background This study conducted a thorough assessment of vertical root fracture (VRF) resistance of endodontically treated teeth filled with various canal-filling systems and techniques through frequentist network meta-analysis (NMA). Methods A systematic literature search was performed to retrieve relevant publications using PubMed, Embase, ScienceDirect, Web of Science, and Cochrane Library databases. The retrieval time range was from Jan 2000 to Sep 2023. The literature selection and data extraction were independently conducted by two investigators. Eligible studies were critically appraised for risk of bias and quality of evidence. Subsequently, we used the ‘network’ package in Stata/MP 17.0 software to compare the VRF resistance of roots treated with different obturating systems or techniques. Results Forty-eight trials involving 2724 single-canal roots were included in the NMA. The surface under the cumulative ranking curves indicated that Resilon/Epiphany (80.8%), although outdated, provided the highest VRF resistance among all obturating systems. This was followed by GP/iRootSP (55.5%), GP/MTA-Plus (47.9%), GP/AH-Plus (47.4%), GP/AH-26 (45.9%), and GP/ZOE (12.3%). The roots filled with Resilon/Epiphany showed better VRF resistance as compared to those filled with gutta-percha/AH-Plus (SMD = 0.77, 95%CI 0.10 to 1.45) and gutta-percha/zinc oxide eugenol (SMD = 1.64, 95%CI 0.47 to 2.80). The single cone technique (SCT) group displayed the highest VRF resistance, and roots filled with all techniques, except Thermafil, outperformed the positive control group. Conclusions Resilon/Epiphany demonstrated the greatest root strength among all six obturating systems, followed by GP/iRootSP and GP/MTA-Plus, which are calcium silicate-based systems. In contrast, the gutta-percha/zinc-oxide eugenol system exhibited the weakest performance. All canal-filling techniques, particularly the SCT, strengthen endodontically treated roots, except for the Thermafil technique. Further well-designed clinical trials with large sample sizes are essential for validation.