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Cotton breeding for the development of early-maturing varieties is an effective way to improve multiple cropping indexes and alleviate the conflict between grains and cotton in the cultivated fields in China. In the present study, we aimed to identify upland cotton quantitative trait loci (QTLs) and candidate genes related to early-maturity traits, including whole growth period (WGP), flowering timing (FT), node of the first fruiting branch (NFFB), height of the node of the first fruiting branch (HNFFB), and plant height (PH). An early-maturing variety, CCRI50, and a late-maturing variety, Guoxinmian 11, were crossed to obtain biparental populations. These populations were used to map QTLs for the early-maturity traits for two years (2020 and 2021). With BSA-seq analysis based on the data of population 2020, the candidate regions related to early maturity were found to be located on chromosome D03. We then developed 22 polymorphic insertions or deletions (InDel) markers to further narrow down the candidate regions, resulting in the detection of five and four QTLs in the 2020 and 2021 populations, respectively. According to the results of QTL mapping, two candidate regions (InDel_G286-InDel_G144 and InDel_G24-InDel_G43) were detected. In these regions, three genes (GH_D03G0451, GH_D03G0649, and GH_D03G1180) have non-synonymous mutations in their exons and one gene (GH_D03G0450) has SNP variations in the upstream sequence between CCRI50 and Guoxinmian 11. These four genes also showed dominant expression in the floral organs. The expression levels of GH_D03G0451, GH_D03G0649 and GH_D03G1180 were significantly higher in CCRI50 than in Guoxinmian 11 during the bud differentiation stages, while GH_D03G0450 showed the opposite trend. Further functional verification of GH_D03G0451 indicated that the GH_D03G0451-silenced plants showed a delay in the flowering time. The results suggest that these are the candidate genes for cotton early maturity, and they may be used for breeding early-maturity cotton varieties.

Abstract Background While the high haemoglobin glycation index (HGI) has been extensively investigated in diabetic populations, its impact on patients with diabetic kidney disease (DKD) remains unclear. Methods We examined data from the National Health and Nutrition Examination Surveys (NHANES) conducted between 1999 and 2018. HGI was determined using the formula recommended by Hempe et al., which calculates the difference between measured and predicted HbA1c. Predicted HbA1c was derived from the equation: 0.024 FPG + 3.1. National death index records up to December 31, 2019, were utilized to assess mortality outcomes. To estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for both all-cause and cardiovascular disease (CVD) mortality, we utilized Cox proportional hazard models. A restricted cubic spline analysis was performed to explore the potential nonlinear relationship between HGI levels and mortality. Results Our cohort study comprised data from 1,057 participants with DKD (mean [SE] age, 61.61 [0.57] years; 48.24% female). The mean HGI level was 0.44 (SE 0.04). Over a median follow-up period of 6.67 years, we observed 381 deaths, including 140 due to CVD. Compared with participants in the second tertile of HGI levels (0.03–0.74), those in the lowest tertile of HGI (-5.29–0.02) exhibited an all-cause mortality hazard ratio of 1.39 (95% CI, 1.02–1.88) and a CVD mortality hazard ratio of 1.10 (95% CI, 0.67–1.81). Conversely, participants in the highest tertile (0.75–9.60) demonstrated an all-cause mortality hazard ratio of 1.48 (95% CI, 1.05–2.08) and a CVD mortality hazard ratio of 2.06 (95% CI, 1.13–3.77) after further adjusting for HbA1c and other important variables. Additionally, a restricted cubic spline analysis revealed a U-shaped relationship between HGI and all-cause mortality (P

Abstract Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the antimicrobial resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, broad-spectrum AMPs. Using deepAMP to reduce antimicrobial resistance and enhance the membrane-disrupting abilities of AMPs, we identify, synthesize, and experimentally test 18 T1-AMP (Tier 1) and 11 T2-AMP (Tier 2) candidates in a two-round design and by employing cross-optimization-validation. More than 90% of the designed AMPs show a better inhibition than penetratin in both Gram-positive (i.e., S. aureus) and Gram-negative bacteria (i.e., K. pneumoniae and P. aeruginosa). T2-9 shows the strongest antibacterial activity, comparable to FDA-approved antibiotics. We show that three AMPs (T1-2, T1-5 and T2-10) significantly reduce resistance to S. aureus compared to ciprofloxacin and are effective against skin wound infection in a female wound mouse model infected with P. aeruginosa. In summary, deepAMP expedites discovery of effective, broad-spectrum AMPs against drug-resistant bacteria.

Recent advancements in satellite remote sensing technology and computer vision have enabled rapid extraction of road networks from massive, Very High-Resolution (VHR) satellite imagery. However, current road extraction methods face the following limitations: 1) Insufficient availability of accurate and diverse training datasets for global-scale road extraction; 2) Costly and time-consuming manual labeling of millions of road samples; and 3) Limited generalization ability of deep learning models across diverse global contexts, resulting in better performance for regions well-represented in the training dataset, but worse performance when faced with domain gaps. To address these challenges, a semi-supervised framework was developed in this study, which includes a global-scale benchmark dataset – termed GlobalRoadSet (GRSet) – and a pseudo-label guided semi-supervised road extraction network – termed GlobalRoadNetSF (GRNetSF). The GRSet dataset was constructed using high-resolution satellite imagery and open-source crowdsourced OpenStreetMap (OSM) data. It comprises 47,210 samples collected from 121 capital cities across six populated continents. The GRNetSF trains the network by generating pseudo-labels for unlabeled images, combined with a few labeled samples from the target region. To enhance the quality of the pseudo-labels, strong data augmentation perturbation and auxiliary feature perturbation techniques are employed to ensure model prediction consistency. The proposed GRNetSF_GRSet framework was implemented in over 30 cities worldwide, where most of the Intersection-over-Union (IoU) values increased by more than 10%. This outcome confirms its strong generalization ability.

Abstract Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

Liver transplantation (LT) is the standard therapy for individuals afflicted with end-stage liver disease. Despite notable advancements in LT technology, the incidence of early allograft dysfunction (EAD) remains a critical concern, exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients. Unfortunately, the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD. Herein, we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients, with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages. Comparison of the 75 231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells, granzyme B+ (GZMB+) granzyme K+ (GZMK+) natural killer cells, and S100 calcium binding protein A12+ (S100A12+) neutrophils. Moreover, we verified this immune niche and its association with EAD occurrence in two independent cohorts. Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level, thus, offering valuable insights into EAD onset.

Abstract Background and objectives To investigate the relationship between body mass index (BMI) and blood biochemical indicators in early adolescence, and to provide ideas for early prevention of diseases and explore possible disease-related predictors. Methods 3125 participants aged 10 ∼ 14 years were selected from China from the survey of “China Nutrition and Health Surveillance ( 2016 ∼ 2017 ) “. Employing advanced statistical methods, including generalized linear models, heatmaps, hierarchical clustering, and generalized additive models, the study delved into the associations between BMI and various biochemical indicators. Results In early adolescence, indicators including systolic pressure, diastolic pressure, weight, height, BMI, hemoglobin, blood uric acid, serum creatinine, albumin, vitamin A presented increasing trends with the increase of age ( P 1, P

Abstract Understanding the endogenous mechanism of adaptive response to drug‐induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin‐induced liver injury (TILI) of mice. Exosomal miR‐106b‐5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR‐106b‐5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR‐106b‐5p protects mice from liver injury. Injured hepatocytes released miR‐106b‐5p‐enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR‐106b‐5p by dual luciferase reporter and siRNA assays. Furthermore, single‐cell RNA‐sequencing analysis of toosendanin‐injured mouse liver revealed a cluster of Vim+ hepatocytes; nonetheless declined following miR‐106b‐5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR‐106b‐5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR‐106b‐5p safeguards restorative tissue repair by targeting vimentin.

The Western Sichuan Plateau stands as a vital ecological barrier in China. In recent years, rapid urbanization and infrastructure development have led to increased ecosystem fragmentation in the region, compression of species habitats, and significant challenges to ecosystem service functions and biodiversity conservation. Constructing ecological corridors can help maintain landscape connectivity and preserve biodiversity by providing habitats for various species. Additionally, they can enhance population viability and species richness at both local and regional scales. Current research focuses on the construction of ecological networks and the potential impacts of corridors. Few studies consider corridor width as an object of study. This study addresses the width of corridor construction, aiming to support the practical implementation of corridor projects and explore the coordination between corridor costs and functionality at different widths. Based on an evaluation of ecosystem service functions and in conjunction with natural reserves, this study identified significant ecological source. Four primary resistance factors—land use type, elevation, slope, and Degree of relief—were selected to construct resistance surfaces. The MAXENT model is introduced to identify potential landslide-prone areas, and the resistance surfaces are accordingly adjusted. Potential corridors are identified utilising circuit theory. Subsequently, by employing the IEW-TOPSIS model, different ecological corridor widths are evaluated in terms of “cost-function-ecological benefits” to determine suitable corridor widths for the Western Sichuan Plateau. Results reveal significant variations in ecological corridor widths across different regions of the plateau. Taking topographical factors into account, 1400 m emerges as the most optimal width twice, while 800 m, 1700 m, and 2000 m each appear once. The corridor width evaluation system can provide decision support for ecological corridor construction in the Western Sichuan Plateau, contributing to the preservation of ecological security in the Qinghai-Tibet Plateau in China.

BackgroundToxoplasma gondii (T. gondii) is a widespread zoonotic parasite transmitted through contaminated food or water. It poses a significant public health threat, especially to pregnant women and immunocompromised individuals. 25-Hydroxyvitamin D [25(OH)D] plays a critical role in regulating both innate and adaptive immune responses, particularly in its anti-infective capacity. However, the relationship between serum 25(OH)D concentrations and T. gondii infection remains uncertain.MethodsWe analyzed the data from the National Health and Nutrition Examination Survey (NHANES) spanning 2009–2014 to explore the association between serum 25(OH)D concentrations and T. gondii infection. Extensive demographic, comorbidity, and dietary data were collected. The status of T. gondii infection was determined using serum anti-IgG antibodies. Serum 25(OH)D levels were measured using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). In addition, weighted logistic regression and restricted cubic spline analyses were performed.ResultsOur analysis included 10,157 participants (mean [SE] age, 45.38 [0.39] years; 49.73% female) who met the inclusion criteria. Serum 25(OH)D levels were categorized into quintiles, with the second quintile serving as the reference group. The final model, adjusted for age, sex, race, education level, poverty income ratio, body mass index, smoking status, hypertension, diabetes, chronic kidney disease, depression, physical activity, alcohol intake, seasonal testing, and dietary vitamin D, revealed the following adjusted odds ratios (ORs) for the quintiles: 0.75 (95% confidence interval [CI]: 0.60–0.93) for the first, 0.87 (95% CI: 0.69–1.10) for the third, 0.75 (95% CI: 0.58–0.95) for the fourth, and 0.66 (95% CI: 0.49–0.91) for the fifth. Additionally, a restricted cubic spline analysis revealed an inverted U-shaped relationship between serum 25(OH)D and T. gondii infection, with an inflection point at approximately 51.29 nmol/L. Odds ratios to the left and right of the inflection point were 1.17 (95% CI: 1.03–1.32) and 0.94 (95% CI, 0.90–0.98) per 10 nmol/L, respectively.ConclusionOur study uncovers an inverted U-shaped relationship between serum 25(OH)D concentrations and T. gondii infection, with an inflection point around 51.29 nmol/L.

Abstract Interleukin 12 (IL-12) is a potent immunostimulatory cytokine mainly produced by antigen-presenting cells (e.g., dendritic cells, macrophages) and plays an important role in innate and adaptive immunity against cancers. Therapies that can synergistically modulate innate immunity and stimulate adaptive anti-tumor responses are of great interest for cancer immunotherapy. Here we investigated the lipid nanoparticle-encapsulated self-replicating RNA (srRNA) encoding IL-12 (referred to as JCXH-211) for the treatment of cancers. Both local (intratumoral) and systemic (intravenous) administration of JCXH-211 in tumor-bearing mice induced a high-level expression of IL-12 in tumor tissues, leading to modulation of tumor microenvironment and systemic activation of antitumor immunity. Particularly, JCXH-211 can inhibit the tumor-infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). When combined with anti-PD1 antibody, it was able to enhance the recruitment of T cells and NK cells into tumors. In multiple mouse solid tumor models, intravenous injection of JCXH-211 not only eradicated large preestablished tumors, but also induced protective immune memory that prevented the growth of rechallenged tumors. Finally, intravenous injection of JCXH-211 did not cause noticeable systemic toxicity in tumor-bearing mice and non-human primates. Thus, our study demonstrated the feasibility of intravenous administration of JCXH-211 for the treatment of advanced cancers.

Abstract Background Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. Methods SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. Results SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. Conclusions SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.

We explore the numerical approximation of the stochastic Burgers equation driven by fractional Brownian motion with Hurst index $ H\in(1/4, 1/2) $ and $ H\in(1/2, 1) $, respectively. The spatial and temporal regularity properties for the solution are obtained. The given problem is discretized in time with the implicit Euler scheme and in space with the standard finite element method. We obtain the strong convergence of semidiscrete and fully discrete schemes, performing the error estimates on a subset $ \Omega_{k, h} $ of the sample space $ \Omega $ with the Gronwall argument being used to overcome the difficulties, caused by the subtle interplay of the nonlinear convection term. Numerical examples confirm our theoretical findings.

Obesity and obesity-related metabolic disorders are global epidemics that occur when there is chronic energy intake exceeding energy expenditure. Growing evidence suggests that healthy dietary patterns not only decrease the risk of obesity but also influence the composition and function of the gut microbiota. Numerous studies manifest that the development of obesity is associated with gut microbiota. One promising supplementation strategy is modulating gut microbiota composition by dietary patterns to combat obesity. In this review, we discuss the changes of gut microbiota in obesity and obesity-related metabolic disorders, with a particular emphasis on the impact of dietary components on gut microbiota and how common food patterns can intervene in gut microbiota to prevent obesity. While there is promise in intervening with the gut microbiota to combat obesity through the regulation of dietary patterns, numerous key questions remain unanswered. In this review, we critically review the associations between dietary patterns, gut microbes, and obesity, aiming to contribute to the further development and application of dietary patterns against obesity in humans.

BackgroundIn natural mangrove communities, mangrove species are often distributed zonally. Leaf-eating crabs are one of the most abundant and iconic arboreal brachyurans in mangrove forests, but variation in the composition of crab diets in different mangrove tidal zones is unknown.MethodsTo determine the contributions of mangrove leaves and other organic carbon (C) sources to leaf-eating crab diets, dual stable C and nitrogen (N) isotope signatures (δ13C and 1δ5N) were used in a Bayesian stable isotope mixing model. We conducted experiments at various tidal levels in the Dongzhaigang Bay National Natural Reserve in China. We analyzed δ13C and δ15N of leaf-eating crabs, mangrove leaves, sediment organic matter (SOM), and animal tissues (prey).ResultsThe food composition of the dominant crab species, Parasesarma continentale, exhibited significant differences among the four tidal zones. From the margin to the high tide zone, the main food source shifted from predominantly mangrove leaves and SOM to primarily SOM and animal tissues. We observed a significant negative relationship between the C/N ratios of mangrove leaves and the proportion of leaves consumed by leaf-eating crabs. Additionally, as the tidal level increased, the C/N ratio of mangrove leaves also increased, whereas the proportion of leaves consumed by crabs decreased.ConclusionLeaf-eating crab diets vary significantly across tidal zones, highlighting the importance of considering tidal zone differentiation when studying consumer diets in mangrove ecosystems.

Abstract Prostate cancer (PC) is one of the most common cancers in men and becoming the second leading cause of cancer fatalities. At present, the lack of effective strategies for prognosis of PC patients is still a problem to be solved. Therefore, it is significant to identify potential gene signatures for PC patients’ prognosis. Here, we summarized 71 different prognostic gene signatures for PC and concluded 3 strategies for signature construction after extensive investigation. In addition, 14 genes frequently appeared in 71 different gene signatures, which enriched in mitotic and cell cycle. This review provides extensive understanding and integrated analysis of current prognostic signatures of PC, which may help researchers to construct gene signatures of PC and guide future clinical treatment.

Granite residual soil is widely distributed in Southeastern China. Such soils exhibit mechanical characteristics such as loose, rich cracks and easy disintegration, resulting in severe soil erosion disasters under rainfall conditions. Microbial-induced carbonate precipitation (MICP) is a green alternative for soil stabilization. In this study, a new strategy for the disintegration control of granite residual soil using MICP technology is proposed. The effects of the bacterial solution concentration, the cementation solution concentration, and the treatment cycle are investigated through a disintegration test. The optimal treatment parameters for granite residual soil using MICP technology are determined by analyzing the disintegration processes and residual quality indicators of disintegration. The results show that the treated samples have three types of disintegration: complete disintegration, incomplete disintegration, and non-disintegration. The precipitated calcium carbonate (CaCO3) bonds the soil particles and fills the pores. Taking into account the effectiveness and cost and a bacterial solution concentration OD600 = 0.75, five cycles of MICP treatment with a cementation solution concentration of 1.2 mol/L is optimal for the disintegration control of granite residual soil. The cementation-action effects of CaCO3 are verified through scanning electron microscopy (SEM) tests with an energy-dispersive X-ray (EDX) spectroscope. These findings suggest that MICP is a promising candidate to control the disintegration of granite residual soil.

Background Controversy exists regarding the association between non-obstructive dyspnoea and the future development of chronic obstructive pulmonary disease (COPD) and mortality. Therefore, we aimed to evaluate the association of non-obstructive dyspnoea with mortality and incident COPD in adults.Methods We searched PubMed, Embase, and Web of Science to identify studies published from inception to 13 May 2023. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Studies were included if they were original articles comparing incident COPD and all-cause mortality between individuals with normal lung function with and without dyspnoea. The primary outcomes were incident COPD and all-cause mortality. The secondary outcome was respiratory disease-related mortality. We used the random-effects model to calculate pooled estimates and corresponding 95% confidence interval (CI). Heterogeneity was determined using the I² statistic.Results Of 6486 studies, 8 studies involving 100 758 individuals fulfilled the inclusion and exclusion criteria and were included in the study. Compared with individuals without non-obstructive dyspnoea, individuals with non-obstructive dyspnoea had an increased risk of incident COPD (relative risk: 1.41, 95% CI: 1.08 to 1.83), and moderate heterogeneity was found (p=0.079, I2=52.2%). Individuals with non-obstructive dyspnoea had a higher risk of all-cause mortality (hazard ratio: 1.21, 95% CI: 1.14 to 1.28, I2=0.0%) and respiratory disease-related mortality (hazard ratio: 1.52, 95% CI: 1.14 to 2.02, I2=0.0%) than those without.Conclusions Individuals with non-obstructive dyspnoea are at a higher risk of incident COPD and all-cause mortality than individuals without dyspnoea. Further research should investigate whether these high-risk adults may benefit from risk management and early therapeutic intervention.PROSPERO registration number CRD42023395192.

This study aimed to evaluate the efficacy and safety of intravitreal dexamethasone implants in the treatment of ocular toxocariasis (OT). A retrospective analysis was performed on 6 cases in which laboratory tests diagnosed OT. All patients were administered with intravitreal dexamethasone implants with or without vitrectomy. The average follow-up time was 19.7 months. All operated eyes achieved anatomic success, and all patients’ visual acuity was improved. Five of these six had a visual acuity of 20/100, and three had final acuity of 20/40 or even better. Intravitreal dexamethasone implants can be used to treat different types of OT, which not only effectively control inflammation and improve the patient’s vision but also reduce the use of systemic glucocorticoids.

Accurate air traffic flow prediction assists controllers formulate control strategies in advance and alleviate air traffic congestion, which is important to flight safety. While existing works have made significant efforts in exploring the high dynamics and heterogeneous interactions of historical air traffic flow, two key challenges still remain. (1) The transfer patterns of air traffic are intricate, subject to numerous constraints and limitations such as controllers, flight regulations, and other regulatory factors. Relying solely on mining historical traffic evolution patterns makes it difficult to accurately predict the constrained air traffic flow. (2) Weather conditions exert a substantial influence on air traffic, making it exceptionally difficult to simulate the impact of external factors (such as thunderstorms) on the evolution of air traffic flow patterns. To address these two challenges, we propose a Spatiotemporal Knowledge Distillation Network (ST-KDN) for air traffic flow prediction. Firstly, recognizing the inherent future insights embedded within flight plans, we develop a “teacher-student” distillation model. This model leverages the prior knowledge of upstream-downstream migration patterns and future air traffic trends inherent in flight plans. Subsequently, to model the influence of external factors and predict air traffic flow disturbed by thunderstorm weather, we propose a student network based on the “parallel-fusion” structure. Finally, employing a feature-based knowledge distillation approach to integrate prior knowledge from flight plans and extract meteorological features, our method can accurately capture complex and constrained spatiotemporal dependencies in air traffic and explicitly model the impact of weather on air traffic flow. Experimental results on real-world flight data demonstrate that our method can achieve better prediction performance than other state-of-the-art comparison methods, and the advantages of the proposed method are particularly prominent in modeling the complicated transfer pattern of air traffic and inferring nonrecurrent flow patterns.

Objective: To develop a risk score model for the occurrence of composite cardiovascular events (CVE) in patients with stable angina pectoris (SA) combined with coronary heart disease (CHD) by comparing the modeling effects of various machine learning (ML) algorithms.Methods: In this prospective study, 690 patients with SA combined with CHD attending the Department of Integrative Cardiology, China-Japan Friendship Hospital, from October 2020 to October 2021 were included. The data set was randomly divided into a training group and a testing group in a 7:3 ratio in the per-protocol set (PPS). Model variables were screened using the least absolute shrinkage selection operator (LASSO) regression, univariate analysis, and multifactor logistic regression. Then, nine ML algorithms are integrated to build the model and compare the model effects. Individualized risk assessment was performed using the SHapley Additive exPlanation (SHAP) and nomograms, respectively. The model discrimination was evaluated by receiver operating characteristic curve (ROC), the calibration ability of the model was evaluated by calibration plot, and the clinical applicability of the model was evaluated by decision curve analysis (DCA). This study was approved by the Clinical Research Ethics Committee of China-Japan Friendship Hospital (2020-114-K73).Results: 690 patients were eligible to finish the complete follow-up in the PPS. After LASSO screening and multifactorial logistic regression analysis, physical activity level, taking antiplatelets, Traditional Chinese medicine treatment, Gensini score, Seattle Angina Questionnaire (SAQ)-exercise capacity score, and SAQ-anginal stability score were found to be predictors of the occurrence of CVE. The above predictors are modeled, and a comprehensive comparison of the modeling effectiveness of multiple ML algorithms is performed. The results show that the Light Gradient Boosting Machine (LightGBM) model is the best model, with an area under the curve (AUC) of 0.95 (95% CI = 0.91–1.00) for the test set, Accuracy: 0.90, Sensitivity: 0.87, and Specificity: 0.96. Interpretation of the model using SHAP highlighted the Gensini score as the most important predictor. Based on the multifactorial logistic regression modeling, a nomogram, and online calculators have been developed for clinical applications.Conclusion: We developed the LightGBM optimization model and the multifactor logistic regression model, respectively. The model is interpreted using SHAP and nomogram. This provides an option for early prediction of CVE in patients with SA combined with CHD.

Abstract The use of exogenous mitochondria to replenish damaged mitochondria has been proposed as a strategy for the treatment of pulmonary fibrosis. However, the success of this strategy is partially restricted by the difficulty of supplying sufficient mitochondria to diseased cells. Herein, we report the generation of high-powered mesenchymal stem cells with promoted mitochondrial biogenesis and facilitated mitochondrial transfer to injured lung cells by the sequential treatment of pioglitazone and iron oxide nanoparticles. This highly efficient mitochondrial transfer is shown to not only restore mitochondrial homeostasis but also reactivate inhibited mitophagy, consequently recovering impaired cellular functions. We perform studies in mouse to show that these high-powered mesenchymal stem cells successfully mitigate fibrotic progression in a progressive fibrosis model, which was further verified in a humanized multicellular lung spheroid model. The present findings provide a potential strategy to overcome the current limitations in mitochondrial replenishment therapy, thereby promoting therapeutic applications for fibrotic intervention.

Gaining a better understanding of autoprotection against drug-induced liver injury (DILI) may provide new strategies for its prevention and therapy. However, little is known about the underlying mechanisms of this phenomenon. We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells (NPCs) in autoprotection against DILI, using acetaminophen (APAP) as a model drug. Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice, followed by a higher dose in a secondary challenge. NPC subsets and dynamic changes were identified in the APAP (hepatotoxicity-sensitive) and APAP-resistant (hepatotoxicity-resistant) groups. A chemokine (C-C motif) ligand 2+ endothelial cell subset almost disappeared in the APAP-resistant group, and an R-spondin 3+ endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection. Moreover, the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation. DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group. In addition, the natural killer cell subsets NK-3 and NK-4 and the Sca-1–CD62L+ natural killer T cell subset may promote autoprotection through interferon-γ-dependent pathways. Furthermore, macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity. Overall, this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.

Achieving high-performance as-cast OSCs is crucial for industrialization in the future, owing to the advantages of better stability, environmental-friendly, and decreasing production cost. In this regard, we synthesized an A-DA′D-A type acceptor, Y6-eC6-BO, by shortening the straight alkyl side-chains on the thiophene position from C11 to C6 as well as lengthening the branched alkyl side-chains on the pyrrole position of Y6 to achieve a stronger crystallization and better miscibility than Y6. As a result, the corresponding chloroform-processed as-cast PM6: Y6-eC6-BO OSC showed a high PCE of 17.33%, which was one of the highest efficiencies of as-cast OSCs. And the as-cast PM6:Y6-eC6-BO OSCs processed from o-xylene displayed a PCE of 16.38%, as far as we know, this is among the highest efficiencies of non-halogenated-solvent processed as-cast OSCs. These results demonstrated tailoring the alkyl side-chain of NFAs is a feasible and simple approach to achieve high performance as-cast OSCs and provides guideline in molecular design in the future.

Abstract Background Immune checkpoint inhibitors (ICIs) have altered the clinical management of non-small cell lung cancer (NSCLC). However, the low response rate, severe immune-related adverse events (irAEs), and hyperprogressive disease following ICIs monotherapy require attention. Combination therapy may overcome these limitations and traditional Chinese medicine with immunomodulatory effects provides a promising approach. Shenmai injection (SMI) is a clinically effective adjuvant treatment for cancer with chemotherapy and radiotherapy. Therefore, the combined effects and mechanisms of SMI and programmed death-1 (PD-1) inhibitor against NSCLC was focused on this study. Methods A Lewis lung carcinoma mouse model and a lung squamous cell carcinoma humanized mouse model were used to investigate the combined efficacy and safety of SMI and PD-1 inhibitor. The synergistic mechanisms of the combination therapy against NSCLC were explored using single-cell RNA sequencing. Validation experiments were performed using immunofluorescence analysis, in vitro experiment, and bulk transcriptomic datasets. Results In both models, combination therapy alleviated tumor growth and prolonged survival without increasing irAEs. The GZMA high and XCL1 high natural killer (NK) cell subclusters with cytotoxic and chemokine signatures increased in the combination therapy, while malignant cells from combination therapy were mainly in the apoptotic state, suggesting that mediating tumor cell apoptosis through NK cells is the main synergistic mechanisms of combination therapy. In vitro experiment confirmed that combination therapy increased secretion of Granzyme A by NK cells. Moreover, we discovered that PD-1 inhibitor and SMI combination blocked inhibitory receptors on NK and T cells and restores their antitumoral activity in NSCLC better than PD-1 inhibitor monotherapy, and immune and stromal cells exhibited a decrease of angiogenic features and attenuated cancer metabolism reprogramming in microenvironment of combination therapy. Conclusions This study demonstrated that SMI reprograms tumor immune microenvironment mainly by inducing NK cells infiltration and synergizes with PD-1 inhibitor against NSCLC, suggested that targeting NK cells may be an important strategy for combining with ICIs. Video Abstract

This study aims to achieve coordination between regional economic development and ecological environmental protection and to mitigate issues such as competition for water use among industries and significant disparities between water supply and demand. A multi-water-source, multi-user, and multi-objective optimal water resource allocation model was developed for Ordos City using general water allocation and simulation (GWAS). This model was applied to optimize water resource allocation on a monthly scale for various users across different administrative units (banners) in both short- and long-term planning periods. The results indicate that Ordos City’s allocated water volume for 2025 and 2030 is projected to be 1833.36 × 106 m3 and 1963.44 × 106 m3, respectively, with an overall water shortage rate of 5.46% and 5.67%, respectively. Water shortages are predicted in Dongsheng District, Dalad Banner, Etuoke Banner, Hangjin Banner, and Wushen Banner, primarily during the agricultural water usage period from March to November. The regional water supply structure was notably optimized, with a gradual decrease in the proportion of groundwater in the total water supply and a corresponding increase in the supply of surface water and unconventional water. These changes effectively improve local groundwater overexploitation and enhance the water supply efficiency. The research findings could offer valuable theoretical and technical support for the development and utilization of water resources, as well as for adjustments in the population–economic–industrial structure of Ordos City. Additionally, this study could provide scientific references for optimizing water resource allocation in other water-deficient cities in arid and semi-arid areas of the Yellow River Basin.

The global increase in building collapses and damage on soft-soil sites due to distant significant earthquakes poses similar challenges for sand-blowing reclamation (SBR) sites on soft-soil layers. This study was initiated to capture the vibration characteristics of the SBR sites and to provide fresh insights into their seismic responses. Initially, considering the heterogeneity and layered structure of soil at SBR sites, we developed a novel stratified shearing model box. This model box enables the simulation of the complex characteristics of soil layers at SBR sites under laboratory conditions, representing a significant innovation in this field. Subsequently, an innovative jack loading system was developed to apply active vertical pressure on the soil layer model, accelerating soil consolidation. Furthermore, a new data collection and analysis system was devised to monitor and record acceleration, pore water pressure, and displacement in real time during the experiments. To verify the model box’s accuracy and innovation, and to examine the seismic response of SBR sites under varying consolidation pressures, four vibration tests were conducted across different pressure gradients to analyze the model’s predominant period evolution due to consolidation pressures. The experimental results demonstrate that the model box accurately simulates the propagation of one-dimensional shear waves in soil layers under various consolidation pressures, with notable repeatability and reliability. Our experiments demonstrated that increasing consolidation pressure results in higher shear wave speeds in both sand and soft-soil layers, and shifts the site’s predominant period towards shorter durations. Concurrently, we established the relationship between the site’s predominant period and the input waves. This study opens new paths for further research into the dynamic response properties of SBR sites under diverse conditions through shaking-table tests.

Abstract We study the chiral-even generalized parton distributions (GPDs) of $${\bar{u}}$$ u ¯ and $${\bar{d}}$$ d ¯ quarks at zero skewness using the overlap representation within the light cone formalism. The GPDs of $${\bar{u}}$$ u ¯ and $${\bar{d}}$$ d ¯ quarks can be expressed as the convolution of the light cone wave functions which are obtained from the baryon-meson fluctuation model in terms of the $$|q{\bar{q}}B\rangle $$ | q q ¯ B ⟩ Fock states. We present the numerical results for $$H^{{\bar{u}}/P}(x,\xi ,\Delta ^2)$$ H u ¯ / P ( x , ξ , Δ 2 ) , $$H^{{\bar{d}}/P}(x,\xi ,\Delta ^2)$$ H d ¯ / P ( x , ξ , Δ 2 ) , $$E^{{\bar{u}}/P}(x,\xi ,\Delta ^2)$$ E u ¯ / P ( x , ξ , Δ 2 ) and $$E^{{\bar{d}}/P}(x,\xi ,\Delta ^2)$$ E d ¯ / P ( x , ξ , Δ 2 ) . We apply the model resulting GPDs to calculate the orbital angular momentum of the $${\bar{u}}$$ u ¯ and $${\bar{d}}$$ d ¯ quarks, showing that $$L^{{\bar{u}}/P}$$ L u ¯ / P , $$L^{{\bar{d}}/P}$$ L d ¯ / P are positive and $$L^{{\bar{u}}/P}$$ L u ¯ / P is smaller than $$L^{{\bar{d}}/P}$$ L d ¯ / P . The sea quark OAM distributions in the impact parameter space $$L_{{\bar{q}}}(x,{\varvec{b}}_{\varvec{T}})$$ L q ¯ ( x , b T ) are also calculated.

Panax ginseng (PG) and Panax notoginseng (PN) are highly valuable Chinese medicines (CM). Although both CMs have similar active constituents, their clinical applications are clearly different. Over the past decade, RNA sequencing (RNA-seq) analysis has been employed to investigate the molecular mechanisms of extracts or monomers. However, owing to the limited number of samples in standard RNA-seq, few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level. Here, we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq (TCM-seq), a high-throughput, low-cost workflow to molecularly evaluate CM perturbations. A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq. Transcriptomes from repeated samples were used to verify the robustness of TCM-seq. We then focused on the primary active components, Panax notoginseng saponins (PNS) and Panax ginseng saponins (PGS) extracted from PN and PG, respectively. We also characterized the transcriptome changes of 10 cell lines, treated with four different doses of PNS and PGS, using TCM-seq to compare the differences in their perturbing effects on genes, functional pathways, gene modules, and molecular networks. The results of transcriptional data analysis showed that the transcriptional patterns of various cell lines were significantly distinct. PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease, whereas PNS resulted in a greater coagulation effect on vascular endothelial cells. This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Bidirectional communication between the gut microbiota and the brain has sparked interest in exploring the link between mobile phone addiction (MPA) and sleep disorders (SD) in microbiome research. However, investigating the role of gut microbiota in this relationship using animal models presents challenges due to the unique nature of MPA, and human research in this area is scarce. We recruited 99 healthy college students to evaluate the gut microbiome using 16S rRNA gene amplicon sequencing and assess MPA and SD at baseline and after a two-month follow-up. Multiple covariate-adjusted statistical models, including linear regression, permutational multivariate analysis of variance and so on, were employed to determine microbiome associations with MPA at baseline and changes in SD at follow-up. Our findings revealed negative associations between MPA and three alpha diversity metrics, along with alterations in bacterial composition. MPA showed negative associations with the relative abundance of Bacteroidetes, while displaying positive associations with Actinobacteria and Bifidobacteriales. Conversely, Actinobacteria exhibited a negative association with increased SD. This study has established a significant link between MPA and a decrease in the alpha diversity of the gut microbiota. Actinobacteria was associated with MPA and SD, respectively. Additional investigation is needed to fully comprehend the relationship between comorbid behavioral disorders and the gut microbiota.

AbstractTriptorelin is a first-line drug for assisted reproductive technology (ART), but the low bioavailability and frequent subcutaneous injection of triptorelin impair the quality of life of women preparing to become pregnant. We report silk fibroin (SF)-based microneedles (MNs) for transdermal delivery of triptorelin-loaded nanoparticles (NPs) to improve bioavailability and achieve safe and efficacious self-administration of triptorelin. Triptorelin was mixed into an aqueous solution of SF with shear force to prepare NPs to control the release and avoid the degradation of triptorelin by enzymes in the skin. Two-step pouring and centrifugation were employed to prepare nanoparticles-encapsulated polymeric microneedles (NPs-MNs). An increased β-sheet content in the conformation ensured that NPs-MNs had good mechanical properties to pierce the stratum corneum. Transdermal release of triptorelin from NPs-MNs was increased to ∼65%. The NPs-MNs exhibited a prolonged drug half-life and increased relative bioavailability after administration to rats. Surging levels of luteinizing hormone and estradiol in plasma and their subsequent prolonged downregulation indicate the potential therapeutic role of NPs-MNs in ART regimens. The triptorelin-loaded NPs-MNs developed in this study may reduce the physical and psychological burden of pregnant women using ART regimens.

AbstractDoxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

AbstractMitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects.

Investigations of runoff and sediment yield changes and their relationships with potential driving factors provide good insights for understanding the mechanisms of hydrological processes. This study attempted to present a comprehensive investigation on the spatiotemporal variations of sediment yield in the Loess Plateau using continuous observed data at 46 hydrological stations during 1961–2016, and its responses to changes of precipitation, land use/cover and vegetation cover were analyzed by using the Partial Least Squares-Structural Equation Model (PLS-SEM). The results indicated that sediment yield reduced pronouncedly during 1961–2016 in the Loess Plateau, and 77.9% of this variation was explained by the combined effects of precipitation, land-use change, vegetation dynamics and runoff reduction. Indirect effects of precipitation, land-use change, and vegetation cover on sediment yield were 0.242, −0.528 and −0.630 (P

Organoids are three-dimensional cell accusations generated from pluripotent stem cells or adult stem cells in vitro. With many advantages over cell and animal models, organoids have been increasingly used in drug and clinical medical research in recent years. Chinese herbal medicine (CHM) is characterized by multi-target and multi-pathway treatment methods; however, there is no commonly accepted study method regarding efficacy and underlying mechanisms. In this review we summarized the important applications of organoid models in pharmacodynamic mechanism studies, efficacy and safety evaluations, and CHM personalized medicine, thus providing the theoretical basis for its development and innovation.

RNA structure plays a crucial role in gene regulation, in RNA stability and the essential biological processes. RNA secondary structure (RSS) motifs are the basic building blocks for investigating the biological mechanisms of structure. Here, we present a strategy for structural motif-based dynamic alignment, namely, RNA secondary-structural motif-comparing (RNAsmc), to identify structural motifs and quantitatively evaluate their underlying molecular functions. RNAsmc also has strong robustness to sequence length, folding protocol and RNA structural profile by chemical probing. Notably, it is also applicable to quantify structural variation in special RNA editing events (SNVs or SNPs, fragment insertion or deletion, etc.). The findings indicate that RNAsmc can uncover the heterogeneity of RNA secondary structure and score for similarities among components, which provides an impetus to cluster RNA families and evaluate allosteric effects. We find that RNAsmc exhibits remarkable detection efficiency for experimentally-derived RiboSNitches. Finally, the pipeline was assembled into an R software package to serve as an automated toolkit to explore, align, and cluster RSS. It is freely available for download at https://CRAN.R-project.org/package=RNAsmc.

The development of electrode materials with excellent performance serves as the key for researchers to enhance the energy density of supercapacitors. Cobalt molybdate (CoMoO4) nanomaterials have been regarded as one of the most prospective electrode materials for supercapacitors due to their high theoretical capacitance and excellent electrical conductivity. In this paper, three kinds of CoMoO4 nanorods were prepared directly via simple and environmentally friendly solid-phase chemical reactions with solid inorganic salts as raw materials. According to X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) test results, different reagents had certain effects on the size and morphology of CoMoO4, and these affected its electrochemical performance. In particular, the samples prepared with Co(NO3)2·6H2O as raw material took on a more uniform micromorphology, with a better crystallinity. Simultaneously, electrochemical test results showed that the samples synthesized with Co(NO3)2·6H2O presented relatively good electrical conductivity and a large specific capacitance (177 F g−1). This may be due to the nitrates reacting more slowly during the reaction and the crystals having difficulty aggregating during growth. Therefore, the structure of the prepared CoMoO4 nanomaterial was more uniform, and it was resistant to collapse during the charging and discharging process; thus, the capacitor presents the best performance.

O3 poses a significant threat to human health and the ecological environment. In recent years, O3 pollution has become increasingly serious, making it difficult to accurately control O3 precursor emissions. Satellite indicator methods, such as the FNR (formaldehyde-to-nitrogen dioxide ratio (HCHO/NO2 ratio)), provide an effective way to identify ozone pollution control areas on a large geographical scale due to their simple acquisition of datasets. This can help determine the primary factors contributing to O3 pollution and assist in managing it. Based on TROPOMI data from May 2018 to December 2022, combined with ground-based monitoring data from the China National Environmental Monitoring Centre, we explored the uncertainty associated with using the HCHO/NO2 ratio (FNR) as an indicator in ozone control area determination. We focused on the four representative regions in China: Jing-Jin-Ji-Lu-Yu (JJJLY), Jiang-Zhe-Hu-Wan (JZHW), Chuan-Yu (CY), and South China. By using the statistical curve-fitting method, we found that the FNR thresholds were 3.5–5.1, 2.0–4.0, 2.5–4.2, and 1.7–3.5, respectively. Meanwhile, we analyzed the spatial and temporal characteristics of the HCHO, NO2, and O3 control areas. The HCHO concentrations and NO2 concentrations had obvious cyclical patterns, with higher HCHO column densities occurring in summer and higher NO2 concentrations in winter. These high values always appeared in areas with dense population activities and well-developed economies. The distribution characteristics of the ozone control areas indicated that during O3 pollution periods, the urban areas with industrial activities and high population densities were primarily controlled by VOCs, and the suburban areas gradually shifted from VOC-limited regimes to transitional regimes and eventually reverted back to VOC-limited regimes. In contrast, the rural and other remote areas with relatively less development were mainly controlled by NOx. The FNR also exhibited periodic variations, with higher values mostly appearing in summer and lower values appearing in winter. This study identifies the main factors contributing to O3 pollution in different regions of China and can serve as a valuable reference for O3 pollution control.

BackgroundCerebrovascular disease (CeVD) is a prominent contributor to global mortality and profound disability. Extensive research has unveiled a connection between CeVD and retinal microvascular abnormalities. Nonetheless, manual analysis of fundus images remains a laborious and time-consuming task. Consequently, our objective is to develop a risk prediction model that utilizes retinal fundus photo to noninvasively and accurately assess cerebrovascular risks.Materials and methodsTo leverage retinal fundus photo for CeVD risk evaluation, we proposed a novel model called Efficient Attention which combines the convolutional neural network with attention mechanism. This combination aims to reinforce the salient features present in fundus photos, consequently improving the accuracy and effectiveness of cerebrovascular risk assessment.ResultOur proposed model demonstrates notable advancements compared to the conventional ResNet and Efficient-Net architectures. The accuracy (ACC) of our model is 0.834 ± 0.03, surpassing Efficient-Net by a margin of 3.6%. Additionally, our model exhibits an improved area under the receiver operating characteristic curve (AUC) of 0.904 ± 0.02, surpassing other methods by a margin of 2.2%.ConclusionThis paper provides compelling evidence that Efficient-Attention methods can serve as effective and accurate tool for cerebrovascular risk. The results of the study strongly support the notion that retinal fundus photo holds great potential as a reliable predictor of CeVD, which offers a noninvasive, convenient and low-cost solution for large scale screening of CeVD.

BackgroundAtopic dermatitis (AD) is a chronic inflammatory cutaneous disease that affects 30.48% of young children; thus, there is a need for epidemiological studies in community settings. Web-based questionnaires (WBQs) are more convenient, time-saving, and efficient than traditional surveys, but the reliability of identifying AD through WBQs and whether AD can be identified without the attendance of doctors, especially in community or similar settings, remains unknown. ObjectiveThis study aimed to develop and validate a web-based instrument for infantile AD identification (electronic version of the modified Child Eczema Questionnaire [eCEQ]) and to clarify the possibility of conducting WBQs to identify infantile AD without the attendance of doctors in a community-representative population. MethodsThis study was divided into 2 phases. Phase 1 investigated 205 children younger than 2 years to develop and validate the eCEQ by comparison with the diagnoses of dermatologists. Phase 2 recruited 1375 children younger than 2 years to implement the eCEQ and verify the obtained prevalence by comparison with the previously published prevalence. ResultsIn phase 1, a total of 195 questionnaires were analyzed from children with a median age of 8.8 (IQR 4.5-15.0) months. The identification values of the eCEQ according to the appropriate rules were acceptable (logic rule: sensitivity 89.2%, specificity 91.5%, positive predictive value 97.1%, and negative predictive value 72.9%; statistic rule: sensitivity 90.5%, specificity 89.4%, positive predictive value 96.4%, and negative predictive value 75%). In phase 2, a total of 837 questionnaires were analyzed from children with a median age of 8.4 (IQR 5.2-14.6) months. The prevalence of infantile AD obtained by the eCEQ (logic rule) was 31.9% (267/837), which was close to the published prevalence (30.48%). Based on the results of phase 2, only 20.2% (54/267) of the participants identified by the eCEQ had previously received a diagnosis from doctors. Additionally, among the participants who were not diagnosed by doctors but were identified by the eCEQ, only 6.1% (13/213) were actually aware of the possible presence of AD. ConclusionsInfantile AD can be identified without the attendance of doctors by using the eCEQ, which can be easily applied to community-based epidemiological studies and provide acceptable identification reliability. In addition, the eCEQ can also be applied to the field of public health to improve the health awareness of the general population.

A novel hyaluronic acid (HA)-modified hybrid nanocomplex HA-SeSe-COOH/siR-93C@PAMAM, which could efficiently deliver siRNA into tumor cells via a redox-mediated intracellular disassembly, was constructed for enhanced antitumor efficacy. Thereinto, siR-93C (siRNA) and positive PAMAM were firstly mixed into the electrostatic nano-intermediate, and then diselenide bond (-SeSe-)-modified HA was coved to shield excessive positive charges. This hybrid nanocomplex displayed uniform dynamic sizes, high stability, controlled zeta potential and narrow PDI distribution. Moreover, the -SeSe- linkage displayed GSH/ROS dual responsive properties, improving intracellular trafficking of siRNA. In vitro assays in A549 cell line presented that HA-SeSe-COOH/siR-93C@PAMAM has low cytotoxicity, rapid lysosomal escape and significant transfection efficiency; besides, an efficient proliferation inhibition ability and enhanced apoptosis. Furthermore, in animal studies, this negative-surfaced hybrid nanocomplex showed a prolonged circulation in blood and improved inhibition of tumor growth. All these results verified our hypothesis in this study that diselenide bonds-modified HA could promote not only stability and safety of nanoparticles in vivo but also intracellular behavior of siRNA via redox-dual sensitive properties; furthermore, this hybrid nanocomplex provided a visible potential approach for siRNA delivery in the antitumor field.

Change detection is a core issue in the study of global change. Inspired by recent success of the UNet3+ architecture originally designed for image semantic segmentation, in this article we proposed a densely connected siamese network for change detection, namely Pre-SiUNet3+-CD (the combination of Pre-processing, Siamese network and UNet3+). First, our proposed pre-processing algorithm can mitigate effects of poor co-registration between bitemporal images, thus alleviating the loss of localization information in the change map. Second, several modifications have been made to UNet3+ in order to improve its fit for change detection tasks using high-resolution imagery and generate highly discriminative and informative representations to locate changed pixels. The effectiveness of the proposed method is demonstrated on several datasets, and experimental results indicated that our model provides very competitive accuracies in terms of precision, recall, F1-score, and visual performance among all the compared methods. This is because it inherits most of the advantages of UNet3+ in object location and boundary production, and the introduction of pre-processing also gives it a significant accuracy boost.

Highlights Shenmai injection attenuates 5-FU-induced myelotoxicity in tumor-bearing mice. Both carbohydrates and ginsenosides in Shenmai injection promote hematopoiesis. Carbohydrates may regulate Glutathione metabolism and B cell receptor pathway.

With the modernization and internationalization of traditional Chinese medicine (TCM), the requirement for quality control has increased. The quality marker (Q-marker) is an important standard in this field and has been implemented with remarkable success in recent years. However, the establishment of Q-markers remains fragmented and the process lacks systematicity, resulting in inconsistent quality control and insufficient correlation with clinical efficacy and safety of TCM. This review introduces four multimodal integrated approaches that contribute to the discovery of more comprehensive and accurate Q-markers, thus aiding in the establishment of new quality control patterns based on the characteristics and principles of TCM. These include the whole-process quality control strategy, chemical-activity-based screening method, efficacy, safety, and consistent combination strategy, and TCM theory-guided approach. Furthermore, methodologies and representative examples of these strategies are described, and important future directions and questions in this field are also proposed.

Current methods to reanalyze bulk RNA-seq at spatially resolved single-cell resolution have limitations. Here, the authors develop Bulk2Space, a spatial deconvolution algorithm using single-cell and spatial transcriptomics as references, providing new insights into spatial heterogeneity within bulk tissue.

Cell-cell communication is a vital feature involving numerous biological processes. Here, the authors develop SpaTalk, a cell-cell communication inference method using knowledge graph for spatially resolved transcriptomic data, providing valuable insights into spatial intercellular tissue dynamics.

Aging is an inevitable process influenced by genetics, lifestyles, and environments. With the rapid social and economic development in recent decades, the proportion of the elderly has increased rapidly worldwide, and many aging-related diseases have shown an upward trend, including nervous system diseases, cardiovascular diseases, metabolic diseases, and cancer. The rising burden of aging-related diseases has become an urgent global health challenge and requires immediate attention and solutions. Natural products have been used for a long time to treat various human diseases. The primary cellular pathways that mediate the longevity-extending effects of natural products involve nutrient-sensing pathways. Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. Several studies have reviewed the effects of individual natural compounds on aging and aging-related diseases along with the underlying mechanisms. Natural products from food sources, such as polyphenols, saponins, alkaloids, and polysaccharides, are classified as antiaging compounds that promote health and prolong life via various mechanisms. In this article, we have reviewed several recently identified natural products with potential antiaging properties and have highlighted their cellular and molecular mechanisms. The discovery and use of dietary supplements and natural products that can prevent and treat multiple aging-related diseases in humans will be beneficial. Thus, this review provides theoretical background for existing dietary supplements and natural products as potential antiaging agents.

IntroductionAge-related macular degeneration (AMD), an ever-increasing ocular disease, has become one of the leading causes of irreversible blindness. Recent advances in single-cell genomics are improving our understanding of the molecular mechanisms of AMD. However, the pathophysiology of this multifactorial disease is complicated and still an ongoing challenge. To better understand disease pathogenesis and identify effective targets, we conducted an in-depth analysis of the single-cell transcriptome of AMD.MethodsThe cell expression specificity of the gene (CESG) was selected as an index to identify the novel cell markers. A computational framework was designed to explore the cell-specific TF regulatory loops, containing the interaction of gene pattern signatures, transcription factors regulons, and differentially expressed genes.ResultsThree potential novel cell markers were DNASE1L3 for endothelial cells, ABCB5 for melanocytes, and SLC39A12 for RPE cells detected. We observed a notable change in the cell abundance and crosstalk of fibroblasts cells, melanocytes, schwann cells, and T/NK cells between AMD and controls, representing a complex cellular ecosystem in disease status. Finally, we identified six cell type related and three disease-associated ternary loops and elaborated on the robust association between key immune-pathway and AMD.DiscussionIn conclusion, this study facilitates the optimization of screening for AMD-related receptor ligand pathways and proposes to further improve the interpretability of disease associations from single-cell data. It illuminated that immune-related regulation paths could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, providing insights into AMD diagnosis and potential interventions.