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Abstract Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that induces an NLRP3-dependent cytokine storm. NLRP3 inflammasome activation triggers not only an inflammatory response but also pyroptosis. However, the exact mechanism underlying S. suis-induced macrophage pyroptosis is not clear. Our results showed that SS2 induced the expression of pyroptosis-associated factors, including lactate dehydrogenase (LDH) release, propidium iodide (PI) uptake and GSDMD-N expression, as well as NLRP3 inflammasome activation and IL-1β secretion. However, GSDMD deficiency and NLRP3 inhibition using MCC950 attenuated the SS2-induced expression of pyroptosis-associated factors, suggesting that SS2 induces NLRP3-GSDMD-dependent pyroptosis. Furthermore, RACK1 knockdown also reduced the expression of pyroptosis-associated factors. In addition, RACK1 knockdown downregulated the expression of NLRP3 and Pro-IL-1β as well as the phosphorylation of P65. Surprisingly, the interaction between RACK1 and P65 was detected by co-immunoprecipitation, indicating that RACK1 induces macrophage pyroptosis by mediating the phosphorylation of P65 to promote the transcription of NLRP3 and pro-IL-1β. Similarly, NEK7 knockdown decreased the expression of pyroptosis-associated factors and ASC oligomerization. Moreover, the results of co-immunoprecipitation revealed the interaction of NEK7-RACK1-NLRP3 during SS2 infection, demonstrating that NEK7 mediates SS2-induced pyroptosis via the regulation of NLRP3 inflammasome assembly and activation. These results demonstrate the important role of RACK1 and NEK7 in SS2-induced pyroptosis. Our study provides new insight into SS2-induced cell death.

Abstract Background Most guidelines propose inducing labor within 24 h following term (37 or more weeks of gestation) prelabor rupture of membranes (PROM). However, the exact timing for initiating induction within the 24 h period remains unknown. This study aims to comparatively assess the efficacy and safety of the use of vaginal dinoprostone within 6 h versus within 6–24 h for singleton pregnancies with PROM and an unfavorable cervix (Bishop score

Microplastics (MPs) have attracted increasing attention worldwide owing to their widespread presence and potential risks to terrestrial and marine ecosystems. Estimating the pollution status and risk levels of MPs in coastal ecosystems is necessary; however, these are poorly understood in coastal megacities. Here, the abundance and characteristics of MPs in seawater, marine sediment, marine organisms, and beaches in the Shenzhen coastal ecosystems and land sources (river and sewage outfall) were simultaneously investigated, and the annual MPs load of rivers and MP-induced ecological risks were evaluated. The results showed that MPs pollution was prevalent in Shenzhen coastal ecosystems, with the average abundances of 2.40 ± 2.48 items/m3, 404.21 ± 431.48 items/kg, 1.66 ± 1.96 items/individual, and 1648.99 ± 1908.19 items/kg in seawater, marine sediment, marine organisms, and beach sands, respectively. The detected MPs were predominantly fibrous/granular, transparent/white, < 1 mm in size, and polyethylene terephthalate/polyethylene/polystyrene. The spatial distribution patterns of marine MPs are influenced mainly by anthropogenic activities and freshwater inflows (rivers and sewage outfalls). Pollution hotspots of MPs were identified in the Pearl River Estuary, which has a high population, gross domestic product, and river and wastewater discharge. Furthermore, the negative correlation between the abundance of MPs in seawater and salinity indicates that freshwater inflow carrying MPs to the sea is an important source of marine MPs pollution. It has been estimated that approximately 8320 billion MPs particles, weighing 274.55 tons, flow into the Shenzhen coast annually through river input. Based on the MPs polymer types and quantities, the ecological risk of MPs pollution in the Shenzhen coastal ecosystem is moderate and deserves further attention. These findings deepen the understanding of MPs pollution, sources, and ecological risks in the southern coastal region of China, and are helpful for employing effective management strategies to control marine MPs pollution.

ObjectiveThis study examines the epidemiology of Mycoplasma pneumoniae (M. pneumoniae) infections among children in Suzhou, China, during various pandemic phases. The goal is to discern evolving epidemic trends and to furnish robust evidence for clinical diagnosis and treatment.MethodsFrom January 1, 2016, to December 31, 2023, 113,625 consecutive patients with respiratory infections from three hospitals in Suzhou, China (Children’s Hospital of Soochow University, Children’s Hospital of Wujiang District, and Affiliated Suzhou Hospital of Nanjing University Medical School), were retrospectively enrolled in a surveillance study. Additionally, in 2023, children hospitalized with M. pneumoniae pneumonia at the Children’s Hospital of Soochow University were tested for genotype (P1 gene typing, SNP genotyping) and macrolide resistance in their bronchoalveolar lavage fluid.ResultsFrom 2016 to 2023, the M. pneumoniae positive detection rate among pediatric respiratory infections fell from a pre-pandemic 21.1% to pandemic lows, then surged to 45.3% post-pandemic. Before the pandemic, peak M. pneumoniae infection rates occurred in summer, followed by autumn. Post-pandemic, the highest peak rates were in autumn. Peak M. pneumoniae detection rates occurred in 2019 and 2023, with a notable increase in children aged 6 and older in 2023. In this study, 200 M. pneumoniae-positive bronchoalveolar lavage fluid (BALF) cases in 2023 were randomly selected and analyzed for P1 genotype and SNP genotype. Among 156 cases, 81.4% were P1 genotype and 18.6% were P2 genotype. The proportion of severe M. pneumoniae pneumonia with the P1 type was significantly higher than that with the P2 type (p

During freeze–thaw cycling, aggregates undergo a dynamic change in breakdown–formation (turnover), however, how the turnover occurs between aggregates of various particle sizes is not clear. To clarify the influence of freeze–thaw cycling on the dynamic changes in the particle size of soil aggregates, soil aggregates from the Black Soil Region of Northeast China were selected as the research objects. The study conducted in situ dynamic monitoring experiments, innovatively applying the rare earth oxide (REO) tracer method to natural conditions of freeze–thaw cycles (autumn freeze–thaw period, freezing period, and spring freeze–thaw period), accurately tracking the turnover paths and quantifying the turnover rates between aggregates of various particle sizes. The results revealed that the total value of the formation paths of the 2–5 mm aggregates and 0.25–2 mm aggregates increased during the autumn freeze–thaw period. The number of freeze–thaw cycles and accumulated snowfall were significantly positively correlated with aggregate stability, with an increase in the number of freeze–thaw cycles and accumulated snowfall resulting in an increase in the proportion of aggregates > 0.25 mm, which improved aggregate stability. In addition, the total value of the breakdown path of macro-aggregates increased during the spring freeze–thaw cycling period. Soil moisture was significantly negatively correlated with aggregate stability, with increased soil moisture resulting in a decrease in the percentage of aggregates > 0.25 mm, which resulted in a decrease in aggregate stability. The study can provide a reference understanding for the effects of freeze–thaw cycles on the structure of black soil and provide a theoretical basis for improving the quality of arable land.

Abstract Background Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence. Results We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs (Sus scrofa) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV’s impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3, whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies. Conclusions This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution.

In complex environments, mobile robots performing tasks with different hazard levels need to consider different road factors, this paper proposes a functional model correlating task hazard levels with road factors, proposing an innovative Hybrid Adaptive Genetic Algorithm (HAGA). The HAGA integrates an optimized two-optimization (2-opt) operator* with an enhanced Adaptive Genetic Algorithm (AGA) for efficient path planning in diverse tasks and complex road conditions. Firstly, pre-optimize the initial paths is performed by introducing a new domain knowledge-based operator that duplicates paths in the path are deleted to avoid the redundant paths, and then they are divided into the TOP layer and the ordinary layer, the TOP layer is optimized by using the adaptive 2-opt* operator that satisfies the hyperbolic tangent function (TANH), and the crossover and variability of the ordinary layer are optimized by using the S-type function (Sigmoid function, Sigmoid) and TANH AGA for the optimization treatment for the crossover and variance of the ordinary layer, respectively, to establish a robot path planning algorithm suitable for multitasking in complex environments. The experiment proves that the improved HAGA has strong global search ability and also improves the local search ability, has good generality and robustness, and reduces the optimal path distance by a minimum of 2.74% and a maximum of 10.86% compared with the comparison algorithm in the experiment. The experimental results showed that the method enables mobile robots to perform tasks with different hazard levels in complex environments with good generalization and robustness, and the coefficient of variation (CV) of repeated experiments at five safety levels was kept within 2 %. which had good universality and versatility. This research has the potential to enhance the safety and efficiency of mobile robot operations in challenging environments.

China’s vulnerability to fluvial floods necessitates extensive exposure studies. Previous large-scale regional analyses often relied on a limited set of assessment indicators due to challenges in data acquisition, compounded by the scarcity of corresponding large-scale flood distribution data. The integration of public datasets offers a potential solution to these challenges. In this study, we obtained four key exposure indicators—population, built-up area (BA), road length (RL), and average gross domestic product (GDP)—and conducted an innovative analysis of their correlations both overall and locally. Utilising these indicators, we developed a comprehensive exposure index employing entropy-weighting and k-means clustering methods and assessed fluvial flood exposure across multiple return periods using fluvial flood maps. The datasets used for these indicators, as well as the flood maps, are primarily derived from remote sensing products. Our findings indicate a weak correlation between the various indicators at both global and local scales, underscoring the limitations of using singular indicators for a thorough exposure assessment. Notably, we observed a significant concentration of exposure and river flooding east of the Hu Line, particularly within the eastern coastal region. As flood return periods extended from 10 to 500 years, the extent of areas with flood depths exceeding 1 m expanded markedly, encompassing 2.24% of China’s territory. This expansion heightened flood risks across 15 administrative regions with varying exposure levels, particularly in Jiangsu (JS) and Shanghai (SH). This research provides a robust framework for understanding flood risk dynamics, advocating for resource allocation towards prevention and control in high-exposure, high-flood areas. Our findings establish a solid scientific foundation for effectively mitigating river flood risks in China and promoting sustainable development.

Hereditary transthyretin amyloid (ATTRv) cardiomyopathy (CM) is caused by mutations in the TTR gene. TTR mutations contribute to TTR tetramer destabilization and dissociation, leading to excessive deposition of insoluble amyloid fibrils in the myocardium and finally resulting in cardiac dysfunction. In this article, we report a case of a Chinese patient with transthyretin mutation p.D58Y and provide detailed information on cardiac amyloidosis, including transthoracic echocardiography, cardiac magnetic resonance, and SPECT imaging for the first time. Our report aims to provide a better understanding of ATTR genotypes and phenotypes.

Abstract The magnetic hyperthermia‐based combination therapy (MHCT) is a powerful tumor treatment approach due to its unlimited tissue penetration depth and synergistic therapeutic effect. However, strong magnetic hyperthermia and facile drug loading are incompatible with current MHCT platforms. Herein, an iron foam (IF)‐drug implant is established in an ultra‐facile and universal way for ultralow‐power MHCT of tumors in vivo for the first time. The IF‐drug implant is fabricated by simply immersing IF in a drug solution at an adjustable concentration for 1 min. Continuous metal structure of IF enables ultra‐high efficient magnetic hyperthermia based on eddy current thermal effect, and its porous feature provides great space for loading various hydrophilic and hydrophobic drugs via “capillary action”. In addition, the IF has the merits of low cost, customizable size and shape, and good biocompatibility and biodegradability, benefiting reproducible and large‐scale preparation of IF‐drug implants for biological application. As a proof of concept, IF‐doxorubicin (IF‐DOX) is used for combined tumor treatment in vivo and achieves excellent therapeutic efficacy at a magnetic field intensity an order of magnitude lower than the threshold for biosafety application. The proposed IF‐drug implant provides a handy and universal method for the fabrication of MHCT platforms for ultralow‐power combination therapy.

ABSTRACTRock-inhabiting fungi (RIF) are slow-growing microorganisms that inhabit rocks and exhibit exceptional stress tolerance owing to their thick melanised cell walls. This study reports the identification of a novel rock-inhabiting fungus, Cladophialophora brunneola sp. nov. which was isolated from a karst landform in Guizhou, China, using a combination of morphological and phylogenetic analyses. The genome of C. brunneola was sequenced and assembled, with a total size of approximately 33.8 Mb, encoding 14,168 proteins and yielding an N50 length of 1.88 Mb. C. brunneola possessed a larger proportion of species-specific genes, and phylogenomic analysis positioned it in an early diverged lineage within Chaetothyriales. In comparison to non-RIF, C. brunneola displayed reduction in carbohydrate-active enzyme families (CAZymes) and secondary metabolite biosynthetic gene clusters (BGCs). Transcriptome analysis conducted under PEG-induced drought stress revealed elevated expression levels of genes associated with melanin synthesis pathways, cell wall biosynthesis, and lipid metabolism. This study contributes to our understanding of the genomic evolution and polyextremotolerance exhibited by rock-inhabiting fungi.

Abstract Background Oral leukoplakia(OLK) is a common oral potentially malignant disorder. The global prevalence of solely OLK was published in 2003, while the prevalence varied among different studies. In recent years, large-scale summary and definition-related analyses obtain insufficient attention. This study aimed to perform a systematic review of prevalence studies of oral leukoplakia and assess predisposing factors of its occurrence. Methods The search terms ("Oral leukoplakia" OR OLK OR leukoplakia) AND (prevalence OR incidence OR epidemiology) were searched in databases (Pubmed, Embase, Scopus, and Web of Science) for OLK studies published from January 1996 until December 2022. The estimated prevalence calculation and risk of bias analysis used STATA 16.0. Results We obtained 69 studies, including 1,263,028 participants, from 28 countries, and 6 continents. The prevalence was 1.39%, varying from 0.12 to 33.33%. The overall pooled estimated prevalence of OLK was 2.23% for population-based studies, 1.36% for clinic-based population studies, and 9.10% for specific populations. The pooled prevalence in different continents ranged from 0.33 to 11.74% with a statistical difference in the population-based calculation. The estimated prevalence of OLK was higher in males than in females. Those who smoked and consumed alcohol had a higher prevalence than those who did not. Conclusion Combining data from 69 published studies, the prevalence of OLK was determined as 1.39% and the pooling estimated global prevalence was 3.41%. The prevalence was relatively consistent and stable across different continents and different definitions. A higher pooled estimated prevalence was found among males, those aged over 60 years old, smokers, and alcohol consumers. The results from the included studies in this systematic review revealed that the prevalence was relatively consistent and stable across various definitions and continents, which may help in developing global treatment and prevention strategies for oral leukoplakia.

The value of statistical life (VSL) reflects the trade-off between money and the risk of death. It is a key indicator for conducting regulatory impact assessments. The main purpose of this study was to estimate the VSL in the field of food safety. At the same time, it investigates respondents’ willingness to pay (WTP) for reducing the risk of death from foodborne illnesses and explores the impact of factors such as the average household monthly income, health status, and education level on WTP. We conducted a survey using an open-ended contingent valuation method among 1307 respondents aged 18 and above to determine their WTP. Based on the WTP survey results, we calculated the VSL in the food safety sector. We used binary logit and Tobit models to analyze the influencing factors. The results of the study show that the median WTP for reducing the risk of foodborne illness is CNY 100 (USD 16), and the estimated VSL is approximately CNY 9.09 million (USD 141 million). Indicators such as the average household monthly income, health status, and education level are important factors affecting WTP. This study will help practitioners, researchers, and policymakers understand the current population’s attitudes towards food safety regulations and determine the priorities for regulatory implementation. Future research can explore the effects of different elicitation methods, cultural differences, and regional variations on WTP and VSL.

Solar energy, as a clean and renewable energy source, holds significant promise for addressing water shortages. Utilizing solar energy for water evaporation is seen as an effective solution in this regard. While many existing interfacial photothermal water evaporation systems rely on nanoparticles or graphene as photothermal or support materials, this study introduced polydopamine (PDA) as a photothermal material due to its environmental friendliness and excellent photon absorption characteristics that closely match the solar spectrum. Polystyrene (PS) was also introduced as a support material for its porous structure and density similar to water, enabling it to float on water. The resulting PS-PDA composite porous structure solar evaporator exhibited a photothermal conversion efficiency comparable to nanoparticles (over 75%), yet with lower production costs and minimal environmental impact. This innovative approach offers a scalable solution for water-scarce regions, providing a cost-effective and efficient means to address water scarcity. The use of PDA and PS in this context highlights the potential for utilizing common materials in novel ways to meet pressing environmental challenges.

Cellular automata (CA) models have been extensively employed to predict and understand the spatiotemporal dynamics of land use. Driving factors play a significant role in shaping and driving land-use changes. Mining land-use transition rules from driving factors and quantifying the contribution of driving factors to land-use dynamics are fundamental aspects of CA simulation. However, existing CA models have limitations in obtaining accurate transition rules and reliable interpretations simultaneously for multiple land-use simulations. In this study, we constructed a CA model based on a tree-based deep learning algorithm, deep cascade forest (DCF), to improve multiple land-use simulations and driving factors analysis. The DCF algorithm was utilized to mine accurate multiple land-use transition rules without overfitting to improve CA simulation accuracy. Additionally, a novel ensemble mean decrease of impurity (MDI) factor importance analysis method (DCF-MDI), which leverages the cascade structure of the DCF model, was proposed to qualify the contribution of each driving factor to land-use dynamics stably and efficiently. To evaluate the effectiveness of the proposed DCF-CA, we applied the model to simulate land-use distributions and explore the driving mechanisms of land-use dynamics in the Pearl River Delta (PRD), China, from 2000 to 2010. Compared to existing models, the proposed DCF-CA model exhibits the highest accuracy (FoM = 23.79%, PA = 39.77%, UA = 36.35%, OA = 91.50%), which demonstrates its superiority in mining accurate transition rules for capturing multiple land-use dynamics. Factor importance analysis reveals that the proposed DCF-MDI method yields more stable ranking orders and lower standard deviation of contribution weights (

Dichloroquinolinic acid is a hormone-type herbicide widely used to control barnyard grass during crop cultivation. However, it can seriously inhibit the growth of susceptible crops, including tobacco, because it degrades slowly under field conditions. Additionally, the mechanism by which it damages crops is unclear. More specifically, the transcriptional changes in plants induced by dichloroquinolinic acid remain unknown. In this study, differentially expressed genes (DEGs) in tobacco treated with dichloroquinolinic acid (varying concentrations and durations) were analyzed and validated to explore the global transcriptome changes. The number of DEGs, which were determined according to the FPKM, varied from 758 to 21,340. The KEGG analysis revealed that many DEGs were involved in starch and sucrose metabolism, phenylpropanoid biosynthesis, photosynthesis, porphyrin and chlorophyll metabolism, and glutathione metabolism. Transcriptomic analyses indicated that dichloroquinolinic acid can inhibit tobacco growth by inhibiting photosynthesis and storage of energy. We discovered that the toxicity mechanism of the hormone herbicide dichloroquinolinic acid differs from that of high concentrations of IAA (Indoleacetic acid), despite studies confirming that the effects of hormone herbicides are consistent with the physiological disturbances and growth inhibition exhibited by plants in IAA overdose. Particularly, dichloroquinolinic acid suppresses photosynthesis while high concentration IAA stimulates nucleotide synthesis and photosynthesis. More importantly, we found by editing the IAA-responsive gene IAA16, tobacco could develop resistance to dichloroquinolinic acid. The results will help clarify plant responses to hormone-type herbicides at the transcriptional level, thereby providing insights into the diversity in the gene’s response to herbicides, the molecular targets of hormone-type herbicides, and the mechanism underlying the susceptibility of tobacco to dichloroquinolinic acid. Accordingly, this study may be helpful for future research to enhance crop resistance to herbicides residues.

Abstract Objective To analyze the risk factors associated with different levels of eye discomfort due to video terminal use among college students at different altitudes. Methods This cross-sectional study was conducted to assess the prevalence and extent of eye discomfort by distributing an questionnaire to university students via the Internet. To analyze the causes and risk factors of eye discomfort among college students at different altitudes after using video terminals. Results A total of 647 participants who met the criteria were included in this survey, of whom 292 (45.1%) were males and 355 (54.9%) were females. The results of the survey showed 194 (30.0%) participants without eye discomfort and 453 (70.0%) participants with eye discomfort. The results of the univariate comparison of the degree of eye discomfort in the study subjects with different characteristics showed that the differences in the degree of eye discomfort were statistically significant (P

BackgroundsObservational studies have shown that cigarette smoking is inversely associated with risk of rosacea, However, it remains uncertain whether this association is causal or it is a result of reverse causation, and whether this association is affected by drinking behaviors.MethodsThis study utilized the summary-level data from the largest genome-wide association study (GWAS) for smoking, alcohol consumption, and rosacea. The objective was to investigate the effect of genetically predicted exposures to smoking and alcohol consumption on the risk of developing rosacea. Two-sample bidirectional Mendelian randomization (MR) was applied, accompanied by sensitive analyses to validate the robustness of findings. Furthermore, multivariable MR was conducted to evaluate the direct impact of smoking on rosacea.ResultsA decreased risk of rosacea was observed in individuals with genetically predicted lifetime smoking [odds ratio (OR)MR − IVW = 0.53; 95% confidence interval (CI), 0.318–0.897; P = 0.017], and number of cigarettes per day (ORMR − IVW = 0.55; 95% CI, 0.358–0.845; P = 0.006). However, no significant associations were found between initiation of regular smoking, smoking cessation, smoking initiation, alcohol consumption and rosacea. Reverse MR analysis did not show any associations between genetic liability toward rosacea and smoking or alcohol drinking. Importantly, the effect of lifetime smoking and the number of cigarettes per day on rosacea remained significant even after adjusting for alcohol consumption in multivariable MR analysis.ConclusionSmoking was causally related to a lower risk of rosacea, while alcohol consumption does not appear to be associated with risk of rosacea.

Oilseed rape is an important oilseed crop planted worldwide. Maturity classification plays a crucial role in enhancing yield and expediting breeding research. Conventional methods of maturity classification are laborious and destructive in nature. In this study, a nondestructive classification model was established on the basis of hyperspectral imaging combined with machine learning algorithms. Initially, hyperspectral images were captured for 3 distinct ripeness stages of rapeseed, and raw spectral data were extracted from the hyperspectral images. The raw spectral data underwent preprocessing using 5 pretreatment methods, namely, Savitzky–Golay, first derivative, second derivative (D2nd), standard normal variate, and detrend, as well as various combinations of these methods. Subsequently, the feature wavelengths were extracted from the processed spectra using competitive adaptive reweighted sampling, successive projection algorithm (SPA), iterative spatial shrinkage of interval variables (IVISSA), and their combination algorithms, respectively. The classification models were constructed using the following algorithms: extreme learning machine, k-nearest neighbor, random forest, partial least-squares discriminant analysis, and support vector machine (SVM) algorithms, applied separately to the full wavelength and the feature wavelengths. A comparative analysis was conducted to evaluate the performance of diverse preprocessing methods, feature wavelength selection algorithms, and classification models, and the results showed that the model based on preprocessing-feature wavelength selection-machine learning could effectively predict the maturity of rapeseed. The D2nd-IVISSA-SPA-SVM model exhibited the highest modeling performance, attaining an accuracy rate of 97.86%. The findings suggest that rapeseed maturity can be rapidly and nondestructively ascertained through hyperspectral imaging.

BackgroundAccording to some recent observational studies, the gut microbiota influences atherosclerosis via the gut microbiota-artery axis. However, the causal role of the gut microbiota in atherosclerosis remains unclear. Therefore, we used a Mendelian randomization (MR) strategy to try to dissect this causative link.MethodsThe biggest known genome-wide association study (GWAS) (n = 13,266) from the MiBioGen collaboration was used to provide summary data on the gut microbiota for a two-sample MR research. Data on atherosclerosis were obtained from publicly available GWAS data from the FinnGen consortium, including cerebral atherosclerosis (104 cases and 218,688 controls), coronary atherosclerosis (23,363 cases and 187,840 controls), and peripheral atherosclerosis (6631 cases and 162,201 controls). The causal link between gut microbiota and atherosclerosis was investigated using inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode approaches, among which inverse variance weighting was the main research method. Cochran’s Q statistic was used to quantify the heterogeneity of instrumental variables (IVs), and the MR Egger intercept test was used to assess the pleiotropy of IVs.ResultsInverse-variance-weighted (IVW) estimation showed that genus Ruminiclostridium 9 had a protective influence on cerebral atherosclerosis (OR = 0.10, 95% CI: 0.01–0.67, P = 0.018), while family Rikenellaceae (OR = 5.39, 95% CI: 1.50–19.37, P = 0.010), family Streptococcaceae (OR = 6.87, 95% CI: 1.60–29.49, P = 0.010), genus Paraprevotella (OR = 2.88, 95% CI: 1.18–7.05, P = 0.021), and genus Streptococcus (OR = 5.26, 95% CI: 1.28–21.61, P = 0.021) had pathogenic effects on cerebral atherosclerosis. For family Acidaminococcaceae (OR = 0.87, 95% CI: 0.76–0.99, P = 0.039), the genus Desulfovibrio (OR = 0.89, 95% CI: 0.80–1.00, P = 0.048), the genus RuminococcaceaeUCG010 (OR = 0.80, 95% CI: 0.69–0.94, P = 0.006), and the Firmicutes phyla (OR = 0.87, 95% CI: 0.77–0.98, P = 0.023) were protective against coronary atherosclerosis. However, the genus Catenibacterium (OR = 1.12, 95% CI: 1.00–1.24, P = 0.049) had a pathogenic effect on coronary atherosclerosis. Finally, class Actinobacteria (OR = 0.83, 95% CI: 0.69–0.99, P = 0.036), family Acidaminococcaceae (OR = 0.76, 95% CI: 0.61–0.94, P = 0.013), genus Coprococcus2 (OR = 0.76, 95% CI: 0.60–0.96, P = 0.022), and genus RuminococcaceaeUCG010 (OR = 0.65, 95% CI: 0.46–0.92, P = 0.013), these four microbiota have a protective effect on peripheral atherosclerosis. However, for the genus Lachnoclostridium (OR = 1.25, 95% CI: 1.01–1.56, P = 0.040) and the genus LachnospiraceaeUCG001 (OR = 1.22, 95% CI: 1.04–1.42, P = 0.016), there is a pathogenic role for peripheral atherosclerosis. No heterogeneity was found for instrumental variables, and no considerable horizontal pleiotropy was observed.ConclusionWe discovered that the presence of probiotics and pathogens in the host is causally associated with atherosclerosis, and atherosclerosis at different sites is causally linked to specific gut microbiota. The specific gut microbiota associated with atherosclerosis identified by Mendelian randomization studies provides precise clinical targets for the treatment of atherosclerosis. In the future, we can further examine the gut microbiota’s therapeutic potential for atherosclerosis if we have a better grasp of the causal relationship between it and atherosclerosis.

Diesel exhaust particulate matter (DEPM) are important components of urban air pollution worldwide. Recent studies proved that airborne DEPM can enter the human brain, which was associated with brain and mental diseases. In this study, we investigated the effects of DEPM exposure on behavior, and explored potential mechanisms from the perspective of metabolism in specific brain regions and short chain fatty acids (SCFAs) in the gut using mice. The results showed that inhalation of DEPM induced locomotor hyperactivity and a tendency for memory decline in mice. Exposure to DEPM disrupted motor behavior generation related cerebellar Purkinje cells, induced widespread reduction of neurotransmitters in the frontal cortex, and downregulated expression of genes encoding Brain-derived neurotrophic factor (BDNF) and involved in the Brain-blood-barrier (BBB) in the hippocampus. Moreover, there was a DEPM dose-dependent increase in fecal SCFA levels. Correlation analysis showed that DEPM-induced locomotor hyperactivity was mainly associated with decreased neurotransmission in the frontal cortex and increased gut SCFAs, and those associations were discussed. This study provides new insights into the mechanisms underpinning behavioral changes caused by air pollution, and extends our knowledge on the toxicity and health effects of airborne pollutants.

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

Abstract Background Both the crystalline and soluble forms of cholesterol increase macrophage secretion of interleukin 1β (IL-1β), aggravating the inflammatory response in atherosclerosis (AS). However, the link between cholesterol and regulatory T cells (Tregs) remains unclear. This study aimed to investigate the effect of cholesterol treatment on Tregs. Methods Differentiation of induced Tregs (iTregs) was analyzed using flow cytometry. The expression of hypoxia-inducible factor-1a (HIF-1a) and its target genes was measured by western blotting and/or RT-qPCR. Two reporter jurkat cell lines were constructed by lentiviral transfection. Mitochondrial function and the structure of natural Tregs (nTregs) were determined by tetramethylrhodamine (TMRM) and mitoSOX staining, Seahorse assay, and electron microscopy. The immunoregulatory function of nTregs was determined by nTreg-macrophage co-culture assay and ELISA. Results Cholesterol treatment suppressed iTreg differentiation and impaired nTreg function. Mechanistically, cholesterol induced the production of mitochondrial reactive oxygen species (mtROS) in naïve T cells, inhibiting the degradation of HIF-1α and unleashing its inhibitory effects on iTreg differentiation. Furthermore, cholesterol-induced mitochondrial oxidative damage impaired the immunosuppressive function of nTregs. Mixed lymphocyte reaction and nTreg-macrophage co-culture assays revealed that cholesterol treatment compromised the ability of nTregs to inhibit pro-inflammatory conventional T cell proliferation and promote the anti-inflammatory functions of macrophages. Finally, mitoTEMPO (MT), a specific mtROS scavenger, restored iTreg differentiation and protected nTreg from further deterioration. Conclusion Our findings suggest that cholesterol may aggravate inflammation within AS plaques by acting on both iTregs and nTregs, and that MT may be a promising anti-atherogenic drug.

Abstract Background Lameness in dairy cattle is primarily caused by foot lesions including the claw horn lesions (CHL) of sole haemorrhage (SH), sole ulcers (SU), and white line disease (WL). This study investigated the genetic architecture of the three CHL based on detailed animal phenotypes of CHL susceptibility and severity. Estimation of genetic parameters and breeding values, single-step genome-wide association analyses, and functional enrichment analyses were performed. Results The studied traits were under genetic control with a low to moderate heritability. Heritability estimates of SH and SU susceptibility on the liability scale were 0.29 and 0.35, respectively. Heritability of SH and SU severity were 0.12 and 0.07, respectively. Heritability of WL was relatively lower, indicating stronger environmental influence on the presence and development of WL than the other two CHL. Genetic correlations between SH and SU were high (0.98 for lesion susceptibility and 0.59 for lesion severity), whereas genetic correlations of SH and SU with WL also tended to be positive. Candidate quantitative trait loci (QTL) were identified for all CHL, including some on Bos taurus chromosome (BTA) 3 and 18 with potential pleiotropic effects associated with multiple foot lesion traits. A genomic window of 0.65 Mb on BTA3 explained 0.41, 0.50, 0.38, and 0.49% of the genetic variance for SH susceptibility, SH severity, WL susceptibility, and WL severity, respectively. Another window on BTA18 explained 0.66, 0.41, and 0.70% of the genetic variance for SH susceptibility, SU susceptibility, and SU severity, respectively. The candidate genomic regions associated with CHL harbour annotated genes that are linked to immune system function and inflammation responses, lipid metabolism, calcium ion activities, and neuronal excitability. Conclusions The studied CHL are complex traits with a polygenic mode of inheritance. Most traits exhibited genetic variation suggesting that animal resistance to CHL can be improved with breeding. The CHL traits were positively correlated, which will facilitate genetic improvement for resistance to CHL as a whole. Candidate genomic regions associated with lesion susceptibility and severity of SH, SU, and WL provide insights into a global profile of the genetic background underlying CHL and inform genetic improvement programmes aiming at enhancing foot health in dairy cattle.

Abstract Hepatocellular carcinoma (HCC) is the most common primary liver tumor, which seriously threatens human health. CircTNPO3 was up‐regulated in HCC tissues. However, the regulatory mechanism of circTNPO3 in HCC was still unclear. We aimed to investigate the circTNPO3 function in the development of HCC. qRT‐PCR and Western blot examined gene and protein levels. CCK8, EdU, flow cytometry, and Transwell assays were used to detect cell viability, proliferation, apoptosis, and invasion abilities. Dual‐luciferase reporter and RIP assays determined the relationship between circTNPO3, miR‐199b‐5p, and striatin (STRN). The effect of CircTNPO3 on HCC progress was investigated in vivo. CircTNPO3 and STRN were significantly increased, while miR‐199b‐5p was repressed in HCC tissues or cells. Afterward, miR‐199b‐5p was negatively correlated with STRN. circTNPO3 was positively correlated with STRN. Knockdown of circTNPO3 inhibited cell viability, proliferation, invasion, and promoted apoptosis, while circTNPO3 overexpression had the opposite results. Furthermore, miR‐199b‐5p inhibition could eliminate the regulatory effect of sh‐circTNPO3 on the proliferation and apoptosis in HCC cells. CircTNPO3 positively regulated STRN expression by targeting miR‐199b‐5p. MiR‐199b‐5p suppressed HCC progression by inhibiting STRN expression. Tumor formation in nude mice showed that knockdown of circTNPO3 significantly inhibited tumor growth and suppressed ki‐67 levels. CircTNPO3 promoted HCC progression through regulating STRN expression by sponging miR‐199b‐5p, which provided a strategy for HCC treatment.

Improving the activation performance and increasing the hydrogen storage capacity are the main problems faced by TiFe-based alloys. In this paper, alloys with chemical composition Ti1.1-xPrxFe0.8Mn0.2 (x = 0, 0.02, 0.04, 0.06, 0.08) are designed to achieve a reversible hydrogen storage capacity of 1.81 wt% in 15 min, which is close to the theoretical hydrogen storage capacity of TiFe alloy of 1.86 wt%. Alloys with Pr content x ≥ 0.04 can be directly activated without the incubation period. Transmission electron microscopy analysis found that doping Pr introduced TiFe (111) crystal plane with smaller surface energy, makes it easy for hydrogen atoms to diffuse from the surface to interior. Moreover, the addition of Pr significantly refines the grains and introduces a large number of grain boundaries and defects, improving the activation rate and kinetics. The physisorption results show that the specific surface area of the TiFe-based alloy after hydrogen absorption is significantly increased by doping Pr.

With L. plantarum (Lactobacillus plantarum 115, LP), L. acidophilus (Lactobacillus acidophilus 14, LA), L. casei (Lactobacillus casei GB, LC), L. Bulgaria (Lactobacillus bulgaricus 134, LB), L. paracasei (Lactobacillus paracasei 37, LPC) and L. rhamnosus (Lactobacillus rhamnosus GG, LGG) as fermentation species, the effect of Lactobacillus fermentation on the content and composition of free phenol and bound phenol of black rice was studied. The results showed that all six strains of Lactobacillus fermentation significantly increased the content of black rice free phenol, but the degree of improvement after different Lactobacillus fermentation varied significantly, among which the most significant improvement was conducted by LB. There were significant differences between the contents of nine free and bound monomers in black rice after fermentation of Lactobacillus. The results also revealed that the contents of free vanillic acid and p-hydroxybenzoic acid were significantly reduced (P

ABSTRACT: Sole hemorrhage and sole ulcers, referred to as sole lesions, are important causes of lameness in dairy cattle. The objective of this study was to estimate the genetic parameters of a novel trait reflecting how well cows recovered from sole lesions and the genetic correlation of this trait with overall susceptibility to sole lesions. A cohort of Holstein dairy cows was prospectively enrolled on 4 farms and assessed at 4 timepoints: before calving, immediately after calving, in early lactation, and in late lactation. At each timepoint, sole lesions were recorded at the claw level by veterinary surgeons and used to define 2 binary traits: (1) susceptibility to sole lesions—whether animals were affected with sole lesions at least once during the study or were unaffected at every assessment, and (2) sole lesion recovery—whether sole lesions healed between early and late lactation. Animals were genotyped and pedigree details extracted from the national database. Analyses were conducted with BLUPF90 software in a single-step framework; genetic parameters were estimated from animal threshold models using Gibbs sampling. The genetic correlation between both traits was approximated as the correlation between genomic estimated breeding values, adjusting for their reliabilities. A total of 2,025 animals were used to estimate the genetic parameters of sole lesion susceptibility; 44% of animals recorded a sole lesion at least once during the study period. The heritability of sole lesion susceptibility, on the liability scale, was 0.25 (95% highest density interval = 0.16–0.34). A total of 498 animals were used to estimate the genetic parameters of sole lesion recovery; 71% of animals had recovered between the early and late lactation assessments. The heritability of sole lesion recovery, on the liability scale, was 0.27 (95% highest density interval = 0.02–0.52). The approximate genetic correlation between each trait was −0.11 (95% confidence interval = −0.20 to −0.02). Our results indicate that recovery from sole lesions is heritable. If this finding is corroborated in further studies, it may be possible to use selective breeding to reduce the frequency of chronically lame cows. As sole lesion recovery appears to be weakly genetically related to sole lesion susceptibility, successful genetic improvement of sole lesion recovery would benefit from selection on this trait directly.

Hybrid beamforming (HBF) has been regarded as one of the most promising technologies in millimeter Wave (mmWave) communication systems. In order to guarantee the communication quality in non-line-of-sight (NLOS) scenarios, joint HBF design for the mmWave amplify-and-forward (AF) relay communication system is studied in this paper. The ideal case is first considered where the mmWave half-duplex (HD) AF relay system operates with channel state information (CSI) accurately known. In order to tackle the non-convex problem, a manifold optimization (MO)-based alternating optimization algorithm is proposed, where an optimization problem containing only constant modulus constraints in Euclidean space can be converted to an unconstrained optimization problem in a Riemann manifold. Furthermore, considering more practical cases with estimation errors of CSI, we investigate the robust joint HBF design with the system operating in full-duplex (FD) mode to obtain higher spectral efficiency (SE). A null-space projection (NP) based self-interference cancellation (SIC) algorithm is developed to attenuate the self-interference (SI). Different from the traditional SI suppression algorithm, there’s no limit on the number of RF chains. Numerical results reveal that our proposed algorithms has a good convergence and can effectively deal with the influence of different CSI estimation errors. A significant performance improvement can be achieved in contrast with other approaches.

Edge computing brings computation and storage resources to the edge of the mobile network to solve the problems of low latency and high real-time demand. However, edge computing is more vulnerable to malicious attacks due to its open and dynamic environments. In this article, we investigate security defense strategies in edge computing systems, focusing on scenarios with one attacker and multiple defenders to determine optimal defense strategies with minimal resource allocation. Firstly, we formulate the interactions between the defenders and the attackers as the mean-field Stackelberg game model, where the state and the objective functions of the defenders are coupled through the mean-field term, and are strongly influenced by the strategy of the attacker. Then, we analyze the local optimal strategies of the defenders given an arbitrary strategy of the attackers. We demonstrate the Nash equilibrium and the mean-field equilibrium for both the defenders and the attackers. Finally, simulation analysis will illustrate the dynamic evolution of the defense strategy of the defenders and the trajectory of the attackers based on the proposed Stackelberg game model.

Amorphous alloys or metallic glasses (MGs) thin films have attracted extensive attention in various fields due to their unique functional properties. Here, we use in situ heating transmission electron microscopy (TEM) to investigate the thermal stability and crystallization behavior of Pd-Au-Si thin films prepared by a pulsed laser deposition (PLD) method. Upon heating treatment inside a TEM, we trace the structural changes in the Pd-Au-Si thin films through directly recording high-resolution images and diffraction patterns at different temperatures. TEM observations reveal that the Pd-Au-Si thin films started to nucleate with small crystalline embryos uniformly distributed in the glassy matrix upon approaching the glass transition temperature Tg=625K, and subsequently, the growth of crystalline nuclei into sub-10 nm Pd-Si nanocrystals commenced. Upon further increasing the temperature to 673K, the thin films transformed to micro-sized patches of stacking-faulty lamellae that further crystallized into Pd9Si2 and Pd3Si intermetallic compounds. Interestingly, with prolonged thermal heating at elevated temperatures, the Pd9Si2 transformed to Pd3Si. Simultaneously, the solute Au atoms initially dissolved in glassy alloys and eventually precipitated out of the Pd9Si2 and Pd3Si intermetallics, forming nearly spherical Au nanocrystals. Our TEM results reveal the unique thermal stability and crystallization processes of the PLD-prepared Pd-Au-Si thin films as well as demonstrate a possibility of producing a large quantity of pure nanocrystals out of amorphous solids for various applications.

The role of estrogen receptor β (ERβ) in bone health is closely associated with its function in vivo, and ERβ−/− mice have been widely utilized to explore the related influences. In this study, ERβ−/− female mice were established to investigate the differential expression of circular RNAs (circRNAs) by RNA-Sequencing (RNA-Seq). Among these circRNAs, mmu_circ_0011379 (named Circ-Spen) exhibited high expression in ERβ−/− female mice. However, the precise mechanism by which Circ-Spen regulates bone health remained unclear. This study identified Circ-Spen as a positive regulator of mouse bone marrow mesenchymal stem cell (mBMSC) viability. The expression of Circ-Spen was markedly increased in ERβ−/− mice femurs tested by RT-qPCR. Moreover, Circ-Spen exhibited an enhanced expression during the bone formation process of mBMSCs. Qualitative experiments also demonstrated that Circ-Spen possessed a circular structure and was localized within the nucleus of mBMSCs. Functionally, it inhibited apoptosis via caspase-3, BCL-2, and BAX, while also promoting autophagy through BECN1 and P62 in mBMSCs tested by MTT assays, transmission electron microscopy (TEM), and Western blotting. These findings reveal the potential of targeting Circ-Spen as a promising therapeutic strategy for rejuvenating senescent mBMSCs and enhancing the efficiency of mBMSC transplantation, which lays the foundation for advancements in the field of bone therapy.

Introduction Exploring the experiences and perspectives of healthcare professionals, patients and caregivers toward serious illness conversations based on the Serious Illness Care Program is vital for improving communication with patients who are seriously ill, as has been shown in previous studies. However, few studies have carried out a systematic review to examine common themes, strengthen conclusions and identify gaps in the literature, the findings of which could help steer further research, policies and practice to improve more timely and person-centred conversations about the values and priorities of patients with serious illnesses. The objective of this qualitative meta-synthesis is to explore how healthcare professionals, patients and caregivers described their own experiences of the processes of serious illness communication through a secondary analysis of published qualitative data.Methods and analysis Meta-aggregation will be used to conduct a systematic review of qualitative studies. We conducted an initial search on 10 October 2023; papers published in English will be searched using electronic databases, including PubMed (MEDLINE), Web of Science, Embase, Ovid and CINAHL. Studies that satisfy the eligibility criteria will be evaluated for methodological quality using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. The meta-aggregative review will consist of the following: (1) extraction of findings of all included studies; (2) categorisation of the findings, with at least two findings per category; and (3) synthesis of one or more findings from at least two categories. Study eligibility screening, data extraction, analysis and JBI Critical Appraisal Checklist and Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research assessments will be undertaken independently by two authors.Ethics and dissemination Secondary data analysis of published literature does not require ethical approval. The results will be disseminated in peer-reviewed journals and presented in conference papers and elsewhere.PROSPERO registration number CRD42022330859.

Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs through oxidative stress. The development of natural extracts that can reduce oxidative damage is a promising method. Lentinan is isolated from Lentinus edodes and has been verified its antioxidant activity. In this study, Caenorhabditis elegans was used to evaluate the protective effects of lentinan against fluopyram-induced toxicity and the possible mechanisms. Results showed that lentinan pretreatment notably increased the survival rate of N2 nematodes by 15.0 % and extended the lifespan by 91.5 %, compared with the fluopyram treatment. Lentinan pretreatment reverted the inhibition of the locomotion and reproduction of C. elegans under the fluopyram stress. In addition, lentinan pretreatment significantly decreased the contents of ROS and MDA in N2 nematodes. Moreover, pretreated with lentinan significantly recovered the decreased activities of CAT, SOD, GST and SDH induced by fluopyram. Lentinan pretreatment enhanced the mRNA levels of daf-16 and skn-1 and their downstream genes in the nematodes compared with the fluopyram group. In daf-16 and skn-1 mutants, the lifespan, ROS and related genes expression were not significantly changed in lentinan pretreatment. Pretreated with lentinan significantly enhanced the fluorescence intensity of SOD-3::GFP and GST-4::GFP, and promoted the nuclear translocation of DAF-16 and SKN-1 under the fluopyram stress. In summary, these findings indicated that lentinan protected C. elegans from fluopyram-induced toxicity via DAF-16 and SKN-1.

Assessing the landscape ecological risk (LER) will facilitate optimal planning of land-use patterns and mitigating regional ecological risks, especially in megacities under rapid urbanization. And selecting the appropriate spatial analysis scales is the prerequisite for accurate assessment of the LER. In this study, we demonstrate the spatio-temporal dynamics of LER by determining the appropriate spatial scales in Beijing, China from 2000 to 2020. The results indicate that a granularity of 50 m and a magnitude of 5 km are optimal for regional LER assessment. The study area had predominantly medium risks, with medium, high and higher risks accounting for approximately 70% that revealed LER was at high level. Fortunately, the high and higher risks decreased by 14.64% while low and lower risks increased by 16.62% over the past two decades, which indicated LER was on a general downward trend. The LER pattern varies from east to west, with high and higher risks clustered in the northeast and southeast of the city center, and gradually dispersing elsewhere. In contrast, low and lower risks were predominantly in the city center and western regions, expanding outward from the city center. The LER was low in built-up land and cropland in the central city, but relatively high in areas away from it. The urban fringe areas dominated by woodland and grassland exhibited a high LER. The regional LER differentiation is spatially correlated with urban expressways and significant changes in LER were predominantly observed in areas adjacent to urban expressways. Specifically, the expansion of low and lower risks occurred outward along the ring roads of Beijing, and a typical case was that the lower risks were primarily enclosed by the fifth ring road in 2000 and gradually expanded towards the areas near the sixth ring road by 2020. Moreover, the LER manifests obvious spatial agglomeration influenced by human disturbance, with apparent high-high and low-low agglomerations. It is suggested to implement landscape optimization by enhancing the landscape diversity and connectivity to effectively mitigate ecological risks. These findings will provide scientific reference for researches aimed at mitigating ecological risks and fostering high-quality sustainable development in metropolitan areas.

This study explores the status quo of preventive care use and social capital among middle-aged and elderly people (≥45 years old) in China, and employs a multi-level model to analyze whether social capital at different levels is associated with preventive care use. The data are derived from the 2018 China Health and Retirement Longitudinal Study (CHARLS), which includes 11,503 respondents and 450 communities. Preventive care use covers the utilization of routine physical examination services. Individual social capital is measured by the level of social network and social activities participation. Social network includes contacting with children or other people, for example, by phone, text message. Social activities participation is measured by the involvement in social activities, for example, playing mahjong, going to community club. Community social capital is evaluated by the richness of community facilities. Results reveals that the utilization of preventive care is 48.94% among middle-aged and elderly in China. The most used preventive service is routine blood test. The intra-class correlation (ICC) coefficient indicates that preventive health behaviors of the respondents are clustered at communities where they live. Multi-level regression shows that influence of social network is not significant to preventive care use (p ＞ 0.05). Community facilities and individual social activities participation are significantly associated with preventive care use (p

Data-driven car-following modeling is of great significance to traffic behavior analysis and the development of connected automated vehicle (CAV) technology. The existing researches focus on reproducing the car-following process by capturing the behavior of the host vehicle using the information of its nearest preceding vehicle. While the other preceding vehicles may affect the host vehicle as well. To fill the gap above, this paper presents an improved sequence-to-sequence deep learning-based (ISDL) car-following model for a CAV system. Firstly, the kinematics information considering the multiple preceding vehicles are organized as the input characteristics. Secondly, an improved sequence-to-sequence deep learning framework is proposed by integrating an encoder with the bidirectional gated recurrent unit (GRU) neural network and a decoder using an attention-based GRU neural network in an end-to-end fashion. Finally, the car-following data with multiple preceding vehicles captured from the NGSIM dataset are employed to train and calibrate the proposed model. Experimental results indicate that the deep learning-based models’ performance in learning heterogeneous driving behavior can be enhanced by adding information about multiple preceding vehicles. In addition, the proposed ISDL model outperforms the benchmark car-following models in terms of the accuracy of the simulated speeds and simulated positions. Through tests on platoon simulation, the ISDL model is capable of reshaping the traffic oscillation phenomenon as well.

A rational investor always pursues a portfolio with the greatest possible return and the least possible risk. Therefore, a core issue of investment decision analysis is how to make an optimal investment choice in the market with fuzzy information and realize the balance between maximizing the return on assets and minimizing the risk. In order to find optimal investment portfolios of financial assets with high volatility, such as gold and Bitcoin, a mathematical model for formulating investment strategies based on the long short-term memory time series and the dynamic programming model combined with the greedy algorithm has been proposed in this paper. The model provides the optimal daily strategy for the five-year trading period so that it can achieve the maximum expected return every day under the condition of a certain investment amount and a certain risk. In addition, a reasonable risk measure based on historical increases is established while considering the weights brought by different investment preferences. The empirical analysis results show that the optimal total assets and initial capital obtained by the model change in the same proportion, and the model is relatively stable and has strong adaptability to the initial capital. Therefore, the proposed model has practical reference value and research significance for investors and promotes a better combination of computer technology and financial investment decision.

Rapid urbanization has profoundly impacted social and environmental systems. China is the world’s largest developing country. Projecting future urban expansion in China is critical to alleviate any adverse impacts and achieve sustainable development goals. However, the existing national-scale urban expansion simulations at low or medium resolutions produce significant distortions in urban spatial patterns, limiting the utility of future projections. High-resolution simulation of urban expansion is challenging on a large scale owing to high computational demands. In this study, we used a high-performance cellular automata model (Tensor-FLUS) to simulate the urban expansion of China from 2015 to 2050, at 30 m spatial resolution, under shared socioeconomic pathways. The high-resolution (30 m) urban expansion simulations preserve greater spatial details and avoid 34.07–37.60% underestimation of the urban area, compared with simulation at 1 km resolution. The environmental impact assessments revealed that future urban expansion mainly encroaches on cropland (88.00–88.29%), with a greater likelihood of occupying productive cropland, placing substantial pressure on food production. Although the proportion of occupied natural land is relatively small (11.32–11.60%), newly expanded urban areas will tend to consume woodland and grassland of high ecological value, leading to profound impacts on the ecosystem. In general, the produced high-resolution future simulations can reduce the uncertainty of environmental impact assessment at the national scale. Furthermore, it can provide consistent projection data for research at the provincial or metropolitan scales to support urban planning and local climate change mitigation.

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. The discovery of tyrosine kinase inhibitors effectively targeting EGFR mutations in lung cancer patients in 2004 represented the beginning of the precision medicine era for this refractory disease. This great progress benefits from the identification of driver gene mutations, and after that, conventional and new technologies such as NGS further illustrated part of the complex molecular pathways of NSCLC. More targetable driver gene mutation identification in NSCLC patients greatly promoted the development of targeted therapy and provided great help for patient outcomes including significantly improved survival time and quality of life. Herein, we review the literature and ongoing clinical trials of NSCLC targeted therapy to address the molecular pathways and targeted intervention progress in NSCLC. In addition, the mutations in EGFR gene, ALK rearrangements, and KRAS mutations in the main sections, and the less common molecular alterations in MET, HER2, BRAF, ROS1, RET, and NTRK are discussed. The main resistance mechanisms of each targeted oncogene are highlighted to demonstrate the current dilemma of targeted therapy in NSCLC. Moreover, we discuss potential therapies to overcome the challenges of drug resistance. In this review, we manage to display the current landscape of targetable therapeutic patterns in NSCLC in this era of precision medicine.

Context Patients with non-alcoholic steatohepatitis (NASH) may have a simultaneous intake of pravastatin and evodiamine-containing herbs. Objective The effect of evodiamine on the pharmacokinetics of pravastatin and its potential mechanisms were investigated in NASH rats. Materials and methods The NASH model was conducted with feeding a methionine choline-deficient (MCD) diet for 8 weeks. Sprague-Dawley rats were randomised equally (n = 6) into NASH group, evodiamine group (10 mg/kg), pravastatin group (10 mg/kg), and evodiamine (10 mg/kg) + pravastatin (10 mg/kg) group. Normal control rats were fed a standard diet. Effects of evodiamine on the pharmacokinetics, distribution, and uptake of pravastatin were investigated. Results Evodiamine decreased Cmax (159.43 ± 26.63 vs. 125.61 ± 22.17 μg/L), AUC0-t (18.17 ± 2.52 vs. 14.91 ± 2.03 mg/min/L) and AUC0-∞ (22.99 ± 2.62 vs. 19.50 ± 2.31 mg/min/L) of orally administered pravastatin in NASH rats, but had no significant effect in normal rats. Evodiamine enhanced the uptake (from 154.85 ± 23.17 to 198.48 ± 26.31 pmol/mg protein) and distribution (from 736.61 ± 108.07 to 911.89 ± 124.64 ng/g tissue) of pravastatin in NASH rat liver. The expression of Oatp1a1, Oatp1a4, and Oatp1b2 was up-regulated 1.48-, 1.38-, and 1.51-fold by evodiamine. Evodiamine decreased the levels of IL-1β, IL-6, and TNF-α by 27.82%, 24.76%, and 29.72% in NASH rats, respectively. Discussion and conclusions Evodiamine decreased the systemic exposure of pravastatin by up-regulating the expression of OATPs. These results provide a reference for further validation of this interaction in humans.

ABSTRACT: The digital cushion is linked to the development of claw horn lesions (CHL) in dairy cattle. The objectives of this study were to (1) estimate genetic parameters for digital cushion thickness (DCT), (2) estimate the genetic correlation between DCT and CHL, and (3) identify candidate genes associated with DCT. A cohort of 2,352 Holstein dairy cows were prospectively enrolled on 4 farms and assessed at 4 time points: before calving, immediately after calving, in early lactation, and in late lactation. At each time point, CHL was recorded by veterinary surgeons, and ultrasonographic images of the digital cushion were stored and retrospectively measured at 2 anatomical locations. Animals were genotyped and pedigree details extracted from the national database. Genetic parameters were estimated following a single-step approach implemented in AIREMLF90. Four traits were analyzed: the 2 DCT measurements, sole lesions (sole hemorrhage and sole ulcers), and white line lesions. All traits were analyzed with univariate linear mixed models; bivariate models were fit to estimate the genetic correlation between traits within and between time points. Single-marker and window-based genome-wide association analyses of DCT traits were conducted at each time point; candidate genes were mapped near (

Abstract Tobacco bacterial wilt has seriously affected tobacco production. Ethyl methanesulfonate (EMS) induced tobacco bacterial wilt resistant mutants are important for the control of tobacco bacterial wilt. High-throughput sequencing technology was used to study the rhizosphere bacterial community assemblages of bacterial wilt resistant mutant tobacco rhizosphere soil (namely KS), bacterial wilt susceptible tobacco rhizosphere soil (namely GS) and bulk soil (namely BS) in Xuancheng, Huanxi, Yibin and Luzhou. Alpha analysis showed that the bacterial community diversity and richness of KS and GS in the four regions were not significantly different. However, analysis of intergroup variation in the top 15 bacterial communities in terms of abundance showed that the bacterial communities of KS and GS were significantly different from BS, respectively. In addition, pH, alkali-hydrolysable nitrogen (AN) and soil organic carbon (SOC) were positively correlated with the bacterial community of KS and negatively correlated with GS in the other three regions except Huanxi. Network analysis showed that the three soils in the four regions did not show a consistent pattern of network complexity. PICRUSt functional prediction analysis showed that the COG functions were similar in all samples. All colonies were involved in RNA processing and modification, chromatin structure and dynamics, etc. In conclusion, our experiments showed that rhizosphere bacterial communities of tobacco in different regions have different compositional patterns, which are strongly related to soil factors.

Summary: Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.

The study investigated the microstructure and mechanical properties of composite strengthened high-chromium cast iron by laser quenching and laser shock peening. Observation of microstructure, measurement of microhardness, residual stress and FWHM (full width at half maximum), impact toughness and wear tests were carried out on untreated, laser quenched, laser quench-laser shock peened high-chromium cast iron specimens. The research results showed that the laser shock peening will not produce new phases in high-chromium cast iron, and can further promote the transformation of retained austenite into martensite. The grains inside the laser quench-laser shock peened sample were obviously refined, and the carbides were uniformly dispersed. The laser quench-laser shock peened specimen produced large residual compressive stress and FWHM value on the surface, reaching −432.49 MPa and 2.124°, respectively. The problem of residual stress difference between the hardened zone and the transition zone caused by laser quenching was eliminated, and the tensile stress was all converted into compressive stress, which further increases the dislocation density and improves the micro-hardness. The impact toughness value of laser quench-laser shock peened specimen was 4.43 J/cm2, which was 16.27% higher than that of the untreated sample. The friction coefficient and wear rate were significantly reduced, and the wear scar was shallow and narrow, showing weak abrasive wear and oxidative wear, the impact toughness and wear resistance of high-chromium cast iron were improved. The results obtained from this study could be used as reference in future research and applications of laser strengthened high-chromium cast iron.

IntroductionThe gut-lung axis has long been recognized as an important mechanism affecting intestinal and lung immunity. Still, few studies have examined the correlation between the intestinal and pharyngeal microbiota in early neonates, especially when feeding patterns are one of the main drivers of microbiota development.MethodsTo explore the composition and function of intestinal and pharyngeal microbiota and to analyze the effect of limited formula feeding on the initial microbiota colonization in early full-term neonates, we characterized the stool and oropharyngeal microbiota of 20 healthy full-term newborns sampled on days 0 and 5–7 after birth using 16S rRNA gene sequencing. Based on the sequencing results, a comparison was made of the compositions and functions of the intestinal and oropharyngeal microbiota for analysis.Results and discussionAt the phylum level, Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes were the most abundant in both niches. At the genus level, the species of pioneer bacteria were rich in the intestine and oropharynx but low in abundance on day 0. On days 5–7, Bifidobacterium (25.40%) and Escherichia-Shigella (22.16%) were dominant in the intestine, while Streptococcus (38.40%) and Staphylococcus (23.13%) were dominant in the oropharynx. There were eight core bacteria genera in the intestine and oropharynx on days 5–7, which were Bifidobacterium, Escherichia-Shigella, Staphylococcus, Streptococcus, Bacteroides, Parabacteroides, Rothia, and Acinetobacter. As indicated by PICRUSt analysis, on days 5–7, the intestinal microbiota was more predictive than the oropharyngeal microbiota in transcription, metabolism, cell motility, cellular processes and signaling, and organismal system function in the KEGG pathway. Compared to exclusive breastfeeding, limited formula feeding (40–60%) had no significant effect on the neonatal intestinal and oropharyngeal microbiota composition during the initial colonization period. Our results suggest that the initial colonization of microbiota is closely related to the ecological niche environment in the intestine and oropharynx, with their core microbiota being closely correlated. We found that early limited formula feeding could not significantly affect the initial colonization of microbiota in the intestine and oropharynx.

The successful application of probiotics in food industry depends on the use of good cryoprotectants. This paper was aimed to evaluate protective effects of enzymatic hydrolysis products of different degrees of pomelo peel cellulose (EHPC) on Lactobacillus plantarum during freeze-drying process. The data showed that in contrast to trehalose, the survival rate of L. plantarum was increased obviously under the optimal composite cryoprotectants, which consisted of trehalose and EHPC for 2 h with the mass ratio of 8:2. In addition, the morphology, water-related indices, glass transition temperature (Tg) and cell membrane integrity of lyophilized L. plantarum powder were also evaluated. The results showed that the water content of L. plantarum prepared by the optimal composite cryoprotectants was lower, which was in a reasonable range and conducive to subsequent storage; the Tg and cell membrane integrity were significantly improved. Furthermore, the macromolecular fibers of composite cryoprotectants provided a good habitat and attachment space for L. plantarum, and the sheet fibers with large area acted as a physical barrier to prevent the damage to cells from adverse external environment. The composite cryoprotectants from this study could be considered for industrial development of probiotics.

Abstract Background Cross-species comparison of transcriptomes is important for elucidating evolutionary molecular mechanisms underpinning phenotypic variation between and within species, yet to date it has been essentially limited to model organisms with relatively small sample sizes. Results Here, we systematically analyze and compare 10,830 and 4866 publicly available RNA-seq samples in humans and cattle, respectively, representing 20 common tissues. Focusing on 17,315 orthologous genes, we demonstrate that mean/median gene expression, inter-individual variation of expression, expression quantitative trait loci, and gene co-expression networks are generally conserved between humans and cattle. By examining large-scale genome-wide association studies for 46 human traits (average n = 327,973) and 45 cattle traits (average n = 24,635), we reveal that the heritability of complex traits in both species is significantly more enriched in transcriptionally conserved than diverged genes across tissues. Conclusions In summary, our study provides a comprehensive comparison of transcriptomes between humans and cattle, which might help decipher the genetic and evolutionary basis of complex traits in both species.

In this paper, quench-tempering (QT) and laser quenching (LQ) treatments were performed on the high-chromium cast iron to obtain better microstructure and mechanical properties. The changes in microhardness, microstructure, retained austenite (RA) content, grain size, phase and elemental content of the QT and LQ samples were compared and analyzed. The results showed that the RA content of the untreated samples was 77.02% and the was 26.8 nm. The QT samples showed an increase in carbide dissolution, gradual rounding from sharp angles, transformation of austenite into martensite, reduction of RA content to 28.48%, average grain size (AGS) of 35.8 nm, increase in surface microhardness by 16.6%, and the friction coefficient was reduced by 6.9%. The LQ samples showed a large amount of fine martensite, daisy-like eutectic carbides and diffusely distributed secondary carbides, and the RA content was reduced to 17.72%, with an AGS of 29.9 nm. Compared with the QT samples, the LQ samples showed a 25.1% reduction in AGS, a 16.5% increase in surface microhardness, and a 9.7% decrease in friction coefficient, which was more wear resistant. However, the hard and brittle surface layer of the LQ samples tended to be a source of cracks during impact, resulting in a final reduction of 8.4% in impact toughness compared to the QT samples.