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Abstract Background The conversion of primary bile acids to secondary bile acids by the gut microbiota has been implicated in colonic inflammation. This study investigated the role of gut microbiota related bile acid metabolism in colonic inflammation in both patients with inflammatory bowel disease (IBD) and a murine model of dextran sulfate sodium (DSS)-induced colitis. Methods Bile acids in fecal samples from patients with IBD and DSS-induced colitis mice, with and without antibiotic treatment, were analyzed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The composition of the microbiota in fecal samples from IBD patients and DSS-colitis mice was characterized via Illumina MiSeq sequencing of the bacterial 16S rRNA gene V3-V4 region. Metagenomic profiling further identified metabolism-related gene signatures in stool samples from DSS-colitis mice. Histological analysis, quantitative PCR (qPCR) and Western Blotting were conducted on colonic samples from DSS-induced colitis mice to assess colonic inflammation, mucosal barrier integrity, and associated signaling pathways. The multivariate analysis of bile acids was conducted using Soft Independent Modelling of Class Analogy (SIMCA, Umetrics, Sweden). The relation between the relative abundance of specific phyla/genera and bile acid concentration was assess through Spearman's correlation analyses. Finally, lithocholic acid (LCA), the key bile acid, was administered via gavage to evaluate its effect on colonic inflammation and mucosal barrier integrity. Results In patients with IBD, the composition of colonic bile acids and gut microbiota was altered. Moreover, changes in the gut microbiota further modulate the composition of bile acids in the intestine. As the gut microbiota continues to shift, the bile acid profile undergoes additional alterations. The aforementioned alterations were also observed in mice with DSS-induced colitis. The study revealed a correlation between dysbiosis of the gut microbiota and modifications in the profile of colonic bile acids, notably LCA observed in both patients with IBD and mice with DSS-induced colitis. Through multivariate analysis, LCA was identified as the key bile acid that significantly affects colonic inflammation and the integrity of mucosal barrier. Subsequent experiments confirmed that LCA supplementation effectively mitigated the inhibitory effects of gut microbiota on colitis progression in mice, primarily through the activation of the sphingosine-1-phosphate receptor 2 (S1PR2)/NF-κB p65 signaling pathway. Analysis of the microbiome and metagenomic data revealed changes in the gut microbiota, notably an increased abundance of an unclassified genus within the family Prevotellaceae in DSS-induced colitis mice. Furthermore, a positive correlation was observed between the relative abundance of Prevotellaceae and bile acid biosynthesis pathways, as well as colonic LCA level. Conclusions These findings suggest that LCA and its positively correlated gut bacteria, Prevotellaceae, are closely associated with intestinal inflammation. Targeting colonic inflammation may involve inhibiting LCA and members of the Prevotellaceae family as potential therapeutic strategies.

Abstract Background Psychological birth trauma represents a significant global public health concern, with an estimated 45% of new mothers reporting such an experience. Researchers mostly focus on the impacts of postpartum mental health issues, such as postpartum post-traumatic stress disorder, minimal attention has been given to the antecedents of psychological birth trauma. This study seeks to investigate the correlation between fear of childbirth and psychological birth trauma among Chinese women who have undergone natural childbirth, as well as the mediating role of coping styles in the association between fear of childbirth and psychological birth trauma. Methods This cross-sectional study was conducted among 420 women who underwent natural childbirth between June and December 2021 in Shandong Province, China. Data were gathered using the Wijma Delivery Experience Questionnaire, Trait Coping Style Questionnaire, and Impact of Event Scale-Revised. The structural equation model (SEM) was employed to examine the relationships between variables and to develop the final model. Results The prevalence of psychological birth trauma among women who had experienced natural childbirth was recorded at 10.27%. The mean score and standard deviation of psychological birth trauma, fear of birth, positive coping (PC), and negative coping (NC) among these women were 19.7 ± 12.5, 76.9 ± 21.3, 35.66 ± 7.05, and 28.20 ± 7.99, respectively. Findings indicated that women’s fear of childbirth was directly (B = 0.340, p = 0.001) and indirectly (B = 0.124, p = 0.001) linked to women’s psychological birth trauma. Additionally, women’s PC was negatively associated with psychological birth trauma (B= -0.352, p = 0.001), while NC was positively associated with psychological birth trauma (B = 0.199, p = 0.001). Conclusions Chinese women who experienced natural childbirth encountered a moderate level of psychological birth trauma. Women’s coping style plays a pivotal mediating role in the connection between fear of childbirth and psychological birth trauma. Consequently, interventions aimed at diminishing women’s fear of childbirth and enhancing PC skills should be devised and implemented to alleviate women’s psychological birth trauma.

Abstract Inflammasomes represent a crucial component of the innate immune system, which respond to threats by recognizing different molecules. These are known as pathogen-associated molecular patterns (PAMPs) or host-derived damage-associated molecular patterns (DAMPs). In neurodegenerative diseases and neuroinflammation, the accumulation of misfolded proteins, such as beta-amyloid and alpha-synuclein, can lead to inflammasome activation, resulting in the release of interleukin (IL)-1β and IL-18. This activation also induces pyroptosis, the release of inflammatory mediators, and exacerbates neuroinflammation. Increasing evidence suggests that inflammasomes play a pivotal role in neurodegenerative diseases. Therefore, elucidating and investigating the activation and regulation of inflammasomes in these diseases is of paramount importance. This review is primarily focused on evidence indicating that inflammasomes are activated through the canonical pathway in these diseases. Inflammasomes as potential targets for treating neurodegenerative diseases are also discussed.

Abstract Background Vibrio parahaemolyticus has emerged as the leading cause of seafood-associated infections worldwide. Previous studies have shown that V. parahaemolyticus can be detected in both environmental and clinical samples. However, the molecular characteristics of V. parahaemolyticus isolated from these sources remain unknown. Results This study examined 128 strains of V. parahaemolyticus isolated from clinical and environmental samples collected between 2020 and 2023 in Huzhou, China. We identified 73 serotypes; O10:K4, O3:K6, and O4:KUT were the dominant serotypes among clinical isolates. We examined the proliferation and motility of major epidemic strains from environmental and clinical samples. Genetic diversity and evolution were assessed by average nucleotide identity (ANI), phylogenetic tree construction, and multilocus sequence typing (MLST). Furthermore, we identified 13 novel sequence types (STs) among the environmental isolates, indicating that V. parahaemolyticus strains are widely distributed and evolve rapidly in the environment in Huzhou, China. We found 206 virulence genes among these isolates, indicating that environmental isolates possess numerous virulence genes. Additionally, we detected 4 strains carrying the tdh or trh gene, which may increase their pathogenicity. The prediction results of antibiotic resistance genes shown that environmental isolates may carry up to 104 resistance genes, compared to 30 in clinical isolates. Conclusions We observed that the environmental serotypes of V. parahaemolyticus exhibit greater diversity compared to clinical isolates, which are predominantly concentrated in three major serotypes. Furthermore, a considerable genetic distance was found between most clinical and environmental isolates. Notably, some clinical isolates show a closer genetic proximity to environmental isolates. Additionally, the distribution of virulence genes, specifically T3SS and tdh, significantly differs among isolates from these two distinct sources. The prediction results for antibiotic resistance genes suggest that environmental isolates may harbor a broader spectrum of resistance genes. The findings of this study provide new insights into the phylogenetic relationships between V. parahaemolyticus strains from clinical and environmental sources, and they enhance the MLST database.

Abstract The transfer of genetic material between stocks and scions of grafted plants has been extensively studied; however, the nature and frequency of the transferred material remain elusive. Here, we report a grafting system involving woody goji as the stock and herbaceous tomato as the scion, which was developed using in vitro and in vivo approaches; the results confirmed horizontal transfer of multiple nuclear DNA fragments from donor goji cells to recipient tomato cells. Tomato tissues containing goji donor DNA fragments at or near the grafting junctions had a perennial-biased anatomical structure, from which roots or shoots were regenerated. Most of the fragments were plasmid-like extrachromosomal circular DNAs (eccDNAs) present in the regenerants derived from the cells and in their asexual offspring. Plants with transferred eccDNAs in regenerated roots or shoots (designated “Go-tomato”) were grown perennially and showed excellent agronomic performance. The present study provides new insights into the replication, expression, and potential function of eccDNAs in the pleiotropic traits of Go-tomato. Mobile eccDNAs offer evidence of stock-to-scion horizontal DNA transfer beyond chromosomes and organelles, thereby contributing to the molecular understanding of graft-induced genetic variation, evolution, and breeding.

Abstract Background Microplastic pollution is a pressing issue with far-reaching environmental and public health consequences. This study delves into the intricacies of predicting microplastic pollution during the COVID-19 pandemic in Tehran, Iran. Methods The research introduces a rigorous comparative analysis that evaluates the predictive prowess of the Deep Random Forest algorithm and established benchmarks, such as Random Forest, Decision Trees, Gradient Boosting, AdaBoost, and Support Vector Machine. The evaluation process encompasses a meticulous 70–30 training–testing split of the main data set. Performance is assessed by analysis metrics, including ROC and statistical errors. The primary data set encompasses distinct categories, including household wastes, hospital wastes, clinics wastes, and unknown-originated susceptible waste which is categorized in Infected items, PPEs, SUPs, Test kits, Medical packages, Unknown-originated pandemic mircoplastic waste. Deliberately, this data set was partitioned into training and testing subsets, ensuring the robustness and reliability of subsequent analyses. Approximately 70% of the main database was allocated to the training data set, with the remaining 30% constituting the testing data set. Results The findings underscore the proposed algorithm’s supremacy, boasting an impressive AUC = 0.941. This exceptional score reflects the model’s precision in categorizing microplastics. These results have profound implications for environmental management and public health during pandemics. Conclusions The study positions the proposed model as a potent tool for microplastic pollution prediction, encouraging further research to refine predictive models and tap into new data sources for a more comprehensive understanding of microplastic dynamics in urban settings.

Abstract Most current studies use body mass index (BMI) or waist circumference (WC) to define obesity, and BMI, which reflects subcutaneous fat independent of visceral fat, is the most commonly used indicator of obesity. WC reflects subcutaneous and visceral fat. This research aims to investigate the effect of obesity on mortality in people with digestive diseases. According to BMI and WC, we divided patients with obesity into the following four groups: general obesity, abdominal obesity, combined obesity, and non-obese. The effects of different obesity types on mortality in a population with digestive diseases were analysed via Cox regression and inverse probability-weighted Cox regression. Our research employed multivariate imputation via the chained equations method to interpolate missing values. A total of 254,445 participants, with a mean age of 57.8 ± 7.8 years, were included in the analysis. Of these participants, 227,111 (89.3%) participants were censored, and 27,334 (10.7%) participants died. Abdominal obesity and combined obesity were independent predictors of mortality in patients with digestive diseases. The combination of BMI and WC was valuable and significant for considering the type of obesity. In addition, our study revealed that sex, socioeconomic status, lifestyle habits, and physical activity were also associated with death in people with digestive disorders. Combined obesity, which is determined by both BMI and WC, is an important factor that influences mortality in a population with digestive diseases, and it plays a stronger role than abdominal obesity alone. These modifiable risk factors for mortality can provide guidance to populations with digestive diseases to avoid poor lifestyles and prolong survival time.

Abstract Background Lung adenocarcinoma (LUAD) is the most common lung cancer subtype, and the prognosis of affected patients is generally poor. The traditional Chinese medicine Uncaria rhychophaylla has been reported to exhibit anti-lung cancer properties. Accordingly, the main bioactive ingredient in Uncaria rhychophaylla, Corynoxine, may hold great value as a treatment for lung cancer. Methods The impact of Corynoxine on the viability of LUAD cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in A549 cells was evaluated via flow cytometry. Migration and invasion capabilities were determined through wound healing and Transwell assays, respectively. The key pathways targeted by Corynoxine in LUAD were identified using a network pharmacology approach. Additionally, Western immunoblotting, quantitative real-time PCR (qRT-PCR), and ELISA assays were conducted to validate the underlying mechanisms. The in vivo anti-tumor efficacy of Corynoxine was assessed in xenograft nude mice. Results In this study, Corynoxine treatment was found to markedly suppress in vitro LUAD cell proliferative, migratory, and invasive activity. It additionally downregulated Vimentin and promoted E-cadherin upregulation consistent with the disruption of epithelial-mesenchymal transition (EMT) induction while also accelerating apoptotic death. Furthermore, network pharmacology analysis revealed that the PI3K/AKT pathway is a potential target of Corynoxine in LUAD. In vitro assays demonstrated that treatment with Corynoxine resulted in the suppression of PI3K/AKT signaling and a consequent drop in cyclooxygenase-2 (COX-2) expression. These findings were further confirmed in vivo in mice harboring A549 tumor xenografts in which Corynoxine was able to interfere with the PI3K/AKT/COX-2 signaling axis. Conclusion This study elucidated the potential effects of Corynoxine in suppressing proliferation and metastasis in LUAD, along with investigating the underlying mechanisms. These data highlight the promise of Corynoxine as a novel therapeutic tool for the treatment of individuals diagnosed with LUAD.

In previous studies, structure vibration control mainly focused on integer-order systems or commensurate fractional-order (FO) dynamics systems. In this paper, we propose an adaptive radial basis function (RBF) neural network feedback (ARBF-FK) controller for FO building structure vibration systems with viscoelastic (VE) dampers, uncertain structure parameters and unknown seismic waves. Firstly, use a FO multi-order state space description for FO building structural vibration systems. Then, the design of the ideal feedback controller is based on the stability theory of FO multi-order systems. Moreover, to reduce the cost and facilitate the practical implementation of the control, unknown earthquake seismic waves is approximated by a RBF neural network, the ARBF-FK controller is proposed. In addition, to guarantee the stability of the closed-loop control system and avoid falling into local optimum, network weights are adapted by the FO Lyapunov stability theory instead of gradient descent algorithms. Finally, the convergence rate of the system is analyzed and perform various tests on the ARBF-FK controller. The simulation results demonstrate that the ARBF-FK controller has superior performance and is very robust to control FO building structure vibration systems with uncertain structure parameters and unknown external earthquake excitation.

To study the antioxidant activity of polysaccharides from Dendrobium officinale, the polysaccharide was extracted and purified from Dendrobium officinale, and its preliminary structure was characterized. Free radical scavenging activity and inhibition of low density lipoprotein (LDL) in vitro oxidation of Dendrobium officinale polysaccharides were evaluated. The results showed that the total sugar content of the obtained Dendrobium officinale polysaccharide was 90.17%±3.90%, the protein content was 0.14%±0.05%, the ash content was 4.47%±1.42% and the glucuronic acid content was 2.53%±1.02%, the relative molecular weight was 23970 Da and the monosaccharides were mainly mannose and glucose in this test. Dendrobium officinale polysaccharide had certain free radical scavenging capacity. It could inhibit the production of conjugated diene in the oxidative modification system of LDL. The inhibition rate of thiobarbituric acid reactive substances (TBARS) by copper ion reached 57.46%±0.56% when the polysaccharide concentration was 3.00 mg·mL−1. This study could provide theoretical support for the development of drugs for diseases such as arteriosclerosis due to LDL oxidation.

Abstract This paper adopts the Mariotte siphon to simplify the nutrient solution preparation structure while improving the liquid mixing accuracy for nutrient solution. A liquid mixing model suitable for EC and pH regulation was constructed by combining fuzzy control algorithms, and a set of fertigation nutrient solution control equipment was designed and developed. During the experiment, comparison was made between the Fuzzy-PID algorithm and the traditional PID algorithm in terms of nutrient solution configuration. The results show that the Fuzzy-PID algorithm is smoother and more stable compared to the PID algorithm. Through analysis of the liquid mixing accuracy with the venturi type fertigation machine, it was found that the fertigation machine designed with the Mariotte structure is more accurate for liquid mixing, and can better meet the needs of crop growth.

Abstract Background Wheat (Triticum aestivum L.) is an important grain crops in the world, and its growth and development in different stages is seriously affected by saline-alkali stress, especially in seedling stage. Therefore, nondestructive detection of wheat seedlings under saline-alkali stress can provide more comprehensive technical support for wheat breeding, cultivation and management. Results This research focused on moisture signal prediction and classification of saline-alkali stress in wheat seedlings using fusion techniques. After collecting and analyzing transverse relaxation time and Multispectral imaging (MSI) information of wheat seedlings, four regression models were used to predict the moisture signal. K-Nearest Neighbor (KNN) and Gaussian-Naïve Bayes (GNB) models were combined with fivefold cross validation to classify the prediction of wheat seedling stress. The results showed that wheat seedlings would increase the bound water content through a certain mechanism to enhance their saline-alkali stress. Under the same Na concentration, the effect of alkali stress on moisture, growth and spectrum of wheat seedlings is stronger than salt stress. The Gradient Boosting Decision Regression Tree model performs the best in predicting wheat moisture signals, with a coefficient of determination (R2P) of 0.98 and a root mean square error of 109.60. It also had a short training time (1.48 s) and an efficient prediction speed (1300 obs/s). The KNN and GNB demonstrated significantly enhanced predictive performance when classifying the fused dataset, compared to using single datasets individually. In particular, the GNB model performing best on the fused dataset, with Precision, Recall, Accuracy, and F1-score of 90.30, 88.89%, 88.90%, and 0.90, respectively. Conclusions Under the same Na concentration, the effects of alkali stress on water content, spectrum, and growth of wheat were stronger than that of salt stress, which was more unfavorable to the growth of wheat. The fusion of low-field nuclear magnetic resonance and MSI technology can improve the classification of wheat stress, and provide an effective technical method for rapid and accurate monitoring of wheat seedlings under saline-alkali stress. Graphical Abstract

Abstract Background Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. Results In this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. Conclusions This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Aristolochic Acid I (AAI) is widely present in traditional Chinese medicines derived from the Aristolochia genus and is known to cause significant damage to renal tubular epithelial cells. Genome-wide screening has proven to be a powerful tool in identifying critical genes associated with the toxicity of exogenous substances. To identify undiscovered key genes involved in AAI-induced renal toxicity, a genome-wide CRISPR library screen was conducted in the human kidney-2 (HK-2) cell line. Among the altered sgRNAs, a significant enrichment of those targeting the E2F transcription factor 1 (E2F1) gene was observed in surviving HK-2 cells in the AAI-treated group. Interestingly, the role of E2F1 had not been previously explored in studies of AAI nephrotoxicity. Further investigations revealed that E2F1 promotes apoptosis by activating the p53 signaling pathway and upregulating pro-apoptotic genes, such as BAK and BAX. Additionally, using the high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB), cannabidiol (CBD) was identified as an inhibitor of E2F1 by suppressing the activity of NF-κB pathway. In vitro and in vivo models confirmed that CBD inhibits AAI-induced upregulation of E2F1, thereby suppressing p53-mediated apoptosis. In conclusion, this study highlights the crucial role of E2F1 in AAI-induced renal cell apoptosis and identifies CBD as a novel therapeutic candidate for mitigating AAI nephrotoxicity.

IntroductionHeart failure (HF) has a very high prevalence in patients with maintenance hemodialysis (MHD). However, there is still a lack of effective and reliable HF diagnostic markers and therapeutic targets for patients with MHD.MethodsIn this study, we analyzed transcriptome profiles of 30 patients with MHD by high-throughput sequencing. Firstly, the differential genes between HF group and control group of patients with MHD were screened. Secondly, HF-related genes were screened by WGCNA, and finally the genes intersecting the two were selected as candidate genes. Machine learning was used to identify hub gene and construct a nomogram model, which was verified by ROC curve and RT-qPCR. In addition, we further explored potential mechanism and function of hub genes in HF of patients with MHD through GSEA, immune cell infiltration analysis, drug analysis and establishment of molecular regulatory network.ResultsTotally 23 candidate genes were screened out by overlapping 673 differentially expressed genes (DEGs) and 147 key module genes, of which four hub genes (DEPDC1B, CDCA2, APOBEC3B and TYMS) were obtained by two machine learning algorithms. Through GSEA analysis, it was found that the four genes were closely related to ribosome, cell cycle, ubiquitin-mediated proteolysis. We constructed a ceRNA regulatory network, and found that 4 hub genes (TYMS, CDCA2 and DEPDC1B) might be regulated by 4 miRNAs (hsa-miR-1297, hsa-miR-4465, hsa-miR-27a-3p, hsa-miR-129-5p) and 21 lncRNAs (such as HCP5, CAS5, MEG3, HCG18). 24 small molecule drugs were predicted based on TYMS through DrugBank website. Finally, qRT-PCR experiments showed that the expression trend of biomarkers was consistent with the results of transcriptome sequencing.DiscussionOverall, our results reveal the molecular mechanism of HF in patients with MHD and provide insights into potential diagnostic markers and therapeutic targets.

IntroductionTumor tissues exhibit significantly lower oxygen partial pressure compared to normal tissues, leading to hypoxia in the tumor microenvironment and result in resistance to tumor treatments. Strategies to mitigate hypoxia include enhancing blood perfusion and oxygen supply, for example,by decomposing hydrogen peroxide within the tumor. Improving hypoxia in the tumor microenvironment could potentially improve the efficacy of cancer treatments. Previous studies have demonstrated that ultrasound of appropriate intensity when combined with microbubbles, can improve tumor blood perfusion. However, its effects on tumor hypoxia remain unclear. This study aimed to assess the effects of low-frequency non-focused ultrasound combined with microbubbles at different intensities on tumor microenvironment hypoxia and to identify the optimal ultrasound parameters for alleviating tumor hypoxia.MethodRabbits with VX2 tumors received ultrasound and microbubble treatments at different acoustic pressures and pulse repetition frequencies. The changes in tumor tissue blood perfusion before and after treatment were observed by contrast enhanced ultrasound (CEUS). The changes in tumor tissue hypoxia before and after treatment were observed by measuring oxygen partial pressure directly with in tumor tissue and immunohistochemical staining for hypoxia-inducible factor-1α (HIF-1α).ResultsResults indicated that low frequency, non-focused ultrasound at 0.5 MPa/20 Hz and 0.5 MPa/40 Hz, when combined with microbubbles, could increase tumor tissue blood perfusion and improve the hypoxia in tumor tissues.DiscussionThis study provides a new method for improving hypoxia in the tumor microenvironment (TME) which could potentially improve the cancer treatments resistance.

Benzene exposure has been linked to various adverse health effects. However, the effective strategy for prevention or treatment of benzene-induced hematotoxicity remains unsolved. We previously administrated hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit) mice with benzene via inhalation for 28 days, and found homozygote (HO) mice exhibited alleviative hematotoxicity compared with wild type (WT) mice. Here, we integrate untargeted metabolomics and transcriptomics data to identify the key metabolic pathways and metabolites attenuating benzene-induced hematotoxicity. Metabolomics analysis revealed the perturbation of nicotinate and nicotinamide metabolism, as well as taurine and hypotaurine metabolism pathways, were implicated in regulating benzene-induced hematotoxicity. Meanwhile, transcriptome analysis showed that immune-, inflammation-, and metabolism-related pathways were obviously disturbed in WT mice groups upon benzene exposure, while sirtuin signaling pathway, associated with nicotinate and nicotinamide metabolism, was activated in HO mice groups. Notably, combined metabolomics and transcriptomics analysis further confirmed the involvement of nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism pathways in relieving benzene-induced hematotoxicity. Specific metabolites, including 1-methylnicotinamide (MNA), nicotinamide (NA), β-nicotinamide mononucleotides (NMN), and taurine were identified as the potential metabolites alleviating benzene-induced adverse effects. In vitro experiments demonstrated the protective effect of MNA and NA against 1,4-benzoquinone (1,4-BQ)-caused cytotoxicity in HL-60 cells. In vivo, MNA supplementation in drinking water could effectively restore the decline in white blood cell (WBC), lymphocyte (LYMPH), and reticulocyte (RET) counts, also mitigate oxidative damage and genotoxicity in response to benzene exposure. These observations highlight the potential of MNA supplementation as a strategy for preventing benzene-caused hematotoxicity.

Gut microbiota-derived extracellular vesicles (mEVs) are reported to regulate inflammatory response by delivering bacterial products into host cells. The complement receptor of the immunoglobulin superfamily macrophages (CRIg+ Mφ) could clear invading bacteria and their derivatives. Here, we investigate the role of CRIg+ Mφ and the mechanism by which mEVs regulate intestinal inflammation. We found that it is exacerbated in IBD patients and colitis mice by mEVs’ leakage from disturbed gut microbiota, enriching microbial DNA in the intestinal mucosa. CRIg+ Mφ significantly decrease in IBD patients, allowing the spread of mEVs into the mucosa. The microbial DNA within mEVs is the key trigger for inflammation and barrier function damage. The cGAS/STING pathway is crucial in mEVs-mediated inflammatory injury. Blocking cGAS/STING signaling effectively alleviates inflammation caused by mEVs leakage and CRIg+ Mφ deficiency. Microbial DNA-containing mEVs, along with CRIg+ Mφ deficiency, stimulate inflammation in IBD, with the cGAS/STING pathway playing a crucial role.

Landslide susceptibility maps (LSMs) can play a bigger role in promoting the understanding of future landslides. This paper explores and compares the capability of three state-of-the-art bivariate models, namely the frequency ratio (FR), statistical index (SI), and weights of evidence (WoE), with ensembles of multivariate logistic regression (LR), for LSM in part of Tibet. Firstly, a landslide inventory map with 829 landslide records is obtained from field surveys and interpretation. Secondly, 15 landslide conditioning factors (LCFs) are considered and prepared from multi-data sources. Subsequently, a multicollinearity analysis is conducted to calculate the independence between different factors. Then, the Information Gain Ratio method (IGR) is performed to confirm the predictive ability of the LCFs. Finally, LSMs are constructed by, SI, WoE, LR and their combination through 12 preferred LCFs. The performance of different methods are validated and compared in term of areas under the receiver operating characteristic curve (AUC) and statistical measures. The results from this study indicate the hybrid models FR-LR, WoE-LR and SI-LR achieved higher AUC value than all corresponding single methods. The ensemble frameworks are well in line with the distribution pattern of historical landslides in the research area. Therefore, the proposed high-performance ensemble frameworks are expected to provide a useful reference for landslide hazard prevention in similar areas.

Abstract Astragali radix (AR, namded Huangqi in Chinese) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. As a widely used ethnomedicine, the biological activities of AR include immunomodulatory, anti-hyperglycemic, anti-oxidant, anti-aging, anti-inflammatory, anti-viral, anti-tumor, cardioprotective, and anti-diabetic effects, with minimum side effects. Currently, it is known that polysaccharides, saponins, and flavonoids are the indispensable components of AR. In this review, we will elaborate the research advancements of AR on ethnobotany, ethnopharmacological practices, phytochemicals, pharmacological activities, clinical uses, quality control, production developments, and toxicology. The information is expected to assist clinicians and scientists in developing useful therapeutic medicines with minimal systemic side effects.

Abstract Background Hypertension, sleep disorders, and depression represent notable public health issues, and their interconnected nature has long been acknowledged. The objective of this study is to explore the interplay between sleep disorders and depression in the context of hypertension. Methods This cross-sectional study involved 42,143 participants aged 18 and above from the NHANES database across seven survey cycles between 2005 and 2018. After excluding those with missing data on depression, sleep disorders, and hypertension, as well as incomplete main variables, 33,383 participants remained. We used weighted logistic regression to examine the relationship between sleep disorders, depression, and hypertension. Additionally, we assessed the interaction between sleep disorders and depression on hypertension using both multiplicative and additive approaches to quantify their combined effect. Results Compared to individuals without sleep disorders, those with sleep disorders have an increased risk of hypertension (OR = 1.51, 95% CI: 1.37–1.67). Furthermore, individuals with depression experience a significantly higher risk of hypertension compared to those with sleep disorders alone (OR = 2.34, 95% CI: 1.95–2.80). Our study reveals a positive interaction between sleep disorders and depression in relation to hypertension risk (OR = 1.07, 95% CI: 1.02–1.13). In addition, we observed the quantitative additive interaction indicators (RERI = 0.73, 95% CI: 0.56 ~ 0.92; API = 0.31, 95% CI: 0.11 ~ 0.46; SI = 2.19, 95% CI: 1.08–3.46) influencing hypertension risk. Furthermore, our research also identified that individuals with less than 7 h of sleep, a sleep latency period between 5 and 30 min, or a latency period exceeding 30 min experience a significantly increased risk of hypertension. Conclusions Our research uncovered separate links between sleep disorders, depression, and hypertension prevalence. Moreover, we identified an interaction between depression and sleep disorders in hypertension prevalence. Enhancing mental well-being and tackling sleep disorders could help prevent and manage hypertension. Yet, more investigation is required to establish causation and clarify mechanisms.

Abstract Since the oncogenic rearranged during transfection (RET) gene fusion was discovered in non-small cell lung cancer (NSCLC) in 2012, multiple-targeted kinase inhibitors (MKIs) cabozantinib and vandetanib have been explored in the clinic for RET positive NSCLC patients. As the nonselective nature of these inhibitors, patients have off-target adverse effects. The discovery of highly potent selective RET inhibitors such as pralsetinib and selpercatinib improve the clinic efficiency and more favorable toxicity profile. However, acquired resistance mediated by secondary mutations in the solvent-front region of the kinase (e.g. G810C/S/R) become a new challenge for selective RET inhibitor therapies. In this review, we highlight typical RET inhibitors developed during these years and provide a reference for more potential RET inhibitors exploration in the future.

Abstract Introduction Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. Methods In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). Results (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p

Acute myeloid leukemia (AML), a malignant disorder of the hematopoietic system, arises from leukemic stem cells (LSCs) and is the most prevalent form of blood cancer in adults. This study aimed to evaluate the therapeutic potential of polydatin (PD) in AML through ex vivo and in vivo studies, respectively. This study was prompted by PD’s novel role in enhancing tumor apoptosis and modulating autophagy. In vitro studies were conducted using the PD-responsive AML cell line KASUMI-1 and found that PD was able to suppress cell proliferation and induce apoptosis by regulating the autophagy pathway. Subsequently, molecular docking was employed to predict the interaction between PD and Autophagy-related protein 5 (ATG5), a key regulator in the autophagy pathway. It was observed that PD inhibited the ubiquitination of ATG5 and enhanced its protein stability, leading to an increase in ATG5 protein levels and subsequent activation of the autophagy pathway (see in Abstract Graphed). The effectiveness and safety of PD in treating AML were confirmed through in vivo experiments using a mouse transplant tumor model, yielding definitive results. Collectively, these results suggest that PD is a promising candidate for the early therapeutic intervention of AML, with a strong potential for clinical application.

BackgroundHerbal products have long been utilized as remedies for various disease conditions, including infections. This study investigates the therapeutic mechanism of a traditional Chinese herbal combination in treating high-risk HPV infections.MethodsThe herbal formula was prepared using common herbs: dry Millettia speciosa, Guanzhong (a spermatophyte), Sarsaparilla, White Fruit, and Cockscomb Flower. Eight female patients diagnosed with high-risk HPV were enrolled from January to September 2023 at Shenzhen Hospital of Beijing University of Traditional Chinese Medicine. Cervicovaginal secretions were collected before and after treatment with the herbal remedy and analyzed using non-targeted metabolomics techniques. In vitro studies were conducted using HeLa cells to determine the optimal effective concentration of the remedy, assessed via the CCK8 method. The proliferation and migration of HeLa cells were evaluated using Transwell assays. Quantitative PCR was employed to measure mRNA levels of endothelial-to-mesenchymal transition (EndMT) markers, including VE-Cadherin, eNOS, α-SMA, and Snail.ResultsIn vivo, significant alterations in cervicovaginal secretion metabolites post-treatment were observed through PCA, OPLS-DA, and volcano plot analyses. KEGG enrichment analysis highlighted crucial signaling pathways such as arginine and proline metabolism, purine metabolism, glycerophospholipid metabolism, and phenylalanine metabolism, indicating the herbal combination’s systemic effects on patients. In vitro experiments demonstrated a dose-dependent reduction in HeLa cell proliferation and migration, confirmed by scratch and Transwell assays. Additionally, qPCR analysis revealed down-regulation of α-SMA and Snail, and up-regulation of VE-Cadherin and eNOS, suggesting inhibition of EndMT in HeLa cells.ConclusionThe traditional Chinese herbal combination modulates key metabolic pathways in vivo and inhibits EndMT in vitro, while reducing HeLa cell proliferation and migration. These findings highlight its potential as a therapeutic approach for managing HPV infections, bridging traditional practices with scientific research.

BackgroundLactate dehydrogenase A (LDHA) has been confirmed as a tumor promoter in various cancers, but its role in endometrial cancer remains unclear.MethodsThe Cancer Genome Atlas (TCGA), quantitative real-time polymerase chain reaction and the Human Protein Atlas were utilized to analyzed the LDHA expression in EC. The LDHA levels of patients with different clinical features were compared based on the TCGA cohort. The Genome Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis of LDHA-related genes were conducted by R language. The influence of LDHA knockdown on cell proliferation, apoptosis, migration and invasion was detected by in vitro experiment. The relationship between LDHA expression and immune infiltration was explored by Tumor Immune Estimation Resource 2.0 and Gene Expression Profiling Interactive Analysis. The association of LDHA level with N6-methyladenosine (m6A) modification and ferroptosis was investigated based on the TCGA-UCEC and the GEO cohort.ResultsThe LDHA was overexpressed in EC tissues and EC cell lines, and had high predictive accuracy for the EC diagnosis. The LDHA level was associated with age, histological type, histologic grade, and radiation therapy. LDHA-related genes participated in multiple biological functions and signaling pathways. LDHA downregulation significantly promoted cell apoptosis and inhibited the proliferation, migration, and invasion of EC cells. LDHA expression was connected to multiple tumor-infiltrating lymphocytes (TILs), m6A-related genes, and ferroptosis-related genes.ConclusionLDHA has the potential to work as an EC biomarker associated with TILs, m6A modification, and ferroptosis in EC.

BackgroundThe global COVID-19 pandemic has highlighted critical concerns surrounding mental health. Social isolation measures, such as the quarantine of incoming travelers, are essential public health strategies for the prevention and control of infectious diseases. However, quarantine can lead to adverse psychological outcomes, including feelings of confinement, boredom, perceived scarcity of supplies and information, financial hardship, and social stigma. This study aims to assess the mental states of quarantined individuals, investigate the factors affecting their mental well-being, and examine their coping mechanisms, with the objective of providing recommendations to enhance mental health in anticipation of future outbreaks, such as Disease X.MethodsWe surveyed 327 individuals in quarantine from September 22, 2020 to January 9, 2021, collecting general demographic data and information related to COVID-19. Depression and anxiety were assessed using the PHQ-9 and GAD-7 scales, respectively, while stress coping was evaluated with a simplified version of the Cope scale. We analyzed the relationships between independent variables and mental health outcomes.ResultsAmong the individuals undergoing entry quarantine, 27.8% reported symptoms of depression, and 20.5% reported symptoms of anxiety. Students were more likely to experience depression compared to those with permanent jobs or no occupation. Significant risk factors for both depression and anxiety included pre-existing health conditions, lack of medical insurance, concerns about shortages of daily necessities during quarantine, and high scores for “guilt and self-blame.” Additionally, participants who worried about the impact of the epidemic on their studies or work, and those with high scores for “denial,” were more likely to exhibit depressive symptoms. On the other hand, participants who were concerned about potential rejection or discrimination from the outside world after quarantine were more prone to anxiety symptoms.ConclusionAttention should be paid to the negative psychological reactions of the entry quarantined personnel, especially those with pre-existing health conditions, those without medical insurance, and students studying abroad. Accurate and effective epidemic dynamic information and preventive and control measures can be provided to the public to prevent fear and stigma against quarantined personnel.

ObjectiveThe purpose of this study was to investigate the epidemiological and genomic characteristics of Vibrio parahaemolyticus (V. parahaemolyticus) isolates from outbreaks in Huzhou, China.MethodsThis study aims to analyze the epidemiological data on V. parahaemolyticus outbreaks reported in Huzhou from 2019 to 2023. A total of 70 V. parahaemolyticus outbreak isolates were collected. The antibiotic resistance, serotypes, molecular typing, and genomic characteristics of these isolates were analyzed.ResultsMost outbreaks of V. parahaemolyticus infection occurred in the summer, and the majority of outbreaks occurred in restaurants and rural banquets. High resistance rates were observed for ampicillin (AMP, 24.29%), followed by tetracycline (TET, 15.71%) and trimethoprim-sulfamethoxazole (SXT, 15.71%). The newly emerged serotype O10:K4 became dominant from 2021 to 2023, with most isolates belonging to ST3. The resistance gene blaCARB was frequently detected among these isolates. The pulsed-field gel electrophoresis (PFGE) and whole-genome single-nucleotide polymorphisms (wgSNPs) effectively differentiated the nine outbreaks.ConclusionThe newly emerged serotype O10:K4 became dominant from 2021 to 2023, with most isolates being ST3. PFGE and WGS technologies provided reliable methods for typing and identifying V. parahaemolyticus for outbreaks.

A variable fractional-order (VFO) fuzzy sliding mode controller is designed to control the speed of a permanent magnet synchronous motor (PMSM). First, a VFO sliding mode surface is established. Then, a VFO fuzzy sliding mode controller is designed, capable of suppressing the effects of parameter uncertainties and disturbances to achieve precise PMSM speed control. The global stability and finite time convergence of the controlled system state are demonstrated using Lyapunov stability theory. The numerical and experimental results validate the effectiveness of the controller, showing better immunity to disturbances and a smaller overshoot compared to PID and fixed-order fuzzy sliding mode controllers.

Addressing the challenges of complex structure, limited modularization capability, and insufficient responsiveness in traditional hydraulically driven inter-plant mechanical weeding equipment, this study designed and developed an electric swing-type opening and closing intra-row weeding control system. The system integrates deep learning technology for accurate identification and localization of cabbage, enabling precise control and dynamic obstacle avoidance for the weeding knives. The system’s performance was comprehensively evaluated through laboratory and field experiments. Laboratory experiments demonstrated that, under conditions of low speed and large plant spacing, the system achieved a weeding accuracy of 96.67%, with a minimum crop injury rate of 0.83%. However, as the operational speed increased, the weeding accuracy decreased while the crop injury rate increased. Two-way ANOVA results indicated that operational speed significantly affected both weeding accuracy and crop injury rate, whereas plant spacing had a significant effect on weeding accuracy but no significant effect on crop injury rate. Field experiment results further confirmed that the system maintained high weeding accuracy and crop protection under varying speed conditions. At a low speed of 0.1 m/s, the weeding accuracy was 96.00%, with a crop injury rate of 1.57%. However, as the speed increased to 0.5 m/s, the weeding accuracy dropped to 81.79%, while the crop injury rate rose to 5.49%. These experimental results verified the system’s adaptability and reliability in complex field environments, providing technical support for the adoption of intelligent mechanical weeding systems. Future research will focus on optimizing control algorithms and feedback mechanisms to enhance the system’s dynamic response capability and adaptability, thereby advancing the development of sustainable agriculture and precision field management.

To address the needs of mechanized tomato leaf pruning, this paper presents the design of an end-effector capable of adaptive positioning at the base of the branch. This design effectively prevents infection at the cut sites of a residual branch and protects the rest of the plant from damage. The design objectives for the pruning actuator were established through the measurement of key parameters related to the morphology and mechanical properties of the lateral branch. Based on this foundation, we developed an innovative gripper featuring a spiral guide groove, enabling simultaneous axial traction and radial cutting of the branch. This design ensures that the branch–stem junction conforms to the cutting blade under shear stress, achieving the required adaptive positioning. By analyzing the mechanical properties of the lateral branch, we modeled the actuator’s traction and cutting forces to determine the key geometric parameters of the spiral fingers and the necessary driving torque. We validated the actuator’s operational effectiveness through discrete element simulation and practical application tests. The experimental results indicate that when removing the branch, a traction force of 32.5 N and a cutting force of 66.3 N are generated. Harvesting effectiveness tests conducted in the tomato field achieved a success rate of 85%. This research offers technical support for the development of handheld pruning devices and pruning robots.

Energy demand has been increasing, and environmental concerns associated with energy consumption have emerged worldwide [...]

Abstract Background Neuroblastoma (NB) is a heterogeneous pediatric solid tumour strongly influenced by epigenetic modifications. Methods This review explores the role of N6‐methyladenosine (m6A) modifications and their readers in NB progression. Results Dysregulation of m6A readers, including YTHDF1/2, YTHDC1, IGF2BP1/2/3, HNRNPA2B1 and HNRNPC, has been associated with susceptibility and progression. Conclusion Understanding the crosstalk between m6A readers and NB could offer new insights into diagnosis, prognosis, and treatment strategies.

Listeria monocytogenes are considered to be the major foodborne pathogen worldwide. To understand the prevalence and potential risk of L. monocytogenes in retail foods, a total of 1243 retail foods in 12 food categories were sampled and screened for L. monocytogenes from 2020 to 2022 in Huzhou, China. A total of 46 out of 1234 samples were confirmed to be L. monocytogenes positive with a total rate of 3.7%. The contamination rate of seasoned raw meat (15.2%) was the highest, followed by raw poultry meat and raw livestock meat (9.9%) and salmon sashimi (9.5%). The L. monocytogenes isolates belonged to four serotypes, 1/2a,1/2b, 1/2c, and 4b, with the most prevalent serotype being 1/2a (47.9%). All isolates were grouped into 15 sequence types (STs) belonging to 14 clonal complexes (CCs) via multilocus sequence typing (MLST). The most prevalent ST was ST9/CC9 (23.9%), followed by ST3/CC3 (19.6%) and ST121/CC121 (17.4%). Notably, 11 STs were detected from ready-to-eat (RTE) foods, some of them have been verified to be strongly associated with clinical origin listeriosis cases, such as ST3, ST2, ST5, ST8, and ST87. Listeria pathogenicity islands 1 (LIPI-1) and LIPI-2 were detected in approximately all L. monocytogenes isolates, whereas the distribution of both LIPI-3 genes and LIPI-4 genes exhibited association with specific ST, with LIPI-3 in ST3 and ST288, and LIPI-4 in ST87. The strains carrying LIPI-3 and LIPI-4 virulence genes in this study were all isolated from RTE foods. Antimicrobial susceptibility tests showed that >90% of isolates were susceptible to PEN, AMP, ERY, CIP, SXT, VAN, CHL, and GEN, indicating the antibiotic treatment might be still efficient for most of the L. monocytogenes strains. However, for the three clinical first-line antibiotics (PEN, AMP, and GEN), we also observed three and four strains showing MIC values greater than the susceptibility standards for PEN and AMP, respectively, and one strain showing resistance to GEN.

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.

BackgroundThe causal relationship between daily habits, diseases, drugs, and knee osteoarthritis (KOA) remains unclear. This study utilized a two-sample Mendelian randomization (MR) method to investigate the causal links between these factors and KOA, providing new insights for KOA prevention.MethodsSNPs strongly associated with exposure factors (daily habits, diseases, drugs) were extracted from publicly available genome-wide association study (GWAS) as instrumental variables (IVs). We then selected GWAS of KOA as the outcome, conducting a two-sample MR analysis.ResultsOur findings revealed significant causal relationships between several factors and KOA. There was a notable association with time spent watching TV (OR = 4.038; 95% CI: 1.859–8.770; P = 4.192E-04), frequency of friend/family visits (OR = 0.415; 95% CI: 0.219–0.788; P = 7.174E-03), smoking history (OR = 0.781; 95% CI: 0.663–0.921; P = 3.235E-03), gastroesophageal reflux disease (GERD) (OR = 1.519; 95% CI: 1.244–1.856; P = 4.183E-05), hypercholesterolemia (OR = 0.498; 95% CI: 0.290–0.855; P = 0.011), hypothyroidism (OR = 1.048; 95% CI: 1.013–1.084; P = 6.645E-03), use of antithrombotic agents (OR = 0.892; 95% CI: 0.816–0.976; P = 0.013), statin medication (OR = 0.956; 95% CI: 0.916–0.998; P = 0.041), and thyroid preparations (OR = 1.042; 95% CI: 1.014–1.071; P = 2.974E-03) with KOA. Specifically, KOA was positively associated with longer time spent watching TV, GERD, hypothyroidism and thyroid preparations, however showed a negative correlation with more frequent visits from friends or family, smoking history, hypercholesterolemia, antithrombotic agents and statin medication. Sensitivity analysis indicated no significant pleiotropy in these studies (P > 0.05).ConclusionThis comprehensive study underscores the significance of modifying certain habits to mitigate the risk of KOA. Additionally, the elevated risk of KOA among individuals with GERD, hypothyroidism, and those using thyroid preparations warrants attention. These results would be beneficial for clinical research and nursing education.

BackgroundStudies have shown that work readiness is closely related to nurses’ role adaptation, career development, and patient safety. However, we know little about the nursing students’ work readiness and its influencing factors before participating in a nurse residency program, and whether factors have changed from before.Aim(1) To investigate the work readiness of nursing students ready to engage in a nurse residency program; (2) to identify the factors affecting the nursing students’ work readiness and the associations between emotional intelligence and work readiness; and (3) to discuss the changes of factors affecting nursing students’ work readiness.DesignAn online, multicenter cross-sectional study.Methods878 nursing students from eight tertiary hospitals in Chongqing, China were recruited. The online investigation used the General Information Questionnaire, the Nursing Students’ Work Readiness Scale, and the Emotional Intelligence scale. The data were analyzed using IBM SPSS V23.0.Results768 valid questionnaires were included in this study. The nurses obtained a work readiness score of 277.08 ± 44.39 and an emotional intelligence score of 89.57 ± 13.89. Univariate analysis revealed that the following factors affected work readiness: age, sex, family support for becoming a nurse, voluntary choice of nursing major, previous experience as a student cadre, scholarship recipient status, willingness to engage in nursing work during the COVID-19 pandemic and confidence in clinical nursing practice. Frequent incidents of violence, poor salary for nurses for the nurse residency program, and low social acceptance were the top three reasons for decreased confidence in clinical nursing among nursing students. Furthermore, multiple linear regression analysis indicated that age, voluntary choice of nursing major, student leadership experience, confidence in clinical nursing work, self-emotion, and emotional application significantly influenced nurses’ work readiness.ConclusionClinical instructors and administrators should dynamically assess nurses’ work readiness, prioritize individuals aged ≤23, who have chosen the nursing profession involuntarily, lack prior experience as student cadres, and exhibit low confidence in clinical nursing work. This focus will enhance their emotional self-management skills and ability to apply emotions effectively, improving their work readiness and training efficacy.

Candidatus Accumulibacter, a prominent polyphosphate-accumulating organism (PAO) in wastewater treatment, plays a crucial role in enhanced biological phosphorus removal (EBPR). The genetic underpinnings of its polyphosphate accumulation capabilities, however, remain largely unknown. Here, we conducted a comprehensive genomic analysis of Ca. Accumulibacter-PAOs and their relatives within the Rhodocyclaceae family, identifying 124 core genes acquired via horizontal gene transfer (HGT) at its least common ancestor. Metatranscriptomic analysis of an enrichment culture of Ca. Accumulibacter revealed active transcription of 44 of these genes during an EBPR cycle, notably including the polyphosphate kinase 2 (PPK2) gene instead of the commonly recognized polyphosphate kinase 1 (PPK1) gene. Intriguingly, the phosphate regulon (Pho) genes showed minimal transcriptions, pointing to a distinctive fact of Pho dysregulation, where PhoU, the phosphate signaling complex protein, was not regulating the high-affinity phosphate transport (Pst) system, resulting in continuous phosphate uptake. To prevent phosphate toxicity, Ca. Accumulibacter utilized the laterally acquired PPK2 to condense phosphate into polyphosphate, resulting in the polyphosphate-accumulating feature. This study provides novel insights into the evolutionary emergence of the polyphosphate-accumulating trait in Ca. Accumulibacter, offering potential advancements in understanding the PAO phenotype in the EBPR process.

Farmland soil organisms frequently encounter pesticide mixtures presented in their living environment. However, the underlying toxic mechanisms employed by soil animals to cope with such combined pollution have yet to be explored. This investigation aimed to reveal the changes in cellular and mRNA levels under chlorpyrifos (CPF) and lambda-cyhalothrin (LCT) co-exposures in earthworms (Eisenia fetida). Results exhibited that the combination of CPF and LCT triggered an acute synergistic influence on the animals. Most exposures resulted in significant alterations in the activities of total superoxide dismutase (T-SOD), copper/zinc superoxide dismutase (Cu/Zn-SOD), caspase 3, and carboxylesterase (CarE) compared to the basal level. Moreover, when exposed to chemical mixtures, the transcription levels of four genes [heat shock protein 70 (hsp70), gst, sod, and calreticulin (crt)] also displayed more pronounced changes compared with their individual exposures. These changes in determined parameters indicated the occurrence of oxidative stress, cell death, detoxification dysfunction, and endoplasmic reticulum damage after co-exposure to CPF and LCT in E. fetida. The comprehensive examination of mixture toxicities of CPF and LCT at different endpoints would help to understand the overall toxicity they cause to soil invertebrates. The augmented deleterious effect of these pesticides in a mixture suggested that mixture toxicity assessment was necessary for the safety evaluation and application of pesticide mixtures.

Introduction: Since its identification in April 2009, influenza A(H1N1)pdm09 virus has continued to cause significant outbreaks of respiratory tract infections, including pandemics in humans. In the course of its evolution, the virus has acquired many mutations that cause increased disease severity. Regular molecular surveillance of the virus is essential to mark the evolutionary changes that may cause a shift in viral behavior. Methods: Twenty-five (H1N1)pdm09 isolates from Huzhou, China, in 2023 were randomly selected for whole-genome sequencing along with analysis of nucleotide and amino acid sequence identity, average genetic distance, antigen variation sites, receptor binding sites, pathogenicity, potential glycosylation sites, and drug resistance gene sites. Results: The 25 (H1N1)pdm09 strains and representative 2023–2024 northern hemisphere vaccine strain A/Wisconsin/67/2022 showed nucleotide and amino acid similarity of 98.41 %–99.22 % and 98.41 %–99.36 %, respectively. This virus belongs to the 6B1A.5a.2a evolutionary lineage. There were 19 amino acid variations in hemagglutinin (HA) protein. Substitutions S137P and R142K occurred in the epitope Ca2 cluster. A total of 13 amino acids were mutated in neuraminidase (NA) protein, and 9 key protease active sites and amino acid sites related to NA inhibitor (NAI) resistance were not mutated. Five amino acid sites of matrix-2 (M2) protein associated with drug resistance were not replaced, but amino acid 31 of M2 protein was shown to be N in the 2023 pandemic strain (H1N1)pdm09 and vaccine strain A/Wisconsin/67/2022. There were seven and eight potential glycosylation sites for HA protein and NA protein, respectively. Compared with the vaccine strains, there were no new or missing potential glycosylation sites in the 25 (H1N1)pdm09 influenza virus isolates. No multiple continuous alkaline amino acids were found in the HA cleavage site of the 25 isolates. Conclusions: The recommended vaccine strain A/Wisconsin/67/2022 has good prevention potential against the current circulating influenza (H1N1)pdm09. At present, NAIs have good therapeutic and preventive effects against (H1N1)pdm09 circulating in Huzhou, China, but the virus is naturally resistant to amantadines. At present, the (H1N1)pdm09 strain circulating in Huzhou, China, is characterized by low pathogenicity. However, regular molecular surveillance of (H1N1)pdm09 is important to monitor the behavior of the virus in terms of increases in virulence, drug resistance, and emergence of novel strains.

BackgroundDespite the known associations of dietary magnesium intake and estimated glomerular filtration rate (eGFR) with cardiovascular diseases, their combined effects on stroke risk remain unclear. Therefore, this study aims to explore the associations of dietary magnesium intake and eGFR with stroke risk.MethodsThe National Health and Nutrition Examination Survey (NHANES) data of 37,637 adult participants (≥18 years) from 2003 to 2018 was analyzed. Dietary magnesium intake was categorized as low (≤ 254 mg/day) and normal (> 254 mg/day) based on experimental data. Multiple logistic regression analyses and interaction tests were conducted to assess the associations of dietary magnesium intake and eGFR with stroke risk, with a focus on the interaction between different chronic kidney disease (CKD) stages based on eGFR levels and dietary magnesium intake. Additional analyses included multiplicative interaction analysis, restricted cubic spline analysis, and subgroup evaluations by age, sex, and ethnicity.ResultsDietary magnesium intake and eGFR were inversely correlated with the risk of stroke. Participants with low dietary magnesium intake had a higher stroke risk than those with normal magnesium intake (odds ratio [OR] 1.09, 95% confidence interval [CI]: 1.03–1.42). Likewise, low eGFR was associated with an elevated stroke risk compared with normal eGFR (OR 1.56, 95% CI: 1.15–2.13). Furthermore, the two factors showed a multiplicative interaction effect on stroke risk (OR 1.05, 95% CI: 1.01–1.09). We observed a significant interaction between stage G3 CKD and low dietary magnesium intake (OR 1.05, 95% CI: 1.01–1.09), suggesting a potential association with stroke risk. However, similar associations were not observed for stages G4 and G5, possibly due to the smaller number of participants with G4 and G5 CKD. The restricted cubic spline analysis revealed a non-linear relationship between dietary magnesium intake, eGFR, and stroke risk. The interaction between magnesium deficiency and low eGFR persisted in participants aged >60 years, as well as in females, non-Hispanic Black people, and people of other races.ConclusionDietary magnesium intake and eGFR correlate negatively with stroke prevalence. Moreover, there was an interaction between dietary magnesium intake and stroke prevalence across different CKD stages. Further large-scale prospective studies are needed to analyze the potential relationship between dietary magnesium intake, eGFR, and stroke.

Ligustrum lucidum W.T. Aiton is an outstanding herb with the homology of medicine and food. Its ripe fruits are traditionally used as an important tonic for kidneys and liver in China. Ligustrum lucidum W.T. Aiton is rich in nutritional components and a variety of bioactive ingredients. A total of 206 compounds have been isolated and identified, they mainly include flavonoids, phenylpropanoids, iridoid glycosides, and triterpenoids. These compounds exert anti-osteoporosis, anti-tumor, liver protective, antioxidant, anti-inflammatory, and immunomodulatory effects. Ligustrum lucidum W.T. Aiton has been traditionally used to treat many complex diseases, including osteoporotic bone pain, rheumatic bone, cancer, related aging symptoms, and so on. In the 2020 Edition of Chinese Pharmacopoeia, there are more than 100 prescriptions containing L. lucidum W.T. Aiton. Among them, some classical preparations including Er Zhi Wan and Zhenqi fuzheng formula, are used in the treatment of various cancers with good therapeutic effects. Additionally, L. lucidum W.T. Aiton has also many excellent applications for functional food, ornamental plants, bioindicator of air pollution, algicidal agents, and feed additives. Ligustrum lucidum W.T. Aiton has rich plant resources. However, the application potential of it has not been fully exploited. We hope that this paper provides a theoretical basis for the high-value and high-connotation development of L. lucidum W.T. Aiton in the future.

Abstract Background At present, neonatal hypoxic‐ischemic encephalopathy (HIE), especially moderate to severe HIE, is a challenging disease for neonatologists to treat, and new alternative/complementary treatments are urgently needed. The neuroinflammatory cascade triggered by hypoxia‐ischemia (HI) insult is one of the core pathological mechanisms of HIE. Early inhibition of neuroinflammation provides long‐term neuroprotection. Plant‐derived monomers have impressive anti‐inflammatory effects. Aloesin (ALO) has been shown to have significant anti‐inflammatory and antioxidant effects in diseases such as ulcerative colitis, but its role in HIE is unclear. To this end, we conducted a series of experiments to explore the potential mechanism of ALO in preventing and treating brain damage caused by HI insult. Materials and Methods Hypoxic‐ischemic brain damage (HIBD) was induced in 7‐day‐old Institute of Cancer Research (ICR) mice, which were then treated with 20 mg/kg ALO. The neuroprotective effects of ALO on HIBD and the underlying mechanism were evaluated through neurobehavioral testing, infarct size measurement, apoptosis detection, protein and messenger RNA level determination, immunofluorescence, and molecular docking. Results ALO alleviated the long‐term neurobehavioral deficits caused by HI insult; reduced the extent of cerebral infarction; inhibited cell apoptosis; decreased the levels of the inflammatory factors interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α; activated microglia and astrocytes; and downregulated the protein expression of members in the TLR4 signaling pathway. In addition, molecular docking showed that ALO can bind stably to TLR4. Conclusion ALO ameliorated HIBD in neonatal mice by inhibiting the neuroinflammatory response mediated by TLR4 signaling.

Cancer-induced bone pain (CIBP) significantly impacts the quality of life and survival of patients with advanced cancer. Despite the established role of neurexins in synaptic structure and function, their involvement in sensory processing during injury has not been extensively studied. In this study using a rat model of CIBP, we observed increased neurexin 2 expression in spinal cord neurons. Knockdown of neurexin 2 in the spinal cord reversed CIBP-related behaviors, sensitization of spinal c-Fos neurons, and pain-related negative emotional behaviors. Additionally, increased acetylation of neurexin 2 mRNA was identified in the spinal dorsal horn of CIBP rats. Decreasing the expression of N-acetyltransferase 10 (NAT10) reduced neurexin 2 mRNA acetylation and neurexin 2 expression. In PC12 cells, we confirmed that neurexin 2 mRNA acetylation enhanced its stability, and neurexin 2 expression was regulated by NAT10. Finally, we discovered that the NAT10/ac4C-neurexin 2 axis modulated neuronal synaptogenesis. This study demonstrated that the NAT10/ac4C-mediated posttranscriptional modulation of neurexin 2 expression led to the remodeling of spinal synapses and the development of conscious hypersensitivity in CIBP rats. Therefore, targeting the epigenetic modification of neurexin 2 mRNA ac4C may offer a new therapeutic approach for the treatment of nociceptive hypersensitivity in CIBP.

Elucidating the genetic basis of natural variation in grain size and weight among rice varieties can help breeders develop high-yielding varieties. We identified a novel gene, GW3a (Grain Weight 3a) (LOC_Os03g27350), that affects rice grain size and weight. gw3a mutants showed higher total starch content and dry matter accumulation than the wild type (WT), Nipponbare, suggesting that GW3a negatively regulates grain size and weight. Moreover, our study found that GW3a interacted with OsATG8 by cleaving it, suggesting that GW3a may be involved in the assembly of autophagosomes and starch degradation in plants. The haplotype analysis of GW3a showed functional differences between indica and japonica rice. Taken together, we conclude that GW3a is expressed in the autophagosome pathway regulating starch metabolism in rice, affecting yield-related traits, such as grain size, grain weight and thousand grain weight (TGW). Our findings also shed new light on autophagy-mediated yield trait regulation, proposing a possible strategy for the genetic improvement of high-yield germplasm in rice.

Abstract Background Attention provides the foundation for cognitions, which was shown to be affected by microwave (MW) radiation. With the ubiquitous of microwaves, public concerns regarding the impact of MW radiation on attention has hence been increased. Our study aims to investigate the potential effect and mechanism of acute microwave exposure on attention. Results We identified obvious impairment of attention in mice by the five-choice serial reaction time (5-CSRT) task. Proteomic analysis of the cerebrospinal fluid (CSF) revealed neuroinflammation and microglial activation potentially due to acute MW exposure. Moreover, biochemical analysis further confirmed microglial activation in the prefrontal cortex (PFC) of mice subjected to acute MW exposure. Finally, minocycline, a commercially available anti-inflammatory compound, attenuated neuroinflammation, inhibited the upregulation of N-methyl-D-aspartic acid receptor (NMDAR) including NR2A and NR2B, and also accelerated the attentional recovery after MW exposure. Conclusions We believe that microglial activation and NMDAR upregulation likely contribute to inattention induced by acute MW exposure, and we found that minocycline may be effective in preventing such process.

Abstract Background Lung cancer is a malignant tumor with the highest mortality worldwide. Abnormalities in the ubiquitin proteasome system are considered to be contributed to lung cancer progression with deleterious effects. DDB1 and CUL4 associated factor 13 (DCAF13) is a substrate receptor of the E3 ubiquitin ligase CRL4, but its role in lung cancer remains unknown. In this study, we aimed to investigate the regulatory mechanisms of DCAF13 in lung adenocarcinoma (LUAD). Methods So as to investigate the effect of DCAF13 on lung adenocarcinoma cell function using in vivo and in vitro. Mechanistically, we have identified the downstream targets of DCAF13 by using RNA-sequencing, as well as ubiquitination assays, co-immunoprecipitation, immunofluorescence, immunohistochemistry and chromatin immunoprecipitation - qPCR experiments. Results Our findings reveal that DCAF13 is a carcinogenic factor in LUAD, as it is highly expressed and negatively correlated with clinical outcomes in LUAD patients. Through RNA-sequencing, it has been shown that DCAF13 negatively regulates the p53 signaling pathway and inhibits p53 downstream targets including p21, BAX, FAS, and PIDD1. We also demonstrate that DCAF13 can bind to p53 protein, leading to K48-linked ubiquitination and degradation of p53. Functionally, we have shown that DCAF13 knockdown inhibits cell proliferation and migration. Our results highlight the significant role of DCAF13 in promoting LUAD progression by inhibiting p53 protein stabilization and the p53 signaling pathway. Furthermore, our findings suggest that high DCAF13 expression is a poor prognostic indicator in LUAD, and DCAF13 may be a potential therapeutic target for treating with this aggressive cancer. Conclusions The DCAF13 as a novel negative regulator of p53 to promote LUAD progression via facilitating p53 ubiquitination and degradation, suggesting that DCAF13 might be a novel biomarker and therapeutical target for LUAD.

This paper investigates iterative learning control for Caputo fractional-order systems with one-sided Lipschitz nonlinearity. Both open- and closed-loop P-type learning algorithms are proposed to achieve perfect tracking for the desired trajectory, and their convergence conditions are established. It is shown that the algorithms can make the output tracking error converge to zero along the iteration axis. A simulation example illustrates the application of the theoretical findings, and shows the effectiveness of the proposed approach.