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Abstract Background Increasing evidences suggest that nonalcoholic fatty liver disease (NAFLD) is associated with neuropsychiatric disorders. Nevertheless, whether there were causal associations between them remained vague. A causal association between neuropsychiatric disorders and NAFLD was investigated in this study. Methods We assessed the published genome-wide association study summary statistics for NAFLD, seven mental disorder-related diseases and six central nervous system dysfunction-related diseases. The causal relationships were first assessed using two-sample and multivariable Mendelian randomization (MR). Then, sensitivity analyses were performed, followed by a reverse MR analysis to determine whether reverse causality is possible. Finally, we performed replication analyses and combined the findings from the above studies. Results Our meta-analysis results showed NAFLD significantly increased the risk of anxiety disorders (OR = 1.016, 95% CI = 1.010–1.021, P value

Abstract Background The association of plastic additive mixture exposure with diabetes and the modifying effects of dietary antioxidants are unclear. Methods The data from the NHANES 2011–2018 were retrieved, and phthalates and organophosphate esters (OPEs) were selected as exposures. The coexposure effect was analyzed by the environmental risk score (ERS) and quantile g-computation. To mitigate any potential bias caused by using the internal weights, another version of ERS was constructed using the cross-validation approach. The level of dietary antioxidant intake was measured by the composite dietary antioxidant index (CDAI). The biological mechanism underlying the association was studied by the adverse outcome pathway (AOP) framework. Results Fifteen chemicals (ten phthalates and five OPEs) were measured in 2824 adult participants. A higher ERS was significantly associated with an increased risk of diabetes (OR per 1-SD increment of ERS: 1.25, 95% CI: 1.13–1.39). This association apparently interacted with the CDAI level (ORlow: 1.83, 95% CI: 1.37–2.55; ORhigh: 1.28, 95% CI: 1.15–1.45; P interaction = 0.038). Moreover, quantile g-computation also revealed higher level of combined exposure was positively associated with diabetes (OR: 1.27, 95% CI: 1.05–2.87), and the addition of dietary antioxidants showed a null association (OR: 1.09, 95% CI: 0.85–2.34). The AOP study identified TCPP and TCEP as key chemicals that cause aberrant glucose metabolism and insulin signaling pathways and result in diabetes. Conclusions Coexposure to phthalates and OPEs is positively associated with diabetes, where an antioxidative diet plays a modifying role. Several potential mechanisms have been proposed by AOP framework.

This study aims to explore the changes in the vitreous proteomics of form deprivation myopia (FDM) in guinea pigs, in order to reveal the molecular mechanisms involved in the onset and development of myopia. The myopia model in guinea pigs was successfully established by covering one eye of the guinea pigs with a latex bead sac for 4 weeks. This study used 4D data-independent acquisition proteomics technology to analyze vitreous body samples from both the FDM group and the control group. The goal of the proteomics analysis was to identify differences in protein expression within the vitreous body of FDM guinea pigs. Myopia was successfully induced in the FDM group after 4 weeks of modeling. A total of 6298 proteins were identified, among which 348 were differentially expressed proteins (DEPs), with 81 upregulated and 267 downregulated. These DEPs were subjected to in-depth bioinformatics analyses, including Gene Ontology, the Eukaryotic Orthologous Groups, and the Kyoto Encyclopedia of Genes and Genomes. These analyses revealed significant involvement in cellular processes, metabolic pathways, biological regulation, cytoskeletal organization, and cell movement. Our results indicate that calcium signaling plays a critical role in mediating eye changes associated with form deprivation, which may bear similarities to mechanisms observed in neurodegenerative diseases. A total of 348 DEPs related to the development and progression of myopia were identified. These changes involve key biological processes, including protein degradation, cell adhesion, and transport, especially alterations in calcium signaling pathways. Stromal interaction molecule 1 (STIM1) is an important biological marker of FDM, which was confirmed by Western blot, immunohistochemistry and ELISA. Our study found clear differences in the expression of proteins in the vitreous during the development of myopic guinea pigs, especially those related to calcium signaling pathway. Our study offers new insights into the pathogenesis of myopia, particularly changes related to protein metabolism pathways.

Abstract Considering the indispensable significance and utilities of meta-substituted pyridines in medicinal, chemical as well as materials science, a direct meta-selective C–H functionalization of pyridines is of paramount importance, but such reactions remain limited and highly challenging. In general, established methods for meta C–H functionalization of pyridines rely on the utilization of tailored electrophilic reagents to realize the intrinsic polarity match. Herein, we report a complementary electrochemical methodology; diverse nucleophilic sulfinates allow meta-sulfonylation of pyridines through a redox-neutral dearomatization-rearomatization strategy by a tandem dearomative cycloaddition/hydrogen-evolution electrooxidative C–H sulfonation of the resulting oxazino-pyridines/acid-promoted rearomatization sequence. Besides, several salient features, including exclusive regiocontrol, remarkable substrate/functional group compatibility, scale-up potential, and facile late-stage modification, have been demonstrated, which further contributes to the practicality and adaptability of this approach.

Abstract Despite the importance of radiation therapy as a non-surgical treatment for non-small cell lung cancer (NSCLC), radiation resistance has always been a concern, due to poor patient response and prognosis. Therefore, it is crucial to uncover novel targets to enhance radiotherapy and investigate the mechanisms underlying radiation resistance. Previously, we demonstrated that NRP1 was connected to radiation resistance in NSCLC cells. In the present study, bioinformatics analysis of constructed radiation-resistant A549 and H1299 cell models revealed that transcription coactivator YAP is a significant factor in cell proliferation and metastasis. However, there has been no evidence linking YAP and NRP1 to date. In this research, we have observed that YAP contributes to radiation resistance in NSCLC cells by stimulating cell proliferation, migration, and invasion. Mechanistically, YAP dephosphorylation after NSCLC cell radiation. YAP acts as a transcription co-activator by binding to the transcription factor TEAD4, facilitating TEAD4 to bind to the NRP1 promoter region and thereby increasing NRP1 expression. NRP1 has been identified as a new target gene for YAP/TEAD4. Notably, when inhibiting YAP binds to TEAD4, it inhibits NRP1 expression, and Rescue experiments show that YAP/TEAD4 influences NRP1 to regulate cell proliferation, metastasis and leading to radiation resistance generation. According to these results, YAP/TEAD4/NRP1 is a significant mechanism for radioresistance and can be utilized as a target for enhancing radiotherapy efficacy.

Abstract Background Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown. Methods Among 1,123 adults from National Health and Nutrition Examination Survey 2011–2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC. Results These models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV1)/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV1, FEV1/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function. Conclusions Co-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects.

Abstract Background Colon cancer remains a major health concern worldwide, with genetic factors playing a crucial role in its development. Toll-like receptors (TLRs) has been implicated in various cancers, but their role in colon cancer is not well understood. This study aims to identify functional polymorphisms in the promoter and 3′UTR regions of TLRs and evaluate their association with colon cancer susceptibility. Methods We conducted a case-control study involving 410 colon cancer patients and 410 healthy controls from the Chinese population. Genotyping of polymorphisms in TLR3, TLR4, TLR5 and TLR7 was performed using PCR-RFLP and TaqMan MGB probes. Using logistic regression analysis, we evaluated the association of TLRs polymorphisms and the susceptibility to colon cancer. To understand the biological implications of the TLR4 rs1927914 polymorphism, we conducted functional assays, including luciferase reporter assay and electrophoretic mobility shift assay (EMSA). Results Our results demonstrated that the G-allele of the TLR4 rs1927914 polymorphism is significantly associated with a decreased risk of colon cancer (OR = 0.68, 95%CI = 0.50–0.91). Stratified analysis showed that TLR4 rs1927914 AG or GG genotype contributed to a decreased risk of colon cancer among younger individuals (OR = 0.52, 95%CI = 0.34–0.81), males (OR = 0.58, 95%CI = 0.38–0.87), non-smokers (OR = 0.58, 95%CI = 0.41–0.83) and non-drinker with OR (95%CI) of 0.66 (0.46–0.93). Functional assays demonstrated that in HCT116 and LOVO colon cancer cells, the luciferase activity driven by the TLR4 promoter with the rs1927914A allele was 5.43 and 2.07 times higher, respectively, compared to that driven by the promoter containing the rs1927914G allele. Electrophoretic mobility shift assay (EMSA) results indicated that the rs1927914G allele enhanced transcription factor binding. Using the transcription factor prediction tool, we found that the G allele facilitates binding of the repressive transcription factor Oct1, while the A allele does not. Conclusion The TLR4 rs1927914 polymorphism influence the susceptibility to colon cancer, with the G allele offering a protective effect through modulation of gene expression. These insights enhance our understanding of the genetic determinants of colon cancer risk and highlight TLR4 as a promising target for cancer prevention strategies.

Abstract Objectives To use T1ρ mapping to assess myocardial fibrosis and to provide a reference for future clinical application, it is necessary to understand the factors influencing T1ρ values. This study explored the influence of different spin-locking frequencies on T1ρ values under a 3.0-T MR system. Methods Fifty-seven healthy subjects were prospectively and consecutively included in this study, and T1ρ mapping was performed on them in 3 short-axis slices with three spin-lock frequencies at the amplitude of 300 Hz, 400 Hz, and 500 Hz, then nine T1ρ images were acquired per subject. Four T1ρ-weighted images were acquired using a spin-lock preparation pulse with varying durations (0 msec, 13.3 msec, 26.6 msec, 40 msec). T1ρ relaxation times were quantified for each slice and each myocardial segment. The results were analyzed using Student’s t-test and one-way analysis of variance (ANOVA) methods. Results Mean T1ρ relaxation times were 43.5 ± 2.8 msec at 300 Hz, 44.9 ± 3.6 msec at 400 Hz, and 46.2 ± 3.1 msec at 500 Hz, showing a significant progressive increase from low to high spin-lock frequency (300 Hz vs. 400 Hz, p = 0.046; 300 Hz vs. 500 Hz, p

Significance Impregnated diamond bits (IDBs) have been widely used in various hard rock drilling activities, especially deep drilling. Drilling process with IDBs relies on diamond edge wrapped by metal matrices to break the rock formation, which means the wear pattern of the diamond bit reflects the interaction between bits and rock, as well as the existence form of broken particles, which directly determine the drilling efficiency and service life of the drilling tools. But up to now there have not been so much in-depth study on its wear mechanism and analysing method in geological drilling. Progress and Analysis Therefore, this paper reviews the research literature on IDBs wear in the field of geological drilling, summarizes the abnormal bit wear problem according to engineering project experineces and industrial standards. Firstly, based on the experiences of geological drilling activities and industry standards, different types of abnormal bit wear of drill bits were summarized. Then, the evaluation methods of drill bit wear were introduced from the aspects of wear images and drilling signals. The wear mechanism and influencing factors of the drill bit in the drilling process were sorted out from three aspects: The overall drill bit, diamond, and metal matrix. In addition, mainstream methods of controlling drill bit wear performance were listed, and the research progress of wear analysis equations was introduced, besides, how machine learning methods can assist in the study of drill bit wear was discussed. Conclusion and Prospect Thus, IDBs have great potentials in deep hard rock drilling, and their wear performance is the key influnencing the whole drilling activity. To this end, research directions such as artificial intelligence assisting data analysis, microscale computational simulation, additive manufacturing, and material processing modification were analyzed and discussed, aiming to explore advanced methods for monitoring, analyzing, and regulating the wear of diamond drill bits, so as to meet the needs of remote monitoring and controlling in drilling activities such as geological deep drilling and extraterrestrial drilling.

Abstract Breast cancer is a prevalent malignant tumor among women with an increasing incidence rate annually. Breast cancer stem cells (BCSCs) are integral in impeding tumor advancement and addressing drug resistance. Bestatin serves as an adjuvant chemotherapy, triggering apoptosis in cancer cells. In this study, the effects of bestatin on sorted BCSCs from breast cancer cell lines have been studied. Our results indicated that bestatin inhibits the migration and proliferation of breast cancer cells by reducing the stemness of BCSCs both in vitro and in vivo. Puromycin-sensitive aminopeptidase is implicated in the process through the regulation of cell cycle, resulting in heightened cell apoptosis and diminished cell proliferation of BCSCs. Our study suggest that targeting cancer stem cell may offer a promising approach in breast cancer treatment, presenting noval therapeutic strategies for patients with breast cancer.

Abstract The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.

Abstract Surface defect detection is an essential task for ensuring the quality of products. Many excellent object detectors have been employed to detect surface defects in resent years, which has achieved outstanding success. To further improve the detection performance, a defect detector based on state‐of‐the‐art YOLOv8, named improved YOLOv8 by neck, head and data (NHD‐YOLO), is proposed. Specifically, YOLOv8 from three crucial aspects including neck, head and data is improved. First, a shortcut feature pyramid network is designed to effectively fuse features from backbone by improving the information transmission. Then, an adaptive decoupled head is proposed to alleviate the feature spatial misalignment between the classification and regression tasks. Finally, to enhance the training on small objects, a data augmentation method named selective small object copy and paste is proposed. Extensive experiments are conducted on three real‐world datasets: detection dataset from Northeastern University (NEU‐DET), printed circuit boards from Peking University (PKU‐Market‐PCB) and common objects in context (COCO). According to the results, NHD‐YOLO achieves the highest detection accuracy and exhibits outstanding inference speed and generalisation performance.

Background: Maternal exposure to multiple antibiotics exposure during pregnancy has attracted extensive attention, but biomonitoring studies linking prenatal antibiotic exposure to emotional and behavioural problems in children are limited. Methods: A total of 2475 pregnant women from the Ma’anshan Birth Cohort were included, and the Strengths and Difficulties Questionnaire was completed when their children turned four years of age. The levels of 41 maternal urinary antibiotics and two metabolites were measured during the first, second and third trimesters. Generalized estimating equations and binary logistic regression models were applied to analyse the associations between maternal antibiotic exposure and emotional and behavioural problems in children and to determine the sensitive period, respectively. A quantile-based g-computation (QGC) approach was employed to examine the combined effects of multiple antibiotics on emotional and behavioural problems in children. Results: Overall, florfenicol and preferred-as-veterinary antibiotic (PVA) exposure during pregnancy increased the risk of emotional problems in children, and ofloxacin exposure increased the risk of hyperactivity-inattention. Maternal exposure to trimethoprime, ciprofloxacin, florfenicol, other antibiotics and PVA exposure during the first trimester was positively associated with emotional problems in children. Second-trimester trimethoprime concentrations and third-trimester ciprofloxacin concentrations were positively associated with hyperactivity-inattention. Third-trimester veterinary antibiotic (VA) exposure was negatively associated with hyperactivity-inattention, and second-trimester VA and PVA exposure was negatively associated with peer problems. The QGC model revealed that mixed antibiotic exposure in the first trimester exacerbated the risk of childhood emotional problems (the contribution of ciprofloxacin is prominent), and mixed antibiotic exposure in the second trimester increased the risk of hyperactivity-inattention (the contribution of trimethoprime is prominent). Conclusion: Maternal mixed antibiotic exposure during the first and second trimesters increases the risk of emotional problems and hyperactivity-inattention in children at four years of age.

Global warming, driven by human activities since the Industrial Revolution, has significantly elevated atmospheric carbon dioxide (CO2) levels, leading to higher global temperatures and a rise in extreme weather events. The ocean, as a major carbon sink, has absorbed about 30% of human-induced carbon emissions, helping mitigate global warming’s impacts. This study examines the spatiotemporal distribution of air-sea CO2 flux in the Northwest Pacific from 1982 to 2021 and its response to El Niño-Southern Oscillation, using Empirical Orthogonal Function and composite analysis. The seasonal patterns of air-sea CO2 flux and the influence of environmental factors were further evaluated. The results show that air-sea CO2 flux in the Northwest Pacific exhibits clear seasonal fluctuations. In winter, high-latitude areas act as significant carbon sources. Strong winds deepen the mixed layer, promoting CO2 release from the ocean into the atmosphere. In contrast, in summer, longer daylight hours, rising SST, and melting sea ice lead to upwelling, which brings nutrients to the surface and stimulates phytoplankton growth. This process turns the region into a carbon sink as phytoplankton growth, driven by intense sunlight, enhances the ocean’s CO2 absorption. The mid-latitude region consistently acts as a carbon sink year-round. During El Niño events, more negative air-sea CO2 flux anomalies appear in the eastern Northwest Pacific, enhancing carbon uptake. La Niña events have the opposite effect in the eastern regions. These findings highlight the Northwest Pacific’s critical role in modulating regional and global carbon cycles under varying climatic conditions. Understanding these dynamics is crucial for improving predictions of future climate impacts and for developing effective strategies to mitigate global warming.

Liposarcoma (LPS) is a rare soft tissue sarcoma that develops from the differentiation of fat cells, typically occurring in the lower extremities and retroperitoneal space. Depending on its histological morphology and molecular changes, LPS can be divided into various subtypes, each exhibiting distinct biological behaviors. During treatment, especially for LPS arising in the retroperitoneum, the extent and quality of the initial surgery are critically important. Treatment strategies must be tailored to the specific type of LPS. Over the past few decades, the treatment of LPS has undergone numerous advancements, with new therapeutic approaches such as targeted drugs and immunotherapies continually emerging. This paper reviews the biological characteristics, molecular alterations, as well as surgical and pharmacological treatments of various LPS subtypes, with the aim of enhancing clinicians' understanding and emphasizing the importance of individualized precision therapy. With a deeper understanding of the biological characteristics and molecular alterations of LPS, future treatment trends are likely to focus more on developing personalized treatment plans to better address the various types of LPS.

There is a close relationship between preconception health and maternal and child health outcomes, and the consequences may be passed down from generation to generation. In 2018, Lancet published three consecutive articles emphasizing the importance of the preconception period. Phthalic acid ester (PAE) exposure during this period may affect gametogenesis and epigenetic information in gametophytes, thereby affecting embryonic development and offspring health. Therefore, this article reviews the effects of parental preconception PAE exposure on reproductive/birth outcomes and offspring health, to provide new evidence on this topic. We searched Web of Science, MEDLINE (through PubMed), the China National Knowledge Infrastructure (CNKI), ScienceDirect, and the VIP Journal Library from the date of database establishment to July 3, 2024. Finally, 12 articles were included. Three studies investigated the health hazards (effects on birth weight, abortion, etc.) of women's preconception PAE exposure. Nine studies involved both parents. Nine studies considered the impacts of PAE preconception exposure on reproductive/birth outcomes, focusing on birth weight, pregnancy loss, preterm birth, embryo quality, and placental weight. Three studies considered the impacts of preconception PAE exposure on offspring behavior. The results of this review suggested that parental preconception PAE exposure may have an impact on reproductive/birth outcomes and offspring behavior, including birth weight, child behavior, and dietary behavior. However, studies on the health hazards of preconception PAE exposure are relatively scarce, and the outcomes of current studies are varied. It is necessary to use systematic reviews to verify an accurate research question to provide recommendations for public health policy making.

Background The majority of extant methodologies for text classification prioritize the extraction of feature representations from texts with high degrees of distinction, a process that may result in computational inefficiencies. To address this limitation, the current study proposes a novel approach by directly leveraging label information to construct text representations. This integration aims to optimize the use of label data alongside textual content. Methods The methodology initiated with separate pre-processing of texts and labels, followed by encoding through a projection layer. This research then utilized a conventional self-attention model enhanced by instance normalization (IN) and Gaussian Error Linear Unit (GELU) functions to assess emotional valences in review texts. An advanced self-attention mechanism was further developed to enable the efficient integration of text and label information. In the final stage, an adaptive label encoder was employed to extract relevant label information from the combined text-label data efficiently. Results Empirical evaluations demonstrate that the proposed model achieves a significant improvement in classification performance, outperforming existing methodologies. This enhancement is quantitatively evidenced by its superior micro-F1 score, indicating the efficacy of integrating label information into text classification processes. This suggests that the model not only addresses computational inefficiencies but also enhances the accuracy of text classification.

ObjectiveThis study aimed to comprehensively investigate hypervirulent carbapenem-resistant Klebsiella pneumoniae (CR-hvKP) in the Ningbo region. Importantly, we sought to elucidate its molecular characteristics and pathogenic mechanisms. This information will provide evidence-based insights for preventing and controlling nosocomial infections and facilitate improved clinical diagnosis and treatment in this region. Methods96 carbapenem-resistant Klebsiella pneumoniae strains were collected from the Ningbo region between January 2021 and December 2022. Whole genome sequencing and bioinformatic methods were employed to identify and characterize CR-hvKP strains at the molecular level. The minimum inhibitory concentrations (MICs) of common clinical antibiotics were determined using the VITEK-2 Compact automatic microbiological analyzer. Plasmid conjugation experiments evaluated the transferability of resistance plasmids. Finally, mouse virulence assays were conducted to explore the pathogenic mechanisms.ResultsAmong the 96 strains, a single CR-hvKP strain, designated CR-hvKP57, was identified, with an isolation frequency of 1.04%. Whole-genome sequencing revealed the strain to be ST23 serotype with a K1 capsule. This strain harbored three plasmids. Plasmid 1, a pLVPK-like virulence plasmid, carried multiple virulence genes, including rmpA, rmpA2, iroB, iucA, and terB. Plasmid 2 contained transposable element sequences such as IS15 and IS26. Plasmid 3, classified as a resistance plasmid, harbored the blaKPC-3 carbapenem resistance gene. Mouse virulence assays demonstrated a high mortality rate associated with CR-hvKP57 infection. Additionally, there was a significant increase in IL-1β, IL-6, and TNF-α levels in response to CR-hvKP57 infection, indicating varying degrees of inflammatory response. Western blot experiments further suggested that the pathogenic mechanism involves activation of the NF-κB signaling pathway.ConclusionThis study confirms the emergence of hypervirulent CR-hvKP in the Ningbo region, which likely resulted from the acquisition of a pLVPK-like virulence plasmid and a blaKPC-3 resistance plasmid by the ST23-K1 type Klebsiella pneumoniae. Our findings highlight the urgent need for more judicious use of antibiotics to limit the emergence of resistance. Additionally, strengthening infection prevention and control measures is crucial to minimize the spread of virulence and resistance plasmids.

Abstract Exosomes are nanoscale vesicles of cellular origin. One of the main characteristics of exosomes is their ability to carry a wide range of biomolecules from their parental cells, which are important mediators of intercellular communication and play an important role in physiological and pathological processes. Exosomes have the advantages of biocompatibility, low immunogenicity, and wide biodistribution. As researchers’ understanding of exosomes has increased, various strategies have been proposed for their use in diagnosing and treating diseases. Here, we provide an overview of the biogenesis and composition of exosomes, describe the relationship between exosomes and disease progression, and focus on the use of exosomes as biomarkers for early screening, disease monitoring, and guiding therapy in refractory diseases such as tumors and neurodegenerative diseases. We also summarize the current applications of exosomes, especially engineered exosomes, for efficient drug delivery, targeted therapies, gene therapies, and immune vaccines. Finally, the current challenges and potential research directions for the clinical application of exosomes are also discussed. In conclusion, exosomes, as an emerging molecule that can be used in the diagnosis and treatment of diseases, combined with multidisciplinary innovative solutions, will play an important role in clinical applications.

The phthalic acid esters (PAEs) are one class of the most abundant and frequently studied pseudo-persistent organic pollutants. Noninvasive urine is an effective substrate for evaluating PAE exposure, but repeated sampling is needed to overcome this bias. This adds much work to on-site collection and the cost of detection increases exponentially. Therefore, the aim of this study was to conduct a scope review to describe the detection methods and validity of the use of other noninvasive matrices, such as nails and hair, for assessing long-term exposure to PAEs. The PubMed, Web of Science and China National Knowledge Infrastructure (CNKI), electronic databases were searched from 1 January 2000 to 3 April 2024, and 12 studies were included. Nine and three studies used hair and nails, respectively, as noninvasive matrices for detecting PAE exposure. Five articles compared the results of nail or hair and urine tests for validity of the assessment of PAE exposure. The preprocessing and detection methods for these noninvasive samples are also described. The results of this review suggest that, compared with nails, hair may be more suitable as a noninvasive alternative matrix for assessing long-term exposure to PAEs. However, sample handling procedures such as the extraction and purification of compounds from hair are not uniform in various studies; therefore, further exploration and optimization of this process, and additional research evidence to evaluate its effectiveness, are needed to provide a scientific basis for the promotion and application of hair detection methods for assessing long-term PAE exposure levels.

Abstract The SiO2–H2O binary system serves as a basis for understanding complex silicate-water systems. In this study, based on limited existing experimental data of solubility, we propose a new thermodynamic model for SiO2–H2O fluid by modifying the traditional non-random two-liquid model with a simplified polymerization reaction. This model is applicable from 773 K to the anhydrous quartz melting temperature and from 0.5 GPa to at least 2 GPa across the critical conditions. It can predict solid–liquid equilibrium and vapor–liquid equilibrium in good agreement with available experiments. The upper critical endpoint of the SiO2–H2O system is predicted to be at ~ 1.14 ± 0.18 GPa and 1344 ± 87 K. With the new model, we obtain a quantitative three-dimensional pressure–temperature–composition phase diagram of the SiO2–H2O fluid, which greatly facilitates the understanding of the complex phase behavior of this binary around the upper critical endpoint. In addition, since the model is based on the Gibbs free energy foundation, we further discuss the derived density variations of SiO2–H2O fluid along with its complex phase changes in typical geochemical processes.

Abstract In recent years, graph neural networks (GNNs) have been widely applied in recommender systems. However, existing recommendation algorithms based on GNNs still face challenges in node aggregation and feature extraction processes because they often lack the ability to capture the interactions between users and items, as well as users’ multiple intentions. This hinders accurate understanding of users’ needs. To address the aforementioned issues, we propose a recommendation model called multi-intent-aware interactive graph convolutional network (Multi-IAIGCN). This model is capable of integrating multiple user intents and adopts an interactive convolution approach to better capture the information on the interaction between users and items. First, before the interaction between users and items begins, user intents are divided and mapped into a graph. Next, interactive convolutions are applied to the user and item trees. Finally, by aggregating different features of user intents, predictions of user preferences are made. Extensive experiments on three publicly available datasets demonstrate that Multi-IAIGCN outperforms existing state-of-the-art methods or can achieve results comparable to those of existing state-of-the-art methods in terms of recall and NDCG, thus verifying the effectiveness of Multi-IAIGCN.

Active Magnetic Bearing (AMB) is a kind of electromagnetic support that makes the rotor movement frictionless and can suppress rotor vibration by controlling the magnetic force. The most common approach to restrain the rotor vibration in AMBs is to adopt a notch filter or adaptive filter in the AMB controller. However, these methods cannot obtain the precise amplitude and phase of the compensation current. Thus, they are not so effective in terms of suppressing the vibrations of the fundamental and other harmonic orders over the whole speed range. To improve the vibration suppression performance of AMBs, an adaptive filter based on Least Mean Square (LMS) is applied to extract the vibration signals from the rotor displacement signal. An Iterative Search Algorithm (ISA) is proposed in this paper to obtain the corresponding relationship between the compensation current and vibration signals. The ISA is responsible for searching the compensating amplitude and shifting phase online for the LMS filter, enabling the AMB controller to generate the corresponding compensation force for vibration suppression. The results of ISA are recorded to suppress vibration using the Look-Up Table (LUT) in variable speed range. Comprehensive simulations and experimental validations are carried out in fixed and variable speed range, and the results demonstrate that by employing the ISA, vibrations of the fundamental and other harmonic orders are suppressed effectively.

Abstract As a typical sub-deep reservoir in the upper reaches of the Yangtze River in the southwest region, Zhangjiayan Reservoir is also an important source of drinking water. Exploring the role of microorganisms in the material cycle of water bodies is of great significance for preventing the exacerbation of eutrophication in the reservoir. In this study, water samples from the overlying water of five points in the reservoir were collected four times in spring (April), summer (July), autumn (November), and winter (January) of 2022–2023 using a gas-tight water sampler. Physicochemical factors were measured, and the microbial community structure was analyzed by high-throughput MiSeq sequencing of the V3–V4 hypervariable region of 16S rRNA gene in order to explore the relationship between physicochemical factors and microbial community structure and the dominant microbial populations that affect eutrophication of the reservoir. The following results were obtained through analysis. Among the 20 overlying water samples from Zhangjiayan Reservoir, a total of 66 phyla, 202 classes, 499 orders, 835 families, 1716 genera, and 27,904 ASVs of the bacterial domain were detected. The phyla Proteobacteria and Actinobacteria were dominant in the microbial community of the overlying water in Zhangjiayan Reservoir. At the genus level, hgcI_clade and Actinobacteria had the highest abundance and was the dominant population. The microbial community in the water of Zhangjiayan Reservoir has a high level of diversity. The diversity index ranked by numerical order was winter > autumn > summer > spring. Significant differences were found in the composition and structure of the microbial community between the spring/summer and autumn/winter seasons (p

Abstract Evidence has revealed that DDOST plays an important role in cancer development and progression. However, there are no reports on functions of DDOST in cervical tumorigenesis. Hence, we investigated the relationship of DDOST with prognosis, mutation, promoter methylation, immune cell infiltration, and drug sensitivity using bioinformatics techniques. Our results demonstrated that DDOST was significantly upregulated in a variety of tumor types and correlated with poor prognosis, including cervical cancer. Cox regression analysis dissected that high DDOST expression was associated with poor survival in cervical cancer patients. Immune infiltration analysis defined that DDOST was negatively correlated with CD8 T cells and NK cells. Strikingly, the sensitivity to multiple drugs was negatively correlated with the expression of DDOST. Therefore, our findings uncovered that DDOST could play an essential role in the tumor microenvironment and tumor immune regulation in cervical cancer, which indicated that DDOST could be a useful biomarker for prognosis and a potential therapeutic target for cancer treatment.

In order to explore whether the addition of quinoa husks can affect the substance composition, flavor and biological activity of fermented Huangjiu, the traditional self-made Chenfuqu was used to ferment Huangjiu and two groups were set up inclouding ordinary Huangjiu and quinoa husks Huangjiu. The content of heavy metals in the two groups of wine samples was determined by atomic absorption spectrophotometer, and the basic physical and chemical indicators, differential compounds and flavor substances of the two groups of Huangjiu were analyzed and compared by high-performance liquid chromatography mass spectrometer (HPLC-MS) and gas chromatography-mass spectrometer (GC-MS), and the antioxidant activity of Huangjiu was analyzed. The results showed that the content of total saponins and total phenolic acids in quinoa husks Huangjiu was significantly higher than that of ordinary Huangjiu, and the lead content was lower. Aflatoxin B1 was not detected in both groups of Huangjiu. There were 48 different compounds in the two kinds of Huangjiu, of which alcohols and amides substances were the most abundant, both of which were ten, followed by four kinds of acid substances and two kinds of carbohydrate substances. There were 19 kinds of volatile substances detected by GC-MS, 12 kinds of direct sampling, 12 kinds of headspace sampling, four kinds of substances were calibrated by external standard method, and the substances in ordinary Huangjiu were butyl formate, acetic acid and butyric acid, the contents were 5.10±1.10, 4.40±1.70, 10.80±2.20 μg/mL respectively. The substances in quinoa husks Huangjiu were butyl formate, n-butanol, acetic acid and butyric acid, the contents were 9.00±1.80, 7.40±2.10, 4.50±1.00, 9.50±2.10 μg/mL respectively. In terms of antioxidant activity, the Fe2+ chelation rates of the quinoa husks Huangjiu and ordinary Huangjiu were 45.79% and 6.51%, and the tyrosinase inhibition rates were 94.84% and 71.11%, respectively. The quinoa husks Huangjiu was significantly better than ordinary Huangjiu. Compared with ordinary Huangjiu, self-made quinoa husks Huangjiu had higher content of non-volatile substances and volatile flavor substances in the wine body, and higher antioxidant capacity. The results of this study would provide a theoretical basis for brewing a new quinoa husks Huangjiu, and lay a foundation for the high-value utilization of quinoa husks.

Objective To investigate the relationship between intraoperative electroencephalographic (EEG) spindle loss and emergence delirium (ED) in elderly patients undergoing joint replacement surgery, and to further analyze the independent risk factors for ED. Methods A total of 69 elderly patients who underwent joint replacement surgery under general anesthesia in The Affiliated Hospital of Qingdao University from November 2020 to February 2021 were selected. Preoperative and intraoperative indicators, as well as length of stay in postanesthesia care unit and postoperative delirium incidence, were recorded. According to the presence or absence of EEG spindle waves, the patients were divided into spindle group and spindle loss group, and the relationship between intraoperative EEG spindle loss and ED was analyzed. The patients were then divided into ED group and non-ED group according to the presence or absence of ED after surgery. A univariate analysis was performed on various indicators of patients in the two groups. Factors with P

Abstract Background Unlike in lower vertebrates, Müller glia (MG) in adult mammalian retinas lack the ability to reprogram into neurons after retinal injury or degeneration and exhibit reactive gliosis instead. Whether a transition in MG cell fate from gliosis to reprogramming would help preserve photoreceptors is still under exploration. Methods A mouse model of retinitis pigmentosa (RP) was established using MG cell lineage tracing mice by intraperitoneal injection of sodium iodate (SI). The critical time point for the fate determination of MG gliosis was determined through immunohistochemical staining methods. Then, bulk-RNA and single-cell RNA seq techniques were used to elucidate the changes in RNA transcription of the retina and MG at that time point, and new genes that may determine the fate transition of MG were screened. Finally, the selected gene was specifically overexpressed in MG cells through adeno-associated viruses (AAV) in the mouse RP model. Bulk-RNA seq technique, immunohistochemical staining methods, and visual function testing were used to elucidate and validate the mechanism of new genes function on MG cell fate transition and retinal function. Results Here, we found the critical time point for MG gliosis fate determination was 3 days post SI injection. Hmga2 was screened out as a candidate regulator for the cell fate transition of MG. After retinal injury caused by SI, the Hmga2 protein is temporarily and lowly expressed in MG cells. Overexpression of Hmga2 in MG down-regulated glial cell related genes and up-regulated photoreceptor related genes. Besides, overexpressing Hmga2 exclusively to MG reduced MG gliosis, made MG obtain cone’s marker, and retained visual function in mice with acute retinal injury. Conclusion Our results suggested the unique reprogramming properties of Hmga2 in regulating the fate transition of MG and neuroprotective effects on the retina with acute injury. This work uncovers the reprogramming ability of epigenetic factors in MG.

Abstract Background Change in asthma burden attributed to specific environmental risk factor has not been evaluated. Objective We aimed to explore the age, period, and cohort effects on asthma burden attributable to smoking and occupational asthmagens in different socio-demographic index (SDI) regions and the region and sex disparities. Methods Risk factor-specific asthma deaths and disability-adjusted life years (DALYs) rates were extracted from Global Burden of Disease study 2019, estimated by standard Combined Cause of Death Model and DisMod-MR 2.1 modeling tool. Age-period-cohort analysis was conducted to decompose age, period, and cohort effects on asthma burden. Results Smoking- and occupational asthmagens-related asthma deaths and DALYs rates dropped by > 45% during 1990–2019. In 2019, Africa, South and Southeast Asia had higher asthma burden than other regions. Male had higher asthma burden than female. Among nearly all age groups, low-middle SDI region had the highest smoking-related asthma burden, and low SDI region had the highest occupational asthmagens-related asthma burden. Inverse “V” shaped trend was observed in the above regions with increasing age. For smoking-related asthma deaths and DALYs rates, the most significant improvement of period rate ratio (RR) occurred in high SDI region, decreased from 1.67 (1.61, 1.74) to 0.34 (0.33, 0.36) and 1.61 (1.57, 1.66) to 0.59 (0.57, 0.61), respectively, as well as the cohort effect on smoking-related asthma burden. For occupational asthmagens-related asthma deaths and DALYs rates, the most sharply decrease of period and cohort RR appeared in the high and high-middle SDI regions. Low SDI region showed least progress in period and cohort RR of smoking- and occupational asthmagens-linked asthma burden. Conclusion Smoking- and occupational asthmagens-related asthma burden sharply decreases, but region and sex disparities exist. Policy makers from low SDI region should reinforce tobacco control and prioritize workplace protection.

ABSTRACT: Avian reovirus (ARV) is the causative agent of avian viral arthritis and causes significant economic losses to the global poultry industry. For clinical diagnosis, detecting ARV-specific antibodies is crucial. We successfully expressed the ARV-σC protein in insect cells using the baculovirus expression vector system, achieving an expression level of approximately 200 mg/L. We developed an indirect enzyme-linked immunosorbent assay (iELISA) using the ARV-σC protein as a coating antigen to detect antibodies against it. The inter-batch and intrabatch coefficients of iELISA variation were less than 10%. Its sensitivity (1:12,800 diluted in serum) was 4 times higher than that of the indirect immunofluorescence assay (IFA; 1:3200 diluted in serum), and it showed no cross-reactivity with antibodies against other common avian viruses (such as Infectious bursal disease virus, Newcastle disease virus). The practicality of the iELISA was further evaluated using clinical samples. 300 clinical sera from chickens vaccinated with the ARV attenuated vaccine and 20 SPF sera were tested using both the iELISA and the IFA, demonstrating a 100% conformity rate. In conclusion, these results suggest that the iELISA developed in this study is a rapid, sensitive, and specific method that could serve as an effective diagnostic tool for monitoring and controlling avian viral arthritis.

BackgroundNeuropathic pain (NP) is a debilitating and refractory chronic pain with a higher prevalence especially in elderly patients. Cell senescence considered a key pathogenic factor in NP. The objective of this research is to discover genes associated with aging in peripheral blood of individuals with NP using bioinformatics techniques.MethodsTwo cohorts (GSE124272 and GSE150408) containing peripheral blood samples of NP were downloaded from the GEO database. By merging the two cohorts, differentially expressed aging-related genes (DE-ARGs) were obtained by intersection with aging-related genes. The potential biological mechanisms of DE-ARGs were further analyzed through GO and KEGG. Three machine learning methods, namely, LASSO, SVM-RFE, and Random Forest, were utilized to identify diagnostic biomarkers. A Nomogram model was developed to assess their diagnostic accuracy. The validation of biomarker expression and diagnostic effectiveness was conducted in three distinct pain cohorts. The CIBERSORT algorithm was employed to evaluate the immune cell composition in the peripheral blood of patients with NP and investigate its association with the expression of diagnostic biomarkers.ResultsThis study identified a total of 24 DE-ARGs, mainly enriched in “Chemokine signaling pathway,” “Inflammatory mediator regulation of TRP channels,” “HIF-1 signaling pathway” and “FOXO signaling pathway”. Three machine learning algorithms identified a total of four diagnostic biomarkers (CEBPA, CEACAM1, BTG3 and IL-1R1) with good diagnostic performance and the similar expression difference trend in different types of pain cohorts. The expression levels of CEACAM1 and IL-1R1 exhibit a positive correlation with the percentage of neutrophils.ConclusionUsing machine learning techniques, our research identified four diagnostic biomarkers related to aging in peripheral blood, providing innovative approaches for the diagnosis and treatment of NP.

Crop straw boards, a novel nursery material, has proven effective for cultivating dense, young rice seedlings suitable for mechanized transplanting, thereby saving labor. However, under high-density nursery conditions, the biomass accumulation and yield formation in rice vary with different seedling ages, necessitating exploration of optimal seeding densities and seedling ages to achieve high yields. This study aims to determine the appropriate seeding densities and seedling ages using crop straw boards to maximize rice yield. Over two years, field studies were conducted using crop straw boards for rice cultivation at seeding densities of 150, 200, 250, 300, and 350 g/tray (labeled as D1, D2, D3, D4, and D5) and seedling ages of 10, 15, 20, and 25 days (labeled as A1, A2, A3, and A4).The results indicated that D4A2 significantly enhanced tiller number, dry matter accumulation, and photosynthetic capacity, resulting in a yield increase of 2.89% compared to the conventional method of D1A3. High-density and short-aged seedlings cultivated with crop straw boards can enhance rice yield by improving photosynthetic capacity and crop quality. This study emphasizes the importance of using crop straw boards for rice nursery practices, as well as selecting the appropriate seeding densities and seedling ages for optimizing rice production.