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Abstract Prehistoric settlement patterns on the Tibetan Plateau, particularly in the Qaidam Basin, have drawn significant scholarly interest. Yet, limited data have hindered a comprehensive understanding the Bronze Age chronology and landscape exploitation in this region. This paper presents 24 newly obtained radiocarbon dates from eight archaeological sites within the Qaidam Basin on the Tibetan Plateau. Integrated with existing 14 C data and spatial analysis, these findings reveal an overall continuous occupation of the basin from ca. 3600–2500 calBP, with a gradual shift from expansive lowland settlements to smaller, ephemeral high-altitude structures, identified around 3350 calBP. This change is consistent with demonstrated periods of climate degradation which likely drove strategic adaptations in landscape management and subsistence methods. Overall, this research not only establishes a more robust chronology for the Qaidam Basin’s Bronze Age, but also advances the discussion on human-environment interactions in high-altitude areas during late prehistory.

Abstract With the population ages, many patients are unable to receive comprehensive care, leading to an increase in hazardous incidents, particularly falls occurring after getting out of bed. To address this issue, this paper proposes a method for recognizing bed-exit intentions using an array air spring mattress. The method integrates convolutional neural networks with feature point matching techniques to identify both global and local features of the array air spring. For global features, a one-dimensional focal loss convolutional neural network (1D-FLCNN) model is employed to classify eight internal pressure time series and determine bed-exit status based on global features. For local features, the distribution matrix and feature point matrix of the internal pressure features are extracted to represent the spatial distribution of bed-exit postures. Euclidean distance is utilized to measure the similarity between these matrices and match bed-exit postures. Finally, the recognition results from both feature types are combined using a logical OR operation to produce the final result. Experimental validation confirms that the proposed method greatly improves the anti-interference capability and effectively avoids the problem of non-recognition due to body position and external environment.

Abstract Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7–78.9%) and the DCR was 76% (95% CI: 54.9–90.6%). The mPFS was 6.0 months (95% CI: 5.4–9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

Abstract Ginseng, from the roots of Panax ginseng C. A. Meyer, is a widely used herbal medicine in Asian countries, known for its excellent therapeutic properties. The growth of P. ginseng is depend on specific and strict environments, with a preference for wetness but intolerance for flooding. Under excessive soil moisture, some irregular rust-like substances are deposited on the root epidermis, causing ginseng rusty symptoms (GRS). This condition leads to a significant reduce in yield and quality, resulting in substantial economic loses. However, there is less knowledge on the cause of GRS and there are no effective treatments available for its treatment once it occurs. Unsuitable environments lead to the generation of large amounts of reactive oxygen species (ROS). We investigated the key indicators associated with the stress response during different physiological stages of GRS development. We observed a significant change in ROS level, MDA contents, antioxidant enzymes activities, and non-enzymatic antioxidants contents prior to the GRS. Through the analysis of soil features with an abundance of moisture, we further determined the source of ROS. The levels of nitrate reductase (NR) and nitric oxide synthase (NOS) activities in the inter-root soil of ginseng with GRS were significantly elevated compared to those of healthy ginseng. These enzymes boost nitric oxide (NO) levels, which in turn showed a favorable correlation with the GRS. The activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase first rose and then decreased as GRS developed. Excess soil moisture causes a decrease in oxygen levels. This activated NR and NOS in the soil, resulting in a production of excess NO. The NO then diffused into the ginseng root and triggered a burst of ROS through NADPH located on the cell membrane. Additionally, Fe2+ in soil was oxidized to red Fe3+, and finally led to GRS. This conclusion was also verified by the Sodium Nitroprusside (SNP), a precursor compound producing NO. The presence of NO from NR and NOS in water-saturated soil is responsible for the generation of ROS. Among these, NO is the main component that contribute to the occurrence of GRS.

Abstract Background Obesity and metabolic syndrome (MetS) have become urgent worldwide health problems, predisposing patients to unfavorable myocardial status and thyroid dysfunction. Low-carbohydrate diet (LCD) and time-restricted eating (TRE) have been confirmed to be effective methods for weight management and improving MetS, but their effects on the myocardium and thyroid are unclear. Methods We conducted a secondary analysis in a randomized clinical diet-induced weight-loss trial. Participants (N = 169) diagnosed with MetS were randomized to the LCD group, the 8 h TRE group, or the combination of the LCD and TRE group for 3 months. Myocardial enzymes and thyroid function were tested before and after the intervention. Pearson’s or Spearman’s correlation was assessed between functions of the myocardium and thyroid and cardiometabolic parameters at baseline. Results A total of 162 participants who began the trial were included in the intention-to-treat (ITT) analysis, and 57 participants who adhered to their assigned protocol were involved in the per-protocol (PP) analysis. Relative to baseline, lactate dehydrogenase, creatine kinase MB, hydroxybutyrate dehydrogenase, and free triiodothyronine (FT3) declined, and free thyroxine (FT4) increased after all 3 interventions (both analyses). Creatine kinase (CK) decreased only in the TRE (− 18 [44] U/L, P

Abstract To clarify the relationship between GNSS (Global Navigation Satellite System) crustal deformation and the preparation of strong earthquakes in the western Chinese Mainland, a series of methods including velocity field, strain rate field, and strain parameter time series are adopted based on the GNSS observation data from the CMONOC (Crustal Movement Observation Network of China). The abnormal characteristics of crustal deformation movement before the M ≥ 5 earthquakes in the area since 1999 are studied. The corresponding variety of the crustal movement before earthquakes is discussed in combination with the seismogenic structure of earthquakes. The abnormalities of the GNSS velocity field, strain field, and strain parameter time series before earthquakes with different magnitudes are proposed. Finally, the anomaly criterion before medium-strong-large earthquakes in the western Chinese Mainland is proposed according to the GNSS and its combination with the characteristics of geological structure. The results can provide a basis for the forecasting of the trend and location of medium-strong-large earthquakes in the western Chinese Mainland.

Abstract Adults with cancer may perceive cannabis as beneficial for managing their cancer-related symptoms, but the evidence supporting its medical use is varied and inconclusive. This study characterized associations of cannabis use with cancer-related symptom trajectories. Participants were adults undergoing cancer treatment at the Stephenson Cancer Center (SCC; n = 218) in Oklahoma; they were 71% female, 10% minoritized race, and 45% had stage III or IV cancer. Participants completed surveys at baseline and 2-, 4-, and 6-months post-baseline. Assessments queried about cannabis use behavior, physical and psychological distress via the Rotterdam Symptoms Checklist (RSCL), respiratory symptoms via the American Thoracic Society Questionnaire (ATSQ), and quality of life indices (physical and social functioning, pain interference, sleep quality, fatigue) via the Patient Reported Outcomes Measurement Information System (PROMIS-29). Cannabis use status was categorized based on self-reported past 30-day cannabis use at each assessment as non-use [no use at any assessment], occasional-use [use at 1–2 assessments], or consistent-use [use at 3–4 assessments]. Longitudinal hierarchical linear modeling evaluated associations of cannabis use status with average symptoms and symptom trajectories across all four assessments. One-third (33%) of participants reported past 30-day cannabis use at ≥ 1 assessment. Participants who reported cannabis use (occasional-use and consistent-use) had more severe symptoms overall across assessments. While most cancer symptom trajectories did not differ by cannabis use status, participants who reported consistent cannabis use uniquely showed worsening physical function over time. Cannabis use was associated with greater cancer-related symptom severity over time.

Abstract We sought to explore the risk factors for anxiety and depression in patients with coronary heart disease and subclinical hypothyroidism through logistic regression analysis. A retrospective analysis was conducted on 168 patients with coronary heart disease and subclinical hypothyroidism admitted to the Department of Cardiology of our hospital from February 2020 to November 2022. Patients were categorized into the control group, anxiety group, and depression group based on the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) scores. All participants were informed about the protocol and provided signed informed consent upon inclusion. The study examined influencing factors for anxiety and depression in patients with coronary heart disease and subclinical hypothyroidism. Collect patients’ gender, age, presence or absence of chronic diseases (including Diabetes, hypertension and hyperthyroidism), sleep quality, dietary habits, psychosocial stress, living environment, social support, education level, and blood TSH levels. The linear relationship between anxiety, depression, and each influencing factor was quantified using the Pearson correlation coefficient. Blood level of TSH and free T4 were detected by chemiluminescence immunoassay. Multiple logistic regression was applied to analyze the factors influencing anxiety and depression in these patients. Various factors were identified as significant influencers of anxiety and depression in patients with coronary heart disease and subclinical hypothyroidism. For anxiety, presence or absence of chronic diseases, sleep quality, dietary habits, psychosocial pressure, living environment, and blood TSH levels were found to be influential (P 0.05). Presence or absence of chronic diseases and TSH levels were positively correlated with depressive symptoms in patients with coronary heart diseaseand subclinical hypothyroidism (P 0.05). Notably, TSH levels in both the anxiety and depression groups were higher than those in the control group (P 0.05). The combination of chronic illness types, living habits (sleep quality, dietary habits), psychosocial pressure, living environment, and TSH levels emerged as risk factors for anxiety in patients with coronary heart disease and subclinical hypothyroidism (P

Abstract This study is aimed at identifying risk factors of Low Anterior Resection Syndrome following ileostomy reversal in rectal cancer patients who had undergone preventive ileostomy. This retrospective analysis was conducted on a cohort of 605 patients treated at the Fourth Hospital of Hebei Medical University between January 2018 and December 2021. These patients were grouped based on LARS score, and Clinical and follow-up data were collected to conduct univariate analyses of potential factors influencing LARS occurrence based on variable type. Variables with statistical significance were included in a logistic regression model to analyze potential influences on the occurrence of LARS. Univariate and Multivariate logistic regression analysis showed that N2 stage (OR = 2.290 95%CI: 1.076–4.873, P = 0.031), chemoradiotherapy (OR = 2.271, 95%CI: 1.246–4.138, P = 0.007), and anastomosis height (OR = 0.836, 95%CI: 0.717–0.975, P = 0.022) were independent influences on the occurrence of LARS. In model 3 (adjusting for all covariates), the relationship between anastomotic height and patient LARS status showed a negative correlation. In subgroup analyses, there were significant differences in the effect of anastomotic height on LARS in subgroups with different hemoglobin concentrations. A high occurrence rate of LARS is observed in rectal cancer patients with preventive ileostomy reversal. N2 stage, history of chemoradiotherapy, and anastomotic height are independent influence factors for the occurrence of major LARS after ileostomy reversal.

Abstract Mycobacteria is a diverse genus that includes both innocuous environmental species and serious pathogens like Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium ulcerans, the causative agents of tuberculosis, leprosy, and Buruli ulcer, respectively. This study focuses on Mycobacterium marinum, a closely related species known for its larger genome and ability to infect ectothermic species and cooler human extremities. Utilizing whole-genome sequencing, we conducted a comprehensive pan-genome analysis of 100 M. marinum strains, exploring genetic diversity and its impact on pathogenesis and host specificity. Our findings highlight significant genomic diversity, with clear distinctions in core, dispensable, and unique genes among the isolates. Phylogenetic analysis revealed a broad distribution of genetic lineages, challenging previous classifications into distinct clusters. Additionally, we examined the synteny and diversity of the virulence factor CpnT, noting a wide range of C-terminal domain variations across strains, which points to potential adaptations in pathogenic mechanisms. This study enhances our understanding of M. marinum's genomic architecture and its evolutionary relationship with other mycobacterial pathogens, providing insights that could inform disease control strategies for M. tuberculosis and other mycobacteria.

Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the initiation and progression of breast cancer. DNA promoter methylation status has the potential to be used as a biomarker for predicting the response to immunotherapy. This study aimed to investigate the biological and clinical significance of IDO1 promoter methylation in breast cancer. We analyzed IDO1 promoter methylation and its relationship with survival, patient prognosis, immune cell infiltration, immune-related pathways, and the expression of key immunomodulators via bioinformatics methods in The Cancer Genome Atlas (TCGA) breast cancer cohort (779 samples). Furthermore, the IDO1 promoter methylation status and expression of the IDO1 gene in the basal subtype of breast cancer were investigated in vitro via a methylation-specific PCR (MSP) assay and quantitative polymerase chain reaction (qPCR). The IDO1 promoter was significantly hypomethylated in the basal subtype of breast cancer tissues compared with normal adjacent tissues, and this effect was correlated with high expression of IDO1, resulting in abundant immune cell infiltration, activation of immune-related pathways, and upregulation of key immunomodulators. The influence of IDO1 promoter hypomethylation on the prognosis of patients with breast cancer was also investigated. The promoter hypomethylation of IDO1 in the basal subtype of breast cancer and its correlation with high expression of IDO1 were also investigated in vitro. Our results showed that IDO1 promoter methylation is vital for regulating its expression, which leads to the development of a tumor microenvironment in breast cancer. IDO1 promoter methylation and expression are associated with prognosis, immune cell infiltration, immune-related pathways, and immunomodulator expression in breast cancer. Our findings provide evidence for the validation of IDO1 promoter methylation as a promising biomarker to predict responses to immune checkpoint inhibitors in patients with breast cancer.

Abstract Background About one in four Chinese people might suffer or have already suffered from anxiety conditions, with a lifetime prevalence rate of 4.8%. However, many of those who could have benefited from psychological or pharmacological treatments fail to be recognized or treated due to the lack of timely recognition and accurate diagnosis. Objective This study used a topic modeling approach to explore people’s anxiety-related concerns raised on a computer-mediated Chinese health platform, YOU WEN BI DA (questioning and answering), to provide implications for accurate diagnosis, targeted education, tailored intervention, and informed policy-making in the course of addressing this condition of public concern. Methods First, we extracted data from YOU WEN BI DA between May 2022 and February 2023. After cleaning the extracted data both using the Python text processing tool spaCy and manually, we ascertained the optimal number of topics by drawing on the coherence scores and used latent Dirichlet allocation (LDA) topic modeling to generate the most salient topics and related terms. We then categorized the topics ascertained into different classes of themes by plotting them onto a 2D plane via multidimensional scaling using the pyLDAvis visualization tool. Finally, we analyzed these topics and themes qualitatively to better understand people’s anxiety-related concerns. Results 5 topics with different overall prevalence were ascertained through data analysis. Topic 2 (tinnitus phobia-incurred concerns, n = 639) is the most popular dominant topic, occurring in 25.1% of the 2545 collected concerns, closely followed by Topics 1 (neurosis-incurred concerns, n = 512;) and 3 (sleep, dyskinesia, bipolar, cognitive, and somatic disorders-incurred concerns, n = 619), which appeared in 20.1% and 24.3% of the 2545 concerns respectively. Topic 5 (social phobia-incurred concerns, n = 428) ranks as the fourth most popular dominant topic, showing up in 16.8% of the 2545 concerns. Topic 4 (autonomic nerve dysfunction-incurred concerns, n = 347) accounts for 13.6% of the 2545 concerns. The t-distributed Stochastic Neighbor Embedding analysis reveals partial similarities between Topics 2 and 5 as well as between Topics 4 and 5 because many concerns involved in Topics 2 and 5 pertain to people’s psychological status of fear and anxiety and the relief and dispelling of such symptoms through medication, and many concerns involved in Topics 4 and 5 relate to people’s worries about the negative impact on their nerves and the adjustment and conditioning of such effects through medication. Conclusion This was the first study that investigated Chinese people’s anxiety-related concerns raised on YOU WEN BI DA using the topic modeling technique. The automatic text analysis and complementary manual interpretation of the collected data allowed for the discovery of the dominant topics hidden in the data and the categorization of these topics into different themes to reveal the overall status of people’s anxiety-related concerns. The research findings can provide some practice implications for health and medical educators, practitioners, and policy-makers to make joint efforts to address this common public concern effectively and efficiently.

Abstract The photothermal sensitivity of tobacco refers to the degree to which tobacco responds to changes in light and temperature conditions in its growth environment, which is crucial for determining the planting area of cultivars and improving tobacco yield and quality. In order to accurately and effectively evaluate the photothermal sensitivity of tobacco cultivars, this study selected five cultivars and their hybrid combinations with significant differences planted under different ecological conditions from 2021 to 2022 as materials. The experiment was conducted in two locations with significant differences in temperature and light. We measured the agronomic traits and biomass of the experimental materials, and constructed an effective tobacco photothermal sensitivity evaluation model using principal component analysis, membership function, and regression analysis. The reliability of the model was evaluated by utilizing the photosynthetic characteristics, chlorophyll content, and antioxidant enzyme system activity of the experimental materials. The results showed that tobacco biomass is the most important principal component in agricultural traits, and the comprehensive evaluation model for tobacco photothermal sensitivity is: y = 0.4571y1 + 0.2406y2 + 0.1725y3, where the fitting coefficients R2 of y1, y2, and y3 are 0.945, 0.851, and 0.977, respectively; The photothermal sensitivity of the experimental materials was calculated using this model, and the comprehensive ranking of the 11 experimental materials is: G3

Abstract With the continuous spread of the SARS-CoV-2 globally, viral mutations have accumulated. As a result, SARS-CoV-2 became more contagious, and has a higher risk of immune escape and reinfection. To identify variants and have an awareness of the prevalence of these variants, this study selected four segments containing mutations on the S gene of the SARS-CoV-2. Then a rapid and convenient variants detection method was established using high-resolution melting(HRM) analysis combined with nested polymerase chain reaction(PCR). The total detection process takes about 5 h. Through comprehensive analysis of the results from the four reaction systems, the identification of seven important Omicron variants(BA.2, BA.2.75, BA.5.2, BF.7, BQ.1, XBB.1 and XBB.2) can be achieved, with significant differentiation in the melting curves of each variant group. The method established in this study was used to genotype positive specimens in COVID-19 nucleic acid testing, the overall concordance rate compared to whole genome sequencing results was 88.9%, and the positive concordance rate of each sublineage was greater than 80% and the negative concordance rate was greater than 94.4%. The detection of clinical specimens has demonstrated that the HRM analysis established in this study is an effective, rapid and convenient variant identification method, which can be used for monitoring SARS-CoV-2 variants and has important value in addressing public health issues caused by the ongoing mutations of the SARS-CoV-2.

Abstract Currently, continuous sign language recognition faces challenges such as difficulty in acquiring skeletal data, long training time for Three-Dimensional convolutional neural networks, and easy occlusion and blurring of hands. To address these problems, this paper proposes a continuous sign language recognition method based on target detection and coding sequence. The algorithm uses Dual-branch Shuffle Attention Mechanis-You Only Look Once version X (DSA-YOLOX) detection network to detect the head and hands, and encodes the sign language video according to the partition to achieve the transformation from Three-Dimensional to One-Dimensional; and then uses the proposed Bi-directional Long Short-Term Memory (BiLSTM) hand coding sequence classification model with jointly weighted Fast Dynamic Time Warping (FastDTW) to extract hand coding similarity and features while reducing the number of parameters to achieve the classification and recognition of unequal-length hand coding sequences. From the results of ablation experiments and comparison experiments, all parts of the improvement perform well. The word error rate (WER) of this paper’s method is reduced by 21.26% compared to Dynamic Time Warping-Hidden Markov Model (DTW-HMM) and 11.53% compared to Long Short-Term Memory-A(LSTM-A); the Giga Floating-point Operations Per Second(GFLOPs) of the algorithm are reduced dramatically, which is about 1/13 of the Visual Alignment Constraint(VAC) model and 1/57 of the Spatial-Temporal Multi-Cue(STMC) model; and the algorithm takes better account of the speed and accuracy of sign language recognition.

Abstract Racing performance traits are the main indicators for evaluating the performance and value of sport horses. The aim of this study was to identify the key genes for racing performance traits in Yili horses by performing a genome-wide association study (GWAS). Breeding values for racing performance traits were calculated for Yili horses (n = 827) using an animal model. Genome-wide association analysis of racing performance traits in horses (n = 236) was carried out using the Blink, and FarmCPU models in GAPIT software, and genes within the significant regions were functionally annotated. The results of GWAS showed that a total of 24 significant SNP markers (P

Abstract Background The relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS. Methods We analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini–Hochberg correction was used to account for multiple comparisons. Results Over the median follow-up period of 11.86 years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91–0.99), 0.68 (0.50–0.92), and 0.76 (0.64–0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02–1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45–0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74–0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77 years for cancer mortality outcome, 5034 cancer deaths were detected. An “L-shaped” nonlinear dose–response relationship between urea concentration and cancer mortality was discovered (p-nonlinear

Abstract Background Uveal melanoma (UM) is a rare and deadly eye cancer with high metastatic potential. Despite the predominance of malignant cells within the tumor microenvironment, the heterogeneity and underlying molecular features remain to be fully characterized. Methods We analyzed single-cell transcriptomic profiling of 37,660 malignant cells from 17 UM tumors. A consensus non-negative factorization algorithm was used to decipher transcriptional programs underlying tumor cell-intrinsic heterogeneity. Tumor-infiltrated immune cells were computationally estimated from bulk transcriptomes and bioinformatics methods. A gene signature was derived for subtyping and prognostic stratification and validated in multicenter cohorts. Results ScRNA-seq analysis revealed the existence of diverse subpopulations and transcriptional variability among malignant cells within and between tumors. Furthermore, we observed that the heterogeneity of malignant cell states and compositions correlated with genomic, immunological, and clinical characteristics. By identifying gene expression programs associated with malignant cell heterogeneity at the single cell level, UM samples were classified into two distinct intra-tumoral subtypes (ITMHlo and ITMHhi) with different prognoses and immune microenvironments. Finally, a machine learning-derived 9-gene signature was developed to translate single-cell information into bulk tissue transcriptomes for patient stratification and was validated in multicenter cohorts. Conclusions Our study provides insight into understanding the intra-tumoral heterogeneity of UM and its potential impact on patient stratification.

Abstract Objectives Allergic rhinitis (AR) is a complex disorder with variable pathogenesis. Increasing evidence suggests that the LRRC8A is involved in maintaining cellular stability, regulating immune cell activation and function, and playing significant roles in inflammation. However, the involvement of LRRC8A in AR inflammation and its underlying mechanisms remain unclear. Methods LRRC8A expression in AR patients, confirmed by qRT-PCR and Western blotting, was analyzed to investigate its relationship with the clinical characteristics of AR patients. In vitro, IL-13 stimulated HNEpCs to establish a Th2 inflammation model, with subsequent LRRC8A knockout or overexpression. NOX1/NOX4 inhibitor (GKT137831) and chloride channel inhibitor (DCPIB) were utilized to investigate AR development mechanisms during LRRC8A overexpression. An OVA-induced AR model with nasal mucosa LRRC8A knockdown confirmed LRRC8A's regulatory role in AR inflammation. Results LRRC8A mRNA and protein levels were significantly elevated in AR patients, positively correlating with NADPH oxidase subunits and Th2 inflammatory markers. In vitro, IL-13 stimulation of HNEpCs resulted in upregulation of LRRC8A and increased expression of NOX1, NOX4, and p22phox, along with mitochondrial dysfunction and NF-κB pathway activation. The knockout of LRRC8A reversed these effects. In nasal mucosal epithelial cells, DCPIB and GKT137831 completely blocked mitochondrial dysfunction caused by the overexpression of LRRC8A, which led to up-regulation of NOX1, NOX4, and p22phox. In vivo, knocking down LRRC8A reduced eosinophil infiltration, downregulated the expression of NOX1, NOX4, p22phox IL-4, IL-5, and IL-13, and decreased NF-κB pathway activation. Conclusion LRRC8A drives the upregulation of NOX1, NOX4, and p22phox, leading to ROS overproduction and mitochondrial dysfunction. It also activates NF-κB, ultimately leading to nasal mucosal epithelial inflammation. LRRC8A may be a potential target for the treatment of AR.

Abstract To investigate the effects of low-intensity pulsed ultrasound combined with microbubble (LIPUS-MB) mediated JNK/c-Jun pathway reversal on multidrug resistance in triple-negative breast cancer and the underlying mechanisms. An orthogonal experiment was designed to screen for the optimal parameters of LIPUS-MB in MDA-MB-231/DOX cells. The CCK-8 assay was used to determine the drug resistance of the cells and to measure their proliferation activity and resistance reversal efficiency at the optimal parameters. Hoechst 33,342 staining and Annexin V-FITC/PI staining were employed to detect cell morphological changes and apoptosis, respectively. The MDA-MB-231/DOX models of transplanted tumor were established in BALB/c. The impact of LIPUS-MB on allograft tumor growth was observed in vivo. Immunohistochemistry was employed to investigate the expression of P-gp, ABCG2, and Ki-67 in tumor tissues, while western blot was utilized to assess the protein expression of P-gp, ABCG2, JNK, p-JNK, c-Jun, p-c-Jun, Bcl-2 and Bax in both MDA-MB-231/DOX cells and allograft tumor tissues. The optimal LIPUS-MB parameters for MDA-MB-231/DOX cells are the microbubble concentration of 20%, ultrasound intensity of 1.0 W/cm2, and irradiation time of 60 s. The drug resistance index of MDA-MB-231/DOX cells is 19.17. Following the optimal parameter application, the IC50 value of the cells decreases by 5.71-fold, with a reversal efficiency of 87.03%, and a simultaneous decrease in cell proliferation activity. Compared with other groups, the DOX + LIPUS-MB group displayed the highest incidence of apoptotic nuclear morphology, and the greatest quantity of cellular apoptosis and the most pronounced decrease in the expression levels of P-gp, ABCG2, p-JNK, p-c-Jun, and Bcl-2 proteins within the cells. Conversely, the expression levels of Bax proteins reach the highest levels (all P

Abstract The bidirectional relationship between sleep duration and pain during the COVID-19 pandemic remains poorly understood. This study explores these interactions and the mediating roles of depression and chronic diseases using data from the China Health and Retirement Longitudinal Study (CHARLS) cohort. A cross-sectional analysis was conducted on 15,979 participants aged 45 and older. Sleep duration was self-reported, and pain was assessed using validated anatomical charts. Depression symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10), and chronic diseases were self-reported. Personal activity during the pandemic was measured using the Personal Activity Score during COVID-19 (PAS-COVID-19). The results showed a significant association between deviations from optimal sleep duration and increased pain frequency. Participants with both shorter and longer sleep durations reported higher pain levels, with depression and chronic diseases acting as significant mediators. However, personal activity did not significantly mediate the association between sleep duration and pain. These findings underscore the complex interplay among sleep duration, pain, depression, and chronic diseases during the COVID-19 pandemic, emphasizing the importance of integrated interventions to manage these interconnected health issues.

Abstract The goal of this study was to compare the advantages of conventional laparoscopic surgery (CLS) and the split-leg supine position single-port plus one laparoscopic surgery (SSP SILS + 1) in esophageal surgery. This study enrolled 73 patients who previously underwent radical esophagectomy for esophageal cancer from August 2021 to February 2023. Among them, 36 patients underwent SSP SILS + 1, whereas the remaining 37 patients underwentCLS. Surgical time, bleeding volume, number of dissected lymph nodes, incision length, and postoperative abdominal pain score between the two groups of patients were compared using either the Student’s t-test or chi-square test. Time of abdominal incision (1.4 ± 0.2 min vs. 5.2 ± 0.7 min, p 0.01) between the two groups. The SSP SILS + 1 intervention offers multiple benefits over conventional surgical procedures, encompassing shorter incision length and pain scores on POD 1. In accelerated rehabilitation surgery for esophageal cancer, this surgical procedure demonstrated high safety, feasibility.

Abstract The nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in NP tissue during IVDD progression. However, the cellular and molecular alterations of diverse cell clusters during IVDD remain to be fully elucidated. NP tissues were isolated from patients with different grades of IVDD undergoing discectomy, and then subjected to single-cell RNA sequencing (scRNA-seq). Cell subsets were identified based on unbiased clustering of gene expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the molecular features of diverse cell clusters. Monocle analysis was used to illustrate the differentiation trajectories of chondrocytes. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocytes and other cells during IVDD. Based on the expression profiles of 47,610 individual cells, eight putative clusters including chondrocytes, endothelial cells, fibroblasts, macrophages, mural cells, osteoclasts, proliferating stromal cells and T cells were identified. The chondrocyte cluster was classified into three subsets, C1-C3, which were associated with stress-resistance, fibrosis and inflammatory responses, respectively. Pseudo-time trajectories suggested that chondrocytes gradually differentiated into fibroblasts during IVDD. Immune cells including cDC2s, macrophages and monocytes were identified. Further analysis showed that chondrocytes might communicate with immune cells via the MIF, TNFSF9, SPP1 and CCL4L2 signaling pathways. In addition, we found that invading endothelial cells might interact with chondrocytes through the COL4A1, CXCL12, VEGFA and SEMA3E signaling pathways. Our results reveal the cellular complexity and phenotypic characteristics of NP tissues at single-cell resolution, which will contribute to the in-depth investigation of preventative and regenerative strategies for IVDD.

Abstract Vehicle re-identification (Vehicle Re-ID) aims at retrieving and tracking the specified target vehicle with multiple other cameras, which can provide help in checking violations and catching fugitives, but there are still the following problems that need to be solved urgently. First, the existing collected Vehicle Re-ID data often have low resolution and blur in local regions, so that the Vehicle Re-ID algorithm cannot accurately extract subtle feature representations. In addition, small features are easy to cause the disappearance of features under the operation of a large convolution kernel, which makes the model unable to capture and learn subtle features, resulting in inaccurate judgment of vehicles. In this study, we propose a Vehicle Re-ID method based on super resolution and pyramidal convolution residual network. Firstly, a super-resolution image generation network leveraging generative adversarial networks (GANs) is proposed. This network employs both content loss and adversarial loss as optimization criteria, ensuring an efficient transformation from a low-resolution image into a super-resolution counterpart, while meticulously preserving intricate high-frequency details. Then, multi levels of pyramidal convolution operations are designed to generate multi-scale features, which can capture information on different scales. Moreover, the concept of residual learning is applied between the multi levels of pyramidal convolution operations to expedite model optimization and enhance recognition capabilities. Ultimately, the double pyramidal convolutions are meticulously employed on both the original image and the super-resolution image, yielding low-noise feature representations and intricate semantic information respectively. By seamlessly fusing these two diverse sources of information, the resultant combined features exhibit heightened discrimination capabilities and significantly bolster the robustness of image features. In order to verify the effectiveness of the proposed method, extensive experiments are carried out on VeRi-776 and VehicleID datasets. The experimental results show that the method proposed in this paper effectively captures the detail information of vehicle images, accurately distinguishes the subtle differences between different vehicles of the same type, and is superior to state-of-the-art methods.

Abstract Microplastics (MPs) in subsurface environments are migratory and can carry heavy metals, increasing the extent of MP and heavy metal pollution. This study used quartz sand-filled column experiments to investigate the adsorption and cotransport behaviours of PS-MPs, O3, UV-aged PS-MPs, and Cu2+ at different MP concentrations, ionic strengths, and ionic valences in a saturated porous medium. The results showed that when MPs migrate alone in the absence of an ionic background, higher concentrations have increased mobility. In contrast, an increase in the background ion concentration or ion valence inhibits the individual transport capacity of PS-MPs. An increase in the concentration of background ions or elevation in the valence state promotes Cu2+ transport because of the action of the double electric layer on the surface of the colloid and the electrostatic repulsive forces combined with the background ions. The adsorption capacity of aged PS-MPs was stronger than that of PS-MPs because of the binding of the aged PS-MPs to Cu2+ through complexation and electrostatic attraction. In the binary system of PS-MPs/Cu2+, PS-MPs promoted Cu2+ transport and the mobility of Cu2+ loaded by PS-MPs decreased with increasing background ion concentration. The cotransport results showed that MPs promote Cu2+ transport in the following order: O3-aged Ps > UV-aged Ps > Ps, as the increasing cation concentration in the MPs and Cu2+ occupies the PS surface adsorption sites. Overall, PS is an effective carrier for Cu2+. These findings offer fresh exploration concepts for the joint migration of MPs and heavy metals in underground settings.

Abstract Color is one of the most important indicators to characteristic the quality of tobacco, which is strongly related to the variations of chemical components. In order to clarify the relationship between the changes of tobacco color and chemical components, here we established several prediction models of chemical components with the color values of tobacco based on machine learning algorithms. The results of correlation analysis showed that tobacco moisture content was highly significantly correlated with the parameters such as a*, H* and H°, the reducing sugar and total sugar content of tobacco was significantly correlated with the color values, and the starch content was highly significantly correlated with the color values except for b* and C*. The random forest models performed best in predicting tobacco moisture, reducing sugar, total sugar and starch constructed with the R 2 of the model validation set was higher than 0.90, and the RPD value was greater than 2.0. The consistent between the predictions and measurements verified the availability and feasibility using color values to predict some chemical components of the tobacco leaves with high accuracy, and which has distinct advantages and potential application to realize the real-time monitoring of some chemical components in the tobacco curing process.

Abstract The interaction between the topography of the slope zone on the edge of the basin and the distribution of sediments is crucial for accurately predicting sediment distribution, but few studies emphasize the impact of stratigraphic overlap on the spatial evolution of sedimentary facies. The tectonic movement and sedimentary environment of Hala’alat Mountain in the northwest margin of the Junggar Basin are complex, and the sedimentary model of the whole Cretaceous system is still unclear. This article uses lithology, logging, and seismic data to explain the evolution process and sedimentary model of the Cretaceous system. The significant overlap of Cretaceous strata in the research area has a significant impact on the distribution of sedimentary facies zones and the development of sedimentary systems. Furthermore, this article explores the genesis mechanism of the Cretaceous stratigraphic overlap phenomenon, clearly defines the boundary range of stratigraphic overlap, and deeply analyzes how sedimentary facies zones are distributed and their subsequent evolution trends after the formation of overlap. The results demonstrate that there are apparent stratigraphic overlap phenomena in the second member (K1q2) and the third member (K1q3) of the Cretaceous Qingshuihe Formation in this area. The lithology at the bottom of the formation is grey sand conglomerate with finer grain size in the upper part, and the sedimentary facies are transitioned from fan delta facies to shore shallow lake beach bar facies. In member 1 (K1h1), member 2 (K1h2) and member 3 (K1h3) of the Hutubi Formation, due to the gradual slope and relatively stable sedimentary environment, the distance of stratigraphic overlap becomes shorter, the stratigraphic overlap phenomenon is no longer apparent and the sedimentary facies zone does not change. The study not only reveals the intrinsic relationship between stratigraphic overlap and the distribution of sedimentary facies zones, but also deepens the understanding of the dynamic evolution laws of sedimentary systems. The study on the overlap sedimentary mechanism of the Hala’alat Mountain in the northwest margin of Junggar Basin has reference significance.

Abstract Natural products, with their extensive chemical diversity, distinctive biological activities, and vast reservoirs, provide a robust foundation for advancing cancer therapeutics. A comprehensive phytochemical investigation of the skins from Bufo bufo gargarizans afforded two new bufadienolide derivatives identified as bufalactamides A and B (1–2), along with six known compounds: argentinogenin (3), desacetylcinobufagin (4), desacetylcinobufaginol (5), cinobufaginol (6), bufalin (7) and gamabufalin (8). The structural elucidation of these compounds was meticulously carried out by analyses of spectroscopic data (1D and 2D NMR, HR-ESIMS), and comparison with the literature data. Plausible biosynthetic pathways for the new compounds were also discussed. Moreover, the cytotoxicity of the compounds was investigated using various cancer cell lines, including lung cancer (A549), colon cancer (HCT-116), liver cancer (SK-Hep-1), and ovarian cancer (SKOV3). Our research findings indicated that compounds 3, and 6–8 exhibit potent cytotoxic activity (IC50 100 µM). From this data, we conducted a comprehensive analysis of the structure-activity relationships among these compounds.

Abstract Background The prevalence of high body mass index (BMI) is increasing in both children and adults worldwide. However, it is unclear whether vulnerabilities to maintenance and transition of weight status vary throughout the lifespan. Objective We aimed to characterize dynamic transitions of weight statuses across different life stages and to identify the sensitive periods for maintenance, onset, and resolution of obesity. Methods This longitudinal study included a total of 23,179 participants aged 6–80 years with 95,994 BMI measurements from the China Health and Nutrition Survey 1989–2015. To examine the heterogeneity in transitions of weight statuses across different life stages, we divided participants into 8 sub-cohorts based on baseline ages by 10-year intervals, i.e., 6–10 years, 11–20 years, 21–30 years, 31–40 years, 41–50 years, 51–60 years, 61–70 years, and 71–80 years. We estimated the probabilities of transitioning between weight statuses at a given follow-up year by baseline age using generalized linear mixed-effects models. Results The predicted prevalence of obesity decreased from 6 years, bottomed at around 20 years, increased thereafter, peaked at around 55 years, and then decreased gradually. In general, participants with underweight had lower probabilities of maintaining the same status compared to those with normal weight, overweight, or obesity for all age groups. For 10-year follow-up, individuals aged 21–30 years had the highest probabilities of transitioning from normal weight to obesity and transitioning from overweight to obesity compared to those in other age groups. Individuals aged 6–20 years had the highest probabilities of transitioning from obesity to normal weight and transitioning from overweight to normal weight. Individuals in all adult age groups had higher probabilities of maintaining obesity status than children and adolescents. Conclusions Young adulthood is the most sensitive period for obesity onset, whereas childhood and adolescence are the most sensitive periods for obesity resolution. The findings suggest the heterogeneity of susceptibilities to weight status transitions across different life stages and highlight the importance of the development of age-appropriate approaches for the prevention and intervention of obesity.

Abstract Intraventricular hemorrhage (IVH) occurs in approximately 30–50% patients with spontaneous intracerebral hemorrhage (ICH), with a high 30-day mortality rate. Excess accumulation of parenchymal or ventricular blood associated with the development of acute hydrocephalus leads to poor outcomes. The prediction of shunt dependency is important to identify patients susceptible to requiring permanent shunt placement and benefit from the diversion. This retrospective analytical study aimed to establish a predictive model of shunt dependency in patients with IVH. This study included 179 patients with primary IVH with supratentorial origin or spontaneous ICH with extension into the ventricles between 2015 and 2021. Patients were grouped into “shunt required” and “shunt not required” groups. Variables, including age, sex, preexisting hypertension and diabetes, initial Glasgow Coma Scale scores, ICH location and volume, urokinase administration, modified Graeb score (mGraeb score), and bicaudate index, were analyzed. The shunt required group had significantly higher mGraeb scores (12.0 (6.5–15.0) vs. 7.0 (4.0–12.0), p = 0.001) and higher bicaudate index (0.20 (0.17–0.23) vs. 0.16 (0.13–0.18), P

Abstract Observational studies have suggested links between standing height, BMI, body fat percentage, and inguinal hernia risk, but with inconsistent results. We conducted Mendelian randomization (MR) method to investigate their causal relationships. Independent SNPs associated with standing height, BMI, and body fat percentage were extracted from GWAS data as instrumental variables (IVs). Two-sample MR initially explored causal relationships between these factors and inguinal hernia risk. Multivariable Mendelian randomization (MVMR) assessed the direct causal effects of exposures on inguinal hernia. Positive findings from the MVMR analysis were independently validated. The inverse-variance weighted Methods (IVW), weighted median(WM), and MR-Egger were used for the MR estimates. Sensitivity analyses were used to examine the stability and reliability of the results. Two-sample MR analysis revealed a suggestive causal association between height and inguinal hernia (OR = 1.091, 95% CI = 1.003–1.186, P = 0.042). BMI (OR = 0.846, 95% CI = 0.774–0.924, P

Abstract Background Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood. Methods To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP). Results Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression. Conclusions Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.

Background Health care workers are vital service providers in primary healthcare, playing a crucial role in safeguarding public health, disease prevention, and chronic disease management. At present, research on healthcare resources mainly focuses on the quantity and structure, and there are few studies on the spatial distribution characteristics of healthcare resources. Objectives To analyze the spatial development trend of healthcare human resources in primary healthcare institutions nationwide, and to provide reference for optimizing the spatial allocation of healthcare resources and upgrading the level of primary healthcare services. Methods The data for this study were obtained during 2013-2017 China Health and Family Planning Statistical Yearbook, the 2018-2022 China Health and Wellness Statistical Yearbook, and the annual data of the National Bureau of Statistics (NBS) by province and the Ministry of Civil Affairs of China. From February to June 2023, the health density index (HRDI) was used to comprehensively reflect the demographic and geographic distribution of primary health care in China from 2012 to 2021, spatial autocorrelation analysis was applied to calculate the global Moran's I index to characterize the spatial distribution of primary health care resources in China from 2012 to 2021 analysis, and calculate the local Getis's G index to analyze the hotspots of primary care resource allocation in China from 2012 to 2021. Results The number of practicing physicians and nurses per 1 000 population at the grassroots level has increased in all regions of China, and the ratio of healthcare to nursing is still low. The high HRDI values for the number of practicing (assistant) physicians and nurses were in the eastern region, while the western region had lower HRDI values. The global Moran's I index for the number of practicing (assistant) physicians turned from negative to positive in 2016. The Moran's I index for nurses was always negative, but the overall trend was gradually approaching 0. Western regions such as Xinjiang and Xizang have low health density indices and are cold spots for resource distribution. Conclusion The allocation of medical and nursing resources to primary health care organizations has been increasing year by year, but there are obvious differences in allocation between provinces. The spatial correlation between physicians has gradually increased, and nurses have become more dispersed in their spatial distribution. It is recommended that the reserve of primary care physicians and nurses be strengthened, and that the ratio and collaboration between physicians and nurses be improved; that the planning of health care resources take into account both demographic and geographic configurations, and that Internet-based health care be promoted to improve the accessibility of health care services; and that the investment of resources in central and western China be increased, and that the construction of health care organizations be pushed forward in order to enhance the capacity of grass-roots-level services.

Background Diabetes is an important health problem due to its high prevalence and associated disability and mortality. Research evidence provides effective information for improving patient health outcomes. Decision aids can help patients obtain evidence and increase physician-patient interaction. Objective To obtain patients' preferences for anti-diabetic drugs and develop an evidence-based decision aid to achieve the integration of evidence, patient values, and decision settings, thus facilitating patient-centered evidence-based decision making. Methods Several literature databases, like PubMed, Web of Science Core Collection, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), VIP Chinese Science Journals Database, and Wanfang Data were searched to determine the value assessment dimensions and attributes of anti-diabetic drugs. The time limit for literature search is from the establishment of the database to December 31, 2022. The questionnaires for investigating patients' preferences for anti-diabetic drugs were designed using the best-worst scaling method. Then, the empirical study to explore preferences was carried out in five hospitals in Jiangsu Province. Based on the analysis of patients' preferences, an evidence-based decision aid was developed using techniques including Vue + Element UI, Spring Boot, Spring Security, Java, etc. Results The most important five attributes in patient decisions were incidence of macrovascular complications, length of extended life years, change of health-related quality of life, incidence of microvascular complications, and control of HbA1c. The evidence-based decision aid provides a structured summary of evidence on the comparative effectiveness, comparative safety, convenience, and affordability of new anti-diabetic drugs. The multi-attribute value assessment module of new anti-diabetic drugs is the core element of the decision aid, supporting patients' evidence-based assessment of the drugs' value. Conclusion Evidence-based decision aid integrates research evidence of new anti-diabetic drugs, patients' preferences and values, and helps realize shared decision-making between physicians and patients.

Objective To investigate the efficacy and safety of 4-week cluster immunotherapy with house dust mite extracts in patients allergic to house dust mites. Methods From August 2022 to May 2024， 80 patients with house dust mite-induced allergic rhinitis， complicated with or without asthma， were recruited from multiple centers （including Peking Union Medical College， et al） to undergo 4-week dose-escalation subcutaneous cluster immunotherapy with house dust mites. Patient symptoms， medication use， quality of life， asthma control test （ACT） results， as well as local and systemic adverse reactions were recorded at 0， 1， 6， and 12 months， respectively. Results Significant differences were observed in the daily total symptom scores （P < 0.001）， daily nasal scores （P < 0.001）， daily ocular scores （P = 0.009）， and total symptom and medication scores （P = 0.003） across different time points during cluster immunotherapy， respectively. Significant differences were also found in the activity RQLQ （P < 0.001）， sleep RQLQ （P = 0.002）， non-eye/nose symptom RQLQ （P = 0.032）， practical problems RQLQ （P < 0.001）， nasal symptom RQLQ （P < 0.001）， emotional RQLQ （P = 0.011）， total RQLQ （P < 0.001）， and children’s ACT scores （P < 0.001）， respectively. The longer the time， the lower the score. During the dose-escalation period， 22 patients （27.5%） experienced local adverse reactions， and 5 patients （6.3%） experienced systemic adverse reactions. A total of 35 （3.6%） injections resulted in adverse reactions， including 27 （2.8%） injections with local reactions and 8 （0.8%） injections with systemic reactions. Conclusion Four-week cluster immunotherapy with house dust mites shows significant efficacy in patients allergic to house dust mites.

In clinical practice， the application of surface disinfectants for skin disinfection is a prerequisite for venipuncture. Chlorhexidine， a widely recognized disinfectant， is frequently employed for this purpose. However， during intravenous infusions， minute quantities of chlorhexidine can be inadvertently introduced into the bloodstream via the puncture needle， potentially precipitating immediate-type （type ） hypersensitivity reactions. Regrettably， these reactions are often erroneously attributed to administered medications， such as antibiotics， which can result in both misdiagnosis and underdiagnosis. This article details a case of an allergic reaction that occurred subsequent to multiple intravenous infusions and was ultimately identified as chlorhexidine-induced after antibiotic allergy was ruled out. The objective of this report is to deepen the clinical physcians’ comprehension of chlorhexidine-induced allergies in the context of infusion-related allergic reactions， thereby offering a valuable reference for accurate diagnosis and effective treatment strategies.

Objective·To measure and analyze age-related changes in cortical bone thickness and alveolar bone height and width in the posterior teeth of the maxilla.Methods·Cone-beam CT (CBCT) data of the implant patients in the Department of Stomatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were collected from January 2019 to December 2022. There were 40 cases in the youth group (18‒30 years) and 40 cases in the elderly group (≥60 years), with a male-to-female ratio of 1∶1. The i-Dixel software was used to measure the thickness of buccal and palatal cortical bone, and the width and height of alveolar bone in three regions of the posterior teeth of the maxilla on the side with regular dentition (part Ⅰ: between the first and the second premolar of maxillary; part Ⅱ: between the second premolar and the first molar of maxillary; part Ⅲ: between the first and the second molar of maxillary), and the differences between different groups were compared.Results·In part Ⅲ, the buccal cortical bone thickness of the elderly men [(1.49±0.29) mm] was significantly greater than that of the young men [(1.11±0.34) mm] (P

Abstract From January to April 2020, the COVID-19 pandemic affected eastern China, leading medical students to adopt home protection measures that significantly altered their physical activity and lifestyle habits. This study aimed to assess the prevalence of musculoskeletal pain (MSP) among medical students during home protection and to analyze the influence of demographic factors, physical exercise habits during normal school life, home protection data on MSP. This research provides a foundation for developing interventions to reduce MSP among medical students. A cross-sectional survey was conducted at Nanjing Medical University in Jiangsu Province from January to April 2020, utilizing the Nordic Musculoskeletal Questionnaire (NMQ) to measure MSP. Multivariate logistic regression identified factors influencing MSP. A total of 859 students participated, with a 40.2% prevalence of MSP during home protection. Multivariate analysis showed that female sex (OR: 1.648; 95% CI: 1.157–2.347), irregular physical exercise during school (OR: 1.648; 95% CI: 1.157–2.347), and less than or equal to six hours of sleep per day during home protection (OR: 1.474; 95% CI: 1.020–2.131) were significant risk factors. The high prevalence of MSP underscores the need for interventions that focus on gender-specific risks, promote regular physical exercise, and ensure adequate sleep.

Abstract This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.

Abstract Citrus red mites (P. citri) are key pests affecting citrus production worldwide due to pesticide resistance. The resistance mechanisms of ten pesticides are known, but a comprehensive study using transcriptome data is missing. This study employed deeptools, cuffdiff, rmats, bcftools and other software to examine gene expression variation, alternative splicing (AS), and mutations in mite resistance. The research highlighted that pesticides can regulate gene transcription, and red mites with resistance increase cytochrome P450, glutathione S-transferases, carboxylesterase, and acetylcholinesterase expression. Pyridaben also induces new AS events. Fluazinam-induced mites show mRNA splicing peaking earlier than transcription, both peaking at one day and returning to baseline after two days. AS profiles are similar in different mite populations with overlapping pesticide resistances. Lastly, specific mitochondrial SNPs in mites might mediate resistance against select pesticides.

Abstract Wind speed prediction is crucial for precisely wind power forecasting and reduced maintenance costs. Highland regions, which possess a considerable wind potential, present complex meteorological conditions, making wind speed prediction challenging. Traditional weather forecasting relies on complex statistical methods and extensive prior knowledge. While recent deep learning models have improved prediction accuracy, they often assume uniform influence weight structure, limiting model effectiveness. This study introduces an enhanced Conditional Local Convolution Recurrent Network (CLCRN) model to improve spatiotemporal wind speed forecasting using multidimensional meteorological inputs such as temperature, pressure, and dew point, alongside wind components. This model addresses uniform influence model weight issue by redesigning convolution kernels to better capture local meteorological features and integrating multiple influencing factors. Our model consistently achieves lower Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE) values across various prediction intervals (3, 6, 9, and 12 h) compared to other models, supported by the meteorological station data from 2019 to 2021. Furthermore, the spatial distribution of the local convolution weights aligns with local wind velocity patterns in Inner Mongolia, enhancing model interpretability. These results demonstrate potential for practical applications in renewable energy planning and wind dynamics simulation.

Abstract Oxidative stress causes diverse neurological disorders. Parthanatos is a type of programmed cell death, characterised by strong activation of poly (ADP-ribose) (PAR) polymerase-1 (PARP-1), PAR polymer accumulation, and nuclear translocation of apoptosis-inducing factor (AIF), and is involved in cellular oxidative injury. Signalling by c-Jun-N-terminal protein kinase (JNK) is activated by reactive oxygen species (ROS), and this also contributes to ROS production. However, the exact relationship between JNK signalling and parthanatos in neurological disorders triggered by oxidative stress is unclear. In this study, glutamate-treated HT22 neurons were used to investigate whether the signalling by JNK contributes a regulatory role to parthanatos in oxidative stress-related neurological disease. JNK signalling was activated in glutamate-treated HT22 neurons, demonstrated via upregulation of p-JNK levels. Pre-treatment with SP600125 markedly inhibited JNK signalling, increased cell viability, and significantly reversed PARP-1 overproduction, PAR polymer accumulation, and nuclear AIF translocation. In addition, inhibition of JNK signalling severely reduced the production of both intracellular ROS and mitochondria superoxide. This study indicated that parthanatos in glutamate-treated HT22 neurons could be suppressed by JNK signalling inhibition. JNK activation participated in parthanatos via an increase in intracellular ROS levels.

Abstract To explore a method to identify the sensory and motor fascicles of the peripheral nerve to achieve accurate peripheral nerve functional fascicle suture. The peripheral nerve Sunderland V injury model, muscle branch of the femoral nerve and saphenous nerve were established in the bilateral femoral nerves of Sprague-Dawley (SD) rats. The specific samples were grouped as follows: the main trunk of the femoral nerve was exposed bilaterally and cut with microscopic scissors in the main trunk of the femoral nerve to prepare a model of Sunderland V injury in the mixed fascicle of peripheral nerves; the muscle branch of the femoral nerve was exposed bilaterally and cut in the middle section of the muscle branch of the femoral nerve to prepare a model of Sunderland V injury in the motor fascicle of peripheral nerves; the saphenous nerve was exposed bilaterally and cut at 1 cm below the patella to prepare a model of Sunderland V injury to the sensory fascicle of the peripheral nerves. A carbon quantum dot (CD)-annexin V antibody complex was prepared and applied to the distal and proximal nerve stumps of the peripheral nerve Sunderland V injury model groups of SD rats. Under the excitation light source of a 380 nm uv lamp, fluorescence color development was observed under a fluorescence microscope after 5, 10, 15, and 20 min. At 5 min, sections of the bilateral femoral nerve trunk, muscular branches of the femoral nerve, and Sunderland V lesion of the saphenous nerve in SD rats were only dark in color under the microscope, and there was no difference in fluorescence. The intensity of the staining increased significantly for 10–20 min. The sensory fascicles and saphenous nerves of the femoral nerve trunk showed blue fluorescence under the CD-Annexin V antibody complex staining, while the motor fascicles and muscle branches of the femoral nerve trunk showed no fluorescence. Fluorescence intensity gradually decreased after 20 min of staining. There was no significant difference in the staining intensity at 5, 10, 15, and 20 min in each group. Our results suggest that the CD-Annexin antibody complex can be used to identify functional fascicles of peripheral nerves in SD rats.

Abstract The coordinate determination of the rotation center of a space TT&C (Telemetry, Tracking and Command) radar is an important task of radar-calibration. The conventional method mostly using total stations is expensive, inefficient, and faces technological limitations. This paper presents a new method of measuring the rotation center coordinates of TT&C radar equipment using GNSS (Global Navigation Satellite System) high precision positioning technology, providing the principle, mathematical model, and data processing algorithm of the new method. According to the exclusively-designed scheme, the new method has been fully tested and validated from both simulation & real-scene radar test. The test result and comparison show that the new method requires fewer equipment, fewer participants, and shorter working hours, with 60% efficiency improvement, compared to the traditional method. The accuracy of the new method could reach millimeter level, with 45% accuracy improvement over the traditional method. In summary, the results show that the new method not only offers higher efficiency and lower cost, but also expands the application method and scene of high-precise GNSS positioning in signal-challenging environment.

Abstract This study employs machine learning and single-cell transcriptome sequencing (scRNA-seq) analysis to unearth novel biomarkers and delineate the immune characteristics of ischemic stroke (IS), thereby contributing fresh insights into IS treatment strategies.Our research leverages gene expression data sourced from the GEO database. We undertake weighted gene co-expression network analysis (WGCNA) to filter pertinent genes and subsequently employ machine learning algorithms for the identification of feature genes. Concurrently, we rigorously execute quality control measures, dimensionality reduction techniques, and cell annotation on the scRNA-seq data to pinpoint differentially expressed genes (DEGs). The identification of core genes, denoted as Hub genes, among the feature genes and DEGs, is achieved through meticulous overlapping analysis. We illuminate the immune characteristics of these Hub genes using a suite of analytical tools, encompassing CIBERSORT, MCPcounter, and pseudotemporal analysis, all based on immune cell annotations and single-cell transcriptome data.Subsequently, we harness the CMap database to prognosticate potential therapeutic drugs and scrutinize their associations with the identified Hub genes. Our findings unveil robust linkages between three pivotal Hub genes—namely, RNF13, VASP, and CD163—and specific immune cell types such as T cells and neutrophils. These Hub genes predominantly manifest in macrophages and microglial cells within the scRNA-seq immune cell population, exhibiting variances across different stages of cellular differentiation. In conclusion, this study unearths highly pertinent biomarkers for IS diagnosis and elucidates IS-induced immune infiltration characteristics, thus providing a firm foundation for a comprehensive exploration of potential immune mechanisms and the identification of novel therapeutic targets for IS.

Abstract The construction of soft robots’s models and controllers remains a significant challenge. In this paper, we propose a new walking control method for the quadruped soft robot named genetic algorithm-optimized PID. First, we construct the control model correlating valve voltage with leg bending based on the geometrical analysis. This modeling approach leverages the characteristics of novel leg structure and bend sensor, thereby streamlining the control model for locomotion of quadruped soft robotic. Moreover, We apply the genetic algorithm to automatically tune parameters and optimize PID controllers, aiming to enhance control performance. The application of the proposed method to the walking control has been uniquely demonstrated on a real 3D-printed quadruped soft robot. Experimental results indicate that the genetic algorithm-optimized PID controller significantly improves trajectory tracking compared to the Ziegler-Nichols tuning method. This optimization increases the robot’s walking speed from 5 mm/s to 8 mm/s, reduces the error rate by 2.4064%, decreases overshoot by 12.55%, and shortens response time by 0.5 s, substantially enhancing the controller’s overall performance. Additionally, compared to particle swarm optimization, the proposed method further improves performance by reducing the error rate by 0.4079%, overshoot by 8.4%, and response time by 1.0 s.

Abstract Ovarian cancer (OC) is one of the most prevalent and lethal malignancies affecting the female reproductive system, due to its tendency for metastasis and recurrence. This study identified the overexpression of LINC01320 (or long intergenic nonprotein coding RNA 1320) in tissues of ovarian cancer through the analysis of patient samples and online datasets. In vitro and in vivo experiments demonstrate that silencing of LINC01320 expression led to inhibition of proliferation and metastasis of OC cells. RNA pull-down followed by liquid chromatography tandem mass spectrometry (RNA pull-down-LC-MS/MS) revealed that LINC01320 interacted with purine-rich element binding protein B (PURB), a transcriptional repressor. Furthermore, the RNA-seq analysis identified damage-specific DNA binding protein 2 (DDB2) as a major common target of LINC01320 and PURB. Mechanistically, LINC01320 could recruit PURB to the promoter region of DDB2 to repress DDB2 transcription; thus, promoting the expression of NEDD4L and impeding the TGF-β/SMAD signaling pathway, and ultimately facilitating the progression of OC. Finally, rescue experiments confirmed the involvement of the DDB2/NEDD4L/TGF-β axis in LINC01320-mediated OC progression. In conclusion, this study unveils for the first time the pivotal function of the LINC01320/PURB/DDB2/NEDD4L/TGF-β axis and explores its prospective clinical implications in OC.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the most universal liver diseases with complicated pathogenesis throughout the world. Insulin resistance is a leading risk factor that contributes to the development of NAFLD. Vascular endothelial growth factor B (VEGFB) was described by researchers as contributing to regulating lipid metabolic disorders. Here, we investigated VEGFB as a main target to regulate insulin resistance and metabolic syndrome. Methods In this study, bioinformatics, transcriptomics, morphological experiments, and molecular biology were used to explore the role of VEGFB in regulating insulin resistance in NAFLD and its molecular mechanism based on human samples, animal models, and cell models. RNA-seq was performed to analyze the signal pathways associated with VEGFB and NAFLD; Palmitic acid and High-fat diet were used to induce insulin-resistant HepG2 cells model and NAFLD animal model. Intracellular glucolipid contents, glucose uptake, hepatic and serum glucose and lipid levels were examined by Microassay and Elisa. Hematoxylin-eosin staining, Oil Red O staining, and Periodic acid-schiff staining were used to analyze the hepatic steatosis, lipid droplet, and glycogen content in the liver. Western blot and quantitative real-time fluorescent PCR were used to verify the expression levels of the VEGFB and insulin resistance-related signals PI3K/AKT pathway. Results We observed that VEGFB is genetically associated with NAFLD and the PI3K/AKT signal pathway. After VEGFB knockout, glucolipids levels were increased, and glucose uptake ability was decreased in insulin-resistant HepG2 cells. Meanwhile, body weight, blood glucose, blood lipids, and hepatic glucose of NAFLD mice were increased, and hepatic glycogen, glucose tolerance, and insulin sensitivity were decreased. Moreover, VEGFB overexpression reduced glucolipids and insulin resistance levels in HepG2 cells. Specifically, VEGFB/VEGFR1 activates the PI3K/AKT signals by activating p-IRS1Ser307 expression, inhibiting p-FOXO1pS256 and p-GSK3Ser9 expressions to reduce gluconeogenesis and glycogen synthesis in the liver. Moreover, VEGFB could also enhance the expression level of GLUT2 to accelerate glucose transport and reduce blood glucose levels, maintaining glucose homeostasis. Conclusions Our studies suggest that VEGFB could present a novel strategy for treating NAFLD as a positive factor. Graphical Abstract

Abstract Background Accurate differentiation between malignant and benign pulmonary nodules, especially those measuring 5–10 mm in diameter, continues to pose a significant diagnostic challenge. This study introduces a novel, precise approach by integrating circulating cell-free DNA (cfDNA) methylation patterns, protein profiling, and computed tomography (CT) imaging features to enhance the classification of pulmonary nodules. Methods Blood samples were collected from 419 participants diagnosed with pulmonary nodules ranging from 5 to 30 mm in size, before any disease-altering procedures such as treatment or surgical intervention. High-throughput bisulfite sequencing was used to conduct DNA methylation profiling, while protein profiling was performed utilizing the Olink proximity extension assay. The dataset was divided into a training set and an independent test set. The training set included 162 matched cases of benign and malignant nodules, balanced for sex and age. In contrast, the test set consisted of 46 benign and 49 malignant nodules. By effectively integrating both molecular (DNA methylation and protein profiling) and CT imaging parameters, a sophisticated deep learning-based classifier was developed to accurately distinguish between benign and malignant pulmonary nodules. Results Our results demonstrate that the integrated model is both accurate and robust in distinguishing between benign and malignant pulmonary nodules. It achieved an AUC score 0.925 (sensitivity = 83.7%, specificity = 82.6%) in classifying test set. The performance of the integrated model was significantly higher than that of individual methylation (AUC = 0.799, P = 0.004), protein (AUC = 0.846, P = 0.009), and imaging models (AUC = 0.866, P = 0.01). Importantly, the integrated model achieved a higher AUC of 0.951 (sensitivity = 83.9%, specificity = 89.7%) in 5–10 mm small nodules. These results collectively confirm the accuracy and robustness of our model in detecting malignant nodules from benign ones. Conclusions Our study presents a promising noninvasive approach to distinguish the malignancy of pulmonary nodules using multiple molecular and imaging features, which has the potential to assist in clinical decision-making. Trial registration: This study was registered on ClinicalTrials.gov on 01/01/2020 (NCT05432128). https://classic.clinicaltrials.gov/ct2/show/NCT05432128 .

Abstract Background Split hand/foot malformation (SHFM) is a congenital limb deficiency characterized by missing or shortened central digits. Several gene loci have been associated with SHFM. Identifying microduplications at the single-cell level is challenging in clinical practice, and traditional detection methods may lead to misdiagnoses in embryos and pregnant women. Results In this research, we utilized a low cell count and whole-genome amplification products to employ single nucleotide polymorphism arrays, next-generation sequencing, and third-generation sequencing methods to detect copy number variants of microduplications in a SHFM3 case with limited DNA. Additionally, Karyomapping and combined linkage analysis were conducted to validate the results. Conclusions This study establishes a new strategy for identifying microduplications or microdeletions at the single-cell level in clinical preimplantation genetic testing, enhancing the efficiency and accuracy of diagnosing microduplication or microdeletion diseases during IVF-PGT and prenatal diagnosis.