Search

Abstract Background Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment, but the role of genes related to T cell-mediated tumor killing (TTK) sensitivity in ovarian cancer (OV) is unclear. Methods This study analyzed 1367 OV patients and 11 independent cohorts. The unsupervised clustering was conducted to identify three tumor subtypes based on genes that regulate tumor cell sensitivity to TTK (GSTTKs). The biological characteristics, genetic variations, immunological landscape, and therapeutic evaluation for each subtype were further explored. Results Patients were divided into three reproducible subtypes based on 61 GSTKKs associated with prognosis. C1 was likely to be an invasive subtype with the worst prognosis and highly unstable genome. C2 might be an immune-active subtype with the best prognosis, high immune infiltration and preferable response to immunotherapy. C3 might be a metabolic subtype, resistant to immunotherapy, but sensitive to drug therapy. Following an extensive exploration into a variety of distinct molecular features between the three subtypes, the results suggested that C2 patients were considered to derive significant efficacy from immunotherapy. For C1 and C3 patients, chemotherapy might be an ideal treatment strategy. Conclusions In this study, three GSTKKs-based subtypes were identified by assessing TTK patterns in OV. These new insights further improved our understanding of GSTTKs and might refine clinical treatment strategies for OV patients.

Abstract Aims Non-suicidal self-injury (NSSI) is a serious issue that is increasingly prevalent among children and adolescents, especially in rural areas. Developing a suitable predictive model for NSSI is crucial for early identification and intervention. Methods This study included 2090 Chinese rural children and adolescents. Participants’ sociodemographic information, symptoms of anxiety as well as depression, personality traits, family environment and NSSI behaviors were collected through a questionnaire survey. Gender, age, grade, and all survey results except sociodemographic information were used as relevant factors for prediction. Support vector machines, decision tree and random forest models were trained and validated by the train set and valid set, respectively. The metrics of each model were tested and compared to select the most suitable one. Furthermore, the mean decrease Gini index was calculated to measure the importance of relevant factors. Results The prevalence of NSSI was 38.3%. Out of the 6 models assessed, the random forest model demonstrated the highest suitability in predicting the prevalence of NSSI. It achieved sensitivity, specificity, AUC, accuracy, precision, and F1 scores of 0.65, 0.72, 0.76, 0.70, 0.57, and 0.61, respectively. Anxiety and depression were the top two contributing factors in the prediction model. Neuroticism and conflict were the factors that contributed the most to personality traits and family environment, respectively, in terms of prediction. In addition, demographic factors contributed little to the prediction in this study. Conclusion This study focused on Chinese children and adolescents in rural areas and demonstrated the potential of using machine learning approaches in predicting NSSI. Our research complements the application of machine learning methods to psychiatric and psychological problems.

Abstract The study utilizes the RBF neural network model to evaluate the green development of the Pearl River Delta urban agglomeration, revealing a consistent increase in development levels from 2005 to 2020 despite notable inter‐city variations. The model adeptly handles complex interactions within urban green development, offering insights into comprehensive impacts and aiding in policy evaluation and optimization. It provides urban planners and decision‐makers with data‐driven support, enhancing the scientific basis and stability of policy‐making.

This study elucidated the optimization conditions, GC-MS analysis conditions, total antioxidant activity, and components closely related to antioxidant activity for supercritical extraction of active ingredients in Huoluo Xiaoling Dan (HLXLD). The yield, octyl acetate content, and total antioxidant activity of HLXLD under different conditions were obtained through orthogonal experiments, and the optimal supercritical extraction conditions were determined to be 45°C, 25 MPa, and 4 h. The supercritical extract was subjected to GC-MS analysis and matched with the WILEY and NIST databases, resulting in the qualitative identification of 37 chemical components with a matching degree above 60. The similarity evaluation system of traditional Chinese medicine fingerprint was used to evaluate all orthogonal experimental samples, with a similarity ranging from 0.522 to 0.989. Thirteen common characteristic peaks were selected, and the quantification of these peaks was performed using peak area normalization method. The combination of the content of common characteristic peaks in different samples and their total antioxidant activity was analyzed using multivariate statistical methods such as principal component analysis and multiple regression equation. It was found that five components, F3, F2, F5, F7 and F12, among the common characteristic peaks were closely related to antioxidant activity.

Abstract Kaempferol has an anti-inflammatory effect on rheumatoid arthritis (RA), but the mechanism by which inflammatory reactions are relieved via pyroptosis is still unclear. In the present study, The bioinformatics technology was used to analyze the relationship between pyroptosis the hub genes and the downstream cytokines in RA from three the Gene Expression Omnibus (GSE12021, GSE1919 and GSE29746). Molecular docking analysis of kaempferol and caspase1 (CASP1) was executed with Autodock tools. RA fibroblast-like synoviocytes (RA-FLS) was used to explore the anti-inflammatory effects of kaempferol on RA via pyroptosis. Thirty-seven differentially expressed genes (DEGs) were identified from the three datasets, and the enrichment analysis was focused mainly on the chemokine signaling pathway. The difference in immune cell infiltration was focused on CD4 T cells, CD8 T cells, M1 macrophages, and M2 macrophages. The expression of CASP1 and caspase3 (CASP3) was higher in the RA group. CASP1 and CASP3 were positively correlated with cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Moreover, molecular docking revealed that kaempferol strongly interacts with CASP1. Kaempferol inhibited the proliferation and migration of RA-FLS in vitro. The expression of CASP1, CASP3, caspase5 (CASP4), caspase5 (CASP5), gasdermin D (GSDMD), N-terminal domain of gasdermin D (GSDMDNT), IL-1β, and cytokines interleukin-18 (IL-18) were significantly affected by kaempferol. Kaempferol alleviated RA-FLS membrane disruption, and it blocked CASP1 to alleviate RA via pyroptosis. The present study demonstrated that kaempferol binds to CASP1 and affects pyroptosis in RA, thereby serving as an anti-immunotherapy strategy.

Abstract Background Giardia duodenalis (G. duodenalis) is a globally distributed zoonotic protozoan that parasitizes the small intestines of humans and various mammals, such as goats and sheep. The objective of this study was to establish a convenient, accurate, and specific method based on restriction fragment length polymorphism (RFLP) for genotyping assemblages A, B and E of G. duodenalis in goats. The β-giardin gene was amplified using primer pairs bgF1, bgR1, bgF2 and bgR2 by nested PCR. The PCR products were digested with the restriction enzymes Hinf I and Bgl I. The established PCR-RFLP method was used to detect and analyze the genetic subtypes of G. duodenalis in 130 fecal samples from goats and compared simultaneously with microscopic examination and nucleic acid sequencing for G. duodenalis. Results Genetic sequencing confirmed that the PCR-RFLP method accurately distinguished G. duodenalis assemblages A, B and E, as well as different combinations of mixed infections of these three assemblages. Among the 130 samples tested by PCR-RFLP, a total of 26 samples (20.00%) tested positive for G. duodenalis, a higher sensitivity than microscopic examination at 13.85% (18/130). Sequence alignment analysis revealed that among the 26 PCR-positive samples, two were identified as assemblage AI, while the remaining 24 were identified as assemblage E or E12. Conclusions This study established an accurate, efficient and rapid PCR-RFLP genotyping method using the bg sequence of G. duodenalis, enabling accurate identification and effective differentiation of goat-derived G. duodenalis assemblages without requiring sequencing.

Abstract Sodium oligomannate (GV-971), an oligosaccharide drug approved in China for treating mild-to-moderate Alzheimer’s disease (AD), was previously found to recondition the gut microbiota and limit altered peripheral Th1 immunity in AD transgenic mice. As a follow-up study, we here made advances by pinpointing a Lactobacillus murinus (L.m.) strain that highly expressed a gene encoding a putative adhesin containing Rib repeats (Ribhigh-L.m.) particularly enriched in 5XFAD transgenic mice. Mechanistically, Ribhigh-L.m. adherence to the gut epithelia upregulated fecal metabolites, among which lactate ranked as the top candidate. Excess lactate stimulated the epithelial production of serum amyloid A (SAA) in the gut via the GPR81-NFκB axis, contributing to peripheral Th1 activation. Moreover, GV-971 disrupted the adherence of Ribhigh-L.m. to gut epithelia via direct binding to Rib, which corrected the excess lactate, reduced SAA, and alleviated Th1-skewed inflammation. Together, we gained further insights into the molecular link between gut bacteria and AD progression and the mechanism of GV-971 in treating AD.

Abstract Objective To construct a highly accurate and interpretable feeding intolerance (FI) risk prediction model for preterm newborns based on machine learning (ML) to assist medical staff in clinical diagnosis. Methods In this study, a sample of 350 hospitalized preterm newborns were retrospectively analysed. First, dual feature selection was conducted to identify important feature variables for model construction. Second, ML models were constructed based on the logistic regression (LR), decision tree (DT), support vector machine (SVM) and eXtreme Gradient Boosting (XGBoost) algorithms, after which random sampling and tenfold cross-validation were separately used to evaluate and compare these models and identify the optimal model. Finally, we apply the SHapley Additive exPlanation (SHAP) interpretable framework to analyse the decision-making principles of the optimal model and expound upon the important factors affecting FI in preterm newborns and their modes of action. Results The accuracy of XGBoost was 87.62%, and the area under the curve (AUC) was 92.2%. After the application of tenfold cross-validation, the accuracy was 83.43%, and the AUC was 89.45%, which was significantly better than those of the other models. Analysis of the XGBoost model with the SHAP interpretable framework showed that a history of resuscitation, use of probiotics, milk opening time, interval between two stools and gestational age were the main factors affecting the occurrence of FI in preterm newborns, yielding importance scores of 0.632, 0.407, 0.313, 0.313, and 0.258, respectively. A history of resuscitation, first milk opening time ≥ 24 h and interval between stools ≥ 3 days were risk factors for FI, while the use of probiotics and gestational age ≥ 34 weeks were protective factors against FI in preterm newborns. Conclusions In practice, we should improve perinatal care and obstetrics with the aim of reducing the occurrence of hypoxia and preterm delivery. When feeding, early milk opening, the use of probiotics, the stimulation of defecation and other measures should be implemented with the aim of reducing the occurrence of FI.

Abstract Background Post-infectious bronchiolitis obliterans (PIBO) is a severe form of chronic obstructive lung disease secondary to severe respiratory tract infections. Knowledge of pediatric PIBO development-associated risk factors may improve selection of appropriate early therapeutic interventions. Objective The aim of this study was to describe the clinical characteristics of children diagnosed with PIBO, and identify the risk factors for development of PIBO after adenovirus pneumonia. Methods First, a retrospective observational study was performed of 308 pediatric patients with PIBO (ages

Abstract Introduction Although with increasing popularity due to aesthetic appeal and comfort, clear aligners (CAs) are facing challenges in efficacy and predictability. Advancement in the underlying biomechanical field is crucial to addressing these challenges. This paper endeavors to provide a comprehensive framework for understanding the biomechanics of CA and enlightening biomechanics-based improvements on treatment strategies. Methods A thorough review of the English-language literature accessible through PubMed and Google Scholar, without any publication year restrictions, was undertaken to unravel the biomechanical aspects of CA. Results This review presented an up-to-date understanding of aligner biomechanics arranged by the framework of the material-dependent mechanical characteristics of CA, the geometric characteristics-dependent force transmission of the CA system, methods for studying the biomechanics of CA, and the biomechanical analyses for different types of tooth movement. Conclusions Biomechanics should be the fundamental concern for concepts, methods and adjuncts attempting to enhance the accuracy and predictability of tooth movement induced by CA. Improvement on material properties and alteration of geometric design of CA are two main approaches to develop biomechanically optimized force system. Exploration of real-world force sensing and monitoring system would make substantial progresses in aligner biomechanics.

Abstract Background 3D brachial plexus MRI scanning is prone to examination failure due to the lengthy scan times, which can lead to patient discomfort and motion artifacts. Our purpose is to investigate the efficacy of artificial intelligence-assisted compressed sensing (ACS) in improving the acceleration efficiency and maintaining or enhancing the image quality of brachial plexus MR imaging. Methods A total of 30 volunteers underwent 3D sampling perfection with application-optimized contrast using different flip angle evolution short time inversion recovery using a 3.0T MR scanner. The imaging protocol included parallel imaging (PI) and ACS employing acceleration factors of 4.37, 6.22, and 9.03. Radiologists evaluated the neural detail display, fat suppression effectiveness, presence of image artifacts, and overall image quality. Signal intensity and standard deviation of specific anatomical sites within the brachial plexus and background tissues were measured, with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) subsequently calculated. Cohen's weighted kappa (κ), One-way ANOVA, Kruskal–Wallis and pairwise comparisons with Bonferroni-adjusted significance level. P 0.05). For subjective scores, ACS 9.03 were lower than the other three sequences in neural details display, image artifacts and overall image quality. There was no significant difference in fat suppression. For objective quantitative evaluation, SNR of right C6 root in ACS 6.22 and ACS 9.03 was higher than that in PI; SNR of left C6 root in ACS 4.37, ACS 6.22 and ACS 9.03 was higher than that in PI; SNR of medial cord in ACS 6.22, ACS 9.03 was higher than that in PI. Conclusion Compared with PI, ACS can shorten scanning time while ensuring good image quality.

Abstract Endometriosis, an estrogen-dependent chronic inflammatory condition, afflicts reproductive-aged women. However, the underlying pathological mechanisms remain to be elucidated. Nicotinamide N-methyltransferase (NNMT) is a critical enzyme involved in cellular metabolism and methylation regulation. This study investigated the role of NNMT in endometriosis. By analyzing datasets GSE5108, GSE7305, GSE141549, GSE23339, and GSE25628, we identified a significant overexpression of NNMT in the eutopic endometrium and ectopic lesions of endometriosis patients compared to normal endometrium. Furthermore, NNMT was upregulated in collected endometrioma specimens and isolated primary endometrial stromal cells (ESCs) compared to their respective controls. Inhibition of NNMT using JBSNF-000088 attenuated the proliferation, migration, and invasion of ESCs. In vivo, treatment of mouse models of endometriosis with JBSNF-000088 resulted in a marked reduction in lesion weight and quantity. NNMT expression in ESCs was dose-dependently upregulated by 17β-estradiol at concentrations of 1 nM, 10 nM, and 100 nM, an effect that was attenuated by 10 nM progesterone. Additionally, treating HESCs with macrophage-conditioned medium elevated NNMT expression at both mRNA and protein levels. Knockdown of NNMT impeded the proliferation, migration, and invasion of ESCs, which was paralleled by decreased phosphorylation levels of Erb-b2 receptor tyrosine kinase 4 (ERBB4), PI3K, and AKT. Conversely, overexpressing ERBB4 mitigated the NNMT knockdown-induced decline in phosphorylated PI3K and AKT and rescued the proliferation of ESCs. Altogether, these results indicate that the overexpression of NNMT induced by estrogen and macrophage interaction modulates ESC proliferation via the NNMT-ERBB4-PI3K/AKT signaling pathway, as well as promotes cellular migration and invasion, contributing to the development of endometriosis.

Abstract COVID-19 survivors concerning about the rehabilitation and sustained sequelae of Coronavirus Disease 2019 (COVID-19) infection. We aimed to investigate the sequelae of patients’ psychological and physical condition and its related factors in the early and late stages. This longitudinal study tracked 281 COVID-19 patients discharged from hospitals in Guangdong, China, for one year. Assessments occurred at 2,4,12,24 and 48 weeks post-discharge. We define 2 weeks, 4 weeks, and 12 weeks as early stage, and 24 weeks and 48 weeks as late stage. Psychological health was measured using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and Pittsburgh Sleep Quality Index (PSQI) scales. Physical health was assessed through laboratory tests, chest computed tomography (CT) scans, and pulmonary function tests. Data were analyzed using multivariate regression models to evaluate the influence of demographic and clinical variables on health outcomes. COVID-19 survivors exhibited psychological and physical sequelae in both the early and late stages. Compared to the early stage, the proportions of patients with depression (early stage 14.6%, late stage 4.6%), anxiety (early stage 8.9%, late stage 5.3%), PTSD(early stage 3.6%, late stage 0.7%), abnormal liver function (early stage 24.6%, late stage 11.0%), abnormal cardiac function (early stage 10.0%, late stage 7.8%), abnormal renal function (early stage 20.6%, late stage 11.0%) and abnormal pulmonary function (early stage 40.9%, late stage 13.5%) were significantly reduced in the late stage. Factors such as gender, age, severity of COVID-19, hospitalization duration, and various comorbidities were significantly associated with these sequelae. We noticed that psychological and physical sequelae occurred to COVID-19 survivors in short and long stages, and these would gradually decrease as time went on. Male gender, age > 50 years old, severe clinical condition, longer hospitalization time and comorbidity history were related factors that significantly affected the rehabilitation of COVID-19 patients.

Abstract Super large-sized cities and very large-sized cities (“mega-cities” for short) have become the backbone of China's socio-economic development, but they also face outstanding challenges of "urban diseases" due to their high concentration. In comparison to their foreign counterparts, China's mega-cities possess unique characteristics such as rapid growth, high population density, and large numbers of residents. They naturally have the attributes of metropolitan areas due to an administrative management system of an urban system within city territory. Promoting coordinated spatial governance of mega-cities via spatial organization of metropolitan areas not only helps mega-cities better allocate resources at a larger scope and helps expedite the transformation of development patterns, but is also crucial for better implementing new-type urbanization strategies. In response to the issues in China’s previous research and practices related to mega-cities and metropolitan areas, leveraging the “Critical Technology for Spatial Optimization of Metropolitan Areas of City Clusters” of the national key R&D plan in the “14th Five-year Plan” period, we have employed a scientific approach that combines data and models to propose spatial governance strategies. These strategies encompass both the overall metropolitan area level and the cross-border regional level. Our primary focus lies in optimizing the spatial layout of the “three domains” – ecological space, production space, and living space, facilitating functional dispersal, enhancing spatial patterns, adjusting land use structures and spatial resource allocation, coordinating rail transit and the organization of functions along transit lines, and innovating service management for improvement of administrative efficiency. Through the implementation of these diverse measures, we aim to establish a comprehensive composite collaborative system.

Abstract Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients.

Abstract The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases of the disease and progress under intense evolutionary pressures. Organ-specific metastasis relies on the formation of pre-metastatic niche (PMN), with diverse cell types and complex cell interactions contributing to this concept, adding a new dimension to the traditional metastasis cascade. Prior to metastatic dissemination, as orchestrators of PMN formation, primary tumor-derived extracellular vesicles prepare a fertile microenvironment for the settlement and colonization of circulating tumor cells at distant secondary sites, significantly impacting cancer progression and outcomes. Obviously, solely intervening in cancer metastatic sites passively after macrometastasis is often insufficient. Early prediction of metastasis and holistic, macro-level control represent the future directions in cancer therapy. This review emphasizes the dynamic and intricate systematic alterations that occur as cancer progresses, illustrates the immunological landscape of organ-specific PMN creation, and deepens understanding of treatment modalities pertinent to metastasis, thereby identifying some prognostic and predictive biomarkers favorable to early predict the occurrence of metastasis and design appropriate treatment combinations.

Abstract Objective This study aimed to evaluate the efficacy of autologous blood preparations, namely Platelet-Rich Plasma (PRP), Platelet-Rich Fibrin (PRF), and Concentrated Growth Factor (CGF), in maxillary sinus floor elevation surgery. The focus was on their impact on new bone formation, maxillary sinus floor height, and soft tissue healing. Methods A systematic search was conducted across PubMed/MEDLINE, Web of Science, Embase, and Scopus databases up to April 2024. This systematic review included both randomized clinical trials (RCTs) and controlled clinical trials (CCTs) that evaluated the efficacy of autologous blood preparations in maxillary sinus floor elevation surgery. The primary outcomes measured were the percentage of new bone formation, maxillary sinus floor height, and he percentage of soft tissue area. Data from the selected studies were extracted and analyzed to determine the impact of autologous blood preparations on these outcomes. The risk of bias was assessed using Cochrane’s risk of bias tool and ROBINS-I, and meta-analyses were performed using Review Manager 5.4 software to calculate effect sizes and integrate results from multiple studies. Results Among the 507 screened articles, 30 studies met the inclusion criteria. The results indicated that the application of PRP significantly increased new bone formation during maxillary sinus floor elevation surgery (primary outcome, MD = 4.40, CI = 0.37 to 8.44, P = 0.03), as well as improving maxillary sinus floor height elevation (secondary outcome, MD = 1.00, CI = 0.78 to 1.23, P

Abstract Pathogens detection is a crucial measure in the prevention of foodborne diseases. This study developed a novel multicolor colorimetric assay to visually detect Salmonella Typhimurium (S. Typhimurium), by utilizing the etching process of gold nanorods (AuNRs) with TMB2+. The strategy involved the construction of nanozyme by assembling magnetic covalent organic framework (MCOF) with aptamer-conjugated AuNPs (Apt-AuNPs), exhibiting remarkable peroxidase-like activity to catalyze the oxidation of TMB/H2O2 and inducing the etching of AuNRs. The presence of S. Typhimurium could inhibit this process, resulting in the generation of vivid colors. The multicolor colorimetric assay could specifically determine S. Typhimurium from 102 to 108 CFU mL−1 in 60 min with visual detection limit of 102 CFU mL−1, and instrumental detection limit of 2.3 CFU mL−1. Moreover, detecting S. Typhimurium in chicken, milk, pork and lettuce samples has shown promise in practical applications.

Abstract Background Tumor-infiltrating lymphocytes (TILs) are significantly implicated in regulating the tumor immune microenvironment (TIME) and immunotherapeutic response. However, little is known about the impact of the resident and exhausted status of TILs in hepatocellular carcinoma (HCC). Methods Single-cell RNA sequencing data was applied to discover resident and exhausted signatures of TILs. Survival outcomes, biological function, immune infiltration, genomic variation, immunotherapeutic efficacy, and sorafenib response were further explored the clinical significance and molecular association of TILs in HCC. Moreover, a candidate gene with predictive capability for the dismal subtype was identified through univariate Cox regression analysis, survival analysis, and the BEST website. Results Single-cell analysis revealed that CD8 + T, CD4 + T, and NK cells were strongly associated with resident and exhausted patterns. Specific resident and exhausted signatures for each subpopulation were extracted in HCC. Further multivariate Cox analysis revealed that the ratio of resident to exhausted CD4 + T cells in TIME was an independent prognostic factor. After incorporating tumor purity with the ratio of resident to exhausted CD4 + T cells, we stratified HCC patients into three subtypes and found that (i) CD4 residencyhighexhaustionlow subtype was endowed with favorable prognosis, immune activation, and sensitivity to immunotherapy; (ii) CD4 exhaustionhighresidencylow subtype was characterized by genome instability and sensitivity to sorafenib; (iii) Immune-desert subtype was associated with malignant-related pathways and poor prognosis. Furthermore, spindle assembly abnormal protein 6 homolog (SASS6) was identified as a key gene, which accurately predicted the immune-desert subtype. Prognostic analysis as well as in vitro and in vivo experiments further demonstrated that SASS6 was closely associated with tumor prognosis, proliferation, and migration. Conclusions The ratio of resident to exhausted CD4 + T cells shows promise as a potential biomarker for HCC prognosis and immunotherapy response and SASS6 may serve as a biomarker and therapeutic target for prognostic assessment of HCC.

Abstract Oral mucosal wounds exhibit accelerated healing with reduced scarring compared to cutaneous wounds, representing an optimal wound healing paradigm. However, the specific cellular subtypes orchestrating the efficient healing of mucosal tissues remain elusive. Through a comprehensive analysis integrating bulk-mRNA and single-cell sequencing data during the wound healing process in oral mucosa and skin, we have delineated a distinct set of genes markedly upregulated during tissue repair. This collection of wound healing-associated genesets was highly enriched in a specific keratinocyte subpopulation identified as STAT3-activated SPRR1B+ keratinocytes. Notably, despite the inherent rapidity of oral mucosal healing, the induction of SPRR1B+ keratinocytes is evident in both skin and mucosal wound healing processes in murine model. Intriguingly, these wound healing-promoting SPRR1B+ keratinocytes, which are induced via STAT3 activation, inherently abundant in unwounded normal mucosa but absent in normal skin. SPRR1B knockdown significantly inhibits mucosal keratinocyte migration, a critical attribute for effective wound healing. In summary, through analysis of human oral and skin wound healing processes at single-cell resolution, coupled with validation in murine model, suggests STAT3-activated SPRR1B+ keratinocytes are associated with the rapid mucosal repair process. This discovery underscores the potential application of SPRR1B+ keratinocytes in the therapeutic management of chronic or non-healing wounds.

Abstract Stereotactic radiation therapy (SBRT) has emerged as a promising treatment modality for locally advanced pancreatic cancer. The aim of this study is to assess the dosimetric efficacy of online adaptive radiotherapy (ART) in comparison to image-guided radiation therapy (IGRT) for pancreatic cancer. We conducted a retrospective analysis involving 8 patients diagnosed with locally advanced pancreatic cancer. The gross tumor volume (GTV) delineates the visible extent of the tumor on imaging, while the planning tumor volume (PTV) was generated by expanding 5 mm from the GTV and ensuring a 3 mm distance from the small intestine, duodenum, and stomach simultaneously. Treatment planning was executed using the United Imaging Healthcare Treatment Planning System workstation. The control group underwent evaluation based on daily validated fan-beam CT (FBCT) scans, assessing both the dose delivered to actual organs at risk (OARs) and the target volume. Radiotherapy plans were developed utilizing simulation CT, and conventional radiotherapy with daily image-guided radiation therapy (IGRT) was administered using FBCT-Linac. Conversely, patients in the study group received daily validated FBCT-guided adaptive radiotherapy plans, with a focus on mean dose assessment of both the target volume and OARs. Subsequently, we compared the average outcomes of each treatment fraction between IGRT and online adaptive radiotherapy (ART). Comparison between ART and IGRT treatment plans revealed significant differences in various dosimetric parameters: For PTV: V98%: ART (96.28%) vs IGRT (89.73%), p = 0.000, V95%: ART (96.28%) vs IGRT (89.73%), p = 0.031, V90%: ART (98.58%) vs IGRT (93.65%), p = 0.000, Dmean: ART (4912.91) vs IGRT (4804.11), p = 0.000. For GTV: V100%: ART (97.96%) vs IGRT (94.85%), p = 0.314, V98%: ART (100.00%) vs IGRT (96.83%), p = 0.000, V90%: ART (100.00%) vs IGRT (97.75%), p = 0.000, Dmean: ART (4972.17) vs IGRT (4907.23), p = 0.000. For the duodenum: D0.5cc: ART (2883.92) vs IGRT (3359.35), p = 0.000, D1cc: ART (2726.32) vs IGRT (3128.66), p = 0.001, D5cc: ART (2051.96) vs IGRT (2273.93), p = 0.015, D10cc: ART (1650.73) vs IGRT (1731.74), p = 0.211. For the small bowel: D0.5cc: ART (3022.3) vs IGRT (3142.64), p = 0.037. D5cc: ART (2151.09) vs IGRT (2389.15), p = 0.043, D10cc: ART (1775.20) vs IGRT (1942.00), p = 0.079. For the stomach: D0.5cc: ART (3353.92) vs IGRT (4117.85), p = 0.000, D5cc: ART (2860.20) vs IGRT (3235.41), p = 0.000, D10cc: ART (2553.72) vs IGRT (2836.73), p = 0.000. For the Dmean of the left kidney and right kidney: Left kidney: ART (248.28) vs IGRT (239.65), p = 0.100. Right kidney: ART (314.55) vs IGRT (307.17), p = 0.345. These results suggest significant improvements in PTV coverage and sparing of OARs with ART compared to IGRT, indicating the potential of ART in optimizing treatment outcomes for pancreatic cancer patients. Compared to conventional IGRT-guided SBRT programs, ART-based SBRT for pancreatic cancer not only enhances the dose distribution to the target volume but also mitigates the radiation exposure to critical organs-at-risk (OARs) such as the duodenum, small intestine, and stomach. This approach may offer a more favorable safety profile while concurrently enhancing treatment efficacy.

Mg–3Y/Al composites were produced through accumulated rolling bonding. During annealing, Al–Y precipitates were synthesized in-situ within the Mg–3Y/Al composites through solid diffusion reactions. In these composites, the volume fraction of the interface layer containing abundant Al–Y precipitates can reach approximately 74% after three passes of accumulated rolling bonding and diffusion annealing. At room temperature, the Mg–3Y/Al composite exhibits increased strength (∼273.9 MPa) but reduced ductility (∼3.5%) compared to the base Mg–3Y alloy (∼191.0 MPa, ∼30%), due to the presence of numerous Al–Y precipitates and residual dislocations. These Al–Y precipitates display remarkable thermal stability, maintaining their size without significant coarsening even after annealing at 400 °C for 1–4 h, thereby contributing to the exceptional thermal stability observed in Mg–3Y/Al samples. After annealing at 400 °C for 4 h, the tensile strength of the Mg–3Y/Al samples remained unchanged, while the ductility increased to 8.5%. At 300 °C, the Mg–3Y/Al composite demonstrates exceptional high-temperature strength (179.9 MPa), significantly surpassing that of the original Mg–3Y alloy (110.6 MPa). Moreover, compared to the original Mg–3Y alloy and magnesium alloys reported in the literature, the Mg–3Y/Al composite exhibits a higher RE-equivalent strength at 300 °C. This enhanced strength is primarily attributed to precipitation strengthening induced by fine Al–Y precipitates. These findings underscore that introducing fine Al–Y precipitates through a solid diffusion reaction is an effective approach for achieving outstanding high-temperature strength in magnesium alloys.

Abstract Background Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). Methods Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran’s Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. Results The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ( $$\:OR\:=\:1.22$$ , $$\:95\%\:CI:\:1.13-1.33$$ , $$\:P

Abstract Immunotherapy has shown promising anti-tumor effects across various tumors, yet it encounters challenges from the inhibitory tumor immune microenvironment (TIME). Infiltrating regulatory T cells (Tregs) are important contributors to immunosuppressive TIME, limiting tumor immunosurveillance and blocking effective anti-tumor immune responses. Although depletion or inhibition of systemic Tregs enhances the anti-tumor immunity, autoimmune sequelae have diminished expectations for the approach. Herein, we summarize emerging strategies, specifically targeting tumor-infiltrating (TI)-Tregs, that elevate the capacity of organisms to resist tumors by reprogramming their phenotype. The regulatory mechanisms of Treg reprogramming are also discussed as well as how this knowledge could be utilized to develop novel and effective cancer immunotherapies.

The continuous growth of the global population has led to a continuous rise in the demand for meat products. However, traditional meat production methods are unable to meet the huge demand of the people, and also bring about a series of problems such as environmental pressure, animal welfare, and so on. Artificial meat technology is expected to solve these problems. At present, artificial meat can be divided into three categories: Plant protein meat, mushroom protein meat, and cell culture meat. This study mainly summarizes the production process, advantages, and market prospects of three types of artificial meat, analyzes the difficulties and technical challenges, and discusses the corresponding development proposals and solution strategies, with a view to provide references for the research of artificial meat and its industrialization.

Background and aim: A surplus of glucocorticoids (GC) is a main cause of non-traumatic osteonecrosis of the femoral head (ONFH), and Jintiange (JTG), as one of the traditional Chinese medicines (TCM), also plays an instrumental role in the alleviation of bone loss simultaneously. Therefore, JTG was thought to be able to reverse GC-induced ONFH (GC-ONFH) to a certain extent. Experimental procedure: In vivo, the effect of JTG on trabeculae in the subchondral bone of the femoral head was investigated using micro-computed tomography (micro-CT), TdT-mediated dUTP nick end labeling (TUNEL) and histological staining; in vitro, proliferation, viability, apoptosis, and senescence of purified bone mesenchymal stem cells (BMSCs) were examined to demonstrate the direct impact of JTG on these cells. Meanwhile after using a series of interventions, the function of JTG on BMSC differentiation could be assessed by measuring of osteogenic and adipogenic markers at levels of protein and mRNA. Results: Our final results demonstrated that with the involvement of Wnt/β-catenin pathway, JTG was able to significantly promote osteogenesis, restrain adipogenesis, delay senescence in BMSCs, reduce osteoclast number, weaken apoptosis, and enhance proliferation of osteocytes, all of which could mitigate the progression of subchondral osteonecrosis. Conclusion: According to the results of experiments in vitro and vivo, JTG was deemed to relieve the early GC-ONFH using the prevention of destruction of subchondral bone, which was contributed to regulating the differentiation of BMSCs and the number of osteoclasts.

Objective: To evaluate the health-care level (HCL), one of the most extensively used indicators to assess the level of medical exposure, and its influencing factors in China. Methods: Based on the data from the China Statistical Yearbook of the National Bureau of Statistics and other public documents, HCL was calculated in terms of the number of physicians per head of population throughout the country. Multiple linear regression was used to analyze the association of HCL with main socioeconomic factors, including population size, area, number of administrative divisions and gross domestic product (GDP). Results: Since 2015, there has been at least one physician for every 1,000 people in China on average. However, by 2019, there has yet been one physician for more than 1,000 people in each of two provinces. By 2020, there was at least one physician for every 1,000 people across all 31 provincial-level administrative districts (provinces). The population size and GDP were the influencing factors on HCL, with correlation coefficients of 0.416 and −0.583, respectively. Furthermore, a moderate correlation was found between HCL and the frequency of medical exposure (FME) to ionizing radiation (r ​= ​−0.620, P ​= ​0.028). Conclusion: There has been at least one physician for every 1,000 people since 2015, but there are great differences between various provinces. HCL as an indicator to evaluate level of medical exposure is warranted further research in China.

Deep storage tunnels (DSTs) are used in densely urbanized areas to relieve stormwater collection systems, thereby reducing urban floods and runoff pollution, due to their substantial storage capacity. The computation of the hydraulic characteristics and flow trajectories of DSTs under rapid filling scenarios can help to predict sediment deposition and pollutant accumulation associated with the stored runoff, as well as the likelihood of operational problems, such as excessive surging. However, such assessments are complicated by various inflow scenarios encountered in tunnel systems during their operation. In this study, the Suzhou River DST in China is selected as a study case. Particles were tracked, and hydraulic analysis was conducted with scaled model experiments and numerical models. The flow field, particle movement, air‒water phase, and pressure patterns in the DST were simulated under various one- and two-sided inflow scenarios. The results showed that with regards to the design conditions involving two-sided inflows, flow reversals occurred with stepwise increases in the water surface and pressure. In contrast, this phenomenon was not observed under the one-sided inflow scenario. Under the asymmetric two-sided inflow scenarios, water inflows led to particle accumulation near the shaft, reducing the received inflows. However, under the symmetric inflow conditions, particles were concentrated near the middle of the tunnel. Compared to those under the symmetric inflow scenario, asymmetric inflow caused surface wave and entrapped air reductions. This study could provide support for regulation of the inflow of the Suzhou River DST and for prediction of sediment and pollutant accumulation.

Abstract Purpose To evaluate the diagnostic performance of image-based artificial intelligence (AI) studies in predicting muscle-invasive bladder cancer (MIBC). (2) To assess the reporting quality and methodological quality of these studies by Checklist for Artificial Intelligence in Medical Imaging (CLAIM), Radiomics Quality Score (RQS), and Prediction model Risk of Bias Assessment Tool (PROBAST). Materials and methods We searched Medline, Embase, Web of Science, and The Cochrane Library databases up to October 30, 2023. The eligible studies were evaluated using CLAIM, RQS, and PROBAST. Pooled sensitivity, specificity, and the diagnostic performances of these models for MIBC were also calculated. Results Twenty-one studies containing 4256 patients were included, of which 17 studies were employed for the quantitative statistical analysis. The CLAIM study adherence rate ranged from 52.5% to 75%, with a median of 64.1%. The RQS points of each study ranged from 2.78% to 50% points, with a median of 30.56% points. All models were rated as high overall ROB. The pooled area under the curve was 0.85 (95% confidence interval (CI) 0.81–0.88) for computed tomography, 0.92 (95% CI 0.89–0.94) for MRI, 0.89 (95% CI 0.86–0.92) for radiomics and 0.91 (95% CI 0.88–0.93) for deep learning, respectively. Conclusion Although AI-powered muscle-invasive bladder cancer-predictive models showed promising performance in the meta-analysis, the reporting quality and the methodological quality were generally low, with a high risk of bias. Critical relevance statement Artificial intelligence might improve the management of patients with bladder cancer. Multiple models for muscle-invasive bladder cancer prediction were developed. Quality assessment is needed to promote clinical application. Key Points Image-based artificial intelligence models could aid in the identification of muscle-invasive bladder cancer. Current studies had low reporting quality, low methodological quality, and a high risk of bias. Future studies could focus on larger sample sizes and more transparent reporting of pathological evaluation, model explanation, and failure and sensitivity analyses. Graphical Abstract

Abstract Background Accurately redirecting reconstructed Positron emission tomography (PET) images into short-axis (SA) images shows great significance for subsequent clinical diagnosis. We developed a system for automatic redirection and quantitative analysis of myocardial PET images. Methods A total of 128 patients were enrolled for 18 F-FDG PET/CT myocardial metabolic images (MMIs), including 3 image classifications: without defects, with defects, and excess uptake. The automatic reorientation system includes five modules: regional division, myocardial segmentation, ellipsoid fitting, image rotation and quantitative analysis. First, the left ventricular geometry-based canny edge detection (LVG-CED) was developed and compared with the other 5 common region segmentation algorithms, the optimized partitioning was determined based on partition success rate. Then, 9 myocardial segmentation methods and 4 ellipsoid fitting methods were combined to derive 36 cross combinations for diagnostic performance in terms of Pearson correlation coefficient (PCC), Kendall correlation coefficient (KCC), Spearman correlation coefficient (SCC), and determination coefficient. Finally, the deflection angles were computed by ellipsoid fitting and the SA images were derived by affine transformation. Furthermore, the polar maps were used for quantitative analysis of SA images, and the redirection effects of 3 different image classifications were analyzed using correlation coefficients. Results On the dataset, LVG-CED outperformed other methods in the regional division module with a 100% success rate. In 36 cross combinations, PSO-FCM and LLS-SVD performed the best in terms of correlation coefficient. The linear results indicate that our algorithm (LVG-CED, PSO-FCM, and LLS-SVD) has good consistency with the reference manual method. In quantitative analysis, the similarities between our method and the reference manual method were higher than 96% at 17 segments. Moreover, our method demonstrated excellent performance in all 3 image classifications. Conclusion Our algorithm system could realize accurate automatic reorientation and quantitative analysis of PET MMIs, which is also effective for images suffering from interference.

Natural fractures are crucial factors influencing productivity and water invasion in the ultra-deep tight sandstone gas wells of the Keshen gas reservoir in the Kuqa Depression, Tarim Basin. Research on fractures is significant for understanding water invasion patterns and formulating effective water control strategies. This study investigated the development characteristics, distribution patterns, and water invasion characteristics of effective fractures using core samples, thin sections, conventional logging, imaging logging, production data, and well testing, as well as the influence of different fracture networks on water invasion. High-angle and nearly vertical shear fractures are the main fracture types. Vertically, the first member of Bashijiqike Formation (K1bs1) is predo-minantly characterized by completely filled fractures, which are ineffective fractures. Conversely, the second and third members of Bashijiqike Formation (K1bs2 and K1bs3) are mostly characterized by partially filled and unfilled fractures, which are effective fractures. Horizontally, the NNW-SSE striking effective fractures are concentrated in the western part of the gas reservoir and have larger average apertures. The eastern part has relatively deve-loped nearly E-W and NWW-SEE striking effective fractures with smaller average apertures. The more deve-loped and the larger the aperture of the effective fractures, the lower the initial water production from gas wells, with more production of condensate water. From production onset to water breakthrough, formation water is produced in various forms: sealed water, condensate water, movable water and pure formation water. The development stage, aperture and orientation of effective fractures are important factors affecting heterogeneous water invasion. Dense, highly effective fracture networks that are nearly parallel to the orientation of water invasion will accelerate the water invasion speed, resulting in significant water production and severely reducing gas well productivity. Integrating the development characteristics of effective fractures with individual well water invasion dynamics reveals three types of water invasion: rapid channeling along faults or dense fractures, slow coning along sparse fractures and slow uplift and invasion of edge-bottom water.

Abstract The Internet of Things (IoT) is an extensive system of interrelated devices equipped with sensors to monitor and track real world objects, spanning several verticals, covering many different industries. The IoT's promise is capturing interest as its value in healthcare continues to grow, as it can overlay on top of challenges dealing with the rising burden of chronic disease management and an aging population. To address difficulties associated with IoT-enabled healthcare, we propose a secure routing protocol that combines a fuzzy logic system and the Whale Optimization Algorithm (WOA) hierarchically. The suggested method consists of two primary approaches: the fuzzy trust strategy and the WOA-inspired clustering methodology. The first methodology plays a critical role in determining the trustworthiness of connected IoT equipment. Furthermore, a WOA-based clustering framework is implemented. A fitness function assesses the likelihood of IoT devices acting as cluster heads. This formula considers factors such as centrality, range of communication, hop count, remaining energy, and trustworthiness. Compared with other algorithms, the proposed method outperformed them in terms of network lifespan, energy usage, and packet delivery ratio by 47%, 58%, and 17.7%, respectively.

Abstract Conventional wireless communication schemes indiscriminately transmit information into the whole space and pose inherent security risks. Recently, directional information modulation (DIM) has attracted enormous attention as a promising technology. DIM generates correct constellation symbols in the desired directions and distorts them in undesired directions, thus ensuring the security of the transmitted information. Although several DIM schemes have been reported, they suffer from defects of bulkiness, energy consumption, high cost, and inability to support two-dimensional (2D) and high-order modulations. Here, we propose a DIM scheme based on a 2-bit programmable metasurface (PM) that overcomes these defects. A fast and efficient discrete optimization algorithm is developed to optimize the digital coding sequences, and the correct constellation symbols can be generated and transmitted in multi-directional beams. As a proof-of-concept, three sets of constellation diagrams (8 phase shift keying (PSK), 16 quadrature amplitude modulation (QAM), and 64QAM) are realized in the multi-channel modes. This work provides an important route of employing DIM for ensuring physical-layer security and serves as a stepping stone toward endogenous secure communications.

In modern highway construction, asphalt pavement is a widely used structural form, which is easily affected by various external conditions, among which the temperature effect is the most significant. In this paper, the cohesion model is used to simulate the structural cracks of asphalt pavement, the finite element method is used to simulate the asphalt concrete pavement model, and the temperature field simulation model of the pavement is established by using ABAQUS software, with the help of which the spatial distribution of stresses under different temperature conditions is deeply explored, and then the crack extension law during the process of temperature change is systematically investigated, and the effect of the temperature load on the degree of damage to the asphalt pavement is also studied. With the temperature change, the pavement surface layer is affected the most, and the soil base layer is affected the least. The higher the external temperature, the larger the crack expansion width inside the pavement structure, and the faster the corresponding expansion rate. The fatigue damage rate of the pavement structure is accelerated along with the increase of temperature. The research results can provide a theoretical basis for improving the high temperature performance of asphalt pavement.

Summary: The endocannabinoid system (ECS), which is composed of endocannabinoids (eCBs), cannabinoid receptors (CBRs), and associated signaling molecules, has been identified within the brain. In neuropathic pain animal models and patients, long-lasting alterations in the ECS have been observed. These changes of neurons and glial cells in the ECS contribute to the modulation of neuropathic pain. Intervention strategies such as the activation of CBRs, the enhancement of hydrolytic enzyme function, and the inhibition of synthetizing enzymes typically alleviate neuropathic pain through CBR-dependent mechanisms. Additionally, emotions such as fear, anxiety, and depression are frequently experienced with neuropathic pain. Exogenous cannabinoids can mitigate these mood disorders via CBR signaling pathways. Therefore, the targeting of long-lasting ECS alterations represents a potential therapeutic approach for both neuropathic pain and emotional disorders. In this review, the long-lasting variations in neurons and glial cells in the ECS related to neuropathic pain and the accompanying emotional comorbidities are elucidated. Furthermore, the cellular and molecular mechanisms underlying synaptic plasticity and neural circuit activities in the brain are reviewed.

ObjectivesTo present our initial experience of robotic ureteroplasty with lower-lip mucosal graft (LLMG) for treating ureteral stenosis longer than 2 cm and evaluate its feasibility and efficacy.Materials and methodsA total of thirteen patients with ureteral stenosis who underwent robotic ureteroplasty with LLMG were retrospectively analyzed. After identification and dissection of the ureteral stenosis segment, the segment was incised longitudinally. Then, the LLMG was harvested according to the characteristics of stenosis and sutured with the ureter in onlay fashion. All procedures were completed successfully.ResultThe median stenosis length was 3.5 cm (ranged: 3.0–4.5 cm). The mean length and width of the LLMG were 3.81 ± 0.60 cm and 1.27 ± 0.26 cm, respectively. The mean operative time and anastomosis time were 212.31 ± 23.06 min and 36.54 ± 6.58 min, respectively. The double-J stent was removed at 8 weeks postoperatively in all patients. Three patients (23.1%) suffered postoperative complications during the follow-up period (range, 6–18 months), including fever, urinary tract infection and stenosis recurrence. The success rate was 92.3% (12/13).ConclusionRobotic ureteroplasty with LLMG is a safe and feasible technique for treating ureteral stenosis.

BackgroundTic disorder, a chronic neurodevelopmental disorder that typically onsets during childhood, is characterized by sudden, involuntary, rapid, and non-rhythmic motor and vocal tics. Individuals with tic disorders often experience physical health issues. The purpose of our retrospective analysis was to elucidate the common comorbid physical diseases and mental disorders and their characteristics of outpatient children with tic disorders in a large public children’s hospital in China over the past 5 years.MethodsParticipants were outpatients with tic disorders who visited Beijing Children’s Hospital, from January 1, 2018 to December 31, 2022. After the inclusion screening, a total of 523,462 patient visits were included in the analysis. Based on the International Classification of Diseases, 10th Revision (ICD-10) diagnostic system, we employed descriptive statistical analysis to examine the frequently co-occurring somatic diseases in patients with tic disorders, as well as the influence of variables such as age and seasonal variation on these comorbidities.ResultsThe top five diseases of total outpatient visits were as follows: Respiratory diseases, Mental and behavioral disorders, Diseases of the eye and adnexal, Digestive disorders, Diseases of the skin and subcutaneous tissue. Among the top five comorbid disease system, the most commonly third- level classification of diseases were upper respiratory tract infections, attention deficit and hyperactivity disorder, conjunctivitis, dyspepsia, dermatitis. Respiratory system diseases experienced a peak in April, while the other four types of diseases reached their peak in August. Additionally, each disease system showed the lowest number of patient visits in February. Additional to the mental and behavioral disorders, the other four disease systems would experience a peak in medical visits between the ages of 4 and 6.ConclusionOur study highlighted the most common physical diseases and mental disorders in tic disorders, namely the respiratory diseases, specifically upper respiratory tract infections, and mental and behavioral disorders, with ADHD being the most common co-occurring condition.

Exosomes have emerged as a crucial focus in advancing the diagnosis and treatment of osteoarthritis (OA). However, there are limited bibliometric studies on this topic. This study aimed to delineate the literature landscape on exosomes in OA, identifying global research trends and key areas. We utilised the Web of Science Core Collection to retrieve articles published from 2004 to 2023. Our analysis included 456 publications across 671 institutions from 40 countries/regions. Publication volume, citations, and emerging research foci and trends were examined. Our results reveal a consistently increased interest in exosomes related to OA over the past two decades. Prominent institutions contributing to this research include Shanghai Jiao Tong University and Shenzhen University. The leading journal for these publications is the International Journal of Molecular Sciences, with Stem Cell Research & Therapy being the most frequently co-cited journal. Notable scholars in this field are Li Duan, Yujie Liang, Xiao Xu, and Wei Seong Toh, with Shipin Zhang emerging as the most co-cited author. The principal research themes were elucidating how exosomes contribute to OA pathology and developing novel therapeutic approaches. Research hotspots and new trends are linked to terms such as “cartilage,” “mesenchymal stem cell,” “miRNA,” “treatment,” and “biomarkers.” This comprehensive analysis offers valuable insights into the prevailing scientific discourse, pivotal topics, and potential future directions. It could serve as a foundational reference for researchers exploring exosomes and their utility in OA diagnostics and therapeutics.

Although medium and deep ground source heat pump system are more advantageous for heating compared to other heat pump systems in winter, there has been limited researches on medium and deep ground source heat pump system in a cold and arid region. In order to study the heating performance of the system and address heating issues in a cold and arid region, the experimental tests were conducted from November 1, 2021, to March 31, 2022, and the results showed that the heating system operates stably, maintaining indoor heating above 18 °C throughout the day. The average coefficient of performance (COP) is 5.67, and the cumulative power consumption is 185971 kWh. Additionally, this study established a new three-dimensional numerical model of a medium and deep borehole heat exchanger (MDBHE) and validated it with experimental test results. The numerical simulation analyzed the impact of different insulation layers, well diameters, flow rate and well depths on the heat pump performance and heating effectiveness. This experimental research and numerical simulation are significant to promote the development of low-carbon as soon as possible.

In this study, the formation mechanism, physicochemical properties, and intermolecular interactions of ball milling pretreated high amylose corn starch (HACS)-ferulic acid (FA) complexes were elucidated by density functional theory (DFT) calculations, and examined their structural and digestive properties. The results showed that the average molecular weight decreased to 92.155 kDa during ball milling pretreatment. The complexation degree of the ball milling pretreated HACS-FA complexes was increased, the relative crystallinity was increased by 11.74 %, and the short-range ordering was significantly improved. Notably, the content of single helix and double helix showed an increasing trend, indicating that HACS-FA complexes had a more compact V-type structure, which corresponded to a 22.39 % increase in resistant starch. DFT calculations further showed that the intermolecular interactions between HACS and FA were mainly hydrophobic, hydrogen bonding, and van der Waals forces. This study is expected to provide a new method for the efficient preparation of HACS-FA complexes.

Researchers have long been working on interpreting and predicting the dynamics of complex systems in various fields. Conventional methods including full-scale simulations and reduced-order models are used to solve related problems, but often yield unsatisfactory results in terms of precision and computational efficiency. This is primarily due to the challenges posed by simulating small-scale dynamics. An alternative consideration is to leverage well-represented and readily accessible large-scale dynamics to assist small-scale modelling. This paper proposes a novel methodology, named as Neural Downscaling (ND), that effectively captures small-scale dynamics within a complementary subspace from corresponding large-scale dynamics well-represented in a low-dimensional space. The framework of ND integrates neural operator techniques with the principles of inertial manifold and nonlinear Galerkin theory. The effectiveness and efficiency of ND are demonstrated in the complex systems governed by Kuramoto–Sivashinsky and Navier–Stokes equations. Being an unprecedentedly deterministic model targeted at general small-scale dynamics, ND sheds light on the intricate spatiotemporal nonlinear dynamics of complex systems and reveals how small-scale dynamics are interacting with large-scale dynamics.

Urban pumping stations often adopt the design of lateral-intake multiple forebays to accommodate multiple pump units in a limited space and to reduce interaction between the operating units. However, a full understanding of the undesired flows and hydraulic characteristics of lateral-intake multiple forebays remains limited, resulting in the design of flow-regulating measures relying on trial and error. This study numerically investigated the undesired flows in lateral-intake multiple forebays and their hydraulic implications, using Asia’s largest urban water supply pumping station as a case study. The results show that the undesired flows, including flow recirculation, helical mainstream and vortex strip, are the main reasons for the deterioration of hydraulic characteristics in the forebays. The undesired flows are more pronounced at higher inflow Froude numbers or for the forebay closer to the diversion channel inlet, resulting in lower flow uniformity and higher hydraulic loss. Further discussion shows that the flow-regulating measures improve the hydraulic characteristics by limiting the generation and development of undesired flows within the forebays. This provides references for the design of flow-regulating measures for similar forebays to reduce the cost of trial and error, which is of general value for the lateral-intake multiple forebays required for urban pumping stations.

Tuberculosis (TB) remains one of the deadliest chronic infectious diseases globally. Early diagnosis not only prevents the spread of TB but also ensures effective treatment. However, the absence of non-sputum-based diagnostic tests often leads to delayed TB diagnoses. Inflammation is a hallmark of TB, we aimed to identify biomarkers associated with TB based on immune profiling. We collected 222 plasma samples from healthy controls (HCs), disease controls (non-TB pneumonia; PN), patients with TB (TB), and cured TB cases (RxTB). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure the levels of 92 immune proteins. Based on differential analysis and the correlation with TB severity, we selected 9 biomarkers (CXCL9, PDL1, CDCP1, CCL28, CCL23, CCL19, MMP1, IFNγ and TRANCE) and explored their diagnostic capabilities through 7 machine learning methods. We identified combination of these 9 biomarkers that distinguish TB cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.89–0.99, with a sensitivity of 82–93% at a specificity of 88–92%. Moreover, the model excels in distinguishing severe TB cases, achieving AUROC exceeding 0.95, sensitivities and specificities exceeding 93.3%. In summary, utilizing targeted proteomics and machine learning, we identified a 9 plasma proteins signature that demonstrates significant potential for accurate TB diagnosis and clinical outcome prediction.

The leno fabric is widely used in production and life for its distinctive style. However, its production and design are hindered by the unique weaving process. In this paper, a three-dimensional simulation algorithm is proposed to enhance the efficiency of leno fabric production. Three geometric models are constructed that systematically address different aspects of fabric simulation. The Yarn Spatial Trajectory Model, in which the centerline trajectory of the yarn is controlled by the weave matrix, allowing for the realistic simulation of intertwined yarns characteristic of leno structures. The Variable Coefficient Elliptic Cross-Section Model, by which yarn collisions are prevented and computational demands are reduced. The Multifilament Model, critical to rendering quality, accurately captures the textural characteristics of yarns and fabrics. Leno fabrics are simulated based on the above models. The simulation results show that: different yarn counts and twists, fabric counts, hexagonal hole sizes, and other simulation effects can be achieved by entering different parameters. By the 3D simulation algorithm developed in this study, simulation fabrics have clear textures, precise structures, and realistic visual effects, thereby advancing the technology of leno fabric production.

ObjectiveThis study investigates the impact of non-standard positioning on the accuracy of 6D-skull tracking using dual-panel imaging systems. It explores whether positioning patients’ heads at various angles during intracranial lesion treatment affects the accuracy of the CyberKnife 6D-skull tracking system.Materials and methodsA heterogeneous density skull phantom was used to simulate various patient skull positioning angles. To accurately compare 6D-skull tracking and fiducial tracking, their center coordinates were pre-set to be identical in the treatment plan. The phantom was positioned using fiducial tracking, and the offset value recorded. The system was then switched to 6D-skull tracking to observe the corresponding offset. The difference between the two tracking methods was calculated, and a paired-sample T-test was conducted to assess statistical significance across different angles. Additionally, the gamma passing rate (criteria: 3%/3mm) was employed to quantitatively delineate dosimetric disparities attributable to positional variations.ResultsPaired sample T-tests on the deviations between rotational and translational parameters of fiducial tracking and skull tracking under identical conditions revealed no statistically significant differences between the methods across all selected angles. The minimal deviations and lack of statistical significance demonstrate that both tracking methods are equivalent in skull positioning. Furthermore, the gamma passing rate analysis showed that in all tested conditions, the rates exceeded 95%, which aligns with clinical requirements. This high passing rate indicates a high degree of dosimetric accuracy and consistency between the two tracking methods, providing robust assurance of treatment precision in skull positioning.ConclusionSince fiducial tracking is not affected by patient or phantom positioning, this study compares the registration results of 6D-skull tracking with fiducial tracking under the same conditions. The results show minimal deviations and no statistically significant differences, indicating that 6D-skull tracking is not dependent on the skull’s positioning angle. Furthermore, the gamma passing rate analysis was conducted to quantitatively assess the dosimetric differences arising from variations in patient positioning. Our results demonstrated that under all tested conditions, the gamma passing rates exceeded the clinically accepted threshold of 95%, confirming the clinical adequacy of both tracking methods in maintaining treatment precision. In clinical practice, patients do not need to maintain a strict supine position; the algorithm can accurately perform registration even if patients need to rotate their heads or lie prone. Clinical recommendations should prioritize patient comfort and safety without imposing overly strict requirements.

Abstract Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed “immunosenescence,” which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underlying immunosenescence, detailing alterations in immunosenescence at molecular, cellular, organ, and disease levels. The role of immunosenescence in tumorigenesis and senescence‐related extracellular matrix (ECM) has also been addressed. Recognizing that immunosenescence is a dynamic process influenced by various factors, we will evaluate treatment strategies targeting hallmarks and molecular mechanisms, as well as methods for immune cell, organ restoration, and present emerging approaches in immunosenescence for tumor immunotherapy. The overarching goal of immunosenescence research is to prevent tumor development, recurrence, and metastasis, ultimately improving patient prognosis. Our review aims to reveal latest advancements and prospective directions in the field of immunosenescence research, offering a theoretical basis for development of practical anti‐immunosenescence and anti‐tumor strategies.

Objectives This study aimed to examine the relationship between measures of kidney function and impaired lung function in individuals with diabetes and to assess all-cause mortality risk associated with having chronic kidney disease (CKD) and or impaired lung function.Design Cross-sectional and retrospective cohort study.Setting The National Health and Nutrition Examination Survey 2007–2012.Participants A total of 10 809 participants aged over 20 years were included in this study: 9503 with normal spirometry, 951 with preserved ratio impaired spirometry (PRISm) and 355 with variable obstruction (VO).Exposure and outcome measures Kidney function measures, including estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), were considered exposure variables. PRISm and VO were outcome variables. PRISm was defined as a forced expiratory volume in 1 s (FEV1)60. After adjustments, an increase in UACR was associated with higher odds of PRISm in individuals with diabetes (OR (95% CI)=1.21 (1.08, 1.36), p=0.002), and UACR ≥300 mg/g significantly increased odds of having PRISm in idividuals with diabetes (OR (95% CI)=2.34 (1.23, 4.47), p=0.01). During a mean follow-up of 12.3 years, 10 500 deaths occurred. In the diabetic group, compared with normal spirometry without CKD, those with both PRISm and CKD had a significantly increased risk of all-cause mortality (HR (95% CI)=3.46 (1.94, 6.16), p

ObjectiveGastroparesis is one of the complications of diabetes mellitus, which has a major impact on the quality of life of patients, and the limited therapeutic options currently available make it a public health problem. No bibliometric studies on diabetic gastroparesis have been published to date. Therefore, the aim of this paper is to summarize and analyze the research hotspots for researchers.MethodsResearch articles related to Diabetic gastroparesis were searched in Web of Science Core Collection (WOSCC), and relevant information was extracted after screening. A comprehensive bibliometric analysis of 699 publications was conducted using Microsoft Excel 2019, Citespace and VOSviewers.ResultA total of 699 papers from 738 institutions in 41 countries were retrieved. Publications in this field have increased rapidly since 1979. USA (n = 370) and Mayo Clinical (n = 69) were the most productive country and institution, respectively. Neurogastroenterology and Motility (n = 67) was the most published journal with Parkman, Henry P. (n = 40) having the highest number of articles; Gastroenterology and Mccallum, Richard W. were the most influential journals and authors.ConclusionsThe research hotspots of Diabetic gastroparesis are mainly focused on treatment modalities and pathological mechanisms. Future research in diabetic gastroparesis will focus on exploring the pathomechanisms, finding long-term effective treatments, and improving patients' quality of life.