Search

Abstract Ultrasonography (US) of thyroid nodules is often time consuming and may be inconsistent between observers, with a low positivity rate for malignancy in biopsies. Even after determining the ultrasound Thyroid Imaging Reporting and Data System (TIRADS) stage, Fine needle aspiration biopsy (FNAB) is still required to obtain a definitive diagnosis. Although various deep learning methods were developed in medical field, they tend to be trained using TI-RADS reports as image labels. Here, we present a large US dataset with pathological diagnosis annotation for each case, designed for developing deep learning algorithms to directly infer histological status from thyroid ultrasound images. The dataset was collected from two retrospective cohorts, which consists of 8508 US images from 842 cases. Additionally, we explained three deep learning models used as validation examples using this dataset.

Abstract The application of medical image segmentation technology enables accurate localization of human tissues, providing doctors with a reliable foundation for diagnosis. While deep learning methods have proven effective in this task, most current approaches rely on a single prediction framework, which overlooks Edge semantic features and results in flawed texture features. Moreover, existing supervised methods face challenges due to limited availability of high‐quality annotations in the field of medical imaging. In this article, a Semi‐supervised Contextual Cognitive Augmentation‐based Cross‐teaching Network is proposed. A Contextual Cognitive Enhancement Module is introduced consisting of two components: data augmentation and information extraction. The data augmentation component provides multi‐level data distribution by incorporating diverse perturbation strategies such as Discrete Cosine Transform and Gaussian noise. The information extraction component employs the Comprehensive Information Extraction module, which consists of Global Perception Information Extraction module and Multi‐channel Information Extraction module to extract perceptual information from images and enhance interaction between image channels, respectively. Additionally, a cross‐teaching strategy is adopted and a hybrid loss function is utilized to encourage knowledge sharing among the networks, leveraging the advantages of dual networks for improved performance. Experimental results demonstrate significant enhancements in multiclass medical image segmentation compared to several state‐of‐the‐art single‐framework networks.

Abstract Moyamoya disease (MMD) suffers from impaired cerebrovascular hemodynamics and high perioperative complications occurrence. This study aims to propose and evaluate the relationship between intraoperative hemodynamics and perioperative complications, and propose a potential compensatory self-recirculation network in MMD. We prospectively enrolled 63 MMD patients undergone combined revascularization, and patients were divided into decreased and increased group according to decreased and increased microvascular transit time (MVTT), respectively. Mean age of all patients was 45.9 ± 9.4 years. The post-bypass hyperperfusion syndrome occurrence was significantly higher in the decreased MVTT group, and the cerebral infarction occurrence was significantly higher in the increased MVTT group. For the hemodynamics of the recipient artery around anastomosis, the parameters of distal site demonstrated a significant higher intensity and shorter time in the decreased MVTT group, while the parameters of the proximal site demonstrated a significant higher intensity and shorter time in the increased MVTT group. Pre-bypass and post-bypass collision of blood flow in artery and vein were firstly observed and illustrated. Intraoperative hemodynamics showed close relationship with perioperative complications. The blood flow of MMD seems to develop a unique compensatory self-recirculation system and contribute to the clinical complications, providing a new insight to the clinical management the pathology of the disease.

Abstract Background The triglyceride glucose (TyG) index, defined as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], provides insights into overall metabolic status. However, the association between the TyG index and gout has not been investigated. Therefore, this study explored the correlation between the TyG index and gout. Methods Using data from the National Health and Nutrition Examination Survey, which was conducted from 2007 to 2018, this study investigated the relationship between the TyG index and gout. Demographic data and potential risk factors were analyzed and compared using t tests for continuous data and chi-square tests for categorical data. Logistic regression and subgroup analysis were performed to examine the association between the TyG index and gout. Results A total of 14,924 participants were enrolled, among whom 726 (4.86%) were diagnosed with gout. Without controlling for any covariates, a significant positive correlation was observed between an elevated TyG index and increased risk of gout, with an odds ratio (OR) of 2.07 and a 95% confidence interval (CI) ranging from 1.76 to 2.43. After full adjustment, this association remained statistically significant, with an adjusted OR of 1.43 and a 95% CI from 1.14 to 1.80. Subgroup analyses revealed significant interactions, particularly for females (OR = 2.55; 95% CI: 2.00-3.26), individuals with no military service history (OR = 2.15; 95% CI: 1.66–2.43), and those without diabetes (OR = 2.00; 95% CI: 1.64–2.43). Conclusion A positive correlation was observed between the TyG index and gout. Consequently, further large-scale prospective studies are warranted for a comprehensive analysis of the role of the TyG index in gout.

Seed size is an important agronomic trait in melons that directly affects seed germination and subsequent seedling growth. However, the genetic mechanism underlying seed size in melon remains unclear. In the present study, we employed Bulked-Segregant Analysis sequencing (BSA-seq) to identify a candidate region (~1.35 Mb) on chromosome 6 that corresponds to seed size. This interval was confirmed by QTL mapping of three seed size-related traits from an F2 population across three environments. This mapping region represented nine QTLs that shared an overlapping region on chromosome 6, collectively referred to as qSS6.1. New InDel markers were developed in the qSS6.1 region, narrowing it down to a 68.35 kb interval that contains eight annotated genes. Sequence variation analysis of the eight genes identified a SNP with a C to T transition mutation in the promoter region of MELO3C014002, a leucine-rich repeat receptor-like kinase (LRR-RLK) gene. This mutation affected the promoter activity of the MELO3C014002 gene and was successfully used to differentiate the large-seeded accessions (C-allele) from the small-seeded accessions (T-allele). qRT-PCR revealed differential expression of MELO3C014002 between the two parental lines. Its predicted protein has typical LRR-RLK family domains, and phylogenetic analyses reveled its similarity with the homologs in several plant species. Altogether, these findings suggest MELO3C014002 as the most likely candidate gene involved in melon seed size regulation. Our results will be helpful for better understanding the genetic mechanism regulating seed size in melons and for genetically improving this important trait through molecular breeding pathways.

Objective Traditional exploration and geochemical studies have primarily focused on the extraction, interpretation and evaluation of metallogenic element anomalies. This approach, however, overlooks valuable ore prospecting information, which may be provided by other major and trace elements. Consequently, altered minerals cannot be effectively extracted, and geochemical data is under utilized for ore prospecting. Therefore, the author extracts alteration minerals from a mineralogical perspective and make metallogenic prediction. Methods This paper introduces a new method for extracting alteration minerals based on geochemical data and the stoichiometric ratios of different elements in the mineral chemical formula, referred to as the general element ratio analysis. Results Based on geochemical data obtained from 1∶ 25 000 debris geochemical survey in the Gaoshishan area of the Beishan orogenic belt, results show that sericite, K-feldspar and other alteration minerals are closely related to porphyry deposits, which can be effectively identified from SiO2, Al2O3, Na2O, K2O and other data. The mapping results reveal that sericite is mostly distributed along the intrusion's margins, while K-feldspar is mainly concentrated in the center of theintrusion. Then, based on the ore-controlling factors and ore-prospecting information, such as alteration minerals, magmatic rocks, structures, and traditional geochemical anomalies. This study further conducts metallogenic prediction for the Gaoshishan area using the weight-of-evidence method, delineating five target areas. Conclusion The alteration information extracted in this study has been validated through field investigations confirming that the proposed method is feasible and can provide critical prospecting insights beyond those offered by traditional metallogenic prediction methods.

Abstract Porcine pasteurellosis is an infectious disease caused by Pasteurella multocida (P. multocida), which seriously endangers the healthy development of pig breeding industry. Early detection of disease transmission in animals is a crucial early warning for humans. Therefore, predicting risk areas for disease is essential for public health authorities to adopt preventive measures and control strategies against diseases. In this study, we developed a predictive model based on multi-criteria decision analysis (MCDA) and assessed risk areas for porcine pasteurellosis in the Chinese mainland. By using principal component analysis, the weights of seven spatial risk factors were determined. Fuzzy membership function was used to standardize all risk factors, and weight linear combination was used to create a risk map. The sensitivity of the risk map was analyzed by calculating the mean of absolute change rates of risk factors, as well as calculating an uncertainty map. The results showed that risk areas for porcine pasteurellosis were predicted to be locate in the south-central of the Chinese mainland, including Sichuan, Chongqing, Guangdong, and Guangxi. The maximum standard deviation of the uncertain map was less than 0.01and the ROC results showed that the prediction model has moderate predictive performance with the area under the curve (AUC) value of 0.80 (95% CI 0.75–0.84). Based on the above process, MCDA was combined with WebGIS technology to construct a system for predicting risk areas of porcine pasteurellosis. Risk factor data was directly linked to the developed model, providing decision support for disease prevention and control through monthly updates.

Abstract Background Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. Methods Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. Results The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. Conclusions In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA.

Abstract Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable ‘gears’ between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.

Introduction: Cardiac hypertrophy is an important contributor of heart failure, and the mechanisms remain unclear. Leucine zipper protein 1 (LUZP1) is essential for the development and function of cardiovascular system; however, its role in cardiac hypertrophy is elusive. Objectives: This study aims to investigate the molecular basis of LUZP1 in cardiac hypertrophy and to provide a rational therapeutic approach. Methods: Cardiac-specific Luzp1 knockout (cKO) and transgenic mice were established, and transverse aortic constriction (TAC) was used to induce pressure overload-induced cardiac hypertrophy. The possible molecular basis of LUZP1 in regulating cardiac hypertrophy was determined by transcriptome analysis. Neonatal rat cardiomyocytes were cultured to elucidate the role and mechanism of LUZP1 in vitro. Results: LUZP1 expression was progressively increased in hypertrophic hearts after TAC surgery. Gain- and loss-of-function methods revealed that cardiac-specific LUZP1 deficiency aggravated, while cardiac-specific LUZP1 overexpression attenuated pressure overload-elicited hypertrophic growth and cardiac dysfunction in vivo and in vitro. Mechanistically, the transcriptome data identified Stat3 pathway as a key downstream target of LUZP1 in regulating pathological cardiac hypertrophy. Cardiac-specific Stat3 deletion abolished the pro-hypertrophic role in LUZP1 cKO mice after TAC surgery. Further findings suggested that LUZP1 elevated the expression of Src homology region 2 domain-containing phosphatase 1 (SHP1) to inactivate Stat3 pathway, and SHP1 silence blocked the anti-hypertrophic effects of LUZP1 in vivo and in vitro. Conclusion: We demonstrate that LUZP1 attenuates pressure overload-induced cardiac hypertrophy through inhibiting Stat3 signaling, and targeting LUZP1 may develop novel approaches to treat pathological cardiac hypertrophy.

Identifying novel compound–protein interactions (CPIs) plays a pivotal role in target identification and drug discovery. Although the recent multimodal methods have achieved outstanding advances in CPI prediction, they fail to effectively learn both intra-modality and inter-modality dynamics, which limits their prediction performance. To address the limitation, we propose a novel multimodal tensor fusion CPI prediction framework, named MMTF-CPI, which contains three unimodal learning modules for structure, heterogeneous network and transcriptional profiling modalities, a tensor fusion module and a prediction module. MMTF-CPI is capable of focusing on both intra-modality and inter-modality dynamics with the tensor fusion module. We demonstrated that MMTF-CPI is superior to multiple state-of-the-art multimodal methods across seven datasets. The prediction performance of MMTF-CPI is significantly improved with the tensor fusion module compared to other fusion methods. Moreover, our case studies confirmed the practical value of MMTF-CPI in target identification. Via MMTF-CPI, we also discovered several candidate compounds for the therapy of breast cancer and non-small cell lung cancer.

Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine–threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named “quadruple WT” GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.

Abstract Background Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. Method This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. Discussion Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. Trial registration ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

Abstract Background Energy allocation between growth and reproduction determines puberty onset and fertility. In mammals, peripheral hormones such as leptin, insulin and ghrelin signal metabolic information to the higher centres controlling gonadotrophin-releasing hormone neurone activity. However, these observations could not be confirmed in lower vertebrates, suggesting that other factors may mediate the energetic trade-off between growth and reproduction. A bioinformatic and experimental study suggested co-regulation of the circadian clock, reproductive axis and growth-regulating genes in zebrafish. While loss-of-function of most of the identified co-regulated genes had no effect or only had mild effects on reproduction, no such information existed about the co-regulated somatostatin, well-known for its actions on growth and metabolism. Results We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20–30% increase in embryonic primordial germ cells, and sst1.2 −/− adults laid 40% more eggs than their wild-type siblings. The sst1.1 −/− and sst1.2 −/− mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass. Conclusions We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility.

Abstract Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease often accompanied by low-grade inflammation. Recently, the neutrophil-to-lymphocyte ratio (NLR) has garnered researchers’ interest as an emerging inflammation biomarker. This study aimed to comprehensively explore the relationship between NLR and T2DM using the National Health and Nutrition Examination Survey (NHANES) database. Method We employed a cross-sectional study design to analyze data from five NHANES cycles from 2007 to 2016, excluding individuals with incomplete data. This study utilized a weighted logistic regression model, subgroup analyses, and restricted cubic spline (RCS) analysis to assess the potential relationship between NLR and T2DM. Results A total of 9903 participants were eligible for the analysis, of which 1280 were diagnosed with T2DM. The T2DM group exhibited significantly higher NLR levels than the non-T2DM group. After adjusting for potential confounders, elevated NLR levels were associated with an increased risk of developing T2DM, indicated by an odds ratio (OR) of 1.14, 95% CI: (1.05,1.24), P = 0.003. The results of the subgroup analyses revealed a significant interaction effect between NLR and T2DM concerning race and hypertension (P for interaction 0.05). RCS analysis showed a significant non-linear relationship between NLR and T2DM, with an inflection point at 2.27 (all P for non-linearity

Abstract Background Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. Methods A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. Results Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. Conclusion The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.

Abstract Background Compared to traditional thoracotomy, transapical transcatheter aortic valve implantation (TAVI) surgery offers reduced trauma and faster recovery, fostering the adoption of enhanced recovery after surgery (ERAS) protocols in cardiac surgery. Despite these advancements, postoperative pain management has received insufficient attention. The potential effects of multi-mode analgesia, including ultrasound-guided serratus anterior plane block (SAPB), on postoperative pain and early quality of recovery have not been widely studied, lacking comprehensive prospective evidence. Therefore, this study aims to investigate the impact of SAPB combined with general anesthesia on early recovery quality and analgesic efficacy in transapical TAVI patients. Methods This prospective, randomized controlled study will enroll 70 patients undergoing transapical TAVI, randomly allocated to either the SAPB group or the control group. The primary outcome, assessed using Quality of Recovery-40 (QOR-40) scale, focuses on the quality of recovery at 24 h and 48 h postoperatively. Secondary outcomes include the visual analog scale (VAS) pain scores at rest and during coughing at 6 h, 12 h, 24 h, and 48 h after surgery, frequency of patient-controlled analgesia (PCA) utilization at 24 h and 48 h, opioid consumption at 24 h and 48 h, time and frequency of rescue analgesia and severe pain at 24 h and 48 h, incidence of nausea and vomiting at 48 h after surgery, and dosage of antiemetic drugs. Discussion The purpose of our study is to evaluate the effects of ultrasound-guided SAPB combined with general anesthesia on postoperative early quality of recovery and analgesia in transapical TAVI patients. The results obtained may provide valuable insight for the implementation of multi-mode analgesia and enhanced ERAS in this specific patient population. Trial registration China Clinical Trial Register ChiCTR2300068584. Registered on 24 February 2023.

Abstract Background Off-pump coronary artery bypass grafting (OPCABG) presents distinct hemodynamic characteristics, yet the relationship between intraoperative hypotension and short-term adverse outcomes remains clear. Our study aims to investigate association between intraoperative hypotension and postoperative acute kidney injury (AKI), mortality and length of stay in OPCABG patients. Methods Retrospective data of 494 patients underwent OPCABG from January 2016 to July 2023 were collected. We analyzed the relationship between intraoperative various hypotension absolute values (MAP > 75, 65 65 mmHg emerges as a significant independent protective factor for AKI in OPCABG and IOH is related to length of hospital stay. Proactive intervention targeting intraoperative hypotension may provide a potential opportunity to reduce postoperative renal injury and hospital stay. Trial registration ChiCTR2400082518. Registered 31 March 2024. https://www.chictr.org.cn/bin/project/edit?pid=225349 .

BACKGROUND: Owing to the adverse effects of unilateral neglect (UN) on rehabilitation outcomes, fall risk, and activities of daily living, this field has gradually got considerable interest. Notwithstanding, there is presently an absence of efficient portrayals of the entire research field; hence, the motivation behind this study was to dissect and evaluate the literature published in the field of UN following stroke and other nonprogressive brain injuries to identify hotspots and trends for future research. MATERIALS AND METHODS: Original articles and reviews related to UN from 1970 to 2022 were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. CiteSpace, VOSviewer, and Bibliometrix software were used to observe publication fields, countries, and authors. RESULTS: A total of 1,202 publications were incorporated, consisting of 92% of original articles, with an overall fluctuating upward trend in the number of publications. Italy, the United Kingdom, and the United States made critical contributions, with Neuropsychologia being the most persuasive academic journal, and Bartolomeo P. ranked first in both the quantity of publications and co-citations. Keywords were divided into four clusters, and burst keyword detection demonstrated that networks and virtual reality might additionally emerge as frontiers of future development and warrant additional attention. CONCLUSIONS: UN is an emerging field, and this study presents the first bibliometric analysis to provide a comprehensive overview of research in the field. The insights and guidance garnered from our research on frontiers, trends, and popular topics could prove highly valuable in facilitating the rapid development of this field while informing future research directions.

Abstract Color-changing melon is an ornamental and edible fruit. Aiming at the problems of slow detection speed and high deployment cost for Color-changing melon in intelligent agriculture equipment, this study proposes a lightweight detection model YOLOv8-CML.Firstly, a lightweight Faster-Block is introduced to reduce the number of memory accesses while reducing redundant computation, and a lighter C2f structure is obtained. Then, the lightweight C2f module fusing EMA module is constructed in Backbone to collect multi-scale spatial information more efficiently and reduce the interference of complex background on the recognition effect. Next, the idea of shared parameters is utilized to redesign the detection head to simplify the model further. Finally, the α-IoU loss function is adopted better to measure the overlap between the predicted and real frames using the α hyperparameter, improving the recognition accuracy. The experimental results show that compared to the YOLOv8n model, the parametric and computational ratios of the improved YOLOv8-CML model decreased by 42.9% and 51.8%, respectively. In addition, the model size is only 3.7 MB, and the inference speed is improved by 6.9%, while mAP@0.5, accuracy, and FPS are also improved. Our proposed model provides a vital reference for deploying Color-changing melon picking robots.

Abstract Due to their high reliability and cost‐efficiency, submarine pipelines are widely used in offshore oil and gas resource engineering. Due to the interaction of waves, currents, seabed, and pipeline structures, the soil around submarine pipelines is prone to local scour, severely affecting their operational safety. With the Yellow River Delta as the research area and based on the renormalized group (RNG) k‐ε turbulence model and Stokes fifth‐order wave theory, this study solves the Navier–Stokes (N–S) equation using the finite difference method. The volume of fluid (VOF) method is used to describe the fluid‐free surface, and a three‐dimensional numerical model of currents and waves–submarine pipeline–silty sandy seabed is established. The rationality of the numerical model is verified using a self‐built waveflow flume. On this basis, in this study, the local scour development and characteristics of submarine pipelines in the Yellow River Delta silty sandy seabed in the prototype environment are explored and the influence of the presence of pipelines on hydrodynamic features such as surrounding flow field, shear stress, and turbulence intensity is analyzed. The results indicate that (1) local scour around submarine pipelines can be divided into three stages: rapid scour, slow scour, and stable scour. The maximum scour depth occurs directly below the pipeline, and the shape of the scour pits is asymmetric. (2) As the water depth decreases and the pipeline suspension height increases, the scour becomes more intense. (3) When currents go through a pipeline, a clear stagnation point is formed in front of the pipeline, and the flow velocity is positively correlated with the depth of scour. This study can provide a valuable reference for the protection of submarine pipelines in this area.

Abstract In this letter, to improve the performance and reduce leakage currents of bulk low‐temperature multi‐layer SiGe/Si superlattice (SL) fin field‐effect transistors (FinFETs), a p‐type omega‐shaped channel (Ω‐channel) SL FinFET is realized by etching a Si/Si0.7Ge0.3 triple‐layer stacked structure in a replacement metal gate (RMG) module on a silicon‐on‐insulator (SOI) substrate. In addition, a self‐allied Ni0.9Pt0.1 silicide process and a low‐thermal‐budget (≤400°C) integration procedure were performed on the Ω‐channel SL FinFET. Test results demonstrate that the on‐state current (Ion) is increased by 5.5 times (from 78 to 429 µA/µm) and the off‐state current (Ioff) is reduced by 78.8% (from 5.2 × 10−3 to 1.1 × 10−3 µA/µm) when compared with the corresponding currents of traditional bulk SL FinFETs.

Tail effect is a unique phenomenon in immunotherapy characterized by the prolonged maintenance of therapeutic efficacy. It can be observable even after treatment cessation. Immunotherapy has gradually become a vital regimen for the treatment of advanced lung cancer patients, among which immune-combined therapies based on immune checkpoint inhibitors (ICIs) have been applied clinically and demonstrates considerable clinical efficacy. In this case report, the patient was pathologically diagnosed with pulmonary sarcomatoid carcinoma (PSC), a rare and highly aggressive subtype of non-small cell lung cancer (NSCLC) known for its poor prognosis due to high invasiveness and metastatic potential. After developing resistance to chemotherapy, the patient was treated with a combined regimen of sintilimab and anlotinib, leading to initial clinical improvement. Following just three cycles of this regimen, treatment was discontinued, and the patient was discharged. Remarkably, over the subsequent months, the patient exhibited a significant tail effect, evidenced by sustained therapeutic stability, continuous tumor regression, stable low levels of serum carcinoembryonic antigen (CEA), and further improvement in clinical symptoms. Tail effect is a golden tail of immunotherapy. This case illustrates that the tail effect of immunotherapy can offer substantial survival benefits for patients with unresectable advanced lung cancer who have failed chemotherapy.

BackgroundUpadacitinib, a specific JAK1 inhibitor, has minimal effect on other JAK subtypes. It influences the inflammatory process in various ways. Upadacitinib has been approved for conditions such as rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, and ulcerative colitis in various countries. The purpose of this study is to assess the clinical efficacy and safety of upadacitinib in patients with refractory palmoplantar pustulosis who have not responded to conventional treatments (e.g., Acitretin, Tripterygium wilfordii Hook F, cyclosporine, methotrexate).MethodsWe conducted a retrospective collection of clinical data from 28 patients who received upadacitinib treatment at the Department of Dermatology, First Affiliated Hospital of Suzhou University, from July 2022 to December 2023. We evaluated the Palmoplantar Pustulosis Area and Severity Index (PPPASI) scores, Dermatology Life Quality Index (DLQI) scores, and Physician’s Global Assessment (PGA) scores before and after treatment. We also recorded any adverse events during the treatment process.ResultsA total of 28 patients were diagnosed with PPP, including 10 males and 18 females, and 8 patients (3 males and 5 females) were diagnosed with SAPHO syndrome. The mean age was (36.3 ± 10.5) years. After 12 weeks of treatment, PPPASI scores decreased from baseline (13.86 ± 2.76) to (5.56 ± 1.08), with a statistically significant difference (p < 0.05). DLQI scores decreased from (12.55 ± 4.56) to (2.03 ± 1.13), also showing a statistically significant difference (p < 0.05). Additionally, 20 patients achieved a PGA score of 0/1. No severe adverse events were reported during the treatment and follow-up period.ConclusionUpadacitinib could be an additional safe and effective treatment for treating refractory palmoplantar pustulosis with a potential benefit on patients’ quality of life. Further studies are needed to assess its short-and long-term efficacy and safety in larger sample sizes in randomized double-blind controlled trials.

Climate change has contributed to an increase in the frequency and intensity of natural disasters such as droughts, wildfires, hurricanes, and floods, leading to both immediate physical harm and long-term mental health consequences. Survivors often experience psychological distress, including anxiety, depression, and post-traumatic stress disorder (PTSD), as a result of these traumatic events. This narrative review explores the intersection of climate change-related disasters, mental health outcomes, and epigenetic modifications. Specifically, we summarize recent findings on how environmental stressors influence both mental health and epigenetic changes, such as DNA methylation. Emerging evidence suggests that epigenetic mechanisms, particularly DNA methylation, could mediate the effects of climate change-related stress on mental health, potentially contributing to the onset of mental disorders like depression, panic disorder, autism spectrum disorder, and attention deficit hyperactivity disorder. We also discuss other epigenetic mechanisms, such as histone modifications and non-coding RNAs, and emphasize the importance of longitudinal studies to capture the dynamic nature of epigenetic changes over time. Finally, we propose future research directions to deepen our understanding of the complex relationships between climate change-related disasters, mental health outcomes, and epigenetic mechanisms, which will pave the way for more effective mental health interventions and policy integration.

Abstract Carotenoids are natural pigments utilized as colourants and antioxidants across food, pharmaceutical and cosmetic industries. They exist in carbon chain lengths of C30, C40, C45 and C50, with C40 variants being the most common. Bacterioruberin (BR) and its derivatives are part of the less common C50 carotenoid group, synthesized primarily by halophilic archaea. This study analysed the compositional characteristics of BR extract (BRE) isolated from ‘Haloferax marinum’ MBLA0078, a halophilic archaeon isolated from seawater near Yeoungheungdo Island in the Republic of Korea, and investigated its antioxidant activity and protective effect on lipopolysaccharide (LPS)‐induced C2C12 myotube atrophy. The main components of BRE included all‐trans‐BR, monoanhydrobacterioruberin, 2‐isopentenyl‐3,4‐dehydrorhodopin and all‐trans‐bisanhydrobacterioruberin. BRE exhibited higher antioxidant activity and DNA nicking protection activity than other well‐known C40 carotenoids, such as β‐carotene, lycopene and astaxanthin. In C2C12 myotubes, LPS treatment led to a reduction in myotube diameter and number, as well as the hypertranscription of the muscle‐specific ubiquitin ligase MAFbx and MuRF1. BRE mitigated these changes by activating the Akt/mTOR pathway. Furthermore, BRE abolished the elevated cellular reactive oxygen species levels and the inflammation response induced by LPS. This study demonstrated that ‘Hfx. marinum’ is an excellent source of natural microbial C50 carotenoids with strong antioxidant capacity and may offer potential protective effects against muscle atrophy.

Abstract During spring, migratory birds are required to optimally balance energetic costs of migration across heterogeneous landscapes and weather conditions to survive and reproduce successfully. Therefore, an individual's migratory performance may influence reproductive outcomes. Given large‐scale changes in land use, climate, and potential carry‐over effects, understanding how individuals migrate in relation to breeding outcomes is critical to predicting how future scenarios may affect populations. We used GPS tracking devices on 56 Greater White‐fronted Geese (Anser albifrons) during four spring migrations to examine whether migration characteristics influenced breeding propensity and breeding outcome. We found a strong longitudinal difference in arrival to the breeding areas (18 days earlier), pre‐nesting duration (90.9% longer), and incubation initiation dates (9 days earlier) between western‐ and eastern‐Arctic breeding regions, with contrasting effects on breeding outcomes, but no migration characteristic strongly influenced breeding outcome. We found that breeding region influenced whether an individual likely pursued a capital or income breeding strategy. Where individuals fell along the capital‐income breeding continuum was influenced by longitude, revealing geographic effects of life‐history strategy among conspecifics. Factors that govern breeding outcomes likely occur primarily upon arrival to breeding areas or are related to individual quality and previous breeding outcome, and may not be directly tied to migratory decision‐making across broad scales.

BackgroundChylous leakage (CL) is a rare but significant complication following cervical lymph node dissection, particularly in patients with papillary thyroid carcinoma (PTC). This condition is characterized by the leakage of lymphatic fluid, which can result in severe consequences such as malnutrition, immunosuppression, and prolonged hospital stays. Conventional treatments for CL include conservative measures and surgical interventions, but these approaches often face limitations and challenges. This case report discusses a successful treatment of CL using thoracic duct lymphangiography combined with local injection of sclerotherapy, demonstrating a novel and effective approach for managing this complication.Case presentationA 72-year-old female patient with PTC underwent total thyroidectomy and bilateral Level VI and left Levels II, III, IV, and V cervical lymph node dissection. Postoperatively, the patient developed milky drainage indicative of CL. Despite initial conservative treatments including pressure bandaging, negative pressure drainage, and nutritional adjustments, the patient's condition did not improve. The patient declined surgical options, leading to the decision to perform thoracic duct lymphangiography combined with local injection of sclerotherapy. Under real-time ultrasound guidance, the inguinal lymph nodes were accessed, and lipiodol was injected to visualize the thoracic duct. Subsequently, foam sclerosant was injected at the leakage site under fluoroscopic guidance. The procedure resulted in a significant reduction of chyle leakage, and the patient was discharged with no recurrence during a 1-year follow-up.ConclusionsThis case illustrates that thoracic duct angiography combined with local injection of sclerotherapy can be an effective treatment for high-output CL when conservative measures fail and surgical intervention is not preferred. The approach offers a minimally invasive alternative that can reduce complications and improve patient outcomes. The successful management of CL in this case underscores the potential of advanced interventional techniques in treating lymphatic system complications and highlights the need for further research to establish standardized treatment protocols.

The park environment is crucial for promoting physical activity (PA). While numerous studies show that park environments influence PA behavior, inconsistencies remain, likely due to varing research methods and parks types. This study employs a fixed spatial grid method to systematically sample four representative parks in Tianjin, China. High-precision orthophoto map (DOM) data from drones provided detailed environmental attributes (like tree canopy area, lawn area, and paved area) and PA characteristics (number of participants, intensity, diversity). The results show: 1) Cluster analysis grouped 1839 park grids into 12 environmental attribute integrations, each correlating with different PA characteristics. “Tree-lined jogging corridors” and “Large sports field areas” exhibit the highest PA intensity, while “Entrance plazas”, “Central plazas,” and “Open sports spaces” have the highest number of participants and PA diversity. 2) Correlation analysis shows that various environmental attributes, including Lawn Area, and Paved Area, are significantly correlated with PA characteristics. 3）Random Forest analysis indicates the key attributes are the paved area for the number of PA participants and PA diversity, and specialized sports facilities area for PA intensity. These findings support urban green space planning and highlight the importance of better park environments for public health.

BackgroundGliomas are aggressive brain tumors associated with a poor prognosis. Cancer stem cells (CSCs) play a significant role in tumor recurrence and resistance to therapy. This study aimed to identify and characterize glioma stem cells (GSCs), analyze their interactions with various cell types, and develop a prognostic signature.MethodsSingle-cell RNA sequencing data from 44 primary glioma samples were analyzed to identify GSC populations. Spatial transcriptomics and gene regulatory network analyses were performed to investigate GSC localization and transcription factor activity. CellChat analysis was conducted to infer cell-cell communication patterns. A GSC signature (GSCS) was developed using machine learning algorithms applied to bulk RNA sequencing data from multiple cohorts. In vitro and in vivo experiments were conducted to validate the role of TUBA1C, a key gene within the signature.ResultsA distinct GSC population was identified, characterized by high proliferative potential and an enrichment of E2F1, E2F2, E2F7, and BRCA1 regulons. GSCs exhibited spatial proximity to myeloid-derived suppressor cells (MDSCs). CellChat analysis revealed an active MIF signaling pathway between GSCs and MDSCs. A 26-gene GSCS demonstrated superior performance compared to existing prognostic models. Knockdown of TUBA1C significantly inhibited glioma cell migration, and invasion in vitro, and reduced tumor growth in vivo.ConclusionThis study offers a comprehensive characterization of GSCs and their interactions with MDSCs, while presenting a robust GSCS. The findings offer new insights into glioma biology and identify potential therapeutic targets, particularly TUBA1C, aimed at improving patient outcomes.

With the improvement of economic level, a continuous rise in building energy consumption brings about serious environmental problems. Therefore, this study proposes a passive energy-consuming residential building envelope thermal insulation and heat preservation method based on building information modeling technology for building energy consumption increasing and envelope structure's performance improving. Firstly, it is a study on the passive low-energy residential building envelope's thermal insulation materials and architecture, and secondly, it is a study on the improvement of the thermal insulation and heat preservation performance of the passive low-energy residential building envelope on the foundation of building information modeling. These experimental results show that in the residential building, the indoor temperature averages around 27.8 °C, of which the highest indoor ambient temperature is found at 21 o'clock, with a temperature value of 28.4 °C, which reduces 2.1 °C when comparing with the indoor temperature under the traditional residential building. Under the exterior wall construction utilizing this technology, the temperature change of the indoor environment is smoother, which satisfies people's requirements for the indoor living environment. At the same time, the area parameters of the ventilation area of the building and the area of the envelope obtained after the analysis of BIM technology have a significant effect on the cooling of the interior. This method reduces the use of resources and lays a good foundation for the further development of building informatization, which is significant in realizing the informatization developing in construction.

The trace element zinc (Zn) is involved in various biological processes in plant, yet its excessive accumulation can result in plant toxicity. In this study, we unveiled a novel NAC transcription factor, AcNRZ1, in kiwifruit, and qRT-PCR analysis showed that the expression of AcNRZ1 can be up-regulated by Zn stress. Furthermore, Zn stress induces the translocation of AcNRZ1 from endoplasmic reticulum (ER) to nucleus. Overexpression of AcNRZ1 in Arabidopsis imparts tolerance and elevates the germination rates under Zn stress. Subsequent studies have demonstrated that the overexpression of AcNRZ1 facilitates the transport of Zn ions from the root to the leaf and enhances the Zn detoxification process in the vacuole by upregulating the expression of the Zn transport-related gene HMA4, as well as Zn detoxification-related genes including MTP1/3/5, GSH1, and PCS1. Additionally, overexpression of AcNRZ1 in Arabidopsis stimulates the expression of antioxidant enzyme related genes (SOD1 and CAT1), thereby leading to reduced accumulation of reactive oxygen species and ultimately enhancing tolerance to Zn stress. These findings suggest that AcNRZ1 influences plant response to Zn stress by modulating Zn ion transport, promoting detoxification processes, and regulating the accumulation of reactive oxygen species, thereby conferring plant tolerance to Zn stress.

Aim: To analyze the clinical phenotype and genetic etiology of three cases of glutaric aciduria type 1 (GA1) in Chinese children. Methods: We performed genetic and metabolic testing using tandem mass spectrometry (MS/MS) and gas chromatography–mass spectrometry (GC/MS), followed by trio whole-exome sequencing (trio-WES) and Sanger sequencing. A literature review on glutaric aciduria type 1 (GA1) in Chinese patients was also conducted. Results: Sequencing results showed each case had compound heterozygous variants in GCDH(NM_000159.4): c.214C > G (p.Arg72Gly) and c.411C > G (p.Tyr137Term) (Case 1), c.214C > G (p.Arg72Gly) and c.1204C > T (p.Arg402Trp) (Case 2), and c.1228G > T (p.Val410Leu) and c.395G > A (p.Arg132Gln) (Case 3). These variants were inherited from their respective parents. Notably, the c.214C > G variant found in two children was a novel variant not previously reported. A review of the literature revealed that, clinically, the majority of patients experienced onset in infancy and early childhood (82%). Additionally, 38.36% were diagnosed through newborn screening, with the primary reasons for the initial visit being delayed development (32.43%) and infections (21.61%). The most common clinical manifestations included increased head circumference (77.19%) and motor developmental delay (65.15%). Biochemically, patients exhibited significant elevations in C5DC (98.51%) and C5DC/C8 (94.87%) in blood, as well as GA (94.37%) and 3OHGA (69.39%) in urine. Radiographically, patients showed a high prevalence of abnormalities in cranial MRI (86.15%) and EEG (73.33%). Genetically, 67 distinct GCDH gene variants were identified among 73 patients, with missense variants being the most prevalent type (73.97%). The most frequent variant was c.1244-2 A > C, observed in 17.12% of cases. Additionally, the majority of variant sites were located in exons 11 (25.37%) and 6 (22.39%). Conclusion: GCDH variants were identified as the causative factors in the three children. The discovery of the novel variant (c.214C > G) expands the spectrum of pathogenic GCDH variants. These findings facilitate the diagnosis and treatment of affected children and provide a basis for genetic counseling and prenatal diagnosis for their families.

Abstract Background The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. Methods This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. Results Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36–2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82–0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32–2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51–5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. Conclusion We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population.

Abstract Viruses are crucial for regulating deep-sea microbial communities and biogeochemical cycles. However, their roles are still less characterized in deep-sea holobionts. Bathymodioline mussels are endemic species inhabiting cold seeps and harboring endosymbionts in gill epithelial cells for nutrition. This study unveiled a diverse array of viruses in the gill tissues of Gigantidas platifrons mussels and analyzed the viral metagenome and transcriptome from the gill tissues of Gigantidas platifrons mussels collected from a cold seep in the South Sea. The mussel gills contained various viruses including Baculoviridae, Rountreeviridae, Myoviridae and Siphovirdae, but the active viromes were Myoviridae, Siphoviridae, and Podoviridae belonging to the order Caudovirales. The overall viral community structure showed significant variation among environments with different methane concentrations. Transcriptome analysis indicated high expression of viral structural genes, integrase, and restriction endonuclease genes in a high methane concentration environment, suggesting frequent virus infection and replication. Furthermore, two viruses (GP-phage-contig14 and GP-phage-contig72) interacted with Gigantidas platifrons methanotrophic gill symbionts (bathymodiolin mussels host intracellular methanotrophic Gammaproteobacteria in their gills), showing high expression levels, and have huge different expression in different methane concentrations. Additionally, single-stranded DNA viruses may play a potential auxiliary role in the virus–host interaction using indirect bioinformatics methods. Moreover, the Cro and DNA methylase genes had phylogenetic similarity between the virus and Gigantidas platifrons methanotrophic gill symbionts. This study also explored a variety of viruses in the gill tissues of Gigantidas platifrons and revealed that bacteria interacted with the viruses during the symbiosis with Gigantidas platifrons. This study provides fundamental insights into the interplay of microorganisms within Gigantidas platifrons mussels in deep sea.

Abstract Background Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. Methods We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. Results The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. Conclusions The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

Abstract Chinese classical gardens are a significant cultural heritage in the history of world gardening, with their central architectural principle of "scenes changing as steps move" (步移景异) embodying traditional Chinese aesthetic ideals. This study employed the variation of visual complexity during a tour as a representation of this principle, using Jingxinzhai (静心斋) Garden as a case study. The visual environmental characteristics were quantified using the Fraclab box-counting, Canny edge detection, and DeepLab V3 + model, and the spatial distribution of fractal dimension and visual index of landscape elements were analyzed. Through partial correlation analysis, hierarchical regression analysis, and one-way ANOVA, the relevant factors (BVI, RVI, GVI, WVI) and influencing factors (BVI, RVI, GVI) and the differences among landscape element combinations of visual complexity were identified. Furthermore, the distribution patterns and causes of visual complexity in Chinese classical gardens were then discussed. This study proposes an effective method for quantifying the visual environmental characteristics of Chinese classical gardens and provides an explanation of the concept of "scenes changing as steps move" from the perspective of visual environment. It offers important references for a deeper understanding of Chinese classical garden design and planning.

Abstract Objective Personality, emotions, and olfaction exhibit partial anatomical overlap in the limbic system structure, establishing potential mechanisms between personality, affective disorders, and olfactory-related aspects. Thus, this study aims to investigate the associations among the Big Five personality traits, alexithymia, anxiety symptoms, and odor awareness. Methods A total of 863 college participants were recruited for this study. All participants completed the Chinese Big Five Personality Inventory-15, the Odor Awareness Scale (OAS), the Toronto Alexithymia Scale-20, and the Generalized Anxiety Disorder Screener-7. Structural equation modeling was employed to examine the hypothesized mediated model. Results The findings revealed the majority of significant intercorrelations among the dimensions of the Big Five personality traits, alexithymia, anxiety symptoms, and OAS (|r| = 0.072–0.567, p

Astrocytes, constituting the predominant glial cells in the brain, undergo significant morphological and functional transformations amidst the progression of Parkinson’s disease (PD). A majority of these reactive astrocytes display a neurotoxic phenotype, intensifying inflammatory responses. Nonetheless, the molecular underpinnings steering neurotoxic astrocyte reactivity during PD progression remain mostly uncharted. Here, we uncover the unique role of cystathionine γ-lyase (CSE) in shaping astrocyte reactivity, primarily channeling astrocytes towards a neurotoxic phenotype, thereby escalating neuroinflammation in PD. Single-cell sequencing data drawn from PD patients coupled with RNA sequencing data from MPP+-treated astrocytes, highlighted a marked positive association between increased expression of Cth, the gene that encodes CSE, and neurotoxic astrocyte reactivity. Employing genetic manipulation of Cth in astrocytes, we evidenced that CSE instigates a transition to a neurotoxic state in PD-afflicted astrocytes under in vitro and in vivo settings. Moreover, we identified a CSE-Yes-associated protein (YAP) complex within astrocytes via label-free mass spectrometry. An increased formation of the CSE-YAP complex was found to facilitate the expression of gene patterns tied to neurotoxic astrocytes, driven by the transcription factor, forkhead box protein D3 (FOXD3). Consequently, our work unveils valuable insights into the cell type-specific function of CSE in the brain, and presents FOXD3 as a novel transcription factor influencing astrocyte phenotypes in PD. These findings lay the groundwork for the development of potential strategies intended to manage conditions associated with neuroinflammation.

Investigating the formation and emergence of local education clusters involving universities and regional stakeholders, this study develops an institutional framework to analyze the interactions and coordination among key cluster actors with respect to the evolution of local strategic human resource development (HRD). A policy document analysis concerning the latest local HRD and semi-structured interviews with various stakeholders of local universities, local government functionaries, and local enterprises were conducted. Based on the findings, the sharing of resources, knowledge, and experience, along with the exchange of professional dispositions, skills, and identity orientations among actors within local clusters, fosters an enriching educational environment for local universities and HRD. This collaborative environment facilitates cooperation and the strengthening of joint efforts among government entities, university faculty, and industry stakeholders in nurturing and advancing local human resources. However, some obstacles hinder this development, resulting in the seeking of quick success and instant benefits. Based on these key findings, various Chinese regions have tried to establish an approach conducive to the development of HRD-oriented higher education quality and outcomes. However, comprehensive efforts to stimulate cluster actors towards their collective implementation are necessary.

Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.

The frequent occurrence of extreme precipitation events notably affects the middle and lower reaches of the Yangtze River (MLYR) during the Mei-yu period. Based on meteorological station data from the China Meteorological Administration collected from 1970 to 2019, we employed nonlinear time series analysis and the state transition networks (STN) to identify the spatiotemporal and evolution characteristics of 10 extreme precipitation indices (EPIs). Although previous studies have largely focused on investigating the spatiotemporal characteristics, the suitability of STN for extreme precipitation has not been extensively explored. This study focused on not only the spatiotemporal characteristics of extreme precipitation but also its evolution using the STN. The results showed that the periodic oscillations in extreme precipitation ranged from 2 to 5 years and an abrupt change occurred primarily around 1990. Extreme precipitation displayed similar network parameters, yet different network structures and transition probabilities. The evolution of extreme precipitation exhibited from decreasing to increasing from 1970 to 2019, with an increasing trend after 1990. Similar network structures tended to exhibit higher Pearson correlations. Spatially, high EPIs values were mainly concentrated in the central region of the MLYR. This study could provide new methods and perspectives for studying the characteristics of extreme precipitation.

Abstract Background Extrachromosomal circular DNAs (eccDNAs), a type of double‐stranded DNAs (dsDNAs) that facilitate the activation of the DNA sensing machinery, have been implicated in the progression and prognosis of various diseases. While the roles of eccDNAs remain contentious, their significance in diffuse large B‐cell lymphoma (DLBCL) has not been reported. Methods Circular DNA sequencing (circle‐seq) was used to demonstrate the expression profile of eccDNAs in DLBCL, and atomic force microscopy to validate the presence of eccDNAs. CCK‐8 and scRNA‐seq techniques were employed to uncover the activation of eccDNA in the STING pathway, leading to enhanced cell proliferation. Chemotherapeutic drugs were used to test the hypothesis that DNA damage induces the production of eccDNA, thereby activating the STING pathway independent of cGAS. GEO databases were used for verification of the prognosis of the eccDNA‐related genes, and animal models were used to investigate the synergistic effects of DNA damage therapy in combination with STING inhibitors on anti‐tumour responses. Results EccDNAs were widely expressed in DLBCL and associated with the prognosis of patients. Elevated abundance of eccDNAs promoted the progression of DLBCL. Chemotherapeutic drugs‐induced DNA damage triggered the generation of eccDNAs, resulting in the activation of the STING signalling in a cGAS‐independent manner. Moreover, inhibition of STING exerted a synergistic anti‐tumour effect with cisplatin. Conclusions EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. This finding offers a rational therapeutic strategy combining chemotherapy with targeting STING. Highlights EccDNAs induced by DNA damage exert an oncogenic role in DLBCL via activating the STING signalling independently of cGAS. The combined treatment of chemotherapeutic drugs with STING inhibitor significantly delayed the tumor progression, providing new insights into the therapeutic strategy for patients with DLBCL, particularly the relapsed and/or refractory (R/R) ones.

Bathymodioline mussels dominate deep-sea methane seep and hydrothermal vent habitats and obtain nutrients and energy primarily through chemosynthetic endosymbiotic bacteria in the bacteriocytes of their gill. However, the molecular mechanisms that orchestrate mussel host–symbiont interactions remain unclear. Here, we constructed a comprehensive cell atlas of the gill in the mussel Gigantidas platifrons from the South China Sea methane seeps (1100 m depth) using single-nucleus RNA-sequencing (snRNA-seq) and whole-mount in situ hybridisation. We identified 13 types of cells, including three previously unknown ones, and uncovered unknown tissue heterogeneity. Every cell type has a designated function in supporting the gill’s structure and function, creating an optimal environment for chemosynthesis, and effectively acquiring nutrients from the endosymbiotic bacteria. Analysis of snRNA-seq of in situ transplanted mussels clearly showed the shifts in cell state in response to environmental oscillations. Our findings provide insight into the principles of host–symbiont interaction and the bivalves' environmental adaption mechanisms.