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Fulminant myocarditis (FM) is characteristically associated with rapid progressive decline in cardiac function and high mortality, with rapid onset of hemodynamic dysfunction and severe arrhythmias. In this report, we describe a case concerning a patient clinically diagnosed with FM, marked by rapid progression leading to intractable ventricular fibrillation and subsequent cardiac arrest. Conventional cardiopulmonary resuscitation (CCPR) was performed 120 min before extracorporeal membrane oxygenation (ECMO) was initiated. This critical situation was effectively addressed through the utilization of extracorporeal cardiopulmonary resuscitation (ECPR). By providing sustained cardiopulmonary support, effective hemodynamics were obtained. Eventually, the patient made a full recovery, and discharged without neurologic complications on hospital day 13.

In this protocol, we detail a seven-stage differentiation methodology for generating pancreatic delta cells (SC-delta cells) from human pluripotent stem cells (hPSCs). In the first step, definitive endoderm is generated by activin A and CHIR99021, followed by induction of primitive gut tube and posterior foregut by treatment with FGF7, SANT1, LDN193189, PdBU, and retinoic acid (RA). The subsequent endocrine generation and directed SC-delta cell induction is achieved by a combined treatment of the FGF7 with FGF2 during stage 4 and 5, together with RA, XXI, ALK5 inhibitor II, SANT1, Betacellulin and LDN193189. The planar cultivation is converted to a suspended system after stage 5, allowing cells to aggregate into delta cell-containing spheroids. The differentiation takes approximately 4-5 weeks for delta cell generation and an additional 1-2 weeks for cell expansion and evaluation. We believe that this amenable and simplified protocol can provide a stable source of SC-delta cells from efficient differentiation, facilitating further investigation of the physiological role of delta cells as well as refinement of islet cell therapeutic strategies.

Pear anthracnose, caused by Colletotrichum bacteria, is a severe infectious disease that significantly impacts the growth, development, and fruit yield of pear trees. Early detection of pear anthracnose before symptoms manifest is of great importance in preventing its spread and minimizing economic losses. This study utilized hyperspectral imaging (HSI) technology to investigate early detection of pear anthracnose through spectral features, vegetation indices (VIs), and texture features (TFs). Healthy and diseased pear leaves aged 1 to 5 days were selected as subjects for capturing hyperspectral images at various stages of health and disease. Characteristic wavelengths (OWs1 and OWs2) were extracted using the Successive Projection Algorithm (SPA) and Competitive Adaptive Reweighted Sampling (CARS) algorithm. Significant VIs were identified using the Random Forest (RF) algorithm, while effective TFs were derived from the Gray Level Co-occurrence Matrix (GLCM). A classification model for pear leaf early anthracnose disease was constructed by integrating different features using three machine learning algorithms: Support Vector Machine (SVM), Extreme Learning Machine (ELM), and Back Propagation Neural Network (BPNN). The results showed that: the classification identification model constructed based on the feature fusion performed better than that of single feature, with the OWs2-VIs-TFs-BPNN model achieving a highest accuracy of 98.61% in detection and identification of pear leaf early anthracnose disease. Additionally, to intuitively and effectively monitor the progression and severity of anthracnose in pear leaves, the visualization of anthracnose lesions was achieved using Successive Maximum Angle Convex Cone (SMACC) and Spectral Information Divergence (SID) techniques. According to our research results, the fusion of multi-source features based on hyperspectral imaging can be a reliable method to detect early asymptomatic infection of pear leaf anthracnose, and provide scientific theoretical support for early warning and prevention of pear leaf diseases.

BackgroundDespite advances in neuro-oncology, treatments of glioma and tools for predicting the outcome of patients remain limited. The objective of this research is to construct a prognostic model for glioma using the Homologous Recombination Deficiency (HRD) score and validate its predictive capability for glioma.MethodsWe consolidated glioma datasets from TCGA, various cancer types for pan-cancer HRD analysis, and two additional glioma RNAseq datasets from GEO and CGGA databases. HRD scores, mutation data, and other genomic indices were calculated. Using machine learning algorithms, we identified signature genes and constructed an HRD-related prognostic risk model. The model’s performance was validated across multiple cohorts. We also assessed immune infiltration and conducted molecular docking to identify potential therapeutic agents.ResultsOur analysis established a correlation between higher HRD scores and genomic instability in gliomas. The model, based on machine learning algorithms, identified seven key genes, significantly predicting patient prognosis. Moreover, the HRD score prognostic model surpassed other models in terms of prediction efficacy across different cancers. Differential immune cell infiltration patterns were observed between HRD risk groups, with potential implications for immunotherapy. Molecular docking highlighted several compounds, notably Panobinostat, as promising for high-risk patients.ConclusionsThe prognostic model based on the HRD score threshold and associated genes in glioma offers new insights into the genomic and immunological landscapes, potentially guiding therapeutic strategies. The differential immune profiles associated with HRD-risk groups could inform immunotherapeutic interventions, with our findings paving the way for personalized medicine in glioma treatment.

BackgroundThere is limited knowledge regarding the association between heart rate (HR) during different exercise phases and coronary artery disease (CAD). This study aimed to evaluate the relationship between four exercise-related HR metrics detected by cardiopulmonary exercise testing (CPET) and CAD. These metrics include HR at the anaerobic threshold (HRAT), HR at respiratory compensatory point (HRRCP), maximal HR (HRmax), and HR 60 s post-exercise (HRRec60s).MethodsThe 705 participants included 383 with CAD and 322 without CAD in Beijing Hospital, who underwent CPET between January 2021 and December 2022. The Logistic regression analysis was applied to estimate the odds ratio and the 95% confidence interval. Additionally, the multivariable Logistic regression analyses with restricted cubic splines were conducted to characterize the dose-response association and explore whether the relationship was linear or nonlinear.ResultsOur primary finding indicates that for each one-beat increase in HRAT, there is a 2.8% reduction in the adjusted risk of CAD in the general population. Similarly, a one-beat increase in HRRCP corresponds to a 2.6% reduction in the adjusted risk of CAD. Subgroup analyses revealed significant interactions between HRAT and factors such as sex, hypertension, and lung cancer, as well as between HRRCP and sex and hypertension, in relation to CAD. The dose-response analysis further confirmed that higher HRAT and HRRCP are associated with a reduced risk of CAD.ConclusionThese results are suggestive of a good association between HRAT, HRRCP, and CAD. The lower HRAT, and HRRCP are signs of poor HR response to exercise in CAD. HRAT and HRRCP are potentially good indicators of poor HR response to exercise without considering maximal effort.

Hybridization can substantially improve growth performance. This study used metagenomics and metabolome sequencing to examine whether the rumen microbiota and its metabolites contributed to this phenomenon. We selected 48 approximately 3 month-old male ♂Hu × ♀Hu (HH, n = 16), ♂Poll Dorset × ♀Hu (DH, n = 16), and ♂Southdown × ♀Hu (SH, n = 16) lambs having similar body weight. The sheep were fed individually under the same nutritional and management conditions for 95 days. After completion of the trial, seven sheep close to the average weight per group were slaughtered to collect rumen tissue and content samples to measure rumen epithelial parameters, fermentation patterns, microbiota, and metabolite profiles. The final body weight (FBW), average daily gain (ADG), and dry matter intake (DMI) values in the DH and SH groups were significantly higher and the feed-to-gain ratio (F/G) significantly lower than the value in the HH group; additionally, the papilla height in the DH group was higher than that in the HH group. Acetate, propionate, and total volatile fatty acid (VFA) concentrations in the DH group were higher than those in the HH group, whereas NH3-N concentration decreased in the DH and SH groups. Metagenomic analysis revealed that several Prevotella and Fibrobacter species were significantly more abundant in the DH group, contributing to an increased ability to degrade dietary cellulose and enrich their functions in enzymes involved in carbohydrate breakdown. Bacteroidaceae bacterium was higher in the SH group, indicating a greater ability to digest dietary fiber. Metabolomic analysis revealed that the concentrations of rumen metabolites (mainly lysophosphatidylethanolamines [LPEs]) were higher in the DH group, and microbiome-related metabolite analysis indicated that Treponema bryantii and Fibrobacter succinogenes were positively correlated with the LPEs. Moreover, we found methionine sulfoxide and N-methyl-4-aminobutyric acid were characteristic metabolites in the DH and SH groups, respectively, and are related to oxidative stress, indicating that the environmental adaptability of crossbred sheep needs to be further improved. These findings substantially deepen the general understanding of how hybridization promotes growth performance from the perspective of rumen microbiota, this is vital for the cultivation of new species and the formulation of precision nutrition strategies for sheep.

The fluctuations in power output from distributed power sources are rapid and dramatic, causing voltage fluctuations in the distribution network that threaten the safety of electricity consumption. Soft open points (SOPs) can replace traditional contact switches and are expected to suppress voltage fluctuations. However, traditional power regulation methods based on the reference values are unable to address rapid and large voltage fluctuations. Therefore, this paper proposes an adaptive power control method for SOPs based on virtual impedance. The SOP is modeled as a series link of adjustable impedance and a voltage source. Then, the voltage difference component is used to calculate the reference for the DQ domain to regulate the power flow in real time automatically. By doing so, the proposed method can smooth the voltage fluctuations in the distribution network. Additionally, the virtual impedance is also optimized to minimize the power loss. Finally, the method is validated through simulation and experiments, demonstrating that this method can automatically regulate power and significantly reduce voltage fluctuations.

During the Mesozoic, the North China Craton experienced intense tectonic movements that resulted in the formation of numerous gold deposits on the Liaodong and Jiaodong Peninsulas in northeastern China. To investigate the relationship between deep crustal structure and gold mineralization in the Liaodong Peninsula, we deployed 334 dense seismic stations in the Wulong goldfield (WLGF) with the idea of analysing numerous receiver functions at different array stations. The purpose focused on knowing the potential for gold mineralization in the area. The study revealed the following: (1) The WLGF is characterized by a crustal thickness of approximately 32 km and an average Vp/Vs ratio of 1.76. The high value of the Vp/Vs ratio near the Wulong gold deposit suggests that mantle materials have penetrated into the crust and contributed to the mineralization process. (2) A low-velocity layer located at a depth of 10–18 km below the WLGF seems to support the existence of a potentially brittle-ductile transition zone. Also, hydrothermal magma upwelling channels are observed in the upper crust beneath the Wulong gold deposit. (3) The presence of a discontinuous low-velocity layer in the middle crust beneath the Liaodong Peninsula suggests promising prospects for gold ore exploration. The receiver functions method based on a dense seismic array employed in this study can offer valuable references and guidance for the fine exploration and research of ore deposits in other regions globally.

BackgroundThe performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC.MethodsWe searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities.ResultsFourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89–0.94), 0.79 (95% CI 0.72–0.85), and 0.90 (95% CI 0.86–0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists.DiscussionIn conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).

ObjectivesThe study aims to examine the associations between exercise self-efficacy, motivation, physical activity, and body composition among emerging adults.DesignCross-sectional.MethodsA convenience sample of 147 emerging adults participated in the Releasing Weight (RELEW) project. The InBody720 analyzer was used to measure body composition, and the International Physical Activity Questionnaire-Short, the Shortened Physical Activity Self-Efficacy Scale, and the Treatment Self-Regulation Questionnaire were used to measure self-reported physical activity, self-efficacy, and motivation. Structural Equation Modeling was used to exam the complex relationships among multiple variables. in this study. The Partial least squares structural equation modeling analysis with bootstrapping in Smart PLS 3 was employed to explore the path coefficients and t-values for the relationships that were thought to exist. Significance was determined using a threshold of p < 0.05.ResultsThe mean age of 147 participants was 18.5 ± 1.87, of whom 51.7% were female, recruited for this study. Exercise self-efficacy has a significant positive correlation with exercise motivation (r = 0.220, p = 0.008) and physical activity (r = 0.279, p < 0.001). Exercise motivation does not demonstrate significant associations with physical activity (r = 0.094, p = 0.298). Utilizing SEM, the model explained 9.2% of exercise self-efficacy, 11.8% of physical activity, and 68.3% of body composition variance. Mediation analysis revealed that exercise self-efficacy partially mediated the relationship between exercise motivation and physical activity (β = 0.106, t = 2.538, p < 0.05), and physical activity partially mediated the relationship between exercise self-efficacy and body composition (β = −0.296, t = 4.280, p < 0.001).ConclusionThis study sheds light on the complex relationships among motivation, self-efficacy, physical activity and body composition during emerging adulthood. Our results highlight the mediating role of self-efficacy and its impact on physical activity behaviors, offering valuable insights for targeted interventions and policy development to improve health outcomes in this demographic.

IntroductionConsiderable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach.Materials and MethodsData for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran’s Q test to evaluate heterogeneity, and “leave-one-out” sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality.ResultsThe IVW results indicated that two gut microbial taxa, the genus Eubacterium fissicatena group and the genus Oxalobacter, have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, “leave-one-out” sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota.ConclusionThis analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.

Introduction: Shizao decoction (SZD) is a traditional Chinese medicine decoction that has therapeutic effects on cirrhotic ascites (CAS). Because of the unclear treatment mechanism, in the current study, the anti-CAS activity of SZD and molecular mechanisms were analyzed by network analysis combined with pharmacokinetics and metabolomics.Methods: Firstly, we assessed the anti-CAS efficacy of SZD by hematoxylin-eosin (H&E), liver function tests, NO and ET-1 levels, and portal venous pressure. Secondly, network analysis was applied to dig out the metabolites, targets, and pathways related to SZD and CAS. Then, the pharmacokinetics of the pharmacokinetically relevant metabolites (PRM) were analyzed. Thirdly, the serum and urine metabolic biomarkers of rats with CAS were identified using metabolomics by comparing them with the SZD treatment group. In addition, MetaboAnalyst was utilized to conduct metabolic pathway analysis. Finally, the correlation analysis established a dynamic connection between absorbed PRM from SZD and CAS-associated endogenous metabolites.Results: Pharmacodynamic analysis indicated that SZD effectively mitigated liver injury symptoms by ameliorating inflammatory cell infiltration in CAS rats. The network analysis results indicated that twelve RPM contribute to the therapeutic efficacy of SZD against CAS; the key signaling pathways involved might be hepatitis B and PI3K-Akt. Pharmacokinetics results showed that the 12 RPM were efficiently absorbed into rat plasma, ensuring desirable bioavailability. The metabolomic analysis yielded 21 and 23 significantly distinct metabolites from the serum and urine, respectively. The 12 bioavailable SZD-PRM, such as luteolin, apigenin, and rutin, may be associated with various CAS-altered metabolites related to tryptophan metabolism, alpha-linolenic acid metabolism, glycine metabolism, etc.Discussion: A novel paradigm was provided in this study to identify the potential mechanisms of pharmacological effects derived from a traditional Chinese medicine decoction.

The rock characteristic and size–frequency distribution (SFD) on Mars are important for understanding the geologic and geomorphic history of the surface, for evaluating the trafficability of roving, and for planning the potential infrastructure construction. Tianwen-1, China’s first autonomous Mars exploration mission, formed an excavated depression during touchdown, which has been the deepest depression on the Martian surface so far compared with others. According to the images captured using the Navigation and Terrain Cameras (NaTeCams) onboard the rover, Zhurong, the SFD of rocks is calculated and compared inside the excavated depression, within and out of the blast zone. For the first time, the rock size distribution inside the excavated depression is obtained, exposing the geological features of the shallow subsurface on Mars at a depth of tens of centimeters, which will surely be important for future drilling missions. It is found that the rock abundance in the depression is smaller than the original abundance on the surface, and the distribution of rocks in the blast zone on the surface is greatly influenced by the touchdown. In addition, based on the fractal dimension of rock sizes, the rocks (>10 mm) at the shallow subsurface of the Zhurong landing site may experience two different geological processes.

The Ailaoshan Orogenic Belt (AOB), located at the southeastern boundary of the Tibetan Plateau, is an ideal place for investigating the mechanisms of lateral growth of Tibet. Using the data recorded by a dense seismic array across the Ailaoshan belt, we investigate the detailed lateral variations of crustal anisotropy on the basis of Pms phase of receiver functions. Remarkable crustal anisotropy is observed throughout this study region with a mean delay time of 0.33 ± 0.19 s, indicating the anisotropy primarily originates in the middle-lower crust. The fast directions beneath the AOB including the Ailaoshan-Red River shear zone (ARRSZ) and its western low-grade metamorphic unit generally align with the NW-SE strike of ARRSZ. The weak anisotropy in the South China Block (SCB) argues that the block is relatively stable, with limited internal deformation. Meanwhile, the anisotropy beneath the western boundary of the SCB is strong, and the N-S oriented fast direction is influenced by both the crustal stress and Xiaojiang Fault. Combining the high Vp/Vs and significant lateral variations of crustal anisotropy parameters, we suggest that the strike-slip motion along the ARRSZ induces the partial melting and pronounced anisotropy in the middle-lower crust of AOB, without the presence of crustal flow. The differences between crustal and mantle anisotropy indicate crust-mantle decoupling deformation of the AOB, supporting the block extrusion model occurring only in the crustal scale as the primary deformation pattern.

It has been 70 years since Barbara McClintock discovered transposable elements (TE), and the mechanistic studies and functional applications of transposable elements have been at the forefront of life science research. As an essential part of the genome, TEs have been discovered in most species of prokaryotes and eukaryotes, and the relative proportion of the total genetic sequence they comprise gradually increases with the expansion of the genome. In humans, TEs account for about 40% of the genome and are deeply involved in gene regulation, chromosome structure maintenance, inflammatory response, and the etiology of genetic and non-genetic diseases. In-depth functional studies of TEs in mammalian cells and the human body have led to a greater understanding of these fundamental biological processes. At the same time, as a potent mutagen and efficient genome editing tool, TEs have been transformed into biological tools critical for developing new techniques. By controlling the random insertion of TEs into the genome to change the phenotype in cells and model organisms, critical proteins of many diseases have been systematically identified. Exploiting the TE’s highly efficient in vitro insertion activity has driven the development of cutting-edge sequencing technologies. Recently, a new technology combining CRISPR with TEs was reported, which provides a novel targeted insertion system to both academia and industry. We suggest that interrogating biological processes that generally depend on the actions of TEs with TEs-derived genetic tools is a very efficient strategy. For example, excessive activation of TEs is an essential factor in the occurrence of cancer in humans. As potent mutagens, TEs have also been used to unravel the key regulatory elements and mechanisms of carcinogenesis. Through this review, we aim to effectively combine the traditional views of TEs with recent research progress, systematically link the mechanistic discoveries of TEs with the technological developments of TE-based tools, and provide a comprehensive approach and understanding for researchers in different fields.

The advancement of Financial Technology (FinTech) is crucial for government entities, the National Grid, and various energy corporations to facilitate the transition towards sustainable and green production methods. This study investigates the relationship between FinTech and Total Factor Energy Efficiency (TFEE) using data from a selected sample of 254 city groups in China. We examine how the development of FinTech impacts TFEE from both non-spatial and spatial perspectives. The results from the non-spatial panel model indicate that FinTech development has a significant positive impact on TFEE. Comparative studies were conducted using fixed effects (FE), feasible generalized least squares (FGLS) models, and system generalized method of moments (GMM) models, and the main findings remained consistent, confirming the robustness of our conclusions. Spatial autocorrelation results reveal a significant positive spatial spillover effect on TFEE. Both the spatial Durbin model and the dynamic spatial Durbin model demonstrate that FinTech also has a significant positive impact on TFEE, and this effect increases over time. These conclusions remain robust even after considering various spatial weight matrices and alternative methods for calculating TFEE. Additionally, we discovered that the digital economy plays a vital role in strengthening the relationship between FinTech and TFEE. Heterogeneity analysis indicates that, compared to cities without resource-based economies, FinTech development in growing resource-based cities has a more substantial impact on TFEE.

BackgroundAlthough many CTC isolation and detection methods can provide information on cancer cell counts, downstream gene and protein analysis remain incomplete. Therefore, it is crucial to develop a technology that can provide comprehensive information on both the number and profile of CTC.MethodsIn this study, we developed a novel microfluidics-based CTC separation and enrichment platform that provided detailed information about CTC.ResultsThis platform exhibits exceptional functionality, achieving high rates of CTC recovery (87.1%) and purification (∼4 log depletion of WBCs), as well as accurate detection (95.10%), providing intact and viable CTCs for downstream analysis. This platform enables successful separation and enrichment of CTCs from a 4 mL whole-blood sample within 15 minutes. Additionally, CTC subtypes, selected protein expression levels on the CTC surface, and target mutations in selected genes can be directly analyzed for clinical utility using immunofluorescence and real-time polymerase chain reaction, and the detected PD-L1 expression in CTCs is consistent with immunohistochemical assay results.ConclusionThe microfluidic-based CTC enrichment platform and downstream molecular analysis together provide a possible alternative to tissue biopsy for precision cancer management, especially for patients whose tissue biopsies are unavailable.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb), and its incidence and mortality are increasing. The BCG vaccine was developed in the early 20th century. As the most widely administered vaccine in the world, approximately 100 million newborns are vaccinated with BCG every year, which has saved tens of millions of lives. However, due to differences in region and race, the average protective rate of BCG in preventing tuberculosis in children is still not high in some areas. Moreover, because the immune memory induced by BCG will weaken with the increase of age, it is slightly inferior in preventing adult tuberculosis, and BCG revaccination cannot reduce the incidence of tuberculosis again. Research on the mechanism of Mtb and the development of new vaccines against TB are the main strategies for preventing and treating TB. In recent years, Pro-Glu motif-containing (PE) and Pro-Pro-Glu motif-containing (PPE) family proteins have been found to have an increasingly important role in the pathogenesis and chronic protracted infection observed in TB. The development and clinical trials of vaccines based on Mtb antigens are in progress. Herein, we review the immunological effects of PE/PPE proteins and the development of common PE/PPE vaccines.

BackgroundMycobacterium tuberculosis antigen (Mtb-Ag) is a polypeptide component with a molecular weight of 10-14 kDa that is obtained from the supernatant of the H37Ra strain after heat treatment. It stimulates the activation and proliferation of γδT cells in the blood to produce an immune response against tuberculosis. Mtb-Ag is therefore crucial for classifying and detecting the central genes and key pathways involved in TB initiation and progression.MethodsIn this study, we performed high-throughput RNA sequencing of peripheral blood mononuclear cells (PBMC) from Mtb-Ag-stimulated and control samples to identify differentially expressed genes and used them for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Meanwhile, we used PPI protein interaction network and Cytoscape analysis to identify key genes and qRT-PCR to verify differential gene expression. Single-gene enrichment analysis (GSEA) was used further to elucidate the potential biological functions of key genes. Analysis of immune cell infiltration and correlation of key genes with immune cells after Mtb-Ag-stimulated using R language.ResultsWe identified 597 differentially expressed genes in Mtb-Ag stimulated PBMCs. KEGG and GSEA enrichment analyzed the cellular pathways related to immune function, and DEGs were found to be primarily involved in the TNF signaling pathway, the IL-17 signaling pathway, the JAK-STAT signaling pathway, cytokine-cytokine receptor interactions, and the NF-κB signaling pathway. Wayne analysis using GSEA, KEGG, and the protein-protein interaction (PPI) network showed that 34 genes, including PTGS2, IL-1β, IL-6, TNF and IFN-γ et al., were co-expressed in the five pathways and all were up-regulated by Mtb-Ag stimulation. Twenty-four DEGs were identified using qRT-PCR, including fourteen up-regulated genes (SERPINB7, IL20, IFNG, CSF2, PTGS2, TNF-α, IL36G, IL6, IL10, IL1A, CXCL1, CXCL8, IL4, and CXCL3) and ten down-regulated genes (RTN1, CSF1R CD14, C5AR1, CXCL16, PLXNB2, OLIG1, EEPD1, ENG, and CCR1). These findings were consistent with the RNA-Seq results.ConclusionThe transcriptomic features associated with Mtb-Ag provide the scientific basis for exploring the intracellular immune mechanisms against Mtb. However, more studies on these DEGs in pathways associated with Mtb-Ag stimulation are needed to elucidate the underlying pathologic mechanisms of Mtb-Ag during Mtb infection.

The early prediction of epileptic seizures holds paramount significance in patient care and medical research. Extracting useful spatial-temporal features to facilitate seizure prediction represents a primary challenge in this field. This study proposes GAMRNN, a novel methodology integrating a dual-layer gated recurrent unit (GRU) model with a convolutional attention module. GAMRNN aims to capture intricate spatial-temporal characteristics by highlighting informative feature channels and spatial pattern dynamics. We employ the Lion optimization algorithm to enhance the model's generalization capability and predictive accuracy. Our evaluation of GAMRNN on the widely utilized CHB-MIT EEG dataset demonstrates its effectiveness in seizure prediction. The results include an impressive average classification accuracy of 91.73%, sensitivity of 88.09%, specificity of 92.09%, and a low false positive rate of 0.053/h. Notably, GAMRNN enables early seizure prediction with a lead time ranging from 5 to 35 min, exhibiting remarkable performance improvements compared to similar prediction models.

ObjectiveThe aim of this study was to evaluate the causes of the dysfunctional tunneled cuffed catheters (TCCs) using multi-spiral computed tomography venography (MSCTV), and to analyze the outcomes of endovascular salvage techniques.Material and methodsThis retrospective review data from 27 patients who experienced TCC dysfunction between July 1, 2016 and January 31, 2021 was conducted. Patients’ demographic data, clinical signs and symptoms, and imaging data were collected from interventional radiology database.ResultsMSCTV showed a range of abnormalities in the hemodialysis (HD) patients, including central venous occlusion (n = 4), fibrin sheath formation (n = 3), malposition of the catheter tips (n = 4), central venous perforation (n = 1), thrombus formation (n = 12), regular catheter exchange without determined lesions (n = 3). Interventional catheter salvage procedures were performed, such as catheter exchange, balloon disruption of a fibrin sheath, angioplasty for central vein stenosis, and stent deployment. The technical success rate for catheter insertions was 100%, and no procedure-related severe complications were observed. The 30-day catheter patency for all assessable catheters was 85.2%.ConclusionThe use of MSCTV showed abnormal findings in almost 88.9% of cases concerning dysfunctional TCC. In this study, the examined appropriate endovascular techniques were found to be safe and technically successful, with a low incidence of procedure-related complications.

IntroductionThe risk of kidney stones in metabolically healthy obesity (MHO) individuals is largely unexplored. This study using percent body fat (%BF) to categorize obesity, to investigate the association between MHO as well as other metabolic syndrome-obesity combined phenotypes and kidney stones in a national representative population.Materials and methodsThis cross-sectional study included 4,287 participants in the National Health and Nutrition Examination Survey from 2011 to 2018. Metabolically healthy status was defined as not having any component of metabolic syndrome or insulin resistance. Obesity was identified by %BF, which was measured and assessed by dual-energy x-ray absorptiometry (DXA) scan. Participants were cross-classified by metabolic health and obesity status. The outcome was self-report kidney stones. Multivariable logistic regression model was used to examine the association between MHO and kidney stones.ResultsA total of 358 participants had kidney stones [weighted prevalence (SE): 8.61% (0.56%)]. The weighted prevalence (SE) of kidney stones in MHN, MHOW, and MHO groups was 3.13% (1.10%), 4.97% (1.36%), and 8.55% (2.09%), respectively. After adjusting for age, sex, race and ethnicity, education level, smoking status, alcohol consumption, physical activity, daily water intake, CKD stage 3–5, and hyperuricemia, MHO individuals (OR: 2.90, 95% CI: 1.18, 7.0) had a significantly higher risk of kidney stones than those with metabolically healthy normal weight. In metabolically healthy participants, a 5% increment in %BF was associated with a significantly higher risk of kidney stones (OR: 1.60, 95% CI: 1.20, 2.14). Furthermore, a nonlinear dose–response relationship between %BF and the kidney stones was observed in metabolically healthy participants (P for non-linearity = 0.046).ConclusionUsing %BF to define obesity, MHO phenotype was significantly associated with higher risks of kidney stones, suggesting that obesity can independently contribute to kidney stones in the absence of metabolic abnormalities and insulin resistance. Regarding kidney stones prevention, MHO individuals might still benefit from lifestyle interventions aimed at healthy body composition maintenance.

BackgroundInternet gaming disorder (IGD) has become a social problem in children. Evidence from previous studies has proven that anxiety is associated with IGD. However, IGD was always assessed as a whole based on total scores, and the fine-grained relationship between anxiety and IGD was hidden.ObjectiveThe present study aims to investigate the fine-grained relationship between anxiety and IGD in elementary school students during the COVID-19 lockdown, and to identify potential targets for psychological interventions.MethodsDuring the lockdown caused by the COVID-19 pandemic, 667 children from a primary school in China were investigated by the Spence Children’s Anxiety Scale-Short Version and Internet Gaming Disorder Scale. R4.1.1 software was used to construct a network model, assess bridge centrality, and test the robustness of the network and conduct a network.ResultsThere were 23 cross-community edges (weight ranged from −0.03 to 0.12), and each node of anxiety was connected to different nodes of IGD. The nodes with the top 80th percentile bridge expected influence were A2 “social phobia” (0.20), A3 “panic disorder” (0.21) and IGD5 “escape” (0.22). The robustness of the network was acceptable.ConclusionFrom the perspective of network analysis, the present study explored the correlation pathways between anxiety and IGD in children and identified social phobia and panic disorder as the best targets for intervention to reduce IGD.

ObjectivesTo investigate the relationship between antibiotic exposure and asthma in adults in the United States.MethodsData was obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. A total of 51,124 participants were included, excluding those who were aged

IntroductionBurn injury has been shown to lead to changes in the composition of the gut microbiome and cause other damage in patients. However, little is known about how the gut microbial community evolves in individuals who have recovered from burn injury.MethodsIn this study, we established a model of deep partial-thickness burn in mice and collected fecal samples at eight time points (pre-burn, 1, 3, 5, 7, 14, 21, and 28 days post-burn) for 16S rRNA amplification and high-throughput sequencing.ResultsThe results of the sequencing were analyzed using measures of alpha diversity, and beta diversity and taxonomy. We observed that the richness of the gut microbiome declined from day 7 post-burn and that the principal component and microbial community structure varied over time. On day 28 after the burn, the microbiome composition largely returned to the pre-burn level, although day 5 was a turning point for change. Some probiotics, such as the Lachnospiraceae_NK4A136_group, decreased in composition after the burn but were restored in the later recovery period. In contrast, Proteobacteria showed an opposite trend, which is known to include potential pathogenic bacteria.ConclusionThese findings demonstrate gut microbial dysbiosis after burn injury and provide new insights into the burn-related dysbiosis of the gut microbiome and strategies for improving the treatment of burn injury from the perspective of the microbiota.

The Ryukyu Trench is located in the northern Philippine Sea. The subduction of the Philippine Sea Plate to the Eurasia Plate along the Ryukyu Trench in the NNW direction leads to extremely complex tectonic processes such as subduction, collision, accretion, and back-arc expansion. It is of great significance to obtain the crustal structure of the Ryukyu Trench for understanding the crustal deformation characteristics, subduction direction and the scale of the Philippine Sea Plate. The ocean bottom seismometer (OBS) could provide important information on the deep structure of the oceanic area, and the wide coverage of gravity anomaly can provide more constraints for the regional crustal structure. In this study, we put the time-delay term of the sedimentary layer into the H-κ stacking formula, which eliminates the influence of the sedimentary layer in traditional H-κ stacking. Based on the accurate crustal thickness at OBS locations, a gravity inversion method is proposed to solve the problem of non-uniqueness in gravity data and limited distribution of OBSs. By using this method, we obtain a crustal structure with higher resolution than Crust1.0 model in Ryukyu Trench. The results show that the crustal thickness in the Ryukyu Trench region thickens along the NNW subduction direction, revealing that the Philippine Plate’s subduction direction towards the Eurasian Plate is in the NNW direction.

Tuberculosis is a worldwide contagion caused by Mycobacterium tuberculosis (MTB). MTB is characterized by intracellular parasitism and is semi-dormant inside host cells. The persistent inflammation caused by MTB can form a granuloma in lesion regions and intensify the latency of bacteria. In recent years, several studies have proven that long non-coding RNAs (lncRNAs) play critical roles in modulating autophagy. In our study, the Gene Expression Omnibus (GEO) databases were searched for lncRNAs that are associated with tuberculosis. We found that lncRNA differentiation antagonizing non-protein coding RNA (DANCR) increased in the peripheral blood samples collected from 54 pulmonary tuberculosis patients compared to 23 healthy donors. By constructing DANCR overexpression cells, we analyzed the possible cellular function of DANCR. After analyzing our experiments, it was found that the data revealed that upregulation of DANCR facilitated the expression of signal transducer and activator of transcription 3, autophagy-related 4D cysteine peptides, autophagy-related 5, Ras homolog enriched in the brain, and microtubule-associated protein 1A/1B light chain 3 (STAT3, ATG4D, ATG5, RHEB, and LC3, respectively) by sponging miR-1301-3p and miR-5194. Immunofluorescence analysis indicated that DANCR played a positive role in both autophagosome formation and fusion of autolysosomes in macrophages. The colony-forming unit (CFU) assay data also showed that the cells overexpressing DANCR were more efficient in eliminating the intracellular H37Ra strain. Consequently, these data suggest that DANCR restrained intracellular survival of M. tuberculosis by promoting autophagy via miR-1301-3p and miR-5194.

IntroductionIn the past two decades, mindfulness-based intervention programs have gradually become popular.Many studies have confirmed that these programs can effectively alleviate prenatal stress and negative emotion.The mindfulness-based stress-buffering hypothesis suggests that mindfulness training can induce changes in the levels of the cortisol secreted by the HPA axis, thereby reducing stress susceptibility. However, to date, only a few high-quality evidence-based medical studies have analyzed the effect of the mindfulness-based intervention in a maternal population.Thus, this study investigated the effects of a mindfulness-based psychosomatic intervention on pregnancy stress and the HYPERLINK “javascript:;” hypothalamic-pituitary-adrenal (HPA) axis of pregnant Chinese women.MethodsWomen experiencing first-time pregnancy (n = 117) were randomly allocated to the intervention group or parallel active control group, and data were collected at baseline and post-intervention periods. The participants completed questionnaires regarding mindfulness and pregnancy stress. Saliva samples was collected at the time of waking up, and 30, 45, and 60 min after waking up for analyzing the salivary cortisol levels. We analyzed differences between the two groups and changes within the same group before and after the intervention.Results and discussionA total of 95 participants completed the trial. Compared with the parallel active control group, the intervention group exhibited lower levels of stress after the intervention (P = 0.047). For HPA-axis-related indicators after the intervention, Delta value (P = 0.01) and AUCM value (P = 0.031) of the intervention group were significantly higher than that of the control group. Mindfulness-based interventions effectively reduced the level of pregnancy stress and adjusted the HPA axis function in pregnant women in China.Clinical Trial Registrationhttps://www.chictr.org.cn, identifier ChiCTR 2000033149.

ObjectiveTo analyze the risk factors of in-stent restenosis (ISR) after the first implantation of drug-eluting stent (DES) patients with coronary heart disease (CHD) and to establish a nomogram model to predict the risk of ISR.MethodsThis study retrospectively analyzed the clinical data of patients with CHD who underwent DES treatment for the first time at the Fourth Affiliated Hospital of Zhejiang University School of Medicine from January 2016 to June 2020. Patients were divided into an ISR group and a non-ISR (N-ISR) group according to the results of coronary angiography. The least absolute shrinkage and selection operator (LASSO) regression analysis was performed on the clinical variables to screen out the characteristic variables. Then we constructed the nomogram prediction model using conditional multivariate logistic regression analysis combined with the clinical variables selected in the LASSO regression analysis. Finally, the decision curve analysis, clinical impact curve, area under the receiver operating characteristic curve, and calibration curve were used to evaluate the nomogram prediction model's clinical applicability, validity, discrimination, and consistency. And we double-validate the prediction model using ten-fold cross-validation and bootstrap validation.ResultsIn this study, hypertension, HbA1c, mean stent diameter, total stent length, thyroxine, and fibrinogen were all predictive factors for ISR. We successfully constructed a nomogram prediction model using these variables to quantify the risk of ISR. The AUC value of the nomogram prediction model was 0.806 (95%CI: 0.739–0.873), indicating that the model had a good discriminative ability for ISR. The high quality of the calibration curve of the model demonstrated the strong consistency of the model. Moreover, the DCA and CIC curve showed the model's high clinical applicability and effectiveness.ConclusionsHypertension, HbA1c, mean stent diameter, total stent length, thyroxine, and fibrinogen are important predictors for ISR. The nomogram prediction model can better identify the high-risk population of ISR and provide practical decision-making information for the follow-up intervention in the high-risk population.

IntroductionPorcine anti-human lymphocyte immunoglobulin (pALG) has been used in kidney transplantation, but its impacts on the lymphocyte cell pool remain unclear.MethodsWe retrospectively analyzed 12 kidney transplant recipients receiving pALG, and additional recipients receiving rabbit anti-human thymocyte immunoglobulin (rATG), basiliximab, or no induction therapy as a comparison group.ResultspALG showed high binding affinity to peripheral blood mononuclear cells (PBMCs) after administration, immediately depleting blood lymphocytes; an effect that was weaker than rATG but stronger than basiliximab. Single-cell sequencing analysis showed that pALG mainly influenced T cells and innate immune cells (mononuclear phagocytes and neutrophils). By analyzing immune cell subsets, we found that pALG moderately depleted CD4+T cells, CD8+T cells, regulatory T cells, and NKT cells and mildly inhibited dendritic cells. Serum inflammatory cytokines (IL-2, IL-6) were only moderately increased compared with rATG, which might be beneficial in terms of reducing the risk of untoward immune activation. During 3 months of follow-up, we found that all recipients and transplanted kidneys survived and showed good organ function recovery; there were no cases of rejection and a low rate of complications.DiscussionIn conclusion, pALG acts mainly by moderately depleting T cells and is thus a good candidate for induction therapy for kidney transplant recipients. The immunological features of pALG should be exploited for the development of individually-optimized induction therapies based on the needs of the transplant and the immune status of the patient, which is appropriate for non-high-risk recipients.

MicroRNAs (miRNAs) mediate the degradation of target mRNA and inhibit mRNA translation to regulate gene expression at the transcriptional and post-transcriptional levels in response to environmental stress in plants. We characterized the post-transcriptional mechanism by deep sequencing small RNA (sRNA) to examine how miRNAs were involved in low night temperature (LNT) stress in tomato and whether the molecular mechanism depended on the abscisic acid (ABA) signaling pathway. We annotated conserved miRNAs and novel miRNAs with four sRNA libraries composed of wild-type (WT) tomato plants and ABA-deficient mutant (sit) plants under normal growth and LNT stress conditions. Reverse genetics analysis suggested that miR162 participated in LNT resistance and the ABA-dependent signaling pathway in tomato. miR162-overexpressing (pRI-miR162) and miR162-silenced (pRNAi-miR162) transgenic tomato plants were generated to evaluate miR162 functions in response to LNT stress. miR162 deficiency exhibited high photosynthetic capacity and regulated stomatal opening, suggesting negative regulation of miR162 in the ABA-dependent signaling pathway in response to LNT stress. As feedback regulation, miR162 positively regulated ABA to maintain homeostasis of tomato under diverse abiotic stresses. The mRNA of DICER-LIKE1 (DCL1) was targeted by miR162, and miR162 inhibited DCL1 cleavage in LNT response, including the regulation of miRNA160/164/171a and their targets. The DCL1-deficient mutants (dcl1) with CRISPR/Cas9 prevented stomatal opening to influence photosynthesis in the ABA signaling pathway under LNT stress. Finally, we established the regulatory mechanism of ABA-miR162-DCL1, which systematically mediated cold tolerance in tomato. This study suggests that post-transcriptional modulators acted as systemic signal responders via the stress hormone signaling pathway, and the model at the post-transcriptional level presents a new direction for research in plant abiotic stress resistance.

Pear anthracnose, caused by Colletotrichum bacteria, is a severe infectious disease that significantly impacts the growth, development, and fruit yield of pear trees. Early detection of pear anthracnose before symptoms manifest is of great importance in preventing its spread and minimizing economic losses. This study utilized hyperspectral imaging (HSI) technology to investigate early detection of pear anthracnose through spectral features, vegetation indices (VIs), and texture features (TFs). Healthy and diseased pear leaves aged 1 to 5 days were selected as subjects for capturing hyperspectral images at various stages of health and disease. Characteristic wavelengths (OWs1 and OWs2) were extracted using the Successive Projection Algorithm (SPA) and Competitive Adaptive Reweighted Sampling (CARS) algorithm. Significant VIs were identified using the Random Forest (RF) algorithm, while effective TFs were derived from the Gray Level Co-occurrence Matrix (GLCM). A classification model for pear leaf early anthracnose disease was constructed by integrating different features using three machine learning algorithms: Support Vector Machine (SVM), Extreme Learning Machine (ELM), and Back Propagation Neural Network (BPNN). The results showed that: the classification identification model constructed based on the feature fusion performed better than that of single feature, with the OWs2-VIs-TFs-BPNN model achieving a highest accuracy of 98.61% in detection and identification of pear leaf early anthracnose disease. Additionally, to intuitively and effectively monitor the progression and severity of anthracnose in pear leaves, the visualization of anthracnose lesions was achieved using Successive Maximum Angle Convex Cone (SMACC) and Spectral Information Divergence (SID) techniques. According to our research results, the fusion of multi-source features based on hyperspectral imaging can be a reliable method to detect early asymptomatic infection of pear leaf anthracnose, and provide scientific theoretical support for early warning and prevention of pear leaf diseases. [ABSTRACT FROM AUTHOR]

Altaids in the Central Asian Orogenic Belt (CAOB) is one of the world’s largest orogenic belts containing mineral deposits. Together with the Junggar terrain they open an important window to study the Paleozoic tectonic evolution of the CAOB. In this paper, we analyze a 637-km-long wide-angle refraction/reflection seismic profile across the Altai-Eastern Tianshan orogenic belt in the southern Altaids, conducted in September 2018 using 10 large explosive charges fired in drilled holes. We use a traveltime inversion method to reconstruct the lithospheric P-wave velocity structure along the profile. The lithosphere is composed of a 43-55-km-thick crust, a ∼10-km-thick crust-mantle transition layer beneath the Altai Mountain, and a ∼25-km-thick layer of lithospheric mantle. The results clearly reveal: a prominent Moho uplift beneath the Yemaquan Island Arc, two major crustal-scale low-velocity anomalies (LVAs) beneath the Yemaquan Arc and Bogda Mountain, and three high-velocity anomalies (HVAs) near the surface around the Kalatongke, Yemaquan and Kalatage mining areas. We hypothesize that the subduction of the Paleo-Asian Ocean occurred with strong mantle upwelling. We suggest that continued compression of the Paleo-Asian Ocean causes the delamination of lithosphere, as well as asthenospheric material upwelling and magma underplating into the crust. Consistently, Paleozoic mafic-ultramafic rocks and mantle-derived minerals related to gold, copper and nickel deposits, are widely extended in the area. Our results show that the P-wave velocity-depth curves for deeper depths (>30 km) in the southern Altai and Junggar Basin are close to those of the continental arcs and global continent average. Despite powerful Paleozoic subduction activity, orogeny and volcanism strongly modified the lower crust in the region, part of ancient continental crust was still preserved below the southern Altai and Junggar Basin. In addition, the upper part (depth 5–30 km) of the velocity-depth curve for the Junggar Basin is close to that of the Costa Rica volcanic front and the British Columbia accreted terrain, suggesting that Paleozoic orogenic activity has intensively reconstructed the upper-middle crust beneath the Junggar Basin.

IntroductionIn this study, the change detection paradigm was used to study the working memory of patterned movements and the relationship of this type of memory with the visuospatial sketchpad in three experiments.MethodsExperiment 1 measured participants’ working memory capacity for patterned movements and explored the influence of stimulus type with indicators such as response time and accuracy rate. Experiments 2 and 3 explored the relationship between patterned movements and the visual and spatial subsystems, respectively.ResultsThe results of Experiment 1 indicated that individuals can store 3–4 patterned movements in working memory; however, a change in stimulus format or an increase in memory load may decrease the speed and efficiency of working memory processing. The results of Experiment 2 showed that working memory and visual working memory are independent when processing patterned movements. The results of Experiment 3 showed that the working memory of patterned movements was affected by spatial working memory.DiscussionChanges in stimulus type and memory load exerted different effects on the working memory capacity of participants. These results provide behavioral evidence that the storage of patterned movement information is independent of the visual subsystem but requires the spatial subsystem of the visuospatial sketchpad.

BackgroundApproximately 94% of sensory information acquired by humans originates from the visual and auditory channels. Such information can be temporarily stored and processed in working memory, but this system has limited capacity. Working memory plays an important role in higher cognitive functions and is controlled by central executive function. Therefore, elucidating the influence of the central executive function on information processing in working memory, such as in audiovisual integration, is of great scientific and practical importance.PurposeThis study used a paradigm that combined N-back and Go/NoGo tasks, using simple Arabic numerals as stimuli, to investigate the effects of cognitive load (modulated by varying the magnitude of N) and audiovisual integration on the central executive function of working memory as well as their interaction.MethodsSixty college students aged 17–21 years were enrolled and performed both unimodal and bimodal tasks to evaluate the central executive function of working memory. The order of the three cognitive tasks was pseudorandomized, and a Latin square design was used to account for order effects. Finally, working memory performance, i.e., reaction time and accuracy, was compared between unimodal and bimodal tasks with repeated-measures analysis of variance (ANOVA).ResultsAs cognitive load increased, the presence of auditory stimuli interfered with visual working memory by a moderate to large extent; similarly, as cognitive load increased, the presence of visual stimuli interfered with auditory working memory by a moderate to large effect size.ConclusionOur study supports the theory of competing resources, i.e., that visual and auditory information interfere with each other and that the magnitude of this interference is primarily related to cognitive load.

Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders characterized by impaired social communication, social interaction, and repetitive behaviors. Several studies have shown an association between cases of ASD and mutations in the genes of SH3 and multiple ankyrin repeat domain protein 3 (SHANK3). These genes encode many cell adhesion molecules, scaffold proteins, and proteins involved in synaptic transcription, protein synthesis, and degradation. They have a profound impact on all aspects of synaptic transmission and plasticity, including synapse formation and degeneration, suggesting that the pathogenesis of ASD may be partially attributable to synaptic dysfunction. In this review, we summarize the mechanism of synapses related to Shank3 in ASD. We also discuss the molecular, cellular, and functional studies of experimental models of ASD and current autism treatment methods targeting related proteins.

Cultivated land protection and quality improvement have become inevitable requirements for alleviating ecological and environmental pressure and sustainable agricultural development. It is of practical significance to explore the differences and causes of cultivated land protection behaviors (CLPB) between smallholders and professional farmers for formulating targeted protection policies and improving their effectiveness. Based on 422 mango farmers' survey data in Hainan Province, this paper explored the internal and external characteristics between smallholders and professional farmers, and used the Fairlie decomposition method to compare and analyze the sources of differences in farmers' CLPB. The results showed that: (1) the CLPB of smallholders and professional farmers differ significantly; (2) the sources of differences in CLPB between smallholders and professional farmers are different, including differences in internal characteristics and differences in external characteristics; (3) differences in internal characteristics are the main cause of the differences in farmer's CLPB, and the contribution of differences in external characteristics was smaller, of which planting years, annual household income and planting scale are the top three factors. It is suggested that differential protection policies should be designed for smallholders and professional farmers, such as guiding smallholders to carry out large-scale operations and improve their organizational level, encouraging and guiding professional farmers to sign long-term contracts to stabilize the land tenure, and formulating subsidy policies for cultivated land protection.

BackgroundHypotension often occurs during hip surgery in elderly adults with conventional posterior lumbosacral plexus block.PurposeWe conducted a randomised controlled trial to determine if simple iliopsoas space block can lower the incidence of intraoperative hypotension (IOH) and provide sufficient perioperative pain relief during hip fracture surgery in elderly adults.MethodsPatients undergoing surgery for elderly hip fracture were randomised to receive either an anterior iliopsoas space block with a lateral femoral cutaneous nerve block or a posterior lumbosacral plexus block. The primary outcome was a composite measure of IOH incidence comprising frequency, absolute and relative hypotension durations.ResultsCompared to the posterior group, the iliopsoas space block group had a decreased median frequency of IOH [1.09 (0–2. 14) vs. 3 (1.6–4.8), p = 0.001, respectively] along with lower absolute [5 (0–10) min] and relative [minutes below systolic blood pressure of 100 mmHg in % of total anaesthesia time, 6.67 (0–7.65)] duration of IOH compared to the posterior group [35 (10–45) min, p = 0.008; 37.6 (12.99–66.18), p = 0.004, respectively]. The median pain levels in the post-anaesthesia care unit and median intraoperative sufentanil usage were comparable between the iliopsoas space group [2 (1–3); 8 (6–10) μg] and posterior group [1 (0–3); 5 (5–8) μg]. Thermal imaging revealed that the limb injected with the iliopsoas space block had a higher skin temperature than the unblocked limb in the sacral plexus innervated region.ConclusionA single iliopsoas space block lowers the IOH incidence and provides comparable perioperative analgesia to conventional lumbosacral plexus block.Clinical Trial RegistrationTrial registration at www.chictr.org.cn (ChiCTR2100051394); registered 22 September 2021.

Activation of mTORC1 is essential for anti-tumor function of iNKT cells. The mechanisms underlying impaired mTORC1 activation in intratumoral iNKT cells remain unclear. Via generating Vam6+/- mice and using flow cytometry, image approach, and RNA sequencing, we studied the role of Vam6 in controlling mTORC1 activation and intratumoral iNKT cell functions. Here, we find that increased Vam6 expression in intratumoral iNKT cells leads to impaired mTORC1 activation and IFN-γ production. Mechanistically, Vam6 in iNKT cells is essential for Rab7a-Vam6-AMPK complex formation and thus for recruitment of AMPK to lysosome to activate AMPK, a negative regulator of mTORC1. Additionally, Vam6 relieves inhibitory effect of VDAC1 on Rab7a-Vam6-AMPK complex formation at mitochondria-lysosome contact site. Moreover, we report that lactic acid produced by tumor cells increases Vam6 expression in iNKT cells. Given the key roles of increased Vam6 in promoting AMPK activation in intratumoral iNKT cells, reducing Vam6 expression signifificantly enhances the mTORC1 activation in intratumoral iNKT cells as well as their anti-tumor effificacy. Together, we propose Vam6 as a target for iNKT cell-based immunotherapy.

The human pain experience is a complex multi-faceted symptom. Effective pain management begins with a comprehensive assessment. However, a plethora of existing assessment tools for pain assessment focus more on self-report of pain intensity but lack of multi-dimensional impersonal assessment. These unidimensional scales, which capture self-reported levels of pain intensity, not only underestimate the complexity of the pain experience, but also lack stability and objectivity in their own assessments of pain intensity. Therefore, we propose a hypothesis that using scientific and technological means, such as visual tracking and surveillance system, ambulatory electroencephalogram and other techniques, combined with psychological assessment pictures and existing scales, to comprehensively evaluate pain may provide a new method for more effective clinical treatment of pain, especially chronic severe pain.

Extreme weather has been more frequent in recent years. Urban agglomerations, as areas with a high density of human activities, have been plagued by storm flooding. Historically, the main focus of attention on flood control in urban agglomerations has gradually shifted from underground pipe networks to the impervious surface, reflecting profound changes in the influencing mechanism of urban flooding. Exploring the evolution of the mechanisms influencing urban flooding in the Guangdong Hong Kong Macao Greater Bay Area (GBA) urban agglomeration is of great reference significance for formulating flood prevention and control measures and promoting high-quality development of the GBA city cluster. In this paper, we fully use the collected information on urban flooding events from 1980 to 2018 in the GBA city cluster. Correlation analysis and geographically weighted regression (GWR) are used to analyze the influence of impervious surface percentage (ISP), impervious surface aggregation index (AI), impervious surface mean shape index (Shape_MN), vegetation cover (FVC), water surface ratio (WSR), relative elevation (RE) and slope on flooding in urban clusters and their evolution characteristics over time from a global perspective and spatial heterogeneity, respectively. The results show that: 1) ISP, AI, Shape_MN, and WSR are positively correlated with urban flooding, while FVC, RE, and Slope are negatively correlated with urban flooding. The correlations of each factor showed a general trend of gradual strengthening over time, and the increase rate slowed down after 2000, while the correlation of WSR showed a relatively noticeable decrease. 2) The GWR results show that each factor’s influence on urban flooding has pronounced spatial-temporal heterogeneity, and each factor shows different distribution characteristics. This study uses long time series of urban flooding point data to explore the spatial-temporal evolution of the influencing mechanism of urban flooding in the GBA urban agglomeration. We hope to provide a scientific basis for an in-depth understanding of the causes of urban flooding in the GBA, intending to provide auxiliary decision-making support for the formulation of waterlogging prevention and control measures.

Liver hepatocellular carcinoma (LIHC) is one of the most common liver malignancies with high mortality and morbidity. Thus, it is crucial to identify potential biomarker that is capable of accurately predicting the prognosis and therapeutic response of LIHC. Kinesin family member 5A (KIF5A) is a microtubule-based motor protein involved in the transport of macromolecules such as organelle proteins in cells. Recent studies have illustrated that the high expression of KIF5A was related to poor prognosis of solid tumors, including bladder cancer, prostate cancer, and breast cancer. However, little is currently known concerning the clinical significance of KIF5A expression in LIHC. Herein, by adopting multi-omics bioinformatics analysis, we comprehensively uncovered the potential function and the predictive value of KIF5A in stratifying clinical features among patients with LIHC, for which a high KIF5A level predicted an unfavorable clinical outcome. Results from KIF5A-related network and enrichment analyses illustrated that KIF5A might involve in microtubule-based process, antigen processing and presentation of exogenous peptide antigen via MHC class II. Furthermore, immune infiltration and immune function analyses revealed upregulated KIF5A could predict a unique tumor microenvironment with more CD8+T cells and a higher level of anti-tumor immune response. Evidence provided by immunohistochemistry staining (IHC) further validated our findings at the protein level. Taken together, KIF5A might serve as a novel prognostic biomarker for predicting immunotherapy response and could be a potential target for anti-cancer strategies for LIHC.

ObjectiveThis stydy aims to assess the value of monitoring of postoperative neutrophil-to-lymphocyte ratio (NLR), D-dimer, and carbohydrate antigen 153 (CA153) for diagnosis of breast cancer (BC) recurrence and metastasis.Materials/MethodsA cohort of 252 BC patients who underwent surgery at the First Affiliated Hospital of Anhui Medical University between August 2008 and August 2018 were enrolled in this retrospective study. All patients were examined during outpatient follow-ups every 3 months for 5 years postoperation and every 6 months thereafter. Recurrence or metastasis was recorded for 131 patients but not for the remaining 121. Retrospective analysis of hematological parameters and clinicopathological characteristics allowed comparison between the two groups and evaluation of these parameters for the recurrent and metastatic patients.ResultsLymph node metastasis, higher tumor node metastasis (TNM) staging, and higher histological grade correlated with BC recurrence and metastasis (p

ObjectiveThis study aimed to investigate the clinical value of ultrasonography combined with tumor markers in the diagnosis and prediction of recurrence of borderline ovarian tumors (BOTs) and analyze the value of the combination of two different auxiliary examinations in the diagnosis and prediction of recurrence of BOTs.MethodsHere, 221 patients with BOTs confirmed by postoperative pathology were enrolled. Their clinical data, including the ultrasonography features, tumor markers, and clinicopathological data, were retrospectively analyzed.ResultsThe statistical data of the 221 cases with BOTs were as follows: 94 (42.5%) with left-sided lesions, 102 (46.2%) with right-sided lesions, and 25 (11.3%) with bilateral lesions. Moreover, 93 cases (42.1%) had a borderline serous tumor, 110 (49.8%) had a borderline mucinous tumor, 12 (5.4%) had a borderline serous mucinous tumor, 2 (0.9%) had a borderline endometrioid tumor, 1 (0.5%) had a borderline Brenner tumor, and 2 (0.9%) had a clear cell BOT. There were 104 cases (47.1%) with a tumor diameter of ≤10 cm and 117 cases (52.9%) with a tumor diameter of >10 cm as suggested by ultrasonography. There were 89 cases (40.3%) with septation, 44 (19.9%) with papilla, and 97 (43.9%) with blood flow as demonstrated by ultrasonography. Carbohydrate antigen 125 (CA 125) was elevated in 132 cases (59.7%), and CA 19-9 was elevated in 52 cases (23.5%).ConclusionIn general, BOTs are difficult to diagnose preoperatively and have a certain recurrence rate. Ultrasonography combined with CA 125 and CA 19-9 is significant for the preoperative diagnosis and selection of surgical modality for BOTs and could be used as a guideline to achieve good preoperative preparation and avoid secondary surgery.

BackgroundTuberculous spondylitis (TS) and brucellar spondylitis (BS) are commonly observed in spinal infectious diseases, which are initially caused by bacteremia. BS is easily misdiagnosed as TS, especially in underdeveloped regions of northwestern China with less sensitive medical equipment. Nevertheless, a rapid and reliable diagnostic tool remains to be developed and a clinical diagnostic model to differentiate TS and BS using machine learning algorithms is of great significance.MethodsA total of 410 patients were included in this study. Independent factors to predict TS were selected by using the least absolute shrinkage and selection operator (LASSO) regression model, permutation feature importance, and multivariate logistic regression analysis. A TS risk prediction model was developed with six different machine learning algorithms. We used several metrics to evaluate the accuracy, calibration capability, and predictability of these models. The performance of the model with the best predictability was further verified with the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the calibration curve. The clinical performance of the final model was evaluated by decision curve analysis.ResultsSix variables were incorporated in the final model, namely, pain severity, CRP, x-ray intervertebral disc height loss, x-ray endplate sclerosis, CT vertebral destruction, and MRI paravertebral abscess. The analysis of appraising six models revealed that the logistic regression model developed in the current study outperformed other methods in terms of sensitivity (0.88 ± 0.07) and accuracy (0.79 ± 0.07). The AUC of the logistic regression model predicting TS was 0.86 (95% CI, 0.81–0.90) in the training set and 0.86 (95% CI, 0.78–0.92) in the validation set. The decision curve analysis indicated that the logistic regression model displayed a higher clinical efficiency in the differential diagnosis.ConclusionsThe logistic regression model developed in this study outperformed other methods. The logistic regression model demonstrated by a calculator exerts good discrimination and calibration capability and could be applicable in differentiating TS from BS in primary health care diagnosis.

The Kawase approach is one of the most used trajectories in skull base surgery. The exposure range of the approach and its correlation with skull base anatomy still demand more exploration. With the help of digital rebuilding, analysis, and measurement, we evaluated the exposure range of the Kawase and extended Kawase approaches and analyzed the correlation between the exposure range and the variants of the petrosal and clival anatomy. The finding of the study demonstrated that compared to the sub-temporal approach, the Kawase approach and the extended Kawase approach significantly added the exposure range in the upper, middle, and partial inferior regions of the clivus. The gains in the exposure volume and area are more when the manipulation angle is less than 135°.