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Using first-principles calculations, we studied the formation energy of point defects in cubic silicon carbide (3C-SiC) and the influences of defects on its electronic band structure, density of states, and optical properties. We found that the formation energy of the interstitial defect is greater than that of the vacancy and antisite defect, with the Si interstitial defect having the highest formation energy. The electronic band structure and density of states have no bandgap due to the vacancy defect, interstitial defect, and Si antisite defect (Si atom occupies the position of C atom), while the changes due to the C antisite defect (C atom occupies the position of Si atom) are not significant. Depending on the type of defect, the optical properties change differently, with the vacancy defect having the most significant impact on the optical properties. The vacancy defect notably increases the optical conductivity, dielectric function, reflectivity, extinction coefficient, and refractive index in the low-energy region, indicating the potential application of 3C-SiC in the field of optoelectronic devices.

Background The incidence of papillary thyroid cancer (PTC) continues to rise all over the world, 10–15% of the patients have a poor prognosis. Although immunotherapy has been applied in clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of the mechanism of PTC immune remodeling and exploration of novel treatment targets.Methods This study conducted a single-cell RNA sequencing (scRNA-seq) analysis using 18 surgical tissue specimens procured from 14 patients diagnosed with adjacent tissues, non-progressive PTC or progressive PTC. Key findings were authenticated through spatial transcriptomics RNA sequencing, immunohistochemistry, multiplex immunohistochemistry, and an independent bulk RNA-seq data set containing 502 samples.Results A total of 151,238 individual cells derived from 18 adjacent tissues, non-progressive PTC and progressive PTC specimens underwent scRNA-seq analysis. We found that progressive PTC exhibits the following characteristics: a significant decrease in overall immune cells, enhanced immune evasion of tumor cells, and disrupted antigen presentation function. Moreover, we identified a subpopulation of lysosomal associated membrane protein 3 (LAMP3+) dendritic cells (DCs) exhibiting heightened infiltration in progressive PTC and associated with advanced T stage and poor prognosis of PTC. LAMP3+ DCs promote CD8+ T cells exhaustion (mediated by NECTIN2-TIGIT) and increase infiltration abundance of regulatory T cells (mediated by chemokine (C-C motif) ligand 17 (CCL17)-chemokine (C-C motif) receptor 4 (CCR4)) establishing an immune-suppressive microenvironment. Ultimately, we unveiled that progressive PTC tumor cells facilitate the retention of LAMP3+ DCs within the tumor microenvironment through NECTIN3-NECTIN2 interactions, thereby rendering tumor cells more susceptible to immune evasion.Conclusion Our findings expound valuable insights into the role of the interaction between LAMP3+ DCs and T-cell subpopulations and offer new and effective ideas and strategies for immunotherapy in patients with progressive PTC.

Early identification of biomarkers that can predict the onset of sepsis-induced coagulopathy (SIC) in septic patients is clinically important. This study endeavors to examine the diagnostic and prognostic utility of serum C1q in the context of SIC. Clinical data from 279 patients diagnosed with sepsis at the Departments of Intensive Care, Respiratory Intensive Care, and Infectious Diseases at the Renmin Hospital of Wuhan University were gathered spanning from January 2022 to January 2024. These patients were categorized into two groups: the SIC group comprising 108 cases and the non-SIC group consisting of 171 cases, based on the presence of SIC. Within the SIC group, patients were further subdivided into a survival group (43 cases) and non-survival group (65 cases). The concentration of serum C1q in the SIC group was significantly lower than that in the non-SIC group. Furthermore, A significant correlation was observed between serum C1q levels and both SIC score and coagulation indices. C1q demonstrated superior diagnostic and prognostic performance for SIC patients, as indicated by a higher area under the curve (AUC). Notably, when combined with CRP, PCT, and SOFA score, C1q displayed the most robust diagnostic efficacy for SIC. Moreover, the combination of C1q with the SOFA score heightened predictive value concerning the 28-day mortality of SIC patients.

This study explored the perceptions of professional identity among three English teachers from diverse academic disciplines at a Korean university. The teacher participants were chosen based on their diverse sociocultural and academic backgrounds that created a small yet diverse sample of cases. Furthermore, each of them possessed a minimum of 10 years of teaching experience. This extensive experience enabled them to engage in profound reflections regarding the development of their professional identities through the lens of these experiences. Taking a poststructuralist approach, we utilized semi-structured interviews, class observations, and course-related documents to delve into the professional identity formation process and the factors influencing their identity formation. Our findings underscore that professional identity construction is an intricate process, shaped by sociocultural and institutional dynamics. Specifically, two dominant factors emerged: the implications of “native speakerism” and the distinctions between tenure and non-tenure academic tracks. These insights contribute to a deeper understanding of professional identity complexities among English instructors in Korean higher education institutions.

Background: As a marker of the GABAergic system, the expression of glutamate decarboxylase 1 (GAD1) is mainly restricted to the central nervous system. Emerging studies have shown that aberrant expression of GAD1 in tumor tissues may promote tumor cell growth. The role of GAD1 in the development of osteosarcoma (OS) remains unclear, so this study sought to investigate the expression status of GAD1 and the effect of its specific inhibitor 3-mercaptopropionic acid (3-MPA) on OS. Methods: The R2 database was used to analyze the relationship between the expression of GAD1 and clinical prognosis in OS patients. Immunohistochemistry was used to compare the expression profile of GAD1 between OS and matched neighboring tissues. The potential antitumor effects of 3-MPA on cell viability, colony formation and the cell cycle were examined. Moreover, the in vivo effect of 3-MPA on tumor growth was investigated using tumor-bearing nude mice. Results: The expression level of GAD1 was aberrantly upregulated in OS tissues, but almost no expression of GAD1 was found in matched neighboring tissues. Western blotting analyses showed upregulation of GAD1 in OS cells compared to human osteoblast cells. In vitro and in vivo, 3-MPA significantly suppressed the growth of OS. Regarding the mechanism, 3-MPA inhibited β-catenin and cyclin D1 in OS cells, thereby inactivating the Wnt/β-catenin pathway. Conclusions: OS displays increased expression of the GABAergic neuronal marker GAD1, and 3-MPA significantly reduces OS growth by inhibiting the Wnt/β-catenin pathway.

BackgroundAnkylosing spondylitis (AS) is a complex condition with a significant genetic component. This study explored circulating proteins as potential genetic drug targets or biomarkers to prevent AS, addressing the need for innovative and safe treatments.MethodsWe analyzed extensive data from protein quantitative trait loci (pQTLs) with up to 1,949 instrumental variables (IVs) and selected the top single-nucleotide polymorphism (SNP) associated with AS risk. Utilizing a two-sample Mendelian randomization (MR) approach, we assessed the causal relationships between identified proteins and AS risk. Colocalization analysis, functional enrichment, and construction of protein-protein interaction networks further supported these findings. We utilized phenome-wide MR (phenMR) analysis for broader validation and repurposing of drugs targeting these proteins. The Drug-Gene Interaction database (DGIdb) was employed to corroborate drug associations with potential therapeutic targets. Additionally, molecular docking (MD) techniques were applied to evaluate the interaction between target protein and four potential AS drugs identified from the DGIdb.ResultsOur analysis identified 1,654 plasma proteins linked to AS, with 868 up-regulated and 786 down-regulated. 18 proteins (AGER, AIF1, ATF6B, C4A, CFB, CLIC1, COL11A2, ERAP1, HLA-DQA2, HSPA1L, IL23R, LILRB3, MAPK14, MICA, MICB, MPIG6B, TNXB, and VARS1) that show promise as therapeutic targets for AS or biomarkers, especially MAPK14, supported by evidence of colocalization. PhenMR analysis linked these proteins to AS and other diseases, while DGIdb analysis identified potential drugs related to MAPK14. MD analysis indicated strong binding affinities between MAPK14 and four potential AS drugs, suggesting effective target-drug interactions.ConclusionThis study underscores the utility of MR analysis in AS research for identifying biomarkers and therapeutic drug targets. The involvement of Th17 cell differentiation-related proteins in AS pathogenesis is particularly notable. Clinical validation and further investigation are essential for future applications.

Objective: Although the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methods: Twenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. Results: After the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. Conclusion: Parietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal–parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

Background Lupus nephritis (LN) is a complication of SLE characterised by immune dysfunction and oxidative stress (OS). Limited options exist for LN. We aimed to identify LN-related OS, highlighting the need for non-invasive diagnostic and therapeutic approaches.Methods LN-differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus datasets (GSE32591, GSE112943 and GSE104948) and Molecular Signatures Database for OS-associated DEGs (OSEGs). Functional enrichment analysis was performed for OSEGs related to LN. Weighted gene co-expression network analysis identified hub genes related to OS-LN. These hub OSEGs were refined as biomarker candidates via least absolute shrinkage and selection operator. The predictive value was validated using receiver operating characteristic (ROC) curves and nomogram for LN prognosis. We evaluated LN immune cell infiltration using single-sample gene set enrichment analysis and CIBERSORT. Additionally, gene set enrichment analysis explored the functional enrichment of hub OSEGs in LN.Results The study identified four hub genes, namely STAT1, PRODH, TXN2 and SETX, associated with OS related to LN. These genes were validated for their diagnostic potential, and their involvement in LN pathogenesis was elucidated through ROC and nomogram. Additionally, alterations in immune cell composition in LN correlated with hub OSEG expression were observed. Immunohistochemical analysis reveals that the hub gene is most correlated with activated B cells and CD8 T cells. Finally, we uncovered that the enriched pathways of OSEGs were mainly involved in the PI3K-Akt pathway and the Janus kinase-signal transducer and activator of transcription pathway.Conclusion These findings contribute to advancing our understanding of the complex interplay between OS, immune dysregulation and molecular pathways in LN, laying a foundation for the identification of potential diagnostic biomarkers and therapeutic targets.

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms. With the increasing research on cardiac fibrosis, redox has been recognized as an important part of cardiac remodeling, and an imbalance in redox homeostasis can adversely affect the function and structure of the heart. The metabolism of metal ions is essential for life, and abnormal metabolism of metal ions in cells can impair a variety of biochemical processes, especially redox. However, current research on metal ion metabolism is still very limited. This review comprehensively examines the effects of metal ion (iron, copper, calcium, and zinc) metabolism-mediated redox homeostasis on cardiac fibrosis, outlines possible therapeutic interventions, and addresses ongoing challenges in this rapidly evolving field.

Purpose: This study aimed to investigate the performance of deep learning algorithms in the opportunistic screening for primary angle-closure disease (PACD) using combined anterior segment parameters. Methods: This was an observational, cross-sectional hospital-based study. Patients with PACD and healthy controls who underwent comprehensive eye examinations, including gonioscopy and anterior segment optical coherence tomography (ASOCT) examinations under both light and dark conditions, were consecutively enrolled from the Department of Ophthalmology at the Beijing Tongren Hospital between November 2020 and June 2022. The anterior chamber, anterior chamber angle, iris, and lens parameters were assessed using ASOCT. To build the prediction models, backward logistic regression was utilized to select the variables to discriminate patients with PACD from normal participants, and the area under the receiver operating characteristic curve was used to evaluate the efficacy of the opportunistic screening. Results: The data from 199 patients (199 eyes) were included in the final analysis and divided into two groups: PACD (109 eyes) and controls (90 eyes). Angle opening distance at 500 μm, anterior chamber area, and iris curvature measured in the light condition were included in the final prediction models. The area under the receiver operating characteristic curve was 0.968, with a sensitivity of 91.74 % and a specificity of 91.11 %. Conclusion: ASOCT-based algorithms showed excellent diagnostic performance in the opportunistic screening for PACD. These results provide a promising basis for future research on the development of an angle-closure probability scoring system for PACD screening.

PurposeDysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study.Patients and methodsA total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database.ResultsmiR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121).ConclusionUpregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

Purpose: To investigate the proportion of zonulopathy in patients with age-related cataract, and further explore demographics and ocular characteristics, as well as potential risk factors. Methods: Hospital-based, observational, cross-sectional study. We enrolled consecutive patients who were 45 years or older and diagnosed with age-related cataract and underwent surgery between October 2022 and April 2023 at the Division of Cataract, Beijing Tongren Hospital. Zonulopathy was diagnosed based on intraoperative signs. We calculated the total proportion, age, and gender specific proportions of zonulopathy. We compared the demographic and ocular characteristics between the cases with and without zonulopathy. Univariate and multivariate logistic regression analyses were employed to determine the risk factors associated with the presence of zonulopathy in patients with age-related cataract. Results: A total of 640 age-related cataract patients with a median age of 70.0 (64.0–77.0) were enrolled. Zonulopathy was diagnosed intraoperatively in 70 patients (10.9%). Compared with the patients having no zonulopathy, those with zonulopathy were likely to be older (P

Popliteal cysts, also termed Baker's cysts, are clinically common cystic lesions in the popliteal fossa. Typically, the contents of a ruptured cyst tend to spread into the myofascial interfaces in any direction, most commonly inferomedially or into a palpable superficial position. However, to our knowledge, reports of Baker's cysts dissecting into the deep intermuscular septum of the lower calf are extremely rare. We present here the details of the successful treatment through arthroscopy combined with lower calf incision of a patient who sustained hematoma of the knee and lower calf secondary to Baker's cyst rupture. Given the rarity of this disease in China, we present this case report to improve our understanding of the disease and avoid misdiagnosis and provide evidence for its clinical treatment, management, and prognosis.

Background: Since the first human infection with H9N2 virus was reported in 1998, the number of cases of H9N2 infection has exceeded one hundred by 2021. However, there is no systematic description of the biological characteristics of H9N2 viruses isolated from humans. Methods: Therefore, this study analyzed the pathogenicity in mice of all available H9N2 viruses isolated from human cases in China from 2013 to 2021. Results: Although most of the H9N2 viruses analyzed showed low or no pathogenicity in mice, the leucine to glutamine substitution at residue 226 (L226Q) in the hemagglutinin (HA) protein rapidly emerged during the adaptation of H9N2 viruses, and was responsible for severe infections and even fatalities. HA amino acid 226Q conferred a remarkable competitive advantage on H9N2 viruses in mice relative to viruses containing 226L, increasing their virulence, infectivity, and replication. Conclusion: Thus, our study demonstrates that the adaptive substitution HA L226Q rapidly acquired by H9N2 viruses during the course of infection in mice contributed to their high pathogenicity.

BackgroundIn China, most of the citizens experienced SARS-CoV-2 infection since the end of 2022. The Coronavirus disease 2019 (COVID-19) pandemic affected people’s physical health and also had a significant impact on mental well-being. The present study aims to discover if the experience of SARS-CoV-2 infection influences patients’ anxiety toward third molar surgery in the Chinese population.Materials and methodsThe present study took the form of a questionnaire survey. From January 1, 2023, to June 30, 2023, patients who went to the Stomatology Center of China-Japan Friendship Hospital (Beijing, China) for the third molar extraction were included according to the inclusion criteria. The information on COVID-19 infection and the Modified Dental Anxiety Scale (MDAS) was collected. The software SPSS 22.0 was used for the statistical analyses.ResultsA total of 574 survey results were harvested in the present study. The infection rate of COVID-19 was 86.6% (p > 0.05). The Average MDAS scores between patients who had been infected with COVID-19 and patients who were never infected were not significantly different (11.65 ± 4.41 vs. 11.42 ± 4.41, p > 0.05). The subgroup analysis was conducted according to the length of time after the recovery of COVID-19 (Model 1), and the highest temperature during the infection (Model 2). In Model 1 and Model 2, the one-way ANOVA test did not find statistical significance between the groups (Model 1 p = 0.114; Model 2 p = 0.481). The MDAS scores in female patients were significantly higher than in male patients (12.29 ± 4.53 vs. 9.91 ± 3.80, p

Introduction: The typical functionality of astrocytes was previously shown to be disrupted by Parkinson's disease (PD), which actively regulates synaptic neurotransmission. However, the morphological changes in astrocytes wrapping glutamatergic synapses in the striatum after dopamine (DA) neuronal degeneration is unclear. Methods: We utilized a range of methodologies, encompassing the 6-hydroxydopamine (6OHDA)-induced PD model, as well as techniques such as immunohistochemistry, Western blotting, immunofluorescence and immunoelectron microscopy (IEM) to delve into the consequences of DA neuronal degeneration on the morphological attributes of perisynaptic astrocytes. Results: Our findings demonstrated a notable rise in glial fibrillary acidic protein (GFAP) + astrocyte density and an upregulation in GFAP protein expression within the striatum due to DA neuronal degeneration, coincided with the enlargement, elongation, and thickening of astrocyte protuberances. However, the expression levels of glutamate transporter 1 (GLT1) and glutamine synthetase (GS), which are related to glutamate–glutamine cycle, were significantly reduced. Double immunofluorescence and IEM results indicated that different proportions of vesicular glutamate transporter 1 (VGlut1)+ and vesicular glutamate transporter 2 (VGlut2) + terminals were wrapped by astrocytes. Additionally, DA neuronal degeneration increased the percentage and area of VGlut1+ and VGlut2+ terminals wrapped by GFAP + astrocytes in the striatum. Furthermore, we noted that DA neuronal degeneration increased the percentage of VGlut1+ and VGlut2+ axo-spinous synapses wrapped by astrocytes but had no effect on axo-dendritic synapses. Conclusion: Hence, perisynaptic astrocytes wrapping striatal glutamatergic synapses exhibit substantial morphological and functional alterations following DA neuronal degeneration making them a potential target for therapeutic interventions in PD.

Introduction:Danggui Buxue Decoction (DBD) is a clinically proven, effective, classical traditional Chinese medicine (TCM) formula for treating blood deficiency syndrome (BDS). However, its effects and effective constituents in the treatment of BDS remain unclear, limiting precise clinical therapy and quality control. This study aimed to accurately evaluate the effects of DBD and identify its effective constituents and quality markers.Methods:BDS was induced in rats by a combined injection of acetylphenylhydrazine and cyclophosphamide, and the efficacy of DBD against BDS was evaluated based on body weight, body temperature, energy metabolism, general status, visceral indices, histopathology, biochemical markers, and metabolomics. The effects of DBD on urinary and serum biomarkers of BDS were investigated, and the associated metabolic pathways were analyzed via metabolomics. Guided by Chinmedomics, the effective constituents and quality markers of DBD were identified by analyzing the dynamic links between metabolic biomarkers and effective constituents in vivo.Results:DBD improved energy metabolism, restored peripheral blood and serum biochemical indices, and meliorated tissue damage in rats with BDS. Correlation analyses between biochemical indices and biomarkers showed that 15(S)-HPETE, LTB4, and taurine were core biomakers and that arachidonic acid, taurine, and hypotaurine metabolism were core metabolic pathways regulated by DBD. Calycosin-7-glucoside, coumarin, ferulic acid sulfate, cycloastragenol, (Z)-ligustilide + O, astragaloside IV, acetylastragaloside I, and linoleic acid were identified as effective constituents improving the hematopoietic function of the rats in the BDS model. Additionally, calycosin-7-glucoside, ferulic acid, ligustilide, and astragaloside IV were identified as quality markers of DBD.Conclusion:The hematopoietic function of DBD was confirmed through analysis of energy metabolism, biochemical markers, histopathology, and metabolomics. Moreover, by elucidating effective constituents of DBD in BDS treatment, quality markers were confirmed using a Chinmedomics strategy. These results strengthen the quality management of DBD and will facilitate drug innovation.

Photodynamic therapy (PDT), a promising treatment modality, employs photosensitizers to generate cytotoxic reactive oxygen species (ROS) within localized tumor regions. This technique involves administering a photosensitizer followed by light activation in the presence of oxygen (O2), resulting in cytotoxic ROS production. PDT’s spatiotemporal selectivity, minimally invasive nature, and compatibility with other treatment modalities make it a compelling therapeutic approach. However, hypoxic tumor microenvironment (TME) poses a significant challenge to conventional PDT. To overcome this hurdle, various strategies have been devised, including in-situ O2 generation, targeted O2 delivery, tumor vasculature normalization, modulation of mitochondrial respiration, and photocatalytic O2 generation. This review aims to provide a comprehensive overview of recent developments in designing tumor-oxygenated nanomaterials to enhance PDT efficacy. Furthermore, we delineate ongoing challenges and propose strategies to improve PDT’s clinical impact in cancer treatment.

Green tea has great potential to enhance the quality of beer. In this study, green tea was added at different stages of beer brewing, and evaluated the antioxidant capacity, volatile components, as well as sensory quality. The results showed that the addition of green tea during the start of boiling has great potential for application, and the green tea beer (GTB) had remarkable antioxidant properties (ABTS radical scavenging ability, 8.67 mmol TE/L; DPPH radical scavenging ability, 3.97 mmol TE/L; reducing power, 3.28 mmol TE/L), and an excellent sensory quality (acceptance, 6.09/9). HPLC analysis indicated that the principal phenolics in GTB were catechin and caffeic acid, in addition, the relative amounts of ferulic acid, gallic acid can be used to differentiate between GTB and beer. HS-SPME-GC–MS analyses showed that ethyl caprylate, ethyl nonanoate, ethyl caprate, linalool, and phenethyl alcohol were potentially significant for the aroma profile of GTB.

Introduction: Baidu San mainly treats viral colds and relieves muscle pain. They are widely used in clinical practice, but their therapeutic effects and anti-inflammatory mechanisms against influenza are unknown. Methods: Active compounds and targets were mined with the help of TCMSP platform, OMIM database and Gene Cards database. Protein-protein interaction networks and component-target networks were established to screen core targets and components, and GO and KEGG enrichment analyses were performed in the DAVID database and visualized by the Microbiology Letter Platform. Finally, the binding affinity between potential targets and active compounds was assessed by molecular docking. Results: Baidu San is effective in the treatment of influenza. network pharmacology studies have shown that TNF, AKT1 and EGFR are the core targets of action of Baidu San in the treatment of influenza. Luteolin, quercetin and kaempferol are the key compounds. GO and KEGG enrichment analyses suggest that the mechanism of action of Baidu San is related to antiviral, anti-inflammatory and modulation of immune function are closely related. Conclusion: This study highlights the potential of combining in vitro experiments and network pharmacology as a promising strategy to explore the potential mechanism of TCMs.

We generated PUMCi005-A, an induced pluripotent stem cell (iPSC) line, from dermal fibroblasts of a 32-year-old female Perrault syndrome patient with double heterozygous (794 G > A and 1181 G > A) mutations in the TWNK gene using Sendai viral delivery of OCT4, SOX2, KLF4, and c-MYC. The PUMCi005-A iPSC line carried the TWNK mutations, displayed typical iPSC morphology, expressed pluripotent stem cell markers, did not have integration of Sendai virus, and exhibited a normal karyotype and differentiation into three germ layers.

Abstract Background Stroke, which is the main element of cerebrovascular disease (CVD), has become the foremost reason for death and disability on a global scale. The systemic inflammation response index (SIRI), a newly developed and comprehensive indicator, has demonstrated promise in forecasting clinical results for diverse ailments. Nevertheless, the uncertainty surrounding the assessment and prediction of clinical outcomes for stroke patients by SIRI persists, and the conflicting findings from the limited studies conducted on this matter further complicate the situation. Consequently, we performed a thorough systematic review and meta-analysis to explore the correlation between SIRI and the clinical results in individuals suffering from stroke. Methods This research was registered in PROSPERO and carried out following the PRISMA guidelines. A thorough investigation was carried out on PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. Furthermore, we conducted a manual search in Chinese databases, such as China national Knowledge Infrastructure (CNKI), WanFang, VIP, and China Biology Medicine (CBM). We assessed the potential for bias in the studies included by utilizing the Newcastle–Ottawa Scale (NOS) tool. Adverse clinical outcomes were the main focus of the study, with secondary endpoints including mortality, the predictive value of SIRI, SIRI values across various endpoints, and clinical parameters associated with subarachnoid hemorrhage (SAH) in relation to low and high SIRI group. Results Following rigorous evaluation, a grand total of 22 investigations, encompassing a populace of 12,737 individuals, were considered suitable for incorporation in the final analysis. The findings from our meta-analysis indicate a strong and consistent correlation between elevated SIRI levels and adverse functional outcomes, irrespective of the method used to evaluate unfavorable outcomes. Furthermore, increased SIRI values have a strong correlation with mortality rates in both the short and long term. Besides, SIRI is a useful indicator of the severity of SAH. SIRI demonstrates strong predictive ability in identifying unfavorable outcomes and stroke-related pneumonia (SAP), as higher SIRI values are typically linked to negative endpoints. Nevertheless, the meta-analysis indicated that there was no significant increase in the risk of early neurological deterioration (END) and acute hydrocephalus (AHC) in high SIRI group when comparing to low SIRI. Conclusion This study could potentially pave the way for groundbreaking insights into the relationship between SIRI and stroke patient outcomes, as it appears to be the first meta-analysis to explore this association. Given the critical role of the inflammatory response in stroke recovery, closely monitoring patients with high SIRI levels could represent a promising strategy for mitigating brain damage post-stroke. Thus, further investigation into SIRI and its impact on clinical outcomes is essential. While our initial findings offer valuable insights into this area, continued research is necessary to fully elucidate the potential of SIRI, ideally through dynamic monitoring and large-scale, multi-center studies. Ultimately, this research has the potential to inform clinical decision-making and improve patient outcomes following stroke. Systematic review registration: https://www.crd.york.ac.uk/prospero/ ; Identifier CRD42023405221.

Abstract Chemical C–N coupling from CO2 and NO3 –, driven by renewable electricity, toward urea synthesis is an appealing alternative for Bosch–Meiser urea production. However, the unmatched kinetics in CO2 and NO3 – reduction reactions and the complexity of C- and N-species involved in the co-reduction render the challenge of C–N coupling, leading to the low urea yield rate and Faradaic efficiency. Here, we report a single-atom copper-alloyed Pd catalyst (Pd4Cu1) that can achieve highly efficient C–N coupling toward urea electrosynthesis. The reduction kinetics of CO2 and NO3 – is regulated and matched by steering Cu doping level and Pd4Cu1/FeNi(OH)2 interface. Charge-polarized Pdδ–-Cuδ+ dual-sites stabilize the key *CO and *NH2 intermediates to promote C–N coupling. The synthesized Pd4Cu1-FeNi(OH)2 composite catalyst achieves a urea yield rate of 436.9 mmol gcat. –1 h–1 and Faradaic efficiency of 66.4%, as well as a long cycling stability of 1000 h. In-situ spectroscopic results and theoretical calculation reveal that atomically dispersed Cu in Pd lattice promotes the deep reduction of NO3 – to *NH2, and the Pd-Cu dual-sites lower the energy barrier of the pivotal C–N coupling between *NH2 and *CO.

Abstract N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmt ft/ft). We show that female Asmt ft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmt ft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a “higher resilience”. Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmt ft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise.

Abstract In face-to-face communication, multimodal cues such as prosody, gestures, and mouth movements can play a crucial role in language processing. While several studies have addressed how these cues contribute to native (L1) language processing, their impact on non-native (L2) comprehension is largely unknown. Comprehension of naturalistic language by L2 comprehenders may be supported by the presence of (at least some) multimodal cues, as these provide correlated and convergent information that may aid linguistic processing. However, it is also the case that multimodal cues may be less used by L2 comprehenders because linguistic processing is more demanding than for L1 comprehenders, leaving more limited resources for the processing of multimodal cues. In this study, we investigated how L2 comprehenders use multimodal cues in naturalistic stimuli (while participants watched videos of a speaker), as measured by electrophysiological responses (N400) to words, and whether there are differences between L1 and L2 comprehenders. We found that prosody, gestures, and informative mouth movements each reduced the N400 in L2, indexing easier comprehension. Nevertheless, L2 participants showed weaker effects for each cue compared to L1 comprehenders, with the exception of meaningful gestures and informative mouth movements. These results show that L2 comprehenders focus on specific multimodal cues – meaningful gestures that support meaningful interpretation and mouth movements that enhance the acoustic signal – while using multimodal cues to a lesser extent than L1 comprehenders overall.

Abstract Background Identifying risk factors for metachronous colorectal cancer (CRC) and metachronous advanced neoplasia could be useful for guiding surveillance. We conducted a systematic review and meta-analysis to investigate risk factors for metachronous CRC and advanced neoplasia. Methods Searches were conducted in MEDLINE, Embase, Web of Science and Cochrane Central Registry of Controlled Trials for articles (searching period: 1945 to Feburary, 2021) that reported the results of an association between any factor and metachronous advanced neoplasia or metachronous CRC. There were no restrictions on the publication date or language. Random effects models were fitted to estimate the combined association between the risk factors and metachronous CRC or advanced neoplasia. The Risk of Bias In Non-Randomised Studies of Interventions tool (ROBINS-I) was used to assess the risk of bias of included studies. Results In total, 22 observational studies with 625,208 participants were included in the systematic review and meta-analysis. Of these, 13 studies investigated risk factors for metachronous CRC and 9 for advanced neoplasia. The risks of metachronous CRC or advanced neoplasia were higher if the first CRC was diagnosed in the presence of a synchronous advanced lesion (pooled risk ratio (RR) from 3 studies: 3.61, 95% confidence interval (CI): 1.44–9.05; and pooled RR from 8 studies: 2.77, 95% CI: 2.23–3.43, respectively). The risk of metachronous CRC was lower, but the risk of metachronous advanced neoplasia was higher if the first CRC was distal (compared with proximal) (pooled RR from 3 studies: 0.48, 95% CI: 0.23–0.98; and pooled RR from 2 studies: 2.99, 95% CI: 1.60–5.58 respectively). The risk of metachronous advanced neoplasia increased with age (pooled RR from 3 studies: 1.07 per year of age, 95% CI: 1.03–1.11). There was no evidence that any lifestyle risk factors studied were associated with the risk of metachronous CRC or advanced neoplasia. Conclusions The identified risk factors for metachronous CRC and advanced neoplasia might be useful to tailor the existing surveillance guidelines after the first CRC. There were potential limitations due to possible misclassification of the outcome, confounding and risk of bias, and the findings cannot be generalised to high-risk genetic syndrome cases.

Abstract Background Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. Methods This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. Results The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713–0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2–62.5% vs. 16.3–18.8%, P

Objective Borehole Televiewer (BHTV) imaging serves as an effective tool for analyzing deep rock formations in geological engineering, offering crucial insights into surface discontinuity extensions and the distribution of buried discontinuities, especially within complex geological environments associated with hydraulic engineering projects. Recognizing the current issues of subjectivity and low efficiency, prevalent in the manual calculation of rock discontinuity morphological characteristics within rock masses, we propose an intelligent approach for segmenting geometric data from digital borehole images. Leveraging the segmentation outcomes, an image thinning technique is employed to facilitate precise quantitative analysis of borehole data. Methods In this research, we employ deep learning models to intelligently identify fractures within BHTV images, utilizing various network structures such as Unet, SegNet, and DeepLabV3. The recognition results are compared with traditional image processing methods, demonstrating the advantages of deep models in accurately segmenting complex geological images. Furthermore, we enhance the model's performance by incorporating an attention mechanism into the encoder-decoder process.Once precise segmentation of rock discontinuities is achieved, the fracture skeleton is extracted using the image thinning method, representing fractures as one-pixel-width curves. Ultimately, automated calculations is completed for dip strike, dip angle, and fracture thickness. Results This method is applied to segment and calculate borehole televiewer images in hydraulic engineering. Comparing the results of manual extraction and automatic extraction of fracture information, the error of dip strike and dip angle is less than 3°, and the fracture thickness error is less than 0.65 mm. Conclusion The results verify that the intelligent calculation method of fracture information proposed in this paper. The proposed method has wide application prospects in hydraulic engineering.

Abstract Background Hypomethylation of the perforin gene promoter in CD4 + T cells, inflammation and oxidative stress, might be involved in alveolar septal cell apoptosis associated with emphysema in rats. This study aimed to investigate the effects of S-adenosylmethionine (SAM) on this kind of apoptosis in rats with autoimmune emphysema. Methods Twenty-four rats were randomly divided into three groups: a normal control group, a model group, and a SAM group. Pathological changes in lung tissues were observed, and the mean linear intercept (MLI) and mean alveolar number (MAN) were measured. The levels of anti-endothelial cell antibodies (AECA) in serum, alveolar septal cell apoptosis, perforin gene promotor methylation in CD4 + T cells in the spleen, and the levels of cytokines, malondialdehyde (MDA), and glutathione (GSH) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in bronchoalveolar lavage fluid (BALF) were investigated. Results The MLI, apoptosis index (AI) of alveolar septal cells, levels of AECA in serum, and levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9) and MDA in BALF were increased, while the MAN, methylation levels, and the activities of GSH, SOD and GSH-Px in BALF were decreased in the model group compared with those in the normal control group and the SAM group (all P

Abstract Background Bladder urothelial carcinoma (BLCA) is the most common genitourinary cancer and the prognosis of patients is often poor. However, studies of basement membrane-related genes (BM-related genes) in BLCA are less reported. Therefore, we established a BM-related genes signature to explore their functional and prognostic value in BLCA. Methods In this study, a BM-related genes signature was constructed by LASSO-Cox regression analysis, and then a series of bioinformatics methods was used to assess the accuracy and validity of the signature. We constructed a nomogram for clinical application and also screened for possible therapeutic drugs. To investigate the functions and pathways affected by BM-related genes in BLCA, we performed functional enrichment analyses. In addition, we analyzed the immune cell infiltration landscape and immune checkpoint-related genes in the high and low-risk groups. Finally, we confirmed the prognostic value of BM-related genes in BLCA in vitro. Results Combining multiple bioinformatics approaches, we identified a seven-gene signature. The accuracy and validity of this signature in predicting BLCA patients were confirmed by the test cohort. In addition, the risk score was strongly correlated with prognosis, immune checkpoint genes, drug sensitivity, and immune cell infiltration landscape. The risk score is an independent prognostic factor for BLCA patients. Further experiments revealed that all seven signature genes were differentially expressed between BLCA cell lines and normal bladder cells. Finally, overexpression of LAMA2 inhibited the migration and invasion ability of BLCA cell lines. Conclusions In summary, the BM-related genes signature was able to predict the prognosis of BLCA patients accurately, indicating that the BM-related genes possess great clinical value in the diagnosis and treatment of BLCA. Moreover, LAMA2 could be a potential therapeutic target, which provides new insights into the application of the BM-related genes in BLCA patients.

Abstract Objective Periodontitis is a common inflammatory disease associated with systemic factors. Visfatin is a pleiotropic adipokine that exerts metabolic and immune functions. Studies have shown visfatin played roles in the development of periodontitis. The present study aims to compare the levels of visfatin in body fluids including serum, saliva, and gingival crevicular fluid (GCF) between periodontitis patients and healthy individuals, and to elucidate the alteration of visfatin levels after periodontal treatments. Materials and methods The database searched included Pubmed, Embase, Web of Science, and Cochrane Library. According to the Eligibility criteria, the records were screened and the eligible studies were included. The methodological qualities of the included case-controlled studies were assessed according to the Newcastle–Ottawa scale (NOS). The Methodological Index for Nonrandomized Studies (MINORS) was applied for assessing the qualities of the included clinical trials. The statistical analyses were processed using STATA 15.0. Results Twenty-three studies were included in the statistical analyses. The meta-analysis showed significantly elevated visfatin levels of GCF, serum, and saliva in the periodontitis population compared with the controls (GCF: SMD = 5.201, 95% CI: 3.886–6.516, Z = 7.75, P

Abstract Background Insomnia predisposes the aging population to reduced quality of life and poor mental and physical health. Evidence of the association between polluted fuel use and insomnia symptoms is limited and is non-existent for the Indian population. Our study aimed to explore the link between polluted fuel use and insomnia symptoms in middle-aged and older (≥ 45 years) Indian populations. Methods We utilized data from nationally representative Longitudinal Aging Study in India (LASI) Wave 1. Participants with complete information on fuel use, insomnia symptoms, and covariates were included. Insomnia symptoms were indicated by the presence of at least one of three symptoms: difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), or early morning awakening (EMA), ≥ 5 times/week. Survey-weighted multivariable logistic regression analyses were conducted to evaluate the association between polluted fuel use and insomnia symptoms. We also assessed the interaction of association in subgroups of age, gender, BMI, drinking, and smoking status. Results Sixty thousand five hundred fifteen participants met the eligibility criteria. Twenty-eight thousand two hundred thirty-six (weighted percentage 48.04%) used polluted fuel and 5461 (weighted percentage 9.90%) reported insomnia symptoms. After full adjustment, polluted fuel use was associated with insomnia symptoms (OR 1.16; 95%CI 1.08–1.24) and was linked with DIS, DMS, and EMA (OR 1.14; 95%CI 1.05–1.24, OR 1.12; 95%CI 1.03–1.22, and OR 1.15; 95%CI 1.06–1.25, respectively). No significant interactions for polluted fuel use and insomnia symptoms were observed for analyses stratified by age, sex, BMI, drinking, or smoking. Conclusions Polluted fuel use was positively related to insomnia symptoms among middle-aged and older Indians. Suggestions are offered within this article for further studies to confirm our results, to explore underlying mechanisms, and to inform intervention strategies.

Abstract Aldehyde dehydrogenase 3A1 (ALDH3A1) is an NAD+-dependent enzyme that is closely related to tumor development. However, its role in non-small-cell lung cancer (NSCLC) has not been elucidated. This study aimed to clarify the mechanism of ALDH3A1 and identify potential therapeutic targets for NSCLC. Here, for the first time, we found that ALDH3A1 expression could be induced by a hypoxic environment in NSCLC. ALDH3A1 was highly expressed in NSCLC tissue, especially in some late-stage patients, and was associated with a poor prognosis. In mechanistic terms, ALDH3A1 enhances glycolysis and suppresses oxidative phosphorylation (OXPHOS) to promote cell proliferation by activating the HIF-1α/LDHA pathway in NSCLC. In addition, the results showed that ALDH3A1 was a target of β-elemene. ALDH3A1 can be downregulated by β-elemene to inhibit glycolysis and enhance OXPHOS, thus suppressing NSCLC proliferation in vitro and in vivo. In conclusion, hypoxia-induced ALDH3A1 is related to the energy metabolic status of tumors and the efficacy of β-elemene, providing a new theoretical basis for better clinical applications in NSCLC.

Abstract Small extracellular–vesicule-associated microRNA (sEV-miRNA) is an important biomarker for cancer diagnosis. However, rapid and sensitive detection of low-abundance sEV-miRNA in clinical samples is challenging. Herein, a simple electrochemical biosensor that uses a DNA nanowire to localize catalytic hairpin assembly (CHA), also called domino-type localized catalytic hairpin assembly (DT-LCHA), has been proposed for sEV-miRNA1246 detection. The DT-LCHA offers triple amplification, (i). CHA system was localized in DNA nanowire, which shorten the distance between hairpin substrate, inducing the high collision efficiency of H1 and H2 and domino effect. Then, larger numbers of CHAs were triggered, capture probe bind DT-LCHA by exposed c sites. (ii) The DNA nanowire can load large number of electroactive substance RuHex as amplified electrochemical signal tags. (iii) multiple DT-LCHA was carried by the DNA nanowire, only one CHA was triggered, the DNA nanowire was trapped by the capture probe, which greatly improve the detection sensitivity, especially when the target concentration is extremely low. Owing to the triple signal amplification in this strategy, sEV-miRNA at a concentration of as low as 24.55 aM can be detected in 20 min with good specificity. The accuracy of the measurements was also confirmed using reverse transcription quantitative polymerase chain reaction. Furthermore, the platform showed good performance in discriminating healthy donors from patients with early gastric cancer (area under the curve [AUC]: 0.96) and was equally able to discriminate between benign gastric tumors and early cancers (AUC: 0.77). Thus, the platform has substantial potential in biosensing and clinical diagnosis. Graphical Abstract

Objective: We evaluated the utility of concurrent chemoradiotherapy (CCRT) compared to surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT) in terms of improving the life expectancy and quality-of-life (QOL) of patients with stage III/IV hypopharyngeal squamous cell carcinomas (HPSCCs). Methods: From January 2010 to July 2018, a total of 299 patients with stage III/IV HPSCC who received surgery followed by adjuvant radiotherapy (with or without concurrent chemotherapy) (SRT, n = 111), or concurrent chemoradiotherapy (CCRT, n = 188) in our hospital were included. We measured overall survival (OS) and disease-free survival (DFS). We used the EORTC QLQ-C30, QLQ-H&N35, and Voice handicap index-30 (VHI-30) instruments to assess the long-term QOL. Results: The OS and DFS afforded by SRT were significantly better than those associated with CCRT (p = 0.039; p = 0.048 respectively), especially for stage N2–N3 patients. CCRT patients experienced better speech outcomes. Conclusion: For resectable stage III/IV HPSCC patients, appropriate treatment plans should be selected comprehensively considering survival rate, QOL, patient preference and multidisciplinary treatment.

Hyperhomocysteinemia (HHcy) causes oxidative stress, induces apoptosis, and leads to damage to the vascular endothelium is the starting point of atherosclerosis. Pterostilbene (Pte) has been reported to have antioxidant and anti-apoptotic effects under various pathological conditions. The purpose of this study was to explore whether Pte can inhibit the oxidative stress and apoptosis of vascular endothelium induced by homocysteine (Hcy) and to explain the possible mechanism by which it occurs. The results showed that 20 μmol/L Pte significantly reduced the accumulation of reactive oxygen species, malondialdehyde, and lipids in cells induced by Hcy and promoted the activities of superoxide dismutase and catalase. The Hoechst 33342/PI staining assay showed that Pte antagonized Hcy-induced apoptosis. Pte inhibited Hcy-induced Akt dephosphorylation, increased p53, and decreased the Bcl-2/Bax ratio and caspase-9/caspase-3 activation in a dose-dependent manner. LY294002 pretreatment partially reversed the protective effect of Pte by blocking the PI3K/Akt pathway. Moreover, Pte reduced lipid deposition in human umbilical vein endothelial cells (HUVECs). This study proposes that Pte can inhibit Hcy-induced oxidative stress and apoptosis of HUVECs, and the PI3K/Akt/p53 signaling pathway of apoptosis was revealed. These results suggest that Pte exhibits significant potential for dealing with HHcy-induced vascular endothelial injury, such as atherosclerosis.