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Abstract Background To compare the performance between one-slice two-dimensional (2D) and whole-volume three-dimensional (3D) computed tomography (CT)-based radiomics models in the prediction of lymphovascular invasion (LVI) status in esophageal squamous cell carcinoma (ESCC). Methods Two hundred twenty-four patients with ESCC (158 LVI-absent and 66 LVI-present) were enrolled in this retrospective study. The enrolled patients were randomly split into the training and testing sets with a 7:3 ratio. The 2D and 3D radiomics features were derived from the primary tumors’ 2D and 3D regions of interest (ROIs) using 1.0 mm thickness contrast-enhanced CT (CECT) images. The 2D and 3D radiomics features were screened using inter-/intra-class correlation coefficient (ICC) analysis, Wilcoxon rank-sum test, Spearman correlation test, and the least absolute shrinkage and selection operator, and the radiomics models were built by multivariate logistic stepwise regression. The performance of 2D and 3D radiomics models was assessed by the area under the receiver operating characteristic (ROC) curve. The actual clinical utility of the 2D and 3D radiomics models was evaluated by decision curve analysis (DCA). Results There were 753 radiomics features from 2D ROIs and 1130 radiomics features from 3D ROIs, and finally, 7 features were retained to construct 2D and 3D radiomics models, respectively. ROC analysis revealed that in both the training and testing sets, the 3D radiomics model exhibited higher AUC values than the 2D radiomics model (0.930 versus 0.852 and 0.897 versus 0.851, respectively). The 3D radiomics model showed higher accuracy than the 2D radiomics model in the training and testing sets (0.899 versus 0.728 and 0.788 versus 0.758, respectively). In addition, the 3D radiomics model has higher specificity and positive predictive value, while the 2D radiomics model has higher sensitivity and negative predictive value. The DCA indicated that the 3D radiomics model provided higher actual clinical utility regarding overall net benefit than the 2D radiomics model. Conclusions Both 2D and 3D radiomics features can be employed as potential biomarkers to predict the LVI in ESCC. The performance of the 3D radiomics model is better than that of the 2D radiomics model for the prediction of the LVI in ESCC.

Abstract Background Promoting health equity has been a worldwide goal, but serious challenges remain globally and within China. Multiple decomposition of the sources and determinants of health inequalities has significant implications for narrowing health inequalities and improve health equity. Methods Life expectancy (LE), healthy life expectancy (HALE), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rates in 31 provinces of mainland China were selected as health status indicators, obtained from the Global Burden of Disease (GBD) database. Temporal convergence analysis was used to test the evolving trends of health status. Dagum’s Gini coefficient decomposition was used to decompose the overall Gini coefficient based on intraregional and interregional differences. Oaxaca-Blinder decomposition was used to calculate contributions of determinants to interregional differences. The factor-decomposed Gini coefficient was used to analyze the absolute and marginal contribution of each component to overall Gini coefficients. Results From 1990-2019, China witnessed notable improvements in health status measured by LE, HALE, ASMR and age-standardized DALY rates.Nevertheless, the three regions (East, Central and West) exhibited significant inter-regional differences in health status, with the differences between the East and West being the largest. The adjusted short-term conditional β-convergence model indicated that the inter-provincial differences in LE, HALE, ASMR, and age-standardized DALY rates significantly converged at annual rates of 0.31%, 0.35%, 0.19%, and 0.28% over 30 years. The overall Gini coefficients of LE, HALE, and age-standardized DALY rates decreased, while the ASMR exhibited an opposite trend. Inter-regional and intra-regional differences accounted for >70% and

Abstract Eczema is common in children, and its onset is affected by both genetic and environmental factors. We investigated the effects of genetic and environmental factors on the incidence of eczema in preschool children. 515 preschool children with eczema and 515 children participating in the physical examination were enrolled. The study included the incidence of childhood eczema, the child’s birth and feeding conditions, the history of eczema in the parents, and relevant environmental risk factors, and to comprehensively analyze the genetic and environmental factors influencing childhood eczema. Among 1030 children, 173 parents (8.4%) had eczema, with a heritability of 73.59% for boys’ parents and 58.59% for girls’ parents. Multivariate logistic regression results showed that premature infants, low birth weight, children who had used antibiotics before the age of 1 year the living environment between the first year of mother pregnancy and the first year of the child is humid, a father with a history of eczema, a mother with a history of eczema are risk factors for eczema in children. Actively preventing environmental factors related to eczema may be an effective means to reduce the risk of eczema in children.

Abstract Precise calling of promiscuous adenosine-to-inosine RNA editing sites from transcriptomic datasets is hindered by DNA mutations and sequencing/mapping errors. Here, we present a stepwise computational framework, called DEMINING, to distinguish RNA editing and DNA mutations directly from RNA sequencing datasets, with an embedded deep learning model named DeepDDR. After transfer learning, DEMINING can also classify RNA editing sites and DNA mutations from non-primate sequencing samples. When applied in samples from acute myeloid leukemia patients, DEMINING uncovers previously underappreciated DNA mutation and RNA editing sites; some associated with the upregulated expression of host genes or the production of neoantigens.

Abstract Rosacea is a chronic inflammatory skin disorder, whose underlying cellular and molecular mechanisms remain obscure. Here, we generate a single-cell atlas of facial skin from female rosacea patients and healthy individuals. Among keratinocytes, a subpopulation characterized by IFNγ-mediated barrier function damage is found to be unique to rosacea lesions. Blocking IFNγ signaling alleviates rosacea-like phenotypes and skin barrier damage in mice. The papulopustular rosacea is featured by expansion of pro-inflammatory fibroblasts, Schwann, endothelial and macrophage/dendritic cells. The frequencies of type 1/17 and skin-resident memory T cells are increased, and vascular mural cells are characterized by activation of inflammatory pathways and impaired muscle contraction function in rosacea. Most importantly, fibroblasts are identified as the leading cell type producing pro-inflammatory and vasodilative signals in rosacea. Depletion of fibroblasts or knockdown of PTGDS, a gene specifically upregulated in fibroblasts, blocks rosacea development in mice. Our study provides a comprehensive understanding of the aberrant alterations of skin-resident cell populations and identifies fibroblasts as a key determinant in rosacea development.

Abstract Objective To summarize the clinical features and genetic mutation characteristics of Chinese children with KCNQ2‐related epilepsy. Methods A cohort of children with genetically caused epilepsy was evaluated at Linyi People's Hospital from January 2017 to December 2023. After next‐generation sequencing and pathogenicity analysis, we summarized the medical records and genetic testing data of the children who had KCNQ2 gene mutations. Results We identified 23 KCNQ2 gene mutations. 73.9% (n = 17) of the mutation sites were located in S5–S6 segments and the C‐terminal region. In addition to the common phenotypes, 2 new phenotypes were identified: infantile convulsion with paroxysmal choreoathetosis (ICCA) and febrile seizure plus (FS+). Of all the cases with abnormal video‐electro‐encephalography, three cases with self‐limited familial infantile epilepsy (SeLNE) exhibited a small number of multifocal discharges. Of the patients who have taken a particular antiepileptic drug, the statistics on the number of patients who have responded to the drug are as follows: oxcarbazepine (8/9, 88.9%), levetiracetam (5/7, 71.4%), phenobarbital (9/16, 56.3%), and topiramate (2/5, 40.0%). However, the efficacy of phenobarbital varied widely in treating SeLNE and KCNQ2‐DEE. At the final follow‐up, 1 case with SeLNE had a transient developmental regression and 7 cases with KCNQ2‐DEE had mild to severe developmental backwardness. Significance Although clinically rare, we report 10 new KCNQ2 mutations and two new phenotypes: ICCA and FS+. This further expands genetic and phenotypic spectrum of KCNQ2‐related epilepsy. The gene mutation sites are mostly located in S5–S6 segments and the C‐terminal region, and the former is usually associated with KCNQ2‐DEE. Sodium channel blockers (including oxcarbazepine and topiramate) and levetiracetam should be prioritized over phenobarbital for KCNQ2‐DEE. Some cases with KCNQ2‐related epilepsy may have transient developmental regression during periods of frequent seizures. Early treatment and early seizure control may be beneficial for willing outcomes in children with KCNQ2‐DEE. Plain Language Summary This article reports 23 cases of children with KCNQ2‐related epilepsy, including 10 new mutation sites and 2 new phenotypes. It further expands the genetic and phenotypic spectrum of KCNQ2‐related epilepsy. In addition, the article summarizes the gene mutation characteristics and clinical manifestations of children with KCNQ2‐related epilepsy, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of such patients.

Abstract Examining tumor-associated macrophages in the immune microenvironment of non-small cell lung cancer (NSCLC) is essential for gaining an understanding of the genesis and development of NSCLC as well as for identifying key clinical therapeutic targets. Although previous studies have reported the diverse phenotypes and functions of macrophages in tumor tissues, thereby highlighting their significant role in the tumor microenvironment, the characteristic differences and correlations between tumor and peritumor tissue-derived macrophages that are necessary for an understanding of NSCLC progression remain unclear. Based on single-cell RNA sequencing, we generated a comprehensive dataset of transcriptomes from NSCLC tumor and peritumor tissues, thereby facilitating comprehensive analysis and providing significant insights. In summary, our dataset will serve as a valuable transcriptomic resource for further studies investigating NSCLC development.

Abstract Integrating the Knowledge Graphs (KGs) into recommendation systems enhances personalization and accuracy. However, the long-tail distribution of knowledge graphs often leads to data sparsity, which limits the effectiveness in practical applications. To address this challenge, this study proposes a knowledge-aware recommendation algorithm framework that incorporates multi-level contrastive learning. This framework enhances the Collaborative Knowledge Graph (CKG) through a random edge dropout method, which constructs feature representations at three levels: user-user interactions, item-item interactions and user-item interactions. A dynamic attention mechanism is employed in the Graph Attention Networks (GAT) for modeling the KG. Combined with the nonlinear transformation and Momentum Contrast (Moco) strategy for contrastive learning, it can effectively extract high-quality feature information. Additionally, multi-level contrastive learning, as an auxiliary self-supervised task, is jointly trained with the primary supervised task, which further enhances recommendation performance. Experimental results on the MovieLens and Amazon-books datasets demonstrate that this framework effectively improves the performance of knowledge graph-based recommendations, addresses the issue of data sparsity, and outperforms other baseline models across multiple evaluation metrics.

The rate of retear after surgical repair remains high. Mesenchymal stem cells (MSCs) have been extensively employed in regenerative medicine for several decades. However, safety and ethical concerns constrain their clinical application. Tendon Stem/Progenitor Cells (TSPCs)-derived exosomes have emerged as promising cell-free therapeutic agents. Therefore, urgent studies are needed to investigate whether TSPC-Exos could enhance tendon-bone healing and elucidate the underlying mechanisms. In this study, TSPC-Exos were found to promote the proliferation, migration, and expression of fibrogenesis markers in BMSCs. Furthermore, TSPC-Exos demonstrated an ability to suppress the polarization of M1 macrophages while promoting M2 macrophage polarization. In a rat model of rotator cuff repair, TSPC-Exos modulated inflammation and improved the histological structure of the tendon-bone interface, the biomechanical properties of the repaired tendon, and the function of the joint. Mechanistically, TSPC-Exos exhibited high expression of miR-21a-5p, which regulated the expression of PDCD4. The PDCD4/AKT/mTOR axis was implicated in the therapeutic effects of TSPC-Exos on proliferation, migration, and fibrogenesis in BMSCs. This study introduces a novel approach utilizing TSPC-Exos therapy as a promising strategy for cell-free therapies, potentially benefiting patients with rotator cuff tear in the future.

Abstract Mesenchymal stem cells (MSCs) in tumor microenvironment (TME) are crucial for the initiation, development, and metastasis of cancer. The impact and mechanism of MSCs on bladder cancer are uncertain. Here we analyzed 205 patient samples to explore the relationships between tumor-stroma ratio and clinicopathological features. A co-culture model and nude mouse transplantation were used to explore the biological roles and molecular mechanisms of MSCs on bladder cancer cells. We found that a high tumor-stroma ratio was significantly associated with a larger tumor size and higher T stage, pathological grade, number of vascular invasions, and poor overall survival. MSCs in TME promoted the ability of bladder cancer cells to proliferate, migrate, and invade in vitro and in vivo. Next, we demonstrated that MSCs enhance mitochondrial autophagy and mitochondrial biogenesis of bladder cancer cells, and increase energy production, thereby promoting bladder cancer cell progression. Kynurenine (Kyn) produced by MSCs could enhance mitochondrial function by activating the AMPK pathway. IDO1 inhibitor could reverse the tumor‑promoting effects of MSCs in vitro and in vivo. Our results demonstrated that tryptophan metabolites Kyn of MSCs in TME could enhance mitochondrial function by activating the AMPK pathway, thereby promoting bladder cancer cell progression.

Abstract Age-related hearing loss (ARHL) or presbycusis is associated with irreversible progressive damage in the inner ear, where the sound is transduced into electrical signal; but the detailed mechanism remains unclear. Here, we sought to determine the potential molecular mechanism involved in the pathogeneses of ARHL with bioinformatics methods. A single-cell transcriptome sequencing study was performed on the cochlear samples from young and aged mice. Detection of identified cell type marker allowed us to screen 18 transcriptional clusters, including myeloid cells, epithelial cells, B cells, endothelial cells, fibroblasts, T cells, inner pillar cells, neurons, inner phalangeal cells, and red blood cells. Cell-cell communications were analyzed between young and aged cochlear tissue samples by using the latest integration algorithms Cellchat. A total of 56 differentially expressed genes were screened between the two groups. Functional enrichment analysis showed these genes were mainly involved in immune, oxidative stress, apoptosis, and metabolic processes. The expression levels of crucial genes in cochlear tissues were further verified by immunohistochemistry. Overall, this study provides new theoretical support for the development of clinical therapeutic drugs.

Abstract The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3+T cells, NK cells, and IFNγ+CD8+ T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance.

Abstract The escalating frequency of environmental pollution incidents has raised significant concerns regarding the potential health impacts of pollutant fluctuations. Consequently, a comprehensive study on the role of pollutants in the prevalence of viral hepatitis is indispensable for the advancement of innovative prevention strategies. Monthly incidence rates of viral hepatitis from 2005 to 2020 were sourced from the Chinese Center for Disease Control and Prevention Infectious Disease Surveillance Information System. Pollution data spanning 2014–2020 were obtained from the National Oceanic and Atmospheric Administration (NOAA), encompassing pollutants such as CO, NO2, and O3. Time series analysis models, including seasonal auto-regressive integrated moving average (SARIMA), Holt-Winters model, and Generalized Additive Model (GAM), were employed to explore prediction and synergistic effects related to viral hepatitis. Spearman correlation analysis was utilized to identify pollutants suitable for inclusion in these models. Concurrently, machine learning (ML) algorithms were leveraged to refine the prediction of environmental pollutant levels. Finally, a weighted quantile sum (WQS) regression framework was developed to evaluate the singular and combined impacts of pollutants on viral hepatitis cases across different demographics, age groups, and environmental strata. The incidence of viral hepatitis in Beijing exhibited a declining trend, primarily characterized by HBV and HCV types. In predicting hepatitis prevalence trends, the Holt-Winters additive seasonal model outperformed the SARIMA multiplicative model ((1,1,0) (2,1,0) [12]). In the prediction of environmental pollutants, the SVM model demonstrated superior performance over the GPR model, particularly with Polynomial and Besseldot kernel functions. The combined pollutant risk effect on viral hepatitis was quantified as βWQS (95% CI) = 0.066 (0.018, 0.114). Among different groups, PM2.5 emerged as the most sensitive risk factor, notably impacting patients with HCV and HEV, as well as individuals aged 35–64. CO predominantly affected HAV patients, showing a risk effect of βWQS (95% CI) = − 0.0355 (− 0.0695, − 0.0016). Lower levels of PM2.5 and PM10 were associated with heightened risk of viral hepatitis incidence with a lag of five months, whereas elevated levels of PM2.5 (100–120 μg/m3) and CO correlated with increased hepatitis incidence risk with a lag of six months. The Holt-Winters model outperformed the SARIMA model in predicting the incidence of viral hepatitis. Among machine learning algorithms, SVM and GPR models demonstrated superior performance for analyzing pollutant data. Patients infected with HAV and HEV were primarily influenced by PM10 and CO, whereas SO2 and PM2.5 significantly impacted others. Individuals aged 35–64 years appeared particularly susceptible to these pollutants. Mixed pollutant exposures were found to affect the development of viral hepatitis with a notable lag of 5–6 months. These findings underscore the importance of long-term monitoring of pollutants in relation to viral hepatitis incidence.

Abstract Background Opioid-reduced multimodal analgesia has been used clinically for many years to decrease the perioperative complications associated with opioid drugs. We aimed to assess the clinical effects of opioid-reduced anesthesia during thoracoscopic sympathectomy. Methods Surgical patients (n = 151) with palmar hyperhidrosis were randomly divided into control (Group C, 73 patients) and test (Group T, 78 patients) groups. All patients were administered general anesthesia using a laryngeal mask. In Group C, patients received propofol, fentanyl, and cisatracurium for anesthesia induction, and maintenance was achieved with propofol and remifentanil, along with mechanical ventilation during the operation. In Group T, anesthesia was induced with propofol, dezocine, and dexmedetomidine (DEX) and maintained with propofol, DEX, and an intercostal nerve block, along with spontaneous breathing throughout the operation. Perioperative complications related to opioid use include hypotension, bradycardia, hypertension, tachycardia, hypoxemia, nausea, vomiting, urine retention, itching, and dizziness were observed. To assess the impact of these complications, we recorded and compared vital signs, blood gas indices, visual analogue scale (VAS) scores, adverse events, and patient satisfaction between the two groups. Results Perioperative complications related to opioid use were similar between groups. There were no significant differences in the type of perioperative sedation, analgesia index, respiratory and circulatory indicators, blood gas analysis, postoperative VAS scores, adverse reactions, propofol dosage, postoperative recovery time, and patient satisfaction. Conclusions In minimally invasive surgeries such as thoracoscopic sympathectomy, opioid-reduced anesthesia was found to be safe and effective; however, this method did not demonstrate clinical advantages. Trial registration Chinese Clinical Trial Register: ChiCTR2100055005, on December 30, 2021.

Background: Acute myeloid leukemia (AML) is a hematological malignancy with a heterogeneous prognosis. Novel markers are required to accurately assess the prognosis and formulate treatment plans. Methods: The association of ARHGAP family genes with prognostic value in acute myeloid leukemia (AML) was assessed using public databases (CCLE, GEPIA, TCGA, and GEO). Results: Elevated expression of ARHGAP43 (SH3BP1) was associated with poor prognosis in patients with acute myeloid leukemia. ARHGAP43 (SH3BP1) expression was higher in the poor/adverse prognosis (P

Introduction: Ischemia-reperfusion injury (IRI) is detrimental to kidney transplants and may contribute to poor long-term outcomes of transplantation. Programmed cell death (PCD), a regulated cell death form triggered by IRI, is often indicative of an unfavorable prognosis following transplantation. However, given the intricate pathophysiology of IRI and the considerable variability in clinical conditions during kidney transplantation, the specific patterns of cell death within renal tissues remain ambiguous. Consequently, accurately predicting the outcomes for transplanted kidneys continues to be a formidable challenge. Methods: Eight Gene Expression Omnibus datasets of biopsied transplanted kidney samples post-IRI and 1,548 PCD-related genes derived from 18 PCD patterns were collected in our study. Consensus clustering was performed to identify distinct IRI subtypes based on PCD features (IRI PCD subtypes). Differential enrichment analysis of cell death, metabolic signatures, and immune infiltration across these subtypes was evaluated. Three machine learning algorithms were used to identify PCD patterns related to prognosis. Genes associated with graft loss were screened for each PCD type. A predictive model for graft loss was constructed using 101 combinations of 10 machine learning algorithms. Results: Four IRI subtypes were identified: PCD-A, PCD-B, PCD-C, and PCD-D. PCD-A, characterized by high enrichment of multiple cell death patterns, significant metabolic paralysis, and immune infiltration, showed the poorest prognosis among the four subtypes. While PCD-D involved the least kind of cell death patterns with the features of extensive activation of metabolic pathways and the lowest immune infiltration, correlating with the best prognosis in the four subtypes. Using various machine learning algorithms, 10 cell death patterns and 42 PCD-related genes were identified as positively correlated with graft loss. The predictive model demonstrated high sensitivity and specificity, with area under the curve values for 0.5-, 1-, 2-, 3-, and 4-year graft survival at 0.888, 0.91, 0.926, 0.923, and 0.923, respectively. Conclusion: Our study explored the comprehensive features of PCD patterns in transplanted kidney samples post-IRI. The prediction model shows great promise in forecasting graft loss and could aid in risk stratification in patients following kidney transplantation.

Abstract Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen–glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

Gnaphalium affine is a plant with various active properties and has been approved for use as a traditional medicine and food ingredient. In this study, liquid chromatography with electrochemical detection was utilized to separate the antioxidant compounds of G. affine, in conjunction with liquid chromatography-triple quadrupole mass spectrometry for identification. The in vitro antioxidant activity of G. affine was evaluated using DPPH and ABTS radical scavenging capacity assays, as well as the ferric reducing antioxidant power assay. The results showed that a total of 25 antioxidant compounds were screened and identified, among which 14 compounds were quantitatively analyzed. G. affine was found to be rich in phenolic substances, with the total phenolic content ranging from 14.62 to 59.30 mg GAE/g DW, which exhibited high antioxidant potential. The antioxidant activities showed a strong positive correlation with the total phenolic content (r > 0.9). The predominant phenolic compounds in G. affine were 5-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, ferulic acid, luteolin-7-O-glucoside, 3,5-O-dicaffeoylquinic acid, 1,5-O-dicaffeoylquinic acid, and luteolin, with 3,5-O-dicaffeoylquinic acid and 1,5-O-dicaffeoylquinic acid exhibiting the highest levels. Statistical analysis indicated that monosubstituted caffeoylquinic acids, disubstituted caffeoylquinic acids, and luteolin derivatives strongly correlated with the antioxidant potential. This study identified and quantified the major chemical constituents responsible for the antioxidant properties of G. affine, demonstrating its potential as a natural source of antioxidants for the use in foods, pharmaceuticals, and health products.

The addition of biogas liquid is a practical way to improve the yield of biological coalbed methane. The microbial composition in biogas liquid is complex, and whether it could participate in the sulfur conversion of coal remains unknown. In this study, sulfur conversion-related microbial communities were enriched from biogas liquid, which was dominated by genera Anaerosolibacter, Bacillus, Hydrogenispora, and Oxobacter. The co-culture of these groups with coal significantly changed the coal microbial community composition but did not increase the content of CH4 and H2S. The changed microbial communities mainly belonged to phyla Firmicutes, Proteobacteria, and Actinobacteriota, and increased the relative abundance of genera Bacillus, Thermicanus, Hydrogenispora, Oxobacter, Lutispora, Anaerovorax, Desulfurispora, Ruminiclostridium, and Fonticella. From the microscopic structure of coal, an increase in the number of holes and roughness on the surface of the coal was found but the change of surface functional groups was weak. In addition, the addition of S-related microbial communities increased the contents of phoxim, methylthiobenzoylglycine and glibornuride M5 in aromatic compounds, as well as the content of lauryl hydrogen sulfate in alkyl compounds. Furthermore, the dibenzothiophene degradation-related microbial communities included Bacillus, Brevibacillus, Brevundimonas, Burkholderia-Caballeronia-Paraburkholderia, and Thermicanus, which can break C-S bonds or disrupt benzene rings to degrade dibenzothiophene. In conclusion, the S-related microbial communities in biogas liquid could rebuild the coal microbial community and be involved in the conversion process of organic sulfur in coal.

Summary: Purpose: The prevalence of psychological distress is frequently observed among old adults with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, current researches are insufficient to clarify the correlation among these relevant factors. This study examined the effects of symptom burden, psychological resilience, coping styles, and social support on psychological distress. Methods: Two hundred fifty five elderly patients with AECOPD were conveniently selected in Taian, Shandong Province. The General Information Questionnaire, Distress Thermometer, The Revised Memorial Symptom Assessment Scale, Connor-Davidson Resilience Scale, Simplified Coping Style Questionnaire, Perceived Social Support Scale were used to investigate. The relationship among factors was estimated by using a structural equation model. Results: Psychological distress score of elderly patients with AECOPD was (5.25 ± 1.01); coping styles, psychological resilience, symptom burden, and social support directly affected psychological distress (the direct effects were −.93, .17, .17, and −.09); coping styles had the largest total effect on psychological distress (the total effect was −.93); psychological resilience indirectly affected psychological distress through coping styles (the indirect effect was −.74); symptom burden indirectly affected psychological distress through psychological resilience (the indirect effect was .25); social support indirectly affected psychological distress through symptom burden, psychological resilience, and coping styles (the indirect effect was −.80). Conclusion: The psychological distress of elderly patients with AECOPD is at a moderate level; coping styles, psychological resilience, and social support have positive effects on alleviating the psychological distress of elderly patients with AECOPD; symptom burden is negatively correlated with psychological distress. Healthcare professionals should pay more attention to elderly patients with AECOPD who are particularly prone to experience higher levels of psychological distress, especially in the presence of low coping style, limited psychological resilience, inadequate levels of social support, and high symptom burden.

China has successfully launched six lunar probes so far. From Chang’E-1 to Chang’E-4, they completed the circling, landing and roving exploration, of which Chang’E-4 was the first landing on the far side of the Moon in human history. Chang’ E-5 was launched in December 2020, bringing back 1731 g of lunar soil samples. Through the detailed analysis of the samples, the scientists understand the history of late lunar volcanism, specifically extending lunar volcanism by about 800 million to 1 billion years, and proposed possible mechanisms. In addition, there are many new understandings of space weathering such as meteorite impacts and solar wind radiation on the Moon. China’s first Mars exploration mission Tianwen-1 was successfully launched in July 2021. Through the study of scientific data, a number of important scientific achievements have been made in the topography, water environment and shallow surface structure of Mars. This paper introduces the main scientific achievements of Chang’E-4, Chang’E-5 and Tianwen-1 in the past two years, excluding technical and engineering contents. Due to the large number of articles involved, this paper only introduces part of the results.

Abstract Bone marrow stromal/stem cells (BMSCs) are generally considered as common progenitors for both osteoblasts and adipocytes in the bone marrow, but show preferential differentiation into adipocytes rather than osteoblasts under aging, thus leading to senile osteoporosis. Accumulated evidences indicate that rejuvenation of BMSCs by autophagic enhancement delays bone aging. Here we synthetized and demonstrated a novel autophagy activator, CXM102 that could induce autophagy in aged BMSCs, resulting in rejuvenation and preferential differentiation into osteoblasts of BMSCs. Furthermore, CXM102 significantly stimulated bone anabolism, reduced marrow adipocytes, and delayed bone loss in middle-age male mice. Mechanistically, CXM102 promoted transcription factor EB (TFEB) nuclear translocation and favored osteoblasts formation both in vitro and in vivo. Moreover, CXM102 decreased serum levels of inflammation and reduced organ fibrosis, leading to a prolonger lifespan in male mice. Our results indicated that CXM102 could be used as an autophagy inducer to rejuvenate BMSCs and shed new lights on strategies for senile osteoporosis and healthyspan improvement.

Abstract The development of a wearable, easy-to-fabricate, and stable intelligent minisystem is highly desired for the closed-loop management of diabetes. Conventional systems always suffer from large size, high cost, low stability, or complex fabrication. Here, we show for the first time a wearable, rapidly manufacturable, stability-enhancing microneedle patch for diabetes management. The patch consists of a graphene composite ink-printed sensor on hollow microneedles, a polyethylene glycol (PEG)-functionalized electroosmotic micropump integrated with the microneedles, and a printed circuit board for precise and intelligent control of the sensor and pump to detect interstitial glucose and deliver insulin through the hollow channels. Via synthesizing and printing the graphene composite ink, the sensor fabrication process is fast and the sensing electrodes are stable. The PEG functionalization enables the micropump a significantly higher stability in delivering insulin, extending its lifetime from days to weeks. The patch successfully demonstrated excellent blood glucose control in diabetic rats. This work may introduce a new paradigm for building new closed-loop systems and shows great promise for widespread use in patients with diabetes.

Abstract Suicide is the second leading cause of death in youth, and depression is a strong proximal predictor of adolescent suicide. It is important to identify psychological factors that may protect against suicide ideation in depressed adolescents. Self-compassion may be such a factor. Converging evidence indicates the inverse association between self-compassion and suicide ideation, but the neural mechanisms underlying their link remain unknown. Because self-referential caudate activity is associated with both self-compassion and suicide ideation, its functional connectivity might explain their relationship. In this study, we examined the relationship between self-compassion and caudate functional connectivity during self-appraisals, a typical self-referential paradigm, and their associations with suicide ideation in both depressed and healthy youth. In the scanner, 79 depressed youth and 36 healthy controls evaluated, from various perspectives, whether phrases they heard were self-descriptive. Self-compassion and suicide ideation were rated with self-report and interview-based measures. We found that self-compassion was associated with stronger left caudate functional connectivity with bilateral posterior superior temporal sulcus/temporoparietal junction, the left middle temporal gyrus (MTG), and the left middle occipital gyrus during positive versus negative self-appraisals. Stronger left caudate connectivity with the left MTG explained the association between higher self-compassion and lower suicide ideation, even controlling for non-suicide ideation depression severity, anxiety severity, and non-suicidal self-injurious behavior. The findings suggest that the left caudate to MTG connectivity during positive versus negative self-referential processing could be a biomarker to be targeted by neural stimulation interventions for reducing suicide ideation in depressed youth, combined with self-compassion interventions.

Abstract Background Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. Methods Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme‐linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos‐tag sodium dodecyl‐sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin‐like protein 4 (ANGPTL4) phosphorylation. Results We identified that an elevated intracellular lipid level represents a crucial characteristic of node‐positive (N+) GC and further demonstrated that a high‐fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity‐related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol‐requiring enzyme‐1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase‐2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. Conclusions Leptin‐induced phosphorylation of ANGPTL4 facilitates LPL‐mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.

Abstract Context There are currently no approved specific clinical drugs for non-alcoholic fatty liver disease (NAFLD). Salvia miltiorrhiza Bunge-Reynoutria japonica Houtt. drug pair (SRDP) has been widely used in the treatment of chronic liver diseases. However, the mechanism of SRDP treating NAFLD remains unclear. Objective Based on network analysis and in vitro experimental verification, we investigated the effect of SRDP on lipid deposition and explored its possible mechanism for the treatment of NAFLD. Methods The TCMSP platform was used to screen the active metabolites of SRDP and corresponding targets. The GeneCards and OMIM databases were used to screen the NAFLD targets. The drug-disease intersecting targets were extracted to obtain the potential targets. Then the protein–protein interaction (PPI) and drug-active metabolites-target-disease network map was constructed. The DAVID database was performed to GO and KEGG pathway enrichment analysis for the intersecting targets. The core active metabolite and signaling pathway were verified by in vitro experiments. Results Network analysis predicted 59 active metabolites and 89 targets of SRDP for the treatment of NAFLD. 112 signaling pathways were enriched for KEGG pathways, including PI3K-AKT signaling pathway,etc. It was confirmed that luteolin, the core active metabolite of SRDP, effectively reduced fat accumulation and intracellular triglyceride content in HepG2 fatty liver cell model. Luteolin could inhibit mTOR pathway by inhibiting PI3K-AKT signaling pathway phosphorylation, thereby activating autophagy to alleviate NAFLD. Discussion and conclusion The results of this study validate and predict the possible role of various active metabolites of SRDP in the treatment of NAFLD through multiple targets and signaling pathways. The core active metabolite of SRDP, luteolin can alleviate NAFLD by acting on the PI3K-AKT-mTOR signaling pathway to induce autophagy.

Abstract Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug’s efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-β, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections.

Abstract Background High-grade serous ovarian cancer (HGSOC) is a common gynecologic malignancy with a poor prognosis. The traditional Chinese medicine formula Erzhimaoling decoction (EZMLD) has anticancer potential. This study aims to elucidate the anticancer effects of EZMLD on HGSOC in vitro and in vivo. Materials and methods EZMLD-containing serum was prepared from Sprague–Dawley rats for treating SKOV3 ovarian cancer cells at varying concentrations for 24 h and 48 h to determine the IC50. Concentrations of 0%, 5%, and 10% for 24 h were chosen for subsequent in vitro experiments. The roles of METTL3 and METTL14 in SKOV3 cells were explored by overexpressing these genes and combining EZMLD with METTL3/14 knockdown. Investigations focused on cell viability and apoptosis, apoptosis-related protein expression, and KRT8 mRNA m6A modification. For in vivo studies, 36 BALB/c nude mice were divided into six groups involving EZMLD (6.75, 13.5, and 27 g/kg) and METTL3 or METTL14 knockdowns, with daily EZMLD gavage for two weeks. Results In vitro, EZMLD-containing serum had IC50 values of 8.29% at 24 h and 5.95% at 48 h in SKOV3 cells. EZMLD-containing serum decreased SKOV3 cell viability and increased apoptosis. EZMLD upregulated METTL3/14 and FAS-mediated apoptosis proteins, while downregulating Keratin 8 (KRT8). EZMLD increased KRT8 mRNA m6A methylation. METTL3/14 overexpression reduced SKOV3 cell viability and increased apoptosis, while METTL3/14 knockdown mitigated EZMLD's effects. In vivo, EZMLD suppressed SKOV3 xenografts growth, causing significant apoptosis and modulating protein expression. Conclusions EZMLD has therapeutic potential for ovarian cancer and may be considered for other cancer types. Future research may explore its broader effects beyond cell apoptosis.

Abstract Objective To test the reliability and validity of the Chinese version of the Child-to-parent Violence Questionnaire (CPV-Q) in a group of Chinese adolescents. Methods A total of 1138 adolescents (15.24 ± 1.17 years old) were tested with the Chinese version of CPV-Q, Parent-Adolescent Conflict Scale, and Adolescent Aggressive Behavior Scale of which 201 adolescents were retested 1 month later. The Chinese version of CPV-Q contains psychological, physical, financial, and control/domain factors with 14 items. Results The four-factor model has good main fit indicators (father: χ 2 /df = 3.28, CFI = 0.96, RMSEA = 0.06; mother: χ 2 /df = 3.30, CFI = 0.96, RMSEA = 0.06); the scale has good criterion-related validity. The Cronbach’s α coefficients of the Chinese version of CPV-Q were 0.89 (father) and 0.88 (mother), and the Cronbach’s α coefficients of the four subscales were 0.81 ~ 0.84 (father) and 0.76 ~ 0.85 (mother). The test–retest reliability of the Chinese version of CPV-Q was 0.85 (father) and 0.83 (mother), and the test–retest reliability of the four subscales was 0.80 ~ 0.83 (father) and 0.75 ~ 0.84 (mother). Conclusion Therefore, the CPV-Q has good reliability and validity for Chinese adolescents and can be used as an effective tool to evaluate Chinese adolescents’ violence toward their parents.

Abstract Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules generated as natural byproducts during cellular processes, including metabolism. Under normal conditions, ROS play crucial roles in diverse cellular functions, including cell signaling and immune responses. However, a disturbance in the balance between ROS production and cellular antioxidant defenses can lead to an excessive ROS buildup, causing oxidative stress. This stress damages essential cellular components, including lipids, proteins, and DNA, potentially culminating in oxidative cell death. This form of cell death can take various forms, such as ferroptosis, apoptosis, necroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis, each displaying distinct genetic, biochemical, and signaling characteristics. The investigation of oxidative cell death holds promise for the development of pharmacological agents that are used to prevent tumorigenesis or treat established cancer. Specifically, targeting key antioxidant proteins, such as SLC7A11, GCLC, GPX4, TXN, and TXNRD, represents an emerging approach for inducing oxidative cell death in cancer cells. This review provides a comprehensive summary of recent progress, opportunities, and challenges in targeting oxidative cell death for cancer therapy.

Abstract The issue of low-frequency structural noise radiated from high-speed railway (HSR) box-girder bridges (BGBs) is a significant challenge worldwide. Although it is known that vibrations in BGBs caused by moving trains can be reduced by installing multiple tuned mass dampers (MTMDs) on the top plate, there is limited research on the noise reduction achieved by this method. This study aims to investigate the noise reduction mechanism of BGBs installed with MTMDs on the top plate. A sound radiation prediction model for the BGB installed with MTMDs is developed, based on the vehicle–track–bridge coupled dynamics and acoustics boundary element method. After being verified by field tested results, the prediction model is employed to study the reduction of vibration and noise of BGBs caused by the MTMDs. It is found that installing MTMDs on top plate can significantly affect the vibration distribution and sound radiation law of BGBs. However, its impact on the sound radiation caused by vibrations dominated by the global modes of BGBs is minimal. The noise reduction achieved by MTMDs is mainly through changing the acoustic radiation contributions of each plate of the bridge. In the lower frequency range, the noise reduction of BGB caused by MTMDs can be more effective if the installation of MTMDs can modify the vibration frequency and distribution of the BGB to avoid the influence of small vibrations and disperse the sound radiation from each plate.

Protein O-glycosylation, also known as mucin-type O-glycosylation, is one of the most abundant glycosylation in mammalian cells. It is initially catalyzed by a family of polypeptide GalNAc transferases (ppGalNAc-Ts). The trimeric spike protein (S) of SARS-CoV-2 is highly glycosylated and facilitates the virus’s entry into host cells and membrane fusion of the virus. However, the functions and relationship between host ppGalNAc-Ts and O-glycosylation on the S protein remain unclear. Herein, we identify 15 O-glycosites and 10 distinct O-glycan structures on the S protein using an HCD-product-dependent triggered ETD mass spectrometric analysis. We observe that the isoenzyme T6 of ppGalNAc-Ts (ppGalNAc-T6) exhibits high O-glycosylation activity for the S protein, as demonstrated by an on-chip catalytic assay. Overexpression of ppGalNAc-T6 in HEK293 cells significantly enhances the O-glycosylation level of the S protein, not only by adding new O-glycosites but also by increasing O-glycan heterogeneity. Molecular dynamics simulations reveal that O-glycosylation on the protomer-interface regions, modified by ppGalNAc-T6, potentially stabilizes the trimeric S protein structure by establishing hydrogen bonds and non-polar interactions between adjacent protomers. Furthermore, mutation frequency analysis indicates that most O-glycosites of the S protein are conserved during the evolution of SARS-CoV-2 variants. Taken together, our finding demonstrate that host O-glycosyltransferases dynamically regulate the O-glycosylation of the S protein, which may influence the trimeric structural stability of the protein. This work provides structural insights into the functional role of specific host O-glycosyltransferases in regulating the O-glycosylation of viral envelope proteins.

With the increasing energy consumption in buildings, the proportion of energy consumption in public buildings continues to grow. As an essential component of public buildings, sports buildings are receiving more attention regarding energy-saving technologies. This paper aims to study the passive energy-saving design methods of small-and medium-sized sports halls in hot summer and cold winter regions, exploring how to reduce building energy consumption by improving the spatial design and thermal performance of the enclosure structures of sports halls. Taking the Wuhu County Sports Center as an example, this study uses computer simulation software to analyze the building’s wind environment and the thermal performance of its external walls and roof. The results show that the large volume of the sports hall significantly impacts the distribution of wind speed and pressure around it, and this impact decreases with height. The thermal simulation of the enclosure structures demonstrates that adding insulation layers to the interior and exterior of the walls and roof of the sports hall is an effective way to reduce energy consumption in both winter and summer. Additionally, wind environment simulations of different roof shapes reveal that flat roofs have the most significant blocking effect on wind and are prone to inducing strong vortices on the leeward side; concave arch roofs have the least blocking effect on airflow, and arch and wave-shaped roofs maintain lower vortex intensity on the leeward side. Hopefully, this study can provide significant references for the energy-saving design of future small- and medium-sized sports buildings.

Objective: This study aimed to analyze and compare the quality and flavor of dromedary and bifocal camel yogurt. Methods: Through physicochemical analysis, texture analysis, rheological analysis, SPME-GC-MC, sensory evaluation, etc., the overall differences in quality and flavor of dromedary and bifocal camel yogurt were determined. Results: The viable bacteria count, protein, fat, total solids content, and antioxidant activity of dromedary camel yogurt were lower than those of bifocal camel yogurt （PPPPPP

Abstract Background Straw incorporation serves as an effective strategy to enhance soil fertility and soil microbial biomass carbon (SMBC), which in turn improves maize yield and agricultural sustainability. However, our understanding of nitrogen (N) fertilization and straw incorporation into soil microenvironment is still evolving. This study explored the impact of six N fertilization rates (N0, N100, N150, N200, N250, and N300) with and without straw incorporation on soil fertility, SMBC, enzyme activities, and maize yield. Results Results showed that both straw management and N fertilization significantly affected soil organic carbon (SOC), total N, SMBC, soil enzyme activities, and maize yield. Specifically, the N250 treatment combined with straw incorporation significantly increased SOC, total N, and SMBC compared to lower fertilization rates. Additionally, enzyme activities such as urease, cellulase, sucrose, catalase, and acid phosphatase reached their peak during the V6 growth stage in the N200 treatment under for both straw management conditions. Compared to N250 and N300 treatments of traditional planting, the N200 treatment with residue incorporation significantly increased yield by 8.30 and 4.22%, respectively. All measured parameters, except for cellulase activity, were significantly higher in spring than in the autumn across both study years, with notable increases observed in 2021. Conclusions These findings suggest that optimal levels of SOC, soil total N (STN), and SMBC, along with increased soil enzyme activities, is crucial for sustaining soil fertility and enhancing maize grain yield under straw incorporation and N200 treatments.

Abstract Background Premature Ventricular Complexes (PVCs) are very common in clinical practice, with frequent PVCs (more than 30 beats per hour) or polymorphic PVCs significantly increasing the risk of mortality. Previous studies have shown that vagus nerve stimulation improves ventricular arrhythmias. Stimulation of the auricular distribution of the vagus nerve has proven to be a simple, safe, and effective method to activate the vagus nerve. Transcutaneous au ricular vagus nerve stimulation (taVNS) has shown promise in both clinical and experimental setting for PVCs; however, high-quality clinical studies are lacking, resulting in insufficient evidence of efficacy. Methods The study is a prospective, randomized, parallel-controlled trial with a 1:1 ratio between the two groups. Patients will be randomized to either the treatment group (taVNS) or the control group (Sham-taVNS) with a 6-week treatment and a subsequent 12-week follow-up period. The primary outcome is the proportion of patients with a ≥ 50% reduction in the number of PVCs monitored by 24-hour Holter. Secondary outcomes include the proportion of patients with a ≥ 75% reduction in PVCs, as well as the changes in premature ventricular beats, total heartbeats, and supraventricular premature beats recorded by 24-hour Holter. Additional assessments compared score changes in PVCs-related symptoms, as well as the score change of self-rating anxiety scale (SAS), self-rating depression scale (SDS), and 36-item short form health survey (SF-36). Discussion The TASC-V trial will help to reveal the efficacy and safety of taVNS for frequent PVCs, offering new clinical evidence for the clinical practice. Trial registration Clinicaltrials.gov: NCT04415203 (Registration Date: May 30, 2020).

Abstract Surface passivation, a desirable natural consequence during initial oxidation of alloys, is the foundation for functioning of corrosion and oxidation resistant alloys ranging from industrial stainless steel to kitchen utensils. This initial oxidation has been long perceived to vary with crystal facet, however, the underlying mechanism remains elusive. Here, using in situ environmental transmission electron microscopy, we gain atomic details on crystal facet dependent initial oxidation behavior in a model Ni-5Cr alloy. We find the (001) surface shows higher initial oxidation resistance as compared to the (111) surface. We reveal the crystal facet dependent oxidation is related to an interfacial atomic sieving effect, wherein the oxide/metal interface selectively promotes diffusion of certain atomic species. Density functional theory calculations rationalize the oxygen diffusion across Ni(111)/NiO(111) interface, as contrasted with Ni(001)/NiO(111), is enhanced. We unveil that crystal facet with initial fast oxidation rate could conversely switch to a slow steady state oxidation.

Abstract Objective Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene‐1 (IRG1) and the IRG1–itaconic acid–NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4‐octyl itaconate (4‐OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute‐onset NMOSD and to investigate the inhibitory effects of 4‐OI on NLRP3 inflammasome activation via the IRG1–itaconic acid–NLRP3 pathway in monocytes and macrophages by using in vitro models. Methods Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3‐related inflammatory factors. Subsequently, the effects of 4‐OI on the IRG1–itaconic acid–NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP‐1 cells) via in vitro experiments. Results Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4‐OI inhibited the activation of the IRG1–itaconic acid–NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. Interpretation 4‐OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD‐derived PBMCs and in a human macrophage model. Thus, 4‐OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

Foreground segmentation (FS) plays a fundamental and important role in computer vision, but it remains a challenging task in dynamic backgrounds. The supervised method has achieved good results, but the generalization ability needs to be improved. To address this challenge and improve the performance of FS in dynamic scenarios, a simple yet effective method has been proposed that leverages superpixel features and a one-dimensional convolution neural network (1D-CNN) named SPF-CNN. SPF-CNN involves several steps. First, the coined Iterated Robust CUR (IRCUR) is utilized to obtain candidate foregrounds for an image sequence. Simultaneously, the image sequence is segmented using simple linear iterative clustering. Next, the proposed feature extraction approach is applied to the candidate matrix region corresponding to the superpixel block. Finally, the 1D-CNN is trained using the obtained superpixel features. Experimental results demonstrate the effectiveness of SPF-CNN, which also exhibits strong generalization capabilities. The average F1-score reaches 0.83.

Abstract Lumpy skin disease (LSD) is a highly contagious disease caused by lumpy skin disease virus (LSDV) in bovines. Rapid and accurate diagnosis is very important to controll it. However, current commercial detection kits need to be improved in terms of sensitivity or specificity. This study aimed to develop a novel diagnostic competitive enzyme-linked immunosorbent assay (cELISA) based on the newly identified antigen gene LSDV034. The rLSDV034 protein was identified as a potential diagnostic antigen, and it was expressed, purified, and used to immunize BALB/c mice. Using laboratory-prepared indirect ELISA (iELISA), the positive cell lines were screened, and their blocking activity was further verified by competitive ELISA (cELISA). The cell line, 1H7, was chosen to produce mouse ascites, which were purified for a monoclonal antibody (mAb, 5.395 mg/mL). The heavy chain type of the 1H7 mAb was identified as IgG1a, and its light chain subtype was identified as κ. Furthermore, cELISA was developed to detect bovine serum antibodies, with rLSDV034 (4 μg/mL) as the coating antigen and HRP-1H7 mAb (1:300) as the competitive antibody. The cutoff value of cELISA was 55%, based on 32 negative bovine serum samples. The analytical sensitivity was 1:8, and no cross-reaction was detected with bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitis virus (IBRV), Pasteurella multocida (P. multocida), or Mycoplasma bovis (M. bovis) from the serum samples. The diagnostic sensitivity and specificity of cELISA were 98.46% (95% confidence interval, CI: 91.7–100) and 100% (95% CI: 89.1–100), respectively, based on the analysis of 30 LSDV-infected bovine serum samples, 35 GTPV-vaccinated samples, and 32 negative samples. The overall coincidence of the cELISA with the virus neutralization test (VNT) reached 98.97% (95% CI: 94.4–100). Furthermore, we used cELISA to analyze 230 clinical bovine serum samples (including 59 infected and 171 vaccinated samples) and found that the serum positivity rates of the immunized samples (on d 60 postimmunization) and infected samples were 77.78% (95% CI: 70.8–83.8%) and 71.19% (95% CI: 57.9–82.2), respectively. These results indicate that the developed cELISA is promising for detecting serum antibodies in naturally infected or vaccinated cattle.

Abstract Low response rate, treatment relapse, and resistance remain key challenges for cancer treatment with immune checkpoint blockade (ICB). Here we report that loss of specific tumor suppressors (TS) induces an inflammatory response and promotes an immune suppressive tumor microenvironment. Importantly, low expression of these TSs is associated with a higher expression of immune checkpoint inhibitory mediators. Here we identify, by using in vivo CRISPR/Cas9 based loss-of-function screening, that NF1, TSC1, and TGF-β RII as TSs regulating immune composition. Loss of each of these three TSs leads to alterations in chromatin accessibility and enhances IL6-JAK3-STAT3/6 inflammatory pathways. This results in an immune suppressive landscape, characterized by increased numbers of LAG3+ CD8 and CD4 T cells. ICB targeting LAG3 and PD-L1 simultaneously inhibits metastatic progression in preclinical triple negative breast cancer (TNBC) mouse models of NF1-, TSC1- or TGF-β RII- deficient tumors. Our study thus reveals a role of TSs in regulating metastasis via non-cell-autonomous modulation of the immune compartment and provides proof-of-principle for ICB targeting LAG3 for patients with NF1-, TSC1- or TGF-β RII-inactivated cancers.

Abstract Background Computed tomography (CT) is the usual modality for diagnosing stroke, but conventional CT angiography reconstructions have limitations. Methods A phantom with tubes of known diameters and wall thickness was scanned for wall detectability, wall thickness, and contrast-to-noise ratio (CNR) on conventional and spectral black-blood (SBB) images. The clinical study included 34 stroke patients. Diagnostic certainty and conspicuity of normal/abnormal intracranial vessels using SBB were compared to conventional. Sensitivity/specificity/accuracy of SBB and conventional were compared for plaque detectability. CNR of the wall/lumen and quantitative comparison of remodeling index, plaque burden, and eccentricity were obtained for SBB imaging and high-resolution magnetic resonance imaging (hrMRI). Results The phantom study showed improved detectability of tube walls using SBB (108/108, 100% versus conventional 81/108, 75%, p

Abstract Background To use an automated system exploiting the advantages of both a neural network and radiomics for analysis of non‐calcified predominant plaque (NCPP). Methods This study retrospectively included 234 patients. Using the workflow of the previous study, the coronary artery was first segmented, images containing plaques were then extracted, and a classifier was built to identify non‐calcified predominant plaques. Radiomics feature analysis and a visualization tool were used to better distinguish NCPP from other plaques. Results Twenty‐six representative radiomics features were selected. DenseNet achieved an area under the curve of 0.889, which was significantly larger (p = 0.001) than that obtained using a gradient‐boosted decision tree (0.859). The feature variances and energy features in calcified predominant plaque were both different from those in NCPP. Conclusions Our automated system provided high‐accuracy analysis of vulnerable plaques using a deep learning approach and predicted useful features of NCPP using a radiomics‐based approach.

Abstract Background Healthy eating is one of the most important nonpharmacologic treatments for patients with atherosclerosis(AS). However, it is unclear how elderly AS patients in western China perceive their dietary status and which type of nutritional assistance they would be willing to receive. Therefore, the primary purpose of this study was to understand the level of knowledge about current dietary habits and healthy eating habits among elderly AS patients in western China, and the secondary purpose was to identify acceptable nutritional assistance measures or pathways for those patients to help them manage disease progression. Methods An implementation study approach was used to recruit elderly patients with AS-related diseases in western China for semistructured interviews. Results 14 participants were included in the study, and the following three themes were identified from the interviews:(1) the diet with regional characteristics; (2) low nutrition-related health literacy; (3) complex attitudes towards nutritional assistance. Most participants had misconceptions about healthy eating, and the sources of their knowledge might not be trustworthy. Participants expressed a preference for personalized nutritional assistance, especially that provided by medical-nursing combined institutions. Conclusion Patients in western China need nutritional assistance for their regional dietary habits; therefore, healthy dietary patterns consistent with the regional culture are proposed to improve the prevailing lack of knowledge about healthy diets, improve the dietary structure of patients, and control the development of the disease.

The transient stability of power systems with high penetration of wind power generation can be significantly improved through the utilization of variable virtual inertia if the energy source of rotational inertia can be expanded by energy storage devices (ESDs). This paper first establishes the relationship of energy conversion between ESD and mechanical kinetic energy inside a synchronous generator (SG). Then, the impact of the controllable inertia on system frequency characteristics and power angle oscillation is analyzed using the small-signal model corresponding to this system. Based on the analysis of the change of transient energy at different stages in the transient process, the control of transient energy dissipation is proposed employing ESDs for reliable inertia support. Finally, a typical simulation system with high penetration of wind power generation is carried out to demonstrate the viability of the proposed control scheme. The test results show that the fluctuation of SG’s power angle and system frequency can be reduced by regulating the variable inertia in transient events, significantly improving the reliability of the inertia support provided by the ESDs.

Abstract A wideband end‐fire stepped slot antenna with gain enhancement and filtering capability is proposed. On one hand, a parasitic dipole serving as a director is introduced in the stepped slot to improve the radiation gain of the slot antenna without increasing its physical size. It is found that a gain enhancement of about 2 dB can be achieved after adopting such approach. On the other hand, an absorptive branch possessing a nearly complementary frequency response with regard to the one of the slot antenna is in‐parallel loaded at the microstrip feedline. It allows the partial dissipation of the out‐of‐band/non‐radiated RF‐signal power of the antenna to attain both an RF‐quasi‐absorptive behaviour and filtering capability. It is found that after loading the dissipative branch, the out‐of‐band radiation efficiency of the slot antenna is reduced to less than 20%. The measured results of a fabricated proof‐of‐concept antenna prototype show a reasonable agreement with the simulated ones and verify the RF performance merits of the proposed stepped slot antenna, such as wide RF operating band covering the 3.39−4.73‐GHz range, end‐fire radiation with a front‐to‐back ratio (FBR) above 10 dB, flat radiation gain, and co‐integrated filtering functionality with RF‐quasi‐absorptive capability.

Abstract Background Several studies have demonstrated a strong correlation between impaired Succinate dehydrogenase (SDH) function and the advancement of tumors. As a subunit of SDH, succinate dehydrogenase complex subunit C (SDHC) has been revealed to play tumor suppressive roles in several cancers, while its specific role in colorectal cancer (CRC) still needs further investigation. Methods Online database were utilized to investigate the expression of SDHC in colorectal cancer and to assess its correlation with patient prognosis. Cell metastasis was assessed using transwell and wound healing assays, while tumor metastasis was studied in a nude mice model in vivo. Drug screening and RNA sequencing were carried out to reveal the tumor suppressor mechanism of SDHC. Triglycerides, neutral lipids and fatty acid oxidation were measured using the Triglyceride Assay Kit, BODIPY 493/503 and Colorimetric Fatty Acid Oxidation Rate Assay Kit, respectively. The expression levels of enzymes involved in fatty acid metabolism and the PI3K/AKT signaling pathway were determined by quantitative real-time PCR and western blot. Results Downregulation of SDHC was found to be closely associated with a poor prognosis in CRC. SDHC knockdown promoted CRC metastasis both in vitro and in vivo. Through drug screening and Gene set enrichment analysis, it was discovered that SDHC downregulation was positively associated with the fatty acid metabolism pathways significantly. The effects of SDHC silencing on metastasis were reversed when fatty acid synthesis was blocked. Subsequent experiments revealed that SDHC silencing activated the PI3K/AKT signaling axis, leading to lipid accumulation by upregulating the expression of aldehyde dehydrogenase 3 family member A2 (ALDH3A2) and reduction of fatty acid oxidation rate by suppressing the expression of acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1A (CPT1A). Conclusions SDHC deficiency could potentially enhance CRC metastasis by modulating the PI3K/AKT pathways and reprogramming lipid metabolism.

Retinal vein occlusion(RVO)is the second most common cause of vision loss due to retinal vascular disease. Macular edema(ME)is a common complication of RVO and a major cause of central vision impairment. Optical coherence tomography(OCT)is a high-resolution imaging technique that can provide detailed cross-sectional images of the retina and choroid. OCT biomarkers play an important role in the early and accurate diagnosis of RVO-ME, prediction of disease progression, and assessment of visual prognosis. This article provides an overview of various OCT biomarkers for RVO-ME, including retinal thickness, disorganization of retinal inner layers, hyper-reflectivity of retinal inner layer, the integrity of external limiting membrane and ellipsoid zone, the third highest reflectance band of the fovea, hyperreflective dots, paracentral acute middle maculopathy, prominent middle limiting membrane sign, serous retinal detachment height, macular volume and choroidal thickness. These biomarkers serve as objective indicators for evaluating the severity of RVO-ME, guiding treatment decisions, and predicting visual outcomes.

Previous studies show that individual investors play a dominant role in China's stock market. Their behavior of chasing-rise being stronger than killing-fall leads to asymmetry of feedback trading. Our article investigates how mutual funds react to this market force. Using China's stock and fund data from 2003 to 2019, we find that mutual funds tend to hold fewer shares when asymmetric feedback trading of the relevant stock gets more intense. This negative relationship is robust after controlling past returns, turnover rates, and firm risk factors, moreover, it attenuates when the market sentiment is bullish or when stocks are allowed short-selling. Further results show that mutual funds' selling towards asymmetric feedback trading does not make excess return but leads to significant risk reduction. Our findings may be related to uncertainty associated with asymmetric feedback trading, and thus support the limit market participation theory from the second largest stock market.

A large amount of residential demand-side resources can be aggregated and utilized under attractive demand response mechanisms. Based on the consumer loyalty program in the research of marketing, a new score-based incentive demand response (SIDR) strategy considering power-score redeem behavior was presented. A bi-level SIDR optimization model that combines the SIDR parameters optimization with the residential consumers’ demand response optimization is proposed. At the lower level, a weight coefficient was modeled based on the construal level theory and fuzzy theory to clarify the influence of incentive step-size and reward distance on residential consumers’ redeem behavior. Then, the optimization model of residential consumers’ demand response was proposed, considering residential consumers’ redeem behavior and comfort in electricity consumption. At the upper level, the optimization model of SIDR incentive parameters is proposed for load aggregators to maximize the demand response profit. The case study on the data of the demand-side bidding market in Zhejiang province, China, illustrates that the SIDR strategy considering power-score redeem behavior can help load aggregators formulate a more reasonable SIDR mechanism and obtain more profit than other incentive-based demand response strategies, thereby enhancing the flexibility and economics of the power system.