6-Aza-2-Thiothymine-Capped Gold Nanoclusters as Robust Antimicrobial Nanoagents for Eradicating Multidrug-Resistant Escherichia coli Infection.

Multidrug-resistant bacterial infections, especially those caused by multidrug-resistant Escherichia coli (E. coli) bacteria, are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Therefore, it is urgently needed to develop a kind of novel, long-term antibacterial agent effectively overcome resistant bacteria. Herein, we present a novel designed antibacterial agent-6-Aza-2-thiothymine-capped gold nanoclusters (ATT-AuNCs), which show excellent antibacterial activity against multidrug-resistant E. coli bacteria. The prepared AuNCs could permeabilize into the bacterial cell membrane via binding with a bivalent cation (e.g., Ca2+), followed by the generation of reactive oxygen species (e.g., •OH and •O2-), ultimately resulting in protein leakage from compromised cell membranes, inducing DNA damage and upregulating pro-oxidative genes intracellular. The AuNCs also speed up the wound healing process without noticeable hemolytic activity or cytotoxicity to erythrocytes and mammalian tissue. Altogether, the results indicate the great promise of ATT-AuNCs for treating multidrug-resistant E. coli bacterial infection.

The impact of liver fibrosis on the progression of hepatocellular carcinoma via a hypoxia-immune-integrated prognostic model.

The impact of liver fibrosis on the deterioration of hepatocellular carcinoma (HCC) remains controversial. We hope to explore this issue through establishing a fibrosis-hypoxia-glycolysis-immune related prognostic model. Liver fibrosis-related genes from Molecular Signatures Database were used to evaluate the degree of fibrosis in HCC patients from the TCGA database. The patients were divided into two groups using the fibrosis-related expression matrix based on the algorithm uniform manifold approximation and projection (UMAP) and evaluated for fibrosis by UMAP cluster and gene enrichment analysis. Prognostic model was constructed by differential analysis, LASSO, and multivariate regression analysis. Immune-infiltration analysis was performed by CIBERSORT. Quantitative PCR and immunohistochemistry were performed to measure the gene expression levels in HCC patients from our hospital. In 365 HCC patients from the TCGA database, 111 HCC patients with high fibrosis score have a worse prognosis than those with low fibrosis based on 129 genes related to liver fibrosis, which may be caused by the interaction between fibrosis, angiogenesis, hypoxia, glycolysis, inflammatory response, and high immune infiltration. We constructed a Fibrosis-Hypoxia-Glycolysis-Immune Prognostic Model (FHGISig), which could significantly predict disease progression in HCC patients. Furthermore, we revealed a close correlation between FHGISig and immune cell infiltration level as well as immune checkpoints. Finally, PCR results found TFF3 mRNA was significantly lower in cirrhotic HCC patients compared with non-cirrhotic ones. Liver fibrosis is a poor-prognostic factor for HCC, and our FHGISig could significantly predict disease progression, which could also be a potential predictive marker for immunotherapy in HCC patients.

CX3CR1 regulates the development of renal interstitial fibrosis through macrophage polarization. / CX3CR1通过调控巨噬细胞极化影响肾间质纤维化.

OBJECTIVES: The binding of CX3C chemokine receptor 1 (CX3CR1) and its unique ligand CX3C chemokine ligand 1 (CX3CL1) can promote the migration of inflammatory cells to the lesion and affect the progression of renal interstitial fibrosis, but the underlying mechanisms remain unclear. This study aims to investigate whether CX3CR1 affects renal interstitial fibrosis by macrophage polarization. METHODS: A mouse model of renal interstitial fibrosis was established by unilateral ureteral obstruction (UUO). C57/B6 mice were divided into a CX3CR1 inhibitor group (injected with CX3CR1 inhibitor AZD8797) and a model group (injected with physiological saline). After continuous intraperitoneal injection for 5 days, the ligated lateral kidneys of mice were obtained on the 7th day. Hematoxylin and eosin (HE) staining and Masson staining were used to observe the infiltration of inflammatory cells and the collagen fiber deposition in renal interstitium, respectively. The mRNA and protein expressions of CX3CR1, alpha-smooth muscle actin (α-SMA) and fibronectin (FN) in the kidneys were detected by reverse transcription PCR (RT-PCR) and Western blotting, respectively. Differentially expressed genes in kidney of the 2 groups were identified by whole genome sequencing and the differential expression of arginase-1 (Arg-1) was verified by RT-PCR. Flow cytometry was used to detect the proportion of M2 type macrophages in kidneys of the 2 groups. RESULTS: The infiltration of inflammatory cells and the collagen fiber deposition in renal interstitium were significantly reduced in the CX3CR1 inhibitor group. The mRNA and protein levels of CX3CR1 and the mRNA levels of α-SMA and FN in the CX3CR1 inhibitor group were significantly lower than those of the model group (all P<0.05). Whole genome sequencing showed that the top 5 differentially expressed genes in kidney of the 2 groups were Ugt1a6b, Serpina1c, Arg-1, Retnla, and Nup62. RT-PCR verified that the expression level of Arg-1 in kidney of the CX3CR1 inhibitor group was significantly higher than that of the model group (P<0.001). Flow cytometry showed that the proportion of Arg1+CD206+M2 macrophages in kidney of the CX3CR1 inhibitor group was significantly higher than that of the model group (P<0.01). CONCLUSIONS: Inhibiting CX3CR1 can effectively prevent the progression of renal interstitial fibrosis. The mechanism may be related to macrophage polarization towards M2 type and upregulation of Arg-1 expression.

Intrahepatic macrophage reprogramming associated with lipid metabolism in hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation and metabolic disorders contribute to the progression of ACLF, but the crosstalk between immunity and metabolism during ACLF is less understood. This study aims to depict the immune microenvironment in the liver during ACLF, and explore the role of lipid metabolic disorder on immunity. METHODS: Single-cell RNA-sequencing (scRNA-seq) was performed using the liver non-parenchymal cells (NPCs) and peripheral blood mononuclear cells (PBMCs) from healthy controls, cirrhosis patients and ACLF patients. A series of inflammation-related cytokines and chemokines were detected using liver and plasma samples. The lipid metabolomics targeted free fatty acids (FFAs) in the liver was also detected. RESULTS: The scRNA-seq analysis of liver NPCs showed a significant increase of monocytes/macrophages (Mono/Mac) infiltration in ACLF livers, whereas the resident Kupffer cells (KCs) were exhausted. A characterized TREM2+ Mono/Mac subpopulation was identified in ACLF, and showed immunosuppressive function. Combined with the scRNA-seq data from PBMCs, the pseudotime analysis revealed that the TREM2+ Mono/Mac were differentiated from the peripheral monocytes and correlated with lipid metabolism-related genes including APOE, APOC1, FABP5 and TREM2. The targeted lipid metabolomics proved the accumulation of unsaturated FFAs associated with α-linolenic acid (α-LA) and α-LA metabolism and beta oxidation of very long chain fatty acids in the ACLF livers, indicating that unsaturated FFAs might promote the differentiation of TREM2+ Mono/Mac during ACLF. CONCLUSIONS: The reprogramming of macrophages was found in the liver during ACLF. The immunosuppressive TREM2+ macrophages were enriched in the ACLF liver and contributed to the immunosuppressive hepatic microenvironment. The accumulation of unsaturated FFAs in the ACLF liver promoted the reprogramming of the macrophages. It might be a potential target to improve the immune deficiency of ACLF patients through regulating lipid metabolism.

Association between serum soluble α-klotho and bone mineral density (BMD) in middle-aged and older adults in the United States: a population-based cross-sectional study.

BACKGROUND: Osteoporosis is a degenerative disease defined by low bone mineral density, has a high prevalence, and causes fractures at multiple sites throughout the body, greatly affecting the quality of patients. α-Klotho is an endocrine factor involved in the regulation of various metabolic processes in humans, and its role in bone metabolism has attracted widespread attention. The relationship between α-klotho and bone mineral density has not been uniformly recognized, and no large-scale correlation analysis has been conducted in the middle-aged and elderly population. OBJECTIVE: To determine the relationship between α-klotho and bone mineral density in middle-aged and elderly people. METHODS: Population data of 3120 individuals aged 40-79 years were obtained from the NHANES database for the period 2011-2016. Regression analysis was performed using a general linear model with serum α-klotho as the independent variable and total bone mineral density, thoracic bone mineral density, lumbar bone mineral density, pelvic bone mineral density, and trunk bone mineral density as the dependent variables, respectively. The generalized additive model was also used for smoothing curve fitting and threshold effect analysis. RESULTS: Serum α-klotho was positively correlated with total bone mineral density at lg (Klotho) < 2.97 and with thoracic bone mineral density at lg (Klotho) > 2.69 (ß = 0.05, p = 0.0006), and negatively correlated (ß = -0.27, p = 0.0341) with lumbar bone mineral density at lg (Klotho) < 2.69. It also positively correlated with trunk bone mineral density (ß = 0.027, p = 0.03657) and had no segmental effect but did not correlate with pelvic bone mineral density. The positive association of serum α-klotho with those aged 40-49 years, female, non-Hispanic White, and without hypertension was clearer. In the population with diabetes, a significantly positive association between total (ß = 0.15, p = 0.01), thoracic (ß = 0.23, p = 0.0404), and lumbar (ß = 0.22, p = 0.0424) bone mineral density and α-klotho was observed. CONCLUSIONS: α-Klotho has different relationships with total, thoracic, lumbar, and trunk bone mineral density. Among them, the positive correlation between α-klotho and trunk bone mineral density is more valuable for predicting osteoporosis. The significant effect of α-klotho on bone mineral density in diabetes patients suggests its potential as a predictive marker of diabetes progression.

Machine learning-based investigation of the relationship between immune status and left ventricular hypertrophy in patients with end-stage kidney disease.

Background: Left ventricular hypertrophy (LVH) is the most frequent cardiac complication among end-stage kidney disease (ESKD) patients, which has been identified as predictive of adverse outcomes. Emerging evidence has suggested that immune system is implicated in the development of cardiac hypertrophy in multiple diseases. We applied machine learning models to exploring the relation between immune status and LVH in ESKD patients. Methods: A cohort of 506 eligible patients undergoing immune status assessment and standard echocardiography simultaneously in our center were retrospectively analyzed. The association between immune parameters and the occurrence of LVH were evaluated through univariate and multivariate logistic analysis. To develop a predictive model, we utilized four distinct modeling approaches: support vector machine (SVM), logistic regression (LR), multi-layer perceptron (MLP), and random forest (RF). Results: In comparison to the non-LVH group, ESKD patients with LVH exhibited significantly impaired immune function, as indicated by lower cell counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, and B cells. Additionally, multivariable Cox regression analysis revealed that a decrease in CD3+ T cell count was an independent risk factor for LVH, while a decrease in NK cell count was associated with the severity of LVH. The RF model demonstrated superior performance, with an average area under the curve (AUC) of 0.942. Conclusion: Our findings indicate a strong association between immune parameters and LVH in ESKD patients. Moreover, the RF model exhibits excellent predictive ability in identifying ESKD patients at risk of developing LVH. Based on these results, immunomodulation may represent a promising approach for preventing and treating this disease.

Promoting the healing of methicillin-resistant Staphylococcus aureus-infected wound by a multi-target antimicrobial AIEgen of 6-Aza-2-thiothymine-decorated gold nanoclusters.

The use of conventional antibiotic therapies is in question owing to the emergence of drug-resistant pathogenic bacteria. Therefore, novel, highly efficient antibacterial agents to effectively overcome resistant bacteria are urgently needed. Accordingly, in this work, we described a novel class luminogen of 6-Aza-2-thiothymine-decorated gold nanoclusters (ATT-AuNCs) with aggregation-induced emission property that possessed potent antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Scanning electron microscopy was performed to investigate the interactions between ATT-AuNCs and MRSA. In addition, ATT-AuNCs exhibited excellent ROS generation efficiency and could effectively ablate MRSA via their internalization to the cells. Finally, tandem mass tag-labeling proteome analysis was carried out to investigate the differential expression proteins in MRSA strains. The results suggested that ATT-AuNCs killed MRSA cells through altering the expression of multiple target proteins involved in DNA replication, aminoacyl-tRNA synthesis, peptidoglycan and arginine biosynthesis metabolism. Parallel reaction monitoring technique was further used for the validation of these proteome results. ATT-AuNCs could also be served as a wound-healing agent and accelerate the healing process. Overall, we proposed ATT-AuNCs could serve as a robust antimicrobial aggregation-induced emission luminogen (AIEgen) that shows the ability to alter the activities of multiple targets for the elimination of drug-resistant bacteria.

The long non-coding RNA KLF3-AS1/miR-10a-3p/ZBTB20 axis improves the degenerative changes in human nucleus pulposus cells.

Excessive apoptosis of intervertebral disc cells, namely nucleus pulposus (NP) cells, results in decreased cell density and extracellular matrix (ECM) catabolism, hence leading to intervertebral disc degeneration (IVDD). As a cell model in the present study, a commercially available human NP cell line was utilized. Long noncoding RNAs and microRNAs may regulate the proliferation or apoptosis of human NP cells, hence exerting a significant influence on the occurrence of IVDD. KLF3-AS1 was discovered to be abnormally downregulated in IVDD tissues. Overexpression of KLF3-AS1 enhanced NP cell viability, prevented cell apoptosis, boosted ECM synthesis, and lowered MMP-13 and ADAMTS4 levels. ZBTB20 and KLF3-AS1 were co-expressed in IVDD; ZBTB20 overexpression had similar effects on NP cells, ECM production, and MMP-13 and ADAMTS4 levels as KLF3-AS1 overexpression. miR-10a-3p may target KLF3-AS1 and ZBTB20 and inhibit the expression of ZBTB20. Inhibition of miR-10a-3p enhanced NP cell viability, reduced apoptosis, and enhanced ECM synthesis. KLF3-AS1 overexpression increased ZBTB20 expression, whereas miR-10a-3p overexpression decreased ZBTB20 expression; miR-10a-3p overexpression reduced the effects of KLF3-AS1 on ZBTB20. Overexpression of miR-10a-3p consistently decreased the effects of KLF3-AS1 overexpression on NP cell survival, apoptosis, and ECM synthesis. In conclusion, KLF3-AS1 overexpression may ameliorate degenerative NP cell alterations through the miR-10a-3p/ZBTB20 axis.

Immune landscape and the key role of APOE+ monocytes of lupus nephritis under the single-cell and spatial transcriptional vista.

BACKGROUND: Lupus nephritis (LN) is among the most common complication of systemic lupus erythematosus (SLE) with high mortality and morbidity. The analysis of LN kidney's local immune response through single-cell and spatial transcriptome enables the study of potential therapeutic targets. METHODS: By single cell sequencing and spatial transcriptome, we profile cells from LN kidney and normal kidney tissues to characterize cellular composition and elucidate the potential upstream monocyte/macrophage (Mono/MΦ) initiating the auto-immune response. After the high-throughput synergy screening, we performed the immunofluorescence to identify the specific cells in LN patients. The function experiments were finished by flow cytometry and Elisa. RESULTS: By immunofluorescence and spatial transcriptome, we identified differential subsets of Mono/MΦ and demonstrated that they exhibit temporal expression of TIMP1, IL1B, SPP1 and APOE. With the function experiments, we found that the APOE+ Mono may be compensatorily increased in LN, and the capacity of antigen presenting was decreased with the overexpression of APOE. Furthermore, how do the LN-specific Mono/MΦ transport in and out the glomerulus to active the local immune response remains unclear. Our results showed that lymphangiogenesis occurred in LN kidneys but not in normal kidneys, suggesting the presence of a new lymphatic vessel may serve as a 'green channel' for LN-specific Mono/MΦ. CONCLUSIONS: In LN, APOE+ Mono are compensatorily elevated, with decreased antigen presenting ability and reduced secretion of interferons. The lymphangiogenesis in LN prompts the trafficking of Mono/MΦ in LN kidney.

Identification of the shared genes and immune signatures between systemic lupus erythematosus and idiopathic pulmonary fibrosis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder which could lead to inflammation and fibrosis in various organs. Pulmonary fibrosis is a severe complication in patients with SLE. Nonetheless, SLE-derived pulmonary fibrosis has unknown pathogenesis. Of pulmonary fibrosis, Idiopathic pulmonary fibrosis (IPF) is a typicality and deadly form. Aiming to investigate the gene signatures and possible immune mechanisms in SLE-derived pulmonary fibrosis, we explored common characters between SLE and IPF from Gene Expression Omnibus (GEO) database. RESULTS: We employed the weighted gene co-expression network analysis (WGCNA) to identify the shared genes. Two modules were significantly identified in both SLE and IPF, respectively. The overlapped 40 genes were selected out for further analysis. The GO enrichment analysis of shared genes between SLE and IPF was performed with ClueGO and indicated that p38MAPK cascade, a key inflammation response pathway, may be a common feature in both SLE and IPF. The validation datasets also illustrated this point. The enrichment analysis of common miRNAs was obtained from the Human microRNA Disease Database (HMDD) and the enrichment analysis with the DIANA tools also indicated that MAPK pathways' role in the pathogenesis of SLE and IPF. The target genes of these common miRNAs were identified by the TargetScan7.2 and a common miRNAs-mRNAs network was constructed with the overlapped genes in target and shared genes to show the regulated target of SLE-derived pulmonary fibrosis. The result of CIBERSORT showed decreased regulatory T cells (Tregs), naïve CD4+ T cells and rest mast cells but increased activated NK cells and activated mast cells in both SLE and IPF. The target genes of cyclophosphamide were also obtained from the Drug Repurposing Hub and had an interaction with the common gene PTGS2 predicted with protein-protein interaction (PPI) and molecular docking, indicating its potential treatment effect. CONCLUSIONS: This study originally uncovered the MAPK pathway, and the infiltration of some immune-cell subsets might be pivotal factors for pulmonary fibrosis complication in SLE, which could be used as potentially therapeutic targets. The cyclophosphamide may treat SLE-derived pulmonary fibrosis through interaction with PTGS2, which could be activated by p38MAPK.

Synthetic Antibacterial Quaternary Phosphorus Salts Promote Methicillin-Resistant Staphylococcus aureus-Infected Wound Healing.

Background: Drug-resistant microbes pose a global health concern, requiring the urgent development of effective antibacterial agents and strategies in clinical practice. Therefore, there is an urgent need to explore novel antibacterial materials to effectively eliminate bacteria. The synthesis of quaternary phosphonium salt in haloargentate systems, wherein the phosphorus atom is represented in a cationic form, is a possible strategy for the development of antibacterial materials. Methods: Using (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 4, 6) as a template, we designed three kinds of quaternary phosphorus salts as effective antibacterial agents against drug-resistant bacteria. Results: The synthesized quaternary phosphorus salt of (1,4-DBTPP)Br2 effectively prevented the formation of the bacterial biofilms, and degraded bacterial membranes and cell walls by promoting the production of reactive oxygen species, which exhibited effective therapeutic effects in a rat model of a superficial wound infected with methicillin-resistant Staphylococcus aureus. Conclusion: The quaternary phosphorus salt (1,4-DBTPP)Br2 demonstrated hemocompatibility and low toxicity, revealing its potential in the treatment of clinical infections.

A meta-validated immune infiltration-related gene model predicts prognosis and immunotherapy sensitivity in HNSCC.

BACKGROUND: Tumor microenvironment (TME) is of great importance to regulate the initiation and advance of cancer. The immune infiltration patterns of TME have been considered to impact the prognosis and immunotherapy sensitivity in Head and Neck squamous cell carcinoma (HNSCC). Whereas, specific molecular targets and cell components involved in the HNSCC tumor microenvironment remain a twilight zone. METHODS: Immune scores of TCGA-HNSCC patients were calculated via ESTIMATE algorithm, followed by weighted gene co-expression network analysis (WGCNA) to filter immune infiltration-related gene modules. Univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression were applied to construct the prognostic model. The predictive capacity was validated by meta-analysis including external dataset GSE65858, GSE41613 and GSE686. Model candidate genes were verified at mRNA and protein levels using public database and independent specimens of immunohistochemistry. Immunotherapy-treated cohort GSE159067, TIDE and CIBERSORT were used to evaluate the features of immunotherapy responsiveness and immune infiltration in HNSCC. RESULTS: Immune microenvironment was significantly associated with the prognosis of HNSCC patients. Total 277 immune infiltration-related genes were filtered by WGCNA and involved in various immune processes. Cox regression identified nine prognostic immune infiltration-related genes (MORF4L2, CTSL1, TBC1D2, C5orf15, LIPA, WIPF1, CXCL13, TMEM173, ISG20) to build a risk score. Most candidate genes were highly expressed in HNSCC tissues at mRNA and protein levels. Survival meta-analysis illustrated high prognostic accuracy of the model in the discovery cohort and validation cohort. Higher proportion of progression-free outcomes, lower TIDE scores and higher expression levels of immune checkpoint genes indicated enhanced immunotherapy responsiveness in low-risk patients. Decreased memory B cells, CD8+ T cells, follicular helper T cells, regulatory T cells, and increased activated dendritic cells and activated mast cells were identified as crucial immune cells in the TME of high-risk patients. CONCLUSIONS: The immune infiltration-related gene model was well-qualified and provided novel biomarkers for the prognosis of HNSCC.

Clinical characteristics and mortality risk prediction model in children with acute myocarditis.

BACKGROUND: Acute myocarditis (AMC) can cause poor outcomes or even death in children. We aimed to identify AMC risk factors and create a mortality prediction model for AMC in children at hospital admission. METHODS: This was a single-center retrospective cohort study of AMC children hospitalized between January 2016 and January 2020. The demographics, clinical examinations, types of AMC, and laboratory results were collected at hospital admission. In-hospital survival or death was documented. Clinical characteristics associated with death were evaluated. RESULTS: Among 67 children, 51 survived, and 16 died. The most common symptom was digestive disorder (67.2%). Based on the Bayesian model averaging and Hosmer-Lemeshow test, we created a final best mortality prediction model (acute myocarditis death risk score, AMCDRS) that included ten variables (male sex, fever, congestive heart failure, left-ventricular ejection fraction < 50%, pulmonary edema, ventricular tachycardia, lactic acid value > 4, fulminant myocarditis, abnormal creatine kinase-MB, and hypotension). Despite differences in the characteristics of the validation cohort, the model discrimination was only marginally lower, with an AUC of 0.781 (95% confidence interval = 0.675-0.852) compared with the derivation cohort. Model calibration likewise indicated acceptable fit (Hosmer‒Lemeshow goodness-of-fit, P» = 0.10). CONCLUSIONS: Multiple factors were associated with increased mortality in children with AMC. The prediction model AMCDRS might be used at hospital admission to accurately identify AMC in children who are at an increased risk of death.

Standardization of neutrophil CD64 and monocyte HLA-DR measurement and its application in immune monitoring in kidney transplantation.

Background: Infections cause high mortality in kidney transplant recipients (KTRs). The expressions of neutrophil CD64 (nCD64) and monocyte HLA-DR (mHLA-DR) provide direct evidence of immune status and can be used to evaluate the severity of infection. However, the intensities of nCD64 and mHLA-DR detected by flow cytometry (FCM) are commonly measured by mean fluorescence intensities (MFIs), which are relative values, thus limiting their application. We aimed to standardize nCD64 and mHLA-DR expression using molecules of equivalent soluble fluorochrome (MESF) and to explore their role in immune monitoring for KTRs with infection. Methods: The study included 50 KTRs diagnosed with infection, 65 immunologically stable KTRs and 26 healthy controls. The blood samples were collected and measured simultaneously by four FCM protocols at different flow cytometers. The MFIs of nCD64 and mHLA-DR were converted into MESF by Phycoerythrin (PE) Fluorescence Quantitation Kit. The intraclass correlation coefficients (ICCs) and the Bland-Altman plots were used to evaluate the reliability between the four FCM protocols. MESFs of nCD64 and mHLA-DR, nCD64 index and sepsis index (SI) with the TBNK panel were used to evaluate the immune status. Comparisons among multiple groups were performed with ANOVA one-way analysis. Receiver operating characteristics (ROC) curve analysis was performed to diagnose infection or sepsis. Univariate and multivariate logistic analysis examined associations of the immune status with infection. Results: MESFs of nCD64 and mHLA-DR measured by four protocols had excellent reliability (ICCs 0.993 and 0.957, respectively). The nCD64, CD64 index and SI in infection group were significantly higher than those of stable KTRs group. Patients with sepsis had lower mHLA-DR but higher SI than non-sepsis patients. ROC analysis indicated that nCD64 had the highest area under the curve (AUC) for infection, and that mHLA-DR had the highest AUC for sepsis. Logistic analysis indicated that nCD64 > 3089 and B cells counts were independent risk factors for infection. Conclusion: The standardization of nCD64 and mHLA-DR made it available for widespread application. MESFs of nCD64 and mHLA-DR had good diagnostic performance on infection and sepsis, respectively, which could be promising indicators for immune status of KTRs and contributed to individualized treatment.

Knowledge mapping of students' mental health status in the COVID-19 pandemic: A bibliometric study.

Objective: The purpose of this study was to investigate the international scientific output on mental health of students during COVID-19 from 2020 to 2022 through a bibliometric analysis and to explore trend and research hotspots in this field. Methods: We searched the Web of Science Core Collection for publications and used a variety of software to analyze and visualize the data such as R, CiteSpace, VOSviewer and Scimago. Results: A total of 2,734 publications were retrieved as of June 4, 2022, published by 3,894 institutions from 120 countries/regions. China and the United States lead in the quantity and quality of publications in this field. According to Bradford's Law, 16 journals are considered core journals in the field. Co-cited references indicate the main psychological problems of students under the epidemic revolve around anxiety, poor sleep and financial difficulty. Their behavior might also be influenced by increased internet and alcohol use. Conclusion: Mental health of students during COVID-19 is attracting increasing attention. It is identified that the research hotspots in this field continue to revolve around emotional anxiety and unhealthy behaviors. Due to the different troubles faced by different groups under COVID-19, further exploration of the relevant factors specific for students are needed, with a hopeful view to providing ideas for intervention measures.

Identification and validation of an immunological microenvironment signature and prediction model for epstein-barr virus positive lymphoma: Implications for immunotherapy.

Background: Epstein-Barr virus (EBV) is considered a carcinogenic virus, which is associated with high risk for poor prognosis in lymphoma patients, and there has been especially no satisfying and effective treatment for EBV+ lymphoma. We aimed to identify the immunological microenvironment molecular signatures which lead to the poor prognosis of EBV+ lymphoma patients. Methods: Differential genes were screened with microarray data from the GEO database (GSE38885, GSE34143 and GSE13996). The data of lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) from the TCGA database and GSE4475 were used to identify the prognostic genes. The data of GSE38885, GSE34143, GSE132929, GSE58445 and GSE13996 were used to eluate the immune cell infiltration. Formalin-fixed, paraffin-embedded tissue was collected for Real Time Quantitative PCR from 30 clinical samples, including 15 EBV+ and 15 EBV- lymphoma patients. Results: Four differential genes between EBV+ and EBV- lymphoma patients were screened out with the significance of the survival and prognosis of lymphoma, including CHIT1, SIGLEC15, PLA2G2D and TMEM163. Using CIBERSORT to evaluate immune cell infiltration, we found the infiltration level of macrophages was significantly different between EBV+ and EBV- groups and was closely related to different genes. Preliminary clinical specimen verification identified that the expression levels of CHIT1 and TMEM163 were different between EBV+ and EBV- groups. Conclusions: Our data suggest that differences in expression levels of CHIT1 and TMEM163 and macrophage infiltration levels may be important drivers of poor prognosis of EBV+ lymphoma patients. These hub genes may provide new insights into the prognosis and therapeutic target for EBV+ lymphoma.

Two-dimensional antiferromagnetic nodal-line semimetal and quantum anomalous Hall state in the van der Waals heterostructure germanene/Mn2S2.

Materials with interactions between the topology and magnetism are triggering increasing interest. We constructed a two-dimensional (2D) van der Waals heterostructure germanene/Mn2S2, where the germanene is a quantum spin Hall insulator and Mn2S2provides antiferromagnetic (AFM) interactions. In this structure, a 2D AFM nodal-line semimetal (NLSM) phase is expected without the spin-orbit coupling (SOC), which is of a high density of states around the Fermi level. The band touching rings originate from the intersection between different spin components ofporbitals of germanene. This result provides a possible 2D realization of NLSMs, which are usually realized in three-dimensional systems. When the SOC is present, a quantum anomalous Hall (QAH) state emerges with the annihilation of the band-touching rings. The nontrivial topology is determined by calculating the Chern number and Wannier charge centers. This provides an alternative platform to realize QAH states. These results could also provide the possibility of further understanding the topological states in NLSM and electronic applications.

Multivalley Superconductivity in Monolayer Transition Metal Dichalcogenides.

In transition metal dichalcogenides (TMDs), Ising superconductivity with an antisymmetric spin texture on the Fermi surface has attracted wide interest due to the exotic pairing and topological properties. However, it is not clear whether the Q valley with a giant spin splitting is involved in the superconductivity of heavily doped semiconducting 2H-TMDs. Here by taking advantage of a high-quality monolayer WS2 on hexagonal boron nitride flakes, we report an ionic-gating induced superconducting dome with a record high critical temperature of ∼6 K, accompanied by an emergent nonlinear Hall effect. The nonlinearity indicates the development of an additional high-mobility channel, which (corroborated by first principle calculations) can be ascribed to the population of Q valleys. Thus, multivalley population at K and Q is suggested to be a prerequisite for developing superconductivity. The involvement of Q valleys also provides insights to the spin textured Fermi surface of Ising superconductivity in the large family of transition metal dichalcogenides.

Tuning 4f-Center Electron Structure by Schottky Defects for Catalyzing Li Diffusion to Achieve Long-Term Dendrite-Free Lithium Metal Battery.

Lithium metal is considered as the most prospective electrode for next-generation energy storage systems due to high capacity and the lowest potential. However, uncontrollable spatial growth of lithium dendrites and the crack of solid electrolyte interphase still hinder its application. Herein, Schottky defects are motivated to tune the 4f-center electronic structures of catalysts to provide active sites to accelerate Li transport kinetics. As experimentally and theoretically confirmed, the electronic density is redistributed and affected by the Schottky defects, offering numerous active catalytic centers with stronger ion diffusion capability to guide the horizontal lithium deposition against dendrite growth. Consequently, the Li electrode with artificial electronic-modulation layer remarkably decreases the barriers of desolvation, nucleation, and diffusion, extends the dendrite-free plating lifespan up to 1200 h, and improves reversible Coulombic efficiency. With a simultaneous catalytic effect on the conversions of sulfur species at the cathodic side, the integrated Li-S full battery exhibits superior rate performance of 653 mA h g-1 at 5 C, high long-life capacity retention of 81.4% at 3 C, and a high energy density of 2264 W h kg-1 based on sulfur in a pouch cell, showing the promising potential toward high-safety and long-cycling lithium metal batteries.

The Association between Regulatory T Cell Subpopulations and Severe Pneumonia Post Renal Transplantation.

Severe pneumonia accounts for the majority of morbidity and mortality in renal allograft recipients due to immunosuppressant maintenance. Regulatory T cells (Tregs), which are involved in tackling infections under immunosuppressive conditions, are rarely uncovered. We aimed to investigate the relationship between various Treg subpopulations and severe pneumonia after kidney transplantation (KTx). KTx recipients with pneumonia were divided into severe pneumonia and mild pneumonia groups. The frequencies and absolute numbers (Ab No.) of total Tregs (CD4+CD25+FoxP3+), six subsets of Tregs (Helios+/-, CD39+/-, and CD45RA+/-), and T cells, B cells, and NK cells were assessed from peripheral blood via flow cytometry using the t or Mann-Whitney test and receiver operating curve analysis. We also determined the median fluorescence intensity (MFI) of human leukocyte antigen- (HLA-) DR on monocytes and CD64 on neutrophils. Logistic regression was used to identify the risk factors of disease progression, and Pearson's correlation analysis was performed to identify relationships between the measured immune indices and patients' clinical information. Our research indicated that Treg subpopulations were strongly associated with severe pneumonia progression post KTx. Based on the monitoring of Treg subpopulations, better-individualized prevention and therapy might be achieved for patients with severe pneumonia post KTx.