The Molecular Characteristics and Therapeutic Implications of O-Glycan Synthesis in Pancreatic Cancer by Integrating Transcriptome and Single-Cell Data.

BACKGROUND: Glycans constitute the primary components of proteins that regulate key carcinogenic processes in cancer progression. This study investigated the significance of O-glycan synthesis in the pathogenesis, outcome, and therapy of pancreatic cancer (PC). METHODS: Transcriptomic data and clinical prognostic information of PC were acquired via TCGA and GEO databases. CSA database was used to obtain single-cell data of PC. The O-glycan biosynthesis signaling pathway and its related genes were acquired via the MSigDB platform. The nonnegative matrix factorization (NMF) clustering was utilized to construct the O-glycan biosynthesis-associated molecular subtypes in PC. The LASSO and Cox regression were utilized to build the prognostic prediction model. We utilized real-time quantitative PCR (qRT-PCR) to verify the expressed levels of model genes. Single-cell analysis was utilized to investigate the levels of target genes and O-glycan biosynthesis signaling pathway in the PC tumour microenvironment. RESULTS: We obtained 30 genes related to O-glycan biosynthesis, among which 15 were associated with the prognosis of PC. All PC samples were grouped into two distinct molecular subtypes associated with O-glycan biosynthesis: OGRGcluster C1 and OGRGcluster C2, and compared to OGRGcluster C1. PCs in OGRGcluster C2 had a more advanced clinical stage and pathological grade, worse prognosis, and more active O-glycan biosynthesis function. Immune analysis indicated that naïve B cell, CD8+ T cell, memory-activated CD4+ T cell, and monocytes displayed remarkably higher infiltration levels in OGRGcluster C1 while resting NK cell, macrophages M0, resting dendritic cell, activated dendritic cell, and neutrophils exhibited markedly higher infiltration levels in OGRGcluster C2. OGRGcluster C1 exhibited higher sensitivities to drugs, such as cisplatin, irinotecan, KRAS(G12C) inhibitor-12, oxaliplatin, paclitaxel, and sorafenib. Besides, we built the O-glycan biosynthesis-related prognostic model (including SPRR1B, COL17A1, and ECT2) with a good prediction performance. SPRR1B, COL17A1, and ECT2 were remarkably highly expressed in PC tissues and linked to a poor outcome. Single-cell analysis revealed that Oglycan biosynthesis was observed only in PC, and consistent with this, the target genes were significantly enriched in PC. CONCLUSION: We first constructed molecular subtypes and prognostic models related to O-glycan biosynthesis in PC. It is clear that O-glycan biosynthesis is related to the development, prognosis, immune microenvironment, and treatment of PC. This provides new strategies for stratification, diagnosis, and treatment of PC patients.

Prognostic effects of different treatment modalities for hypopharyngeal squamous cell carcinoma: Experience of two tertiary hospitals in Southwestern China.

Background: The prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. Methods: HPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan-Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). Results: A total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p < 0.0001). In comparison with RT alone, both surgery alone (all cases: hazard ratio [HR] = 0.39, p = 0.0018; stage IV cases: HR = 0.38, p = 0.0085) and surgery-based multimodality treatment (SBMT; all cases: HR = 0.27, p < 0.0001; stage IV cases: HR = 0.30, p = 0.00025) showed prognostic benefits, while SBMT also showed survival priority over chemoradiotherapy (CRT; all cases: HR = 0.52, p < 0.0001; stage IV cases: HR = 0.59, p = 0.0033). Moreover, patients who underwent surgery alone had comparable OS to those who underwent SBMT (all patients: p = 0.13; stage IV cases: p = 0.34), while CRT yielded similar prognostic outcomes as RT alone (all patients: p = 0.054; stage IV cases: p = 0.11). Conclusions: Surgery alone was comparable to SBMT and superior to RT/CRT in terms of OS in patients with HPSCC. We suggest that surgery should be encouraged for the treatment of HPSCC, even in patients with advanced-stage disease.

Provenance and family variations in early growth of Manchurian walnut (Juglans mandshurica Maxim.) and selection of superior families.

This study, conducted in China in November 2020, was aimed at exploring the variations in growth traits among different provenances and families as well as to select elite materials of Juglans mandshurica. Thus, seeds of 44 families from six J. mandshurica provenances in Heilongjiang and Jilin provinces were sown in the nursery and then transplanted out in the field. At the age of 5 years, seven growth traits were assessed, and a comprehensive analysis was conducted as well as selection of provenance and families. Analysis of variance revealed statistically significant (P < 0.01) differences in seven growth traits among different provenances and families, thereby justifying the pursuit of further breeding endeavors. The genetic coefficient of variation (GCV) for all traits ranged from 5.44% (branch angle) to 21.95% (tree height) whereas the phenotypic coefficient of variation (PCV) ranged from 13.74% (tapering) to 38.50% (branch number per node), indicating considerable variability across the traits. Further, all the studied traits except stem straightness degree, branch angle and branch number per node, showed high heritability (Tree height, ground diameter, mean crown width and tapering, over 0.7±0.073), indicating that the variation in these traits is primarily driven by genetic factors. Correlation analysis revealed a strong positive correlation (r > 0.8) between tree height and ground diameter (r = 0.86), tree height and mean crown width (r = 0.82), and ground diameter and mean crown width (r = 0.83). This suggests that these relationships can be employed for more precise predictions of the growth and morphological characteristics of trees, as well as the selection of superior materials. There was a strong correlation between temperature factors and growth traits. Based on the comprehensive scores in this study, Sanchazi was selected as elite provenance. Using the top-percentile selection criteria, SC1, SC8, DJC15, and DQ18 were selected as elite families. These selected families exhibit genetic gains of over 10% in tree height, ground diameter and mean crown width, signifying their significant potential in forestry for enhancing timber production and reducing production cycles, thereby contributing to sustainable forest management. In this study, the growth traits of J. mandshurica were found to exhibit stable variation, and there were correlations between these traits. The selected elite provenance and families of J. mandshurica showed faster growth, which is advantageous for the subsequent breeding and promotion of improved J. mandshurica varieties.

Detection and Analysis of Commonly Used Infection Indicators in Patients with Acute Urticaria.

INTRODUCTION: In this study, we investigated the correlation and clinical significance of peripheral blood leukocytes, neutrophils, C-reactive protein (CRP), and procalcitonin (PCT) in patients with acute urticaria. METHODS: Complete blood count with differential, CRP, and PCT tests were conducted on patients with acute urticaria. A total of 614 patients with acute urticaria were divided into three groups: the first group consisted of patients with elevated leukocyte and neutrophil count, the second group consisted of patients with normal leukocyte and neutrophil count, and the third group consisted of patients with abnormal leukocyte and neutrophil count. A correlation analysis was conducted to investigate the levels of leukocytes, neutrophils, CRP, and PCT in the three groups. RESULTS: The results of Kruskal-Wallis' nonparametric test revealed statistically significant variations in leukocytes, neutrophils, CRP, and PCT among the three groups (p < 0.001). However, CRP and PCT showed no statistically significant differences between the second and third groups (p < 0.001, p = 0.0041, p = 0.0032). Additional multiple comparisons in Spearman correlation analysis indicated statistically significant differences (p = 0.55). Across all groups, there was a statistically significant difference in the correlation between CRP-PCT and leukocytes-neutrophils (p = 0.53). CONCLUSION: Leukocytes and neutrophils are sensitive to the impact of medications and stress on the body. Combining CRP and PCT, as well as routine blood test, may be a comprehensive assessment of infection presence and severity in patients, providing guidance for antibiotic treatment.

CXCL13-neutralizing Antibody Alleviate Chronic Skeletal Muscle Degeneration in a Mouse Model.

INTRODUCTION: Skeletal muscle degeneration is a common effect of chronic muscle injuries, including fibrosis and fatty infiltration, which is the replacement of preexisting parenchymal tissue by extracellular matrix proteins and abnormal invasive growth of fibroblasts and adipocytes. METHOD: This remodeling limits muscle function and strength, eventually leading to reduced quality of life for those affected. Chemokines play a major role in the regulation of immunocyte migration, inflammation, and tissue remodeling and are implicated in various fibrotic and degenerative diseases. In this study, we aimed to investigate the role of the B-cell chemokine CXCL13 in the gastrocnemius muscle of the Achilles tendon rupture model mouse. We hypothesize that CXCL13 may promote fibrosis and aggravate skeletal muscle degeneration. We performed RNA sequencing and bioinformatics analysis of gastrocnemius muscle from normal and model mice to identify differentially expressed genes and signal pathways related to skeletal muscle degeneration and fibrosis. RESULTS: Our results show that CXCL13 is highly expressed in chronically degenerating skeletal muscle. Furthermore, CXCL13-neutralising antibodies with therapeutic potential were observed to inhibit fibrosis and adipogenesis in vivo and in vitro. CONCLUSION: Our study reveals the underlying therapeutic implications of CXCL13 inhibition for clinical intervention in skeletal muscle degeneration, thereby improving patient prognosis.

Novel membrane-targeting isoxanthohumol-amine conjugates for combating methicillin-resistant Staphylococcus aureus (MRSA) infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is a widespread pathogen causing clinical infections and is multi-resistant to many antibiotics, making it urgent need to develop novel antibacterials to combat MRSA. Here, a series of novel isoxanthohumol-amine conjugates were synthesized as antibacterials. After bioactivity evaluation, a compound E2 was obtained, which showed excellent antibacterial activity against S. aureus and clinical MRSA isolates (MICs = 0.25-1 µg/mL), superior to vancomycin, and with negligible hemolysis and good membrane selectivity. Additionally, E2 exhibited fast bacterial killing, less susceptible to resistance, relatively low cytotoxicity, and good plasma stability. Mechanism investigation revealed that E2 can disrupt bacterial membranes by specifically binding to phosphatidylglycerol on the bacterial membrane, thus causing elevated intracellular ROS and leakage of DNA and proteins, and ultimately killing bacteria. Noticeably, E2 displayed a good in vivo safety profile and better in vivo therapeutic efficacy than the same dose of vancomycin, allowing it to be a potential antibacterial to conquer MRSA infections.

Time-series transcriptome reveals inflammatory signature in monocytes and neutrophils following acute heat exposure in mine rescuers.

Occupational exposure to extreme high temperatures and the increasing global temperatures necessitates a deeper understanding of the impact of heat exposure on human health. However, the molecular mechanisms underlying the response of monocytes and neutrophils to heat exposure in occupational population remain to be fully elucidated. This study used longitudinal transcriptome to assess the impact of acute heat exposure (50°C for 30 min) in 10 subjects from a mine rescue team before acute heat exposure (baseline) and at 5 min, 30 min, 1 h, and 24 h after acute heat exposure (recovery). The time-series analysis revealed a coordinated molecular choreography of changes involving inflammation, coagulation, extracellular matrix, and energy metabolism. Importantly, the study characterized the inflammatory signature associated with heat exposure in monocytes and neutrophils, as evidenced by the rapid activation of the inflammation-related transcriptome following heat exposure. Additionally, we pinpointed potential regulators, such as NR4A1, FOSL1, EGR3, and ATF3. In summary, the study suggested that the initial response to heat stress in monocytes and neutrophils from mine rescue team member was primarily characterized by a pro-inflammatory stress response, which could potentially lead to the development of inflammation and ultimately result in a systemic inflammatory response in heatstroke.

Identification of novel biomarkers based on lipid metabolism-related molecular subtypes for moderately severe and severe acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an unpredictable and potentially fatal disorder. A derailed or unbalanced immune response may be the root of the disease's severe course. Disorders of lipid metabolism are highly correlated with the occurrence and severity of AP. We aimed to characterize the contribution and immunological characteristics of lipid metabolism-related genes (LMRGs) in non-mild acute pancreatitis (NMAP) and identify a robust subtype and biomarker for NMAP. METHODS: The expression mode of LMRGs and immune characteristics in NMAP were examined. Then LMRG-derived subtypes were identified using consensus clustering. The weighted gene co-expression network analysis (WGCNA) was utilized to determine hub genes and perform functional enrichment analyses. Multiple machine learning methods were used to build the diagnostic model for NMAP patients. To validate the predictive effectiveness, nomograms, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) were used. Using gene set variation analysis (GSVA) and single-cell analysis to study the biological roles of model genes. RESULTS: Dysregulated LMRGs and immunological responses were identified between NMAP and normal individuals. NMAP individuals were divided into two LMRG-related subtypes with significant differences in biological function. The cluster-specific genes are primarily engaged in the regulation of defense response, T cell activation, and positive regulation of cytokine production. Moreover, we constructed a two-gene prediction model with good performance. The expression of CARD16 and MSGT1 was significantly increased in NMAP samples and positively correlated with neutrophil and mast cell infiltration. GSVA results showed that they are mainly upregulated in the T cell receptor complex, immunoglobulin complex circulating, and some immune-related routes. Single-cell analysis indicated that CARD16 was mainly distributed in mixed immune cells and macrophages, and MGST1 was mainly distributed in exocrine glandular cells. CONCLUSIONS: This study presents a novel approach to categorizing NMAP into different clusters based on LMRGs and developing a reliable two-gene biomarker for NMAP.

A Nucleotide Metabolism-Related Gene Signature for Risk Stratification and Prognosis Prediction in Hepatocellular Carcinoma Based on an Integrated Transcriptomics and Metabolomics Approach.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. The in-depth study of genes and metabolites related to nucleotide metabolism will provide new ideas for predicting the prognosis of HCC patients. This study integrated the transcriptome data of different cancer types to explore the characteristics and significance of nucleotide metabolism-related genes (NMGRs) in different cancer types. Then, we constructed a new HCC classifier and prognosis model based on HCC samples from TCGA and GEO, and detected the gene expression level in the model through molecular biology experiments. Finally, nucleotide metabolism-related products in serum of HCC patients were examined using untargeted metabolomics. A total of 97 NMRGs were obtained based on bioinformatics techniques. In addition, a clinical model that could accurately predict the prognostic outcome of HCC was constructed, which contained 11 NMRGs. The results of PCR experiments showed that the expression levels of these genes were basically consistent with the predicted trends. Meanwhile, the results of untargeted metabolomics also proved that there was a significant nucleotide metabolism disorder in the development of HCC. Our results provide a promising insight into nucleotide metabolism in HCC, as well as a tailored prognostic and chemotherapy sensitivity prediction tool for patients.

Oxidative stress and autophagy-mediated immune patterns and tumor microenvironment infiltration characterization in gastric cancer.

Recent years have seen a sharp rise in the amount of research on the connection between oxidative stress, autophagy, and cancer cells. However, the significant functions of oxidative stress and autophagy-related genes (OARGs) in gastric cancer (GC) are yet to be investigated integrally. Therefore, it will be a new and promising concept to search for novel OARG-related biomarkers to predict the prognosis and treatment response of GC. First, we assessed changes in prognosis and tumor microenvironment (TME) characteristics across the various oxidative stress and autophagy-related modification patterns based on a detailed analysis of 17 OARGs with prognostic significance of 808 GC samples. We identified three distinct OARG alteration patterns which displayed unique biological characteristics and immune cell infiltration features. Using principal component analysis methods, the OARGscore was developed to evaluate the OARG modification patterns of certain tumors. The negative connection between OARGscore and immune cells was statistically significant. Increased survival, a higher incidence of mutations, and a better response to immunotherapy were all predicted to be related to patients' high-OARGscore. In addition, the candidate chemotherapeutic drugs were predicted using the oncoPredict program. The low-OARGscore group was predicted to benefit more from Ribociclib, Alisertib, Niraparib, Epirubicin, Olaparib, and Axitinib, while patients in the high-OARGscore group were predicted to benefit more from Afatinib, Oxaliplatin, Paclitaxel, 5-Fluorouracil, Dabrafenib and Lapatinib. Our findings offer a specific method for predicting a patient's prognosis and susceptibility to immunotherapy, as well as a promising insight of oxidative stress and autophagy in GC.

A Case of Tuberculosis Cutis Orificialis.

This work reports a case of a 49-year-old male suffering from chronic tuberculosis who developed painful ulcers around the anus for approximately eight months. The colonoscopy revealed the presence of ulcers in the transverse colon, which were also found in the skin and intestine, as revealed by microscopic examination. The skin ulcer was positive for tuberculosis bacilli, leading to the final diagnosis of Tuberculosis cutis orificialis. The patient had a previous history of tuberculosis, which indicated that the infection in the lungs moved down to invade the intestines and finally the skin.

Molecular characteristics and therapeutic implications of Toll-like receptor signaling pathway in melanoma.

Melanoma is a malignant tumor of melanocytes and is often considered immunogenic cancer. Toll-like receptor-related genes are expressed differently in most types of cancer, depending on the immune microenvironment inside cancer, and the key function of Toll-like receptors (TLRs) for melanoma has not been fully elucidated. Based on multi-omics data from TCGA and GEO databases, we first performed pan-cancer analysis on TLR, including CNV, SNV, and mRNA changes in TLR-related genes in multiple human cancers, as well as patient prognosis characterization. Then, we divided melanoma patients into three subgroups (clusters 1, 2, and 3) according to the expression of the TLR pathway, and explored the correlation between TLR pathway and melanoma prognosis, immune infiltration, metabolic reprogramming, and oncogene expression characteristics. Finally, through univariate Cox regression analysis and LASSO algorithm, we selected six TLR-related genes to construct a survival prognostic model, divided melanoma patients into the training set, internal validation set 1, internal validation set 2, and external validation set for multiple validations, and discussed the correlation between model genes and clinical features of melanoma patients. In conclusion, we constructed a prognostic survival model based on TLR-related genes that precisely and independently demonstrated the potential to assess the prognosis and immune traits of melanoma patients, which is critical for patients' survival.

Clinical Observation and Analysis of Thyroglossal Duct Cyst Carcinoma: A Report of 5 Cases.

Thyroglossal duct cyst carcinoma (TGDCCa) is a rare condition with only approximately 300 cases reported to date. There is a lack of comprehensive reporting on its clinical manifestations, ultrasound, contrast-enhanced computed tomography, magnetic resonance imaging (MRI) features, immunophenotyping, procedure, and prognosis following modified Sistrunk's procedure. This study aimed to address these gaps by analyzing and summarizing the clinical features of 5 cases of papillary carcinoma arising in thyroglossal duct cysts (TGDC).Five patients with papillary carcinoma in TGDC treated by modified Sistrunk's procedure were included. Their clinical manifestation, physical examination findings, iconography, pathological findings, treatment, and outcomes were analyzed in aiding the diagnosis and treatment of TGDCCa. Immunohistochemistry was used to confirm the papillary carcinoma subtype. The BRAFV600E mutation was detected in 2 patients. No evidence of cancer recurrence, distant metastases, and malignant changes in the thyroid was found after a mean follow-up of 29.8 months.The management of TGDCCa with papillary carcinoma in low-risk patients can be accomplished by performing a modified Sistrunk's procedure along with a regular follow-up imaging of the thyroid and neck. Although postoperative pathological diagnosis is the gold standard for diagnosis, it is equally crucial to comprehend the clinical manifestations and auxiliary diagnostic techniques before surgical intervention.

Integrated multi-omics identified the novel intratumor microbiome-derived subtypes and signature to predict the outcome, tumor microenvironment heterogeneity, and immunotherapy response for pancreatic cancer patients.

Background: The extremely malignant tumour known as pancreatic cancer (PC) lacks efficient prognostic markers and treatment strategies. The microbiome is crucial to how cancer develops and responds to treatment. Our study was conducted in order to better understand how PC patients' microbiomes influence their outcome, tumour microenvironment, and responsiveness to immunotherapy. Methods: We integrated transcriptome and microbiome data of PC and used univariable Cox regression and Kaplan-Meier method for screening the prognostic microbes. Then intratumor microbiome-derived subtypes were identified using consensus clustering. We utilized LASSO and Cox regression to build the microbe-related model for predicting the prognosis of PC, and utilized eight algorithms to assess the immune microenvironment feature. The OncoPredict package was utilized to predict drug treatment response. We utilized qRT-PCR to verify gene expression and single-cell analysis to reveal the composition of PC tumour microenvironment. Results: We obtained a total of 26 prognostic genera in PC. And PC samples were divided into two microbiome-related subtypes: Mcluster A and B. Compared with Mcluster A, patients in Mcluster B had a worse prognosis and higher TNM stage and pathological grade. Immune analysis revealed that neutrophils, regulatory T cell, CD8+ T cell, macrophages M1 and M2, cancer associated fibroblasts, myeloid dendritic cell, and activated mast cell had remarkably higher infiltrated levels within the tumour microenvironment of Mcluster B. Patients in Mcluster A were more likely to benefit from CTLA-4 blockers and were highly sensitive to 5-fluorouracil, cisplatin, gemcitabine, irinotecan, oxaliplatin, and epirubicin. Moreover, we built a microbe-derived model to assess the outcome. The ROC curves showed that the microbe-related model has good predictive performance. The expression of LAMA3 and LIPH was markedly increased within pancreatic tumour tissues and was linked to advanced stage and poor prognosis. Single-cell analysis indicated that besides cancer cells, the tumour microenvironment of PC was also rich in monocytes/macrophages, endothelial cells, and fibroblasts. LIPH and LAMA3 exhibited relatively higher expression in cancer cells and neutrophils. Conclusion: The intratumor microbiome-derived subtypes and signature in PC were first established, and our study provided novel perspectives on PC prognostic indicators and treatment options.

Progress in biological and medical research in the deep underground: an update.

As the growing population of individuals residing or working in deep underground spaces for prolonged periods, it has become imperative to understand the influence of factors in the deep underground environment (DUGE) on living systems. Heping Xie has conceptualized the concept of deep underground medicine to identify factors in the DUGE that can have either detrimental or beneficial effects on human health. Over the past few years, an increasing number of studies have explored the molecular mechanisms that underlie the biological impacts of factors in the DUGE on model organisms and humans. Here, we present a summary of the present landscape of biological and medical research conducted in deep underground laboratories and propose promising avenues for future investigations in this field. Most research demonstrates that low background radiation can trigger a stress response and affect the growth, organelles, oxidative stress, defense capacity, and metabolism of cells. Studies show that residing and/or working in the DUGE has detrimental effects on human health. Employees working in deep mines suffer from intense discomfort caused by high temperature and humidity, which increase with depth, and experience fatigue and sleep disturbance. The negative impacts of the DUGE on human health may be induced by changes in the metabolism of specific amino acids; however, the cellular pathways remain to be elucidated. Biological and medical research must continue in deep underground laboratories and mines to guarantee the safe probing of uncharted depths as humans utilize the deep underground space.

Identification and immunological characterization of lipid metabolism-related molecular clusters in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now the major contributor to chronic liver disease. Disorders of lipid metabolism are a major element in the emergence of NAFLD. This research intended to explore lipid metabolism-related clusters in NAFLD and establish a prediction biomarker. METHODS: The expression mode of lipid metabolism-related genes (LMRGs) and immune characteristics in NAFLD were examined. The "ConsensusClusterPlus" package was utilized to investigate the lipid metabolism-related subgroup. The WGCNA was utilized to determine hub genes and perform functional enrichment analysis. After that, a model was constructed by machine learning techniques. To validate the predictive effectiveness, receiver operating characteristic curves, nomograms, decision curve analysis (DCA), and test sets were used. Lastly, gene set variation analysis (GSVA) was utilized to investigate the biological role of biomarkers in NAFLD. RESULTS: Dysregulated LMRGs and immunological responses were identified between NAFLD and normal samples. Two LMRG-related clusters were identified in NAFLD. Immune infiltration analysis revealed that C2 had much more immune infiltration. GSVA also showed that these two subtypes have distinctly different biological features. Thirty cluster-specific genes were identified by two WGCNAs. Functional enrichment analysis indicated that cluster-specific genes are primarily engaged in adipogenesis, signalling by interleukins, and the JAK-STAT signalling pathway. Comparing several models, the random forest model exhibited good discrimination performance. Importantly, the final five-gene random forest model showed excellent predictive power in two test sets. In addition, the nomogram and DCA confirmed the precision of the model for NAFLD prediction. GSVA revealed that model genes were down-regulated in several immune and inflammatory-related routes. This suggests that these genes may inhibit the progression of NAFLD by inhibiting these pathways. CONCLUSIONS: This research thoroughly emphasized the complex relationship between LMRGs and NAFLD and established a five-gene biomarker to evaluate the risk of the lipid metabolism phenotype and the pathologic results of NAFLD.

Subsecond periodic radio oscillations in a microquasar.

Powerful relativistic jets are one of the ubiquitous features of accreting black holes in all scales1-3. GRS 1915 + 105 is a well-known fast-spinning black-hole X-ray binary4 with a relativistic jet, termed a 'microquasar', as indicated by its superluminal motion of radio emission5,6. It has exhibited persistent X-ray activity over the last 30 years, with quasiperiodic oscillations of approximately 1-10 Hz (refs. 7-9) and 34 and 67 Hz in the X-ray band10. These oscillations probably originate in the inner accretion disk, but other origins have been considered11. Radio observations found variable light curves with quasiperiodic flares or oscillations with periods of approximately 20-50 min (refs. 12-14). Here we report two instances of approximately 5-Hz transient periodic oscillation features from the source detected in the 1.05- to 1.45-GHz radio band that occurred in January 2021 and June 2022. Circular polarization was also observed during the oscillation phase.

Identification of lipid metabolism-related biomarkers for diagnosis and molecular classification of atherosclerosis.

BACKGROUND: Atherosclerosis is now the main cause of cardiac-cerebral vascular diseases around the world. Disturbances in lipid metabolism have an essential role in the development and progression of atherosclerosis. Thus, we aimed to investigate lipid metabolism-related molecular clusters and develop a diagnostic model for atherosclerosis. METHODS: First, we used the GSE100927 and GSE43292 datasets to screen differentially expressed lipid metabolism-related genes (LMRGs). Subsequent enrichment analysis of these key genes was performed using the Metascape database. Using 101 atherosclerosis samples, we investigated the LMRG-based molecular clusters and the corresponding immune cell infiltration. After that, a diagnostic model for atherosclerosis was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Finally, a series of bioinformatics techniques, including CIBERSORT, gene set variation analysis, and single-cell data analysis, were used to analyze the potential mechanisms of the model genes in atherosclerosis. RESULTS: A total of 29 LMRGs were found to be differentially expressed between atherosclerosis and normal samples. Functional and DisGeNET enrichment analyses indicated that 29 LMRGs are primarily engaged in cholesterol and lipid metabolism, the PPAR signaling pathway, and regulation of the inflammatory response and are also closely associated with atherosclerotic lesions. Two LMRG-related molecular clusters with significant biological functional differences are defined in atherosclerosis. A three-gene diagnostic model containing ADCY7, SCD, and CD36 was subsequently constructed. Receiver operating characteristic curves, decision curves, and an external validation dataset showed that our model exhibits good predictive performance. In addition, three model genes were found to be closely associated with immune cell infiltration, especially macrophage infiltration. CONCLUSIONS: Our study comprehensively highlighted the intricate association between lipid metabolism and atherosclerosis and created a three-gene model for future clinical diagnosis.

PRMT1 inhibition promotes ferroptosis sensitivity via ACSL1 upregulation in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy with an alarming mortality rate. The development of novel therapeutic targets or drugs for AML is urgently needed. Ferroptosis is a form of regulated cell death driven by iron-dependent lipid peroxidation. Recently, ferroptosis has emerged as a novel method for targeting cancer, including AML. Epigenetic dysregulation is a hallmark of AML, and a growing body of evidence suggests that ferroptosis is subject to epigenetic regulation. Here, we identified protein arginine methyltransferase 1 (PRMT1) as a ferroptosis regulator in AML. The type I PRMT inhibitor GSK3368715 promoted ferroptosis sensitivity in vitro and in vivo. Moreover, PRMT1-knockout cells exhibited significantly increased sensitivity to ferroptosis, suggesting that PRMT1 is the primary target of GSK3368715 in AML. Mechanistically, both GSK3368715 and PRMT1 knockout upregulated acyl-CoA synthetase long-chain family member 1 (ACSL1), which acts as a ferroptosis promoter by increasing lipid peroxidation. Knockout ACSL1 reduced the ferroptosis sensitivity of AML cells following GSK3368715 treatment. Additionally, the GSK3368715 treatment reduced the abundance of H4R3me2a, the main histone methylation modification mediated by PRMT1, in both genome-wide and ACSL1 promoter regions. Overall, our results demonstrated a previously unknown role of the PRMT1/ACSL1 axis in ferroptosis and suggested the potential value and applications of the combination of PRMT1 inhibitor and ferroptosis inducers in AML treatment.

Synergistic Photon Management and Strain-Induced Band Gap Engineering of Two-Dimensional MoS2 Using Semimetal Composite Nanostructures.

2D MoS2 attracts increasing attention for its application in flexible electronics and photonic devices. For 2D material optoelectronic devices, the light absorption of the molecularly thin 2D absorber would be one of the key limiting factors in device efficiency, and conventional photon management techniques are not necessarily compatible with them. In this study, we show two semimetal composite nanostructures deposited on 2D MoS2 for synergistic photon management and strain-induced band gap engineering: (1) the pseudo-periodic Sn nanodots, (2) the conductive SnOx (x < 1) core-shell nanoneedle structures. Without sophisticated nanolithography, both nanostructures are self-assembled from physical vapor deposition. Optical absorption enhancement spans from the visible to the near-infrared regime. 2D MoS2 achieves >8× optical absorption enhancement at λ = 700-940 nm and 3-4× at λ = 500-660 nm under Sn nanodots, and 20-30× at λ = 700-900 nm under SnOx (x < 1) nanoneedles. The enhanced absorption in MoS2 results from strong near-field enhancement and reduced MoS2 band gap due to the tensile strain induced by the Sn nanostructures, as confirmed by Raman and photoluminescence spectroscopy. Especially, we demonstrate that up to 3.5% biaxial tensile strain is introduced to 2D MoS2 using conductive nanoneedle-structured SnOx (x < 1), which reduces the band gap by ∼0.35 eV to further enhance light absorption at longer wavelengths. To the best of our knowledge, this is the first demonstration of a synergistic triple-functional photon management, stressor, and conductive electrode layer on 2D MoS2. Such synergistic photon management and band gap engineering approach for extended spectral response can be further applied to other 2D materials for future 2D photonic devices.