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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019, which was found to be associated with a large seafood and animal market in Wuhan. Airway epithelial cells from infected patients were used to isolate a novel coronavirus, named the SARS-CoV-2, on January 12, 2020, which is the seventh member of the coronavirus family to infect humans. Phylogenetic analysis of full-length genome sequences obtained from infected patients showed that SARS-CoV-2 is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. The possible person-to-person disease rapidly spread to many provinces in China as well as other countries. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. In this review, we introduced current diagnostic methods and criteria for the SARS-CoV-2 in China and discuss the advantages and limitations of the current diagnostic methods, including chest imaging and laboratory detection.

N 6 -Methyladenosine (m6A), the most abundant internal modification associated with eukaryotic mRNAs, has emerged as a dynamic regulatory mechanism controlling the expression of genes involved in many physiological activities by affecting various steps of mRNA metabolism, including splicing, export, translation, and stability. Here, we review the general role of m6A, highlighting recent advances related to the three major types enzymes that determine the level of m6A modification (i.e., writers, erasers, and readers) and the regulatory mechanism by which m6A influences multiple stages of RNA metabolism. This review clarifies the close connection and interaction between m6A modification and nuclear gene expression, and provides key background information for further studies of its roles in numerous physiological and pathophysiological processes. Among them, perhaps the most eye-catching process is tumorigenesis. Clarifying the molecular mechanism of tumorigenesis, development and metastasis in various tissues of the human body is conducive to curbing out-of-control cell activities from the root and providing a new strategy for human beings to defeat tumors.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system was originally discovered in prokaryotes and functions as part of the adaptive immune system. The experimental research of many scholars, as well as scientific and technological advancements, has allowed prokaryote-derived CRISPR/Cas genome-editing systems to transform our ability to manipulate, detect, image, and annotate specific DNA and RNA sequences in the living cells of diverse species. Through modern genetic engineering editing technology and high-throughput gene sequencing, we can edit and splice covalently closed circular DNA to silence it, and correct the mutation and deletion of liver cancer genes to achieve precise in situ repair of defective genes and prohibit viral infection or replication. Such manipulations do not destroy the structure of the entire genome and facilitate the cure of diseases. In this review, we discussed the possibility that CRISPR/Cas could be used as a treatment for patients with liver cancer caused by hepatitis B virus infection, and reviewed the challenges incurred by this effective gene-editing technology.

To explore the diagnostic value of serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein assay in the early stages of SARS-COV-2 infection. Serum N protein level in SARS-COV-2 infected patients and non-SARS-COV-2 infected population was measured by enzyme-linked immunosorbent assay (ELISA) double antibody sandwich assay. Colloidal gold immunochromatography assay was used to detect serum N protein antibodies in the above populations. Fifty cases of SARS-CoV-2 nucleic acid-positive and SARS-CoV-2 antibody-negative patients had a serum N protein positivity rate of 76%. Thirty-seven patients who were positive for serum SARS-CoV-2 antibody after infection had a serum SARS-CoV-2 N protein positivity rate of 2.7%. Serum N protein test results of 633 non-SARS-COV-2 infected patients, including pregnant women, patients with other respiratory infections, and individuals with increased rheumatoid factor were all negative, with serum N protein concentration <10.00 pg/mL at 100% specificity. Using SPSS 19.0 to calculate the receiver operating characteristic curve, the area under the curve was determined to be 0.9756 (95% confidence interval 0.9485-1.000, < 0.0001), and sensitivity and specificity were 92% (95% confidence interval 81.16-96.85%) and 96.84% (95% confidence interval 95.17-97.15%), respectively. The best CUT-OFF value was 1.850 pg/mL. The measurement of serum SARS-COV-2 N protein has a high diagnostic value for infected patients before the antibody appears and shortens the window period of serological diagnosis. It is recommended that the manufacturer establish two different CUT-OFF values according to the purpose of the application. One CUT-OFF value is used for the diagnosis of clinical SARS-COV-2 infection, and the other is used to screen out as many suspected cases as possible.

Background m6A is the most prevalent and abundant form of mRNA modifications and is closely related to tumor proliferation, differentiation, and tumorigenesis. In this study, we try to conduct an effective prediction model to investigated the function of m6A RNA methylation modulators in pancreatic adenocarcinoma and estimated the potential association between m6A RNA methylation modulators and tumor microenvironment infiltration for optimization of treatment. Methods Expression of 28 m6A RNA methylation modulators and clinical data of patients with pancreatic adenocarcinoma and normal samples were obtained from TCGA and GTEx database. Differences in the expression of 28 m6A RNA methylation modulators between tumour ( n  = 40) and healthy ( n  = 167) samples were compared by Wilcoxon test. LASSO Cox regression was used to select m6A RNA methylation modulators to analyze the relationship between expression and clinical characteristics by univariate and multivariate regression. A risk score prognosis model was conducted based on the expression of select m6A RNA methylation modulators. Bioinformatics analysis was used to explore the association between the m6Ascore and the composition of infiltrating immune cells between high and low m6Ascore group by CIBERSORT algorithm. Evaluation of m6Ascore for immunotherapy was analyzed via the IPS and three immunotherapy cohort. Besides, the biological signaling pathways of the m6A RNA methylation modulators were examined by gene set enrichment analysis (GSEA). Results Expression of 28 m6A RNA methylation modulators were upregulated in patients with PAAD except for MTEEL3. An m6Ascore prognosis model was established, including KIAA1429, IGF2BP2, IGF2BP3, METTL3, EIF3H and LRPPRC was used to predict the prognosis of patients with PAAD, the high risk score was an independent prognostic indicator for pancreatic adenocarcinoma, and a high risk score presented a lower overall survival. In addition, m6Ascore was related with the immune cell infiltration of PAAD. Patients with a high m6Ascore had lower infiltration of Tregs and CD8 + T cells but a higher resting CD4 + T infiltration. Patients with a low m6Ascore displayed a low abundance of PD-1, CTLA-4 and TIGIT , however, the IPS showed no difference between the two groups. The m6Ascore applied in three immunotherapy cohort (GSE78220, TCGA-SKCM, and IMvigor210) did not exhibit a good prediction for estimating the patients’ response to immunotherapy, so it may need more researches to figure out whether the m6A modulator prognosis model would benefit the prediction of pancreatic patients’ response to immunotherapy. Conclusion Modulators involved in m6A RNA methylation were associated with the development of pancreatic cancer. An m6Ascore based on the expression of IGF2BP2, IGF2BP3, KIAA1429, METTL3, EIF3H and LRPPRC is proposed as an indicator of TME status and is instrumental in predicting the prognosis of pancreatic cancer patients.

This study compared the laboratory indexes in 40 non-severe COVID-19 patients with those in 57 healthy controls. In the peripheral blood system of non-severe symptom COVID-19 patients, lymphocytes, eosinophils, basophils, total procollagen type 1 amino-terminal propeptide, osteocalcin N-terminal, thyroid-stimulating hormone, growth hormone, and insulin-like growth factor–binding protein 3 significantly decreased, and total protein, albumin, alanine transaminase, alkaline phosphatase, γ-glutamyl transferase, activated partial thromboplastin time, prothrombin time, fibrinogen, D-dimer, fibrinogen degradation products, human epididymal protein 4, serum ferritin, and C-reactive protein were elevated. SARS-CoV-2 infection can affect hematopoiesis, hemostasis, coagulation, fibrinolysis, bone metabolism, thyroid, parathyroid glands, the liver, and the reproductive system.

Background Triple negative breast cancer (TNBC) is a heterogeneous and aggressive disease characterized by a high risk of mortality and poor prognosis. It has been reported that Laminin γ2 (LAMC2) is highly expressed in a variety of tumors, and its high expression is correlated with cancer development and progression. However, the function and mechanism by which LAMC2 influences TNBC remain unclear. Methods Kaplan–Meier survival analysis and Immunohistochemical (IHC) staining were used to examine the expression level of LAMC2 in TNBC. Subsequently, cell viability assay, wound healing and transwell assay were performed to detect the function of LAMC2 in cell proliferation and migration. A xenograft mouse model was used to assess tumorigenic function of LAMC2 in vivo . Luciferase reporter assay and western blot were performed to unravel the underlying mechanism. Results In this study, we found that higher expression of LAMC2 significantly correlated with poor survival in the TNBC cohort. Functional characterization showed that LAMC2 promoted cell proliferation and migration capacity of TNBC cell lines via up-regulating CD44. Moreover, LAMC2 exerted oncogenic roles in TNBC through modulating the expression of epithelial-mesenchymal transition (EMT) markers. Luciferase reporter assay verified that LAMC2 targeted ZEB1 to promote its transcription. Interestingly, LAMC2 regulated cell migration in TNBC via STAT3 signaling pathway. Conclusion LAMC2 targeted ZEB1 via activating CD44/STAT3 signaling pathway to promote TNBC proliferation and migration, suggesting that LAMC2 could be a potential therapeutic target in TNBC patients.

Background Triple negative breast cancer (TNBC), characterized by its aggressive clinical behavior and propensity for distant metastasis, presents critical challenges in therapeutic management. Emerging evidence implicates lipid metabolic reprogramming as a key facilitator of tumor progression and metastatic dissemination. However, the precise molecular mechanisms underlying lipid metabolic dysregulation in TNBC metastasis remain poorly characterized. Our work systematically elucidates the mechanistic role of ALDH3A2 in orchestrating lipid metabolic adaptations that drive breast cancer metastasis. Methods Transcriptomic analysis of clinical datasets identified metastasis-related metabolic regulators. Cellular migration/invasion assays and murine metastasis models were utilized to assess metastatic effects of ALDH3A2. Lipidomic profiling coupled with pathway analysis characterized metabolic alterations. Mechanistic studies integrated western blot analysis with lipid droplet quantification. Computational approaches including structure-based virtual screening and molecular docking simulations were employed for inhibitor discovery. Results ALDH3A2 was significantly upregulated in TNBC clinical specimens and showed significant association with adverse clinical outcomes. Functional validation confirmed that ALDH3A2 potentiates TNBC cell migration/invasion through epithelial-mesenchymal transition (EMT) activation. Metabolic profiling revealed ALDH3A2-driven lipid accumulation, evidenced by increased lipid droplet formation and elevated triglyceride levels. Specifically, arachidonic acid (AA) enrichment was observed in ALDH3A2-overexpressing cells, corresponding to enhanced glycerophospholipid metabolism. Mechanistic studies demonstrated that ALDH3A2-mediated AMP/ATP imbalance suppresses AMPK phosphorylation while activating mTOR/SREBP1 signaling. mTOR inhibition effectively attenuated ALDH3A2-induced lipid metabolic alterations. Importantly, oxaliplatin was identified as a potential therapeutic agent targeting ALDH3A2-mediated AA metabolism to suppress metastasis. Conclusions Our work establishes ALDH3A2 as a pivotal regulator of lipid metabolic reprogramming in TNBC metastasis, providing mechanistic insights into AA-mediated tumor progression. These findings position ALDH3A2 as a promising therapeutic target and prognostic biomarker for TNBC management.

Severe fever with thrombocytopenia syndrome (SFTS), a widely prevalent infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV) that carries with it a high mortality rate, has emerged to be a public health concern. This study aimed to investigate the epidemiological and clinical characteristics of patients infected with SFTSV, seeking novel prognostic risk factors for SFTS. In this retrospective and cross-sectional study, confirmed SFTS patients from the First Affiliated Hospital of Anhui Medical University were enrolled from September 1, 2019, to December 12, 2020. Cases were analyzed for epidemiological, demographic, clinical, and laboratory data. Logistic regression models were used to assess the association between predictors and outcome variables. A generalized additive mixed model (GAMM) was conducted to analyze the trending shift of aspartate aminotransferase/alanine transaminase-ratio (AST/ALT-ratio) and platelet (PLT) in SFTS patients treated with ribavirin. p values ≤ 0.05 were considered statistically significant. Clinical and laboratory results of 107 hospitalized patients with SFTSV infection were retrospectively described. The mean age at onset of disease was 60.38 ± 11.29 years old and the ratio between male and female was 1:1.2. Fever and thrombocytopenia are hallmark features of SFTS. Furthermore, multiple cases also experienced neurological complications, gastrointestinal/skeletal muscle symptoms together with other non-specific clinical manifestations; laboratory dataset outcomes reported dysregulated levels for routine blood biomarkers, coagulation function, and biochemistry. Overall, 107 patients were segregated into two groups according to patient condition at the clinical endpoint (survivors/non-survivors). SFTS survivors had a higher level of PLT- counts, total protein (TP), and estimated glomerular filtration rate (eGFR), while levels of activated partial thromboplastin time (APTT), thrombin time (TT), D-dimer (D-D), fibrinogen degradation products (FDP), ALT, AST, AST/ALT-ratio, creatinine (Cr), creatine phosphokinase (CK) and procalcitonin (PCT) was higher in non-survivors. Results from univariate Cox regression revealed that elevated levels of FDP, TT, AST/ALT-ratio, PCT, as well as decreased eGFR level and presence of central nervous system symptoms (CNS), were significant predictors for SFTS prognostic, results from multivariate logistic regression analysis in three adjusted models showed AST/ALT-ratio and PCT were independent risk factors for the prognosis of SFTS patients. Kaplan-Meier survival analysis showed that SFTS patients with AST/ALT-ratio >2.683 were associated with a shorter futime (means survival time), therefore indicating an unfavorable prognosis. Treatment with ribavirin could increase PLT count while decreasing AST/ALT-ratio within SFTS patients. SFTS is an emerging infectious disease, possibly leading to multiple-organ injury; AST/ALT-ratio was an independent risk factor for the prognosis of SFTS patients. Further investigation should be performed in order to gain more knowledge on this disease and guide clinical management.

Approximately 5–10% of all cancer types are hereditary cancer syndromes, which are caused by pathogenic mutations in cancer susceptibility genes. In this investigation, a hereditary cancer pedigree was collected from a province in southern China, and the proband was a 31-year-old woman with breast cancer. Utilizing blood whole exome sequencing technology and bioinformatics analysis, the sole heterozygous missense mutation in PIBF1 that exhibits trait segregation was identified: PIBF1 (p.R405Q). The pedigree also included two other mutations that may be linked to carcinogenesis: RAD51D (p.K91Ifs*13) and BRCA2 (p.G3134Afs*29). This research concentrated on PIBF1 (p.R405Q) and employed breast cancer as a tumor model. In vitro and in vivo experiments showed that PIBF1-WT suppressed breast cancer cell proliferation, colony formation, invasive ability, and tumorigenesis. However, PIBF1 (p.R405Q) attenuated or inhibited the function of PIBF1-WT. Mechanistically, PIBF1-WT resisted cisplatin-induced DNA damage, significantly down-regulated the expression of γ-H2AX, and affected DNA damage repair, thus exerting a cancer inhibitory function. Interestingly, PIBF1 (p.R405Q) affects protein stability, thereby mitigating or eliminating the inhibitory effect of PIBF1. Furthermore, this family’s polygenic risk factors for cancer are analyzed, and there is speculation about potential synergistic effects between PIBF1 and DNA damage repair genes like BRCA2 and RAD51D. In conclusion, PIBF1 regulates the cell cycle and DNA damage repair, PIBF1(p.R405Q) increases susceptibility to cancer, multiple DNA damage repair gene mutations may synergistically promote cancer progression in this cancer family lineage, and PIBF1(p.R405Q) may be one of the polygenic risk factors for familial hereditary cancer syndromes.