Current Progress of Ferroptosis Study in Hepatocellular Carcinoma.

Ferroptosis, an emerging type of programmed cell death, is initiated by iron-dependent and excessive ROS-mediated lipid peroxidation, which eventually leads to plasma membrane rupture and cell death. Many canonical signalling pathways and biological processes are involved in ferroptosis. Furthermore, cancer cells are more susceptible to ferroptosis due to the high load of ROS and unique metabolic characteristics, including iron requirements. Recent investigations have revealed that ferroptosis plays a crucial role in the progression of tumours, especially HCC. Specifically, the induction of ferroptosis can not only inhibit the growth of hepatoma cells, thereby reversing tumorigenesis, but also improves the efficacy of immunotherapy and enhances the antitumour immune response. Therefore, triggering ferroptosis has become a new therapeutic strategy for cancer therapy. In this review, we summarize the characteristics of ferroptosis based on its underlying mechanism and role in HCC and provide possible therapeutic applications.

Extracellular matrix marker LAMC2 targets ZEB1 to promote TNBC malignancy via up-regulating CD44/STAT3 signaling pathway.

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.

Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N-terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild-type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper-activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.

Notch signaling and targeted therapy in non-small cell lung cancer.

The Notch signaling pathway plays pivotal roles in cell proliferation, stemness and invasion of non-small cell lung cancer (NSCLC). The human Notch family consists of four receptors, namely Notch1, Notch2, Notch3, and Notch4. These receptors are transmembrane proteins that play crucial roles in various cellular processes. Notch1 mostly acts as a pro-carcinogenic factor in NSCLC but sometimes acts as a suppressor. Notch2 has been demonstrated to inhibit the growth and progression of NSCLC, whereas Notch3 facilitates these biological behaviors of NSCLC. The role of Notch4 in NSCLC has not been fully elucidated, but it is evident that Notch4 promotes tumor progression. At present, drugs targeting the Notch pathway are being explored for NSCLC therapy, a majority of which are already in the stage of preclinical research and clinical trials, with bright prospects in the clinical treatment of NSCLC.

Characterization of a germline variant TNS1 c.2999-1G > C in a hereditary cancer syndrome family.

Hereditary cancer syndromes result from the presence of inherited pathogenic variants within susceptibility genes. However, the susceptibility genes associated with hereditary cancer syndrome remain predominantly unidentified. Here, we reported a case of hereditary cancer syndrome observed in a Chinese family harboring a germline mutation in Tensin1 (TNS1). We described a 59-year-old female patient presented with Multiple myeloma and Thyroid carcinoma. The proband and her family members exhibited suspected tumor syndrome due to occurrences of other cancer cases. After oncogenetic counseling, whole-exome sequencing and Sanger sequencing were conducted and a primary driver mutation of TNS1 (NM_022648.7:c.2999-1G > C) was detected. Gene Expression Profiling Interactive Analysis revealed that TNS1 was expressed lower in different tumors when compared to normal, including Pancreatic adenocarcinoma, Breast invasive carcinoma, Thyroid carcinoma andColon adenocarcinoma cells. Despite the well-established role of TNS1 as a tumor suppressor in breast cancer and colorectal cancer, its potential utility as a marker gene for diagnosis and treatment of pancreatic cancer remains uncertain. Here, our data demonstrated that knockdown of TNS1 could promote cell proliferation and migration in Pancreatic adenocarcinoma (PDAC) cells. In addition, TNS1 regulated migration through EMT signaling pathway in PDAC cells. Our findings proposed that this variant was likely involved in cancer predisposition by disrupting the normal splicing process. In summary, we presented a genetic disease by linking an intronic mutation inTNS1. We aim to provide early detection of cancers by identifying germline variants in susceptibility genes.

Therapeutic potential of anti-PIK3CG treatment for multiple myeloma via inhibiting c-Myc pathway.

Multiple myeloma (MM) is a malignant plasma cell disease. The activity of PIK3CG (PI3K catalytic subunit γ) is regulated directly by G-protein-coupled receptor and has been confirmed to be highly expressed in MM cells. This study aimed to determine the effect of pharmacological inhibition of PIK3CG on MM. We found that different concentrations of the PIK3CG inhibitor AS-605240 could suppress the growth of MM cell lines and the expression of c-Myc. The combination of PIK3CG inhibitor and the chemotherapy Melphalan could effectively inhibit the proliferation and migration of MM cells, promote the cell apoptosis, and decrease the ratio of Bcl-2/Bax and the expression of vimentin. The expression of proto-oncogene c-Myc was decreased and the sensitivity of cells to chemotherapeutic drugs was enhanced. Collectively, PIK3CG regulates growth of MM via c-Myc pathway, thus emerging as a promising molecular targeted therapy.

STAT5a and SH2B3 novel mutations display malignancy roles in a triple-negative primary myelofibrosis patient.

Primary myelofibrosis (PMF) patients frequently have JAK2 (V617F), CALR (exon 9), or MPL (W515 or exon 10) strong driver gene mutation, which triggers abnormal activation of the JAK2-STATs signaling pathway that plays a complex role in the occurrence of PMF. However, about 10-15% of PMF patients have no above typical mutations in these strong driver genes, known as being "triple-negative", which are associated with poor prognosis. In this paper, we reported a unique secondary acute myeloid leukemia (sAML) case transformed from triple-negative PMF combined with lung cancer and erythroderma occurrence at the same time, which has not been reported so far. Through whole blood exome sequencing, four novel noncanonical mutations were detected in key regulatory genes SH2B3 (Q748 and S710) and STAT5a (C350 and K354). Meanwhile, STAT5a-S710 and SH2B3-K354 noncanonical mutations gained strong malignant biofunction on promoting cell growth and tumorigenesis by accelerating the G1/S transition. In the mechanistic study, these pernicious phenotypes driven by noncanonical mutations might be initial PMF by activating p-STAT5a/c-Myc/CyclinD1 and p-STAT3/p-AKT/p-ERK1/2 signaling axes. Therefore, our study explored the deleterious roles of novel noncanonical mutations in STAT5a and SH2B3, which may serve as susceptibility genes and display the oncogenic biofunction in the progression of PMF to acute myeloid leukemia-M2a (AML-M2a).

Toxic effects of organophosphate pesticide monocrotophos in aquatic organisms: A review of challenges, regulations and future perspectives.

In recent times, usage of pesticide, herbicides and synthetic fertilizers in farming lands has made the environment worse. The pesticide residues and toxic byproducts from agricultural lands were found to contaminate the aquatic ecosystem. The misuse of synthetic pesticide not only affects the environment, but also affects the health status of aquatic organisms. The organophosphate pesticide pollutants are emerging contaminants, which threatens the terrestrial and aquatic ecosystem. Monocrotophos (MCP) is an organophosphate insecticide, utilized on crops including rice, maize, sugarcane, cotton, soybeans, groundnuts and vegetables. MCP is hydrophilic in nature and their solubilizing properties reduce the soil sorption which leads to groundwater contamination. The half-life period of MCP is 17-96 and the half-life period of technical grade MCP is 2500 days if held stable at 38 °C in a container. MCP causes mild to severe confusion, anxiety, hyper-salivation, convulsion and respiratory distress in mammals as well as aquatic animals. The MCP induced toxicity including survival rate, behavioural changes, reproductive toxicity and genotoxicity in different aquatic species have been discussed in this review. Furthermore, the ultimate aim of this review is to highlight the international regulations, future perspectives and challenges involved in using the MCP.

Deubiquitinase OTUD3: a double-edged sword in immunity and disease.

Deubiquitination is an important form of post-translational modification that regulates protein homeostasis. Ovarian tumor domain-containing proteins (OTUDs) subfamily member OTUD3 was identified as a deubiquitinating enzyme involved in the regulation of various physiological processes such as immunity and inflammation. Disturbances in these physiological processes trigger diseases in humans and animals, such as cancer, neurodegenerative diseases, diabetes, mastitis, etc. OTUD3 is aberrantly expressed in tumors and is a double-edged sword, exerting tumor-promoting or anti-tumor effects in different types of tumors affecting cancer cell proliferation, metastasis, and metabolism. OTUD3 is regulated at the transcriptional level by a number of MicroRNAs, such as miR-520h, miR-32, and miR101-3p. In addition, OTUD3 is regulated by a number of post-translational modifications, such as acetylation and ubiquitination. Therefore, understanding the regulatory mechanisms of OTUD3 expression can help provide insight into its function in human immunity and disease, offering the possibility of its use as a therapeutic target to diagnose or treat disease.

Changes in nitrogen metabolism of phosphorus-starved bloom-forming cyanobacterium Microcystis aeruginosa: Implications for nutrient management.

The surplus of nitrogen plays a key role in the maintenance of cyanobacterial bloom when phosphorus has already been limited. However, the interplay between high nitrogen and low phosphorus conditions is not fully understood. Nitrogen metabolism is critical for the metabolism of cyanobacteria. Transcriptomic analysis in the present study suggested that nitrogen metabolism and ribosome biogenesis were the two most significantly changed pathways in long-term phosphorus-starved bloom-forming cyanobacteria Microcystis aeruginosa FACHB-905. Notably, the primary glutamine synthetase/glutamate synthase cycle, crucial for nitrogen metabolism, was significantly downregulated. Concurrently, nitrogen uptake showed a marked decrease due to reduced expression of nitrogen source transporters. The content of intracellular nitrogen reservoir phycocyanin also showed a drastic decrease upon phosphorus starvation. Our study demonstrated that long-term phosphorus-starved cells also suffered from nitrogen deficiency because of the reduction in nitrogen assimilation, which might be limited by the reduced ribosome biogenesis and the shortage of adenosine triphosphate. External nitrogen supply will not change the transcriptions of nitrogen metabolism-related genes significantly like that under phosphorus-rich conditions, but still help to maintain the survival of phosphorus-starved cells. The study deepens our understanding about the survival strategies of Microcystis cells under phosphorus starvation and the mutual dependence between nitrogen and phosphorus, which would provide valuable information for nutrient management in the eutrophicated water body.

A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome.

Screening tumor susceptibility genes helps in identifying powerful biomarkers for hereditary cancer monitoring, prevention, and diagnosis, providing opportunities for understanding potential molecular mechanisms and biomarkers for the precise treatment of hereditary cancer syndromes. Whole-exome sequencing of blood and bioinformatics analysis uncovered a novel RBBP8(p.E281*) germline mutation in a family with hereditary cancer syndrome, which was verified by Sanger sequencing. Cell proliferation, colony formation, cell migration, and in vivo tumorigenesis were investigated by CCK8, colony formation, Transwell, and in vivo xenograft assays. Protein localization and interaction were detected by immunofluorescence, nuclear and cytoplasmic protein extraction kits, and Co-IP. A new heterozygous germline mutation of the RBBP8(p.E281*) gene was found to be associated with familial hereditary cancer syndrome. RBBP8-WT was mainly detected in the nucleus and interacts with BRCA1. In contrast, RBBP8(p.E281*) is mainly located in the cytoplasm, with no interaction with BRCA1. RBBP8(p.E281*) variant plays an oncogenic role in the cytoplasm in addition to its loss of function in the nucleus, which promotes breast cancer proliferation, in vivo tumorigenesis, and migration. Compared with the control group, RBBP8(p.E281*) showed elevated cell death in response to cisplatin and olaparib treatment. A novel RBBP8(p.E281*) germline mutation was identified from familial hereditary cancer syndrome. RBBP8(p.E281*) is not able to enter the nucleus or interact with BRCA1 through the lost binding motif, and RBBP8(p.E281*) variant appears to promote tumorigenesis in the cytoplasm in addition to its loss of function in the nucleus. RBBP8(p.E281*) variant may promote tumor susceptibility and serve as a precision medicine biomarker in familial hereditary cancer syndrome. KEY MESSAGES: RBBP8(p.E281*) is a susceptibility gene in this familial hereditary cancer syndrome RBBP8(p.E281*) lost its ability to enter the nucleus and the BRCA1 binding motif A novel RBBP8(p.E281*) germline mutation promotes breast cancer tumorigenesis Patients with RBBP8(p.E281*) germline mutation may benefit from Olaparib, Cisplatin.

Chitin, chitosan and chitooligosaccharides as potential growth promoters and immunostimulants in aquaculture: A comprehensive review.

There is a stable growth in aquaculture production to avoid seafood scarcity. The usage of eco-friendly feed additives is not only associated with aquatic animal health but also reduces the risk of deleterious effects to the environment and consumers. Aquaculture researchers are seeking dietary solutions to improve the growth performance and yield of target organisms. A wide range of naturally derived compounds such as probiotics, prebiotics, synbiotics, complex carbohydrates, nutritional factors, herbs, hormones, vitamins, and cytokines was utilized as immunostimulants in aquaculture. The use of polysaccharides derived from natural resources, such as alginate, agar, laminarin, carrageenan, fucoidan, chitin, and chitosan, as supplementary feed in aquaculture species has been reported. Polysaccharides are prebiotic substances which are enhancing the immunity, disease resistance and growth of aquatic animals. Further, chitin (CT), chitosan (CTS) and chitooligosaccharides (COS) were recognized for their biodegradable properties and unique biological functions. The dietary effects of CT, CTS and COS at different inclusion levels on growth performance, immune response and gut microbiota in aquaculture species has been reviewed. The safety regulations, challenges and future outlooks of CT, CTS and COS in aquatic animals have been discussed in this review.

The role of zinc finger proteins in malignant tumors.

Zinc finger proteins (ZNFs) are the largest family of transcriptional factors in mammalian cells. Recently, their role in the development, progression, and metastasis of malignant tumors via regulating gene transcription and translation processes has become evident. Besides, their possible involvement in drug resistance has also been found, indicating that ZNFs have the potential to become new biological markers and therapeutic targets. In this review, we summarize the oncogenic and suppressive roles of various ZNFs in malignant tumors, including lung, breast, liver, gastric, colorectal, pancreatic, and other cancers, highlighting their role as prognostic markers, and hopefully provide new ideas for the treatment of malignant tumors in the future.

Recombinant production, purification, and biochemical characterization of a novel L-lactate dehydrogenase from Bacillus cereus NRC1 and inhibition study of mangiferin.

Lactate dehydrogenase (LDH, EC 1.1.1.27) is one of the vital glycolytic conditions, especially during anaerobic conditions. It is a significant diagnostic, prognostic, and monitoring biomarker parameter. A 950-bp DNA fragment containing the gene (LDH) encoding LDH was amplified from Bacillus cereus NRC1. The deduced amino acid sequence reveals that B. cereus LDH (Bc-LDH) is highly homologous to the LDHs of Bacillus organisms. All LDH enzymes have a significant degree of conservation in their active site and several additional domains with unidentified functions. The gene for LDH, which catalyzes lactate synthesis, was cloned, sequenced (accession number: LC706200.1), and expressed in Escherichia coli BL21 (DE3). In this investigation, Bc-LDH was purified to homogeneity with a specific activity of 22.7 units/mg protein and a molecular weight of 35 kDa. It works optimally at pH 8.0. The purified enzyme was inhibited by FeCl2, CuCl2, ZnCl2, and NiCl, whereas CoCl2 was found to boost the activity of Bc-LDH. The molecular docking of the 3D model of the Bc-LDH structure with a natural inhibitor, mangiferin, demonstrated excellent LDH inhibition, with a free binding energy of -10.2 kcal/mol. Moreover, mangiferin is a potent Bc-LDH inhibitor that inhibits Bc-LDH competitively and has one binding site with a Ki value of 0.075 mM. The LDH-mangiferin interaction exhibits a low RMSF value (>1.5 Å), indicating a stable contact at the residues. This study will pave the way for more studies to improve the understanding of mangiferin, which could be considered an intriguing candidate for creating novel and improved LDH inhibitors.

The role of amino acid metabolism alterations in pancreatic cancer: From mechanism to application.

The incidence of pancreatic cancer is increasing in both developed and developing Nations. In recent years, various research evidence suggested that reprogrammed metabolism may play a key role in pancreatic cancer tumorigenesis and development. Therefore, it has great potential as a diagnostic, prognostic and therapeutic target. Amino acid metabolism is deregulated in pancreatic cancer, and changes in amino acid metabolism can affect cancer cell status, systemic metabolism in malignant tumor patients and mistakenly involved in different biological processes including stemness, proliferation and growth, invasion and migration, redox state maintenance, autophagy, apoptosis and even tumor microenvironment interaction. Generally, the above effects are achieved through two pathways, energy metabolism and signal transduction. This review aims to highlight the current research progress on the abnormal alterations of amino acids metabolism in pancreatic cancer, how they affect tumorigenesis and development of pancreatic cancer and the application prospects of them as diagnostic, prognostic and therapeutic targets.

Upregulated GATA3/miR205-5p Axis Inhibits MFNG Transcription and Reduces the Malignancy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast carcinomas and has the worst prognosis of all breast cancer subtypes due to the lack of an effective target. Therefore, understanding the molecular mechanism underpinning TNBC progression could explore a new target for therapy. While the Notch pathway is critical in the development process, its dysregulation leads to TNBC initiation. Previously, we found that manic fringe (MFNG) activates the Notch signaling and induces breast cancer progression. However, the underlying molecular mechanism of MFNG upstream remains unknown. In this study, we explore the regulatory mechanisms of MFNG in TNBC. We show that the increased expression of MFNG in TNBC is associated with poor clinical prognosis and significantly promotes cell growth and migration, as well as Notch signaling activation. The mechanistic studies reveal that MFNG is a direct target of GATA3 and miR205-5p and demonstrate that GATA3 and miR205-5p overexpression attenuate MFNG oncogenic effects, while GATA3 knockdown mimics MFNG phenotype to promote TNBC progression. Moreover, we illustrate that GATA3 is required for miR205-5p activation to inhibit MFNG transcription by binding to the 3' UTR region of its mRNA, which forms the GATA3/miR205-5p/MFNG feed-forward loop. Additionally, our in vivo data show that the miR205-5p mimic combined with polyetherimide-black phosphorus (PEI-BP) nanoparticle remarkably inhibits the growth of TNBC-derived tumors which lack GATA3 expression. Collectively, our study uncovers a novel GATA3/miR205-5p/MFNG feed-forward loop as a pathway that could be a potential therapeutic target for TNBC.

Fringe family genes and their modulation of Notch signaling in cancer.

Fringes are glycosyltransferases that transfer N-acetylglucosamine to the O-linked fucose of Notch receptors. They regulate the Notch signaling activity that drives tumor formation and progression, resulting in poor prognosis. However, the specific tumor-promoting role of Fringes differs depending on the type of cancer. Although a particular Fringe member could act as a tumor suppressor in one cancer type, it may act as an oncogene in another. This review discusses the tumorigenic role of the Fringe family (lunatic fringe, manic fringe, and radical fringe) in modulating Notch signaling in various cancers. Although the crucial functions of Fringes continue to emerge as more mechanistic studies are being pursued, further translational research is needed to explore their roles and therapeutic benefits in various malignancies.

MicroRNA-146a promotes proliferation, migration, and invasion of HepG2 via regulating FLAP.

Abnormal expression of 5-Lipoxygenase Activating Protein (FLAP) has been detected in many tumor cells. MicroRNAs (miRNAs) negatively regulate gene expression post-transcriptionally by binding to the 3'-untranslated region (3'-UTR) of the target mRNA sequences and have been shown to be involved in various types of cancers. Herein, we aimed to demonstrate the expression of miR-146a and FLAP in human HCC tissues and liver cancer cell lines. We demonstrated that miR-146a expression is overexpressed, while FLAP protein and mRNA are suppressed in hepatocellular carcinoma tissues and HepG2 cells compared to para-carcinoma tissues and HL-7702 cells. Dual luciferase reporter gene assay showed that miR-146a-5p can directly target FLAP mRNA. Knockdown of miR-146a also resulted in increased FLAP expression of cancer cells. Additionally, miR-146a silencing or restoration of FLAP led to a reduction of HepG2 cell proliferation, cell cycle progression, migration, and invasion. This study showed that miR-146a has a stimulatory role in HepG2 cells and promotes HepG2 cell migration and invasion by targeting FLAP mRNA. Thus, miR-146a may be a tumor promoter and a potential therapeutic target for the treatment of HCC patients.

The AST/ALT Ratio (De Ritis Ratio) Represents an Unfavorable Prognosis in Patients in Early-Stage SFTS: An Observational Cohort Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Dynamic regulation and functions of mRNA m6A modification.

N6-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.