Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To observe the effects of pegylated losenatide injection combined with metformin tablets on serum metabolism,lipid levels and intestinal flora in obese type 2 diabetes mellitus(T2DM)patients after axial gastrectomy.Methods Obese T2DM patients who underwent axial gastrectomy were divided into treatment group and control group by cohort methods.The control group was treated with metformin hydrochloride tablet 0.5 g orally,tid.The treatment group was treated by subcutaneous injection of pegylated losenatide injection 0.2 mg once a week on the basis of control group.Both groups were treated continuously for 3 months.Body mass index(BMI),serum metabolic indexes,blood lipid levels,blood glucose levels,intestinal flora and adverse drug reactions were compared between the two groups.Results In this study,a total of 70 subjects were included in the treatment group,and 50 subjects were included in the control group.After three months of treatment,the BMI indices of the treatment and control groups were(26.35±2.36)and(29.34±3.59)kg·m-2,respectively;the glutathione peroxidase levels were(192.42±13.18)and(134.27±12.86)U;interleukin-6 levels were(6.14±1.78)and(7.65±2.09)μg·L-1;fasting blood glucose levels were(5.36±0.41)and(7.43±0.78)mmol·L-1;total cholesterol levels were(2.55±0.67)and(3.47±0.79)mmol·L-1 for the treatment and control groups,respectively.The levels of Bifidobacteria,Bacteroides,Lactobacilli,Enterobacteria,and Enterococci in the treatment group were(8.79±1.36),(9.62±1.37),(6.74±2.15),(7.98±0.61),and(7.23±1.29)logN·g-1,respectively;in the control group,these levels were(7.98±1.79),(8.13±1.45),(5.71±2.41),(9.21±0.88),and(8.15±1.54)logN·g-1.The differences in the above indicators between the treatment and control groups were statistically significant(all P＜0.05).The main adverse drug reactions in the treatment group included nausea,headache,dizziness,elevated blood pressure,and indigestion.In the control group,the main adverse drug reactions were nausea,headache,and indigestion.The total incidence of adverse drug reactions in the treatment and control groups was 8.57％and 6.00％,respectively,with no statistically significant difference(P＞0.05).Conclusion Pegylated losenatide injection combined with metformin tablets has a significant effect on axial gastrectomy in obese type 2 diabetes patients.

With the continuous development of science and technology,environmental pollution has become increasingly severe,which makes environmental monitoring crucial.In recent years,electrochemical sensing strategy has attracted wide attention due to its advantages such as low cost,easy operation and fast detection speed.However,the detection performance still faces many challenges such as low sensitivity,high limit of detection and poor selectivity.Metal-organic frameworks(MOFs)is a kind of ordered network porous crystal formed by the coordination bond of organic ligands and metal ions/ion clusters,which can be used to prepare high-performance electrode materials for construction of electrochemical sensors because of their characteristics of large specific surface area,adjustable pore size and diverse structure.However,the poor conductivity and stability of MOFs result in poor electrochemical detection performance,which seriously limits their extensive applications in the field of electrochemistry.Combining MOFs with other functional materials can not only overcome the inherent defects of MOFs but also have the superior properties of both MOFs and functional materials,and the synergistic effect between MOFs and functional materials is conducive to improving the detection performance.Therefore,MOFs composites have been widely used in the electrochemical detection of environmental pollutants.This paper reviewed the applications progress of electrochemical sensors based on MOFs composites(MOFs combine with carbon materials,conductive polymers,metal nanoparticles or MOFs)in detection of environmental pollutants(Pesticides,heavy metal ions,phenolic compounds and nitrites)in the past five years.The prospects and challenges of electrochemical sensors based on MOFs composites for detection of environmental pollutants were also discussed.

Humans ; Bayes Theorem ; Age Factors ; Age Distribution ; Mouth Neoplasms/epidemiology* ; China/epidemiology* ; Mortality

Humans ; Epstein-Barr Virus Infections ; Immune Checkpoint Inhibitors ; Herpesvirus 4, Human

CRISPR/Cas(the clustered regularly interspaced short palindromic repeats-CRISPR associated)system exists in most bacteria and all archaea. It is an important strategy for bacteria and archaea to resist foreign nucleic acid invasion and use for self-defense. The CRISPR/Cas system is a simple, fast, and specific diagnostic tool, which is widely used in agriculture, industry, animal husbandry, and medicine. This article mainly introduces and discusses recently advantages and limitations of biosensors combining CRISPR/Cas system with fluorescence, visualization and surface enhanced raman related technologies, as well as future research directions.
Animals ; CRISPR-Cas Systems ; Bacteria/genetics* ; Archaea

Objective:To explore the phenotype and mechanism of ferroptosis in steatosis liver ischemia reperfusion injury (IRI) and elucidate the mechanism of targeted inhibition of ferroptosis down-regulating steatosis liver IRI.Methods:First, 20 mice are divided into 2 group according to the different feeding mode: Normal chow diet(NCD group, n=10)and high fat diet(HFD group, n=10). The fatty liver constructs are successful as verified by laboratory tests for relevant indicators and oil red staining.NCD and HFD mice were randomized into two groups sham and IRI.The expression of glutathione peroxidase 4(Gpx4)in liver tissues of each group is detected by Western blot.Morphological phenotypes of mitochondria in liver tissue are observed by transmission electron microscope.Accordingly, it was determined whether ferroptosis occurred in mouse liver IRIs.NCD(n=30)and HFD(n=30)are further randomized into 3 groups: sham(n=10), IRI(n=10)and inhibitor(IRI-fer-1 group, n=10). The serum contents of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)are detected by ALT/AST kits.Hematoxylin-eosin(HE)stain is employed for detecting the degree of liver injury; immunohistochemistry(IHC)and enzyme-linked immunosorbent assay(ELISA)for detecting the levels of inflammatory factors and inflammatory cell infiltration.Similarly, primary hepatocytes from NCD/HFD mice are extracted and the occurrence of ferroptosis is verified by detecting C11-BODIPY(581/591)by fluorescent stain after hypoxia-reoxygenation(H/R).Results:As compared with NCD-IRI group, Gpx4 protein expression declined obviously in HFD-IRI group while serum ALT/AST level spiked markedly( P<0.01). IHC staining of 4-HNE is positive, mitochondrial specific damage is more pronounced and inflammatory infiltration became enhanced.As compared with IRI group, serum level of ALT/AST dropped obviously and infiltration of inflammatory cells and secretion of inflammatory factors are blunted markedly in IRI-fer-1 group( P<0.01). Conclusions:A high degree of ferroptosis and severe inflammatory response during fatty liver IR are features of distinguishing steatosis liver IRI from ordinary liver IRI.Targeted inhibition of ferroptosis lowers inflammation and damage during IR in steatosis liver.

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans ; U937 Cells ; RUNX1 Translocation Partner 1 Protein ; Leukemia/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Oncogene Proteins, Fusion/genetics* ; Leukemia, Myeloid, Acute/genetics*