Alpha and beta diversity of functional traits in subtropical evergreen broad-leaved secondary forest communities.

Introduction: Intra-speciic variation is the main source of functional trait diversity and has similar ecological effects as inter-speciic variation. Methods: We studied 79 species and 3546 individuals from 50 ixed monitoring plots in subtropical evergreen broad - leaved secondary forests in Zhejiang Province, China. Using trait gradient analysis, we examined nine traits (speciic leaf area, leaf dry matter content, wood density, leaf area, chlorophyll content, leaf nitrogen content, leaf phosphorus content, leaf potassium content, and nitrogen-phosphorus ratio) by decomposing species functional traits into alpha (within-community) and beta (among-communities) measure the impact of environmental gradients and the presence of other species on the variation of traits. Result: All nine functional traits showed some degree of differentiation in the forest communities, with a greater range of variation in alpha values than in beta values . Correlations were signiicantly different between the trait differences in the communities. The alpha values of each trait showed a higher correlation with other components than the beta values. The factors affecting intra-speciic trait variation were relatively complex. The alpha component had a more signiicant and stronger effect on intra-speciic trait variation compared to the beta component. Abiotic factors, such as soil nutrient content, soil nitrogen-phosphorus content, directly affected the beta component. In contrast, biotic factors, such as tree height variation, had a direct and stronger effect on the alpha component. Discussion: Our results demonstrate that alpha and beta components, as independent differentiation axes among coexisting species, have different sensitivities to different environmental factors and traits in different ecological strategies and spatial scales. Trait gradient analysis can more clearly reveal the variation patterns of species traits in communities, which will help to understand the scale effects and potential mechanisms of trait relationships.

Sea cucumber plasmalogen enhance lipophagy to alleviate abnormal lipid accumulation induced by high-fat diet.

Sea cucumber phospholipids, including the plasmalogen (PlsEtn) and plasmanylcholine (PakCho), have been shown to play a regulatory role in lipid metabolism disorders, but their mechanism of action remains unclear. Therefore, high-fat diet (HFD) and palmitic acid were used to establish lipid accumulation models in mice and HepG2 cells, respectively. Results showed that PlsEtn can reduce lipid deposition both in vivo and in vitro. HFD stimulation abnormally activated lipophagy through the phosphorylation of the AMPK/ULK1 pathway. The lipophagy flux monitor revealed abnormalities in the fusion stage of lipophagy. Of note, only PlsEtn stimulated the dynamic remodeling of the autophagosome membrane, which was indicated by the significantly decreased LC3 II/I ratio and p62 level. In all experiments, the effect of PlsEtn was significantly higher than that of PakCho. These findings elucidated the mechanism of PlsEtn in alleviating lipid accumulation, showed that it might be a lipophagy enhancer, and provided new insights into the high-value utilization of sea cucumber as an agricultural resource.

Multihydrogen Bond Modulated Polyzwitterionic Removable Adhesive Hydrogel with Antibacterial and Hemostatic Function for Wound Healing.

Wound management is a major challenge worldwide, placing a huge financial burden on the government of every nation. Wound dressings that can protect wounds, accelerate healing, prevent infection, and avoid secondary damage continue to be a major focus of research in the health care and clinical communities. Herein, a novel zwitterionic polymer (LST) hydrogel incorporated with [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), mussel-inspired N-[tris(hydroxymethyl)methyl] acrylamide (THMA), and lithium magnesium salt was prepared for functional wound dressings. The incorporation of the THMA monomer containing three hydroxyl groups gives the hydrogel suitable adhesion properties (∼6.0 KPa). This allows the LST zwitterionic hydrogels to bind well to the skin, which not only protects the wound and ensures its therapeutic efficacy but also allows for painless removal and reduced patient pain. Zwitterionic sulfobetaine units of SBMA provide antimicrobial and mechanical properties. The chemical structure and microscopic morphology of LST zwitterionic hydrogels were systematically studied, along with their swelling ratio, adhesion, and mechanical properties. The results showed that the LST zwitterionic hydrogels had a uniform and compact porous structure with the highest swelling and mechanical strain of 1607% and 1068.74%, respectively. The antibacterial rate of LST zwitterionic hydrogels was as high as 99.49%, and the hemostatic effect was about 1.5 times that of the commercial gelatin hemostatic sponges group. In further studies, a full-thickness mouse skin model was selected to evaluate the wound healing performance. Wounds covered by LST zwitterionic hydrogels had a complete epithelial reformation and new connective tissue, and its vascular regenerative capacity was increased to about 2.4 times that of the commercial group, and the wound could completely heal within 12-13 days. This study provides significant advances in the design and construction of multifunctional zwitterionic hydrogel adhesives and wound dressings.

Sea Cucumber Plasmalogen Regulates the Lipid Profile in High-Fat Diet Mouse Liver via Lipophagy.

The sea cucumber plasmalogen PlsEtn has been shown to be associated with various chronic diseases related to lipid metabolism. However, the mechanism is unclear. Therefore, the present study used the sea cucumber plasmanylcholine PakCho as a structural contrast to PlsEtn and assessed its effect in 8 week high-fat diet (HFD)-fed mice. The lipidomic approach based on high-resolution mass spectrometry combined with molecular biology techniques was used to evaluate the mechanism of PlsEtn. The results showed that both PlsEtn and PakCho significantly inhibited an increase in mouse body weight and liver total triglyceride and total cholesterol levels caused by HFD. In addition, oil red O staining demonstrated that lipid droplets stored in the liver were degraded. Meanwhile, untargeted lipidomic experiments revealed that total lipids (increased by 42.8 mmol/mg prot; p < 0.05), triglycerides (increased by 38.9 mmol/mg prot; p < 0.01), sphingolipids (increased by 1.5 mmol/mg prot; p < 0.0001), and phospholipids (increased by 2.5 mmol/mg prot; p < 0.05) were all significantly elevated under HFD. PlsEtn resolved lipid metabolism disorders by alleviating the abnormal expression of lipid subclasses. In addition, five lipid molecular species, PE (18:1/20:4), PE (18:1/20:3), PE (18:1/18:3), TG (16:0/16:0/17:0), and TG (15:0/16:0/18:1), were identified as the biomarkers of HFD-induced lipid metabolism disorders. Finally, lipophagy-associated protein expression analysis showed that HFD abnormally activated lipophagy via ULK1 phosphorylation and PlsEtn alleviated lipophagy disorder through lysosomal function promotion. In addition, PlsEtn performed better than PakCho. Taken together, the current study results unraveled the mechanism of PlsEtn in alleviating lipid metabolism disorder and offered a new theoretical foundation for the high-value development of sea cucumber.

Enhanced emulsification performance and interfacial properties of Janus-like rapeseed cruciferin through asymmetric acylation modification.

Plant protein emulsifiers, particularly rapeseed protein isolate with its superior amino acid composition and predominantly globular protein, have captured significant interest in the food industry. Nonetheless, the application of these proteins has been stymied by their lackluster emulsification properties. Addressing this challenge, our study implements an innovative asymmetric acylation technique to modify the surface of rapeseed cruciferin (RC), morphing it into a structure resembling Janus nanoparticles. This alteration amplifies the emulsification prowess of RC by a remarkable 2.7 times compared to its natural form, and 1.43 times over its conventionally acylated counterpart. The asymmetrically acylated RC, marked by a distinctive three-phase contact angle of 90.4°, manifests an outstanding amphiphilic character. Moreover, it surpasses both the natural and conventionally acylated RC in terms of diffusion, penetration, and rearrangement rates, as well as protein concentration at the oil-water interface. Compared to commonly used emulsifiers in the food industry, such as lecithin and soy protein, the asymmetrically acylated RC stands out, stabilizing emulsions with the tiniest particle size and effectively staving off emulsion stratification over a longer duration. This study underscores that asymmetric acylation serves as a reliable methodology for producing efficient plant protein emulsifiers, considerably amplifying their utility in the food industry.

Docosahexaenoic Acid-Acylated Astaxanthin Monoester Ameliorates Amyloid-ß Pathology and Neuronal Damage by Restoring Autophagy in Alzheimer's Disease Models.

SCOPE: Astaxanthin (AST) is ubiquitous in aquatic foods and microorganisms. The study previously finds that docosahexaenoic acid-acylated AST monoester (AST-DHA) improves cognitive function in Alzheimer's disease (AD), although the underlying mechanism remains unclear. Moreover, autophagy is reportedly involved in amyloid-ß (Aß) clearance and AD pathogenesis. Therefore, this study aims to evaluate the preventive effect of AST-DHA and elucidates the mechanism of autophagy modulation in Aß pathology. METHODS AND RESULTS: In the cellular AD model, AST-DHA significantly reduces toxic Aß1-42 levels and alleviated the accumulation of autophagic markers (LC3II/I and p62) in Aß25-35 -induced SH-SY5Y cells. Notably, AST-DHA restores the autophagic flux in SH-SY5YmRFP-GFP-LC3 cells. In APP/PS1 mice, a 3-month dietary supplementation of AST-DHA exceeded free-astaxanthin (F-AST) capacity to increase hippocampal and cortical autophagy. Mechanistically, AST-DHA restores autophagy by activating the ULK1 signaling pathway and restoring autophagy-lysosome fusion. Moreover, AST-DHA relieves ROS production and mitochondrial stress affecting autophagy in AD. As a favorable outcome of restored autophagy, AST-DHA mitigates cerebral Aß and p-Tau deposition, ultimately improving neuronal function. CONCLUSION: The findings demonstrate that AST-DHA can rectify autophagic impairment in AD, and confer neuroprotection in Aß-related pathology, which supports the future application of AST as an autophagic inducer for maintaining brain health.

MLKL polymerization-induced lysosomal membrane permeabilization promotes necroptosis.

Mixed lineage kinase-like protein (MLKL) forms amyloid-like polymers to promote necroptosis; however, the mechanism through which these polymers trigger cell death is not clear. We have determined that activated MLKL translocates to the lysosomal membrane during necroptosis induction. The subsequent polymerization of MLKL induces lysosome clustering and fusion and eventual lysosomal membrane permeabilization (LMP). This LMP leads to the rapid release of lysosomal contents into the cytosol, resulting in a massive surge in cathepsin levels, with Cathepsin B (CTSB) as a significant contributor to the ensuing cell death as it cleaves many proteins essential for cell survival. Importantly, chemical inhibition or knockdown of CTSB protects cells from necroptosis. Furthermore, induced polymerization of the MLKL N-terminal domain (NTD) also triggers LMP, leading to CTSB release and subsequent cell death. These findings clearly establish the critical role of MLKL polymerization induced lysosomal membrane permeabilization (MPI-LMP) in the process of necroptosis.

Astaxanthin alleviates ganglioside metabolism disorder in the cortex of Alzheimer's disease mice.

The present study analyzed the amelioration effect and mechanism of two kinds of astaxanthin (AST), including free-AST (F-AST) and docosahexaenoic acid-acylated AST monoester (AST-DHA), on ganglioside (GLS) metabolism in the cortex of APP/PS1 mice using the LC-MS strategy in combination with molecular biology. Water maze and immunohistochemical experiments demonstrated that AST significantly improved the cognitive level of APP/PS1 mice and reduced Aß deposition in the cortex. After the dietary intake of AST, the composition and level of 84 GLS molecular species in the mouse cortex were determined using the LC-MS strategy. The results showed that the total GLS was reduced, most complex GLS was decreased, and simple GLS (GM3 and GM1a) was increased in the APP/PS1 mouse cortex. Notably, F-AST mainly regulated complex GLS (p < 0.001), whereas AST-DHA primarily reacted with simple GLS (p < 0.001). OAc-GQ1a(38:1), OAc-GQ1a(36:1), GD1a(36:1), and GM3(38:1) decreased 3.73, 2.31, and 2.29-fold and increased 3.54-fold, respectively, and were identified as potential AD biomarkers in the cortices of APP/PS1 mice. Additionally, the AST diet significantly upregulated the mRNA expression of GLS synthesizing genes (st3gal5, st8sia1, b3galt4, st3fal2, and soat) and siae (p < 0.05) and down-regulated that of the GLS catabolizing gene hexa (p < 0.01). In conclusion, improving GLS homeostasis in the AD mouse cortex might be a critical pathway to explain the AD-preventing effect of AST.

In-Depth Analysis of the Mechanism of Astaxanthin Succinate Diester in Reducing Ulcerative Colitis in C57BL/6J Mice Based on Microbiota Informatics.

This paper aims to explore the effect and mechanism of water-soluble astaxanthin succinate diester (Asta-SD) on ulcerative colitis (UC) induced by dextran sodium sulfate in zebrafish and C57BL/6J mice. Asta-SD was synthesized with hydrophilic fatty acid succinic anhydride and the hydroxyl groups at the ends of F-Asta were synthesized by esterifying. Through the construction of a zebrafish intestinal inflammation model, it was found that Asta-SD could effectively reduce the levels of ROS and increase the number of healthy intestinal lysosomes in zebrafish. After continuous gavage of Asta-SD for seven days, the body weight, disease activity index, colonic length, colonic histopathology, expression of inflammatory factors, and intestinal flora of the mice were measured. The results showed that Asta-SD could significantly alleviate weight loss and colonic shrinkage, as well as reducing pro-inflammatory cytokines and recess injury in UC mice. The 16S rRNA gene sequencing showed that Asta-SD significantly increased the beneficial bacteria (Lactobacillus, Anaerotruncus) and decreased the relative abundance of pathogenic bacteria, effectively maintaining intestinal microbiota homeostasis in mice. Based on Pearson analysis, Bacteroides, Parabacteroides, and Butyrimionas were expected to be associated with the significant difference in the expression of inflammatory factors between the UC and the corresponding host. Thus, Asta-SD significantly improves UC and maintains intestinal microbiota homeostasis.

Antioxidants ameliorate oxidative stress in alcoholic liver injury by modulating lipid metabolism and phospholipid homeostasis.

Alcoholic liver disease (ALD) is a significant risk factor in the global disease burden. The antioxidants vitamin C (Vc) and N-acetyl cysteine (NAC) have shown hepatoprotective effects in preventing and treating ALD. However, the correlation between the improved effect of antioxidants and lipid metabolism is still unclear. In this study, AML12 cells and C57BL/6 mice stimulated with alcohol were used to investigate the protective effects and potential mechanisms of two antioxidants (Vc and NAC) on alcoholic liver injury. Results showed that Vc and NAC attenuated intracellular lipid accumulation and oxidative damage induced by excessive alcohol exposure in hepatic AML12 cells. The in vivo results indicated that antioxidants ameliorated alcohol-induced changes in histopathology, reducing the levels of alcohol metabolizing factors and aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) contents, which demonstrated that antioxidants effectively mitigated liver injury in ALD mice. Further studies showed that antioxidants reversed the disruption of fatty acid (FA) synthesis and lipid transport induced by alcohol exposure, and restored phospholipid levels. Especially, Vc and NAC increased the endogenous antioxidant plasmenyl phosphatidylethanolamine (PlsEtn). Additionally, antioxidants ameliorated the alcohol-impaired mitochondrial function and inhibited excessive oxidative stress. In conclusion, antioxidants can regulate lipid metabolism and phospholipid homeostasis, which in turn inhibit oxidative stress and thereby exert protective effects against ALD.

Effects of high-sugar, high-cholesterol, and high-fat diet on phospholipid profile of mouse tissues with a focus on the mechanism of plasmalogen synthesis.

High-sugar diet (HSD), high-cholesterol diet (HCD), and high-fat diet (HFD) all modulate the levels of lipids. However, there is a lack of comparative data on the effects of different diets on phospholipids (PLs). Given their important role in physiology and disease, there has been an increasing focus on altered PLs in liver and brain disorders. This study aims to determine the effects of HSD, HCD, and HFD for 14-week feeding on the PL profile of the mouse liver and hippocampus. Quantitative analysis of 116 and 113 PL molecular species in liver and hippocampus tissues revealed that the HSD, HCD, and HFD significantly affected the PLs in liver and hippocampus, especially decreased the levels of plasmenylethanolamine (pPE) and phosphatidylethanolamine (PE). Overall, the impact of HFD on liver PLs was more significant, consistent with the morphological changes in the liver. Compared to HSD and HCD, HFD induced a significant decrease in PC (P-16:0/18:1) and an increase in LPE (18:0) and LPE (18:1) in liver. In the liver of mice fed with different diets, the expression of the key enzymes Gnpat, Agps in the pPE biosynthesis pathway and peroxisome-associated membrane proteins pex14p were decreased. In addition, all diets significantly reduced the expression of Gnpat, pex7p, and pex16p in hippocampus tissue. In conclusion, HSD, HCD, and HFD enhanced lipid accumulation in the liver, led to liver injury, significantly affected the liver and hippocampus PLs, and decreased the expression of genes related to plasmalogen synthesis in mouse liver and hippocampus, which caused severe plasmalogen reduction.

Study on the hypolipidemic activity of rapeseed protein-derived peptides.

Hyperlipidaemia, a common chronic disease, is the cause of cardiovascular diseases such as myocardial infarction and atherosclerosis. Generally, drugs for lowering blood lipids have disadvantages such as short or poor efficacy, high toxicity, and side effects. Rapeseed active peptides are excellent substitutes for lipid-lowering drugs because of their high biological safety, strong penetration, and easy absorption by the human body. This study separated and purified the rapeseed peptides using gel chromatography and mass spectrometry. Rapeseed peptides amino acid sequences were determined to obtain Glu-Phe-Leu-Glu-Leu-Leu (EFLELL) peptides with good hypolipidaemic activity and IC50 values of 0.1973 ± 0.05 mM (sodium taurocholate), 0.375 ± 0.03 mM (sodium cholate), and 0.203 ± 0.06 mM (sodium glycine cholate). The EFLELL hypolipidaemic activity was evaluated, and its mechanism of action was investigated using cell lines. Rapeseed peptide treatment significantly decreased the total cholesterol (T-CHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the protein and gene expression levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein cholesterol (LDLR) suggested the mechanism. Molecular docking revealed that the binding energy between rapeseed peptide and LDLR-PCSK9 molecules was -6.3 kcal/mol and -8.1 kcal/mol. In conclusion, the rapeseed peptide EFLELL exerts a favourable hypolipidaemic effect by modulating the LDLR-PCSK9 signalling pathway.

Sepsis-related immunosuppression: a bibliometric analysis.

Background: Sepsis is one of the main causes of death in critically ill patients. Immunosuppression was involved deeply in the process of sepsis. The status of research on sepsis-related immunosuppression remains unclear. In this study, a bibliometric analysis was conducted to provide a preliminarily analysis of the current research status in sepsis-related immunosuppression. Methods: The Science Citation Index Expanded (SCI-E) database in the Web of Science Core Collection was used as the data source for the literature search, and the time was set from the inception of the database to the last retrieval time for this study (i.e., May 21, 2022). Using the topic search, we searched for "sepsis" and then for "immunosuppression" in the results to obtain the final results. On the search page of the SCI-E database, we selected the document type, topic direction, MeSH topic heading, MeSH qualifier, keywords, author, journal, country, research institution, language, etc., to obtain the distribution results, and manually removed any duplicate records. We analyzed the use of keywords in the literature and the centrality of the authors, countries, and research institutions. Results: A total of 4,132 articles were retrieved from the database over the search period of 1900 to May 21, 2022. The number of articles published increased annually. A trend of rapid growth was also observed in the number of citations. The most common topic words were humans, male, and female. The most used keywords were sepsis, immunosuppression, and male. The most published researcher was Monneret from Lyon, France. The authors of the article mainly specialized in immunology and surgery. Moldawer and Chaudry from the United States (US) had engaged in the most collaborations with other researchers. The journals that publish literature in this field are mainly journals related to critical care medicine, and the core journals included Shock, Critical Care, and Critical Care Medicine. Conclusions: More and more studies are being published on sepsis-related immunosuppression and largely being conducted in developed countries. Chinese researchers need to carry out more collaborative research.

Co-encapsulation of rutinoside and ß-carotene in liposomes modified by rhamnolipid: Antioxidant activity, antibacterial activity, storage stability, and in vitro gastrointestinal digestion.

The surfactant rhamnolipid (RL) was used to modify the liposomes. ß-carotene (ßC) and rutinoside (Rts) were utilized to generate co-encapsulated liposomes through an ethanol injection method that used both hydrophilic and hydrophobic cavities to fabricate a novel cholesterol-free composite delivery system. The RL complex-liposomes loaded with ßC and Rts (RL-ßC-Rts) showed higher loading efficiency and good physicochemical properties (size = 167.48 nm, zeta-potential = -5.71 mV, and polydispersity index = 0.23). Compared with other samples, the RL-ßC-Rts showed better antioxidant activities and antibacterial ability. Moreover, dependable stability was uncovered in RL-ßC-Rts with still 85.2% of ßC storage from nanoliposome after 30 days at 4°C. Furthermore, in simulated gastrointestinal digestion, ßC exhibited good release kinetic properties. The present study demonstrated that liposomes constructed from RLs offer a promising avenue for the design of multicomponent nutrient delivery systems using both hydrophilic.

Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C.

This study investigated the effect of combined thymosin α1 and vitamin C (Tα1 + VitC) on the immunological responses of septic rats. Five groups were designed. The septic model was established by the cecal ligation puncture (CLP) method. The sham group did not undergo CLP, the model group was given normal saline solution, the Tα1 group was given Tα1 (200 µg/kg), the VitC group was given VitC (200 mg/kg), and the Tα1 + VitC group was given Tα1 + VitC. Specimens for immunological analyses were collected at 6, 12, 24, and 48 h posttreatment in each group except for the sham group (only at 48 h). CD4 + CD25 + T cells in the peripheral blood and dendritic cell (DC) proportions in the spleen were analyzed by flow cytometry. Tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), transforming growth factor-ß (TGF-ß1), and nuclear factor kappa-B (NF-κB) were measured by ELISA. CD4 + CD25 + T cells and OX62 + DCs levels significantly increased in the model group and decreased in the Tα1 and/or VitC treatment groups. Similarly, the levels of TNF-α, IL-6, TGF-ß1, and NF-κB significantly increased in the model group and decreased in the Tα1, VitC, and Tα1 + VitC groups, indicating that combined Tα1 and VitC therapy may help regulate the immunological state of patients with sepsis, thereby improving prognosis.

Enhancing electrical outputs of the fuel cells with Geobacter sulferreducens by overexpressing nanowire proteins.

Protein nanowires are critical electroactive components for electron transfer of Geobacter sulfurreducens biofilm. To determine the applicability of the nanowire proteins in improving bioelectricity production, their genes including pilA, omcZ, omcS and omcT were overexpressed in G. sulfurreducens. The voltage outputs of the constructed strains were higher than that of the control strain with the empty vector (0.470-0.578 vs. 0.355 V) in microbial fuel cells (MFCs). As a result, the power density of the constructed strains (i.e. 1.39-1.58 W m-2 ) also increased by 2.62- to 2.97-fold as compared to that of the control strain. Overexpression of nanowire proteins also improved biofilm formation on electrodes with increased protein amount and thickness of biofilms. The normalized power outputs of the constructed strains were 0.18-0.20 W g-1 that increased by 74% to 93% from that of the control strain. Bioelectrochemical analyses further revealed that the biofilms and MFCs with the constructed strains had stronger electroactivity and smaller internal resistance, respectively. Collectively, these results demonstrate for the first time that overexpression of nanowire proteins increases the biomass and electroactivity of anode-attached microbial biofilms. Moreover, this study provides a new way for enhancing the electrical outputs of MFCs.

Docosahexaenoic acid-acylated astaxanthin monoester ameliorates chronic high-fat diet-induced autophagy dysfunction via ULK1 pathway in the hypothalamus of mice.

BACKGROUND: Dietary astaxanthin (AST) exhibits the ability to resist lipid accumulation and stimulate hepatic autophagy. Natural AST predominantly exists in stable esterified forms. More importantly, in our previous study, docosahexaenoic acid-acylated AST monoester (AST-DHA) possessed better stability, bioavailability, and neuroprotective ability than AST in free and diester form. However, the AST-DHA mechanisms of action in regulating the obese phenotype and autophagy of the central nervous system remain unclear. RESULTS: High-fat diet (HFD)-fed C57BL/6J mice were orally administered AST-DHA (50 mg/kg body weight/d) for 3 days or 8 weeks. AST-DHA supplementation alleviated HFD-induced abnormal body weight gain, significantly enhanced autophagy with an increased microtubule-associated protein light chain 3 II/I (LC3II/I) ratio, and reduced the accumulation of p62/sequestosome 1 (SQSTM1) in the hypothalamus rather than in the hippocampus. Mechanistically, AST-DHA effectively promoted autophagy and autophagosome formation, and most notably rescued the HFD-impaired autophagosome-lysosome fusion (indicated by the colocalization of LC3 and LAMP1) by regulating mTOR- and AMPK-induced phosphorylation of ULK1. Consequently, AST-DHA enhanced hypothalamic autophagy, leading to pro-opiomelanocortin (POMC) cleavage to produce alpha-melanocyte-stimulating hormone (α-MSH). CONCLUSIONS: This study identified AST-DHA as an enhancer of autophagy that plays a beneficial role in restoring hypothalamic autophagy, and as a new potential therapeutic agent against HFD-induced obesity. © 2023 Society of Chemical Industry.

The novel biomarker circ_0020339 drives septic acute kidney injury by targeting miR-17-5p/IPMK axis.

PURPOSE: Sepsis is a systemic life-threatening inflammatory disease, which leads to septic acute kidney injury (AKI). Circular RNAs (circRNAs) are involved in septic AKI. Herein, we aimed to expound the action of circ_0020339 in septic AKI. The dysregulation of plasma circRNAs between patients with septic non-AKI and patients with septic AKI were screened by circRNA chip. METHODS: The dysregulation of circ_0020339, microRNA (miR)-17-5p, and inositol polyphosphate multi kinase (IPMK) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. The release of serum creatinine (SCr), tissue inhibitor metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), tumor necrosis factor (TNF)α and interleukin (IL)-1ß was evaluated by enzyme-linked immunosorbent assay (ELISA). Bioinformatic analysis, dual-luciferase reporter assay and miRNA pull down assay were used to confirm the interaction between miR-17-5p and circ_0020339 or IPMK 3'untranslated region (UTR). Protein level of IPMK, TNF receptor-associated factor 6 (TRAF6), phosphorylated AKT (p-AKT)/total (t)-AKT, p-nuclear factor kappa-B (NF-κB) kinase (p-IKK)/t-IKK, p-inhibitor of NF-κB (p-IκB)α/t-IκBα, and p-p65/t-p65 were conducted by western blot. RESULTS: Circ_0020339 was upregulated in the plasma of patients with septic AKI as well as LPS-treated HK2 cells and C57BL/6 mice relative to the corresponding counterparts. Functionally, circ_0020339 was positively correlated with markers of renal functional injury and inflammation in patients with septic AKI; si-circ_0020339 facilitated cell proliferation, while restrained cell apoptosis and inflammation in LPS-triggered HK2 cells; meanwhile, si-circ_0020339 restrained survival rate, renal functional injury and inflammation in LPS-triggered C57BL/6 mice. Furthermore, circ_0020339 and IPMK 3'UTR shared the same complementary sites with miR-17-5p. CONCLUSION: si-circ_0020339 attenuated LPS-induced cell damage by targeting miR-17-5p/IPMK axis and inactivation of TRAF6/p-AKT/p-IKK/p-IκBα/p-p65. Altogether, plasma circ_0020339 serves as a novel diagnostic marker of patients with septic AKI.

Rapeseed peptide inhibits HepG2 cell proliferation by regulating the mitochondrial and P53 signaling pathways.

BACKGROUND: Rapeseed peptide, extracted from rapeseed protein, is known to have a variety of biological activities. In this study, the anti-proliferation effect and molecular mechanism of rapeseed peptide on HepG2 cells were investigated. RESULTS: In vitro anticancer experiments showed that the rapeseed peptide NDGNQPL could inhibit HepG2 cell proliferation in a concentration-dependent manner [half maximal inhibitory concentration (IC50 ), 1.56 mmol L-1 ). HepG2 cells were induced by NDGNQPL at a 0.5 mmol L-1 concentration and exhibited a 28.39 ± 0.80% apoptosis rate and a cell cycle arrest in the G0/G1 phase. Meanwhile, rapeseed peptide induced a decrease in mitochondrial membrane potential, an increase in reactive oxygen species (ROS) release, and changes in the nuclear morphology of HepG2 cells, indicating that rapeseed peptide could induce cell apoptosis through the mitochondrial pathway. In addition, rapeseed peptide activated the proliferation-related P53 signaling pathway, in which the expression levels of P53, P21, and cleaved-caspase3 were up-regulated, while the expression levels of murine double minute 2 (MDM2) were down-regulated. In molecular docking simulations, NDGNQPL exhibited a good affinity for the MDM2 molecule, which supported the notion that the rapeseed peptide is able to inhibit MDM2, a negative regulator of P53. CONCLUSION: The current results indicate that the rapeseed-derived NDGNQPL peptide has the potential to inhibit the proliferation of HepG2 cells and promote human health. © 2022 Society of Chemical Industry.

[Effect of admission mode of septic patients in intensive care unit on acute kidney injury and prognosis].

OBJECTIVE: To investigate the effect of intensive care unit (ICU) admission model on acute kidney injury (AKI) development and the prognosis in patients with sepsis. METHODS: Patients with sepsis admitted to the ICU of Xinjiang Uygur Autonomous Region People's Hospital from January 2019 to July 2020 were retrospectively analyzed. According to the ICU admission model, the patients were divided into emergency group (first admission or emergency transfer from relevant surgical departments) and delayed group (transferred from the general ward due to disease evolution). Patients were divided into AKI group and non-AKI group according to whether AKI was accompanied. The gender, age, underlying diseases, surgical history, heart rate, laboratory test indicators, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), organ failure and acute complications were collected. The incidence of AKI, 28-day mortality and length of ICU stay were recorded. Univariate and multivariate Logistic regression was used to analyze the risk factors of AKI in patients with sepsis. RESULTS: A total of 185 patients with sepsis were enrolled, including 96 cases in the emergency group and 89 cases in the delayed group. 119 cases of AKI occurred while 66 cases without AKI development. The incidence of AKI within 7 days and the 28-day mortality of patients in the delayed group were significantly higher than those in the emergency group [AKI incidence rate: 77.53% (69/89) vs. 52.08% (50/96), 28-day mortality: 24.72% (22/89) vs. 10.42% (10/96), both P < 0.05], and the length of ICU stay was significantly longer than that of the emergency group (days: 18.70±7.29 vs. 14.56±4.75, P < 0.05). Univariate Logistic analysis showed that there were significant differences in age, diabetes, hypertension, organ failure, heart failure, APACHE II score, SOFA score, white blood cell count (WBC), absolute neutrophil value, platelet count (PLT), blood lactate, total bilirubin, and ICU transferred from general wards between AKI group and non-AKI group. Multivariate Logistic regression analysis showed that transfer from general ward to ICU due to disease evolution was an independent risk factor for AKI in ICU sepsis patients [odds ratio (OR) = 5.165, 95% confidence interval (95%CI) was 3.911-6.823, P < 0.001]. CONCLUSIONS: Septic patients transferred from general ward to ICU due to disease evolution are more likely to develop AKI, and also had a higher mortality and longer ICU stay. It may be an independent risk factor for AKI complicated by patients with sepsis in ICU.