FABP5 Deficiency Impaired Macrophage Inflammation by Regulating AMPK/NF-κB Signaling Pathway.

Fatty acid binding protein 5 (FABP5) is mainly involved in the uptake, transport, and metabolism of fatty acid in the cytoplasm, and its role in immune cells has been recognized in recent years. However, the role of FABP5 in macrophage inflammation and its underlying mechanisms were not fully addressed. In our study, the acute liver injury and sepsis mouse models were induced by i.p. injection of LPS and cecal contents, respectively. Oleic acid (0.6 g/kg) was injected four times by intragastric administration every week, and this lasted for 1 wk before the LPS or cecal content challenge. We found that myeloid-specific deletion of FABP5 mitigated LPS-induced acute liver injury with reduced mortality of mice, histological liver damage, alanine aminotransferase, and proinflammatory factor levels. Metabolic analysis showed that FABP5 deletion increased the intracellular unsaturated fatty acids, especially oleic acid, in LPS-induced macrophages. The addition of oleic acid also decreased LPS-stimulated macrophage inflammation in vitro and reduced acute liver injury in LPS-induced or cecal content-induced sepsis mice. RNA-sequencing and molecular mechanism studies showed that FABP5 deletion or oleic acid supplementation increased the AMP/ATP ratio and AMP-activated protein kinase (AMPK) activation and inhibited the NF-κB pathway during the inflammatory response to LPS stimulation of macrophages. Inhibiting AMPK activation or expression by chemical or genetic approaches significantly rescued the decreased NF-κB signaling pathway and inflammatory response in LPS-treated FABP5-knockout macrophages. Our present study indicated that inhibiting FABP5 or supplementation of oleic acid might be used for the treatment of sepsis-caused acute liver injury.

Prevalence of intrinsic capacity decline among community-dwelling older adults: a systematic review and meta-analysis.

BACKGROUND: The concept of intrinsic capacity (IC) was introduced to define healthy aging and active aging based on functional capacity, yet there is limited understanding of the risk of IC decline at a population level. AIMS: To consolidate existing evidence for rates of IC decline and risk factors among community-dwelling adults 60 years or older. METHODS: According to the PRISMA guidelines, the literature search was independently conducted by two researchers in 8 databases from inception to January 2024 without language restrictions using combinations of free words and subject words. Qualities of included studies were assessed using Joanna Briggs Institute's (JBI's) critical appraisal checklist for prevalence studies. To pool the data, a random-effect meta-analysis was performed, followed by subgroup analysis and sensitivity analysis. All analyses were performed by Stata14.0. RESULTS: From 1594 records, 15 studies were extracted with 33,070 participants for meta-analysis. The pooled prevalence of IC decline in community settings was 67.8% (95% CI: 57.0-78.5%; P < 0.001). The prevalence of IC decline in China (66.0%; 95% CI: 53.2-78.9%) was found to be slightly lower than in other countries/regions (73.0%; 95% CI: 59.8-86.3%); however, this difference was not statistically significant. Other subgroup analyses revealed no statistically significant differences in prevalence. Age, hypertension, diabetes, gender, education level, living status, smoking, regular exercise, marital status, and osteoarthritis are associated with IC decline. CONCLUSION: More than two-thirds of older adults in the community are affected by IC decline, and age, hypertension, diabetes, female sex, low education level, living alone, smoking, irregular exercise, unmarried, and osteoarthritis are all risk factors for IC decline.

Psychiatric assessment and therapy in an adolescent with ALG6-CDG: a six-month follow-up case report.

ALG6-congenital disorder of glycosylation (ALG6-CDG) is a complex of rare inherited disorders caused by mutations in the ALG6 gene, which encodes the α-1,3-glucosyltransferase enzyme required for N-glycosylation. ALG6-CDG affects multiple systems and exhibits clinical heterogeneity. Besides developmental delays and neurological signs and symptoms, behavioral and psychological symptoms are also an important group of clinical features of ALG6-CDG. Here, we present the case of a 17-year-old Chinese girl with ALG6-CDG who first visited the psychiatric department with apathy, language reduction, and substupor symptoms. The psychiatric assessments and treatment processes performed are described and discussed in this report. During diagnostic process, we found a novel mutation, c.849delT, in ALG6 by whole-exome sequencing. The patient's symptoms improved with escitalopram and risperidone treatment. However, above a certain dosage, she was sensitive to extrapyramidal side effects. This study accumulates clinical experience for diagnosing and treating ALG6-CDG and improves our understanding of this rare genetic disorder.

Proteomic analysis of ITPR2 as a new therapeutic target for curcumin protection against AFB1-induced pyroptosis.

Aflatoxin B1 (AFB1) is extremely carcinogenic and can cause liver cancer in humans and animals with continued ingestion. As a natural compound, curcumin (Cur) exhibits excellent anti-inflammatory, and anti-cancer properties with few side effects. In this study, a total of 60 male mice (6-week-olds, 15 per group). After one week of acclimatization feeding, the mice were divided into control group (Con), AFB1 group, curcumin group (Cur), and AF+Cur group. The mice were gavaged with curcumin (Cur, 100 mg/kg) and/or AFB1 (0.75 mg/kg). To identify a new therapeutic target for AFB1-induced pyroptosis, we performed proteomic profiling for curcumin alleviating liver injury caused by AFB1 to further validate the targets through volcano plot analysis, Venn analysis, heatmap analysis, correlation, cluster analysis, GO and KEGG enrichment. AFB1 exposure resulted in the loss of hepatocyte membrane, swelling of the endoplasmic reticulum, and a significant increase in transaminase (ALT and AST) contents, while curcumin greatly improved these changes. We found that differentially expressed proteins are enriched in the endoplasmic reticulum membrane and identified ITPR2 as a target of curcumin that alleviates AFB1-induced liver injury by proteomics. Furthermore, ITPR2 expression was detected by immunofluorescence, and qRT-PCR for mRNA expression of genes downstream of ITPR2 (calpain1, calpain2, caspase-12, caspase-3). ITPR2-activated endoplasmic reticulum stress-related proteins (calpain1, calpaini2, bcl-2, BAX, cl-caspase-12, cl-caspase-3), apoptosis (PARP) and pyroptosis (DFNA5) related proteins were examined by western blotting. The analysis showed that it effectively prevents AFB1-induced pyroptosis by lowering endoplasmic reticulum stress via interfering with ITPR2 and its downstream proteins (calpain1, calpain2, bcl-2, Bax) and inhibiting caspase-12/caspase-3 pathway. Conclusively, this study applied proteomic profiling to elucidate ITPR2 as a new target, which might give a new perspective on the mechanism of curcumin alleviating AFB1-induced pyroptosis.

Protective role of curcumin on broiler liver by modulating aflatoxin B1-induced DNA methylation and CYPs expression.

The purpose of this study was to investigate the role of epigenetic DNA methylation and CYPs expression in AFB1-exposed broiler liver and the protective effect of curcumin. Sixty-four one-day-old AA broilers were randomly divided into four groups, including control group, AFB1 group (1 mg/kg AFB1), curcumin + AFB1 group (1 mg/kg curcumin) and curcumin group (300 mg/kg curcumin). Histological observation, CYP450 enzyme activities, the expression levels of DNA methyltransferases and CYP450 enzymes, and the overall DNA methylation level in broiler liver were investigated. Dietary AFB1 was found to induce severe liver injury in broilers, upregulate the mRNA and protein expression of CYP450 enzymes (CYP1A1, CYP1A2 and CYP3A4) and the enzyme activities of CYP1A2 and CYP3A4. According to HPLC, qPCR and western blot analyses, the overall DNA methylation level and the mRNA and protein expression of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) in the liver were significantly increased after AFB1 exposure. Importantly, the Pearson test and correlation analysis data revealed that the overall DNA methylation level of broiler liver was positively correlated with DNMTs, while CYP1A1, CYP1A2 and CYP3A4 were negatively correlated. Surprisingly, curcumin supplementation strongly ameliorated AFB1-induced hepatotoxicity by restoring the histological changes, decreasing the expression and enzymatic activity of liver CYP450 enzymes (CYP1A1, CYP1A2, and CYP3A4), and increasing the overall DNA methylation level and the expression of DNMTs. Taken together, we concluded that curcumin could protect against AFB1-induced liver injury by mediating the effects of DNA methylation and CYPs expression.

Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction.

Argpyrimidine (APMD), a methylglyoxal-arginine-derived product, is one of the main products of diabetes mellitus. We aimed to systematically investigate the role of APMD in regulating autophagy activity, with a specific focus on the finding of APDM binding molecule, matching amino acid residues, autophagy flux and proteins, cell cycle arrest, cell skeleton and migration, PI3K/AKT/mTOR pathways, inflammatory signals, alveolar bone destruction, and inhibition verification. In this study, binding to 59/94/121 amino acid residues of advanced glycosylation end product receptor (RAGE), APMD suppressed PI3K/AKT/mTOR pathway to attenuate cell survival of periodontal ligament cells (PDLCs). Simultaneously, autophagy proteins ATG5, Beclin1, and LC3-II/I expression ratio were upregulated while P62/SQSTM was downregulated. Cell cycle arrested at G0/G1 with enhancing Cyclin D1/CDK4 and decreasing Cyclin A/CDK2 expression. Inhibition of autophagy abrogated APMD-induced cell cycle arrest. Furthermore, the inflammation regulation network of matrix metalloproteinase (MMP)-2, MMP-9, MAPKs and NF-κB pathways were activated by APMD. Rat periodontal models confirmed that APMD induced alveolar bone resorption, increased inflammatory infiltrates, and degraded collagen fibers through RAGE and PI3K. APMD-induced autophagy, G0/G1 arrest, pro-inflammatory signals activating and periodontal destruction were reversed by RAGE knockdown while aggravated by PI3K inhibitor. This study provides the first evidence that APMD bind to RAGE to regulate autophagy and cell cycle of PDLCs through the PI3K/AKT/mTOR pathway, thereby promoting periodontal destruction.

Engineering Single-Atom Sites into Pore-Confined Nanospaces of Porphyrinic Metal-Organic Frameworks for the Highly Efficient Photocatalytic Hydrogen Evolution Reaction.

As a type of heterogeneous catalyst expected for the maximum atom efficiency, a series of single-atom catalysts (SACs) containing spatially isolated metal single atoms (M-SAs) have been successfully prepared by confining M-SAs in the pore-nanospaces of porphyrinic metal-organic frameworks (MOFs). The prepared MOF composites of M-SAs@Pd-PCN-222-NH2 (M = Pt, Ir, Au, and Ru) display exceptionally high and persistent efficiency in the photocatalytic hydrogen evolution reaction with a turnover number (TON) of up to 21713 in 32 h and a beginning/lasting turnover frequency (TOF) larger than 1200/600 h-1 based on M-SAs under visible light irradiation (λ ≥ 420 nm). The photo-/electrochemical property studies and density functional theory calculations disclose that the close proximity of the catalytically active Pt-SAs to the Pd-porphyrin photosensitizers with the confinement and stabilization effect by chemical binding could accelerate electron-hole separation and charge transfer in pore-nanospaces, thus promoting the catalytic H2 evolution reaction with lasting effectiveness.

Protective role of curcumin on aflatoxin B1-induced TLR4/RIPK pathway mediated-necroptosis and inflammation in chicken liver.

This study set out to assess the mitigative effects of curcumin on AFB1-induced necroptosis and inflammation in chicken liver. Ninety-six one-day-old AA broiler chickens were separated into four groups, including control group, AFB1 (1 mg/kg) group, curcumin (300 mg/kg) + AFB1 (1 mg/kg) group and curcumin (300 mg/kg) group. After 28 days treatment, livers were collected for different experimental analyses. The morphological observation results showed obvious necrotic characteristics, including cell swelling, rupture of cell and mitochondrial membranes and inflammation in chicken livers. AFB1 exposure increased oxidative stress index (ROS and MDA) and decreased the antioxidant activity markers (SOD, CAT and GSH) and ATPase activities in chickens' liver. ELISA results showed that AFB1 exposure significantly induced the cytokines (TNF-α, iNOS, IL-6 and IL-1ß) release from the liver tissues. While, western blot and qRT-PCR results showed that the protein and mRNA expressions of inflammatory (TLR4/myd88/NF-κB) and necroptosis (RIPK1/RIPK3/MLKL) genes were up-regulated by AFB1 exposure. We suspect that signal crosstalk between TLR4 and TNF-α triggers inflammation and RIPK1/RIPK3 mediating necroptosis in AFB1-induced chicken liver injury. Curcumin can regulate the TLR4/RIPK signaling pathway, reduced oxidative stress biomarkers and inflammatory cytokines levels and attenuated the expression of necroptosis and inflammation genes altered by AFB1 to reduce necroptosis of chicken liver tissue. In conclusion, curcumin can protect against AFB1-induced necroptosis and inflammation by TLR4/RIPK pathway in chicken liver.

Spatial congruency or mismatch? Analyzing the COVID-19 potential infection risk and urban density as businesses reopen.

Countries worldwide are reopening their businesses despite the continuing COVID-19 crisis and the emergence of new variants. In this context, knowing whether the reopening of businesses at various locations exposes higher risk to the public is essential. Whether urban density correlates with the potential infection risk as concluded by previous studies of the COVID-19 pandemic remains unknown. In this study, taking the Macau Peninsula as a testbed, we first identified business locations for daily activities according to the latest point of interest (POI) data and generated the potential risk surface for COVID-19 infection. Then, using the cellular phone network and urban footprint data, we further analyzed the spatial relationship between COVID-19 potential risk and urban density of population and morphology through visual analytics. Results show that while some degree of spatial congruency exists between medium-risk peaks and urban density hotspots, apparent spatial mismatch exists for high-risk peaks, indicating that the traditional planning control based on urban density is inadequate for mitigating public health risks. POI-based spatial layout and configuration better reflecting business services and associated human activities are recommended in future planning and policy-making for more resilient cities in the post-pandemic era.

Curcumin protects against Aflatoxin B1-induced liver injury in broilers via the modulation of long non-coding RNA expression.

Aflatoxin B1 (AFB1) is a potent hepatotoxic and carcinogenic agent. Curcumin possesses potential anti-inflammatory, anti-oxidative and hepatoprotective effects. However, the role of LncRNAs in the protective mechanisms of curcumin against AFB1-induced liver damage is still elusive. Experimental broilers were randomly divided into 1) control group, 2) AFB1 group (1 mg/kg feed), 3) cur + AFB1 group (1 mg/kg AFB1 plus 300 mg/kg curcumin diet) and 4) curcumin group (300 mg/kg curcumin diet). Liver transcriptome analyses and qPCR were performed to identify shifts in genes expression. In addition, histopathological assessment and oxidant status were determined. Dietary AFB1 caused hepatic morphological injury, significantly increased the production of ROS, decreased liver antioxidant enzymes activities and induced inflammation and apoptosis. However, dietary curcumin partially attenuated the abnormal morphological changes, oxidative stress, and apoptosis in liver tissues. Transcriptional profiling results showed that 34 LncRNAs and 717 mRNAs were differentially expressed with AFB1 and curcumin co-treatment in livers of broilers. Analysis of the LncRNA-mRNA network, GO and KEGG enrichment data suggested that oxidative stress, inflammation and apoptosis pathway were crucial in curcumin's alleviating AFB1-induced liver damage. In conclusion, curcumin prevented AFB1-induced oxidative stress, inflammation and apoptosis through LncRNAs. These results provide new insights for unveiling the protective mechanisms of curcumin against AFB1-induced liver damage.

Virtual versus jaw simulation in Oral implant education: a randomized controlled trial.

BACKGROUND: This research aims to investigate the evaluation methods of teaching oral implant clinical courses and estimate the effectiveness of a virtual simulation platform. METHODS: Eighty second- and third-year undergraduates in Lanzhou University were recruited and randomized to either three experimental groups or one control group. The subjects undertook theoretical examinations to test their basic level of knowledge after training in similarly unified knowledge courses. Each student group then participated in an eight-hour operating training session. An operation test on pig mandible was conducted, followed by a second theoretical examination. The assessment consists of three distinct parts: a subjective operating score by a clinical senior teacher, an implant accuracy analysis in cone-beam computed tomography (angular, apical, and entrance deviation), and comparison of the two theoretical examinations. Finally, students completed a questionnaire gauging their understanding of the virtual simulation. RESULTS: There was no significant difference between the four groups in first theoretical examination (P > 0.05); the second theoretical scores of the V-J and J-V group (62.90 ± 3.70, 60.05 ± 2.73) were significantly higher than the first time (57.05 ± 3.92, P < 0.05), while no difference between the V (57.10 ± 3.66) and J (56.89 ± 2.67) groups was found. Thus, the combination of V-J was effective in improving students' theoretical scores. The V-J and J-V groups had higher scores on operation (73.98 ± 4.58, 71.85 ± 4.67) and showed better implant precision. CONCLUSION: Virtual simulation education, especially with a jaw simulation model, could improve students' implantology achievements and training. Currently study found that the V-J group may performed better than the J-V group in oral implant teaching.

Detection of Aflatoxin adducts as potential markers and the role of curcumin in alleviating AFB1-induced liver damage in chickens.

In this study, we identified AFB1 adducts as potential markers and investigated the role of curcumin in alleviating AFB1-induced liver damage by suppressing the production of AFB1 adducts and oxidative stress in AA broilers liver. A total of 64 one-day-old Arbor Acres (AA) broilers were randomly divided into four groups, including control group, AFB1 group (5 mg/kg AFB1), cur + AFB1 group (300 mg/kg curcumin+5 mg/kg AFB1) and curcumin group (300 mg/kg). Serum biochemical parameters, liver antioxidant abilities, AFB1 adducts and oxidative stress mechanism were studied in broilers. AFB1 administration accompany with signs of liver injury, including hepatic histological lesions, increased serum enzymes activities, decreased liver antioxidant enzymes activities and the suppression of ROS and 8-OHdG. Meanwhile, Nrf2/HO-1 pathway was depressed by AFB1 treatment. Immunohistochemistry and ELISA showed that AFB1 significantly increased AFB1-DNA adduct in liver (p < 0.05) and AFB1-lysine adduct in serum (p < 0.05). Importantly, supplementation of curcumin can ameliorate these alterations. Intriguingly, curcumin alleviated AFB1-induced toxicity and oxidative stress by inhibiting the generation of ROS, 8-OHdG and AFB1 adducts, and activated Nrf2 signaling pathway in broilers. Conclusively, our experiments suggest that curcumin could be considered as a potential agent for prevention of AFB1-induced toxicity and oxidative stress, and AFB1 adducts could be suitable therapeutic targets.

Curcumin confers hepatoprotection against AFB1-induced toxicity via activating autophagy and ameliorating inflammation involving Nrf2/HO-1 signaling pathway.

The current study demonstrated curcumin intervention against AFB1-indeuced hepatotoxicity. The hallmarks of autophagy and inflammation were assessed by transmission electron microscopy, RT-PCR and western blot. Besides, normal cellular morphology, autophagosomes were found in control and curcumin control group. In contrast, fragmented and swollen mitochondria, irregular shaped nuclei and fat droplets were visible but autophagosomes disappear in AFB1-treated group. The mRNA and protein expression levels of autophagy-related genes indicated that AFB1 significantly inhibited autophagy and induced inflammation. In addition, Nrf2 and HO-1 mRNA and protein level was significantly (p < 0.05) reduced in AFB1-fed group. Intriguingly, dietary curcumin supplementation modulated autophagy through the activation of beclin-1, ATG5, Dynein, LC3a, LC3b-I/II and downregulation of p53 & mTOR expression level. Curcumin significantly ameliorated AFB1-induced inflammation. Moreover, curcumin treatment significantly (p < 0.05) elevated AFB1-induced decrease in Nrf2 and HO-1 mRNA and protein expression level. In summary, curcumin activated autophagy and ameliorated inflammation involving Nrf2 signaling pathway which may become a new targeted therapy to prevent AFB1-induced hepatotoxicity.

Association between biological aging and periodontitis using NHANES 2009-2014 and mendelian randomization.

Aging is a recognized risk factor for periodontitis, while biological aging could provide more accurate insights into an individual's functional status. This study aimed to investigate the potential association between biological aging and periodontitis. Epidemiological data from 9803 participants in the 2009-2014 National Health and Nutrition Examination Survey were analyzed at a cross-sectional level to assess this link. Three biological ages [Klemera-Doubal method (KDM), PhenoAge, and homeostatic dysregulation (HD)] and two measures of accelerated biological aging (BioAgeAccel and PhenoAgeAccel) were set as primary exposure and were calculated. Logistic regression and restricted cubic spline regression were employed to examine the relationship between biological aging and periodontitis. Additionally, Mendelian randomization analysis was conducted to explore the causal connection between accelerated biological aging and periodontitis. After adjusting for age, gender, race, educational level, marital status, ratio of family income, and disease conditions, this study, found a significant association between subjects with older higher biological ages, accelerated biological aging, and periodontitis. Specifically, for a per year increase in the three biological ages (HD, KDM, and PhenoAge), the risk of periodontitis increases by 15%, 3%, and 4% respectively. Individuals who had positive BioAgeAccel or PhenoAgeAccel were 20% or 37% more likely to develop periodontitis compared with those who had negative BioAgeAccel or PhenoAgeAccel. Furthermore, a significant non-linear positive relationship was observed between the three biological ages, accelerated biological aging, and periodontitis. However, the Mendelian randomization analysis indicated no causal effect of accelerated biological aging on periodontitis. Our findings suggest that biological aging may contribute to the risk of periodontitis, highlighting the potential utility of preventive strategies targeting aging-related pathways in reducing periodontitis risk among older adults.

Deep learning based approach: automated gingival inflammation grading model using gingival removal strategy.

Gingival inflammation grade serves as a well-established index in periodontitis. The aim of this study was to develop a deep learning network utilizing a novel feature extraction method for the automatic assessment of gingival inflammation. T-distributed Stochastic Neighbor Embedding (t-SNE) was utilized for dimensionality reduction. A convolutional neural network (CNN) model based on DenseNet was developed for the identification and evaluation of gingival inflammation. To enhance the performance of the deep learning (DL) model, a novel teeth removal algorithm was implemented. Additionally, a Grad-CAM + + encoder was applied to generate heatmaps for computer visual attention analysis. The mean Intersection over Union (MIoU) for the identification of gingivitis was 0.727 ± 0.117. The accuracy rates for the five inflammatory degrees were 77.09%, 77.25%, 74.38%, 73.68% and 79.22%. The Area Under the Receiver Operating Characteristic (AUROC) values were 0.83, 0.80, 0.81, 0.81 and 0.84, respectively. The attention ratio towards gingival tissue increased from 37.73% to 62.20%, and within 8 mm of the gingival margin, it rose from 21.11% to 38.23%. On the gingiva, the overall attention ratio increased from 51.82% to 78.21%. The proposed DL model with novel feature extraction method provides high accuracy and sensitivity for identifying and grading gingival inflammation.

The Global Research Trends on Intrinsic Capacity of Older Adults: A Bibliometric and Visual Analysis of Papers Published During 2015-2023.

Objective: The concept of intrinsic capacity (IC) revolves around healthy aging and active aging. Since the Introduction of the concept by the World Health Organization in 2015, a series of studies have been conducted by scholars from multiple fields. However, no bibliometric analysis has systematically investigated this issue. We aim to identify the current landscape and frontier trends of scientific achievements on IC in older adults through bibliometric approaches. Methods: Quantitative analysis of publications relating to IC in older adults from 2015 to 2023 was interpreted and graphed through the Web of Science Core Collection database on December 5, 2023. A variety of quantitative variables was analyzed, including publication and citation counts, H-index, and journal citation reports. Co-authorship, citation, co-citation, and co-occurrence analyses were performed for countries/regions, institutions, authors, and keywords using the VOSviewer and CiteSpace. Results: A total of 952 original and review articles in English were identified. The European countries possessed an absolute advantage in this field. The most contributive institution was the University of São Paulo. The most productive author is Cesari Matteo from France, followed by Qaisar Rizwan from the United Arab Emirates. However, a relatively low level of research cooperation existed between institutions and authors. Important topics mainly include the connotations, theoretical framework models, evaluation, screening tools, and application scenarios of IC. Among the promising hotspots, "biological aging", "ICOPE", "Covid-19", "prevention", "inflammation", "caf22", "prevalence", and "randomized controlled trial" displayed relatively latest average appearing year. Conclusion: Global trends indicate a growing scientific output on IC in older adults, and developed countries are leading the way. There is still room for improvement in research team collaboration. The focus gradually shifts from theoretical research to empirical research. It is recommended to pay attention to the latest hot spots, such as "biological aging", "ICOPE implementation", "post-COVID-19 syndrome", and "biomarkers".

Curcumin alleviates Aflatoxin B1-triggered chicken liver necroptosis by targeting the LOC769044/miR-1679/STAT1 axis.

Aflatoxin B1 (AFB1) is an unavoidable environmental toxin. The accumulation of AFB1 and its metabolites in the liver poses a threat to both human and animal health. Curcumin exhibits anti-oxidative, anti-tumor, and anti-inflammatory properties. There is no report on the mechanism regarding how curcumin relived liver necroptosis in chickens induced by AFB1 based on the regulatory network of ceRNA. To explore this, we performed transmission electron microscopy and sequenced lncRNA and mRNA in chicken livers treated with AFB1 and/or curcumin for 28 d in vivo. We observed substantial alterations in the lncRNA and mRNA expression profiles within the chicken liver, indicating that curcumin can mitigate AFB1-induced necroptosis both in vivo and in vitro. Further analysis, including the establishment of an lncRNA-miRNA-mRNA network and the utilization of a dual luciferase reporter assay, revealed that LOC769044 acts as a competing endogenous RNA (ceRNA) for miR-1679. In addition, STAT1 was identified as a direct target of miR-1679. Modulating miR-1679 levels through overexpression, and silencing LOC769044 and STAT1, effectively reversed the necroptotic effects induced by AFB1, a reversal that was also observed with curcumin supplementation. In conclusion, our data demonstrate that curcumin alleviates AFB1-induced liver necroptosis through the LOC769044/miR-1679/STAT1 signaling axis. This study suggests that LOC769044 may serve as a novel therapeutic target for managing AFB1-mediated liver toxicity.

Renal Tissue-Derived Exosomal miRNA-34a in Diabetic Nephropathy Induces Renal Tubular Cell Fibrosis by Promoting the Polarization of M1 Macrophages.

Background: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease, and the activation and infiltration of phagocytes are critical steps of DN. This study aimed to explore the mechanism of exosomes in macrophages and diabetes nephropathy and the role of miRNA-34a, which might provide a new path for treating DN. Materials and Methods: The DN model was established, and the success of the model establishment was confirmed by detecting general indicators, HE staining, and immunohistochemistry. Electron microscopy and NanoSight Tracking Analysis (NTA) were used to see the morphology and size of exosomes. MiRNA-34a inhibitor, miRNA-34a mimics, pc-PPARGC1A, and controls were transfected in macrophages with or without kidney exosomal. A dual-luciferase reporter gene experiment verifies the targeting relationship between miRNA-34a and PPARGC1A. After exosomal culture, macrophages are co-cultured with normal renal tubular cells to detect renal tubular cell fibrosis. Q-PCR and western blot were undertaken to detect related RNA and proteins. Results: An animal model of diabetic nephropathy was successfully constructed. Macrophages could phagocytose exosomes. After ingesting model exosomes, M1 macrophages were activated, while M2 macrophages were weakened, indicating the model mice's kidney exosomes caused the polarization. MiRNA-34a inhibitor increased PPARGC1A expression. MiRNA-34a expressed higher in diabetic nephropathy Model-Exo. MiRNA-34a negatively regulated PPARGC1A. PPARGC1A rescued macrophage polarization and renal tubular cell fibrosis. Conclusion: Exosomal miRNA-34a of tubular epithelial cells promoted M1 macrophage activation in diabetic nephropathy via negatively regulating PPARGC1A expression, which may provide a new direction for further exploration of DN treatment.

Core items selection and psychometric properties of the adult attention-deficit hyperactivity disorder self-report scale-chinese short version (ASRS-CSV).

OBJECTIVE: This study aimed to develop and validate the Chinese Short Version of the Adult ADHD Self-Report Scale (ASRS-CSV), addressing the need for culturally appropriate diagnostic tools for Attention-Deficit Hyperactivity Disorder (ADHD) in the Chinese adult population. METHODS: Utilizing a combination of intergroup difference analysis, factor analysis, and network analysis, we identified core ADHD symptoms pertinent to the Chinese cultural context. The study involved two samples: a vocational and technical school sample (N=1144) and an internet sample (N=1654), comprising adults aged 16-25 years. Reliability, validity, and diagnostic efficacy of the ASRS-CSV were assessed through psychometric testing. RESULTS: The ASRS-CSV demonstrated high internal consistency (Cronbach's alpha > 0.9) and robust convergent validity (AVE > 0.7). The scale's diagnostic cutoff points were optimized, revealing high sensitivity and specificity for ADHD screening. Cross-cultural analysis highlighted differences in core ADHD symptoms between Chinese and Western populations, underscoring the scale's cultural sensitivity. CONCLUSION: The ASRS-CSV is a reliable, valid, and efficient tool for screening ADHD in Chinese adults, reflecting the socio-cultural nuances of ADHD symptomatology. Its development marks a significant advancement in the field of psychiatry, offering a tailored approach for ADHD assessment in China and contributing to the global discourse on cross-cultural psychiatric diagnosis.

Downregulation of nutrition sensor GCN2 in macrophages contributes to poor wound healing in diabetes.

Poor skin wound healing, which is common in patients with diabetes, is related to imbalanced macrophage polarization. Here, we find that nutrition sensor GCN2 (general control nonderepressible 2) and its downstream are significantly upregulated in human skin wound tissue and mouse skin wound macrophages, but skin wound-related GCN2 expression and activity are significantly downregulated by diabetes and hyperglycemia. Using wound healing models of GCN2-deleted mice, bone marrow chimeric mice, and monocyte-transferred mice, we show that GCN2 deletion in macrophages significantly delays skin wound healing compared with wild-type mice by altering M1 and M2a/M2c polarization. Mechanistically, GCN2 inhibits M1 macrophages via OXPHOS-ROS-NF-κB pathway and promotes tissue-repairing M2a/M2c macrophages through eukaryotic translation initiation factor 2 (eIF2α)-hypoxia-inducible factor 1α (HIF1α)-glycolysis pathway. Importantly, local supplementation of GCN2 activator halofuginone efficiently restores wound healing in diabetic mice with re-balancing M1 and M2a/2c polarization. Thus, the decreased macrophage GCN2 expression and activity contribute to poor wound healing in diabetes and targeting GCN2 improves wound healing in diabetes.