Maternal high fat diet induces circadian clock-independent endocrine alterations impacting the metabolism of the offspring.

Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.

Integration of proteomics and metabolomics reveals energy and metabolic alterations induced by glucokinase (GCK) partial inactivation in hepatocytes.

AIMS: Glucokinase (GCK) acts as the glucose sensor in maintaining glucose homeostasis. The inactivating mutation of the GCK gene leads to glucokinase-maturity onset diabetes of the young (GCK-MODY). This study aims to gain further insights into the molecular alterations triggered by GCK partial inactivation in hepatocytes, potentially underlying the favorable prognosis of GCK-MODY. MAIN METHODS: A GCK knockdown HepG2 cell model was established, and the integration of proteomics and metabolomics was used to gain a comprehensive understanding of the molecular pathway changes caused by GCK inactivation in the liver. KEY FINDINGS: Proteomic analysis identified 257 differential proteins. KEGG pathway enrichment analysis showed that protein expression changes in the GCK knockdown group were significantly enriched in central carbon metabolism, the TCA cycle, amino acid metabolism and the oxidative phosphorylation pathway. Among them, enzymes in the TCA cycle (PC, IDH2, SDH) were significantly downregulated in GCK-knockdown group. Targeted metabolomics revealed that in the GCK knockdown hepatocytes, TCA cycle intermediates were significantly decreased, including pyruvate, oxaloacetate, citrate and succinic acid, and three metabolites increased including glycine, betaine and homocysteine. These metabolic alterations in turn reduced the accumulation of reactive oxygen species in GCK knockdown hepatocytes. Correlation analysis indicated that TCA cycle metabolites were positively correlated with proteins involved in the TCA cycle, carbon metabolism, glycolysis, Ras signaling, fibrosis and inflammation. SIGNIFICANCE: In conclusion, GCK knockdown reduced TCA cycle flux and oxidative stress in hepatocytes by influencing the levels of key transcription factors and enzymes, providing a comprehensive understanding of the effects of GCK partial inactivation on liver metabolism and molecular mechanisms.

Association of systemic immune-inflammation-index with all-cause and cause-specific mortality among type 2 diabetes: a cohort study base on population.

PURPOSE: There have been limited studies examining the prospective association between the Systemic Immune-Inflammation Index (SII), a novel inflammatory marker, and mortality among individuals with diabetes in the United States. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of US adults, linked with information from the National Death Index. RESULTS: Our study included 8697 individuals from NHANES spanning the years 1999 to 2018. SII was calculated by dividing the platelet count by the neutrophil count and then dividing that result by the lymphocyte count. We employed multivariable Cox proportional hazards regression analysis to investigate the associations between SII levels and all-cause as well as cause-specific mortality, while adjusting for potential confounding factors. SII levels were categorized into quartiles based on the study population distribution. Over a median follow-up period of 94.8 months (with a maximum of 249 months), we observed a total of 2465 all-cause deaths, 853 deaths from cardiovascular causes, 424 deaths from cancer, and 88 deaths related to chronic kidney disease. After adjusting for multiple variables, higher SII levels were significantly and non-linearly associated with an increased risk of all-cause mortality in Quartile 4 (HR 1.74, 95% CI 1.15-2.63, P for trend = 0.043) when Quartile 1 was used as the reference group. Additionally, we identified a linear association between SII and cardiovascular mortality, with a 70% higher risk of cardiovascular mortality in Quartile 4 (HR 1.70, 95% CI 1.18-3.30, P for trend = 0.041) compared to Quartile 1. CONCLUSION: Our findings indicate that SII is significantly associated with an elevated risk of all-cause and cardiovascular mortality in US adults with diabetes.

Efficacy and mechanism of Shenqi Compound in inhibiting diabetic vascular calcification.

BACKGROUND: Shenqi Compound (SQC) has been used in clinic for several decades in the prevention and treatment of diabetes and its complications. But this is merely a heritage of experience. The primary aim of this study is to scientifically validate the therapeutic effects of SQC on diabetic vascular calcification (DVC) in an animal model and, simultaneously, uncover its potential underlying mechanisms. METHOD: Spontaneous diabetic rat- Goto Kakizaki (GK) rats were selected for rat modeling. We meticulously designed three distinct groups: a control group, a model group, and an SQC treatment group to rigorously evaluate the influence of SQC. Utilizing a comprehensive approach that encompassed methods such as pathological staining, western blot analysis, qRT-PCR, and RNA sequencing, we thoroughly investigated the therapeutic advantages and the underlying mechanistic pathways associated with SQC in the treatment of DVC. RESULT: The findings from this investigation have unveiled the extraordinary efficacy of SQC treatment in significantly mitigating DVC. The underlying mechanisms driving this effect encompass multifaceted facets, including the restoration of aberrant glucose and lipid metabolism, the prevention of phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteogenic-like states, the subsequent inhibition of cell apoptosis, the modulation of inflammation responses, the remodeling of the extracellular matrix (ECM), and the activation of the Hippo-YAP signaling pathway. Collectively, these mechanisms lead to the dissolution of deposited calcium salts, ultimately achieving the desired inhibition of DVC. CONCLUSION: Our study has provided compelling and robust evidence of the remarkable efficacy of SQC treatment in significantly reducing DVC. This reduction is attributed to a multifaceted interplay of mechanisms, each playing a crucial role in the observed therapeutic effects. Notably, our findings illuminate prospective directions for further research and potential clinical applications in the field of cardiovascular health.

Characterization of the horse chestnut genome reveals the evolution of aescin and aesculin biosynthesis.

Horse chestnut (Aesculus chinensis) is an important medicinal tree that contains various bioactive compounds, such as aescin, barrigenol-type triterpenoid saponins (BAT), and aesculin, a glycosylated coumarin. Herein, we report a 470.02 Mb genome assembly and characterize an Aesculus-specific whole-genome duplication event, which leads to the formation and duplication of two triterpenoid biosynthesis-related gene clusters (BGCs). We also show that AcOCS6, AcCYP716A278, AcCYP716A275, and AcCSL1 genes within these two BGCs along with a seed-specific expressed AcBAHD6 are responsible for the formation of aescin. Furthermore, we identify seven Aesculus-originated coumarin glycoside biosynthetic genes and achieve the de novo synthesis of aesculin in E. coli. Collinearity analysis shows that the collinear BGC segments can be traced back to early-diverging angiosperms, and the essential gene-encoding enzymes necessary for BAT biosynthesis are recruited before the splitting of Aesculus, Acer, and Xanthoceras. These findings provide insight on the evolution of gene clusters associated with medicinal tree metabolites.

Quantitative profiling and diagnostic potential of one-carbon and central metabolism pools in MODY2 and T1DM.

BACKGROUND: Maturity-onset diabetes of the young type 2 (MODY2) is a rare genetic disorder characterized as mild fasting hyperglycemia with low risk of vascular complications caused by glucokinase gene mutation. This study aims to investigate metabolites alteration associated with MODY2, exploring possible mechanism underlying characteristic clinical manifestations and low cardiovascular risks of MODY2 and providing serum metabolite biomarkers to facilitating MODY2 diagnosis. METHODS: Fasting serum samples from MODY2, type 1 diabetes (T1DM) and healthy individuals were collected. By using targeted metabolomics via liquid chromatography-tandem mass spectrometry platform, we quantified the metabolites involved in tricarboxylic acid (TCA) cycle and one-carbon metabolism. RESULTS: Metabolomic profiling revealed significant difference of intermediates from central metabolism cycle, methionine cycle and several amino acids between MODY2 and T1DM groups. Among these, serum citrate, α-ketoglutaric acid, serine, glycine, glutamine and homocysteine were significantly elevated in MODY2 patients compared with T1DM patients; and compared with healthy subjects, malate and methionine levels were significantly increased in the two groups of diabetic patients. The correlation analysis with clinical indexes showed that α- ketoglutarate, serine, glycine, and glutamine were negatively correlated with blood glucose indicators including fasting blood glucose, HbA1c, and GA, while citrate was positively correlated with C-peptide. And homocysteine displayed positive correlation with HDL and negative with C-reactive protein, which shed light on the mechanism of mild symptoms and low risk of cardiovascular complications in MODY2 patients. A panel of 4 metabolites differentiated MODY2 from T1DM with AUC of 0.924, and a combination of clinical indices and metabolite also gained good diagnostic value with AUC 0.948. CONCLUSION: In this research, we characterized the metabolite profiles of TCA cycle and one-carbon metabolism in MODY2 and T1DM and identified promising diagnostic biomarkers for MODY2. This study may provide novel insights into the pathogenesis and clinical manifestations of MODY2.

Modular characteristics and mechanism of action of herbs for type 2 diabetes treatment in Chinese medicine.

Type 2 diabetes (T2D) has emerged as a global epidemic, and conventional treatment approaches often face limitations in achieving long-term glycemic control and preventing complications. Traditional Chinese Medicine (TCM) offers a valuable alternative for managing T2D, with a long history of effectively using herbal formulations in clinical practice. However, the modular characteristics of these herbs and their specific mechanisms of action remain poorly understood. To comprehensively investigate the modular characteristics and mechanisms of Chinese herbs in treating T2D, as well as explore the synergistic interactions among different herbs and their modular components, we employed data mining, systematic pharmacology, and molecular docking. Our aim was to gain a comprehensive understanding of the potential therapeutic targets and pathways involved in herbal T2D treatment. In this study, a total of 1114 studies investigating the effects of TCM interventions in the treatment of T2D in adults were included. The analysis revealed 170 distinct types of Chinese herbs, 118 active components, and 238 common targets shared between the medicine and T2D. Additionally, this study identified six hub proteins (TNF, MMP2, PTGS, CASP3, CASP8, and CASP9) and two key chemicals (Diosgenin and Formononetin) found in TCM-mediated T2D suppression. It was observed that these proteins could bind with the ingredients. The MMP2-Diosgenin interaction exhibited the lowest binding free energy (-13.05 kJ/mol) and was primarily driven by hydrogen bonds with ALA-165. TNF-Diosgenin (-10.5 kcal/mol) showed three hydrogen bonds with LEU-37, ARG-82, and ASN-30. PTGS2 and Diosgenin (-8.71 kJ/mol) demonstrated a hydrogen bond with HIS-214. Furthermore, CASP9-Formononetin (-6.53 kcal/mol) exhibited the lowest binding free energy and hydrogen bonds with GLU-261 and SER-339 as the primary forces involved. CASP3-Formononetin (-6.07 kcal/mol) displayed three hydrogen bonds with ASN-342, TRP-348, and GLU-379. Lastly, CASP8 and Formononetin (-6.06 kJ/mol) formed a hydrogen bond with THR-390, TYR-392, and TYR-334. Moreover, critical therapeutic pathways, such as the immune inflammatory response, AGE-RAGE, and IL-17 signaling pathway, were found to be associated with T2D Chinese herb therapy. In conclusion, this study sheded light on the modular characteristics and mechanism of action of herbs used in Chinese Medicine for the treatment of T2D, which provided valuable insights for both researchers and practitioners in the field of Chinese Medicine, offering potential avenues for improved treatment strategies and personalized approaches to address the complex nature of T2D.

Recent progress in identification of water disinfection byproducts and opportunities for future research.

Numerous disinfection by-products (DBPs) are formed from reactions between disinfectants and organic/inorganic matter during water disinfection. More than seven hundred DBPs that have been identified in disinfected water, only a fraction of which are regulated by drinking water guidelines, including trihalomethanes, haloacetic acids, bromate, and chlorite. Toxicity assessments have demonstrated that the identified DBPs cannot fully explain the overall toxicity of disinfected water; therefore, the identification of unknown DBPs is an important prerequisite to obtain insights for understanding the adverse effects of drinking water disinfection. Herein, we review the progress in identification of unknown DBPs in the recent five years with classifications of halogenated or nonhalogenated, aliphatic or aromatic, followed by specific halogen groups. The concentration and toxicity data of newly identified DBPs are also included. According to the current advances and existing shortcomings, we envisioned future perspectives in this field.

Cannabis sativa: origin and history, glandular trichome development, and cannabinoid biosynthesis.

Is Cannabis a boon or bane? Cannabis sativa has long been a versatile crop for fiber extraction (industrial hemp), traditional Chinese medicine (hemp seeds), and recreational drugs (marijuana). Cannabis faced global prohibition in the twentieth century because of the psychoactive properties of ∆9-tetrahydrocannabinol; however, recently, the perspective has changed with the recognition of additional therapeutic values, particularly the pharmacological potential of cannabidiol. A comprehensive understanding of the underlying mechanism of cannabinoid biosynthesis is necessary to cultivate and promote globally the medicinal application of Cannabis resources. Here, we comprehensively review the historical usage of Cannabis, biosynthesis of trichome-specific cannabinoids, regulatory network of trichome development, and synthetic biology of cannabinoids. This review provides valuable insights into the efficient biosynthesis and green production of cannabinoids, and the development and utilization of novel Cannabis varieties.

The protective role of shenqi compound in type 2 diabetes: A comprehensive investigation of pancreatic ß-cell function and mass.

Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by impaired insulin secretion and insulin resistance, resulting in elevated blood glucose levels. The dysfunction and loss of pancreatic ß-cells, responsible for producing insulin, contribute to the development of T2D. Traditional Chinese medicine (TCM) has emerged as a potential source of innovative therapeutic interventions. However, limited research exists on Chinese herbal formulations specifically targeting the protection of pancreatic ß-cell function and mass. One such formulation is the Shenqi compound (SQC), widely used in China and consisting of Panax Ginseng, Astragali Radix, Rhizoma Dioscoreae, Corni Fructus, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Radix Trichosanthis, and Rhei Radix et Rhizoma. Understanding the mechanisms underlying the therapeutic effects of SQC is crucial for developing novel treatment strategies for T2D. This study aims to comprehensively investigate the scientific evidence supporting the role of SQC in alleviating T2D by targeting the protection of pancreatic ß-cell function and mass. Spontaneously diabetic GK rats were used as the animal model, receiving SQC (14.4 g/kg/d) for 8 weeks. The results demonstrate multiple beneficial effects of SQC, including significant control of blood glucose levels (P < 0.05), inhibition of insulin resistance (measured by Western Blot), reduction of hyperinsulinemia (P < 0.05), attenuation of oxidative stress (P < 0.05), suppression of inflammation (P < 0.05), protection against islet hypertrophy and beta cell proliferation (evaluated through pathological staining), and inhibition of ß-cell apoptosis and senescence (also assessed through pathological staining). These findings indicate the promotion of ß-cell survival and function. In vitro experiments using isolated islets further support these results, revealing improvements in insulin secretion (P < 0.05) and ß-cell function following SQC therapy (P < 0.05). This represents a significant breakthrough in addressing ß-cell dysfunction and preserving mass within the context of TCM. Overall, SQC shows promise as a natural therapeutic approach for T2D, with potential benefits in preserving pancreatic ß-cell function and mass. This enhances the practical applicability and significance of the research by bridging the gap between experimental findings and clinical practice, thereby providing important clinical value in TCM treatment of T2D. Further research is necessary to elucidate its precise mechanisms of action and optimize its clinical application.

Combination of Pioglitazone and Metformin Actions on Liver Lipid Metabolism in Obese Mice.

BACKGROUND: Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. METHODS: Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. RESULTS: The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Cd36, Fads1, Fads2, Fasn, Scd1, Elovl5 and Pklr in the combined therapy group. CONCLUSIONS: Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects.

Screening and Metabolomic Analysis of Lactic Acid Bacteria-Antagonizing Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a conditional Gram-negative pathogen that produces extracellular virulence factors that can lead to bloodstream invasion, severely harm tissues, and disseminate bacteria, ultimately leading to various diseases. In this study, lactic acid bacteria (LAB) with strong antagonistic ability against P. aeruginosa were screened, and the regulatory mechanism of LAB against P. aeruginosa was evaluated. The results showed that the three selected LAB strains had strong inhibition ability on the growth, biofilm formation, and pyocyanin expression of P. aeruginosa and a promoting effect on the expression of autoinducer-2. Among them, Lactipantibacillus plantarum (Lp. plantarum) LPyang is capable of affecting the metabolic processes of P. aeruginosa by influencing metabolic substances, such as LysoPC, oxidized glutathione, betaine, etc. These results indicate that LPyang reduces the infectivity of P. aeruginosa through inhibition of its growth, biofilm formation, pyocyanin expression, and regulation of its metabolome. This study provides new insights into the antagonistic activity of Lp. plantarum LPyang against P. aeruginosa.

Glucokinase Inactivation Ameliorates Lipid Accumulation and Exerts Favorable Effects on Lipid Metabolism in Hepatocytes.

Glucokinase-maturity onset diabetes of the young (GCK-MODY) is a kind of rare diabetes with low incidence of vascular complications caused by GCK gene inactivation. This study aimed to investigate the effects of GCK inactivation on hepatic lipid metabolism and inflammation, providing evidence for the cardioprotective mechanism in GCK-MODY. We enrolled GCK-MODY, type 1 and 2 diabetes patients to analyze their lipid profiles, and found that GCK-MODY individuals exhibited cardioprotective lipid profile with lower triacylglycerol and elevated HDL-c. To further explore the effects of GCK inactivation on hepatic lipid metabolism, GCK knockdown HepG2 and AML-12 cell models were established, and in vitro studies showed that GCK knockdown alleviated lipid accumulation and decreased the expression of inflammation-related genes under fatty acid treatment. Lipidomic analysis indicated that the partial inhibition of GCK altered the levels of several lipid species with decreased saturated fatty acids and glycerolipids including triacylglycerol and diacylglycerol, and increased phosphatidylcholine in HepG2 cells. The hepatic lipid metabolism altered by GCK inactivation was regulated by the enzymes involved in de novo lipogenesis, lipolysis, fatty acid ß-oxidation and the Kennedy pathway. Finally, we concluded that partial inactivation of GCK exhibited beneficial effects in hepatic lipid metabolism and inflammation, which potentially underlies the protective lipid profile and low cardiovascular risks in GCK-MODY patients.

Emerging Role of Protein O-GlcNAcylation in Liver Metabolism: Implications for Diabetes and NAFLD.

O-linked b-N-acetyl-glucosaminylation (O-GlcNAcylation) is one of the most common post-translational modifications of proteins, and is established by modifying the serine or threonine residues of nuclear, cytoplasmic, and mitochondrial proteins. O-GlcNAc signaling is considered a critical nutrient sensor, and affects numerous proteins involved in cellular metabolic processes. O-GlcNAcylation modulates protein functions in different patterns, including protein stabilization, enzymatic activity, transcriptional activity, and protein interactions. Disrupted O-GlcNAcylation is associated with an abnormal metabolic state, and may result in metabolic disorders. As the liver is the center of nutrient metabolism, this review provides a brief description of the features of the O-GlcNAc signaling pathway, and summarizes the regulatory functions and underlying molecular mechanisms of O-GlcNAcylation in liver metabolism. Finally, this review highlights the role of O-GlcNAcylation in liver-associated diseases, such as diabetes and nonalcoholic fatty liver disease (NAFLD). We hope this review not only benefits the understanding of O-GlcNAc biology, but also provides new insights for treatments against liver-associated metabolic disorders.

Key circRNAs, lncRNAs, and mRNAs of ShenQi Compound in Protecting Vascular Endothelial Cells From High Glucose Identified by Whole Transcriptome Sequencing.

ABSTRACT: Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.

Serum metabolomics identified metabolite biomarkers and distinguished maturity-onset diabetes of the young from type 1 diabetes in the Chinese population.

BACKGROUND: Maturity-onset diabetes of the young (MODY) patients have unique clinical manifestations and need individualized treatments. We identified novel serum metabolic biomarkers to distinguish MODY and explore the possible mechanism of the clinical manifestation and complications of MODY. METHODS: Fasting serum samples were collected from MODY3 (n = 17), MODY2 (n = 33), type 1 diabetes (T1DM) (n = 34) and healthy individuals (n = 30), and were analyzed using the ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolomic platform. RESULTS: 4 metabolites were found significantly fluctuated between groups, including glycerophosphocholine, LysoPC(18:2(9Z,12Z)), sphinganine and l-Phenylalanine. Glycerophosphocholine was selected as a diagnostic biomarker. The the area under the ROC curve (AUC) for distinguishing MODYs from healthy controls and differentiating MODY3 from T1DM reached 1.0. The combination of metabolites also gained good diagnostic value. The AUC of the combination of LysoPC(18:2(9Z,12Z)), sphinganine and l-Phenylalanine for discriminating MODY3 from T1DM was 0.983. Besides, the combination of clinical indices and metabolites helped to better differentiate the 2 MODY subtypes. CONCLUSIONS: We identified the metabolic profiles of MODY2 and MODY3 and found promising biomarkers for distinguishing MODY from T1DM, which provides evidence for the pathogenesis and characteristic clinical manifestations of patients with MODY2 and MODY3.

Novel biomarkers and therapeutic approaches for diabetic retinopathy and nephropathy: Recent progress and future perspectives.

The global burden due to microvascular complications in patients with diabetes mellitus persists and even increases alarmingly, the intervention and management are now encountering many difficulties and challenges. This paper reviews the recent advancement and progress in novel biomarkers, artificial intelligence technology, therapeutic agents and approaches of diabetic retinopathy and nephropathy, providing more insights into the management of microvascular complications.

Arctigenin Attenuates Vascular Inflammation Induced by High Salt through TMEM16A/ESM1/VCAM-1 Pathway.

Salt-sensitive hypertension is closely related to inflammation, but the mechanism is barely known. Transmembrane member 16A (TMEM16A) is the Ca2+-activated chloride channel in epithelial cells, smooth muscle cells, and sensory neurons. It can promote inflammatory responses by increasing proinflammatory cytokine release. Here, we identified a positive role of TMEM16A in vascular inflammation. The expression of TMEM16A was increased in high-salt-stimulated vascular smooth muscle cells (VSMCs), whereas inhibiting TMEM16A or silencing TMEM16A with small interfering RNA (siRNA) can abolish this effect in vitro or in vivo. Transcriptome analysis of VSMCs revealed some differential downstream genes of TMEM16A related to inflammation, such as endothelial cell-specific molecule 1 (ESM1) and CXC chemokine ligand 16 (CXCL16). Overexpression of TMEM16A in VSMCs was accompanied by high levels of ESM1, CXCL16, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1). We treated VSMCs cultured with high salt and arctigenin (ARC), T16Ainh-A01 (T16), and TMEM16A siRNA (siTMEM16A), leading to greatly decreased ESM1, CXCL16, VCAM-1, and ICAM-1. Beyond that, silencing ESM1, the expression of VCAM-1 and ICAM-1, and CXCL16 was attenuated. In conclusion, our results outlined a signaling scheme that increased TMEM16 protein upregulated ESM1, which possibly activated the CXCL16 pathway and increased VCAM-1 and ICAM-1 expression, which drives VSMC inflammation. Beyond that, arctigenin, as a natural inhibitor of TMEM16A, can reduce the systolic blood pressure (SBP) of salt-sensitive hypertension mice and alleviate vascular inflammation.

Effect of microplastics on nasal and intestinal microbiota of the high-exposure population.

Background: Microplastic has become a growing environmental problem. A balanced microbial environment is an important factor in human health. This study is the first observational cross-sectional study focusing on the effects of microplastics on the nasal and gut microbiota in a highly exposed population. Methods: We recruited 20 subjects from a Plastic Factory (microplastics high-exposure area) and the other 20 from Huanhuaxi Park (microplastics low-exposure area) in Chengdu, China. We performed the microplastic analysis of soil, air, and intestinal secretions by laser infrared imaging, and microbiological analysis of nasal and intestinal secretions by 16S rDNA sequencing. Results: The result shows that the detected points of microplastics in the environment of the high-exposure area were significantly more than in the low-exposure area. Polyurethane was the main microplastic component detected. The microplastic content of intestinal secretions in the high-exposure group was significantly higher than in the low-exposure group. Specifically, the contents of polyurethane, silicone resin, ethylene-vinyl acetate copolymer, and polyethylene in the high-exposure group were significantly higher than in the low-exposure group. Moreover, high exposure may increase the abundance of nasal microbiotas, which are positively associated with respiratory tract diseases, such as Klebsiella and Helicobacter, and reduce the abundance of those beneficial ones, such as Bacteroides. Simultaneously, it may increase the abundance of intestinal microbiotas, which are positively associated with digestive tract diseases, such as Bifidobacterium, Streptococcus, and Sphingomonas, and reduce the abundance of intestinal microbiotas, which are beneficial for health, such as Ruminococcus Torquesgroup, Dorea, Fusobacterium, and Coprococcus. A combined analysis revealed that high exposure to microplastics may not only lead to alterations in dominant intestinal and nasal microbiotas but also change the symbiotic relationship between intestinal and nasal microbiotas. Conclusion: The results innovatively revealed how microplastics can affect the intestinal and nasal microecosystems. Clinical trial registration: ChiCTR2100049480 on August 2, 2021.

The Influence of Culture and Art Management on the Healthy Development of Cultural Economy Industry under the Background of Sustainable Ecological Environment.

In the context of sustainable ecological environment, strengthening the scientific management of cultural industry can promote the rapid development of China's cultural industry and further promote the construction of spiritual civilization in China. Starting from culture and art management, this study expounds its position in the development of cultural economy industry and its impact on the development of cultural economy. Through two different methods of culture and art management and conventional management, this paper discusses the social and economic market benefit value, the demand for the healthy development of industry, and the impact of innovative cultural industry resources on the development of cultural industry. It can be concluded that culture and art management plays a certain role in promoting the healthy development of cultural economy industry; we should constantly sum up experience in the actual process of cultural industry management, find and solve problems in time, and gradually form a set of scientific and complete cultural and art management mode, which can realize the transformation of cultural and art industry faster and better promote the sustainable development of cultural economy and industry.