Effects of myo-inositol on regulating glucose and lipid metabolism and alternative splicing events coexpressed with lncRNAs in the liver tissues of diabetic mice.

Objective: Recent studies have shown that gene alternative splicing (AS) and long noncoding RNAs (lncRNAs) are involved in diabetes mellitus (DM) and its complications. Currently, myo-inositol (MI) is considered as effective for the treatment of insulin resistance and lipid metabolism disorders in diabetes patients. We hope to better explore the potential roles of gene AS and lncRNAs in liver glucose and lipid metabolism in diabetes, as well as the effects of myo-inositol treatment, through transcriptome analysis. Methods: This study analysed glucose and lipid metabolism-related biochemical indicators and liver HE staining in four groups of mice: the control group (Ctrl group), the diabetes group (DM group), the myo-inositol treatment group (MI group), and the metformin treatment group (Met group). The changes in relevant gene-regulated alternative splicing events (RASEs) and lncRNAs were analysed by RNA sequencing of liver tissue, and coexpression analysis and functional enrichment analysis were used to predict the possible lncRNAs and RASEs involved in liver glucose and lipid metabolism. Result: Metformin and myo-inositol alleviated insulin resistance, lipid metabolism disorders, and hepatic steatosis in diabetic mice. Transcriptome sequencing analysis revealed differential splicing events of genes related to lipid metabolism and differentially expressed lncRNAs (DElncRNAs). Six different lncRNAs and their potentially interacting splicing events were predicted. Conclusion: The present study revealed novel changes in RASEs and lncRNAs in the livers of diabetic mice following treatment with myo-inositol, which may shed light on the potential mechanisms by which myo-inositol delays and treats the progression of hepatic glucose and lipid metabolism in diabetes.

ZmABF4-ZmVIL2/ZmFIP37 module enhances drought tolerance in maize seedlings.

Drought, as a primary environmental factor, imposes significant constraints on developmental processes and productivity of plants. PHDs were identified as stress-responsive genes in a wide range of eukaryotes. However, the regulatory mechanisms governing PHD genes in maize under abiotic stress conditions are still largely unknown and require further investigation. Here, we identified a mutant, zmvil2, in the EMS mutant library with a C to T mutation in the exon of the Zm00001d053875 (VIN3-like protein 2, ZmVIL2), resulting in premature termination of protein coding. ZmVIL2 belongs to PHD protein family. Compared to WT, zmvil2 mutant exhibited increased sensitivity to drought stress. Consistently, overexpression of ZmVIL2 enhances drought resistance in maize. Y2H, BiFC, and Co-IP experiments revealed that ZmVIL2 directly interacts with ZmFIP37 (FKBP12-interacting protein of 37). zmfip37 knockout mutants also exhibit decreased drought tolerance. Interestingly, we demonstrated that ZmABF4 directly binds to the ZmVIL2 promoter to enhance its activity in yeast one hybrid (Y1H), electrophoretic mobility shift assay (EMSA) and dual luciferase reporter assays. Therefore, we uncovered a novel model ZmABF4-ZmVIL2/ZmFIP37 that promotes drought tolerance in maize. Overall, these findings have enriched the knowledge of the functions of PHD genes in maize and provides genetic resources for breeding stress-tolerant maize varieties.

Effects of GLP-1 receptor agonists on the degree of liver fibrosis and CRP in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: A systematic review and meta-analysis.

BACKGROUND: Based on the rapidly growing global burden of non-alcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH), in order to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of NAFLD or NASH this paper presents a systematic review and meta-analysis of randomized controlled trials(RCTs). METHODS: In this systematic review and meta-analysis, We searched PubMed, Medline, Web of Science and The Cochrane Library databases. All randomized controlled trials involving GLP-1RAs and NAFLD or NASH were collected since the database was established. A meta-analysis of proportions was done with the generalised linear mixed model. Continuous variables were represented by Mean and Standard Deviation (SD), and binary variable were represented by Relative Risk (RR) and 95% Confidence Interval (CI) as effect indicators. The research results were presented by Revman 5.4. This study is registered with PROSPERO (CRD42023390735). FINDING: We included 16 placebo-controlled or active drug-controlled randomized controlled trials (involving 2178 patients) that used liraglutide, exenatide, dulaglutide, or semaglutie in the treatment of NAFLD or NASH, as measured by liver biopsy or imaging techniques. This study found that the effect of GLP-1RAs on histologic resolution of NASH with no worsening of liver fibrosis (n=2 RCTs; WMD:4.08, 95%CI 2.54-6.56, p < 0.00001) has statistically significant. At the same time, GLP-1RAs affected CRP (n = 7 RCTs; WMD:-0.41, 95% CI-0.78 to -0.04, p =0.002) and other serological indicators were significantly improved. CONCLUSION: This study evaluated the efficacy of GLP-1RAs in patients with NAFLD and NASH. These results suggest that GLP-1RAs may be a potential and viable therapeutic approach as a targeted agent to intervene in disease progression of NAFLD and NASH.

Increased GPC4 and clusterin associated with insulin resistance in patients with PCOS.

The aim of the study was to investigate the changes in serum glypican 4 (GPC4) and clusterin (CLU) levels in patients with polycystic ovary syndrome (PCOS) as well as their correlation with sex hormones and metabolic parameters. A total of 40 PCOS patients and 40 age-matched healthy women were selected. Serum GPC4 and CLU levels were compared between the PCOS and control groups, and binary logistic regression was used to analyze the relative risk of PCOS at different tertiles of serum GPC4 and CLU concentrations. Stepwise linear regression was used to identify the factors influencing serum GPC4 and CLU levels in PCOS patients. Serum GPC4 (1.82 ± 0.49 vs 1.30 ± 0.61 ng/mL, P < 0.001) and CLU (468.79 ± 92.85 vs 228.59 ± 82.42 µg/mL, P < 0.001) were significantly higher in PCOS patients than in healthy women after adjustment for body mass index (BMI). In the PCOS group, serum GPC4 was positively correlated with follicle-stimulating hormone, fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, and CLU (P < 0.05), whereas serum CLU was positively correlated with BMI, FPG, FINS, and HOMA-IR (P < 0.05). Multiple stepwise linear regression analysis showed that HOMA-IR was independently associated with serum GPC4, and BMI and HOMA-IR were independently associated with CLU (P < 0.05). Serum GPC4 and CLU levels were significantly higher in PCOS patients than in healthy women, suggesting that GPC4 and CLU may be markers associated with insulin resistance in women with PCOS.

Dysregulated lncRNAs regulate human umbilical cord mesenchymal stem cell differentiation into insulin-producing cells by forming a regulatory network with mRNAs.

OBJECTIVE: In recent years, cell therapy has emerged as a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cell (MSC) differentiation necessary to form such treatment have not been clarified. METHODS: In this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSC (S0) and four induced stage (S1-S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). RESULTS: We found that the number of differentially expressed lncRNAs and mRNAs trended downwards during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signalling pathway, MAPK signalling pathway, HIPPO signalling pathway, PI3K-Akt signalling pathway, and p53 signalling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA CTBP1-AS2 with PROX1 and the lncRNAs AC009014.3 and GS1-72M22.1 with JARID2 mRNA was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs: XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells. CONCLUSION: In this study, HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signalling pathways. The lncRNAs AC009014.3, Gs1-72m21.1, and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalogue for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future.

ZmELF6-ZmPRR37 module regulates maize flowering and salt response.

The control of flowering time in maize is crucial for reproductive success and yield, and it can be influenced by environmental stresses. Using the approaches of Ac/Ds transposon and transposable element amplicon sequencing techniques, we identified a Ds insertion mutant in the ZmPRR37 gene. The Ds insertion showed a significant correlation with days to anthesis. Further research indicated that ZmPRR37-CR knockout mutants exhibited early flowering, whereas ZmPRR37-overexpression lines displayed delayed flowering compared to WT under long-day (LD) conditions. We demonstrated that ZmPRR37 repressed the expression of ZmNF-YC2 and ZmNF-YA3 to delay flowering. Association analysis revealed a significant correlation between flowering time and a SNP2071-C/T located upstream of ZmPRR37. The SNP2071-C/T impacted the binding capacity of ZmELF6 to the promoter of ZmPRR37. ZmELF6 also acted as a flowering suppressor in maize under LD conditions. Notably, our study unveiled that ZmPRR37 can enhance salt stress tolerance in maize by directly regulating the expression of ABA-responsive gene ZmDhn1. ZmDhn1 negatively regulated maize salt stress resistance. In summary, our findings proposed a novel pathway for regulating photoperiodic flowering and responding to salt stress based on ZmPRR37 in maize, providing novel insights into the integration of abiotic stress signals into floral pathways.

Exploring the repairing mechanisms of reduced graphene oxide (rGo) on the dysregulation of Xenopus Laevis larva hypothalamus-pituitary-thyroid (HPT) axis caused by chiral triazole fungicide metconazole.

Replacing chair fungicide racemate marketed product by its enantiomer with high activity and low environmental risk for application is a more environmentally friendly methods to control crop diseases. Moreover, carbon-based nanomaterials, with the desirable chemical and mechanical properties, exhibits latent reduce fungicide toxicity capability, while the mechanism is still poorly understood. Therefore, the present study characterized the toxicity of rac-metconazole (Mez; (1RS,5RS;1RS,5SR)-5-(4-chlorobenzyl)-2,2-dimethyl-1-(1H)) and its two cis-enantiomers as well as the repairing effect of reduced graphene oxide (rGo) on Xenopus Laevis larva by examining growth appearance indexes, Mez bioaccumulation, and hypothalamus-pituitary-thyroid (HPT) axis related hormone contents and gene expression after 14 and 28 days exposure. Compared with two cis-Mez, rac-Mez was preferentially bioaccumulated in tadpoles, and rac-Mez treatment showed a higher toxicity effect on tadpole including growth stage and body weight inhibition by dysregulating tadpole thyroid stimulating hormone (TSH) and thyroid hormone (TH) contents and related gene expression. Enantioselectivity was observed in two cis-Mez treatments. Compared with R,S-Mez, S,R-Mez treatment showed more severe damage on tadpole HPT axis related physiological and biochemical processes. rGo could effectively decrease the toxicity of Mez, especially shown the capacity of repairing the hormone dysregulation caused by R,S-Mez treatment. Moreover, the addition of rGo can decrease the bioaccumulation of Mez in tadpoles. Therefore, R,S-Mez is less toxic to Xenopus Laevis larva growth, and its toxicity could be effectively repaired by the addition of rGO.

Association between gestational blood lipids and TSH levels and pregnancy outcome of patients with subclinical hypothyroidism.

Objective: To investigate the association between gestational blood lipids and thyroid stimulating hormone (TSH) levels and pregnancy outcomes of patients with subclinical hypothyroidism (SCH). Methods: In this retrospective observational study, we analyzed the clinical data of 82 patients (case group) with gestational SCH treated in our hospital from January 2021 to January 2022 at gestational weeks 25-33 and grouped them according to whether SCH was well controlled by treatment (case Group-A: well controlled, n=55; case Group-B: poorly controlled, n=27), and the clinical data of 41 pregnant women (control group) undergoing physical examination during the same period. After comparing the blood lipids and TSH levels of the three groups, we compared their adverse pregnancy outcomes to assess the possible correlations between blood lipids and TSH levels and pregnancy outcomes. Results: The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and TSH in the case Group-B were significantly higher than those in the case Group-A and the control group (P<0.05). Compared with case Group-B and the control group, the incidence of premature delivery, abortion and neonatal growth restriction was higher in case Group-A (P<0.05). Among 82 patients in the case group 42 presented adverse pregnancy outcomes. The levels of TC, TG, LDL-C and TSH in mothers and infants in the adverse outcome group were significantly higher than those in the favorable outcome group (P<0.05). Our Pearson analysis results showed that the levels of TC, TG and LDL-C were positively correlated with the TSH levels and the pregnancy outcomes, and that TSH was positively correlated with pregnancy outcomes (P<0.05). Conclusion: The levels of TC, TG, LDL-C and TSH in patients with poorly controlled SCH were increased during pregnancy, and were associated with the pregnancy outcomes and positively correlated with each other.

ZmGI2 regulates flowering time through multiple flower development pathways in maize.

GIGANTEA (GI) encodes a component of the circadian clock core oscillator and has been identified as a regulatory pathway of the circadian rhythm and photoperiodic flowering in model plants. However, the regulatory pathway of GI affecting flowering time is unknown in maize. Here, we identified that the zmgi2 mutant flowered earlier than the wild type under long day (LD) conditions, whereas the difference in flowering time was not apparent under short day (SD) conditions. The 24 h optimal expression of the gene in the stem apex meristems (SAM) appeared at 9 h after dawn under LD conditions and at 11 h after dawn under SD conditions. DAP-Seq and RNA-Seq further revealed that ZmGI2 delays flowering by directly binding to the upstream regions of ZmVOZs, ZmZCN8 and ZmFPF1 to repress the expression of these genes and by directly binding to the upstream regions of ZmARR11, ZmDOF and ZmUBC11 to promote the expression of these genes. The genetic and biochemical evidence suggests a model for the potential role of ZmGI2 in regulating the flowering time-dependent photoperiodic pathway. This study provides novel insights into the function of ZmGIs in maize and further demonstrates their potential importance for floral transition. These results contribute to a comprehensive understanding of the molecular mechanisms and regulatory networks of GI transcription factors in regulating flowering time in maize.

Cardiac Autonomic Dysfunction Is Associated With Risk of Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus.

Background: Evidence on the relationship between heart rate variability (HRV) and albumin-to-creatinine ratio (ACR) combined with estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) is rare. Thus, this study aimed to investigate the relationship between heart rate variability and the risk of diabetic kidney disease (DKD) progression in diabetes patients. Method: Overall, 747 T2DM patients who were admitted to the Second Affiliated Hospital of Nanchang University underwent 24-hour dynamic electrocardiograms for HRV analysis. Time-domain HRV measures included mean heart rate, standard deviation of the R-R interval (SDNN), SDNN index, root mean squared difference of successive RR intervals (RMSSD), and percent of adjacent RR intervals with a difference greater than 50 ms (PNN50). Frequency-domain measures included low frequency (LF), very low frequency (VLF), high frequency (HF) components and LF-to-HF ratio. The risk of DKD progression was determined by combining ACR and eGFR and stratified as low risk (Group A), moderately increased risk (Group B), high risk (Group C), and very high risk (Group D) based on the Kidney Disease: Improving Global Outcomes guidelines. Result: There were significant differences in HRV parameters among the four risk groups (SDNN: 113 ms vs 109 ms vs 101 ms vs 81 ms, P<0.01; LF: 240.2 ms2 vs 241.1 ms2 vs 155.2 ms2 vs 141.9 ms2, P<0.01; LF-to-HF ratio: 1.70 vs 1.24 vs 1.12 vs 0.93, P<0.01; VLF: 723.7 ms2 vs 601.1 ms2 vs 446.4 ms2 vs 356.3 ms2, P<0.01). A very high risk of DKD progression was significantly associated with a lower SDNN (ß=-19.5, 95% CI: -30.0 to -10.0, P<0.01), and moderately increased, high, and very high risks were associated with lower LF-to-HF ratio and VLF (P<0.05). Logistic regression analysis showed that group D had a higher risk of reduced SDNN, LF-to-HF ratio, and VLF compared with group A after adjusting for systolic blood pressure, glycated haemoglobin, haemoglobin, high-density lipoprotein cholesterol, and age (odds ratio (95% CI): 0.989 (0. 983-0.996), 0.674 (0.498-0.913), and 0.999 (0.999-1.000), respectively). Conclusion: Cardiac autonomic dysfunction is associated with a risk of DKD progression in adults with T2DM, and reduced heart rate variability increased such risk. Thus, HRV screening may be necessary in patients with T2DM, especially those with high proteinuria.

Identification of ZmNF-YC2 and its regulatory network for maize flowering time.

Flowering time is an important agronomic trait that determines the distribution and adaptation of plants. The accurate prediction of flowering time in elite germplasm is critical for maize breeding. However, the molecular mechanisms underlying the photoperiod response remain elusive in maize. Here we cloned the flowering time-controlling gene, ZmNF-YC2, by map-based cloning and confirmed that ZmNF-YC2 is the nuclear transcription factor Y subunit C-2 protein and a positive regulator of flowering time in maize under long-day conditions. Our results show that ZmNF-YC2 promotes the expression of ZmNF-YA3. ZmNF-YA3 negatively regulates the transcription of ZmAP2. ZmAP2 suppresses the expression of ZMM4 to delay flowering time. We then developed a gene regulatory model of flowering time in maize using ZmNF-YC2, ZmNF-YA3, ZmAP2, ZMM4, and other key genes. The cascading regulation by ZmNF-YC2 of maize flowering time has not been reported in other species.

Synthesis of C5-Allylindoles through an Iridium-Catalyzed Asymmetric Allylic Substitution/Oxidation Reaction Sequence of N-Alkyl Indolines.

Iridium/Brønsted acid cooperative catalyzed asymmetric allylic substitution reactions at the C5 position of indolines have been reported for the first time. The highly efficient protocol allows rapid access to various C5-allylated products in good to high yields (48-97%) and enantioselectivities (82% to >99% ee) with wide functional group tolerance. The transformations allow not only the formation of C5-allylindoline derivatives but also the synthesis of C5-allylindole analogues in good yields and excellent stereoselectivities via an allylation/oxidation reaction sequence.

CLA4 regulates leaf angle through multiple hormone signaling pathways in maize.

Leaf angle is an important agronomic trait in cereals and shares a close relationship with crop architecture and grain yield. Although it has been previously reported that ZmCLA4 can influence leaf angle, the underlying mechanism remains unclear. In this study, we used the Gal4-LexA/UAS system and transactivation analysis to demonstrate in maize (Zea mays) that ZmCLA4 is a transcriptional repressor that regulates leaf angle. DNA affinity purification sequencing (DAP-Seq) analysis revealed that ZmCLA4 mainly binds to promoters containing the EAR motif (CACCGGAC) as well as to two other motifs (CCGARGS and CDTCNTC) to inhibit the expression of its target genes. Further analysis of ZmCLA4 target genes indicated that ZmCLA4 functions as a hub of multiple plant hormone signaling pathways: ZmCLA4 was found to directly bind to the promoters of multiple genes including ZmARF22 and ZmIAA26 in the auxin transport pathway, ZmBZR3 in the brassinosteroid signaling pathway, two ZmWRKY genes involved in abscisic acid metabolism, ZmCYP genes (ZmCYP75B1, ZmCYP93D1) related to jasmonic acid metabolism, and ZmABI3 involved in the ethylene response pathway. Overall, our work provides deep insights into the ZmCLA4 regulatory network in controlling leaf angle in maize.

Effects of passive smoking and its duration on the prevalence of prediabetes and type 2 diabetes mellitus in Chinese women.

Several studies have shown that active smoking is a risk factor for type 2 diabetes mellitus (T2DM). However, the effects of passive smoking on T2DM remains unknown. In this study, we investigated the effects of passive smoking and its duration on the prevalence of prediabetes and T2DM. According to passive smoking status, participants were divided into Group A (passive smokers) and Group B (controls). Furthermore, Group A was divided into three subgroups according to the duration of passive smoking: Group A1 (≤10 years), Group A2 (10-20 years), and Group A3 (>20 years). We found that the prevalence of impaired glucose tolerance (IGT) in Group A (26.6%), Group A2 (28%), and Group A3 (37.8%) was significantly higher than that in Group B (19.6%), and the prevalence gradually increased with an increase in the duration of passive smoking. Multiple logistic regression analysis showed that passive smoking for >10 years was a risk factor for impaired fasting glucose (IFG), IGT, and T2DM. Therefore, passive smoking not only increases the prevalence of IGT in a time-dependent manner, but also a risk factor for IFG, IGT, and T2DM when its duration is over 10 years.

ZmIBH1-1 regulates plant architecture in maize.

Leaf angle (LA) is a critical agronomic trait in maize, with more upright leaves allowing higher planting density, leading to more efficient light capture and higher yields. A few genes responsible for variation in LA have been identified by map-based cloning. In this study, we cloned maize ZmIBH1-1, which encodes a bHLH transcription factor with both a basic binding region and a helix-loop-helix domain, and the results of qRT-PCR showed that it is a negative regulator of LA. Histological analysis indicated that changes in LA were mainly caused by differential cell wall lignification and cell elongation in the ligular region. To determine the regulatory framework of ZmIBH1-1, we conducted RNA-seq and DNA affinity purification (DAP)-seq analyses. The combined results revealed 59 ZmIBH1-1-modulated target genes with annotations, and they were mainly related to the cell wall, cell development, and hormones. Based on the data, we propose a regulatory model for the control of plant architecture by ZmIBH1-1 in maize.

Bilateral cataracts as the first manifestation of type 1 diabetes mellitus: A case report.

RATIONALE: Cataracts can occur in children and adolescents with Type 1 Diabetes Mellitus who have poorly controlled glycemia. Here, we report a case of a 16-year-old female, who was diagnosed with bilateral cataracts, and genetic screening identified a mutation in the PRRC2A gene which is rarely reported. After surgery, retinopathy was found in this patient, combined with the published literature, we encourage that postoperative monitoring for retinal lesions during the follow-up visits should be conducted. PATIENT CONCERNS: In this article, we present an adolescent diagnosed with bilateral cataracts, and developed retinopathy during the follow-up visits. Genetic screening identified a mutation in the PRRC2A gene. DIAGNOSES: The diagnoses of Diabetic cataracts, Type 1 diabetes and Diabetic retinopathy was made. INTERVENTIONS: The patient underwent surgery in both eyes, and hypoglycemic treatment was provided. OUTCOMES: The surgery achieved satisfactory results, during the follow-up visits, her visual acuity was reported as 0.8 in the right eye and 1.0 in the left eye. Besides, her blood glucose was well controlled, and her glycated hemoglobin was reduced to 6.9% after three months of continuous treatment. LESSONS: This case highlights the importance of genetic screening for detecting mutations in diabetes-related genes, and postoperative monitoring for retinal lesions during the follow-up visits.

[A discussion on the concentration assay for hemihydrate gypsum in plaster of paris bandage-viscose form].

This essay is to present an improvement on the concentration assay for hemihydrate gypsum in plaster of Paris bandage-Viscose form.