Research status and challenges of plant-derived exosome-like nanoparticles.

In recent years, there has been an increasing number of related studies on exosomes. Most studies have focused on exosomes derived from mammals, confirming the important role that exosomes play in cell communication. Plants, as a natural ingredient, plant-derived exosomes have been confirmed to have similar structures and functions to mammalian-derived exosomes. Plant-derived exosome-like nanoparticles (PELNs) are lipid bilayer membrane nanovesicles containing bioactive constituents such as miRNA, mRNA, protein, and lipids obtained from plant cells, that can participate in intercellular communication and mediate transboundary communication, have high bioavailability and low immunogenicity, are relatively safe, and have been shown to play an important role in maintaining cell homeostasis and preventing, and treating a variety of diseases. In this review, we describe the biogenesis, isolation and purification methods, structural composition, stability, safety, function of PELNs and challenges. The functions of PELNs in anti-inflammatory, antioxidant, antitumor and drug delivery are mainly described, and the status of research on exosome nanoparticles of Chinese herbal medicines is outlined. Overall, we summarized the importance of PELNs and the latest research results in this field and provided a theoretical basis for the future research and clinical application of PELNs.

α-Hederin induces paraptosis by targeting GPCRs to activate Ca2+/MAPK signaling pathway in colorectal cancer.

BACKGROUND: Non-apoptotic cell death is presently emerging as a potential direction to overcome the apoptosis resistance of cancer cells. In the current study, a natural plant agent α-hederin (α-hed) induces caspase-independent paraptotic modes of cell death. PURPOSE: The present study is aimed to investigate the role of α-hed induces paraptosis and the associated mechanism of it. METHODS: The cell proliferation was detected by CCK-8. The cytoplasm organelles were observed under electron microscope. Calcium (Ca2+) level was detected by flow cytometry. Swiss Target Prediction tool analyzed the potential molecule targets of α-hed. Molecular docking methods were used to evaluate binding abilities of α-hed with targets. The expressions of genes and proteins were analyzed by RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. Xenograft models in nude mice were established to evaluate the anticancer effects in vivo. RESULTS: α-hed exerted significant cytotoxicity against a panel of CRC cell lines by inhibiting proliferation. Besides, it induced cytoplasmic vacuolation in all CRC cells. Electron microscopy images showed the aberrant dilation of endoplasmic reticulum and mitochondria. Both mRNA and protein expressions of Alg-2 interacting proteinX (Alix), the marker of paraptosis, were inhibited by α-hed. Besides, both Swiss prediction and molecular docking showed that the structure of α-hed could tightly target to GPCRs. GPCRs were reported to activate the phospholipase C (PLC)-ß3/ inositol 1,4,5-trisphosphate receptor (IP3R)/ Ca2+/ protein kinase C alpha (PKCα) pathway, and we then found all proteins and mRNA expressions of PLCß3, IP3R, and PKCα were increased by α-hed. After blocking the GPCR signaling, α-hed could not elevate Ca2+ level and showed less CRC cell cytotoxicity. MAPK cascade is the symbol of paraptosis, and we then demonstrated that α-hed activated MAPK cascade by elevating Ca2+ flux. Since non-apoptotic cell death is presently emerging as a potential direction to overcome chemo-drug resistance, we then found α-hed also induced paraptosis in 5-fluorouracil-resistant (5-FU-R) CRC cells, and it reduced the growth of 5-FU-R CRC xenografts. CONCLUSIONS: Collectively, our findings proved α-hed as a promising candidate for inducing non-apoptotic cell death, paraptosis. It may overcome the resistance of apoptotic-based chemo-resistance in CRC.

Prediction of rear-seat belt use: Application of extended theory of planned behavior.

OBJECTIVES: Rear-seat belts have been shown to significantly reduce the severity of road vehicle collisions and fatalities. However, their use by rear-seat passengers is significantly less than that by front-seat passengers. Thus, the psychological factors underlying individuals' decision to wear a seat belt in the rear seat require further investigation. METHODS: An extended theory of planned behavior (eTPB) was used to examine individuals' behavior of wearing a rear-seat belt. An online survey was conducted and a total of 515 valid questionnaires were collected in China. RESULTS: While attitude, descriptive norms, and law enforcement all have a significant effect on individuals' intention to wear a seat belt in the rear, subjective norms and perceived behavioral control do not. Individuals' attitudes toward wearing a seat belt in the rear seat are significantly influenced by law enforcement and behavioral intention, but not by perceived behavioral control. The mediation effect analysis reveals that law enforcement has the greatest overall effect on behavior, followed by attitude and descriptive norms. CONCLUSIONS: The results of this paper contribute to more effective recommendations to improve the use of rear seat belts and to safeguard rear seat passengers.

The Effect of Health Literacy on Disease Management Self-Efficacy in Chronic Disease Patients: The Mediating Effects of Social Support and the Moderating Effects of Illness Perception.

Purpose: To test a hypothetical pathway model to estimate the links between health literacy, social support, illness perception, and disease management self-efficacy. Methods: This cross-sectional study, conducted from June to October 2022, involved the recruitment of 210 patients with chronic diseases at two primary care facilities. Participants completed the Health Literacy Management Scale, Self-Efficacy for Managing Chronic Disease 6-Item Scale, Social Support Rating Scale and Brief Illness Perception Questionnaire. We used the PROCESS macro for R to determine the hypothetical pathway model. Results: The direct effect of health literacy on self-efficacy was significant (ß=0.1792, 95% CI: 0.0940-0.2644), and social support played a partial mediating role between health literacy and self-efficacy (ES=0.0761, 95% CI: 0.0398-0.1204). Illness perception moderated the relationship between social support and self-efficacy (ß=-0.0153, 95% CI: -0.0268- -0.0039). Conclusion: Proposed a conceptual model including the mediating effect of social support and the moderating effect of illness perception, which helps to clarify the underlying mechanisms between health literacy and self-efficacy.

Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China.

BACKGROUND: Impact of preoperative infection on liver transplantation (LT) needs further investigation. MATERIALS AND METHODS: From January 1, 2015 to December 31, 2022, 24,122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. RESULTS: Compared to the non-infection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding and biliary complications (all P<0.01), and they had shorter 30-day, 90-day survival and overall survival (OS) (all P<0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the OS in the infection group (both P<0.05). Besides, compared to the non-pulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P<0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P<0.05). Patients in the non-abdominal group also had a higher proportion of postoperative infection than those in the abdominal group (P<0.05). Furthermore, compared to the number=1 group, patients in the number≥2 group were more prone to postoperative effusion and infection (both P<0.01), and they also had shorter 30-day and 90-day survival (both P<0.05). CONCLUSION: Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.

Cell phone distraction behavior of young pedestrians: evidence from China.

Cell phone use while walking escalates pedestrian safety risks, particularly among students, given their heavy reliance on these devices. Psychological factors wield significant influence on individual behavior, particularly among adolescents who navigate a blend of rational and social-reactive pathways in decision-making. Therefore, this paper employs the Prototype Willingness Model (PWM) to scrutinize psychological determinants of students' cell phone use while walking, drawing on data from 368 valid samples. Structural equation modeling (SEM) dissects the impact of psychological constructs on this behavior, highlighting the significance of both the social response and reasoning pathways within PWM. The study comprehensively analyzes direct, indirect, and overall effects of exogenous variables on behavioral intention and behavior.

Circ-phkb promotes cell apoptosis and inflammation in LPS-induced alveolar macrophages via the TLR4/MyD88/NF-kB/CCL2 axis.

BACKGROUND: Circular RNAs (CircRNAs) have been associated with acute lung injury (ALI), but their molecular mechanisms remain unclear. METHODS: This study developed a rat model of lipopolysaccharide (LPS)-induced ALI and evaluated the modeling effect by hematoxylin and eosin staining, Masson's trichrome staining, lung wet-to-dry weight ratio, terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL), and enzyme-linked immunosorbent assay (ELISA) detection of inflammatory factors (interleukin-1ß, tumor necrosis factor alpha, and interleukin-6). Using lung tissues from a rat model of LPS-induced ALI, we then conducted circRNA sequencing, mRNA sequencing, and bioinformatics analysis to obtain differential circRNA and mRNA expression profiles as well as potential ceRNA networks. Furthermore, we performed quantitative real-time polymerase chain reaction (qRT-PCR) assays to screen for circ-Phkb in ALI rat lung tissues, alveolar macrophages, and LPS-induced NR8383 cells. We conducted induction with or without LPS with circ-Phkb siRNA and overexpression lentivirus in NR8383. Cell Counting Kit-8, C5-Ethynyl-2'-deoxyuridine (Edu), TUNEL, and cytometry were used to identify proliferation and apoptosis, respectively. We detected inflammatory factors using ELISA. Finally, we used Western blot to detect the apoptosis-related proteins and TLR4/MyD88/NF-kB/CCL2 pathway activation. RESULTS: Our results revealed that both circRNA and mRNA profiles are different from those of the Sham group. We observed a significant circ-Phkb upregulation in NR8383 cells and LPS-exposed rats. Apoptosis and inflammation were greatly reduced when circ-Phkb expression was reduced in NR8383 cells, cell proliferation was increased, and circ-Phkb overexpression was decreased. CONCLUSIONS: In terms of mechanism, circ-Phkb suppression inhibits CCL2 expression via the TLR4/MyD88/NF-kB pathway in LPS-induced alveolar macrophages.

Berberine Protects Against Dihydrotestosterone-Induced Human Ovarian Granulosa Cell Injury and Ferroptosis by Regulating the Circ_0097636/MiR-186-5p/SIRT3 Pathway.

Polycystic ovarian syndrome (PCOS) is an endocrine syndrome in women of reproductive age. Berberine (BBR) is a Chinese herbal monomer that exhibits many pharmacological properties related to PCOS treatment. This study aims to analyze the effect of BBR on a cell model of PCOS and the underlying mechanism. Human ovarian granulosa (KGN) cells were treated with dihydrotestosterone (DHT) to mimic a PCOS cell model. The RNA expression of circ_0097636, miR-186-5p, and sirtuin3 (SIRT3) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was detected by western blotting. Cell viability was analyzed by CCK-8 assay. Cell proliferation and apoptosis were investigated by 5-ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry assay, respectively. The levels of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) were analyzed by enzyme-linked immunosorbent assays (ELISAs). Fe2+ concentration was assessed by an iron assay kit. Oxidative stress was assessed by detecting reactive oxygen species (ROS) level and malondialdehyde (MDA) level using commercial kits. The association of miR-186-5p with circ_0097636 and SIRT3 was identified by dual-luciferase reporter assay and RNA pull-down assay. Circ_0097636 expression was downregulated in the follicular fluid of PCOS patients and DHT-treated KGN cells when compared with control groups. BBR treatment partially relieved the DHT-induced inhibitory effect on cell proliferation and promoted effects on cell apoptosis, inflammation, ferroptosis, and oxidative stress in KGN cells. Additionally, circ_0097636 bound to miR-186-5p, and SIRT3 was identified as a target gene of miR-186-5p in KGN cells. BBR treatment ameliorated DHT-induced KGN cell injury by upregulating circ_0097636 and SIRT3 expression and downregulating miR-186-5p expression. Moreover, circ_0097636 overexpression protected KGN cells from DHT-induced injury by increasing SIRT3 expression. BBR ameliorated DHT-induced KGN cell injury and ferroptosis by regulating the circ_0097636/miR-186-5p/SIRT3 pathway.

The efficacy and safety of beinaglutide alone or in combination with insulin glargine in Chinese patients with type 2 diabetes mellitus who are inadequately controlled with oral antihyperglycemic therapy: A multicenter, open-label, randomized trial.

BACKGROUND: To compare glycemic control in Chinese patients with type 2 diabetes mellitus (T2DM) whose blood glucose levels were inadequately controlled with oral antidiabetic drugs after beinaglutide alone or combined with insulin glargine (IGlar). METHODS: In this 16-week multicenter, randomized clinical trial, 68 participants randomly received beinaglutide or IGlar for 8 weeks, then the two drugs in combination for 8 weeks. The primary outcomes were the proportion of individuals achieving their glycemic target and the change in glucose variability as measured with a continuous glucose monitoring system from baseline to 8 and 16 weeks. RESULTS: Both the beinaglutide and IGlar groups showed increased proportions achieving their glycemic target at 8 weeks, and the combination augmented the proportion reaching the glycated hemoglobin target from 25.42% at 8 weeks to 40.68% at 16 weeks. The beinaglutide group showed a significant reduction in body weight, body mass index, waist circumference, and systolic blood pressure. Beinaglutide elevated high-density lipoprotein cholesterol by 0.08 mmol/L (95% confidence interval [CI], 0.00-0.16), and diminished low-density lipoprotein cholesterol by 0.21 mmol/L (95% CI, 0.05-0.48), whereas IGlar showed no effect. Though IGlar was more efficient in lowering fasting plasma glucose than beinaglutide at comparable efficacies (to -1.57 mmol/L [95% CI, -2.60 to -0.54]), this difference was abolished in patients whose fasting C-peptide was ≥0.9 ng/mL. CONCLUSION: Beinaglutide exhibited a favorable hypoglycemic effect on patients with T2DM, and in combination with IGlar, glucose level was further decreased. Low fasting C-peptide in patients may reduce the glycemic response to beinaglutide therapy. We recommend that C-peptide levels be evaluated when using or switching to the novel glucagon-like peptide-1 receptor agonists beinaglutide. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03829891.

Machine learning-based identification of CYBB and FCAR as potential neutrophil extracellular trap-related treatment targets in sepsis.

Objective: Sepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis. Methods: Datasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN). Results: Analysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level. Conclusion: CYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.

Friend leukemia integration 1 overexpression decreases endometrial receptivity and induces embryo implantation failure by promoting PART1 transcription in the endometrial epithelial cells.

Background: In vitro fertilization-embryo transfer (IVF-ET) is a crucial assisted reproductive technology for treating infertility. However, recurrent implantation failure (RIF), a significant challenge in IVF-ET success, remains unresolved. This study aimed to explore the role and mechanism of FLI1 in endometrial receptivity and RIF. Methods: Differential endometrial cell proportions between patients with RIF and control subjects were assessed using single-cell RNA sequencing (scRNA-seq) analysis. The chromatin accessibility of FLI1 in the luteal endometrial tissue of patients with RIF and control subjects was examined using the single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq). FLI1 mRNA and protein levels were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Cell viability and migration were examined via cell counting kit (CCK)-8 and scratch healing assays. Epithelial-mesenchymal transition markers were analyzed using western blotting. Mechanisms underlying FLI1's regulation of PART1 transcription and expression in endometrial epithelial cells were explored using chromatin immunoprecipitation and dual-luciferase reporter assays. Adeno-associated virus (AAV) carrying epithelial cell-specific FLI1/PART1 overexpression sequences was uterinely injected in mice to assess FLI1/PART1 effects. Results: scRNA-seq revealed diminished endometrial epithelial cell proportions in RIF patients. Meanwhile, scATAC-seq indicated enhanced chromatin accessibility of FLI1 in these cells. FLI1 exhibited specific expression in RIF patients' endometrial epithelial cells. Specific FLI1 overexpression inhibited embryo implantation, while knockdown enhanced it. Pregnant mice injected with AAV encoding FLI1 overexpression had significantly lower implantation than AAV-negative controls. FLI1 binding to PART1 promoter heightened PART1 transcription and expression in endometrial epithelial cells. Rescue experiments illustrated FLI1's role in embryo implantation by boosting PART1 expression. PART1 was notably elevated in RIF patients' luteal endometrial tissue and non-receptive endometrial epithelial cells (HEC-1-A). Specific PART1 overexpression dampened embryo implantation, whereas knockdown promoted it. Pregnant mice injected with AAV encoding PART1 had lower implantation than negative controls. PART1 knockdown mitigated FLI1's inhibitory impact on HEC-1-A cell viability and migration. Conclusions: FLI1 overexpression in the endometrial epithelial cells of patients with RIF inhibited embryo implantation by binding to the PART1 promoter region to promote PART1 expression. These findings can aid in the development of novel therapeutic targets for RIF.

Predictors of parents' use of child restraint systems: Evidence from China.

OBJECTIVE: Child restraint systems (CRS) can significantly lower the chance of child harm and death. Despite the benefit of CRS, their use in developing countries is low. Therefore, examining the factors that affect parents' use of CRS is essential. METHODS: In this study, the associations of demographic characteristics and the exogenous constructs in the health belief model (HBM) and the theory of planned behavior (TPB) with parents' CRS use were investigated with structural equation modeling. RESULTS: Demographic factors alone explained 23.1% of the variance in CRS use. The model's explanatory power increased greatly when exogenous constructs were incorporated from the HBM and TPB. Having a college degree, knowledge about CRS, perceived susceptibility, self-efficacy, and attitude significantly impacted parents' use of CRS. CONCLUSIONS: The use of CRS in China is still low. Much effort should be done to increase the use of CRS in China, including education, and publicity.

Effects of Liver-Regulating Herb Compounds on Varicocele-Associated Testicular Dysfunction Through Restoring Hormones and Spermatocytes Apoptosis.

PURPOSE: Varicocele is considered one of the causes of male infertility. Though varicocelectomy is supposed to improve semen parameters in adult infertile men, some patients with varicocele were still infertile after varicocelectomy. Previous studies showed Traditional Chinese Medicine, Liver-regulating herb compounds (LRHC) could improve the semen quality and increase fertility rates of infertile patients with varicocele. This study aimed to throw light on the mechanism of LRHC on varicocele-associated infertility. MATERIALS AND METHODS: Rats with varicocele-induced were treated with LRHC at dosage of 1mL/100g by intragastric administration for 90 days. The effects of LRHC on hormones and spermatocytes apoptosis were examined using ELISA assay, Western blotting, and flow cytometry. RESULTS: Rats induced with varicocele showed a higher level of follicle stimulating hormone (FSH) in serum, which was brought back to normal level by LRHC. After treatment with LRHC, both testicular tissue in vivo and Sertoli cell TM4 cells in vitro showed elevated expressions of FSHR. Cell viabilities of TM4 cells and spermatocyte GC-2 cells were improved by LRHC treatment under normoxia and hypoxia conditions. Moreover, LRHC protected GC-2 cells from apoptosis induced by hypoxia. The expression of Bax reduced, while that of Bcl-2 increased after treatment with LRHC. CONCLUSION: This study revealed that LRHC had protective effects on spermatogenic disturbance caused by varicocele through regulating hormones and reducing spermatogenic cell apoptosis under hpoxia conditions.

Predictors of older people's intention to engage in cycling violation behaviour with an integrative model.

In China, bicycles are a popular mode of transportation for senior citizens. A disproportionate number of traffic-related fatalities and injuries involve cyclists. The violation of cycling laws is a significant cause of cyclist crashes. Few studies have analyzed the cycling violation behaviour of seniors. Therefore, it is essential to examine the factors that influence older individuals' intention to engage in cycling violation behaviours. In this study, the effects of social-demographic characteristics, the exogenous constructs in the health belief model (HBM), and the theory of planned behaviour (TPB) on senior cyclists' violation intention were investigated using hierarchical regression analysis. Interviews were conducted with older cyclists in urban areas of Wuhan City, all above 60 years of age. The results showed that very little variance in behavioural intention could be explained by social-demographic factors. The TPB has a significantly greater capacity than the HBM to explain variance in behavioural intention. Perceived susceptibility, perceived benefit, cues to action, subjective norm and attitude significantly impacted behavioural intention, whereas perceived severity, perceived barrier and self-efficacy did not.

Adolescent Aggressive Riding Behavior: An Application of the Theory of Planned Behavior and the Prototype Willingness Model.

Cycling has always been popular in China, especially during the years when the government encouraged green travel. Many people participate in rides to ease traffic congestion and increase transfer convenience. Due to the disorganized and tidal nature of cycling, cyclists create many conflicts with other groups. Adolescents are vulnerable road users with a strong curiosity and risk-taking mindset. Identifying the factors influencing adolescents' aggressive riding behavior can assist in developing strategies to prevent this behavior. An online questionnaire was used to collect data on bicycling among students in a middle school in Guangzhou, China. The theory of planned behavior (TPB) and prototype willingness model (PWM) have been applied to study travel behavior and adolescent risk behavior. To investigate the impact of psychological variables on adolescent aggressive behavior, we used TPB, PWM, TPB + PWM, and an integrated model. Behavioral intentions are greatly influenced by attitudes, subjective norms, and perceived behavioral control. Both descriptive and moral norms played a role in behavioral willingness. The integrated model explained 18.3% more behavioral variance than the TPB model. The social reactive pathway explained more variance in behavior than the rational path.

Association of long-term triglyceride-glucose index level and change with the risk of cardiometabolic diseases.

Objective: The triglyceride-glucose (TyG) index is considered as a pivotal factor for various metabolic, cardiovascular, and cerebrovascular diseases. However, there is currently a paucity of relevant studies on the association between long-term level and change of TyG-index and cardiometabolic diseases (CMDs) risk. We aimed to explore the risk of CMDs in relation to the long-term level and change of TyG-index. Methods: Based on the prospective cohort study, a total of 36359 subjects who were free of CMDs, had complete data of triglyceride (TG) and fasting blood glucose (FBG) and underwent four health check-ups from 2006 to 2012 consecutively were followed up for CMDs until 2021. The associations between long-term level and change of TyG-index and CMDs risk were assessed by Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs). The TyG-index was calculated as ln [TG, mg/dL) × FBG, mg/dL)/2]. Results: During the median observation period of 8 years, 4685 subjects were newly diagnosed with CMDs. In multivariable-adjusted models, a graded positive association was observed between CMDs and long-term TyG-index. Compared with the Q1 group, subjects with the Q2-Q4 group had increased progressively risk of CMDs, with corresponding HRs of 1.64(1.47-1.83), 2.36(2.13-2.62), 3.15(2.84-3.49), respectively. The association was marginally attenuated, after further adjustment for the baseline TyG level. In addition, compared with stable TyG level, both loss and gain in TyG level were associated with increased CMDs risk. Conclusions: Long-term elevated level and change of TyG-index are risk factors for the incident CMDs. Elevated TyG-index in the early stage remains to exert cumulative effects on the occurrence of CMDs even after accounting for the baseline TyG-index.

CHD8 mutations increase gliogenesis to enlarge brain size in the nonhuman primate.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that affects social interaction and behavior. Mutations in the gene encoding chromodomain helicase DNA-binding protein 8 (CHD8) lead to autism symptoms and macrocephaly by a haploinsufficiency mechanism. However, studies of small animal models showed inconsistent findings about the mechanisms for CHD8 deficiency-mediated autism symptoms and macrocephaly. Using the nonhuman primate as a model system, we found that CRISPR/Cas9-mediated CHD8 mutations in the embryos of cynomolgus monkeys led to increased gliogenesis to cause macrocephaly in cynomolgus monkeys. Disrupting CHD8 in the fetal monkey brain prior to gliogenesis increased the number of glial cells in newborn monkeys. Moreover, knocking down CHD8 via CRISPR/Cas9 in organotypic monkey brain slices from newborn monkeys also enhanced the proliferation of glial cells. Our findings suggest that gliogenesis is critical for brain size in primates and that abnormal gliogenesis may contribute to ASD.

Relationship between early-onset stroke and triglyceride-glucose index among young Chinese adults.

BACKGROUND: The triglyceride-glucose index (TyG index), an alternative indicator of peripheral insulin resistance (IR), is associated with cardiovascular disease (CVD) in the general population. The aim of this research was to determine the correlation between early-onset stroke and the TyG index among young Chinese adults. METHODS: Participants (age ≤ 40 years) who attended their first physical examination in Kailuan General Hospital or its 11 subsidiary hospitals between 2006 and 2012 were enrolled. The subjects were divided into four equal points according to the quartile of the TyG index, with the lowest quartile (Q1) as the reference group. A Cox proportional hazard model was employed to assess the correlation between early-onset stroke incidence and the TyG index. Restricted cubic spline analysis was further conducted to examine nonlinear associations. The TyG index was calculated as Ln [Triglyceride (TG, mg/dL) × Fasting Blood Glucose (FBG, mg/dL)/2]. RESULTS: Overall, 35,999 subjects met the inclusion criteria. Their mean age was 30.8 ±  5.7 years, and 77.1% of subjects were males. During a median observation period of 11 years, 281 stroke events occurred (62 hemorrhagic strokes and 219 ischemic strokes). Compared to the Q1 group (as the lowest group), subjects in groups Q2-Q4 had significantly higher risks of early-onset stroke (P < 0.05) after adjustment for relevant confounders in the Cox proportional hazards model. Similar results were consistent with ischemic stroke. However, no significant associations were observed between the risk of hemorrhage and the baseline TyG index. The restricted cubic splines revealed that the risk of stroke progressively increased with a high TyG index ≥ 8.41. CONCLUSIONS: The TyG index may be a major risk factor for early-onset stroke among young Chinese adults. A TyG index ≥ 8.41 can be used as an indicator for screening high-risk stroke groups.