Involvement and regulation of the left anterior cingulate cortex in the ultrasonic communication deficits of autistic mice.

Introduction: Autism spectrum disorder (ASD) is a group of diseases often characterized by poor sociability and challenges in social communication. The anterior cingulate cortex (ACC) is a core brain region for social function. Whether it contributes to the defects of social communication in ASD and whether it could be physiologically modulated to improve social communication have been poorly investigated. This study is aimed at addressing these questions. Methods: Fragile X mental retardation 1 (FMR1) mutant and valproic acid (VPA)-induced ASD mice were used. Male-female social interaction was adopted to elicit ultrasonic vocalization (USV). Immunohistochemistry was used to evaluate USV-activated neurons. Optogenetic and precise target transcranial magnetic stimulation (TMS) were utilized to modulate anterior cingulate cortex (ACC) neuronal activity. Results: In wild-type (WT) mice, USV elicited rapid expression of c-Fos in the excitatory neurons of the left but not the right ACC. Optogenetic inhibition of the left ACC neurons in WT mice effectively suppressed social-induced USV. In FMR1-/-- and VPA-induced ASD mice, significantly fewer c-Fos/CaMKII-positive neurons were observed in the left ACC following USV compared to the control. Optogenetic activation of the left ACC neurons in FMR1-/- or VPA-pretreated mice significantly increased social activity elicited by USV. Furthermore, precisely stimulating neuronal activity in the left ACC, but not the right ACC, by repeated TMS effectively rescued the USV emission in these ASD mice. Discussion: The excitatory neurons in the left ACC are responsive to socially elicited USV. Their silence mediates the deficiency of social communication in FMR1-/- and VPA-induced ASD mice. Precisely modulating the left ACC neuronal activity by repeated TMS can promote the social communication in FMR1-/- and VPA-pretreated mice.

Correlation Between Serum Vitamin E and HOMA-IR in Patients with T2DM.

Background: Peroxidation is one of the important causes of insulin resistance (IR), and vitamin E is a natural antioxidant, and there may be some correlation between serum vitamin E levels and insulin resistance. Purpose: The correlation between serum vitamin E and insulin resistance in type 2 diabetes mellitus (T2DM) population. Methods: Two hundred and forty-two people (119 with T2DM) were included. One hundred and nineteen patients with T2DM were selected as the case group, and 123 people with non-T2DM were selected as the control group. People insulin resistance was detected by the homeostasis model assessment method (HOMA-IR) greater than 2.69 were included in the diabetic insulin resistance group, and those with HOMA-IR less than 2.69 were included in the diabetic non-insulin resistance group. Record the general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Correlation analysis, logistic regression, trend analysis, and restricted cubic spline (RCS) were performed using SPSS 25.0 and R 4.1.1 software. Correlation analysis, logistic regression, trend analysis, restricted cubic spline (RCS) analysis were conducted on general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Results: The logistic regression results showed that after adjusting for confounding factors, vitamin E was an independent influencing factor for insulin resistance in T2DM patients (P < 0.001). The trend analysis results show that with the decrease of serum vitamin E levels, the risk of insulin resistance in T2DM patients gradually increases. The RCS results showed that the risk of insulin resistance was significantly increased when the serum vitamin E level was lower than 10,575.23 ng/mL. Conclusion: Serum vitamin E levels are lower in T2DM patients than in healthy populations; Vitamin E is an independent influencing factor for HOMA-IR in T2DM patients. The risk of insulin resistance gradually increases in T2DM patients as serum vitamin E levels decrease. Vitamin E is a risk factor for insulin resistance at serum vitamin E levels below 10,575.23 ng/mL. At higher serum vitamin E levels than 10,575.23 ng/mL, vitamin E is a protective factor for insulin resistance.

Elevated ITGA1 levels in type 2 diabetes: implications for cardiac function impairment.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies. METHODS: Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals' left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF. RESULTS: Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p=0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF. CONCLUSIONS/INTERPRETATION: ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes. DATA AVAILABILITY: The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org .

The Effect of Different Diluents and Curing Agents on the Performance of Epoxy Resin-Based Intumescent Flame-Retardant Coatings.

The epoxy resin-based (ESB) intumescent flame-retardant coatings were modified with 1,4-butanediol diglycidyl ether (14BDDE) and butyl glycidyl ether (BGE) as diluents and T403 and 4,4'-diaminodiphenylmethane (DDM) as curing agents, respectively. The effects of different diluents and curing agents on the flame-retardant and mechanical properties, as well as the composition evolution of the coatings, were investigated by using large-plate combustion, the limiting oxygen index (LOI), vertical combustion, a cone calorimeter, X-ray diffraction, FTIR analysis, a N2 adsorption and desorption test, a scanning electron microscope (SEM), a tensile strength test, and a viscosity test. The results showed that the addition of 14BBDE and T403 promoted the oxidation of B4C and the formation of boron-containing glass or ceramics, increased the residual mass of char, densified the surface char layer, and increased the specific surface area of porous residual char. When their dosage was 30%, ESB-1T-3 coating exhibited the most excellent flame-retardant properties. During the 2 h large-plate combustion test, the backside temperature was only 138.72 °C, without any melting pits. In addition, the peak heat release rate (PHRR), total heat release rate (THR), total smoke production (TSP), and peak smoke production (PSPR) were reduced by 13.15%, 13.9%, 5.48%, and 17.45%, respectively, compared to the blank ESB coating. The LOI value reached 33.4%, and the vertical combustion grade was V-0. In addition, the tensile strength of the ESB-1T-3 sample was increased by 10.94% compared to ESB. In contrast, the addition of BGE and DDM promoted the combustion of the coating, affected the ceramic process of the coating, seriously affected the formation of borosilicate glass, and exhibited poor flame retardancy. The backside temperature reached 190.93 °C after 2 h combustion. A unified rule is that as the amount of diluent and curing agent increases, the flame retardancy improves while the mechanical properties decrease. This work provides data support for the preparation and process optimization of resin-based coatings.

Comparing Protein and Gene Expression Signature between Nasal Polyps and Nasal Fluids in Chronic Rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a serious inflammatory condition. Nasal fluids (NFs) present a noninvasive alternative to nasal biopsy for studying CRSwNP pathogenesis. We aimed to compare the protein and mRNA inflammation signature between nasal polyps (NPs) and NFs. METHOD: The performance of polyvinyl alcohol (PVA) sponges and NFs absorbable device (NFAD) for collecting NFs from 20 patients with CRSwNP was compared using the Luminex assay. The other group consisted of four healthy controls and an additional 21 CRSwNP patients (including eosinophilic CRSwNP [ECRSwNP] and non-eosinophilic CRSwNP [NECRSwNP]) for protein quantification by Olink platform and gene expression evaluation by RNA-sequencing. Spearman's analysis was performed to detect correlations between protein expression levels in NFs and clinical assessment variables. RESULTS: NFAD-collected NFs contained at least a 2-fold higher concentration of cytokines than that obtained using PVA sponge, and these cytokines levels are significantly associated with NPs (ρ > 0.45, p < 0.05). Differentially expressed proteins between NFs and NPs were significantly correlated in the ECRSwNP subgroup compared with controls (ρ = 0.41, p < 0.01). Levels of Th2/IL-13, MCP4, and CCL4, characteristic of eosinophilic infiltration, were increased in ECRSwNP patients. A significant correlation between gene and protein expression was observed (ρ = 0.34, p < 0.01). PDL2 levels in NFs were positively correlated with ECRSwNP postoperative recurrence, the nasal VAS, and SNOT-22 scores (ρ > 0.68, p < 0.05 for all). CONCLUSION: Our study revealed similarities and discrepancies in inflammatory signatures between NPs and NFs in the same CRSwNP patient.

Correlation Between the Levels of ANGPTL3, ANGPTL4, ANGPTL8 and Postprandial Triglyceride-Rich Lipoprotein (TRL).

Purpose: To investigate the effects of different angiopoietin-like proteins (ANGPTLs) on postprandial hypertriglyceridemia (PPT) by analyzing changes in serum lipid, ANGPTL3, ANGPTL4, and ANGPTL8 levels before and after a high-fat diet in individuals with normal fasting lipid and oral glucose tolerance test results. Patients and Methods: Exactly 103 volunteers were recruited for an oral fat tolerance test (OFTT). Blood samples were obtained at 0, 2, and 4 h after eating to detect relevant indicators. PPT was defined as triglyceride (TG) levels ≥ 2.5 mmol/L. According to the test results, the participants were divided into two groups: postprandial normal triglycerides (PNT) and PPT. The levels of blood lipids and ANGPTL3, ANGPTL4, and ANGPTL8 were compared between the two groups. Results: There were differences in the body mass index (BMI), waist circumference (WC), fasting total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), triglyceride-rich lipoprotein cholesterol (TRL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), ApoA1/ApoB, fasting blood glucose (FBG), fasting insulin (FINS), ANGPTL4, and ANGPTL8 between the two groups. In the PNT group, the TG level increased from baseline at 2 and 4 h, TRL-C increased from baseline at 4 h, and ANGPTL8 decreased from baseline at 2 and 4 h. After OFTT, the levels of TG, TRL-C, ANGPTL3, and ANGPTL4 in the PPT group gradually increased; ANGPTL8 gradually decreased. Fasting ANGPTL3 was positively associated with age, TC, HDL-C, TRL-C, and ApoA1, and negatively associated with systolic blood pressure. Fasting ANGPTL4 was positively correlated with weight, WC, BMI, TC, TG, LDL-C, TRL-C, non-HDL-C, ApoB, FBG, and FINS, and negatively correlated with ApoA1/ApoB and fasting ANGPTL8. Binary logistic regression analysis indicated that ANGPTL4 and ANGPTL8 were significant predictors of PPT. Conclusion: PPT occurrence is closely associated with changes in ANGPTL4 and ANGPTL8 levels.

A bibliometric analysis and visualization of literature on non-fasting lipid research from 2012 to 2022.

Background: Non-fasting lipid assessment can help predict cardiovascular disease risks and is linked to multiple diseases, particularly diabetes. The significance of non-fasting lipid levels in routine screening and postprandial lipid tests for potential dyslipidemia has not been conclusively determined. Various new lipid-lowering strategies have been developed to improve non-fasting dyslipidemia. Therefore, analysis of scientific outputs over the past decade is essential to reveal trends, hotspots, and frontier areas for future research in this field. Methods: The Science Citation Index Expanded in the Web of Science Core Collection database was searched for publications related to non-fasting lipid research from 2012 to 2022. The regional distributions, authors, disciplines, journals, references, and keywords of the studies were analyzed using the bibliometric software VOSviewer and CiteSpace. Results: A total of 4160 articles and reviews that met the inclusion criteria were included in this study. The output trend was established to be stable and the number of citation indices has been persistently increasing. A total of 104 countries/regions, 4668 organizations, and 20782 authors were involved in this research area. In terms of country, the United States had the largest number of publications (979). The University of Copenhagen was the most productive institution, publishing 148 papers. Professor Børge G Nordestgaard has made the most significant contribution to this field. Nutrients was the most productive journal while the American Journal of Clinical Nutrition was the highest co-cited journal. Analysis of co-cited references indicated that lipid-lowering strategies, statin therapy, high-fat meals, insulin resistance, physical exercise, and fructose were hotspots. Analysis of co-cited keywords revealed that apolipoprotein B, especially apolipoprotein B48, is becoming a key research focus. The keywords "gut microbiota" and "meal timing" were the most extensively studied. Conclusion: The causal relationship between non-fasting dyslipidemia and diseases is currently being explored and the standards for non-fasting or postprandial lipid assessment are continuously being updated. Among the hotspots, lipid-lowering strategies are a potential research direction. Apolipoprotein B48, gut microbiota, and chrononutrition are the research frontiers. This initial bibliometric analysis of non-fasting lipids will enable researchers to monitor swift transformations and recognize novel concepts for upcoming research.

Associations Between Serum Folate Level and HOMA-IR in Chinese Patients with Type 2 Diabetes Mellitus.

Background: Adequate intake of folic acid (FA) has been proven essential for metabolism, cellular homeostasis, and antioxidant effects in diabetic patients. Our aim was to evaluate the association between serum folate levels and the risk of insulin resistance in patients with type 2 diabetes mellitus (T2DM) and to provide new ideas and approaches for reducing the risk of T2DM. Methods: This was a case-control study involving 412 participants (206 with T2DM). Anthropometric parameters, islet function, biochemical parameters and body composition of T2DM group and control group were determined. Correlation analysis and logistic regression were used to evaluate the risk factors associated with the onset of insulin resistance in T2DM. Results: The folate levels in type 2 diabetic patients with insulin resistance were significantly lower than those in patients without insulin resistance. Logistic regression showed that FA and high-density lipoprotein were independent influencing factors for insulin resistance in diabetic patients (P < 0.05). After adjusting for confounding factors, the degree of insulin resistance in diabetic patients was in a significant inverse relationship with folate levels (P< 0.05). We also found that below the serum FA threshold of 7.09 ng/mL insulin resistance was significantly more elevated. Conclusion: Our findings suggest that the risk of insulin resistance increases with the decrease in serum FA levels in T2DM patients. Monitoring folate levels in these patients and FA supplementation are warranted preventive measures.

Association of Bone Turnover Markers with Type 2 Diabetes Mellitus and Microvascular Complications: A Matched Case-Control Study.

Purpose: The aim of this study was to evaluate the association of bone turnover markers (BTMs) with type 2 diabetes mellitus (T2DM) and microvascular complications. Methods: A total of 166 T2DM patients and 166 non-diabetic controls matched by gender and age were enrolled. T2DM patients were sub-classified into groups based on whether they had diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). Clinical data including demographic characteristics and blood test results [serum levels of osteocalcin (OC), N-terminal propeptide of type 1 procollagen (P1NP), and ß-crosslaps (ß-CTX)] were collected. Logistic regression and restrictive cubic spline curves were performed to examine the association of BTMs with the risk of T2DM and microvascular complications. Results: After adjusting for family history of diabetes, sex and age, an inverse association was observed between elevated serum OC levels [O, p < 0.001] and increased serum P1NP levels , p < 0.001] with the risk of T2DM. Moreover, there was an inverse linear association of serum OC and P1NP levels with the risk of T2DM. However, ß-CTX was not associated with T2DM. Further analysis showed a nonlinear association between OC and the risk of DR, while P1NP and ß-CTX were not correlated with DR. Serum concentrations of BTMs were not associated with the risks of DPN and DKD. Conclusion: Serum OC and P1NP levels were negatively correlated with T2DM risk. Particularly, serum OC levels were associated with DR risk. Given that BTMs are widely used as markers of bone remodeling, the present finding provides a new perspective for estimating the risk of diabetic microvascular complications.

Meta-analysis of Serum Vitamin B12 Levels and Diabetic Retinopathy in Type 2 Diabetes.

BACKGROUND: Previous studies have shown an association between low serum vitamin B12 levels and the risk of diabetic retinopathy (DR) in type 2 diabetes, but the conclusions from various studies were inconsistent. Therefore, we collected relevant data from various databases to perform a meta-analysis and address the inconsistencies in these studies. METHODS: We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang and CQVIP for eligible studies published up to April 10, 2022, and performed a meta-analysis using Stata software to assess the association between serum vitamin B12 levels and DR. RESULTS: A total of 15 studies were included in this meta-analysis. Statistical analysis showed that serum vitamin B12 levels were significantly reduced in patients with type 2 diabetic retinopathy ,WMD 95% CI = -68.91 (-76.76, -61.06) (p <0.00001, I2 = 88.30%). In subgroup analyses by ethnicity, an association between low serum vitamin B12 levels and DR risk was found in East Asian, South Asian and mixed populations, but not in Caucasian populations. CONCLUSIONS: This meta-analysis analyzed vitamin B12 in patients with type 2 diabetic retinopathy and emphasized the importance of monitoring serum vitamin B12 levels in patients with type 2 diabetic retinopathy, but this meta-analysis still has deficiencies and limitations, and more clinical studies are needed to confirm this conclusion in the future.

Plasma exosomal miR-122 regulates the efficacy of metformin via AMPK in type 2 diabetes and hepatocellular carcinoma.

Metformin is a drug that has been applied in clinical use for many years for the treatment of type 2 diabetes mellitus (T2DM). It achieves its function through multiple targets and modulation of multiple signaling pathways. To date, the mechanism of the action of metformin is still not fully understood. Along with glycemic control, metformin has shown good inhibitory effects on the development of many tumors. Here, we elucidated that plasma exosomal microRNA-122-5p (miR-122) is closely related to the mechanism of metformin. MiR-122 regulates glycogen-glucose metabolism in hepatocytes or hepatocellular carcinoma cells (HCC) by inhibiting the phosphorylation of AMPK. Since miR-122 and metformin regulate glucose metabolism homeostasis through similar mechanisms, miR-122 can antagonize the effects of metformin. MiR-122 expression increases the sensitivity of hepatocytes or HCC to metformin. Conversely, decreased expression of miR-122 results in hepatocyte insensitivity to metformin. Therefore, significantly elevated levels of miR-122 in plasma exosomes of hepatocellular carcinoma patients could enhance their sensitivity to metformin. The results of the present study revealed a key regulatory role of plasma exosomal miR-122 on the molecular mechanism of metformin. The regulation of key molecules of related signaling pathways by miR-122 may lead to similar glycemic lowering and tumor suppression therapeutic effects as metformin. This provides new ideas for the development of new therapeutic strategies for hepatocellular carcinoma based on the mechanism of miR-122 and metformin.

Control Strategies of Plastic Biodegradation through Adjusting Additives Ratios Using In Silico Approaches Associated with Proportional Factorial Experimental Design.

Plastics, as a polymer material, have long been a source of environmental concern. This paper uses polystyrene plastics as the research object, and the relative contribution of each component of plastic additives to plastic degradation is screened using the molecular dynamics method. The factorial experimental design method is combined with molecular dynamics simulation to adjust the additive composition scheme, analyze the mechanism of interaction between the additive components, and select the plastic additive combination that is most readily absorbed and degraded by microorganisms. Seven different types of plastic additives, including plasticizers, antioxidants, light and heat stabilizers, flame retardants, lubricants, and fillers, are chosen as external stimuli affecting the biodegradability of plastics. Using molecular dynamics simulation technology, it is demonstrated that plastic additives can promote the biodegradability of plastics. The factorial experimental design analysis revealed that all plastic additives can promote plastic biodegradation and plasticizer is the most favorable factor affecting plastic degradation, that hydrophobicity interactions are the primary reason for enhancing plastic degradation, and that screening No. 116-45 (plasticizer A, light stabilizer C, flame retardant E) is the most advantageous combination of biodegradable plastic additives. The plastic biodegradation effect regulation scheme proposed in this study is based on optimizing the proportion of additive components. To continue research on aquatic biodegradable plastics, the optimal combination of plastic components that can be absorbed and degraded by microorganisms is recommended.

HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway.

As a group of nonspecific inflammatory diseases affecting the intestine, inflammatory bowel disease (IBD) exhibits the characteristics of chronic recurring inflammation, and was proven to be increasing in incidence (Kaplan, 2015). IBD induced by genetic background, environmental changes, immune functions, microbial composition, and toxin exposures (Sasson et al., 2021) primarily includes ulcerative colitis (UC) and Crohn's disease (CD) with complicated clinical symptoms featured by abdominal pain, diarrhea, and even blood in stools (Fan et al., 2021; Huang et al., 2021). UC is mainly limited to the rectum and the colon, while CD usually impacts the terminal ileum and colon in a discontinuous manner (Ordás et al., 2012; Panés and Rimola, 2017). In recent years, many studies have suggested the lack of effective measures in the diagnosis and treatment of IBD, prompting an urgent need for new strategies to understand the mechanisms of and offer promising therapies for IBD.

Effect of glucagon-like peptide-1 receptor agonists on fat distribution in patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS/INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1Ras) are widely used to treat type 2 diabetes. They not only reduce glucose, but also have a positive effect on weight loss. However, few studies have reported the effect of GLP-1Ras on fat distribution. MATERIALS AND METHODS: PubMed, Cochrane, Embase and ClinicalTrials.gov were searched for randomized controlled trials on GLP-1Ras and type 2 diabetes, published from inception to June 2021. Our main outcomes were the reductions of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Other anthropometric outcomes were also assessed. We used the Cochrane Collaboration tools to assess the risk of bias in the included studies. The quality of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation profiler version 3.6. Review Manager 5.4.1 and Stata 16.0 were used for data analysis. RESULTS: A total of 10 studies involving 541 patients were included. Compared with the control groups, the GLP-1Ras groups showed reductions in VAT (standard mean difference -0.54, 95% confidence interval [CI] -0.92, -0.17, I2 = 79%, P = 0.005) and SAT (standard mean difference -0.44, 95% CI -0.60, -0.27, I2 = 44%, P < 0.00001). In addition, bodyweight (weighted mean difference -3.59, 95% CI -4.30, -2.88, I2 = 0%, P < 0.00001), waist circumference (weighted mean difference -3.09, 95% CI -4.66, -1.52, I2 = 70%, P = 0.0001) and body mass index (weighted mean difference -1.11, 95% CI -1.35, -0.86, I2 = 47%, P < 0.00001) were significantly decreased. According to the Grades of Recommendation, Assessment, Development and Evaluation approach, the level of evidence was low or moderate. CONCLUSION: This study highlights that GLP-1Ras, especially liraglutide and exenatide, might play an active role in fat distribution in patients with type 2 diabetes. After treatment with GLP-1Ras, both VAT and SAT decreased, and the decrease of VAT was numerically greater than that of SAT.

Rational Design of Zinc/Zeolite Catalyst: Selective Formation of p-Xylene from Methanol to Aromatics Reaction.

The production of p-xylene from the methanol to aromatics (MTA) reaction is challenging. The catalytic stability, which is inversely proportional to the particle size of the zeolite, is not always compatible with p-xylene selectivity, which is inversely proportional to the external acid sites. In this study, based on a nano-sized zeolite, we designed hollow triple-shelled Zn/MFI single crystals using the ultra-dilute liquid-phase growth technique. The obtained composites possessed one ZSM-5 layer (≈30 nm) in the middle and two silicalite-1 layers (≈20 nm) epitaxially grown on two sides of ZSM-5, which exhibited a considerably long lifetime (100 % methanol conversion >40 h) as well as an enhanced shape selectivity of p-xylene (>35 %) with a p-xylene/xylene ratio of ≈90 %. Importantly, using this sandwich-like zeolite structure, we directly imaged the Zn species in the micropores of only the ZSM-5 layer and further determined the specific structure and anchor location of the Zn species.

Molecular design of high-efficacy and high drug safety Fluoroquinolones suitable for a variety of aerobic biodegradation bacteria.

The present study attempted to improve the biodegradation removal rate of Fluoroquinolones (FQs) in sewage treatment plants. The similarity index analysis (CoMSIA) model for combined biodegradability was constructed, and 33 kinds of molecular derivatives of FQs suitable for a variety of aerobic biodegradation microorganisms were designed. Further, derivative-20 and derivative-28, with high drug efficiency, drug safety, and environmental friendliness were selected through pharmacokinetics (ADMET), toxicokinetics (TOPKAT), FQs functional characteristics, and environmental friendliness evaluations. Compared with the target molecules, the combined biodegradability of the above two FQ-derivative molecules were increased by 193.57 % and 205.07 %, respectively, while their environment-friendly characteristics were improved to a certain degree. Through molecular docking and molecular dynamic simulation analysis, it showed that van der Waals force (decreased by 2.73 %-61.74 %) was the main factor influencing the binding ability of the modified FQ molecules to the receptor proteins. In addition, the relationship among the non-bonding interaction resultant force, the binding effect of the FQ-derivative molecules, and the receptor protein-related amino acid residues were studied for the first time. It was observed that the higher the value of the non-bonding interaction resultant force, the better was the binding effect, which demonstrating the significantly improved biodegradability of the designed FQ-derivative molecules.

Temozolomide chemotherapy combined with radiotherapy versus radiotherapy alone after surgery in patients with high-risk low-grade gliomas.

PURPOSE: The purpose of this study was to compare the clinical efficacy and safety of temozolomide (TMZ) combined with three-dimensional conformal radiotherapy (3D-CRT) and radiotherapy alone after surgery in patients with high-risk low-grade gliomas (LGGs). METHODS: Patients (N=110) with LGGs were enrolled. Patients receiving TMZ chemotherapy combined with radiotherapy were considered as combination group (n=55), while those treated with radiotherapy alone were regarded as control group (n=55). The patients were followed up, and the overall survival (OS) and progression-free survival (PFS) were recorded. Finally, factors possibly affecting prognosis were analyzed. RESULTS: The follow-up results exhibited median OS [(67.4±8.8) months vs. (63.9±8.6) months] and median PFS [(51.1±7.6) months vs. (46.8±6.9) months] as well as three-year OS rate and three-year PFS rate in combination group and control group. Log-rank test indicated that the difference in OS was not statistically significant between the two groups of patients, and PFS in combination group was significantly superior to that in control group. The results of univariate and multivariate analysis displayed that age <40 years old and complete tumor resection were independent factors affecting the three-year OS of patients with high-risk LGGs. Besides, age <40 years old, complete tumor resection and TMZ chemotherapy combined with radiotherapy after surgery were independent factors affecting the three-year PFS of patients with high-risk LGGs. CONCLUSION: TMZ chemotherapy combined with radiotherapy after surgery in patients with high-risk LGGs can prominently improve clinical efficacy, prolong PFS, and facilitate tolerance to adverse reactions, but not prolong the OS of patients. The OS is notably prolonged in patients aged <40 years old and receiving complete tumor resection.

Disruption of the autism-related gene Pak1 causes stereocilia disorganization, hair cell loss, and deafness in mice.

Several clinical studies have reported that hearing loss is correlated with autism in children. However, little is known about the underlying mechanism between hearing loss and autism. p21-activated kinases (PAKs) are a family of serine/threonine kinases that can be activated by multiple signaling molecules, particularly the Rho family of small GTPases. Previous studies have shown that Pak1 mutations are associated with autism. In the present study, we take advantage of Pak1 knockout (Pak1-/-) mice to investigate the role of PAK1 in hearing function. We find that PAK1 is highly expressed in the postnatal mouse cochlea and that PAK1 deficiency leads to hair cell (HC) apoptosis and severe hearing loss. Further investigation indicates that PAK1 deficiency downregulates the phosphorylation of cofilin and ezrin-radixin-moesin and the expression of ßII-spectrin, which further decreases the HC synapse density in the basal turn of cochlea and disorganized the HC stereocilia in all three turns of cochlea in Pak1-/- mice. Overall, our work demonstrates that the autism-related gene Pak1 plays a crucial role in hearing function. As the first candidate gene linking autism and hearing loss, Pak1 may serve as a potential target for the clinical diagnosis of autism-related hearing loss.

miR-93-5p promotes insulin resistance to regulate type 2 diabetes progression in HepG2 cells by targeting HGF.

Insulin resistance is a common feature of type 2 diabetes mellitus (T2DM). However, the mechanisms underlying insulin resistance are not completely understood. The present study aimed to investigate the effect of microRNA (miR)­93­5p on insulin resistance in T2DM cells. Human hepatocellular carcinoma (HCC; HepG2) cells were cultured in medium with high glucose content (30 mM glucose) to establish an in vitro insulin­resistant cell model (IR group). Glucose consumption and glycogen synthesis assays were performed to assess glucose consumption and glycogen synthesis, respectively. By performing immunoprecipitation assays, the abundance of the Met­insulin receptor complex was detected in HepG2 cells. miR­93­5p and hepatocyte growth factor (HGF) mRNA expression levels were measured via reverse transcription­quantitative PCR, and HGF protein expression levels were measured via western blotting. A dual­luciferase reporter assay was conducted to investigate the interaction between miR­93­5p and HGF. Cell Counting Kit­8, BrdU and caspase­3 activity assays were performed to evaluate cell viability, proliferation and apoptosis, respectively, in insulin­resistant HepG2 cells following transfection with small interfering RNA­HGF, HGF overexpression vector, miR­93­5p mimic or miR­93­5p inhibitor. The results demonstrated that miR­93­5p expression was significantly increased and HGF expression was significantly decreased in HCC tissues isolated from patients with or without T2DM compared with adjacent healthy tissues isolated from patients without T2DM. Compared with the IR group, miR­93­5p overexpression significantly increased cell proliferation, glucose consumption and glycogen synthesis, but significantly inhibited apoptosis in insulin­resistant HepG2 cells. By contrast, compared with the IR group, HGF overexpression significantly inhibited cell proliferation, glucose consumption and glycogen synthesis, but significantly enhanced cell apoptosis in insulin­resistant HepG2 cells. Following co­transfection with HGF overexpression vector and miR­93­5p mimic, miR­93­5p mimic­mediated induction of HepG2 cell proliferation, glucose consumption and glycogen synthesis in insulin­resistant HepG2 cells was inhibited. Collectively, the results of the present study indicated that miR­93­5p enhanced insulin resistance to regulate T2DM progression in HepG2 cells by targeting HGF.

LF-rTMS ameliorates social dysfunction of FMR1-/- mice via modulating Akt/GSK-3ß signaling.

Autism spectrum disorders (ASD) are a group of neurological disorders which affect approximately 1% of children around the world. Social dysfunction is one of the two core syndromes of ASD, and still lacks effective treatment. Transcranial magnetic stimulation (TMS) is a noninvasive and safe procedure that uses magnetic fields to modulate neural activity. Whether it were effective in modulating social function remains unclear. By using 3-chamber test, ultrasonic vocalization recording and Western-blotting, we demonstrated that FMR1 (fragile X mental retardation protein) mutant mice, a model of ASD, exhibited obvious defects in social preference and ultrasonic communication. In addition, we detected increase of p-Akt (S473) and p-GSK-3ß (S9), and decrease of p-PSD-95 (T19) in the anterior cingulate cortex (ACC) of FMR1-/- mice. Treating FMR1-/- mice with 1 Hz repetitive TMS (rTMS) exerted a long lasting effect in improving both the ultrasonic communication and social preference, as well as restoring the levels of Akt/GSK-3ß activity and spine density in the FMR1-/-ACC. Our data, for the first time, demonstrated a beneficial effect of low frequency rTMS (LF-rTMS) on the social function of FMR1-/- mice and an involvement of Akt/GSK-3ß signaling in this process, indicating LF-rTMS as a potential therapeutic strategy for ASD patients.