Proteomics in Cardiovascular disease.

This study focuses on recent advances in proteomics and provides an up-to-date use of this technology in identifying cardiovascular disease (CVD) biomarkers. A total of eight electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang, Vip, Sinomed, and CNKI) were searched and five were used for integrative analysis of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR) and 1 secondary indicator area under the curve (AUC). This systematic review and integrative analysis summarized potential biomarkers previously identified by proteomics. The integrative analysis suggested that proteomics technology had high clinical value in CVD diagnosis. The findings provided new possible directions for the prevention or diagnosis of CVD.

Purification of dredged water by magnetic coagulation: Response surface optimization and dissolved organic matter removal characteristics.

In the present study, magnetic coagulation was used to treat dredged water and the response surface method was used to optimize process parameters. The dissolved organic matter (DOM) removal characteristics were characterized by three-dimensional fluorescence spectrometry and ultra-high resolution mass spectrometry. During the magnetic coagulation process, the suspended solids (SS) removal rate increased initially and then decreased under conditions of increasing magnetic powder dosage and stirring rate. After magnetic coagulation and precipitation for 20 min, the contents of SS, ammonia nitrogen, chemical oxygen demand, and total phosphorus in the treated dredged water met the requirements of the discharge standard (GB8978-1996, China). Three-dimensional fluorescence results showed that magnetic coagulation selectively removed fulvic acids and humic acid substances. After magnetic coagulation with precipitation for 10 min and 20 min, the total relative content of lignins, tannins, proteins, lipids, aminosugars, unsaturated hydrocarbons, condensed aromatic structures, and carbohydrates decreased by 26.3% and 39.4%, respectively. After magnetic coagulation, the distribution range of small molecule DOM shifted to the low H/C and high O/C regions. This study provides a novel perspective for studies on the removal of DOM in dredged water by magnetic coagulation. PRACTITIONER POINTS: SS and DOM removal were significantly enhanced by the use of magnetic coagulation. SS removal efficiency was affected by stirring rate and magnetic powder dosage. Magnetic coagulation selectively removed fulvic acids and humic acid substances. DOM molecule shifted to low H/C and high O/C regions after magnetic coagulation.

Knowledge, attitudes and practices towards advance directives among clinical nurses: Multicenter cross-sectional survey.

AIMS AND OBJECTIVES: This study aimed to describe the knowledge, attitudes and practices (KAP) of nurses in implementing advance directives (ADs) for older patients and analyze the influencing factors before the establishment of the first advance directives act in China. DESIGN: Multicenter cross-sectional survey. The standards for reporting the STROBE checklist are used. METHODS: This cross-sectional study developed a self-designed structured questionnaire to assess nurses' knowledge, attitudes and practices about ADs. Nurses were recruited by stratified random sampling through the Nursing Departments of 12 hospitals in southwest China and were asked to fill out the questionnaire face to face about knowledge, attitudes and practices. Data were analyzed following descriptive statistics, rank-sum test and multiple linear regression. RESULTS: This study included 950 nurses. The study found that nurses were extremely supportive of ADs. Unmarried nurses had better knowledge of ADs than married ones. Nevertheless, there was a discrepancy between the participants' knowledge, attitude and practice. The participants' practice was lower (4.3%) compared with their attitude (81.9%) and knowledge (42.2%). Knowledge on, attitudes towards and standardized procedures for ADs in the workplace affected nursing practice. CONCLUSIONS: The study recommends that courses on ADs and appropriate support from medical institutions should be provided to nurses to increase their knowledge and confidence in implementing ADs. Healthcare professionals should be sufficiently equipped to implement ADs and handle their execution appropriately to provide adequate end-of-life care corresponding to patients' wishes. RELEVANCE TO CLINICAL PRACTICE: The study results inform rich insights as it discusses the numerous interrelating factors influencing these three fundamental aspects that affect the success of any AD policy by surveying the knowledge, attitudes and practices of clinical nurses. Furthermore, our results hint at distinct areas of improvement in the nursing practice to facilitate the wider implementation and acceptance of ADs in China. PATIENT OR PUBLIC CONTRIBUTION: This study involved no patient.

Association of phenotypic frailty and frailty index with type 2 diabetes and dyslipidemia in middle-aged and elderly Chinese: A longitudinal cohort study.

PURPOSE: Frailty, type 2 diabetes (T2D) and dyslipidemia are highly prevalent in middle-aged and elderly populations. However, evidence on the longitudinal association of frailty with T2D and dyslipidemia is limited. The aim of our study was to explore the cross-sectional and longitudinal effects of frailty levels on T2D and dyslipidemia in combination with phenotypic frailty and frailty index (FI). MATERIALS AND METHODS: Multivariate logistic regression model was used to explore the association of frailty status with T2D and dyslipidemia. Area under curve (AUC) of the receiver operating characteristic curve (ROC) to estimate the predictive values of phenotypic frailty and frailty index for T2D and dyslipidemia. In addition, depressive symptom was used as a mediating variable to examine whether it mediates the association between frailty and T2D or dyslipidemia. RESULTS: 10,203 and 9587 participants were chosen for the longitudinal association analysis of frailty with T2D and dyslipidemia. Frailty was associated with T2D (phenotypic frailty: OR=1.50, 95 %CI=1.03, 2.17; FI: OR=1.17, 95 %CI=1.08, 1.26) and dyslipidemia (phenotypic frailty: OR=1.56, 95 %CI=1.16, 2.10; FI: OR=1.17, 95 %CI=1.10, 1.25). Phenotypic frailty and frailty index significantly improved the risk discrimination of T2D and dyslipidemia (p<0.05). Depressive symptoms played a mediating role in the association between frailty and long-term T2D or dyslipidemia (p<0.05). CONCLUSION: Frailty had adverse effects on type 2 diabetes and dyslipidemia, with depressive symptoms acting as the mediator.

Trilobatin rescues fulminant hepatic failure by targeting COX2: Involvement of ROS/TLR4/NLRP3 signaling.

BACKGROUND: Fulminant hepatic failure (FHF) lacks efficient therapies notwithstanding increased comprehending of the inflammatory response and oxidative stress play crucial roles in the pathogenesis of this type of hepatic damage. Trilobatin (TLB), a naturally occurring food additive, is endowed with anti-inflammation and antioxidant properties. PURPOSE: In current study, we evaluated the effect of TLB on FHF with a mouse model with d-galactosamine/lipopolysaccharide (GalN/LPS)-induced FHF and LPS-stimulated Kupffer cells (KCs) injury. METHODS: Mice were randomly divided into seven groups: control group, TLB 40 mg/kg + control group, GalN/LPS group, TLB 10 mg/kg + GalN/LPS group, TLB 20 mg/kg + GalN/LPS group, TLB 40 mg/kg + GalN/LPS group, bifendate 150 mg/kg + GalN/LPS group. The mice were administered intragastrically TLB (10, 20 and 40 mg/kg) for 7 days (twice a day) prior to injection of GalN (700 mg/kg)/LPS (100 µg/kg). The KCs were pretreated with TLB (2.5, 5, 10 µM) for 2 h or its analogue (10 µM) or COX2 inhibitor (10 µM), and thereafter challenged by LPS (1 µg/ml) for 24 h. RESULTS: TLB effectively rescued GalN/LPS-induced FHF. Furthermore, TLB inhibited TLR 4/NLRP3/pyroptosis pathway, and caspase 3-dependent apoptosis pathway, along with reducing excessive cellular and mitochondrial ROS generation and enhancing mitochondrial biogenesis. Intriguingly, TLB directly bound to COX2 as reflected by transcriptomics, molecular docking technique and surface plasmon resonance assay. Furthermore, TLB failed to attenuate LPS-induced inflammation and oxidative stress in KCs in the absence of COX2. CONCLUSION: Our findings discover a novel pharmacological effect of TLB: protecting against FHF-induced pyroptosis and apoptosis through mediating ROS/TLR4/NLRP3 signaling pathway and reducing inflammation and oxidative stress. TLB may be a promising agent with outstanding safety profile to treat FHF.

Hsa_circ_0001402 alleviates vascular neointimal hyperplasia through a miR-183-5p-dependent regulation of vascular smooth muscle cell proliferation, migration, and autophagy.

INTRODUCTION: Vascular neointimal hyperplasia, a pathological process observed in cardiovascular diseases such as atherosclerosis and pulmonary hypertension, involves the abundant presence of vascular smooth muscle cells (VSMCs). The proliferation, migration, and autophagy of VSMCs are associated with the development of neointimal lesions. Circular RNAs (circRNAs) play critical roles in regulating VSMC proliferation and migration, thereby participating in neointimal hyperplasia. However, the regulatory roles of circRNAs in VSMC autophagy remain unclear. OBJECTIVES: We aimed to identify circRNAs that are involved in VSMC autophagy-mediated neointimal hyperplasia, as well as elucidate the underlying mechanisms. METHODS: Dual-luciferase reporter gene assay was performed to validate two competing endogenous RNA axes, hsa_circ_0001402/miR-183-5p/FKBP prolyl isomerase like (FKBPL) and hsa_circ_0001402/miR-183-5p/beclin 1 (BECN1). Cell proliferation and migration analyses were employed to investigate the effects of hsa_circ_0001402, miR-183-5p, or FKBPL on VSMC proliferation and migration. Cell autophagy analysis was conducted to reveal the role of hsa_circ_0001402 or miR-183-5p on VSMC autophagy. The role of hsa_circ_0001402 or miR-183-5p on neointimal hyperplasia was evaluated using a mouse model of common carotid artery ligation. RESULTS: Hsa_circ_0001402 acted as a sponge for miR-183-5p, leading to the suppression of miR-183-5p expression. Through direct interaction with the coding sequence (CDS) of FKBPL, miR-183-5p promoted VSMC proliferation and migration by decreasing FKBPL levels. Besides, miR-183-5p reduced BECN1 levels by targeting the 3'-untranslated region (UTR) of BECN1, thus inhibiting VSMC autophagy. By acting as a miR-183-5p sponge, overexpression of hsa_circ_0001402 increased FKBPL levels to inhibit VSMC proliferation and migration, while simultaneously elevating BECN1 levels to activate VSMC autophagy, thereby alleviating neointimal hyperplasia. CONCLUSION: Hsa_circ_0001402, acting as a miR-183-5p sponge, increases FKBPL levels to inhibit VSMC proliferation and migration, while enhancing BECN1 levels to activate VSMC autophagy, thus alleviating neointimal hyperplasia. The hsa_circ_0001402/miR-183-5p/FKBPL axis and hsa_circ_0001402/miR-183-5p/BECN1 axis may offer potential therapeutic targets for neointimal hyperplasia.

Excision of mesenteric lymph nodes alters gut microbiota and impairs social dominance in adult mice.

INTRODUCTION: Mesenteric lymph nodes (MLNs) are central in immune anatomy. MLNs are associated with the composition of gut microbiota, affecting the central system and immune system. Gut microbiota was found to differ among individuals of different social hierarchies. Nowadays, excision of MLNs is more frequently involved in gastrointestinal surgery; however, the potential side effects of excision of MLNs on social dominance are still unknown. METHODS: MLNs were removed from male mice (7-8 weeks old). Four weeks after MLN removal, social dominance test was performed to investigate social dominance; hippocampal and serum interleukin (IL)-1ß, IL-10, and tumor necrosis factor-alpha (TNF-α) were investigated; and histopathology was used to evaluate local inflammation of the ileum. The composition of the gut microbiota was then examined to understand the possible mechanism, and finally intraperitoneal injection of IL-10 was used to validate the effect of IL-10 on social dominance. RESULTS: There was a decrease in social dominance in the operation group compared to the control group, as well as a decrease in serum and hippocampal IL-10 levels, but no difference in serum and hippocampal IL-1ß and TNF-α levels, and no local inflammation of the ileum after MLN removal. 16S rRNA sequencing analysis showed that the relative abundance of the class Clostridia was decreased in the operation group. This decrease was positively associated with serum IL-10 levels. Furthermore, intraperitoneal injection of IL-10 in a subset of mice increased social dominance. CONCLUSIONS: Our findings suggested that MLNs contributed to maintaining social dominance, which might be associated with reduced IL-10 and the imbalance of specific flora in gut microbiota.

Modification of fluorescence staining method for small-sized microplastic quantification: Focus on the interference exclusion and exposure time optimization.

Microplastics are an emerging pollutant of global concern, and fluorescence staining as an efficient method for small-sized microplastic qualification often undergoes the serious interference from external environments. The key steps affecting the accuracy of fluorescent staining and the corresponding quality assurance measures were rarely known. Therefore, this study took the Nile Red/DAPI co-staining method as an example to explore the key factors affecting its accuracy and effective measures to avoid interference. High background microplastic contamination in typical lab waters (up to 1115 MP/L), glass fiber filter membrane and glassware were identified as dominant factors affecting microplastic quantification. The background microplastics in lab waters mainly originated from the process of water production and storage. A simple filtration process removed 99% of the background microplastic in the lab waters. After burning at 500 °C for 1 h, the microplastic contamination in the filter membrane and glassware was completely eliminated. H2O2 pretreatment and exposure time caused erroneous microplastic size assessment, and were suggested to be set at 48 h and 10 ms, respectively. During the extraction process, the residue in beakers reached ~ 20% and > 50% for 5 µm and 20 µm sized microplastics, respectively, greatly contributing to the microplastic loss. The comprehensive modified measures caused microplastic concentrations in the three typical samples detected by Nile Red/DAPI co-staining method to decrease by 65.7 - 92.2% and to approach the micro-Raman results. This study clarified the reasons for interfering with quantitative microplastics by fluorescent staining and the effective measures to avoid interference, which were conducive to improving the accuracy of quantitative methods of microplastics.

CircSYNDIG1 ameliorates stress-induced abnormal behaviors by suppressing miR-344-5p in mice.

Circular RNA (circRNA) plays an important role in diverse stress-related neuropsychiatric disorders like depression, anxiety and cognitive disorders. Here, using a circRNA microarray, we found that circSYNDIG1, an unreported circRNA, was significantly downregulated in the hippocampus of chronic unpredictable mild stress (CUMS) mice and further validated this finding in corticosterone (CORT) and lipopolysaccharide (LPS) mice by qRT-PCR, and it was negatively correlated with depressive- and anxiety-like behaviors of these three stressed mice. Furthermore, the interaction of miR-344-5p and circSYNDIG1 was confirmed by in situ hybridization (FISH) assay in hippocampus and dual luciferase reporter assay in 293 T cells. And miR-344-5p mimics could simulate the dendritic spine density reduction, depressive- and anxiety-like behaviors and memory impairment induced by CUMS. Overexpression of circSYNDIG1 in hippocampus significantly ameliorated these abnormal changes induced by CUMS or miR-344-5p. It indicated that circSYNDIG1 functions as an miR-344-5p sponge to inhibit miR-344-5p impact, resulting in the increase of dendritic spine density and the subsequent amelioration of the abnormal behaviors. Therefore, the downregulation of circSYNDIG1 in hippocampus participates in CUMS-induced depressive and anxiety-like behavior of mice though miR-344-5p. These findings represent the first evidence for the involvement of circSYNDIG1 and its coupling mechanism in depression and anxiety, suggesting that circSYNDIG1 and miR-344-5p might be new targets for the treatment of stress-related disorder.

Heat-Killed Lactobacillus rhamnosus ATCC 7469 Improved UVB-Induced Photoaging Via Antiwrinkle and Antimelanogenesis Impacts.

Exposure of ultraviolet B (UVB) radiation is the main factor from the environment to cause skin photoaging. Lactobacillus rhamnosus ATCC 7469, is a probiotic strain with a good track record for enhancing human health. The present study conducted the impacts of heat-killed L. rhamnosus ATCC 7469 (RL) on photoaging in vitro using mouse skin fibroblast (MSF) cells and human epidermal melanocytes (HEM) exposed to UVB. The results showed that (1) RL-protected UVB-induced cytotoxicity relating to absorb UVB and reduce DNA damage. (2) RL exerted the antiwrinkle impact involved in two aspects. Firstly, RL downregulated MMP-1, 2, 3 expressions associating with MAPK signaling, resulting in the increased the protein expression of COL1A1, further booting type I collagen abundant thereby promoting the antiwrinkle impact in MSF cells. Secondly, RL reduced ROS content, further decreasing oxidative damage relating to Nrf2/Sirt3/SOD2 signaling, thereby promoting the antiwrinkle impact in MSF cells. (3) RL suppressed tyrosinase and TYRP-2 activity and/or levels associating with PKA/CREB/MITF signaling, thereby promoting antimelanogenesis impact in HEM cells. In conclusion, our findings suggest that RL could reduce photoaging caused by UVB via antiwrinkle and antimelanogenesis properties and may be a potential antiphotoaging beneficial component, which is applied in the cosmetic industry.

Hematodinium perezi naturally infects Asian brush-clawed crab (Hemigrapsus takanoi).

The parasitic dinoflagellates of the genus Hematodinium have been considered one of the most important emerging pathogens for a broad range of marine crustaceans around the world. In China, frequent outbreaks of Hematodinium infections have caused serious economic losses for local farmers since 2004. Wild crabs were recently indicated to play a vital role in the transmission and spreading of the Hematodinium disease in polyculture pond systems. Based on PCR amplification and histopathological examination, we demonstrated that H. perezi can naturally infect a wild crab species, Hemigrapsus takanoi, which were collected from the waterways located on the coast of Rizhao or Weifang, Shandong Peninsula, China. According to the sequence similarity analysis and phylogenetic analysis, the Hematodinium isolates were identified as H. perezi and belonged to genotype II. The prevalence of H. perezi ranged from 3.3% to 5.7% in H. takanoi originating from Rizhao (n = 165 wild crabs) and from 0.9% to 20.0% in that originating from Weifang (n = 1386 wild crabs), respectively. To our knowledge, H. takanoi is, for the first time, reported as a new host for Hematodinium. Given the wide distribution of H. takanoi on the coasts along the Shandong Peninsula and the relative high prevalence of infection we monitored in our study, we speculate that H. takanoi contributes to the introducing and spreading parasitic Hematodinium between ponds via waterways in a poly-culturing system. Findings in this study broaden the host range of this parasite and expand the scope of our surveillance for Hematodinium disease in China.

Heat-Killed Lacticaseibacillus paracasei Ameliorated UVB-Induced Oxidative Damage and Photoaging and Its Underlying Mechanisms.

Ultraviolet B (UVB) radiation is a major environmental causative factor of skin oxidative damage and photoaging. Lacticaseibacillus paracasei is a well-known probiotic strain that can regulate skin health. The present study investigated the effects of heat-killed Lacticaseibacillus paracasei (PL) on UVB linked oxidative damage and photoaging in skin cells (Normal human dermal fibroblast (NHDF) cells and B16F10 murine melanoma cells). Results demonstrated that: (1) PL prevented UVB-induced cytotoxicity relating to decreased DNA damage in NHDF and B16F10 cells; (2) PL alleviated UVB-induced oxidative damage through increasing GSH content, as well as antioxidant enzyme activities and mRNA levels (except MnSOD activity and mRNA levels as well as CAT mRNA level) relating to the activation of Sirt1/PGC-1α/Nrf2 signaling in NHDF cells; (3) PL attenuated UVB-induced photoaging was noticed with a decrease in the percentage of SA-ß-gal positive cells in NHDF cells model. Moreover, PL attenuated UVB-induced photoaging through exerting an anti-wrinkling effect by enhancing the type I collagen level relating to the inhibition (JNK, p38)/(c-Fos, c-Jun) of signaling in NHDF cells, and exerting an anti-melanogenic effect by suppressing tyrosinase and TYRP-1 activity and/or expressions relating to the inhibition of PKA/CREB/MITF signaling in B16F10 cells. In conclusion, PL could ameliorate UVB-induced oxidative damage and photoaging. Therefore, PL may be a potential antioxidant and anti-photoaging active ingredient for the cosmetic industry.

Association between HBV Infection and the Prevalence of Coronary Artery Disease in the US Population.

Aims: This study aims to investigate the association between HBV infection and coronary artery disease (CAD) prevalence in the US population. A nomogram was proposed to predict CAD based on HBV infection. Methods: 25,749 individuals were collected from the 2001-2014 National Health and Nutrition Examination Survey. Participants with hepatitis B core antibody seropositivity were identified with HBV infection, including current and previous HBV infection status. We used adjusted logistic regression and performed sensitivity analysis to investigate the association between HBV infection and the prevalence of CAD. The effect size was evaluated by odds ratio (OR) with a 95% confidence interval (CI). Then, we created a nomogram to predict coronary artery disease. Additionally, we applied the Cox regression model to assess the association between HBV infection and all-cause mortality in those with baseline CAD. Results: 1790 (6.95%) individuals were with HBV infection. In the adjusted model, individuals with HBV showed a decreased CAD risk than those without (OR, 0.81; 95% CI, 0.67-0.98). Consistently, reduced risk in self-reported angina (OR, 0.72; 95% CI, 0.52-0.98) and coronary heart disease (OR, 0.76; 95% CI, 0.58-0.98) was observed in the hepatitis B core antibody seropositivity group. The subgroup analysis showed a consistent trend in the subgroups of age (<45 or ≥45), gender (male or female), hypertension (no or yes), and diabetes (no or yes). In the testing set, the proposed predictive model showed good performance with an area under the curve of 0.85 (95% CI, 0.83-0.86). There was no significant association between HBV infection and all-cause mortality in CAD patients (adjusted P = 0.202). Conclusion: Our study suggests that HBV infection was associated with lower CAD risk. The proposed nomogram showed good performance in predicting CAD. However, no significant association was observed between HBV and all-cause mortality in CAD patients.

Influence of reaction parameters on the fate of nitrogen during the supercritical water gasification of dewatered sewage sludge.

This study investigated the effects of different parameters on the fate of nitrogen (N) in products after supercritical water gasification (SCWG) of dewatered sewage sludge (DSS). N distribution and morphology were most affected by temperature, followed by reaction time and heating rate, while reaction pressure had little effect on them. In terms of specific performance, higher temperature, longer reaction time, and slower heating rate were beneficial to the increase of NH4+-N content in the liquid phase. Compared with raw sludge, after SCWG, the solid phase contained more inorganic-N and less protein-N, a certain proportion of quaternary-N and nitrile-N. The proportion of N-containing compounds in the biocrude phase was between 0.26%-20.34%, suggesting the importance of more research on N in the biocrude phase. The recovery rate of N in all samples was between 64.34%-93.82%. The major proportion of N (42.27%-60.91%) was transformed into the liquid phase, while the remaining entered the solid phase (10.54%-21.45%) and the biocrude phase (6.18%-15.78%). These findings are helpful to better understand the principle of N distribution in products of DSS after SCWG and provide some new ideas for reducing N-containing by-product formation in the future.

Hippocampal semaphorin 3B improves depression-like behaviours in mice by upregulating synaptic plasticity and inhibiting neuronal apoptosis.

Depression is a global health problem, and there is a pressing need for a better understanding of its pathogenesis. Semaphorin 3B (Sema 3B) is an important axon guidance molecule that is primarily expressed in neurons and contributes to synaptic plasticity. Our previous studies using a high-throughput microarray assay suggested that Sema 3B expression was tremendously decreased during the development of depression, but the specific role and mechanisms of Sema 3B in depression are still unknown. Herein, we report that levels of Sema 3B protein are decreased in the hippocampus and serum of chronic mild stress (CMS)-treated mice. Increasing the levels of Sema 3B, either by injecting AAV-Sema 3B into the hippocampus or by injecting recombinant Sema 3B protein into the lateral ventricles, alleviated CMS-induced depression-like behaviours and enhanced the resistance to acute stress by increasing dendritic spine density in hippocampal neurons. In contrast, interfering with the function of Sema 3B by injecting anti-Sema 3B antibody into the lateral ventricles decreased the resistance to acute stress. In vitro, corticosterone (CORT) treatment decreased the survival rate and protein levels of Sema 3B and synapse-associated proteins in HT22 cells. Overexpression of Sema 3B improved the decreased survival rate caused by CORT by inhibiting apoptosis and increasing levels of synaptic-associated proteins, and knockdown of Sema 3B reduces the cellular resistance to CORT and the levels of synapse-associated proteins. These findings represent the first evidence for the neuroprotective mechanism of Sema 3B against stresses, suggesting that Sema 3B could be a promising novel target for the prevention and treatment of depression.

Maternal exposure to triclosan during lactation alters social behaviors and the hippocampal ultrastructure in adult mouse offspring.

We recently reported that exposure to triclosan (TCS), a broad-spectrum antibacterial agent, affects social behaviors in adult mice, however, the long-lasting effects of TCS exposure during early life on social behaviors are still elusive. The present study aimed to investigate the long-lasting impacts of adding TCS to the maternal drinking water during lactation on the social behaviors of adult mouse offspring and to explore the potential mechanism underlying these effects. The behavioral results showed that TCS exposure decreased body weight, increased depression-like behavior and decreased social dominance in both male and female offspring, as well as increased anxiety-like behavior and bedding preference in female offspring. In addition, enzyme-linked immunosorbent assay (ELISA) indicated that TCS exposure increased peripheral proinflammatory cytokine levels, altered serum oxytocin (OT) levels, and downregulated the expression of postsynaptic density protein 95 (PSD-95) in the hippocampus. Morphological analysis by transmission electron microscopy (TEM) demonstrated that exposure to TCS induced morphological changes to synapses and neurons in the hippocampus of offspring. These findings suggested that TCS exposure during lactation contributed to abnormal social behaviors accompanied by increased peripheral inflammation and altered hippocampal neuroplasticity, which provides a deeper understanding of the effects of TCS exposure during early life on brain function and behavioral phenotypes.

Integrated analysis of tRNA-derived small RNAs in proliferative human aortic smooth muscle cells.

BACKGROUND: Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling diseases. Recently, it has been discovered that tRNA-derived small RNAs (tsRNAs), a new type of noncoding RNAs, are related to the proliferation and migration of VSMCs. tsRNAs regulate target gene expression through miRNA-like functions. This study aims to explore the potential of tsRNAs in human aortic smooth muscle cell (HASMC) proliferation. METHODS: High-throughput sequencing was performed to analyze the tsRNA expression profile of proliferative and quiescent HASMCs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the sequence results and subcellular distribution of AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076. Based on the microRNA-like functions of tsRNAs, we predicted target promoters and mRNAs and constructed tsRNA-promoter and tsRNA-mRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the function of target genes. EdU incorporation assay, Western blot, and dual-luciferase reporter gene assay were utilized to detect the effects of tsRNAs on HASMC proliferation. RESULTS: Compared with quiescent HASMCs, there were 1838 differentially expressed tsRNAs in proliferative HASMCs, including 887 with increased expression (fold change > 2, p < 0.05) and 951 with decreased expression (fold change < ½, p < 0.05). AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076 were increased in proliferative HASMCs and were mainly located in the nucleus. Bioinformatics analysis suggested that the four tsRNAs involved a variety of GO terms and pathways related to VSMC proliferation. AS-tDR-000067 promoted HASMC proliferation by suppressing p53 transcription in a promoter-targeted manner. AS-tDR-000076 accelerated HASMC proliferation by attenuating mitofusin 2 (MFN2) levels in a 3'-untranslated region (UTR)-targeted manner. CONCLUSIONS: During HASMC proliferation, the expression levels of many tsRNAs are altered. AS-tDR-000067 and AS-tDR-000076 act as new factors promoting VSMC proliferation.

Long-lasting effects of postweaning sleep deprivation on cognitive function and social behaviors in adult mice.

Sleep deprivation (SD) has adverse effects on physical and mental health. Recently increasing attention has been given to SD in the early-life stage. However, the effects and mechanisms of postweaning SD on cognitive function and social behaviors are still unclear. In this study, SD was conducted in mice from postnatal Day 21 (PND21) to PND42, 6 h a day. Meanwhile, changes in body weight, food and water intake were continuously monitored. Behavioral tests were carried out in adulthood of mice. The levels of serum corticosterone, the proinflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and the anti-inflammatory cytokines interleukin-10 (IL-10), vasopressin (VP) and oxytocin (OT) were measured by ELISA. Golgi staining was used to calculate neural dendritic spine density in the dorsal hippocampus (dHPC) CA1 region and medial prefrontal cortex (mPFC). We found that postweaning SD increased the food intake and the weight of female mice. Behavioral results showed that postweaning SD caused cognitive impairment and lowered social dominance in adult male mice but not in female mice. ELISA results showed that SD increased the levels of serum corticosterone, VP and OT in male mice and serum OT in female mice. Golgi staining analysis showed that SD decreased neural dendritic spine density in the dHPC in male mice. These results suggest that postweaning SD has a long-term effect on social dominance and cognitive function in male mice, which may provide a new insight into the role of SD in regulating cognitive function and social behaviors.

Elevation of N-acetyltransferase 10 in hippocampal neurons mediates depression- and anxiety-like behaviors.

Major depressive disorder (MDD) is one of the most debilitating and severe mental diseases globally. Increasing evidence has shown that epigenetics is critical for understanding brain function and brain disorders, including MDD. N-acetyltransferase 10 (NAT10), acting on histones, mRNA and other substrates, has been reported to be involved in epigenetic events, including histone acetylation and mRNA modifications. NAT10 is highly expressed in the brain. However, the potential effects of NAT10 on MDD are still unknown. Here, we exploited chronic mild stress (CMS) to induce anxiety- and depression-like behaviors in mice and found that the expression of NAT10 in the mouse hippocampus was upregulated after CMS treatment. Inhibition of NAT10 by pharmacological methods produced anxiolytic- and antidepressant-like effects. Neuron-specific overexpression of NAT10 in the hippocampus resulted in anxiety- and depression-like behaviors, accompanied by higher SIRT1 protein levels, and lower dendritic spine densities. Overall, it was found that elevation of NAT10 in hippocampal neurons is involved in the occurrence of anxiety- and depression-like behaviors, suggesting that NAT10 could be a potential new target for developing anxiolytics and antidepressants.

Sex-dependent and long-lasting effects of bisphenol AF exposure on emotional behaviors in mice.

We recently reported that maternal exposure to bisphenol AF (BPAF), an environmental endocrine disruptor (EED), induced significant alterations in emotional behaviors in offspring mice during adolescence in a sex-dependent manner. However, the effects of adult BPAF exposure and the potential long-lasting effects of maternal exposure to BPAF on offspring mice are still unknown. The present study aimed to investigate the neurobehavioral effects of adult and maternal exposure to BPAF, intragastrically (0.4, 4 mg•kg-1, i.g.), by using a series of classic emotional behavioral tests, mainly referring to depression, anxiety, and memory. The results showed that adult BPAF exposure significantly attenuated anxiety- and depression-like behaviors in adult male mice, while increasing anxiety-like behaviors, promoting novel object recognition memory formation, and impairing contextual fear conditioning memory formation in adult female mice. Maternal exposure to BPAF induced anxiety-like effects and anti-depression-like effects in male offspring mice during adulthood, while maternal BPAF exposure increased anxiety- and depression-like behaviors in female offspring mice during adulthood. Our present findings indicate that BPAF exposure significantly affects emotional behaviors in adult/offspring mice in a sex-dependent manner and that female adult mice are more likely to have adverse consequences to BPAF exposure during adulthood, even during early life stages.