Extraction and identification of exosomes from three different sources of human ovarian granulosa cells and analysis of their differential miRNA expression profiles.

OBJECTIVE: As important functional cells in the ovary, ovarian granulosa cells are involved in the regulation of oocyte growth and development and play an important role in the study of female fertility preservation. Based on the importance of granulosa cell functionalism, in this study, we analyzed the exosome secretion capacity of human ovarian granulosa cells (SVOG/KGN-cell line, PGC-primary cells) and the differences in their miRNA expression. METHODS: Cells were identified by hematoxylin-eosin staining (HE) and FSHR immunofluorescence staining; CCK8 and colony-forming assay were performed to compare cell proliferation capacity; exosomes were extracted and identified by ultra-high speed centrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot analysis (WB), and the expression profile of each cellular exosomal miRNA was analyzed by miRNA high-throughput sequencing. RESULTS: The proliferative abilities of the three granulosa cells differed, but all had the ability to secrete exosomes. In the exosomes of SVOG, KGN, and PGC cells, 218, 327, and 471 miRNAs were detected, respectively. When compared to the exosomal miRNAs of PGC cells, 111 miRNAs were significantly different in SVOG, and 70 miRNAs were washed two significantly different in KGN cells. These differential miRNA functions were mainly enriched in the cell cycle, cell division/differentiation, multicellular biogenesis, and protein binding. CONCLUSION: Human ovarian granulosa cells of different origins are capable of secreting exosomes, but there are still some differences in their exosomes and exosomal miRNAs, and experimental subjects should be selected rationally according to the actual situation.

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial.

BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734).

Biomimetic Cell Structures: Probing Induced pH-Feedback Loops and pH Self-Monitoring in Cytosol Using Binary Enzyme-Loaded Polymersomes in Proteinosome.

Structures and functions of eukaryotic cells with an outer permeable membrane, a cytoskeleton, functional organelles, and motility can be mimicked by giant multicompartment protocells containing various synthetic organelles. Herein, two kinds of artificial organelles with stimuli-triggered regulation ability, glucose oxidase-(GOx)-loaded pH-responsive polymersomes A (GOx-Psomes A) and urease-loaded pH-responsive polymersomes B (Urease-Psomes B), and a pH-sensor (Dextran-FITC) are encapsulated into proteinosomes via the Pickering emulsion method. Thus, a polymersomes-in-proteinosome system is constructed which is able to probe biomimetic pH homeostasis. Alternating fuels (glucose or urea) introduced from outside the protocell penetrate the membrane of proteinosomes and enter into GOx-Psomes A and Urease-Psomes B to produce chemical signals (gluconic acid or ammonia) resulting in pH-feedback loops (pH jump and pH drop). This will counteract the catalytic "switch on" or "switch off" of enzyme-loaded Psomes A and B owing to their different pH-responsive membranes. Dextran-FITC in the proteinosome allows self-monitoring of slight pH fluctuations in the lumen of protocells. Overall, this approach shows heterogeneous polymersome-in-proteinosome architectures with sophisticated features such as input-regulated pH changes mediated by negative and positive feedback in loops and cytosolic pH self-monitoring, features that are imperative for advanced protocell design.

CMKLR1 Antagonist Alpha-NETA Protects against Diabetic Nephropathy in Mice.

INTRODUCTION: Diabetic nephropathy (DN) is a common complication in diabetic patients. Chemerin, a novel adipokine, has been associated with renal damage in DN. The chemerin chemokine-like receptor 1 (CMKLR1) has been reported to participate in DN. In this study, we aimed to investigate the effect of a CMKLR1 antagonist, 2-(anaphthoyl)ethyltrimethylammonium iodide (α-NETA), on DN. METHODS: To induce diabetes, 8-week-old male C57BL/6J mice were given a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Diabetic mice were randomly assigned to receive daily doses of 0, 5, or 10 mg/kg α-NETA for 4 weeks. RESULTS: α-NETA dose-dependently induced body weight and reduced fasting blood glucose levels in STZ-induced diabetic mice. Furthermore, α-NETA significantly reduced the expressions of renal injury markers, including serum creatinine, kidney weight/body weight, urine volume, total proteins, and albumin in the urine, and increased creatinine clearance. Periodic acid-Schiff staining also indicated that α-NETA could effectively ameliorate renal injuries in DN mice. In addition, α-NETA inhibited renal inflammation and the expressions of chemerin and CMKLR1 in mice with DN. CONCLUSION: In summary, our findings suggested that α-NETA has beneficial effects on the management of DN. Specifically, α-NETA effectively ameliorated renal damage and inflammation in a dose-dependent manner in mice with DN. Thus, targeting the chemerin and CMKLR1 axis with α-NETA may be a promising therapeutic strategy for the treatment of DN.

Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats.

BACKGROUND: Salvianolic acids possess anti-inflammatory properties. This study investigated the therapeutic effect of salvianolic acids on chronic mild stress (CMS)-induced depressive-like behaviors in rats and the involvement of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). METHODS: Eighty male Sprague-Dawley rats were randomly subjected to CMS or non-CMS protocol for 6 weeks. Starting 3 weeks after CMS exposure, the rats in each group were administered saline, fluoxetine (positive control), salvianolic acids, or salvianolic acids + fluoxetine daily for 3 weeks. The body weight change, sucrose preference, and immobility duration in forced swimming were examined before and after drug treatment. The rats were sacrificed at 3 weeks after drug treatment. Quantitative real-time PCR was performed to measure the mRNA levels of TLR4 and MyD88 in the prefrontal cortex and hippocampus of rats. RESULTS: Compared with non-CMS rats, CMS rats had significantly reduced weight gains and sucrose preference, along with significantly increased immobility durations and elevated mRNA levels of TLR4 and MyD88 in both the prefrontal cortex and hippocampus. Treatment with fluoxetine and salvianolic acids, alone or in combination, facilitated weight gains, alleviated depressive-like behaviors, and reduced cerebral TLR4/MyD88 mRNA levels in CMS rats. Besides, fluoxetine and salvianolic acids additively suppressed TLR4/MyD88 mRNA expression in the prefrontal cortex of rats. Furthermore, TLR4 mRNA levels in both hippocampus and prefrontal cortex positively correlated with MyD88 mRNA expression, inflammatory cytokine secretion, and immobility duration but negatively correlated with sucrose preference. CONCLUSIONS: Thus, salvianolic acids alleviate depressive-like behaviors, possibly by suppressing TLR4/MyD88-mediated inflammatory signaling in the brain.

Research Updates on the Mechanism and Influencing Factors of the Photocatalytic Degradation of Perfluorooctanoic Acid (PFOA) in Water Environments.

Perfluorooctanoic acid is ubiquitous in water bodies and is detrimental to the health of organisms. Effectively removing perfluorooctanoic acid (PFOA), a persistent organic pollutant, has been a hot topic around the world. With traditional physical, chemical, and biological methods, it is difficult to effectively and completely remove PFOA, the costs are high, and it is easy to cause secondary pollution. There are difficulties in applying some technologies. Therefore, more efficient and green degradation technologies have been sought. Photochemical degradation has been shown to be a low-cost, efficient, and sustainable technique for PFOA removal from water. Photocatalytic degradation technology offers great potential and prospects for the efficient degradation of PFOA. Most studies on PFOA have been conducted under ideal laboratory conditions at concentrations that are higher than those detected in real wastewater. This paper summarizes the research status of the photo-oxidative degradation of PFOA, and it summarizes the mechanism and kinetics of PFOA degradation in different systems, as well as the influence of key factors on the photo-oxidative degradation and defluoridation process, such as system pH, photocatalyst concentration, etc. PFOA photodegradation technology's existing problems and future work directions are also presented. This review provides a useful reference for future research on PFOA pollution control technology.

[Mechanism of Liuwei Dihuang Pills in treatment of mice with diminished ovarian reserve based on proteomics].

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.

Childhood adversity, adulthood adversity and suicidal ideation in Chinese patients with major depressive disorder: in line with stress sensitization.

The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini-International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19-2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567.

Uncover diagnostic immunity/hypoxia/ferroptosis/epithelial mesenchymal transformation-related CCR5, CD86, CD8A, ITGAM, and PTPRC in kidney transplantation patients with allograft rejection.

The aim of this study was to identify predictive immunity/hypoxia/ferroptosis/epithelial mesenchymal transformation (EMT)-related biomarkers, pathways and new drugs in allograft rejection in kidney transplant patients. First, gene expression data were downloaded followed by identification of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis. Second, diagnostic model was construction based on key genes, followed by correlation analysis between immune/hypoxia/ferroptosis/EMT and key diagnostic genes. Finally, drug prediction of diagnostic key genes was carried out. Five diagnostic genes were further identified, including CCR5, CD86, CD8A, ITGAM, and PTPRC, which were positively correlated with allograft rejection after the kidney transplant. Highly infiltrated immune cells, highly expression of hypoxia-related genes and activated status of EMT were significantly positively correlated with five diagnostic genes. Interestingly, suppressors of ferroptosis (SOFs) and drivers of ferroptosis (DOFs) showed a complex regulatory relationship between ferroptosis and five diagnostic genes. CD86, CCR5, and ITGAM were respectively drug target of ABATACEPT, MARAVIROC, and CLARITHROMYCIN. PTPRC was drug target of both PREDNISONE and EPOETIN BETA. In conclusion, the study could be useful in understanding changes in the microenvironment within transplantation, which may promote or sustain the development of allograft rejection after kidney transplantation.

Overcoming Spectral Dependence: A General Strategy for Developing Far-Red and Near-Infrared Ultra-Fluorogenic Tetrazine Bioorthogonal Probes.

Bioorthogonal fluorogenic dyes are indispensable tools in wash-free bioimaging of specific biological targets. However, the fluorogenicity of existing tetrazine-based bioorthogonal probes deteriorates as the emission wavelength shifts towards the NIR window, greatly limiting their applications in live cells and tissues. Herein, we report a generalizable molecular design strategy to construct ultra-fluorogenic dyes via a simple substitution at the meso-positions of various far-red and NIR fluorophores. Our probes demonstrate significant fluorescence turn-on ratios (102 -103 -fold) in the range 586-806 nm. These results will greatly expand the applications of bioorthogonal chemistry in NIR bioimaging and biosensing.

Construction of Eukaryotic Cell Biomimetics: Hierarchical Polymersomes-in-Proteinosome Multicompartment with Enzymatic Reactions Modulated Protein Transportation.

The eukaryotic cell is a smart compartment containing an outer permeable membrane, a cytoskeleton, and functional organelles, presenting part structures for life. The integration of membrane-containing artificial organelles (=polymersomes) into a large microcompartment is a key step towards the establishment of exquisite cellular biomimetics with different membrane properties. Herein, an efficient way to construct a hierarchical multicompartment composed of a hydrogel-filled proteinosome hybrid structure with an outer homogeneous membrane, a smart cytoskeleton-like scaffold, and polymersomes is designed. Specially, this hybrid structure creates a micro-environment for pH-responsive polymersomes to execute a desired substance transport upon response to biological stimuli. Within the dynamic pH-stable skeleton of the protein hydrogels, polymersomes with loaded PEGylated insulin biomacromolecules demonstrate a pH-responsive reversible swelling-deswelling and a desirable, on-demand cargo release which is induced by the enzymatic oxidation of glucose to gluconic acid. This stimulus responsive behavior is realized by tunable on/off states through protonation of the polymersomes membrane under the enzymatic reaction of glucose oxidase, integrated in the skeleton of protein hydrogels. The integration of polymersomes-based hybrid structure into the proteinosome compartment and the stimuli-response on enzyme reactions fulfills the requirements of eukaryotic cell biomimetics in complex architectures and allows mimicking cellular transportation processes.

Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial.

BACKGROUND: This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. METHODS: This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18-60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. RESULTS: A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. CONCLUSIONS: After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway.

Many factors are involved in the process of nerve regeneration. Understanding the mechanisms regarding how these factors promote an efficient remyelination is crucial to deciphering the molecular and cellular processes required to promote nerve repair. Schwann cells (SCs) play a central role in the process of peripheral nerve repair/regeneration. Using a model of facial nerve crush injury and repair, we identified Annexin A1 (ANXA1) as the extracellular trigger of SC proliferation and migration. ANXA1 activated formyl peptide receptor 2 (FPR2) receptors and the downstream adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling cascade, leading to SC proliferation and migration in vitro. SCs lacking FPR2 or AMPK displayed a defect in proliferation and migration. After facial nerve injury (FNI), ANXA1 promoted the proliferation of SCs and nerve regeneration in vivo. Collectively, these data identified the ANXA1/FPR2/AMPK axis as an important pathway in SC proliferation and migration. ANXA1-induced remyelination and SC proliferation promotes FNI regeneration.

Effects of hydrogenation on the tensile and shear mechanical properties of defective penta-graphene.

Penta-graphene (PG) is a new theoretical two-dimensional metastable carbon allotrope composed entirely of carbon pentagons. In this paper, molecular dynamics simulations are performed to investigate the effects of the hydrogenation on the tensile and shear mechanical properties, together with the failure mechanism of PG with vacancy defects. The results show that hydrogenation can effectively tune the mechanical properties and failure mechanism of PG with vacancy defects. The defective PG (DPG) with low hydrogenation coverages exhibits obvious plastic deformation features under tensile and shear loading, and pentagon-to-polygon structural transformation is observed, while complete hydrogenation can change the failure mechanism of DPG from plastic deformation to brittle fracture. Both the tensile and shear moduli and elastic limit of DPG first decrease dramatically and then increase slowly with the increase of hydrogenation coverage, while tensile and shear strain increases almost monotonically with rising hydrogenation coverage. Complete hydrogenation can result in large enhancement of tensile and shear elastic stress limit and strain. These results may provide an important guideline for effectively tuning the mechanical properties of PG and other two-dimensional nanomaterials.

Mechanics of penta-graphene with vacancy defects under large amplitude tensile and shear loading.

Penta-graphene is a new two-dimensional metastable carbon allotrope composed entirely of carbon pentagons with unique electronic and mechanical properties. In this work we evaluate the mechanical properties of new classes of defective penta-graphene (DPG) subjected to tensile and shear loading by using molecular dynamics simulations. The types of defects considered here are monovacancy at either 4-coordinated C1 site or 3-coordinated C2 site, and double vacancy (DV). We focus in particular on the effects of the different topologies of defects and their concentrations on the elastic constants and the nonlinear mechanics of this allotropic form of carbon. The results indicate that DPG has a plastic behavior similar to pristine penta-graphene, which is caused by the irreversible pentagon-to-polygon structural transformation occurring during tensile and shear loading. The tensile and shear moduli decrease linearly with the concentration of defects. Monotonic reductions of the tensile yield and shear stresses are also present but less pronounced, while the yield strains are unaffected. Penta-graphene with 4-coordinated and DVs feature a change of the Poisson's ratio from negative to positive when the defect concentration rises to about 3% and 6%. Temperature can trigger structural reconstruction for free-standing DPG. The critical transition temperature increases due to the vacancy defects and the defects can delay the structure transition. These findings are expected to provide important guidelines for the practical applications of penta-graphene based micro/nano electromechanical systems.

Severe sleep disturbance is associated with executive function impairment in patients with first-episode, treatment-naïve major depressive disorders.

BACKGROUND: Sleep disturbance and executive function impairment are common in patients with major depressive disorder (MDD), though the relationship between the two remains unclear. We investigated this association in first-episode, treatment-naïve patients with MDD. METHODS: We analyzed data from 242 patients with MDD. We divided the patients into 2 groups based on sleep disturbance severity and compared the executive function odds ratios between the groups. RESULTS: A total of 121 pairs of patients were matched (age 39.4 ± 10.1, 70.2% female). After propensity score matching, the odds ratios for cognitive impairment in patients with MDD and severe sleep disturbance were 1.922 (1.068-3.459, P = 0.029, q = 0.044) in executive functioning; 2.023 (1.211-3.379, P = 0.007, q = 0.021) in executive shifting. CONCLUSIONS: Sleep disturbance is associated with executive functioning impairment in first-episode, treatment-naïve patients with MDD. Severe sleep disturbance can be a marker and aid in recognizing executive function impairment in patients with first-episode treatment-naïve MDD. Severe sleep disturbance can be a potential modifiable factor to improve executive function in MDD, as well as an effective measurement to improve cognition for sleep symptom management that should be enforced at initial treatment of first-episode MDD. Further study is required to confirm our results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02023567 ; registration date: December 2013.

Prevalence and risks of mild cognitive impairment of Chinese community-dwelling women aged above 60 years: A cross-sectional study.

Evidence has shown that risks of cognitive impairment differ between genders. This cross-sectional study sought to determine the prevalence of mild cognitive impairment (MCI) in Chinese community-dwelling women aged above 60 years and identify risks of MCI by multivariate logistic regression analysis. Totally, 1760 Chinese community-dwelling women entered the study. Cognitive function was assessed with Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). MCI was diagnosed by Petersen's criteria. Sociodemographic information, past medical conditions, and age at menopause were screened. The primary study outcome was prevalence of MCI. MCI was diagnosed in 378 (21.5%) women. Older age was a significant risk of MCI (OR 1.621, 95%CI 1.386-1.894; P < 0.001). Low education was associated a 4-fold increase in the risk of MCI (OR 4.036, 95%CI 3.168-5.142). Furthermore, current depression was associated with 2.6-fold increase in the risk of MCI (OR 2.618, 95%CI 1.499-4.587, P = 0.001). Moreover, frequent physical exercise and more leisure and social time activities were associated with significantly reduced risks of MCI, while poor financial status was associated with a significantly increased risk of MCI. Slightly more than 20% of Chinese women aged above 60 years had MCI, and independent risks included older age, low education status, and current depression, highlighting the importance of screening for and removing or minimizing risks of MCI in this specific population.

Functional deficit of sense organs as a risk factor for cognitive functional disorder in Chinese community elderly people.

OBJECTIVE: To explore the relationship between mild cognitive impairment (MCI) and sense organs functional deficit in community elderly people. METHODS: A total of 3095 community elderly people above 60 years in Hebei Province were selected by cross-sectional random cluster sampling method, who were evaluated face-to-face for general demographic data, the condition of sense organs functional deficit (vision, hearing, gustation, olfactory sensation, taste) and cognitive function by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). RESULTS: A total of 3075 valid questionnaires were obtained. (a) 1368 old people (44.49%) were defined with sense organs functional deficit (defined as one or more of glaucoma, fundus disease, hearing impairment, olfactory disorder and taste disorder) in 3095 elderly people. According to questionnaires, MCI was diagnosed in 689 of 3075 participants (22.41%). The hearing disorder and glaucoma of MCI group were higher than that of the normal control group (X2 were 5.998 and 7.430, respectively, P were .014 and .006, respectively). (b) The MMSE score of the hearing disorder were significantly lower than those of non-hearing disorder group (t = 2.046, P = .041). (c) Multinomial logistics regression analysis was applied by MCI as the dependent variable and the various sensory organs defects as independent variables. The hearing impairment (Wald = 8.582, P = .003, OR = 1.485, 95% CI: 1.140-1.934) and glaucoma (Wald = 8.020, P = .005, OR = 1.847, 95% CI: 1.208-2.824) were associated with MCI. CONCLUSION: The sensory organs functional defects is associated with the mild cognitive impartment in Chinese elderly, especially in vision and hearing disorder.

Functional Characterization of PsnNAC036 under Salinity and High Temperature Stresses.

Plant growth and development are challenged by biotic and abiotic stresses including salinity and heat stresses. For Populus simonii × P. nigra as an important greening and economic tree species in China, increasing soil salinization and global warming have become major environmental challenges. We aim to unravel the molecular mechanisms underlying tree tolerance to salt stress and high temprerature (HT) stress conditions. Transcriptomics revealed that a PsnNAC036 transcription factor (TF) was significantly induced by salt stress in P. simonii × P. nigra. This study focuses on addressing the biological functions of PsnNAC036. The gene was cloned, and its temporal and spatial expression was analyzed under different stresses. PsnNAC036 was significantly upregulated under 150 mM NaCl and 37 °C for 12 h. The result is consistent with the presence of stress responsive cis-elements in the PsnNAC036 promoter. Subcellular localization analysis showed that PsnNAC036 was targeted to the nucleus. Additionally, PsnNAC036 was highly expressed in the leaves and roots. To investigate the core activation region of PsnNAC036 protein and its potential regulatory factors and targets, we conducted trans-activation analysis and the result indicates that the C-terminal region of 191-343 amino acids of the PsnNAC036 was a potent activation domain. Furthermore, overexpression of PsnNAC036 stimulated plant growth and enhanced salinity and HT tolerance. Moreover, 14 stress-related genes upregulated in the transgenic plants under high salt and HT conditions may be potential targets of the PsnNAC036. All the results demonstrate that PsnNAC036 plays an important role in salt and HT stress tolerance.

Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/ß-catenin signaling pathway.

Facial paralysis can result in severe implications for patients. A good prognosis depends on the degree of nerve regeneration. Schwann cells (SCs) play an important role in facial nerve development and regeneration through migration. Forkhead box C1 (Foxc1), a member of the forkhead transcription factor family, is implicated in cell migration. However, the role of Foxc1 in the progression after facial nerve crush remains unknown. Our aim was to evaluate the effect of Foxc1 overexpression on SC migration and recovery of facial nerves after crush injury. The rat facial nerve crush injury model was established through the use of unilateral surgery. The results showed that the expression of Foxc1 was increased in the surgery group compared to that of the control group. SCs were isolated from the sciatic nerves and cultured. Foxc1, delivered by an adeno-associated virus in vivo, or adenovirus in vitro, both induced overexpression of Foxc1, and increased the expression of CXCL12 and ß-catenin. After the transfection of Foxc1, the migration of SC was increased both in vitro and in vivo, was reduced by the inhibition of CXCL12 or ß-catenin. The facial nerve function and the nerve axon remyelination of the rats transfected with Foxc1 were significantly improved after nerve crush injury. Overall, the results demonstrated that overexpression of Foxc1 promoted SC migration by regulating CXCL12 via the Wnt/ß-catenin pathway, thus contributing to improved facial nerve function after crush injury.