Exosomes derived from human umbilical cord mesenchymal stem cells alleviate Parkinson’s disease and neuronal damage through inhibition of microglia

Microglia-mediated inflammatory responses have been shown to play a crucial role in Parkinson’s disease. In addition, exosomes derived from mesenchymal stem cells have shown anti-inflammatory effects in the treatment of a variety of diseases. However, whether they can protect neurons in Parkinson’s disease by inhibiting microglia-mediated inflammatory responses is not yet known. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells and injected into a 6-hydroxydopamine-induced rat model of Parkinson’s disease. We found that the exosomes injected through the tail vein and lateral ventricle were absorbed by dopaminergic neurons and microglia on the affected side of the brain, where they repaired nigral-striatal dopamine system damage and inhibited microglial activation. Furthermore, in an in vitro cell model, pretreating lipopolysaccharide-stimulated BV2 cells with exosomes reduced interleukin-1β and interleukin-18 secretion, prevented the adoption of pyroptosis-associated morphology by BV2 cells, and increased the survival rate of SH-SY5Y cells. Potential targets for treatment with human umbilical cord mesenchymal stem cells and exosomes were further identified by high-throughput microRNA sequencing and protein spectrum sequencing. Our findings suggest that human umbilical cord mesenchymal stem cells and exosomes are a potential treatment for Parkinson’s disease, and that their neuroprotective effects may be mediated by inhibition of excessive microglial proliferation.

Differences in Non-suicidal Self-injury Behaviors between Unipolar Depression and Bipolar Depression in Adolescent Outpatients

Objective Non-suicidal self-injury(NSSI)has a higher prevalence in adolescents with depressive disorders than in community adolescents.This study examined the differences in NSSI behaviors between adolescents with unipolar depression(UD)and those with bipolar depression(BD).Methods Adolescents with UD or BD were recruited from 20 general or psychiatric hospitals across China.The methods,frequency,and function of NSSI were assessed by Functional Assessment of Self-Mutilation.The Beck Suicide Ideation Scale was used to evaluate adolescents’suicidal ideation,and the 10-item Kessler Psychological Distress Scale to estimate the anxiety and depression symptoms.Results The UD group had higher levels of depression(19.16 vs.17.37,F=15.23,P<0.001)and anxiety symptoms(17.73 vs.16.70,F=5.00,P=0.026)than the BD group.Adolescents with BD had a longer course of NSSI than those with UD(2.00 vs.1.00 year,Z=−3.39,P=0.001).There were no statistical differences in the frequency and the number of methods of NSSI between the UD and BD groups.Depression(r=0.408,P<0.01)and anxiety(r=0.391,P<0.01)were significantly and positively related to NSSI frequency.Conclusion Adolescents with BD had a longer course of NSSI than those with UD.More importantly,NSSI frequency were positively and strongly correlated with depression and anxiety symptoms,indicating the importance of adequate treatment of depression and anxiety in preventing and intervening adolescents’NSSI behaviors.

Reduction of Electron Leakage of AlGaN-Based Deep Ultraviolet Laser Diodes Using an Inverse-Trapezoidal Electron Blocking Layer

To improve the optical and electrical properties of AlGaN-based deep ultraviolet lasers,an inverse-trapezoidal electron blocking layer is designed.Lasers with three different structural electron blocking layers of rectangular,trapezoidal and inverse-trapezoidal structures are established.The energy band,electron concentration,electron current density,P-I and V-I characteristics,and the photoelectric conversion efficiency of different structural devices are investigated by simulation.The results show that the optical and electrical properties of the inversetrapezoidal electron blocking layer laser are better than those of rectangular and trapezoidal structures,owing to the effectively suppressed electron leakage.

Proportions of acetyl-histone-positive hepatocytes indicate the functional status and prognosis of cirrhotic patients

AIM:To investigate whether the proportions of acetylhistone-positive hepatocytes could be used as markers of deteriorating liver function.METHODS:In total,611 cirrhotic cases from 3701 patients who were diagnosed during the past 15 years were screened,and 152 follow-up cases were selected.Paraffin tissue microarray was prepared for immunohistochemistry to examine acetyl-histone expression.The proportions of positive hepatocytes were recorded,and their correlations to clinical and laboratory indicators were analyzed statistically.RESULTS:The proportions of H2AK5ac+,H3K9/K14ac+ and H3K27ac+ hepatocytes gradually increased with deteriorating liver function and with increasing levels of serum markers of liver injury.In the follow-up cases,patients with > 70% H2AK5ac+,H3K9/K14ac+ or H3K27ac+ hepatocytes had statistically lower survival rates(P < 0.05).Furthermore,> 70% H2AK5ac+ or H3K27ac+ hepatocytes were strong independent predictors of overall survival(P < 0.05).CONCLUSION:The proportions of acetyl-histonepositive hepatocytes are closely associated with the liver function and prognosis of cirrhotic patients.

Role of perceived family support in psychological distress for pregnant women during the COVID-19 pandemic

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has caused major public panic in China.Pregnant women may be more vulnerable to stress,which may cause them to have psychological problems.AIM To explore the effects of perceived family support on psychological distress in pregnant women during the COVID-19 pandemic.METHODS A total of 2232 subjects were recruited from three cities in China.Through the online surveys,information on demographic data and health status during pregnancy were collected.Insomnia severity index,generalized anxiety disorder 7-item scale,patient health questionnaire-9,somatization subscale of the symptom check list 90 scale,and posttraumatic stress disorder checklist were used to assess the psychological distress.RESULTS A total of 1015(45.4%)women reported having at least one psychological distress.The women who reported having inadequate family support were more likely to suffer from multiple psychological distress(≥2 psychological distress)than women who received adequate family support.Among the women who reported less family support,41.8%reported depression,31.1%reported anxiety,8.2%reported insomnia,13.3%reported somatization and 8.9%reported posttraumatic stress disorder(PTSD),which were significantly higher than those who received strong family support.Perceived family support level was negatively correlated with depressive symptoms(r=-0.118,P<0.001),anxiety symptoms(r=-0.111,P<0.001),and PTSD symptoms(r=-0.155,P<0.001).CONCLUSION Family support plays an important part on pregnant women’s mental health during the COVID-19 pandemic.Better family support can help improve the mental health of pregnant women.

Overexpression of transcription factor 3 drives hepatocarcinoma development by enhancing cell proliferation via activating Wnt signaling pathway

Background:Transcription factor 3(TCF3)plays pivotal roles in embryonic development,stem cell maintenance and carcinogenesis.However,its role in hepatocellular carcinoma(HCC)remains largely unknown.This study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC,and further explore the underlying mechanism in HCC progression.Methods:The expression of TCF3 was collected from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO)HCC datasets,and further confirmed by immunostaining and Western blotting assays.The correlation between TCF3 expression and the clinicopathological features was evaluated.Bioinformatical analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC development.Results:Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues compared to tumor adjacent tissues(P<0.001 and P<0.01).Analysis based on TCGA datasets showed that TCF3 was positively correlated with tumor clinical stage and grade,and patients with high TCF3 expression had shorter overall survival(P=0.012),disease-specific survival(P=0.022)and progression-free survival(P=0.013).Similarly,the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size(P=0.001)and TNM stage(P=0.002),and TCF3 was an independent risk factor of HCC.In vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell proliferation,and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling pathways.Conclusions:TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage,as well as poor prognosis of HCC patients.The mechanism might be that TCF3 promotes cancer cell proliferation via activating Wnt signaling pathway.

Elevated expression of Gsα in intrahepatic cholangiocarcinoma associates with poor prognosis

BACKGROUND:The stimulatory G protein α subunit(Gsα)plays important roles in diverse cell processes including tu morigenesis. Activating mutations in Gsα gene(GNAS) have been reported to be associated with poor prognosis in various human carcinomas. Furthermore, Gsα signaling is crucial in promoting liver regeneration by interacting with growth factor signaling, indicating that Gsα might play a promoting role in cancer development. However, little is known about the correlation between Gsα levels and clinicopathological pa rameters in intrahepatic cholangiocarcinoma(ICC). METHODS:We performed immunoblotting to examine the expression levels of Gsα and Ki67 proteins in tumor tissues and the corresponding adjacent tissues. A total of 74 pair of specimens resected from 74 ICC patients were examined. The association between Gsα levels and clinicopathological find ings and prognosis of the patients was evaluated.RESULTS:Western blotting demonstrated that the expression of Gsα was significantly higher in ICC tissues compared with that in their corresponding adjacent tissues. Gsα protein was highly expressed in about half of ICC tissues(48.6%, 36/74)while only 28.4%(21/74) of tumor adjacent tissues showed Gsα high expression(P=0.011). High Gsα expression in ICC was significantly associated with the numbers of tumor nodules(P=0.037) and lymph node metastases(P=0.010)Moreover, the level of Gsα was significantly and positivelycorrelated with Ki67 expression(P<0.001). In addition, the recurrence-free survival rate and overall survival rate in the Gsα high group were significantly lower than those in the Gsα low group(P=0.004 and P=0.005, respectively).CONCLUSIONS:High Gsα expression is correlated with poor prognosis in ICC patients. Gsα might serve as a potential prognostic indicator of ICC.

Loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation

AIM:To investigate the continuous hepatic histopathological processes which occur in response to the loss of Dicer1.METHODS:We generated a hepatocyte-selective Dicer1 knockout mouse and observed the gradual hepatic histopathological changes in the mutant liver.Immunohistochemistry and Western blotting were performed to detect Dicer1 expression.We performed hematoxylin and eosin staining,Periodic acid-Schiff staining,Oil Red O staining,and Masson's trichrome staining to detect histological changes in Dicer1-deficient livers.Ki67 immunohistochemistry,terminal deoxynucleotidyl transferase-mediated d UTP nickend labeling assay,and Western blotting were used to determine hepatocyte proliferation and apoptosis.Serum biochemistry,cytokine assays,and flow cytometric analysis were performed to quantity liver necrosis and inflammation.Fibrogenic markers were determined by Western blotting and q PCR.CK19,CD133,and OV6 immunofluorescence were used to observe liver progenitor cells.Immunofluorescence and q PCR were performed to reveal embryonic gene expression.We also performed histological staining and Western blotting to analyze hepatocellular carcinoma(HCC) development.RESULTS:Dicer1 inactivation resulted in significant architecture disorganization and metabolism disruptionin the liver.Dicer1 disruption impaired hepatocyte survival and resulted in profound cell apoptosis and continuous necrosis.In contrast to previous reports,the mutant liver exhibited chronic inflammation and progressive fibrosis,and could not be repopulated by Dicer1-positive cells.In addition,extensive activation of hepatic progenitor cells was observed.Primary HCC was observed as early as 4 mo after birth.CONCLUSION:Hepatic loss of Dicer1 results in complex chronic pathological processes,including hepatocyte death,inflammatory infiltration,chronic fibrosis,compensatory proliferation,progenitor activation,and spontaneous hepatocarcinogenesis.

Prevalence and clinical characteristics of COVID-19 in inpatients with schizophrenia in Wuhan,China

BACKGROUND In contrast to many Western countries,China has maintained its large psychiatric hospitals.The prevalence and clinical characteristics of coronavirus disease 2019(COVID-19)in inpatients with schizophrenia(SCZ)are unclear.AIM To assess the prevalence of COVID-19 among inpatients with SCZ and compare the infected to uninfected SCZ patients in a Wuhan psychiatric hospital.METHODS We retrospectively collected demographic characteristics and clinical profiles of all SCZ patients with COVID-19 at Wuhan’s Youfu Hospital.RESULTS Among the 504 SCZ patients,84 had COVID-19,and we randomly sampled 174 who were uninfected as a comparison group.The overall prevalence of COVID-19 in SCZ patients was 16.7%.Among the 84 SCZ patients with confirmed COVID-19,the median age was 54 years and 76.2%were male.The most common symptom was fever(82%),and less common symptoms were cough(31%),poor appetite(20%),and fatigue(16%).Compared with SCZ patients without COVID-19,those with COVID-19 were older(P=0.006)and significantly lighter(P=0.002),and had more comorbid physical diseases(P=0.001).Surprisingly,those infected were less likely to be smokers(<0.001)or to be treated with dozapine(P=0.03).Further logistic regression showed that smoking[odds ratio(OR)=5.61],clozapine treated(OR=2.95),and male(OR=3.48)patients with relatively fewer comorbid physical diseases(OR=0.098)were at a lower risk for COVID-19.SCZ patients with COVID-19 presented primarily with fever,but only one-third had a cough,which might otherwise be the most common mode of transmission between individuals.CONCLUSION Two unexpected protective factors for COVID-19 among SCZ inpatients are smoking and dozapine treatment.

Alterations of Thymic Epithelial Cells in Lipopolysaccharide-induced Neonatal Thymus Involution

Background： Vascular endothelial growth factor （VEGF） in the thymus was mainly produced by the thymic epithelial cells （TECs）, the predominant component of the thymic microenvironment. The progression of TECs and the roles of VEGF in the neonatal thymus during sepsis have not been reported. This study aimed to explore the alterations of TECs and VEGF level in the neonatal thymus involution and to explore the possible mechanisms at the cellular level. Methods： By establishing a model of clinical sepsis, the changes of TECs were measured by hematoxylin-eosin staining. confocal microscopy, and flow cytometry. Moreover, the levels of VEGF in serum and thymus were assessed based on enzyme-linked immunosorbent assay and Western blotting. Results： The number ofthymocytes and TECs was significantly decreased 2411 after lipopolysaccharide （LPS） challenge. （2.40 ± 0,46）× 10^7 vs. （3.93 ± 0.66）× 10^7 and （1.16 ± 0.14）× 10^5 vs. （2.20 ± 0.19）× 10^5, P 〈 0.05, respectively. Cortical TECs and medullary TECs in the LPS-treated mice were decreased 1.5-fold and 3.9-fold, P 〈 0.05, respectively, lower than those in the controls. The number of thymic epithelial progenitors was also decreased. VEGF expression in TECs was down-regulated in a time-dependent manner. Conclusion： VEGF in thymic cells subsets might contribute to the development of TECs in neonatal sepsis.

Developing a new nomogram to predict early allograft dysfunction after liver transplantation:a nudge in the right direction

Liver transplantation(LTx)is an established option for the treatment of end-stage liver disease,acute liver failure,and hepatic malignancies(1-3).Despite significant advances in clinical practice and scientific research on LTx,liver allograft dysfunction remains a significant clinical problem.Early allograft dysfunction(EAD)is a milder form of primary graft dysfunction that correlates with postoperative complications,higher mortality rates,and decreased graft survival(4).The frequency of EAD ranges from 15%to 30%after LTx from donors after brain death(DBD),reaching 68.4%after LTx from donors after cardiac death(DCD)(5).For living donor liver transplantation(LDLT),the prevalence of EAD is comparatively low,accounting for 18.1%of the recipients in our transplant center(4).