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Studies show that residents from urban, high-risk neighborhoods fair worse on multiple behavioral and health outcomes than their counterparts from more socially and economically advantaged neighborhoods. However, few research efforts have been devoted to examining how formerly incarcerated individuals’ concerns over neighborhood environment are associated with reentry outcomes. Using longitudinal data that captured the reentry experiences of individuals released from prison, the present study quantifies how returning citizens’ concerns over neighborhood environment predict their social withdrawal and mental health deterioration. Findings suggest that when respondents’ post-release family bonds, financial difficulty, drug use, and past mental health histories are all taken into account, their concerns over neighborhood environment exert a significant and positive effect on social withdrawal, depression, and hostility. Returning citizens who believe it is hard to stay out of trouble and prison in their neighborhoods tend to avoid social interactions with others and experience depression and increased hostility and vigilance. Implications for reentry programing and interventions are discussed.

Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI., Graphical abstract Image 1, Highlights • SpGel provides a novel platform for hiPSC culture and differentiation. • SpGel provides a proper microenvironment for cell implants against oxidant stress damage in vitro. • iEC/iCM-laden SpGel improves cell graft retention, promotes cardiac function recovery and inhibits cardiac fibrosis. • SpGel could also be used as a biocompatible bioink for 3D printing cardiac organoids in the future.

While numerous studies have unpacked gender-based disparities in judges’ sentencing decisions, few studies have examined the gender gap in correction settings. This study examines inmates’ gender g...

As the United States enters a decarceration era, the factors predicting reentry success have received a rapidly growing body of research attention. Numerous studies expand beyond individual-level attributes to assess the contextual effect of neighborhoods to which released prisoners return. However, past studies predominantly used neighborhood structural/economic characteristics as the proxies of neighborhood context, leaving the roles of community cohesion and disorder understudied in the context of reentry. Using longitudinal data, this study examines the influence of neighborhood cohesion and disorder on reentry outcomes, represented by released prisoners’ determination to desist and social isolation. The results of linear regression analyses show that net of the effects of individual-level risk factors, released prisoners’ perception of neighborhood disorder exhibit profound influence on reentry outcomes. Implications for reentry programming and interventions are presented.

Early adverse experiences have been identified as a salient risk factor for crime and delinquency. However, past empirical studies predominantly used youth and young adult samples; much less is kno...

The study on the safety of nanomaterials in eyes is still in its early stages. In this study, we put our focus on the effect of one important nanoparticle feature - large surface area - to assess eye safety. To this end, mesoporous silica nanoparticles (MSiNPs) were for the first time employed as a model to evaluate their toxicity in eyes. The porosity of the MSiNPs endows them with a large surface area and the ability to attach to surrounding chemical or biological molecules, further enhancing their surface reactivity and toxic effects. Therefore, to better mimic MSiNP exposure in real environments, we also introduced other hazardous substances such as silver ions (Ag+) to the system and then investigated their synergistic nanotoxicity. Our results showed that the exposure to MSiNPs-Ag+ and even Ag+ at a safe dose, resulted in more significant toxicity than the MSiNPs alone, as evidenced from cell viability, apoptosis, reactive oxygen species (ROS) production, and DNA damage experiments. RNA-Sequencing analysis revealed that the mRNA surveillance signalling pathway plays a unique role in regulating MSiNPs-Ag+-induced cytotoxicity. Besides this, severe corneal damage and dry eye were observed in rat models upon exposure to MSiNPs-Ag+ compared to MSiNPs. Most importantly, we also proposed a protein corona-based therapy to treat MSiNP-induced corneal disease, where the corneal damage could be rescued by fetal bovine serum (FBS) treatment.

To date, there have been few reports examining the correlation between biochar treatments, crop species, and microbiome shifts. In this study, shifts in the soil bacterial community were investigated 4 years after a single incorporation of biochar in soils planted with soybeans and maize. Clear changes in the bacterial community composition and structure were detected in the soybean-planted soil amended with low-titer biochar (7.89 t/ha), whereas such changes in the maize-planted soil were not observed at the same biochar amendment rate, suggesting a more sensitive influence on the bacterial community in the soybean-planted soil than that in the maize-planted soil. Bacterial abundance in the maize-planted soil was reduced significantly with increasing biochar addition (15.78 and 47.34 t/ha), which was probably due to the inhibitory substances originating from biochar. Both the bacterial community and biomarkers in soil under biochar amendment varied with planted crops, bacterial communities responding differently to biochar amendment. All these results suggested that biochar might influence the bacterial community in maize- and soybean-growing soils under different mechanisms. Our findings should be valuable for an in-depth understanding of the potential mechanism of soil microbiome changes following biochar incorporation and for biochar application in agriculture.

This paper discusses regression analysis of incomplete event history studies with a focus on simultaneous estimation and variable selection. Such studies are commonly performed in areas such as medical studies and social sciences, and a great deal of literature has been devoted to their analysis except for the problem considered here (Sun and Zhao, 2013). We develop a new method, which will be referred to as a broken adaptive ridge regression approach. We establish its asymptotic properties, including the oracle property and clustering effect. We also report simulation results which indicate that the proposed method performs well, and better than the existing methods, in practice. In addition, an application is provided.

Although the percutaneous coronary intervention (PCI)treatment can improve the survival rate of acute myocardial infarction (AMI) patients, the early granulocytes response within 6 hours can induce second injuries during the reperfusion process. The new drug delivery system MMP9 hydrolytic microspheres (NMM) with negatively charged surface was designed out and MCC950 (MCC) was loaded into NMM (NMM-M), MCC is the inhibitor of nucleotide binding oligomerization domain (NOD)-like receptor, pyrin containing domain 3 (NLRP3)-inflammasome which is the key promoter of granulocytes-induced injury. NMM-M could effectively escape the phagocytosis of immune phagocytes in the blood, and target the ischemic region based on the electrostatic attraction and the attraction of enzyme to substrate, and sudden release the loaded MCC within 2 hours. The released MCC can inhibit the NLRP3-inflammasome activity, and then further inhibit the secretion of inflammatory factors in granulocytes which are the main factors of early inflammatory damage, and improving cardiac function, realizing the goal of pre-treatment. Therefore, NMM may be a new delivery system, which can provide the accurately, sufficient and rapidly drug deliver, and MCC may be a novel candidate drug in AMI treatment, which may be hopeful in the future.

Background: SARS-CoV-2 has been a global pandemic, but the emergence of asymptomatic patients has caused difficulties in the prevention of the epidemic. Therefore, it is significant to understand the epidemiological characteristics of asymptomatic patients with SARS-CoV-2 infection. Methods: In this single-center, retrospective and observational study, we collected data from 167 patients with SARS-CoV-2 infection treated in Chongqing Public Health Medical Center (Chongqing, China) from January to March 2020. The epidemiological characteristics and variable of these patients were collected and analyzed. Findings: 82.04% of the SARS-CoV-2 infected patients had a travel history in Wuhan or a history of contact with returnees from Wuhan, showing typical characteristics of imported cases, and the proportion of severe COVID-19 patients was 13.2%, of which 59% were imported from Wuhan. For the patients who was returnees from Wuhan, 18.1% was asymptomatic patients. In different infection periods, compared with the proportion after 1/31/2020, the proportion of asymptomatic patient among SARS-CoV-2 infected patient was higher(19% VS 1.5%). In different age groups, the proportion of asymptomatic patient was the highest(28.6%) in children group under 14, next in elder group over 70 (27.3%). Compared with mild and common COVID-19 patients, the mean latency of asymptomatic was longer (11.25 days VS 8.86 days), but the hospital length of stay was shorter (14.3 days VS 16.96 days). Conclusion: The SARS-CoV-2 prevention needs to focus on the screening of asymptomatic patients in the community with a history of contact with the imported population, especially for children and the elderly population. Funding Statement: This work was supported by the National Key Research and Development Program (No.2016YFC1101100) and National Science Fund for Distinguished Young Scholars (No. 31625011). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of Chongqing Public Health Medical Treatment Center (NO.2020-018-01-KY), informed consent was allowed to be waived.

Recurrent event data occur in many areas such as medical studies and social sciences and a great deal of literature has been established for their analysis. On the other hand, only limited research exists on the variable selection for recurrent event data, and the existing methods can be seen as direct generalizations of the available penalized procedures for linear models and may not perform as well as expected. This article discusses simultaneous parameter estimation and variable selection and presents a new method with a new penalty function, which will be referred to as the broken adaptive ridge regression approach. In addition to the establishment of the oracle property, we also show that the proposed method has the clustering or grouping effect when covariates are highly correlated. Furthermore, a numerical study is performed and indicates that the method works well for practical situations and can outperform existing methods. An application is provided.

The human cornea is exposed directly to particulate matter (PM) in polluted air. This exposure can cause eye discomfort and corneal injury. Ultrafine PM (diameter

An accelerated life test (ALT) is often well planned to yield the most statistical information given limited test resources. Nevertheless, ALT planning requires rough estimates of the model parameters as an input, called planning values. The discrepancy between the planning values and the true values may result in insufficient or even no failures at the low-stress level, making the subsequent data analysis difficult. Motivated by the need in the ALTs of data acquisition devices used in smart grids, an adaptive ALT scheme is proposed. The key idea is based on the observation that, when the product reliability is underestimated during the ALT design phase, it is unlikely to observe failures at the early stage of the test. Therefore, the low-stress level should be elevated to protect against insufficient failures. Under this adaptive ALT framework, order statistics techniques are used to derive the likelihood function by assuming a general log-location-scale distribution for the product lifetime. Confidence intervals for the parameters are constructed based on the large-sample approximation as well as the accelerated bootstrap method. A simulation study is conducted to demonstrate the advantages of the adaptive ALT compared with the simple constant-stress ALT. Its application is illustrated using the motivating example from smart grids.

Neural stem cells are characterized by self-renewal and multipotency, and a capacity to regenerate in response to brain injury or neurodegenerative disease. Silicon dioxide nanoparticles (SiO2 NPs) are novel materials, which enable the delivery of specific payloads to stem cells; for example, genes or proteins, to enable cell-fate manipulation, or tracer materials, to enable in vivo tracing. However, little is known about the dose-dependent cytotoxicity of SiO2 NPs, and how exposure to SiO2 NPs changes mRNA expression profiles in neural stem cells. In this study, a mouse C17.2 neural stem cell line was treated with 90 nm monodisperse fluorescein isothiocyanate-SiO2 NPs at 0, 100, 200 and 400 μg mL−1 for 48 hours. Internalization of SiO2 NPs was observed in C17.2 cells in a dose-dependent manner. SiO2 NP exposure induced apoptosis and inhibited cell proliferation in the C17.2 cell line at dosage levels of 200 μg mL−1 and above. Microscopically, mitochondrial swelling and cristae fracture were observed. Furthermore, next generation RNA sequencing (RNA-Seq) indicated that high-dose SiO2 NP exposure specifically inhibited transcription of glutathione-S-transferase (GST) genes, including GSTM1, GSTM7 and GSTT1. These results suggest that application of high-dose SiO2 NPs to the nervous system may cause neurotoxicity, induce apoptosis and reduce neural stem cell proliferation by inhibiting GST gene expression.

A great deal of literature has been established for regression analysis of longitudinal data but most of the existing methods assume that covariates can be observed completely or at the same observation times for the response variable, and the observation process is independent of the response variable completely or given covariates. As pointed out by many authors, in practice, one may face the situation where the response variable and covariates are observed intermittently at different time points, leading to sparse asynchronous longitudinal data, or the observation process may be related to the response variable even given covariates. It is apparent that sometimes both issues can occur in the same time and although some literature has been developed to address each of the two issues, it does not seem to exist an established approach that can deal with both together. To address this, in this paper, a flexible semiparametric transformation conditional model is presented and for estimation, a kernel-weighted estimating equation-based approach is proposed. The proposed estimators of regression parameters are shown to be consistent and asymptotically follow the normal distribution. For the assessment of the finite sample performance of the method, an extensive simulation study is carried out and suggests that it performs well for practical situations. The approach is applied to a prospective HIV study that motivated this investigation.

// Liang Liu 1,2 , Qin Zhang 1 , Yulong Cai 1 , Dayu Sun 1,2 , Xie He 1 , Lian Wang 1 , Dan Yu 1 , Xin Li 1 , Xiaoyi Xiong 2 , Haiwei Xu 3 , Qingwu Yang 2 and Xiaotang Fan 1 1 Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing, China 2 Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, China 3 Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, Chongqing, PR China Correspondence to: Xiaotang Fan, email: // Qingwu Yang, email: // Keywords : resveratrol; depression; neurogenesis; LPS; radial glial cells; Pathology Section Received : May 26, 2016 Accepted : July 20, 2016 Published : August 10, 2016 Abstract Radial glial-like cells (RGLs) in the adult dentate gyrus (DG) function as progenitor cells for adult hippocampal neurogenesis, a process involved in the stress-related pathophysiology and treatment efficiency of depression. Resveratrol (RSV) has been demonstrated to be a potent activator of neurogenesis. The present study investigated whether chronic RSV treatment has antidepressant potential in relation to hippocampal neurogenesis. Mice received two weeks of RSV (20 mg/kg) or dimethylsulfoxide (DMSO) treatment, followed by lipopolysaccharide (LPS; 1 mg/kg) or saline injections for 5 days. We found that RSV treatment abrogated the increased immobility in the forced swimming test and tail suspension test induced by LPS. Immunohistochemical staining revealed that RSV treatment reversed the increase in microglial activation and the inhibition in DG neurogenesis. RSV treatment also attenuated LPS-induced defects in the expanding of RGLs through promoting symmetric division. In addition, RSV ameliorated LPS-induced NF-κB activation in the hippocampus coincides with the up-regulation levels of Sirt1 and Hes1. Taken together, these data indicated that RSV-induced Sirt1 activation counteracts LPS-induced depression-like behaviors via a neurogenic mechanism. A new model to understand the role of RSV in treating depression may result from these findings.

Recurrent event data occur in many areas such as medical studies and social sciences and a great deal of literature has been established for their analysis. On the other hand, only limited research exists on the variable selection for recurrent event data, and the existing methods can be seen as direct generalizations of the available penalized procedures for linear models and may not perform as well as expected. This article discusses simultaneous parameter estimation and variable selection and presents a new method with a new penalty function, which will be referred to as the broken adaptive ridge regression approach. In addition to the establishment of the oracle property, we also show that the proposed method has the clustering or grouping effect when covariates are highly correlated. Furthermore, a numerical study is performed and indicates that the method works well for practical situations and can outperform existing methods. An application is provided.Une riche littérature traite de l’analyse des événements récurrents, un type de données observé notamment dans les études médicales et dans les projets de recherche en sciences sociales. Par contre, peu de résultats de recherche portent sur la sélection de variables pour ces modèles. Les méthodes existantes peuvent être vues comme une généralisation directe de procédures pénalisées disponibles pour les modèles linéaires et peuvent offrir des performances inférieures aux attentes. Les auteurs proposent l’approche de régression ridge brisée adaptative où ils procèdent simultanément à l’estimation de paramètres et à la sélection de variables en exploitant une nouvelle fonction de pénalité. Ils prouvent la propriété d’oracle de leur méthode et montrent qu’elle possède une propriété de regroupement lorsque les covariables sont hautement corrélées. Ils présentent une étude numérique qui indique que leur méthode fonctionne bien dans des situations pratiques et peut même s’avérer plus performante que les approches existantes. Ils fournissent également un exemple d’application.

Induced neural stem cells (iNSCs) reprogrammed from somatic cells have great potentials in cell replacement therapies and in vitro modeling of neural diseases. Direct conversion of fibroblasts into iNSCs has been shown to depend on a couple of key neural progenitor transcription factors (TFs), raising the question of whether such direct reprogramming can be achieved by non-neural progenitor TFs. Here we report that the non-neural progenitor TF Ptf1a alone is sufficient to directly reprogram mouse and human fibroblasts into self-renewable iNSCs capable of differentiating into functional neurons, astrocytes and oligodendrocytes, and improving cognitive dysfunction of Alzheimer’s disease mouse models when transplanted. The reprogramming activity of Ptf1a depends on its Notch-independent interaction with Rbpj which leads to subsequent activation of expression of TF genes and Notch signaling required for NSC specification, self-renewal, and homeostasis. Together, our data identify a non-canonical and safer approach to establish iNSCs for research and therapeutic purposes., Fibroblasts can be reprogrammed into induced neural stem cells (iNSCs) using transcription factors expressed in neural progenitors. Here the authors show that Ptf1a, which is normally expressed in postmitotic neurons, can reprogram fibroblasts to iNSCs through Notch independent interaction with Rbpj.

The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor β (LXRβ) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXRβ in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRβ-null mice. In addition, LXRβ deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRβ in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXRβ-deficient mice.

In view of the shortcomings such as the short control distance of the traditional air conditioner remote controller on the market nowadays and combining with the current smart home new mode “Cloud+ Terminal” mode, a smart home system based on internet is designed and designed to be fully applied to the simple and reliable features of the LPC1114 chip. The controller is added with temperature control module, timing module and other modules. Through the actual test, it achieved remote control air conditioning, with reliability and stability and brought great convenience to people’s lives.

Alzheimer's disease (AD) is the most common cause of dementia. In addition to cognitive impairments, deficits in non-cognitive behaviors are also common neurological sequelae in AD. Here, we show that complex behavioral deficits in 7-month-old APPswe/PSEN1dE9 (APP/PS1) mice include impairments in object recognition, deficient social interaction, increased depression and buried marbles. Citalopram, one of the selective serotonin reuptake inhibitors (SSRIs), ameliorated the amyloid deposition in AD patients and transgenic animal models. After treatment for 4 weeks, citalopram rescued the deficits in short-term memory, sociability and depression in these mice. Further immunohistochemical analysis showed chronic citalopram treatment significantly attenuated β-amyloid deposition and microglial activation in the brains of APP/PS1 mice as demonstrated previously. Parvalbumin (PV) interneurons, which are the primary cellular subtype of GABAergic neurons and considered indispensable for short-term memory and social interaction, also contributed to the progress of depression. Additionally, we found the citalopram could significantly increase the PV-positive neurons in the cortex of APP/PS1 mice without alteration in the hippocampus, which might contribute to the improvement of behavioral performance. Our findings suggest that citalopram might be a potential candidate for the early treatment of AD.

Background/Aims: Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

The failure of adult neurogenesis in the hippocampal dentate gyrus (DG) is closely correlated with memory decline in Alzheimer's disease (AD). Radial glial-like cells (RGLs) localized to the adult DG generate intermediate progenitor cells and immature neurons and thus contribute to adult hippocampus neurogenesis. Memantine (MEM) has been indicated to dramatically increase hippocampal neurogenesis by promoting the proliferation of RGLs. In this study, we examined the effect of MEM on the capacity for hippocampal cell proliferation and the amount of RGLs in APPswe/PS1∆E9 transgenic (APP/PS1) mice between 9 and 13 months of age. MEM could enhance hippocampal neurogenesis and increase the number of RGLs in the DG subgranular zone (DG-SGZ) of APP/PS1 mice of both ages. Moreover, MEM decreased amyloidogenesis in 13-month-old APP/PS1 mice and protected cultured radial glia cells (RGCs, L2.3 cells) from apoptosis induced by the β amyloid peptide (Aβ). Additionally, MEM inhibited microglial activation in a vertical process in DG-SGZ of APP/PS1 mice and decreased interacting with RGL processes. Reelin is involved in the proliferation of RGLs in the hippocampus, which was typically upregulated in the hippocampus of APP/PS1 mice by MEM and thought to be an active signaling pathway associated with the MEM-induced increase in RGLs. Our data suggest a previously uncharacterized role for MEM in treating AD.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble β-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuroprotection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application.

Cerebellar Purkinje cell and granule cell development are coordinated by Bergmann glia, and are particularly sensitive to ethanol (EtOH) exposure. The liver X receptor (LXR) plays important roles in Bergmann glial development. However, the effect of LXR activation on EtOH-mediated impairment of Bergmann glia and subsequently on Purkinje cell dendritogenesis remains undetermined. Therefore, using immunohistochemistry, quantitative real-time PCR and Western blot, we tested the possible protection of LXR agonist T0901317 (T0) on Bergmann glia and Purkinje cell dendritogenesis in mice exposed to ethanol. Results showed that a brief exposure of EtOH on postnatal day (PD 5) significantly decreased the average body weight of mice at PD 6 without alteration in the brain weight. In EtOH-exposed mice, the number of migrating granule cells in the molecular layer was significantly decreased, and this effect was attenuated by pretreatment of T0. EtOH exposure also resulted in the significant reduction of calbindin-labeled Purkinje cells, their maximum dendrite length, and impairment of Purkinje cell dendritogenesis. Furthermore, EtOH induced the activation of microglia in the Purkinje cell layer and impaired the development of Bergmann glia. However, pretreatment of T0 effectively blocked all of these responses. These responses were found to be mediated by the inhibition of upregulated levels of β-catenin and transcription factor LEF1 in the cerebellum. Overall, the results suggest that activating LXRs on postnatal mice exposed to EtOH is protective to Bergmann glia, and thus may play a critical role in preventing EtOH-induced defects during cerebellar development.

// Xiao He 1, 2 , Dayu Sun 1, 2 , Siyu Chen 1, 2 and Haiwei Xu 1, 2 1 Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China 2 Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, 400038, China Correspondence to: Haiwei Xu, email: haiweixu2001@163.com Keywords: retinal degeneration, liver X receptors, JAK-STAT pathway, microglia, apoptosis Received: November 16, 2016 Accepted: March 01, 2017 Published: March 29, 2017 ABSTRACT Retinal degeneration (RD), including retinitis pigmentosa (RP), is an inherited eye disease characterized by progressive degeneration of photoreceptors. Recently, immune cells, including microglia, Muller cells and astrocytes, in degenerative retina are demonstrated to play key roles in the development of RD and can be used as potential therapeutic targets. Liver X receptors (LXRs) are important immuno-inflammatory response transcription factors that have been reported to be a new potential therapeutic drug target for neurodegenerative diseases. However, the potential therapeutic utility of LXRs for RP has not been evaluated. In the present study, Pde6β (rd1) mice received intraperitoneal injections of T0901317 (T0, 50 mg/kg/d) or vehicle (2% DMSO) for 7 days with age-matched C57/BL6 mice as controls. The effect of T0 was examined by quantitating photoreceptor apoptosis, microglial density and the expression of inflammatory mediators; the underlying mechanisms were then explored with a microarray assay. T0 markedly delayed apoptosis of the photoreceptors, partially through suppressing the activation of microglia and the gliosis of Muller cells, and decreased the expression levels of IL-6, iNOS, COX-2 and ENG in rd1 mice; as a result, the visual function of T0-treated rd1 mice measured with electroretinograms (ERG) was preserved for a longer time than that of vehicle-treated rd1 mice. The microarray assay showed that the Janus kinase/Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway was significantly affected in the retina of rd1 mice with T0 treatment. Our data suggested that T0 modulated the immunologic function of glia cells in the degenerative retina through the JAK3/STAT pathway and delayed the apoptosis of photoreceptors.

This study aimed to observe the therapeutic effects of magnesium lithospermate B on acute and chronic colitis induced by dextran sodiumsulfate (DSS) and the role of inflammasome complex (NOD-like receptor protein, NLRP; apoptosis-associated speck-like protein containing, ASC; caspase-1). Establishment of acute and chronic colitis models were by using 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (240 mg/kg body weight) was given by subcutaneous injection. Samples were collected for biomarker assay, histological examination, immunohistochemical evaluation and western blot. There was obvious increase in TNF-α level and NLPR3, ASC, and caspase-1 expressions in acute and chronic colitis groups compared with the normal control. Significant decrease of the tumor necrosis factor-α level and the expressions of NLPR3, ASC, and caspase-1 were observed after treatment with magnesium lithospermate B. This study showed that magnesium lithospermate B could be used to treat acute and chronic colitis by inhibiting the activation of the NLRP3/ASC/Caspase-1 pathway.

Alzheimer's disease (AD) is the most prevalent type of dementia, and its neuropathology is characterized by deposition of insoluble β-amyloid peptides, intracellular neurofibrillary tangles, and the loss of diverse neurons. Current pharmacological treatments for AD relieve symptoms without affecting the major pathological characteristics of the disease. Therefore, it is essential to develop new and effective therapies. Stem-cell types include tissue-specific stem cells, such as neural stem cells and mesenchymal stem cells, embryonic stem cells derived from blastocysts, and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells. Recent preclinical evidence suggests that stem cells can be used to treat or model AD. The mechanisms of stem cell based therapies for AD include stem cell mediated neuroprotection and trophic actions, antiamyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model AD, investigate sporadic and familial AD pathogenesis, and screen for anti-AD drugs. Although considerable progress has been achieved, a series of challenges must be overcome before stem cell based cell therapies are used clinically for AD patients. This review highlights the recent experimental and preclinical progress of stem-cell therapies for AD, and discusses the translational challenges of their clinical application.

Anti-platelet drugs have been used to treat inflammatory bowel disease. In this study, we observed the therapeutic effects of magnesium lithospermate B, a main component of salvianolate, on colitis induced by dextran sodiumsulfate (DSS). Colitis was induced by 5% DSS oral administration in BALB/C male mice. Magnesium lithospermate B (60–240 mg/kg) was given by subcutaneous injection for 2 weeks. Then, mice were sacrificed; serum and colon tissues were collected for biomarker assay, histological examination, immunohistochemical study and real-time quantitative polymerase chain reaction. DSS induced gross bleeding, inflammation, crypt damage and mucosal damage in colon. Treatment with magnesium lithospermate B could reduce colon inflammation induced by DSS. Magnesium lithospermate B could reverse the high CD40/CD40L expression and hypercoagulable state induced by DSS in colon. This study showed that magnesium lithospermate B could be used to treat colitis. The protective effects of magnesium lithospermate B may be due to its effects on CD40/CD40L expression and blood clotting status.