GluN2B-containing NMDA receptor attenuated neuronal apoptosis in the mouse model of HIBD through inhibiting endoplasmic reticulum stress-activated PERK/eIF2α signaling pathway.

Introduction: Neonatal hypoxic-ischemic brain damage (HIBD) refers to brain damage in newborns caused by hypoxia and reduced or even stopped cerebral blood flow during the perinatal period. Currently, there are no targeted treatments for neonatal ischemic hypoxic brain damage, primarily due to the incomplete understanding of its pathophysiological mechanisms. Especially, the role of NMDA receptors is less studied in HIBD. Therefore, this study explored the molecular mechanism of endogenous protection mediated by GluN2B-NMDAR in HIBD. Method: Hypoxic ischemia was induced in mice aged 9-11 days. The brain damage was examined by Nissl staining and HE staining, while neuronal apoptosis was examined by Hoechst staining and TTC staining. And cognitive deficiency of mice was examined by various behavior tests including Barnes Maze, Three Chamber Social Interaction Test and Elevated Plus Maze. The activation of ER stress signaling pathways were evaluated by Western blot. Results: We found that after HIBD induction, the activation of GluN2B-NMDAR attenuated neuronal apoptosis and brain damage. Meanwhile, the ER stress PERK/eIF2α signaling pathway was activated in a time-dependent manner after HIBE. Furthermore, after selective inhibiting GluN2B-NMDAR in HIBD mice with ifenprodil, the PERK/eIF2α signaling pathway remains continuously activated, leading to neuronal apoptosis, morphological brain damage. and aggravating deficits in spatial memory, cognition, and social abilities in adult mice. Discussion: The results of this study indicate that, unlike its role in adult brain damage, GluN2B in early development plays a neuroprotective role in HIBD by inhibiting excessive activation of the PERK/eIF2α signaling pathway. This study provides theoretical support for the clinical development of targeted drugs or treatment methods for HIBD.

DVT: a high-throughput analysis pipeline for locomotion and social behavior in adult Drosophila melanogaster.

BACKGROUND: Drosophila melanogaster is excellent animal model for understanding the molecular basis of human neurological and motor disorders. The experimental conditions and chamber design varied between studies. Moreover, most previously established paradigms focus on fly trace detection algorithm development. A comprehensive understanding on how fly behaves in the chamber is still lacking. RESULTS: In this report, we established 74 unique behavior metrics quantifying spatiotemporal characteristics of adult fly locomotion and social behaviors, of which 49 were newly proposed. By the aiding of the developed analysis pipeline, Drosophila video tracking (DVT), we identified siginificantly different patterns of fly behavior confronted with different chamber height, fly density, illumination and experimental time. Meanwhile, three fly strains which are widely used as control lines, Canton-S(CS), w1118 and Oregon-R (OR), were found to exhibit distinct motion explosiveness and exercise endurance. CONCLUSIONS: We believe the proposed behavior metrics set and pipeline should help identify subtle spatial and temporal differences of drosophila behavior confronted with different environmental factors or gene variants.

Biglycan regulated colorectal cancer progress by modulating enteric neuron-derived IL-10 and abundance of Bacteroides thetaiotaomicron.

Biglycan (BGN) is a proteoglycan with branch chains and highly expressed in enteric neurons in the tumor tissue of colorectal cancer (CRC), which is negatively associated with survival rates in patients with CRC. However, how the proteoglycan promotes the progress of CRC through interacting with bacteria and regulating the immune response of enteric neurons remains largely unknown. In the present study, we found that biglycan deficiency changed tumor distribution in a colitis-associated colon cancer model. Furthermore, we revealed that BGN deficiency inhibits tumor growth in an allograft tumor model and the migration of cancer cell by upregulating interleukin-10 expression in enteric neurons. Significantly, we demonstrated that biglycan deficiency enriched the abundance of Bacteroides thetaiotaomicron through competing with it for chondroitin sulfate to inhibit CRC progress. Our work provided new insights into the interaction between host proteoglycan and gut microbiota as well as the role of enteric neurons in the tumor microenvironment.

A Frog-Derived Cathelicidin Peptide with Dual Antimicrobial and Immunomodulatory Activities Effectively Ameliorates Staphylococcus aureus-Induced Peritonitis in Mice.

As antimicrobial resistance poses an increasing threat to public health, it is urgent to develop new antimicrobial agents. In this paper, we identify a novel 30-residue peptide (Nv-CATH, NCNFLCKVKQRLRSVSSTSHIGMAIPRPRG) from the skin of the frog Nanorana ventripunctata, which belongs to the cathelicidin family. Nv-CATH exhibited broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria. Nv-CATH significantly protected mice from lethal infections caused by Staphylococcus aureus. Furthermore, the peptide suppressed excessive and harmful inflammatory responses by repressing the production of NO, IL-6, TNF-α, and IL-1ß. The NF-κB-NLRP3 and MAPK inflammatory signaling pathways were involved in the protection in vitro and in vivo. Nv-CATH also modulated macrophage/monocyte and neutrophil trafficking to the infection site by stimulating CXCL1, CXCL2, and CCL2 production in macrophages. Nv-CATH augmented immunocyte-mediated bacterial killing by modestly promoting neutrophils' phagocytosis and PMA-induced NET formation. Thus, Nv-CATH protects mice against bacterial infection by antimicrobial-immunomodulatory duality. The combination of these two characteristics makes Nv-CATH a promising molecule template for the development of novel antimicrobial and antibiotic-resistant agents.

The landscape in the gut microbiome of long-lived families reveals new insights on longevity and aging - relevant neural and immune function.

Human longevity has a strong familial and genetic component. Dynamic characteristics of the gut microbiome during aging associated with longevity, neural, and immune function remained unknown. Here, we aim to reveal the synergistic changes in gut microbiome associated with decline in neural and immune system with aging and further obtain insights into the establishment of microbiome homeostasis that can benefit human longevity. Based on 16S rRNA and metagenomics sequencing data for 32 longevity families including three generations, centenarians, elderly, and young groups, we found centenarians showed increased diversity of gut microbiota, severely damaged connection among bacteria, depleted in microbial-associated essential amino acid function, and increased abundance of anti-inflammatory bacteria in comparison to young and elderly groups. Some potential probiotic species, such as Desulfovibrio piger, Gordonibacter pamelaeae, Odoribacter splanchnicus, and Ruminococcaceae bacterium D5 were enriched with aging, which might possibly support health maintenance. The level of Amyloid-ß (Aß) and brain-derived neurotrophic factor (BDNF) related to neural function showed increased and decreased with aging, respectively. The elevated level of inflammatory factors was observed in centenarians compared with young and elderly groups. The enriched Bacteroides fragilis in centenarians might promote longevity through up-regulating anti-inflammatory factor IL-10 expression to mediate the critical balance between health and disease. Impressively, the associated analysis for gut microbiota with the level of Aß, BDNF, and inflammatory factors suggests Bifidobacterium pseudocatenulatum could be a particularly beneficial bacteria in the improvement of impaired neural and immune function. Our results provide a rationale for targeting the gut microbiome in future clinical applications of aging-related diseases and extending life span.Abbreviations: 16S rRNA: 16S ribosomal RNA; MAGs: Metagenome-assembled genomes; ASVs: Amplicon sequence variants; DNA: Deoxyribonucleic acid; FDR: False discovery rate: KEGG: Kyoto Encyclopedia of Genes and Genomes; PCoA: Principal coordinates analysis; PCR: Polymerase chain reaction; PICRUSt: Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; Aß: Amyloid-ß (Aß); BDNF: Brain-derived neurotrophic factor.

Rain Classroom assisted by WeChat for preliminary online physiology teaching during the COVID-19 pandemic.

Due to the COVID-19 pandemic during spring semester 2020, teachers and students were forced to engage in online instruction. However, there is little evidence on the feasibility of online physiology teaching. This study demonstrated a 3-wk preliminary online physiology course based on Rain Classroom assisted by the mobile application WeChat. Eighty-seven nursing undergraduate students attended an online physiology course during the spring semester of the 2019-2020 academic year from March 9 to March 29. We determined the effects of the online physiology learning based on in-class tests, preclass preparation, and review rates for the course materials. We also measured the students' perceptions and attitudes about online learning with a questionnaire survey. Posttest scores from the first week to the third week in online physiology course (7.22 ± 1.83, 7.68 ± 2.09, and 6.21 ± 2.92, respectively) exceeded the pretest scores (5.32 ± 2.14, 6.26 ± 2.49, and 3.72 ± 2.22, respectively), and this finding was statistically significant (all P < 0.001). Moreover, the pretest scores were significant positive predictors of final grade (all P < 0.01). In addition, the percentage of preclass preparation increased in 3 wk, from 43.68% to 57.47% to 68.97%. From the first week to the third week, the review rate increased from 86.21% to 91.95%; however, the second week was the lowest of all (72.41%). Finally, students' perceptions about their online physiology learning experiences were favorable. In conclusion, online physiology instruction based on Rain Classroom assisted by WeChat was an effective strategy during the COVID-19 pandemic.

Cathelicidin-NV from Nanorana ventripunctata effectively protects HaCaT cells, ameliorating ultraviolet B-induced skin photoaging.

Cathelicidins are diverse effector molecules in the vertebrate immune system and are related to immune regulation, inflammatory response, wound healing, and blood vessel formation. However, little is known about their free radical scavenging ability, especially in vivo. In this study, a cathelicidin molecule (cathelicidin-NV, ARGKKECKDDRCRLLMKRGSFSYV) previously identified from the spot-bellied plateau frog (Nanorana ventripunctata) (Anura, Dicroglossidae, Dicroglossinae) by us was shown to alleviate ultraviolet B (UVB)-induced skin photoaging in mice. Cathelicidin-NV effectively suppressed cytotoxicity, DNA fragmentation, apoptosis and reduced the protein expression levels of JNK, c-Jun, and MMP-1, which are involved in the regulation of collagen degradation in HaCaT cells induced by UVB irradiation. Furthermore, cathelicidin-NV also scavenged UVB-induced intracellular reactive oxygen species (ROS). Taken together, cathelicidin-NV directly scavenged excessive intracellular ROS to protect HaCaT cells, and subsequently alleviated UVB-induced skin photoaging. This study extends reports on the antioxidant function of the cathelicidin family. In addition, the properties of cathelicidin-NV make it an excellent candidate for the prevention and treatment of UV-induced skin photoaging.

Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder.

OBJECTIVE: Recent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota. DESIGN: A large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing. RESULT: In subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets. CONCLUSION: Our large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.

Identification of Prognostic miRNAs Associated With Immune Cell Tumor Infiltration Predictive of Clinical Outcomes in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: A detailed means of prognostic stratification in patients with non-small cell lung cancer (NSCLC) is urgently needed to support individualized treatment plans. Recently, microRNAs (miRNAs) have been used as biomarkers due to their previously reported prognostic roles in cancer. This study aimed to construct an immune-related miRNA signature that effectively predicts NSCLC patient prognosis. METHODS: The miRNAs and mRNA expression and mutation data of NSCLC was obtained from The Cancer Genome Atlas (TCGA). Immune-associated miRNAs were identified using immune scores calculated by the ESTIMATE algorithm. LASSO-penalized multivariate survival models were using for development of a tumor immune-related miRNA signature (TIM-Sig), which was evaluated in several public cohorts from the Gene Expression Omnibus (GEO) and the CellMiner database. The miRTarBase was used for constructing the miRNA-target interactions. RESULTS: The TIM-Sig, including 10 immune-related miRNAs, was constructed and successfully predicted overall survival (OS) in the validation cohorts. TIM-Sig score negatively correlated with CD8+ T cell infiltration, IFN-γ expression, CYT activity, and tumor mutation burden. The correlation between TIM-Sig score and genomic mutation and cancer chemotherapeutics was also evaluated. A miRNA-target network of 10 miRNAs in TIM-Sig was constructed. Further analysis revealed that these target genes showed prognostic value in both lung squamous cell carcinoma and adenocarcinoma. CONCLUSIONS: We concluded that the immune-related miRNAs demonstrated a potential value in clinical prognosis.

SARS-CoV-2 encoded microRNAs are involved in the process of virus infection and host immune response.

The outbreak of COVID-19 caused by SARS-CoV-2 is spreading worldwide, with the pathogenesis mostly unclear. Both virus and host-derived microRNA (miRNA) play essential roles in the pathology of virus infection. This study aims to uncover the mechanism for SARS-CoV-2 pathogenicity from the perspective of miRNA. We scanned the SARS-CoV-2 genome for putative miRNA genes and miRNA targets and conducted in vivo experiments to validate the virus-encoded miRNAs and their regulatory role on the putative targets. One of such virus-encoded miRNAs, MR147-3p, was overexpressed that resulted in significantly decreased transcript levels of all of the predicted targets in human, i.e., EXOC7, RAD9A, and TFE3 in the virus-infected cells. The analysis showed that the immune response and cytoskeleton organization are two of the most notable biological processes regulated by the infection-modulated miRNAs. Additionally, the genomic mutation of SARS-CoV-2 contributed to the changed miRNA repository and targets, suggesting a possible role of miRNAs in the attenuated phenotype of SARS-CoV-2 during its evolution. This study provided a comprehensive view of the miRNA-involved regulatory system during SARS-CoV-2 infection, indicating possible antiviral therapeutics against SARS-CoV-2 through intervening miRNA regulation.

Comprehensive characterization of a drug-resistance-related ceRNA network across 15 anti-cancer drug categories.

Cancer is still a major health problem around the world. The treatment failure of cancer has largely been attributed to drug resistance. Competitive endogenous RNAs (ceRNAs) are involved in various biological processes and thus influence the drug sensitivity of cancers. However, a comprehensive characterization of drug-sensitivity-related ceRNAs has not yet been performed. In the present study, we constructed 15 ceRNA networks across 15 anti-cancer drug categories, involving 217 long noncoding RNAs (lncRNAs), 158 microRNAs (miRNAs), and 1,389 protein coding genes (PCGs). We found that these ceRNAs were involved in hallmark processes such as "self-sufficiency in growth signals," "insensitivity to antigrowth signals," and so on. We then identified an intersection ceRNA network (ICN) across the 15 anti-cancer drug categories. We further identified interactions between genes in the ICN and clinically actionable genes (CAGs) by analyzing the co-expressions, protein-protein interactions, and transcription factor-target gene interactions. We found that certain genes in the ICN are correlated with CAGs. Finally, we found that genes in the ICN were aberrantly expressed in tumors, and some were associated with patient survival time and cancer stage.

PM2RA: A Framework for Detecting and Quantifying Relationship Alterations in Microbial Community.

The dysbiosis of gut microbiota is associated with the pathogenesis of human diseases. However, observing shifts in the microbe abundance cannot fully reveal underlying perturbations. Examining the relationship alterations (RAs) in the microbiome between health and disease statuses provides additional hints about the pathogenesis of human diseases, but no methods were designed to detect and quantify the RAs between different conditions directly. Here, we present profile monitoring for microbial relationship alteration (PM2RA), an analysis framework to identify and quantify the microbial RAs. The performance of PM2RA was evaluated with synthetic data, and it showed higher specificity and sensitivity than the co-occurrence-based methods. Analyses of real microbial datasets showed that PM2RA was robust for quantifying microbial RAs across different datasets in several diseases. By applying PM2RA, we identified several novel or previously reported microbes implicated in multiple diseases. PM2RA is now implemented as a web-based application available at http://www.pm2ra-xingyinliulab.cn/.

A Frog Peptide Ameliorates Skin Photoaging Through Scavenging Reactive Oxygen Species.

Although many bioactive peptides have been identified from the frog skins, their protective effects and the molecular mechanisms against skin photodamage are still poorly understood. In this study, a novel 20-residue peptide (antioxidin-NV, GWANTLKNVAGGLCKMTGAA) was characterized from the skin of plateau frog Nanorana ventripunctata. Antioxidin-NV obviously decreased skin erythema, thickness and wrinkle formation induced by Ultraviolet (UV) B exposure in hairless mice. In UVB-irradiated keratinocytes (HaCaT cells) and hairless mice, it effectively inhibited DNA damage through reducing p-Histone H2A.X (γH2AX) expression, alleviated cell apoptosis by decreasing the expression of apoptosis-specific protein (cleaved caspase 3), and reduced interleukin-6 (IL-6) production via blocking UVB-activated Toll-like receptor 4 (TLR4)/p38/JNK/NF-κB signaling. In UVB-irradiated human skin fibroblasts (HSF cells) and hairless mice, it effectively restored HSF cells survival rate, and rescued α-SMA accumulation and collagen (especially type I collagen) production by restoring transforming growth factor-ß1 (TGF-ß1)/Smad2 signaling. We found that antioxidin-NV directly and rapidly scavenged intracellular and mitochondrial ROS in HaCaT cells upon UVB irradiation, and quickly eliminated the artificial free radicals, 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+). Taken together, antioxidin-NV directly and rapidly scavenged excessive ROS upon UVB irradiation, subsequently alleviated UVB-induced DNA damage, cell apoptosis, and inflammatory response, thus protecting against UVB-induced skin photoaging. These properties makes antioxidin-NV an excellent candidate for the development of novel anti-photoaging agent.

Characterizing heterogeneity of non-small cell lung tumour microenvironment to identify signature prognostic genes.

Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in non-small cell lung cancer (NSCLC). This study focused on the characterization of immune infiltration profiling in patients with NSCLC and its correlation with survival outcome. All TCGA samples were divided into three heterogeneous clusters based on immune cell profiles: cluster 1 ('low infiltration' cluster), cluster 2 ('heterogeneous infiltration' cluster) and cluster 3 ('high infiltration' cluster). The immune cells were responsible for a significantly favourable prognosis for the 'high infiltration' community. Cluster 1 had the lowest cytotoxic activity, tumour-infiltrating lymphocytes and interferon-gamma (IFN-γ), as well as immune checkpoint molecules expressions. In addition, MHC-I and immune co-stimulator were also found to have lower cluster 1 expressions, indicating a possible immune escape mechanism. A total of 43 differentially expressed genes (DEGs) that overlapped among the groups were determined based on three clusters. Finally, based on a univariate Cox regression model, prognostic immune-related genes were identified and combined to construct a risk score model able to predict overall survival (OS) rates in the validation datasets.

Construction and Analysis of Human Diseases and Metabolites Network.

The relationship between aberrant metabolism and the initiation and progression of diseases has gained considerable attention in recent years. To gain insights into the global relationship between diseases and metabolites, here we constructed a human diseases-metabolites network (HDMN). Through analyses based on network biology, the metabolites associated with the same disorder tend to participate in the same metabolic pathway or cascade. In addition, the shortest distance between disease-related metabolites was shorter than that of all metabolites in the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic network. Both disease and metabolite nodes in the HDMN displayed slight clustering phenomenon, resulting in functional modules. Furthermore, a significant positive correlation was observed between the degree of metabolites and the proportion of disease-related metabolites in the KEGG metabolic network. We also found that the average degree of disease metabolites is larger than that of all metabolites. Depicting a comprehensive characteristic of HDMN could provide great insights into understanding the global relationship between disease and metabolites.

[Multiscale influences of urbanized landscape metrics on the diversity of indigenous plant species: A case study in Shunyi District of Beijing, China.] / åŸŽå¸‚åŒ–æ™¯è§‚æ ¼å±€å¯¹æœ¬åœŸæ¤ç‰©å¤šæ ·æ€§çš„å¤šå°ºåº¦å½±å“­­ä»¥åŒ—京市顺义区为例.

The effects of landscape pattern on plant diversity have been widely reported in literature, with that of urban landscape remaining largely unknown. To explore the impacts of urbanization landscape pattern on plant diversity and its scale effect, 105 plots were investigated in Shunyi District, Beijing. The α and ß diversity of each plot were calculated, and 43 urban landscape indices of 10 scales in the range of 100-1000 m were analyzed with 100 m as the step. The results showed that the urban landscape area metric, core metrics and edge metrics were negatively related with diversity of indigenous plant species at all the examined scales. Shape complexity metrics contributed to plant diversity at small scale, while the area-weighted complexity metrics contributed at large scale. Other metrics, such as connection, proximity, cohesion, fragmentation and interspersion juxtaposition of urban patches showed a slight and unsteady relationship with the diversity of indigenous plant species. The urbanization intensity was negatively related with scales and with plant diversity at all scales. Urban landscape could better conserve indigenous plant diversity by reasonably dividing an urbanized area into many small patches with simple edge. Our results presented suitable urban landscape indicators for preserving plant diversity and suggestions for the construction of ecological cities.

RNAactDrug: a comprehensive database of RNAs associated with drug sensitivity from multi-omics data.

Drug sensitivity has always been at the core of individualized cancer chemotherapy. However, we have been overwhelmed by large-scale pharmacogenomic data in the era of next-generation sequencing technology, which makes it increasingly challenging for researchers, especially those without bioinformatic experience, to perform data integration, exploration and analysis. To bridge this gap, we developed RNAactDrug, a comprehensive database of RNAs associated with drug sensitivity from multi-omics data, which allows users to explore drug sensitivity and RNA molecule associations directly. It provides association data between drug sensitivity and RNA molecules including mRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) at four molecular levels (expression, copy number variation, mutation and methylation) from integrated analysis of three large-scale pharmacogenomic databases (GDSC, CellMiner and CCLE). RNAactDrug currently stores more than 4 924 200 associations of RNA molecules and drug sensitivity at four molecular levels covering more than 19 770 mRNAs, 11 119 lncRNAs, 438 miRNAs and 4155 drugs. A user-friendly interface enriched with various browsing sections augmented with advance search facility for querying the database is offered for users retrieving. RNAactDrug provides a comprehensive resource for RNA molecules acting in drug sensitivity, and it could be used to prioritize drug sensitivity-related RNA molecules, further promoting the identification of clinically actionable biomarkers in drug sensitivity and drug development more cost-efficiently by making this knowledge accessible to both basic researchers and clinical practitioners. Database URL: http://bio-bigdata.hrbmu.edu.cn/RNAactDrug.

System level characterization of small molecule drugs and their affected long noncoding RNAs.

Long noncoding RNAs (lncRNAs) have multiple regulatory roles and are involved in many human diseases. A potential therapeutic strategy based on targeting lncRNAs was recently developed. To gain insight into the global relationship between small molecule drugs and their affected lncRNAs, we constructed a small molecule lncRNA network consisting of 1206 nodes (1033 drugs and 173 lncRNAs) and 4770 drug-lncRNA associations using LNCmap, which reannotated the microarray data from the Connectivity Map (CMap) database. Based on network biology, we found that the connected drug pairs tended to share the same targets, indications, and side effects. In addition, the connected drug pairs tended to have a similar structure. By inferring the functions of lncRNAs through their co-expressing mRNAs, we found that lncRNA functions related to the modular interface were associated with the mode of action or side effects of the corresponding connected drugs, suggesting that lncRNAs may directly/indirectly participate in specific biological processes after drug administration. Finally, we investigated the tissue-specificity of drug-affected lncRNAs and found that some kinds of drugs tended to have a broader influence (e.g. antineoplastic and immunomodulating drugs), whereas some tissue-specific lncRNAs (nervous system) tended to be affected by multiple types of drugs.

Functional Role of SIL1 in Neurodevelopment and Learning.

Background: Sil1 is the causative gene of Marinesco-SjÓ§gren Syndrome (MSS). The mutated Sil1 generates shortened SIL1 protein which will form aggregation and be degraded rapidly. Mental retardation is a major symptom of MSS which suggests a role of SIL1 in the development of the central nervous system, but how SIL1 functions remains unclear. Objectives: The aim of this study is to explore the role of SIL1 in regulating cerebral development and its underlying molecular mechanism. Methods: The basic expression pattern of SIL1 in tissues and cultured cortical neurons is measured by immunostaining and Western blot. The expression of SIL1 is reduced in vitro and in vivo through RNA interference delivered by a lentivirus. The expression of NMDA receptor subunits and the function of the Reelin signaling pathway are then examined by surface biotinylation and Western blot subsequently. Finally, the spatial learning of young mice was assessed by the Barnes maze task. Results: SIL1 deficiency caused a diminished expression of both Reelin receptors and therefore impaired the Reelin signaling pathway. It then inhibited the developmental expression of GluN2A and impaired the spatial learning of 5-week-old mice. Conclusions: These results suggested that SIL1 is required for the development of the central nervous system which is associated with its role in Reelin signaling.

A frog cathelicidin peptide effectively promotes cutaneous wound healing in mice.

Although cathelicidins in mammals have been well characterized, little is known about the function of cathelicidin in amphibians. In the present study, a novel 24-residue peptide (cathelicidin-NV, ARGKKECKDDRCRLLMKRGSFSYV) belonging to the cathelicidin family was identified from the skin of the plateau frog Nanorana ventripunctata Cathelicidin-NV showed strong wound healing-promoting activity in a murine model with a full-thickness dermal wound. It directly enhanced the proliferation of keratinocyte cells, resulting in accelerated re-epithelialization of the wound site. Cathelicidin-NV also promoted the proliferation of fibroblasts, the differentiation of fibroblasts to myofibroblasts and collagen production in fibroblasts, which are implicated in wound contraction and repair processes. Furthermore, cathelicidin-NV promoted the release of monocyte chemoattractant protein-1, tumor necrosis factor-α, vascular endothelial growth factor and transforming growth factor-ß1 in vivo and in vitro, which are essential in the wound-healing processes such as migration, proliferation and differentiation. The MAPK (ERK, JNK and p38) signaling pathways were involved in the wound healing-promoting effect. Additionally, unlike other cathelicidins, cathelicidin-NV did not have any direct effect on microbes and showed no cytotoxicity and hemolytic activity toward mammalian cells at concentrations up to 200 µg/ml. This current study may facilitate the understanding of the cellular and molecular events that underlie quick wound healing in N. ventripunctata In addition, the combination of these properties makes cathelicidin-NV an excellent candidate for skin wound therapeutics.