Identification of Differentially Expressed mRNAs and lncRNAs Contributes to Elucidation of Underlying Pathogenesis and Therapeutic Strategy of Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a complex and poorly understood clinical disorder characterized by failure to conceive after repeated embryo transfers. Endometrial receptivity (ER) is a prerequisite for implantation, and ER disorders are associated with RIF. However, little is known regarding the molecular mechanisms underlying ER in RIF. In the present study, RNA sequencing data from the mid-secretory endometrium of patients with and without RIF were analyzed to explore the potential long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in RIF. The analysis revealed 213 and 1485 differentially expressed mRNAs and lncRNAs, respectively (fold change ≥ 2 and p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these genes were mostly involved in processes related to immunity or inflammation. 5 key genes (TTR, ALB, TF, AFP, and CFTR) and a key module including 14 hub genes (AFP, ALB, APOA1, APOA2, APOB, APOH, FABP1, FGA, FGG, GC, ITIH2, SERPIND1, TF and TTR) were identified in the protein-protein interaction (PPI) network. The 5 key genes were used to further explore the lncRNA-miRNA-mRNA regulatory network. Finally, the drug ML-193 based on the 14 hub genes was identifed through the CMap. After ML-193 treatment, endometrial cell proliferation was increased, the hub genes were mostly down-regulated, and the ER marker HOXA10 was up-regulated. These results offer insights into the regulatory mechanisms of lncRNAs and mRNAs and suggest ML-193 as a therapeutic agent for RIF by enhancing ER.

Genome-wide identification of the Q-type C2H2 zinc finger protein gene family and expression analysis under abiotic stress in lotus (Nelumbo nucifera G.).

BACKGROUND: Lotus (Nelumbo nucifera G.) is an important aquatic plant with high ornamental, economic, cultural and ecological values, but abiotic stresses seriously affect its growth and distribution. Q-type C2H2 zinc finger proteins (ZFPs) play an important role in plant growth development and environmental stress responses. Although the Q-type C2H2 gene family has been identified in some plants, limited reports has been carried out it in lotus. RESULTS: In this study, we identified 45 Q-type NnZFP members in lotus. Based on the phylogenetic tree, these Q-type NnZFP gene family members were divided into 4 groups, including C1-1i, C1-2i, C1-3i and C1-4i. Promoter cis-acting elements analysis indicated that most Q-type NnZFP gene family members in lotus were associated with response to abiotic stresses. Through collinearity analyses, no tandem duplication gene pairs and 14 segmental duplication gene pairs were identified, which showed that duplication events might play a key role in the expansion of the Q-type NnZFP gene family. The synteny results suggested that 54 and 28 Q-type NnZFP genes were orthologous to Arabidopsis and rice, respectively. The expression patterns of these Q-type NnZFP genes revealed that 30 Q-type NnZFP genes were expressed in at least one lotus tissue. Nn5g30550 showed relatively higher expression levels in all tested tissues. 12 genes were randomly selected with at least one gene from each phylogenetic clade, and the expression of these selected genes were confirmed by qRT-PCR (quantitative real-time polymerase chain reaction). The results indicated that Q-type NnZFP genes were extensively involved in cadmium, drought, salt and cold stresses responses. Among them, 11 genes responded to at least three different stress treatments, especially Nn2g12894, which induced by all four treatments. CONCLUSIONS: These results could increase our understanding of the characterization of the Q-type NnZFP gene family and provide relevant information for further functional analysis of Q-type NnZFP genes in plant development, and abiotic stress tolerance in lotus.

MRE11 is essential for the long-term viability of undifferentiated spermatogonia.

In the meiotic prophase, programmed SPO11-linked DNA double-strand breaks (DSBs) are repaired by homologous recombination (HR). The MRE11-RAD50-NBS1 (MRN) complex is essential for initiating DNA end resection, the first step of HR. However, residual DNA end resection still occurs in Nbs1 knockout (KO) spermatocytes for unknown reasons. Here, we show that DNA end resection is completely abolished in Mre11 KO spermatocytes. In addition, Mre11 KO, but not Nbs1 KO, undifferentiated spermatogonia are rapidly exhausted due to DSB accumulation, proliferation defects, and elevated apoptosis. Cellular studies reveal that a small amount of MRE11 retained in the nucleus of Nbs1 KO cells likely underlies the differences between Mre11 and Nbs1 KO cells. Taken together, our study not only demonstrates an irreplaceable role of the MRE11 in DNA end resection at SPO11-linked DSBs but also unveils a unique function of MRE11 in maintaining the long-term viability of undifferentiated spermatogonia.

Lama1 upregulation prolongs the lifespan of the dyH/dyH mouse model of LAMA2-related congenital muscular dystrophy.

LAMA2-related congenital muscular dystrophy (LAMA2-CMD), characterized by laminin-α2 deficiency, is debilitating and ultimately fatal. To date, no effective therapy has been clinically available. Laminin-α1, which shares significant similarities with laminin-α2, has been proven as a viable compensatory modifier. To evaluate its clinical applicability, we establish a Lama2 exon-3 deletion mouse model (dyH/dyH). The dyH/dyH mice exhibit early lethality and typical LAMA2-CMD phenotypes, allowing the evaluation of various endpoints. In dyH/dyH mice treated with synergistic activation mediator-based CRISPRa-mediated Lama1 upregulation, a nearly doubled median survival is observed, as well as improvements in weight and grip. Significant therapeutical effects are revealed by MRI, serum biochemical indices, and muscle pathology studies. Treating LAMA2-CMD with LAMA1 upregulation is feasible and that early intervention can alleviate symptoms and extend lifespan. Additionally, we reveal limitations of LAMA1 upregulation, including high-dose mortality and non-sustained expression, which require further optimization in future studies.

BRCA1 safeguards genome integrity by activating chromosome asynapsis checkpoint to eliminate recombination-defective oocytes.

In the meiotic prophase, programmed DNA double-strand breaks are repaired by meiotic recombination. Recombination-defective meiocytes are eliminated to preserve genome integrity in gametes. BRCA1 is a critical protein in somatic homologous recombination, but studies have suggested that BRCA1 is dispensable for meiotic recombination. Here we show that BRCA1 is essential for meiotic recombination. Interestingly, BRCA1 also has a function in eliminating recombination-defective oocytes. Brca1 knockout (KO) rescues the survival of Dmc1 KO oocytes far more efficiently than removing CHK2, a vital component of the DNA damage checkpoint in oocytes. Mechanistically, BRCA1 activates chromosome asynapsis checkpoint by promoting ATR activity at unsynapsed chromosome axes in Dmc1 KO oocytes. Moreover, Brca1 KO also rescues the survival of asynaptic Spo11 KO oocytes. Collectively, our study not only unveils an unappreciated role of chromosome asynapsis in eliminating recombination-defective oocytes but also reveals the dual functions of BRCA1 in safeguarding oocyte genome integrity.

[Research Progress in the Roles of MRE11-RAD50-NBS1 Complex and Human Diseases].

DNA is susceptible to various factors in vitro and in vivo and experience different forms of damage,among which double-strand break(DSB)is a deleterious form.To maintain the stability of genetic information,organisms have developed multiple mechanisms to repair DNA damage.Among these mechanisms,homologous recombination(HR)is praised for the high accuracy.The MRE11-RAD50-NBS1(MRN)complex plays an important role in HR and is conserved across different species.The knowledge on the MRN complex mainly came from the previous studies in Saccharomyces cerevisiae and Caenorhabditis elegans,while studies in the last decades have revealed the role of mammalian MRN complex in DNA repair of higher animals.In this review,we first introduces the MRN complex regarding the composition,structure,and roles in HR.In addition,we discuss the human diseases such as ataxia-telangiectasia-like disorder,Nijmegen breakage syndrome,and Nijmegen breakage syndrome-like disorder that are caused by dysfunctions in the MRN complex.Furthermore,we summarize the mouse models established to study the clinical phenotypes of the above diseases.

Visual Cognitive Assessment Test: Utility of the brief cognitive battery for early screening of cognitive impairment in Chongqing, China.

OBJECTIVES: Early detection of cognitive impairment is essential for timely intervention. Currently, most widely used cognitive screening tests are influenced by language and cultural differences; therefore, there is a need for the development of a language-neutral, visual-based cognitive assessment tool. The Visual Cognitive Assessment Test (VCAT), a 30-point test that assesses memory, executive function, visuospatial function, attention, and language, has demonstrated its utility in a multilingual population. In this study, we evaluated the reliability, validity, and diagnostic performance of the VCAT for screening early cognitive impairment in Chongqing, China METHODS: A total of 134 individuals (49 healthy controls (HCs), 52 with mild cognitive impairment (MCI), and 33 with mild dementia) completed the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), VCAT, and domain-specific neuropsychological assessments. The diagnostic performances of MMSE, MoCA, and VCAT were evaluated using the area under the curve (AUC), sensitivity, and specificity. Construct validity of the VCAT was assessed with well-established domain-specific cognitive assessments. Reliability was measured using Cronbach's alpha. RESULTS: The VCAT and its subdomains demonstrated both good construct validity and internal consistency (α = 0.577). The performance of VCAT was comparable to that of MoCA and MMSE in differentiating mild dementia from nondemented groups (AUC: 0.940 vs. 0.902 and 0.977, respectively; p = .098 and .053) and in distinguishing cognitive impairment (CI) from HC (AUC: 0.929 vs. 0.899 and 0.891, respectively; p = .239 and .161), adjusted for education level. The optimal score range for VCAT in determining dementia, MCI, and HC was 0-14, 15-19, and 20-30, respectively. CONCLUSION: The VCAT proves to be a reliable screening test for early cognitive impairment within our cohort. Being both language and cultural neutral, the VCAT has the potential to be utilized among a wider population within China.

Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina.

Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.

The development and evolution of the research topic on the mental health of college students: A bibliometric review based on CiteSpace and VOSviewer.

Background: With the advances in society and in response to changing times, college students have had to face multiple challenges. These challenges frequently affect the mental health of college students, leading to significant consequences for their social lives, personal well-being, and academic achievements, thereby attracting extensive societal attention. Therefore, examining the current status of research topics related to the mental health of college students can assist academia in dissecting the influencing factors and seeking solutions at their source or through early intervention. This can contribute to a better understanding of and effectively address this challenge. Method: CiteSpace and VOSviewer were used to conduct a bibliometric analysis of 1609 journal articles indexed in the Web of Science (WoS) database over the past two decades (2000-2022), which helped identify the current state of research and hot topics in the field based on development trends. Furthermore, this study analyzes and discusses the core authors, high-productivity countries and organizations, key journals, and keyword clustering in this field. This study clarifies the current research landscape, analyzes evolving trends based on developmental trajectories, and identifies forefront research hotspots. This study provides scholars with reference research directions and ideas for conducting subsequent studies. Results: Since the beginning of the 21st century, research on college students' mental health has increased, especially in the past three years, and due to the impact of the COVID-19 pandemic and online distance learning, the number of publications has increased rapidly. With the increase in attention and publication volume, the countries and organizations contributing papers as well as core journals have all started to take shape. Cluster and evolution analyses found that several stable research topics have been formed in this research field, and many new and diverse topics are continuously emerging with time. Conclusion: and prospect: The findings prove that the field of college students' mental health has begun to take shape, gradually shifting from conceptual research to the implementation of specific interventions. However, whether specific interventions are effective and how effective they are require further investigation.

Kurarinone regulates Th17/Treg balance and ameliorates autoimmune uveitis via Rac1 inhibition.

INTRODUCTION: Autoimmune uveitis (AU) is a severe intraocular autoimmune disorder with a chronic disease course and a high rate of blindness. Kurarinone (KU), a major component of the traditional Chinese medicine Sophorae Flavescentis Radix, possesses a wide spectrum of activities and has been used to treat several inflammation-related diseases. OBJECTIVE: We aimed to investigate the effects of KU on AU and its modulatory mechanisms. METHODS: We used an experimental autoimmune uveitis (EAU) animal model and characterized the comprehensive immune landscape of KU-treated EAU mice using single-cell RNA sequencing (scRNA-seq). The retina and lymph nodes were analyzed. The siRNAs and selective inhibitors were used to study the signaling pathway. The effect of KU on peripheral blood mononuclear cells (PBMCs) from uveitis patients was also examined. RESULTS: We found that KU relieved chorioretinal lesions and immune cell infiltration in EAU model mice. Subsequent single-cell analysis revealed that KU downregulated the EAU-upregulated expression of inflammatory and autoimmune-related genes and suppressed pathways associated with immune cell differentiation, activation, and migration in a cell-specific manner. KU was implicated in restoring T helper 17 (Th17)/regulatory T (Treg) cell balance by alleviating inflammatory injury and elevating the expression of modulatory mediators in Tregs, while simultaneously ameliorating excessive inflammation by Th17 cells. Furthermore, Rac1 and the Id2/Pim1 axis potentiated the pathogenicity of Th17 cells during EAU, which was inhibited by KU treatment, contributing to the amelioration of EAU-induced inflammation and treatment of AU. In addition, KU suppressed inflammatory cytokine production in activated human PBMCs by inhibiting Rac1. Integration of the glucocorticoid-treated transcriptome suggests that KU has immunomodulatory effects on lymphocytes. CONCLUSION: Our study constructed a high-resolution atlas of the immunoregulatory effects of KU treatment on EAU and identified its potential therapeutic mechanisms, which hold great promise in treating autoimmune disorders.

Photochemical engineering unsaturated Pt islands on supported Pd nanocrystals for a robust pH-universal hydrogen evolution reaction.

The rational design of heterostructured nanocrystals (HNCs) is of great significance for developing highly efficient hydrogen evolution reaction (HER) electrocatalysts. However, a significant challenge still lies in realizing the controllable synthesis of desired HNCs directly onto a support and exploring their structure-activity-dependent HER performance. Herein, we reported various controllable Pd7@Ptx core-shell HNCs with optimal hybrid structures via a photochemical deposition strategy. The growth patterns of a Pt shell can be finely controlled by adjusting the growth kinetics, resulting in a varying deposition rate. In particular, the as-prepared Pd7@Pt3 HNCs with a Pt shell in the Stranski-Krastanov mode showed the best performances over a wide pH range media, delivering low overpotentials of 33, 18 and 49 mV, resulting in a catalytic current density of 10 mA cm-2 at a low effective catalyst loading of 0.021 mg cm-2. The resulting Tafel slopes were 23.1, 52.6 and 42.7 mV dec-1 in 0.5 M H2SO4, 1.0 M phosphate-buffered saline (PBS) and 1.0 M KOH electrolyte, respectively. It was found that the increased fraction of unsaturated coordination of Pt islands in the resultant material is the key to the enhanced and robust HER activity, which has been confirmed through density functional theory (DFT) calculations. This strategy could be extended to the rational design and synthesis of other heterostructured catalysts for energy conversion and storage.

An aging-related immune landscape in the hematopoietic immune system.

BACKGROUND: Aging is a holistic change that has a major impact on the immune system, and immunosenescence contributes to the overall progression of aging. The bone marrow is the most important hematopoietic immune organ, while the spleen, as the most important extramedullary hematopoietic immune organ, maintains homeostasis of the human hematopoietic immune system (HIS) in cooperation with the bone marrow. However, the overall changes in the HIS during aging have not been described. Here, we describe a hematopoietic immune map of the spleen and bone marrow of young and old mice using single-cell sequencing and flow cytometry techniques. RESULTS: We observed extensive, complex changes in the HIS during aging. Compared with young mice, the immune cells of aged mice showed a marked tendency toward myeloid differentiation, with the neutrophil population accounting for a significant proportion of this response. In this change, hypoxia-inducible factor 1-alpha (Hif1α) was significantly overexpressed, and this enhanced the immune efficacy and inflammatory response of neutrophils. Our research revealed that during the aging process, hematopoietic stem cells undergo significant changes in function and composition, and their polymorphism and differentiation abilities are downregulated. Moreover, we found that the highly responsive CD62L + HSCs were obviously downregulated in aging, suggesting that they may play an important role in the aging process. CONCLUSIONS: Overall, aging extensively alters the cellular composition and function of the HIS. These findings could potentially give high-dimensional insights and enable more accurate functional and developmental analyses as well as immune monitoring in HIS aging.

Prevalence of Adeno-Associated Virus-9-Neutralizing Antibody in Chinese Patients with Duchenne Muscular Dystrophy.

The delivery of a mini-dystrophin gene to skeletal muscles using recombinant adeno-associated virus serotype (AAV) holds great potential as a gene therapy for Duchenne muscular dystrophy (DMD). However, the presence of anti-AAV-neutralizing antibodies (NAbs) may impede the effectiveness of gene transduction. This study aimed to evaluate the prevalence of anti-AAV9 NAbs in Chinese patients with DMD, and to characterize the target population for an AAV gene therapy. A total of one hundred male patients with DMD were included in this study, and demographic and clinical data were collected. A blood specimen was obtained from each participant for the purpose of evaluating the existence of anti-AAV9 NAbs through a cell-based functional assay conducted at a central laboratory. A NAb titer exceeding 1:4 was considered positive. The positivity rates of anti-AAV9 NAb were compared among different subgroups. The median age of this DMD cohort was 8 years old, ranging from 3 to 15 years of age. Forty-two percent of patients tested positive for anti-AAV9 NAb. Notably, all samples from patients under 4 years of age tested negative, and the positivity rates of anti-AAV9 NAb differed significantly across the three age subgroups (<4 years old, ≥4 years old and <12 years old, and ≥12 years old, χ2 = 7.221, p = 0.023). Further investigation into the living environment revealed a higher positivity rate of anti-AAV9 NAb in rural patients compared with urban patients (χ2 = 3.923, p = 0.048). Moreover, the prevalence in patients from different cities/provinces varied greatly (χ2 = 16.550, p = 0.003). There was no statistically significant difference in the positivity rate of NAb among subgroups of patients with different motor functions (ambulatory or nonambulatory) and different treatment strategies (taking or not taking glucocorticoid). In Chinese DMD patients, the prevalence of anti-AAV9 NAb was found to reach 42%. Moreover, the antibody-positive rate in children <4 years of age was low and revealed notable regional discrepancies.

Fabrication of heterogeneous bimetallic nanochains through photochemical welding for promoting the electrocatalytic hydrogen evolution reaction.

Heterogeneous bimetallic nanochains (NCs) have gained significant attention in the field of catalysis due to their abundant active sites, multi-component synergistic catalytic, and exotic electronic structures. Here, we present a novel approach to synthesize one-dimensional heterogeneous bimetallic nanochains using a local surface plasmon resonance (LSPR) based strategy of liquid-phase photochemical welding method containing self-assembly and subsequent welding processes. Initially, we introduce additives that facilitate the self-assembly and alignment of Au nanoparticles (NPs) into orderly lines. Subsequently, the LSPR effect of the Au NPs is stimulated by light, enabling the second metal precursor to overcome the energy barrier and undergo photodeposition in the gap between the arranged Au NPs, thereby connecting the nano-metal particles. This strategy can be extended to the photochemical welding of Au NPs-Ag and Au NRs. Using electrocatalytic hydrogen evolution reaction (HER) as a proof-of-concept application, the obtained one-dimensional structure of Au5Pt1 NCs exhibit promoted HER performances, where the mass activity of the Au5Pt1 nanochains is found to be 4.8 times higher than that of Au5Pt1 NPs and 10.4 times higher than that of commercial 20 wt% Pt/C catalysts. The promoted HER performance is benefited from the electron conduction ability and abundant active sites.

Empagliflozin targets Mfn1 and Opa1 to attenuate microglia-mediated neuroinflammation in retinal ischemia and reperfusion injury.

BACKGROUND: Neuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function as a promising target for immunomodulation. Empagliflozin (EMPA), an anti-diabetic drug, has exhibited great potential as both an anti-inflammatory agent and a protector of mitochondrial health. This study aimed to assess the therapeutic efficacy of EMPA in retinal IR injury. METHODS: To evaluate the protective effects of EMPA, the drug was injected into the vitreous body of mice post-retinal IR. Single-cell RNA sequencing (scRNA-seq) analysis was conducted to uncover the underlying mechanisms, and the results were further validated through in vivo and in vitro experiments. RESULTS: EMPA effectively protected retinal ganglion cells (RGCs) from IR injury by attenuating local retinal inflammation. The scRNA-seq analysis revealed that EMPA downregulated the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) signaling pathway and restored mitochondrial dynamics by upregulating the expression of mitochondrial fusion-related genes, Mitofusin 1 (Mfn1) and optic atrophy 1 (Opa1). These findings were further corroborated by Western blotting. In vitro experiments provided additional insights, demonstrating that EMPA suppressed lipopolysaccharide (LPS)-induced cell inflammation and NLRP3 inflammasome activation. Moreover, EMPA enhanced mitochondrial fusion, neutralized mitochondrial reactive oxygen species (mtROS), and restored mitochondrial membrane potential (MMP) in BV2 microglia. Notably, genetic ablation of Mfn1 or Opa1 abolished the anti-inflammatory effects of EMPA. CONCLUSIONS: Our findings highlight the positive contribution of Mfn1 and Opa1 to the anti-inflammatory therapeutic effect of EMPA. By restoring mitochondrial dynamics, EMPA effectively mitigates microglia-mediated neuroinflammation and prevents RGC loss in retinal IR injury.

Early long-term low-dosage colchicine and major adverse cardiovascular events in patients with acute myocardial infarction: a systematic review and meta-analysis.

Background: Current evidence on the efficacy and safety of colchicine after acute myocardial infarction (AMI) remains controversial. This study aims to clarify early low-dose long-term colchicine's exact efficacy and safety in AMI patients via more studies. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases for randomized controlled trials assessing the efficacy of colchicine on major adverse cardiovascular events (MACE) in recent AMI patients from inception to January 29, 2023, without any restriction. Additionally, we conducted subgroup analyses to assess the impact of early (≤3 days) long-term (≥1 year) low-dosage (0.5 mg/d) colchicine. Summary estimates were computed using Mantel-Haenszel and reported as risk ratios (RRs) or standard mean differences (SMDs), mean differences (MDs) with 95% confidence intervals (CIs). Sensitivity analyses were performed to explore the potential sources of heterogeneity. Review Manager software was used for the meta-analysis. Results: Eight studies identified from 564 screened records were analyzed, with 5,872 patients after AMI. The length of follow-up varied from five days to 22.7 months, and 0.5-1.0 mg colchicine was administered daily. In summary, compared to the control group, colchicine reduced the occurrence of MACE (RR, 0.56; 95% CI, 0.48-0.67) with 2.99-fold gastrointestinal adverse events in patients with recent AMI. Moreover, the relation referred to a gradual decrease in the occurrence of MACE with a longer follow-up duration (≥1 year) and lower dosage (0.5 mg/d) without leading more gastrointestinal adverse events. Colchicine decreased the follow-up levels of C-reactive protein (CRP) (MD -0.66, 95% CI, -0.98- -0.35) and neutrophils (SMD -0.22, 95% CI, -0.39- -0.55) when the follow-up period was 30 days. Conclusion: Early long-term low-dose colchicine decreases the risk of MACE via anti-inflammation without leading more gastrointestinal adverse events in patients with AMI.

Gastrodin ameliorates cognitive dysfunction in diabetes by inhibiting PAK2 phosphorylation.

Diabetes is associated with higher prevalence of cognitive dysfunction, while the underlying mechanism is still elusive. In this study, we aim to explore the potential mechanism of diabetes-induced cognitive dysfunction and assess the therapeutic effects of Gastrodin on cognitive dysfunction. Diabetes was induced by a single injection of streptozotocin. The Morris Water Maze Test was employed to assess the functions of spatial learning and memory. Transcriptome was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired in diabetic rats, coupled with damaged hippocampal pyramidal neurons. Gastrodin intervention ameliorated the spatial learning impairments and neuronal damages. Transcriptomics analysis identified differential expression genes critical for diabetes-induced hippocampal damage and Gastrodin treatment, which were further confirmed by qPCR and western blot. Moreover, p21 activated kinase 2 (PAK2) was found to be important for diabetes-induced hippocampal injury and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and could be a therapeutic target for Gastrodin intervention.

A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain.

BACKGROUND: The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to reduce pain across all stages of the disease. Although many antiviral agents via oral or intravenous administration were recommended by clinical practice, the best approach to prevent HZ-associated pain remains uncertain. OBJECTIVES: The purpose of this study was to compare the efficacy and adverse events of various antiviral agents used for the treatment of HZ-associated pain through a network meta-analysis. STUDY DESIGN: A systematic review and meta-analysis. SETTING: The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to Feb 2020. METHODS: Randomized clinical trials evaluating antiviral agents currently available for treating HZ-associated pain were included. We extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted network meta-analyses with random-effects models. The primary outcome was the presence of acute pain at the end of anti-virus treatment, and the secondary outcomes included the presence of pain at 28-30 days after the onset of the acute herpetic rash, the presence of postherpetic neuralgia (PHN), and any other adverse events. RESULTS: A total of 17 randomized control trials with 5,579 participants were included in this study. According to the results of the network meta-analysis, for the treatment of acute pain, there was no significant difference between oral acyclovir and intravenous acyclovir. Furthermore, oral famciclovir was the most effective treatment concerning both the odds ratio (OR) (superior to placebo OR = 0.25; 95% CI: 0.13~0.48) and the surface under the cumulative ranking curve (SUCRA) values of 0.84 for the treatment of acute pain among all the oral antiviral agents. For the presence of pain at 28-30 days, no significant difference was observed in efficacy between all antiviral treatments and placebo concerning the OR; however, oral valaciclovir ranked first (SUCRA values of 0.96). For the presence of NPH, oral famciclovir was determined to be the most effective (SUCRA values of 0.77) treatment with an efficacy of 0.42 (95% CI: 0.18~0.99) versus placebo. For adverse events, there was no significant difference between oral antivirals and placebo; however, intravenous acyclovir ranked last with a score of OR 4.31 (95% CI: 1.26~14.75) versus placebo. LIMITATIONS: The distribution of severity of pain was different in various studies; then, the lack of availability of individual data prevented us from analyzing the effects of the risk factors. CONCLUSIONS: For the treatment of acute pain and PHN, oral famciclovir was the most effective treatment among all the oral antiviral agents. For alleviating pain after 28-30 days, oral valaciclovir appeared to be the most effective among all antiviral agents. Additionally, all oral antiviral agents were well tolerated. CLINICAL TRIAL REGISTRATION INFORMATION: PROSPERO under the identification CRD42020212834.

A Surfactant-Free and General Strategy for the Synthesis of Bimetallic Core-Shell Nanocrystals on Reduced Graphene Oxide through Targeted Photodeposition.

Tunable physicochemical properties of bimetallic core-shell heterostructured nanocrystals (HNCs) have shown enormous potential in electrocatalytic reactions. In many cases, HNCs are required to load on supports to inhibit catalyst aggregation. However, the introduction of supports during the process of growing core-shell HNCs makes the synthesis much more complicated and difficult to control precisely. Herein, we reported a universal photochemical synthetic strategy for the controlled synthesis of well-defined surfactant-free core-shell metal HNCs on a reduced graphene oxide (rGO) support, which was assisted by the fine control of photogenerated electrons directly transferring to the targeted metal seeds via rGO and the precisely tuned adsorption capacity of the added second metal precursors. The surface photovoltage microscopy (SPVM) platform proved that photogenerated electrons flowed through rGO to Pd particles under illumination. We have successfully synthesized 24 different core-shell metal HNCs, i.,e., MA@MB (MA = Pd, Au, and Pt; MB = Au, Ag, Pt, Pd, Ir, Ru, Rh, Ni and Cu), on the rGO supports. The as-prepared Pd@Cu core-shell HNCs showed outstanding performance in the electrocatalytic reduction of CO2 to CH4. This work could shed light on the controlled synthesis of more functional bimetallic nanostructured materials on diverse supports for various applications.