Gut microbiome is implicated in the onset and progression of major depressive disorder (MDD), but the dynamic alterations of depressive symptoms, gut microbiome, and fecal metabolome across different stages of stress exposure remain unclear. Here, we modified the chronic social defeat stress (CSDS) model to evaluate mice subjected to social defeat stress for 1, 4, 7, and 10 days. Behavioral tests, 16S rRNA, metagenomics, and fecal metabolomics were conducted to investigate the impact of stress exposure on behaviors, gut microbiota and fecal metabolites. We observed that depressive-like behaviors, such as anhedonia and social avoidance, worsened significantly as stress exposure increased. The microbial composition, function, and fecal metabolites exhibited distinct separations across the different social defeat stress groups. Mediation analysis identified key bacteria, such as Lachnospiraceae_UCG-001 and Bacteroidetes, and fecal metabolites like valeric acid and N-acetylaspartate. In our clinical depression cohort, we confirmed that fecal valeric acid levels, were significantly lower in depressive-like mice and MDD patients, correlating closely with stress exposure and anhedonia in mice. Further analysis of serum and brain metabolites in mice revealed sustained changes of N-acetylaspartate abundance in fecal, serum, and cortical samples following increasing stress exposure. Together, this study elucidated the characteristics of depressive-like behaviors, gut microbiome, and fecal metabolome across various social defeat stress exposure, and identified key bacteria and fecal metabolites potentially involved in modulating social defeat stress response and depressive-like behaviors, providing new insights into the pathogenesis and intervention of depression.

Mapping genome-wide DNA-protein interactions (DPIs) provides insights into the epigenetic landscape of complex biological systems and elucidates the mechanisms of epigenetic regulation in biological progress. However, current technologies in DPI profiling still suffer from high cell demands, low detection sensitivity, and large reagent consumption. To address these problems, we developed DMF-ChIP-seq that builds on digital microfluidic (DMF) technology to profile genome-wide DPIs in a highly efficient, cost-effective, and user-friendly way. The entire workflow including cell pretreatment, antibody recognition, pA-Tn5 tagmentation, fragment enrichment, and PCR amplification is programmatically manipulated on a single chip. Leveraging closed submicroliter reaction volumes and a superhydrophobic interface, DMF-ChIP-seq presented higher sensitivity in peak enrichment than other current methods, with high accuracy (Pearson Correlation Coefficient (PCC) > 0.86) and high repeatability (PCC > 0.92). Furthermore, DMF-ChIP-seq was capable of processing the samples with as few as 8 cells while maintaining a high signal-to-noise ratio. By applying DMF-ChIP-seq, H3K27ac histone modification of early embryonic cells during differentiation was profiled for the investigation of epigenomic landscape dynamics. With the benefits of high efficiency and sensitivity in DPI analysis, the system provides great promise in studying epigenetic regulation during various biological processes.

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.

Toxoplasma gondii is an opportunistic and pathogenic obligate intracellular parasitic protozoan that is widespread worldwide and can infect most warm-blooded animals, seriously endangering human health and affecting livestock production. Toxoplasmosis caused by T. gondii infection has different clinical manifestations, which are mainly determined by the virulence of T. gondii and host differences. Among the manifestations of this condition, abortion, stillbirth, and fetal malformation can occur if a woman is infected with T. gondii in early pregnancy. Here, we discuss how the T. gondii rhoptry protein affects host pregnancy outcomes and speculate on the related signaling pathways involved. The effects of rhoptry proteins of T. gondii on the placental barrier are complex. Rhoptry proteins not only regulate interferon-regulated genes (IRGs) to ensure the survival of parasites in activated cells but also promote the spread of worms in tissues and the invasive ability of the parasites. The functions of these rhoptry proteins and the associated signaling pathways highlight relevant mechanisms by which Toxoplasma crosses the placental barrier and influences fetal development and will guide future studies to uncover the complexity of the host-pathogen interactions.

Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary sequences of mRNAs or other ncRNAs or by directly engaging in protein interactions. Over the past few decades, the pervasiveness of ncRNAs in cell physiology and their pivotal roles in various diseases have been identified. One target regulated by ncRNAs is connexin (Cx), a protein that forms gap junctions and hemichannels and facilitates intercellular molecule exchange. The aberrant expression and misdistribution of connexins have been implicated in central nervous system diseases, cardiovascular diseases, bone diseases, and cancer. Current databases and technologies have enabled researchers to identify the direct or indirect relationships between ncRNAs and connexins, thereby elucidating their correlation with diseases. In this review, we selected the literature published in the past five years concerning disorders regulated by ncRNAs via corresponding connexins. Among it, microRNAs that regulate the expression of Cx43 play a crucial role in disease development and are predominantly reviewed. The distinctive perspective of the ncRNA-Cx axis interprets pathology in an epigenetic manner and is expected to motivate research for the development of biomarkers and therapeutics.

The mammalian genome encodes thousands of non-coding RNAs (ncRNAs), ranging in size from about 20 nucleotides (microRNAs or miRNAs) to kilobases (long non-coding RNAs or lncRNAs). ncRNAs contribute to a layer of gene regulation that could explain the evolution of massive phenotypic complexity even as the number of protein-coding genes remains unaltered. We propose that low conservation, poor expression, and highly restricted spatiotemporal expression patterns-conventionally considered ncRNAs may affect behavior through direct, rapid, and often sustained regulation of gene expression at the transcriptional, post-transcriptional, or translational levels. Besides these direct roles, their effect during neurodevelopment may manifest as behavioral changes later in the organism's life, especially when exposed to environmental cues like stress and seasonal changes. The lncRNAs affect behavior through diverse mechanisms like sponging of miRNAs, recruitment of chromatin modifiers, and regulation of alternative splicing. We highlight the need for synthesis between rigorously designed behavioral paradigms in model organisms and the wide diversity of behaviors documented by ethologists through field studies on organisms exquisitely adapted to their environmental niche. Comparative genomics and the latest advancements in transcriptomics provide an unprecedented scope for merging field and lab studies on model and non-model organisms to shed light on the role of ncRNAs in driving the behavioral responses of individuals and groups. We touch upon the technical challenges and contentious issues that must be resolved to fully understand the role of ncRNAs in regulating complex behavioral traits. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

The risk of depression is influenced by both genetic and environmental factors. It has been suggested that epigenetic mechanisms may mediate the risk of depression following exposure to adverse life events. Epigenetics encompasses stable alterations in gene expression that are controlled through transcriptional, post-transcriptional, translational, or post-translational processes, including DNA modifications, chromatin remodeling, histone modifications, RNA modifications, and non-coding RNA (ncRNA) regulation, without any changes in the DNA sequence. In this review, we explore recent research advancements in the realm of epigenetics concerning depression. Furthermore, we evaluate the potential of epigenetic changes as diagnostic and therapeutic biomarkers for depression.

Our previous study reported that the single-nucleotide polymorphism (SNP) rs155979 GC in the promoter region of long-chain non-coding RNA (lncRNA) NONHSAT102891 affects depression susceptibility in a Chinese population.

To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population.

This this case-control association study was approved by the Ethics Committee of Chengdu Medical College (approval number: 201815). Patient diagnosis was based on DSM-IV criteria. We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology, and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects. The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells.

Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times [TC/CC vs TT: odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.08-2.35, P = 0.019]. The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230, and the double SNP CG haplotype was more common in the control group compared to case group, indicating that this haplotype significantly reduced the risk of depression (C/G vs T/A: OR = 0.42, 95%CI: 0.21-0.83, P = 0.01). There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group (P > 0.05), indicating that the double SNP haplotype has no transcriptional activity.

The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

The brain constantly adapts to changes in the environment, a capability that underlies memory and behavior. Long-term adaptations require the remodeling of neural circuits that are mediated by activity-dependent alterations in gene expression. Over the last two decades, it has been shown that the expression of protein-coding genes is significantly regulated by a complex layer of non-coding RNA (ncRNA) interactions. The aim of this review is to summarize recent discoveries regarding the functional involvement of ncRNAs during different stages of neural circuit development, activity-dependent circuit remodeling, and circuit maladapations underlying neurological and neuropsychiatric disorders. In addition to the intensively studied microRNA (miRNA) family, we focus on more recently added ncRNA classes, such as long ncRNAs (lncRNAs) and circular RNAs (circRNAs), and discuss the complex regulatory interactions between these different RNAs. We conclude by discussing the potential relevance of ncRNAs for cell-type and -state-specific regulation in the context of memory formation, the evolution of human cognitive abilities, and the development of new diagnostic and therapeutic tools in brain disorders.