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Laser-induced graphene (LIG) possesses characteristics of easy handling, miniaturization, and unique electrical properties. We modified the surface of LIG by electropolymerizing β-cyclodextrin (β-CD), which was used to immobilize antibodies on the electrode surface for highly sensitive detection of targets. N6-methyladenosine (m6A) is the most prevalent reversible modification in mammalian messenger RNA and noncoding RNA, influencing the development of various cancers. Here, β-CD was electropolymerized to immobilize the anti-m6A antibody, which subsequently recognized the target m6A. This was integrated into the catalytic hydrogen peroxide–hydroquinone (H2O2-HQ) redox system using phos-tag-biotin to generate electrochemical signals from streptavidin-modified horseradish peroxidase (SA-HRP). Under optimal conditions, the biosensor exhibited a linear range from 0.1 to 100 nM with a minimum detection limit of 96 pM. The method was successfully applied to the recovery analysis of m6A from HeLa cells through spiking experiments and aims to inspire strategies for point-of-care testing (POCT).

Abstract Background The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs. Results We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD . Conclusions As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases.

Abstract Objectives To explore the mediating role of self‐esteem in social anxiety and QoL during the COVID‐19 local epidemic in China. Design A cross‐sectional survey. Methods This study conveniently selected 344 hypertensive patients from a Grade‐A tertiary hospital in Wuhu, Anhui Province, as the study population. Participants completed the demographic questionnaire, the social phobia inventory, the self‐esteem scale and the 36‐item short‐form health survey. Results Social anxiety, self‐esteem and QoL were significantly correlated with each other. Social anxiety showed no direct effect on QoL (β = 0.011, p > 0.05). Social anxiety showed an indirect effect on QoL (β = −0.248, p

Abstract Background The COVID-19 pandemic has posed significant threats to both the physical and psychological health of healthcare workers working in the front-line combating COVID-19. However, studies regarding the medium to long term impact of COVID-19 on mental health among healthcare workers are limited. Therefore, we conducted this cross-sectional survey to investigate the prevalence, factors and impact of post-traumatic stress disorder (PTSD) in healthcare workers exposed to COVID-19 8 months after the end of the outbreak in Wuhan, China. Methods A web-based questionnaire was delivered as a link via the communication application WeChat to those healthcare workers who worked at several COVID-19 units during the outbreak (from December 2019 to April 2020) in Wuhan, China. The questionnaire included questions on social-demographic data, the post-traumatic stress disorder checklist-5 (PCL-5), the family care index questionnaire (Adaptation, Partnership, Growth, Affection and Resolve, APGAR), and the quality-of-life scale (QOL). The prevalence, risk and protective factors, and impact of PTSD on healthcare workers were subsequently analyzed. Results Among the 659 participants, 90 healthcare workers were still suffering from PTSD 8 months after the end of the outbreak of COVID-19 in Wuhan, in which avoidance and negative impact were the most affected dimensions. Suffering from chronic disease, experiencing social isolation, and job dissatisfaction came up as independent risk factors for PTSD, while obtaining COVID-19 related information at an appropriate frequency, good family function, and working in well-prepared mobile cabin hospitals served as protective factors. The impact of PTSD on COVID-19 exposed healthcare workers was apparent by shortened sleeping time, feeling of loneliness, poorer quality of life and intention to resign. Conclusions Eight months after the end of the COVID-19 outbreak in Wuhan, the level of PTSD in healthcare workers exposed to COVID-19 was still high. Apart from the commonly recognized risk factors, comorbid chronic disease was identified as a new independent risk factor for developing PTSD. For countries where the pandemic is still ongoing or in case of future outbreaks of new communicable diseases, this study may contribute to preventing cases of PTSD in healthcare workers exposed to infectious diseases under such circumstances.

The beneficial metabolites of the microbiome could be used as a tool for screening drugs that have the potential for the therapy of various human diseases. Narrowing down the range of beneficial metabolite candidates in specific diseases was primarily a key step for further validation in model organisms. Herein, we proposed a reasonable hypothesis that the metabolites existing commonly in multiple beneficial (or negatively associated) bacteria might have a high probability of being effective drug candidates for specific diseases. According to this hypothesis, we screened metabolites associated with seven human diseases. For type I diabetes, 45 out of 88 screened metabolites had been reported as potential drugs in the literature. Meanwhile, 18 of these metabolites were specific to type I diabetes. Additionally, metabolite correlation could reflect disease relationships in some sense. Our results have demonstrated the potential of bioinformatics mining gut microbes' metabolites as drug candidates based on reported numerous microbe-disease associations and the Virtual Metabolic Human database. More subtle methods would be developed to ensure more accurate predictions.

Single embryonic and adult neural stem cells (NSCs) are characterized by their self-renewal and differentiation potential. Lineage tracing via clonal analysis allows for specific labeling of a single NSC and tracking of its progeny throughout development. Over the past five decades, a plethora of clonal analysis methods have been developed in tandem with integration of chemical, genetic, imaging and sequencing techniques. Applications of these approaches have gained diverse insights into the heterogeneous behavior of NSCs, lineage relationships between cells, molecular regulation of fate specification and ontogeny of complex neural tissues. In this review, we summarize the history and methods of clonal analysis as well as highlight key findings revealed by single-cell lineage tracking of stem cells in developing and adult brains across different animal models. Keywords: In vivo clonal analysis, Lineage tracing, Neural stem cells, Neural development, Nuclear brain structure

The secondary motor cortex (MOs) plays crucial roles in cognitive and executive processes and has reciprocal connections with numerous cortices in rodents. However, descriptions of the neuronal morphologies and projection patterns of the MOs at the level of a single neuron are lacking, severely hindering the comprehensive understanding of the wiring diagram of the MOs. Herein, we used a Cre-dependent adeno-associated virus (AAV) to fluorescently label ~80 pyramidal neurons nearby or in the MOs and acquired an uninterrupted whole-brain 3D dataset at a voxel resolution of 0.2 × 0.2 × 1 μm with a whole-brain fluorescence imaging system (fMOST). Based on our 3D dataset, we reconstructed the complete morphologies of 36 individual intratelencephalic (IT) neurons nearby or in the MOs and analyzed the projection patterns and projection strengths of these neurons at a single-neuron level based on several parameters, including the projection areas, the total number of branches, the fiber length, and the total number of terminal tips. We obtained a neuron with an axonal length of 318.43 mm, which is by far the longest reported axonal length. Our results show that all individual neurons in the MOs, regardless of whether they are located in layer 2/3 or layer 5, display diverse projection patterns and projection strengths, implying that these neurons might be involved in different brain circuits at different intensities. The results lay a solid foundation for exploring the relationship between neuronal morphologies and behavioral functions of the MOs at the level of a single neuron.

Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model. [ABSTRACT FROM AUTHOR]

The article presents a study on T-box transcription factor 3 (Tbx3)-derived neuronal lineage and Tbx3-dependent neuronal specification which found that Tbx3 hierarchically established and maintained the identity of KNDy neurons for triggering puberty. Topics include effect of Tbx3 deficiency on the identity establishment of KNDy, specific deletion of Tbx3 in KNDy neurons which undermines their identity maintenance, and significance of identity maintenance of KNDy neurons for puberty onset.