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Development and severity of alcohol use disorder (AUD) has been linked to variations in gut microbiota and their associated metabolites in both animal and human studies. However, the involvement of the gut microbiome in alcohol consumption of individuals with AUD undergoing treatment remains unclear. To address this, stool samples ( n  = 32) were collected at screening (baseline) and trial completion from a double-blind, placebo-controlled trial of zonisamide in individuals with AUD. Alcohol consumption was measured both at baseline and endpoint of 16-week trial period. Fecal microbiome was analyzed via 16 S rRNA sequencing and metabolome via untargeted LC-MS. Both sex ( p  = 0.003) and psychotropic medication usage ( p  = 0.025) are associated with baseline microbiome composition. The relative abundance of 11 genera at baseline was correlated with percent drinking reduction (p.adj < 0.1). Overall microbiome community structure at baseline differed between high and low reducers of alcohol drinking (67–100% and 0–33% drinking reduction, respectively; p  = 0.034). A positive relationship between baseline fecal GABA levels and percent drinking reduction ( R  = 0.43, p.adj < 0.07) was identified by microbiome function prediction and confirmed by ELISA and metabolomics. Metabolomics analysis also found 3-hydroxykynurenine, a neurotoxic intermediate metabolite of tryptophan, was negatively correlated with drinking reduction (p.adj = 0.047), and was over-represented in low reducers. These findings highlight importance of baseline microbiome and amino acid metabolites in drinking reduction in AUD participants undergoing zonisamide treatment. It may hold significant value as a predictive tool in clinical settings to better personalize intervention and improve reduction in alcohol consumption in future.

Background Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. The development of novel therapeutic and preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between the gut microbiome and microbial metabolites with drinking behavior, but druggable targets and their underlying mechanism of action are understudied. Results Here, using a drink-in-the-dark mouse model, we identified a microbiome metabolite-based novel treatment (sodium valerate) that can reduce excessive alcohol drinking. Sodium valerate is a sodium salt of valeric acid short-chain fatty acid with a similar structure as γ-aminobutyric acid (GABA). Ten days of oral sodium valerate supplementation attenuates excessive alcohol drinking by 40%, reduces blood ethanol concentration by 53%, and improves anxiety-like or approach-avoidance behavior in male mice, without affecting overall food and water intake. Mechanistically, sodium valerate supplementation increases GABA levels across stool, blood, and amygdala. It also significantly increases H4 acetylation in the amygdala of mice. Transcriptomics analysis of the amygdala revealed that sodium valerate supplementation led to changes in gene expression associated with functional pathways including potassium voltage-gated channels, inflammation, glutamate degradation, L-DOPA degradation, and psychological behaviors. 16S microbiome profiling showed that sodium valerate supplementation shifts the gut microbiome composition and decreases microbiome-derived neuroactive compounds through GABA degradation in the gut microbiome. Conclusion Our findings suggest that sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms. 4EUMY4VU8ayPcKT8VYWNUC Video Abstract

The powerful immune responses elicited by the mRNA vaccines targeting the SARS-CoV-2 Spike protein contribute to their high efficacy. Yet, their efficacy can vary greatly between individuals. For vaccines not based on mRNA, cumulative evidence suggests that differences in the composition of the gut microbiome, which impact vaccine immunogenicity, are some of the factors that contribute to variations in efficacy. However, it is unclear if the microbiome impacts the novel mode of immunogenicity of the SARS-CoV-2 mRNA vaccines. We conducted a prospective longitudinal cohort study of individuals receiving SARS-CoV-2 mRNA vaccines where we measured levels of anti-Spike IgG and characterized microbiome composition, at pre-vaccination (baseline), and one week following the first and second immunizations. While we found that microbial diversity at all timepoints correlated with final IgG levels, only at baseline did microbial composition and predicted function correlate with vaccine immunogenicity. Specifically, the phylum Desulfobacterota and genus Bilophila, producers of immunostimulatory LPS, positively correlated with IgG, while Bacteroides was negatively correlated. KEGG predicted pathways relating to SCFA metabolism and sulfur metabolism, as well as structural components such as flagellin and capsular polysaccharides, also positively correlated with IgG levels. Consistent with these findings, depleting the microbiome with antibiotics reduced the immunogenicity of the BNT162b2 vaccine in mice. These findings suggest that gut microbiome composition impacts the immunogenicity of the SARS-CoV-2 mRNA vaccines.

Multiple sclerosis (MS) is an autoimmune condition associated with dysbiosis in the bacterial element of microbiome, yet limited information exists regarding dysbiosis in the virome. In this study, we examined the virome in 20 relapsing-remitting MS (RRMS) patients and 22 healthy controls (HC). We extracted virus-like particles (VLP) genomic DNA through sequential filtration, followed by deep metagenomic sequencing approaches with and without multiple displacement amplification (MDA). We found significantly lower diversity in the gut virome of RRMS patients relative to HC, consistent across both sequencing methods. MDA method identified reduced relative abundance of Microviridae and Myoviridae bacteriophage, and eukaryotic virus such as Herpesviridae and Phycodnaviridae in RRMS patients compared to HC. Non-MDA methods showed reduction in relative abundance of Siphoviridae bacteriophage and eukaryotic viruses such as Ackermannviridae, Demerecviridae, Dicistroviridae, Herelleviridae, Mesnidovirineae in RRMS patients. Cluster analysis revealed that the whole virome family was dominated by Podoviridae and Siphoviridae clusters. Comparing dietary metadata between these clusters, RRMS patients in the Siphoviridae-dominated Cluster B showed significantly higher consumption of refined grains and salad dressings compared to those in the Podoviridae-dominated Cluster A. Correlation analysis between gut viruses and bacteria demonstrated that Siphoviridae exhibited positive correlations with many different bacterial genera. Conversely, Microviridae displayed negative correlations with many different bacterial genera. These findings underscore the alterations in viral diversity and taxonomic composition of the gut virome in RRMS patients. Our study represents the first step in understanding the gut virome in MS patients, providing a groundwork for future research on the role of the gut virome in the context of MS. Keywords: RRMS, MDA, VLP, ViromeCompeting Interest StatementThe authors have declared no competing interest.

According to the WHO, the number of mental disorder patients, especially depression patients, has overgrown and become a leading contributor to the global burden of disease. With the rising of tools such as artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and recordings of spoken language data from clinically depressed patients and matching normal controls, who were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes data collected using a traditional 128-electrodes mounted elastic cap and a wearable 3-electrode EEG collector for pervasive computing applications. The 128-electrodes EEG signals of 53 participants were recorded as both in resting state and while doing the Dot probe tasks; the 3-electrode EEG signals of 55 participants were recorded in resting-state; the audio data of 52 participants were recorded during interviewing, reading, and picture description.Measurement(s)Human Brainwave • spoken languageTechnology Type(s)EEG collector • audio recorderSample Characteristic - OrganismHomo SapiensSample Characteristic - LocationChina

Biomass‐derived carbon as energy storage materials have gradually attracted widespread attention due to their low cost, sustainability, and inherent structural advantages. Herein, hard carbon (H‐1200) and porous carbon (PC‐800) for sodium‐ion batteries (SIBs), sodium‐ion capacitors (SICs) half cells and sodium‐ion hybrid capacitors (SIHCs) have been synthesized from the same biomass precursor of Camellia shells through different treatments. H‐1200 synthesized by directly high‐temperature carbonization possesses a rational graphitic layer structure and plentiful heteroatoms. When applied as anode for SIBs, it exhibits a reversible capacity of 365.5 mAh g–1 at 25 mA g–1 and capacity retention 89.0% after 400 cycles at 200 mA g–1. Additionally, PC‐800 prepared by catalytic carbonization of K2C2O4/CaC2O4 hybrid catalyst has a sophisticated porous structure and a high surface area of 2186.9 m2 g–1. When employed as a cathode for SICs, it delivers a maximum capacity 104.2 mAh g–1 at 100 mA g–1 and 35.0 mAh g–1 at 5 A g–1. Furthermore, the all carbon assembled SIHC (H‐1200||PC‐800) using H‐1200 as anode and PC‐800 as cathode, features a broad output voltage range (0.01 ~ 4.1 V), high energy density of 161.5 Wh kg–1, power density of 12896.1 W kg–1, and superior capacity retention of 90.32% after 10000 cycles at 10 A g–1. This research result provide a new horizon for constructing low‐cost and large‐scale production of biomass derived carbon for energy storage materials. A novel hybrid catalyst is developed to prepare multifunctional carbon derived from Camellia shell for high‐performance SIB and SIHC. H‐1200 exhibits a capacity of 365.5 mAh g–1 at 25 mA g–1 and PC‐800 delivers a capacity 104.2 mAh g–1 at 100 mA g–1. Furthermore, SIHC (H‐1200||PC‐800) demonstrates high energy density and power density.

Recently, the association between handgrip strength (HGS) asymmetry and cognition has been revealed, but evidences are still scarce. Particularly, the association between asymmetric HGS and cognitive performance in various cognitive domains is unclear and whether this association is stable across ethnic groups is unknown. The population was from a longitudinal study in rural areas of Fuxin, Liaoning, China. The Chinese version of Montreal Cognitive Assessment-Basic (MOCA-BC) was used to evaluate the cognitive function. The HGS ratio was calculated as maximal non-dominant HGS divided by maximal dominant HGS. HGS ratio <0.9 or >1.1 was classified as asymmetric dominant/non-dominant HGS, respectively. Generalized linear models were used to analyze the relationship between asymmetric HGS and cognitive function adjusted for HGS, handedness, wave, age, sex, education, ethnicity, smoking, drinking, physical labor level, BMI, hypertension, diabetes and dyslipidemia. A total of 2,969 participants ≥50 years were included in this study. Adjusted for HGS and other confunding variables, there was an inverted U-shaped association between HGS ratio and MoCA-BC scores ( = 0.004). The association between HGS ratio and MoCA-BC scores was inconsistent among ethnic groups ( = 0.048). In Han, only asymmetric non-dominant HGS was associated with lower cognitive scores [β = -0.67, 95% confidence interval (CI): -1.26 ∼-0.08, = 0.027]; in Mongolians, asymmetric dominant HGS(β = -0.60, 95% CI: -1.35 ∼ 0.15, = 0.115) and asymmetric non-dominant HGS (β = -0.56, 95% CI: -1.42 ∼ 0.31, = 0.206) were all associated with lower cognitive scores, although no statistical significance was found. Asymmetric non-dominant HGS and lower HGS, but not asymmetric dominant HGS were all independently associated with impairment of Delayed Recall (OR = 1.35, 95% CI: 1.05 ∼ 1.74; OR = 1.10, 95% CI: 1.01 ∼ 1.21) and Fluency (OR = 1.43, 95% CI: 1.15 ∼ 1.78; OR = 1.10, 95% CI: 1.02 ∼ 1.19). Both asymmetric dominant HGS (OR = 1.34, 95% CI: 1.07 ∼ 1.67) and lower HGS (OR = 1.21, 95% CI: 1.10 ∼ 1.32) were associated with impairment of visuoperception. HGS and HGS asymmetry were all independently related to lower global cognitive performance. The association between HGS asymmetry and cognitive function varies among ethnic groups.

Background The sex difference in the association between grip strength and mild cognitive impairment (MCI) remains controversial and unclear. Methods This is a part of a chronic disease cohort study conducted in rural areas, Fuxin, Liaoning Province, China. At the baseline survey, a total of 2633 participants aged 35- 85 were included in the cross-sectional study. Handgrip strength (HGS, kg) was measured by a dynamometer (Jamar +). MCI were assessed using the Chinese version of the Montreal Cognitive Assessment-Basic (MOCA-BC). Then, a total of 1667 cognitively normal individuals (NCs) were planed to follow up and to assess the incident MCI after two years. We used logistic regression to examine the association between HGS (as a continuous variable and quintiles) and MCI and analyzed the interaction between sex and HGS on MCI. Models stratified by sex were adjusted for demographic information (age, ethnicity, education, marital status, income, physical labor level), modifiable risk factors (body mass index, smoking, drinking) and disease history (hypertension, diabetes, dyslipidemia and coronary heart disease). Baseline MOCA-BC scores were additionally adjusted in the longitudinal study. Results In the cross-sectional study, participants were on average 56.6 ± 9.8 years, and 1713 (65.1%) were females. In the cohort study, 743 individuals were followed up with an average age of 55.9 ± 9.6 years, which included 530 (71.3%) females. The cumulative incidence of MCI over a two-year period was 17.1%. In the cross-sectional study, compared to the highest quintile of HGS, the lowest HGS was associated with higher risk of MCI in males (odds ratio [OR]: 2.66; 95% confidence interval [CI]: 1.54, 4.64) and females (OR: 1.70; 95% CI: 1.17, 2.49) with adjustment of potential confounding factors. In the cohort study, compared to the highest quintile of HGS, the lowest HGS was associated with an increased risk of incident MCI in females (OR: 3.93; 95% CI: 1.39, 13.01) but not in males (OR: 0.56; 95% CI: 0.11, 2.94, P   for interaction  = 0.015). Conclusions Lower grip strength is a risk factor for mild cognitive impairment and predicts a higher risk of MCI in females.

Odontoblasts are primarily responsible for synthesizing and secreting extracellular matrix proteins, which are crucial for dentinogenesis. Our previous single-cell profile and RNAscope for odontoblast lineage revealed that cyclic adenosine monophosphate responsive element-binding protein 3 like 1 (Creb3l1) was specifically enriched in the terminal differentiated odontoblasts. In this study, deletion of Creb3l1 in the Wnt1+ lineage led to insufficient root elongation and dentin deposition. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing were performed to revealed that in CREB3L1-deficient mouse dental papilla cells (mDPCs), the genes near the closed chromatin regions were mainly associated with mesenchymal development and the downregulated genes were primarily related to biological processes including cell differentiation, protein biosynthesis and transport, all of which were evidenced by a diminished ability of odontoblastic differentiation, a significant reduction in intracellular proteins, and an even greater decline in extracellular supernatant proteins. Dentin matrix protein 1 (Dmp1), dentin sialophosphoprotein (Dspp), and transmembrane protein 30B (Tmem30b) were identified as direct transcriptional regulatory targets. TMEM30B was intensively expressed in the differentiated odontoblasts, and exhibited a significant decline in both CREB3L1-deficient odontoblasts in vivo and in vitro. Deletion of Tmem30b impaired the ability of odontoblastic differentiation, protein synthesis, and protein secretion in mDPCs. Moreover, overexpressing TMEM30B in CREB3L1-deficient mDPCs partially rescued the extracellular proteins secretion. Collectively, our findings suggest that CREB3L1 participates in dentinogenesis and facilitates odontoblastic differentiation by directly enhancing the transcription of Dmp1, Dspp, and other differentiation-related genes and indirectly promoting protein secretion partially via TMEM30B.

COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns. Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects. Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement ( = 0.49, 95% confidence interval (CI) [0.19-0.79], = 0.001) and this difference was greatest for social cognition (2.62 [0.94-4.30], = 0.002). We found that this association was modulated by parental agreeableness in a protective way (-0.11 [-0.17 to -0.05], = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus. This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.