BackgroundRepetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability, and may be beneficial for motor recovery after stroke. However, the neuroplasticity effects of rTMS have not been thoroughly investigated in the early stage after stroke.ObjectiveTo comprehensively assess the effects of high- and low-frequency repetitive transcranial magnetic stimulations on motor recovery in early stroke patients, using a randomized controlled trial based on clinical, neurophysiological and functional imaging assessments.MethodsSixty hospitalized, first-ever ischemic stroke patients (within 2 weeks after stroke) with motor deficits were randomly allocated to receive, in addition to standard physical therapy, five consecutive sessions of either: (1) High-frequency (HF) rTMS at 10 Hz over the ipsilesional primary motor cortex (M1); (2) Low-frequency (LF) rTMS at 1 Hz over the contralesional M1; (3) sham rTMS. The primary outcome measure was a motor impairment score (Upper Extremity Fugl-Meyer) evaluated at baseline, after rTMS intervention, and at 3-month follow-up. Cortical excitability and functional magnetic resonance imaging (fMRI) data were obtained within 24 h before and after rTMS intervention. Analyses of variance were conducted to compare the recovery effects among the three rTMS groups, assessed using clinical, neurophysiological and fMRI tests.ResultsMotor improvement was significantly larger in the two rTMS groups than in the control group. The HF-rTMS group showed significantly increased cortical excitability and motor-evoked fMRI activation in ipsilesional motor areas, whereas the LF-rTMS group had significantly decreased cortical excitability and motor-evoked fMRI activation in contralesional motor areas. Activity in ipsilesional motor cortex significantly correlated with motor function, after intervention as well as at 3-month follow-up.ConclusionHF- and LF-rTMS can both improve motor function by modulating motor cortical activation in the early phase of stroke.

Repetitive transcranial magnetic stimulation is a beneficial neurorehabilitative strategy for enhancing motor recovery in the acute and subacute phase after stroke.

Sepsis‐induced liver injury is recognized as a key problem in intensive care units. The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis‐induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis‐induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was used to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis‐resistant (Res; survived to 7 days after CLP) and sepsis‐sensitive (Sen; moribund before or approximately 24 hours after CLP) mice. Mice gavaged with feces from Sen mice displayed more‐severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5‐hydroxytryptamine 3 (5‐HT3) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP‐induced death and liver injury. Moreover, proinflammatory cytokine expression by macrophages after lipopolysaccharide (LPS) challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5‐HT3A receptor in cells suppressed nuclear factor kappa B (NF‐кB) transactivation and phosphorylated p38 (p‐p38) accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels in septic patients. Conclusion: Our study indicated that gut microbiota plays a key role in the sensitization of sepsis‐induced liver injury and associates granisetron as a hepatoprotective compound during sepsis development.

Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Intestinal I/R induced disturbance of gut microbiota and significant changes in metabolites. We found that CAT is a metabolite of the gut microbiota and that CAT levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with intestinal I/R injury. Furthermore, CAT reduced ferroptosis-dependent intestinal I/R injury in vivo and in vitro. However, the protective effects of CAT against ferroptosis-dependent intestinal I/R injury were abolished by RSL3, an inhibitor of glutathione peroxidase 4 (Gpx4), which is a negative regulator of ferroptosis. We also found that the ability of CAT to promote Gpx4 expression and inhibit ferroptosis-dependent intestinal I/R injury was abrogated by JNJ-17203212, an antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). This study suggests that the gut microbiota metabolite CAT enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal I/R injury, providing a potential avenue for the management of intestinal I/R injury.

Based on the Dual Systems Model (Somerville et al., 2010; Steinberg, 2010a) and the biosocial-affect model (Romer and Hennessy, 2007) of adolescent sensation seeking and problem behaviors, the present study examined how (affective associations with online games as a mediator) and when (impulsivity as a moderator) did sensation seeking influence online gaming addiction in adolescence. A total of 375 Chinese male adolescents (mean age = 16.02 years, SD = 0.85) from southern China completed anonymous questionnaires regarding sensation seeking, positive affective associations with online games, impulsivity, and online gaming addiction. Our findings revealed that sensation seeking, positive affective associations with online games and impulsivity were each significantly and positively associated with online gaming addiction in adolescents. Positive affective associations mediated the relationship between sensation seeking and online gaming addiction. Further, impulsivity moderated the relationship between positive affective associations and online gaming addiction, such that the association between positive affective association and online gaming addiction was stronger for high than for low impulsivity adolescents. These findings underscore the importance of integrating the biosocial-affect model and the Dual Systems Model to understand how and when sensation seeking impacts adolescent online gaming addiction.

Chronic high-salt diet-associated renal injury is a key risk factor for the development of hypertension. However, the mechanism by which salt triggers kidney damage is poorly understood. Our study investigated how high salt (HS) intake triggers early renal injury by considering the ‘gut-kidney axis’. We fed mice 2% NaCl in drinking water continuously for 8 weeks to induce early renal injury. We found that the ‘quantitative’ and ‘qualitative’ levels of the intestinal microflora were significantly altered after chronic HS feeding, which indicated the occurrence of enteric dysbiosis. In addition, intestinal immunological gene expression was impaired in mice with HS intake. Gut permeability elevation and enteric bacterial translocation into the kidney were detected after chronic HS feeding. Gut bacteria depletion by non-absorbable antibiotic administration restored HS loading-induced gut leakiness, renal injury and systolic blood pressure elevation. The fecal microbiota from mice fed chronic HS could independently cause gut leakiness and renal injury. Our current work provides a novel insight into the mechanism of HS-induced renal injury by investigating the role of the intestine with enteric bacteria and gut permeability and clearly illustrates that chronic HS loading elicited renal injury and dysfunction that was dependent on the intestine.

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