The orbitofrontal cortex (OFC) plays a crucial role in mood disorders; however, its specific role in the emotional behaviors of mice remains unclear.This study investigates the bidirectional control of emotional behaviors using population calcium dynamics and optogenetic manipulation of OFC neurons. Fiber photometry of OFC neurons revealed that OFC excitatory neurons consistently responded to the onset and offset of aversive conditions, showing decreased activation in response to anxiogenic and stressful stimuli, including tail suspension, restraint stress, and exposure to the center of the open field. The selective activation of excitatory neurons in the OFC reduced the time spent in the center of the open field, whereas optogenetic activation of inhibitory neurons in the OFC induced the opposite behavioral changes. We also provided a brain-wide activation map for OFC excitatory and inhibitory neuron activation. Our findings demonstrate that excitatory and inhibitory neurons in the OFC play opposing roles in the regulation of emotional behaviors. These results provide new insights into the neural mechanisms underlying emotional control and suggest that targeting these specific neuronal populations may offer novel therapeutic strategies for emotional disorders.

The orbitofrontal cortex (OFC) plays a crucial role in mood disorders; however, its specific role in the emotional behaviors of mice remains unclear.This study investigates the bidirectional control of emotional behaviors using population calcium dynamics and optogenetic manipulation of OFC neurons. Fiber photometry of OFC neurons revealed that OFC excitatory neurons consistently responded to the onset and offset of aversive conditions, showing decreased activation in response to anxiogenic and stressful stimuli, including tail suspension, restraint stress, and exposure to the center of the open field. The selective activation of excitatory neurons in the OFC reduced the time spent in the center of the open field, whereas optogenetic activation of inhibitory neurons in the OFC induced the opposite behavioral changes. We also provided a brain-wide activation map for OFC excitatory and inhibitory neuron activation. Our findings demonstrate that excitatory and inhibitory neurons in the OFC play opposing roles in the regulation of emotional behaviors. These results provide new insights into the neural mechanisms underlying emotional control and suggest that targeting these specific neuronal populations may offer novel therapeutic strategies for emotional disorders.

The orbitofrontal cortex (OFC) plays a crucial role in mood disorders; however, its specific role in the emotional behaviors of mice remains unclear.This study investigates the bidirectional control of emotional behaviors using population calcium dynamics and optogenetic manipulation of OFC neurons. Fiber photometry of OFC neurons revealed that OFC excitatory neurons consistently responded to the onset and offset of aversive conditions, showing decreased activation in response to anxiogenic and stressful stimuli, including tail suspension, restraint stress, and exposure to the center of the open field. The selective activation of excitatory neurons in the OFC reduced the time spent in the center of the open field, whereas optogenetic activation of inhibitory neurons in the OFC induced the opposite behavioral changes. We also provided a brain-wide activation map for OFC excitatory and inhibitory neuron activation. Our findings demonstrate that excitatory and inhibitory neurons in the OFC play opposing roles in the regulation of emotional behaviors. These results provide new insights into the neural mechanisms underlying emotional control and suggest that targeting these specific neuronal populations may offer novel therapeutic strategies for emotional disorders.

The orbitofrontal cortex (OFC) plays a crucial role in mood disorders; however, its specific role in the emotional behaviors of mice remains unclear.This study investigates the bidirectional control of emotional behaviors using population calcium dynamics and optogenetic manipulation of OFC neurons. Fiber photometry of OFC neurons revealed that OFC excitatory neurons consistently responded to the onset and offset of aversive conditions, showing decreased activation in response to anxiogenic and stressful stimuli, including tail suspension, restraint stress, and exposure to the center of the open field. The selective activation of excitatory neurons in the OFC reduced the time spent in the center of the open field, whereas optogenetic activation of inhibitory neurons in the OFC induced the opposite behavioral changes. We also provided a brain-wide activation map for OFC excitatory and inhibitory neuron activation. Our findings demonstrate that excitatory and inhibitory neurons in the OFC play opposing roles in the regulation of emotional behaviors. These results provide new insights into the neural mechanisms underlying emotional control and suggest that targeting these specific neuronal populations may offer novel therapeutic strategies for emotional disorders.

Circadian rhythm is a 24-hour cycle of behavioral and physiological changes. Disrupted sleep-wake patterns and circadian dysfunction are common in patients of Alzheimer Disease (AD) and are closely related with neuroinflammation. However, it is not well known how circadian rhythm of immune cells is altered during the progress of AD. Previously, we found presenilin 2 (Psen2) N141I mutation, one of familial AD (FAD) risk genes, induces hyperimmunity through the epigenetic repression of REV-ERBα expression in microglia and bone marrow-derived macrophage (BMDM) cells. Here, we investigated whether repression of REV-ERBα is associated with dysfunction of immune cell-endogenous or central circadian rhythm by analyses of clock genes expression and cytokine secretion, bioluminescence recording of rhythmic PER2::LUC expression, and monitoring of animal behavioral rhythm. Psen2 N141I mutation down-regulated REV-ERBα and induced selective over-production of IL-6 (a well-known clock-dependent cytokine) following the treatment of toll-like receptor (TLR) ligands in microglia, astrocytes, and BMDM. Psen2 N141I mutation also lowered amplitude of intrinsic daily oscillation in these immune cells representatives of brain and periphery. Of interest, however, the period of daily rhythm remained intact in immune cells. Furthermore, analyses of the central clock and animal behavioral rhythms revealed that central clock remained normal without down-regulation of REV-ERBα. These results suggest that Psen2 N141I mutation induces hyperimmunity mainly through the suppression of REV-ERBα in immune cells, which have lowered amplitude but normal period of rhythmic oscillation. Furthermore, our data reveal that central circadian clock is not affected by Psen2 N141I mutation.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization.However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccineinduced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARSCoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins.Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein.The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.

Intermittent fasting has become an increasingly popular strategy in losing weight and associated reduction in obesity-related medical complications. Overwhelming studies support metabolic improvements from intermittent fasting in blood glucose levels, cardiac and brain function, and other health benefits, in addition to weight loss. However, concerns have also been raised on side effects including muscle loss, ketosis, and electrolyte imbalance. Of particular concern, the effect of intermittent fasting on hormonal circadian rhythms has received little attention. Given the known importance of circadian hormonal changes to normal physiology, potential detrimental effects by dysregulation of hormonal changes deserve careful discussions. In this review, we describe the changes in circadian rhythms of hormones caused by intermittent fasting. We covered major hormones commonly pathophysiologically involved in clinical endocrinology, including insulin, thyroid hormones, and glucocorticoids. Given that intermittent fasting could alter both the level and frequency of hormone secretion, decisions on practicing intermittent fasting should take more considerations on potential detrimental consequences versus beneficial effects pertaining to individual health conditions.

Intermittent fasting has become an increasingly popular strategy in losing weight and associated reduction in obesity-related medical complications. Overwhelming studies support metabolic improvements from intermittent fasting in blood glucose levels, cardiac and brain function, and other health benefits, in addition to weight loss. However, concerns have also been raised on side effects including muscle loss, ketosis, and electrolyte imbalance. Of particular concern, the effect of intermittent fasting on hormonal circadian rhythms has received little attention. Given the known importance of circadian hormonal changes to normal physiology, potential detrimental effects by dysregulation of hormonal changes deserve careful discussions. In this review, we describe the changes in circadian rhythms of hormones caused by intermittent fasting. We covered major hormones commonly pathophysiologically involved in clinical endocrinology, including insulin, thyroid hormones, and glucocorticoids. Given that intermittent fasting could alter both the level and frequency of hormone secretion, decisions on practicing intermittent fasting should take more considerations on potential detrimental consequences versus beneficial effects pertaining to individual health conditions.

The short release half-life of carbon monoxide (CO) is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2 (CORM-2). The potential of CORM-2-entrapped ultradeformable liposomes (CORM-2-UDLs) to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study. CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator. The deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure. The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality in East Asia. This study aimed to develop, for primary care providers, a prediction score using initial symptoms and basic laboratory blood tests to differentiate between SFTS and other endemic zoonoses in Korea.METHODS: Patients aged ≥ 18 years diagnosed with endemic zoonoses during a 3-year period (between January 2015 and December 2017) were retrospectively enrolled from 4 tertiary university hospitals. A prediction score was built based on multivariate logistic regression analyses.RESULTS: Of 84 patients, 35 with SFTS and 49 with other endemic zoonoses were enrolled. In multivariate logistic regression analysis, independent predictors of SFTS included neurologic symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 2.173–76.747), diarrhea (OR, 10.306; 95% CI, 1.588–66.895), leukopenia (< 4,000/mm3) (OR, 19.400; 95% CI, 3.290–114.408), and normal C-reactive protein (< 0.5 mg/dL) (OR, 24.739; 95% CI, 1.812–337.742). We set up a prediction score by assigning one point to each of these four predictors. A score of ≥ 2 had 82.9% sensitivity (95% CI, 71.7%–87.5%) and 95.9% specificity (95% CI, 88.0%–99.2%). The area under the curve of the clinical prediction score was 0.950 (95% CI, 0.903–0.997).CONCLUSION: This study finding suggests a simple and useful scoring system to predict SFTS in patients with endemic zoonoses. We expect this strategic approach to facilitate early differentiation of SFTS from other endemic zoonoses, especially by primary care providers, and to improve the clinical outcomes.