A Chiral Metal-Organic Framework Prepared on Large-Scale for Sensitive and Enantioselective Fluorescence Recognition.

MOF-based luminescent sensors have garnered considerable attention due to their potential in recognition and discrimination with high sensitivity, selectivity, and fast response in the last decades. Herein, this work describes the bulk preparation of a novel luminescent homochiral MOF, namely, [Cd(s-L)](NO3)2 (MOF-1), from an enantiopure pyridyl-functionalized ligand with rigid binaphthol skeleton under mild synthetic condition. Except for the features of porosity and crystallinity, the MOF-1 has also been characterized with water-stability, luminescence, and homochirality. Most important, the MOF-1 exhibits highly sensitive molecular recognition toward the4-nitrobenzoic acid (NBC) and moderate enantioselective detection of proline, arginine, and 1-phenylethanol.

Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt.

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.

The circadian nuclear receptor RORα negatively regulates cerebral ischemia-reperfusion injury and mediates the neuroprotective effects of melatonin.

Disruptions of the circadian rhythm and reduced circulating levels of the circadian hormone melatonin predispose to ischemic stroke. Although the nuclear receptor RORα is considered as a circadian rhythm regulator and a mediator of certain melatonin effects, its potential role in cerebral ischemia-reperfusion (CI/R) injury and in the neuroprotective effects of melatonin remain undefined. Here, we observed that CI/R injury in RORα-deficient mice was associated with greater cerebral infarct size, brain edema, and cerebral apoptosis compared with wild-type model. In contrast, transgenic mice with brain-specific overexpression of RORα versus non-transgenic controls exerted significantly reduced infarct volume, brain edema and apoptotic response induced by CI/R. Mechanistically, RORα deficiency was found to exacerbate apoptosis pathways mediated by endoplasmic-reticulum stress and mitochondria and aggravate oxidative/nitrative stress after CI/R. Further studies revealed that RORα deficiency intensified the activation of nuclear factor-κB signaling induced by CI/R. Given the emerging evidence of RORα as an essential melatonin activity mediator, we further investigated the RORα roles in melatonin-exerted neuroprotection against acute ischemic stroke. Melatonin treatment significantly decreased infarct volume and cerebral apoptosis; mitigated endoplasmic reticulum stress and mitochondrial dysfunction; and inhibited CI/R injury-induced oxidative/nitrative stress and nuclear factor-κB activation, which was eradicated in RORα-deficient mice. Collectively, current findings suggest that RORα is a novel endogenous neuroprotective receptor, and a pivotal mediator of melatonin's suppressive effects against CI/R injury.

Serum Systemic Autoantibodies in Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Objective: The aim of this retrospective study was to investigate the relationship between serum systemic autoantibodies and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Thirty-nine patients with anti-NMDAR encephalitis were examined for serum systemic autoantibodies (antinuclear antibodies, extractable nuclear antigen autoantibodies, rheumatoid factors, and anti-neutrophil cytoplasmic antibodies), in comparison with 39 neuromyelitis optica spectrum disorder (NMOSD) and 78 healthy controls. Clinical features, cerebrospinal fluid characteristics, and outcomes were compared between the two subgroups of anti-NMDAR patients with positive and negative systemic autoantibodies, respectively. Results: Anti-NMDAR encephalitis patients had higher frequency of positive serum systemic autoantibodies than healthy controls (23.1 vs. 2.6%, p = 0.001) and lower frequency than NMOSD (23.1 vs. 48.7%, p = 0.018). No patients were diagnosed comorbidities with non-organ-specific autoimmune diseases. Consciousness disturbance was more frequent in autoantibodies positive group than in the negative group (88.9 vs. 40.0%, p = 0.02). Autoantibody positive group had a poorer outcome than autoantibody negative group (55.6 vs. 86.7%, p = 0.043). There was a negative correlation between serum autoantibodies and outcomes in anti-NMDAR encephalitis patients (r = -0.325, p = 0.044). Conclusion: Our data demonstrated serum systemic autoantibodies were more frequent in anti-NMDAR encephalitis patients than in healthy controls and less frequent than NMOSD, which were associated with higher severity of disease.

Sitagliptin protects the cognition function of the Alzheimer's disease mice through activating glucagon-like peptide-1 and BDNF-TrkB signalings.

BACKGROUND: Sitagliptin is an anti-diabetic drug and its effects on Alzheimer's disease (AD) remain controversial. This study aimed to investigate the protective effect of sitagliptin on the cognition in AD and its underlying molecular mechanism. METHODS: The APP/PS1 (a model of AD) mice received daily gastric gavage administration of sitagliptin (20 mg/kg) for 8 weeks. Then animals were subjected to behavioral experiment or sacrificed to histological staining and protein level analysis. RESULTS: The MWM test showed that sitagliptin treatment significantly reduced the escape latency times in APP/PS1 mice in the learning phase (day 3-5) and elongated the time spent in the target quadrant in the probe test. Sitagliptin significantly reduced amyloid plaque deposition and elevated the spine density and the protein levels of synaptoneurosome GluA1- and GluA2-containing AMPA receptor (GluA1R and GluA2R) in the brain of the APP/PS1 mice. Sitagliptin treatment significantly up-regulated the brain BNDF protein and phosphorylation of tyrosine receptor kinase B (TrkB). Furthermore, exendin-(9-39) (a glucagon-like peptide-1 [GLP-1] receptor antagonist) and K252a (a Trk tyrosine kinase inhibitor) treatment significantly abolished the cognitive protective effect of sitagliptin in the MWM test. CONCLUSION: Sitagliptin treatment effectively protected the cognition function of the AD mice by regulating synaptic plasticity, at least partially, through activating GLP-1 and BDNF-TrkB signalings.