Serum visfatin levels may be related to visceral obesity in men, and the visfatin gene may account for variation of glucose and lipid parameters in Chinese subjects.

In the heart, glycosylation is involved in a variety of physiological and pathological processes. Cardiac glycosylation is dynamically regulated, which remains challenging to monitor in vivo. Here we describe a chemical approach for analyzing the dynamic cardiac glycome by metabolically labeling the cardiac glycans with azidosugars in living rats. The azides, serving as a chemical reporter, are chemoselectively conjugated with fluorophores using copper-free click chemistry for glycan imaging; derivatizing azides with affinity tags allows enrichment and proteomic identification of glycosylated cardiac proteins. We demonstrated this methodology by visualization of the cardiac sialylated glycans in intact hearts and identification of more than 200 cardiac proteins modified with sialic acids. We further applied this methodology to investigate the sialylation in hypertrophic hearts. The imaging results revealed an increase of sialic acid biosynthesis upon the induction of cardiac hypertrophy. Quantitative proteomic analysis identified multiple sialylated proteins including neural cell adhesion molecule 1, T-kininogens, and α2-macroglobulin that were upregulated during hypertrophy. The methodology may be further extended to other types of glycosylation, as exemplified by the mucin-type O-linked glycosylation. Our results highlight the applications of metabolic glycan labeling coupled with bioorthogonal chemistry in probing the biosynthesis and function of cardiac glycome during pathophysiological responses.

Aristolochic acids (AAs) are a group of toxins commonly present in the plants of genus Aristolochia and Asarum , which are spread all over the world. Since the 1990s, AA-induced nephropathy (AAN) and upper tract urothelial carcinoma (UTUC) have been reported in many countries. The underlying mechanisms of AAN and AA-induced UTUC have been extensively investigated. AA-derived DNA adducts are recognized as specific biomarkers of AA exposure, and a mutational signature predominantly characterized by A→T transversions has been detected in AA-induced UTUC tumor tissues. In addition, various enzymes and organic anion transporters are involved in AA-induced adverse reactions. The progressive lesions and mutational events initiated by AAs are irreversible, and no effective therapeutic regimen for AAN and AA-induced UTUC has been established until now. Because of several warnings on the toxic effects of AAs by the US Food and Drug Administration and the regulatory authorities of some other countries, the sale and use of AA-containing products have been banned or restricted in most countries. However, AA-related adverse events still occur, especially in the Asian and Balkan regions. Therefore, the use of AA-containing herbal remedies and the consumption of food contaminated by AAs still carry high risk. More strict precautions should be taken to protect the public from AA exposure.

Beyond the benefits of usual education, peer support was effective in reducing diabetes distress for Type 2 diabetes mellitus. (Clinical Trials Registry no: NCT02119572).

Purpose: To evaluate sleep and mood status in patients with dry eye disease (DED) and analyze the association between sleep quality, mood status, and ocular surface characteristics. Methods: Consecutive patients with DED (N = 106) and age- and sex-matched healthy controls (N = 50) were enrolled. Tear fluid break up time (TBUT), corneal fluorescein staining, and Schirmer I tests were performed in the order listed here to evaluate dry eye. A visual analog scale was used to assess dry eye symptom severity. All subjects also completed the Pittsburgh Sleep Quality Index (PSQI, scores ≥5.5 indicated poor sleep), Patient Health Questionnaire (scores ≥5 indicated depression), and General Anxiety Disorder Scale (scores ≥5 indicated anxiety). Results: Mean Pittsburgh Sleep Quality Index global score was significantly higher in patients with DED than that in controls (7.8 ± 3.9 vs. 5.4 ± 3.0, respectively; P < 0.001). Patients with DED demonstrated higher respective depression and anxiety scores compared with controls (P < 0.001 and 0.013, respectively). In the DED group, patients with poor sleep quality had more severe DED indicated by shorter TBUT and lower Schirmer I findings. A significant correlation was found between sleep quality and mood status in patients with DED. Regression analysis revealed that shorter TBUT and lower Schirmer I test results were associated with poorer sleep quality (adjusted p = 0.011 and 0.037, respectively). More severe symptoms of dry eye were significantly associated with a higher level of anxiety in patients with DED (adjusted p = 0.011). Conclusions: Sleep quality may play an important role in the development of DED by influencing tear secretion and tear film stability and/or by indirectly aggravating anxiety and depression, leading to higher self-reported symptom scores. It is also possible that DED contributes to reduced sleep quality, as well as the development of anxiety and depression.

Background There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses. Methods We describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape. Findings We found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape. Interpretation Our results highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered.

The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

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