Kang Li

BACKGROUND: Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. METHODS: A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured. RESULTS: The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05). CONCLUSIONS: High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.

Rational: Myocardial infiltrating macrophages play an important role in the pathogenesis of viral myocarditis in male BALB/c mice following coxsackievirus B3 (CVB3) infection. Interestingly, comparable macrophage numbers were observed in the myocardium of female mice during acute myocarditis. Objective: Given CVB3 infection causes severe myocarditis in male but not female mice, we postulated that macrophages infiltrating the myocardium of female mice may display distinct functional properties that contribute to differential susceptibility to CVB3 myocarditis. Methods and Results: Here, we found that myocardial infiltrating macrophages from CVB3-infected male mice expressed high levels of classically activated macrophages (M1) markers, including inducible nitric oxide synthase, interleukin-12, tumor necrosis factor-α, and CD16/32, whereas those of females showed enhanced expression of arginase 1, interleukin-10, macrophage mannose receptor (MMR) and macrophage galactose type C-type lectin (MGL) that were associated with alternatively activated macrophage (M2) phenotype. Moreover, distinct myocardial-derived cytokines were found to play a critical role in differential macrophage polarization between sexes after CVB3 infection. Adoptive transfer of ex vivo programmed M1 macrophages, as expectedly, significantly increased myocarditis in both male and female mice. Strikingly, transfer of M2 macrophages into susceptible male mice remarkably alleviated myocardial inflammation by modulating local cytokine profile and promoting peripheral regulatory T cell (Treg) differentiation. Conclusions: Taken together, this study may facilitate the understanding of the mechanism underlying gender bias in susceptibility to CVB3 myocarditis and the development of therapeutic strategies based on macrophage polarization for inflammatory heart disease.

Thiol is known to act as a hydrogen atom transfer catalyst working in synergy with a photocatalyst in photoredox catalysis, but we report herein that an arene thiolate with an appropriate substituent can be photoactivated under visible light to function as both a strongly reducing electron-donating redox catalyst and a HAT catalyst to enable catalytic C–F activation of trifluoromethyl substrates for selective hydrodefluorination and coupling with various alkenes in the presence of formate salts. These reactions demonstrate the promising utility of arenethiolates as dual function photocatalysts. The synthetic utility of this method is demonstrated by the broad scope of amenable trifluoromethyl substrates, including trifluoromethylated (hetero)arenes, trifluoroacetates, and trifluoroacetamides, which exhibited high levels of chemoselectivity. The reaction efficacy allows site-selective late-stage functionalization of multitrifluoromethylated bioactive compounds and pharmaceuticals

Red fluorescent carbon dots (r-CDs) with narrow dual emissions (600 nm and 658-683 nm, full width at half-maximums (FWHMs) of 20 nm and 30 nm), fluorescence quantum yield of 41.0%, and yield of 83.3% are prepared by hydrothermal method using o-phenylenediamine as precursor and inorganic oxidant as yield enhancer, and they have graphite nitrate-like structures. The long-wavelength side emission is aggregation-induced emission (AIE). A logarithmic relationship between the AIE wavelength (y) and the concentration (x) (y = 8.853ln(x) + 688.53, R = 0.998) is found. This regularity and the high monochromaticity of AIE are related to the existence of highly ordered structures proved by X-ray diffraction. Its intrinsic emission (FWHM: 20 nm) is the narrowest among the r-CDs prepared by hydrothermal method. The reason is that the decrease of oxygen content makes the FWHMs become narrow, and the decrease of the pyridine nitrogen content and the increase of pyrrole nitrogen content make them narrower further. The Fourier-transform infrared spectra and control experiment prove that oxidative polymerization is a necessary preparation step. The linear relationship between the amount of the oxidant and the CDs yield indicates that the yield can be increased only by increasing the conversion rate of the polymerization process.