Search

Abstract High-spin carbon-based polyradicals exhibit significant potential for applications in quantum information storage and sensing; however, their practical application is hampered by limited structural diversity and chemical instability. Here, we report a straightforward synthetic and isolation method for synthesizing a nonalternant nanographene (1) with a triplet ground state. Moving beyond the classic m-xylylene scaffold for high-spin organic molecules, seven-five-seven (7–5–7)-membered rings are introduced to create stable high-spin diradicals with half-lives (t 1/2) as long as 101 days. Moreover, considering the spin relaxation of compound 1, with a spin–lattice relaxation time (T 1) of 53.55 ms and a coherence time (T m) of 3.41 μs at 10 K, the compound 1 shows great promise for applications in spin-based information retention and quantum computing.

Globally, obesity has become the fifth leading risk factor for death, and discoverying prebiotics with preventive and therapeutic effects on obesity is a hot topic in current research. Marine polysaccharides, a special class of bioactive substances from marine organisms, have novel structural features and unique bioactivities due to the unique environment of the ocean. Marine polysaccharides have an excellent potential to treat obesity by regulating glucose and lipid metabolism, inflammatory factor levels, and the gut microbiota. This article reviews the types of marine polysaccharides, the effects of their structures and compositions on their antiobesity activity, and the underlying mechanisms of action. With the aim of providing a basis for the development of antiobesity drugs using marine polysaccharides, the article focuses on discussing the signaling pathways by which marine polysaccharides inhibit obesity through the gut microbiota, and gives an outlook on the application of marine polysaccharides for obesity inhibition.

Abstract Backgrounds Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. Methods Denervation‐induced muscle atrophy model was constructed in wild‐type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol‐free RBP4 (apo‐RBP4), retinol‐bound RBP4 (holo‐RBP4) or oral gavage of RBP4 inhibitor A1120. Holo‐RBP4‐stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross‐sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. Results The expression levels of RBP4 in skeletal muscles were significantly up‐regulated more than 2‐fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation‐induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin‐1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol‐bound holo‐RBP4 aggregated denervation‐induced ectopic fat accumulation and muscle atrophy. Consistently, holo‐RBP4 stimulation also had a dose‐dependent effect on the reduction of C2C12 myotube diameter and myofibre cross‐sectional area, as well as on the increase of Atrogin‐1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo‐RBP4 treatment increased the expression of its membrane receptor STRA6 (>3‐fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin‐1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3‐fold) in holo‐RBP4‐treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation‐induced muscle atrophy (30% increased myofibre cross‐sectional area) in mice. Conclusions In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6‐dependent and JAK2/STAT3 pathway‐mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.

The gene (PsHex) encoding β-N-acetylglucosaminidase from the marine bacterium Pseudoalteromonas sp. DL-6 was cloned into the pET-28a(+) vector and then successfully heterologously expressed in Escherichia coli BL21(DE3). The expressed protein was purified through nickel-nitrilotriacetic acid affinity chromatography. The results showed that PsHex encoded 876 amino acids, and the predicted molecular mass and pI were 99.46 kD and 5.65, respectively. Phylogenetic analysis and multiple sequence alignments showed that PsHex belonged to the glycosyl hydrolase 20 (GH20) family. The optimal temperature and pH for the recombinant enzyme were 30 ℃ and 8.5, respectively, its specific activity was 11.30 U/mg and it displayed the highest stability at 20 ℃ and pH 7.5. This enzyme could degrade various substrates, including agarose, chitosan, soluble starch and carrageenan and could be activated by metal ions (Na+, Mg2+, Fe3+, K+, and Ca2+), DL-dithiothreitol, tween-80, ethylenediaminetetraacetic acid and β-mercaptoethanol. The Michaelis constant (Km), catalytic rate constant (Kcat), maximum reaction rate (vmax) and Kcat/Km values toward the substrate 4-nitrophenyl 2-acetamido-2-deoxy-β-d-glucopyranoside were 2.523 mol/L, 79.035 min-1, 2.081 U/mg and 31.326, respectively. This study provides a theoretical reference for the enzymatic degradation of chitin to produce N-acetylglucosamine.

Abstract Background Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample‐based methylation changes of skeletal muscle function‐related factors in patients with sarcopenia. Methods The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age‐ and sex‐matched non‐sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation‐specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut‐off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. Results Among 1149 cytosine‐phosphate‐guanine (CpG) sites of 27 skeletal muscle function‐related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation‐specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P