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Abstract Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Primate tourism brings many benefits, but also some problems. How to better evaluate primate tourism is of significance for formulating tourism management strategies. In this study, we compared the aggressive behavior of three Sichuan snub-nosed monkey groups that encounter ecotourists and found that male aggressive behavior is a useful indicator for assessing ecotourism of these and, by inference, other groups. In high-risk tourism groups multiple monkeys direct aggression towards tourists, whereas low-risk tourism groups are characterized by low rates of such aggression. We found that tourists touching or attempting to touch the monkeys can trigger aggressive behaviors in all groups, while carrying food and eating have different effects across groups. In well-managed groups, tourist-directed aggressive behaviors are milder than in less well-managed groups. We propose that male monkey aggressive behavior elicited by tourists’ behavior is a useful indicator in assessing primate tourism, and can help guide further improvements in tourism management.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product—vaccarin (VAC)—that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.

Carbon-based materials, metal oxides and metal nanoparticles have been widely used in propellants, explosives and pyrotechnics. Cold plasma technique has been developed for material fabrication and modification at temperatures lower than 200 ⁰C. Due to the low temperatures, cold plasma can efficiently modify material surface properties, and simultaneously maintain material structures well, especially for temperature-sensitive materials. Cold plasma applies gas, e.g. Ar, N2, O2, H2 and air, as working gas, without any harmful substance like acid, alkali and organic solvent. Moreover, material surface properties can be efficiently tuned by simply changing plasma properties, e.g. power, time and working gas. The present review discusses recent progresses in using cold plasma to fabricate carbon-based materials, metal oxides and metal nanoparticles, and to modify surface properties of carbon-based materials, metal oxides and metal nanoparticles. Future research opportunities and challenges are also proposed. It is believed that the present review will stimulate more studies on material fabrication and modification by cold plasma, and help to construct more efficient materials for propellants, explosives and pyrotechnics.

ObjectiveTo study the structure and characteristics of national policies on the containment of antimicrobial resistance (AMR) in China for providing a reference to the improvement of relevant policy-making.MethodsBy searching websites of governmental agencies and China National Knowledge Infrastructure, we retrieved all AMR containment-related documents issued from January 2004 through July 2020. Using the content analysis method, we conducted textual quantitative analysis on 75 policy documents issued by government agencies with Nvivo 12 software.ResultsOf the 75 policy documents, 22, 51, and 2 were about AMR containment in health, agriculture, and environment sectors. From the text of the 75 documents, totally 316 policy tool-related item elements were coded. Of the 316 item elements, 175, 130, and 11 corresponded to policy items involving health, agriculture, and environment sectors; in terms of policy tool category, 155 item elements belong to the compulsory category and 86, 17, 49, and 9 belong to categories of capability construction, value judgment, incentive, and innovation promotion, respectively.ConclusionIn China, the national AMR containment-related policies are under the government administration; the policies act mainly on health and agriculture sectors and on aspects of mandatory management and capability construction. More policy tools need to be developed for environment-related AMR containment and in the categories of value judgment and innovation promotion.

Herein, we report a concise and divergent synthesis of the complex hasubanan alkaloids metaphanine and oxoepistephamiersine from commercially available and inexpensive cyclohexanedione monoethylene acetal. Our synthesis features a palladium‐catalyzed cascade cyclization reaction to set the tricyclic carbon framework of the desired molecules, a regioselective Baeyer–Villiger oxidation followed by a MeNH2 triggered skeletal reorganization cascade to construct the benzannulated aza[4.4.3]propellane, and a strategically late‐stage regio‐/diastereoselective oxidative annulation of sp3 C−H bond to form the challenging THF ring system and hemiketal moiety in a single step. In addition, a highly enantioselective alkylation of cyclohexanedione monoethylene acetal paved the way for the asymmetric synthesis of target molecular. [ABSTRACT FROM AUTHOR]

Based on various comparable salen ligands, three synthesized CuIINaI-complexes present efficient catalytic activities for the coupling and cyclization reaction of 1,2-diaminopropane with nitriles towards 2-imidazolines. The catalytic results show that salen ligands with an electron-donating substituent and small steric hindrance improve the catalytic activity. [ABSTRACT FROM AUTHOR]