Autophagic LC3+ calcified extracellular vesicles initiate cartilage calcification in osteoarthritis.

Pathological cartilage calcification plays an important role in osteoarthritis progression but in which the origin of calcified extracellular vesicles (EVs) and their effects remain unknown. Here, we demonstrate that pathological cartilage calcification occurs in the early stage of the osteoarthritis in which the calcified EVs are closely involved. Autophagosomes carrying the minerals are released in EVs, and calcification is induced by those autophagy-regulated calcified EVs. Autophagy-derived microtubule-associated proteins 1A/1B light chain 3B (LC3)-positive EVs are the major population of calcified EVs that initiate pathological calcification. Release of LC3-positive calcified EVs is caused by blockage of the autophagy flux resulted from histone deacetylase 6 (HDAC6)-mediated microtubule destabilization. Inhibition of HDAC6 activity blocks the release of the LC3-positive calcified EVs by chondrocytes and effectively reverses the pathological calcification and degradation of cartilage. The present work discovers that calcified EVs derived from autophagosomes initiate pathological cartilage calcification in osteoarthritis, with potential therapeutic targeting implication.

Aerobic Cu-catalyzed oxidative 1 : 2 coupling of benzynes with terminal alkynes.

Cu-Catalyzed oxidative 1 : 2 couplings of arynes with nucleophilic terminal alkynes under aerobic conditions are described herein. A mechanistic investigation revealed a plausible involvement of an aryl-Cu(iii)-generating pathway. By this method, ubiquitous arenediynes can be efficiently assembled in a single step under mild conditions.

Knockdown of TNF­α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL­10 expression.

Intestinal ischemia and reperfusion (II/R) injury often triggers severe injury in remote organs, with the lungs being considered the main target. Excessive elevation of proinflammatory cytokines is a major contributor in the occurrence and development of II/R­induced acute lung injury (ALI). Therefore, the present study aimed to investigate whether blocking tumor necrosis factor­α (TNF­α) expression could protect the lungs from injury following II/R, and to explore the possible underlying mechanism involving interleukin­10 (IL­10). Briefly, II/R was induced in rats by 40 min occlusion of the superior mesenteric artery and celiac artery, followed by 8, 16 or 24 h of reperfusion. Subsequently, lentiviral vectors containing TNF­α short hairpin (sh)RNA were injected into the right lung tissues, in order to induce TNF­α knockdown. The severity of ALI was determined according to lung injury scores and lung edema (lung wet/dry weight ratio). The expression levels of TNF­α were analyzed by quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence (IF) staining. IL­10 expression, in response to TNF­α knockdown, was detected in lung tissues by qPCR and IF. The results detected marked inflammatory responses, and increased levels of lung wet/dry weight ratio and TNF­α expression, in the lungs of II/R rats. Conversely, treatment with TNF­α shRNA significantly alleviated the severity of ALI and upregulated the expression levels of IL­10 in lung tissues. These findings suggested that TNF­α RNA interference may exert a protective effect on II/R­induced ALI via the upregulation of IL­10. Therefore, TNF­α knockdown may be considered a potential strategy for the prevention or treatment of ALI induced by II/R in future clinical trials.

A Familial Cluster of Human Brucellosis Attributable to Contact with Imported Infected Goats in Shuyang, Jiangsu Province, China, 2013.

Brucellosis remains a serious public health issue in developing countries, including China. On August 8, 2013, four cases of brucellosis from one extended family were reported at Shuyang County, Jiangsu Province, China. Active case finding was performed to identify the source and the risk factors of the infection and to prevent additional cases. Multiple-locus variable number tandem repeat analysis (MLVA) was used for molecular subtyping analysis. Six people from two extended families met the case definition for brucellosis infection; four were blood culture positive for Brucella melitensis biotype 3. Four additional family members were found seropositive by using a serological test. Isolates from the four patients were indistinguishable by MLVA profiling, displaying a unique type for Jiangsu Province. Field epidemiological data combined with MLVA genotyping supported a common source of the isolates from the different patients. We recommend stronger reinforcement measures for animal quarantine practices, enhanced cooperation with veterinary service organizations, and implementation of measures that strengthen public education on brucellosis to prevent further human outbreaks in Jiangsu Province.