Objective To estimate systematic and anatomic site–specific age‐standardized prevalence rates (ASRs) and analyze the secular trends of osteoarthritis (OA) at global, regional, and national levels. Methods Data were derived from the Global Burden of Disease Study 2019. ASRs and their estimated annual percentage changes (EAPCs) were used to describe the secular trends of OA according to age group, sex, region, country, and territory, as well as the joints involved. Results Globally, prevalent cases of OA increased by 113.25%, from 247.51 million in 1990 to 527.81 million in 2019. ASRs were 6,173.38 per 100,000 in 1990 and 6,348.25 per 100,000 in 2019, with an average annual increase of 0.12% (95% confidence interval [95% CI] 0.11%, 0.14%). The ASR of OA increased for the knee, hip, and other joints, but decreased for the hand, with EAPCs of 0.32 (95% CI 0.29, 0.34), 0.28 (95% CI 0.26, 0.31), 0.18 (95% CI 0.18, 0.19), and −0.36 (95% CI −0.38, −0.33), respectively. OA prevalence increased with age and revealed female preponderance, geographic diversity, and disparity with regard to anatomic site. OA of the knee contributed the most to the overall burden, while OA of the hip had the highest EAPC in most regions. Conclusion OA has remained a major public health concern worldwide over the past decades. The prevalence of OA has increased and diversified by geographic location and affected joint. Prevention and early treatment are pivotal to mitigating the growing burden of OA.

Perihematomal edema (PHE) occurs within hours after intracerebral hemorrhage (ICH), leading to secondary injury manifested by impaired blood–brain barrier (BBB) integrity and destruction of adjacent tissue. To dissect the mechanisms underlying PHE formation, we profiled human and mouse perihematomal tissues and identified natural killer (NK) cells as the predominant immune cell subset that outnumbers other infiltrating immune cell types during early stages of ICH. Unbiased clustering of single-cell transcriptional profiles revealed two major NK cell subsets that respectively possess high cytotoxicity or robust chemokine production features in the brain after ICH, distinguishing them from NK cells of the periphery. NK cells exacerbate BBB disruption and brain edema after ICH via cytotoxicity toward cerebral endothelial cells and recruitment of neutrophils that augment focal inflammation. Thus, brain-bound NK cells acquire new features that contribute to PHE formation and neurological deterioration following ICH.

SummaryLong noncoding RNAs (lncRNAs) regulate gene expression and biological processes. With the development of high-throughput RNA sequencing technology, lncRNAs have been extensively studied in recent years. Nevertheless, the expression and evolution of lncRNAs in plants remain poorly understood.Here, we identified 413 and 709 multi-exon noncoding transcripts from 353 and 595 loci of the cultivar tomato Heinz1706 and its wild relative LA1589, respectively. Systematic comparison of the sequence and expression of lncRNAs showed that they are poorly conserved in Solanaceae, with only < 0.4% lncRNAs present in all sequenced genomes of tomato and potato. Sequence analysis of Lycopersicon-specific lncRNA loci in Solanum lycopersicum and S. pennellii showed that the origins of these molecules are associated with transposable elements (TEs).LncRNA-314, a fruit-specific lncRNA expressed in S. lycopersicum and S. pimpinellifolium, but not in S. pennellii, originated through two evolutionary events: speciation of S. pennellii resulted in insertion of a long terminal repeat (LTR) retrotransposon into chromosome 10 and contributed to most of the transcribed region of lncRNA-314; and a large deletion in Lycopersicon generated the promoter region and part of the transcribed region of lncRNA-314.These results provide novel insights into the evolution of lncRNAs in plants.

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IntroductionIntra-articular injection of hyaluronic acid (HA) is often used as therapy for knee osteoarthritis because it is less expensive and less aggressive than total knee replacement. Therefore, it is important to document whether HA is safe and efficacious. We tested whether single and multiple injection viscosupplementation with HA is associated with clinically meaningful pain relief in a new randomized clinical trial (RCT). Our objective was to compare safety and efficacy of intra-articular HA in two formulations: one 3.0 ml injection of Durolane versus five 2.5 ml injections of Artz for the treatment of knee osteoarthritis pain.MethodsPatients (N = 349) from the People’s Republic of China were randomized to treatment (Durolane = 175, Artz = 174). The Durolane group received a 3.0 ml injection at week 0 (baseline), with sham skin punctures at weeks 1, 2, 3, and 4. The Artz group received one 2.5 ml injection at each of the same time points. The primary assessment tool was the Likert-type Western Ontario and McMaster University (WOMAC) pain scale at weeks 0, 6, 10, 14, 18, and 26. Secondary assessments were WOMAC physical function, knee stiffness, and global self-assessment, at identical time points. Statistically-controlled analyses were non-inferiority of Durolane over 18, then over 26 weeks, with a priori non-inferiority defined as 8% of the relevant scale. Acetaminophen was permitted as rescue analgesia and all adverse events (AEs) were recorded.ResultsOverall study retention was excellent; 332 patients (95.1%) completed 18 weeks and 319 (91.4%) completed 26 weeks, with no significant retention difference between treatment arms. All variables met non-inferiority criteria over 18 and 26 weeks. Efficacy response in both arms was >90%. Treatment-related AEs were 9.8% (17/174) for Artz and 13.1% (23/175) for Durolane.ConclusionsA single injection of Durolane is non-inferior to 5 injections of Artz over 18 and 26 weeks for pain, physical function, global self-assessment, and knee stiffness. Both treatments were efficacious, safe, and well tolerated.Trial registrationClinicalTrials.gov NCT01295580. Registered 11 February 2011.

BackgroundRecent studies have shown that autophagy was associated with the development of osteoarthritis (OA), the purpose of this research was to determine the exact role of autophagy in OA and investigate effective therapeutic drugs to inhibit the pathological progression of OA.MethodsIn this study, a cellular OA model was generated by stimulating SW1353 cells with IL-1β and a rabbit OA model was established by intra-articular injection of collagenase, followed by treatment with Torin 1 or 3-Methyladenine (3-MA). The mRNA expression levels of VEGF, MMP-13 and TIMP-1 were determined by quantitative real-time PCR. The caitilage degeneration was examined by histological evaluation, chondrocytes degeneration and autophagosomes were observed by transmission electron microscopy. Expression levels of Beclin-1 and LC3 were evaluated by western blotting and immunofluorescence.ResultsThe degeneration of SW 1353 cells, cartilage and chondrocytes was related to the loss of autophagy in experimental OA. 3-MA increased the severity of degeneration of cells and cartilage by autophagy inhibition, while Torin 1 reduced that by autophagy activation.ConclusionsThe loss of autophagy is linked with the experimental OA and autophagy may play a protective role in the pathogenesis of OA. Treatment of Torin 1 can inhibit the degenerative changes of experimental OA by activating autophagy and it may be a useful therapeutic drug for OA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-0995-x) contains supplementary material, which is available to authorized users.

Accumulating evidence suggests that autophagy is closely related to the pathogenesis of osteoarthritis (OA). The aim of this study was to determine the changes in autophagy during the progression of OA and to elucidate the specific role of autophagy in OA. For this purpose, a cellular model of OA was generated by stimulating SW1353 cells with interleukin (IL)-1β and a rabbit model of OA was also established by an intra-articular injection of collagenase, followed by treatment with the autophagy specific inhibitor, 3-methyladenine (3-MA). Cell viability was analyzed by MTS assay, and the mRNA expression levels of matrix metalloproteinases (MMP)-13 and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by RT-qPCR. Cartilage degeneration was examined under a light microscope, and autophagosome and chondrocyte degeneration was observed by transmission electron microscopy. The protein expression of Beclin-1 and light chain 3 (LC3)B was evaluated by western blot analysis and immunofluorescence staining. We found that the autophagy was enhanced during the early stages and was weakened during the late stages of experimental OA. The inhibition of autophagy by 3-MA significantly aggravated the degeneration of chondrocytes and cartilage in experimental OA. Our results thus determine the changes in autophagy during different stages of OA, as well as the role of impaired autophagy in the development of OA. Our data suggest that the regulation of autophagy may be a potential therapeutic strategy with which to attenuate OA.

Tomato ( Solanum lycopersicum ) is one of the highest-value vegetable crops worldwide. Understanding the genetic regulation of primary metabolite levels can inform efforts aimed toward improving the nutrition of commercial tomato cultivars, while maintaining key traits such as yield and stress tolerance. We identified 388 suggestive association loci (including 126 significant loci) for 92 metabolic traits including nutrition and flavor-related loci by genome-wide association study from 302 accessions in two different environments. Among them, an ascorbate quantitative trait locus TFA9 ( T OMATO F RUIT A SCORBATEON CHROMOSOME 9 ) co-localized with SlbHLH59 , which promotes high ascorbate accumulation by directly binding to the promoter of structural genes involved in the D-mannose/L-galactose pathway. The causal mutation of TFA9 is an 8-bp InDel, named InDel_8, located in the promoter region of SlbHLH59 and spanned a 5’UTR Py-rich stretch motif affecting its expression. Phylogenetic analysis revealed that differentially expressed SlbHLH59 alleles were selected during tomato domestication. Our results provide a dramatic illustration of how ascorbate biosynthesis can be regulated and was selected during the domestication of tomato. Furthermore, the findings provide novel genetic insights into natural variation of metabolites in tomato fruit, and will promote efficient utilization of metabolite traits in tomato improvement.