One-sentence summary: Map-based cloning of a gene underlying grain shape in 22 wheat suggests that modest genetic changes induce dramatic phenotypic variations 23 associated with a new wheat subspecies during evolution. ABSTRACT 29 Six subspecies of hexaploid wheat (Triticum spp.) have been identified, but the origin 30 of Indian dwarf wheat (Triticum sphaerococcum Perc.), the only subspecies with 31 round grains, is currently unknown. Here, we isolated the grain-shape gene Tasg-D1 32 in T. sphaerococcum Perc. via positional cloning. Tasg-D1 encodes a serine/threonine 33 protein kinase glycogen synthase kinase 3 (STKc_GSK3) that negatively regulates 34 brassinosteroid signaling. Expression of TaSG-D1 and the mutant form Tasg-D1 in 35 Arabidopsis thaliana suggested that a single amino acid substitution in the TREE 36 domain of TaSG-D1 enhances protein stability in response to brassinosteroids, likely 37 leading to formation of round grains in wheat. This gain-of-function mutation has 38 pleiotropic effects on plant architecture and exhibits incomplete dominance. 39 Haplotype analysis of 898 wheat accessions indicated that the origin of T. 40 sphaerococcum Perc. in ancient India involved at least two independent mutations of 41 TaSG-D1. Our results demonstrate that modest genetic changes in a single gene can 42 induced dramatic phenotypic changes. 43 44 108 glycogen synthase kinase 3 (STKc_GSK3), the wheat orthologue of BIN2. In T. 109 sphaerococcum, a single amino acid substitution of STKc_GSK3 enhances protein 110 5 stability in response to BR, leading to round grain formation. Evolutionary analysis 111 provided evidence that the origin of T. sphaerococcum wheat involved at least two 112 independent mutations of TaSG-D1.

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ObjectiveVitamin D deficiency is prevalent in critically ill patients and may contribute to suboptimal clinical outcomes, but little is known about alterations of the calcium-parathyroid hormone (PTH)-vitamin D axis and prognosis in these individuals.MethodsA prospective observational study was conducted on 216 patients admitted to a university-affiliated, tertiary-care medical intensive care unit(MICU) between June 2011 and December 2012. Serum levels of 25-hydroxyvitamin D, ionised calcium and intact PTH were determined within 24 h of MICU admission. The primary end point was all-cause hospital mortality within 90-days of admission.Results95 patients (44%) showed 25-hydroxyvitamin D deficiency. Patients deficient in vitamin D showed significantly higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, rate of positive blood culture, incidence of multiple organ dysfunction syndrome, and 90-day mortality rate than did patients with vitamin D insufficiency or sufficiency (P<0.05), as well as lower levels of serum IgG. 25-Hydroxyvitamin D deficiency was identified as an independent risk factor for mortality (OR = 3.018, 95%CI 1.329–6.854, P = 0.008). Hypovitaminosis D in PTH-responders was associated with higher mortality than was the same condition in non-responders (P<0.05).ConclusionsThese results suggest that vitamin D deficiency is prevalent among MICU patients, suggesting a significant derangement of the calcium-PTH-vitamin D axis in critically ill patients. Vitamin D deficiency is an independent risk factor for 90-day mortality, and hypovitaminosis D in PTH-responders is associated with higher mortality than is the same condition in non-responders.

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Background Tofacitinib is an oral Janus kinase (JAK) inhibitor that targets JAK1 and JAK3, and thus regulates immune response. Therefore, tofacitinib is used to treat immune-mediated inflammatory diseases such as chronic plaque psoriasis. The objective of this study was to systematically assess the efficacy and safety of tofacitinib in treating chronic plaque psoriasis. Objective To systematically review the efficacy and safety of tofacitinib in the treatment of chronic plaque psoriasis, we performed a meta-analysis to evaluate the efficacy and safety of tofacitinib in patients with chronic plaque psoriasis. Methods Databases including PubMed, Embase, and The Cochrane Library were searched for randomized controlled trials about the efficacy and safety of tofacitinib in treating chronic plaque psoriasis from inception to August 2017 (PROSPERO Code No: CRD42017076587). Results Six articles (seven randomized controlled trial studies) involving 3743 patients were included. The meta-analysis results showed that for efficacy, tofacitinib (5 mg or 10 mg) compared with placebo can significantly improve the Physician’s Global Assessment response, PASI75, and PASI90 after treatment. For safety, the incidence of adverse reactions was statistically significantly higher for tofacitinib compared with placebo. Conclusion Treatment of chronic plaque psoriasis with tofacitinib is effective, but there may be more adverse reactions.

According to statistics from the World Health Organisation (WHO), 1 the total number of people aged 60 years and older in the world is expected to reach 2 billion, and the geriatric population aged 80 years and older in China will reach 120 million by 2050.China has the largest geriatric population in the world. By the end of 2019, China's population over 1.4 billion, of which people aged ≥65 years account for 12.6% (176.8 million) of the total population. 2 Due to ageing, they become a group that is susceptible to multiple diseases, especially chronic diseases. WHO data showed that 41 million people die from chronic diseases each year, and the death toll from chronic diseases in China accounts for 89% of all deaths. 3,4 Currently, the coexistence of multiple diseases in the geriatric is common, compared with the young; they often take many different medicines, which will further increase the burden on the liver and kidney function. And changes in pharmacokinetics and pharmacodynamics have led to an increased risk of drug-drug