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ABSTRACTBackgroundAt present, there is no predictive model that can predict the prevalence of potentially inappropriate medication (PIM) use in older lung cancer outpatients.Research design and methodsWe measured PIM by the 2019 Beers criteria. Significant factors were identified to develop the nomogram using logistic regression. We validated the nomogram internally and externally in two cohorts. The discrimination, calibration, and clinical practicability of the nomogram were verified using receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow test, and decision curve analysis (DCA), respectively.ResultsA total of 3300 older lung cancer outpatients were divided into a training cohort (n = 1718) and two validation cohorts, including an internal validation cohort (n = 739) and an external validation cohort (n = 843). A nomogram for predicting PIM use patients was developed using six significant factors. ROC curve analysis showed that the area under the curve was 0.835 in the training cohort and 0.810 and 0.826 in the internal validation and external validation cohorts, respectively. The Hosmer‒Lemeshow test yielded P = 0.180, 0.779 and 0.069, respectively. The nomogram demonstrated a high net benefit in DCA.ConclusionsThe nomogram could be a convenient, intuitive, and personalized clinical tool for assessing the risk of PIM in older lung cancer outpatients.

Type VI Secretion System (T6SS) plays significant roles in microbial activities via injecting effectors into adjacent cells or environments. T6SS increasingly gained attention due to its important influence on pathogenesis, microbial competition, etc. T6SS-associated research is explosively expanding on numerous grounds that call for an efficient resource. The SecReT6 version 3 provides comprehensive information on T6SS and the interactions between T6SS and T6SS-related proteins such as T6SS regulators and T6SS effectors. To assist T6SS researches like microbial competition and regulatory mechanisms, SecReT6 v3 developed online tools for detection and analysis of T6SS and T6SS-related proteins and estimation of T6SS-dependent killing risk. We have identified a novel T6SS regulator and T6SS-dependent killing capacity in Acinetobacter baumanniiclinical isolates with the aid of SecReT6 v3. 17,212 T6SSs and plentiful T6SS-related proteins in 26,573 bacterial complete genomes were also detected, analyzed and incorporated into the database. The database is freely available at https://bioinfo-mml.sjtu.edu.cn/SecReT6/.

Modern green revolution varieties of wheat (Triticum aestivumL.) confer semi-dwarf and lodging-resistant plant architecture owing to the Reduced height-B1b(Rht-B1b) and Rht-D1balleles1. However, both Rht-B1band Rht-D1bare gain-of-function mutant alleles encoding gibberellin signalling repressors that stably repress plant growth and negatively affect nitrogen-use efficiency and grain filling2–5. Therefore, the green revolution varieties of wheat harbouring Rht-B1bor Rht-D1busually produce smaller grain and require higher nitrogen fertilizer inputs to maintain their grain yields. Here we describe a strategy to design semi-dwarf wheat varieties without the need for Rht-B1bor Rht-D1balleles. We discovered that absence of Rht-B1and ZnF-B(encoding a RING-type E3 ligase) through a natural deletion of a haploblock of about 500 kilobases shaped semi-dwarf plants with more compact plant architecture and substantially improved grain yield (up to 15.2%) in field trials. Further genetic analysis confirmed that the deletion of ZnF-Binduced the semi-dwarf trait in the absence of the Rht-B1band Rht-D1balleles through attenuating brassinosteroid (BR) perception. ZnF acts as a BR signalling activator to facilitate proteasomal destruction of the BR signalling repressor BRI1 kinase inhibitor 1 (TaBKI1), and loss of ZnFstabilizes TaBKI1 to block BR signalling transduction. Our findings not only identified a pivotal BR signalling modulator but also provided a creative strategy to design high-yield semi-dwarf wheat varieties by manipulating the BR signal pathway to sustain wheat production.

Nicotine withdrawal symptoms, mainly anxiety, cause high level of relapse rate after quitting smoking. Vitamin D supplementation has shown its potential for the prevention and treatment of anxiety disorders; however, neurobiological studies about the effect of vitamin D on nicotine withdrawal-induced anxiety are limited. To investigate the effect and molecular mechanism of vitamin D3 supplement by dietary on anxiety-like behavior during nicotine withdrawal, male C57/BL6 mice were divided into four groups: vehicle, nicotine only, vitamin D3 only, and nicotine plus vitamin D3. Mice were administrated with nicotine in drinking water (200 µg/mL), and vitamin D3 in feed for 6 weeks. During nicotine withdrawal, vitamin D3-treated mice showed significantly less anxiety-like behavior by an open-field test and marble buried test that performed an increase in the duration of the central zone and a decrease buried marble, respectively. Moreover, vitamin D3 supplementation attenuated the hippocampal NR2A expression on both protein and mRNA levels in nicotine and vitamin D3-treated mice. Our data showed that dietary supplementation with vitamin D3 ameliorated nicotine withdrawal-induced anxiety, which may be related to downregulation of NR2A expression in hippocampus. Vitamin D3 may provide a new dietary intervention with the easy access for smoking cessation.

Root hairs are fast growing, ephemeral tubular extensions of the root epidermis that aid nutrient and water uptake. The aim of the present study was to identify QTL for root hair length (RHL) using 227 F8recombinant inbred lines (RILs) derived from a cross of Zhou 8425B (Z8425B) and Chinese Spring (CS), and to develop convenient molecular markers for marker-assisted breeding in wheat. Analysis of variance of root hair length showed significant differences (P < 0.01) among RILs. The genetic map for QTL analysis consisted of 3389 unique SNP markers. Using composite interval mapping, four major QTL (LOD > 2.5) for RHL were identified on chromosomes 1B (2), 2D and 6D and four putative QTL (2 ≤ LOD ≤ 2.5) were detected on chromosomes 1A, 3A, 6B, and 7B, explaining 3.32%–6.52% of the phenotypic variance. The positive alleles for increased RHL of QTL on chromosomes 2D, 6B and 6D (QRhl.cau-2D, qRhl.cau-6B, and QRhl.cau-6D) were contributed by Z8425B, and CS contributed positive QTL alleles on chromosomes 1A (qRhl.cau-1A), 1B (QRhl.cau-1B.1and QRhl.cau-1B.2), 3A (qRhl.cau-3A) and 7B (qRhl.cau-7B). STARP markers were developed for QRhl.cau-1B.1, QRhl.cau-2D, QRhl.cau-6D, and qRhl.cau-7B. Haplotype and association analysis indicated that the positive allele of QRhl.cau-6Dhad been strongly selected in Chinese wheat breeding programs. Collectively, the identified QTL for root hair length are likely to be useful for marker-assisted selection.

Grain number, one of the major determinants of yield in Triticeae crops, is largely determined by spikelet number and spike rachis node number (SRN). Here, we identified three quantitative trait loci (QTLs) for SRN using 145 recombinant inbred lines derived from a barley R90/1815D cross. qSRN1, the major-effect QTL, was mapped to chromosome 2H and explained up to 38.77% of SRN variation. Map-based cloning revealed that qSRN1encodes the RAWUL domain-containing protein HvSRN1. Further analysis revealed that two key SNPs in the HvSRN1promoter region (∼2 kb upstream of the transcription start site) affect the transcript level of HvSRN1and contribute to variation in SRN. Similar to its orthologous proteins OsLAX2 and ZmBA2, HvSRN1 showed protein–protein interactions with HvLAX1, suggesting that the LAX2–LAX1 model for spike morphology regulation may be conserved in Poaceae crops. CRISPR-Cas9-induced HvSRN1mutants showed reduced SRN but increased grain size and weight, demonstrating a trade-off effect. Our results shed light on the role of HvSRN1variation in regulating the balance between grain number and weight in barley.

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.

Awns are important morphological markers for wheat and exert a strong physiological effect on wheat yield. The awn elongation suppressor B1has recently been cloned through association and linkage analysis in wheat. However, the mechanism of awn inhibition centered around B1 remains to be clarified. Here, we identified an allelic variant in the coding region of B1through analysis of re-sequencing data; this variant causes an amino acid substitution and premature termination, resulting in a long-awn phenotype. Transcriptome analysis indicated that B1 inhibited awn elongation by impeding cytokinin- and auxin-promoted cell division. Moreover, B1 directly repressed the expression of TaRAE2and TaLks2, whose orthologs have been reported to promote awn development in rice or barley. More importantly, we found that TaTCP4 and TaTCP10 synergistically inhibited the expression of B1, and a G-to-A mutation in the B1promoter attenuated its inhibition by TaTCP4/10. Taken together, our results reveal novel mechanisms of awn development and provide genetic resources for trait improvement in wheat.

Exploitation of new gene resources and genetic networks contributing to the control of crop yield-related traits, such as plant height and grain size and shape, may enable us to breed modern high-yielding wheat varieties through molecular methods. In this study, via ethylmethanesulfonate mutagenesis, we identified a wheat mutant plant, mu-597, that shows semidwarf plant architecture and round grain shape. Through bulked segregant RNA-seq and map-based cloning, the causal gene for the semidwarf phenotype of mu-597was located. We found that a single-base mutation in the coding region of TaACTIN7-D(TaACT7-D), leading to a Gly-to-Ser (G65S) amino acid mutation at the 65th residue of the deduced TaACT7-D protein, can explain the semidwarfism and round grain shape of mu-597. Further evidence shows that the G65S mutation in TaACT7-D hinders the polymerization of actin from monomeric (G-actin) to filamentous (F-actin) status while attenuates wheat responses to multiple phytohormones, including brassinosteroids, auxin, and gibberellin. Together, these findings not only define a new semidwarfing gene resource that can be potentially used to design plant height and grain shape of bread wheat but also establish a direct link between actin structure modulation and phytohormone signal transduction.

The purpose of this study was to explore whether the time from pelvic and abdominal non-urological surgery-induced iatrogenic ureteral injuries to repair associates with outcomes. We retrospectively reviewed 81 cases of pelvic and abdominal nonurological surgery-induced iatrogenic ureteral injuries occurring in 78 patients treated at our hospital from January 2000 to December 2009. Time between injury and surgical repair, operative times, and incidence of complications were compared. Lower ureteral segment injuries occurred in 66 cases, middle segment injuries in 13, and upper segment injuries in two. Surgical repair methods included 36 ureteroneocystostomies, 17 ureteroneocystostomy with psoas hitch, 14 ureteroureterostomies/ureteral end-to-end anastomosis, and 10 ureteroneocystostomies with a Boari flap. Immediate intraoperative repair was carried out in 23 cases. In 42 cases, repair was delayed as a result of late identification and performed within 1 month after surgery. In 10 cases, repair was performed 3 months after surgery. No significant differences were observed in operative times of repair surgeries or incidence of postoperative complications. Delayed discovery of iatrogenic ureteral injury can still result in good therapeutic effects if the surgical repair is done within 1 month after injury under the premise that no serious urinary tract infection is present and the patient can tolerate surgery.