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Summary: Seminal roots play a critical role in water and nutrient absorption, particularly in the early developmental stages of wheat. However, the genes responsible for controlling SRN in wheat remain largely unknown.Genetic mapping and functional analyses identified a candidate gene (TraesCS3D01G137200, TaSRN‐3D) encoding a Ser/Thr kinase glycogen synthase kinase 3 (STKc_GSK3) that regulated SRN in wheat. Additionally, experiments involving hormone treatment, nitrate absorption and protein interaction were conducted to explore the regulatory mechanism of TaSRN‐3D.Results showed that the TaSRN‐3D4332 allele inhibited seminal roots initiation and development, while loss‐of‐function mutants showed significantly higher seminal root number (SRN). Exogenous application of epi‐brassinolide could increase the SRN in a HS2‐allelic background. Furthermore, chlorate sensitivity and 15N uptake assays revealed that a higher number of seminal roots promoted nitrate accumulation. TaBSR1 (BIN2‐related SRN Regulator 1, orthologous to OsGRF4/GL2 in rice) acts as an interactor of TaSRN‐3D and promotes TaBSR1 degradation to reduce SRN.This study provides valuable insights into understanding the genetic basis and regulatory network of SRN in wheat, highlighting their roles as potential targets for root‐based improvement in wheat breeding. [ABSTRACT FROM AUTHOR]

Deprescribing reduces polypharmacy in older adults. A thorough study of the effect of deprescribing interventions on clinical outcomes in older adults is presently lacking. As a result, we evaluated the impact of deprescribing on clinical outcomes in older patients. Meta-analysis and systematic review of randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane Library were searched from the time of creation to March 2023. Randomized controlled trial with participants at least 60 years old. Mortality, falls (number of fallers), hospitalization rates, emergency department visits, medication adherence, HRQoL (health-regulated quality of life), incidence of ADR (adverse drug reactions), PIM (potentially inappropriate medication), and PPO (potentially prescription omission) were evaluated in the meta-analysis. A total of 32 RCTs (18,670 patients) were included. Deprescribing interventions significantly reduced proportions of older adults with PIM, PPO, and the incidence of ADRs. The interventions group also improved medication compliance. Compared to routine care, deprescribing interventions significantly improve clinical outcome indicators for older adults. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the efficacy of prophylactic use amphotericin B in patients with hematologic disorders complicated by neutropenia. We searched the PubMed, EMBASE, The Cochrane Library, CBM, CNKI, VIP and WanFang Data database and the China Clinical Trials Registry (www.chictr.org.cn) to collect randomized controlled trials (RCTs) of amphotericin B for patients with hematologic disorders complicated by neutropenia from inception to May 2023. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. The meta-analysis was performed using RevMan 5.3 software. A total of 6 studies with a total of 1019 patients were included. The results of the meta-analysis showed that the treatment group was superior to the control group in terms of the fungal infection rate, and the differences were statistically significant [RR = 0.47, 95% CI (0.32, 0.69), P < 0.0001]. There was no significant difference between the two groups in terms of the mortality [RR = 0.87, 95% CI (0.61, 1.23), P = 0.43] and the incidence of colonization [OR = 0.51, 95% CI (0.25, 1.03), P = 0.06]. The evidence shows that amphotericin B prophylactic use for patients with hematologic disorders complicated by neutropenia can decrease the fungal infection rate. However, there was no significant difference in reducing mortality or the incidence of colonization. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion. [ABSTRACT FROM AUTHOR]

Animal experiments play an essential role in advances in the research and treatment of burns. Currently, researchers often rely on personal experience or the literature to complete the construction of animal disease models, which may lead to a lack of scientific rigor and a wide range of animal disease models with reference value. The purposes of this study were to establish a third-degree burn model of rats using the Delphi method to provide a reference. Two rounds of a Delphi expert consultation survey were conducted on experts (n = 13) in this study, and then the boundary value method was used to screen, modify and supplement the indicators. Next, the indicator weight was determined by dividing the boundary value, and finally, the index system of the rat model of third-degree burns was established. The statistical analysis results show that the positive coefficients of the two rounds of expert consultation are 100% and 88.67% respectively. The expert authority coefficient values were 0.73 and 0.67, respectively, and the expert coordination coefficient test was P < 0.001. According to the experts' suggestion, the third-degree burn model of rats with 8 first-degree indexes, 14 second-degree indexes and 46 third-degree indexes was finally established. According to the characteristics and quality requirements of animal models, this study constructs a rat model of third degree burns, which is expected to expressively improve the overall proficiency of burn research quality. [ABSTRACT FROM AUTHOR]

Summary: The spikelet number and heading date are two crucial and correlated traits for yield in wheat. Here, a quantitative trait locus (QTL) analysis was conducted in F8 recombinant inbred lines (RILs) derived from crossing two common wheats with different spikelet numbers. A total of 15 stable QTL influencing total spikelet number (TSN) and heading date (HD) were detected. Notably, FT‐D1, a well‐known flowering time gene in wheat, was located within the finely mapped interval of a major QTL on 7DS (QTsn/Hd.cau‐7D). A causal indel of one G in the third exon of FT‐D1 was significantly associated with total spikelet number and heading date. Consistently, CRISPR/Cas9 mutant lines with homozygous mutations in FT‐D1 displayed an increase in total spikelet number and heading date when compared with wild type. Moreover, one simple and robust marker developed according to the polymorphic site of FT‐D1 revealed that this one G indel had been preferentially selected to adapt to different environments. Collectively, these data provide further insights into the genetic basis of spikelet number and heading date, and the diagnostic marker of FT‐D1 will be useful for marker‐assisted pyramiding in wheat breeding. [ABSTRACT FROM AUTHOR]

Polish wheat (Triticum polonicum) is a unique tetraploid wheat species characterized by an elongated outer glume. The genetic control of the long-glume trait by a single semi-dominant locus, P1 (from P olish wheat), was established more than 100 years ago, but the underlying causal gene and molecular nature remain elusive. Here, we report the isolation of VRT-A2 , encoding an SVP-clade MADS-box transcription factor, as the P1 candidate gene. Genetic evidence suggests that in T. polonicum , a naturally occurring sequence rearrangement in the intron-1 region of VRT-A2 leads to ectopic expression of VRT-A2 in floral organs where the long-glume phenotype appears. Interestingly, we found that the intron-1 region is a key ON/OFF molecular switch for VRT-A2 expression, not only because it recruits transcriptional repressors, but also because it confers intron-mediated transcriptional enhancement. Genotypic analyses using wheat accessions indicated that the P1 locus is likely derived from a single natural mutation in tetraploid wheat, which was subsequently inherited by hexaploid T. petropavlovskyi. Taken together, our findings highlight the promoter-proximal intron variation as a molecular basis for phenotypic differentiation, and thus species formation in Triticum plants. A naturally occurring sequence rearrangement in the intron-1 region of the MADS-box gene VRT-A2 , featuring a 560-bp deletion coupled with a 157-bp sequence substitution, leads to ectopic expression of VRT-A2 in floral organs and underlies the origin of Polish wheat (Triticum polonicum) and 'Daosuimai' (T. petropavlovskyi), species with elongated outer glumes and grains. [ABSTRACT FROM AUTHOR]

Key message: Three pleiotropic QTL regions associated with spikelet number and heading date were identified, with FT-A1 considered the candidate gene for QTspn/Hd.cau-7A. Spikelet number traits and heading date (HD) play key roles in yield improvement of wheat and its wide adaptation to different environments. Here, we used a Recombinant Inbred Lines population derived from a cross between Yi5029 (5029) and Nongda4332 (4332) to construct a high-density genetic linkage map and identify quantitative trait loci (QTL) associated with total spikelet number per spike (TSPN), fertile spikelet number per spike (FSPN), sterile spikelet number per spike (SSPN) and HD. A total of 22 environmentally stable QTL for TSPN, FSPN, SSPN and HD were identified. Notably, three pleiotropic QTL regions for TSPN and HD were detected on chromosomes 2A, 7A and 7D. The QTL associated with TSPN and HD on chromosome 7AS was designated QTspn/Hd.cau-7A. Furthermore, the candidate gene FT-A1 located in the region of QTspn/Hd.cau-7A had a single-nucleotide polymorphism (T–G) within the third exon, which might be the cause of diversity in spikelet number and HD between the two parents. Additionally, we developed a semi-thermal asymmetric reverse PCR (STARP) marker to analyze the geographical distribution and evolution of FT-A1 (T or G) alleles. This study contributes to our understanding of the molecular mechanisms of the four traits (TSPN, FSPN, SSPN and HD) and provides further insights into the genetic relationship between spikelet number traits and HD in wheat. [ABSTRACT FROM AUTHOR]

Key message: Thirty environmentally stable QTL controlling grain size and/or plant height were identified, among which QTgw.cau-7D was delimited into the physical interval of approximately 4.4 Mb. Grain size and plant height (PHT) are important agronomic traits in wheat breeding. To dissect the genetic basis of these traits, we conducted a quantitative trait locus (QTL) analysis using recombinant inbred lines (RILs). In total, 30 environmentally stable QTL for thousand grain weight (TGW), grain length (GL), grain width (GW) and PHT were detected. Notably, one major pleiotropic QTL on chromosome arm 3DS explained the highest phenotypic variance for TGW, GL and PHT, and two stable QTL (QGw.cau-4B and QGw.cau-7D) on chromosome arms 4BS and 7DS contributed greater effects for GW. Furthermore, the stable QTL controlling grain size (QTgw.cau-7D and QGw.cau-7D) were delimited into the physical interval of approximately 4.4 Mb harboring 56 annotated genes. The elite NILs of QTgw.cau-7D increased TGW by 12.79–21.75% and GW by 4.10–8.47% across all three environments. Collectively, these results provide further insight into the genetic basis of TGW, GL, GW and PHT, and the fine-mapped QTgw.cau-7D will be an attractive target for positional cloning and marker-assisted selection in wheat breeding programs. [ABSTRACT FROM AUTHOR]

Glioblastoma, a cancer that originates from astrocytes, is the most prevalent malignant glioma in the adult population. The aim of the present study was to evaluate the cost-effectiveness of bevacizumab (BEV) as a supplement to standard temozolomide (TMZ) treatment for unresected glioblastoma. The analyzed data were from a phase II trial that showed a survival benefit following combination therapy, when compared with TMZ monotherapy. According to the clinical symptoms and disease progression, a Markov model was constructed to estimate the incremental cost-effectiveness ratio (ICER) from a Chinese societal perspective. Health outcomes were retrieved from the GENOM 009 trial, and utility parameters were obtained from published literature. Uncertainties within the model were addressed through one-way deterministic and probabilistic sensitivity analyses. The addition of BEV to TMZ therapy increased overall costs by $30,894.99, with a gain of 0.18 quality-adjusted life-years (QALYs), resulting in an ICER of $171,638.83/QALY. Both one-way sensitivity and probabilistic sensitivity analyses confirmed that BEV/TMZ co-treatment was not cost-effective in the context of a $26,508.00/QALY willingness-to-pay (WTP) threshold. The utility of the progression-free survival state had the most noticeable impact on the ICER. In summary, the combination of BEV and TMZ should not be considered a cost-effective neoadjuvant treatment option for patients with unresected glioblastoma in China, from a societal perspective. However, in view of the survival benefits conferred, an appropriate price discount or the use of medical insurance could make BEV affordable for this patient population. [ABSTRACT FROM AUTHOR]

Key message: Two QTL with pleiotropic effects on plant height and spike length linked in coupling phase on chromosome 2DS were dissected, and diagnostic marker for each QTL was developed. Plant height (PHT) is a crucial trait related to plant architecture and yield potential, and dissection of its underlying genetic basis would help to improve the efficiency of designed breeding in wheat. Here, two quantitative trait loci (QTL) linked in coupling phase on the short arm of chromosome 2D with pleiotropic effects on PHT and spike length, QPht/Sl.cau-2D.1 and QPht/Sl.cau-2D.2, were separated and characterized. QPht/Sl.cau-2D.1 is a novel QTL located between SNP makers BS00022234_51 and BobWhite_rep_c63957_1472. QPht/Sl.cau-2D.2 is mapped between two SSR markers, SSR-2062 and Xgwm484, which are located on the same genomic interval as Rht8. Moreover, the diagnostic marker tightly linked with each QTL was developed for the haplotype analysis using diverse panels of wheat accessions. The frequency of the height-reduced allele of QPht/Sl.cau-2D.1 is much lower than that of QPht/Sl.cau-2D.2, suggesting that this novel QTL may be an attractive target for genetic improvement. Consistent with a previous study of Rht8, a significant difference in cell length was observed between the NILs of QPht/Sl.cau-2D.2. By contrast, there was no difference in cell length between NILs of QPht/Sl.cau-2D.1, indicating that the underlying molecular mechanism for these two QTL may be different. Collectively, these data provide a new example of QTL dissection, and the developed diagnostic markers will be useful in marker-assisted pyramiding of QPht/Sl.cau-2D.1 and/or QPht/Sl.cau-2D.2 with the other genes in wheat breeding. [ABSTRACT FROM AUTHOR]

Key message: Two QTL with pleiotropic effects on plant height and spike length linked in coupling phase on chromosome 2DS were dissected, and diagnostic marker for each QTL was developed.Abstract: Plant height (PHT) is a crucial trait related to plant architecture and yield potential, and dissection of its underlying genetic basis would help to improve the efficiency of designed breeding in wheat. Here, two quantitative trait loci (QTL) linked in coupling phase on the short arm of chromosome 2D with pleiotropic effects on PHT and spike length, QPht/Sl.cau-2D.1 and QPht/Sl.cau-2D.2, were separated and characterized. QPht/Sl.cau-2D.1 is a novel QTL located between SNP makers BS00022234_51 and BobWhite_rep_c63957_1472. QPht/Sl.cau-2D.2 is mapped between two SSR markers, SSR-2062 and Xgwm484, which are located on the same genomic interval as Rht8. Moreover, the diagnostic marker tightly linked with each QTL was developed for the haplotype analysis using diverse panels of wheat accessions. The frequency of the height-reduced allele of QPht/Sl.cau-2D.1 is much lower than that of QPht/Sl.cau-2D.2, suggesting that this novel QTL may be an attractive target for genetic improvement. Consistent with a previous study of Rht8, a significant difference in cell length was observed between the NILs of QPht/Sl.cau-2D.2. By contrast, there was no difference in cell length between NILs of QPht/Sl.cau-2D.1, indicating that the underlying molecular mechanism for these two QTL may be different. Collectively, these data provide a new example of QTL dissection, and the developed diagnostic markers will be useful in marker-assisted pyramiding of QPht/Sl.cau-2D.1 and/or QPht/Sl.cau-2D.2 with the other genes in wheat breeding. [ABSTRACT FROM AUTHOR]

This study aims to develop and validate a prediction model in-hospital mortality in critically ill patients with sepsis-associated acute kidney injury (SA-AKI) based on machine learning algorithms. Patients who met the criteria for inclusion were identified in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and divided according to the validation (n = 2440) and development (n = 9756, 80%) queues. Ensemble stepwise feature selection method was used to screen for effective features. The prediction models of short-term mortality were developed by seven machine learning algorithms. Ten-fold cross-validation was used to verify the performance of the algorithm in the development queue. The area under the receiver operating characteristic curve (ROC-AUC) was used to evaluate the differentiation accuracy and performance of the prediction model in the validation queue. The best-performing model was interpreted by Shapley additive explanations (SHAP). A total of 12,196 patients were enrolled in this study. Eleven variables were finally chosen to develop the prediction model. The AUC of the random forest (RF) model was the highest value both in the Ten-fold cross-validation and evaluation (AUC: 0.798, 95% CI: 0.774–0.821). According to the SHAP plots, old age, low Glasgow Coma Scale (GCS) score, high AKI stage, reduced urine output, high Simplified Acute Physiology Score (SAPS II), high respiratory rate, low temperature, low absolute lymphocyte count, high creatinine level, dysnatremia, and low body mass index (BMI) increased the risk of poor prognosis. The RF model developed in this study is a good predictor of in-hospital mortality for patients with SA-AKI in the intensive care unit (ICU), which may have potential applications in mortality prediction. [ABSTRACT FROM AUTHOR]

This article was unintentionally published twice in this journal. [ABSTRACT FROM AUTHOR]

This article was unintentionally published twice in this journal. [ABSTRACT FROM AUTHOR]

Background: DNA marker profiles play a crucial role in the identification and registration of germplasm, as well as in the distinctness, uniformity, and stability (DUS) testing of new plant variety protection. However, selecting minimal marker sets from large-scale SNP dataset can be challenging to distinguish a maximum number of samples. Results: Here, we developed the CoreSNP pipeline using a "divide and conquer" strategy and a "greedy" algorithm. The pipeline offers adjustable parameters to guarantee the distinction of each sample pair with at least two markers. Additionally, it allows datasets with missing loci as input. The pipeline was tested in barley, soybean, wheat, rice and maize. A few dozen of core SNPs were efficiently selected in different crops with SNP array, GBS, and WGS dataset, which can differentiate thousands of individual samples. The core SNPs were distributed across all chromosomes, exhibiting lower pairwise linkage disequilibrium (LD) and higher polymorphism information content (PIC) and minor allele frequencies (MAF). It was shown that both the genetic diversity of the population and the characteristics of the original dataset can significantly influence the number of core markers. In addition, the core SNPs capture a certain level of the original population structure. Conclusions: CoreSNP is an efficiency way of core marker sets selection based on Genome-wide SNP datasets of crops. Combined with low-density SNP chip or genotyping technologies, it can be a cost-effective way to simplify and expedite the evaluation of genetic resources and differentiate different crop varieties. This tool is expected to have great application prospects in the rapid comparison of germplasm and intellectual property protection of new varieties. [ABSTRACT FROM AUTHOR]

• A systematic review and meta-analysis examining the efficacy and safety of molnupiravir treatment for COVID-19. • No significant difference was observed between two groups in terms of mortality and hospitalisation. • The clinical improvement and RT-PCR negativity rate were higher in the molnupiravir group than the control group within 10 days. • There was no significant difference in terms of adverse events and serious adverse events between the two groups. There are currently some differences in the research results of molnupiravir. This study aimed to evaluate the efficacy and safety of molnupiravir in the treatment of COVID-19. PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), ClinicalTrials.gov, ICTRP (International Clinical Trials Registry Platform) and medRxiv were searched to identify relevant randomised controlled trials (RCTs) from inception to 1 January 2023. The Cochrane risk of bias tool for randomised trials was used to assess the bias risk of the included studies. Revman 5.4 software was used for meta-analysis. Nine RCTs were included, including 31 573 COVID-19 patients, of whom 15 846 received molnupiravir. The meta-analysis results showed that the molnupiravir group had a higher proportion in terms of clinical improvement (Day 5 RR 2.41, 95% CI 1.18–4.92; Day 10 RR 1.45, 95% CI 1.04–2.01) and real-time polymerase chain reaction negativity (Day 5 RR 2.78, 95% CI 1.38–5.62; Day 10 RR 1.18, 95% CI 1.07–1.31). However, no significant difference was observed between the two groups in terms of mortality, hospitalisation, adverse events and serious adverse events. Molnupiravir can accelerate the rehabilitation of COVID-19 patients, but it does not significantly reduce mortality and hospitalisation. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NBL) is an extracranial malignant tumor in children deriving from the neural crest in the sympathetic nervous system. Although various immunotherapy interventions have made significant breakthroughs in many adult cancers, the efficacy of these immunotherapies was still limited in NBL. NBL has low immunogenicity which results in a lack of tumor-infiltrating T lymphocytes in the tumor microenvironment (TME). Moreover, tumor cells can wield many immune evasion strategies both in the TME and systemically to impede lymphocyte infiltration and activation. All these factors hamper the anti-tumor effects of CD8+ T cells during immunotherapy and the levels of infiltrating CD8+ T cells correlate with therapy response. Materials and methods: In this study, we utilized multidimensional bioinformatic methods to establish a risk model based on CD8+ T cells -related genes (CD8+ TRGs). Results: We obtained 33 CD8+ TRGs with well-predictive ability for prognosis in both GSE49711 and E-MTAB-8248 cohorts. Then, 12 CD8+ TRGs including HK2, RP2, HPSE, ELL2, GFI1, SLC22A16, FCGR3A, CTSS, SH2D1A, RBP5, ATF5, and ADAM9 were finally identified for risk model construction and validation. This model revealed a stable performance in prognostic prediction of the overall survival (OS) and event-free survival (EFS) in patients with NBL. Additionally, our research indicated that the immune and stromal scores, immune-related pathways, immune cell infiltration, the expression of major histocompatibility complex (MHC) and immune checkpoint molecules, immunotherapy response, and drug susceptibility revealed significant differences between high and low-risk groups. Conclusions: According to our analyses, the constructed CD8+ TRGs-based risk model may be promising for the clinical prediction of anti-tumor therapy responses and prognoses in NBL. [ABSTRACT FROM AUTHOR]

Background Bacterial toxin-antitoxin (TA) modules respond to various stressful conditions. The Gcn5-related N -acetyltransferase-type toxin (GNAT) protein encoded by the GNAT-RHH TA locus is involved in the antibiotic tolerance of Klebsiella pneumoniae. Objectives To investigate the transcriptional mechanism of the GNAT-RHH operon kacAT under antibiotic stress. Methods The transcriptional level of the kacAT operon of K. pneumoniae was measured by quantitative real-time (qRT) PCR assay. The degradation of antitoxin KacA was examined by western blot and fluorescent protein. The ratio of [KacA]:[KacT] was calculated by the fluorescence intensity of KacA-eGFP and mCherry-KacT. Mathematical modelling predicted protein and transcript synthesis dynamics. Results A meropenem-induced increase in transcript levels of kacA and kacT resulted from the relief from transcriptional autoregulation of the kacAT operon. Meropenem induces the degradation of KacA through Lon protease, resulting in a reduction in the ratio of [KacA]:[KacT]. The decreased ratio causes the dissociation of the KacAT complex from its promoter region, which eliminates the repression of kacAT transcription. In addition, our dynamic model of kacAT expression regulation quantitatively reproduced the experimentally observed reduction of the [KacA]:[KacT] ratio and a large increase in kacAT transcript levels under the condition of strong promoter autorepression by the KacAT complex. Conclusions Meropenem promotes the degradation of antitoxin by enhancing the expression of Lon protease. Degradation of antitoxin reduces the ratio of intracellular [antitoxin]:[toxin], leading to detachment of the TA complex from its promoter, and releasing repression of TA operon transcription. These results may provide an important insight into the transcriptional mechanism of GNAT-RHH TA modules under antibiotic stress. [ABSTRACT FROM AUTHOR]

Rht8 is a gibberellin-sensitive Reduced height (Rht) locus that has been widely used in crop wheat semi-dwarfing breeding. In this study, the authors reported the map-based cloning of Rht8 candidate gene, and confirmed that loss of Ribonuclease H-Like 1 (RNHL-D1) is responsible for Rht8 semi-dwarfing effect. [ABSTRACT FROM AUTHOR]

Key message: This study demonstrated that the aberrant transcription of DvGW2 contributed to the increased grain width and thousand-grain weight in wheat-Dasypyrum villosum T6VS·6DL translocation lines. Due to the high immunity to powdery mildew, Dasypyrum villosum 6VS has been one of the most successful applications of the wild relatives in modern wheat breeding. Along with the desired traits, side-effects could be brought when large alien chromosome fragments are introduced into wheat, but little is known about effects of 6VS on agronomic traits. Here, we found that T6VS·6DL translocation had significantly positive effects on grain weight, plant heightand spike length, and small negative effects on total spikelet number and spikelet compactness using recipient and wheat-D. villosum T6VS·6DL allohexaploid wheats, Wan7107 and Pm97033. Further analysis showed that the 6VS segment might exert direct genetic effect on grain width, then driving the increase of thousand-grain weight. Furthermore, comparative transcriptome analysis identified 2549 and 1282 differentially expressed genes (DEGs) and 2220 and 1496 specifically expressed genes (SEGs) at 6 days after pollination (DAP) grains and 15 DAP endosperms, respectively. Enrichment analysis indicated that the process of cell proliferation category was over-represented in the DEGs. Notably, two homologous genes, TaGW2-D1 and DvGW2, were identified as putative candidate genes associated with grain weight and yield. The expression analysis showed that DvGW2 had an aberrant expression in Pm97033, resulting in significantly lower total expression level of GW2 than Wan7107, which drives the increase of grain weight and width in Pm97033. Collectively, our data indicated that the compromised expression of DvGW2 is critical for increased grain width and weight in T6VS·6DL translocation lines. [ABSTRACT FROM AUTHOR]

Summary: Grain yield in bread wheat (Triticum aestivum L.) is largely determined by inflorescence architecture. Zang734 is an endemic Tibetan wheat variety that exhibits a rare triple spikelet (TRS) phenotype with significantly increased spikelet/floret number per spike. However, the molecular basis underlying this specific spike morphology is completely unknown.Through map‐based cloning, the causal genes for TRS trait in Zang734 were isolated. Furthermore, using CRISPR/Cas9‐based gene mutation, transcriptome sequencing and protein–protein interaction, the downstream signalling networks related to spikelet formation and awn elongation were defined.Results showed that the null mutation in WFZP‐A together with deletion of WFZP‐D led to the TRS trait in Zang734. More interestingly, WFZP plays a dual role in simultaneously repressing spikelet formation gene TaBA1 and activating awn development genes, basically through the recruitments of chromatin remodelling elements and the Mediator complex.Our findings provide insights into the molecular bases by which WFZP suppresses spikelet formation but promotes awn elongation and, more importantly, define WFZP‐D as a favourable gene for high‐yield crop breeding. [ABSTRACT FROM AUTHOR]

Objective: The aim was to evaluate the performance of the initial Chinese geriatric trigger tool to detect adverse drug events (ADEs) in Chinese older patients, to attempt to shorten this list for improving the efficiency of the trigger tool, and to study the incidence and characteristics of ADEs in this population. Methods: A sample of 25 cases was randomly selected per half a month from eligible patients who aged 60 years and older, hospitalized more than 24 hours, and discharged or died between January 1, 2015 and December 31, 2017 in West China hospital. A two-stage retrospective chart review of the included inpatients were conducted. ADEs were detected using a list of 42 triggers previously selected by an expert panel by means of a Delphi method. The number of triggers identified and ADEs detected were recorded and the positive predictive value (PPV) of each trigger was calculated to select the most efficient triggers. Several variables were recorded, including age, sex, number of diseases, length of hospital stay and so on, to analyze the risk factor of ADEs. Results: Among 1800 patients, 1646 positive triggers and 296 ADEs were detected in 234 (13.00%) patients. Older patients who were younger, had more medications, longer stays or more admission, and did not experience surgical operation more likely experienced ADEs. Triggers with PPV less than 5% were eliminated, which resulted in the upgraded version of Chinese geriatric trigger tool of 20 triggers with a PPV of 28.50%. This upgraded tool accounted for 99.66% of all ADEs detected. Conclusions: The upgraded version of Chinese geriatric trigger tool was an efficient tool for identifying ADEs in Chinese older patients. Future, the trigger tool could be incorporated into routine screen systems to provide real-time identification of ADEs, thereby enabling timely clinical interventions. [ABSTRACT FROM AUTHOR]

Key message: The semidominant EMS-induced mutant w5 affects epicuticular wax deposition and mapped to an approximately 194-kb region on chromosome 7DL. Epicuticular wax is responsible for the glaucous appearance of plants and protects against many biotic and abiotic stresses. In wheat (Triticum aestivum L.), β-diketone is a major component of epicuticular wax in adult plants and contributes to the glaucousness of the aerial organs. In the present study, we identified an ethyl methanesulfonate-induced epicuticular wax-deficient mutant from the elite wheat cultivar Jimai22. Compared to wild-type Jimai22, the mutant lacked β-diketone and failed to form the glaucous coating on all aerial organs. The mutant also had significantly increased in cuticle permeability, based on water loss and chlorophyll efflux. Genetic analysis indicated that the mutant phenotype is controlled by a single, semidominant gene on the long arm of chromosome 7D, which was not allelic to the known wax gene loci W1–W4, and was therefore designated W5. W5 was finely mapped to an ~ 194-kb region (flanked by the molecular markers SSR2 and STARP11) that harbored four annotated genes according to the reference genome of Chinese Spring (RefSeq v1.0). Collectively, these data will broaden the knowledge of the genetic basis underlying epicuticular wax deposition in wheat. [ABSTRACT FROM AUTHOR]

Six subspecies of hexaploid wheat (Triticum   aestivum) have been identified, but the origin of Indian dwarf wheat (Triticum sphaerococcum), the only subspecies with round grains, is currently unknown. Here, we isolated the grain-shape gene Tasg-D1 in T. sphaerococcum via positional cloning. Tasg-D1 encodes a Ser/Thr protein kinase glycogen synthase kinase3 (STKc_GSK3) that negatively regulates brassinosteroid signaling. Expression of TaSG-D1 and the mutant form Tasg-D1 in Arabidopsis (Arabidopsis thaliana) suggested that a single amino acid substitution in the Thr-283-Arg-284-Glu-285-Glu-286 domain of TaSG-D1 enhances protein stability in response to brassinosteroids, likely leading to formation of round grains in wheat. This gain-of-function mutation has pleiotropic effects on plant architecture and exhibits incomplete dominance. Haplotype analysis of 898 wheat accessions indicated that the origin of T. sphaerococcum in ancient India involved at least two independent mutations of TaSG-D1. Our results demonstrate that modest genetic changes in a single gene can induce dramatic phenotypic changes. [ABSTRACT FROM AUTHOR]

Objective: Vitamin 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. Methods: A 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. Results: 95 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). Conclusions: These 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. [ABSTRACT FROM AUTHOR]