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Abstract. Background:. Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening. Methods:. We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial. Results:. This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios. Conclusion:. This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

PURPOSESurvival from esophageal cancer (EC) is poor, partly reflecting the delay in diagnosis. To inform the potential measures for downstaging the disease, we estimated diagnosis delay, that is, the length of interval from symptom-to-diagnosis (STD), and investigated its correlates among patients with EC in a high-risk resource-limited rural area in China.METHODSPatients newly diagnosed with EC (N = 411) were recruited in a secondary hospital in Henan province in China between August 1, 2018, and October 21, 2020. A face-to-face structured questionnaire was used to collect patient-level and health-seeking data from patients and/or proxies. Association between the length of STD interval and stage at diagnosis was examined using logistic regression. Correlates of the length of the STD interval were identified using negative binomial regression.RESULTSThe median STD interval was 61 (IQR, 24-155) days, with the time from symptom onset to first health care contact representing 90.1% (IQR, 7.8%-100%) of its length. The odds of being diagnosed at stages III-IV increased by 3% (age- and sex-adjusted odds ratio, 1.03 [95% CI, 0.99 to 1.08]) for every 2-month increase in the STD interval. Higher awareness of EC risk factors was associated with shorter STD intervals (incidence rate ratio [95% CI] for awareness score ≥2 v ≤0: 0.65 [0.46 to 0.93]), whereas patients who first visited secondary or tertiary/cancer hospitals had much longer STD intervals than those who first visited a primary health care facility (1.69 [1.19 to 2.40]; 2.22 [1.24 to 3.97]).CONCLUSIONThe median length of the STD interval was 2 months, but with considerable interindividual variability. Improving EC awareness, coupled with effective referral pathways, may promote timely diagnosis of this disease.

Some haplotypes of the sucrose synthase gene TaSus1 are associated with thousand-grain weight (TGW) in wheat (Triticum aestivum L.). However, no mutations have been identified within the gene to test this association. The effects of TaSus1 on grain number per spike (GNS) also are largely unknown. Our previous genome-wide association study identified TaSus-A1 as a candidate gene controlling fertile spikelet number per spike (FSN). In the present study, we generated two independent mutants for the three TaSus1 homoeologs by CRISPR/Cas9-mediated genome editing. The triple mutants displayed lower FSN, GNS, grain number per spikelet (GNST), and TGW than wild-type plants. In 306 hexaploid wheat accessions, two single-nucleotide polymorphisms in TaSus-A1 contributed differently to GNS. Introgression of the two alleles into a wheat genetic background confirmed their effects. The alleles differed in geographical distribution among the accessions.

PURPOSETo characterize the pattern of post-treatment quality of life (QoL) for esophageal cancer (EC) survivors and construct models predicting their long-term QoL.METHODSOn the basis of a randomized trial in an EC high-risk region in China, we interviewed 363 EC survivors and 25,245 permanent residents matched with the survivors on age, sex, and township as the baseline. QoL was measured using three-level version of European Quality of Life 5-Dimensions instrument. We constructed piecewise mixed models estimating the QoL of EC survivors that varied by age, sex, patient type, hospital level, and therapy to ascertain QoL determinants.RESULTSThe post-treatment QoL of EC survivors dropped by 15.7% within the first year and recovered by 9.3% between 1 and 9 years compared with the baseline. Therapy was found to be a determinant of QoL, and a series of therapy-specific models were fitted accordingly, which all showed the pattern of decreasing rapidly and recovering gradually. Endoscopic treatment had the least impact on post-treatment QoL (7.5% drop within 5 years) compared with esophagectomy (12.2% drop within 1 year) and chemoradiotherapy (37.8% drop within 2 years). The usual activities dimension showed the greatest impairment among those patients (34.4% drop within 1 year).CONCLUSIONThis community-based study described the long-term QoL trajectory for EC survivors after different therapeutic modalities and constructed models to predict therapy-specific QoL at different time points after treatment. It provided new insights into decision making in treatment for EC from the perspective of QoL protection, offering a convenient tool for estimating quality-adjusted life-years.

Abstract Background Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population. Patients and Methods We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire‐9 (PHQ‐9), respectively. A multivariable logistic regression model was employed to establish the model structure. Results In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS‐A score, HADS‐D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82–0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types. Conclusion This study built an easy‐to‐use, good‐performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.

Summary: Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.

Despite recent advances in crop metabolomics, the genetic control and molecular basis of the wheat kernel metabolome at different developmental stages remain largely unknown. Here, we performed widely targeted metabolite profiling of kernels from three developmental stages (grain-filling kernels [FKs], mature kernels [MKs], and germinating kernels [GKs]) using a population of 159 recombinant inbred lines. We detected 625 annotated metabolites and mapped 3173, 3143, and 2644 metabolite quantitative trait loci (mQTLs) in FKs, MKs, and GKs, respectively. Only 52 mQTLs were mapped at all three stages, indicating the high stage specificity of the wheat kernel metabolome. Four candidate genes were functionally validated by in vitro enzymatic reactions and/or transgenic approaches in wheat, three of which mediated the tricin metabolic pathway. Metabolite flux efficiencies within the tricin pathway were evaluated, and superior candidate haplotypes were identified, comprehensively delineating the tricin metabolism pathway in wheat. Finally, additional wheat metabolic pathways were re-constructed by updating them to incorporate the 177 candidate genes identified in this study. Our work provides new information on variations in the wheat kernel metabolome and important molecular resources for improvement of wheat nutritional quality.

Abstract Background Current guidelines recommend only severe dysplasia and above (SDA) lesions of the esophageal squamous epithelium for clinical intervention. However, the histopathologic diagnosis derived from tissue biopsies may be subject to underestimation of severity. Methods 1073 participants from whom biopsies were taken at baseline chromoendoscopic examination in a population‐based screening trial were enrolled in this study. The size of the Lugol‐unstained lesions (LULs) was mainly analyzed. The outcome was defined as SDA lesions either identified at baseline screening, or during follow‐up, collectively referred to as the cumulative risk of SDA. Multivariable logistic regression models were used to evaluate the cumulative risk of SDA. Results One hundred and forty‐six SDA cases were identified in the study period. Participants with large LULs had a high cumulative incidence of SDA (cumulative incidence16–20mm: 55.88%; cumulative incidence>20mm: 76.92%) in the median of 7‐year duration. LULs of large size were significantly associated with a higher cumulative risk of SDA, regardless of the pathologic diagnosis (adjusted OR16–20mmvs.≤5mm = 21.02, 95% CI: 7.56–58.47; adjusted OR>20mmvs.≤5mm = 33.62, 95% CI: 11.79–95.87). Conclusions Results from this study suggest physician–patient shared decision‐making regarding clinical treatment or intensive surveillance should be carried out for LULs >20 mm in the esophagus, regardless of the histologic diagnosis. For those with LULs of 16–20 mm, intensive surveillance would also best be considered.

Many genetic loci for wheat plant height (PH) have been reported, and 26 dwarfing genes have been catalogued. To identify major and stable genetic loci for PH, here we thoroughly summarized these functionally or genetic verified dwarfing loci from QTL linkage analysis and genome-wide association study published from 2003 to 2022. A total of 332 QTL, 270 GWAS loci and 83 genes for PH were integrated onto chromosomes according to their locations in the IWGSC RefSeq v2.1 and 65 QTL-rich clusters (QRC) were defined. Candidate genes in each QRC were predicted based on IWGSC Annotation v2.1 and the information on functional validation of homologous genes in other species. A total of 38 candidate genes were predicted for 65 QRC including three GA2ox genes in QRC-4B-IV, QRC-5A-VIII and QRC-6A-II (Rht24) as well as GA 20-oxidase 2 (TaSD1-3A) in QRC-3A-IV. These outcomes lay concrete foundations for map-based cloning of wheat dwarfing genes and application in breeding.

Abstract Background Large-scale genotype–phenotype association studies of crop germplasm are important for identifying alleles associated with favorable traits. The limited number of single-nucleotide polymorphisms (SNPs) in most wheat genome-wide association studies (GWASs) restricts their power to detect marker-trait associations. Additionally, only a few genes regulating grain number per spikelet have been reported due to sensitivity of this trait to variable environments. Results We perform a large-scale GWAS using approximately 40 million filtered SNPs for 27 spike morphology traits. We detect 132,086 significant marker-trait associations and the associated SNP markers are located within 590 associated peaks. We detect additional and stronger peaks by dividing spike morphology into sub-traits relative to GWAS results of spike morphology traits. We propose that the genetic dissection of spike morphology is a powerful strategy to detect signals for grain yield traits in wheat. The GWAS results reveal that TaSPL17 positively controls grain size and number by regulating spikelet and floret meristem development, which in turn leads to enhanced grain yield per plant. The haplotypes at TaSPL17 indicate geographical differentiation, domestication effects, and breeding selection. Conclusion Our study provides valuable resources for genetic improvement of spike morphology and a fast-forward genetic solution for candidate gene detection and cloning in wheat.

Pre-harvest sprouting (PHS) is one of the serious global issues in wheat production. Identification of quantitative trait loci (QTL) and closely-linked markers is greatly helpful for wheat improvement. In the present study, a recombinant inbred line (RIL) population derived from the cross of Zhongmai 578 (ZM578)/Jimai 22 (JM22) and parents were phenotyped in five environments and genotyped by the wheat 50 K single-nucleotide polymorphism (SNP) array. Two QTL of germination index (GI), QGI.caas-3A and QGI.caas-5A, were detected, explaining 4.33%–5.58% and 4.43%–8.02% of the phenotypic variances, respectively. The resistant effect of QGI.caas-3A was contributed by JM22, whereas that of QGI.caas.5A was from ZM578. The two QTL did not correspond to any previously identified genes or genetic loci for PHS-related traits according to their locations in the Chinese Spring reference genome, indicating that they are likely to be new loci for PHS resistance. Four kompetitive allele-specific PCR (KASP) markers K_AX-109605367and K_AX-179559687 flanking QGI.caas-3A, and K_AX-111258240 and K_AX-109402944 flanking QGI.caas-5A, were developed and validated in a natural population of 100 wheat cultivars. The distribution frequency of resistance alleles at Qphs.caas-3A and Qphs.caas-5A loci were 82.7% and 57.1%, respectively, in the natural population. These findings provide new QTL and tightly linked KASP markers for improvement of PHS resistance in wheat.

Abstract Background Plant architecture associated with increased grain yield and adaptation to the local environments is selected during wheat (Triticum aestivum) breeding. The internode length of individual stems and tiller length of individual plants are important for the determination of plant architecture. However, few studies have explored the genetic basis of these traits. Results Here, we conduct a genome-wide association study (GWAS) to dissect the genetic basis of geographical differentiation of these traits in 306 worldwide wheat accessions including both landraces and traditional varieties. We determine the changes of haplotypes for the associated genomic regions in frequency in 831 wheat accessions that are either introduced from other countries or developed in China from last two decades. We identify 83 loci that are associated with one trait, while the remaining 247 loci are pleiotropic. We also find 163 associated loci are under strong selective sweep. GWAS results demonstrate independent regulation of internode length of individual stems and consistent regulation of tiller length of individual plants. This makes it possible to obtain ideal haplotype combinations of the length of four internodes. We also find that the geographical distribution of the haplotypes explains the observed differences in internode length among the worldwide wheat accessions. Conclusion This study provides insights into the genetic basis of plant architecture. It will facilitate gene functional analysis and molecular design of plant architecture for breeding.

Grain weight and grain number are important yield component traits in wheat and identification of underlying genetic loci is helpful for improving yield. Here, we identified eight stable quantitative trait loci (QTL) for yield component traits, including five loci for thousand grain weight (TGW) and three for grain number per spike (GNS) in a recombinant inbred line population derived from cross Yangxiaomai/Zhongyou 9507 across four environments. Since grain size is a major determinant of grain weight, we also mapped QTL for grain length (GL) and grain width (GW). QTGW.caas-2D, QTGW.caas-3B, QTGW.caas-5A and QTGW.caas-7A.2 for TGW co-located with those for grain size. QTGW.caas-2D also had a consistent genetic position with QGNS.caas-2D, suggesting that the pleiotropic locus is a modulator of trade-off effect between TGW and GNS. Sequencing and linkage mapping showed that TaGL3-5A and WAPO-A1 were candidate genes of QTGW.caas-5A and QTGW.caas-7A.2, respectively. We developed Kompetitive allele specific PCR (KASP) markers linked with the stable QTL for yield component traits and validated their genetic effects in a diverse panel of wheat cultivars from the Huang-Huai River Valley region. KASP-based genotyping analysis further revealed that the superior alleles of all stable QTL for TGW but not GNS were subject to positive selection, indicating that yield improvement in the region largely depends on increased TGW. Comparative analyses with previous studies showed that most of the QTL could be detected in different genetic backgrounds, and QTGW.caas-7A.1 is likely a new QTL. These findings provide not only valuable genetic information for yield improvement but also useful tools for marker-assisted selection.

Abstract We evaluated root system architecture (RSA) of a set of 58 historical spring wheat cultivars from Pakistan representing 105 years of selection breeding. The evaluations were carried out under control and water-limited conditions using a high-throughput phenotyping system coupled with RhizoVision Explorer software. The cultivars were classified into three groups based on release year as cultivars released pre-1965, released between 1965 and 2000, and cultivars released post-2000. Under water-limited conditions a decline in 20 out of 25 RSA component traits was observed in pre-1965 cultivars group. Whereas cultivars released after the 1965, so-called green revolution period, showed a decline in 17 traits with significant increments in root length, depth, and steep angle frequency which are important root traits for resource-uptake under water-limited conditions. Similarly, cultivars released after 2000 indicated an increase in the number of roots, depth, diameter, surface area, and steep angle frequency. The coefficient of correlation analysis showed a positive correlation between root depth and yield-related traits under water-limited conditions. We also investigated the effects of green-revolution genes (Rht1) and some phenology-related genes such as DRO1, TaMOR, TaLTPs, TaSus-2B on RSA and identified significant associations of these genes with important root traits. There was strong selection pressure on DRO1 gene in cultivated wheat indicating the allele fixed in modern wheat cultivars is different from landraces. The expression of DRO1, and TaMOR were retrieved from an RNAseq experiment, and results were validated using qRT-PCR. The highest expression of DRO1 and TaMOR was found in Chakwal-50, a rainfed cultivar released in 2008, and MaxiPak-65 released in 1965. We conclude that there is a positive historic change in RSA after 1965 that might be attributed to genetic factors associated with favored RSA traits. Furthermore, we suggest root depth and steep angle as promising traits to withstand water-limited environments and may have implications in selection for breeding.

BackgroundTumor markers are routinely used in clinical practice. However, for resectable patients with esophageal squamous cell carcinoma (ESCC), they are applied infrequently as their prognostic significance is incompletely understood.MethodsThis historical cohort study included 2769 patients with resected ESCC from 2011 to 2018 in a high-risk area in northern China. Their clinical data were extracted from the Electronic Medical Record. Survival analysis of eight common tumor markers was performed with multivariable Cox proportional hazards regressions.ResultsWith a median follow-up of 39.5 months, 901 deaths occurred. Among the eight target markers, elevated postoperative serum SCC (Squamous cell carcinoma antigen) and CEA (Carcinoembryonic antigen) predicted poor overall survival (SCC HRadjusted: 2.67, 95% CI: 1.70-4.17; CEA HRadjusted: 2.36, 95% CI: 1.14-4.86). In contrast, preoperative levels were not significantly associated with survival. Stratified analysis also demonstrated poorer survival in seropositive groups of postoperative SCC and CEA within each TNM stage. The above associations were generally robust using different quantiles of concentrations above the upper limit of the clinical normal range as alternative cutoffs. Regarding temporal trends of serum levels, SCC and CEA were similar. Their concentrations fell rapidly after surgery and thereafter remained relatively stable.ConclusionPostoperative serum SCC and CEA levels predict the overall survival of ESCC surgical patients. More importance should be attached to the use of these markers in clinical applications.

The increase in root hair length and density is considered an effective way to deal with external phosphorous (P) limitation. The identification of useful loci for root hair traits is crucial for wheat breeding. Here, We employed a simple, cost-effective, and medium-throughput screening method using cigar rolls to assess P-responsive root hair length (RHL) and density (RHD) in bread wheat at the seedling stage. A set of 113 historical bread wheat cultivars was screened for root hair length and density (RHL/D) under low (0.005 mM KH2PO4) and high P-levels (0.25 mM KH2PO4). Significant variations (p

Spike number (SN) per unit area is one of the major determinants of grain yield in wheat. Development of high-throughput techniques to count SN from large populations enables rapid and cost-effective selection and facilitates genetic studies. In the present study, we used a deep-learning algorithm, i.e., Faster Region-based Convolutional Neural Networks (Faster R-CNN) on Red-Green-Blue (RGB) images to explore the possibility of image-based detection of SN and its application to identify the loci underlying SN. A doubled haploid population of 101 lines derived from the Yangmai 16/Zhongmai 895 cross was grown at two sites for SN phenotyping and genotyped using the high-density wheat 660K SNP array. Analysis of manual spike number (MSN) in the field, image-based spike number (ISN), and verification of spike number (VSN) by Faster R-CNN revealed significant variation (P

Polyphenol oxidase (PPO) activity is a major cause of the undesirable brown color of wheat-based products. Ppo1, a major gene for PPO activity, was cloned based on sequence homology in previous studies; however, its function and regulation mechanism remain unclear. In this study, the function and genetic regulation of Ppo1 were analyzed using RNA interference (RNAi) and Targeting Induced Local Lesions IN Genomes (TILLING) technology, and superior mutants were identified. Compared with the control, the level of Ppo1 transcript in RNAi transgenic lines was drastically decreased by 15.5%–60.9% during grain development, and PPO activity was significantly reduced by 12.9%–20.4%, confirming the role of Ppo1 in PPO activity. Thirty-two Ppo1 mutants were identified in the ethyl methanesulfonate (EMS)-mutagenized population, including eight missense mutations, 16 synonymous mutations, and eight intron mutations. The expression of Ppo1 was reduced significantly by 6.7%–37.1% and 10.1%–54.4% in mutants M092141 (G311S) and M091098 (G299R), respectively, in which PPO activity was decreased by 29.7% and 28.8%, respectively, indicating that mutation sites of two mutants have important effects on PPO1 function. Sequence and structure analysis revealed that the two sites were highly conserved among 74 plant species, where the frequency of glycine was 94.6% and 100%, respectively, and adjacent to the entrance of the hydrophobic pocket of the active site. The M092141 and M091098 mutants can be used as important germplasms to develop wheat cultivars with low grain PPO activity. This study provided important insights into the molecular mechanism of Ppo1 and the genetic improvement of wheat PPO activity.

Wheat coleoptile is a sheath-like structure that helps to deliver the first leaf from embryo to the soil surface. Here, a RIL population consisting of 245 lines derived from Zhou 8425B × Chinese Spring cross was genotyped by the high-density Illumina iSelect 90K assay for coleoptile length (CL) QTL mapping. Three QTL for CL were mapped on chromosomes 2BL, 4BS and 4DS. Of them, two major QTL QCL.qau-4BS and QCL.qau-4DS were detected, which could explain 9.1%–22.2% of the phenotypic variances across environments on Rht-B1 and Rht-D1 loci, respectively. Several studies have reported that Rht-B1b may reduce the length of wheat CL but no study has been carried out at molecular level. In order to verify that the Rht-B1 gene is the functional gene for the 4B QTL, an overexpression line Rht-B1b-OE and a CRISPR/SpCas9 line Rht-B1b-KO were studied. The results showed that Rht-B1b overexpression could reduce the CL, while loss-of-function of Rht-B1b would increase the CL relative to that of the null transgenic plants (TNL). To dissect the underlying regulatory mechanism of Rht-B1b on CL, comparative RNA-Seq was conducted between Rht-B1b-OE and TNL. Transcriptome profiles revealed a few key pathways involving the function of Rht-B1b in coleoptile development, including phytohormones, circadian rhythm and starch and sucrose metabolism. Our findings may facilitate wheat breeding for longer coleoptiles to improve seedling early vigor for better penetration through the soil crust in arid regions.

Abstract Background The association of early-life undernutrition and dyslipidemia found in previous studies may be confounded by the uncontrolled age difference between exposed and unexposed participants. The study aimed to investigate the association of early-life undernutrition and the risk of dyslipidemia in adulthood with good control of the age variable. Methods We took the Great Chinese Famine (1959–1961) as a natural experiment of severe undernutrition. This study was based on the baseline investigation of a population-based cohort in rural China. Undernutrition in early life was defined as being exposed to famine at younger than 3 years of age. Three approaches including Adjustment, Restriction, and Matching were applied to control the confounding effect of age. Logistic regression models were applied to evaluate the association between early-life famine and the presence of dyslipidemia. Stratified analysis by gender was also performed, and potential effect modification was tested by adding the interaction term of the famine exposure variable and gender into the model. Results Undernutrition in early life was associated with increased risk of borderline high and above (BHA) levels of total cholesterol (TC, ORAdjustment = 1.61; ORRestriction = 1.56; ORMatching = 1.87), triglycerides (TG, ORAdjustment = 1.33; ORRestriction = 1.30; ORMatching = 1.34), low-density lipoprotein cholesterol (LDL-C, ORAdjustment = 1.75; ORRestriction = 1.53; ORMatching = 1.77) and dyslipidemia (ORAdjustment = 1.52; ORRestriction = 1.45; ORMatching = 1.60), as well as high levels of TC, TG, LDL-C and dyslipidemia. An inverse association of undernutrition and risk of low high-density lipoprotein cholesterol (HDL-C) was found. Female participants with undernutrition experience had an increased risk of BHA TG and LDL-C (TG: ORAdjustment, female = 1.45; ORRestriction, female = 1.39; ORMatching, female = 1.51; LDL-C: ORAdjustment, female = 2.11; ORRestriction, female = 1.80; ORMatching, female = 2.15), but this association was not found in males. Conclusion Early-life undernutrition increased the risk of TC, TG, LDL-C, and dyslipidemia. Gender would significantly modify this effect for TG and LDL-C. These results emphasize the importance of nutritional conditions in the early stages of life to long-term health consequences.

BackgroundConventional universal endoscopic screening with pathology-based endoscopic re-examination for esophageal squamous cell carcinoma is in need of reform in China. We established a “two-step” precision screening strategy using two risk prediction models and have evaluated the cost-effectiveness of this precision strategy compared with the traditional strategy based on a large population-level randomized controlled trial from a healthcare provider’s perspective.MethodsFour precision screening strategies with different risk cutoffs at baseline screening and endoscopic surveillance were constructed, and then compared with traditional strategy through modeling using subjects from the screening cohort of the ESECC (Endoscopic Screening for Esophageal Cancer in China) trial. Total screening costs and the number of SDA (severe dysplasia and above in lesions of the esophagus) cases were obtained to calculate the average screening cost per SDA detected, the incremental cost-effectiveness ratio (ICER) and protection rates. Sensitivity analysis was conducted to evaluate uncertainties.ResultsCompared to traditional strategy, all precision screening strategies have much lower average costs for detection of one SDA case ($7,148~$11,537 vs. $14,944). In addition, precision strategies 1&2 (strategies 1,2,3,4 described below) achieved higher effectiveness (143~150 vs. 136) and higher protection rates (87.7%~92.0% vs. 83.4%) at lower cost ($1,649,727~$1,672,221 vs. $2,032,386), generating negative ICERs (-$54,666/SDA~-$25,726/SDA) when compared to the traditional strategy. The optimal strategies within different willingness-to-pay (WTP) ranges were all precision screening strategies, and higher model sensitivities were adopted as WTP increased.ConclusionsPrecision screening strategy for esophageal cancer based on risk stratification is more cost-effective than use of traditional screening strategy and has practical implications for esophageal cancer screening programs in China.

Abstract Background Phosphorus (P) is an important in ensuring plant morphogenesis and grain quality, therefore an efficient root system is crucial for P-uptake. Identification of useful loci for root morphological and P uptake related traits at seedling stage is important for wheat breeding. The aims of this study were to evaluate phenotypic diversity of Yangmai 16/Zhongmai 895 derived doubled haploid (DH) population for root system architecture (RSA) and biomass related traits (BRT) in different P treatments at seedling stage using hydroponic culture, and to identify QTL using 660 K SNP array based high-density genetic map. Results All traits showed significant variations among the DH lines with high heritabilities (0.76 to 0.91) and high correlations (r = 0.59 to 0.98) among all traits. Inclusive composite interval mapping (ICIM) identified 34 QTL with 4.64–20.41% of the phenotypic variances individually, and the log of odds (LOD) values ranging from 2.59 to 10.43. Seven QTL clusters (C1 to C7) were mapped on chromosomes 3DL, 4BS, 4DS, 6BL, 7AS, 7AL and 7BL, cluster C5 on chromosome 7AS (AX-109955164 - AX-109445593) with pleiotropic effect played key role in modulating root length (RL), root tips number (RTN) and root surface area (ROSA) under low P condition, with the favorable allele from Zhongmai 895. Conclusions This study carried out an imaging pipeline-based rapid phenotyping of RSA and BRT traits in hydroponic culture. It is an efficient approach for screening of large populations under different nutrient conditions. Four QTL on chromosomes 6BL (2) and 7AL (2) identified in low P treatment showed positive additive effects contributed by Zhongmai 895, indicating that Zhongmai 895 could be used as parent for P-deficient breeding. The most stable QTL QRRS.caas-4DS for ratio of root to shoot dry weight (RRS) harbored the stable genetic region with high phenotypic effect, and QTL clusters on 7A might be used for speedy selection of genotypes for P-uptake. SNPs closely linked to QTLs and clusters could be used to improve nutrient-use efficiency.

Synthetic hexaploid wheats and their derived advanced lines were subject to empirical selection in developing genetically superior cultivars. To investigate genetic diversity, patterns of nucleotide diversity, population structure, and selection signatures during wheat breeding, we tested 422 wheat accessions, including 145 synthetic-derived wheats, 128 spring wheat cultivars, and 149 advanced breeding lines from Pakistan. A total of 18,589 high-quality GBS-SNPs were identified that were distributed across the A (40%), B (49%), and D (11%) genomes. Values of population diversity parameters were estimated across chromosomes and genomes. Genome-wide average values of genetic diversity and polymorphic information content were estimated to be 0.30 and 0.25, respectively. Neighbor-joining (NJ) tree, principal component analysis (PCA), and kinship analyses revealed that synthetic-derived wheats and advanced breeding lines were genetically diverse. The 422 accessions were not separated into distinct groups by NJ analysis and confirmed using the PCA. This conclusion was validated with both relative kinship and Rogers' genetic distance analyses. EigenGWAS analysis revealed that 32 unique genome regions had undergone selection. We found that 50% of the selected regions were located in the B-genome, 29% in the D-genome, and 21% in the A-genome. Previously known functional genes or QTL were found within the selection regions associated with phenology-related traits such as vernalization, adaptability, disease resistance, and yield-related traits. The selection signatures identified in the present investigation will be useful for understanding the targets of modern wheat breeding in Pakistan.

Summary: Background: Previous risk prediction models taking esophageal malignant lesions detected during endoscopy as the primary outcome are not always sufficient to identify prevalent cases which are “overlooked” at screening. We aimed to update and externally validate our previous risk prediction model for malignant esophageal lesions by redefining the predicted outcome. Methods: 15,192 individuals from the Endoscopic Screening for Esophageal Cancer in China randomized controlled trial (ESECC trial, NCT01688908) were included as the training set, and 4576 participants from another population-based esophageal squamous cell carcinoma (ESCC) screening cohort (Anyang Esophageal Cancer Cohort Study, AECCS) served as the external validation set. Lesions with severe dysplasia or worse diagnosed at chromoendoscopy or identified via follow-up within 1 year after screening were defined as main outcome. Logistic regressions were applied to reconstruct the questionnaire-based prediction model using information collected before screening, with Akaike Information Criterion to determine the model structure. Findings: The final prediction model included age and its quadratic term, family history of ESCC, low body mass index (≤22 kg/m2), use of coal or wood as main fuel for cooking, eating rapidly, and ingestion of leftover food. The area under the curve was 0·77 (95% CI: 0·73–0·80) and 0·71 (95% CI: 0·65–0·78) in the training and validation set. When screening the top 50% or 10% of high-risk individuals within population, the detection rates can be increased in both cohorts, as compared to universal screening. Interpretation: The described tool may promote the efficiency of current national screening programs for ESCC and contribute to a precision screening strategy in high-risk regions in China. Funding: This work was supported by the National Natural Science Foundation of China (82073626, 81773501), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Key R&D Program of China (2021YFC2500405), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204) and the Beijing Nova Program (Z201100006820093). Sponsors had no role in the study design, data collection, analysis, and interpretation of data.

Stripe or yellow rust (YR) and leaf rust (LR) cause large losses in wheat production worldwide. Resistant cultivars curtail the levels of losses. The present study aimed to identify quantitative trait loci (QTL) for YR and LR resistance in 147 F2:6 recombinant inbred lines (RIL) derived from the cross Fuyu 3/Zhengzhou 5389. The RIL population and parents were genotyped with the Wheat55K single nucleotide polymorphism (SNP) array and simple sequence repeat (SSR) markers. All materials were also phenotyped for YR severity at Mianyang in Sichuan province and Baoding in Hebei province in the 2015/2016, 2016/2017, and 2017/2018 cropping seasons, and LR severity at Zhoukou in Henan province and at Baoding in 2017/2018. Eleven QTL for YR resistance and five for LR resistance were detected using inclusive composite interval mapping (IciMapping). Four of these QTL on chromosomes 1BL, 2BS, 3AL, and 5AL conferred resistance to both YR and LR. The QTL on 1BL was Lr46/Yr29, and that on 7BL might be Lr68. The QTL on chromosome 2BS was detected at a similar position to previously detected loci. QYr.hebau-3AL/QLr.hebau-3AL, QYr.hebau-5AL/QLr.hebau-5AL, QYr.hebau-7DL, QYr.hebau-4BS, QYr.hebau-6DL, and QYr.hebau-2AS are likely to be new. An SSR marker for QYr.hebau-7DL was developed and validated in a diverse wheat panel from China, suggesting effectiveness in different genetic backgrounds. These QTL with closely linked SNP and SSR markers could be useful for marker-assisted selection in wheat breeding programs targeting durable resistance to both diseases.

Abstract Background This study aims to compare the performance of the recently developed Chinese (city) tariff of the EQ-5D-3L against the UK, US, Japanese and Korean tariffs in a general rural population in China. Methods From November 2015 to September 2016, 12,085 permanent residents aged 45–69 from 257 villages randomly selected from Hua County, Henan Province, China, were interviewed using EQ-5D-3L, and a one-on-one questionnaire investigation was used to collect data on factors associated with HRQOL. The health utility scores were calculated using the UK, US, Japanese, Korean and Chinese (city) tariffs. The agreement, known-groups validity and sensitivity of these five tariffs were evaluated. Transition scores for pairs of observed EQ-5D-3L health states were calculated and compared. Results The Korean tariff yielded the highest mean health utility score (0.963), followed by the Chinese (city) (0.948), US (0.943), UK (0.930) and Japanese (0.921) tariffs, but the differences in the scores of any two tariffs did not exceed the MCID. The Chinese (city) tariff showed higher ICC values (ICCs> 0.89, 95% CI:0.755–0.964) and narrower limits of agreement (0.099–0.167) than the Korean tariff [(ICCs> 0.71, 95% CI:0.451–0.955); (0.146–0.253)]. The Chinese (city) tariff had a higher relative efficiency and effect size statistics in 10 out of 11 variables as compared to the UK, US and Japanese tariffs. The Chinese (city) tariff (0.215) was associated with moderate mean absolute transition scores compared with the UK (0.342), US (0.230), Japanese (0.149) and Korean (0.189) tariffs for 1485 observed pairs of the EQ-5D-3L health states. Conclusions Health utility scores derived from the five tariffs differed. The Chinese (city) tariff was the most suitable of these tariffs and was without obvious weakness. We recommend adopting the Chinese (city) tariff when applying EQ-5D-3L to assess quality of life among the elderly in China’s agricultural region with socio-economic status similar to Hua County. Results of this study had provided a crucial basis for health surveys, health promotion projects, health intervention trials, and health economic evaluation taking HRQOL as a target in rural areas of China.

Abstract Background Heterogeneity should be carefully addressed to facilitate establishment of effective population-level blood lipid management. The primary aim of the study was to investigate gender heterogeneity in prevalence of dyslipidemia, including trends with age and associated factors in middle age rural Chinese. Methods This is a cross-sectional study based on a baseline investigation of a population-based randomized controlled trial in rural China, involving 26,378 permanent residents of age 45–69. The age-specific prevalence of dyslipidemia was estimated for men and women, and the trends of prevalence with age were compared. Logistic regression was used to explore the factors associated with prevalent risk of dyslipidemia. Results The overall prevalence of dyslipidemia was significantly higher in females than in males for borderline high and above (BHA) total cholesterol (TC ≥ 200 mg/dL), BHA triglycerides (TG ≥ 150 mg/dL) and BHA low-density lipoprotein cholesterol (LDL-C ≥ 130 mg/dL), but was lower for low high-density lipoprotein cholesterol (HDL-C

Biofortification is a sustainable strategy to alleviate micronutrient deficiency in humans. It is necessary to improve grain zinc (GZnC) and iron concentrations (GFeC) in wheat based on genetic knowledge. However, the precise dissection of the genetic architecture underlying GZnC and GFeC remains challenging. In this study, high-resolution genome-wide association studies were conducted for GZnC and GFeC by three different models using 166 wheat cultivars and 373,106 polymorphic markers from the wheat 660K and 90K single nucleotide polymorphism (SNP) arrays. Totally, 25 and 16 stable loci were detected for GZnC and GFeC, respectively. Among them, 17 loci for GZnC and 8 for GFeC are likely to be new quantitative trait locus/loci (QTL). Based on gene annotations and expression profiles, 28 promising candidate genes were identified for Zn/Fe uptake (8), transport (11), storage (3), and regulations (6). Of them, 11 genes were putative wheat orthologs of known Arabidopsis and rice genes related to Zn/Fe homeostasis. A brief model, such as genes related to Zn/Fe homeostasis from root uptake, xylem transport to the final seed storage was proposed in wheat. Kompetitive allele-specific PCR (KASP) markers were successfully developed for two major QTL of GZnC on chromosome arms 3AL and 7AL, respectively, which were independent of thousand kernel weight and plant height. The 3AL QTL was further validated in a bi-parental population under multi-environments. A wheat multidrug and toxic compound extrusion (MATE) transporter TraesCS3A01G499300, the ortholog of rice gene OsPEZ2, was identified as a potential candidate gene. This study has advanced our knowledge of the genetic basis underlying GZnC and GFeC in wheat and provides valuable markers and candidate genes for wheat biofortification.

ObjectivesUpper gastrointestinal (G.I.) cancer screening has been conducted in China for decades. However, the economic burden for treatment “intensively” occurred in advance due to screening in resource-limited communities remain unclear.MethodsWe compared the treatment costs for upper G.I. cancers from the screening and control arms of a population-based randomized trial in a high-risk area for esophageal cancer (EC) in China based on claims data from the health insurance system in the local area which included whole population coverage.ResultsThe average out-of-pocket cost per treatment of EC in the screening arm was lower than that in the control arm ($5,972 vs. $7,557). This difference was a consequence of down-staging from screening which resulted in lower cost therapy for earlier stage cancers. Moreover, this result is similar for cardial and non-cardial gastric cancer in the two study arms ($7,933 vs. $10,605). However, three times as many (103 vs. 36) families in the screening arm suffered catastrophic health expenditure for all cancer types. The overall treatment cost for all EC patients in the screening arm ($1,045,119) was 2.44 times that in the control arm ($428,292), and the ratio for cardial and non-cardial gastric cancer was 1.12 ($393,261 vs. $351,557).ConclusionCancer treatment secondary to screening may triple the likelihood of catastrophic patient medical expenditure, and sharply increase the economic pressure on the local community, particularly for cancer types which are of high prevalence. Financial support for patients and the health insurance system should be taken into consideration when planning budgets for cancer screening programs in communities which are resource-limited.

Stripe rust caused by Puccnina striiformis (Pst) is an economically important disease attacking wheat all over the world. Identifying and deploying new genes for Pst resistance is an economical and long-term strategy for controlling Pst. A genome-wide association study (GWAS) using single nucleotide polymorphisms (SNPs) and functional haplotypes were used to identify loci associated with stripe rust resistance in synthetic-derived (SYN-DER) wheats in four environments. In total, 92 quantitative trait nucleotides (QTNs) distributed over 65 different loci were associated with resistance to Pst at seedling and adult plant stages. Nine additional loci were discovered by the linkage disequilibrium-based haplotype-GWAS approach. The durable rust-resistant gene Lr34/Yr18 provided resistance in all four environments, and against all the five Pst races used in this study. The analysis identified several SYN-DER accessions that carried major genes: either Yr24/Yr26 or Yr32. New loci were also identified on chr2B, chr5B, and chr7D, and 14 QTNs and three haplotypes identified on the D-genome possibly carry new alleles of the known genes contributed by the Ae. tauschii founders. We also evaluated eleven different models for genomic prediction of Pst resistance, and a prediction accuracy up to 0.85 was achieved for an adult plant resistance, however, genomic prediction for seedling resistance remained very low. A meta-analysis based on a large number of existing GWAS would enhance the identification of new genes and loci for stripe rust resistance in wheat. The genetic framework elucidated here for stripe rust resistance in SYN-DER identified the novel loci for resistance to Pst assembled in adapted genetic backgrounds.

Improving canopy photosynthetic light use efficiency and energy conversion efficiency (εc) is a major option to increase crop yield potential. However, so far, the diurnal and seasonal variations of canopy light use efficiency (LUE) and εc are largely unknown due to the lack of an efficient method to estimate εc in a high temporal resolution. Here we quantified the dynamic changes of crop canopy LUE and εc during a day and a growing season with the canopy gas exchange method. A response curve of whole-plant carbon dioxide (CO2) flux to incident photosynthetically active radiation (PAR) was further used to calculate εc and LUE at a high temporal resolution. Results show that the LUE of two wheat cultivars with different canopy architectures at five stages varies between 0.01 to about 0.05 mol CO2 mol–1 photon, with the LUE being higher under medium PAR. Throughout the growing season, the εc varies from 0.5 to 3.7% (11–80% of the maximal εc for C3 plants) with incident PAR identified as a major factor controlling variation of εc. The estimated average εc from tillering to grain filling stages was about 2.17%, i.e., 47.2% of the theoretical maximal. The estimated season-averaged radiation use efficiency (RUE) was 1.5–1.7 g MJ–1, which was similar to the estimated RUE based on biomass harvesting. The large variations of LUE and εc imply a great opportunity to improve canopy photosynthesis for greater wheat biomass and yield potential.

Canopy photosynthesis is the sum of photosynthesis of all above-ground photosynthetic tissues. Quantitative roles of nonfoliar tissues in canopy photosynthesis remain elusive due to methodology limitations. Here, we develop the first complete canopy photosynthesis model incorporating all above-ground photosynthetic tissues and validate this model on wheat with state-of-the-art gas exchange measurement facilities. The new model precisely predicts wheat canopy gas exchange rates at different growth stages, weather conditions, and canopy architectural perturbations. Using the model, we systematically study (1) the contribution of both foliar and nonfoliar tissues to wheat canopy photosynthesis and (2) the responses of wheat canopy photosynthesis to plant physiological and architectural changes. We found that (1) at tillering, heading, and milking stages, nonfoliar tissues can contribute ~4, ~32, and ~50% of daily gross canopy photosynthesis (Acgross; ~2, ~15, and ~-13% of daily net canopy photosynthesis, Acnet) and absorb ~6, ~42, and ~60% of total light, respectively; (2) under favorable condition, increasing spike photosynthetic activity, rather than enlarging spike size or awn size, can enhance canopy photosynthesis; (3) covariation in tissue respiratory rate and photosynthetic rate may be a major factor responsible for less than expected increase in daily Acnet; and (4) in general, erect leaves, lower spike position, shorter plant height, and proper plant densities can benefit daily Acnet. Overall, the model, together with the facilities for quantifying plant architecture and tissue gas exchange, provides an integrated platform to study canopy photosynthesis and support rational design of photosynthetically efficient wheat crops.

Abstract Characterization of genomic regions underlying adaptation of landraces can reveal a quantitative genetics framework for local wheat (Triticum aestivum L.) adaptability. A collection of 512 wheat landraces from the eastern edge of the Fertile Crescent in Iran and Pakistan were genotyped using genome‐wide single nucleotide polymorphism markers generated by genotyping‐by‐sequencing. The minor allele frequency (MAF) and the heterozygosity (H) of Pakistani wheat landraces (MAF = 0.19, H = 0.008) were slightly higher than the Iranian wheat landraces (MAF = 0.17, H = 0.005), indicating that Pakistani landraces were slightly more genetically diverse. Population structure analysis clearly separated the Pakistani landraces from Iranian landraces, which indicates two separate adaptability trajectories. The large‐scale agro‐climatic data of seven variables were quite dissimilar between Iran and Pakistan as revealed by the correlation coefficients. Genome‐wide association study identified 91 and 58 loci using agroclimatic data, which likely underpin local adaptability of the wheat landraces from Iran and Pakistan, respectively. Selective sweep analysis identified significant hits on chromosomes 4A, 4B, 6B, 7B, 2D, and 6D, which were colocalized with the loci associated with local adaptability and with some known genes related to flowering time and grain size. This study provides insight into the genetic diversity with emphasis on the genetic architecture of loci involved in adaptation to local environments, which has breeding implications.

Wheat occupies a special role in global food security since, in addition to providing 20% of our carbohydrates and protein, almost 25% of the global production is traded internationally. The importance of wheat for food security was recognised by the Chief Agricultural Scientists of the G20 group of countries when they endorsed the establishment of the Wheat Initiative in 2011. The Wheat Initiative was tasked with supporting the wheat research community by facilitating collaboration, information and resource sharing and helping to build the capacity to address challenges facing production in an increasingly variable environment. Many countries invest in wheat research. Innovations in wheat breeding and agronomy have delivered enormous gains over the past few decades, with the average global yield increasing from just over 1 tonne per hectare in the early 1960s to around 3.5 tonnes in the past decade. These gains are threatened by climate change, the rapidly rising financial and environmental costs of fertilizer, and pesticides, combined with declines in water availability for irrigation in many regions. The international wheat research community has worked to identify major opportunities to help ensure that global wheat production can meet demand. The outcomes of these discussions are presented in this paper.

Preharvest sprouting (PHS) significantly reduces grain yield and quality. Identification of genetic loci for PHS resistance will facilitate breeding sprouting-resistant wheat cultivars. In this study, we constructed a genetic map comprising 1,702 non-redundant markers in a recombinant inbred line (RIL) population derived from cross Yangxiaomai/Zhongyou9507 using the wheat 15K single-nucleotide polymorphism (SNP) assay. Four quantitative trait loci (QTL) for germination index (GI), a major indicator of PHS, were identified, explaining 4.6–18.5% of the phenotypic variances. Resistance alleles of Qphs.caas-3AL, Qphs.caas-3DL, and Qphs.caas-7BL were from Yangxiaomai, and Zhongyou9507 contributed a resistance allele in Qphs.caas-4AL. No epistatic effects were detected among the QTL, and combined resistance alleles significantly increased PHS resistance. Sequencing and linkage mapping showed that Qphs.caas-3AL and Qphs.caas-3DL corresponded to grain color genes Tamyb10-A and Tamyb10-D, respectively, whereas Qphs.caas-4AL and Qphs.caas-7BL were probably new QTL for PHS. We further developed cost-effective, high-throughput kompetitive allele-specific PCR (KASP) markers tightly linked to Qphs.caas-4AL and Qphs.caas-7BL and validated their association with GI in a test panel of cultivars. The resistance alleles at the Qphs.caas-4AL and Qphs.caas-7BL loci were present in 72.2 and 16.5% cultivars, respectively, suggesting that the former might be subjected to positive selection in wheat breeding. The findings provide not only genetic resources for PHS resistance but also breeding tools for marker-assisted selection.

The objective of this paper is to review progress made in wheat breeding for Fusarium head blight (FHB) resistance in China, the United States of America (USA), and Canada. In China, numerous Chinese landraces possessing high levels of FHB resistance were grown before the 1950s. Later, pyramiding multiple sources of FHB resistance from introduced germplasm such as Mentana and Funo and locally adapted cultivars played a key role in combining satisfactory FHB resistance and high yield potential in commercial cultivars. Sumai 3, a Chinese spring wheat cultivar, became a major source of FHB resistance in the USA and Canada, and contributed to the release of more than 20 modern cultivars used for wheat production, including the leading hard spring wheat cultivars Alsen, Glenn, Barlow and SY Ingmar from North Dakota, Faller and Prosper from Minnesota, and AAC Brandon from Canada. Brazilian wheat cultivar Frontana, T. dicoccoides and other local germplasm provided additional sources of resistance. The FHB resistant cultivars mostly relied on stepwise accumulation of favorable alleles of both genes for FHB resistance and high yield, with marker-assisted selection being a valuable complement to phenotypic selection. With the Chinese Spring reference genome decoded and resistance gene Fhb1 now cloned, new genomic tools such as genomic selection and gene editing will be available to breeders, thus opening new possibilities for development of FHB resistant cultivars. Keywords: Fhb1, Fusarium head blight resistance, Fusarium graminearum, Triticum aestivum, Wheat breeding

Abstract Background Wheat is a momentous crop and feeds billions of people in the world. The improvement of wheat yield is very important to ensure world food security. Normal development of grain is the essential guarantee for wheat yield formation. The genetic study of grain phenotype and identification of key genes for grain filling are of great significance upon dissecting the molecular mechanism of wheat grain morphogenesis and yield potential. Results Here we identified a pair of defective kernel (Dek) isogenic lines, BL31 and BL33, with plump and shrunken mature grains, respectively, and constructed a genetic population from the BL31/BL33 cross. Ten chromosomes had higher frequency of polymorphic single nucleotide polymorphism (SNP) markers between BL31 and BL33 using Wheat660K chip. Totally 783 simple sequence repeat (SSR) markers were chosen from the above chromosomes and 15 of these were integrated into two linkage groups using the genetic population. Genetic mapping identified three QTL, QDek.caas-3BS.1, QDek.caas-3BS.2 and QDek.caas-4AL, explaining 14.78–18.17%, 16.61–21.83% and 19.08–28.19% of phenotypic variances, respectively. Additionally, five polymorphic SNPs from Wheat660K were successfully converted into cleaved amplified polymorphic sequence (CAPS) markers and enriched the target regions of the above QTL. Biochemical analyses revealed that BL33 has significantly higher grain sucrose contents at filling stages and lower mature grain starch contents than BL31, indicating that the Dek QTL may be involved in carbohydrate metabolism. As such, the candidate genes for each QTL were predicated according to International Wheat Genome Sequence Consortium (IWGSC) RefSeq v1.0. Conclusions Three major QTL for Dek were identified and their causal genes were predicted, laying a foundation to conduct fine mapping and dissect the regulatory mechanism underlying Dek trait in wheat.

China and CIMMYT have collaborated on wheat improvement for over 40 years and significant progress has been achieved in five aspects in China. A standardized protocol for testing Chinese noodle quality has been established with three selection criteria, i.e., gluten quality, starch viscosity and flour color are identified as being responsible for noodle quality. Genomic approaches have been used to develop and validate gene-specific markers, leading to the establishment of a KASP platform, and seven cultivars have been released through application of molecular marker technology. Methodology for breeding adult-plant resistance to yellow rust, leaf rust and powdery mildew, based on the pleiotropic effect of minor genes has been established, resulting in release of six cultivars. More than 330 cultivars derived from CIMMYT germplasm have been released and are now grown over 9% of the Chinese wheat production area. Additionally, physiological approaches have been used to characterize yield potential and develop high-efficiency phenotyping platforms. CIMMYT has also provided valuable training for Chinese scientists. Development of climate-resilient cultivars with application of new technology will be the priority for future collaboration.

Crop-wild introgressions have long been exploited without knowing the favorable recombination points. Synthetic hexaploid wheats are one of the most exploited genetic resources for bread wheat improvement. However, despite some QTL with major effects, much less is known about genome-wide patterns of introgressions and their effects on phenotypes. We used two genome-wide association approaches: SNP-GWAS and haplotype-GWAS to identify SNPs and haplotypes associated with productivity under water-limited conditions in a synthetic-derived wheat (SYN-DER) population. Haplotype-GWAS further enriched and identified 20 more genomic regions associated with drought adaptability that did not overlap with SNP-GWAS. Since GWAS is biased to the phenotypes in the study and may fail to detect important genetic diversity during breeding, we used five complementary analytical approaches (t-test, Tajima’s D, nucleotide diversity (π), Fst, and EigenGWAS) to identify divergent selections in SYN-DER compared to modern bread wheat. These approaches consistently pinpointed 89 ‘selective sweeps’, out of which 30 selection loci were identified on D-genome. These key selections co-localized with important functional genes of adaptive traits such as TaElf3-D1 (1D) for earliness per se (Eps), TaCKX-D1 (3D), TaGS1a (6D) and TaGS-D1 (7D) for grain size, weight and morphology, TaCwi-D1 (5D) influencing drought tolerance, and Vrn-D3 (7D) for vernalization. Furthermore, 55 SNPs and 23 haplotypes of agronomic and physiological importance such as grain yield, relative water content and thousand grain weight in SYN-DER, were among the top 5% of divergent selections contributed by synthetic hexaploid wheats. These divergent selections associated with improved agronomic performance carry new alleles that have been introduced to wheat. Our results demonstrated that GWAS and selection sweep analyses are powerful approaches for investigating favorable introgressions under strong selection pressure and the use of crop-wild hybridization to assist the improvement of wheat yield and productivity under moisture limiting environments.

Abstract Background Plant height is an important selection target since it is associated with yield potential, stability and particularly with lodging resistance in various environments. Rapid and cost-effective estimation of plant height from airborne devices using a digital surface model can be integrated with academic research and practical wheat breeding programs. A bi-parental wheat population consisting of 198 doubled haploid lines was used for time-series assessments of progress in reaching final plant height and its accuracy was assessed by quantitative genomic analysis. UAV-based data were collected at the booting and mid-grain fill stages from two experimental sites and compared with conventional measurements to identify quantitative trait loci (QTL) underlying plant height. Results A significantly high correlation of R 2 = 0.96 with a 5.75 cm root mean square error was obtained between UAV-based plant height estimates and ground truth observations at mid-grain fill across both sites. Correlations for UAV and ground-based plant height data were also very high (R 2 = 0.84–0.85, and 0.80–0.83) between plant height at the booting and mid-grain fill stages, respectively. Broad sense heritabilities were 0.92 at booting and 0.90–0.91 at mid-grain fill across sites for both data sets. Two major QTL corresponding to Rht-B1 on chromosome 4B and Rht-D1 on chromosome 4D explained 61.3% and 64.5% of the total phenotypic variations for UAV and ground truth data, respectively. Two new and stable QTL on chromosome 6D seemingly associated with accelerated plant growth was identified at the booting stage using UAV-based data. Genomic prediction accuracy for UAV and ground-based data sets was significantly high, ranging from r = 0.47–0.55 using genome-wide and QTL markers for plant height. However, prediction accuracy declined to r = 0.20–0.31 after excluding markers linked to plant height QTL. Conclusion This study provides a fast way to obtain time-series estimates of plant height in understanding growth dynamics in bread wheat. UAV-enabled phenotyping is an effective, high-throughput and cost-effective approach to understand the genetic basis of plant height in genetic studies and practical breeding.

Abstract Background Identification of loci for grain yield (GY) and related traits, and dissection of the genetic architecture are important for yield improvement through marker-assisted selection (MAS). Two genome-wide association study (GWAS) methods were used on a diverse panel of 166 elite wheat varieties from the Yellow and Huai River Valleys Wheat Zone (YHRVWD) of China to detect stable loci and analyze relationships among GY and related traits. Results A total of 326,570 single nucleotide polymorphism (SNP) markers from the wheat 90 K and 660 K SNP arrays were chosen for GWAS of GY and related traits, generating a physical distance of 14,064.8 Mb. One hundred and twenty common loci were detected using SNP-GWAS and Haplotype-GWAS, among which two were potentially functional genes underpinning kernel weight and plant height (PH), eight were at similar locations to the quantitative trait loci (QTL) identified in recombinant inbred line (RIL) populations in a previous study, and 78 were potentially new. Twelve pleiotropic loci were detected on eight chromosomes; among these the interval 714.4–725.8 Mb on chromosome 3A was significantly associated with GY, kernel number per spike (KNS), kernel width (KW), spike dry weight (SDW), PH, uppermost internode length (UIL), and flag leaf length (FLL). GY shared five loci with thousand kernel weight (TKW) and PH, indicating significantly affected by two traits. Compared with the total number of loci for each trait in the diverse panel, the average number of alleles for increasing phenotypic values of GY, TKW, kernel length (KL), KW, and flag leaf width (FLW) were higher, whereas the numbers for PH, UIL and FLL were lower. There were significant additive effects for each trait when favorable alleles were combined. UIL and FLL can be directly used for selecting high-yielding varieties, whereas FLW can be used to select spike number per unit area (SN) and KNS. Conclusions The loci and significant SNP markers identified in the present study can be used for pyramiding favorable alleles in developing high-yielding varieties. Our study proved that both GWAS methods and high-density genetic markers are reliable means of identifying loci for GY and related traits, and provided new insight to the genetic architecture of GY.

Wheat high-molecular-weight glutenin subunits (HMW-GS) determine dough elasticity and play an essential role in processing quality. HMW-GS are encoded by Glu-1 genes and controlled primarily at transcriptional level, implemented through the interactions between cis-acting elements and trans-acting factors. However, transcriptional mechanism of Glu-1 genes remains elusive. Here we made a comprehensive analysis of cis-regulatory elements within 1-kb upstream of the Glu-1 start codon (−1000 to −1) and identified 30 conserved motifs. Based on motif distribution pattern, three conserved cis-regulatory modules (CCRMs), CCRM1 (−300 to −101), CCRM2 (−650 to −400), and CCRM3 (−950 to −750), were defined, and their functions were characterized in wheat stable transgenic lines transformed with progressive 5′ deletion promoter::GUS fusion constructs. GUS staining, qPCR and enzyme activity assays indicated that CCRM2 and CCRM3 could enhance the expression level of Glu-1, whereas the 300-bp promoter (−300 to −1), spanning CCRM1 and core region (−100 to −1), was enough to ensure accurate Glu-1 initiation at 7 days after flowering (DAF) and shape its spatiotemporal expression pattern during seed development. Further transgenic assays demonstrated that CCRM1-2 (−300 to −209) containing Complete HMW Enhancer (−246 to −209) was important for expression level but had no effect on expression specificity in the endosperm. In contrast, CCRM1-1 (−208 to −101) was critical for both expression specificity and level of Glu-1. Our findings not only provide new insights to uncover Glu-1 transcription regulatory machinery but also lay foundations for modifying Glu-1 expression. Keywords: Conserved cis-regulatory modules, Glu-1, Transcriptional regulation, Transgenic wheat, Triticum aestivum

Grain yield (GY) prediction for wheat based on canopy spectral reflectance can improve selection efficiency in breeding programs. Time-series spectral information from different growth stages such as flowering to maturity is considered to have high accuracy in predicting GY and combining this information from multiple growth stages could effectively improve prediction accuracy. For this, 207 wheat cultivars and breeding lines were grown in full and limited irrigation treatments, and their canopy spectral reflectance was measured at the flowering, early, middle, and late grain fill stages. The potential of temporal spectral information at multiple growth stages for GY prediction was evaluated by a new method based on stacking the multiple growth stages data. Twenty VIs derived from spectral reflectance were used as the input feature of a support vector regression (SVR) to predict GY at each growth stage. The predicted GY values at multiple growth stages were trained by multiple linear regression (MLR) to establish a second-level prediction model. Results suggested that the prediction accuracy (R2) of VIs data from single growth stages ranged from 0.60 to 0.66 and 0.35 to 0.42 in the full and limited irrigation treatments, respectively. The prediction accuracy was increased by an average of 0.06, 0.07, and 0.07 after stacking the VIs of two, three, and four growth stages, respectively, under full irrigation. Similarly, under limited irrigation, the prediction accuracy was increased by 0.03, 0.04, and 0.04 by stacking the VIs of two, three, and four growth stages, respectively. Stacking of VIs of multiple important growth stages can increase the accuracy of GY prediction and application of a stable stacking model could increase the usefulness of data obtained from different phenotyping platforms.

Root hairs play an important role in absorbing water and nutrients in crop plants. Here we optimized high-throughput root hair length (RHL) and root hair density (RHD) phenotyping in wheat using a portable Dinolite™ microscope. A collection of 24 century wide spring wheat cultivars released between 1911 and 2016 were phenotyped for RHL and RHD. The results revealed significant variations for both traits with five and six-fold variation for RHL and RHD, respectively. RHL ranged from 1.01 mm to 1.77 mm with an average of 1.39 mm, and RHD ranged from 17.08 mm−2 to 20.8 mm−2 with an average of 19.6 mm−2. Agronomic and physiological traits collected from five different environments and their best linear unbiased predictions (BLUPs) were correlated with RHL and RHD, and results revealed that relative-water contents (RWC), biomass and grain per spike (GpS) were positively correlated with RHL in both water-limited and well-watered conditions. While RHD was negatively correlated with grain yield (GY) in four environments and their BLUPs. Both RHL and RHD had positive correlation indicating the possibility of simultaneous selection of both phenotypes during wheat breeding. The expression pattern of TaRSL4 gene involved in regulation of root hair length was determined in all 24 wheat cultivars based on RNA-seq data, which indicated the differentially higher expression of the A- and D- homeologues of the gene in roots, while B-homeologue was consistently expressed in both leaf and roots. The results were validated by qRT-PCR and the expression of TaRSL4 was consistently high in rainfed cultivars such as Chakwal-50, Rawal-87, and Margallah-99. Overall, the new phenotyping method for RHL and RHD along with correlations with morphological and physiological traits in spring wheat cultivars improved our understanding for selection of these phenotypes in wheat breeding.

The health benefits of whole wheat grains are partially attributed to their phenolic acid composition, especially that of trans-ferulic acid (TFA), which is a powerful natural antioxidant. Breeders and producers are becoming interested in wheat with enhanced health-promoting effects. This study investigated the effects of different nitrogen (N) application rates (0, 42, 84, 126, and 168 N kg ha−1) on the phenolic acid composition of three wheat varieties in four locations for two years. The results indicate that the different N rates did not affect the TFA concentration but that they significantly affected the concentrations of para-coumaric acid, sinapic acid, and cis-ferulic acid in the wheat grains. A statistical analysis suggested that the wheat phenolic acid composition was predominantly determined by wheat variety, though there existed some interaction effect between the wheat variety and environments. The TFA concentration of the variety Jimai 22 was generally higher (with a mean value of 726.04 µg/g) but was easily affected by the environment, while the TFA concentration of the variety Zhongmai 578 (with a mean value of 618.01 µg/g) was more stable across the different environments. The results also suggest that it is possible to develop new wheat varieties with high yield potential, good end-use properties, and enhanced nutraceutical values.

Background: To fully realize efficacy in cancer screening, timely and appropriate treatment for participants with malignant lesions is critical. However, the health-seeking behavior of patients with upper gastrointestinal (G.I.) cancer identified in population-level screening programs in China is unknown. Methods: A community-based real-world investigation was conducted with 136 upper G.I. cancer patients detected in a large screening cohort in an area of high-risk for upper G.I. cancer in China. Using local medical claims data and semi-structured face-to-face interview, we collected information regarding the clinical treatment regimen and factors which result in the lack of timely and appropriate treatment. Findings: The treatment records for 133 upper G.I. cancer patients were acquired. Among these, 48 (36•09%) patients did not receive treatment within three months of initial diagnosis, and treatment of early-stage cancer was more likely to be delayed. Sixteen patients did not seek further diagnostic testing due to their low health-awareness and socio-economic status. Another 20 participants proactively sought further diagnostic evaluation in health care facilities but were prevented from receiving further treatment due to low sensitivity of given diagnostic test(s), failure to recognize the significance of screening results, and/or lack of basic knowledge of diagnosis and treatment for early cancer on the part of clinicians. The treatment regimen offered to patients depended largely on the level of health care facilities they visited, and non-medical factors were the main reasons for choice of health care facilities. Interpretation: A coordinated, system-based management strategy is urgently needed to support the design of upper G.I. cancer screening programs in rural populations in China. Funding: The Charity Project of the National Ministry of Health (201202014), the National Key R & D Program of China (2016YFC0901404), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), and the National Natural Science Foundation of China (82073626).

Deficiency of micronutrient elements, such as zinc (Zn) and iron (Fe), is called “hidden hunger,” and bio-fortification is the most effective way to overcome the problem. In this study, a high-density Affymetrix 50K single-nucleotide polymorphism (SNP) array was used to map quantitative trait loci (QTL) for grain Zn (GZn) and grain Fe (GFe) concentrations in 254 recombinant inbred lines (RILs) from a cross Jingdong 8/Bainong AK58 in nine environments. There was a wide range of variation in GZn and GFe concentrations among the RILs, with the largest effect contributed by the line × environment interaction, followed by line and environmental effects. The broad sense heritabilities of GZn and GFe were 0.36 ± 0.03 and 0.39 ± 0.03, respectively. Seven QTL for GZn on chromosomes 1DS, 2AS, 3BS, 4DS, 6AS, 6DL, and 7BL accounted for 2.2–25.1% of the phenotypic variances, and four QTL for GFe on chromosomes 3BL, 4DS, 6AS, and 7BL explained 2.3–30.4% of the phenotypic variances. QTL on chromosomes 4DS, 6AS, and 7BL might have pleiotropic effects on both GZn and GFe that were validated on a germplasm panel. Closely linked SNP markers were converted to high-throughput KASP markers, providing valuable tools for selection of improved Zn and Fe bio-fortification in breeding.

Background: We aimed to establish a new approach for surveillance of cancer prevalence and survival in China, based on the Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS). Methods: We constructed a standard procedure for data collection, cleaning, processing, linkage, verification, analysis, and estimation of cancer prevalence and survival (including both actual observations and model estimates) by conjoint use of medical insurance claims data and all-cause death surveillance data. As a proof-of-principle study, we evaluated the performance of this surveillance approach by estimating the latest prevalence and survival for upper gastrointestinal cancers in Hua County, a high-risk region for oesophageal cancer in China. Findings: In Hua County, the age-standardised relative 5-year survival was 39·2% (male: 36·8%; female: 43·6%) for oesophageal cancer and 33·3% (male: 29·6%; female: 43·4%) for stomach cancer. For oesophageal cancer, better survival was observed in patients of 45–64 years compared with national average estimates, and women of

Unmanned aerial vehicle (UAV) based remote sensing is a promising approach for non-destructive and high-throughput assessment of crop water and nitrogen (N) efficiencies. In this study, UAV was used to evaluate two field trials using four water (T0 = 0 mm, T1 = 80 mm, T2 = 120 mm, and T3 = 160 mm), and four N (T0 = 0, T1 = 120 kg ha–1, T2 = 180 kg ha–1, and T3 = 240 kg ha–1) treatments, respectively, conducted on three wheat genotypes at two locations. Ground-based destructive data of water and N indictors such as biomass and N contents were also measured to validate the aerial surveillance results. Multispectral traits including red normalized difference vegetation index (RNDVI), green normalized difference vegetation index (GNDVI), normalized difference red-edge index (NDRE), red-edge chlorophyll index (RECI) and normalized green red difference index (NGRDI) were recorded using UAV as reliable replacement of destructive measurements by showing high r values up to 0.90. NGRDI was identified as the most efficient non-destructive indicator through strong prediction values ranged from R2 = 0.69 to 0.89 for water use efficiencies (WUE) calculated from biomass (WUE.BM), and R2 = 0.80 to 0.86 from grain yield (WUE.GY). RNDVI was better in predicting the phenotypic variations for N use efficiency calculated from nitrogen contents of plant samples (NUE.NC) with high R2 values ranging from 0.72 to 0.94, while NDRE was consistent in predicting both NUE.NC and NUE.GY by 0.73 to 0.84 with low root mean square errors. UAV-based remote sensing demonstrates that treatment T2 in both water 120 mm and N 180 kg ha–1 supply trials was most appropriate dosages for optimum uptake of water and N with high GY. Among three cultivars, Zhongmai 895 was highly efficient in WUE and NUE across the water and N treatments. Conclusively, UAV can be used to predict time-series WUE and NUE across the season for selection of elite genotypes, and to monitor crop efficiency under varying N and water dosages.

Summary: Background: We aimed to establish a Medical-Insurance-System-based Cancer Surveillance System (MIS-CASS) in China and evaluate the completeness and timeliness of this system through reporting cancer incidence rates using claims data in two regions in northern and southern China. Methods: We extracted claims data from medical insurance systems in Hua County of Henan Province, and Shantou City in Guangdong Province in China from Jan 1, 2012 to Jun 30, 2019. These two regions have been considered to be high risk regions for oesophageal cancer. We developed a rigorous procedure to establish the MIS-CASS, which includes data extraction, cleaning, processing, case ascertainment, privacy protection, etc. Text-based diagnosis in conjunction with ICD-10 codes were used to determine cancer diagnosis. Findings: In 2018, the overall age-standardised (Segi population) incidence rates (ASR World) of cancer in Hua County and Shantou City were 167·39/100,000 and 159·78/100,000 respectively. In both of these areas, lung cancer and breast cancer were the most common cancers in males and females respectively. Hua County is a high-risk region for oesophageal cancer (ASR World: 25·95/100,000), whereas Shantou City is not a high-risk region for oesophageal cancer (ASR World: 11·43/100,000). However, Nanao island had the highest incidence of oesophageal cancer among all districts and counties in Shantou (ASR World: 36·39/100,000). The age-standardised male-to-female ratio for oesophageal cancer was lower in Hua County than in Shantou (1·69 vs. 4·02). A six-month lag time was needed to report these cancer incidences for the MIS-CASS. Interpretation: MIS-CASS efficiently reflects cancer burden in real-time, and has the potential to provide insight for improvement of cancer surveillance in China. Funding: The National Key R&D Program of China (2016YFC0901404), the Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (XXZ0204), the Sanming Project of Shenzhen (SZSM201612061), and the Shantou Science and Technology Bureau (190829105556145, 180918114960704). Keywords: Medical insurance system, Claims data, Cancer surveillance, Cancer incidence, China