Genome-wide association study of agronomic traits related to nitrogen use efficiency in Henan wheat.

BACKGROUND: Nitrogen use efficiency (NUE) is closely related to crop yield and nitrogen fertilizer application rate. Although NUE is susceptible to environments, quantitative trait nucleotides (QTNs) for NUE in wheat germplasm populations have been rarely reported in genome-wide associated study. RESULTS: In this study, 244 wheat accessions were phenotyped by three NUE-related traits in three environments and genotyped by 203,224 SNPs. All the phenotypes for each trait were used to associate with all the genotypes of these SNP markers for identifying QTNs and QTN-by-environment interactions via 3VmrMLM. Among 279 QTNs and one QTN-by-environment interaction for low nitrogen tolerance, 33 were stably identified, especially, one large QTN (r2 > 10%), qPHR3A.2, was newly identified for plant height ratio in one environment and multi-environment joint analysis. Among 52 genes around qPHR3A.2, four genes (TraesCS3A01G101900, TraesCS3A01G102200, TraesCS3A01G104100, and TraesCS3A01G105400) were found to be differentially expressed in low-nitrogen-tolerant wheat genotypes, while TaCLH2 (TraesCS3A01G101900) was putatively involved in porphyrin metabolism in KEGG enrichment analyses. CONCLUSIONS: This study identified valuable candidate gene for low-N-tolerant wheat breeding and provides new insights into the genetic basis of low N tolerance in wheat.

The involvement of transient receptor potential channels in mast cell activation by microbubbles.

This study was to explore the activation of mast cells by microbubbles, with the focus on transient receptor potential (TRP) channels mediated degranulation and calcium influx. Bone marrow-derived mast cells (BMMCs) were primarily obtained from femurs in mice and induced differentiation for 4 weeks. After the purity identification, BMMCs were contacted by homogeneous microbubbles with the diameter of 1 mm for 1 h. ß-hexosaminidase and histamine levels in supernatants were assessed by enzyme-linked immunosorbent assay (ELISA) and the CD63 expression was tested by flow cytometry. The intracellular calcium binding with Fluo-4 AM dyes in BMMCs was observed under the fluorescence microscope and the mean fluorescence intensity was quantitatively measured by flow cytometry. ß-hexosaminidase release, histamine concentration, CD63 expression and calcium influx were significantly increased in BMMCs group upon microbubble stimulation compared to the control groups. After preconditioning with the available inhibitors and microbubble contact, only transient receptor potential vanilloid 1 (TRPV1) and TRPV4 inhibitors robustly suppressed the microbubble-induced degranulation. Likewise, the elevated fluorescence intensity of cytosolic calcium level was also significantly weaken. The results demonstrated microbubble stimulus effectively promoted BMMCs degranulation, which could be substantially restrained by inhibitors targeted for blocking TRPV1 or TRPV4 channel. The alternation of intracellular calcium level in BMMCs was consistent with the changes of degranulation capacity. It's suggested that the activation of BMMCs by microbubbles may involve specific TRP calcium dependent channels.

Access to Fully Substituted Dihydroindazoles Via Hexadehydro-Diels-Alder/[3 + 2] Cycloaddition.

A cascade hexadehydro-Diels-Alder (HDDA)/[3 + 2] cycloaddition reaction between tetrayne and N,N'-cyclic acylhydrazone is described. This strategy allows the efficient construction of fully substituted 2,3-dihydro-1H-indazole scaffolds which have insecticidal activity against the third instar larvae of Mythimna separata.

Mapping Quantitative Trait Loci for Type II Fusarium Head Blight Resistance in Two Wheat Recombinant Inbred Line Populations Derived from Yangmai 4 and Yangmai 5.

Fusarium head blight (FHB) is a destructive wheat disease worldwide and significantly affects grain yield and quality in wheat. To understand the genetic basis underlying type II FHB resistance in two elite wheat cultivars-Yangmai 4 (YM4) and Yangmai 5 (YM5)-quantitative trait loci (QTL) mapping was conducted in two recombinant inbred line (RIL) populations derived from the crosses of YM4 and YM5 with susceptible cultivar Yanzhan 1 (YZ1), respectively. A survey with markers linked to Fhb1, Fhb2, Fhb4, and Fhb5 in landrace Wangshuibai indicated the nonexistence of these known FHB resistance genes or QTL in YM4, YM5, and YZ1. One overlapped resistance QTL was identified in both RIL populations (namely, QFhb.Y4.2D/QFhb.Y5.2D) with a large effect on FHB resistance. One novel resistance QTL (QFhb.Y4.5A) mapped on chromosome 5A was detected only in the YM4/YZ1 population. The resistance alleles of both QFhb.Y4.2D/QFhb.Y5.2D and QFhb.Y4.5A did not increase the plant height and did not significantly affect the heading date and flowering date. Kompetitive allele-specific PCR markers for QFhb.Y4.2D/QFhb.Y5.2D and QFhb.Y4.5A had been developed to verify in an additional set of 244 geographically diverse cultivars or lines. Pyramiding of the two resistance alleles decreased the percentage of symptomatic spikelets by 51.77% relative to the cultivars or lines without these two resistance alleles. QFhb.Y4.2D/QFhb.Y5.2D and QFhb.Y4.5A were shown to be useful alternatives in FHB resistance breeding programs. The results will facilitate marker-assisted selection for introgression of the favorable alleles for improving FHB resistance in breeding programs.

Identification and validation of a novel locus, Qpm-3BL, for adult plant resistance to powdery mildew in wheat using multilocus GWAS.

BACKGROUND: Powdery mildew (PM), one of the major diseases in wheat, severely damages yield and quality, and the most economical and effective way to address this issue is to breed disease-resistant cultivars. Accordingly, 371 landraces and 266 released cultivars in Henan Province were genotyped by a 660 K microarray and phenotyped for adult plant resistance (APR) to PM from 2017 to 2020, and these datasets were used to conduct multilocus genome-wide association studies (GWASs). RESULTS: Thirty-six varieties showed stable APR in all the environments, and eleven quantitative trait nucleotides (QTNs) were found by multiple methods across multiple environments and best linear unbiased prediction (BLUP) values to be significantly associated with APR. Among these stable QTNs, four were previously reported, three were newly discovered in this study, and the others need to be further investigated. The major and newly discovered QTN, Qpm-3BL, was located at chr03BL_AX-109,052,670, while another newly discovered QTN, Qpm-1BL, was located between chr01BL_AX-108,771,002 and chr01BL_AX-110,117,322. Five and eight landraces were identified to be resistant based on Qpm-1BL (haplotype TC) and Qpm-3BL (allele T), respectively. To validate Qpm-3BL, a new kompetitive allele-specific PCR (KASP) marker was developed to scan 155 F2 individuals, and the average resistance score supported the value of Qpm-3BL in marker-assisted breeding. Near Qpm-3BL, PmBMYD was identified by KEGG, gene expression and comparative genomics analyses to be a candidate. Its resistance mechanism may involve gene tandem repeats. CONCLUSIONS: This study reveals a previously unknown gene for PM resistance that is available for marker-assisted breeding.

Associations between alcohol intake and diabetic retinopathy risk: a systematic review and meta-analysis.

BACKGROUND: Some previous studies have reported inconsistent results on the association between alcohol intake and diabetic retinopathy (DR) risk. This study aimed to evaluate the potential effects of alcohol intake on subsequent DR risk using a meta-analytic approach. METHODS: Three electronic databases (PubMed, EmBase, and the Cochrane library) were systematically searched for observational studies from their inception till November 2019. The pooled odds ratio (OR) with 95% confidence interval (CI) were applied for the summary effect estimate using a random-effects model. RESULTS: A total of 15 studies (5 cohort studies, 4 case-control studies, and 6 cross-sectional studies) with 37,290 participants and 12,711 DR cases were selected for the final meta-analysis. The pooled OR indicated no significant association between alcohol intake and DR risk (OR: 0.91; 95%CI: 0.78-1.06; P = 0.225), irrespective of the studies being pooled cohort (OR: 0.95; 95%CI: 0.66-1.36; P = 0.761), case-control (OR: 0.97; 95%CI: 0.77-1.23; P = 0.818), or cross-sectional (OR: 0.86; 95%CI: 0.69-1.08; P = 0.190) ones. However, this association might have been affected by the type of diabetes mellitus and the adjusted status. CONCLUSION: The results of this study showed that the potential impact of alcohol intake on DR risk may differ according to the type of diabetes mellitus and adjusted status. Further large-scale, prospective cohort studies should be conducted to verify the findings of this study and to evaluate DR risk in relation to the dose and type of alcohol intake.

Biphasic effects of autophagy on decompression bubble-induced endothelial injury.

Endothelial dysfunction induced by bubbles plays an important role in decompression sickness (DCS), but the mechanism of which has not been clear. The present study was to investigate the role of autophagy in bubble-induced endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with bubbles, autophagy markers and endothelial injury indices were determined, and relationship strengths were quantified. Effects of autophagy inhibitor 3-methyladenine (3-MA) were observed. Bubble contact for 1, 5, 10, 20 or 30 minutes induced significant autophagy with increases in LC3-II/I ratio and Beclin-1, and a decrease in P62, which correlated with bubble contact duration. Apoptosis rate, cytochrome C and cleaved caspase-3 increased, and cell viability decreased following bubble contact for 10, 20 or 30 minutes, but not for 1 or 5 minutes. Injuries in HUVECs were correlated with LC3-II/I ratio and partially reversed by 3-MA in 10, 20 or 30 minutes contact, but worsened in 1 or 5 minutes. Bubble pre-conditioning for 1 minutes resulted in increased cell viability and decreased apoptosis rate compared with no pre-conditioning, and 30-minutes pre-conditioning induced opposing changes, all of which were inhibited by 3-MA. In conclusion, autophagy was involved and played a biphasic role in bubble-induced endothelial injury.

Elevated plasma S100A1 level is a risk factor for ST-segment elevation myocardial infarction and associated with post-infarction cardiac function.

AIM: To investigate the association between plasma S100A1 level and ST-segment elevation myocardial infarction (STEMI) and potential significance of S100A1 in post-infarction cardiac function. METHODS: We examined the plasma S100A1 level in 207 STEMI patients (STEMI group) and 217 clinically healthy subjects for routine physical examination without a history of coronary artery disease (Control group). Baseline characteristics and concentrations of relevant biomarkers were compared. The relationship between S100A1 and other plasma biomarkers was detected using correlation analysis. The predictive role of S100A1 on occurrence of STEMI was then assessed using multivariate ordinal regression model analysis after adjusting for other covariates. RESULTS: The plasma S100A1 level was found to be significantly higher (P<0.001) in STEMI group (3197.7±1576.0 pg/mL) than in Control (1423.5±1315.5 pg/mL) group. Furthermore, the correlation analysis demonstrated plasma S100A1 level was significantly associated correlated with hypersensitive cardiac troponin T (hs-cTnT) (r = 0.32; P < 0.001), creatine kinase MB (CK-MB) (r = 0.42, P < 0.001), left ventricular eject fraction (LVEF) (r = -0.12, P = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.61; P < 0.001) and hypersensitive C reactive protein (hs-CRP) (r = 0.38; P < 0.001). Moreover, the enrolled subjects who with a S100A1 concentration ≤ 1965.9 pg/mL presented significantly better cardiac function than the rest population. Multivariate Logistic regression analysis revealed that S100A1 was an independent predictor for STEMI patients (OR: 0.671, 95% CI 0.500-0.891, P<0.001). In addition, higher S100A1 concentration (> 1965.9 pg/mL) significantly increased the risk of STEMI as compared with the lower level (OR: 6.925; 95% CI: 4.15-11.375; P<0.001). CONCLUSION: These results indicated that the elevated plasma S100A1 level is an important predictor of STEMI in combination with several biomarkers and also potentially reflects the cardiac function following the acute coronary ischemia.

A Novel Approach to Estimate ROS Origination by Hyperbaric Oxygen Exposure, Targeted Probes and Specific Inhibitors.

BACKGROUND/AIMS: Reactive oxygen species (ROS) are considered fundamental in various physiological/pathophysiological processes and prevention/treatment measures such as hyperbaric oxygen (HBO) therapy. In this study, the origination of ROS in human umbilical vein endothelial cells was investigated under basal and HBO conditions. METHODS: Whole cell or mitochondria-targeted fluorescent probes were applied to mark superoxide anion (O2-), and the ROS produced from mitochondrial respiratory chain (MRC), NADPH oxidase (NOX) and xanthine oxidase (XO) were identified by flow cytometry, confocal imaging and microplate fluorometry with or without specific inhibitors. An algorithm was established to calculate ROS proportion of each source. RESULTS: HBO increased ROS to about 2.14-2.44 fold in mitochondria and 1.32-1.42 fold in whole cell. Then ROS levels were significantly decreased by MRC inhibition about 30% and 16%, respectively. NOX or XO inhibition did not affect HBO-induced ROS generation. Based on these data, it could be further estimated that mitochondrial ROS accounted for 32%-39% of basal whole-cell ROS including 3% from MRC complex II, and NOX accounted for at least 24%-29%. Following HBO treatment, almost all increased ROS originated from mitochondria, and MRC complex II contributed at least 45%-60%. CONCLUSION: This study provided a simple but effective method to estimate the origination of intracellular ROS and found that MRC were the main source of HBO-induced ROS generation.

Bubbles Induce Endothelial Microparticle Formation via a Calcium-Dependent Pathway Involving Flippase Inactivation and Rho Kinase Activation.

BACKGROUND/AIMS: Intravascular bubbles can exert pleiotropic detrimental effects, partly by inducing endothelial microparticles (EMPs) production, which play critical roles in cell communication and vascular inflammation cascades. However, the underlying mechanisms remain unclear. This study aimed to delineate the possible mechanisms involving bubble-induced EMPs formation. METHODS: Human umbilical vein endothelial cells (HUVECs) were contacted by bubbles and EMPs level in supernatant were quantified by flow cytometry. Cytoplasmic calcium (Ca2+) was measured by the Ca2+ binding dyes Fluo-3 AM and flippase activity was assessed by translocation rate of fluorescent phosphatidylserine (PS) analogue NBD-PS. Protein levels of phospho-myosin light chain (MLC, a Rho kinase substrate) and phospho-extracellular signal-regulated kinase 1 or 2 (ERK1/2) were determined by western blotting. The score of actin colocalization was assessed by phalloidin-FITC using an immunofluorescent microscopy. RESULTS: EMPs level markedly increased after bubble stimulus. Cytoplasmic calcium (Ca2+) significantly elevated (P< 0.05), flippase activity decreased (P< 0.05), protein levels of phospho- MLC and phospho- ERK1/2 significantly increased (P< 0.05, P < 0.05), and the score of actin colocalization markedly reduced (P< 0.05) in bubble-stimulated HUVECs. All the above changes except the increase in phospho-ERK1/2 can be reversed by Ca2+ channel blocker LaCl3 (P< 0.05). Additionally, MLC phosphorylation was significantly inhibited and actin colocalization markedly increased by Rho kinase inhibitor pretreatment and more importantly, bubble-induced EMPs markedly decreased. CONCLUSIONS: These results demonstrate that bubble stimulates EMPs formation by cytoplasmic Ca2+ elevation and subsequently activating Rho kinase pathway and cytoskeleton reorganization. Simultaneously, cytoplasmic Ca2+ inhibits the flippase activity and subsequently increases phosphatidylserine exposure, which also contributes to EMPs formation.

Benefits of hyperbaric oxygen pretreatment for decompression sickness in Bama pigs.

Decompression sickness (DCS) occurs when ambient pressure is severely reduced during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models. In the first part of our investigation, six swine were subjected to a session of HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In the second part of our investigation, another 10 swine were randomly assigned into two groups (five per group). All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air: the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second; the second group were pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly (P<0.05), with the greatest expression appearing at 18 h for HSP32 and 70. HBO pretreatment significantly reduced all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs.

Metal- and base-free reductive coupling reaction of P(O)-H with aryl/alkyl sulfonyl chlorides: a novel protocol for the construction of P-S-C bonds.

Novel and efficient synthesis of S-aryl/alkyl phosphinothioates from P(O)-H and aryl/alkyl sulfonyl chlorides under metal- and base-free conditions is described. This reaction provides an alternative strategy for the construction of P-S-C bonds in moderate to excellent yields. Moreover, this method can be readily applied to gram-scale preparation.

Effects of rapid decompression on HUVECs in vitro.

OBJECTIVE: To explore the possible effects of rapid decompression on the activity and function of vascular endothelial cells in vitro. METHODS: Human umbilical vein endothelial cell (HUVEC) cultures were exposed at 7 atmospheres absolute (atm abs) air for two hours before decompression. Two decompression profiles were used at the rate of 30 atm abs min-1 (rapid decompression) or 1 atm abs min-1 (normal decompression). Three hours after decompression, cell activity was detected by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) activity assay; cell permeability was measured by electrical resistance determinations. Twelve hours after decompression, cell apoptosis was detected by flow cytometry with Annexin V FITC/PI double staining. RESULTS: There was no significant statistical difference between rapid and normal decompression groups in all the determined parameters (P=0.59, 0.87, 0.86 and 0.81, respectively). CONCLUSIONS: HUVECs endure rapid decompression well from 7 atm abs at the rate of 30 atm abs min-1, or the current determinations are not sensitive enough to reveal the possible injuries. Further research with more sensitive indexes is warranted to reveal the possible effects and mechanisms.

Pravastatin protects hyperbaric hyperoxia-induced lung injury via inhibiting inflammation in mice.

This study aimed to investigate the protective effects of pravastatin on hyperbaric hyperoxia-induced lung injury (HILI). C57BL/6 mice were randomly assigned into three groups: control group, HILI group and pravastatin (Pra) group. Mice in the HILI and Pra groups were subjected to exposure to pure oxygen at 2.5 atm abs for six hours. Mice in the Pra group were intraperitoneally treated with pravastatin at 15 mg/kg. immediately after exposure. At 24 hours, the lungs were collected for HE staining, TUNEL staining and detection of lung edema, myeloperoxidase (MPO) activity and cytokines, and bronchoalveolar lavage fluid (BALF) was harvested for cell-counting. Pravastatin treatment significantly improved the pathology of the lung after HILI (reduction in thickness of alveolar septum, attenuation of lung edema, fracturing of alveolar septa and decrease in infiltrated leukocytes); reduced the number of apoptotic cells; inhibited lung MPO activity; and regulated the balance between pro-inflammatory and anti-inflammatory cytokines. Our findings suggest that pravastatin may exert a protective effect on lung injury after hyperbaric hyperoxia exposure by inhibiting inflammation.

Simvastatin decreases incidence of decompression sickness in rats.

Decompression sickness (DCS) is a specific diving injury which sometimes may be life-threatening. Previous studies suggested that simvastatin (SIM) can protect against pathological inflammation and tissue damage. This study aimed to investigate whether SIM pretreatment could exert its beneficial effects on DCS. SIM was administered orally to adult male Sprague-Dawley rats for two weeks (2 mg/kg/day), then rats were subjected to a simulated dive at 700 kPa air pressure for 100 minutes before rapid decompression. After 30 minutes of symptom observation, lung tissue and blood samples were collected for further analysis. Compared to the vehicle-control, SIM pretreatment significantly decreased the incidence of DCS and ameliorated all parameters of pulmonary injuries, including lung dry/wet weight ratio, bronchoalveolar lavage fluid protein concentration, lung tissue malondialdehyde level and morphology. Moreover, SIM pretreatment abolished increases in systemic and pulmonary inflammation by reducing tumor necrosis factor-α levels in blood plasma and lung tissue. The results indicate that SIM may offer a novel pharmacological protection against injuries in DCS rats by inhibiting inflammatory responses. Further study is needed to understand the exact mechanisms.

Advances in the therapy of hyperoxia-induced lung injury: findings from animal models.

Oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia at elevated partial pressure leads to inflammation and acute lung injury. The population at risk for this condition has markedly increased with the advent of efficient systems for delivery of high concentrations of oxygen in hospitals. Thus, the therapy of hyperoxia-induced lung injury has been a focus in studies of pediatrics and pulmonary medicine. In this paper, we briefly summarized the advances in the therapies of hyperoxia-induced lung injury on the basis of its pathogenesis. We hope our summary will help provide evidence for further investigation of therapeutic measures for hyperoxia-induced lung injury.

Protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury in a rat model.

Hyperbaric oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia leads to inflammation and acute lung injury. This study aimed to investigate the protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury. Rats were intraperitoneally treated with sodium hydrosulphide (NaHS) at 28 µmol/kg immediately before hyperoxia exposure and then exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) with continuous ventilation for six hours, Immediately after hyperoxia exposure, rats were sacrificed via anesthesia. The bronchoalveolar lavage fluid (BALF) was harvested for the detection of protein concentration and IL-1 content, and the lungs were collected for HE staining, TUNEL staining and detection of wet/dry weight ratio. Our results showed hyperbaric hyperoixa exposure could significantly damage the lung (HE staining), increase the protein and IL-13 in the BALF, elevate the wet/dry Weight ratio and raise the TUNEL positive cells. However, pre-treatment with hydrogen sulfide improved the lung morphology, reduced the TUNEL positive cells and attenuated the lung inflammation (reduction in IL-13 of BALF and HE staining). Taken together, our findings indicate that hydrogen sulfide pretreatment may exert protective effects on hyperbaric hyperoxia-induced lung injury.

Accurate Recognition of Vascular Lumen Region from 2D Ultrasound Cine Loops for Bubble Detection.

BACKGROUND: Accurate identification of vascular lumen region founded the base of bubble detection and bubble grading, which played a significant role in the detection of vascular gas emboli for the diagnosis of decompression sickness. OBJECTIVES: To assist in the detection of vascular bubbles, it is crucial to develop an automatic algorithm that could identify vascular lumen areas in ultrasound videos with the interference of bubble presence. METHODS: This article proposed an automated vascular lumen region recognition (VLRR) algorithm that could sketch the accurate boundary between vessel lumen and tissues from dynamic 2D ultrasound videos. It adopts 2D ultrasound videos of the lumen area as input and outputs the frames with circled vascular lumen boundary of the videos. Normalized cross-correlation method, distance transform technique, and region growing technique were adopted in this algorithm. Results A double-blind test was carried out to test the recognition accuracy of the algorithm on 180 samples in the images of 6 different grades of bubble videos, during which, intersection over union and pixel accuracy were adopted as evaluation metrics. The average IOU on the images of different bubble grades reached 0.76. The mean PA on 6 of the images of bubble grades reached 0.82. CONCLUSION: It is concluded that the proposed method could identify the vascular lumen with high accuracy, potentially applicable to assist clinicians in the measurement of the severity of vascular gas emboli in clinics.

Mapping quantitative trait loci and developing their KASP markers for pre-harvest sprouting resistance of Henan wheat varieties in China.

Introduction: Pre-harvest Sprouting (PHS) seriously affects wheat quality and yield. However, to date there have been limited reports. It is of great urgency to breed resistance varieties via quantitative trait nucleotides (QTNs) or genes for PHS resistance in white-grained wheat. Methods: 629 Chinese wheat varieties, including 373 local wheat varieties from 70 years ago and 256 improved wheat varieties were phenotyped for spike sprouting (SS) in two environments and genotyped by wheat 660K microarray. These phenotypes were used to associate with 314,548 SNP markers for identifying QTNs for PHS resistance using several multi-locus genome-wide association study (GWAS) methods. Their candidate genes were verified by RNA-seq, and the validated candidate genes were further exploited in wheat breeding. Results: As a result, variation coefficients of 50% and 47% for PHS in 629 wheat varieties, respectively, in 2020-2021 and 2021-2022 indicated large phenotypic variation, in particular, 38 white grain varieties appeared at least medium resistance, such as Baipimai, Fengchan 3, and Jimai 20. In GWAS, 22 significant QTNs, with the sizes of 0.06% ~ 38.11%, for PHS resistance were stably identified by multiple multi-locus methods in two environments, e.g., AX-95124645 (chr3D:571.35Mb), with the sizes of 36.390% and 45.850% in 2020-2021 and 2021-2022, respectively, was detected by several multi-locus methods in two environments. As compared with previous studies, the AX-95124645 was used to develop Kompetitive Allele-Specific PCR marker QSS.TAF9-3D (chr3D:569.17Mb~573.55Mb) for the first time, especially, it is available in white-grain wheat varieties. Around this locus, nine genes were significantly differentially expressed, and two of them (TraesCS3D01G466100 and TraesCS3D01G468500) were found by GO annotation to be related to PHS resistance and determined as candidate genes. Discussion: The QTN and two new candidate genes related to PHS resistance were identified in this study. The QTN can be used to effectively identify the PHS resistance materials, especially, all the white-grained varieties with QSS.TAF9-3D-TT haplotype are resistant to spike sprouting. Thus, this study provides candidate genes, materials, and methodological basis for breeding wheat PHS resistance in the future.

Screening of genes interacting with high myopia and neuropsychiatric disorders.

Clinical studies have demonstrated an association between high myopia (HM) and neuropsychiatric disorders; however, the underlying mechanism of the association is not clear. We used whole exome sequencing (WES) in combination with the Genetic Variants Classification Criteria and Guidelines published by the American College of Medical Genetics (ACMG) and bioinformatics analysis to clarify the interrelationship between candidate genes. Causative genes for ocular diseases (45.38%) followed by neuropsychiatric disorders (22.69%) accounted for the highest proportion of genes that exhibited high pathogenicity in HM patients were found. Four pathogenic gene mutations were identified according to ACMG guidelines: c.164_165insACAGCA and c.C1760T in POLG, c.G1291A in COL5A1, and c.G10242T in ZNF469. Three causative genes for neuropsychiatric diseases, PTPRN2, PCDH15 and CDH23, were found to fall at the HM locus. The above results suggest that these genes may interact in high myopia and neuropsychiatric diseases.