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Background The ability of p38 to phosphorylate substrates in the nucleus and the role of nuclear p38 in the regulation of inflammation have focused attention on the subcellular localization of the kinase. Although it is clear that p38 shuttles to the nucleus upon stimulation, the mechanisms that regulate p38 nuclear input in response to mechanical stretch remain to be determined. Methods Cyclic stretch (CS)-induced nuclear translocation of p38 was determined by Western blotting and immunofluorescence. The p38 interacting protein was identified using endogenous pull-down and protein binding assays. The potential role of importin-7 (Imp7) in CS-induced nuclear translocation of p38 and p38-dependent gene expression was confirmed using a series of in vitro and in vivo experiments. Furthermore, we tested the therapeutic potential of intratracheal administration of Imp7 siRNA-loaded nanoparticles in the ventilator-induced lung injury (VILI) mouse model. Results We show that CS induced phosphorylation-dependent nuclear translocation of p38, which required the involvement of microtubules and dynein. Endogenous pull-down assay revealed Imp7 to be a potential p38-interacting protein, and the direct interaction between p38 and Imp7 was confirmed by in vitro and in vivo binding assays. Furthermore, silencing Imp7 inhibited CS-induced nuclear translocation of p38 and subsequent cytokine production. Notably, intratracheal administration of Imp7 siRNA nanoparticles attenuated lung inflammation and histological damage in the VILI mouse model. Conclusions Our findings uncover a key role for Imp7 in the process of p38 nuclear import after CS stimulation and highlight the potential of preventing p38 nuclear translocation in treatment of VILI.

Spike architecture influences grain yield in wheat. We report the map-based cloning of a gene determining the number of spikelet nodes per spike in common wheat. The cloned gene is named TaCOL-B5 and encodes a CONSTANS-like protein that is orthologous to COL5 in plant species. Constitutive overexpression of the dominant TaCol-B5 allele but without the region encoding B-boxes in a common wheat cultivar increases the number of spikelet nodes per spike and produces more tillers and spikes, thereby enhancing grain yield in transgenic plants under field conditions. Allelic variation in TaCOL-B5 results in amino acid substitutions leading to differential protein phosphorylation by the protein kinase Ta K4. The TaCol-B5 allele is present in emmer wheat but is rare in a global collection of modern wheat cultivars.

Background Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB. Methods This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days. Results Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC50 (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26–1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log10 IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log10 copies/mL, respectively. Conclusions Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection. Trial registration ClinicalTrials.gov, number NCT05470829).

The growth of the fusarium head blight (FHB) pathogen at the grain formation stage is a deadly threat to wheat production through disruption of the photosynthetic processes of wheat spikes. Real-time nondestructive and frequent proxy detection approaches are necessary to control pathogen propagation and targeted fungicide application. Therefore, this study examined the ch\lorophyll-related phenotypes or features from spectral and chlorophyll fluorescence for FHB monitoring. A methodology is developed using features extracted from hyperspectral reflectance (HR), chlorophyll fluorescence imaging (CFI), and high-throughput phenotyping (HTP) for asymptomatic to symptomatic disease detection from two consecutive years of experiments. The disease-sensitive features were selected using the Boruta feature-selection algorithm, and subjected to machine learning-sequential floating forward selection (ML-SFFS) for optimum feature combination. The results demonstrated that the biochemical parameters, HR, CFI, and HTP showed consistent alterations during the spike–pathogen interaction. Among the selected disease sensitive features, reciprocal reflectance (RR=1/700) demonstrated the highest coefficient of determination (R2) of 0.81, with root mean square error (RMSE) of 11.1. The multivariate k-nearest neighbor model outperformed the competing multivariate and univariate models with an overall accuracy of R2 = 0.92 and RMSE = 10.21. A combination of two to three kinds of features was found optimum for asymptomatic disease detection using ML-SFFS with an average classification accuracy of 87.04% that gradually improved to 95% for a disease severity level of 20%. The study demonstrated the fusion of chlorophyll-related phenotypes with the ML-SFFS might be a good choice for crop disease detection.

The promotion of vape products on social media has been implicated in increasing rates of e-cigarette usage, particularly among youth and young adults. While research has examined overall trends in vape-related content across a number of platforms, the role that social media "influencers" play in promoting vaping and potentially augmenting this public health crisis has been insufficiently explored. The present study examined 44,052 Instagram posts by 60 male presenting and 60 female presenting vape influencers to understand how influencer gender mediates the performance of vape culture online. Our textual and visual analysis of these influencers' posts over one year revealed significant bifurcations based on gender. Independent sample t-tests showed statistically significant gender differences in word frequency. Male-presenting influencers tended to emphasize their expertise with vape devices as technologies, while female-presenting influencers tended to focus on their own appearance. Further, factor analysis indicated six major categories of textual features, and multiple linear regression tests showed varying levels of user engagement with the different categories across both genders. Chi-square tests indicated that female-presenting influencers highlighted their own bodies in the visual content of their posts, whereas male presenting influencers often posted images of vape devices or their component parts alone. These findings suggest that gender presentation plays an important role in shaping vape influencers' promotional tactics and vape-related content on Instagram, and also provides insights into what kinds of content receive the most user engagement. This study can therefore help inform interventions to mitigate the impact of social media vape promotion.

Babesiosis is an emerging zoonosis worldwide that is caused by tick-borne apicomplexans, Babesia spp., which threatens the health of domesticated and wild mammals and even humans. Although it has done serious harm to animal husbandry and public health, the study of Babesia is still progressing slowly. Until now, no effective anti-Babesia vaccines have been available, and administration of combined drugs tends to produce side effects. Therefore, non-targeted metabolomics was employed in the present study to examine the temporal dynamic changes in the metabolic profile of the infected erythrocytes. The goal was to obtain new insight into pathogenesis of Babesia and to explore vaccine candidates or novel drug targets.C57BL/6 mice were infected with B. microti and erythrocytes at different time points (0, 3, 6 , 9, 12, and 22-days post-infection) were subjected to parasitemia surveillance and then metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS). Multivariate statistical analyses were performed to clearly separate and identify dysregulated metabolites in Babesia-infected mice. The analyses included principal components analysis (PCA) and orthogonal partial least squares-discrimination analysis (OPLS-DA). The time-series trends of the impacted molecules were analyzed using the R package Mfuzz and the fuzzy clustering principle. The temporal profiling of amino acids, lipids, and nucleotides in blood cells infected with B. microti were also investigated.B. microti infection resulted in a fast increase of parasitemia and serious alteration of the mouse metabolites. Through LC-MS metabolomics analysis, 10,289 substance peaks were detected and annotated to 3,705 components during the analysis period. There were 1,166 dysregulated metabolites, which were classified into 8 clusters according to the temporal trends. Consistent with the trend of parasitemia, the numbers of differential metabolites reached a peak of 525 at 6-days post-infection (dpi). Moreover, the central carbon metabolism in cancer demonstrated the most serious change during the infection process except for that observed at 6 dpi. Sabotage occurred in components involved in the TCA cycle, amino acids, lipids, and nucleotide metabolism.Our findings revealed a great alteration in the metabolites of Babesia-infected mice and shed new light on the pathogenesis of B. microti at the metabolic level. The results might lead to novel information about the mechanisms of pathopoiesis, babesisosis, and anti-parasite drug/vaccine development in the future.

Narrowing the health gap and promoting health equality is the key to effectively blocking the intergenerational transmission of rural poverty. Previous studies have mainly focused on the relationship between health and poverty, but assessments of health poverty are lacking, especially with regard to the health poverty of rural residents. Based on China’s large sample household survey data, this study uses the Alkire–Foster (AF) method to measure and decompose the health poverty of rural residents. The results show that the health poverty of Chinese rural residents greatly improved from 2016 to 2018. However, significant regional differences exist with regard to the level of health poverty. The marginal contribution of economic poverty alleviation is diminishing; the equalization of health services and security has shifted to a policy focus. Community environmental management has also become an important aspect of health poverty governance, and individual health literacy and behavior have played an important role in endogenous poverty alleviation. Ultimately, this paper offers some insightful policy implications. This study extends the multidimensional poverty measurement system and reveals the relationship between health poverty and regional economic and social development. The findings also enhance the understanding of the health poverty of rural residents in developing countries.

Molecular markers are developed to accelerate deployment of genes for desirable traits segregated in a bi-parental population of recombinant inbred lines (RILs) or doubled haplotype (DH) lines for mapping. However, it would be the most effective if such markers for multiple traits could be identified in an F2 population. In this study, single nucleotide polymorphisms (SNP) chips were used to identify major genes for heading date and awn in an F2 population without developing RILs or DH lines. The population was generated from a cross between a locally adapted spring wheat cultivar “Ningmaizi119” and a winter wheat cultivar “Tabasco” with a diverse genetic background. It was found that the dominant Vrn-D1 allele could make Ningmaizi119 flowered a few months earlier than Tabasco in the greenhouse and without vernalization. The observed effects of the allele were validated in F3 populations. It was also found that the dominant Ali-A1 allele for awnless trait in Tabasco or the recessive ali-A1 allele for awn trait in Ningmaizi119 was segregated in the F2 population. The allelic variation in the ALI-A1 gene relies not only on the DNA polymorphisms in the promoter but also on gene copy number, with one copy ali-A1 in Ningmaizi119 but two copies Ali-A1 in Tabasco based on RT-PCR results. According to wheat genome sequences, cultivar “Mattis” has two copies Ali-A1 and cultivar “Spelta” has four copies Ali-A in a chromosome that was uncharacterized (ChrUN), in addition to one copy on chromosome 5A. This study rapidly characterized the effects of the dominant Vrn-D1 allele and identified the haplotype of Ali-A1 in gene copy number in the F2 segregation population of common wheat will accelerate their deployment in cycling lines in breeding.

RNA interference (RNAi) plays important roles in organism development through post-transcriptional regulation of specific target mRNAs. Target specificity is largely controlled by base-pair complementarity between micro-RNA (miRNA) regulatory elements and short regions of the target mRNA. The pattern of miRNA production in a cell interacts with the cell’s mRNA transcriptome to generate a specific network of post-transcriptional regulation that can play critical roles in cellular metabolism, differentiation, tissue/organ development and developmental timing. In plants, miRNA production is orchestrated in the nucleus by a suite of proteins that control transcription of the pri-miRNA gene, post-transcriptional processing and nuclear export of the mature miRNA. In the model plant, Arabidopsis thaliana, post-transcriptional processing of miRNAs is controlled by a pair of physically-interacting proteins, HYL1 and DCL1. However, the evolutionary history of the HYL1-DCL1 interaction is unknown, as is its structural basis. Here we use ancestral sequence reconstruction and functional characterization of ancestral HYL1 in vitro and in vivo to better understand the origin and evolution of the HYL1-DCL1 interaction and its impact on miRNA production and plant development. We found the ancestral plant HYL1 evolved high affinity for both double-stranded RNA (dsRNA) and its DCL1 partner very early in plant evolutionary history, before the divergence of mosses from seed plants (~500 Ma), and these high-affinity interactions remained largely conserved throughout plant evolutionary history. Structural modeling and molecular binding experiments suggest that the second of two double-stranded RNA-binding motifs (DSRMs) in HYL1 may interact tightly with the first of two C-terminal DCL1 DSRMs to mediate the HYL1-DCL1 physical interaction necessary for efficient miRNA production. Transgenic expression of the nearly 200 Ma-old ancestral flowering-plant HYL1 in A. thaliana was sufficient to rescue many key aspects of plant development disrupted by HYL1− knockout and restored near-native miRNA production, suggesting that the functional partnership of HYL1-DCL1 originated very early in and was strongly conserved throughout the evolutionary history of terrestrial plants. Overall, our results are consistent with a model in which miRNA-based gene regulation evolved as part of a conserved plant ‘developmental toolkit’; its role in generating developmental novelty is probably related to the relatively rapid evolution of miRNA genes.

Bread wheat (Triticum aestivum L.) is a major crop that feeds 40% of the world's population. Over the past several decades, advances in genomics have led to tremendous achievements in understanding the origin and domestication of wheat, and the genetic basis of agronomically important traits, which promote the breeding of elite varieties. In this review, we focus on progress that has been made in genomic research and genetic improvement of traits such as grain yield, end-use traits, flowering regulation, nutrient use efficiency, and biotic and abiotic stress responses, and various breeding strategies that contributed mainly by Chinese scientists. Functional genomic research in wheat is entering a new era with the availability of multiple reference wheat genome assemblies and the development of cutting-edge technologies such as precise genome editing tools, high-throughput phenotyping platforms, sequencing-based cloning strategies, high-efficiency genetic transformation systems, and speed-breeding facilities. These insights will further extend our understanding of the molecular mechanisms and regulatory networks underlying agronomic traits and facilitate the breeding process, ultimately contributing to more sustainable agriculture in China and throughout the world.

Plant height affects directly the yield potential of wheat, and constitutes an important component of plant resistance to lodging. Although a large number of QTLs for plant height were detected, most of them have not been evaluated for their genetic effects yet. In the previous study, a major QTL Qph . nau-5B controlling wheat plant height was identified through association mapping in wheat variety collection. To evaluate the dwarfing effect of this QTL, three near-isogenic lines (NILs) with different alleles of Qph . nau-5B were developed using marker-assisted selection with Nanda 2419, Jichun 1016, and Zhengmai 9023 as donor and Zhongyou 9507 as receptor. The recipient genome compositions of these NILs were higher than 93%. Seven independent field trials were conducted and revealed that, compared with the recurrent parent, all NILs indicated a significant decrease in plant height (11.1 cm or 10.3% on average). Three alleles of Qph . nau-5B showed different degrees of dwarfing effects. The alleles coming from Jichun 1016 and Zhengmai 9023 displayed a similar effect on plant height (12.4 cm) in all environments, stronger than that of Nanda 2419 (8.6 cm). However, the relative dwarfism effects of different alleles were affected by different environments. Further analysis elucidated that this QTL had little detrimental influence on other agronomical traits such as spike number per plant, spike length and 1000-grain weight. These results suggested the breeding value of Qph . nau-5B that would be utilized for molecular design breeding of plant architecture in wheat.

Increasing evidence indicates that miRNAs are involved in tumorigenesis of human renal cell carcinoma (RCC). However, the role of miR-206 is still unknown. This study aimed to investigate the possible mechanism of miR-206 in progression of RCC. Here, compared with adjacent normal renal tissues and HK-2 cells, miR-206 level was markedly decreased, whereas CDK6 level was obviously increased in RCC tissues and cell lines. MiR-206 was inversely associated with lymph node metastasis and TNM stage, and acted as an independent prognostic factor in RCC. MiR-206 effectively caused apoptosis and cell cycle arrest at G0/G1 phase, and affected the growth of xenograft tumor of nude mice. MiR-206 also inhibited migration and invasion of RCC cells by modulating the expressions of EMT-related genes. Dual-luciferase assay demonstrated CDK6 was a direct target of miR-206. CDK6 silencing aggravated the inhibition effects of miR-206. In conclusion, miR-206 suppresses proliferation and EMT of RCC by inhibiting CDK6 expression. The miR-206/CDK6 axis may provide a novel insight into tumorigenesis of RCC.

The function of miR-186 in the progression of renal cell carcinoma (RCC) remains poorly investigated. Our study aims to identify the molecular mechanism underlying miR-186-regulated proliferation, migration and invasion of RCC. Firstly, our data confirmed that miR-186 was significantly reduced and CDK6 was obviously increased in RCC tissues and cells. MiR-186 or CDK6 was associated with advanced TNM stage, lymph node metastasis and poor prognosis. MiR-186 significantly inhibited cell proliferation, migration, invasion and in vivo tumor growth, induced apoptosis, and blocked cell cycle progression in G0/G1 phase. MiR-186 also induced Bax expression and inhibited the expressions of Bcl-2, cyclin D1 and epithelial-mesenchymal transition (EMT)-related genes. Additionally, CDK6 expression was downregulated by miR-186 via binding to its 3'-untranslated region (3'-UTR). Moreover, ectopic expression of CDK6 could partially abrogate the inhibitory effect of miR-186. In conclusion, miR-186 suppresses proliferation, migration and invasion of RCC by inhibiting CDK6 expression.

Lineage-specific genes (LSGs) are a set of genes in a given taxon without significant sequence similarity to genes and intergenic sequences of other taxa and are functional. The tribe Triticeae mainly includes species of different ploidy levels, such as staple food crops wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.). This study is aimed at mining and characterizing the Triticeae-specific genes (TSGs) using expressed sequence data of wheat. A total of 3812 TSGs was identified and they were generally characterized by smaller size, fewer exons, shorter open reading frames and lower expression levels. Most TSGs were expressed with tissue preference and many of them were predominantly expressed in reproduction related tissues, especially in young stamen. Nearly one third of the TSGs were stress-responsive and inducible under abiotic and/or biotic stresses. A co-expression-based annotation supported the relevance of some TSGs with reproduction and stress responses, indicating their potential economic importance.

The foundry development of integrated photonics has revolutionized today’s optical interconnect and datacenters. Over the last decade, we have witnessed the rising of silicon nitride (Si3N4) integrated photonics, which is currently transferring from laboratory research to foundry manufacturing. The development and transition are triggered by the ultimate need for low optical loss offered by Si3N4, which is beyond the reach of silicon and III-V semiconductors. Combined with modest Kerr nonlinearity, tight optical confinement, and dispersion engineering, Si3N4 has today become the leading platform for linear and Kerr nonlinear photonics, and it has enabled chip-scale lasers featuring ultralow noise on par with table-top fiber lasers. However, so far all the reported fabrication processes of tight-confinement, dispersion-engineered Si3N4 photonic integrated circuits (PICs) with optical loss down to few dB/m have only been developed on 4-inch (100 mm diameter) or smaller wafers. Yet, to transfer these processes to established CMOS foundries that typically operate 6-inch or even larger wafers, challenges remain. In this work, we demonstrate the first foundry-standard fabrication process of Si3N4 PICs with only 2.6 dB/m loss, thickness above 800 nm, and near 100% fabrication yield on 6-inch (150 mm diameter) wafers. Such thick and ultralow-loss Si3N4 PIC enables low-threshold generation of soliton frequency combs. Merging with advanced heterogeneous integration, active ultralow-loss Si3N4 integrated photonics could pave an avenue to addressing future demands in our increasingly information-driven society.

Research on access to health services during the COVID-19 pandemic is limited, and the conceptualization of access has not typically included access to community resources. We developed and tested an access-to-health-services measure and examined disparities in access among individuals in the U.S. during the pandemic. Data are from a U.S. sample of 1491 respondents who completed an online survey in August 2021. Linear regression models assessed the relationships between the access-to-health-services-measure components, including impact on access to medicine and medical equipment, impact on access to healthcare visits, and confidence in accessing community resources, and predictor variables, including sociodemographic- and health-related factors. Disparities in access to healthcare during the pandemic were associated with sociodemographic characteristics (i.e., race, gender, and age) and health-related characteristics (i.e., chronic illness, mental health condition, and disability). Factors such as race, gender, income, and age were associated with individuals’ degree of confidence in accessing community services. Our study presents a new access-to-health-services measure, sheds light on which populations may be most vulnerable to experiencing reduced access to health services, and informs the development of programmatic interventions to address the salient needs of these populations.

Rainfall-runoff and water flooding are the driving mechanisms of agricultural nonpoint source pollution (ANPSP), but existing research has hardly focused on water level-driven ANPSP. Danjiangkou Reservoir was the second largest reservoir in China, and its water quality was dominated by ANPSP. This study explored the effect of water level on water quality of Danjiangkou Reservoir and aimed to provide basis for water quality management of large reservoirs. The effect of water level-driven ANPSP on the concentration of reservoir ammonia was studied employing the methods of factor decomposition and multiple regression on a extensive time series data of reservoir ammonia, water level, rainfall, fertilizer usage, and inflow river ammonia. The long-term trend revealed the reservoir ammonia peaked in 2011 and the inflow river ammonia peaked in 2012 (Han River) and 2013 (Dan River), which indicated the success of point source control in the past 15 years and the dominant role of ANPSP in the reservoir ammonia in recent years. With the long-term trend series, the multiple regression results showed that 56% of the variation of the reservoir ammonia concentration was due to the water level (standardized regression coefficient 0.422), fertilizer usage (standardized regression coefficient 0.522), and inflow river ammonia (standardized regression coefficient 0.219). However, the rainfall was insignificant. The predominance of water level and fertilizer usage in explanation of the reservoir ammonia variation indicated that water level-driven ANPSP was the primary factor influencing the reservoir ammonia. The effect of water level was primarily reflected in the long-term variation of ammonia concentration rather than the seasonal variation within the year. This study showed that when compared with rainfall-driven ANPSP, water level-driven ANPSP had a greater impact on the reservoir ammonia. Water quality protection should center on the management of the water level-fluctuation zone.

KT1 was validated as a novel thickness QTL with major effects on wheat kernel dimensions and weight and fine mapped to a 0.04 cM interval near the chromosome-5A centromere. Kernel size, the principal grain weight determining factor of wheat and a target trait for both domestication and artificial breeding, is mainly defined by kernel length (KL), kernel width (KW) and kernel thickness (KT), of which KW and KT have been shown to be positively related to grain weight (GW). Qkt.nau-5A, a major QTL for KT, was validated using the QTL near-isogenic lines (NILs) in three genetic backgrounds. Genetic analysis using two F

In animals, endocytosis of a 7-transmembrane GPCR is mediated by arrestins to propagate or arrest cytoplasmic G-protein-mediated signaling, depending on the bias of the receptor or ligand, which determines how much one transduction pathway is used compared to another. In Arabidopsis thaliana, GPCRs are not required for G protein-coupled signaling because the heterotrimeric G protein complex spontaneously exchanges nucleotide. Instead, the 7-transmembrane protein AtRGS1 modulates G protein signaling through ligand-dependent endocytosis, which initiates de-repression of signaling without the involvement of canonical arrestins. Here, we found that endocytosis of AtRGS1 initiated from two separate pools of plasma membrane: Sterol-dependent domains and a clathrin-accessible neighborhood, each with a select set of discriminators, activators, and candidate arrestin-like adaptors. Ligand identity (either the pathogen-associated molecular pattern flg22 or the sugar glucose) determined the origin of AtRGS1 endocytosis. Different trafficking origins and trajectories led to different cellular outcomes. Thus, in this system, compartmentation with its associated signalosome architecture drives biased signaling.

In animals, endocytosis of a seven-transmembrane GPCR is mediated by arrestins to propagate or arrest cytoplasmic G protein-mediated signaling, depending on the bias of the receptor or ligand, which determines how much one transduction pathway is used compared to another. In Arabidopsis thaliana, GPCRs are not required for G protein-coupled signaling because the heterotrimeric G protein complex spontaneously exchanges nucleotide. Instead, the seven-transmembrane protein AtRGS1 modulates G protein signaling through ligand-dependent endocytosis, which initiates derepression of signaling without the involvement of canonical arrestins. Here, we found that endocytosis of AtRGS1 initiated from two separate pools of plasma membrane: sterol-dependent domains and a clathrin-accessible neighborhood, each with a select set of discriminators, activators, and candidate arrestin-like adaptors. Ligand identity (either the pathogen-associated molecular pattern flg22 or the sugar glucose) determined the origin of AtRGS1 endocytosis. Different trafficking origins and trajectories led to different cellular outcomes. Thus, in this system, compartmentation with its associated signalosome architecture drives biased signaling.

Powdery mildew, caused by the biotrophic fungus Blumeria graminis f. sp. tritici (Bgt), is a prevalent disease in common wheat (Triticum aestivum L.) and causes serious yield losses worldwide. We used a map-based approach to clone the major broad-spectrum powdery mildew resistance gene PmCH1357 from wheat breeding line CH1357. PmCH1357 was mapped to a 526 kb region containing only TraesCS5D01G044600. The TraesCS5D01G044600 sequence of the susceptibility allele in Taichung 29 (TC29) was identical to that in Chinese Spring, whereas the sequence of the resistance allele in CH1357 was identical to Pm2a previously cloned from the germplasm Ulka/*8Cc. The susceptibility allele in TC29 contained a 7 bp deletion in exon 1, resulting in loss of 856 of the 1277 amino acids in the predicted nucleotide-binding domain leucine-rich repeat containing Pm2a protein. PmCH1357/Pm2a sequence was also isolated from the Chinese wheat landraces and cultivars that were previously reported to possess the resistance gene Pm2b, Pm2c, PmLX66, or PmND399. The PmCH1357/Pm2a resistance allele was present in 10 of 495 accessions in core germplasm and contemporary cultivars from China and the USA. A newly developed diagnostic marker for the 7 bp InDel in the resistance gene can be used to eliminate the susceptibility allele in wheat breeding programs. Keywords: Map-based cloning, Natural variation, Bgt isolate E09, Triticum aestivum, Molecular breeding

Although the development of stimulated reservoir volume (SRV) fracturing treatment promotes the exploitation of the tight oil reservoirs, the well production performance has not been modele...

It has been widely reported that cellulose nanocrystals (CNCs) demonstrate a special structural color, which stems from chiral nematic domains. Herein, the humidity and heat dual response nanocompo...

Plant tissue brittleness is related to cellular structure and lodging. MED0031 is a mutant identified previously from ethyl methane sulfonate treatment of diploid wheat accession TA2726, showing brittleness in both stem and leaf. In microscopic and histological observations, the mutant was found to have less large vascular bundles per unit area, a thinner sclerenchyma cell wall, and a broader parenchyma, compared with the wild type. The mutated gene, TmBr1, was mapped to a 0.056 cM interval on chromosome 5Am. This gene was cloned using a MapRseq approach that searched the candidate gene through combination of the prior target gene mapping information with SNP calling and discovery of differentially expressed genes from RNA_seq data of the wild type and a BC3F2 bulk showing the mutant phenotype. TmBr1 encodes a COBL protein and a nonsense mutation within the region coding for the conserved COBRA domain caused premature translation termination. Introduction of TmBr1 to Arabidopsis AtCOBL4 mutant rescued the phenotype, demonstrating their functional conservation. Apart from the effect on cellulose content, the TmBr1 mutation might modulate synthesis of noncellulosic polysaccharide pectin as well. Application of the MapRseq approach to isolation of genes present in recombination cold spots and complicated genomes was discussed.

In this paper, core-shell structured poly (indole‑5‑carboxylic acid) @ poly (3, 4‑ethylenedioxythiophene) (PIn‑5‑COOH@PEDOT) composite was prepared by a facile two-step chemical oxidation method. The composite possesses large specific surface area, high stability, good electrical conductivity and redox activity, which was designed as label-free electrochemical immunosensing platform for the monitor of the prostate specific antigen (PSA). In this sensing system, PIn-5-COOH served as both signal molecule and antibody carrier. The coating PEDOT was used to enhance the conductivity and stability of PIn-5-COOH. Benefiting from the synergistic effects between PIn-5-COOH and PEDOT, the fabricated immunosensor exhibited a wide linear range of 0.01–25 ng mL−1 and low detection limit of 3.4 pg mL−1 (S/N = 3) for the assay of PSA, coupled with good selectivity, reproducibility and stability. The immunosensor is simple, sensitive, specific and reproducible, which could provide a potential approach for clinical diagnosis.

Dendranthema morifolium cv. ‘jinsidaju’, cultivated only in Kaifeng, has been eaten for more than 1000 years. During the antioxidant-activity-guided studies on its chemistry and health care function, two new bisabolane-type sesquiterpenes, (6R,7R)-7-hydroxybisabol-2,9E,11-triene-4-one (jinsidajuol A, 1) and (6R,7R)-7-hydroxy-11-methoxybisabol-2,9E-diene-4-one (jinsidajuol B, 2), and thirteen known compounds (3–15) were isolated from the flowers. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS. 1 and 2 are the first example of bisabolane-type sesquiterpenes isolated from the genus Dendranthema. Compounds 6–8, 12 and 13 exhibited strong scavenging activities on the ABTS radical cation with IC50 3.33, 5.67, 2.00, 2.50, 5.33 μg/mL, respectively. The IC50 values of all compounds on HepG2 human hepatoma tumor cell line were higher than 50 μM.

In this work, electrode based on poly(3,4-ethylenedioxythiophene) (PEDOT) was employed for the fabrication of an efficient sensor for 4-chloro-3-methylphenol (PCMC) detection. To improve the dispersity and increase the specific surface area of PEDOT, core-shell structured UiO-66-NH2@PEDOT was designed by in-situ oxidation method using Zr-based metal-organic framework (UiO-66-NH2) as template. In addition, to achieve a further increased active surface area and electron transfer rate of the modified materials, graphene aerogel (GA) was utilized as substrate material for the assembly of UiO-66-NH2@PEDOT. Then, the obtained UiO-66-NH2@ PEDOT/GA modified electrode was employed as an electrochemical sensor for PCMC detection. Experiment parameters, such as pH value of acetate buffer solution and accumulation time, were optimized in detail. Under the optimized experiment condition, the UiO-66-NH2@PEDOT/GA electrode showed a good linear range of 0.6–18 μM, as well as a low detection limit of 0.2 μM (S/N = 3). The UiO-66-NH2@PEDOT/GA electrode was applied toward the detection of PCMC in tap water with good recovery. All these features suggest that the prepared PEDOT-based composite could serve as a promising sensing platform for monitoring water pollutants.

A major QTL QSpl.nau-7D, named HL2, was validated for its effects on head length and kernel number per spike using NIL, and mapped to a 0.2 cM interval using recombinants. Improvement in wheat inflorescence traits such as spike or head length and spikelet number provides an important avenue to increase grain yield potential. In a previous study, QSpl.nau-7D, the major QTL for head length on chromosome 7D, was identified in the recombinant inbred lines derived from Nanda2419 and Wangshuibai. To validate and precisely map this QTL, the Wangshuibai allele was transferred to elite cultivar Yangmai15 through marker-assisted selection. Compared with the recurrent parent, the resultant near-isogenic line (NIL) yielded not only 28% longer spikes on the average but also more spikelets and kernels per spike. Moreover, the NIL had a lower spikelet density and did not show significant kernel weight change. In the F2 population derived from the NIL, QSpl.nau-7D acted like a single semi-dominant gene controlling head length and was therefore designated as Head Length 2 (HL2). With this population, a high-density genetic map was constructed mainly using newly developed markers, and 100 homozygous recombinants including 17 genotypes were obtained. Field experiments showed that the recombinants carrying the 0.2-cM interval flanked by Xwgrb1588 and Xwgrb1902 from Wangshuibai produced longer spikes than those without this Wangshuibai allele. Comparative mapping of this interval revealed a conserved synteny among cereal grasses. HL2 is beneficial to wheat breeding for more kernels per spike at a lower spikelet density, which is a favored morphological trait for Fusarium head blight resistance.

Vernalization genes underlying dramatic differences in flowering time between spring wheat and winter wheat have been studied extensively, but little is known about genes that regulate subtler differences in flowering time among winter wheat cultivars, which account for approximately 75% of wheat grown worldwide. Here, we identify a gene encoding an O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) that differentiates heading date between winter wheat cultivars Duster and Billings. We clone this TaOGT1 gene from a quantitative trait locus (QTL) for heading date in a mapping population derived from these two bread wheat cultivars and analyzed in various environments. Transgenic complementation analysis shows that constitutive overexpression of TaOGT1b from Billings accelerates the heading of transgenic Duster plants. TaOGT1 is able to transfer an O-GlcNAc group to wheat protein TaGRP2. Our findings establish important roles for TaOGT1 in winter wheat in adaptation to global warming in the future climate scenarios., Little is known about genes that regulate flowering time difference among winter wheat cultivars. Here, via map-based cloning, the authors show the role of an O-linked N-acetylglucosamine (O-GlcNAc) transferase TaOGT1 in regulating flowering time difference among winter wheat cultivars.

Functional diversification of transcription factor families through variation in modular domain architectures has played a central role in the independent evolution of gene regulatory networks underlying complex development in plants and animals. Here we show that architecture has in turn constrained evolution of B3 DNA binding domains in the B3 network regulating embryo formation in plants. B3 domains of ABI3, FUS3, LEC2 and VAL1 proteins recognize the same cis-element. ABI3 and VAL1 have complex architectures that physically integrate cis-element recognition with other signals, whereas LEC2 and FUS3 have reduced architectures conducive to their roles as pioneer activators. Qualitatively different activities of LEC2 and ABI3 B3 domains measured in vivo and in vitro are attributed in part to clade-specific substitutions in three amino acids that interact with the DNA backbone. Activities of FUS3 and VAL1 B3 domains show a similar correlation with architectural complexity. Domain-swap analyses in planta show that in a complex architecture setting the attenuated activities of ABI3 and VAL1 B3 domains are required for proper integration of ciselement recognition with hormone signalling. These results highlight modes of structural variation affecting non-specific, electrostatic interactions with the DNA backbone as a general mechanism allowing adaptation of DNA binding affinity to architectural constraints while preserving DNA sequence specificity.

Hyperspectral reflectance (HR) technology as proxy approach to diagnose fusarium head blight (FHB) in wheat crop could be a real-time and non-invasive approach for its in-field management to reduce grain damage. In-field canopy’s non-imaging HR (400–2400 nm using ground-based spectrometer system), photosynthesis rate (Pn) and disease severity (DS) data were simultaneously acquired from artificially inoculated wheat plots over a period of two years (2020 and 2021) in the field. Subsequently, continuous wavelet transform (CWT) was employed to select the consistent spectral bands (CSBs) and to develop the canopy-based difference indices with criterion of variable importance score using random forest—recursive feature elimination. Thereby, different machine learning algorithms were employed for FHB classification and multivariate estimation, and linear regression models to evaluate the newly developed indices against conventional vegetation indices. The results showed that inoculation reduced the Pn rate of spikes, elevated reflectance in visible and short-wave infrared regions and decreased in near infrared region at different days after inoculation (DAI). CWT analysis selected five CSBs (401, 460, 570, 786 and 840 nm) employing datasets from 2020 and 2021. These spectral bands were employed to develop wheat fusarium canopy indices (WFCI1 and WFCI2). Considering the average classification accuracy (ACA) in both years of experiments, WFCI1 manifested a maximum ACA of 75% at 5 DAI with DS of 9.73% which raised to 100% at 10 DAI with a DS of 18%. ACA mentions the averaged results of all machine learning classifiers (MLC). While in the perspective of MLC, random forest (RF) outperformed the rest of the MLC, individually, it revealed 100% classification accuracy through WFCI1 at DS 10.78% on the eight DAI. The univariate estimation of disease based on WFCI1 and WFCI2 with independent data produced R2 and root mean square error (RMSE) values of 0.80 and 14.7, and 0.81 and13.50, respectively. However, Knn regression analysis with both canopy indices (WFCI1 and WFCI2) manifested the maximum accuracy for disease estimation with RMSE of 11.61 and R2 = 0.83. Conclusively, the newly proposed HR indices show great potential as proxy approach for detecting FHB at early stage and understanding the physical state of crops in field conditions for the better management and control of plant diseases.

Stably expressed type I and type II resistance QTL were identified using two Yangmai 158-derived RIL populations, and plant-height and flowering-time QTL intervals detected did not contribute to the FHB resistance variations. Yangmai 158 (Y158) is an elite wheat cultivar widely grown in China with stable Fusarium head blight (FHB) resistance. To enrich the genetic basis underlying FHB resistance, QTL mapping was conducted using two recombinant inbred line (RIL) populations derived from crosses of Y158 with susceptible lines Annong 8455 and Veery. Survey with makers linked to Fhb1, Fhb2, Fhb4 and Fhb5 in resistance cultivar Wangshuibai indicated that both Y158 and the susceptible lines do not contain these QTL. The RIL populations were surveyed with 65 PCR markers and 55 K chip, which generated 23,159 valid marker data, to produce genetic maps for whole genome scanning of quantitative trait loci (QTL). A total of six QTL, all with the Y158 alleles for better resistance and including one stably expressed QTL for type I resistance (Qfhi.nau-2D) and one stably expressed QTL for type II resistance (Qfhs.nau-2A), were identified. Moreover, taking advantage of the great genetic variations in plant height and flowering time, QTL conditioning these two traits were determined. Of six plant-height QTL and three flowering-time QTL intervals detected, none were associated with FHB resistance. The FHB resistance QTL in Y158 were shown to be useful alternatives in FHB resistance breeding programs. The SNP markers flanking Qfhs.nau-2A and Qfhi.nau-2D have been converted to breeder-friendly PCR-based markers to facilitate their applications.

A bio-based pressure-responsive sensor with adjustable structural color is prepared by combining aerogel skeleton of cellulose nanocrystals (CNCs)/poly(ethylene glycol) (PEG) obtained via the ice-templating method with flexible polyacrylamide (PAAM) elastomer. The white aerogel is composed of consecutive ribbons, demonstrating chiral nematic structure. These ribbons are rearranged to be vertical to the force direction, leading to immediate appearance of the structural color when the 3D aerogel transforms to a 2D plane. Helical pitches are regulated by the PEG content that the wavelength of structural color covers up to 178 nm. There is an excellent linear correlation between pressure and transmittance of reflectance peak, and the sensitivity to pressure can be regulated by changing solid content of PAAM. Furthermore, the pressure-responsive color is still vivid after 16 cycles of compression. This flexible material with pressure-responsive structural color is promising in sensing, intelligent display, information transmission, and etc.

The current study investigated whether hyperoxia may reverse hypoxia-induced radioresistance (RR) in cervical cancer. Human HeLa cells exposed to hypoxic, normoxic or hyperoxic conditions were irradiated using X-rays. Cell proliferation and apoptosis were analyzed using MTT assays and flow cytometry. The expression levels of hypoxia-inducible factor-1α (HIF-1α), VEGF165, VEGFRs, Akt and ERK were measured via western blotting and/or ELISA. The results demonstrated that hypoxia stimulated HIF-1α and VEGF expression, and induced RR in HeLa cells. The administration of recombinant VEGF or the forced expression of VEGF promoted RR, whereas inactivating HIF-1α or blocking the VEGF-VEGFR interaction abrogated hypoxia-induced RR. Notably, hyperoxia decreased the level of hypoxia-stimulated HIF-1α and VEGF, and enhanced radiosensitivity in hypoxic HeLa cells. The results demonstrated that hyperoxia suppressed the hypoxia-activated Akt and ERK signaling pathways in HeLa cells. Therefore, a high O2 concentration may be considered as a radiotherapeutic sensitizer for hypoxic HeLa cells.