The extensive use of two alleles (Rht-B1b and Rht-D1b) at the Rht-1 locus in wheat allowed dramatic increases in yields, triggering the so-called "Green Revolution." Here, we found that a new natural allelic variation (Rht-B1i) containing a single missense SNP (A614G) in the coding region significantly increased plant height against the genetic background of both Rht-D1a (11.68%) and Rht-D1b (7.89%). To elucidate the molecular mechanism of Rht-B1i, we investigated the promoter region. Sequence analysis showed that the Rht-B1i promoter could be divided into two classes depending on the presence or absence of a specific 160 bp insertion: Rht-B1i-1 (with the 160 bp insertion) and Rht-B1i-2 (without the 160 bp insertion). The promoter of Rht-B1i-1 contained 32 more possible cis-acting elements than Rht-B1a, including a unique auxin response element AUXREPSIAA4. Quantitative RT-PCR analysis indicated that the 160 bp insertion is likely to promote the transcription of the Rht-B1i-1 gene. The coleoptile lengths of wheat varieties treated with IAA, GA3, and IAA/GA3, combined with the histochemical staining of transgenic Arabidopsis containing the Rht-B1i-1 promoter, showed that the height-increasing effect of Rht-B1i-1 may be due to the synergistic action of IAA and GA3. These results augment our understanding of the regulatory mechanisms of Rht-1 in wheat and provide new genetic resources for wheat improvement.

Kernel hardness, which has great influence on the end-use properties of common wheat, is mainly controlled by Puroindoline genes, Pina and Pinb. Using EcoTILLING platform, we herein investigated the allelic variations of Pina and Pinb genes and their association with the Single Kernel Characterization System (SKCS) hardness index in a diverse panel of wheat germplasm.

The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.

Pathological cardiac hypertrophy eventually leads to heart failure without adequate treatment. REGγ is emerging as 11S proteasome activator of 20S proteasome to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner. Here, we found that REGγ was significantly upregulated in the transverse aortic constriction (TAC)-induced hypertrophic hearts and angiotensin II (Ang II)-treated cardiomyocytes. REGγ deficiency ameliorated pressure overload-induced cardiac hypertrophy were associated with inhibition of cardiac reactive oxygen species (ROS) accumulation and suppression of protein phosphatase 2A catalytic subunit α (PP2Acα) decay. Mechanistically, REGγ interacted with and targeted PP2Acα for degradation directly, thereby leading to increase of phosphorylation levels and nuclear export of Forkhead box protein O (FoxO) 3a and subsequent of SOD2 decline, ROS accumulation, and cardiac hypertrophy. Introducing exogenous PP2Acα or SOD2 to human cardiomyocytes significantly rescued the REGγ-mediated ROS accumulation of Ang II stimulation in vitro. Furthermore, treatment with superoxide dismutase mimetic, MnTBAP prevented cardiac ROS production and hypertrophy features that REGγ caused in vivo, thereby establishing a REGγ-PP2Acα-FoxO3a-SOD2 pathway in cardiac oxidative stress and hypertrophy, indicates modulating the REGγ-proteasome activity may be a potential therapeutic approach in cardiac hypertrophy-associated disorders.

Mycoplasma gallisepticum (MG) infection is the main cause of chronic respiratory disease (CRD) characterized by severe respiratory inflammation in chickens. Polydatin (PD) is a resveratrol glycoside isolated from Polygonum cuspidatum, which has prominent anti-inflammatory effect. The purpose of this study was to investigate the therapeutic effect of PD against MG-induced inflammation in chicken and its underlying mechanism. Histopathological analysis showed that PD treatment (15, 30, and 45 mg/kg) apparently alleviated MG-induced pathological changes of chicken embryonic lung. In chicken embryo fibroblast (DF-1) cells, PD treatment (15, 30, and 60 μg/mL) could effectively suppress MG propagation, promote MG-infected cell proliferation and cell cycle progress, and inhibit MG-induced cell apoptosis. ELISA and qPCR assays showed that PD treatment significantly suppressed the expression of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) induced by MG both in vivo and in vitro. Besides, molecular studies indicated that the MG-induced levels of toll-like receptor-6 TLR6, myeloid differentiation-88 (MyD88) and nuclear factor κB (NF-κB) were significantly decreased by PD treatment. Moreover, immunofluorescence analysis showed that PD treatment restrained the MG-induced NF-κB-p65 nuclear translocation. Taken together, these results indicate the protective effects of PD against MG-induced inflammation injury in chicken were mainly by inhibiting the TLR6/MyD88/NF-κB pathway.

The intensive and extensive application of imidacloprid in agriculture has resulted in water pollution and risks to aquatic invertebrates. However, pure bacteria remediation of imidacloprid in surface water environments has not been studied. Here, we isolated an imidacloprid-degrading bacterium from a water environment, examined its imidacloprid degradation in pure culture and surface water, sequenced its genome, and compared its Clusters of Orthologous Groups (COG) protein categorization with that for another imidacloprid-degrading bacterium. The isolate was an obligate oligotrophic bacterium, Hymenobacter latericoloratus CGMCC 16346, which degraded imidacloprid via hydroxylation by co-metabolism in pure culture. Resting cells degraded 64.4% of 100 mg/L imidacloprid in 6 days in the presence of co-substrate maltose, and growing culture degraded 40.8% of imidacloprid in 10 days. H. latericoloratus CGMCC 16346 degraded imidacloprid in surface water without co-substrate supplementation and retained imidacloprid-degrading activity after 30 days. The half-life of imidacloprid in surface water was decreased from 173.3 days in the control to 57.8 days by CGMCC 16346 inoculation. Genome sequencing and COG analysis indicated that carbohydrate metabolism and transport, cell wall/membrane biogenesis, and defense mechanisms are enriched in H. latericoloratus CGMCC 16346 compared with the copiotrophic imidacloprid-degrading Pseudoxanthomonas indica CGMCC 6648, indicating that H. latericoloratus CGMCC 16346 is adapted to live in oligotrophic water environments and biofilms. H. latericoloratus CGMCC 16346 is a promising bioremediation agent for elimination of imidacloprid contamination from surface water.

High mobility group box-1 (HMGB1) plays an important role in various liver injuries. In the case of acute liver injury, it leads to aseptic inflammation and other reactions, and also regulates specific cell death responses in chronic liver injury. HMGB1 has been demonstrated to be a good therapeutic target for treating liver failure. Quercetin (Que), as an antioxidant, is a potential phytochemical with hepatocyte protection and is also considered to be an inhibitor of HMGB1. However, the mechanism of its hepatoprotective effects remains to be characterized. The present study explored whether the hepatoprotective effect of Que antagonizes HMGB1, and subsequent molecular signaling events. Our results indicated that Que protects L02 cells from d-galactosamine (d-GaLN)-induced cellular damage by reducing intracellular reactive oxygen species (ROS) production and apoptotic responses in the mitochondrial pathway. Immunofluorescence and Western blot assays showed that HMGB1 was involved in d-GaLN-induced L02 cell damage. Further research showed that after transfection with HMGB1 short hairpin RNA (shRNA), cell viability was improved, and intracellular ROS production and apoptosis were suppressed. When co-treated with Que, the expression of HMGB1 was decreased significantly, the expression of proteins in the corresponding signal pathway were further reduced, and the production of ROS and apoptosis were further suppressed. Molecular docking also indicated the binding of Que and HMGB1. Taken together, these results indicate that Que significantly improves d-GaLN-induced cellular damage by inhibiting oxidative stress and mitochondrial apoptosis via inhibiting HMGB1.

Objective: Serum uric acid is associated with tumor progression and hepatocarcinogenesis. Here, we aimed to determine whether serum uric acid is related to the survival time of patients with hepatocellular carcinoma (HCC) and whether the inhibition of uric acid production affects the progression and survival of rats with HCC. Methods: The follow-up data of 288 patients with advanced HCC were analyzed. Ten purine metabolites in serum and liver samples of diethylnitrosamine (DEN)-induced HCC rats were quantitatively determined by an established UPLC-MS/MS method. On this basis, febuxostat, a specific inhibitor of xanthine oxidase (XOD), was used to interfere with HCC rats. Results: The serum uric acid level of HCC patients was significantly negatively correlated with survival days (r = -0.155). The median survival time was 133.5 days in the high uric acid group (>360 μmol/L, n = 80) and 176.0 days in the normal serum uric acid group (<360 μmol/L, n = 208, p = 0.0013). The levels of hypoxanthine, guanine, and uric acid; XOD activity; and xanthine dehydrogenase mRNA expression in the serum or liver samples of HCC rats were significantly upregulated compared with those in the control group. After febuxostat intervention in DEN-induced HCC rats, the number of atypical cells and inflammatory cells decreased significantly; the serum alpha fetoprotein level and Fisher's ratio tended to return to normal; the median survival time increased from 36 to 96 days (p = 0.08). In addition, serum malondialdehyde, superoxide dismutase, and glutathione activity nearly returned to the level of the healthy control group. Conclusion: The elevation of serum uric acid implies a risk of poor survival in advanced HCC patients and Febuxostat can reduce the generation of reactive oxygen species, thereby playing a role in delaying the progression of liver cancer.

Polyploidy and the subsequent ploidy reduction and genome shuffling are the major driving forces of genome evolution. Here, we revealed short-term allopolyploid genome evolution by sequencing a synthetic intergeneric hybrid (Raphanobrassica, RRCC). In this allotetraploid, the genome deletion was quick, while rearrangement was slow. The core and high-frequency genes tended to be retained while the specific and low-frequency genes tended to be deleted in the hybrid. The large-fragment deletions were enriched in the heterochromatin region and probably derived from chromosome breaks. The intergeneric translocations were primarily of short fragments dependent on homoeology, indicating a gene conversion origin. To accelerate genome shuffling, we developed an efficient genome editing platform for Raphanobrassica. By editing Fanconi Anemia Complementation Group M (FANCM) genes, homoeologous recombination, chromosome deletion and secondary meiosis with additional ploidy reduction were accelerated. FANCM was shown to be a checkpoint of meiosis and controller of ploidy stability. By simultaneously editing FLIP genes, gene conversion was precisely introduced, and mosaic genes were produced around the target site. This intergeneric hybrid and genome editing platform not only provides models that facilitate experimental evolution research by speeding up genome shuffling and conversion but also accelerates plant breeding by enhancing intergeneric genetic exchange and creating new genes.

Seed storage proteins (SSPs) are determinants of wheat end-product quality. SSP synthesis is mainly regulated at the transcriptional level. Few transcriptional regulators of SSP synthesis have been identified in wheat and this study aims to identify novel SSP gene regulators. Here, the R2R3 MYB transcription factor TuODORANT1 from Triticum urartu was found to be preferentially expressed in the developing endosperm during grain filling. In common wheat (Triticum aestivum) overexpressing TuODORANT1, the transcription levels of all the SSP genes tested by RNA-Seq analysis were reduced by 49.71% throughout grain filling, which contributed to 13.38%-35.60% declines in the total SSP levels of mature grains. In in vitro assays, TuODORANT1 inhibited both the promoter activities and the transcription of SSP genes by 1- to 13-fold. The electrophoretic mobility shift assay (EMSA) and ChIP-qPCR analysis demonstrated that TuODORANT1 bound to the cis-elements 5'-T/CAACCA-3' and 5'-T/CAACT/AG-3' in SSP gene promoters both in vitro and in vivo. Similarly, the homolog TaODORANT1 in common wheat hindered both the promoter activities and the transcription of SSP genes by 1- to 112-fold in vitro. Knockdown of TaODORANT1 in common wheat led to 14.73%-232.78% increases in the transcription of the tested SSP genes, which contributed to 11.43%-19.35% elevation in the total SSP levels. Our data show that both TuODORANT1 and TaODORANT1 are repressors of SSP synthesis.

Low-molecular-weight glutenin subunits (LMW-GS), encoded by a complex multigene family, play an important role in the processing quality of wheat flour. Although members of this gene family have been identified in several wheat varieties, the allelic variation and composition of LMW-GS genes in common wheat are not well understood. In the present study, using the LMW-GS gene molecular marker system and the full-length gene cloning method, a comprehensive molecular analysis of LMW-GS genes was conducted in a representative population, the micro-core collections (MCC) of Chinese wheat germplasm. Generally, >15 LMW-GS genes were identified from individual MCC accessions, of which 4-6 were located at the Glu-A3 locus, 3-5 at the Glu-B3 locus, and eight at the Glu-D3 locus. LMW-GS genes at the Glu-A3 locus showed the highest allelic diversity, followed by the Glu-B3 genes, while the Glu-D3 genes were extremely conserved among MCC accessions. Expression and sequence analysis showed that 9-13 active LMW-GS genes were present in each accession. Sequence identity analysis showed that all i-type genes present at the Glu-A3 locus formed a single group, the s-type genes located at Glu-B3 and Glu-D3 loci comprised a unique group, while high-diversity m-type genes were classified into four groups and detected in all Glu-3 loci. These results contribute to the functional analysis of LMW-GS genes and facilitate improvement of bread-making quality by wheat molecular breeding programmes.

Plant mitochondria, semiautonomous organelles that function as manufacturers of cellular ATP, have their own genome that has a slow rate of evolution and rapid rearrangement. Cytoplasmic male sterility (CMS), a common phenotype in higher plants, is closely associated with rearrangements in mitochondrial DNA (mtDNA), and is widely used to produce F1 hybrid seeds in a variety of valuable crop species. Novel chimeric genes deduced from mtDNA rearrangements causing CMS have been identified in several plants, such as rice, sunflower, pepper, and rapeseed, but there are very few reports about mtDNA rearrangements in wheat. In the present work, we describe the mitochondrial genome of a wheat K-type CMS line and compare it with its maintainer line.

Low-molecular-weight glutenin subunits (LMW-GSs) play an important role in determining the bread-making quality of bread wheat. However, LMW-GSs display high polymorphic protein complexes encoded by multiple genes, and elucidating the complex LMW-GS gene family in bread wheat remains challenging. In the present study, using conventional polymerase chain reaction (PCR) with conserved primers and high-resolution capillary electrophoresis, we developed a new molecular marker system for identifying LMW-GS gene family members. Based on sequence alignment of 13 LMW-GS genes previously identified in the Chinese bread wheat variety Xiaoyan 54 and other genes available in GenBank, PCR primers were developed and assigned to conserved sequences spanning the length polymorphism regions of LMW-GS genes. After PCR amplification, 17 DNA fragments in Xiaoyan 54 were detected using capillary electrophoresis. In total, 13 fragments were identical to previously identified LMW-GS genes, and the other 4 were derived from unique LMW-GS genes by sequencing. This marker system was also used to identify LMW-GS genes in Chinese Spring and its group 1 nulli-tetrasomic lines. Among the 17 detected DNA fragments, 4 were located on chromosome 1A, 5 on 1B, and 8 on 1D. The results suggest that this marker system is useful for large-scale identification of LMW-GS genes in bread wheat varieties, and for the selection of desirable LMW-GS genes to improve the bread-making quality in wheat molecular breeding programmes.

Femur Head Necrosis (FHN) is a common clinical joint orthopedic-related disease, and its incidence is increasing year by year. Symptoms include dull pain and dull pain in the affected hip joint or its surrounding joints. More severely, it can lead to limited joint movement and inability to walk autonomously. Surgical treatment has many sequelae. The high cost makes it unaffordable for patients, and the side effects of drug treatment are unknown. A large number of clinical studies have shown that acupuncture is effective in treating femoral head necrosis. Therefore, this systematic review aims to explore the safety and effectiveness of acupuncture in the treatment of femoral head necrosis.

De Quervain disease (DQD) is a common clinical disease. As a strainingdisease, DQD is more common in women who frequently engage in manual operations. The main clinical symptoms are local pain and dysfunction. Many clinical studies have reported that moxibustion has a good effect on the treatment of DQD, but there is no relevant systematic review. So the purpose of this study is to evaluate the effectiveness and safety of moxibustion in treating DQD.

Triple-negative breast cancer (TNBC) patients are at high risk of recurrence and metastasis in the early stages, although receiving standard treatment. However, the underlying mechanism of TNBC remains unclear. Here, the critical effect of E3 ubiquitin ligase RBX1 in the metastasis of TNBC was reported for the first time. We discovered that RBX1 expression was evidently raised in the tissues of TNBC. Our clinical research displayed that high RBX1 expression was markedly related to poor distant invasion and survival. Functional analysis exhibited that RBX1 facilitated metastasis of TNBC cells through increasing EMT. Furthermore, we demonstrated that RBX1 knockdown increased the levels of the Twist family bHLH transcription factor 1 (TWIST1), is a significant regulator in the EMT process in some cancers. It can be observed an evident positive correlation between the TWIST1 and RBX1 levels, further confirming that EMT induced by RBX1 in TNBC cells is determined by TWIST1. Mechanistically, RBX1 modulates the expression of TWIST1 via modulating FBXO45, directly binding to FBXO45, and facilitating its degradation and ubiquitination. Briefly, our findings confirm that RBX1 is probably a new biomarker of TNBC carcinogenesis, thus suggesting that targeting the RBX1/FBXO45/TWIST1 axis may be an underlying strategy for TNBC treatment.

Triticum urartu is the progenitor of the A subgenome in tetraploid and hexaploid wheat. Uncovering the landscape of genetic variations in T. urartu will help us understand the evolutionary and polyploid characteristics of wheat. Here, we investigated the population genomics of T. urartu by genome-wide sequencing of 59 representative accessions collected around the world. A total of 42.2 million high-quality single-nucleotide polymorphisms and 3 million insertions and deletions were obtained by mapping reads to the reference genome. The ancient T. urartu population experienced a significant reduction in effective population size (Ne) from ∼3 000 000 to ∼140 000 and subsequently split into eastern Mediterranean coastal and Mesopotamian-Transcaucasian populations during the Younger Dryas period. A map of allelic drift paths displayed splits and mixtures between different geographic groups, and a strong genetic drift towards hexaploid wheat was also observed, indicating that the direct donor of the A subgenome originated from northwestern Syria. Genetic changes were revealed between the eastern Mediterranean coastal and Mesopotamian-Transcaucasian populations in genes orthologous to those regulating plant development and stress responses. A genome-wide association study identified two single-nucleotide polymorphisms in the exonic regions of the SEMI-DWARF 37 ortholog that corresponded to the different T. urartu ecotype groups. Our study provides novel insights into the origin and genetic legacy of the A subgenome in polyploid wheat and contributes a gene repertoire for genomics-enabled improvements in wheat breeding.

Banana is one of the most important fruits in the world due to its status as a major food source for more than 400 million people. Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) causes substantial losses of banana crops every year, and molecular host resistance mechanisms are currently unknown. We here performed a genomewide analysis of the autophagy-related protein 8 (ATG8) family in a wild banana species. The banana genome was found to contain 10 MaATG8 genes. Four MaATG8s formed a gene cluster in the distal part of chromosome 4. Phylogenetic analysis of ATG8 families in banana, Arabidopsis thaliana, citrus, rice, and ginger revealed five major phylogenetic clades shared by all of these plant species, demonstrating evolutionary conservation of the MaATG8 families. The transcriptomic analysis of plants infected with Foc TR4 showed that nine of the MaATG8 genes were more highly induced in resistant cultivars than in susceptible cultivars. Finally, MaATG8F was found to interact with MaATG4B in vitro (with yeast two-hybrid assays), and MaATG8F and MaATG4B all positively regulated banana resistance to Foc TR4. Our study provides novel insights into the structure, distribution, evolution, and expression of the MaATG8 family in bananas. Furthermore, the discovery of interactions between MaATG8F and MaATG4B could facilitate future research of disease resistance genes for the genetic improvement of bananas.

Gliadins are the major components of storage proteins in wheat grains, and they play an essential role in the dough extensibility and nutritional quality of flour. Because of the large number of the gliadin family members, the high level of sequence identity, and the lack of abundant genomic data for Triticum species, identifying the full complement of gliadin family genes in hexaploid wheat remains challenging. Triticum urartu is a wild diploid wheat species and considered the A-genome donor of polyploid wheat species. The accession PI428198 (G1812) was chosen to determine the complete composition of the gliadin gene families in the wheat A-genome using the available draft genome. Using a PCR-based cloning strategy for genomic DNA and mRNA as well as a bioinformatics analysis of genomic sequence data, 28 gliadin genes were characterized. Of these genes, 23 were α-gliadin genes, three were γ-gliadin genes and two were ω-gliadin genes. An RNA sequencing (RNA-Seq) survey of the dynamic expression patterns of gliadin genes revealed that their synthesis in immature grains began prior to 10 days post-anthesis (DPA), peaked at 15 DPA and gradually decreased at 20 DPA. The accumulation of proteins encoded by 16 of the expressed gliadin genes was further verified and quantified using proteomic methods. The phylogenetic analysis demonstrated that the homologs of these α-gliadin genes were present in tetraploid and hexaploid wheat, which was consistent with T. urartu being the A-genome progenitor species. This study presents a systematic investigation of the gliadin gene families in T. urartu that spans the genome, transcriptome and proteome, and it provides new information to better understand the molecular structure, expression profiles and evolution of the gliadin genes in T. urartu and common wheat.

The Flo2 gene is a member of a conserved gene family in plants. This gene has been found to be related to thousand grain weight (TGW) in rice. Its orthologs in hexaploid wheat were cloned, and the haplotype variation in TaFlo2-A1 was tested for association with TGW.