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Hybrid sterility restricts the utilization of superior heterosis of indica-japonica inter-subspecific hybrids. In this study, we report the identification of RHS12, a major locus controlling male gamete sterility in indica-japonica hybrid rice. We show that RHS12 consists of two genes (iORF3/DUYAO and iORF4/JIEYAO) that confer preferential transmission of the RHS12-i type male gamete into the progeny, thereby forming a natural gene drive. DUYAO encodes a mitochondrion-targeted protein that interacts with OsCOX11 to trigger cytotoxicity and cell death, whereas JIEYAO encodes a protein that reroutes DUYAO to the autophagosome for degradation via direct physical interaction, thereby detoxifying DUYAO. Evolutionary trajectory analysis reveals that this system likely formed de novo in the AA genome Oryza clade and contributed to reproductive isolation (RI) between different lineages of rice. Our combined results provide mechanistic insights into the genetic basis of RI as well as insights for strategic designs of hybrid rice breeding.
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Tecnologia de Impulso Genético , Oryza , Hibridização Genética , Oryza/genética , Melhoramento Vegetal/métodos , Isolamento Reprodutivo , Infertilidade das PlantasRESUMO
Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.
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Reparo do DNA , Ubiquitina-Proteína Ligases , Humanos , Quebras de DNA de Cadeia Dupla , Histonas/metabolismo , Histonas/genética , Poliubiquitina/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , UbiquitinaçãoRESUMO
Plants have evolved sophisticated mechanisms to coordinate their growth and stress responses via integrating various phytohormone signaling pathways. However, the precise molecular mechanisms orchestrating integration of the phytohormone signaling pathways remain largely obscure. In this study, we found that the rice (Oryza sativa) short internodes1 (shi1) mutant exhibits typical auxin-deficient root development and gravitropic response, brassinosteroid (BR)-deficient plant architecture and grain size as well as enhanced abscisic acid (ABA)-mediated drought tolerance. Additionally, we found that the shi1 mutant is also hyposensitive to auxin and BR treatment but hypersensitive to ABA. Further, we showed that OsSHI1 promotes the biosynthesis of auxin and BR by activating the expression of OsYUCCAs and D11, meanwhile dampens ABA signaling by inducing the expression of OsNAC2, which encodes a repressor of ABA signaling. Furthermore, we demonstrated that 3 classes of transcription factors, AUXIN RESPONSE FACTOR 19 (OsARF19), LEAF AND TILLER ANGLE INCREASED CONTROLLER (LIC), and OsZIP26 and OsZIP86, directly bind to the promoter of OsSHI1 and regulate its expression in response to auxin, BR, and ABA, respectively. Collectively, our results unravel an OsSHI1-centered transcriptional regulatory hub that orchestrates the integration and self-feedback regulation of multiple phytohormone signaling pathways to coordinate plant growth and stress adaptation.
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Oryza , Reguladores de Crescimento de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Ácidos Indolacéticos/metabolismo , Brassinosteroides/metabolismo , Hormônios , Crescimento e Desenvolvimento , Regulação da Expressão Gênica de PlantasRESUMO
RAP80 has been characterized as a component of the BRCA1-A complex and is responsible for the recruitment of BRCA1 to DNA double-strand breaks (DSBs). However, we and others found that the recruitment of RAP80 and BRCA1 were not absolutely temporally synchronized, indicating that other mechanisms, apart from physical interaction, might be implicated. Recently, liquid-liquid phase separation (LLPS) has been characterized as a novel mechanism for the organization of key signaling molecules to drive their particular cellular functions. Here, we characterized that RAP80 LLPS at DSB was required for RAP80-mediated BRCA1 recruitment. Both cellular and in vitro experiments showed that RAP80 phase separated at DSB, which was ascribed to a highly disordered region (IDR) at its N-terminal. Meanwhile, the Lys63-linked poly-ubiquitin chains that quickly formed after DSBs occur, strongly enhanced RAP80 phase separation and were responsible for the induction of RAP80 condensation at the DSB site. Most importantly, abolishing the condensation of RAP80 significantly suppressed the formation of BRCA1 foci, encovering a pivotal role of RAP80 condensates in BRCA1 recruitment and radiosensitivity. Together, our study disclosed a new mechanism underlying RAP80-mediated BRCA1 recruitment, which provided new insight into the role of phase separation in DSB repair.
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Endosperm is the main storage organ in cereal grain and determines grain yield and quality. The molecular mechanisms of heat shock proteins in regulating starch biosynthesis and endosperm development remain obscure. Here, we report a rice floury endosperm mutant flo24 that develops abnormal starch grains in the central starchy endosperm cells. Map-based cloning and complementation test showed that FLO24 encodes a heat shock protein HSP101, which is localized in plastids. The mutated protein FLO24T296I dramatically lost its ability to hydrolyze ATP and to rescue the thermotolerance defects of the yeast hsp104 mutant. The flo24 mutant develops more severe floury endosperm when grown under high-temperature conditions than normal conditions. And the FLO24 protein was dramatically induced at high temperature. FLO24 physically interacts with several key enzymes required for starch biosynthesis, including AGPL1, AGPL3 and PHO1. Combined biochemical and genetic evidence suggests that FLO24 acts cooperatively with HSP70cp-2 to regulate starch biosynthesis and endosperm development in rice. Our results reveal that FLO24 acts as an important regulator of endosperm development, which might function in maintaining the activities of enzymes involved in starch biosynthesis in rice.
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Endosperma , Oryza , Proteínas de Plantas , Amido , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/biossíntese , Endosperma/genética , Endosperma/crescimento & desenvolvimento , Endosperma/metabolismo , Regulação da Expressão Gênica de Plantas , Teste de Complementação Genética , Mutação/genética , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plastídeos/metabolismo , Ligação Proteica , Amido/biossíntese , Amido/genética , Termotolerância , Fatores de TranscriçãoRESUMO
Extranodal NK/T cell lymphoma (ENKTCL) is an extremely aggressive form of lymphoma and lacks of specific diagnostic markers. The study intended to unearth the role of interleukin-33 (IL-33) in ENKTCL. RT-qPCR was conducted to assess mRNA levels of ENKTCL tissues and cells, while western blot assay was performed for evaluating protein levels. Plate cloning experiment and transwell assay were employed to measure aggressiveness of ENKTCL. Tube formation assay was executed to determine the angiogenesis ability. Mice ENKTCL xenograft model was designed to probe the impacts of IL-33 in vivo. IL-33 and suppression of tumorigenicity 2 receptor (ST2, receptor of IL-33) were enhanced in ENKTCL. IL-33 inhibition suppressed viability, migration, and invasion of ENKTCL cells. Moreover, IL-33 knockdown restricted angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, Wnt/ß-catenin pathway associated proteins (ß-catenin, c-myc, and cyclin D1) were downregulated by loss of IL-33. However, these impacts were overturned by Wnt/ß-catenin signaling agonist lithium chloride (LiCl). Additionally, IL-33 silencing exerted anti-tumor effect via Wnt/ß-catenin pathway in vivo. Silencing of IL-33 inhibited ENKTCL tumorigenesis and angiogenesis by inactivating Wnt/ß-catenin signaling pathway. As such, IL-33 might be a prospective treatment target for ENKTCL.
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"Carbon peaking and carbon neutralization" is an important measure to promote China's ecological and environmental protection and high-quality economic development, and the innovation and application of green technology are critical factors in achieving the "double carbon" goal. Based on the number of citations of green patents of listed enterprises in 30 provinces in China from 2011 to 2020, this paper uses GGDP to replace traditional GDP and calculate carbon emission intensity. Based on the relevant panel data at the provincial level, this paper constructs a spatial Durbin model to analyze the impact mechanism of whether the promotion and application of green technologies promote regional carbon emission reduction. The specific research results are as follows: (1) Through regression of the core explanatory variables with a one-stage lag, it is verified that the promotion and application of green technology has a significant positive promoting effect on regional carbon emission reduction, and there are significant spatial spillover effects and "learning by doing" effects. (2) In the part of heterogeneity test, the impact of green technology promotion and application on carbon emission reduction presents apparent regional heterogeneity and factor endowment heterogeneity. (3) The mediating effect test verifies the mediating effect of energy structure and industrial structure on the influence of green technology promotion and application on regional carbon emission reduction. (4) In the part moderating effect test, it is verified that marketization level and new infrastructure construction have a positive moderating effect in their influencing process, financial development, and government support will weaken the influence of green technology promotion and application on carbon emission reduction effect, and human capital level has a nonlinear regulating effect. The research conclusions of this paper provide necessary enlightenment for the coordination and unification of China's economic transition to innovation-driven and green and low-carbon development.
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Objetivos , Aprendizagem , Humanos , China , Carbono , Desenvolvimento Econômico , TecnologiaRESUMO
Wheat (Triticum aestivum L.) is a major foodstuff for over 40% of the world's population. However, hexavalent chromium [Cr(VI)] in contaminated soil significantly affects wheat production and its ecological environment. Streptomyces sp. HU2014 was first used to investigate the effects of Cr (VI) stress on wheat growth. We analyzed the Cr(VI) concentration, physicochemical properties of wheat and soil, total Cr content, and microbial community structures during their interactions. HU2014 reduced the toxicity of Cr(VI) and promoted wheat growth by increasing total nitrogen, nitrate nitrogen, total phosphorus, and Olsen-phosphorus in Cr(VI)-contaminated soil. These four soil variables had strong positive effects on two bacterial taxa, Proteobacteria and Bacteroidota, in the HU2014 treatments. In addition, the level of the dominant Proteobacteria positively correlated with the total Cr content in the soil. Among the fungal communities, which had weaker correlations with soil variables compared with bacterial communities, Ascomycota was the most abundant. Our findings suggest that HU2014 can promote the phytoremediation of Cr(VI)-contaminated soil.
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Biodegradação Ambiental , Cromo , Rizosfera , Microbiologia do Solo , Poluentes do Solo , Streptomyces , Triticum , Cromo/toxicidade , Streptomyces/efeitos dos fármacos , Triticum/crescimento & desenvolvimento , Triticum/microbiologia , Triticum/efeitos dos fármacos , Poluentes do Solo/toxicidade , Solo/química , Proteobactérias/efeitos dos fármacos , Nitrogênio/metabolismo , FósforoRESUMO
Cu-based catalysts possess great potential in the electrocatalytic nitrate (NO3-) reduction reaction for ammonia (NH3) synthesis. However, the low atomic economy limits their further application. Here we report a Cu single-atom (SA) incorporated in nitrogen-doped carbon (Cu SA/NC) with high atomic economy, which exhibits superior NH3 Faradaic efficiency (FE) of 100% along with an impressive NH3 yield rate of 7480 µg h-1 mgcat.-1. As counterparts, Cus+n/NC, with mixed SA and nanoparticles (NPs), shows decreasing NH3 FE with decreasing SA content, but the production of N2 and N2O increases gradually, which reaches the maximum on pure Cu NPs. In situ characterizations and theoretical calculations reveal that a higher NH3 FE of Cu SA/NC is ascribed to a lower free energy of the rate-limiting step (HNO* â N*) and effective inhibition for the N-N coupled process. This work provides the intuitive activity trends of Cu-based catalysts, opening an avenue for subsequent catalysts design.
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Although similar to trunk and limb skeletal muscles, masticatory muscles are believed as unique in both developmental origins and myogenesis. Gαi2 has been demonstrated to promote muscle hypertrophy and muscle satellite cell differentiation in limb muscles. However, the effect of Gαi2 on masticatory muscles is still unexplored. This study aimed to identify the role of Gαi2 in the proliferation and differentiation of masticatory muscle satellite cells, further exploring the metabolic mechanism of masticatory muscles. The proliferation rate, myotube size, fusion index of masticatory muscle satellite cells and Pax7, Myf5, MyoD, Tcf21 and Musculin expressions were significantly decreased by Gαi2 knockdown, while in cells infected with AdV4-Gαi2, the proliferation rate, myotube size, fusion index and Tbx1 expression were significantly increased. Masticatory muscle satellite cells also displayed phenotype transformation as Gαi2 changed. In addition, Gαi2 altered myosin heavy chain (MyHC) isoforms of myotubes with less MyHC-2A expression in siGαi2 group and more MyHC-slow expression in AdV4-Gαi2 group. In conclusion, Gαi2 could positively affect the adult myogenesis of masticatory muscle satellite cells and maintain the superiority of MyHC-slow. Masticatory muscle satellite cells may have their unique Gαi2-regulated myogenic transcriptional networks, although they may share some common characteristics with trunk and limb muscles.
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Células Satélites de Músculo Esquelético , Células Satélites de Músculo Esquelético/metabolismo , Células Cultivadas , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/genética , Diferenciação Celular/genética , Desenvolvimento Muscular/genéticaRESUMO
KEY MESSAGE: We identified a dosage-dependent dominant negative form of Sar1c, which confirms the essential role of COPII system in mediating ER export of storage proteins in rice endosperm. Higher plants accumlate large amounts of seed storage proteins (SSPs). However, mechanisms underlying SSP trafficking are largely unknown, especially the ER-Golgi anterograde process. Here, we showed that a rice glutelin precursor accumulation13 (gpa13) mutant exhibited floury endosperm and overaccumulated glutelin precursors, which phenocopied the reported RNAi-Sar1abc line. Molecular cloning revealed that the gpa13 allele encodes a mutated Sar1c (mSar1c) with a deletion of two conserved amino acids Pro134 and Try135. Knockdown or knockout of Sar1c alone caused no obvious phenotype, while overexpression of mSar1c resulted in seedling lethality similar to the gpa13 mutant. Transient expression experiment in tobacco combined with subcellular fractionation experiment in gpa13 demonstrated that the expression of mSar1c affects the subcellular distribution of all Sar1 isoforms and Sec23c. In addition, mSar1c failed to interact with COPII component Sec23. Conversely, mSar1c competed with Sar1a/b/d to interact with guanine nucleotide exchange factor Sec12. Together, we identified a dosage-dependent dominant negative form of Sar1c, which confirms the essential role of COPII system in mediating ER export of storage proteins in rice endosperm.
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Oryza , Proteínas de Armazenamento de Sementes , Proteínas de Armazenamento de Sementes/metabolismo , Oryza/genética , Transporte Proteico/genética , Glutens/genética , Retículo Endoplasmático/metabolismoRESUMO
High-energy radiation that is compatible with renewable energy sources enables direct H2 production from water for fuels; however, the challenge is to convert it as efficiently as possible, and the existing strategies have limited success. Herein, we report the use of Zr/Hf-based nanoscale UiO-66 metal-organic frameworks as highly effective and stable radiation sensitizers for purified and natural water splitting under γ-ray irradiation. Scavenging and pulse radiolysis experiments with Monte Carlo simulations show that the combination of 3D arrays of ultrasmall metal-oxo clusters and high porosity affords unprecedented effective scattering between secondary electrons and confined water, generating increased precursors of solvated electrons and excited states of water, which are the main species responsible for H2 production enhancement. The use of a small quantity (<80 mmol/L) of UiO-66-Hf-OH can achieve a γ-rays-to-hydrogen conversion efficiency exceeding 10% that significantly outperforms Zr-/Hf-oxide nanoparticles and the existing radiolytic H2 promoters. Our work highlights the feasibility and merit of MOF-assisted radiolytic water splitting and promises a competitive method for creating a green H2 economy.
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As a traditional method of ammonia (NH3 ) synthesis, Haber-Bosch method expends a vast amount of energy. An alternative route for NH3 synthesis is proposed from nitrate (NO3 - ) via electrocatalysis. However, the structure-activity relationship remains challenging and requires in-depth research both experimentally and theoretically. Here an N-coordinated Cu-Ni dual-single-atom catalyst anchored in N-doped carbon (Cu/Ni-NC) is reported, which has competitive activity with a maximal NH3 Faradaic efficiency of 97.28%. Detailed characterizations demonstrate that the high activity of Cu/Ni-NC mainly comes from the contribution of Cu-Ni dual active sites. That is, (1) the electron transfer (Ni â Cu) reveals the strong electron interaction of Cu-Ni dual-single-atom; (2) the strong hybridizations of Cu 3d-and Ni 3d-O 2p orbitals of NO3 - can accelerate electron transfer from Cu-Ni dual-site to NO3 - ; (3) Cu/Ni-NC can effectively decrease the rate-limiting step barriers, suppress N-N coupling for N2 O and N2 formation and hydrogen production.
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Topologically associated domains (TADs) are one of the important higher order chromatin structures with various sizes in the eukaryotic genomes. TAD boundaries, as the flanking regions between adjacent domains, can restrict the interactions of regulatory elements, including enhancers and promoters, and are generally dynamic and variable in different cells. However, the influence of sequence and epigenetic profile-based features in the identification of TAD boundaries is largely unknown. In this work, we proposed a method called pTADS (prediction of TAD boundary and strength), to predict TAD boundaries and boundary strength across multiple cell lines with DNA sequence and epigenetic profile information. The performance was assessed in seven cell lines and three TAD calling methods. The results demonstrate that the TAD boundary can be well predicted by the selected shared features across multiple cell lines. Especially, the model can be transferable to predict the TAD boundary from one cell line to other cell lines. The boundary strength can be characterized by boundary score with good performance. The predicted TAD boundary and TAD boundary strength are further confirmed by three Hi-C contact matrix-based methods across multiple cell lines. The codes and datasets are available at https://github.com/chrom3DEpi/pTADS.
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Algoritmos , Cromatina/genética , Biologia Computacional/métodos , Epigênese Genética , Epigenômica/métodos , Sequências Reguladoras de Ácido Nucleico/genética , Linhagem Celular , Cromatina/metabolismo , DNA/genética , DNA/metabolismo , Elementos Facilitadores Genéticos/genética , Genoma Humano/genética , Humanos , Células K562 , Regiões Promotoras Genéticas/genética , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Whether serum vitamin D mediate vascular diseases in prediabetic populations remains unclear. This study aimed to determine the associations between circulating 25-hydroxyvitamin D [25(OH)D] levels and vitamin D receptor (VDR) polymorphisms with the risk of macrovascular complications, including myocardial infarction and stroke, and microvascular complications such as diabetic nephropathy and retinopathy, among adults with prediabetes. METHODS: Participants with prediabetes in UK Biobank were included (N = 56,387). Multivariable dose-response and Cox proportion models were used to explore the relationship of serum 25(OH)D status and the risks of vascular complications. The interaction of VDR polymorphisms with serum 25(OH)D level on risks of vascular events was also assessed. RESULTS: During a median follow-up of 12 years, higher levels of 25(OH)D were significantly and nonlinearly associated with a lower risk of macrovascular diseases among prediabetic individuals. The adjusted hazard ratios (95% confidential interval) of serum 25(OH)D levels of ≥ 75.0 nmol/L versus < 25 nmol/L were 0.75 (0.63-0.88) for myocardial infarction, 0.74 (0.55-1.00) for stroke, 1.02 (0.60-1.74) for diabetic nephropathy, and 1.30 (0.92-1.84) for diabetic retinopathy, respectively. The rs2228570 (FokI) polymorphisms significantly interacted with 25(OH)D on incident myocardial infarction (P-interaction = 0.042) and stroke (P-interaction = 0.033). The individuals with serum 25(OH)D level of 50.0-74.9 nmol/L and rs2228570 (FokI) homozygotes had the lowest risks of vascular complications. CONCLUSIONS: Lower serum 25(OH)D levels are significantly and nonlinearly associated with an increased risk of cardiocerebrovascular diseases in prediabetic individuals, with VDR polymorphisms of rs2228570 (FokI) modify such associations. Monitoring a safe 25(OH)D concentration is suggested to prevent the vascular complications for prediabetes.
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Nefropatias Diabéticas , Infarto do Miocárdio , Estado Pré-Diabético , Acidente Vascular Cerebral , Deficiência de Vitamina D , Adulto , Humanos , Estudos Prospectivos , Estado Pré-Diabético/genética , Vitamina D , Infarto do Miocárdio/genéticaRESUMO
Dense vesicles (DVs) are vesicular carriers, unique to plants, that mediate post-Golgi trafficking of storage proteins to protein storage vacuoles (PSVs) in seeds. However, the molecular mechanisms regulating the directional targeting of DVs to PSVs remain elusive. Here, we show that the rice (Oryza sativa) glutelin precursor accumulation5 (gpa5) mutant is defective in directional targeting of DVs to PSVs, resulting in discharge of its cargo proteins into the extracellular space. Molecular cloning revealed that GPA5 encodes a plant-unique phox-homology domain-containing protein homologous to Arabidopsis (Arabidopsis thaliana) ENDOSOMAL RAB EFFECTOR WITH PX-DOMAIN. We show that GPA5 is a membrane-associated protein capable of forming homodimers and that it is specifically localized to DVs in developing endosperm. Colocalization, biochemical, and genetic evidence demonstrates that GPA5 acts in concert with Rab5a and VPS9a to regulate DV-mediated post-Golgi trafficking to PSVs. Furthermore, we demonstrated that GPA5 physically interacts with a class C core vacuole/endosome tethering complex and a seed plant-specific VAMP727-containing R-soluble N-ethylmaleimide sensitive factor attachment protein receptor complex. Collectively, our results suggest that GPA5 functions as a plant-specific effector of Rab5a required for mediating tethering and membrane fusion of DVs with PSVs in rice endosperm.
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Complexo de Golgi/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Armazenamento de Sementes/metabolismo , Endosperma/metabolismo , Glutens/metabolismo , Complexo de Golgi/ultraestrutura , Proteínas de Membrana/metabolismo , Modelos Biológicos , Mutação/genética , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas de Plantas/química , Ligação Proteica , Multimerização Proteica , Transporte Proteico , Proteínas de Armazenamento de Sementes/química , Vacúolos/metabolismo , Vacúolos/ultraestruturaRESUMO
Imaging through scattering layers based on the optical memory effect (OME) concept has been widely investigated in recent years. Among many scattering scenarios, it is very important to recover hidden targets with proper spatial distribution in the scene where multiple targets out of the OME range exist. In this Letter, we put forward a method for multi-target object scattering imaging. With the help of intensity correlation between the structured illumination patterns and recorded speckle images, the relative position of all hidden targets can be obtained and the movement of the targets within the OME range can be tracked. We experimentally implement scattering imaging with 16 targets and the motion tracking of them. Our results present a significant advance in a large field of view scattering imaging with multiple targets.
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BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision are standard treatment regimen for patients with locally advanced rectal cancer (LARC). This sphincter-saving treatment strategy may be accompanied by a series of anorectal functional disorders. Yet, prospective studies that dynamically evaluating the respective roles of radiotherapy, chemotherapy and surgery on anorectal function are lacking. PATIENTS/DESIGN: The study is a prospective, observational, controlled, multicentre study. After screening for eligibility and obtaining informed consent, a total of 402 LARC patients undergoing NCRT followed by surgery, or neoadjuvant chemotherapy followed by surgery, or surgery only would be included in the trial. The primary outcome measure is the average resting pressure of anal sphincter. The secondary outcome measures are maximum anal sphincter contraction pressure, Wexner continence score and low anterior resection syndrome (LARS) score. Evaluations will be carried out at the following stages: baseline (T1), after radiotherapy or chemotherapy (before surgery, T2), after surgery (before closing the temporary stoma, T3), and at follow-up visits (every 3 to 6 months, T4, T5 ). Follow-up for each patient will be at least 2 years. DISCUSSION: We expect the program to provide more information of neoadjuvant radiotherapy and/or chemotherapy on anorectal function, and to optimize the treatment strategy to reduce anorectal dysfunction for LARC patients. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05671809). Registered on 26 December 2022.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Neoplasias Retais/patologia , Estudos Prospectivos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Quimiorradioterapia/métodos , Estadiamento de Neoplasias , Estudos Observacionais como Assunto , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVE: To design a cross-inverted triangular pattern to insert compression screw nails for the treatment of femoral neck fractures and to compare the biomechanics of inserting compression screw nails in cross-inverted triangular patterns and inverted triangular patterns. I am very sorry that a corresponding author needs to be added to the article. I do not know how to insert it, so I make a note here. Please check the attachment I uploaded. METHODS: The reasonableness of the model is first analyzed using finite elements. A total of 6 adult human specimens were selected, of which 3 males and 3 females were divided into the A1, B1, and C1 groups and the A2, B2, and C2 groups by the random number table method. The A1 and A2 groups were made into subhead femoral neck fracture models, the B1 and B2 groups were made into trans-neck femoral neck fracture models, and the C1 and C2 groups were made into basal femoral neck fracture models. The right femur of each group had a compression screw nail inserted in the crossed-inverted triangular pattern, and the left femur of each group had a compression screw nail inserted in the inverted triangular pattern. The static compression test was performed by an electronic universal testing machine. The maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head were read according to the pressure-displacement curve drawn in the experiment. RESULTS: The finite element analysis showed that the cross-inverted triangular hollow threaded nail has better conductivity and more stable fixation than the inverted triangular hollow threaded nail. The maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head of the left femur were greater than those of the right femur in the A1, A2, B1, B2 and C2 groups, while the maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head of the left femur were smaller than those of the right femur in the C1 group. There was no statistically significant difference in the maximum load of the femoral neck or the load of 3.00 mm axial displacement of the femoral head between the A1 and A2 groups, the B1 and B2 groups, or the C1 and C2 groups (P > 0.05). After the K-S test, the maximum load of the femoral neck and the load of 3.00 mm axial displacement of the femoral head were normally distributed (P = 0.20), and the LSD-t test was conducted for the two load data; the difference was not statistically significant (P = 0.235). CONCLUSION: The effect of compression screw nails in the cross-inverted triangular pattern was the same in males and females, and stability was better in the fixation of subhead and trans-neck femoral neck fractures. However, its stability in fixation of basal femoral neck fracture is worse than that of the inverted triangular pattern. The cross-inverted triangular hollow threaded nail has better conductivity and more stable fixation than the inverted triangular hollow threaded nail.
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Fraturas do Fêmur , Fraturas do Colo Femoral , Adulto , Humanos , Unhas , Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Fraturas do Colo Femoral/cirurgia , Fêmur/cirurgia , Fenômenos Biomecânicos , Análise de Elementos Finitos , Fraturas do Fêmur/cirurgiaRESUMO
Five psoralen derivatives were synthesized and the structures of them were characterized by 1 H-NMR, 13 C-NMR, and IR. The antioxidant properties of the compounds were tested by inhibiting the free radical-initiated DNA oxidation and scavenging the radical reaction. The results showed that the effective stoichiometric factors (n) of the compounds V and IV could reach 2.00 and 2.11 in the system of inhibiting the DNA oxidation reaction initiated by 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). In the inhibition of â OH-oxidation of the DNA system, compounds I~V showed antioxidant properties. The thiobarbituric acid absorbance (TBARS) percentages of compounds IV and V were 76.19 % and 78.84 %. Compounds I~V could also inhibit Cu2+ /GSH-oxidation of DNA, and all compounds exhibited good antioxidant properties except compound II (94.00 %). All the five compounds were able to trap diammonium 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) salt radical (ABTS+ â ), 2,2-diphenyl-1-picrylhydrazyl radical (DPPHâ ) and 2,6-di-tert-butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-p-tolylox radical (galvinoxylâ ). The ability of compounds I~V to scavenge those free radicals can be measured by the k values. The k values ranged from 0.07 to 0.82 in scavenging ABTS+ â , galvinoxyl, and DPPH radicals, respectively.