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Wheat crops are frequently devastated by pandemic stripe rust caused by Puccinia striiformis f. sp. tritici (Pst). Here, we identify and characterize a wheat receptor-like cytoplasmic kinase gene, TaPsIPK1, that confers susceptibility to this pathogen. PsSpg1, a secreted fungal effector vital for Pst virulence, can bind TaPsIPK1, enhance its kinase activity, and promote its nuclear localization, where it phosphorylates the transcription factor TaCBF1d for gene regulation. The phosphorylation of TaCBF1d switches its transcriptional activity on the downstream genes. CRISPR-Cas9 inactivation of TaPsIPK1 in wheat confers broad-spectrum resistance against Pst without impacting important agronomic traits in two years of field tests. The disruption of TaPsIPK1 leads to immune priming without constitutive activation of defense responses. Taken together, TaPsIPK1 is a susceptibility gene known to be targeted by rust effectors, and it has great potential for developing durable resistance against rust by genetic modifications.
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Basidiomycota , Triticum , Basidiomycota/genética , Basidiomycota/metabolismo , Enfermedades de las Plantas , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Triticum/genética , Triticum/metabolismo , Triticum/microbiología , Virulencia/genéticaRESUMEN
A thorough comprehension of age-related variances in orthodontic tooth movement (OTM) and bone remodeling response to mechanical force holds significant implications for enhancing orthodontic treatment. Mitophagy plays a crucial role in bone metabolism and various age-related diseases. However, the impact of mitophagy on the bone remodeling process during OTM remains elusive. Using adolescent (6 weeks old) and adult (12 months old) rats, we established OTM models and observed that orthodontic force increased the expression of the mitophagy proteins PTEN-induced putative kinase 1 (PINK1) and Parkin, as well as the number of tartrate-resistant acid phosphatase-positive osteoclasts and osteocalcin-positive osteoblasts. These biological changes were found to be age-related. In vitro, compression force loading promoted PINK1/Parkin-dependent mitophagy in periodontal ligament stem cells (PDLSCs) derived from adolescents (12-16 years old) and adults (25-35 years old). Furthermore, adult PDLSCs exhibited lower levels of mitophagy, impaired mitochondrial function, and a decreased ratio of RANKL/OPG compared to young PDLSCs after compression. Transfection of siRNA confirmed that inhibition of mitophagy in PDLSC resulted in decreased mitochondrial function and reduced RANKL/OPG ratio. Application of mitophagy inducer Urolithin A enhanced bone remodeling and accelerated OTM in rats, while the mitophagy inhibitor Mdivi-1 had the opposite effect. These findings indicate that force-stimulated PDLSC mitophagy contributes to alveolar bone remodeling during OTM, and age-related impairment of mitophagy negatively impacts the PDLSC response to mechanical stimulus. Our findings enhance the understanding of mitochondrial mechanotransduction and offer new targets to tackle current clinical challenges in orthodontic therapy.
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Mitocondrias , Mitofagia , Osteoprotegerina , Ligamento Periodontal , Ligando RANK , Técnicas de Movimiento Dental , Animales , Mitofagia/fisiología , Ratas , Ligando RANK/metabolismo , Ligamento Periodontal/metabolismo , Osteoprotegerina/metabolismo , Mitocondrias/metabolismo , Masculino , Proteínas Quinasas/metabolismo , Ratas Sprague-Dawley , Adolescente , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Células Madre/metabolismo , Remodelación Ósea/fisiología , Células CultivadasRESUMEN
Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.
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Artritis Reumatoide , Proteína Disulfuro Isomerasas , Factor de Transcripción STAT1 , Proteína Disulfuro Isomerasas/metabolismo , Proteína Disulfuro Isomerasas/genética , Humanos , Artritis Reumatoide/metabolismo , Ratones , Animales , Factor de Transcripción STAT1/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Transporte Activo de Núcleo Celular , Proteínas Portadoras/metabolismo , Transducción de Señal , Proteínas de Unión a Hormona Tiroide , Factores de Transcripción NFATC/metabolismo , Activación de Linfocitos , Hormonas Tiroideas/metabolismo , Regulación de la Expresión Génica , Células Th17/metabolismo , Células Th17/inmunología , Células TH1/inmunología , Células TH1/metabolismo , Modelos Animales de Enfermedad , Piruvato QuinasaRESUMEN
Adenine base editors (ABEs) are genome-editing tools that have been harnessed to introduce precise Aâ¢T to Gâ¢C conversion. The discovery of split genes revealed that all introns contain two highly conserved dinucleotides, canonical "AG" (acceptor) and "GT" (donor) splice sites. ABE can directly edit splice acceptor sites of the adenine (A) base, leading to aberrant gene splicing, which may be further adopted to remodel splicing. However, spliced isoforms triggered with ABE have not been well explored. To address it, we initially generated a cell line harboring C-terminal enhanced GFP (eGFP)-tagged ß-actin (ACTB), in which the eGFP signal can track endogenous ß-actin expression. Expectedly, after the editing of splice acceptor sites, we observed a dramatical decrease in the percentage of eGFP-positive cells and generation of splicing products with the noncanonical splice site. Furthermore, we manipulated Peroxidasin in mouse embryos with ABE, in which a noncanonical acceptor was activated to remodel splicing, successfully generating a mouse disease model of anophthalmia and severely malformed microphthalmia. Collectively, we demonstrate that ABE-mediated splicing remodeling can activate a noncanonical acceptor to manipulate human and mouse genomes, which will facilitate the investigation of basic and translational medicine studies.
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Adenina , Sitios de Empalme de ARN , Animales , Humanos , Ratones , Actinas/genética , Secuencia de Bases , Edición Génica , Intrones , Empalme del ARN , Células HEK293RESUMEN
Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.
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IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.
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Alphacoronavirus , Infecciones por Coronavirus , Endopeptidasas , Glicoproteínas , Enfermedades de los Porcinos , Porcinos , Internalización del Virus , Animales , Alphacoronavirus/fisiología , Infecciones por Coronavirus/enzimología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Endopeptidasas/metabolismo , Glicoproteínas/química , Glicoproteínas/metabolismo , Porcinos/virología , Enfermedades de los Porcinos/enzimología , Enfermedades de los Porcinos/metabolismo , Enfermedades de los Porcinos/virología , Internalización del Virus/efectos de los fármacos , Tunicamicina/farmacología , GlicosilaciónRESUMEN
BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. METHODS AND RESULTS: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. CONCLUSION: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
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Diabetes Mellitus Tipo 1 , Cardiomiopatías Diabéticas , Ferroptosis , Humanos , Animales , Ratones , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/prevención & control , Sirtuina 1 , Fibronectinas , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Proteína p53 Supresora de Tumor , Miocitos CardíacosRESUMEN
Flexible metal-organic frameworks (FMOFs) exhibit reversible structural transitions ("breathing" behaviors), which can regulate the proton transport passageway effectively. This property offers remarkable advantages for improving the proton conductivity. Our objective of this work is to design a single-variable flexibility synergistic strategy for the fabrication of FMOFs with high conductivity. Herein, four two-dimensional FMOFs, {[Co(4-bpdb)(R-ip)]·xsolvents}n (x = rich, 1-4), have been successfully designed and assembled (4-bpdb = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene and R-ip = MeO/EtO/n-PrO/n-BuO-isophthalate). Upon the release and/or absorption of different solvent molecules, they display reversible breathing behaviors, thereby resulting in the formation of the partial and complete solvent-free compounds {[Co(4-bpdb)(R-ip)]·ysolvents}n (y = free or poor, 1A-4A). This breathing behavior involves the synergistic self-adaption of the dynamic torsion of alkoxy groups and reversible structural transformation, leading to remarkable changes in cell parameters and void space, as evidenced by single-crystal X-ray diffraction, powder X-ray diffraction, and N2 and CO2 adsorption analyses. At 363 K and 98% relative humidity, 2A exhibits the best proton conductivity among the FMOFs. Its conductivity reaches 4.08 × 10-2 S cm-1 and is one of the highest conductivities shown by reported unmodified MOF-based proton conductors.
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BACKGROUND: Community-acquired respiratory infections are a leading cause of illness and death globally. The aetiologies of community-acquired pneumonia remain poorly defined. The RESPIRO study is an ongoing prospective observational cohort study aimed at developing pragmatic logistical and analytic platforms to accurately identify the causes of moderate-to-severe community-acquired pneumonia in adults and understand the factors influencing disease caused by individual pathogens. The study is currently underway in Singapore and has plans for expansion into the broader region. METHODS: RESPIRO is being conducted at three major tertiary hospitals in Singapore. Adults hospitalised with acute community-acquired pneumonia or lower respiratory tract infections, based on established clinical, laboratory and radiological criteria, will be recruited. Over the course of the illness, clinical data and biological samples will be collected longitudinally and stored in a biorepository for future analysis. DISCUSSION: The RESPIRO study is designed to be hypothesis generating, complementary to and easily integrated with other research projects and clinical trials. The detailed clinical database and biorepository will yield insights into the epidemiology and outcomes of community-acquired lower respiratory tract infections in Singapore and the surrounding region and offers the opportunity to deeply characterise the microbiology and immunopathology of community-acquired pneumonia.
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Enfermedades Transmisibles , Neumonía , Infecciones del Sistema Respiratorio , Adulto , Humanos , Estudios Prospectivos , Evaluación de Resultado en la Atención de Salud , Estudios Observacionales como AsuntoRESUMEN
Janus TiPX (X = F, Cl, and Br) monolayers were systematically investigated through first-principles calculations. The Janus TiPX monolayers exhibit mechanical and dynamic stability. Two monolayers are indirect bandgap semiconductors, except the TiPBr monolayer, which has the features of a quasi-direct bandgap semiconductor. Biaxial strain can modify the band gap of single layers. The Janus TiPX monolayers have remarkable flexibility and piezoelectric properties. In particular, the TiPF monolayer shows high horizontal (44.18 pm V-1) and vertical piezoelectric coefficients (-3.59 pm V-1). These values exceed those of conventional bulk materials, like GaN (3.1 pm V-1) and α-quartz (2.3 pm V-1). All of the monolayers have absorption coefficients of 105 cm-1 for visible and ultraviolet (UV) light, which are one order of magnitude greater than that of MoSSe. Furthermore, TiPX monolayers have high carrier mobility. Janus TiPX monolayers represent a class of two-dimensional (2D) materials with exceptional properties and multifunctionality, holding significant promise for various applications in piezoelectric sensors, solar cells, and nano-electronic devices.
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Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.
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2-Pentanone is a significant carbon-neutral fuel. To better understand 2-pentanone combustion, the CCSD(T)/CBS method was used to calculate the potential energy surfaces (PES) for H-abstraction, isomerization, and ß-scission reactions of 2-pentanone. Rate constants for the above reactions were calculated by the MESS employing conventional transition state theory (CTST) at 300-2000 K. The findings reveal adherence to the Evans-Polanyi principle in the H-abstraction reactions of 2-pentanone by H atoms. Specifically, the 2-site shows more competitive kinetics due to having the lowest energy barrier of 7.8 kcal/mol. The 4-position has the highest energy barrier, making the reaction difficult to occur. In the subsequent reactions, the breaking of C-H bonds is most competitive at low temperatures. In particular, the H transfer from INT1 to INT3 has a potential well height of 24.8 kcal/mol. The ß-scission reactions become the main pathway for the depletion of pentanone radicals with increasing temperature. This study significantly extends the kinetic parameters of 2-pentanone combustion over a wide range of temperatures and pressures, which is expected to contribute to the development of 2-pentanone combustion models.
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Chemotherapy toxicity and tumor multidrug resistance remain the main reasons for clinical treatment failure in cervical cancer. In this study, 79 novel chalcone derivatives were designed and synthesized using the principle of active substructure splicing with the parent nucleus of licorice chalcone as the lead compound and VEGFR-2 and P-gp as the target of action and their potentials for anticervical cancer activity were preliminarily evaluated. The results showed that the IC50 values of candidate compound B20 against HeLa and HeLa/DDP cells were 3.66 ± 0.10 and 4.35 ± 0.21 µΜ, respectively, with a resistance index (RI) of 1.18, which was significantly higher than that of the positive drug cisplatin (IC50:13.60 ± 1.63, 100.03 ± 7.94 µΜ, RI:7.36). In addition, B20 showed significant inhibitory activity against VEGFR-2 kinase and P-gp-mediated rhodamine 123 efflux, as well as the ability to inhibit the phosphorylation of VEGFR-2 and downstream PI3K/AKT signaling pathway proteins, inducing apoptosis, blocking cells in the S-phase, and inhibiting invasive migration and tubule generation by HUVEC cells. Acceptable safety was demonstrated in acute toxicity tests when B20 was at 200 mg/kg. In the nude mouse HeLa/DDP cell xenograft tumor model, the inhibition rate of transplanted tumors was 39.2 % and 79.2 % when B20 was at 10 and 20 mg/kg, respectively. These results suggest that B20 is a potent VEGFR-2 and P-gp inhibitor with active potential for treating cisplatin-resistant cervical cancer.
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Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias del Cuello Uterino , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Femenino , Resistencia a Antineoplásicos/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Chalconas/farmacología , Chalconas/química , Chalconas/síntesis química , Animales , Chalcona/química , Chalcona/farmacología , Chalcona/síntesis química , Células HeLa , Apoptosis/efectos de los fármacos , RatonesRESUMEN
BACKGROUND AND AIMS: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US. METHODS AND RESULTS: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively. CONCLUSION: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them.
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Causas de Muerte , Enfermedad Coronaria , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Factores de Tiempo , Anciano , Medición de Riesgo , Adulto , Pronóstico , Estado de Salud , Prevalencia , Factores Protectores , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Indicadores de Salud , Conducta de Reducción del RiesgoRESUMEN
BACKGROUND AND AIMS: Since the global burden of chronic kidney disease (CKD) is rising rapidly, the study aimed to assess the association of cardiovascular health (CVH) metrics with all-cause and cardiovascular disease (CVD) mortality among individuals with CKD. METHODS AND RESULTS: The cohort study included 5834 participants with CKD from the National Health and Nutrition Examination Survey 1999-2018. A composite CVH score was calculated based on smoking status, physical activity, body mass index, blood pressure, total cholesterol, diet quality, and glucose control. Primary outcomes were all-cause and CVD mortality as of December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between CVH metrics and deaths in CKD patients. During a median follow-up of 7.2 years, 2178 all-cause deaths and 779 CVD deaths were documented. Compared to participants with ideal CVH, individuals with intermediate CVH exhibited a 46.0% increase in all-cause mortality (hazard ratio, 1.46; 95% confidence interval: 1.17, 1.83), while those with poor CVH demonstrated a 101.0% increase (2.01; 1.54, 2.62). For CVD mortality, individuals with intermediate CVH experienced a 56.0% increase (1.56; 1.02, 2.39), and those with poor CVH demonstrated a 143.0% increase (2.43; 1.51, 3.91). Linear trends were noted for the associations of CVH with both all-cause mortality (P for trend <0.001) and CVD mortality (P for trend = 0.02). CONCLUSIONS: Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD, which highlights the importance of maintaining good CVH in CKD patients.
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Enfermedades Cardiovasculares , Causas de Muerte , Factores de Riesgo de Enfermedad Cardiaca , Encuestas Nutricionales , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Persona de Mediana Edad , Medición de Riesgo , Anciano , Factores de Tiempo , Estados Unidos/epidemiología , Pronóstico , Adulto , Presión Sanguínea , Glucemia/metabolismo , Ejercicio Físico , Dieta Saludable , Colesterol/sangre , Fumar/efectos adversos , Fumar/mortalidad , Fumar/epidemiología , Estado de Salud , Índice de Masa Corporal , Factores de RiesgoRESUMEN
Stripe rust and powdery mildew are serious diseases that severely decrease the yield of wheat. Planting wheat cultivars with powdery mildew and stripe rust resistance genes is the most effective way to control these two diseases. Introducing disease resistance genes from related species into the wheat genome via chromosome translocation is an important way to improve wheat disease resistance. In this study, nine novel T1RS.1AL translocation lines were developed from the cross of wheat cultivar Chuannong25 (CN25) and a Chinese rye Qinling. The results of non-denaturing fluorescence in situ hybridization and PCR showed that all new lines were homozygous for the T1RS.1AL translocation. These new T1RS.1AL translocation lines exhibited strong resistance to stripe rust and powdery mildew. The cytogenetics results indicated that the resistance of the new lines was conferred by the 1RS chromosome arms, which came from Qinling rye. The genetic analysis indicated that there were new dominant resistance genes on the 1RS chromosome arm resistant to stripe rust and powdery mildew, and their resistance patterns were different from those of Yr9, Pm8, and Pm17 genes. In addition, the T1RS.1AL translocation lines generally exhibited better agronomic traits in the field relative to CN25. These T1RS.1AL translocations have great potential in wheat-breeding programs in the future.
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Ascomicetos , Basidiomycota , Cromosomas de las Plantas , Resistencia a la Enfermedad , Enfermedades de las Plantas , Secale , Translocación Genética , Triticum , Triticum/genética , Triticum/microbiología , Triticum/inmunología , Secale/genética , Secale/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Ascomicetos/fisiología , Basidiomycota/fisiología , Cromosomas de las Plantas/genética , Hibridación Fluorescente in Situ , Pueblos del Este de AsiaRESUMEN
Spermatogenesis is a developmental process driven by interactions between germ cells and Sertoli cells. This process depends on appropriate gene expression, which might be regulated by transcription factors. This study focused on Rreb1, a zinc finger transcription factor, and explored its function and molecular mechanisms in spermatogenesis in a mouse model. Our results showed that RREB1 was predominantly expressed in the Sertoli cells of the testis. The decreased expression of RREB1 following injection of siRNA caused impaired Sertoli cell development, which was characterized using a defective blood-testis barrier structure and decreased expression of Sertoli cell functional maturity markers; its essential trigger might be SMAD3 destabilization. The decreased expression of RREB1 in mature Sertoli cells influenced the cell structure and function, which resulted in abnormal spermatogenesis, manifested as oligoasthenoteratozoospermia, and we believe RREB1 plays this role by regulating the transcription of Fshr and Wt1. RREB1 has been reported to activate Fshr transcription, and we demonstrated that the knockdown of Rreb1 caused a reduction in follicle-stimulating hormone receptor (FSHR) in the testis, which could be the cause of the increased sperm malformation. Furthermore, we confirmed that RREB1 directly activates Wt1 promoter activity, and RREB1 downregulation induced the decreased expression of Wt1 and its downstream polarity-associated genes Par6b and E-cadherin, which caused increased germ-cell death and reduced sperm number and motility. In conclusion, RREB1 is a key transcription factor essential for Sertoli cell development and function and is required for normal spermatogenesis.
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Células de Sertoli , Espermatogénesis , Factores de Transcripción , Animales , Masculino , Ratones , Barrera Hematotesticular/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Ratones Endogámicos C57BL , Receptores de HFE/genética , Receptores de HFE/metabolismo , Células de Sertoli/metabolismo , Proteína smad3/metabolismo , Proteína smad3/genética , Espermatogénesis/genética , Testículo/metabolismo , Testículo/citología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas WT1/genética , Proteínas WT1/metabolismoRESUMEN
With the emergence of digital transformation, China confronts the dual challenge of fostering sustainable economic and social development while fulfilling its "dual-carbon" commitments. Is the digital-real economy integration a blessing or a curse for inclusive green development? The study was conducted under this backdrop. This paper explores the impacts and mechanisms of digital-real economy integration on carbon emission efficiency, utilizing panel data from 274 Chinese cities over the period from 2011 to 2021. The results indicate that this profound integration significantly enhances urban carbon emission efficiency, although this relationship is partially mediated by industrial structure upgrading. Additionally, natural resources dependence may compromise efficiency gains, exhibiting varying effects across different contexts. The impact of digital-real economy integration on carbon efficiency (Cee) manifests as a non-linear U-shaped relationship that intensifies with increased integration. Heterogeneity analysis reveals that major, eastern, coastal, and resource-scarce cities experience the most profound benefits. These findings highlight the urgency of advancing digital carbon neutrality and offer strategies for emerging economies to transcend traditional constraints, thereby achieving green economic recovery and inclusive development.
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Genomic prediction has emerged as a pivotal technology for the genetic evaluation of livestock, crops, and for predicting human disease risks. However, classical genomic prediction methods face challenges in incorporating biological prior information such as the genetic regulation mechanisms of traits. This study introduces a novel approach that integrates mRNA transcript information to predict complex trait phenotypes. To evaluate the accuracy of the new method, we utilized a Drosophila population that is widely employed in quantitative genetics researches globally. Results indicate that integrating mRNA transcript data can significantly enhance the genomic prediction accuracy for certain traits, though it does not improve phenotype prediction accuracy for all traits. Compared with GBLUP, the prediction accuracy for olfactory response to dCarvone in male Drosophila increased from 0.256 to 0.274. Similarly, the accuracy for cafe in male Drosophila rose from 0.355 to 0.401. The prediction accuracy for survival_paraquat in male Drosophila is improved from 0.101 to 0.138. In female Drosophila, the accuracy of olfactory response to 1hexanol increased from 0.147 to 0.210. In conclusion, integrating mRNA transcripts can substantially improve genomic prediction accuracy of certain traits by up to 43%, with range of 7% to 43%. Furthermore, for some traits, considering interaction effects along with mRNA transcript integration can lead to even higher prediction accuracy.
Asunto(s)
Drosophila , Genómica , ARN Mensajero , Animales , ARN Mensajero/genética , Masculino , Genómica/métodos , Femenino , Drosophila/genética , FenotipoRESUMEN
The stability of aqueous zinc metal batteries is significantly affected by side reactions and dendrite growth on the anode interface, which primarily originate from water and anions. Herein, we introduce a multi H-bond site additive, 2, 2'-Sulfonyldiethanol (SDE), into an aqueous electrolyte to construct a sieving-type electric double layer (EDL) by hydrogen bond interlock in order to address these issues. On the one hand, SDE replaces H2O and SO4 2- anions that are adsorbed on the zinc anode surface, expelling H2O/SO4 2- from the EDL and thereby reducing the content of H2O/SO4 2- at the interface. On the other hand, when Zn2+ are de-solvated at the interface during the plating, the strong hydrogen bond interaction between SDE and H2O/SO4 2- can trap H2O/SO4 2- from the EDL, further decreasing their content at the interface. This effectively sieves them out of the zinc anode interface and inhibits the side reactions. Moreover, the unique characteristics of trapped SO4 2- anions can restrict their diffusion, thereby enhancing the transference number of Zn2+ and promoting dendrite-free deposition and growth of Zn. Consequently, utilizing an SDE/ZnSO4 electrolyte enables excellent cycling stability in Zn//Zn symmetrical cells and Zn//MnO2 full cells with lifespans exceeding 3500â h and 2500â cycles respectively.