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BACKGROUND: Base editing is a powerful tool for artificial evolution to create allelic diversity and improve agronomic traits. However, the great evolutionary potential for every sgRNA target has been overlooked. And there is currently no high-throughput method for generating and characterizing as many changes in a single target as possible based on large mutant pools to permit rapid gene directed evolution in plants. RESULTS: In this study, we establish an efficient germline-specific evolution system to screen beneficial alleles in Arabidopsis which could be applied for crop improvement. This system is based on a strong egg cell-specific cytosine base editor and the large seed production of Arabidopsis, which enables each T1 plant with unedited wild type alleles to produce thousands of independent T2 mutant lines. It has the ability of creating a wide range of mutant lines, including those containing atypical base substitutions, and as well providing a space- and labor-saving way to store and screen the resulting mutant libraries. Using this system, we efficiently generate herbicide-resistant EPSPS, ALS, and HPPD variants that could be used in crop breeding. CONCLUSIONS: Here, we demonstrate the significant potential of base editing-mediated artificial evolution for each sgRNA target and devised an efficient system for conducting deep evolution to harness this potential.
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Arabidopsis , Edición Génica , Variación Genética , Arabidopsis/genética , Edición Génica/métodos , Sistemas CRISPR-Cas , Evolución Molecular Dirigida , Alelos , Mutación , Fitomejoramiento/métodos , Resistencia a los Herbicidas/genéticaRESUMEN
In search of potential anticancer agents, we synthesized SNO-donor salicylaldimine main ligand-based Pt(II) complexes bearing NH3 as co-ligand at trans-position (C1-C6). These complexes showed similarity in structure with transplatin as the two N donor atoms of the main ligand and NH3 co-ligand were coordinated to Pt in trans position to each other. Each complex with different substituents on the main ligand was characterized thoroughly by detailed spectroscopic and spectrophotometric methods. Four of these complexes were studied in solid state by single crystal X-ray analysis. The stability of reference complex C1 was measured in solution state in DMSOd6 or its mixture with D2O using 1H NMR methods. These complexes were further investigated for their anticancer activity in triple-negative-breast (TNBC) cells including MDA-MB-231, MDA-MB-468 and MDA-MB-436 cells. All these complexes showed satisfactory cytotoxic effect as revealed by the MTT results. Importantly, the highly active complex C4 anticancer effect was compared to the standard chemotherapeutic agents including cisplatin, oxaliplatin and 5-fluorouracil (5-FU). Functionally, C4 suppressed invasion, spheroids formation ability and clonogenic potential of cancer cells. C4 showed synergistic anticancer effect when used in combination with palbociclib, JQ1 and paclitaxel in TNBC cells. Mechanistically, C4 inhibited cyclin-dependent kinase (CDK)4/6 pathway and targeted the expressions of MYC/STAT3/CCND1/CNNE1 axis. Furthermore, C4 suppressed the EMT signaling pathway that suggested a role of C4 in the inhibition of TNBC metastasis. Our findings may pave further in detailed mechanistic study on these complexes as potential chemotherapeutic agents in different types of human cancers.
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Antineoplásicos , Ciclina D1 , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Transición Epitelial-Mesenquimal , Factor de Transcripción STAT3 , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Transición Epitelial-Mesenquimal/efectos de los fármacos , Línea Celular Tumoral , Ciclina D1/metabolismo , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 4 Dependiente de la Ciclina/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proteínas Proto-Oncogénicas c-myc/metabolismo , Femenino , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Ligandos , Carcinogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Platino (Metal)/química , Platino (Metal)/farmacología , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/química , Compuestos Organoplatinos/síntesis químicaRESUMEN
Objective: The incidence of stroke worldwide is increasing year by year. With the enhancement of public health awareness, people's demand for the quality of stroke rehabilitation is getting higher and higher, so better quality care measures are needed in the treatment of stroke. Based on this, this paper explores the impact of a new type of nursing care measure, the complementary health care model combined with condition tracking, on stroke patients. Methods: 238 stroke patients were randomly divided into a conventional group (n=119) and a combined group (n=119). 238 stroke patients were randomly divided into conventional group (n=119) and combined group (n=119). The conventional group received routine care, in which doctors and nursing carried out their own work without cooperation after the patients were admitted to the hospital; the combined group received a complementary health care model and condition tracking, in which doctors and nurses jointly checked the rooms, discussed cases, jointly formulated treatments and nursing care plans, and jointly formulated the patients' discharge and rehabilitation plans after the patients were admitted to the hospital. Before the intervention, at the time of discharge, and 6 months after discharge, the neurological function of the patients in both groups was assessed using the National Institutes of Health Stroke Scale (NIHSS) and the Fugl-Meyer (FMA) scale, the cognitive function of the patients in both groups was assessed using the Montreal Cognitive Assessment (MoCA) scale and the Measured Mental State Examination (MMSE), and the cognitive function of the patients in both groups was assessed using the General Self-Efficacy Scale (GSS) and the Montreal Cognitive Assessment (MCA) scale. General Self-Efficacy Scale (GSES) to assess self-efficacy, Exercise Adherence Questionnaire (EAQ) to assess adherence to functional exercise and Specific Quality of Life Scale (SSQoL-12) to assess the quality of life of patients in both groups, and the self-developed satisfaction with nursing care to assess patients' satisfaction with the care model. Results: Before the intervention, there was no difference in the National Institutes of Health Stroke Scale (NIHSS), the Fugl-Meyer Assessment (FMA), the Montreal Cognitive Assessment (MoCA), the Mental State Examination (MMSE), the General Self-Efficacy Scale (GSES), the Exercise Adherence Questionnaire (EAQ) and the Stroke-Specific Quality of Life Scale-12 (SSQoL-12) scores between the two groups (P > .05). At discharge and six months later, NIHSS scores continued to decrease in both groups, with the joint group being lower than the conventional group (P < .05); scores for all other items continued to increase, with the joint being higher than the conventional group (P < .05). Satisfaction with care was higher in the combined group than in the conventional group (P < .05). Conclusion: The complementary healthcare model combined with condition tracking can effectively promote the prognosis of rehabilitation of stroke patients, and has a positive effect in promoting the recovery of neurological and cognitive functions, strengthening self-efficacy, and improving the quality of life, which can be promoted in the clinic.
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Electrocatalytic nitrate reduction reaction (EC-NITRR) shows a significant advantage for green reuse of the nitrate (NO3-) pollutant. However, the slow diffusion reaction limits the reaction rate in practical EC-NITRR, causing an unsatisfactory ammonia (NH3) yield. In this work, a multifunctional NiFe-LDH/CeO2 with the dual adsorption effect (physisorption and chemisorption) and dual-metal sites (Ce3+ and Fe2+) was fabricated by the electrodeposition method. NiFe-LDH/CeO2 performed an expected ability of enrichment for NO3- through the pseudo-first-order and pseudo-second-order kinetic models, and the polymetallic structure provided abundant sites for effective reaction of NO3-. At-0.6 V vs RHE, the ammonia (NH3) yield of NiFe-LDH/CeO2 reached 335.3 µg h-1 cm-2 and the selectivity of NH3 was 24.2 times that of NO2-. The nitrogen source of NH3 was confirmed by 15NO3- isotopic labeling. Therefore, this work achieved the recycling of the NO3- pollutant by synergy of enrichment and catalysis, providing an alternative approach for the recovery of NO3- from wastewater.
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Diabetic kidney disease (DKD) is a significant healthcare burden worldwide that substantially increases the risk of kidney failure and cardiovascular events. To reduce the prevalence of DKD, extensive research is being conducted to determine the risk factors and consequently implement early interventions. Patients with type 2 diabetes mellitus (T2DM) are more likely to be obese. Abdominal adiposity is associated with a greater risk of kidney damage than general obesity. Abdominal adipose tissue can be divided into different fat depots according to the location and function, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PAT), and renal sinus adipose tissue (RSAT), which can be accurately measured by radiology techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Abdominal fat depots may affect the development of DKD through different mechanisms, and radiologic abdominal adipose characteristics may serve as imaging indicators of DKD risk. This review will first describe the CT/MRI-based assessment of abdominal adipose depots and subsequently describe the current studies on abdominal adipose tissue and DKD development, as well as the underlying mechanisms in patients of T2DM with DKD.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Adiposidad , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico por imagen , Obesidad , Grasa Abdominal/diagnóstico por imagen , Obesidad AbdominalRESUMEN
Plants produce a burst of reactive oxygen species (ROS) after pathogen infection to successfully activate immune responses. During pattern-triggered immunity (PTI), ROS are primarily generated by the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). RBOHD is degraded in the resting state to avoid inappropriate ROS production; however, the enzyme mediating RBOHD degradation and how to prevent RBOHD degradation after pathogen infection is unclear. In this study, we identified an Arabidopsis (Arabidopsis thaliana) vacuole-localized papain-like cysteine protease, XYLEM CYSTEINE PEPTIDASE 1 (XCP1), and its inhibitor CYSTATIN 6 (CYS6). Pathogen-associated molecular pattern-induced ROS burst and resistance were enhanced in the xcp1 mutant but were compromised in the cys6 mutant, indicating that XCP1 and CYS6 oppositely regulate PTI responses. Genetic and biochemical analyses revealed that CYS6 interacts with XCP1 and depends on XCP1 to enhance PTI. Further experiments showed that XCP1 interacts with RBOHD and accelerates RBOHD degradation in a vacuole-mediated manner. CYS6 inhibited the protease activity of XCP1 toward RBOHD, which is critical for RBOHD accumulation upon pathogen infection. As CYS6, XCP1, and RBOHD are conserved in all plant species tested, our findings suggest the existence of a conserved strategy to precisely regulate ROS production under different conditions by modulating the stability of RBOHD.
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Proteínas de Arabidopsis , Arabidopsis , Proteasas de Cisteína , Proteínas de Arabidopsis/metabolismo , Cisteína/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Cistatina M/metabolismo , Reconocimiento de Inmunidad Innata , Arabidopsis/metabolismo , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Proteasas de Cisteína/metabolismo , Inmunidad de la Planta/genéticaRESUMEN
Sorghum is an important crop for food, forage, wine and biofuel production. To enhance its transformation efficiency without negative developmental by-effects, we investigated the impact of GRF4-GIF1 chimaera and GRF5 on sorghum transformation. Both GRF4-GIF1 and GRF5 effectively improved the transformation efficiency of sorghum and accelerated the transformation process of sorghum to less than 2 months which was not observed when using BBM-WUS. As agrobacterium effectors increase the ability of T-DNA transfer into plant cells, we checked whether ternary vector system can additively enhance sorghum transformation. The combination of GRF4-GIF1 with helper plasmid pVS1-VIR2 achieved the highest transformation efficiency, reaching 38.28%, which is 7.71-fold of the original method. Compared with BBM-WUS, overexpressing GRF4-GIF1 caused no noticeable growth defects in sorghum. We further developed a sorghum CRISPR/Cas9 gene-editing tool based on this GRF4-GIF1/ternary vector system, which achieved an average gene mutation efficiency of 41.36%, and null mutants were created in the T0 generation.
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Sorghum , Sorghum/genética , Plantas Modificadas Genéticamente/genética , Transformación Genética , Edición Génica/métodos , Agrobacterium/genética , Grano Comestible/genética , Sistemas CRISPR-CasRESUMEN
Jasmonic acid (JA) is a crucial phytohormone that regulates plant immunity. The endogenous JA level is determined by the rates of its biosynthesis and catabolism in plants. The activation of JA biosynthesis has been well documented; however, how plants repress JA catabolism upon pathogen infection remains elusive. In this study, we identified and characterized Botrytis cinerea-induced F-box protein 1 (BFP1) in Arabidopsis. The expression of BFP1 was induced by B. cinerea in a JA signaling-dependent manner, and BFP1 protein was critical for plant defense against B. cinerea and plant response to JA. In addition, BFP1 overexpression increased plant defenses against broad-spectrum pathogens without fitness costs. Further experiments demonstrated that BFP1 interacts with and mediates the ubiquitination and degradation of jasmonic acid oxidases (JAOs, also known as jasmonate-induced oxygenases, JOXs), the enzymes that hydroxylate JA to 12OH-JA. Consistent with this, BFP1 affects the accumulation of JA and 12OH-JA during B. cinerea infection. Moreover, mutation of JAO2 complemented the phenotypes of the bfp1 mutant. Collectively, our results unveil a new mechanism used by plants to activate immune responses upon pathogen infection: suppressing JA catabolism.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Resistencia a la Enfermedad , Proteínas de Arabidopsis/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Botrytis/fisiología , Enfermedades de las Plantas , Regulación de la Expresión Génica de las Plantas , Ácido Salicílico/metabolismoRESUMEN
Rice is a staple crop for over half of the global population. However, blast disease caused by Magnaporthe orzae can result in more than a 30% loss in rice yield in epidemic years. Although some major resistance genes bolstering blast resistance have been identified in rice, their stacking in elite cultivars usually leads to yield penalties. Here we report that OsUBC45, a ubiquitin-conjugating enzyme functioning in the endoplasmic reticulum-associated protein degradation system, promotes broad-spectrum disease resistance and yield in rice. OsUBC45 is induced upon infection by M. oryzae, and its overexpression enhances resistance to blast disease and bacterial leaf blight by elevating pathogen-associated molecular pattern-triggered immunity (PTI) while nullifying the gene-attenuated PTI. The OsUBC45 overexpression also increases grain yield by over 10%. Further, OsUBC45 enhances the degradation of glycogen synthase kinase 3 OsGSK3 and aquaporin OsPIP2;1, which negatively regulate the grain size and PTI, respectively. The OsUBC45 reported in our study has the potential for improving yield and disease resistance for sustainable rice production.
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Resistencia a la Enfermedad , Oryza , Resistencia a la Enfermedad/genética , Oryza/genética , Enzimas Ubiquitina-Conjugadoras/genética , Degradación Asociada con el Retículo Endoplásmico , Enfermedades de las Plantas/genéticaRESUMEN
Objective To explore the impact of sinomenine on bleomycin A5-induced pulmonary fibrosis (PF) in rats and the underlying mechanism. Methods MRC-5 cells were cultured and treated with sinomenine to determine its optimal concentration and time through the MTT assay. Subsequently, MRC-5 cells were incubated with 80 µmol/L sinomenine for 48 hours or transfected with miR-21 mimic/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) siRNA prior to sinomenine treatment. The expression of miR-21, ADAMTS-1, collagen type 1 (Col1) and collagen type 3 (Col3) was detected by quantitative real-time PCR (qRT-PCR) and/or Western blot analysis. Thirty SD rats were randomly divided into control group, sinomenine group and sinomenine combined with miR-21 agomir group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to establish the PF model. Then, rats in control group, sinomenine group and sinomenine +miR-21 agomir group were treated with 9 g/L sodium chloride solution, sinomenine and sinomenine+miR-21 agomir, respectively. On day 28, all rats were sacrificed. HE and Masson staining was performed in pulmonary tissue. The expression of ADAMTS-1, Col1 and Col3 in pulmonary tissue were detected by qRT-PCR and/or Western blot analysis. ELISA was used to measure serum procollagen type 1 carboxyterminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) levels. Results Administration of sinomenine decreased miR-21 levels, up-regulated ADAMTS-1 expression, and promoted Col1 and Col3 degradation in MRC-5 cells. Importantly, interfering with the miR-21/ADAMTS-1 signaling pathway partially reversed the promotive effect of sinomenine on Col1 and Col3 degradation. Treatment of SD rats with sinomenine reduced alveolitis and PF scores, decreased serum P1CP and P3NP levels, up-regulated pulmonary ADAMTS-1 expression, and down-regulated Col1 and Col3 expression. However, these effects were reversed by miR-21 agomir. Conclusion Sinomenine promotes Col1 and Col3 degradation and inhibits PF in rats by miR-21/ADAMTS-1 pathway.
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MicroARNs , Fibrosis Pulmonar , Ratas , Animales , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/genética , Procolágeno/metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Bleomicina/efectos adversos , Colágeno Tipo III/metabolismo , MicroARNs/metabolismoRESUMEN
The high adaptability of insects to food sources has contributed to their ranking among the most abundant and diverse species on Earth. However, the molecular mechanisms underlying the rapid adaptation of insects to different foods remain unclear. We explored the changes in gene expression and metabolic composition of the Malpighian tubules as an important metabolic excretion and detoxification organ in silkworms (Bombyx mori) fed mulberry leaf and artificial diets. A total of 2436 differentially expressed genes (DEGs) and 245 differential metabolites were identified between groups, with the majority of DEGs associated with metabolic detoxification, transmembrane transport, and mitochondrial function. Detoxification enzymes, such as cytochrome P450 (CYP), glutathione-S-transferase (GST), and UDP-glycosyltransferase, and ABC and SLC transporters of endogenous and exogenous solutes were more abundant in the artificial diet group. Enzyme activity assays confirmed increased CYP and GST activity in the Malpighian tubules of the artificial diet-fed group. Metabolome analysis showed increased contents of secondary metabolites, terpenoids, flavonoids, alkaloids, organic acids, lipids, and food additives in the artificial diet group. Our findings highlight the important role of the Malpighian tubules in adaptation to different foods and provide guidance for further optimization of artificial diets to improve silkworm breeding.
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Bombyx , Animales , Bombyx/genética , Túbulos de Malpighi/metabolismo , Fitomejoramiento , Insectos/metabolismo , Dieta , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismoRESUMEN
Mouding sufu, a traditional fermented soybean product in China, has been recognized by the public in the southwestern regions of China. To reveal the microbial community succession and their relationship with the flavor formation during the natural fermentation of Mouding sufu, microbial community, non-volatile flavor compounds and volatile flavor compounds were analyzed by high-throughput sequencing, high-performance liquid chromatography, gas chromatography ion migration spectroscopy, respectively. The results showed that Lactobacillus and Klebsiella were the most abundant bacterial genus, whereas the main fungal genera were unclassified-f-Dipodascaeae and Issatchenkia. In addition, Glutamic acid, Aspartic acid, Alanine, Valine, Lysine, Histidine, lactic acid, succinic acid, and acetic acid were the main non-volatile flavor substances. Furthermore, the taste activity values of glutamic acid, aspartic acid and lactic acid reached 132, 68.9, 18.18 at H60, respectively, meaning that umami and sour were the key taste compounds. Simultaneously, ethyl 3-methylbutanoate-M, ethyl propanoate, methyl 2-methylbutanoate, ethyl 2-methylbutanoate, ethyl 3-methylbutanoate-D, ethyl isobutyrate, linalool-M, linalool-D, cis-4-heptenal, 2-methylpropanal were the characteristic volatile flavor of Mouding sufu. Finally, correlation analysis showed that g__Erwinia and g__Acremonium correlated with most of the key aroma compounds. 20 bacteria and 21 fungi were identified as core functional microbe for Mouding sufu production.
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Objective To observe the role of tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-B (PDGF-B) in kiwi fruit essence-mediated protection of radiation-induced lung injury (RILI) in rats. Methods 96 male healthy Sprague-Dawley rats were divided into normal control group, model group, and kiwi fruit essence treatment group(60 and 240 mg/kg) by the random number table method, with 24 animals in each group. The whole lungs underwent 6 MV X-ray irradiation (18 Gy) to induce RILI animal models in rats of the latter three groups. On the next day after irradiation, rats in the latter two groups were intragastrically administrated with 60 or 240 mg/kg kiwi fruit essence, once a day. The rats in the normal control and model groups were treated with 9 g/L sodium chloride solution. Eight rats in the latter three groups were randomly sacrificed on days 14, 28, and 56, while normal control rats were sacrificed on day 56 as the overall control. Blood samples were collected and separated. Serum concentrations of TNF-α and PDGF-B were detected using ELISA. The lung tissues were isolated for HE and Masson staining to evaluate alveolitis and pulmonary fibrosis (PF). The hydroxyproline (HYP) content in lung tissues was detected. The mRNA and protein expression of pulmonary TNF-α and PDGF-B were determined by quantitative real-time PCR and immunohistochemistry. Results Compared with the model group, treatment with 60 and 240 mg/kg kiwi fruit essence group significantly reduced alveolitis on days 14 and 28 as well as PF lesions on days 28 and 56. Compared with the normal control group, HYP content in the lung tissue of the model group increased on day 28 and day 56, while TNF-α and PDGF-B levels in the serum and lung tissues increased at each time point. Compared with the model group during the same period, 60 and 240 mg/kg kiwi fruit essence element treatment group reported the diminished levels of serum and pulmonary TNF-α on day 14 and day 28. Consistently, the lung tissue HYP content and serum and pulmonary PDGF-B levels on day 28 and day 56 were reduced. In addition, the above indicators in the 240 mg/kg kiwi fruit essence treatment group were lower than those for the 60 mg/kg kiwi fruit essence treatment group. Conclusion Kiwi fruit essence can alleviate RILI in rats, which is related to the down-regulation of TNF-α expression at the early stage and decreased PDGF-B level at the middle and late stages.
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Actinidia , Lesión Pulmonar , Aceites Volátiles , Proteínas Proto-Oncogénicas c-sis , Fibrosis Pulmonar , Factor de Necrosis Tumoral alfa , Animales , Masculino , Ratas , Frutas/metabolismo , Pulmón/patología , Pulmón/efectos de la radiación , Lesión Pulmonar/etiología , Lesión Pulmonar/prevención & control , Proteínas Proto-Oncogénicas c-sis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-sis/metabolismo , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Actinidia/químicaRESUMEN
By developing a filtering framework and a sector-level multi-regional input-output structural decomposition model, this study identifies key common emission sources, motivation sources, and inter-provincial emission flows of both GHGs and air pollutants and reveals the key driving forces of changes in different emissions from 2012 to 2017. Results show that key common emission sources are electricity sector, non-metallic mineral products, and smelting and processing of metals in Shandong and Hebei. However, key common motivation sources are the construction sectors in Guangdong, Henan, Jiangsu, Zhejiang, and Shandong. The key inflow regions include Guangdong and Zhejiang and key outflow regions include Jiangsu and Hebei. The emission reductions are attributed to the emission intensity effect of the construction sector; contrastingly, the emission increase is from the investment scale of the construction sector. Here, Jiangsu could be a key target for future emission reduction because of its high absolute emissions and low past reduction. The scale of investment in construction might be a significant factor in reducing emissions in Shandong and Guangdong. Henan and Zhejiang could concentrate on sound new building planning and resource recycling.
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Contaminantes Atmosféricos , Gases de Efecto Invernadero , Contaminantes Atmosféricos/análisis , ChinaRESUMEN
The recognition of pathogen effectors by their cognate nucleotide-binding leucine-rich repeat (NLR) receptors activates effector-triggered immunity (ETI) in plants. ETI is associated with correlated transcriptional and translational reprogramming and subsequent death of infected cells. Whether ETI-associated translation is actively regulated or passively driven by transcriptional dynamics remains unknown. In a genetic screen using a translational reporter, we identified CDC123, an ATP-grasp protein, as a key activator of ETI-associated translation and defense. During ETI, an increase in ATP concentration facilitates CDC123-mediated assembly of the eukaryotic translation initiation factor 2 (eIF2) complex. Because ATP is required for the activation of NLRs as well as the CDC123 function, we uncovered a possible mechanism by which the defense translatome is coordinately induced during NLR-mediated immunity. The conservation of the CDC123-mediated eIF2 assembly suggests its possible role in NLR-mediated immunity beyond plants.
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Factor 2 Eucariótico de Iniciación , Proteínas , Factor 2 Eucariótico de Iniciación/metabolismo , Plantas/metabolismo , Dominios Proteicos , Adenosina Trifosfato/metabolismo , Inmunidad de la Planta , Enfermedades de las Plantas , Proteínas NLR/metabolismoRESUMEN
The necessity of increasing the efficiency of organ preservation has encouraged researchers to explore the mechanisms underlying diabetes-related myocardial injuries. This study intended to evaluate the protective effects of oxymatrine (OMT) in myocardial injury caused by type 2 diabetes mellitus. A model of diabetic rats was established to simulate type 2 diabetes mellitus using an intraperitoneal injection of a single dose of 65 mg/kg streptozotocin with a high-fat and high-cholesterol diet, and diabetic rats were subsequently treated with OMT (60, 120 mg/kg) by gavage for 8 weeks. Thereafter, diabetic rats demonstrated notable decreases in left ventricular systolic pressure (LVSP), ±dp/dtmax, and in the activities of glutathione peroxidase, superoxide dismutase, and catalase. Moreover, we found notable increases in left ventricular end-diastolic pressure, fasting blood glucose, and malondialdehyde, as well as changes in cell apoptosis and decreased expression levels of Nrf2, HO-1, tyrosine protein kinase JAK (JAK), and signal transducer and transcription activator (STAT). Treatment with OMT alleviated all of the measured parameters. Collectively, these findings suggest that activation of the Nrf2/HO-1 and inhibition of the JAK/STAT signaling are involved in mediating the cardioprotective effects of OMT and also highlight the benefits of OMT in ameliorating myocardial injury in diabetic rats.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratas , Animales , Miocardio/metabolismo , Quinasas Janus/metabolismo , Transducción de Señal , Factor 2 Relacionado con NF-E2/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factores de Transcripción STAT/metabolismo , Factores de Transcripción STAT/farmacología , Factores de Transcripción STAT/uso terapéutico , Apoptosis , Estrés OxidativoRESUMEN
Plant defense responses under unfavorable conditions are often associated with reduced growth. However, the mechanisms underlying the growth-defense tradeoff remain to be fully elucidated, especially at the transcriptional level. Here, we revealed a Cys2/His2-type zinc finger transcription factor, namely, ZAT18, which played dual roles in plant immunity and growth by oppositely regulating the signaling of defense- and growth-related hormones. ZAT18 was first identified as a salicylic acid (SA)-inducible gene and was required for plant responses to SA in this study. In addition, we observed that ZAT18 enhanced the plant immunity with growth penalties that may have been achieved by activating SA signaling and repressing auxin signaling. Further transcriptome analysis of the zat18 mutant showed that the biological pathways of defense-related hormones, including SA, ethylene and abscisic acid, were repressed and that the biological pathways of auxin and cytokinin, which are growth-related hormones, were activated by abolishing the function of ZAT18. The ZAT18-mediated regulation of hormone signaling was further confirmed using qRT-PCR. Our results explored a mechanism by which plants handle defense and growth at the transcriptional level under stress conditions.
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Proteínas de Arabidopsis , Arabidopsis , Dedos de Zinc CYS2-HIS2 , Arabidopsis/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo , Proteínas de Arabidopsis/metabolismo , Ácido Salicílico/farmacología , Ácido Salicílico/metabolismo , Hormonas/metabolismo , Enfermedades de las Plantas/genéticaRESUMEN
Objective To observe the role of connective tissue growth factor (CTGF) and collagen synthesis in anti-pulmonary fibrosis (PF) by Kiwi fruit essence(unsaturated fatty acid of actinidia chinesis planch seed oil)in rats. Methods Sixty male SD rats were randomly divided into control group, model group, Kiwi fruit essence (60, 120, 240 mg/kg) treatment groups, and 5 mg/kg prednisone acetate group, with 10 animals in each group. Rats in control group were intratracheally administered with 9 g/L sodium chloride solution, and animals in other groups were intratracheally administered with bleomycin A5 to establish PF model. From the second day on, rats in the latter 4 groups were intragastrically treated with Kiwi fruit essence of 60, 120 and 240 mg/kg and prednisone acetate of 5 mg/kg, respectively. Rats in control and model groups were treated with 9 g/L sodium chloride solution once a day. All rats were sacrificed on day 28, and then pulmonary tissues were removed. The extent of PF lesions were evaluated using HE and Masson staining. The contents of hydroxyproline (HYP) were measured by a commercial kit. The mRNA expressions of CTGF and α-smooth muscle actin (α-SMA) in pulmonary tissues was detected by quantitative real-time PCR. The protein expressions of CTGF, α-SMA, collagen type 1 (Col1) and Col3 were measured by Western blotting. The protein levels of CTGF were analyzed using immunohistochemical staining. Results Compared with the model group, the alveolitis and PF extent in 60, 120, 240 mg/kg Kiwi fruit essence treatment groups as well as 5 mg/kg prednisone acetate group were significantly alleviated, and the content of HYP and the expression of CTGF, α-SMA, Col1 and Col3 decreased. The changes of above indicators were dose-dependent among the (60, 120, 240) mg/kg Kiwi fruit essence treatment groups. Moreover, the above indicators were found higher in (60, 120) mg/kg Kiwi fruit essence treatment groups than those in 5 mg/kg prednisone acetate group, which, however, showed no significantly difference between 240 mg/kg Kiwi fruit essence treatment group and 5 mg/kg prednisone acetate group. Conclusion Kiwi fruit essence down-regulates CTGF expression and decreases the levels of α-SMA, leading to inhibition of Col1 and Col3 synthesis and alleviation of PF.
Asunto(s)
Actinidia , Aceites Volátiles , Fibrosis Pulmonar , Ratas , Masculino , Animales , Actinidia/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Prednisona , Cloruro de Sodio , Ratas Sprague-Dawley , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/prevención & control , Fibrosis Pulmonar/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Ácidos Grasos Insaturados , Aceites de Plantas/farmacología , AcetatosRESUMEN
Viruses cause many severe diseases in both plants and animals, urging us to explore new antiviral strategies. In their natural reservoirs, viruses live and replicate while causing mild or no symptoms. Some animals, such as bats, are the predicted natural reservoir of multiple viruses, indicating that they possess broad-spectrum antiviral capabilities. Mechanisms of host defenses against viruses are generally studied independently in plants and animals. In this article, we speculate that some antiviral strategies of natural reservoirs are conserved between kingdoms. To verify this hypothesis, we created null mutants of 10-formyltetrahydrofolate synthetase (AtTHFS), an Arabidopsis thaliana homologue of methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (MTHFD1), which encodes a positive regulator of viral replication in bats. We found that disruption of AtTHFS enhanced plant resistance to three different types of plant viruses, including the tomato spotted wilt virus (TSWV), the cucumber mosaic virus (CMV) and the beet severe curly top virus (BSCTV). These results demonstrate a novel antiviral strategy for plant breeding. We further discuss the approaches used to identify and study natural reservoirs of plant viruses, especially those hosting many viruses, and highlight the possibility of discovering new antiviral strategies from them for plant molecular breeding and antiviral therapy.