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Seed deterioration during storage is a major problem in agricultural and forestry production and for germplasm conservation. Our previous studies have shown that a mitochondrial outer membrane protein VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) is involved in programmed cell death-like viability loss during the controlled deterioration treatment (CDT) of elm (Ulmus pumila L.) seeds, but its underlying mechanism remains unclear. In this study, we demonstrate that the oxidative modification of GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) is functioned in the gate regulation of VDAC during the CDT of elm seeds. Through biochemical and cytological methods and observations of transgenic material [Arabidopsis (Arabidopsis thaliana), Nicotiana benthamiana, and yeast (Saccharomyces cerevisiae)], we demonstrate that cysteine S-glutathionylated UpGAPDH1 interacts with UpVDAC3 during seed aging, which leads to a mitochondrial permeability transition and aggravation of cell death, as indicated by the leakage of the mitochondrial proapoptotic factor cytochrome c and the emergence of apoptotic nucleus. Physiological assays and inductively coupled plasma mass spectrometry analysis revealed that GAPDH glutathionylation is mediated by increased glutathione, which might be caused by increases in the concentrations of free metals, especially Zn. Introduction of the Zn-specific chelator TPEN [(N,N,N',N'-Tetrakis (2-pyridylmethyl)ethylenediamine)] significantly delayed seed aging. We conclude that glutathionylated UpGAPDH1 interacts with UpVDAC3 and serves as a proapoptotic protein for VDAC-gating regulation and cell death initiation during seed aging.
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Morte Celular , Glutationa , Sementes , Sementes/metabolismo , Glutationa/metabolismo , Canais de Ânion Dependentes de Voltagem/metabolismo , Canais de Ânion Dependentes de Voltagem/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Nicotiana/genética , Nicotiana/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Mitocôndrias/metabolismo , Saccharomyces cerevisiae/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/genética , Glicólise , Plantas Geneticamente Modificadas , Zinco/metabolismoRESUMO
Interleukin-6 (IL-6) is a cytokine generated by healthy constituents of the skin, but is also up-regulated by a wide range of skin lesions and inflammatory conditions to trigger cytopathy of skin cells. TRIM27 was identified to contribute to the functional effects of IL-6 on skin cells. However, the underlying mechanism was not clear. Lentivirus infection was used for gene overexpression or silencing. RT-PCR and Western blot were used to respectively assess mRNA and protein levels. Cell viability was assessed by CCK-8 assay. Extracellular flux analysis was used to assess the levels of oxygen consumption rate and extracellular acidification rate. Mouse back skin was treated with imiquimod to produce psoriasis-like inflammation in vivo. Histological assessment and immunohistochemistry staining were respectively applied to analyse lesioned mouse and human skin samples. IL-6-induced increased viability, glycolysis and inflammation in keratinocytes was inhibited both by a chemical methylation inhibitor and by METTL14 knockdown. Further investigation found that METTL14 induces m6A methylation of TRIM27, which is recognized by a m6A reader, IGF2BP2. Elevation of TRIM27 level and activation of IL-6/STAT3 signalling pathway were found in an in vivo psoriasis-like inflammation model, whereas inhibition m6A methylation strongly alleviated the inflammation. Finally, METTL14, TRIM27, STAT3, p-STAT3 and IL-6 expressions were all found to be increased in clinical skin samples of psoriatic patients. Our results unravelled METTL14/TRIM27/IGF2BP2 signalling axis in keratinocyte cytopathy, which plays a critical role in facilitating the activation of IL-6/STAT3 signalling pathway. Our findings should provide inspirations for the design of new therapeutics for skin inflammatory diseases including psoriasis.
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Adenina , Interleucina-6 , Metiltransferases , Psoríase , Animais , Humanos , Camundongos , Adenina/análogos & derivados , Proteínas de Ligação a DNA , Glicólise , Células HaCaT , Inflamação/patologia , Interleucina-6/farmacologia , Queratinócitos/patologia , Proteínas Nucleares , Psoríase/patologia , Proteínas de Ligação a RNA , Fatores de Transcrição , Proteínas com Motivo TripartidoRESUMO
The nitridation of noble metals-based catalysts to further enhance their hydrogen evolution reaction (HER) kinetics in neutral and alkaline conditions would be an effective strategy for developing high-performance wide pH HER catalysts. Herein, a facile molten urea method is employed to construct the nitrided Rh nanoclusters (RhxN) supported on N-doped carbon (RhxN-NC). The uniformly distributed RhxN clusters exhibited optimized water bonding and splitting effects, therefore resulting in excellent pH-universal HER performance. The optimized RhxN-NC catalyst only requires 8, 12, and 109 mV overpotentials to reach the current density of 10 mA cm-2 in 0.5 M H2SO4, 1.0 M KOH, and 1.0 M PBS electrolytes, respectively. The spectroscopic characterizations and theoretical calculation further confirm the vital role of Rh-N moieties in RhxN clusters in improving the transfer of electrons and facilitating the generation of H2. This work not only provides a suitable nitridation method for noble metal species in mild conditions but also makes a breakthrough in synthesizing noble metal nitrides-based electrocatalysts to achieve an exceptional wide-pH HER performance and other catalysis.
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Redox-active tetrathiafulvalene (TTF)-based covalent organic frameworks (COFs) exhibit distinctive electrochemical and photoelectrical properties, but their prevalent two-dimensional (2D) structure with densely packed TTF moieties limits the accessibility of redox center and constrains their potential applications. To overcome this challenge, an 8-connected TTF linker (TTF-8CHO) is designed as a new building block for the construction of three-dimensional (3D) COFs. This approach led to the successful synthesis of a 3D COF with the bcu topology, designated as TTF-8CHO-COF. In comparison to its 2D counterpart employing a 4-connected TTF linker, the 3D COF design enhances access to redox sites, facilitating controlled oxidation by I2 or Au3+ to tune physical properties. When irradiated with a 0.7 W cm-2 808 nm laser, the oxidized 3D COF samples ( I X - ${\mathrm{I}}_{\mathrm{X}}^{-}$ @TTF-8CHO-COF and Au NPs@TTF-8CHO-COF) demonstrated rapid temperature increases of 239.3 and 146.1 °C, respectively, which surpassed those of pristine 3D COF (65.6 °C) and the 2D COF counterpart (6.4 °C increment after I2 treatment). Furthermore, the oxidation of the 3D COF heightened its photoelectrical responsiveness under 808 nm laser irradiation. This augmentation in photothermal and photoelectrical response can be attributed to the higher concentration of TTF·+ radicals generated through the oxidation of well-exposed TTF moieties.
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BACKGROUND: Subarachnoid hemorrhage (SAH) represents a form of cerebrovascular event characterized by a notable mortality and morbidity rate. Fibroblast growth factor 21 (FGF21), a versatile hormone predominantly synthesized by the hepatic tissue, has emerged as a promising neuroprotective agent. Nevertheless, the precise impacts and underlying mechanisms of FGF21 in the context of SAH remain enigmatic. METHODS: To elucidate the role of FGF21 in inhibiting the microglial cGAS-STING pathway and providing protection against SAH-induced cerebral injury, a series of cellular and molecular techniques, including western blot analysis, real-time polymerase chain reaction, immunohistochemistry, RNA sequencing, and behavioral assays, were employed. RESULTS: Administration of recombinant fibroblast growth factor 21 (rFGF21) effectively mitigated neural apoptosis, improved cerebral edema, and attenuated neurological impairments post-SAH. Transcriptomic analysis revealed that SAH triggered the upregulation of numerous genes linked to innate immunity, particularly those involved in the type I interferon (IFN-I) pathway and microglial function, which were notably suppressed upon adjunctive rFGF21 treatment. Mechanistically, rFGF21 intervention facilitated mitophagy in an AMP-activated protein kinase (AMPK)-dependent manner, thereby preventing mitochondrial DNA (mtDNA) release into the cytoplasm and dampening the activation of the DNA-sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Conditional knockout of STING in microglia markedly ameliorated the inflammatory response and mitigated secondary brain injuries post-SAH. CONCLUSION: Our results present the initial evidence that FGF21 confers a protective effect against neuroinflammation-associated brain damage subsequent to SAH. Mechanistically, we have elucidated a novel pathway by which FGF21 exerts this neuroprotection through inhibition of the cGAS-STING signaling cascade.
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Fatores de Crescimento de Fibroblastos , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Mitofagia , Doenças Neuroinflamatórias , Nucleotidiltransferases , Transdução de Sinais , Hemorragia Subaracnóidea , Animais , Proteínas de Membrana/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/etiologia , Mitofagia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Nucleotidiltransferases/metabolismo , Masculino , Camundongos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Microglia/metabolismo , Microglia/patologia , Microglia/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondii infection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii-infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1ß and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii-infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii-infected cells reversed these effects. Collectively, these findings show that T. gondii induces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1-mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis.
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Inflamassomos , Toxoplasma , Camundongos , Animais , Humanos , Feminino , Gravidez , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Trofoblastos/metabolismo , Catepsina B/metabolismo , Catepsina B/farmacologia , Placenta/metabolismo , RNA Interferente Pequeno , Caspases/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas NLR/metabolismoRESUMO
Alternative splicing (AS) is an important regulatory mode at the post-transcriptional level, through which many flowering genes regulate floral transition by producing multiple transcripts, and splicing factors have essential roles in this process. Hydrogen sulphide (H2S) is a newly found gasotransmitter that has critical physiological roles in plants, and one of its potential modes of action is via persulfidation of target proteins at specific cysteine sites. Previously, it has been shown that both the splicing factor AtU2AF65a and H2S are involved in the regulation of plant flowering. This study found that, in Arabidopsis, the promoting effect of H2S on flowering was abolished in atu2af65a-4 mutants. Transcriptome analyses showed that when AtU2AF65a contained mutations, the regulatory function of H2S during the AS of many flowering genes (including SPA1, LUH, LUG and MAF3) was inhibited. The persulfidation assay showed that AtU2AF65a can be persulfidated by H2S, and the RNA immunoprecipitation data indicated that H2S could alter the binding affinity of AtU2AF65a to the precursor messenger RNA of the above-mentioned flowering genes. Overall, our results suggest that H2S may regulate the AS of flowering-related genes through persulfidation of splicing factor AtU2AF65a and thus lead to early flowering in plants.
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Proteínas de Arabidopsis , Arabidopsis , Sulfeto de Hidrogênio , Arabidopsis/genética , Arabidopsis/metabolismo , Fatores de Processamento de RNA/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sulfeto de Hidrogênio/metabolismo , Processamento Alternativo/genética , Precursores de RNA/genética , Regulação da Expressão Gênica de Plantas , Flores/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.
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Aterosclerose , Inflamação , Lipoproteína(a) , Humanos , Lipoproteína(a)/metabolismo , Lipoproteína(a)/sangue , Aterosclerose/metabolismo , Aterosclerose/imunologia , Inflamação/metabolismo , Animais , Fatores de RiscoRESUMO
Bacterial ClpB is an ATP-dependent disaggregate that belongs to the Hsp100/Clp family and facilitates bacterial survival under hostile environmental conditions. Streptococcus agalactiae, which is regarded as the major bacterial pathogen of farmed Nile tilapia (Oreochromis niloticus), is known to cause high mortality and large economic losses. Here, we report a ClpB homologue of S. agalactiae and explore its functionality. S. agalactiae with a clpB deletion mutant (∆clpB) exhibited defective tolerance against heat and acidic stress, without affecting growth or morphology under optimal conditions. Moreover, the ΔclpB mutant exhibited reduced intracellular survival in RAW264.7 cells, diminished adherence to the brain cells of tilapia, increased sensitivity to leukocytes from the head kidney of tilapia and whole blood killing, and reduced mortality and bacterial loads in a tilapia infection assay. Furthermore, the reduced virulence of the ∆clpB mutant was investigated by transcriptome analysis, which revealed that deletion of clpB altered the expression levels of multiple genes that contribute to the stress response as well as certain metabolic pathways. Collectively, our findings demonstrated that ClpB, a molecular chaperone, plays critical roles in heat and acid stress resistance and virulence in S. agalactiae. This finding provides an enhanced understanding of the functionality of this ClpB homologue in gram-positive bacteria and the survival strategy of S. agalactiae against immune clearance during infection.
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Doenças dos Peixes , Chaperonas Moleculares , Infecções Estreptocócicas , Streptococcus agalactiae , Estresse Fisiológico , Animais , Camundongos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ciclídeos , Doenças dos Peixes/microbiologia , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Células RAW 264.7 , Infecções Estreptocócicas/veterinária , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/fisiologia , Streptococcus agalactiae/patogenicidade , Streptococcus agalactiae/genética , VirulênciaRESUMO
BACKGROUND: Patient education contributes to improve public awareness of Helicobacter pylori. Large language models (LLMs) offer opportunities to revolutionize patient education transformatively. This study aimed to assess the quality of patient educational materials (PEMs) generated by LLMs and compared with physician sourced. MATERIALS AND METHODS: Unified instruction about composing a PEM about H. pylori at a sixth-grade reading level in both English and Chinese were given to physician and five LLMs (Bing Copilot, Claude 3 Opus, Gemini Pro, ChatGPT-4, and ERNIE Bot 4.0). The assessments of the completeness and comprehensibility of the Chinese PEMs were conducted by five gastroenterologists and 50 patients according to three-point Likert scale. Gastroenterologists were asked to evaluate both English and Chinese PEMs and determine the accuracy and safety. The accuracy was assessed by six-point Likert scale. The minimum acceptable scores were 4, 2, and 2 for accuracy, completeness, and comprehensibility, respectively. The Flesch-Kincaid and Simple Measure of Gobbledygook scoring systems were employed as readability assessment tools. RESULTS: Accuracy and comprehensibility were acceptable for English PEMs of all sources, while completence was not satisfactory. Physician-sourced PEM had the highest accuracy mean score of 5.60 and LLM-generated English PEMs ranged from 4.00 to 5.40. The completeness score was comparable between physician-sourced PEM and LLM-generated PEMs in English. Chinese PEMs from LLMs proned to have lower score in accuracy and completeness assessment than English PEMs. The mean score for completeness of five LLM-generated Chinese PEMs was 1.82-2.70 in patients' perspective, which was higher than gastroenterologists' assessment. Comprehensibility was satisfactory for all PEMs. No PEM met the recommended sixth-grade reading level. CONCLUSION: LLMs have potential in assisting patient education. The accuracy and comprehensibility of LLM-generated PEMs were acceptable, but further optimization on improving completeness and accounting for a variety of linguistic contexts are essential for enhancing the feasibility.
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Inteligência Artificial , Infecções por Helicobacter , Educação de Pacientes como Assunto , Humanos , Educação de Pacientes como Assunto/métodos , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Masculino , Feminino , Pessoa de Meia-Idade , AdultoRESUMO
Multivalent-ion batteries have garnered significant attention due to their high energy density, low cost, and superior safety. Calcium-ion batteries (CIBs) are regarded as the next-generation energy storage systems for their abundant natural resources and bivalent characteristics. However, the absence of high-performance anode materials poses a significant obstacle to the progress of battery technology. Two-dimensional (2D) Dirac materials have excellent conductivity and abundant active sites, rendering them promising candidates as anode materials. A novel 2D Dirac material known as "graphene+" has been theoretically reported, exhibiting prominent properties including good stability, exceptional ductility, and remarkable electronic conductivity. By using first-principles calculations, we systematically investigate the performance of graphene+ as an anode material for CIBs. Graphene+ exhibits an ultra-high theoretical capacity (1487.7 mA h g-1), a small diffusion barrier (0.21 eV), and a low average open-circuit voltage (0.51 V). Furthermore, we investigate the impact of the electrolyte solvation on the performance of Ca-ion adsorption and migration. Upon contact with electrolyte solvents, graphene+ exhibits strong adsorption strength and rapid migration of Ca-ions on its surface. These results demonstrate the promising potential of graphene+ as a high-performance anode material for CIBs.
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Herein, we aimed to evaluate the efficacy and safety of camrelizumab combined with docetaxel and carboplatin as a neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma (OSCC). Fifty-one patients with OSCC, treated from July 2020 to October 2022, were analyzed. Of them, 41 patients underwent surgery 4-8 weeks after undergoing two cycles of camrelizumab (200 mg IV Q3W) combined with docetaxel (75 mg/m2 IV Q3W) and carboplatin (area under the curve = 5-6 IV Q3W). The primary endpoint was the pathological complete response rate. All 51 patients (100%) experienced treatment-related grades 1-2 adverse events, and 2 patients (3.9%) experienced grade 4 events (including elevated alanine transaminase/aspartate transferase levels and Guillain-Barre syndrome). Fifty patients were evaluated for the treatment efficacy. Of them, 13 achieved complete response, and the objective response rate was 74%. Only 41 patients underwent surgical treatment. The pathological complete response rate was 17.1%, the major pathological response rate was 63.4%, and the R0 resection rate was 100%. Approximately 22% of the patients had tumor regression grades 0. Eight patients (19.5%) developed surgery-related complications. The median follow-up time was 18 months (range: 3-29 months). Four patients experienced disease progression, while four died. The median disease-free survival and overall survival were not reached. Camrelizumab combined with docetaxel and carboplatin is an effective and safe neoadjuvant treatment for locally advanced OSCC. This regimen may afford a potential strategy to treat patients with locally advanced OSCC.
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Anticorpos Monoclonais Humanizados , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Docetaxel/uso terapêutico , Carboplatina , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/patologiaRESUMO
Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.
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Artemisininas , Neoplasias Pulmonares , Mitocôndrias , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Piroptose , Neoplasias Pulmonares/tratamento farmacológico , Artemisininas/farmacologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Piroptose/efeitos dos fármacos , Camundongos , Animais , Linhagem Celular Tumoral , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , DNA Mitocondrial , Células A549 , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
Maize is an important crop used for food, feed, and fuel. Abiotic stress is an important factor affecting maize yield. The EPF/EPFL gene family encodes class-specific secretory proteins that play an important role in the response to abiotic stress in plants. In order to explore and utilize the EPF/EPFL family in maize, the family members were systematically identified, and their chromosomal localization, physicochemical properties, cis-acting element prediction in promoters, phylogenetic tree construction, and expression pattern analysis were carried out using bioinformatics techniques. A total of 18 ZmEPF/EPFL proteins were identified in maize, which are mostly alkaline and a small portion acidic. Subcellular localization results showed that ZmEPF6, ZmEPF12, and ZmEPFL2 are localized in the nucleus and cytoplasm. Analysis of cis-acting elements revealed that members of the ZmEPF/EPFL family contain regulatory elements such as light response, anoxic, low temperature, and hormone response regulatory elements. RT-qPCR results showed that these family members are indeed responding to cold stress and hormone treatments. These results of this study provide a theoretical basis for improving the abiotic stress resistance of maize in future research.
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Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Zea mays , Zea mays/genética , Zea mays/metabolismo , Zea mays/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Regiões Promotoras GenéticasRESUMO
Ridge-furrow with full ï¬lm mulching has been widely applied to increase crop yield and water productivity on the Loess Plateau, but it may stimulate carbon (C) mineralization. How to integrate other technological benefits based on this technology for long-term maintenance of high yield and soil fertility is a pressing issue. With the local farmers' practice (FP) as a control, three integrated soil-crop system management (ISSM) practices integrating fertilizer rates, fertilizer types and planting densities (ISSM-N1, ISSM-N2 and ISSM-MN) were established to improve maize yield and soil quality. Compared with the FP, the maize yield increased by 13.34%, 21.83% and 30.24%, and the soil quality index (SQI) increased by 9.66%, 14.91% and 38.38% for ISSM-N1, ISSM-N2 and ISSM-MN, respectively. However, ISSM-N1 did not significantly increase yield, and ISSM-N2 increased residual soil nitrate and decreased nitrogen (N) partial factor productivity significantly. Compared to the FP, ISSM practices increased soil organic carbon (SOC), labile organic C fractions (LOCFs) and potassium permanganate organic C fractions in the topsoil to varying degrees, but only ISSM-MN reached significant levels for most C fractions. The sensitivity index indicated very easily oxidizable C (24.6%), easily oxidizable C (24.7%), hot-water extractable C (30.8%), labile organic C (24.7%) and particulate organic C (57.3%) were more sensitive than SOC (22.7%). ISSM-MN sequestered significantly higher C than the other treatments. The results of the relative importance analysis and the structural equation model indicated that LOCFs were the direct contributors to yield, while recalcitrant C (CO) was the indirect contributor, revealing the underlying mechanism that CO decomposed to replenish LOCFs and the total N pool with the water soluble C pool as the transit station. Overall, ISSM-MN is the most promising strategy to improve crop yield and soil fertility in the long term on the Loess Plateau.
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Agricultura , Solo , Solo/química , Agricultura/métodos , Carbono/análise , Fertilizantes/análise , Zea mays , Nitrogênio/análise , Água/análise , ChinaRESUMO
Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF-ß3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF-ß3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross-sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF-ß3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF-ß3, pro-inflammatory and anti-inflammatory markers. A subset of patients were administered topical TGF-ß3 in order to evaluate its therapeutic effects. The expression pattern of TGF-ß3 was found to be stage-dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF-ß3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF-ß3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF-ß3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF-ß3, which functions as an anti-inflammatory and pro-inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.
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Aterosclerose , Fator de Crescimento Transformador beta3 , Humanos , Anti-Inflamatórios , Estudos Transversais , Inflamação , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta3/uso terapêutico , Fator de Crescimento Transformador beta3/farmacologia , Úlcera , CicatrizaçãoRESUMO
Objective: To explore factors influencing the acceptance of allergen immunotherapy (AIT) for the treatment of allergic respiratory diseases by pediatric patients and their families. Methods: A total of 406 children (210 males and 196 females) attending the pediatric outpatient clinics and wards of the Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2020 to April 2022. Those who met the criteria for the AIT treatment, were included in the survey. An online 20-item questionnaire was developed. Data on patient's general characteristics, allergic disease status, family history of allergies, general family information, parental knowledge of allergic diseases, and whether the AIT treatment was recommended by a physician, were collected. The patients were divided into two groups according to their willingness to receive AIT: a reluctant or neutral group (n = 182), and a willing group (n = 224). A univariate analysis of the willingness to undergo AIT was done to detect parameters that significantly differed between the groups, and the identified factors were used as independent variables in the multifactorial logistic regression analysis. Results: The severity of allergic disease, presence of drug allergy, occurrence of severe allergic reactions, mother's education, distance from home to the hospital, parental knowledge of allergic diseases, and whether the doctor recommended AIT were all statistically different between the groups (p < 0.05). Multifactorial logistic regression analysis showed that the degree of allergic rhinitis (AR), or asthma (AS), parental knowledge of allergic diseases, and doctor's recommendation of AIT were the factors that influenced the willingness of pediatric patients to receive AIT. Conclusions: The severity of AR and AS, parental knowledge of allergic diseases, and doctor's recommendation influenced the willingness of pediatric patients to receive AIT.
RESUMO
Total triterpenoids from the fruits of Chaenomeles speciosa(TCS) are active components in the prevention and treatment of gastric mucosal damage, which have potential anti-aging effects. However, it is still unclear whether TCS can improve gastric aging, especially its molecular mechanism against gastric aging. On this basis, this study explored the effect and mechanism of TCS on senescent GES-1 cells induced by D-galactose(D-gal) to provide scientific data for the clinical use of TCS to prevent gastric aging. GES-1 cells cultured in vitro and those transfected with overexpression GLS1(GLS1-OE) plasmid of glutaminase 1(GLS1) were induced to aging by D-gal, and then TCS and or GLS1 inhibitor bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide(BPTES) were given. Cell survival rate, positive rate of ß-galactosidase(SA-ß-gal) staining, mitochondrial membrane potential(MMP), and apoptosis were investigated. GLS1 activity, levels of glutamine(Gln), glutamate(Glu), α-ketoglutarate(α-KG), urea, and ammonia in supernatant and cells were detected by enzyme-linked immunosorbent assay(ELISA) and colorimetric methods. The mRNA and protein expressions of GLS1 and the related genes of the mitochondrial apoptosis signaling pathway were measured by real-time fluorescence quantitative PCR and Western blot. The results manifested that compared with the D-gal model group and GLS1-OE D-gal model group, TCS significantly decreased the SA-ß-gal staining positive cell rate and MMP of D-gal-induced senescent GES-1 cells and GLS1-OE senescent GES-1 cells, inhibited the survival of senescent cells, and promoted their apoptosis(P<0.01). It decreased the activity of GLS1 and the content of Gln, Glu, α-KG, urea, and ammonia in supernatant and cell(P<0.01), reduced the concentration of cytochrome C(Cyto C) in mitochondria and the mRNA and protein expressions of GLS1 and proliferating nuclear antigen in cells(P<0.01). The mRNA expression of Bcl-2 and Bcl-xl, the protein expression of pro-caspase-9 and pro-caspase-3, and the ratio of Bcl-2/Bax and Bcl-xl/Bad in cells were decreased(P<0.01). Cyto C concentration in the cytoplasm, the mRNA expressions of Bax, Bad, apoptosis protease activating factor 1(Apaf-1), and protein expressions of cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 were increased(P<0.01). The aforementioned results indicate that TCS can counteract the senescent GES-1 cells induced by D-gal, and its mechanism may be closely related to suppressing the Gln/GLS1/α-KG metabolic axis, activating the mitochondrial apoptosis pathway, and thereby accelerating the apoptosis of the senescent cells and eliminating senescent cells.
Assuntos
Apoptose , Frutas , Galactose , Glutaminase , Glutamina , Mitocôndrias , Transdução de Sinais , Triterpenos , Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Triterpenos/farmacologia , Triterpenos/química , Humanos , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Frutas/química , Glutamina/farmacologia , Glutamina/metabolismo , Glutaminase/metabolismo , Glutaminase/genética , Senescência Celular/efeitos dos fármacos , Ácidos Cetoglutáricos/farmacologia , Ácidos Cetoglutáricos/metabolismoRESUMO
With the sharp rise of antibiotic-resistant pathogens worldwide, it is of enormous importance to create new strategies for combating pathogenic bacteria. Here, we create an iron oxide-based spiky artificial peroxidase (POD) with V-O-Fe pair sites (V-Fe2 O3 ) for combating methicillin-resistant Staphylococcus aureus (MRSA). The experimental studies and theoretical calculations demonstrate that the V-Fe2 O3 can achieve the localized "capture and killing" bifunction from the spiky morphology and massive reactive oxygen species (ROS) production. The V-Fe2 O3 can reach nearly 100 % bacterial inhibition over a long period by efficiently oxidizing the lipid membrane. Our wound disinfection results identify that the V-Fe2 O3 can not only efficiently eliminate MRSA and their biofilm but also accelerate wound recovery without causing noticeable inflammation and toxicity. This work offers essential insights into the critical roles of V-O-Fe pair sites and localized "capture and killing" in biocatalytic disinfection and provides a promising pathway for the de novo design of efficient artificial peroxidases.
Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Peroxidases , BiofilmesRESUMO
Tuning the interfacial structure of metal oxide substrates is an essential strategy to induce electronic structure reconstruction of supported catalysts, which is of great importance in optimizing their catalytic activities. Herein, vanadium oxides-supported Ir catalysts (Ir-V2O3, Ir-VO2, and Ir-V2O5) with different interfacial bonding environments (Ir-V, Ir-Obri, and Ir-O, respectively) were investigated for hydrogen evolution reaction (HER). The regulating mechanism of the influence of different interfacial bonding environments on HER activity was investigated by both experimental results and computational evidence. Benefiting from the unique advantages of interfacial Ir-V direct metal bonds in Ir-V2O3, including enhanced electron transfer and electron donation ability, an optimized HER performance can be obtained with lowest overpotentials of 16 and 26â mV at 10â mA cm-2, high mass activities of 11.24 and 6.66â A mg-1, and turnover frequency values of 11.20 and 6.63â s-1, in acidic and alkaline conditions respectively. Furthermore, the assembled Ir-V2O3||RuO2 anion exchange membrane (AEM) electrolyzer requires only 1.92â V to achieve a high current density of 500â mA cm-2 and realizes long-term stability. This study provides essential insights into the regulating mechanism of interfacial chemical bonding in electrocatalysts and offers a new pathway to design noble metal catalysts for different applications.