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Despite substantial evidence suggesting that hydrogen gas (H2) can enhance osmotic tolerance in plants, the conventional supply method of hydrogen-rich water (HRW) poses challenges for large-scale agricultural applications. Recently, magnesium hydride (MgH2), a hydrogen storage material in industry, has been reported to yield beneficial effects in plants. This study aimed to investigate the effects and underlying mechanisms of MgH2 in plants under osmotic stress. Mung bean seedlings were cultured under control conditions or with 20% polyethylene glycol (PEG)-6000, with or without MgH2 addition (0.01 g L-1). Under our experimental conditions, the MgH2 solution maintained a higher H2 content and longer retention time than HRW. Importantly, PEG-stimulated endogenous H2 production was further triggered by MgH2 application. Further results revealed that MgH2 significantly alleviated the inhibition of seedling growth and reduced oxidative damage induced by osmotic stress. Pharmacological evidence suggests the MgH2-reestablished redox homeostasis was associated with activated antioxidant systems, particularly the ascorbate-glutathione cycle. The above observations were further supported by the enhanced activities and gene transcriptional levels of ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase. Overall, this study demonstrates the importance of MgH2 in mitigating osmotic stress in mung bean seedlings, providing novel insights into the potential agricultural applications of hydrogen storage materials.
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Avermectin (AVM) is a broad-spectrum antibiotic from the macrolide class, extensively employed in fisheries and aquaculture. Nevertheless, its indiscriminate utilisation has resulted in a substantial accumulation of remnants in the aquatic ecosystem, potentially inflicting significant harm to the cardiovascular system of aquatic species. Ferulic acid (FA) is a naturally occurring compound in wheat grain husks. It possesses potent anti-inflammatory and antioxidant properties, which can help reduce cardiovascular damage. Additionally, its affordability makes it an excellent option for aquaculture usage as a feed additive. This article explored the potential of FA as a feed additive to protect against AVM-induced heart damage in carp. We subjected carp to AVM for 30 days and provided them with a diet of 400 mg/kg of FA. FA substantially reduced the pathogenic damage to heart tissue caused by AVM, as shown through hematoxylin-eosin staining. The biochemical analysis revealed that FA markedly enhanced the activity of antioxidant enzymes catalase (CAT), glutathione (GSH), and total antioxidant capacity (T-AOC) while reducing the malondialdehyde (MDA) content. Furthermore, qPCR analysis demonstrated a substantial increase in the mRNA levels of transforming growth factor-ß1 (tgf-ß1) and interleukin-10 (il-10) simultaneously, significantly reducing the expression levels of interleukin-10 (il-6), interleukin-1ß (il-1ß), tumor necrosis factor-α (tnf-α) and inductible nitric oxide synthase (inos). Through the mitochondrial apoptotic route, FA reduced AVM-induced cell death in carp heart cells by upregulating bcl-2 while downregulating the mRNA expression levels of bax, fas, caspase8 and caspase9. In summary, FA alleviated cardiac injury by inhibiting AVM-induced oxidative stress, inflammatory response, and apoptosis in carp heart tissue.
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Background: Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor in locally advanced colon cancer (LACC) and improve the R0 resection rate. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC remain poorly understood. This study aimed to compare the effects and safety of NACRT and NACT on R0 resection and survival rates in initially unresectable LACC. Methods: This was an open-label, single-center, randomized, controlled trial conducted between May 11, 2019 and May 30, 2022. Forty-five patients with initially unresectable LACC were randomly allocated to the NACT (control, n = 20) or NACRT (research, n = 25) group. The NACT group received XELOX (oxaliplatin 100-130 mg/m2, qd, d1, every 3 weeks; and capecitabine 1000 mg/m2, bid, d1-d14, every 3 weeks) for 4 cycles. The NACRT group, in addition to chemotherapy, received daily irradiation (GTV 45-50 Gy/25 F; CTV 42.5-45 Gy/25 F). Surgery was scheduled 6-12 weeks after neoadjuvant treatment and adjuvant chemotherapy was administered if the patient developed resectable LACC. The primary endpoint was the 5-year overall survival (OS) rate. The secondary outcomes included the 3-year progression-free survival (PFS) and R0 resection rates. This study was registered with ClinicalTrials.gov (NCT03970694). Findings: In short-term outcome analysis, NACRT significantly improved the R0 resection rate (80% for NACRT vs. 20% for NACT, P < 0.001). The NACRT and NACT groups had a 3-year OS of 87.6% and 75% (P = 0.037) and a 3-year PFS of 76% and 45% (P = 0.049), respectively. The 5-year OS was not reached. In the NACRT group, no local or regional recurrence was observed in patients who underwent surgery during the follow-up period, compared to two patients in the NACT group. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. The most commonly observed grade 3-4 AE was myelosuppression (39% for NACRT and 47% for NACT, P = 0.609). No grade 5 AEs were observed between the two groups. Interpretation: Adding radiation to NACT increased the R0 resection rate, prolonged the PFS, and potentially improved OS in selected patients with initially unresectable LACC. The trial findings indicate that this approach is safe, feasible, and may confer a survival benefit. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373213 to Dr Gao, 82202952 to Dr Wang); and the Natural Science Foundation of Guangdong Province (2023A1515010290 to Dr Chang). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.
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PM2.5 bound mercury (PBM2.5) in the atmosphere is a major component of total mercury, which is a pollutant of global concern and a potent neurotoxicant when converted to methylmercury. Despite its importance, comprehensive macroanalyses of PBM2.5 on large scales are still lacking. To explore the driving factors, spatiotemporal pollution distribution, and associated health risks, we compiled a comprehensive dataset consisting of PBM2.5 concentrations and spatiotemporal information across China from 2000 to 2023 that was collected from the published scientific literature with valid data. By incorporating corresponding multidimensional predicting variables, the best-fitted random forest model was applied to predict PBM2.5 concentrations with a high spatial resolution of 0.25° × 0.25°, and the health risk assessment model was used for subsequent health risk assessment. Our results indicated that population density and PM2.5 emissions from power generation were the main contributors to PBM2.5 concentrations. In 2020, the pollution was primarily concentrated in northern, central, and eastern China, with the highest annual average concentration of 815.91 pg/m3 in Shanghai. Beijing experienced the most significant seasonal increase, with PBM2.5 concentrations rising by 146.92 % from summer to winter. Nationally, the annual average PBM2.5 pollution decreased extensively and markedly from 2015 to 2020. The non-carcinogenic risk of PBM2.5 alone was negligible in 2020, with HQ values generally <0.02 in winter. This study may provide an important assessment of the effectiveness of China's measures against mercury pollution and offer valuable insights for future prevention and control of PBM2.5 pollution.
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Background: Accumulating evidence suggests that an imbalance of gut microbiota is commonly observed in patients with rheumatoid arthritis (RA). However, it remains unclear whether gut microbiota dysbiosis is a cause or consequence of RA, and the mechanisms by which gut dysbiosis contributes to RA have not been fully understood. This study aimed to investigate the causal relationship between gut microbiota and metabolites with RA. Methods: A two-sample Mendelian randomization analysis was performed to estimate the causality of gut microbiota and metabolites on RA. A genome-wide association study (GWAS) of 211 gut microbiota and 217 metabolites was used as the exposure, whereas RA was treated as the outcome. Inverse variance weighted (IVW) was regarded as the primary approach for calculating causal estimates. MR Egger method, Weighted median method, Simple mode method, and weighted mode method were used for sensitive analysis. Metabolic pathway analysis was performed via the web-based Metaconflict 5.0. Additionally, an animal study was undertaken to evaluate the results inferred by Mendelian randomization. Result: This study indicated that six gut microbiota taxa (RuminococcaceaeUCG013, Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, Clostridia, and Veillonellaceae) were estimated to exert a positive impact on RA. Conversely, seven gut microbiota taxa (Oxalobacter, Cyanobacteria, RuminococcaceaeUCG002, LachnospiraceaeUCG010, Christensenellaceae, Oxalobacteraceae, Anaerostipes) were estimated to exert a negative impact on RA. Three metabolites, namely indole-3-propionate (IPA), glycine and sphingomyelin (SM 16:1), were found to be linked to lower RA risk, while five metabolites (argininosuccinate, CE 20_4, TAG 58_8, PC 40_6, and LPC 20_4) were linked to higher RA risk. Additionally, four metabolic pathways were identified by metabolic pathway analysis. The collagen-induced arthritis (CIA) rats exhibited a higher relative abundance of Class_Clostridia and a lower abundance of Genus_Lachnospiraceae (p < 0.05) than the healthy controls. Conclusion: This study identified causal associations between specific gut microbiota, metabolites, and RA. These findings support the significant role of gut microbiota and metabolites in RA pathogenesis.
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Powdery mildew and stripe rust are major diseases on wheat worldwide that cause significant reductions in wheat production. The ribosomal silencing factor (RsfS) has been proven to regulate protein biosynthesis by inhibiting the translation process in bacterial response to stress. However, the role of RsfS in plant resistance to biotic stresses remains unclear. In this study, the RsfS homolog, TaRsfS was isolated from wheat. Overexpression of TaRsfS (TaRsfS-OE) reduces wheat resistance to powdery mildew and stripe rust and TaRsfS knockout (TaRsfS-KO) increases wheat resistance to both diseases without affecting key agronomic traits. The interaction protein of TaRsfS, 12-oxo-phytodienoic acid reductase 1 (TaOPR1), a key enzyme in the biosynthesis of jasmonic acid (JA), was screened and identified. Knocking-down and overexpression of TaOPR1 indicated that TaOPR1 positively regulates wheat resistance to powdery mildew and stripe rust. TaRsfS may regulate TaOPR1 at upstream, bind to the enzyme activity pocket of TaOPR1 and affect TaOPR1 enzyme activity, resulting in a reduced JA biosynthesis and wheat susceptible to powdery mildew and stripe rust. Collectively, TaRsfS is a susceptibility gene and negatively regulates wheat resistance to powdery mildew and stripe rust, and it has good potential for improving wheat resistance by genetic modifications.
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The dormancy of cancer stem cells is a major factor leading to drug resistance and a high rate of late recurrence and mortality in estrogen receptor-positive (ER+) breast cancer. Previously, we demonstrated that a stiffer matrix induces tumor cell dormancy and drug resistance, whereas a softened matrix promotes tumor cells to exhibit a stem cell state with high proliferation and migration. In this study, we present a comprehensive analysis of the proteome and phosphoproteome in response to gradient changes in matrix stiffness, elucidating the mechanisms behind cell dormancy-induced drug resistance. Overall, we found that antiapoptotic and membrane transport processes may be involved in the mechanical force-induced dormancy resistance of ER+ breast cancer cells. Our research provides new insights from a holistic proteomic and phosphoproteomic perspective, underscoring the significant role of mechanical forces stemming from the stiffness of the surrounding extracellular matrix as a critical regulatory factor in the tumor microenvironment.
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Neoplasias da Mama , Matriz Extracelular , Células-Tronco Neoplásicas , Fosfoproteínas , Proteômica , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Matriz Extracelular/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Feminino , Proteômica/métodos , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Proteoma/análise , Proteoma/metabolismo , Microambiente Tumoral , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Células MCF-7RESUMO
Improving battery health and safety motivates the synergy of a powerful duo: physics and machine learning. Through seamless integration of these disciplines, the efficacy of mathematical battery models can be significantly enhanced. This paper delves into the challenges and potentials of managing battery health and safety, highlighting the transformative impact of integrating physics and machine learning to address those challenges. Based on our systematic review in this context, we outline several future directions and perspectives, offering a comprehensive exploration of efficient and reliable approaches. Our analysis emphasizes that the integration of physics and machine learning stands as a disruptive innovation in the development of emerging battery health and safety management technologies.
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Not required for Clinical Vignette.
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Hormônio do Crescimento Humano , Micrognatismo , Humanos , Hormônio do Crescimento Humano/uso terapêutico , Masculino , Micrognatismo/tratamento farmacológico , Deformidades Congênitas da Mão/tratamento farmacológico , Deformidades Congênitas da Mão/genética , Resultado do Tratamento , Anormalidades Múltiplas/tratamento farmacológico , Anormalidades Múltiplas/genética , Deficiência Intelectual/tratamento farmacológico , Pescoço/anormalidades , Face/anormalidades , Proteínas Recombinantes/uso terapêuticoRESUMO
Previous studies on BSC2 have shown that it enhances yeast cell resistance to AmB via antioxidation and induces multidrug resistance by contributing to biofilm formation. Herein, we found that BSC2 overexpression could reverse the sensitivity of pmp3Δ to AmB and help the tested strains restore the intracellular sodium/potassium balance under exposure to AmB. Meanwhile, overexpression of the chitin gene CHS2 could simulate BSC2 to reverse the sensitivity of pmp3Δ and nha1Δ to high salt or AmB. However, BSC2 overexpression in flo11Δ failed to induce AmB resistance, form biofilms, and affect cell wall biogenesis, while CHS2 overexpression compensated the resistance of flo11Δ to AmB. Additionally, BSC2 levels were positively correlated with maintaining cell membrane integrity under exposure to AmB, CAS, or a combination of both. BSC2 overexpression in nha1Δ exhibited a similar function of CHS2, which can compensate for the sensitivity of the mutant to high salt. Altogether, the results demonstrate for the first time that BSC2 may promote ion equilibrium by strengthening cell walls and inhibiting membrane damage in a FLO path-dependent manner, thus enhancing the resistance of yeast cells to AmB. This study also reveals the possible mechanism of antifungal drugs CAS and AmB combined to inhibit fungi.
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Fungal diseases not only reduce the yield of edible mushrooms but also pose potential threats to the preservation and quality of harvested mushrooms. Cobweb disease, caused primarily by fungal pathogens from the Hypocreaceae family, is one of the most significant diseases affecting edible mushrooms. Deciphering the genomes of these pathogens will help unravel the molecular basis of their evolution and identify genes responsible for pathogenicity. Here, we present high-quality genome sequences of three cobweb disease fungi: Hypomyces aurantius Cb-Fv, Cladobotryum mycophilum CB-Ab, and Cladobotryum protrusum CB-Mi, isolated from Flammulina velutipes, Agaricus bisporus, and Morchella importuna, respectively. The assembled genomes of H. aurantius, C. mycophilum, and C. protrusum are 33.19 Mb, 39.83 Mb, and 38.10 Mb, respectively. This is the first report of the genome of H. aurantius. Phylogenetic analysis revealed that cobweb disease pathogens are closely related and diverged approximately 17.51 million years ago. CAZymes (mainly chitinases, glucan endo-1,3-beta-glucosidases, and secondary metabolite synthases), proteases, KP3 killer proteins, lipases, and hydrophobins were found to be conserved and strongly associated with pathogenicity, virulence, and adaptation in the three cobweb pathogens. This study provides insights into the genome structure, genome organization, and pathogenicity of these three cobweb disease fungi, which will be a valuable resource for comparative genomics studies of cobweb pathogens and will help control this disease, thereby enhancing mushroom quality.
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Central poststroke pain (CPSP) is a medical complication that arises poststroke and significantly impacts the quality of life and social functioning of affected individuals. Despite ongoing research, the exact pathomechanisms of CPSP remain unclear, and practical treatments are still unavailable. Our review aims to systematically analyse current clinical and preclinical studies on CPSP, which is critical for identifying gaps in knowledge and guiding the development of effective therapies. The review will clarify the clinical characteristics, evaluation scales and contemporary therapeutic approaches for CPSP based on clinical investigations. It will particularly emphasise the CPSP model initiated by stroke, shedding light on its underlying mechanisms and evaluating treatments validated in preclinical studies. Furthermore, the review will not only highlight methodological limitations in animal trials but also offer specific recommendations to researchers to improve the quality of future investigations and guide the development of effective therapies. This review is expected to provide valuable insights into the current knowledge regarding CPSP and can serve as a guide for future research and clinical practice. The review will contribute to the scientific understanding of CPSP and help develop effective clinical interventions.
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Oxygen vacancies (VO) in metal oxide semiconductors play an important role in improving gas-sensing performance of chemiresistive gas sensors. Nonetheless, there is still a lack of clear understanding of the inherent mechanism of the influence of oxygen vacancies on gas sensing due to generally focusing on the concentration of VO. Herein, oxygen vacancies were rationally modulated in WO3 nanoflower structures via an annealing process, resulting in a transformation of VO from neutral (VO0) to a doubly ionized (VO2+) state. Density functional theory (DFT) calculations indicate that VO2+ is significantly more efficient than VO0 for NO2 detection in competition with atmospheric O2. Benefiting from a high concentration of VO2+, the WO3-450 (WO3 annealed at 450 °C) sensor exhibits excellent sensing performance with an ultrahigh sensitivity (3674.1 to 5 ppm NO2), superior selectivity, and long-term stability (one month). Furthermore, the sensor with the wide range of concentration detection not only can detect NO2 gas with parts per million (ppm) but also can detect NO2 with parts per billion (ppb) level concentration, with a high sensibility reaching 2.8 to 25 ppb NO2 and over 100 to 100 ppb NO2. This study elucidates the oxygen vacancy mediated sensing mechanism toward NO2 and provides an effective strategy for the rational design of gas sensors with high sensing performance.
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Establishment of a new method for improved shoot tip cryopreservation is crucial to facilitate the long-term preservation of plant germplasm as well as the use of cryotherapy for pathogen eradication. The present study reported a vitrification (V) cryo-foil method for shoot tip cryopreservation and virus eradication in apple. Shoot tip regrowth levels after cryopreservation were comparable among V cryo-foil (53 %), V cryo-plate (46 %) and conventional droplet vitrification (Dr-vi, 48 %). The V cryo-foil is more efficient to perform than Dr-vi as more shoot tips can be cryopreserved by one person. In the histological study applying an image-overlaying strategy, shoot tips cryopreserved by V cryo-foil showed a higher survival chance in the youngest leaf primordia than in the apical dome. When V cryo-foil was tested for virus eradication, fifty-five percent (55 %) of cryo-derived shoots were free of the apple stem pitting virus (ASPV), while none and less than 10 % were free of the apple stem grooving virus (ASGV) and the apple chlorotic leaf spot virus (ACLSV), respectively. Thus, these two viruses were efficiently preserved by V cryo-foil cryopreservation. Noticeably, although the shoot regrowth level was reduced to 27 %, a higher frequency (81 %) of ASPV eradication was achieved when a reduced duration of cryoprotectant exposure was applied in V cryo-foil, supporting the use of insufficient cryoprotection for improved virus eradication.
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Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.
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Anticorpos Monoclonais Humanizados , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/terapia , Neoplasias Retais/imunologia , Neoplasias Retais/patologia , Neoplasias Retais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Terapia Neoadjuvante/métodos , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Reparo de Erro de Pareamento de DNA , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Quimiorradioterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The proposal of discrete memristors has made memristive chaotic maps based on them an important research topic. In this study, a new two-dimensional chaotic map without fixed points is constructed, and numerical simulation results display its rich dynamical behaviors. The analysis reveals the map's center inversion symmetry and Lyapunov exponent controller. The map exhibits complex dynamical behaviors, including memristor initial-boosting and single-parameter-offset boosting. Embedding the absolute value function within the memristor results in the emergence of localized boosting-free regions. Moreover, a class of multicavity transients is captured that greatly enhances the system's complexity. Ultimately, this map is implemented on the STM32 platform, demonstrating its practical applicability in potential practical application scenarios.
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Wildfires generate abundant smoke primarily composed of fine-mode aerosols. However, accurately measuring the fine-mode aerosol optical depth (fAOD) is highly uncertain in most existing satellite-based aerosol products. Deep learning offers promise for inferring fAOD, but little has been done using multiangle satellite data. We developed an innovative angle-dependent deep-learning model (ADLM) that accounts for angular diversity in dual-angle observations. The model captures aerosol properties observed from dual angles in the contiguous United States and explores the potential of Greenhouse gases Observing Satellite-2's (GOSAT-2) measurements to retrieve fAOD at a 460 m spatial resolution. The ADLM demonstrates a strong performance through rigorous validation against ground-based data, revealing small biases. By comparison, the official fAOD product from the Moderate Resolution Imaging Spectroradiometer (MODIS), the Visible Infrared Imaging Radiometer Suite (VIIRS), and the Multiangle Imaging Spectroradiometer (MISR) during wildfire events is underestimated by more than 40% over western USA. This leads to significant differences in estimates of aerosol radiative forcing (ARF) from wildfires. The ADLM shows more than 20% stronger ARF than the MODIS, VIIRS, and MISR estimates, highlighting a greater impact of wildfire fAOD on Earth's energy balance.
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Aerossóis , Incêndios Florestais , Estados Unidos , Imagens de Satélites , Monitoramento AmbientalRESUMO
Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks.
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Depsipeptídeos , Hepatócitos , Metabolismo dos Lipídeos , Depsipeptídeos/toxicidade , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Simulação de Acoplamento Molecular , Micotoxinas/toxicidade , Micotoxinas/metabolismo , Sobrevivência Celular/efeitos dos fármacosRESUMO
The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.
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Maintenance of intracellular ion balance, especially Na+ and K+, plays an important role in plant responses to salt stress. Vessels in xylem are responsible for long-distance ion transport in vascular plants. Knowledge on the salt stress response in woody plants in limited. In this study, we identified miR319a as an important regulator in respond to salt stress in poplar. miR319a overexpression transgenic poplar showed a salt-tolerant phenotype, and cytological observation showed reduced cambium cell layers, wider xylem, increased number and lumen area of vessels and fibers, and thinner cell wall thickness in the transgenics. The miR319a-MIMIC plants, meanwhile, had opposite phenotypes, with narrower xylem, reduced number and lumen area of vessels and fibers cells, and increased wall thickness. In addition, overexpression of miR319a driven by the vessel-specific promoter significantly improved the salt tolerance compared with the fiber-specific promoter. The expression levels of PagHKT1;2 and PagSKOR1-b, which encoded high-affinity K+ and Na+ transporters for Na+ efflux and K+ influx, respectively, were positively correlated with the vessel number and lumen area. These results suggest that miR319 not only promotes ion transport rates by increasing vessel number and lumen area and reducing cell wall thickness, but also regulates the concentrations of Na+ and K+ in the xylem by up-regulating PagHKT1;2 and PagSKOR1-b. We demonstrate that miR319 may coordinate the response of poplar to salt stress through both mechanisms, enriching our understanding of the synergistic effects of the secondary xylem structure and long-distance ion transport balance in the salt tolerance of poplar.