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Pancreatic fat is associated with obesity and type 2 diabetes mellitus (T2DM); however, the relationship between different types of pancreatic fat and diabetes status remains unclear. Therefore, we aimed to determine the potential of different types of pancreatic fat accumulation as a risk factor for T2DM in overweight or obese patients. In total, 104 overweight or obese patients were recruited from January 2020 to December 2022. The patients were divided into three groups: normal glucose tolerance (NGT), impaired fasting glucose or glucose tolerance (IFG/IGT), and T2DM. mDixon magnetic resonance imaging (MRI) was used to detect pancreatic fat in all three groups of patients. The pancreatic head fat (PHF), body fat (PBF), and tail fat (PTF) in the IFG/IGT group were 21, 20, and 31% more than those in the NGT group, respectively. PHF, PBF, and PTF were positively associated with glucose metabolic dysfunction markers in the NGT group, and inter-lobular fat volume (IFV) was positively associated with these markers in the IFG/IGT group. The areas under the receiver operating characteristic curves for PHF, PBF, and PTF (used to evaluate their diagnostic potential for glucose metabolic dysfunction) were 0.73, 0.73, and 0.78, respectively, while those for total pancreatic volume (TPV), pancreatic parenchymal volume, IFV, and IFV/TPV were 0.67, 0.67, 0.66, and 0.66, respectively. These results indicate that intra-lobular pancreatic fat, including PHF, PTF, and PBF, may be a potential independent risk factor for the development of T2DM. Additionally, IFV exacerbates glucose metabolic dysfunction. Intra-lobular pancreatic fat indices were better than IFV for the diagnosis of glucose metabolic dysfunction.
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Connective tissue attaches to bone across an insertion with spatial gradients in components, microstructure, and biomechanics. Due to regional stress concentrations between two mechanically dissimilar materials, the insertion is vulnerable to mechanical damage during joint movements and difficult to repair completely, which remains a significant clinical challenge. Despite interface stress concentrations, the native insertion physiologically functions as the effective load-transfer device between soft tissue and bone. This review summarizes tendon, ligament, and meniscus insertions cross-sectionally, which is novel in this field. Herein, the similarities and differences between the three kinds of insertions in terms of components, microstructure, and biomechanics are compared in great detail. This review begins with describing the basic components existing in the four zones (original soft tissue, uncalcified fibrocartilage, calcified fibrocartilage, and bone) of each kind of insertion, respectively. It then discusses the microstructure constructed from collagen, glycosaminoglycans (GAGs), minerals and others, which provides key support for the biomechanical properties and affects its physiological functions. Finally, the review continues by describing variations in mechanical properties at the millimeter, micrometer, and nanometer scale, which minimize stress concentrations and control stretch at the insertion. In summary, investigating the contrasts between the three has enlightening significance for future directions of repair strategies of insertion diseases and for bioinspired approaches to effective soft-hard interfaces and other tough and robust materials in medicine and engineering.
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Tendões , Humanos , Fenômenos Biomecânicos/fisiologia , Tendões/fisiologia , Tendões/anatomia & histologia , Animais , Osso e Ossos/fisiologia , Ligamentos/fisiologia , Fibrocartilagem/fisiologia , Fibrocartilagem/química , Fibrocartilagem/metabolismo , Colágeno/química , Colágeno/metabolismo , Estresse MecânicoRESUMO
BACKGROUND: There is a clear demand for innovative therapeutics for bipolar disorder (BD). METHODS: We integrated the largest BD genome-wide association study (GWAS) dataset (NCase = 41 917, NControl = 371 549) with protein quantitative trait loci from brain, cerebrospinal fluid, and plasma. Using a range of integrative analyses, including Mendelian randomization (MR), Steiger filter analysis, Bayesian colocalization, and phenome-wide MR analysis, we prioritized novel drug targets for BD. Additionally, we incorporated data from the UK Biobank (NCase = 1064, NControl = 365 476) and the FinnGen study (NCase = 7006, NControl = 329 192) for robust biological validation. RESULTS: Through MR analysis, we found that in the brain, downregulation of DNM3, MCTP1, ABCB8 and elevation of DFNA5 and PDF were risk factors for BD. In cerebrospinal fluid, increased BD risk was associated with increased levels of FRZB, AGRP, and IL36A and decreased CTSF and LRP8. Plasma analysis revealed that decreased LMAN2L, CX3CL1, PI3, NCAM1, and TIMP4 correlated with increased BD risk, but ITIH1 did not. All these proteins passed Steiger filtering, and Bayesian colocalization confirmed that 12 proteins were colocalized with BD. Phenome-wide MR analysis revealed no significant side effects for potential drug targets, except for LRP8. External validation further underscored the concordance between the primary and validation cohorts, confirming MCTP1, DNM3, PDF, CTSF, AGRP, FRZB, LMAN2L, NCAM1, and TIMP4 are intriguing targets for BD. CONCLUSIONS: Our study identified druggable proteins for BD, including MCTP1, DNM3, and PDF in the brain; CTSF, AGRP, and FRZB in cerebrospinal fluid; and LMAN2L, NCAM1, and TIMP4 in plasma, delineating promising avenues to development of novel therapies.
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Purpose: The levels of human epididymis protein 4 (HE4) is associated not only with the prognosis of patients with acute heart failure (AHF), but also with chronic kidney disease (CKD). Our study aims to understand the prediction value of HE4 on prognosis in patients with AHF combined with CKD. Patients and Methods: This study prospectively enrolled patients diagnosed with AHF combined with CKD at the Department of Cardiology of Hunan Provincial People's Hospital from March 2019 to December 2022. Serum levels of HE4 were measured using a chemiluminescence microparticle immunoassay. The endpoint events included heart failure readmission and cardiovascular death. Results: A total of 130 patients with AHF combined with CKD were included in the stud. The median age is 73 years (interquartile range: 65-79 years). Among the patients, 94 experienced the endpoint events. The multivariable Cox analysis reveals that LnHE4 (HR=2.280, 95% CI 1.300-3.998, P = 0.004) and age (HR=1.024, 95% CI 1.003-1.045, P = 0.025) are independent predictors of the endpoint events. The Kaplan-Meier survival curve demonstrates that patients with HE4 levels>276.15 pmol/L has a significantly higher incidence of endpoint events compared to those with HE4 levels≤276.15 pmol/L (Log rank test: χ2=19.689, P < 0.001). After adjusting for age and gender, the HR is 2.520 (95% CI: 1.626-3.906, P < 0.001). Conclusion: HE4 is an independent predictor of heart failure readmission and cardiovascular death in patients with AHF combined with CKD.
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Monochlorodifluoromethane (HCFC-22) has been identified as a significant contributor to the depletion of the Earth's ozone layer, garnering considerable attention within the scientific community. Consequently, the investigation of Freon degradation has become a central focus of current research efforts. In this study, we opted to employ catalytic hydrolysis as it offers numerous advantages for the degradation of HCFC-22. Specifically, we prepared ZnO/ZrO2 catalysts with hexahedral rod-like structures through citric acid complexation. We examined the impact of various preparation conditions (such as the molar ratio of ZnO to ZrO2, calcination temperature, and calcination time) as well as catalytic hydrolysis conditions (including the amount of catalyst, total flow rate, and catalytic hydrolysis temperature) on the hydrolysis rate of HCFC-22. Characterization of the catalysts was performed using techniques such as XRD, SEM, EDS, TG-DTG, FTIR, N2 adsorption-desorption, CO2-TPD, and NH3-TPD. Our experimental findings revealed the optimal preparation conditions: a catalytic hydrolysis temperature of 100 °C, a molar ratio of ZnO to ZrO2 of 0.7, a water bath temperature of 90 °C, a roasting temperature of 400 °C, and a roasting time of 4 h. At a catalytic hydrolysis temperature of 100 °C, the hydrolysis rate of HCFC-22 reached 99.81%, with the main hydrolyzed products being HCl, HF, and CO2.
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Clorofluorcarbonetos de Metano , Óxidos , Óxido de Zinco , Temperatura , Óxidos/química , Oxirredução , Hidrólise , Dióxido de CarbonoRESUMO
BACKGROUND: Bupivacaine, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Crocin has been widely reported as a potential neuroprotective agent in neural injury models. OBJECTIVE: The aim of this study was to investigate the role and regulatory mechanism of crocin underlying bupivacaine-induced neurotoxicity. METHOD: Human neuroblastoma SH-SY5Y cells were treated with bupivacaine and/or crocin for 24 h, followed by detecting cell viability using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effect of crocin or bupivacaine on SH-SY5Y cell proliferation was measured by Ki67 immunofluorescence assay. The levels of apoptosis-related proteins and the markers in the PI3K/Akt signaling pathway were examined using western blot analysis. The activities of caspase 3, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were tested using respective commercial assay kits. Flow cytometry analysis was executed for detecting SH-SY5Y cell apoptosis. RESULT: Crocin attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells. Meanwhile, crocin inhibited SH-SY5Y cell apoptosis induced by bupivacaine via repressing the activity of caspase-3, reducing Bax expression, and elevating Bcl-2 expression. Moreover, crocin mitigated oxidative stress in SH-SY5Y cells by increasing the content of CAT, SOD, GSH-Px and reducing the content of MDA. Additionally, crocin protected against bupivacaine-induced dephosphorylation of Akt and GSK-3ß. The protective effects of crocin against bupivacaine-induced neurotoxicity in SH-SY5Y cells were counteracted by the Akt inhibitor. CONCLUSION: These results suggested that crocin may exert a neuroprotective function by promoting cell proliferation and suppressing apoptosis and oxidative stress in SH-SY5Y cells. Thus, crocin might become a promising drug for the treatment of bupivacaine-induced neurotoxicity.
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Carotenoides , Neuroblastoma , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Bupivacaína/toxicidade , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/farmacologia , Linhagem Celular Tumoral , Transdução de Sinais , Superóxido Dismutase/metabolismoRESUMO
Inactive elemental doping is commonly used to improve the structural stability of high-voltage layered transition-metal oxide cathodes. However, the one-step co-doping strategy usually results in small grain size since the low diffusivity ions such as Ti4+ will be concentrated on grain boundaries, which hinders the grain growth. In order to synthesize large single-crystal layered oxide cathodes, considering the different diffusivities of different dopant ions, we propose a simple two-step multi-element co-doping strategy to fabricate core-shell structured LiCoO2 (CS-LCO). In the current work, the high-diffusivity Al3+/Mg2+ ions occupy the core of single-crystal grain while the low diffusivity Ti4+ ions enrich the shell layer. The Ti4+-enriched shell layer (~ 12 nm) with Co/Ti substitution and stronger Ti-O bond gives rise to less oxygen ligand holes. In-situ XRD demonstrates the constrained contraction of c-axis lattice parameter and mitigated structural distortion. Under a high upper cut-off voltage of 4.6 V, the single-crystal CS-LCO maintains a reversible capacity of 159.8 mAh g-1 with a good retention of ~ 89% after 300 cycles, and reaches a high specific capacity of 163.8 mAh g-1 at 5C. The proposed strategy can be extended to other pairs of low- (Zr4+, Ta5+, and W6+, etc.) and high-diffusivity cations (Zn2+, Ni2+, and Fe3+, etc.) for rational design of advanced layered oxide core-shell structured cathodes for lithium-ion batteries.
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Tactile sensing is required for electronic skin and intelligent robots to function properly. However, the dielectric layer's poor structural compressibility in conventional pressure sensors results in a limited pressure sensing range and low sensitivity. To solve this issue, a flexible pressure sensor with a crocodile-inspired fillable gradient structure is provided. The fillable gradient structure and grooves in the pressure sensor accommodate the deformed microstructure that permits the enhancement of the media layer compressibility via COMSOL finite element simulation and optimization. The pressure sensor exhibits a high sensitivity of up to 0.97 k Pa-1 (0-4 kPa), a wide pressure detection range (7 Pa-380 kPa), and outstanding repeatability. The sensor can detect Morse code, robotic grabbing, and human motion monitoring. As a result, flexible sensors with a bionic fillable gradient structure pave the way for wearable devices and offer a novel method for achieving highly precise tactile perception.
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Dispositivos Eletrônicos Vestíveis , Humanos , Pressão , Biônica/métodosRESUMO
OBJECTIVE: Unfavorable outcomes in patients with subarachnoid hemorrhage (SAH) are mainly attributed to early brain injury (EBI). Reduction of neuronal death can improve the prognosis in SAH patients. Autophagy and apoptosis are critical players in neuronal death. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins and ellagic acid. Here, we detected the role of UA in EBI post-SAH. METHODS: We established an animal model of SAH in rats by endovascular perforation, with administration of UA, 3-methyladenine (3-MA) and Compound C. SAH grading, neurological function, brain water content, western blotting analysis of levels of proteins related to apoptosis, autophagy and pathways, blood-brain barrier (BBB) integrity, TUNEL staining, and immunofluorescence staining of LC3 were evaluated at 24h after SAH. RESULTS: SAH induction led to neurological dysfunctions, BBB disruption, and cerebral edema at 24h post-SAH in rats, which were relieved by UA. Additionally, cortical neuronal apoptosis in SAH rats was also attenuated by UA. Moreover, UA restored autophagy level in SAH rats. Mechanistically, UA activated the AMPK/mTOR pathway. Furthermore, inhibition of autophagy and AMPK limited UA-mediated protection against EBI post-SAH CONCLUSION: UA alleviates neurological deficits, BBB permeability, and cerebral edema by inhibiting cortical neuronal apoptosis through regulating the AMPK/mTOR pathway-dependent autophagy in rats following SAH.
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Edema Encefálico , Lesões Encefálicas , Hemorragia Subaracnóidea , Humanos , Ratos , Animais , Hemorragia Subaracnóidea/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Ratos Sprague-Dawley , Lesões Encefálicas/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Autofagia/fisiologiaRESUMO
Rechargeable batteries are of great significance for alleviating the growing energy crisis by providing efficient and sustainable energy storage solutions. However, the multiple issues associated with the diverse components in a battery system as well as the interphase problems greatly hinder their applications. Proteins and their subunits, peptides, and amino acids, are versatile biomolecules. Functional groups in different amino acids endow these biomolecules with unique properties including self-assembly, ion-conducting, antioxidation, great affinity to exterior species, etc. Besides, protein and its subunit materials can not only work in solid forms but also in liquid forms when dissolved in solutions, making them more versatile to realize materials engineering via diverse approaches. In this review, it is aimed to offer a comprehensive understanding of the properties of proteins and their subunits, and research progress of using these versatile biomolecules to address the engineering issues of various rechargeable batteries, including alkali-ion batteries, lithium-sulfur batteries, metal-air batteries, and flow batteries. The state-of-the-art advances in electrode, electrolyte, separator, binder, catalyst, interphase modification, as well as recycling of rechargeable batteries are involved, and the impacts of biomolecules on electrochemical properties are particularly emphasized. Finally, perspectives on this interesting field are also provided.
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Aminoácidos , Antioxidantes , Fontes de Energia Elétrica , Eletrodos , EngenhariaRESUMO
Ce0.8Zr0.2O2 catalysts were prepared via the co-precipitation method under different pH conditions. The catalysts were characterized via TEM, XRD, XPS, BET, Raman, and FTIR. The oxidation performance of formaldehyde was tested. Precipitation pH affects the physicochemical properties and performance of the Ce0.8Zr0.2O2 catalyst. By controlling the precipitation pH at 10.5, the Ce0.8Zr0.2O2 catalyst with the largest specific surface area, the smallest grain size with the best formaldehyde removal rate (98.85%), abundant oxygen vacancies, and the best oxidation performance were obtained. Meanwhile, the kinetic parameters of the catalyst were experimentally investigated and the calculated activation energy was 12.6 kJ/mol and the number of reaction steps was 1.4 and 1.2.
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Guaranteeing satisfactory catalytic behavior while ensuring high metal utilization has become the problem that needs to be addressed when designing noble-metal-based catalysts for electrochemical reactions. Here, well-dispersed ruthenium (Ru) based clusters with adjacent Ru single atoms (SAs) on layered sodium cobalt oxide (Ru/NC) are demonstrated as a superb electrocatalyst for alkaline HER. The Ru/NC catalyst demonstrates an activity increase by a factor of two relative to the commercial Pt/C. Operando characterizations in conjunction with density functional theory (DFT) simulations uncover the origin of the superior activity and establish a structure-performance relationship, that is, under HER condition, the real active species are Ru SAs and metallic Ru clusters supported on the NC substrate. The excellent alkaline HER activity of the Ru/NC catalyst can be understood by a spatially decoupled water dissociation and hydrogen desorption mechanism, where the NC substrate accelerates the water dissociation rate, and the generated H intermediates would then migrate to the Ru SAs or clusters and recombine to have H2 evolution. More importantly, comparing the two forms of Ru sites, it is the Ru cluster that dominates the HER activity.
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In this study, we demonstrate inverted PTB7:PC71BM polymer solar cells (PSCs) featuring a solution-processed s-MoO3 hole transport layer (HTL) that can, after thermal aging at 85 °C, retain their initial power conversion efficiency (PCE) for at least 2200 h. The T80 lifetimes of the PSCs incorporating the novel s-MoO3 HTL were up to ten times greater than those currently reported for PTB7- or low-band-gap polymer:PCBM PSCs, the result of the inhibition of burn-in losses and long-term degradation under various heat-equivalent testing conditions. We used X-ray photoelectron spectroscopy (XPS) to study devices containing thermally deposited t-MoO3 and s-MoO3 HTLs and obtain a mechanistic understanding of how the robust HTL is formed and how it prevented the PSCs from undergoing thermal degradation. Heat tests revealed that the mechanisms of thermal inter-diffusion and interaction of various elements within active layer/HTL/Ag electrodes controlled by the s-MoO3 HTL were dramatically different from those controlled by the t-MoO3 HTL. The new prevention mechanism revealed here can provide the conceptual strategy for designing the buffer layer in the future. The PCEs of PSCs featuring s-MoO3 HTLs, measured in damp-heat (65 °C/65% RH; 85 °C per air) and light soaking tests, confirmed their excellent stability. Such solution-processed MoO3 HTLs appear to have great potential as replacements for commonly used t-MoO3 HTLs.
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Background: Molecular categorization of lung cancer in medical care is becoming increasingly important on a regular basis. One of the molecular classifications of NSCLC (early-stage NSCLC) supports that tumors of different biological varieties differ in terms of their genomes and clinical characteristics. Methods: Based on published immune cell signatures and early-stage NSCLC gene expression data including cancer genome maps, we used consensus cluster analysis to identify immune molecular subtypes associated with early-stage NSCLC expression subtypes. These subtypes were correlated with early-stage NSCLC expression subtypes. Next, applying a wide range of statistical techniques, we evaluated the link between molecular subtypes and clinical features, immunological microenvironment, and immunotherapy reactivity. Molecular subtypes were defined as a classification of cancerous cells. Results: Multiple RNAseq cross-platform datasets of immune genes were used to identify two molecular subtypes (C1 and C2) of NSCLC, with C1 showing a more favorable prognosis than C2. The results were validated on the CSE datasets. In terms of clinical characteristics, C2 subtype samples with a worse prognosis showed a more advanced tumor stage and higher mortality. C2 showed immuno-infiltrative characteristics but had depletion of T-cells. Biological functions such as EMT were enriched on C2. A low TIDE score in C1 indicated that C1 samples could benefit from taking immunotherapy. C2 were more susceptible to standard chemotherapeutic treatments such paclitaxel, cisplatin, sorafenib, crizotinib, and erlotinib. Conclusion: According to our findings, early-stage NSCLC patients may benefit from receiving treatment with immune checkpoint blockade therapy.
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In this work, a novel co-precipitation coupled solvothermal procedure is proposed to prepare a SmMnOx catalyst (SmMnOx-CP + ST) with a reed flower-like structure for the selective catalytic reduction of NOx by NH3 (NH3-SCR). Over 90% NOx conversion and N2 selectivity was achieved at a low temperature range (25-200 °C), and 96% NOx conversion was achieved in the presence of 100 ppm SO2 at 75 °C. While the NH3-SCR of the SmMnOx catalysts prepared by co-precipitation (SmMnOx-CP) and solvothermal (SmMnOx-ST) methods performed much poorer than the SmMnOx-CP + ST catalyst. All catalysts were characterized by XRD, BET, SEM, XPS, H2-TPR, NH3-TPD, NOx-TPD, and FT-IR. The results revealed that the superior performance of the SmMnOx-CP + ST is due to the unique reed flower-like structure morphology, which endows the SmMnOx-CP + ST with the largest surface area, the strongest synergistic reaction of Sm and Mn, abundant surface oxygen species and surface active sites, and significantly enhances the redox ability. Furthermore, the amorphous reed flower-like structure showed strong short-range ordered interaction between the active components and weaken the formation of sulfates species. In addition, the highest content of Mn4+ and Mn3++Mn4+ greatly promotes the redox cycles of Sm2+âMn4+ and Sm2+âMn3+, and suppresses the production of sulfate species in the presence of SO2.
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Amônia , Oxigênio , Amônia/química , Catálise , Oxirredução , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfatos , TemperaturaRESUMO
The ecological environment of the hilly and gully area of the Loess Plateau in northern Shaanxi is fragile and the soil fertility is low. As a result, the yield and quality of Pear-jujube which constitute one of the dominant economic forests in this region, have been severely restricted. At present, the scientific application of fertilizer is important for comprehensively improving the quality of fruit trees, and for devising the optimal management of fruit trees. In particular, the application of organic fertilizers plays an important role in improving soil and improving fruit quality. In this experiment, a field study was conducted to understand the effects of different organic fertilizer applications on physiological growth, photosynthetic characteristics, reproductive growth and nutritional quality of Pear-jujube in the Loess Plateau. The results showed that organic fertilizer significantly promoted the physiological growth of Pear-jujube. The Pear-jujube bearing branch and leaf area under the soybean cake fertilizer (SC) treatment were 20.17 cm and 1246 mm2/leaf, respectively, which are increased by 34% and 44.46% compared with the no fertilizer treatment, which was a control check (CK). The total chlorophyll content of fertilization treatment was significantly higher than that of CK (P < 0.05). The maximum of chlorophyll content was 10.90 mg/dm2 under the biogas fertilizer (BM). The content of LAI was in the order BM > conventional fertilizer (CF) > sheep manure (SM) > SC > CK. The changing trend of gap fraction was opposite to that of LAI, and the density of light was consistent with that of LAI. The density of light BM was the largest, reached 38.06 mol/(m2 d), which was 15.13% higher than that of CK. Organic fertilizer significantly improved the net photosynthetic rate (Pn) and water use efficiency (WUEp) of Pear-jujube. The WUEp of SC was up to 3.30%. Organic fertilizer significantly promoted the reproductive growth and improved the nutritional quality of Pear-jujube. The yield under the SC was 19,177 kg/hm2, increased by 138.5% compared with that of CK. The fruit water content (FWC), total soluble solids (TSS), solid-acid ratio (TSS/TA), Vc and total flavonoids content improved, and the maxima of FWC, TSS, TSS/TA, Vc and total flavonoids content under the SC treatment were 86.30%, 18.48%, 40.17, 46.18 mg/kg and 14.35 mg/kg, respectively, which were significantly different from those of CK (P < 0.05). Organic fertilization effectively promotes the growth, development, yield and fruit quality of Pear-jujube in the Loess Plateau and the effect of the soybean cake fertilizer is the most significant.
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Pyrus , Ziziphus , Agricultura/métodos , Animais , China , Clorofila , Fertilizantes , Flavonoides , Florestas , Frutas , Nitrogênio , Ovinos , Solo , ÁguaRESUMO
Altered glucose metabolism is an important characteristic of cancer cells, which is referred to as Warburg effect or aerobic glycolysis. Ewing sarcoma (EWS) is a highly malignant tumor that occurs in children and adolescents. However, the functions of aerobic glycolysis in EWS remain to be elucidated. The present study identified a transcription factor, E2F transcription factor 1 (E2F1), as a new regulator of cancer the aerobic glycolysis and progression in EWS. The present study showed that E2F1 modulated aerobic glycolysis in EWS cells by effecting glucose uptake, lactate production and ATP generation. Altered E2F1 expression increased or decreased cell viability and invasion in EWS. Mechanistically, the results demonstrated that E2F1 may promote the Warburg effect and cancer progression in EWS via upregulating enolase 2 expression. Generally, these findings indicated that E2F1 involvement in the progression of EWS and could serve as a clinical therapeutic target in EWS.
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Fator de Transcrição E2F1 , Fosfopiruvato Hidratase , Sarcoma de Ewing , Adolescente , Linhagem Celular Tumoral , Criança , Fator de Transcrição E2F1/genética , Fator de Transcrição E2F1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Sarcoma de Ewing/patologia , Fatores de Transcrição/metabolismoRESUMO
In the planar flow casting (PFC) process, the cooling rate significantly affects the structure and properties of a cast ribbon. The influence of the thermal conductivity of the cooling wheel substrate on cooling rate was simulated by a numerical method, and it is shown that a higher thermal conductivity of the cooling wheel substrate leads to a higher cooling rate in the PFC process. Two copper-beryllium (Cu-2Be) rings with thermal conductivities of 175.3 W/m·K and 206.5 W/m·K were manufactured and installed onto a wheel core as the substrate of the cooling wheel. The effects of cooling rate on the soft magnetic properties of Fe-Si-B amorphous ribbons were investigated by pragmatic ribbon casting. The results show that the increment in the thermal conductivity of the cooling wheel substrate from 175.3 W/m·K to 206.5 W/m·K lowered the coercive force of amorphous ribbon from 2.48 A/m to 1.92 A/m and reduced the core losses at 1.4 T and 50 Hz by up to 22.1%.
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Fusarium head blight (FHB), which is primarily caused by Fusarium graminearum, is a widespread and devastating disease of wheat. In the absence of resistant varieties, the control of FHB relies heavily on the application of fungicides, and the new generation SDHI fungicide, pydiflumetofen, has recently been registered in China for the control of FHB in wheat. The current study explored three genetically stable, highly resistant laboratory mutants (S2-4-2R, S27-3R, and S28-2R, with EC50 values of 25.10, 28.57, and 19.22 µg/mL, respectively) to investigate the potential risks associated with pydiflumetofen resistance. Although the mycelial growth of the mutants differed little compared to their parental isolates, the study found that the resistant mutants exhibited significantly reduced (p < 0.05) levels of sporulation and pathogenicity, which suggests a significant fitness cost associated with pydiflumetofen resistance in F. graminearum. Sequence analysis of the Sdh target protein identified numerous amino acid substitutions in the predicted sequences of the four subunits: FgSdhA, FgSdhB, FgSdhC, and FgSdhD. Indeed, the mutants were found to have a series of substitution in multiple subunits such that all three exhibited five identical changes, including Y182F in the FgSdhA subunit; H53Q, C90S, and A94V in FgSdhB; and S31F in FgSdhC. In addition, gene expression analysis revealed that all of the FgSdh genes had significantly altered expression (p < 0.05), particularly FgSdhA and FgdhC, which exhibited remarkably low levels of expression. However, the study found no evidence of cross-resistance between pydiflumetofen and tebuconazole, fludioxonil, prochloraz, fluazinam, carbendazim, pyraclostrobin, or difenoconazole, which indicates that these fungicides, either in rotation or combination with pydiflumetofen, could mitigate the risk of resistance emerging and provide ongoing control of FHB to ensure high and stable wheat yields.