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Rechargeable hydrogen gas batteries, driven by hydrogen evolution and oxidation reactions (HER/HOR), are emerging grid-scale energy storage technologies owing to their low cost and superb cycle life. However, compared with aqueous electrolytes, the HER/HOR activities in nonaqueous electrolytes have rarely been studied. Here, for the first time, we develop a nonaqueous proton electrolyte (NAPE) for a high-performance hydrogen gas-proton battery for all-climate energy storage applications. The advanced nonaqueous hydrogen gas-proton battery (NAHPB) assembled with a representative V2(PO4)3 cathode and H2 anode in a NAPE exhibits a high discharge capacity of 165 mAh g-1 at 1 C at room temperature. It also efficiently operates under all-climate conditions (from -30 to +70 °C) with an excellent electrochemical performance. Our findings offer a new direction for designing nonaqueous proton batteries in a wide temperature range.
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BACKGROUND: Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). RESULTS: Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. CONCLUSION: This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars.
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Brassica napus , Congelación , Proteínas de Plantas , Brassica napus/genética , Brassica napus/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Familia de Multigenes , Genoma de Planta , Respuesta al Choque por Frío/genéticaRESUMEN
PURPOSE: For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. PATIENTS AND METHODS: The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. RESULTS: A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. CONCLUSION: There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.
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Quimioradioterapia , Radioterapia Adyuvante , Neoplasias del Cuello Uterino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/terapia , Humanos , Adulto , Estudios Retrospectivos , Estadificación de Neoplasias , Histerectomía , Escisión del Ganglio Linfático , Dosis de Radiación , Resultado del Tratamiento , Tasa de Supervivencia , Persona de Mediana Edad , AncianoRESUMEN
Health risks of microplastic exposure have drawn growing global concerns due to the widespread distribution of microplastics in the environment. However, more evidence is needed to understand the exposure characteristics of microplastics owing to the limitation of current spectrum technologies, especially the missing information on small-sized particles. In the present study, laser direct infrared spectroscopy and thermal desorption-gas chromatography-mass spectrometry combined pyrolysis using a tubular furnace (TD-GC/MS) were employed to comprehensively detect the presence of plastic particles down to 0.22 µm in human excreted samples. The results showed that polyethylene (PE), polyvinyl chloride, PE terephthalate (PET), and polypropylene dominated large-sized (>20 µm) and small-sized plastic plastics (0.22-20 µm) in feces and urine. Moreover, fragments accounted for 60.71 and 60.37% in feces and urine, respectively, representing the most pervasive shape in excretion. Surprisingly, the concentration of small-sized particles was significantly higher than that of large-sized microplastics, accounting for 56.54 and 50.07% in feces (345.58 µg/g) and urine (6.49 µg/mL). Significant positive correlations were observed between the level of plastic particles in feces and the use of plastic containers and the consumption of aquatic products (Spearman correlation analysis, p < 0.01), suggesting the potential sources for plastic particles in humans. Furthermore, it is estimated that feces was the primary excretory pathway, consisting of 94.0% of total excreted microplastics daily. This study provides novel evidence regarding small-sized plastic particles, which are predominant fractions in human excretion, increasing the knowledge of the potential hazards of omnipresent microplastics to human exposure.
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Heces , Microplásticos , Plásticos , Humanos , Heces/química , Tamaño de la Partícula , Cromatografía de Gases y Espectrometría de Masas , Monitoreo del AmbienteRESUMEN
OPINION STATEMENT: The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.
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Quimioradioterapia , Neoplasias del Recto , Humanos , Resultado del Tratamiento , Preservación de Órganos , Calidad de Vida , Neoplasias del Recto/cirugía , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/prevención & control , Espera Vigilante/métodosRESUMEN
In this work, monodisperse and nano-porous poly(bismaleimide-co-divinylbenzene) microspheres with large specific surface area (427.6 m2 /g) and rich pore structure were prepared by one-pot self-stable precipitation polymerization of 2,2'-bis[4-(4-maleimidophenoxy) phenyl] propane and divinylbenzene. The prepared poly(bismaleimide-co-divinylbenzene) microspheres were employed as dispersive solid-phase extraction (DSPE) adsorbent for the extraction of triazine herbicides. Under optimized conditions, good linearities were obtained between the peak area and the concentration of triazine herbicides in the range of 1-400 µg/L (R2 ≥ 0.9987) with the limits of detection of 0.12-0.31 µg/L. Triazine herbicides were detected using the described approach in vegetable samples (i.e., cucumber, tomato, and maize) with recoveries of 93.6%-117.3% and relative standard deviations of 0.4%-3.5%. In addition, the recoveries of triazine herbicides remained above 80.7% after being used for nine DSPE cycles, showing excellent reusability of poly(bismaleimide-co-divinylbenzene) microspheres. The adsorption of poly(bismaleimide-co-divinylbenzene) microspheres toward triazine herbicides was a monolayer and chemical adsorption. The adsorption mechanism between triazine herbicides and adsorbents might be a combination of hydrogen bonding, electrostatic interaction, and π-π conjugation. The results confirmed the potential use of the poly(bismaleimide-co-divinylbenzene) microspheres-based DSPE coupled to the high-performance liquid chromatography method for the detection of triazine herbicide residues in vegetable samples.
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Herbicidas , Verduras , Compuestos de Vinilo , Verduras/química , Cromatografía Líquida de Alta Presión/métodos , Microesferas , Porosidad , Triazinas/análisis , Extracción en Fase Sólida/métodos , Herbicidas/análisis , Límite de DetecciónRESUMEN
A sensitive, rapid, and simple HPLC-MS/MS method was first developed and fully validated to determine the icaritin (ICT) and its novel 3-methylcarbamate prodrug (3N) simultaneously in rat plasma. Analytes were extracted from rat plasma using a liquid-liquid extraction (LLE) method. Chromatographic separation was performed on ACE Excel 2 C18-Amide column. Quantitation of analytes was conducted on an LCMS-8060 triple-quadrupole tandem mass spectrometer. The quantitation mode was the multiple reaction monitoring via positive electrospray ionization. The calibration curve was linear over the concentration range of 1 to 200 ng/ml for ICT with a correlation coefficient of r = 0.9950 and 1 to 400 ng/ml for 3N with a correlation coefficient of r = 0.9956. The intra-precision RSDs were ≤12% for ICT and 3N. The inter-day precision RSDs were ≤10% for ICT and 3N. The accuracy RE was between -2.6% and 7.8% for ICT and 3N. The average ICT, 3N and IS recoveries were 87.9%, 83.6%, and 84.3%. The plasma matrix of ICT and 3N complied with the guidelines. ICT and 3N were stable in rat plasma under various tested conditions. This work has been successfully applied to studying the pharmacokinetics of ICT and 3N.
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Monascus pigments (MPs) have been used as natural food pigments for many years. There is a high demand for Monascus red pigments (MRPs) to enhance color and for antibacterial and cancer prevention therapies in food and medicine. Most MRPs are not water soluble, and the yield of water-soluble MRPs is naturally low. On the other hand, water-soluble MRP is more cost effective for application in industrial mass production. Therefore, it is important to improve the yield of water-soluble MRPs. Environmental factors have a significant influence on the synthesis of water-soluble MRPs, which is crucial for the development of industrial production of water-soluble MRPs. This review introduces the biosynthetic pathways of water-soluble MRPs and summarizes the effects of environmental factors on the yield of water-soluble MRPs. Acetyl coenzyme A (acetyl-CoA) is a precursor for MPs synthesis. Carbon and nitrogen sources and the carbon/nitrogen ratio can impact MP production by regulating the metabolic pathway of acetyl-CoA. Optimization of fermentation conditions to change the morphology of Monascus can stimulate the synthesis of MPs. The appropriate choice of nitrogen sources and pH values can promote the synthesis of MRPs from MPs. Additives such as metal ions and non-ionic surfactants can affect the fluidity of Monascus cell membrane and promote the transformation of MRPs into water-soluble MRPs. This review will lay the foundation for the industrial production of water-soluble MRPs. © 2024 Society of Chemical Industry.
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Various factors contribute to different types of surgical site infections (SSI) in gastric cancer patients undergoing surgery, and the risk factors remain uncertain. This meta-analysis aims to clarify the relationship between various factors and SSI, resolving existing controversies. Thirty-four eligible articles with 66 066 patients were included in the meta-analysis. Significant risk factors for SSI included age ≥65 years, male gender, BMI ≥25 kg/m2, diabetes, hypertension, advanced TNM stage ≥III, pathologic T stage ≥T3, pathologic N stage ≥N1, ASA ≥3, open surgery, blood transfusion, extensive resection, combined resection, splenectomy, D2 or more lymph node dissection, and operative time ≥240 min. Operative time showed a nonlinear relationship with SSI risk. Subgroup analysis revealed significant differences in the effects of risk factors among different infection types. These findings inform the development of targeted preventive measures to reduce SSI rates.
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Neoplasias Gástricas , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/epidemiología , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones , Factores de Riesgo , Masculino , Femenino , Anciano , Persona de Mediana Edad , Adulto , Anciano de 80 o más AñosRESUMEN
Teaching presence is the core role of teachers in online education and is the most promising mechanism for developing online learning communities. Drawing on the theoretical framework of teaching presence, and based on data from an online survey of university students from 334 Chinese universities, this study constructs a framework for teaching presence and compares the differences in teaching presence among different student groups, and further explores the impact of teaching presence on students' online learning experience and its heterogeneity in terms of gender and discipline. The study finds that teaching presence includes three dimensions: instructional design and organization, facilitating interaction, and direct instruction, and there are differences among different groups. Teaching presence has a significant impact on the online learning experience, among which facilitating interaction is the most important influencing factor. Heterogeneity examination reveals that the direct instruction dimension has a greater impact on the online learning experience of female students and students in science and engineering, while the facilitating interaction dimension has a greater impact on the experience of male students and students in science and engineering. For the development of online teaching, it is necessary to help online teachers comprehensively improve teaching presence, adopt different teaching strategies and improvement measures for different student groups, and pay attention to collecting and analyzing student behavioral data for teachers to reflect on and improve teaching.
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Epilepsy is a prevalent chronic neurological disorder characterized by recurrent seizures and brain dysfunction. Existing antiepileptic drugs (AEDs) mainly act on neurons and provide symptomatic control of seizures, but they do not modify the progression of epilepsy and may cause serious adverse effects. Increasing evidence suggests that reactive astrogliosis is critical in the pathophysiology of epilepsy. However, the function of reactive astrocytes in epilepsy has not been thoroughly explored. To provide a new perspective on the role of reactive astrocytes in epileptogenesis, we identified human astrocyte-specific genes and found 131 of these genes significantly differentially expressed in human temporal lobe epilepsy (TLE) datasets. Multiple astrocytic functions, such as cell adhesion, cell morphogenesis, actin filament-based process, apoptotic cell clearance and response to oxidative stress, were found to be promoted. Moreover, multiple altered astrocyte-specific genes were enriched in phagocytosis, perisynaptic astrocyte processes (PAPs), plasticity, and synaptic functions. Nine hub genes (ERBB2, GFAP, NOTCH2, ITGAV, ABCA1, AQP4, LRP1, GJA1, and YAP1) were identified by protein-protein interaction (PPI) network analysis. The correlation between the expression of these hub genes and seizure frequency, as well as epilepsy-related factors, including inflammatory mediators, complement factors, glutamate excitotoxicity and astrocyte reactivity, were analyzed. Additionally, upstream transcription factors of the hub genes were predicted. Finally, astrogliosis and the expression of the hub genes were validated in an epileptic rat model. Our findings reveal the various changes in astrocyte function associated with epilepsy and provide candidate astrocyte-specific genes that could be potential antiepileptogenic targets.
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Epilepsia del Lóbulo Temporal , Epilepsia , Ratas , Humanos , Animales , Epilepsia del Lóbulo Temporal/metabolismo , Astrocitos/metabolismo , Gliosis/metabolismo , Convulsiones/metabolismo , Epilepsia/metabolismoRESUMEN
BACKGROUND: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammatory pathway is implicated in the development of epilepsy and can be suppressed by the activation of the silent information regulator 1 (SIRT1). However, the expression and correlation of the NLRP3 pathway and SIRT1 in drug-resistant epilepsy (DRE) remain unknown. METHODS: This study evaluated the histopathology of the cerebral cortex from nine patients with DRE and eight patients with cavernous haemangioma undergoing surgical treatment. It analysed the expression of the NLRP3, interleukin-1ß (IL-1ß), caspase-1 and SIRT1 using immunohistochemistry. Additionally, the contents of NLRP3, caspase-1, IL-1ß and SIRT1 in the serum samples of the included study participants were determined using ELISA method. The correlation between the NLRP3 pathway and the SIRT1 was assessed using Spearman's correlation analysis. RESULTS: The expression of NLRP3, caspase-1 and IL-1ß in the cerebral cortex of patients with DRE was elevated, with the NLRP3 expression being negatively correlated with the SIRT1 expression. Furthermore, IL-1ß in serum was upregulated in patients with DRE. The correlation between the content of serum SIRT1 and NLRP3, caspase-1 and IL-1ß in patients with DRE was not significant. Notably, serum caspase-1 levels were obviously higher in patients with bilateral hippocampal sclerosis than in patients with unilateral hippocampal sclerosis. CONCLUSIONS: The current results indicate that the expression of the NLRP3/caspase-1/IL-1ß pathway is significantly upregulated in patients with DRE and that it is partially correlated with the SIRT1 expression. This study is important for understanding the pathophysiology of DRE and developing new treatment strategies for it.
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Esclerosis del Hipocampo , Inflamasomas , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR , Dominio Pirina , Sirtuina 1/metabolismo , Caspasa 1/metabolismo , Interleucina-1beta/metabolismoRESUMEN
Background: The 4-hydroxysesamin (4-HS, a di-tetrahydrofuran lignin) is a modified sesamin that was prepared in the laboratory. This preclinical study was designed to preliminarily investigate the neuroprotective properties of 4-HS. Methods: In vitro, neuronal injury and inflammation were simulated by oxygen-glucose deprivation and lipopolysaccharide (LPS) exposure in mouse hippocampal neuronal HT22 cell line, and treated with 4-HS and/or metformin (MET, MAPK pathway activator for exploring mechanism). CCK-8, flow cytometry, and enzyme-linked immunosorbent assay were performed to evaluate cell viability, apoptosis, and inflammation. Apoptosis- and pathway-related proteins were detected by Western blotting. Middle cerebral artery occlusion (MCAO) was constructed as a stroke model and treated with 4-HS for in vivo confirmation. Histological staining was used for in vivo evaluation of 4-HS properties. Results: The 4-HS showed similar anti-inflammatory activity to sesamin but did not affect the cell viability of HT22 cells. In vitro, 4-HS improved the cell viability, ameliorated neuronal apoptosis, along with the reversion of apoptotic proteins (Bax, cleaved-caspase 3/9, Bcl-2) expression and inflammatory cytokines (IL-6, TNF-α, IL-10) in LPS-treated HT22 cells. The 4-HS suppressed the phosphorylation of ERK, JNK, and p38 but the addition of MET reversed 4-HS-induced changes of phenotype and protein expression in LPS-treated cells. In vivo, 4-HS showed apparent improvement in cerebral infarction, brain tissue morphology, neuronal architecture, apoptosis, and inflammation of MCAO mice, and also showed inhibiting effects on the phosphorylation of ERK, JNK, and p38, confirming in vivo results. Conclusion: In this first pre-clinical study on 4-HS, we preliminarily demonstrated the neuroprotective properties of 4-HS both in cell and animal models, and proposed that the underlying mechanism might be associated with the MAPK pathway.
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The drill-blasting method is a commonly used mining technique in open-pit mines, and the peak particle velocity (PPV) caused by blasting vibrations is an important indicator for evaluating the rationality of blasting mining design parameters. To develop an effective PPV prediction model, a parameter self-optimizing RUN-XGBoost prediction model is implemented using the Runge-Kutta optimization algorithm (RUN) combined with extreme gradient boosting (XGBoost). The factors affecting the prediction of PPV, including maximum explosive (ME), total explosive (TE), blast center distance (BCD), blast hole depth (BHD), and height difference between the measurement location and the blast location (DH), are selected as the influencing indicators. 188 pieces of blasting operation data were measured at the RK open pit copper-cobalt mine. Then, the RUN-XGBoost prediction model for PPV is studied and compared with the Sadovsky empirical formula, traditional XGBoost model, PSO-XGBoost model, and some traditional machine learning models (Ridge, LASSO, SVM, and SVR) using R2, RMSE, VAF, MAE, and MBE as evaluation indicators for model prediction results. Finally, the Shapley Additive Explanations (SHAP) method is used to evaluate the contribution of different influencing indicators to the PPV prediction results. The results show that the RUN-XGBoost prediction model is significantly better than other machine learning models and the Sadovsky empirical formula in the prediction of PPV, further demonstrating that the RUN-XGBoost prediction model can handle the nonlinear features of multiple factors and provide a reliable, simple, and effective PPV prediction model, forming a rapid prediction and evaluation method for blasting vibrations in open-pit mining.
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It holds significant practical importance to screen and investigate endophytic bacteria with salt-tolerant activity in rice for the development of relevant microbial agents. A total of 179 strains of endophytic bacteria were isolated from 24 samples of salt-tolerant rice seeds, with almost 95 % of these bacteria exhibiting tolerance to a salt content of 2 % (0.34 mol/L). Following the screening process, a bacterium named G9H01 was identified, which demonstrated a salt tolerance of up to 15 % (2.57 mol/L) and resistance to Magnaporthe oryzae, the causal agent of rice blast disease. Phylogenetic analysis confirmed G9H01 as a strain of Bacillus paralicheniformis. The complete genome of G9H01 was sequenced and assembled, revealing a considerable number of genes encoding proteins associated with salt tolerance. Further analysis indicated that G9H01 may alleviate salt stress in a high-salt environment through various mechanisms. These mechanisms include the utilization of proteins such as K+ transporters, antiporters, and Na+/H+ antiporters, which are involved in K+ absorption and Na+ excretion. G9H01 also demonstrated the ability to uptake and accumulate betaine, as well as secrete extracellular polysaccharides. Collectively, these findings suggest that Bacillus paralicheniformis G9H01 has potential as a biocontrol agent, capable of promoting rice growth under saline-alkali-tolerant conditions.
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Ascomicetos , Bacillus , Oryza , Tolerancia a la Sal , Álcalis , Filogenia , Bacterias/metabolismo , Antiportadores/genéticaRESUMEN
Breast cancer (BC) is a lethal disorder that threatens the life safety of the majority of females globally, with rising morbidity and mortality year by year. Doxorubicin is a cytotoxic anthracycline antibiotic that is widely used as one of the first-line chemotherapy agents for patients with BC. However, the efficacy of doxorubicin in the clinic is largely limited by its serious side effects and acquired drug resistance. Allicin (diallyl thiosulfinate), as the major component and key active compound present in freshly crushed garlic, has shown potential effects in suppressing chemotherapy resistance in various cancers. Our research aimed to explore the relationship between allicin and doxorubicin resistance in BC. To generate doxorubicin-resistant BC cell lines (MCF-7/DOX and MDA-MB-231/DOX), doxorubicin-sensitive parental cell lines MCF-7 and MDA-MB-231 were continuously exposed to stepwise increased concentrations of doxorubicin over a period of 6 months. CCK-8, colony formation, flow cytometry, RT-qPCR, and western blotting assays were performed to investigate the effects of allicin and/or doxorubicin treatment on the viability, proliferation and apoptosis and the expression of Nrf2, HO-1, phosphate AKT and AKT in doxorubicin-resistant BC cells. Our results showed that combined treatment of allicin with doxorubicin exhibited better effects on inhibiting the proliferation and enhancing the apoptosis of doxorubicin-resistant BC cells than treatment with allicin or doxorubicin alone. Mechanistically, allicin suppressed the levels of Nrf2, HO-1, and phosphate AKT in doxorubicin-resistant BC cells. Collectively, allicin improves the doxorubicin sensitivity of BC cells by inactivating the Nrf2/HO-1 signaling pathway.
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Alpha rhythm slowing is an important electroencephalogram(EEG) feature associated with (AD). This study aims to understand the correlation between alpha band deceleration and molecular changes from the perspective of neural computing. Considering the effect of Aß amyloid deposition on the inhibitory changes in the thalamic, a thalamic cortical model coupled with Aß amyloid is established. The results show that Aß amyloid deposition may induce neurotoxicity in thalamic reticular nucleus neurons, which results in inhibitory changes in the thalamus and slows the alpha rhythm of EEG output from the thalamus. In order to understand the pathogenesis more intuitively, some numerical simulations are provided to illustrate the obtained theories. This research is helpful to understand the pathogenesis of AD, so as to provide theoretical basis for the intervention and control of the disease.
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OBJECTIVE: To explore effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with restless legs syndrome (RLS). METHODS: In total, 18 patients with primary RLS were divided into rTMS group and sham stimulation group. The rTMS treatment group received 15-Hz high-frequency rTMS to stimulate the leg motor representative area of the frontal cortex for 14 days, and the sham stimulation group received 15 Hz high-frequency rTMS sham stimulation in primary motor cortex for 14 days. RESULTS: After rTMS, RLS severity scale score, Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), as well as Hamilton Depression Rating Scale 24 (HAMD24) in rTMS treatment group were significantly lower than before treatment; 1 month and 2 months after treatment, the score remained at low level. Meanwhile, no significant changes have been observed in the aforementioned index before rTMS stimulation for the sham stimulation group after 14 days or after 1 month and 2 months. In addition, the results of correlation analysis suggested for all the 18 patients with RLS, there was a positive correlation between PSQI score and HAMA as well as HAMD24 scores before and after rTMS stimulation. In addition, the RLS severity score was also positively correlated with PSQI, HAMA, and HAMD24 scores. CONCLUSIONS: High-frequency rTMS stimulation reduces the frequency and severity of RLS; improves the quality of sleep, anxiety, as well as depression of the patients; and the curative effect can be sustained for 2 months. High-frequency rTMS may be used as an alternative treatment option for improving the quality of life of patients with RLS.
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Síndrome de las Piernas Inquietas , Estimulación Magnética Transcraneal , Humanos , Síndrome de las Piernas Inquietas/terapia , Proyectos Piloto , Masculino , Femenino , Estimulación Magnética Transcraneal/métodos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Anciano , Corteza Motora/fisiopatología , Índice de Severidad de la EnfermedadRESUMEN
Protein-based drugs have shown unique advantages to treat various diseases in recent years. However, most protein therapeutics in clinical use are limited to extracellular targets with low delivery efficiency. To realize targeted protein delivery, a series of stimuli-triggered nanoparticle formulations have been developed to improve delivery efficiency and reduce off-target release. These smart nanoparticles are designed to release cargo proteins in response to either internal or external stimuli at pathological tissues. In this way, varieties of protein-based drugs including antibodies, enzymes, and pro-apoptotic proteins can be effectively delivered to desired sites for the treatment of cancer, inflammation, metabolic diseases, and so on with minimal side effects. In this review, recent advances in the design of stimuli-triggered nanomedicine for targeted protein delivery in different biomedical applications will be discussed. A deeper understanding of these emerging strategies helps develop more efficient protein delivery systems for clinical use in the future.
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An ultra-performance liquid chromatography-tandem mass spectrometry was developed to assay the concentration for the quantification of cycloicaritin and its carbamate prodrug (3-O-L-valyl carbamate prodrug of cycloicaritin) in the plasma of Sprague-Dawley rats. Analytes were separated on an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7 µm) after liquid-liquid extraction with methyl tert-butyl ether. Acetonitrile and water containing 0.1 % formic acid were the mobile phases of the method. Using electrospray ionization in the positive ion mode, the method was performed with a total run time of 2.60 min. The response of the experiments was linear over the concentration ranges from 1 to 250 ng/mL for cycloicaritin and 1-250 ng/mL for prodrug. The intra- and inter-day precision and accuracy were within the recommended limits of the FDA. The matrix effect that we observed met the criteria. The method was successfully applied to the pharmacokinetics of cycloicaritin and its carbamate prodrug in Sprague-Dawley rats.