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Radiotherapy has long been a main treatment option for nasopharyngeal carcinoma (NPC). However, during clinical treatment, NPC is prone to developing radioresistance, resulting in treatment failure. This study aims to examine the role of histone methylation in the induction of radioresistance. It was found that the radioresistance of NPC cells was related to the increase of the level of histone H3 lysine 27 trimethylation (H3K27me3). Treatment of cells with histone methyltransferase inhibitor GSK126 increased the radiosensitivity of NPC cells by triggering Bcl2 apoptosis regulator/BCL2-associated X, apoptosis regulator (Bcl2/BAX) signaling pathway. Bioinformatics analysis indicated that the expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) was reduced in the radioresistant cells but increased in the GSK126-treated cells. Chromatin immunoprecipitation assay confirmed that the decrease of OAS1 expression in radioresistant cells was mainly due to the enrichment of H3K27me3 in its promoter region. Furthermore, downregulation of OAS1 reduced apoptosis due to the inhibition of Bcl2/BAX pathway after irradiation, while OAS1 overexpression increased radiosensitivity. Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, the histone methyltransferase inhibitor GSK126 could overcome the radioresistance and thus might be a potential therapeutic strategy for NPC.NEW & NOTEWORTHY Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, we demonstrated that the histone methyltransferase inhibitor GSK126 could be a promising therapeutic strategy for NPC by overcoming radioresistance, providing valuable insights into the clinical treatment of NPC.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Histonas/genética , Histonas/metabolismo , Carcinoma/metabolismo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/radioterapia , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Histona Metiltransferasas/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , 2',5'-Oligoadenilato Sintetasa/metabolismoRESUMEN
BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.
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Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , China/epidemiología , Adulto , Prevalencia , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Adolescente , Anciano , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , ADN Viral/genética , Cuello del Útero/virologíaRESUMEN
This paper proposes a novel circuit-level design in order to enhance the radiation tolerance of an analog switch integrated circuit. After analyzing the mechanisms of single-particle sensitivity in a high-voltage analog switch chip fabricated using a commercial 1µm complementary metal-oxide-semiconductor process, a diode unit was employed to reduce theVGS(voltage between the gate and the base) of the parasitic triode within the metal-oxide-semiconductor field-effect transistor of the switch. This reduction lowered the probability of activating the parasitic triode in response to single-event effect (SEE). Subsequently, single-particle irradiation experiments proceeded with the high-voltage analog switch chip, both with and without the diode unit. In the unreinforced device, the current of the power supply reached 100 mA within 11 s of single-particle irradiation at 75.8 MeVâ¢cm2mg-1. In contrast, in the reinforced device, the current of the power supply remained relatively stable under irradiation at both 37.2 and 75.8 MeVâ¢cm2mg-1. These findings indicate that the reinforced analog switch chip exhibits an SEE tolerance exceeding 75.8 MeVâ¢cm2mg-1, highlighting its potential to enhance the radiation tolerance of analog switches.
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In order to predict the single particle irradiation of tunnel field effect transistor (TFET) devices, a deep learning algorithm network model was built to predict the key characterization parameters of the single particle transient. Computer aided design (TCAD) technique is used to study the influence of single particle effect on the novel stacked source trench gate TFET device. The results show that with the increase of drain voltage, incident width of heavy ions (less than 0.04µm), and linear energy transfer, the drain transient current and collected charge also increase. The prediction results of deep learning algorithm show that the relative error percentage of drain current pulse peak (IDMAX) and collected charge (Qc) is less than 10%, and the relative error percentage of most predicted values is less than 1%. Comparison experiments with five traditional machine learning methods (support vector machine, decision tree, K-nearest algorithm, ridge regression, linear regression) show that the deep learning algorithm has the best performance and has the smallest average error percentage. This data-driven deep learning algorithm model not only enables researchers who are not familiar with semiconductor devices to quickly obtain the transient data of a single particle under any conditions; at the same time, it can be applied to digital circuit design as a data-driven device model reflecting the reliability of single particle transient. The application of deep learning in the field of device irradiation prediction has a highly promising prospect in the future.
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PIN diodes, due to their simple structure and variable resistance characteristics under high-frequency high-power excitation, are often used in radar front-end as limiters to filter high power microwaves (HPM) to prevent its power from entering the internal circuit and causing damage. This paper carries out theoretical derivation and research on the HPM effects of PIN diodes, and then uses an optimized neural network algorithm to replace traditional physical modeling to calculate and predict two types of HPM limiting indicators of PIN diode limiters. We proposes a neural network model for each of the following two prediction scenarios: in the scenario of time-junction temperature curves under different HPM irradiation, the weighted mean squared error (MSE) between the predicted values from the test dataset and the simulated values is below 0.004. While in predicting PIN limiter's power limitation threshold, insertion loss, and maximum isolation under different HPM irradiation, the MSE of the test set prediction values and simulation values are all less than 0.03. The method proposed in this research, which applies an optimized neural network algorithm to replace traditional physical modeling algorithms for studying the high-power microwave effects of PIN diode limiters, significantly improves the computational and simulation speed, reduces the calculation cost, and provides a new method for studying the high-power microwave effects of PIN diode limiters.
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As device feature sizes continue to decrease and fin field effect transistors reach their physical limits, gate all around field effect transistors (GAAFETs) have emerged with larger gate control areas and stackable characteristics for better suppression of second-order effects such as short-channel effects due to their gate encircling characteristics. Traditional methods for studying the electrical characteristics of devices are mostly based on the technology computer-aided design. Still, it is not conducive to developing new devices due to its time-consuming and inefficient drawbacks. Deep learning (DL) and machine learning (ML) have been well-used in recent years in many fields. In this paper, we propose an integrated learning model that integrates the advantages of DL and ML to solve many problems in traditional methods. This integrated learning model predicts the direct current characteristics, capacitance characteristics, and electrical parameters of GAAFET better than those predicted by DL or ML methods alone, with a linear regression factor (R2) greater than 0.99 and very small root mean square error. The proposed integrated learning model achieves fast and accurate prediction of GAAFET electrical characteristics, which provides a new idea for device and circuit simulation and characteristics prediction in microelectronics.
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BACKGROUND: Flies are acknowledged as vectors of diseases transmitted through mechanical means and represent a significant risk to human health. The study aimed to determine the prevalence of enteropathogens carried by flies in Pudong New Area to inform strategies for preventing and controlling flies. METHODS: Samples were collected from various locations in the area using cage trapping techniques between April and November 2021, encompassing various habitats such as parks, residential areas, restaurants, and farmers' markets. The main fly species were identified using cryomicrography and taxonomic enumeration, with 20 samples per tube collected from different habitats. Twenty-five enteropathogens were screened using GI_Trial v3 TaqManTM microbial arrays. RESULTS: A total of 3,875 flies were collected from 6,400 placements, resulting in an average fly density of 0.61 flies per cage. M. domestica were the most common species at 39.85%, followed by L. sericata at 16.57% and B. peregrina at 13.14%. Out of 189 samples, 93 tested positive for enteropathogens, with nine different pathogens being found. 12.70% of samples exclusively had parasites, a higher percentage than those with only bacteria or viruses. The study found that M. domestica had fewer enteropathogens than L. sericata and B. peregrina, which primarily harbored B. hominis instead of bacteria and viruses such as E. coli, Astrovirus, and Sapovirus. During spring testing, all three fly species exhibited low rates of detecting enteropathogens. M. domestica were found in residential areas with the highest number of pathogen species, totaling six. In contrast, L. sericata and B. peregrina were identified in farmers' markets with the highest number of pathogen species, totaling six and seven, respectively. CONCLUSIONS: Flies have the potential to serve as vectors for the transmission of enteropathogens, thereby posing a substantial risk to public health.
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Insectos Vectores , Animales , Humanos , Insectos Vectores/microbiología , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias/genética , China/epidemiología , Dípteros/microbiología , Virus/aislamiento & purificación , Virus/clasificación , Virus/genética , Muscidae/microbiologíaRESUMEN
Wheat culms, comprising four to six internodes, are critically involved in determining plant height and lodging resistance, essential factors for field performance and regional adaptability. This study revealed the regulatory function of miR319 in common wheat plant height. Repression of tae-miR319 through short tandem target mimics (STTM) caused an increased plant height, while overexpression (OE) of tae-miR319 had the opposite effect. Overexpressing a miR319-resistant target gene TaPCF8 (rTaPCF8), increased plant height. TaPCF8 acted as a transcription repressor of downstream genes TaIAAs, which interact physically with TaSPL14. The significant differences of indole-3-acetic acid (IAA) contents indicate the involvement of auxin pathway in miR319-mediated plant height regulation. Finally, we identified two TaPCF8 haplotypes in global wheat collections. TaPCF8-5A-Hap2, as per association and evolution examinations, was subjected to strong substantial selection throughout wheat breeding. This haplotype, associated with shorter plant height, aligns with global breeding requirements. Consequently, in high-yield wheat breeding, we proposed a potential molecular marker for marker-assisted selection (MAS). Our findings offer fresh perspectives into the molecular mechanisms that underlie the miR319-TaPCF8 module's regulation of plant height by orchestrating auxin signaling and biosynthesis in wheat.
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BACKGROUND: Founder parents play extremely important roles in wheat breeding. Studies into the genetic basis of founder parents and the transmission rules of favorable alleles are of great significance in improving agronomically important traits in wheat. RESULTS: Here, a total of 366 founder parents, widely grown cultivars, and derivatives of four representative founder parents were genotyped based on efficient kompetitive allele-specific PCR (KASP) markers in 87 agronomically important genes controlling yield, quality, adaptability, and stress resistance. Genetic composition analysis of founder parents and widely grown cultivars showed a consistently high frequency of favorable alleles for yield-related genes. This analysis further showed that other alleles favorable for resistance, strong gluten, dwarf size, and early heading date were also subject to selective pressure over time. By comparing the transmission of alleles from four representative founder parents to their derivatives during different breeding periods, it was found that the genetic composition of the representative founder parents was optimized as breeding progressed over time, with the number and types of favorable alleles carried gradually increasing and becoming enriched. There are still a large number of favorable alleles in wheat founder parents that have not been fully utilized in breeding selection. Eighty-seven agronomically important genes were used to construct an enrichment map that shows favorable alleles of four founder parents, providing an important theoretical foundation for future identification of candidate wheat founder parents. CONCLUSIONS: These results reveal the genetic basis of founder parents and allele transmission for 87 agronomically important genes and shed light on breeding strategies for the next generation of elite founder parents in wheat.
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Pan , Triticum , Alelos , Triticum/genética , Fitomejoramiento , GenotipoRESUMEN
Grain size and filling are two key determinants of grain thousand-kernel weight (TKW) and crop yield, therefore they have undergone strong selection since cereal was domesticated. Genetic dissection of the two traits will improve yield potential in crops. A quantitative trait locus significantly associated with wheat grain TKW was detected on chromosome 7AS flanked by a simple sequence repeat marker of Wmc17 in Chinese wheat 262 mini-core collection by genome-wide association study. Combined with the bulked segregant RNA-sequencing (BSR-seq) analysis of an F2 genetic segregation population with extremely different TKW traits, a candidate trehalose-6-phosphate phosphatase gene located at 135.0 Mb (CS V1.0), designated as TaTPP-7A, was identified. This gene was specifically expressed in developing grains and strongly influenced grain filling and size. Overexpression (OE) of TaTPP-7A in wheat enhanced grain TKW and wheat yield greatly. Detailed analysis revealed that OE of TaTPP-7A significantly increased the expression levels of starch synthesis- and senescence-related genes involved in abscisic acid (ABA) and ethylene pathways. Moreover, most of the sucrose metabolism and starch regulation-related genes were potentially regulated by SnRK1. In addition, TaTPP-7A is a crucial domestication- and breeding-targeted gene and it feedback regulates sucrose lysis, flux, and utilization in the grain endosperm mainly through the T6P-SnRK1 pathway and sugar-ABA interaction. Thus, we confirmed the T6P signalling pathway as the central regulatory system for sucrose allocation and source-sink interactions in wheat grains and propose that the trehalose pathway components have great potential to increase yields in cereal crops.
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Ácido Abscísico , Grano Comestible , Ácido Abscísico/metabolismo , Grano Comestible/genética , Grano Comestible/metabolismo , Triticum/genética , Triticum/metabolismo , Azúcares/metabolismo , Retroalimentación , Estudio de Asociación del Genoma Completo , Fitomejoramiento , Sacarosa/metabolismo , Almidón/metabolismoRESUMEN
KEY MESSAGE: Wheat NAC-A18 regulates both starch and storage protein synthesis in the grain, and a haplotype with positive effects on grain weight showed increased frequency during wheat breeding in China. Starch and seed storage protein (SSP) directly affect the processing quality of wheat grain. The synthesis of starch and SSP are also regulated at the transcriptional level. However, only a few starch and SSP regulators have been identified in wheat. In this study, we discovered a NAC transcription factor, designated as NAC-A18, which acts as a regulator of both starch and SSP synthesis. NAC-A18, is predominately expressed in wheat developing grains, encodes a transcription factor localized in the nucleus, with both activation and repression domains. Ectopic expression of wheat NAC-A18 in rice significantly decreased starch accumulation and increased SSP accumulation and grain size and weight. Dual-luciferase reporter assays indicated that NAC-A18 could reduce the expression of TaGBSSI-A1 and TaGBSSI-A2, and enhance the expression of TaLMW-D6 and TaLMW-D1. A yeast one hybrid assay demonstrated that NAC-A18 bound directly to the cis-element "ACGCAA" in the promoters of TaLMW-D6 and TaLMW-D1. Further analysis indicated that two haplotypes were formed at NAC-A18, and that NAC-A18_h1 was a favorable haplotype correlated with higher thousand grain weight. Based on limited population data, NAC-A18_h1 underwent positive selection during Chinese wheat breeding. Our study demonstrates that wheat NAC-A18 regulates starch and SSP accumulation and grain size. A molecular marker was developed for the favorable allele for breeding applications.
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Almidón , Triticum , Almidón/metabolismo , Triticum/genética , Triticum/metabolismo , Proteínas de Plantas/metabolismo , Fitomejoramiento , Grano Comestible/metabolismo , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: The GINA recommends inhaled corticosteroids (ICSs) for the treatment of steps 2-3 of childhood asthma. However, the difference in efficacy between these drugs remains unclear. The purpose of this study was to compare the efficacy of different ICS drugs in the treatment of childhood asthma. METHODS: We searched PubMed and EMBASE for randomized controlled trials of ICSs in the treatment of childhood asthma. Using forced expiratory volume in the first second (FEV1) as the primary outcome, a time-course model of ICSs was constructed. In addition, the symptom-free days% were analyzed as a secondary outcome. RESULTS: Six studies involving 2237 children that reported FEV1 were included. The results showed that the ET50 of ciclesonide (CIC) and budesonide (BUD) was 1.23 and 2.97 weeks, respectively. Compared with them, FP had a higher efficacy. In terms of symptom-free days%, we found that the efficacy of beclometasone dipropionate was lower than that of CIC and fluticasone propionate. CONCLUSION: In this study, the efficacy of three ICS drugs was quantitatively compared, providing necessary information for the implementation of medication guidelines for steps 2-3 of asthma in children. IMPACT: This study analyzed the entire time-course of the drug efficacy of Inhaled corticosteroids in the treatment of asthma in children aged 5-12, which found that although the maximum efficacy of both ciclesonide and budesonide was the same, the onset speed of ciclesonide was faster than that of budesonide. The above information provides the necessary quantitative information for the implementation of medication guidelines for steps 2-3 asthma in children.
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Antiasmáticos , Asma , Niño , Humanos , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Budesonida/uso terapéutico , Corticoesteroides/uso terapéutico , Fluticasona/uso terapéutico , Administración por InhalaciónRESUMEN
The potential of neuromorphic computing in synaptic simulation has led to a renewed interest in memristor. However, the demand for multilevel resistive switching with high reliability and low power consumption is still a great resistance in this application. In this work, the electronic synaptic plasticity and simulated bipolar switching behavior of Pt/Al2O3(2 nm)/HfO2(10 nm)/Al2O3(2 nm)/Ti tri-layer memristor is investigated. The effect of Al2O3layer embedded at the top electrode and the bottom electrode on the resistive performance of the memristor was studied. It is found that both of them can effectively improve the reliability of the device (104cycles), the resistive window (>103), the tunable synaptic linearity and reduce of the operating voltage. RRAM with Al2O3embedded at the top electrode have higher uniformity and LTP linearity, while those with Al2O3embedded at the bottom electrode significantly reduce the operating current (â¼10µA) and improve LTD linearity. Electron transport mechanisms were compared between single-layer HfO2and tri-layer Al2O3/HfO2/Al2O3samples under DC scanning. The results showed that the thin Al2O3layer at the top electrode led to Fowler Northeim tunneling in the low-resistance state, while the thin Al2O3layer at the bottom electrode led to Schottky emission in the high-resistance state. The Al2O3/HfO2/Al2O3memristors were successfully used to achieve synaptic properties, including enhancement, inhibition, and spike time-dependent plasticity, demonstrating an important role in high-performance neuromorphic computing applications.
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Self-powered photodetectors that do not require external power support are expected to play a key role in future photodetectors due to their low power characteristics, but achieving high responsivity remains a challenge. 2D van der Waals heterojunctions are a promising technology for high-performance self-powered photodetectors due to their excellent optical and electrical properties. Here, we fabricate a self-powered photodetector based on In2Se3/WSe2/ReS2van der Waals heterojunction self-powered photodetector. Due to the presence of ReS2layer, photocurrent is enhanced as a result of the increase in light absorption efficiency and the effective region for generating photogenerated carriers. The built-in electric field is enhanced by a negative 'back-gate voltage' along the p-n junction vertical direction generated by the electrons in the photo-generated electrons accumulation layer. Accordingly, the optical responsivity and the photoresponse speed of this heterojunction self-powered photodetector are greatly boosted. The proposed self-powered photodetector based on the In2Se3/WSe2/ReS2heterojunction exhibits a high responsivity of 438 mA W-1, which is 17 times higher compared to the In2Se3/WSe2photodetector, a self-powered current (1.1 nA) that is an order of magnitude higher than that of the In2Se3/WSe2photodetector, and a fast response time that is 250% faster. Thus the self-powered photodetector with a stronger built-in electric field and a wider depletion zone can provide a new technological support for the fabrication of high responsivity, low power consumption and high speed self-powered photodetectors based on van der Waals heterojunctions.
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In order to probe into the mechanism of solvolysis (alcoholysis/hydrolysis) of propylene oxide (PO), the formation of propylene glycol (PG), 1-methoxy-2-propanol (PPM) and 2-methoxy-1-propanol (SPM) over the TS-1 catalyst with tetrahedral Ti and Ti/defect sites was systematically discussed using an embedded quantum mechanical/molecular mechanics (QM/MM) approach. The results showed that the activity of PO solvolysis is closely related to the ring-opening ability of active substances, and the ring-opening ability is in the following order: Si-O(H)-Ti > Ti-OH > 5MR Ti-OOH > Ti-OCH3 (tetrahedral Ti site); 3MR Ti-OOH > Ti-OH > 5MR Ti-OOH > Ti-OCH3 (Ti/defect site). At the tetrahedral site, the concerted mechanism is the dominant pathway for PO ring opening to form PPM, while a competitive relationship exists between stepwise and concerted mechanisms to form PG and SPM. Si-O(H)-Ti exhibits excellent PO ring-opening activity because of its strong Brønsted acidity, but it is difficult to form. At the Ti/defect site, the stepwise mechanism via PO ring opening with 3MR Ti-OOH and then successive hydrolysis/alcoholysis to form product is the dominant pathway. The overall energy barrier of the optimal route is relatively lower as compared to the tetrahedral Ti site. This work opens up a new path for providing more information on the detailed mechanism in the solvolysis of PO over the TS-1 catalyst from a theoretical point of view.
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Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Induction of aHSCs senescence by inhibiting SASP may be a potential therapeutic model against hepatic fibrosis. To evaluate the role of atractylenolide III (ATR III) in the development of chemotherapeutic drug-induced SASPs in hepatic stellate cells. Etoposide-induced senescent HSC-LX2 model was established and treated with ATR III at different concentrations (20, 30 and 40 µM). We found that ATR III dose-dependently enhanced senescence in etoposide-induced LX2 cells. ATR III dose-dependently decreased the release and expression of SASP factors (interleukin [IL]-1α, IL-1ß, IL6 and IL-8) in senescent cells. ATR III regulated cyclic GMP-AMP synthase (cGAS)/nuclear factor κ (NF-κB) signalling to affect SASP expression in senescent cells. The addition of 2'3' cGAMP counteracted the effect of ATR III. The release of SASP factors in the conditioned medium from senescent cells could affect cell migration, proliferation and contraction through paracrine manner. Our results indicated ATR III could still enter senescence and prevent the production of SASP and its paracrine effects in senescent cells, an effect that may be related to the possible inhibition of cGAS/NF-κB signalling by ATR III. Our study proves that ATR III may be an effective potential drug against liver fibrosis by promoting aHSC senescence, which can provide a new choice for the future clinical treatment of liver fibrosis.
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Células Estrelladas Hepáticas , FN-kappa B , Humanos , Senescencia Celular , Etopósido/farmacología , Cirrosis Hepática , FN-kappa B/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/farmacología , SecretomaRESUMEN
A diet supplemented with cholic acid (CA), the primary 12α-hydroxylated bile acid, can induce hepatic lipid accumulation in rats without obesity. This study examined the effects of a CA-supplemented diet on blood pressure (BP). After acclimation, WKAH/HkmSlc rats (3 weeks old) were divided into two groups and fed with a control AIN-93-based diet or a CA-supplemented diet (0.5 g CA/kg) for 13 weeks. The CA diet increased systolic and diastolic BP as well as hepatic lipid concentrations in the rats. No changes were found in the blood sodium concentration. Urinary albumin concentration increased in CA-fed rats. An increase was observed in the hepatic expression of ATP-binding cassette subfamily B member 1B that correlated BPs and urinary albumin concentration accompanied by an increase in portal taurocholic acid concentration. These results suggest that 12α-hydroxylated bile acids are involved in increased BP and albuminuria via alteration of hepatic function.
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Albuminuria , Ácidos y Sales Biliares , Ratas , Animales , Ácido Cólico , Presión Sanguínea , Albuminuria/metabolismo , Ácidos y Sales Biliares/metabolismo , Dieta , Lípidos/farmacología , Hígado/metabolismoRESUMEN
The globus pallidus has emerged as a crucial node in the basal ganglia motor control circuit under both healthy and parkinsonian states. Previous studies have shown that angiotensin II (Ang II) and angiotensin subtype 1 receptor (AT1R) are closely related to Parkinson's disease (PD). Recent morphological study revealed the expression of AT1R in the globus pallidus of mice. To investigate the functions of Ang II/AT1R on the globus pallidus neurons of both normal and parkinsonian rats, electrophysiological recordings and behavioral tests were performed in the present study. Electrophysiological recordings showed that exogenous and endogenous Ang II mainly excited the globus pallidus neurons through AT1R. Behavioral tests further demonstrated that unilateral microinjection of Ang II into the globus pallidus induced significantly contralateral-biased swing in elevated body swing test (EBST), and bilateral microinjection of Ang II into the globus pallidus alleviated catalepsy and akinesia caused by haloperidol. AT1R was involved in Ang II-induced behavioral effects. Immunostaining showed that AT1R was expressed in the globus pallidus of rats. On the basis of the present findings, we concluded that pallidal Ang II/AT1R alleviated parkinsonian motor deficits through activating globus pallidus neurons, which will provide a rationale for further investigations into the potential of Ang II in the treatment of motor disorders originating from the basal ganglia.
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Globo Pálido , Hormonas Peptídicas , Animales , Ratas , Angiotensina II/farmacología , Angiotensina II/metabolismo , Globo Pálido/metabolismo , Haloperidol/farmacología , Neuronas/metabolismoRESUMEN
One of the most important qualities of jujube fruit is its color. Chlorophyll, carotenoid, and anthocyanin all play important roles in the coloring of jujube fruit. However, few studies have focused on the pigment molecular mechanism. In the present study, jujube peels of 'Sanbianhong' in three growth stages were evaluated for their gene expression characteristics and gene regulation related to pigment formation using the transcriptome sequencing analysis. A total of 84.86 Gb of clean data were obtained in the analysis. In the FS1 vs. FS3, FS1 vs. FS5, and FS3 vs. FS5, 4,530, 11,012, and 9,072 differentially expressed genes (DEGs) were identified, respectively. The inter-group screening among the three comparisons yielded 1430 common DEGs. Among these DEGs, 27, 16, and 28 genes were enriched in chlorophyll, carotenoid, and anthocyanin metabolic pathways, respectively. Twelve genes were chosen at random, and the accuracy of the transcriptome data were confirmed using qRT-PCR. The molecular mechanism underlying the pigmentation of jujube fruit was elucidated at the transcriptome level, which would provide a scientific basis for the subsequent functional studies on the color-regulating genes of jujube fruits.
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Transcriptoma , Ziziphus , Ziziphus/genética , Ziziphus/metabolismo , Frutas/metabolismo , Antocianinas/genética , Carotenoides/metabolismo , Clorofila/metabolismoRESUMEN
Objective: To explore the effect of glutathione on serum oxidative stress, inflammatory reaction, and brain injury in patients with Sevoflurane inhalation general anesthesia based on iron metabolism pathway. Methods: From January 2018 to January 2023, 120 patients undergoing Sevoflurane inhalation anesthesia in Xingtai Third Hospital were divided into a control group and an observation group. The control group was given routine treatment, and the observation group patients were given oral glutathione tablets 2 weeks before anesthesia based on the control group. Relevant basic data of patients were collected 3 days before operation (T0), 1 day after the operation (T1), 3 days (T2), and 7 days (T3) respectively, and the serum oxidative stress indicators of patients in each group were measured by ELISA: SOD, MDA, GSH, Hif-1α, ferroptosis related indicators: SIRT3, GPX4; related inflammatory indicators: IL-1ß, TGF-ß, IL-33; neuronal injury related proteins: MBP, NGF, and statistical analysis of the data. Results: There was no significant difference in general conditions and operation time between the two groups (P > .05). Compared with the control group, the observation group showed significant differences in oxidative stress indicators: SOD in the observation group at T1, SOD, and Hif-1α in the observation group at T2, and SOD, MDA, GSH and Hif-1α in the observation group at T3. 1α, there were significant differences compared with the indicators of the control group at the same time (P < .001). In terms of inflammatory factor indicators, compared with the control group, there were significant differences in IL-1ß at T1, TGF-ß, and IL-33 at T2, and IL-1ß, TGF-ß and IL-33 at T3. (P < .001). In terms of ferroptosis indicators, compared with the control group, there were significant differences in SIRT3 at T1, SIRT3, and GPX4 at T2, and SIRT3 and GPX4 at T3 (P < .001). In terms of nerve injury-related proteins, in patients, MBP levels were negatively correlated with SIRT3 (r=-0.8979, P < .0001), MBP levels were positively correlated with GPX4 (r=0.528, P < .0001), and NGF levels were positively correlated with SIRT3 (r=0.8979, P < .0001), NGF level was negatively correlated with GPX4 (r=0.528, P < .0001). Conclusion: Glutathione tablets can alleviate sevoflurane-induced ferroptosis and oxidative stress by elevating GPX4 protein levels, and glutathione tablets have an ameliorative effect on brain injury in patients with sevoflurane inhalation anesthesia.