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BACKGROUND: Alfalfa is a perennial forage crop of high importance, but its cultivation is often affected by drought stress. Currently, the investigation of drought-related small RNAs is a popular research topic to uncover plant drought resistance mechanisms. Among these small RNAs, microRNA166 (miR166) is associated with drought in numerous plant species. Initial small RNA sequencing studies have shown that miR166 is highly responsive to exogenous nitric oxide (NO) and drought. Therefore, analyzing the expression of Msa-miR166 under nitric oxide and drought treatment is significant. RESULT: Bioinformatics analysis revealed that the miR166 family is widely distributed among plants, ranging from mosses to eudicots, with significant distribution differences between species. The evolutionary degree of Msa-miR166s is highly similar to that of Barrel medic (Medicago truncatula) and Soybean (Glycine max), but significantly different from the model plant Arabidopsis (Arabidopsis thaliana). It is suggested that there are no significant differences in miR166s within the species, and members of Msa-miR166s can form a typical stem-loop. The lowest level of exogenous nitric oxide was observed in Msa-miR166s under drought stress, followed by individual drought, and the highest level was observed after removing endogenous nitric oxide. CONCLUSION: In response to short-term drought, Msa-miR166s down-regulate expression in alfalfa (Medicago sativa L.). Exogenous nitric oxide can reduce the expression of Msa-miR166s in response to short-term drought. These findings suggest that Msa-miR166e-5p is responsive to environmental changes. The expression levels of target genes showed an opposite trend to Msa-miR166s, verifying the accuracy of Degradome sequencing in the early stage. This suggests that alfalfa experiences drought stress when regulated by exogenous nitric oxide, targeting HD ZIP-III, FRI, and CoA ligase genes. Additionally, the expression of Msa-miR166s in response to drought stress varies between leaves and roots, indicating spatiotemporal specificity.
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Proteínas de Arabidopsis , Arabidopsis , MicroARNs , Medicago sativa/genética , Proteínas de Plantas/genética , Óxido Nítrico/metabolismo , Sequías , Secuencia de Bases , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Proteínas de Arabidopsis/genética , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: Alfalfa (Medicago sativa. L) is one of the best leguminous herbage in China and even in the world, with high nutritional and ecological value. However, one of the drawbacks of alfalfa is its sensitivity to dry conditions, which is a global agricultural problem. The objective of this study was to investigate the regulatory effects of endogenous nitric oxide (NO) on endogenous hormones and related miRNAs in alfalfa seedling leaves under drought stress. The effects of endogenous NO on endogenous hormones such as ABA, GA3, SA, and IAA in alfalfa leaves under drought stress were studied. In addition, high-throughput sequencing technology was used to identify drought-related miRNAs and endogenous NO-responsive miRNAs in alfalfa seedling leaves under drought stress. RESULT: By measuring the contents of four endogenous hormones in alfalfa leaves, it was found that endogenous NO could regulate plant growth and stress resistance by inducing the metabolism levels of IAA, ABA, GA3, and SA in alfalfa, especially ABA and SA in alfalfa. In addition, small RNA sequencing technology and bioinformatics methods were used to analyze endogenous NO-responsive miRNAs under drought stress. It was found that most miRNAs were enriched in biological pathways and molecular functions related to hormones (ABA, ETH, and JA), phenylpropane metabolism, and plant stress tolerance. CONCLUSION: In this study, the analysis of endogenous hormone signals and miRNAs in alfalfa leaves under PEG and PEG + cPTIO conditions provided an important basis for endogenous NO to improve the drought resistance of alfalfa at the physiological and molecular levels. It has important scientific value and practical significance for endogenous NO to improve plant drought resistance.
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MicroARNs , Plantones , Plantones/genética , Plantones/metabolismo , Medicago sativa/genética , Óxido Nítrico/metabolismo , Sequías , MicroARNs/genética , MicroARNs/metabolismo , Hormonas/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.
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Variaciones en el Número de Copia de ADN , Factor de Transcripción GATA3 , PPAR gamma , Receptor ErbB-2 , Humanos , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Femenino , PPAR gamma/genética , PPAR gamma/metabolismo , Masculino , Neoplasias Urológicas/genética , Neoplasias Urológicas/patología , Anciano , Persona de Mediana Edad , Amplificación de Genes , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Regulación Neoplásica de la Expresión GénicaRESUMEN
Global outbreaks and the spread of viral diseases in the recent years have led to a rapid increase in the usage of antiviral drugs (ATVs), the residues and metabolites of which are discharged into the natural environment, posing a serious threat to human health. There is an urgent need to develop sensitive and rapid detection tools for multiple ATVs. In this study, we developed a highly sensitive electrochemical sensor comprising a glassy carbon electrode (GCE) modified with graphitized hydroxylated multi-walled carbon nanotubes (G-MWCNT-OH) and 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6, IL) for the detection of six ATVs including famciclovir (FCV), remdesivir (REM), favipiravir (FAV), hydroxychloroquine sulfate (HCQ), cepharanthine (CEP) and molnupiravir (MOL). The morphology and structure of the G-MWCNT-OH/IL nanocomposites were characterized comprehensively, and the electroactive surface area and electron conductivity of G-MWCNT-OH/IL/GCE were determined using cyclic voltammetry and electrochemical impedance spectroscopy. The thermodynamic stability and non-covalent interactions between the G-MWCNT-OH and IL were evaluated through quantum chemical simulation calculations, and the mechanism of ATV detection using the G-MWCNT-OH/IL/GCE was thoroughly examined. The detection conditions were optimized to improve the sensitivity and stability of electrochemical sensors. Under the optimal experimental conditions, the G-MWCNT-OH/IL/GCE exhibited excellent electrocatalytic performance and detected the ATVs over a wide concentration range (0.01-120 µM). The limit of detections (LODs) were 42.3 nM, 55.4 nM, 21.9 nM, 15.6 nM, 10.6 nM, and 3.2 nM for FCV, REM, FAV, HCQ, CEP, and MOL, respectively. G-MWCNT-OH/IL/GCE was also highly stable and selective to the ATVs in the presence of multiple interfering analytes. This sensor exhibited great potential for enabling the quantitative detection of multiple ATVs in actual water environment.
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Antivirales , Técnicas Electroquímicas , Líquidos Iónicos , Nanotubos de Carbono , Antivirales/análisis , Antivirales/química , Nanotubos de Carbono/química , Líquidos Iónicos/química , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Límite de Detección , Electrodos , Grafito/químicaRESUMEN
Isobavachalcone (IBC) is a flavonoid component of the traditional Chinese medicine Psoraleae Fructus, with a range of pharmacological properties. However, IBC causes some hepatotoxicity, and the mechanism of toxicity is unclear. The purpose of this paper was to investigate the possible mechanism of toxicity of IBC on HepG2 cells and zebrafish embryos. The results showed that exposure to IBC increased zebrafish embryo mortality and decreased hatchability. Meanwhile, IBC induced liver injury and increased expression of ALT and AST activity. Further studies showed that IBC caused the increase of ROS and MDA the decrease of CAT, GSH, and GSH-Px; the increase of Fe2+ content; and the changes of ferroptosis related genes (acsl4, gpx4, and xct) and iron storage related genes (tf, fth, and fpn) in zebrafish embryos. Through in vitro verification, it was found that IBC also caused oxidative stress and increased Fe2+ content in HepG2 cells. IBC caused depolarization of mitochondrial membrane potential (MMP) and reduction of mitochondrial ATP, as well as altered expression of ACSl4, SLC7A11, GPX4, and FTH1 proteins. Treatment of HepG2 cells with ferrostatin-1 could reverse the effect of IBC. Targeting the System Xc--GSH-GPX4 pathway of ferroptosis and preventing oxidative stress damage might offer a theoretical foundation for practical therapy and prevention of IBC-induced hepatotoxicity.
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Chalconas , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Transducción de Señal , Pez Cebra , Pez Cebra/embriología , Animales , Humanos , Chalconas/toxicidad , Chalconas/farmacología , Ferroptosis/efectos de los fármacos , Células Hep G2 , Transducción de Señal/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Embrión no Mamífero/efectos de los fármacos , Glutatión/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Estrés Oxidativo/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Nature-inspired supramolecular self-assemblies are attractive photocatalysts, but their quantum yields are limited by poor charge separation and transportation. A promising strategy for efficient charge transfer is to enhance the built-in electric field by symmetry breaking. Herein, an unsymmetric protonation, N-heterocyclic π-conjugated anthrazoline-based supramolecular photocatalyst SA-DADK-H+ was developed. The unsymmetric protonation breaks the initial structural symmetry of DADK, resulting in ca. 50-fold increase in the molecular dipole, and facilitates efficient charge separation and transfer within SA-DADK-H+. The protonation process also creates numerous active sites for H2O adsorption, and serves as crucial proton relays, significantly improving the photocatalytic efficiency. Remarkably, SA-DADK-H+ exhibits an outstanding hydrogen evolution rate of 278.2â mmol g-1 h-1 and a remarkable apparent quantum efficiency of 25.1 % at 450â nm, placing it among the state-of-the-art performances in organic semiconductor photocatalysts. Furthermore, the versatility of the unsymmetric protonation approach has been successfully applied to four other photocatalysts, enhancing their photocatalytic performance by 39 to 533â times. These findings highlight the considerable potential of unsymmetric protonation induced symmetry breaking strategy in tailoring supramolecular photocatalysts for efficient solar-to-fuel production.
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We assessed the efficacy and safety of sintilimab [an anti-programmed death (PD-1)] plus bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC). The patients received sintilimab (200 mg) plus IBI305 (7.5 mg/kg) and HAIC (FOLFOX for 23 h) and were treated every 3 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC) per mRECIST v1.1. Twenty-nine patients were enrolled in our clinical trial (1 patient voluntarily withdrew due to adverse events after the initial treatment). Objective response was reached in 17/29 (58.6%) patients per mRECIST. A total of 19/29 (65.5%) patients became eligible for further treatment; 14 of them completed surgical resection; 1 (5.3%) achieved pathological complete response (pCR); and 5 (26.3%) reached major partial response (mPR). The 1-year OS rate was better in the PR or pCR+mPR+PR group than in the PD+SD group by either mRECIST or pathological assessment (p=0.039 and 0.006). The 1-year EFS rate was better in the PR group than in the PD+SD group by pathological assessment (p=0.007). The most common treatment-related adverse events (TEAEs) in 30 HCC patients included thrombocytopenia (40.0%), hypertension (23.3%), and leukopenia (23.3%). The grade 3-5 TEAEs that were observed were hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). Sintilimab plus IBI305 and HAIC showed promising efficacy and manageable safety in patients with unresectable HCC. It might represent a novel treatment option for these patients.
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Anticuerpos Monoclonales Humanizados , Biosimilares Farmacéuticos , Carcinoma Hepatocelular , Hipertensión , Neoplasias Hepáticas , Humanos , Bevacizumab/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Biosimilares Farmacéuticos/uso terapéutico , Estudios Prospectivos , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Treatment options for patients with metastatic urothelial carcinoma ineligible for cisplatin-based chemotherapy have historically been limited. O'Donnell et al. recently reported the results of EV-103 Cohort K,1 leading to accelerated approval of enfortumab vedotin and pembrolizumab for cisplatin-ineligible patients and raising additional questions of how to best utilize this effective regimen.
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Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Cisplatino/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patologíaRESUMEN
BACKGROUND: Complement components could contribute to the tumor microenvironment and the systemic immune response. Nevertheless, their role in colorectal cancer (CRC) remains a contentious subject. AIM: To elucidate the relationship between complement components and CRC risk and clinical characteristics. METHODS: Searches were conducted in PubMed, the Cochrane Library, and the China National Knowledge Infrastructure database until June 1, 2023. We included cohort studies encompassing participants aged ≥ 18 years, investigating the association between complement components and CRC. The studies were of moderate quality or above, as determined by the Agency for Healthcare Research and Quality. The meta-analysis employed fixed-effects or random-effects models based on the I² test, utilizing risk ratio (RR) and their corresponding 95% confidence interval (CI) for outcomes. Sensitivity and subgroup analyses were performed to validate the robustness of the collective estimates and identify the source of heterogeneity. RESULTS: Data from 15 studies, comprising 1631 participants that met the inclusion criteria, were included in the meta-analysis. Our findings indicated that protein levels of cluster of differentiation 46 (CD46) (RR = 3.66, 95%CI: 1.75-7.64, P < 0.001), CD59 (RR = 2.86, 95%CI: 1.36-6.01, P = 0.005), and component 1 (C1) (RR = 5.88, 95%CI: 1.75-19.73, P = 0.004) and serum levels of C3 (standardized mean difference = 1.82, 95%CI: 0.06-3.58, P = 0.040) were significantly elevated in patients with CRC compared to healthy controls. Strong expression of CD55 or CD59 was associated with a higher incidence of lymph node metastasis, whereas strong CD46 expression correlated with a higher incidence of tumor differentiation compared to low CD46 expression (P < 0.05 for all). Although specific pooled results demonstrated notable heterogeneity, subgroup analyses pointed to regional differences as the primary source of inconsistency among the studies. CONCLUSION: Our analysis underscores that increased levels of specific complement components are associated with a heightened risk of CRC, emphasizing the potential significance of monitoring elevated complement component levels.
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OBJECTIVE: Insomnia is a significant health issue associated with various systemic diseases. Transcranial alternating current stimulation (tACS) has been proposed as a potential intervention for insomnia. However, the efficacy and mechanisms of tACS in chronic insomnia remain unclear. Accordingly, this study aimed to investigate the efficacy of tACS in treating chronic insomnia in adults and assess the impact of age on its effectiveness using a large sample from two centers. METHODS: A total of 120 participants with chronic insomnia underwent 20 daily sessions of tACS (duration: 40 min, frequency: 77.5 Hz, and intensity: 15 mA) or sham tACS targeting the forehead and both mastoid areas over 4 weeks. Assessments were conducted at baseline, post-treatment, and 4-week follow-up. Primary outcomes included sleep quality and efficiency, onset latency, total sleep time, and daily disturbances. Secondary outcomes included depression, anxiety, and clinical impression. RESULTS: Compared with the control group, the tACS group demonstrated improved sleep quality and efficiency, increased total sleep time, and reduced daily disturbance (all ps < 0.01). Moreover, tACS had a significant effect on clinical impression (p < 0.001), but not depression and anxiety scores. Subgroup analyses revealed that older participants experienced significant benefits from tACS in sleep quality, efficiency, and overall insomnia reduction at post-treatment and follow-up (p < 0.001). Notably, improved insomnia correlated with attenuated depressive and anxiety symptoms. CONCLUSIONS: These findings suggest that tACS may be an effective intervention for chronic insomnia within an eight-week timeframe, and age affects the response to tACS in terms of insomnia improvement.
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Trastornos del Inicio y del Mantenimiento del Sueño , Estimulación Transcraneal de Corriente Directa , Adulto , Humanos , Trastornos de Ansiedad , Método Doble Ciego , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Resultado del TratamientoRESUMEN
Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether aprepitant, a substance P receptor blocker could be utilized to alleviate poststroke pneumonia which is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 hours, 48 hours, and 72 hours poststroke. On the other hand, different concentrations of aprepitant (0.5, 1, and 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-hour poststroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate poststroke pneumonia in mice suggesting its potential therapeutic use in the clinic.
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Aprepitant , Líquido del Lavado Bronquioalveolar , Citocinas , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Ratones Endogámicos C57BL , Neumonía , Animales , Aprepitant/farmacología , Aprepitant/uso terapéutico , Masculino , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Neumonía/complicaciones , Neumonía/patología , Líquido del Lavado Bronquioalveolar/química , Citocinas/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/patología , Sustancia P/metabolismo , Pulmón/patología , Pulmón/efectos de los fármacos , Ratones , Morfolinas/farmacología , Morfolinas/uso terapéuticoRESUMEN
Growing evidence has increasingly suggested a potential linkage between the oral microbiome and various diseases, including pancreatic ductal adenocarcinoma (PDAC). However, the utilization of gene-level information derived from the oral microbiome for diagnosing PDAC remains unexplored. In this study, we sought to investigate the novel potential of leveraging genomic signatures associated with antibiotic resistance genes (ARGs) within the oral microbiome for the diagnosis of PDAC. By conducting an analysis of oral microbiome samples obtained from PDAC patients, we successfully identified specific ARGs that displayed distinct sequence abundance profiles correlated with the presence of PDAC. In the healthy group, three ARGs were found to be enriched, whereas 21 ARGs were enriched in PDAC patients. Remarkably, these ARGs from oral microbiome exhibited promising diagnostic capabilities for PDAC (AUROC = 0.79), providing a non-invasive and early detection method. Our findings not only provide novel modal data for diagnosing PDAC but also shed light on the intricate interplay between the oral microbiome and PDAC.
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Carcinoma Ductal Pancreático , Microbiota , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/microbiología , Neoplasias Pancreáticas/diagnóstico , Microbiota/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/microbiología , Carcinoma Ductal Pancreático/diagnóstico , Femenino , Masculino , Boca/microbiología , Persona de Mediana Edad , Farmacorresistencia Microbiana/genética , Anciano , Genómica/métodosRESUMEN
BACKGROUND: The incidence of ulcerative colitis (UC) is on the rise globally and the development of drugs targeting UC is urgent. Finding the target of action of natural products is important for drug discovery, elucidation of drug action mechanism, and disease mechanism. San-Ye-Qing (SYQ), is an ancient herbal medicine, but whether the powder of its rhizome has pharmacological effects against UC and its mechanism of action are not clear. PURPOSE: To evaluate the therapeutic effectiveness of rhizome powder of SYQ in treating UC, and conduct an isolation and characterization of the chemical constituents of the powder. Further, screen the most potent compounds among them and determine the potential mechanism for treating UC. METHODS: In vivo, the therapeutic effect of SYQ's rhizome powder on UC was assessed by mice's body weight, DAI score, colon length, tissue MPO activity, serum inflammatory markers, etc. Additionally, HPLC was used to isolate and identify the specific chemical components of SYQ's rhizome powder. Then, the most effective compounds and their therapeutic targets were analysed and screened in SYQ rhizome powder using network pharmacology, combined with CCK-8 assay, NO release assay and molecular docking assay, in conjunction with CETSA, DARTS, SPR and enzyme activity assay. Finally, the biological effects of the key compound on the targets were validated using Western blot and ELISA. RESULTS: In vivo, SYQ rhizome powder effectively restored mice's body weight, lowered DAI and pathological score, downregulated the expression of inflammatory biomarkers, and restored colon length, as well as the colonic epithelial and mucus barriers. Afterward, 9 compounds were isolated and identified from the powder of the rhizomes of SYQ by HPLC. Nicotiflorin is the primary compound in SYQ with the highest concentration. According to both CCK-8 and NO release tests, Nicotiflorin is also the most efficacious compound. Combined with network pharmacological prediction, molecular docking analysis, CETSA, DARTS, SPR and enzyme activity assay, Nicotiflorin may ultimately suppress inflammation by targeting p65 and inhibiting the NF-κB pathway, thereby attenuating the activation of NLRP3 inflammasome. To verify this conclusion, Western blot and ELISA experiments were conducted. CONCLUSIONS: Our results suggest that the extract from SYQ rhizomes has therapeutic properties for UC. Its active ingredient Nicotiflorin exerted potent anti-UC effects by binding to p65 and inhibiting the activation of NF-κB and NLRP3 inflammasomes.
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Antiinflamatorios , Colitis Ulcerosa , Medicamentos Herbarios Chinos , Rizoma , Colitis Ulcerosa/tratamiento farmacológico , Animales , Rizoma/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Antiinflamatorios/farmacología , Masculino , Simulación del Acoplamiento Molecular , Colon/efectos de los fármacos , Células RAW 264.7 , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , FN-kappa B/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Farmacología en RedRESUMEN
BACKGROUND: In China, traditional Chinese medicines (TCMs), as a complementary therapy combined with chemotherapy, is widely used in the treatment of gastric cancer (GC). In order to systematically evaluate and synthesize existing evidence to provide a scientific basis for the efficacy and safety of this complementary therapy, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TCMs as a complementary therapy in combination with chemotherapy for the treatment of GC. METHODS: SRs/MAs on TCMs combined with chemotherapy for GC were comprehensively searched in 8 databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. RESULTS: Thirteen published SRs/MAs were included in our study. In terms of methodology, all SRs/MAs were considered to be of very low quality. Only 3 SRs/MAs has been assessed as low risk of bias. None of the SRs/MAs has been fully reported on the checklist. A total of 97 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. CONCLUSIONS: TCMs may be an effective and safe complementary therapy in combination with chemotherapy for the treatment of GC. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.
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Terapia por Acupuntura , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Medicina Tradicional China , China , Bases de Datos FactualesRESUMEN
Recently, group activity recognition (GAR) has drawn growing interests in video analysis and computer vision communities. The current models of GAR tasks are often impractical in that they suppose that all interactions between actors are pairwise, which only models and leverages part of the information in real entire interactions. Motivated by this, we design a distinct dynamical attention hypergraph convolutional network framework, referred to as DAHGCN, for precise GAR, modeling the entire interactions and capturing the high-order relationships among involved actors in a real-life scenario. Specifically, to learn complementary feature representations for fine-grained GAR, a multilevel feature descriptor (MLFD) module is proposed. Furthermore, for learning higher order interaction relationships, we construct a DAHGCN to accommodate complex group interactions, which can dynamically change the topology of the hypergraph and learn these key representations by virtue of the "similarity-based shared nearest-neighbor (SSNN) clustering" and "attention mechanisms" on hypergraph. Finally, a multiscale temporal convolution (MSTC) module is utilized to explore various long-range temporal dynamic correlations across different frames. In addition, comprehensive experiments on three commonly used GAR datasets clearly demonstrate that, when compared with the state-of-the-art methods, our proposed method can achieve the most optimal performance.
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Postharvest rot is an urgent problem affecting the storage of winter jujube. Therefore, the development of new technologies for efficient and safe preservation is very important. This study aimed to elucidate the fungal microbiota found on the epidermis of jujube during the storage period using high-throughput sequencing, as well as to monitor the changes in quality indexes throughout this period. Through internal transcribed spacer (ITS) sequencing, we identified two phyla (Basidiomycota and Ascomycota) and six genera (Cryptococcus, Bulleromyces, Sporidiobolus, Alternaria, Pseudozyma, and Sporobolomyces), which potentially contribute to the spoilage and deterioration of jujube, referred to as "core fungal taxa". A high correlation was further found between preservation indices (including decay rate, firmness, and total soluble solids) and the growth of multiple core fungi over time. These findings will provide insights and a theoretical basis for further research on preservation techniques related to biological control during date fruit storage.
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Microbial ferroptosis has been proved to combat drug-resistant pathogens, but whether this pattern can be applied to the prevention and control of Escherichia coli remains to be further explored. In this study, ferrous gluconate (FeGlu) showed remarkable efficacy in killing E. coli MG1655 with a mortality rate exceeding 99.9%, as well as enterotoxigenic E. coli H10407 (ETEC H10407) and enterohemorrhagic E. coli O157:H7 (EHEC O157:H7). Bacteria death was instigated by the infiltration of Fe2+, accompanied by a burst of intracellular reactive oxygen species (ROS) and lipid peroxidation. Notably, mitigating lipid peroxidation failed to alleviate death of E. coli. Further findings confirmed that FeGlu induced DNA damage, and ΔrecA mutant showed more sensitive, implicating that DNA damage was involved in the death of E. coli. The direct interaction of Fe2+ with DNA was demonstrated by fluorescent staining, gel electrophoresis, and circular dichroism (CD). Moreover, proteomic analysis unveiled 50 differentially expressed proteins (DEPs), including 18 significantly down-regulated proteins and 32 significantly up-regulated proteins. Among them, the down-regulation of SOS-responsive transcriptional suppressor LexA indicated DNA damage induced severely by FeGlu. Furthermore, FeGlu influenced pathways such as fatty acid metabolism (FadB, FadE), iron-sulfur cluster assembly (IscA, IscU, YadR), iron binding, and DNA-binding transcription, along with α-linolenic acid metabolism, fatty acid degradation, and pyruvate metabolism. These pathways were related to FeGlu stress, including lipid peroxidation and DNA damage. In summary, FeGlu facilitated ferroptosis in E. coli through mechanisms involving lipid peroxidation and DNA damage, which presents a new strategy for the development of innovative antimicrobial strategies targeting E. coli infections.
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Daño del ADN , Escherichia coli , Ferroptosis , Compuestos Ferrosos , Peroxidación de Lípido , Especies Reactivas de Oxígeno , Ferroptosis/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Compuestos Ferrosos/metabolismo , Compuestos Ferrosos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Proteómica , Escherichia coli O157/efectos de los fármacos , Escherichia coli O157/genética , Escherichia coli O157/metabolismoRESUMEN
AIM: This study aims to explore the impact of emergency department internships on the attitudes towards death among undergraduate nursing students and their preferences for end-of-life care settings. Additionally, the study analyzes the reasons behind nursing students' choices of end-of-life care settings and provides insights for improving undergraduate education on attitudes towards death and end-of-life care, and provide reference for the development of emergency hospice care. DESIGN: This study adopts an observational design with a self-controlled before-and-after approach. METHODS: A questionnaire survey was conducted with 96 nursing interns between July 2021 to June 2022. Demographic information and data on attitudes towards death, and preferences for end-oflife care location were collected by online questionnaire. Paired test were conducted to compare differences between groups. RESULTS: The study included a total of 96 nursing students with an average age of 21.11 years. The scores for the avoidance-acceptance dimension of death attitudes before and after the internship were 2.40 (1.80, 3.00) and 2.20 (1.60, 3.00), respectively, showing a significant difference (Z = -2.084, p = 0.037). Factors such as gender, experience in caring for critically ill or dying patients, knowledge of death education, and discussions about death at home were found to influence nursing students' attitudes towards death. Nursing students expressed a preference for receiving end-of-life care and treatment in their homes or in hospice/palliative care wards, while the intensive care unit, emergency department, and nursing homes were the least preferred settings. There were significant differences in nursing students' preferences for end-of-life care settings before and after the internship (p = 0.000). Importantly, the number of nursing students expressing a desire to receive end-of-life care in the emergency department increased from 2 to 7 after the internship, while the number of students not wanting end-of-life care in the emergency department decreased by 5.
Asunto(s)
Actitud del Personal de Salud , Actitud Frente a la Muerte , Internado y Residencia , Estudiantes de Enfermería , Cuidado Terminal , Humanos , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Masculino , Femenino , Cuidado Terminal/psicología , Encuestas y Cuestionarios , Adulto Joven , AdultoRESUMEN
Purpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy. Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR. Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P=0.0182), PCT (P=0.0029), and CRP (P=0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P=0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA<7 was lower than that of the SOFA≥7 (P=0.0334). ddPCR (OR: 1.789, P=0.035) monitoring combined with PCT (OR: 1.787, P=0.035) holded predictive value for SOFA progression (AUC=0.7913, P=0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P=0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P=0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P=0.0003). Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.