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BACKGROUND: This study investigated drug-drug interactions in patients with atrial fibrillation taking both a direct oral anticoagulant (DOAC) and an antiarrhythmic drug. METHODS AND RESULTS: Using data from the National Health Insurance database (2012-2018), we identified 78 805 patients with atrial fibrillation on DOACs, with 24 142 taking amiodarone, 8631 taking propafenone, 2784 taking dronedarone, 297 taking flecainide, 177 taking sotalol, and 42 772 on DOACs alone. Patients with bradycardia, heart block, heart failure, mitral stenosis, prosthetic valves, or incomplete data were excluded. Propensity score matching compared those taking both DOACs and antiarrhythmic drugs with those on DOACs alone. There was an increased risk of major bleeding in patients concomitantly taking DOACs with amiodarone when compared with matched patients taking DOACs alone (hazard ratio [HR],1.13 [95% CI, 1.04-1.23]; P=0.0044), particularly in patients taking dabigatran (HR, 1.19 [95% CI, 1.03-1.38]; P=0.0175). No significant difference in bleeding risk was found for propafenone, dronedarone, flecainide, or sotalol. The small sample sizes in the flecainide and sotalol groups limit interpretation. Notably, intracranial bleeding risk was higher in patients on DOACs and amiodarone, regardless of age. Additionally, patients <80 years old taking dabigatran with amiodarone or propafenone had a higher risk of gastrointestinal bleeding. CONCLUSIONS: Concomitant use of DOACs with amiodarone, but not dronedarone or propafenone, increases the risk of major bleeding, particularly intracranial bleeding. This study provides new evidence to guide clinicians to tailor concomitant anticoagulation and antiarrhythmic therapy for patients with atrial fibrillation.
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Antiarrítmicos , Fibrilação Atrial , Interações Medicamentosas , Hemorragia , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Antiarrítmicos/efeitos adversos , Antiarrítmicos/administração & dosagem , Masculino , Feminino , Idoso , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Administração Oral , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Amiodarona/efeitos adversos , Amiodarona/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Taiwan/epidemiologia , Fatores de Risco , Bases de Dados Factuais , Estudos Retrospectivos , Medição de Risco , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Dronedarona/efeitos adversos , Dronedarona/administração & dosagem , Dabigatrana/efeitos adversos , Dabigatrana/administração & dosagem , Sotalol/efeitos adversos , Sotalol/administração & dosagem , Quimioterapia CombinadaRESUMO
BACKGROUND: CNSLBP accounts for 85% of all LBP cases and impairs physical health, quality of life, and work productivity, posing a significant health and economic burden. Baduanjin (BDJ) exercises are traditional Chinese Qi Gong mind-body exercises that have been practiced for over 1,000 years. However, the standard BDJ protocol established by the State Sports General Administration does not stimulate core muscles, limiting the effectiveness of low back pain rehabilitation. Therefore, it is necessary to improve the original BDJ protocol. METHODS: This 24-week single-center, single-blind, parallel-group randomized control superiority trial will allocate 100 patients into two groups (control and intervention) at a 1:1 ratio. The patients in the control group will perform the standard BDJ protocol established by the State Sports General Administration. The patients in the patients in the control group will perform the standard BDJ protocol established by the State Sports General Administration. The intervention group will perform intervention. The primary outcomes will be Quebec back pain disability scale. Secondary outcomes will include visual analog scale pain scores, Surface electromyography. The assessments of the tests will be performed at four time points. Adverse events will be recorded faithfully during the study. DISCUSSION: This randomized control trial is the first to compare a standard BDJ protocol and an optimized protocol in patients with CNSLBP. This study can help guide rehabilitation programs. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200065618, Registered on 10 Nov. 2022. This protocol is the first version 1, which was approved on 26 Aug 2022.
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Dor Lombar , Humanos , Dor Lombar/terapia , Método Simples-Cego , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Dor Crônica/terapia , Qigong/métodos , Terapia por Exercício/métodos , Medição da Dor , Adulto Jovem , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The challenge of preventing in-patient falls remains one of the most critical concerns in health care. OBJECTIVE: This study aims to investigate the effect of an integrated Internet of Things (IoT) smart patient care system on fall prevention. METHODS: A quasi-experimental study design is used. The smart patient care system is an integrated IoT system combining a motion-sensing mattress for bed-exit detection, specifying different types of patient calls, integrating a health care staff scheduling system, and allowing health care staff to receive and respond to alarms via mobile devices. Unadjusted and adjusted logistic regression models were used to investigate the relationship between the use of the IoT system and bedside falls compared with a traditional patient care system. RESULTS: In total, 1300 patients were recruited from a medical center in Taiwan. The IoT patient care system detected an average of 13.5 potential falls per day without any false alarms, whereas the traditional system issued about 11 bed-exit alarms daily, with approximately 4 being false, effectively identifying 7 potential falls. The bedside fall incidence during hospitalization was 1.2% (n=8) in the traditional patient care system ward and 0.1% (n=1) in the smart ward. We found that the likelihood of bedside falls in wards with the IoT system was reduced by 88% (odds ratio 0.12, 95% CI 0.01-0.97; P=.047). CONCLUSIONS: The integrated IoT smart patient care system might prevent falls by assisting health care staff with efficient and resilient responses to bed-exit detection. Future product development and research are recommended to introduce IoT into patient care systems combining bed-exit alerts to prevent inpatient falls and address challenges in patient safety.
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Acidentes por Quedas , Internet das Coisas , Segurança do Paciente , Humanos , Acidentes por Quedas/prevenção & controle , Segurança do Paciente/estatística & dados numéricos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Taiwan , Idoso de 80 Anos ou mais , Assistência ao Paciente/métodos , AdultoRESUMO
The regulation of adipose tissue metabolism by irisin involves modulating gene expressions related to energy metabolism and insulin sensitivity via miRNA-mediated signaling pathways within adipose tissue. Understanding the molecular mechanisms behind the role of irisin is vital for addressing obesity and related metabolic complications. In this study, we undertook an extensive miRNA transcriptomic approach to identify differentially expressed miRNAs following irisin exposure in adipocytes and murine white adipose tissue. Our findings spotlighted two miRNAs, miRNA-758 and miRNA-668, as being influenced by irisin. To understand the impact of the modulations of these miRNAs by irisin, we performed a signaling pathway and network analysis. After irisin exposure, both, miRNA-758 and miRNA-668, emerged as key regulators in leptin and CDK5 signaling pathways. Leptin, a hormone originating from adipose tissue, is primarily produced by adipocytes, and its effects are known to be mediated by CDK5. In essence, this study identifies pivotal genes and miRNAs in irisin-driven mechanisms in adipose tissue, offering valuable insights for crafting novel therapeutic strategies for metabolic and associated disorders.
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Adipócitos , Quinase 5 Dependente de Ciclina , Fibronectinas , MicroRNAs , Transdução de Sinais , MicroRNAs/genética , MicroRNAs/metabolismo , Fibronectinas/metabolismo , Fibronectinas/genética , Animais , Camundongos , Adipócitos/metabolismo , Quinase 5 Dependente de Ciclina/metabolismo , Quinase 5 Dependente de Ciclina/genética , Leptina/metabolismo , Leptina/genética , Regulação da Expressão Gênica , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Células 3T3-L1 , Humanos , Perfilação da Expressão Gênica , Metabolismo Energético/genética , Obesidade/metabolismo , Obesidade/genéticaRESUMO
OBJECTIVE: Language is one of the most celebrated hallmarks of human cognition. With the continuous improvement of medical technology, functional MRI (fMRI) has been used in aphasia. Although many related studies have been carried out, most studies have not extensively focused on brain regions with reduced activation in aphasic patients. The aim of this study was to identify brain regions normally activated in healthy controls but with reduced activation in aphasic patients during fMRI language tasks. METHODS: We collected all previous task-state fMRI studies of secondary aphasia. The brain regions showed normal activation in healthy controls and reduced activation in aphasic patients were conducted activation likelihood estimation (ALE) meta-analysis to obtain the brain regions with consistently reduced activation in aphasic patients. RESULTS: The ALE meta-analysis revealed that the left inferior frontal gyrus, left middle temporal gyrus, left superior temporal gyrus, left fusiform gyrus, left lentiform nucleus and the culmen of the cerebellum were the brain regions with reduced activation in aphasic patients. DISCUSSION: These findings from the ALE meta-analysis have significant implications for understanding the language network and the potential for recovery of language functions in individuals with aphasia.
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We compared infant bone marrow-derived mesenchymal stem cells (infant BMSCs) with umbilical cord-derived mesenchymal stem cells (UCSCs) by assessing multilineage differentiation. Proliferation was gauged through changes in cell numbers and doubling time. Senescence-related genes (p16, p21, and p53), senescence-associated ß-galactosidase (SA-ß-gal), and γH2AX immunofluorescence determined senescence presence. Superoxide dismutases (SODs) and genes related to various differentiations were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Differentiation was confirmed through histochemical, immunohistochemical, and immunofluorescence staining. Infant BMSCs surpassed UCSCs in proliferation. Infant BMSCs exhibited lower senescence-related gene expression at late passages, upregulated antioxidant enzymes during early passages, and reduced SA-ß-gal staining. Chondrogenic gene expression (SOX9, COL2, and COL10) was enhanced in infant BMSCs, along with improved immunohistochemical staining. Infant BMSCs showed higher expression of osteogenic (ALP and OCN) and adipogenic (PPARγ and LPL) genes, confirmed by histochemical staining. However, UCSCs had higher expression of tenogenic genes (MMP3, SCX, DCN, and TNC). Hepatogenic differentiation potential was similar, with no significant difference in hepatogenic gene expression (ALB and TAT). Compared to UCSCs, infant BMSCs demonstrated superior proliferation, reduced senescence, increased antioxidant capacity, and enhanced differentiation potential toward chondrogenic, osteogenic, and adipogenic lineages.
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BACKGROUND: The ecosystems of marine ranching have enhanced marine biodiversity and ecological balance and have promoted the natural recovery and enhancement of fishery resources. The microbial communities of these ecosystems, including bacteria, fungi, protists, and viruses, are the drivers of biogeochemical cycles. Although seasonal changes in microbial communities are critical for ecosystem functioning, the current understanding of microbial-driven metabolic properties and their viral communities in marine sediments remains limited. Here, we employed amplicon (16S and 18S) and metagenomic approaches aiming to reveal the seasonal patterns of microbial communities, bacterial-eukaryotic interactions, whole metabolic potential, and their coupling mechanisms with carbon (C), nitrogen (N), and sulfur (S) cycling in marine ranching sediments. Additionally, the characterization and diversity of viral communities in different seasons were explored in marine ranching sediments. RESULTS: The current study demonstrated that seasonal variations dramatically affected the diversity of microbial communities in marine ranching sediments and the bacterial-eukaryotic interkingdom co-occurrence networks. Metabolic reconstruction of the 113 medium to high-quality metagenome-assembled genomes (MAGs) was conducted, and a total of 8 MAGs involved in key metabolic genes and pathways (methane oxidation - denitrification - S oxidation), suggesting a possible coupling effect between the C, N, and S cycles. In total, 338 viral operational taxonomic units (vOTUs) were identified, all possessing specific ecological characteristics in different seasons and primarily belonging to Caudoviricetes, revealing their widespread distribution and variety in marine sediment ecosystems. In addition, predicted virus-host linkages showed that high host specificity was observed, with few viruses associated with specific hosts. CONCLUSIONS: This finding deepens our knowledge of element cycling and viral diversity in fisheries enrichment ecosystems, providing insights into microbial-virus interactions in marine sediments and their effects on biogeochemical cycling. These findings have potential applications in marine ranching management and ecological conservation. Video Abstract.
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Bactérias , Biodiversidade , Pesqueiros , Sedimentos Geológicos , Microbiota , Estações do Ano , Vírus , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/virologia , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificação , Ecossistema , Metagenoma , Enxofre/metabolismo , Metagenômica , Carbono/metabolismo , Nitrogênio/metabolismoRESUMO
INTRODUCTION: Eleclazine is a highly selective late sodium current inhibitor, possibly effective in reducing ventricular fibrillation (VF) in heart failure (HF) with ischemia-reperfusion (IR) injury. The electrophysiological effects of eleclazine at therapeutic hypothermia (TH) are unknown. We investigated the effects of eleclazine in suppressing VF in failing rabbit hearts with IR injury undergoing TH. METHOD: HF was induced by right ventricular pacing. An IR model was created using coronary artery ligation for 60 min, followed by reperfusion for 30 min. Hearts were excised and Langendorff-perfused for optical mapping and electrophysiological studies. Electrophysiological studies were repeated after TH (33 oC) for 30 min or eleclazine (1 µM) infusion for 20 min. RESULTS: In failing IR-injured hearts, eleclazine reduced action potential duration (APD) dispersion and accelerated intracellular Ca2+ uptake to suppress arrhythmogenic alternans, but also exacerbated rate-dependent conduction slowing, resulting in neutral effects on VF inducibility at normothermia. TH increased VF severity. Eleclazine after TH ameliorated TH-induced APD dispersion and further depressed conduction to reduce VF inducibility and severity. TH after eleclazine also slowed conduction to a greater extent to reduce VF inducibility and severity by extrastimulus pacing. In control IR-injured hearts, eleclazine increased VF severity by dynamic pacing at normothermia, which was counteracted by TH. CONCLUSIONS: Eleclazine does not prevent VF at normothermia, but reduces VF inducibility and severity by extrastimulus pacing at TH in isolated failing hearts with regional IR injury.
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The injudicious use of water and fertilizer to maximize crop yield not only leads to environmental pollution, but also causes enormous economic losses. For this reason, we investigated the effect of nitrogen (N) (N0 (0), N60 (60 kg ha-1), and N120 (120 kg ha-1)) at different irrigation levels (I0 (0), I1200 (budding 600 m3 ha-1 + kernel 600 m3 ha-1), and I1800 (budding 900 m3 ha-1 + kernel 900 m3 ha-1)) on oilseed flax in the Loess Plateau of China in 2019 and 2020. The objective was to establish appropriate irrigation and fertilizer management strategies that enhance the grain yield (GY) of oilseed flax and maximize water and N productivity. The results demonstrated that irrigation and N application and their coupling effects promoted dry matter accumulation (DMA) and non-structural carbohydrate (NSC) synthesis, and increased the GY of oilseed flax. The contents of NSC in various organs of flax were closely related to grain yield and yield components. Higher NSC in stems was conducive to increased sink capacity (effective capsule number per plant (EC) and thousand kernel weight (TKW)), and the coupling of irrigation and N affected GY by promoting NSC synthesis. Higher GY was obtained by the interaction of irrigation and N fertilizer, with the increase rate ranging from 15.84% to 35.40%. Additionally, in the increased yield of oilseed flax, 39.70-78.06%, 14.49-54.11%, and -10.6-24.93% were contributed by the application of irrigation and nitrogen and the interaction of irrigation and nitrogen (I × N), respectively. Irrigation was the main factor for increasing the GY of oilseed flax. In addition, different climatic conditions changed the contribution of irrigation and N and their interaction to yield increase in oilseed flax. Drought and low temperature induced soluble sugar (SS) and starch (ST) synthesis to resist an unfavorable environment, respectively. The structural equation model showed that the key factors to increasing the GY of oilseed flax by irrigation and nitrogen fertilization were the differential increases in DMA, EC, and TKW. The increases in EC and TKW were attributed to the promotion of DMA and NSC synthesis in oilseed flax organs by irrigation, nitrogen fertilization, and their coupling effects. The I1200N60 treatment obtained higher water use efficiency (WUE) and N partial factor productivity (NPFP) due to lower actual evapotranspiration (ETa) and lower N application rate. Therefore, the strategy of 1200 m3 ha-1 irrigation and 60 kg ha-1 N application is recommended for oilseed flax in semi-arid and similar areas to achieve high grain yield and efficient use of resources.
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Aims/Background To investigate the application value of a machine learning model in predicting mild depression associated with migraine without aura (MwoA). Methods 178 patients with MwoA admitted to the Department of Neurology of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from March 2022 to March 2024 were selected as subjects. According to their inpatient medical records, 38 patients were selected as the validation group by random number method, and the remaining 140 patients were included in the modelling group. According to the diagnosis results, the patients in the modelling group and validation group were further divided into a MwoA with mild depression group and a MwoA without mild depression group. Results The results of univariate analysis and Multivariate logistic regression analysis showed that gender, course of disease, attack frequency, headache duration, Migraine Disability Assessment Questionnaire (MIDAS), and Headache Impact Test-6 (HIT-6) score were independent influencing factors for mild depression in MwoA patients (p < 0.05). The receiver operating characteristic (ROC) analysis results showed that the area under the curve of the established prediction model for MwoA patients with mild depression in the modelling group and the validation group was 0.982 and 0.901, respectively, the sensitivity was 0.978 and 0.857, respectively, and the specificity was 0.892 and 0.929, respectively. Conclusion Gender, course of disease, seizure frequency, headache duration, MIDAS score, and HIT-6 score are independent influencing factors for mild depression in patients with MwoA. The model displays good performance for the prediction of mild depression in patients with MwoA.
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Depressão , Aprendizado de Máquina , Enxaqueca sem Aura , Humanos , Feminino , Masculino , Adulto , Enxaqueca sem Aura/diagnóstico , Depressão/diagnóstico , Pessoa de Meia-Idade , Curva ROC , Modelos LogísticosRESUMO
Supramalleolar osteotomy (SMO) is a representative procedure to restore a malalignment in the varus ankle deformity by shifting the concentrated pressure on the medial ankle joint to the lateral area. Additionally, fibula osteotomy (FO) is selectively selected and performed according to the surgeon's preference. However, it is controversial whether FO is effective in shifting the abnormal pressure from the medial to the lateral area on the ankle joint. Some cadaveric studies have been performed to prove this. However, it is difficult to consistently reconstruct amount of the varus ankle deformities angle in cadavers and to guarantee reliable contact pressure between the ankle joint. Thus, the aim of this study was predicted and quantitatively compared a peak pressure between single SMO and SMO with FO procedure by using a finite element analysis as a powerful biomechanical tool to those limitations of cadaveric study. This study reconstructed total 4 3D foot and ankle models including a normal and pre-op model and 2 post-op models. The pre-op model was modified by assigning 10° varus tilting corresponding to stage 3b in the classification of varus ankle osteoarthritis based on the validated normal model. Also, the post-op models were reconstructed by applying single SMO and SMO with FO, respectively. All of the models were assumed as one-leg standing position and to mimic smooth ankle joint motion. Peak contact pressure change was predicted at the medial ankle joint by using computational simulation. As a result, 2 post-op models showed a remarkably peak pressure reduction by up to 5.5 times on the medial tibiotalar joint. However, a comparison between single SMO and SMO with FO model showed no appreciable differences. In conclusion, this study predicted that single SMO may be as effective as SMO with FO in reducing peak contact pressure on the medial tibiotalar joint in varus ankle osteoarthritis.
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INTRODUCTION AND OBJECTIVES: The impact of sleep on metabolic dysfunction-associated steatotic liver disease (MASLD) in American adults remains unclear. This study aimed to address the relationship of sleep patterns and disorders with MASLD and liver fibrosis comprehensively. MATERIALS AND METHODS: This cross-sectional study included adult participants from the National Health and Nutrition Examination Survey 2017-2020. Multivariate adjusted regression analysis were used to examine the association of sleep with MASLD and liver fibrosis. We further addressed these associations using restricted cubic splines, mediation analysis, stratified analysis and multiple sensitivity analysis. RESULTS: We enrolled 5368 participants. Certain sleep disorders, sleep duration, high sleep debt and specific sleep-wake time were associated with MASLD. Late workday sleep was a shared risk factor for MASLD and liver fibrosis. Short sleep on workdays and free days favored MASLD, whereas average weekly long sleep protected against MASLD. Workday, free day and average weekly optimal sleep duration was 7.5 h, 8 h and 7.78 h, respectively. Mediation analysis suggested that fasting glucose and high-density lipoprotein cholesterol indirectly mediated the relationship between sleep duration and MASLD, whereas stratified analysis showed that sex influenced the relationship, and that the correlation was only observed in women and specific age groups. CONCLUSIONS: Sleep duration independently affected MASLD but only in women and specific age groups. Moreover, late sleep on workdays was a shared risk factor for MASLD and liver fibrosis. These results suggest targeting sleep behaviors for MASLD prevention and developing age- and sex-specific strategies.
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Carbon dots (CDs)-minute carbon nanoparticles with remarkable luminescent properties, photostability, and low toxicity-show potential for various applications. CDs synthesized using citric acid and urea are the least toxic to biological environments. Here, we aimed to explore the effect of CDs synthesized using citric acid and urea at 50, 33, and 25% (CDs 1/1, 1/2, and 1/3, respectively) weight ratios in a microwave on bacterial cell fluorescence sensing and labeling. The nanoscale properties of CDs were investigated via transmission electron microscopy and dynamic light scattering particle size analysis. X-ray powder diffraction confirmed the graphitic structures of CDs. X-ray photoelectron spectroscopy revealed that the nitrogen content increased gradually with increasing urea ratios, indicating functional group changes. Transient photoluminescence decay periods demonstrated superior fluorescence intensity of CDs 1/3 under blue, green, and red lights. The use of CDs was notably more efficient than traditional methods in staining bacterial cells. Fluorescence microscopy of 10 g-positive and 10 g-negative bacteria revealed enhanced staining of Gram-positive strains, with CDs 1/3 presenting the best results. The CDs exhibited excellent photostability, maintaining poststaining fluorescence for 100 min, surpassing the performance of conventional dyes. CDs could serve as potential fluorescent dyes for the rapid discrimination of Gram-positive and Gram-negative bacteria.
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Programmable metasurfaces have garnered significant attention for their capacity to dynamically manipulate electromagnetic (EM) waves. In particular, the programmable metasurfaces offer to generate a wide range of EM beams when the appropriate digital coding patterns are designed. Traditionally, optimizing the coding patterns involves time-consuming nonlinear optimization algorithms due to the high computational complexity. In this study, we propose a physics-assisted deep learning (DL) model that can calculate the coding pattern in milliseconds, requiring only a simple depiction of the desired beam. An extended version of the macroscopic model for digital coding metasurface is introduced as the physics-driven component, which can compute the radiation pattern rapidly based on the provided coding pattern. The integration of the macroscopic model ensures to generate the physics-compliant coding designs. We validate the proposed method experimentally by measuring several coding patterns for both single-beam and dual-beam scenarios, which demonstrate good performance of beamforming.
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The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.
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Oryza , Doenças das Plantas , Proteínas de Plantas , Ativação Transcricional , Ubiquitina-Proteína Ligases , Ubiquitinação , Doenças das Plantas/microbiologia , Oryza/microbiologia , Oryza/metabolismo , Oryza/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fosforilação , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Imunidade Vegetal/genética , AscomicetosRESUMO
BACKGROUND: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM: To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS: Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS: A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION: In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.
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Cirrose Hepática , Transplante de Células-Tronco Mesenquimais , Animais , Humanos , Terapia Combinada/métodos , Modelos Animais de Doenças , Progressão da Doença , Fígado/patologia , Fígado/efeitos dos fármacos , Cirrose Hepática/patologia , Cirrose Hepática/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
During an investigation of fungal diversity from freshwater environments in different regions in Jiangxi Province, China, four interesting species were collected. Morphology coupled with combined gene analysis of an ITS, LSU, SSU, and rpb2 DNA sequence data showed that they belong to the family Pleurotheciaceae. Four new species, Pleurotheciella ganzhouensis, Pla. irregularis, Pla. verrucosa, and Pleurothecium jiangxiense are herein described. Pleurotheciella ganzhouensis is characterized by its capsule-shaped conidia and short conidiophores, while Pla. irregularis has amorphous conidiophores and 3-septate conidia. Pleurotheciella verrucosa has cylindrical or verrucolose conidiogenous cells, 1-septate, narrowly fusiform, meniscus or subclavate conidia. Pleurothecium jiangxiense characterized in having conidiogenous cells with dense cylindrical denticles and short conidiophores. Pleurothecium obovoideum was transferred to Neomonodictys based on phylogenetic evidence. All species are compared with other similar species and comprehensive descriptions, micrographs, and phylogenetic data are provided.
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BACKGROUND: Preoperative risk stratification is significant for the management of endometrial cancer (EC) patients. Radiomics based on magnetic resonance imaging (MRI) in combination with clinical features may be useful to predict the risk grade of EC. AIM: To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI. METHODS: The study comprised 112 EC patients. The participants were randomly separated into training and validation groups with a 7:3 ratio. Logistic regression analysis was applied to uncover independent clinical predictors. These predictors were then used to create a clinical nomogram. Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images, the Mann-Whitney U test, Pearson test, and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features, which were subsequently utilized to generate a radiomic signature. Seven machine learning strategies were used to construct radiomic models that relied on the screening features. The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators. RESULTS: Having an accuracy of 0.82 along with an area under the curve (AUC) of 0.915 [95% confidence interval (CI): 0.806-0.986], the random forest method trained on radiomics characteristics performed better than expected. The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram (AUC: 0.75, 95%CI: 0.611-0.899) and the combined nomogram (AUC: 0.869, 95%CI: 0.702-0.986) that integrated clinical parameters and radiomic signature. CONCLUSION: The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.
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The hallmark pathological features of Alzheimer's disease (AD) consist of senile plaques, which are formed by extracellular ß-amyloid (Aß) deposition, and neurofibrillary tangles, which are formed by the hyperphosphorylation of intra-neuronal tau proteins. With the increase in clinical studies, the in vivo imbalance of iron homeostasis and the dysfunction of synaptic plasticity have been confirmed to be involved in AD pathogenesis. All of these mechanisms are constituted by the abnormal accumulation of misfolded or conformationally altered protein aggregates, which in turn drive AD progression. Proteostatic imbalance has emerged as a key mechanism in the pathogenesis of AD. Ubiquitination modification is a major pathway for maintaining protein homeostasis, and protein degradation is primarily carried out by the ubiquitin-proteasome system (UPS). In this review, we provide an overview of the ubiquitination modification processes and related protein ubiquitination degradation pathways in AD, focusing on the microtubule-associated protein Tau, amyloid precursor protein (APP), divalent metal transporter protein 1 (DMT1), and α-amino-3-hyroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. We also discuss recent advances in ubiquitination-based targeted therapy for AD, with the aim of contributing new ideas to the development of novel therapeutic interventions for AD.