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BACKGROUND: Current treatments do not support direct exposure of fracture fragments, resulting in the inability to directly observe the articular surface during surgery for accurate reduction and firm fixation. OBJECTIVE: The aim of the study was to explore the treatment effect of digital virtual reduction combined with individualized guide plate of lateral tibial condyle osteotomy on tibial plateau fracture involving the lateral posterior condyle collapse. METHODS: 41 patients with tibial plateau fracture involving the lateral posterior condyle collapse were recruited in the trial. All patients underwent Computed Tomography (CT) scanning before operation. After operation, fracture reduction was evaluated using Rasmussen score and function of knee joint was assessed using hospital for special surgery (HSS) score. RESULTS: 41 patients were followed-up 6-26 months (mean, 15.2 months). Fracture reduction was good after operation, with an average of 13.3 weeks of fracture healing without serious complications. The excellent and good rate was 97.6%. The joint movement degree was -5∘â¼0∘â¼135∘ with an average of 125.5∘. CONCLUSIONS: Digital virtual reduction combined with individualized guide plate of lateral tibial condyle osteotomy was effectively for treating tibial plateau fracture involving the lateral posterior condyle collapse.
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Although nanozymes have shown significant potential in wastewater treatment, enhancing their degradation performance remains challenging. Herein, a novel catalytic behavior was revealed for defective nanozymes with catalase-mimicking characteristics that efficiently degraded tetracycline (TC) in wastewater. Hydroxyl groups adsorbed on defect sites facilitated the in-situ formation of vacancies during catalysis, thereby replenishing active sites. Additionally, electron transfer considerably enhanced the catalytic reaction. Consequently, numerous reactive oxygen species (ROS) were generated through these processes and subsequent radical reactions. The defective nanozymes, with their unique catalytic behavior, proved effective for the catalytic degradation of TC. Experimental results demonstrate that â¢OH, â¢O2-, 1O2 and e- were the primary contributors to the degradation process. In real wastewater samples, the normalized degradation rate constant for defective nanozymes reached 26.0 min-1 g-1 L, exceeding those of other catalysts. This study reveals the new catalytic behavior of defective nanozymes and provides an effective advanced oxidation process for the degradation of organic pollutants.
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Tomatoes, widely cherished for their high nutritional value, necessitate precise ripeness identification and selective harvesting of mature fruits to significantly enhance the efficiency and economic benefits of tomato harvesting management. Previous studies on intelligent harvesting often focused solely on identifying tomatoes as the target, lacking fine-grained detection of tomato ripeness. This deficiency leads to the inadvertent harvesting of immature and rotten fruits, resulting in economic losses. Moreover, in natural settings, uneven illumination, occlusion by leaves, and fruit overlap hinder the precise assessment of tomato ripeness by robotic systems. Simultaneously, the demand for high accuracy and rapid response in tomato ripeness detection is compounded by the need for making the model lightweight to mitigate hardware costs. This study proposes a lightweight model named PDSI-RTDETR to address these challenges. Initially, the PConv_Block module, integrating partial convolution with residual blocks, replaces the Basic_Block structure in the legacy backbone to alleviate computing load and enhance feature extraction efficiency. Subsequently, a deformable attention module is amalgamated with intra-scale feature interaction structure, bolstering the capability to extract detailed features for fine-grained classification. Additionally, the proposed slimneck-SSFF feature fusion structure, merging the Scale Sequence Feature Fusion framework with a slim-neck design utilizing GSConv and VoVGSCSP modules, aims to reduce volume of computation and inference latency. Lastly, by amalgamating Inner-IoU with EIoU to formulate Inner-EIoU, replacing the original GIoU to expedite convergence while utilizing auxiliary frames enhances small object detection capabilities. Comprehensive assessments validate that the PDSI-RTDETR model achieves an average precision mAP50 of 86.8%, marking a 3.9% enhancement over the original RT-DETR model, and a 38.7% increase in FPS. Furthermore, the GFLOPs of PDSI-RTDETR have been diminished by 17.6%. Surpassing the baseline RT-DETR and other prevalent methods regarding precision and speed, it unveils its considerable potential for detecting tomato ripeness. When applied to intelligent harvesting robots in the future, this approach can improve the quality of tomato harvesting by reducing the collection of immature and spoiled fruits.
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The emergence and widespread of tigecycline resistance undoubtedly poses a serious threat to public health globally. The exploration of combination therapies has become preferred antibacterial strategies to alleviate this global burden. In this study, tigecycline-resistant tet(X4)-positive Escherichia coli were selected for adjuvant screening. Interestingly, 9-aminominocycline (9-AMC), one of the tigecycline metabolites, exhibits synergistic antibacterial activity with tigecycline using checkerboard assay. The efficacy in vitro and in vivo was evaluated, and the synergistic mechanism was further explored. The results suggested that 9-AMC combined with tigecycline could inhibit the growth of antibiotic resistant bacteria, efficiently retard the evolution of tet(X4) gene and narrow the drug mutant selection window. In addition, the combination of tigecycline and 9-AMC could destroy the normal membrane structure of bacteria, inhibit the formation of biofilm, remarkably reduce the level of intracellular ATP level, and accelerate the oxidative damage of bacteria. Furthermore, 9-AMC is more stable in the bind of Tet(X4) inactivating enzyme. The transcriptomics analysis revealed that the genes related to the 9-AMC and tigecycline were mainly enriched in ABC transporters. Collectively, the results reveal the potentiation effects on tigecycline and the probability of 9-AMC as a novel tigecycline adjuvant against tet(X4)-positive Escherichia coli, which provides new insights for adjuvant screening.
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Rhodiola, belonging to the Crassulaceae family, is a perennial herbaceous plant genus. There are about 90 Rhodiola species worldwide, some of which have been reported to have medicinal properties. Rhodiola sachalinensis is a perennial medicinal herb within this genus and, in the present study, its chloroplast genome was sequenced, assembled, annotated and compared with 24 other Rhodiola species. The results obtained show that the chloroplast genome of R. sachalinensis is 151 595 bp long and has a CG content of 37.7%. The inverted repeats (IR) region of the Rhodiola chloroplast genome is the most conserved region, with the main differences being observed in the ycf1 and ndhF genes at the IRb-small single copy boundary, and rps19 and trnH genes at the IRa-large single copy boundary. Phylogenetic analysis showed that Rhodiola species form two major clades, and species with recorded medicinal properties, clustered together in one branch except for R. dumulosa. Within the genus, R. sachalinensis is most closely related to Rhodiola rosea, although comparative analyses showed that only R. sachalinensis and Rhodiola subopposita contained the psbZ gene, which encodes a highly conserved protein subunit of the Photosystem II core complex. Overall, the present study contributes to the understanding of the chloroplast genome of Rhodiola species, and provides a theoretical basis for the study of their genetic diversity and possible use as medicinal plants.
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Genoma de Cloroplastos , Filogenia , Rhodiola , Rhodiola/genética , Genoma de Cloroplastos/genética , Plantas Medicinais/genéticaRESUMO
To determine the expression of chemokine 8 (CXCL8) in non-small cell lung cancer (NSCLC) patients and analyze its correlation with tumor characteristics and patient prognosis. We conducted a retrospective analysis of 149 NSCLC patients treated between January 2016 and April 2018, measuring serum CXCL8 expression upon admission or prior to treatment. The clinical characteristics, including lymph node metastasis and staging, based on CXCL8 expression levels, were analyzed. Receiver Operating Characteristic (ROC) curves was drawn to assess its predictive value for lymph node metastasis and staging in NSCLC patients. Furthermore, the Kaplan-Meier curve was plotted to assess the impact of CXCL8 on 5-year survival in NSCLC Patients. NSCLC patients exhibited significantly higher serum CXCL8 levels than those with benign tumors (P<0.001), with the high CXCL8 expression group showing a higher incidence of lymph node metastasis or stage III NSCLC (P<0.01). CXCL8 was identified as an independent predictor of lymph node metastasis (AUC=0.730) and higher TNM stage (AUC=0.708), as well as a validated biomarker for predicting five-year survival in NSCLC patients. This study highlights the strong association between CXCL8 expression in NSCLC and patient prognosis, particularly regarding lymph node metastasis and clinical staging, suggesting the need for further research to explore CXCL8's specific role in the tumor microenvironment and its impact on different NSCLC subtypes.
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Purpose To demonstrate the myocardial strain characteristics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), based on revised Task Force Criteria (rTFC), and to explore the prognostic value of strain analysis in ARVC. Materials and Methods This retrospective study included 247 patients (median age, 38 years [IQR, 28-48 years]; 167 male, 80 female) diagnosed with ARVC, based on rTFC, between 2014 and 2018. Patients were divided into "possible" (n =25), "borderline" (n = 40), and "definite" (n = 182) ARVC groups following rTFC. Biventricular global strain parameters were calculated using cardiac MRI feature tracking (FT). The primary outcome was defined as a composite of cardiovascular events, including cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator discharge. Univariable and multivariable cumulative logistic regression and Cox proportional hazards regression analysis were used to evaluate the diagnostic and prognostic value of right ventricle (RV) strain parameters. Results Patients with definite ARVC had significantly reduced RV global strain in all three directions compared with possible or borderline groups (all P < .001). RV global longitudinal strain (GLS) was an independent predictor for disease (odds ratio, 1.09 [95% CI: 1.02, 1.16]; P = .009). During a median follow-up of 3.4 years (IQR, 2.0-4.9 years), 55 patients developed primary end point events. Multivariable analysis showed that RV GLS was independently associated with the occurrence of cardiovascular events (hazard ratio, 1.15 [95% CI: 1.07, 1.24]; P < .001). Kaplan-Meier analysis showed that patients with RV GLS worse than median had a higher risk of combined cardiovascular events (log-rank P < .001). Conclusion RV GLS derived from cardiac MRI FT demonstrated good diagnostic and prognostic value in ARVC. Keywords: MR Imaging, Image Postprocessing, Cardiac, Right Ventricle, Cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy, Revised Task Force Criteria, Cardiovascular MR, Feature Tracking, Cardiovascular Events Supplemental material is available for this article. © RSNA, 2024.
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Displasia Arritmogênica Ventricular Direita , Ventrículos do Coração , Humanos , Displasia Arritmogênica Ventricular Direita/diagnóstico por imagem , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Prognóstico , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/patologia , Imagem Cinética por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Função Ventricular Direita/fisiologiaRESUMO
In this study, large yellow croaker (Larimichthys crocea) was frozen using multi-frequency ultrasound-assisted freezing (MUIF) with different powers (160 W, 175 W, and 190 W, respectively) and stored at -18 °C for ten months. The effect of different ultrasound powers on the myofibrillar protein (MP) structures and lipid oxidation of large yellow croaker was investigated. The results showed that MUIF significantly slowed down the oxidation of MP by inhibiting carbonyl formation and maintaining high sulfhydryl contents. These treatments also held a high activity of Ca2+-ATPase in the MP. MUIF maintained a higher ratio of α-helix to ß-sheet during frozen storage, thereby protecting the secondary structure of the tissue and stabilizing the tertiary structure. In addition, MUIF inhibited the production of thiobarbituric acid reactive substances value and the loss of unsaturated fatty acid content, indicating that MUIF could better inhibit lipid oxidation of large yellow croaker during long-time frozen storage.
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Congelamento , Oxirredução , Perciformes , Animais , Fatores de Tempo , Armazenamento de Alimentos , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Ondas Ultrassônicas , ATPases Transportadoras de Cálcio/metabolismoRESUMO
Fluorophores with color-shifting characteristics have attracted enormous research interest in the quantitative application of RNA sensors. It reports here a simple synthesis, luminescent properties, and co-transcription ability of de-conjugated triphenylmethane leucomalachite green (LMG). This novel clusteroluminescence fluorophore is rapidly synthesized from malachite green (MG) in reductive transcription system containing dithiothreitol, emitting fluorescence in the UV region through space conjugation. The co-transcribed MG RNA aptamer (MGA) bound to the ligand, resulting in red fluorescence from the through-bond conjugation. Given the equilibrated color-shifting fluorophores, they are rationally employed in a 3WJ-based rolling circle transcription switch, with the target-aptamer acting as an activator to achieve steric allosterism. This one-pot system allows the target to compete continuously for allosteric sites, and the activated transcription switches continue to amplify MGA forward, achieving accurate Aflatoxin 1 quantification at the picomolar level in 1 h. Due to the programmability of this RNA sensor, the design method of target-competitive aptamers is standardized, making it universally applicable.
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Bisphenol S (BPS), a substitute for bisphenol A, is widely used in the manufacture of food packaging materials, raising concern over its toxicity. However, evidence is still lacking on whether gut microbiota involved in BPS induced intestinal inflammation in mammals, as well as its underlying mechanism. Using mouse BPS exposure model, we found intestinal inflammation characterized by shortened colon length, crypt distortion, macrophage accumulation and increased apoptosis. As for gut microbiota, 16s rRNA gene amplicon sequencing showed BPS exposure induced gut dysbiosis, including increased pro-inflammatory microbes such as Ileibacterium, and decreased anti-inflammatory genera such as Lactobacillus, Blautia and Romboutsia. Besides, LC-MS/MS-based untargeted metabolomic analysis indicated BPS impaired both bacteria and host metabolism. Additionally, transcriptome analysis of the intestine revealed abnormal gene expression in intestinal mucosal barrier and inflammation. More importantly, treating mice with antibiotics significantly attenuated BPS-induced gut inflammation via the regulation of both bacterial and host metabolites, indicating the role of gut microbiota. Collectively, BPS exposure induces intestinal inflammation via altering gut microbiota in mouse. This study provides the possibility of madecassic acid, an anti-inflammatory metabolite, to prevent BPS-induced intestinal inflammation and also new insights in understanding host-microbiota interaction in BPS toxicity.
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Microbioma Gastrointestinal , Fenóis , Sulfonas , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Fenóis/toxicidade , Camundongos , Sulfonas/toxicidade , Inflamação/induzido quimicamente , Camundongos Endogâmicos C57BL , Masculino , Bactérias/efeitos dos fármacos , Bactérias/classificação , Disbiose/induzido quimicamente , Disbiose/microbiologia , RNA Ribossômico 16S/genética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismoRESUMO
We designed the discrete direction selection (DDS) decoder for intracortical brain computer interface (iBCI) cursor control and showed that it outperformed currently used decoders in a human-operated real-time iBCI simulator and in monkey iBCI use. Unlike virtually all existing decoders that map between neural activity and continuous velocity commands, DDS uses neural activity to select among a small menu of preset cursor velocities. We compared closed-loop cursor control across four visits by each of 48 naïve, able-bodied human subjects using either DDS or one of three common continuous velocity decoders: direct regression with assist (an affine map from neural activity to cursor velocity), ReFIT, and the velocity Kalman Filter. DDS outperformed all three by a substantial margin. Subsequently, a monkey using an iBCI also had substantially better performance with DDS than with the Wiener filter decoder (direct regression decoder that includes time history). Discretizing the decoded velocity with DDS effectively traded high resolution velocity commands for less tortuous and lower noise trajectories, highlighting the potential benefits of simplifying online iBCI control.
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BACKGROUND: Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. OBJECTIVES: This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. METHODS: We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER) (≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. RESULTS: There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0% to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (OR: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7%-65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8-42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. CONCLUSIONS: Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.
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Terapia de Ressincronização Cardíaca , Cicatriz , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Cicatriz/fisiopatologia , Cicatriz/diagnóstico por imagem , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/fisiopatologia , Ecocardiografia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Cardiomiopatias/complicações , Bloqueio de Ramo/fisiopatologia , Bloqueio de Ramo/terapia , Resultado do Tratamento , Volume Sistólico/fisiologia , Remodelação Ventricular/fisiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapiaRESUMO
BACKGROUND: Japanese encephalitis (JE) is a serious health concern in China, with approximately 80 % of global infections occurring in China. To develop effective prevention and control strategies, this study explored the epidemiological characteristics of JE in China based on spatiotemporal data, to understand the patterns and trends of JE incidence in different regions and time periods. METHOD: The incidence and mortality rates of JE were extracted from the Public Health Data Center, the official website of the National Health Commission of the People's Republic of China, and the National Notifiable Infectious Disease Surveillance System from 2004 to 2019. Joinpoint regression was applied to examine the spatiotemporal patterns and annual percentage change in incidence and mortality of the JE. RESULTS: From 2004 to 2019, a total of 43,569 cases of JE were diagnosed, including 2081 deaths. The annual incidence rate of JE decreased from 0.4171/100,000 in 2004 to 0.0298/100,000 in 2019, with an annual percentage change (APC) of -13.5 % (P < 0.001). The annual mortality rate of JE showed three stages of change, with inflection points in 2006 and 2014. The incidence and mortality rates of JE have declined in all provinces of China, and more cases were reported in 0-14 years of age, accounting for nearly 80 % of all patients. CONCLUSIONS: The morbidity and mortality rates of JE in China are generally on a downward trend, and emphasis should be placed on strengthening disease surveillance in special areas and populations, popularizing vaccination, and increasing publicity.
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Encefalite Japonesa , Vigilância da População , Análise Espaço-Temporal , Humanos , Encefalite Japonesa/epidemiologia , Encefalite Japonesa/mortalidade , China/epidemiologia , Incidência , Criança , Pré-Escolar , Adolescente , Lactente , Adulto , Feminino , Masculino , Adulto Jovem , Pessoa de Meia-Idade , Recém-NascidoRESUMO
The current quality control method for Turkish gall (TG) is limited to assessing total tannin or gallic acid (GA), which offers a basic level of quality control but does not fully capture the true quality of TG. Therefore, it is essential to establish a comprehensive method that utilizes multiple indicators to assess the intrinsic quality of TG. This research utilized UPLC-Q-TOF-MS/MS technology to qualitatively analyze the chemical composition of TG. Subsequently, the potential main active ingredients, targets, and pathways of TG in treating recurrent aphthous ulcers (RAU) were explored and analyzed using network pharmacology technology. Quantitative analysis of multicomponents by single marker (QAMS) was then employed to quantify the primary pharmacodynamic components in TG. Finally, chemometrics analysis was utilized to interpret the measured results and identify the markers of scavenging quality. The study identified 36 chemical components in TG, highlighting ellagic acid (EA), GA, and so on as key components in treating RAU. A method for simultaneously determining GA, EA, 1,2,3,6-tetra-O-galloyl-ß-D-glucose (TEGG) and 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PEGG) in TG was established. Statistical analysis revealed significant differences in the content of these 4 components across 14 batches of TG, with GA and PEGG identified as the primary contributors to the variations. This study determined a quality index for TG, providing a reference for quality evaluation and introducing a cost-effective and efficient quality control method. Furthermore, it addressed the challenge of developing new Chinese medicine by overcoming the lack of reference substances.
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Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.
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Dicetopiperazinas , Talaromyces , Talaromyces/química , Dicetopiperazinas/química , Dicetopiperazinas/farmacologia , Dicetopiperazinas/isolamento & purificação , Humanos , Estrutura Molecular , Prenilação , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Células Hep G2 , Proliferação de Células/efeitos dos fármacos , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Monoéster Fosfórico Hidrolases/metabolismo , Linhagem Celular TumoralRESUMO
Background: Hepatic Ischemia-Reperfusion Injury (HIRI) is a major complication in liver transplants and surgeries, significantly affecting postoperative outcomes. The role of mitophagy, essential for removing dysfunctional mitochondria and maintaining cellular balance, remains unclear in HIRI. Methods: To unravel the role of mitophagy-related genes (MRGs) in HIRI, we assembled a comprehensive dataset comprising 44 HIRI samples alongside 44 normal control samples from the Gene Expression Omnibus (GEO) database for this analysis. Using Random Forests and Support Vector Machines - Recursive Feature Elimination (SVM-RFE), we pinpointed eight pivotal genes and developed a logistic regression model based on these findings. Further, we employed consensus cluster analysis for classifying HIRI patients according to their MRG expression profiles and conducted weighted gene co-expression network analysis (WGCNA) to identify clusters of genes that exhibit high correlation within different modules. Additionally, we conducted single-cell RNA sequencing data analysis to explore insights into the behavior of MRGs within the HIRI. Results: We identified eight key genes (FUNDC1, VDAC1, MFN2, PINK1, CSNK2A2, ULK1, UBC, MAP1LC3B) with distinct expressions between HIRI and controls, confirmed by PCR validation. Our diagnostic model, based on these genes, accurately predicted HIRI outcomes. Analysis revealed a strong positive correlation of these genes with monocytic lineage and a negative correlation with B and T cells. HIRI patients were divided into three subclusters based on MRG profiles, with WGCNA uncovering highly correlated gene modules. Single-cell analysis identified two types of endothelial cells with different MRG scores, indicating their varied roles in HIRI. Conclusions: Our study highlights the critical role of MRGs in HIRI and the heterogeneity of endothelial cells. We identified the macrophage migration inhibitory factor (MIF) and cGAS-STING (GAS) pathways as regulators of mitophagy's impact on HIRI. These findings advance our understanding of mitophagy in HIRI and set the stage for future research and therapeutic developments.
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Células Endoteliais , Fígado , Mitofagia , Traumatismo por Reperfusão , Humanos , Mitofagia/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Células Endoteliais/metabolismo , Fígado/metabolismo , Fígado/patologia , Perfilação da Expressão Gênica , Masculino , Redes Reguladoras de Genes , Transcriptoma , FemininoRESUMO
Beyond the antimicrobial activity, doxycycline (DOX) exhibits longevity-promoting effect in nematodes, while its effect on mammals is unclear. Here, we applied a mouse model of Hutchinson-Gilford progeria syndrome (HGPS), Zmpste24 knockout (KO) mice, and analyzed the antiaging effect of DOX. We found that the DOX treatment prolongs lifespan and ameliorates progeroid features of Zmpste24 KO mice, including the decline of body and tissue weight, exercise capacity and cortical bone density, and the shortened colon length. DOX treatment alleviates the abnormal nuclear envelope in multiple tissues, and attenuates cellular senescence and cell death of Zmpste24 KO and HGPS fibroblasts. DOX downregulates the level of proinflammatory IL6 in both serum and tissues. Moreover, the elevated α-tubulin (K40) acetylation mediated by NAT10 in progeria, is rescued by DOX treatment in the aorta tissues in Zmpste24 KO mice and fibroblasts. Collectively, our study uncovers that DOX can decelerate aging in progeria mice via counteracting IL6 expression and NAT10-mediated acetylation of α-tubulin.
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Envelhecimento , Doxiciclina , Camundongos Knockout , Progéria , Animais , Progéria/tratamento farmacológico , Progéria/metabolismo , Progéria/patologia , Camundongos , Envelhecimento/efeitos dos fármacos , Doxiciclina/farmacologia , Metaloendopeptidases/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Senescência Celular/efeitos dos fármacosRESUMO
Uyghur medicine is one of the four major ethnic medicines in China and is a component of traditional Chinese medicine. The intrinsic quality of Uyghur medicinal materials will directly affect the clinical efficacy of Uyghur medicinal preparations. However, in recent years, problems such as adulteration of Uyghur medicinal materials and foreign bodies with the same name still exist, so it is necessary to strengthen the quality control of Uyghur medicines to guarantee Uyghur medicinal efficacy. Identifying the components of Uyghur medicines can clarify the types of medicinal materials used, is a crucial step to realizing the quality control of Uyghur medicines, and is also an important step in screening the effective components of Uyghur medicines. Currently, the method of identifying the components of Uyghur medicines relies on manual detection, which has the problems of high toxicity of the unfolding agent, poor stability, high cost, low efficiency, etc. Therefore, this paper proposes a method based on Raman spectroscopy and multi-label deep learning model to construct a model Mix2Com for accurate identification of Uyghur medicine components. The experiments use computer-simulated mixtures as the dataset, introduce the Long Short-Term Memory Model (LSTM) and Attention mechanism to encode the Raman spectral data, use multiple parallel networks for decoding, and ultimately realize the macro parallel prediction of medicine components. The results show that the model is trained to achieve 90.76% accuracy, 99.41% precision, 95.42% recall value and 97.37% F1 score. Compared to the traditional XGBoost model, the method proposed in the experiment improves the accuracy by 49% and the recall value by 18%; compared with the DeepRaman model, the accuracy is improved by 9% and the recall value is improved by 14%. The method proposed in this paper provides a new solution for the accurate identification of Uyghur medicinal components. It helps to improve the quality standard of Uyghur medicinal materials, advance the research on screening of effective chemical components of Uyghur medicines and their action mechanisms, and then promote the modernization and development of Uyghur medicine.
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Medicina Tradicional do Leste Asiático , Análise Espectral Raman , Análise Espectral Raman/métodosRESUMO
Probiotics, recognized as beneficial and active microorganisms, often face challenges in maintaining their functionality under harsh conditions such as exposure to stomach acid and bile salts. In this investigation, we developed probiotic microcapsules and assessed their protective effects and underlying mechanisms in a murine model of dextran sulfate sodium (DSS)-induced colitis using male C57BL/6J mice. The administration of the probiotic microcapsules significantly mitigated body weight loss, prevented colon length shortening, decreased the disease activity index scores, and reduced histopathological scores in mice with DSS-induced colitis. Concurrently, the microencapsulated probiotics preserved intestinal barrier integrity by upregulating the expressions of tight junction proteins ZO-1 and occludin, as well as the mucus layer component MUC-2. Moreover, the treatment with probiotic microcapsules suppressed the activation of the NLRP3 inflammasome signaling pathway in the context of DSS-induced colitis. In conclusion, these findings support the utilization of probiotic microcapsules as a potential functional food ingredient to maintain the permeability of the intestinal barrier and alleviate colonic inflammation in UC.
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Colite , Lactobacillus plantarum , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Cápsulas , Colite/induzido quimicamente , Colite/prevenção & controle , InflamaçãoRESUMO
BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapy for advanced heart failure (HF) with prolonged QRS duration. However, 30% of patients have shown no benefit from the treatment. OBJECTIVE: This study aimed to examine the value of left atrial (LA) mechanics by cardiac magnetic resonance (CMR) to predict response to CRT and clinical outcomes. METHODS: A total of 163 CRT recipients with preimplantation CMR examination were retrospectively recruited. CMR feature tracking was used to evaluate LA size and function. The end points include (1) improvement of at least 5% in left ventricular ejection fraction combined with a reduction of at least 1 New York Heart Association functional class at 6-month follow-up and (2) any all-cause death or HF hospitalization during follow-up. RESULTS: Overall, 82 (50.3%) were CRT responders. CRT nonresponders had larger LA and worse LA reservoir and booster pump function than did responders (P < .001 for all). LA structural (maximum volume index < 47 mL/m2) and functional (booster pump strain > 8.5%) criteria were incremental to traditional indicators in detecting CRT response (χ2, 40.83 vs 9.98; P < .001). During follow-up (median 41 months), survival free from death or HF hospitalization increased with the number of positive LA criteria (log-rank, P < .001). After adjustment for clinical confounders, the absence of the 2 criteria remained associated with a considerably increased risk of death or HF hospitalization (adjusted hazard ratio 6.2; 95% confidence interval 2.15-17.88; P = .001). CONCLUSION: The preprocedure LA mechanics evaluated using CMR may be useful to predict response to CRT and improve risk stratification in CRT recipients.