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BACKGROUND: Acute appendicitis (AA) is the most common cause of acute abdomen in children. Anesthesia significantly influences the surgical treatment of AA in children, making the scientific and effective selection of anesthetics crucial. AIM: To assess the clinical effect of atropine (ATR) in combination with remifentanil (REMI) in children undergoing surgery for AA. METHODS: In total, 108 cases of pediatric AA treated between May 2020 and May 2023 were selected, 58 of which received ATR + REMI [research group (RG)] and 50 who received REMI [control group (CG)]. Comparative analyses were conducted on the time to loss of eyelash reflex, pain resolution time, recovery time from anesthesia, incidence of adverse events (AEs; respiratory depression, hypoxemia, bradycardia, nausea and vomiting, and hypotension), intraoperative responses (head shaking, limb activity, orientation recovery, safe departure time from the operating room), hemodynamic parameters [oxygen saturation (SPO2), mean arterial pressure, heart rate, and respiratory rate], postoperative sedation score (Ramsay score), and pain level [the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale]. RESULTS: Compared with the CG, the RG showed significantly shorter time to loss of eyelash reflex, pain resolution, recovery from anesthesia, and safe departure from the operating room. Furthermore, the incidence rates of overall AEs (head shaking, limb activity, etc.) were lower, and influences on intraoperative hemodynamic parameters and stress response indexes were fewer. The Ramsay score at 30 min after extubation and the FLACC score at 60 min after extubation were significantly lower in the RG than in the CG. CONCLUSION: ATR + REMI is superior to REMI alone in children undergoing AA surgery, with a lower incidence of AEs, fewer influences on hemodynamics and stress responses, and better post-anesthesia recovery.
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Introduction: The activation of cerebral endothelial cells (CECs) has recently been reported to be the earliest acute neuroinflammation event in the CNS during sepsis-associated encephalopathy (SAE). Importantly, adenosine-to-inosine (A-to-I) RNA editing mediated by ADARs has been associated with SAE, yet its role in acute neuroinflammation in SAE remains unclear. Methods: Our current study systematically analyzed A-to-I RNA editing in cerebral vessels, cerebral endothelial cells (CECs), and microglia sampled during acute neuroinflammation after treatment in a lipopolysaccharide (LPS)-induced SAE mouse model. Results: Our results showed dynamic A-to-I RNA editing activity changes in cerebral vessels during acute neuroinflammation. Differential A-to-I RNA editing (DRE) associated with acute neuroinflammation were identified in these tissue or cells, especially missense editing events such as S367G in antizyme inhibitor 1 (Azin1) and editing events in lincRNAs such as maternally expressed gene 3 (Meg3), AW112010, and macrophage M2 polarization regulator (Mm2pr). Importantly, geranylgeranyl diphosphate synthase 1 (Ggps1) and another three genes were differentially edited across cerebral vessels, CECs, and microglia. Notably, Spearman correlation analysis also revealed dramatic time-dependent DRE during acute neuroinflammation, especially in GTP cyclohydrolase1 (Gch1) and non-coding RNA activated by DNA damage (Norad), both with the editing level positively correlated with both post-LPS treatment time and edited gene expression in cerebral vessels and CECs. Discussion: The findings in our current study demonstrate substantial A-to-I RNA editing changes during acute neuroinflammation in SAE, underlining its potential role in the disease.
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BACKGROUND: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment. METHODS: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western-blot, immunofluorescence staining were performed. RESULTS: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results. CONCLUSION: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.
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Sepsis-associated encephalopathy is a diffuse brain dysfunction secondary to infection. It has been established that factors such as age and sex can significantly contribute to the development of sepsis-associated encephalopathy. Our recent study implicated a possible link between adenosine-to-inosine RNA editing and sepsis-associated encephalopathy, yet the dynamics of adenosine-to-inosine RNA editing during sepsis-associated encephalopathy and how it could be influenced by factors such as age, sex and antidepressants remain uninvestigated. Our current study analysed and validated transcriptome-wide changes in adenosine-to-inosine RNA editing in the hippocampus of different septic mouse models. Seventy-four sites in 64 genes showed significant differential RNA editing over time in septic mice induced by caecal ligation and perforation. The differential RNA editing might contribute to the RNA expression regulation of the edited genes, with 42.2% differentially expressed. These differentially edited genes, especially those with missense editing, such as glutamate receptor, ionotropic, kainate 2 (Grik2, p.M620V), filamin A (Flna, p.S2331G) and capicua transcriptional repressor (Cic, p.E2270G), were mainly involved in abnormal social behaviour and neurodevelopmental and psychiatric disorders. Significant effects of age and sex were also observed on sepsis-associated RNA editing. Further comparison highlighted 40 common differential RNA editing sites that caecal ligation and perforation-induced and lipopolysaccharide-induced septic mouse models shared. Interestingly, these findings demonstrate temporal dynamics of adenosine-to-inosine RNA editing in the mouse hippocampus during sepsis, add to the understanding of age and sex differences in the disease and underscore the role of the epigenetic process in sepsis-associated encephalopathy.
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BACKGROUND: Gastric cancer (GC) is a common malignant tumor, long non-coding RNA and microRNA (miRNA) are important regulators that affect tumor proliferation, metastasis and chemotherapy resistance, and thus participate in tumor progression. CASC19 is a new bio-marker which can promote tumor invasion and metastasis. However, the mechanism by which CASC19 affects the progression of GC through miRNA is not clear. AIM: To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC. METHODS: To explore the expression and prognosis of CASC19 in GC through clinical samples, and investigate the effects of inhibiting CASC19 on the proliferation, migration, invasion and other functions of GC cells through cell counting Kit-8 (CCK-8), ethynyldeoxyuridine, Wound healing assay, Transwell, Western blot and flow cytometry experiments. The effect of miR-491-5p and HMGA2 in GC were also proved. The regulatory relationship between CASC19 and miR-491-5p, miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR. Then CCK-8, Transwell, Wound healing assay, flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis. RESULTS: The expression level of CASC19 is related to the T stage, N stage, and tumor size of patients. Knockdown of the expression of CASC19 can inhibit the ability of proliferation, migration, invasion and EMT conversion of GC cells, and knocking down the expression of CASC19 can promote the apoptosis of GC cells. Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells, miR-491-5p mimics can inhibit EMT conversion, and promote the apoptosis of GC cells, while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells. The expression of HMGA2 in GC tissues is higher than that in adjacent tissues. At the same time, the expression level of HMGA2 is related to the N and T stages of the patients. Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells. Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p, thereby affecting the biological functions of GC. CONCLUSION: CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC. This axis may serve as a potential biomarker and therapeutic target of GC.
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Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.
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PURPOSE: Radiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms. MATERIALS AND METHODS: A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1ß were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT-qPCR, molecular docking and CETSA. RESULTS: ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1ß, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells. CONCLUSIONS: ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets.
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Green energy technology is generally becoming one of hot issues that need to be solved due to the adverse effects on the environment of fossil fuels. One of the strategies being studied and developed by theorists and experimentalists is the use of photoelectrochemical (PEC) cells, which are emerging as a candidate to produce hydrogen from water splitting. However, creating photoelectrodes that meet the requirements for PEC water splitting has emerged as the primary obstacle in bringing this technology to commercial fruition. Here, we construct a heterostructure, which consists of MoS2/TiO2/Au nanoparticles (NPs) to overcome the drawbacks of the photoanode. Owing to the dependence on charge transfer, the bandgap of MoS2/TiO2and the utilization the Au NPs as a stimulant for charges separation of TiO2by localized surface plasmon resonances effect as well as the increase of hot electron injection to cathode, leading to photocatalytic activities are improved. The results have recorded a significant increase in the photocurrent density from 2.3µAcm-2of TiO2to approximately 16.3µAcm-2of MoS2/TiO2/Au NPs. This work unveils a promising route to enhance the visible light adsorption and charge transfer in photo-electrode of the PEC cells by combining two-dimensional materials with metal NPs.
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Near-infrared light-emitting diodes (NIR LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiency (EQE) of ~15%. However, these high-performance NIR-QLEDs suffer from immediate carrier quenching because of the accumulation of migratable ions at the surface of the QDs. These uncoordinated ions and carriers - if not bound to the nanocrystal surface - serve as centers for exciton quenching and device degradation. In this work, we overcome this issue and fabricate high-performance NIR QLEDs by devising a ligand anchoring strategy, which entails dissolving the strong-binding ligand (Guanidine Hydroiodide, GAI) in the mediate-polar solvent. By employing the dye-sensitized device structure (phosphorescent indicator), we demonstrate the elimination of the interface defects. The treated QDs films exhibit an exciton binding energy of 117 meV: this represents a 1.5-fold increase compared to that of the control (74 meV). We report, as a result, the NIR QLEDs with an EQE of 21% which is a record among NIR perovskite QLEDs. These QLEDs also exhibit a 7-fold higher operational stability than that of the best previously reported NIR QLEDs. Furthermore, we demonstrate that the QDs are compatible with large-area QLEDs: we showcase 900 mm2 QLEDs with EQE approaching 20%.
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An inverse sandwich structure has been computationally predicted for uranium boride and extended to the series of actinide elements (An) from Th to Cm. The electronic structure and chemical bonding of these novel compounds have been analyzed using density functional theory and multireference wave-function based methods. We report the trends in electronic structure and bonding for An2B8, and found that (d-π)π and (d-p)δ are the most important factors in the stability of An2B8. The (f-p)δ bond provides extra stabilization for Pa2B8 and U2B8, owing to the extensive interactions of An-B8-An, resulting in a short distance for the Pa-Pa and U-U bonds.
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BACKGROUND: Acute graft-versus-host disease (aGVHD), which is mainly mediated by allogeneic T cells, is a decisive factor in the success of allogeneic hematopoietic stem cell transplantation (allo-HCT). Prophylaxis for aGVHD in clinical patients is unsatisfactory, and there is still a huge unmet need for novel approaches. Icariin (ICA) shows potent anti-inflammatory activity and suppresses T cell-mediated immune responses. Thus, ICA is a potential drug for the prevention of aGVHD. However, there is no data assessing the impact of ICA on aGVHD after allo-HCT. PURPOSE: This study aimed to investigate the protective effect of ICA against aGVHD and its mechanisms. Moreover, the impact of ICA on the graft-versus-leukemia (GVL) effect and engraftment of donor hematopoietic and immune cells were assessed. METHODS: Different murine models of allo-HCT were developed to study the influence of the ICA on GVHD and GVL effect. Flow cytometry was used to analyze the growth of leukemia cells, alterations in different immune cells, and apoptosis. Cell proliferation was determined using a CCK-8 assay. RNA sequencing and quantitative proteomic analysis were performed to elucidate the underlying mechanisms, which were further verified by polymerase chain reaction or functional experiments. RESULTS: Different concentrations of ICA exhibited opposite effects: low-concentration ICA promoted, while high concentrations suppressed the proliferation and function of T cells. A high dose of ICA administration during days +3 to +5 post-allo-HCT can alleviate murine aGVHD but does not affect the course of chronic GVHD (cGVHD), the GVL effect against both acute myeloid and lymphoblastic leukemia, or the recovery of donor hematological and immune cells. ICA extensively represses the expansion, function, and infiltration of donor alloreactive T cells, while preserving regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). Quantitative proteomic analysis showed that downregulation of integrin-linked kinase (ILK) and lymphocyte cytosolic protein 2 (LCP2) expression was possibly associated with ICA-mediated aGVHD protective effects. Furthermore, an inhibitor of ILK, which can alleviate murine aGVHD administered early after allo-HCT. CONCLUSION: These findings suggest that the bioactivities of ICA are associated with its concentration and that ICA can effectively mitigate aGVHD without losing GVL activity or engraftment of donor hematopoietic and immune cells. Thus, ICA may be a promising drug for preventing aGVHD in clinical settings.
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Flavonoides , Doença Enxerto-Hospedeiro , Efeito Enxerto vs Leucemia , Transplante de Células-Tronco Hematopoéticas , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Doença Enxerto-Hospedeiro/prevenção & controle , Animais , Flavonoides/farmacologia , Efeito Enxerto vs Leucemia/efeitos dos fármacos , Camundongos , Transplante Homólogo , Modelos Animais de Doenças , Masculino , Feminino , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
ABSTRACT: Tan, WZN and Lum, D. Predicting 1 repetition maximum squat with peak force obtained from isometric squat at multiple positions. J Strength Cond Res XX(X): 000-000, 2024-This study investigated whether the use of peak force (PF) obtained from multiple joint positions during isometric squat (IsoSqt) can predict of 1-repetition maximum (1RM) squat with high precision. Twenty-nine male and female resistance-trained athletes (age = 23.0 ± 3.7 years, height = 1.57 ± 0.06 m, body mass = 56.6 ± 9.1 kg, 1RM squat = 104.6 ± 24.2) performed the 1RM squat, and IsoSqt at 60°, 90°, and 120° knee angles on 3 separate occasions. Peak force obtained from IsoSqt at all positions significantly correlated with 1RM squat (r = 0.684-0.940, p < 0.05). Linear regression analysis based on group data showed r2 = 0.903, based on male data only, r2 = 0.826, and based on female data only, r2 = 0.855. Predicted 1RM squat using linear regression equations based on group, male-only, and female-only data showed nonsignificant differences of 0.02-0.6% from actual 1RM squat (p = 0.812-0.947, 95% CI = -8.00 to 10.08), with error of estimate of 1.5-2.3%. In addition, Bland-Altman analysis showed a mean bias of -1.04 to 0.35 kg, 95% CI = -10.08 to 8.00 kg. The results showed that using PF obtained from IsoSqt at multiple positions was able to predict 1RM squat with low difference from actual 1RM squat. Furthermore, using linear regression equation derived from gender-specific data was able to predict 1RM squat with higher precision than that based on group data.
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The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson's disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.
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Fezes , Microbioma Gastrointestinal , Macaca fascicularis , Animais , Fezes/microbiologia , Modelos Animais de Doenças , Disbiose/microbiologia , Masculino , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Transtornos Parkinsonianos/microbiologia , Transtornos Parkinsonianos/metabolismo , Metabolômica/métodos , Metaboloma , Interações entre Hospedeiro e Microrganismos , MultiômicaRESUMO
For chronic wounds, frequent replacement of bandages not only increases the likelihood of secondary damage and the risk of cross infection but also wastes medication. Therefore, in situ real-time monitoring of the concentrations of residual drugs in bandages is crucial. Here, we propose a novel strategy that combines a triboelectric nanogenerator (TENG) with medical bandages to develop a smart bandage based on zeolite imidazolate framework TENG. During the process of wound healing, the electrical output of TENG changes with the continuous release of drugs. Based on the correlation between the electrical signal of TENG and drug concentration, the concentration of residual drugs in the bandage can be monitored in real-time in situ, guiding medical staff to replace the bandage at the most appropriate time. The smart bandage based on TENG provides a new strategy for in situ real-time monitoring of drug concentration and also provides an ideal and feasible solution for the field of biomedical drug sensing.
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Bandagens , Zeolitas/química , Animais , Cicatrização/efeitos dos fármacos , Humanos , Nanotecnologia/instrumentação , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Estruturas Metalorgânicas/químicaRESUMO
BACKGROUND: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study. METHODS: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR). RESULTS: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003). CONCLUSION: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up.
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The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers.
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Adenosina Desaminase , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Edição de RNA , Proteínas de Ligação a RNA , Neoplasias Gástricas , Humanos , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Estudos de Coortes , Regiões 3' não Traduzidas/genética , Linhagem Celular Tumoral , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Masculino , FemininoRESUMO
Swine influenza viruses (SIVs), including H1N1, H1N2, and H3N2, have spread throughout the global pig population. Potential pandemics are a concern with the recent sporadic cross-species transmission of SIVs to humans. We collected 1421 samples from Guangdong, Fujian, Henan, Yunnan and Jiangxi provinces during 2017-2018 and isolated 29 viruses. These included 21H1N1, 5H1N2, and 3H3N2 strains. Genome analysis showed that the domestic epidemic genotypes of H1N1 were mainly G4 and G5 reassortant EA swine H1N1. These genotypes have a clear epidemic advantage. Two strains were Clade 6B.1 pdm/09H1N1, suggesting a possible pig-to-human transmission route. Notably, three new H1N2 genotypes were identified using the genomic backbones of G4 or G5 viruses for recombination. The identification of various subtypes and genotypes highlight the complexity and diversity of SIVs in China and need for continuous monitoring of SIV evolution to assess the risks and prepare for potential influenza pandemics.
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Evolução Molecular , Genótipo , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Infecções por Orthomyxoviridae , Filogenia , Doenças dos Suínos , Animais , China/epidemiologia , Suínos , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/classificação , Humanos , Genoma Viral , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/classificação , Variação Genética , Vírus da Influenza A Subtipo H1N2/genética , Vírus da Influenza A Subtipo H1N2/isolamento & purificação , Vírus da Influenza A Subtipo H1N2/classificação , Influenza Humana/virologia , Influenza Humana/epidemiologia , Saúde Pública , Vírus da Influenza A/genética , Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificaçãoRESUMO
OBJECTIVES: To investigate the clinical character of differentiated thyroid cancer (DTC) coexisting with Hashimoto's thyroiditis (HT) and provide state-of-art evidence for personalized radioactive iodine-131 therapy (RAIT) for patients coexisting with HT. METHODS: From January 2000 to January 2023, PubMed, Embase, and Web of Science databases were searched for relevant original articles that published in English on the RAIT efficacy for DTC with HT. RevMan 5.4 and Stata 17.0 were used for data analysis. RESULTS: Eleven studies involving 16 605 DTC patients (3321 with HT) were included. HT was more frequent in female (OR: 2.90, 95% confidence interval [CI]: 1.77-4.76, P < .00001). The size of tumour (MD: -0.20, 95% CI: -0.30 to -0.11), extrathyroidal extension rate (OR: 0.77, 95% CI: 0.67-0.90), and metastasis rate (OR: 0.18, 95% CI: 0.08-0.41) were less in HT, but tumour, node, metastasis (TNM) stage had no significant difference among HT and non-HT group. Disease-free survival (DFS) rate (OR: 1.96, 95% CI: 1.57-2.44, P < .00001), 5-year DFS (OR: 1.73, 95% CI: 1.04-2.89, P = .04), and 10-year DFS (OR: 1.56, 95% CI: 1.17-2.09, P = .003) were higher in HT group. The recurrent (OR: 0.62, 95% CI: 0.45-0.83, P = .002), RAIT dosage (MD = -38.71, 95% CI: -60.86 to -16.56, P = .0006), and treatment (MD: -0.13, 95% CI: -0.22 to -0.03, P = .008) were less in HT group. CONCLUSIONS: DTC coexisting with HT was associated with less invasion. DFS of HT group was higher than non-HT group after RAIT. Low-dose treatment did not impair the efficacy of RAIT in DTC with HT. ADVANCES IN KNOWLEDGE: Hashimoto's thyroiditis is a risk for DTC, but it minimalizes the progression of cancer and enhance the efficacy of RAIT, which should be considered in personalizing RAIT.
Assuntos
Doença de Hashimoto , Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Feminino , Humanos , Doença de Hashimoto/complicações , Doença de Hashimoto/radioterapia , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/complicações , MasculinoRESUMO
BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the ß but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90ß would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms. EXPERIMENTAL APPROACH: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90ß. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms. KEY RESULTS: The selective pharmacological inhibitor (HSP90ßi) and shHSP90ß significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically-transformed Th17 cells by HSP90ßi or shHSP90ß were able to inhibit lymphocyte proliferation and colitis in mice. HSP90ßi and shHSP90ß selectively weakened glycolysis by stopping the direct association of HSP90ß and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate-STAT5-TET2" cascade. CONCLUSION AND IMPLICATIONS: HSP90ß shapes the fate of Th17 cells via glycolysis-controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC.
RESUMO
The growing demand for wearable and attachable displays has sparked significant interest in flexible quantum-dot light-emitting diodes (QLEDs). However, the challenges of fabricating and operating QLEDs on flexible substrates persist due to the lack of stable and low-temperature processable charge-injection/-transporting layers with aligned energy levels. In this study, we utilized NiOx nanoparticles that are compatible with flexible substrates as a hole-injection layer (HIL). To enhance the work function of the NiOx HIL, we introduced a self-assembled dipole modifier called 4-(trifluoromethyl)benzoic acid (4-CF3-BA) onto the surface of the NiOx nanoparticles. The incorporation of the dipole molecules through adsorption treatment has significantly changed the wettability and electronic characteristics of NiOx nanoparticles, resulting in the formation of NiO(OH) at the interface and a shift in vacuum level. The alteration of surface electronic states of the NiOx nanoparticles not only improves the carrier balance by reducing the hole injection barrier but also prevents exciton quenching by passivating defects in the film. Consequently, the NiOx-based red QLEDs with interfacial modification demonstrate a maximum current efficiency of 16.1 cd/A and a peak external quantum efficiency of 10.3%. This represents a nearly twofold efficiency enhancement compared to control devices. The mild fabrication requirements and low annealing temperatures suggest potential applications of dipole molecule-modified NiOx nanoparticles in flexible optoelectronic devices.