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Functionally diverse devices with artificial neuron and synapse properties are critical for neuromorphic systems. We present a two-terminal artificial leaky-integrate-fire (LIF) neuron based on 6 nm Hf0.1Zr0.9O2 (HZO) antiferroelectric (AFE) thin films and develop a synaptic device through work function (WF) engineering. LIF neuron characteristics, including integration, firing, and leakage, are achieved in W/HZO/W devices due to the accumulated polarization and spontaneous depolarization of AFE HZO films. By engineering the top electrode with asymmetric WFs, we found that Au/Ti/HZO/W devices exhibit synaptic weight plasticity, such as paired-pulse facilitation and long-term potentiation/depression, achieving >90% accuracy in digit recognition within constructed artificial neural network systems. These findings suggest that AFE HZO capacitor-based neurons and WF-engineered artificial synapses hold promise for constructing efficient spiking neuron networks and artificial neural networks, thereby advancing neuromorphic computing applications based on emerging AFE HZO devices.
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In situ growth of intertwined trinuclear copper complexes (nCu3) on a cellulose-derived carbon support (CMC) produced a high-performance electrocatalyst (CMC-nCu3) for the oxygen reduction reaction (ORR), which demonstrated superior performance in zinc-air batteries compared to a commercial Pt/C catalyst. This work highlights the importance of copper-based molecular catalysts with rich and intertwined tricopper structures for boosting both ORR activity and stability.
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BACKGROUND AND AIMS: This study assessed whether a model incorporating clinical features and a polygenic score for ascending aortic diameter would improve diameter estimation and prediction of adverse thoracic aortic events over clinical features alone. METHODS: Aortic diameter estimation models were built with a 1.1 million-variant polygenic score (AORTA Gene) and without it. Models were validated internally in 4394 UK Biobank participants and externally in 5469 individuals from Mass General Brigham (MGB) Biobank, 1298 from the Framingham Heart Study (FHS), and 610 from All of Us. Model fit for adverse thoracic aortic events was compared in 401 453 UK Biobank and 164 789 All of Us participants. RESULTS: AORTA Gene explained more of the variance in thoracic aortic diameter compared to clinical factors alone: 39.5% (95% confidence interval 37.3%-41.8%) vs. 29.3% (27.0%-31.5%) in UK Biobank, 36.5% (34.4%-38.5%) vs. 32.5% (30.4%-34.5%) in MGB, 41.8% (37.7%-45.9%) vs. 33.0% (28.9%-37.2%) in FHS, and 34.9% (28.8%-41.0%) vs. 28.9% (22.9%-35.0%) in All of Us. AORTA Gene had a greater area under the receiver operating characteristic curve for identifying diameter ≥ 4 cm: 0.836 vs. 0.776 (P < .0001) in UK Biobank, 0.808 vs. 0.767 in MGB (P < .0001), 0.856 vs. 0.818 in FHS (P < .0001), and 0.827 vs. 0.791 (P = .0078) in All of Us. AORTA Gene was more informative for adverse thoracic aortic events in UK Biobank (P = .0042) and All of Us (P = .049). CONCLUSIONS: A comprehensive model incorporating polygenic information and clinical risk factors explained 34.9%-41.8% of the variation in ascending aortic diameter, improving the identification of ascending aortic dilation and adverse thoracic aortic events compared to clinical risk factors.
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Cholesterol and Helicobacter pylori (H. pylori) are both risk factors for gastric cancer (GC). However, the relationship between cholesterol and H. pylori and their function in the progression of GC are controversial. In this study, we addressed that H. pylori could induce mitochondrial cholesterol accumulation and promote GC proliferation and protect GC cells against apoptosis via cholesterol. Metabolomic and transcriptomic sequencing were used to identify CYP11A1 responsible for H. pylori-induced cholesterol accumulation. In vitro and in vivo function experiments revealed that cholesterol could promote the proliferation of GC and inhibit apoptosis. Mechanically, the interaction of Cytotoxin-associated gene A (CagA) and CYP11A1 redistributed mitochondrial CYP11A1 outside the mitochondria and subsequently caused mitochondrial cholesterol accumulation. The CYP11A1-knockdown upregulated cholesterol accumulation and reproduced the effect of cholesterol on GC in a cholesterol-dependent manner. Moreover, CYP11A1-knockdown or H. pylori infection inhibited mitophagy and maintained the mitochondria homeostasis. H. pylori could contribute to the progression of GC through the CagA/CYP11A1-mitoCHO axis. This study demonstrates that H. pylori can contribute to the progression of GC via cholesterol, and eradicating H. pylori is still prognostically beneficial to GC patients.
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Colesterol , Helicobacter pylori , Mitocôndrias , Neoplasias Gástricas , Helicobacter pylori/metabolismo , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Colesterol/metabolismo , Humanos , Mitocôndrias/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Animais , Antígenos de Bactérias/metabolismo , Antígenos de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Linhagem Celular Tumoral , Camundongos , Apoptose , Masculino , Proliferação de CélulasRESUMO
Ubiquitination plays a pivotal regulatory role in tumor progression. Among the components of the ubiquitin-proteasome system (UPS), ubiquitin-protein ligase E3 has emerged as a key molecule. Nevertheless, the biological functions of E3 ubiquitin ligases and their potential mechanisms orchestrating glycolysis in gastric cancer (GC) remain to be elucidated. In this study, we conducted a comprehensive transcriptomic analysis to identify the core E3 ubiquitin ligases in GC, followed by extensive validation of the expression patterns and clinical significance of Tripartite motif-containing 50 (TRIM50) both in vitro and in vivo. Remarkably, we found that TRIM50 was downregulated in GC tissues, associated with malignant progression and poor patient survival. Functionally, overexpression of TRIM50 suppressed GC cell proliferation and indirectly mitigated the invasion and migration of GC cells by inhibiting the M2 polarization of tumor-associated macrophages (TAMs). Mechanistically, TRIM50 inhibited the glycolytic pathway by ubiquitinating Phosphoglycerate Kinase 1 (PGK1), thereby directly suppressing GC cell proliferation. Simultaneously, the reduction in lactate led to diminished M2 polarization of TAMs, indirectly inhibiting the invasion and migration of GC cells. Notably, the downregulation of TRIM50 in GC was mediated by the METTL3/YTHDF2 axis in an m6A-dependent manner. In our study, we definitively identified TRIM50 as a tumor suppressor gene (TSG) that effectively inhibits glycolysis and the malignant progression of GC by ubiquitinating PGK1, thus offering novel insights and promising targets for the diagnosis and treatment of GC.
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Glicólise , Fosfoglicerato Quinase , Neoplasias Gástricas , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Ubiquitinação , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Humanos , Fosfoglicerato Quinase/metabolismo , Fosfoglicerato Quinase/genética , Linhagem Celular Tumoral , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Proliferação de Células/genética , Animais , Camundongos , Camundongos Nus , Progressão da Doença , Movimento Celular/genética , Camundongos Endogâmicos BALB C , Regulação Neoplásica da Expressão Gênica , Metiltransferases/metabolismo , Metiltransferases/genéticaRESUMO
INTRODUCTION: Recombinant allergens produced by Escherichia coli (E. coli) system play an important role in the component-resolved diagnostics of allergy and vaccine development. However, incorrect folding of recombinant allergens may affect their application. Therefore, it is very important to monitor the correct folding of recombinant allergens. Currently, there is still a lack of a quality control strategy to solve this problem. In this study, a mite allergen, Der f 2, was taken as an example to establish a novel quality control strategy, which was based on chromatography to isolate the allergen, and on enzyme-linked immunosorbent assay to verify the IgE reactivity of the isolated allergen. METHODS: The nucleotide sequence encoding Der f 2 was codon-optimized and cloned into pET-28a (+) plasmid. Best conditions for the expression of Der f 2 in E. coli were sought. The inclusion body of Der f 2 was denatured and purified by nickel affinity chromatography. Refolding processes were compared using glutathione redox system. The fully and partially folded proteins were separated by anion exchange chromatography, and the IgE reactivity of the isolated proteins was verified by indirect enzyme-linked immunosorbent assay. RESULTS: An optimized 387 bp segment of the Der f 2 coding gene was successfully expressed in E. coli. Best induction conditions included preinduction bacterial density with absorbance value at 600 nm was 0.6, 1 mM isopropyl beta-
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Objective: The incidence of intensive care unit acquired weakness (ICU-AW) has shown an increasing trend with still a lack of effective treatment options. The early assessment of the risk of developing ICU-AW can provide patients with targeted interventions. This study aimed to determine the independent risk factors of ICU-AW in patients receiving mechanical ventilation (MV) and develop a nomogram and verify its predictive efficacy. Methods: This observational study included patients receiving MV therapy in the ICU of our hospital between January 2020 and January 2023. They were divided into the ICU-AW and non-ICU-AW groups. The training cohort (n = 264) and the validation cohort (n = 143) were constructed. Multivariate logistic regression analyses were used to select the risk factors, and a nomogram model was established. Calibration, receiver operating characteristic (ROC), and decision curves were used to evaluate the effectiveness of the model. Results: The MV duration (OR = 1.24, 95%CI[1.11, 1.38]), APACHE II score (OR = 1.34, 95%CI[1.20, 1.50]), SOFA score (OR = 1.36, 95%CI[1.21, 1.53]), age (OR = 1.05, 95%CI[1.00, 1.10]), nerve blockers (OR = 3.26, 95%CI[1.34, 7.92]), and diabetes mellitus (OR = 3.12, 95%CI[1.10, 8.87]) were independent risk factors for ICU-AW. The nomogram had good predictive efficacy for both the training (area under the curve (AUC) = 0.950, 95%CI [0.93, 0.97]) and validation cohorts (AUC = 0.823, 95%CI [0.75, 0.89]). Conclusion: The MV duration, APACHE II, SOFA, age, use of nerve blockers, and diabetes mellitus are independent risk factors for ICU-AW. The nomogram model based on them had good predictive efficacy and may be clinically useful.
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OBJECTIVE: To investigate how antiretroviral therapy (ART) regimens and body mass index (BMI) interact to affect triglyceride (TG) levels in people living with HIV (PLWH). METHODS: This research involved 451 men living with HIV for cross-sectional analysis, and 132 underwent follow-up assessments in 2021 and 2023. Multivariate logistic regression identified key factors, while covariance regression models assessed interactions between ART regimens and BMI on TG levels. RESULTS: The result of this cross-sectional study indicated that advanced AIDS (acquired immune deficiency syndrome) stage (OR = 2.756, P = 0.003), higher BMI (OR = 1.131, P = 0.003), and waist-hip ratio (WHR, OR = 44.684, P = 0.019) are closely associated with high triglyceride levels. Additionally, regimens containing zidovudine (AZT) (OR = 3.927, P < 0.001) or protease inhibitors/integrase strand transfer inhibitors (PI/INSTI) (OR = 5.167, P < 0.001) were significantly linked to hypertriglyceridemia. Cross-sectional and longitudinal analyses from 2021 to 2023 emphasized that changes in BMI interact with antiretroviral treatment regimens to affect TG levels in PLWH (Pinteraction < 0.05). Especially in the AZT-based drug regimen, the correlation between BMI and TG is more prominent. CONCLUSION: The interaction between ART regimens and BMI influences TG levels in PLWH, indicating that weight management is crucial for reducing the risk of hypertriglyceridemia in this population.
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Índice de Massa Corporal , Infecções por HIV , Triglicerídeos , Zidovudina , Humanos , Masculino , Triglicerídeos/sangue , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Infecções por HIV/sangue , Estudos Longitudinais , Adulto , Pessoa de Meia-Idade , Zidovudina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Relação Cintura-Quadril , Hipertrigliceridemia/sangue , Terapia Antirretroviral de Alta AtividadeRESUMO
OBJECTIVE: The accurate measurement of Cobb angles is crucial for the effective clinical management of patients with adolescent idiopathic scoliosis (AIS). The Lenke classification system plays a pivotal role in determining the appropriate fusion levels for treatment planning. However, the presence of interobserver variability and time-intensive procedures presents challenges for clinicians. The purpose of this study is to compare the measurement accuracy of our developed artificial intelligence measurement system for Cobb angles and Lenke classification in AIS patients with manual measurements to validate its feasibility. METHODS: An artificial intelligence (AI) system measured the Cobb angle of AIS patients using convolutional neural networks, which identified the vertebral boundaries and sequences, recognized the upper and lower end vertebras, and estimated the Cobb angles of the proximal thoracic, main thoracic, and thoracolumbar/lumbar curves sequentially. Accordingly, the Lenke classifications of scoliosis were divided by oscillogram and defined by the AI system. Furthermore, a man-machine comparison (n = 300) was conducted for senior spine surgeons (n = 2), junior spine surgeons (n = 2), and the AI system for the image measurements of proximal thoracic (PT), main thoracic (MT), thoracolumbar/lumbar (TL/L), thoracic sagittal profile T5-T12, bending views PT, bending views MT, bending views TL/L, the Lenke classification system, the lumbar modifier, and sagittal thoracic alignment. RESULTS: In the AI system, the calculation time for each patient's data was 0.2 s, while the measurement time for each surgeon was 23.6 min. The AI system showed high accuracy in the recognition of the Lenke classification and had high reliability compared to senior doctors (ICC 0.962). CONCLUSION: The AI system has high reliability for the Lenke classification and is a potential auxiliary tool for spinal surgeons.
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Inteligência Artificial , Escoliose , Humanos , Escoliose/classificação , Escoliose/cirurgia , Escoliose/diagnóstico por imagem , Adolescente , Masculino , Feminino , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Criança , Variações Dependentes do ObservadorRESUMO
Nanoplastics (NPs), identified as emerging pollutants, pose a great risk to environment and global public health, exerting profound influences on the prevalence and dissemination of antibiotic resistance genes (ARGs). Despite evidence suggesting that nano-sized plastic particles can facilitate the horizontal gene transfer (HGT) of ARGs, it is imperative to explore strategies for inhibiting the transfer of ARGs. Currently, limited information exists regarding the characteristics of environmentally aged NPs and their impact on ARGs propagation. Herein, we investigated the impact of photo-aged NPs on the transfer of ARG-carrying plasmids into Escherichia coli (E. coli) cells. Following simulated sunlight irradiation, photo-aged nano-sized polystyrene plastics (PS NPs) exhibited multiple enzyme-like activities, including peroxidase (POD) and oxidase (OXD), leading to a burst of reactive oxygen species (ROS). At relatively low concentrations (0.1, 1 µg/mL), both pristine and aged PS NPs facilitated the transfer of pUC19 and pHSG396 plasmids within E. coli due to moderate ROS production and enhanced cell membrane permeability. Intriguingly, at relatively high concentrations (5, 10 µg/mL), aged PS NPs significantly suppressed plasmids transformation. The non-unidirectional impact of aged PS NPs involved the overproduction of ROS (â¢OH and â¢O2-) via nanozyme activity, directly degrading ARGs and damaging plasmid structure. Additionally, oxidative damage to bacteria resulted from the presence of much toxic free radicals, causing physical damage to cell membranes, reduction of the SOS response and restriction of adenosine-triphosphate (ATP) supply, ultimately leading to inactivation of recipient cells. This study unveils the intrinsic multienzyme-like activity of environmentally aged NPs, highlighting their potential to impede the transfer and dissemination of ARGs.
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Escherichia coli , Transferência Genética Horizontal , Plasmídeos , Espécies Reativas de Oxigênio , Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Plasmídeos/genética , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Nanopartículas/toxicidade , Resistência Microbiana a Medicamentos/genética , Poliestirenos/química , Luz Solar , Farmacorresistência Bacteriana/genética , Oxirredutases/genética , Oxirredutases/metabolismoRESUMO
Purpose: Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota's contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods. Methods: Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. "Probiotics" and "inflammation" are the keywords in the research. Conclusion: This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed.
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Raman spectroscopy enables the non-destructive characterization of chemical composition, crystallinity, defects, or strain in countless materials. However, the Raman response of surfaces or thin films is often weak and obscured by dominant bulk signals. Here we overcome this limitation by placing a transferable porous gold membrane, (PAuM) on the surface of interest. Slot-shaped nanopores in the membrane act as plasmonic antennas and enhance the Raman response of the surface or thin film underneath. Simultaneously, the PAuM suppresses the penetration of the excitation laser into the bulk, efficiently blocking its Raman signal. Using graphene as a model surface, we show that this method increases the surface-to-bulk Raman signal ratio by three orders of magnitude. We find that 90% of the Raman enhancement occurs within the top 2.5 nm of the material, demonstrating truly surface-sensitive Raman scattering. To validate our approach, we quantify the strain in a 12.5 nm thin Silicon film and analyze the surface of a LaNiO3 thin film. We observe a Raman mode splitting for the LaNiO3 surface-layer, which is spectroscopic evidence that the surface structure differs from the bulk. These results validate that PAuM gives direct access to Raman signatures of thin films and surfaces.
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Gastric cancer (GC) is one of the most common cancer worldwide. Neural invasion (NI) is considered as the symbiotic interaction between nerves and cancers, which strongly affects the prognosis of GC patients. Small extracellular vesicles (sEVs) play a key role in intercellular communication. However, whether sEVs mediate GC-NI remains unexplored. In this study, sEVs release inhibitor reduces the NI potential of GC cells. Muscarinic receptor M3 on GC-derived sEVs regulates their absorption by neuronal cells. The enrichment of sEV-circVAPA in NI-positive patients' serum is validated by serum high throughput sEV-circRNA sequencing and clinical samples. sEV-circVAPA promotes GC-NI in vitro and in vivo. Mechanistically, sEV-circVAPA decreases SLIT2 transcription by miR-548p/TGIF2 and inhibits SLIT2 translation via binding to eIF4G1, thereby downregulates SLIT2 expression in neuronal cells and finally induces GC-NI. Together, this work identifies the preferential absorption mechanism of GC-derived sEVs by neuronal cells and demonstrates a previously undefined role of GC-derived sEV-circRNA in GC-NI, which provides new insight into sEV-circRNA based diagnostic and therapeutic strategies for NI-positive GC patients.
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Vesículas Extracelulares , Peptídeos e Proteínas de Sinalização Intercelular , Invasividade Neoplásica , Proteínas do Tecido Nervoso , Neurônios , Neoplasias Gástricas , Animais , Feminino , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Vesículas Extracelulares/metabolismo , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Pessoa de Meia-Idade , Camundongos Nus , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT). METHODS: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies. RESULTS: Analyses comprised 2384 AVNRT cases and 106â 489 referents, and 2811 AVAP/AVRT cases and 1,483â 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A, SCN10A, and TTN/CCDC141. Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals. CONCLUSIONS: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.
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Estudo de Associação Genômica Ampla , Taquicardia Supraventricular , Humanos , Taquicardia Supraventricular/genética , Predisposição Genética para Doença , Taquicardia por Reentrada no Nó Atrioventricular/genética , Polimorfismo de Nucleotídeo Único , Conectina/genética , TranscriptomaRESUMO
Polyethylene glycol modification (PEGylation) is a widely used strategy to improve the physicochemical properties of various macromolecules, especially protein drugs. However, its application in enhancing the performance of enzymes for molecular biology remains underexplored. This study explored the PEGylation of Bst DNA polymerase, determining optimal modification reaction conditions. In comparison to the unmodified wild-type counterpart, the modified Bst DNA polymerase exhibited significantly improved activity, thermal stability, and inhibitor tolerance during loop-mediated isothermal amplification. When applied for the detection of Salmonella in crude samples, the modified enzyme demonstrated a notably accelerated reaction rate. Therefore, PEGylation emerges as a viable strategy for refining DNA polymerases, helping in the development of novel molecular diagnostic reagents.
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DNA Polimerase Dirigida por DNA , Estabilidade Enzimática , Polietilenoglicóis , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , DNA Polimerase Dirigida por DNA/metabolismo , DNA Polimerase Dirigida por DNA/química , Temperatura , Salmonella/genética , Salmonella/enzimologia , Salmonella/efeitos dos fármacos , Técnicas de Amplificação de Ácido Nucleico/métodos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/químicaRESUMO
Central serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10-9). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0×10-4) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3×10-11) and glaucoma (OR=0.82, P=6.9×10-9). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases.
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Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.
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Establishing a deep learning model for transformer fault diagnosis using transformer oil chromatogram data requires a large number of fault samples. The lack and imbalance of oil chromatogram data can lead to overfitting, lack of representativeness of the model, and unsatisfactory prediction results on test set data, making it difficult to accurately diagnose transformer faults. A conditional Wasserstein generative adversarial network with gradient penalty optimization (CWGAN-GP) is adopted in this paper, which based on gradient penalty optimization and expand the oil chromatography fault samples of 500 sets of transformer oil chromatography data with 5 types of faults. The proposed method is used to classify transformer faults using a deep autoencoder, and the sample quality of the neural network model proposed in this paper is compared with several other variants of generative adversarial neural network models. The research results show that after using the method proposed in this paper for sample expansion, the overall accuracy of fault diagnosis can reach 93.2 %, which is 4.98 % higher than the original imbalanced samples. Compared with other sample expansion methods, the accuracy of fault diagnosis of the algorithm in this paper is improved by 1.70 %-3.05 %.
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Developing high performance noble-metal-free electrocatalysts as an alternative to Pt-based catalysts for the oxygen reduction reaction (ORR) in energy conversion devices is highly desirable. We report herein the preparation of a coordination-polymer (CP)-derived Fe/CP/C composite as an electrocatalyst for the ORR with excellent activity and stability both in solution and in Zn-air batteries. The Fe/CP/C catalyst was obtained from the pyrolysis of an iron porphyrin Fe(TPP)Cl (5,10,15,20-tetraphenyl-21H,23H-porphyrin iron(III) chloride) grafted Zn-coordination polymer with dangling functional groups 4,4'-oxybisbenzoic acid and 4,4'-bipyridine ligands. The Fe/CP/C catalyst showed much higher ORR activity with a half-wave potential (E1/2) of 0.90 V (vs. RHE) than the Fe/C catalyst (E1/2 = 0.85 V) derived from the carbon-black-supported Fe porphyrins in 0.1 M KOH solution. When Fe/CP/C was used as the cathode electrocatalyst in Zn-air batteries (ZABs), the ZABs achieved a significantly higher open circuit voltage (OCV = 1.43 V) and maximum power density (Pmax = 142.8 mW cm-2) compared with Fe/C (OCV = 1.38 V, Pmax = 104.5 mW cm-2) and commercial 20 wt% Pt/C (OCV = 1.41 V, Pmax = 117.6 mW cm-2). Using dangling functional groups in CP to increase the loading efficiency of iron porphyrins offered a facile method to prepare high-performance noble-metal-free electrocatalysts for the ORR, which may provide promising applications to energy conversion devices.
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The newly discovered high-temperature superconductivity in La_{3}Ni_{2}O_{7} under pressure has attracted a great deal of attention. The essential ingredient characterizing the electronic properties is the bilayer NiO_{2} planes coupled by the interlayer bonding of 3d_{z^{2}} orbitals through the intermediate oxygen atoms. In the strong coupling limit, the low-energy physics is described by an intralayer antiferromagnetic spin-exchange interaction J_{â¥} between 3d_{x^{2}-y^{2}} orbitals and an interlayer one J_{â¥} between 3d_{z^{2}} orbitals. Taking into account Hund's rule on each site and integrating out the 3d_{z^{2}} spin degree of freedom, the system reduces to a single-orbital bilayer t-J model based on the 3d_{x^{2}-y^{2}} orbital. By employing the slave-boson approach, the self-consistent equations for the bonding and pairing order parameters are solved. Near the physically relevant 1/4-filling regime (doping δ=0.3â¼0.5), the interlayer coupling J_{â¥} tunes the conventional single-layer d-wave superconducting state to the s-wave one. A strong J_{â¥} could enhance the interlayer superconducting order, leading to a dramatically increased T_{c}. Interestingly, there could exist a finite regime in which an s+id state emerges.