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Homologous recombination (HR) is essential for the maintenance of genome stability. During HR, Replication Protein A (RPA) rapidly coats the 3'-tailed single-strand DNA (ssDNA) generated by end resection. Then, the ssDNA-bound RPA must be timely replaced by Rad51 recombinase to form Rad51 nucleoprotein filaments that drive homology search and HR repair. How cells regulate Rad51 assembly dynamics and coordinate RPA and Rad51 actions to ensure proper HR remains poorly understood. Here, we identified that Rtt105, a Ty1 transposon regulator, acts to stimulate Rad51 assembly and orchestrate RPA and Rad51 actions during HR. We found that Rtt105 interacts with Rad51 in vitro and in vivo and restrains the adenosine 5' triphosphate (ATP) hydrolysis activity of Rad51. We showed that Rtt105 directly stimulates dynamic Rad51-ssDNA assembly, strand exchange, and D-loop formation in vitro. Notably, we found that Rtt105 physically regulates the binding of Rad51 and RPA to ssDNA via different motifs and that both regulations are necessary and epistatic in promoting Rad51 nucleation, strand exchange, and HR repair. Consequently, disrupting either of the interactions impaired HR and conferred DNA damage sensitivity, underscoring the importance of Rtt105 in orchestrating the actions of Rad51 and RPA. Our work reveals additional layers of mechanisms regulating Rad51 filament dynamics and the coordination of HR.
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DNA de Cadeia Simples , Rad51 Recombinase , Reparo de DNA por Recombinação , Proteína de Replicação A , Proteínas de Saccharomyces cerevisiae , Rad51 Recombinase/metabolismo , Proteína de Replicação A/metabolismo , Proteína de Replicação A/genética , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Ligação ProteicaRESUMO
The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20-H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner. In parallel, RPA recruits RNF20 to chromosomal breaks upon DNA damage. Disruption of the RPA-RNF20 interaction or depletion of RNF20 increases mitotic lagging chromosomes and chromosome bridges and impairs BRCA1 and RAD51 loading and homologous recombination repair, leading to elevated chromosome breaks, genome instability, and sensitivities to DNA-damaging agents. Mechanistically, the RPA-RNF20 pathway promotes local H2Bub, H3K4 dimethylation, and subsequent SNF2H recruitment, ensuring proper Aurora B kinase activation at centromeres and efficient loading of repair proteins at DNA breaks. Thus, the RPA-RNF20-SNF2H cascade plays a broad role in preserving genome stability by coupling H2Bub to chromosome segregation and DNA repair.
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Reparo de DNA por Recombinação , Proteína de Replicação A , Humanos , Cromatina , Segregação de Cromossomos , Reparo do DNA , Instabilidade Genômica , Histonas/genética , Histonas/metabolismo , Recombinação Homóloga , Proteína de Replicação A/genética , Proteína de Replicação A/metabolismoRESUMO
The single-stranded DNA (ssDNA) binding protein complex RPA plays a critical role in promoting DNA replication and multiple DNA repair pathways. However, how RPA is regulated to achieve its functions precisely in these processes remains elusive. Here, we found that proper acetylation and deacetylation of RPA are required to regulate RPA function in promoting high-fidelity DNA replication and repair. We show that yeast RPA is acetylated on multiple conserved lysines by the acetyltransferase NuA4 upon DNA damage. Mimicking constitutive RPA acetylation or blocking its acetylation causes spontaneous mutations with the signature of micro-homology-mediated large deletions or insertions. In parallel, improper RPA acetylation/deacetylation impairs DNA double-strand break (DSB) repair by the accurate gene conversion or break-induced replication while increasing the error-prone repair by single-strand annealing or alternative end joining. Mechanistically, we show that proper acetylation and deacetylation of RPA ensure its normal nuclear localization and ssDNA binding ability. Importantly, mutation of the equivalent residues in human RPA1 also impairs RPA binding on ssDNA, leading to attenuated RAD51 loading and homologous recombination repair. Thus, timely RPA acetylation and deacetylation likely represent a conserved mechanism promoting high-fidelity replication and repair while discriminating the error-prone repair mechanisms in eukaryotes.
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Proteína de Replicação A , Proteínas de Saccharomyces cerevisiae , Humanos , Acetilação , Reparo do DNA , Replicação do DNA , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/genética , Histona Acetiltransferases/metabolismo , Rad51 Recombinase/metabolismo , Proteína de Replicação A/genética , Proteína de Replicação A/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Células HeLaRESUMO
Blue afterglow constitutes of one of the primary afterglow colors and can convert into other afterglow colors through energy transfer. The reported studies show the fabrication of blue afterglow emitters, but most of them are formed by room-temperature phosphorescence mechanism and require UVB lights as excitation source (these high-energy lights may damage organic systems). Here we report visible-light-excitable blue thermally activated delayed fluorescence type (TADF-type) afterglow materials via delicate control of excited states in difluoroboron ß-diketonate (BF2bdk) systems. Tiny change of the substituents in BF2bdk system has been found to pose significant influence on excited state energy levels and consequently narrow the singlet-triplet splitting energy of the system. As a result, both forward and reverse intersystem crossing have been accelerated, leading to the emergence of BF2bdk's TADF-type organic afterglow in rigid crystalline matrices. The resultant TADF-type afterglow materials exhibit emission lifetimes of several hundred milliseconds, photoluminescence quantum yield (PLQY) of 24.7 % and display temperature responsive property.
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Poly(l-lactic acid) (PLLA) featuring desirable biodegradability and biocompatibility has been recognized as one of the promising eco-friendly biomaterials. However, low crystallization and poor mechanical and chemical performances dramatically hamper its practical application. In this work, we report that functionalized cellulose/PLLA composite superhydrophobic stereocomplex films with controllable water adhesion and protein adsorption can be fabricated by a facile approach for the first time. First, cellulose is surface-modified by means of two silanization modification methods. Then, superhydrophobic cellulose/PLLA composite films are prepared through a solvent-evaporation-induced phase separation method. The two cellulose/PLLA composite films exhibit extreme water repellency but tunable water adhesion from sticky to slippery. The protein adsorption capacity of the cellulose/PLLA composite films can also be regulated. In addition, the stereocomplexation of the composite film provides excellent mechanical properties with an elongation at break of 22.36%, which is 237.8% higher than that of a pure PLLA film, which is more suitable for biomaterials. Furthermore, good biodegradability of the PLLA composite films in nature enables the bio-based composites as alternative materials to replace conventional petroleum-based polymers. The superhydrophobic films have also been demonstrated for many applications, including slippery surfaces, liquid transportation without loss, and antifouling.
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PURPOSE: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality worldwide. Statins, which are effective in preventing ASCVD, are underused, particularly for primary prevention. This study examined trends in statin use for primary ASCVD prevention from 1999 to 2020, focusing on demographic variations. METHODS: Utilizing data from the National Health and Nutrition Examination Survey, the present study includes individuals aged 18 years and older who had a greater than 10% risk of ASCVD over 10 years, and excluded patients with existing ASCVD. Subgroup analyses by demographic categories were performed. We calculated the changes in statin usage and used linear and quadratic tests to assess the linear and nonlinear trends in those changes. RESULTS: A total of 10,037 participants were included. Statin usage increased from 16.16% in 1999 to 36.24% in 2010, and 41.74% in 2020 (quadratic P-value < 0.001). In the 18-44 years age group, statin usage increased from 2.52% in 1999 to 8.14% in 2020 (linear P-value = 0.322), showing no significant linear trend. In the "never-married" group, statin usage increased from 19.16% in 1999 to 30.05% in 2020 (linear P-value = 0.256). CONCLUSION: Statin usage has shown a positive trend among populations requiring primary prevention for ASCVD. Currently, health policies are proving effective. However, the overall statin usage rate remains less than 50%. Additionally, young and never-married individuals should also receive special attention regarding statin usage as primary treatment for ASCVD.
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Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Inquéritos Nutricionais , Prevenção Primária , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Aterosclerose/prevenção & controle , Aterosclerose/epidemiologia , Adolescente , Adulto Jovem , Idoso , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologiaRESUMO
BACKGROUND AND AIMS: The clinical effects of multivessel interventions in patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI), multivessel disease (MVD) and chronic kidney disease (CKD) remain uncertain. This study aimed to investigate the safety and effectiveness of intervention in non-culprit lession(s) among this cohort. METHODS: We consecutively included patients diagnosed with UA/NSTEMI, MVD and CKD between January 2008 and December 2018 at our centre. After successful percutaneous coronary intervention (PCI), we compared 48-month overall mortality between those undergoing multivessel PCI (MV-PCI) through a single-procedure or staged-procedure approach and culprit vessel-only PCI (CV-PCI) after 1:1 propensity score matching. We conducted stratified analyses and tests for interaction to investigate the modifying effects of critical covariates. Additionally, we recorded the incidence of contrast-induced nephropathy (CIN) to assess the perioperative safety of the two treatment strategies. RESULTS: Of the 749 eligible patients, 271 pairs were successfully matched. Those undergoing MV-PCI had reduced all-cause mortality (hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.48-0.67). Subgroup analysis showed that those with advanced CKD (estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2 ) could not benefit from MV-PCI (P = 0.250), and the survival advantage also tended to diminish in diabetes (P interaction < 0.01; HR = 0.95, 95% CI = 0.65-1.45). Although the staged-procedure approach (N = 157) failed to bring additional survival benefits compared to single-procedure MV-PCI (N = 290) (P = 0.460), it showed a tendency to decrease the death risk. CIN risks in MV-PCI and CV-PCI groups were not significantly different (risk ratio = 1.60, 95% CI = 0.94-2.73). CONCLUSION: Among patients with UA/NSTEMI and non-diabetic CKD and an eGFR > 30 mL/min/1.73 m2 , MV-PCI was associated with a reduced risk of long-term death but did not increase the incidence of CIN during the management of MVD compared to CV-PCI. And staged procedures might be a preferable option over single-procedure MV-PCI.
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Doença da Artéria Coronariana , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Intervenção Coronária Percutânea/métodos , Angina Instável , Insuficiência Renal Crônica/complicações , Rim , Resultado do TratamentoRESUMO
5-Methyl-cytosine (5mC) is one of the most important DNA modifications and plays versatile biological roles. It is well known that 5mC stabilizes DNA duplexes. However, it remains unclear how 5mC affects the kinetics of DNA melting and hybridization. Here, we studied the kinetics of unzipping and rezipping using a 502-bp DNA hairpin by single-molecule magnetic tweezers. Under constant loading rates, 5mC increases the unzipping force but counterintuitively decreases the rezipping force at various salt and temperature conditions. Under constant forces, the non-methylated DNA hops between metastable states during unzipping and rezipping, which implies low energy barriers. Surprisingly, the 5mC DNA can't rezip after fully unzipping unless much lower forces are applied, where it rezips stochastically in a one-step manner, which implies 5mC kinetically hinders DNA hybridization and high energy barriers in DNA hybridization. All-atom molecular dynamics simulations reveal that the 5mC kinetically hinders DNA hybridization due to steric effects rather than electrostatic effects caused by the additional methyl groups of cytosines. Considering the possible high speed of DNA unzipping and zipping during replication and transcription, our findings provide new insights into the biological roles of 5mC.
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5-Metilcitosina , DNA , Citosina , DNA/química , Fenômenos Magnéticos , Conformação de Ácido Nucleico , Hibridização de Ácido NucleicoRESUMO
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age < 32 weeks and to verify nutritional risk factors related to BPD development. METHODS: A prospective multicenter cohort study of very preterm infants was conducted in 40 tertiary neonatal intensive care units across mainland China between January 1, 2020, and December 31, 2021. Preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and had a respiratory score > 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors. RESULTS: The primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99-0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02-1.04; p < 0.001), parenteral protein > 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25-2.17; p < 0.001), feeding type (formula: OR 3.48, 95% CI 2.21-5.49; p < 0.001, mixed feed: OR 1.92, 95% CI 1.36-2.70; p < 0.001; breast milk as reference), hsPDA (OR 1.98, 95% CI 1.44-2.73; p < 0.001), and EUGR ats 36 weeks (OR 1.40, 95% CI 1.02-1.91; p = 0.035). CONCLUSIONS: A longer duration to achieve full enteral nutrition in very preterm infants was associated with increased BPD development. Breastfeeding was demonstrated to have a protective effect against BPD. Early and rapidly progressive enteral nutrition and breastfeeding should be promoted in very preterm infants. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000030125 on 24/02/2020) and in www.ncrcch.org (No. ISRCTN84167642 on 25/02/2020).
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Displasia Broncopulmonar , Doenças do Prematuro , Síndrome do Desconforto Respiratório , Humanos , Recém-Nascido , Displasia Broncopulmonar/terapia , Estudos de Coortes , Nutrição Enteral , Retardo do Crescimento Fetal , Idade Gestacional , Recém-Nascido Prematuro , Estudos ProspectivosRESUMO
The ubiquitin E3 ligase Bre1-mediated H2B monoubiquitination (H2Bub) is essential for proper DNA replication and repair in eukaryotes. Deficiency in H2Bub causes genome instability and cancer. How the Bre1-H2Bub pathway is evoked in response to DNA replication or repair remains unknown. Here, we identify that the single-stranded DNA (ssDNA) binding factor RPA acts as a key mediator that couples Bre1-mediated H2Bub to DNA replication and repair in yeast. We found that RPA interacts with Bre1 in vitro and in vivo, and this interaction is stimulated by ssDNA. This association ensures the recruitment of Bre1 to replication forks or DNA breaks but does not affect its E3 ligase activity. Disruption of the interaction abolishes the local enrichment of H2Bub, resulting in impaired DNA replication, response to replication stress, and repair by homologous recombination, accompanied by increased genome instability and DNA damage sensitivity. Notably, we found that RNF20, the human homolog of Bre1, interacts with RPA70 in a conserved mode. Thus, RPA functions as a master regulator for the spatial-temporal control of H2Bub chromatin landscape during DNA replication and recombination, extending the versatile roles of RPA in guarding genome stability.
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Reparo do DNA , Replicação do DNA , Histonas/metabolismo , Proteína de Replicação A/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , DNA de Cadeia Simples , Histonas/genética , Recombinação Homóloga , Metanossulfonato de Metila/toxicidade , Domínios e Motivos de Interação entre Proteínas/genética , Proteína de Replicação A/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding. Here, we describe an important role of Rtt105 in high-fidelity DNA replication and recombination and demonstrate that these functions of Rtt105 primarily depend on its regulation of RPA. The deletion of RTT105 causes elevated spontaneous DNA mutations with large duplications or deletions mediated by microhomologies. Rtt105 is recruited to DNA double-stranded break (DSB) ends where it promotes RPA assembly and homologous recombination repair by gene conversion or break-induced replication. In contrast, Rtt105 attenuates DSB repair by the mutagenic single-strand annealing or alternative end joining pathway. Thus, Rtt105-mediated regulation of RPA promotes high-fidelity replication and recombination while suppressing repair by deleterious pathways. Finally, we show that the human RPA-interacting protein hRIP-α, a putative functional homolog of Rtt105, also stimulates RPA assembly on ssDNA, suggesting the conservation of an Rtt105-mediated mechanism.
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Reparo do DNA , Replicação do DNA , Proteínas de Ligação a RNA/metabolismo , Proteína de Replicação A/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Transporte Ativo do Núcleo Celular , Proteínas de Transporte/metabolismo , Núcleo Celular/metabolismo , Quebras de DNA de Cadeia Dupla , DNA de Cadeia Simples/metabolismo , Conversão Gênica , Deleção de Genes , Duplicação Gênica , Humanos , Modelos Biológicos , Ligação Proteica , Rad51 Recombinase/metabolismoRESUMO
A novel label-free optical fiber biosensor, based on a microcavity fiber Mach-Zehnder interferometer, was developed and practically demonstrated for DNA detection. The biosensor was fabricated using offset splicing standard communication single-mode fibers (SMFs). The light path of the sensor was influenced by the liquid sample in the offset open cavity. In the experiment, a high sensitivity of -17,905 nm/RIU was achieved in the refractive index (RI) measurement. On this basis, the probe DNA (pDNA) was immobilized onto the sensor's surface using APTES, enabling real-time monitoring of captured complementary DNA (cDNA) samples. The experimental results demonstrate that the biosensor exhibited a high sensitivity of 0.32 nm/fM and a limit of detection of 48.9 aM. Meanwhile, the sensor has highly repeatable and specific performance. This work reports an easy-to-manufacture, ultrasensitive, and label-free DNA biosensor, which has significant potential applications in medical diagnostics, bioengineering, gene identification, environmental science, and other biological fields.
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Engenharia Biomédica , Comércio , DNA Complementar , Fibras ÓpticasRESUMO
Dam construction alters the hydrodynamic conditions, consequently impacting the swimming behavior of fish. To explore the effect of flow hydrodynamics on fish swimming behavior, five endemic fish species in the upper Yangtze River basin were selected. Through high-speed video visualization and computer analysis, these species' swimming patterns under different flow velocities (0.1-1.2 m/s) were investigated. The kinematic and morphological characteristics of the fish were presented. The principal component analysis was used to analyse the main factors influencing the swimming ability of fish and to determine the correlation coefficients among fish behavior indicators. Fish exhibited three different swimming patterns under different flow velocities. Low velocity (0.1-0.3 m/s) corresponds to free motion, middle velocity (0.4-0.7 m/s) corresponds to cruising motion, and high velocity corresponds to stress motion (0.8-1.2 m/s). The fish kinematic index curves were obtained, and four of five fish species showed two extreme points, which means the optimal and adverse swimming strategies can be determined. With the increase in flow velocity, the tail-beat frequency showed an increasing trend, whereas the tail-beat angle and amplitude showed a decreasing trend. Morphological and kinematic parameters were the two main indexes that affect the swimming ability of fish, which accounts for 41.9% and 26.9%, respectively.
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Hidrodinâmica , Rios , Natação , Animais , China , Fenômenos Biomecânicos , Peixes/fisiologia , Peixes/anatomia & histologia , Análise de Componente Principal , Gravação em VídeoRESUMO
Background: Total arterial revascularization (TAR) has gradually become accepted and recognized, but its effect and safety in diabetic patients are not clear. We performed a systematic review and meta-analysis to summarize the safety and efficacy of TAR and additionally evaluated the clinical outcomes of arterial revascularization using different arterial deployments in patients with diabetes. Methods: PubMed, Embase, and the Cochrane Library databases from inception to July 2022 for studies that studied the effect of arterial revascularization in diabetic patients undergoing isolated coronary artery bypass graft (CABG) were searched. The primary outcome was long-term ( ≥ 12 months of follow-up) death by any cause. The secondary efficacy endpoints were long-term ( ≥ 12 months) cardiovascular death, early sternal wound infection (SWI) and death ( ≤ 30 days or in hospital). Risk ratios (RRs), hazard ratios (HRs), and their corresponding 95% confidence intervals (CIs) were calculated to describe short-term results and long-term survival outcomes. Two different ways were used to analyze the effect of TAR and the impact of diabetes on the clinical outcomes of TAR. Results: Thirty-five studies were included in the study, covering 178,274 diabetic patients. Compared to conventional surgery with saphenous veins, TAR was not associated with increased early mortality (RR 0.77, 95% CI 0.48-1.23) and risk of SWI (RR 0.77, 95% CI 0.46-1.28). The overall Kaplan-Meier survival curves based on reconstructed patient data indicated a significant association between TAR and reduced late mortality (HR 0.52, 95% CI 0.48-0.67) and the curves based on the propensity-score matched (PSM) analyses suggested a similar result (HR 0.74, 95% CI 0.66-0.85). TAR could also effectively decrease the risk of cardiovascular death (HR 0.42, 95% CI 0.24-0.75). Through comparing the effect of TAR in patients with and without diabetes, we found that the presence of diabetes did not elevate the risk of early adverse events (death: RR 1.50, 95% CI 0.64-3.49; SWI: RR 2.52, 95% CI 0.91-7.00). Although diabetes increased long-term mortality (HR 1.06; 95% CI 1.35-2.03), the cardiovascular death rate was similar in patients with diabetes and patients without diabetes (HR 1.09; 95% CI 0.49-2.45). Regarding the selection of arterial conduits, grafting via the bilateral internal mammary artery (BIMA) decreased the risk of overall death (HR 0.67, 95% CI 0.52-0.85) and cardiovascular death (HR 0.55, 95% CI 0.35-0.87) without resulting in a significantly elevated rate of early death (RR 0.95, 95% CI 0.82-1.11). However, the evidence from PSM studies indicated no difference between the long-term mortality of the BIMA group and that of the single internal mammary arteries (SIMA) groups (HR 0.76, 95% CI 0.52-1.11), and the risk of SWI was significantly increased by BIMA in diabetes (RR 1.65, 95% CI 1.42-1.91). The sub-analysis indicated the consistent benefit of the radial artery (RA) application in diabetic patients (HR 0.71, 95% CI 0.63-0.79) compared to saphenous vein graft. In two propensity-score-matched studies, the evidence showed that the survival outcomes of the BIMA group were similar to that of the SIMA plus RA group but that grafting via the RA reduced the risk of sternal wound infection. Conclusions: Compared with conventional surgery using SVG, TAR was associated with an enhanced survival benefit in diabetes and this long-term gain did not increase the risk of early mortality or SWI. Given the increased infection risk and controversial long-term survival gains of grafting via the BIMA in diabetes, its wide use for grafting in this cohort should be seriously considered. Compared to using the right internal mammary artery (RIMA), RA might be a similarly effective but safer option for patients with diabetes.
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Background: The prognosis of patients with acute coronary syndrome (ACS) varies greatly, and risk assessment models can help clinicians to identify and manage high-risk patients. While the Global Registry of Acute Coronary Events (GRACE) model is widely used, the clinical pathways for acute coronary syndromes (CPACS), which was constructed based on the Chinese population, and acute coronary treatment and intervention outcomes network (ACTION) have not yet been validated in the Chinese population. Methods: Patients with ACS who underwent coronary angiography or percutaneous coronary intervention from 2011 to 2020, were retrospectively recruited and the appropriate corresponding clinical indicators was obtained. The primary endpoint was in-hospital mortality. The performance of the GRACE, GRACE 2.0, ACTION, thrombolysis in myocardial infarction (TIMI) and CPACS risk models was evaluated and compared. Results: A total of 19,237 patients with ACS were included. Overall, in-hospital mortality was 2.2%. ACTION showed the highest accuracy in predicting discriminated risk (c-index 0.945, 95% confidence interval [CI] 0.922-0.955), but the calibration was not satisfactory. GRACE and GRACE 2.0 did not significantly differ in discrimination (p = 0.1480). GRACE showed the most accurate calibration in all patients and in the subgroup analysis of all models. CPACS (c-index 0.841, 95% CI 0.821-0.861) and TIMI (c-index 0.811, 95% CI 0.787-0.835) did not outperform (c-index 0.926, 95% CI 0.911-0.940). Conclusions: In contemporary Chinese ACS patients, the ACTION risk model's calibration is not satisfactory, although outperformed the gold standard GRACE model in predicting hospital mortality. The CPACS model developed for Chinese patients did not show better predictive performance than the GRACE model.
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It remains challenging to fabricate highly-efficient and long-lived organic afterglow materials, especially in the case of red afterglow systems. Here we develop advanced charge transfer (CT) technology to boost afterglow efficiency and lifetimes in fluoranthene-containing dopant-matrix systems. First, organic CT molecules possess singlet-triplet splitting energy (ΔEST ) of around 0.5â eV, much smaller than localized excitation systems. Second, upon doping into suitable organic matrices, dipole-dipole interactions between 1 CT states and organic matrices reduce 1 CT levels with less effect on 3 CT levels, and thus further narrow ΔEST and enhance intersystem crossing. Third, the rigid planar structure of fluoranthene groups and the rigid microenvironment provided by organic matrices can suppress phosphorescence quenching. Forth, the multiple donor design enables spectral red-shifts to red region and switches on TADF mechanism to improve afterglow efficiency to 13.1 % and maintain afterglow lifetime of 0.1â s. Such high-performance afterglow materials have been rarely explored in reported studies.
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The catalytic field aims to decrease reaction barriers, accelerate reaction processes, and enhance the selectivity toward a target product. This study uses first-principles calculations to design a modified direct Z-scheme SnS2/ß-As heterostructure as a potential photocatalyst for overall water splitting. Our previous investigations have demonstrated that the SnS2/ß-As heterostructure can realize a hydrogen evolution reaction (HER) under light, while the oxygen evolution reaction (OER) follows a pathway involving the intermediate HOOH*. Interestingly, by substituting an S atom of SnS2 with a Se or Te atom, the rate-determining step of the OER is significantly reduced from 3.76 eV to 2.56 or 2.22 eV. Moreover, the OER can occur directly without the transition via HOOH*. Isoelectronic doping effectively trades off the adsorption strength of OER intermediates and promotes the OER process. This work highlights the dual benefits of isoelectronic doping, namely lowering the reaction barrier of the rate-determining step and promoting the selectivity of end products. These findings provide insights into the rational design of high-efficiency photocatalysts for water splitting.
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Inspired by natural photosynthesis, two-dimensional van der Waals (vdW) heterostructures are considered as promising photocatalysts for solar-driven water splitting and they attract ever-growing interest. A type-II vdW hetero-photocatalyst (CdTe/B4C3) integrating the polarized CdTe into metal-free B4C3 was constructed, which could achieve solar-driven spontaneous overall water splitting at pH = 0-7 and exhibit a high solar-to-hydrogen (STH) efficiency of 19.64%. Our calculation results show that the interlayer interaction between the CdTe and B4C3 monolayers in the heterostructure creates an interfacial electric field enhanced by the intrinsic dipole of polarized CdTe, which accelerates the effective separation of photogenerated carriers and makes the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) take place separately on the B4C3 and CdTe layers. Furthermore, the CdTe/B4C3 heterostructure has decent band edge positions to promote the redox reaction to decompose water due to the significant electrostatic potential difference in the CdTe/B4C3 heterostructure and it could trigger spontaneous redox reaction under light at pH = 0-7. This work is helpful for us to design type-II heterojunction photocatalysts with high efficiency of photogenerated carrier separation for overall water splitting.
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Vibrio alginolyticus is an important foodborne pathogen that can infect both humans and marine animals and cause massive economic losses in aquaculture. Small noncoding RNAs (sRNAs) are emerging posttranscriptional regulators that affect bacterial physiology and pathological processes. In the present work, a new cell density-dependent sRNA, Qrr4, was characterized in V. alginolyticus based on a previously reported RNA-seq analysis and bioinformatics approach. The effects of Qrr4 actions on the physiology, virulence, and metabolism of V. alginolyticus were comprehensively investigated based on molecular biology and metabolomics approaches. The results showed that qrr4 deletion markedly inhibited growth, motility and extracellular protease activities. Additionally, nontargeted metabolism and lipidomics analyses revealed that qrr4 deletion induced significant disturbance of multiple metabolic pathways. The key metabolic remodelling that occurred in response to qrr4 deletion was found to involve phospholipid, nucleotide, carbohydrate and amino acid metabolic pathways, providing novel clues about a potential mechanism via which mutation of qrr4 could interfere with cellular energy homeostasis, modulate membrane phospholipid composition and inhibit nucleic acid and protein syntheses to regulate the motility, growth and virulence characteristics of V. alginolyticus. Overall, this study provides a comprehensive understanding of the regulatory roles of the new cell density-dependent sRNA Qrr4 in V. alginolyticus. KEY POINTS: ⢠A novel cell density-dependent sRNA, Qrr4, was cloned in V. alginolyticus. â¢Qrr4 regulated growth and virulence factors of V. alginolyticus. ⢠Phospholipid, nucleotide and energy metabolisms were modulated obviously by Qrr4.
Assuntos
Pequeno RNA não Traduzido , Vibrio alginolyticus , Animais , Humanos , Vibrio alginolyticus/genética , Virulência/genética , Fatores de Virulência/metabolismo , Nucleotídeos/metabolismo , Pequeno RNA não Traduzido/genética , Proteínas de Bactérias/genéticaRESUMO
The underwater sound absorption technique in low-frequency and broadband has far-reaching prospects since it is essential for noise reduction of deep-sea operation requirements and evading advanced underwater target detection. Here, we propose an underwater sound-absorbing composite lattice with low-frequency and ultra-broadband characteristics. The composite lattice is constructed by regular spatially stacking cells with different sizes of metallic core spheres. All the core spheres are coated with silicon rubbers, and cells are embedded in the rubber matrix. In the composite lattice stereostructure, the lattice cells convert incident longitudinal waves into transverse waves through multiple local resonance coupling and multiple scattering. The energy is localized and dissipated in the composite lattice. We analyze the relationship among the corresponding absorption spectrums, the displacement clouds, and the resonance modes of lattice cells. Then, we construct a composite lattice and realize low-frequency broadband absorption from 693 to 1106 Hz with absorptance above 0.8. Further, our investigation demonstrates that the absorption bandwidth can be extended to ultra-broadband from 1077 to 10 000 Hz, where the thickness of the composite lattice is λ/17.05. The proposed composite lattice provides a practical approach to designing ultrathin low-frequency and ultra-broadband acoustic absorption coating for underwater noise suppression.