RESUMO
BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.
Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Heparina/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Proteínas Recombinantes , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Resultado do TratamentoRESUMO
Guangzhou has been the city most affected by the dengue virus (DENV) in China, with a predominance of DENV serotype 1 (DENV-1). Viral factors such as dengue serotype and genotype are associated with severe dengue (SD). However, none of the studies have investigated the relationship between DENV-1 genotypes and SD. To understand the association between DENV-1 genotypes and SD, the clinical manifestations of patients infected with different genotypes were investigated. A total of 122 patients with confirmed DENV-1 genotype infection were recruited for this study. The clinical manifestations, laboratory tests, and levels of inflammatory mediator factors were statistically analyzed to investigate the characteristics of clinical manifestations and immune response on the DENV-1 genotype. In the case of DENV-1 infection, the incidence of SD with genotype V infection was significantly higher than that with genotype I infection. Meanwhile, patients infected with genotype V were more common in ostealgia and bleeding significantly. In addition, levels of inflammatory mediator factors including IFN-γ, TNF-α, IL-10, and soluble vascular cell adhesion molecule 1 were higher in patients with SD infected with genotype V. Meanwhile, the concentrations of regulated upon activation normal T-cell expressed and secreted and growth-related gene alpha were lower in patients with SD infected with genotype V. The higher incidence of SD in patients infected with DENV-1 genotype V may be attributed to elevated cytokines and adhesion molecules, along with decreased chemokines.
Assuntos
Vírus da Dengue , Genótipo , Sorogrupo , Dengue Grave , Humanos , Vírus da Dengue/genética , Vírus da Dengue/classificação , China/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Dengue Grave/virologia , Dengue Grave/epidemiologia , Adulto Jovem , Citocinas/sangue , Adolescente , Idoso , Incidência , Criança , Dengue/virologia , Dengue/epidemiologiaRESUMO
The use of precise epitope peptides as antigens is essential for accurate serological diagnosis of viral-infected individuals, but now it remains an unsolvable problem for mapping precise B cell epitopes (BCEs) recognized by human serum. To address this challenge, we propose a novel epitope delimitation (ED) method to uncover BCEs in the delineated human IgG-reactive (HR) antigenic peptides (APs). Specifically, the method based on the rationale of similarities in humoral immune responses between mammalian species consists of a pair of elements: experimentally delineated HR-AP and rabbit-recognized (RR) BCE motif and corresponding pair of sequence alignment analysis. As a result of using the ED approach, after decoding four RR-epitomes of human papillomavirus types 16/18-E6 and E7 proteins utilizing rabbit serum against each recombinant protein and sequence alignment analysis of HR-APs and RR-BCEs, 19 fine BCEs in 17 of 22 known HR-APs were defined based on each corresponding RR-BCE motifs, including the type-specificity of each delimited BCE in homologous proteins. The test with 22 known 16/20mer HR-APs demonstrated that the ED method is effective and efficient, indicating that it can be used as an alternative method to the conventional identification of fine BCEs using overlapping 8mer peptides.
Assuntos
Proteínas Oncogênicas Virais , Peptídeos , Animais , Humanos , Coelhos , Sequência de Aminoácidos , Peptídeos/genética , Epitopos de Linfócito B , Alinhamento de Sequência , Imunoglobulina G , Mapeamento de Epitopos/métodos , MamíferosRESUMO
One key difficulty in realizing Majorana zero modes (MZMs) is the required high magnetic field, which causes serious issues, e.g., shrinks the superconducting gap, reduces topological region, and weakens their robustness against disorders. In this Letter, we propose that the Meissner effect can bring the topological superconducting phase to a superconductor/topological-insulator/superconductor (SC/TI/SC) hybrid system. Remarkably, the required magnetic field strength (<10 mT) to support MZMs has been reduced by several orders of magnitude compared to that (>0.5 T) in the previous schemes. Tuning the phase difference between the top and bottom superconductors can control the number and position of the MZMs. In addition, we account for the electrostatic potential in the superconductor/topological-insulator (SC/TI) interface through the self-consistent Schrödinger-Poisson calculation, which shows the experimental accessibility of our proposal. Our proposal only needs a small magnetic field of less than 10 mT and is robust against the chemical potential fluctuation, which makes the SC/TI/SC hybrid an ideal Majorana platform.
RESUMO
BACKGROUND: Dengue is an important public health problem, which caused by the dengue virus (DENV), a single-stranded RNA virus consisted of four serotypes. Central nervus system (CNS) impairment in dengue usually results from DENV-2 or DENV-3 infection, which lead to life-threatening outcomes. Furthermore, neurological complications due to DENV-1 was rare especially in adult patients. CASE PRESENTATION: A 44-year-old man without comorbidities had lethargy after hyperpyrexia and a positive DENV NS1 antigen was detected for confirming the diagnosis of dengue on day 8 of onset. Then logagnosia, decreased muscle strength, delirium and irritability were occurred even radiographic examination were normal. He was treated with low-dose hormone, sedatives and gamma goblin with a short duration of 6 days. The cerebrospinal fluid (CSF) tests were persistent normal. However, presence of DENV-1 RNA was confirmed both in CSF and serum. Furthermore, the complete sequence of the DENV isolated from the patient's serum was performed (GenBank No.: MW261838). The cytokines as IL-6, IL-10 and sVCAM-1 were increased in critical phase of disease. Finally, the patient was discharged on day 24 of onset without any neurological sequelae. CONCLUSION: Encephalopathy caused by a direct CNS invasion due to DENV-1 during viremia was described in an adult patient. Treatment with low-dose hormone and gamma goblin was helpful for admission.
Assuntos
Encefalopatias , Vírus da Dengue , Dengue , Adulto , Masculino , Humanos , Dengue/complicações , Dengue/diagnóstico , Sorogrupo , Hormônios , Anticorpos AntiviraisRESUMO
The current work investigates bioremediation (BIO) and electrokinetic (EK) remediation of crude oil hydrocarbons utilizing the biomass-electrokinetic (BIO-EK) approaches. The use of natural surfactants derived from plant biomass may improve remediation capacity by enhancing the solubility of organic pollutants. Sapindus mukorossi, a natural surfactant producer, was extracted from plant biomass in this study. The crude oil biodegradation efficiency was reported to be 98 %. In nature, FTIR confirms that plant biomass is lipopeptide. GCMS revealed that the crude oil (C7 - C23) was efficiently bio-degraded from lower to higher molecular weight. The application of natural surfactants in electokinetic remediation increased the plant biomass degradation of crude oil polluted soil by 98% compared to electrokinetic 55% in 2 days. Natural surfactant improves hydrocarbon solubilization and accelerates hydrocarbon electro migration to the anodic compartment, as confirmed by the presence of greater total organic content than the electrokinetic. This study proves that BIO-EK compared with a natural surfactant derived from plant biomass may be utilized to improve in situ bioremediation of crude oil polluted soils.
Assuntos
Petróleo , Poluentes do Solo , Tensoativos , Petróleo/metabolismo , Solo , Biomassa , Biodegradação Ambiental , Hidrocarbonetos , Poluentes do Solo/análise , Microbiologia do SoloRESUMO
Using physical vapor deposition (PVD) technology, GeSe nanowires were successfully fabricated by heating GeSe powder at temperatures of 500 °C, 530 °C, 560 °C, 590 °C, and 620 °C. The microstructure, crystal morphology, and chemical composition of the resulting materials were thoroughly analyzed employing methods like Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), plus Raman Spectroscopy. Through a series of photoelectric performance tests, it was discovered that the GeSe nanowires prepared at 560 °C exhibited superior properties. These nanowires not only possessed high crystalline quality but also featured uniform diameters, demonstrating excellent consistency. Under illumination at 780 nm, the GeSe nanowires prepared at this temperature showed higher dark current, photocurrent, and photoresponsivity compared to samples prepared at other temperatures. These results indicate that GeSe nanomaterials hold substantial potential in the field of photodetection. Particularly in the visible light spectrum, GeSe nanomaterials exhibit outstanding light absorption capabilities and photoresponse.
RESUMO
We present a novel target-driven methodology devised to predict the Heyd-Scuseria-Ernzerhof (HSE) band gap of two-dimensional (2D) materials leveraging the comprehensive C2DB database. This innovative approach integrates machine learning and density functional theory (DFT) calculations to predict the HSE band gap, conduction band minimum (CBM), and valence band maximum (VBM) of 2176 types of 2D materials. Subsequently, we collected a comprehensive data set comprising 3539 types of 2D materials, each characterized by its HSE band gaps, CBM, and VBM. Considering the lattice disparities between MoSi2N4 (MSN) and 2D materials, our analysis predicted 766 potential MSN/2D heterostructures. These heterostructures are further categorized into four distinct types based on the relative positions of their CBM and VBM: Type I encompasses 230 variants, Type II comprises 244 configurations, Type III consists of 284 permutations, and 0 band gap comprises 8 types.
RESUMO
This is the Preface to Special Topic: Challenges to Achieving Room-Temperature Superconductivity in Superhydrides under Pressure.
RESUMO
Van Hove singularities in proximity to the Fermi level promote electronic interactions and generate diverse competing instabilities. It is also known that a nontrivial Berry phase derived from spin-orbit coupling can introduce an intriguing decoration into the interactions and thus alter correlated phenomena. However, it is unclear how and what type of new physics can emerge in a system featured by the interplay between van Hove singularities (VHSs) and the Berry phase. Here, based on a general Rashba model on the square lattice, we comprehensively explore such an interplay and its significant influence on the competing electronic instabilities by performing a parquet renormalization group analysis. Despite the existence of a variety of comparable fluctuations in the particle-particle and particle-hole channels associated with higher-order VHSs, we find that the chiral p±ip pairings emerge as two stable fixed trajectories within the generic interaction parameter space, namely the system becomes a robust topological superconductor. The chiral pairings stem from the hopping interaction induced by the nontrivial Berry phase. The possible experimental realization and implications are discussed. Our work sheds new light on the correlated states in quantum materials with strong spin-orbit coupling (SOC) and offers fresh insights into the exploration of topological superconductivity.
RESUMO
Dengue virus (DENV) infection causes dengue fever, the most prevalent arthropod-transmitted viral disease worldwide. Viruses are acellular parasites and obligately rely on host cell machinery for reproduction. Previous studies have indicated metabolomic changes in endothelial cell models and sera of animal models and patients with dengue fever. To probe the immunometabolic mechanism of DENV infection, here, we report the metabolomic landscape of a human macrophage cell model of DENV infection and its antibody-dependent enhancement. DENV infection of THP-1-derived macrophages caused 202 metabolic variants, of which amino acids occupied 23.7%, fatty acids 21.78%, carbohydrates 10.4%, organic acids 13.37%, and carnitines 10.4%. These metabolomic changes indicated an overall anabolic signature, which was characterized by the global exhaustion of amino acids, increases of cellular fatty acids, carbohydrates and pentoses, but decreases of acylcarnitine. Significant activation of metabolic pathways of glycolysis, pentose phosphate, amino acid metabolism, and tricarboxylic acid cycle collectively support the overall anabolism to meet metabolic demands of DENV replication and immune activation by viral infection. Totally 88 of 202 metabolic variants were significantly changed by DENV infection, 36 of which met the statistical standard (P<0.05, VIP>1.5) of differentially expressed metabolites, which were the predominantly decreased variants of acylcarnitine and the increased variants of fatty acids and carbohydrates. Remarkably, 11 differentially expressed metabolites were significantly distinct between DENV only infection and antibody-dependent enhancement of viral infection. Our data suggested that the anabolic activation by DENV infection integrates the viral replication and anti-viral immune activation.
Assuntos
Carnitina/análogos & derivados , Vírus da Dengue , Dengue , Viroses , Animais , Humanos , Vírus da Dengue/fisiologia , Anticorpos Facilitadores , Replicação Viral , Macrófagos , Carboidratos , Aminoácidos , Ácidos GraxosRESUMO
Micro/nano-plastics (MNPs) are emerging non-point source pollutants that have garnered increasing attention owing to their threat to ecosystems. Studies on the effects of MNPs on horticultural crops are scarce. Specifically, whether MNPs can be absorbed and transported by grapevines have not been reported. To fill this gap, we added polystyrene nanoplastics (PS-NPs, 100 nm) to a hydroponic environment and observed their distribution in grape seedlings of Thompson Seedless (TS, Vitis vinifera L.). After 15 d of exposure, plastic nanospheres were detected on the cell walls of the roots, stems, and leaves using confocal microscopy and scanning electron microscopy. This indicated that PS-NPs can also be absorbed by the root system through the epidermis-cortex interface in grapevines and transported upward along the xylem conduit. Furthermore, we analyzed the molecular response mechanisms of TS grapes to the PS-NPs. Through the measurement of relevant indicators and combined omics analysis, we found that plant hormone signal transduction, flavonoid and flavonol biosynthesis, phenylpropanoid biosynthesis, and MAPK signaling pathway biosynthesis played crucial roles in its response to PS-NPs. The results not only revealed the potential risk of MNPs being absorbed by grapevines and eventually entering the food chain but also provided valuable scientific evidence and data for the assessment of plant health and ecological risk.
RESUMO
Pair density wave (PDW) is a distinct superconducting state characterized by a periodic modulation of its order parameter in real space. Its intricate interplay with the charge density wave (CDW) state is a continuing topic of interest in condensed matter physics. While PDW states have been discovered in cuprates and other unconventional superconductors, the understanding of diverse PDWs and their interactions with different types of CDWs remains limited. Here, utilizing scanning tunneling microscopy, we unveil the subtle correlations between PDW ground states and two distinct CDW phases - namely, anion-centered-CDW (AC-CDW) and hollow-centered-CDW (HC-CDW) - in 2H-NbSe2. In both CDW regions, we observe coexisting PDWs with a commensurate structure that aligns with the underlying CDW phase. The superconducting gap size, Δ(r), related to the pairing order parameter is in phase with the charge density in both CDW regions. Meanwhile, the coherence peak height, H(r), qualitatively reflecting the electron-pair density, exhibits a phase difference of approximately 2π/3 relative to the CDW. The three-fold rotational symmetry is preserved in the HC-CDW region but is spontaneously broken in the AC-CDW region due to the PDW state, leading to the emergence of nematic superconductivity.
RESUMO
Herein, poly(pentanediamine terephthalamide) (PA5T) homopolymer was synthesized via a salt-forming reaction+solid state polycondensation method using bio-based 1,5-pentanediamine and terephthalic acid as the primary raw materials. To address the issue of its narrower processing window, poly(hexamethylene terephthalamide)(PA6T), which also cannot be melt processed due to the processing window is negative, was introduced into its molecular chain to synthesize poly (pentanediamine/hexanediamine terephthaloyl) (PA5T-co-6T) copolymers. The structures were investigated by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance carbon spectroscopy (13C-NMR). Furthermore, the melting temperature, crystallization temperature, thermal stability, and crystal growth mode of the polymer were tested and analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and wide-angle x-ray diffraction (WAXD), respectively. The results demonstrate that the crystal growth mode gradually changes from three-dimensional spherical growth to two-dimensional disk-like or three-dimensional spherical growth with the increase of 6T chain segment content. Simultaneously, the crystallization temperature, melting temperature, and crystallization rate of the polymer all showed a trend of decreasing first and then increasing, which was due to the combined effects of the increase in the content of 6T chain segments on the molecular-chain structure and crystal structure of the polymer. Bio-based PA5T-co-6T has excellent heat resistance and a wider processing window than PA5T and PA6T, which possesses great application prospects in the fields of automotive, electronic appliances, and LED optics.
RESUMO
Guangdong, China, has experienced several dengue epidemics involving thousands of confirmed cases in recent decades, and elderly individuals suffered severe dengue (SD) most seriously. However, the clinical characteristics and risk factors for SD among elderly patients in Guangdong have not been investigated. Patients older than 65 years were recruited and divided into a dengue fever (DF) group and an SD group according to the 2009 Dengue Guidelines of the WHO. We analyzed the clinical manifestations of the elderly patients with dengue and then assessed the risk factors for SD. Of a total of 1,027 patients, 868 patients were diagnosed as having DF and 159 as having SD. Of the 159 elderly patients with SD, 129 (81%) had comorbidities, with hypertension being the most common. Severe organ impairment (SOI) (115, 54%) was the most common presentation in SD patients, followed by severe plasma leakage (52, 24.4%) and severe hemorrhage (46, 21.6%). The most common symptom of SOI was kidney injury, followed by heart injury and central nervous system injury. Furthermore, multivariate regression revealed that the presence of chronic obstructive pulmonary disease (COPD), a lower red blood cell (RBC) count (≤3.5 × 1012/L; odds ratio [OR], 0.35; 95% CI, 0.17-0.55; P <0.001), lower serum albumin (ALB) (≤35 U/L; OR, 0.18; 95% CI, 0.09-0.32; P <0.001), and hyperpyrexia (body temperature ≥39°C; OR, 1.8; 95% CI, 1.2-2.6, P <0.001) were risk factors for SD. Severe organ impairment was the predominant manifestation in elderly individuals with SD characterized by kidney injury. The potential risk factors of SD such as presence of COPD and hyperpyrexia and lower RBC and ALB levels might help clinicians identify patients with SD early.
RESUMO
In this comprehensive investigation, we explore the effectiveness of 55 dual-atom catalysts (DACs) supported on graphitic carbon nitride (gCN) for both alkaline and acidic hydrogen evolution reactions (HER). Employing density functional theory (DFT), we scrutinize the thermodynamic and kinetic profiles of these DACs, revealing their considerable potential across a diverse pH spectrum. For acidic HER, our results identify catalysts such as FePd-gCN, CrCr-gCN, and NiPd-gCN, displaying promising ΔGH* values of 0.0, 0.0, and -0.15 eV, respectively. This highlights their potential effectiveness in acidic environments, thereby expanding the scope of their applicability. Within the domain of alkaline HER, this study delves into the thermodynamic and kinetic profiles of DACs supported on gCN, utilizing DFT to illuminate their efficacy in alkaline HER. Through systematic evaluation, we identify that DACs such as CrCo-gCN, FeRu-gCN, and FeIr-gCN not only demonstrate favorable Gibbs free energy change (ΔGmax) for the overall water splitting reaction of 0.02, 0.27, and 0.38 eV, respectively, but also feature low activation energies (Ea) for water dissociation, with CrCo-gCN, FeRu-gCN, and FeIr-gCN notably exhibiting the Ea of just 0.42, 0.33, and 0.42 eV, respectively. The introduction of an electronic descriptor (φ), derived from d electron count (Nd) and electronegativity (ETM), provides a quantifiable relationship with catalytic activity, where a lower φ corresponds to enhanced reaction kinetics. Specifically, φ values between 4.0-4.6 correlate with the lowest kinetic barriers, signifying a streamlined HER process. Our findings suggest that DACs with optimized φ values present a robust approach for the development of high-performance alkaline HER electrocatalysts, offering a pathway towards the rational design of energy-efficient catalytic systems.
RESUMO
Fractional quantum Hall (FQH) states are exotic quantum many-body phases whose elementary charged excitations are anyons obeying fractional braiding statistics. While most FQH states are believed to have Abelian anyons, the Moore-Read type states with even denominators - appearing at half filling of a Landau level (LL) - are predicted to possess non-Abelian excitations with appealing potential in topological quantum computation. These states, however, depend sensitively on the orbital contents of the single-particle LL wavefunctions and the LL mixing. Here we report magnetotransport measurements on Bernal-stacked trilayer graphene, whose multiband structure facilitates interlaced LL mixing, which can be controlled by external magnetic and displacement fields. We observe robust FQH states including even-denominator ones at filling factors ν = - 9/2, - 3/2, 3/2 and 9/2. In addition, we fine-tune the LL mixing and crossings to drive quantum phase transitions of these half-filling states and neighbouring odd-denominator ones, exhibiting related emerging and waning behaviour.
RESUMO
Seedlessness is a crucial quality trait in table grape (Vitis vinifera L.) breeding. However, the development of seeds involved intricate regulations, and the polygenic basis of seed abortion remains unclear. Here, we combine comparative genomics, population genetics, quantitative genetics, and integrative genomics to unravel the evolution and polygenic basis of seedlessness in grapes. We generated the haplotype-resolved genomes for two seedless grape cultivars, "Thompson Seedless" (TS, syn. "Sultania") and "Black Monukka" (BM). Comparative genomics identified a â¼4.25 Mb hemizygous inversion on Chr10 specific in seedless cultivars, with seedless-associated genes VvTT16 and VvSUS2 located at breakpoints. Population genomic analyses of 548 grapevine accessions revealed two distinct clusters of seedless cultivars, and the identity-by-descent (IBD) results indicated that the origin of the seedlessness trait could be traced back to "Sultania." Introgression, rather than convergent selection, shaped the evolutionary history of seedlessness in grape improvement. Genome-wide association study (GWAS) analysis identified 110 quantitative trait loci (QTLs) associated with 634 candidate genes, including previously unidentified candidate genes, such as three 11S GLOBULIN SEED STORAGE PROTEIN and two CYTOCHROME P450 genes, and well-known genes like VviAGL11. Integrative genomic analyses resulted in 339 core candidate genes categorized into 13 functional categories related to seed development. Machine learning-based genomic selection achieved a remarkable prediction accuracy of 97% for seedlessness in grapevines. Our findings highlight the polygenic nature of seedlessness and provide candidate genes for molecular genetics and an effective prediction for seedlessness in grape genomic breeding.
Assuntos
Estudo de Associação Genômica Ampla , Genômica , Locos de Características Quantitativas , Sementes , Vitis , Vitis/genética , Vitis/crescimento & desenvolvimento , Sementes/genética , Sementes/crescimento & desenvolvimento , Genoma de Planta/genética , Herança Multifatorial/genética , Melhoramento VegetalRESUMO
BACKGROUND: The strong invasiveness and rapid expansion of dengue virus (DENV) pose a great challenge to global public health. However, dengue epidemic patterns and mechanisms at a genetic scale, particularly in term of cross-border transmissions, remain poorly understood. Importation is considered as the primary driver of dengue outbreaks in China, and since 1990 a frequent occurrence of large outbreaks has been triggered by the imported cases and subsequently spread to the western and northern parts of China. Therefore, this study aims to systematically reveal the invasion and diffusion patterns of DENV-1 in Guangdong, China from 1990 to 2019. METHODS: These analyses were performed on 179 newly assembled genomes from indigenous dengue cases in Guangdong, China and 5152 E gene complete sequences recorded in Chinese mainland. The genetic population structure and epidemic patterns of DENV-1 circulating in Chinese mainland were characterized by phylogenetics, phylogeography, phylodynamics based on DENV-1 E-gene-based globally unified genotyping framework. RESULTS: Multiple serotypes of DENV were co-circulating in Chinese mainland, particularly in Guangdong and Yunnan provinces. A total of 189 transmission clusters in 38 clades belonging to 22 subgenotypes of genotype I, IV and V of DENV-1 were identified, with 7 Clades of Concern (COCs) responsible for the large outbreaks since 1990. The epidemic periodicity was inferred from the data to be approximately 3 years. Dengue transmission events mainly occurred from Great Mekong Subregion-China (GMS-China), Southeast Asia (SEA), South Asia Subcontinent (SASC), and Oceania (OCE) to coastal and land border cities respectively in southeastern and southwestern China. Specially, Guangzhou was found to be the most dominant receipting hub, where DENV-1 diffused to other cities within the province and even other parts of the country. Genome phylogeny combined with epidemiological investigation demonstrated a clear local consecutive transmission process of a 5C1 transmission cluster (5C1-CN4) of DENV-1 in Guangzhou from 2013 to 2015, while the two provinces of Guangdong and Yunnan played key roles in ongoing transition of dengue epidemic patterns. In contextualizing within Invasion Biology theories, we have proposed a derived three-stage model encompassing the stages of invasion, colonization, and dissemination, which is supposed to enhance our understanding of dengue spreading patterns. CONCLUSIONS: This study demonstrates the invasion and diffusion process of DENV-1 in Chinese mainland within a global genotyping framework, characterizing the genetic diversities of viral populations, multiple sources of importation, and periodic dynamics of the epidemic. These findings highlight the potential ongoing transition trends from epidemic to endemic status offering a valuable insight into early warning, prevention and control of rapid spreading of dengue both in China and worldwide.
Assuntos
Vírus da Dengue , Dengue , Genótipo , Filogenia , Sorogrupo , Vírus da Dengue/genética , Vírus da Dengue/classificação , Vírus da Dengue/fisiologia , China/epidemiologia , Dengue/epidemiologia , Dengue/virologia , Dengue/transmissão , Humanos , Surtos de Doenças , Filogeografia , Genoma ViralRESUMO
Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.