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1.
Cell Rep Med ; : 101558, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38733986

RESUMO

The investigation of the mechanisms behind p53 mutations in acute myeloid leukemia (AML) has been limited by the lack of suitable mouse models, which historically have resulted in lymphoma rather than leukemia. This study introduces two new AML mouse models. One model induces mutant p53 and Mdm2 haploinsufficiency in early development, showing the role of Mdm2 in myeloid-biased hematopoiesis and AML predisposition, independent of p53. The second model mimics clonal hematopoiesis by inducing mutant p53 in adult hematopoietic stem cells, demonstrating that the timing of p53 mutation determines AML vs. lymphoma development. In this context, age-related changes in hematopoietic stem cells (HSCs) collaborate with mutant p53 to predispose toward myeloid transformation rather than lymphoma development. Our study unveils new insights into the cooperative impact of HSC age, Trp53 mutations, and Mdm2 haploinsufficiency on clonal hematopoiesis and the development of myeloid malignancies.

2.
ChemSusChem ; : e202301942, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735842

RESUMO

Aqueous zinc ion batteries (AZIBs) with metallic Zn anode have the potential for large-scale energy storage application due to their cost-effectiveness, safety, environmental-friendliness, and ease of preparation. However, the concerns regarding dendrite growth and side reactions on Zn anode surface hamper AZIB's commercialization. This review aims to give a comprehensive evaluation of the protective interphase construction and provide guildance to further improve the electrochemical performance of AZIBs. The failure behaviors of Zn metal anode including dendrite growth, corrosion, and hydrogen evolution are analyzed. Then, the applications and mechanisms of the constructed interphases are introduced, classified by the material species. The fabrication methods of the artificial interfaces are summarized and evaluated, including the in-situ strategy and ex-situ strategy. Finally, the characterization means of the interphases are discussed to give a full view for the study of Zn anode protection. Based on the analysis of this review, a stable and high-performance Zn anode could be designed by carefully choosing applied material, corresponding protective mechanism, and appropriate construction technique. Additionally, this review for Zn anode modification and construction techniques for anode protection in AZIBs may be helpful in other aqueous metal batteries with similar problems.

3.
Small ; : e2403136, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770989

RESUMO

Hollandite-type manganese dioxide (α-MnO2) is recognized as a promising cathode material upon high-performance aqueous zinc-ion batteries (ZIBs) owing to the high theoretical capacities, high working potentials, unique Zn2+/H+ co-insertion chemistry, and environmental friendliness. However, its practical applications limited by Zn2+ accommodation, where the strong coulombic interaction and sluggish kinetics cause significant lattice deformation, fast capacity degradation, insufficient rate capability, and undesired interface degradation. It remains challenging to accurately modulate H+ intercalation while suppressing Zn2+ insertion for better lattice stability and electrochemical kinetics. Herein, proton Grotthuss transfer channels are first tunneled by shielding MnO2 with hydrophilic-zincophobic heterointerface, fulfilling the H+-dominating diffusion with the state-of-the-art ZIBs performance. Local atomic structure and theoretical simulation confirm that surface-engineered α-MnO2 affords to the synergy of Mn electron t2g-eg activation, oxygen vacancy enrichment, selective H+ Grotthuss transfer, and accelerated desolvation kinetics. Consequently, fortified α-MnO2 achieves prominent low current density cycle stability (≈100% capacity retention at 1 C after 400 cycles), remarkable long-lifespan cycling performance (98% capacity retention at 20 C after 12 000 cycles), and ultrafast rate performance (up to 30 C). The study exemplifies a new approach of heterointerface engineering for regulation of H+-dominating Grotthuss transfer and lattice stabilization in α-MnO2 toward reliable ZIBs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38571296

RESUMO

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

5.
Sci Total Environ ; 927: 172165, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38575024

RESUMO

8:2 fluorotelomer sulfonic acid (8:2 FTSA) has been commonly detected in the environment, but its behaviors in plants are not sufficiently known. Here, the regular and multi-omics analyses were used to comprehensively investigate the bioaccumulation, biotransformation, and toxicity of 8:2 FTSA in Arabidopsis thaliana. Our results demonstrated that 8:2 FTSA was taken up by A. thaliana roots and translocated to leaves, stems, flowers, and seeds. 8:2 FTSA could be successfully biotransformed to several intermediates and stable perfluorocarboxylic acids (PFCAs) catalyzed by plant enzymes. The plant revealed significant growth inhibition and oxidative damage under 8:2 FTSA exposure. Metabolomics analysis showed that 8:2 FTSA affected the porphyrin and secondary metabolisms, resulting in the promotion of plant photosynthesis and antioxidant capacity. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were related to transformation and transport processes. Integrative transcriptomic and metabolomic analysis revealed that DEGs and differentially expressed metabolites (DEMs) in plants were predominantly enriched in the carbohydrate metabolism, amino acid metabolism, and lipid metabolism pathways, resulting in greater energy consumption, generation of more nonenzymatic antioxidants, alteration of the cellular membrane composition, and inhibition of plant development. This study provides the first insights into the molecular mechanisms of 8:2 FTSA stress response in plants.


Assuntos
Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Biotransformação , Ácidos Sulfônicos , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Metabolômica
6.
Sci Total Environ ; 930: 172506, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38636862

RESUMO

Atmospheric brown carbon (BrC), a short-lived climate forcer, absorbs solar radiation and is a substantial contributor to the warming of the Earth's atmosphere. BrC composition, its absorption properties, and their evolution are poorly represented in climate models, especially during atmospheric aqueous events such as fog and clouds. These aqueous events, especially fog, are quite prevalent during wintertime in Indo-Gangetic Plain (IGP) and involve several stages (e.g., activation, formation, and dissipation, etc.), resulting in a large variation of relative humidity (RH) in the atmosphere. The huge RH variability allowed us to examine the evolution of water-soluble brown carbon (WS-BrC) diurnally and as a function of aerosol liquid water content (ALWC) and RH in this study. We explored links between the evolution of WS-BrC mass absorption efficiency at 365 nm (MAEWS-BrC-365) and chemical characteristics, viz., low-volatility organics and water-soluble organic nitrogen (WSON) to water-soluble organic carbon (WSOC) ratio (org-N/C), in the field (at Kanpur in central IGP) for the first time worldwide. We observed that WSON formation governed enhancement in MAEWS-BrC-365 diurnally (except during the afternoon) in the IGP. During the afternoon, the WS-BrC photochemical bleaching dwarfed the absorption enhancement caused by WSON formation. Further, both MAEWS-BrC-365 and org-N/C ratio increased with a decrease in ALWC and RH in this study, signifying that evaporation of fog droplets or bulk aerosol particles accelerated the formation of nitrogen-containing organic chromophores, resulting in the enhancement of WS-BrC absorptivity. The direct radiative forcing of WS-BrC relative to that of elemental carbon (EC) was ∼19 % during wintertime in Kanpur, and âˆ¼ 40 % of this contribution was in the UV-region. These findings highlight the importance of further examining the links between the evolution of BrC absorption behavior and chemical composition in the field and incorporating it in the BrC framework of climate models to constrain the predictions.

7.
Phytomedicine ; 129: 155612, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38669968

RESUMO

BACKGROUND: Colorectal cancer (CRC) continues to be a major global health challenge, ranking as a top cause of cancer-related mortality. Alarmingly, the five-year survival rate for CRC patients hovers around a mere 10-30 %. The disruption of fibroblast growth factor receptor (FGFRs) signaling pathways is significantly implicated in the onset and advancement of CRC, presenting a promising target for therapeutic intervention in CRC management. Further investigation is essential to comprehensively elucidate FGFR1's function in CRC and to create potent therapies that specifically target FGFR1. PURPOSE: This study aims to demonstrate the oncogenic role of FGFR1 in colorectal cancer and to explore the potential of ß,ß-dimethylacrylalkannin (ß,ß-DMAA) as a therapeutic option to inhibit FGFR1. METHODS: In this research, we employed a comprehensive suite of techniques including tissue array, kinase profiling, computational docking, knockdown assay to predict and explore the inhibitor of FGFR1. Furthermore, we utilized kinase assay, pull-down, cell proliferation tests, and Patient derived xenograft (PDX) mouse models to further investigate a novel FGFR1 inhibitor and its impact on the growth of CRC. RESULTS: In our research, we discovered that FGFR1 protein is markedly upregulated in colorectal cancer tissues, suggesting a significant role in regulating cellular proliferation, particularly in patients with colorectal cancer. Furthermore, we conducted a computational docking, kinase profiling analysis, simulation and identified that ß,ß-DMAA could directly bind with FGFR1 within ATP binding pocket domain. Cell-based assays confirmed that ß,ß-DMAA effectively inhibited the proliferation of colon cancer cells and also triggered cell cycle arrest, apoptosis, and altered FGFR1-mediated signaling pathways. Moreover, ß,ß-DMAA effectively attenuated the development of PDX tumors in mice that were FGFR1-positive, with no notable toxicity observed. In summary, our study highlights the pivotal role of FGFR1 in colorectal cancer, suggesting that inhibiting FGFR1 activity could be a promising strategy for therapeutic intervention. We present strong evidence that targeting FGFR1 with ß,ß-DMAA is a viable approach for the management of colorectal cancer. Given its low toxicity and high efficacy, ß,ß-DMAA, as an FGFR1 inhibitor, warrants further investigation in clinical settings for the treatment of FGFR1-positive tumors.

8.
Environ Sci Technol ; 58(15): 6564-6574, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38578220

RESUMO

Formation of highly oxygenated molecules (HOMs) such as organic peroxides (ROOR, ROOH, and H2O2) is known to degrade food and organic matter. Gas-phase unimolecular autoxidation and bimolecular RO2 + HO2/RO2 reactions are prominently renowned mechanisms associated with the formation of peroxides. However, the reaction pathways and conditions favoring the generation of peroxides in the aqueous phase need to be evaluated. Here, we identified bulk aqueous-phase ROOHs in varying organic precursors, including a laboratory model compound and monoterpene oxidation products. Our results show that formation of ROOHs is suppressed at enhanced oxidant concentrations but exhibits complex trends at elevated precursor concentrations. Furthermore, we observed an exponential increase in the yield of ROOHs when UV light with longer wavelengths was used in the experiment, comparing UVA, UVB, and UVC. Water-soluble organic compounds represent a significant fraction of ambient cloud-water components (up to 500 µM). Thus, the reaction pathways facilitating the formation of HOMs (i.e., ROOHs) during the aqueous-phase oxidation of water-soluble species add to the climate and health burden of atmospheric particulate matter.


Assuntos
Peróxido de Hidrogênio , Peróxidos , Material Particulado/análise , Oxidantes , Água , Aerossóis
9.
ACS Omega ; 9(16): 17817-17831, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38680317

RESUMO

An effective palladium nanocatalyst (Fe3O4@SiO2-FPBA-DTPA-Pd) was proposed and prepared, which was immobilized on magnetic silica with ethylenediamine pentaacetic acid and formylphenylboronic acid as biligands. A series of characterizations showed that Fe3O4@SiO2-FPBA-DTPA-Pd was 5-15 nm and contained 1.44 mmol/g Pd2+/Pd0. It was stable below 232.7 °C, and its saturation magnetization value was 21.17 emu/g which was easily recycled by a magnet. Its catalytic ability was evaluated through 7 Suzuki reactions and 15 Heck reactions. Results showed that the yields of 14 reactions catalyzed by Fe3O4@SiO2-FPBA-DTPA-Pd were more than 90%, while were better than those of the other two immobilized Pd catalysts on a single diethyltriamine pentaacetic acid (DTPA) group or boronic acid group. Moreover, Fe3O4@SiO2-FPBA-DTPA-Pd showed good reusability in both Suzuki and Heck reactions. In two model Suzuki and Heck reactions, after seven cycles, its yields were still above 95% without significant loss, which exceeded those of many reported catalysts; therefore, it has great potential in future large-scale industrial production.

10.
Yi Chuan ; 46(4): 279-289, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38632091

RESUMO

H2A.Z, one of the most well-known variants of histone H2A, has been extensively investigated on its dual roles in gene transcription in recent years. In this review, we focus on the intricate involvement of H2A.Z in transcriptional regulation, including the assembly of distinct H2A.Z subtypes, post-translational modifications and genomic distributions. Emphasis is placed on the biological and pathophysiological implications, particularly in tumorigenesis and nervous system development. We summarize the dynamic regulatory mechanisms governing H2A.Z deposition or eviction on chromatin to provide insights for understanding the diversity of histone variants and promoting the search of new targets in concerned disease diagnosis and treatment.


Assuntos
Histonas , Nucleossomos , Histonas/metabolismo , Cromatina , Regulação da Expressão Gênica , Genoma
11.
Sci Bull (Beijing) ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38670850

RESUMO

The merging of transition metal catalysis with electrochemistry has become a powerful tool for organic synthesis because catalysts can govern the reactivity and selectivity. However, coupling catalysts with alkyl radical species generated by anodic oxidation remains challenging because of electrode passivation, dimerization, and overoxidation. In this study, we developed convergent paired electrolysis for the coupling of nickel catalysts with alkyl radicals derived from photoinduced ligand-to-metal charge-transfer of cyclic alcohols and iron catalysts, providing a practical method for site-specific and remote arylation of ketones. The synergistic use of photocatalysis with convergent paired electrolysis can provide alternative avenues for metal-catalyzed radical coupling reactions.

12.
iScience ; 27(4): 109461, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38550997

RESUMO

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

14.
Animals (Basel) ; 14(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38473140

RESUMO

Fish species identification plays a vital role in marine fisheries resource exploration, yet datasets related to marine fish resources are scarce. In open-water environments, various fish species often exhibit similar appearances and sizes. To solve these issues, we propose a few-shot learning approach to identifying fish species. Our approach involves two key components. Firstly, the embedding module was designed to address the challenges posed by a large number of fish species with similar phenotypes by utilizing the distribution relationships of species in the embedding space. Secondly, a metric function was introduced, effectively enhancing the performance of fish species classification and successfully addressing the issue of limited sample quantity. The proposed model is trained end to end on fish species public datasets including the Croatian fish dataset, Fish4Knowledge and WildFish. Compared with the prototypical networks, our method performs more effectively and improves accuracy by 2% to 10%; it is able to identify fish effectively in small samples sizes and complex scene scenarios. This method provides a valuable technological tool for the development of fisheries resources and the preservation of fish biodiversity.

15.
Cell Death Discov ; 10(1): 132, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472215

RESUMO

Small bowel vascular malformation disease (SBVM) commonly causes obscure gastrointestinal bleeding (OGIB). However, the pathogenetic mechanism and the role of lncRNAs in SBVM remain largely unknown. Here, we found that hypoxia and low-glucose environments co-augment angiogenesis and existed in SBVM. Mechanistically, hypoxia and low-glucose environments supported angiogenesis via activation of hypoxia and glucose deprivation-induced lncRNA (HGDILnc1) transcription by increasing binding of the NeuroD1 transcription factor to the HGDILnc1 promoter. Raised HGDILnc1 acted as a suppressor of α-Enolase 1 (ENO1) small ubiquitin-like modifier modification (SUMOylation)-triggered ubiquitination, and an activator of transcription of Aldolase C (ALDOC) via upregulation of Histone H2B lysine 16 acetylation (H2BK16ac) level in the promoter of ALDOC, and consequently promoting glycolysis and angiogenesis. Moreover, HGDILnc1 was clinically positively correlated with Neurogenic differentiation 1 (NeuroD1), ENO1, and ALDOC in SBVM tissues, and could function as a biomarker for SBVM diagnosis and therapy. These findings suggest that hypoxia and low-glucose environments were present in SBVM tissues, and co-augmented angiogenesis. Hypoxia and low-glucose environments co-induced HGDILnc1, which is higher expressed in SBVM tissue compared with normal tissue, could promoted glycolysis and angiogenesis.

16.
J Nanobiotechnology ; 22(1): 94, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38449005

RESUMO

BACKGROUND: Impaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin's clinical application is limited due to its poor water solubility and low bioavailability. RESULTS: In this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA--miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway. CONCLUSION: In summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.


Assuntos
NF-kappa B , Periodontite , Humanos , Quercetina/farmacologia , Periodontite/tratamento farmacológico , Flavonoides , Inflamação , Proteínas de Ligação a RNA , Proteínas Reguladoras de Apoptose
17.
Adv Sci (Weinh) ; 11(14): e2306311, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38298116

RESUMO

The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-Gi complexes in synthetic agonist-bound forms have been resolved to date. However, the commercial drug recognition and Gq coupling mechanisms of CB1 remain elusive. Herein, the cryo-electron microscopy (cryo-EM) structure of CB1-Gq complex, in fenofibrate-bound form, at near-atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and Gq protein coupling by CB1 and will facilitate future drug discovery and design.


Assuntos
Canabinoides , Fenofibrato , Humanos , Receptor CB1 de Canabinoide , Microscopia Crioeletrônica , Proteínas de Ligação ao GTP
18.
J Virol ; 98(3): e0191523, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38334327

RESUMO

As an intrinsic cellular mechanism responsible for the internalization of extracellular ligands and membrane components, caveolae-mediated endocytosis (CavME) is also exploited by certain pathogens for endocytic entry [e.g., Newcastle disease virus (NDV) of paramyxovirus]. However, the molecular mechanisms of NDV-induced CavME remain poorly understood. Herein, we demonstrate that sialic acid-containing gangliosides, rather than glycoproteins, were utilized by NDV as receptors to initiate the endocytic entry of NDV into HD11 cells. The binding of NDV to gangliosides induced the activation of a non-receptor tyrosine kinase, Src, leading to the phosphorylation of caveolin-1 (Cav1) and dynamin-2 (Dyn2), which contributed to the endocytic entry of NDV. Moreover, an inoculation of cells with NDV-induced actin cytoskeletal rearrangement through Src to facilitate NDV entry via endocytosis and direct fusion with the plasma membrane. Subsequently, unique members of the Rho GTPases family, RhoA and Cdc42, were activated by NDV in a Src-dependent manner. Further analyses revealed that RhoA and Cdc42 regulated the activities of specific effectors, cofilin and myosin regulatory light chain 2, responsible for actin cytoskeleton rearrangement, through diverse intracellular signaling cascades. Taken together, our results suggest that an inoculation of NDV-induced Src-mediated cellular activation by binding to ganglioside receptors. This process orchestrated NDV endocytic entry by modulating the activities of caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPases and downstream effectors. IMPORTANCE: In general, it is known that the paramyxovirus gains access to host cells through direct penetration at the plasma membrane; however, emerging evidence suggests more complex entry mechanisms for paramyxoviruses. The endocytic entry of Newcastle disease virus (NDV), a representative member of the paramyxovirus family, into multiple types of cells has been recently reported. Herein, we demonstrate the binding of NDV to induce ganglioside-activated Src signaling, which is responsible for the endocytic entry of NDV through caveolae-mediated endocytosis. This process involved Src-dependent activation of the caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPase and downstream effectors, thereby orchestrating the endocytic entry process of NDV. Our findings uncover a novel molecular mechanism of endocytic entry of NDV into host cells and provide novel insight into paramyxovirus mechanisms of entry.


Assuntos
Macrófagos , Doença de Newcastle , Vírus da Doença de Newcastle , Transdução de Sinais , Internalização do Vírus , Animais , Endocitose , Gangliosídeos/metabolismo , Macrófagos/metabolismo , Macrófagos/virologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/fisiologia , Proteínas rho de Ligação ao GTP/metabolismo
20.
JAMA Netw Open ; 7(2): e2354937, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38335001

RESUMO

Importance: Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. Objective: To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. Design, Setting, and Participants: This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Interventions: Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. Main Outcomes and Measures: The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Results: Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. Conclusions and Relevance: In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.


Assuntos
Pré-Hipertensão , Tai Chi Chuan , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea , Exercício Físico , Pré-Hipertensão/terapia , Estudos Prospectivos , Adolescente , Adulto Jovem , Idoso
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