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1.
Plant Cell ; 35(8): 2848-2870, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37154077

RESUMO

C3 and C4 grasses directly and indirectly provide the vast majority of calories to the human diet, yet our understanding of the molecular mechanisms driving photosynthetic productivity in grasses is largely unexplored. Ground meristem cells divide to form mesophyll or vascular initial cells early in leaf development in C3 and C4 grasses. Here we define a genetic circuit composed of SHORT ROOT (SHR), INDETERMINATE DOMAIN (IDD), and PIN-FORMED (PIN) family members that specifies vascular identify and ground cell proliferation in leaves of both C3 and C4 grasses. Ectopic expression and loss-of-function mutant studies of SHR paralogs in the C3 plant Oryza sativa (rice) and the C4 plant Setaria viridis (green millet) revealed the roles of these genes in both minor vein formation and ground cell differentiation. Genetic and in vitro studies further suggested that SHR regulates this process through its interactions with IDD12 and 13. We also revealed direct interactions of these IDD proteins with a putative regulatory element within the auxin transporter gene PIN5c. Collectively, these findings indicate that a SHR-IDD regulatory circuit mediates auxin transport by negatively regulating PIN expression to modulate minor vein patterning in the grasses.


Assuntos
Oryza , Setaria (Planta) , Humanos , Oryza/genética , Oryza/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Ácidos Indolacéticos/metabolismo , Setaria (Planta)/metabolismo , Diferenciação Celular , Regulação da Expressão Gênica de Plantas/genética
2.
Circ Res ; 134(1): 9-29, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38047378

RESUMO

BACKGROUND: T cells are central to the immune responses contributing to hypertension. LGMN (legumain) is highly expressed in T cells; however, its role in the pathogenesis of hypertension remains unclear. METHODS: Peripheral blood samples were collected from patients with hypertension, and cluster of differentiation (CD)4+ T cells were sorted for gene expression and Western blotting analysis. TLGMNKO (T cell-specific LGMN-knockout) mice (Lgmnf/f/CD4Cre), regulatory T cell (Treg)-specific LGMN-knockout mice (Lgmnf/f/Foxp3YFP Cre), and RR-11a (LGMN inhibitor)-treated C57BL/6 mice were infused with Ang II (angiotensin II) or deoxycorticosterone acetate/salt to establish hypertensive animal models. Flow cytometry, 4-dimensional label-free proteomics, coimmunoprecipitation, Treg suppression, and in vivo Treg depletion or adoptive transfer were used to delineate the functional importance of T-cell LGMN in hypertension development. RESULTS: LGMN mRNA expression was increased in CD4+ T cells isolated from hypertensive patients and mice, was positively correlated with both systolic and diastolic blood pressure, and was negatively correlated with serum IL (interleukin)-10 levels. TLGMNKO mice exhibited reduced Ang II-induced or deoxycorticosterone acetate/salt-induced hypertension and target organ damage relative to wild-type (WT) mice. Genetic and pharmacological inhibition of LGMN blocked Ang II-induced or deoxycorticosterone acetate/salt-induced immunoinhibitory Treg reduction in the kidneys and blood. Anti-CD25 antibody depletion of Tregs abolished the protective effects against Ang II-induced hypertension in TLGMNKO mice, and LGMN deletion in Tregs prevented Ang II-induced hypertension in mice. Mechanistically, endogenous LGMN impaired Treg differentiation and function by directly interacting with and facilitating the degradation of TRAF6 (tumor necrosis factor receptor-associated factor 6) via chaperone-mediated autophagy, thereby inhibiting NF-κB (nuclear factor kappa B) activation. Adoptive transfer of LGMN-deficient Tregs reversed Ang II-induced hypertension, whereas depletion of TRAF6 in LGMN-deficient Tregs blocked the protective effects. CONCLUSIONS: LGMN deficiency in T cells prevents hypertension and its complications by promoting Treg differentiation and function. Specifically targeting LGMN in Tregs may be an innovative approach for hypertension treatment.


Assuntos
Hipertensão , Fator 6 Associado a Receptor de TNF , Animais , Humanos , Camundongos , Acetatos/efeitos adversos , Acetatos/metabolismo , Angiotensina II/toxicidade , Angiotensina II/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Desoxicorticosterona/efeitos adversos , Desoxicorticosterona/metabolismo , Hipertensão/induzido quimicamente , Hipertensão/genética , Hipertensão/prevenção & controle , Camundongos Endogâmicos C57BL , Camundongos Knockout , Linfócitos T Reguladores , Fator 6 Associado a Receptor de TNF/metabolismo
3.
Small ; : e2400063, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461517

RESUMO

Most mechanochromic luminescent compounds are crystalline and highly hydrophobic; however, mechanochromic luminescent molecular assemblies comprising amphiphilic molecules have rarely been explored. This study investigated mechanochromic luminescent supramolecular fibers composed of dumbbell-shaped 9,10-bis(phenylethynyl)anthracene-based amphiphiles without any tetraethylene glycol (TEG) substituents or with two TEG substituents. Both amphiphiles formed water-insoluble supramolecular fibers via linear hydrogen bond formation. Both compounds acquired water solubility when solid samples composed of supramolecular fibers are ground. Grinding induces the conversion of 1D supramolecular fibers into micellar assemblies where fluorophores can form excimers, thereby resulting in a large redshift in the fluorescence spectra. Excimer emission from the ground amphiphile without TEG chains is retained after dissolution in water. The micelles are stable in water because hydrophilic dendrons surround the hydrophobic luminophores. By contrast, when water is added to a ground amphiphile having TEG substituents, fragmented supramolecular fibers with the same molecular arrangement as the initial supramolecular fibers are observed, because fragmented fibers are thermodynamically preferable to micelles as the hydrophobic arrays of fluorophores are covered with hydrophilic TEG chains. This leads to the recovery of the initial fluorescent properties for the latter amphiphile. These supramolecular fibers can be used as practical mechanosensors to detect forces at the mesoscale.

4.
J Transl Med ; 22(1): 259, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461346

RESUMO

BACKGROUND: Amino acids (AAs) are one of the primary metabolic substrates for cardiac work. The correlation between AAs and both atrial fibrillation (AF) and aging has been documented. However, the relationship between AAs and age-related AF remains unclear. METHODS: Initially, the plasma AA levels of persistent AF patients and control subjects were assessed, and the correlations between AA levels, age, and other clinical indicators were explored. Subsequently, the age-related AF mouse model was constructed and the untargeted myocardial metabolomics was conducted to detect the level of AAs and related metabolites. Additionally, the gut microbiota composition associated with age-related AF was detected by a 16S rDNA amplicon sequencing analysis on mouse fecal samples. RESULTS: Higher circulation levels of lysine (Student's t-test, P = 0.001), tyrosine (P = 0.002), glutamic acid (P = 0.008), methionine (P = 0.008), and isoleucine (P = 0.014), while a lower level of glycine (P = 0.003) were observed in persistent AF patients. The feature AAs identified by machine learning algorithms were glutamic acid and methionine. The association between AAs and age differs between AF and control subjects. Distinct patterns of AA metabolic profiles were observed in the myocardial metabolites of aged AF mice. Aged AF mice had lower levels of Betaine, L-histidine, L-alanine, L-arginine, L-Pyroglutamic acid, and L-Citrulline compared with adult AF mice. Aged AF mice also presented a different gut microbiota pattern, and its functional prediction analysis showed AA metabolism alteration. CONCLUSION: This study provided a comprehensive network of AA disturbances in age-related AF from multiple dimensions, including plasma, myocardium, and gut microbiota. Disturbances of AAs may serve as AF biomarkers, and restoring their homeostasis may have potential benefits for the management of age-related AF.


Assuntos
Aminoácidos , Fibrilação Atrial , Adulto , Humanos , Animais , Camundongos , Idoso , Aminoácidos/metabolismo , Fibrilação Atrial/metabolismo , Metabolômica/métodos , Metionina , Glutamatos
5.
Heart Fail Rev ; 29(2): 417-430, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37940727

RESUMO

Device therapy is a nonpharmacological approach that presents a crucial advancement for managing patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). This review investigated the impact of device-based interventions and emphasized their potential for optimizing treatment for this complex patient demographic. Cardiac resynchronization therapy, augmented by atrioventricular node ablation with His-bundle pacing or left bundle-branch pacing, is effective for enhancing cardiac function and establishing atrioventricular synchrony. Cardiac contractility modulation and vagus nerve stimulation represent novel strategies for increasing myocardial contractility and adjusting the autonomic balance. Left ventricular expanders have demonstrated short-term benefits in HFpEF patients but require more investigation for long-term effectiveness and safety, especially in patients with AF. Research gaps regarding complications arising from left ventricular expander implantation need to be addressed. Device-based therapies for heart valve diseases, such as transcatheter aortic valve replacement and transcatheter edge-to-edge repair, show promise for patients with AF and HFpEF, particularly those with mitral or tricuspid regurgitation. Clinical evaluations show that these device therapies lessen AF occurrence, improve exercise tolerance, and boost left ventricular diastolic function. However, additional studies are required to perfect patient selection criteria and ascertain the long-term effectiveness and safety of these interventions. Our review underscores the significant potential of device therapy for improving the outcomes and quality of life for patients with AF and HFpEF.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Volume Sistólico/fisiologia , Qualidade de Vida , Resultado do Tratamento , Função Ventricular Esquerda
6.
Microb Cell Fact ; 23(1): 107, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609931

RESUMO

Cryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections. This study exposed that the minimum inhibitory concentration (MIC) of isobavachalcone (IBC) against C. neoformans H99 was 8 µg/mL, and IBC dispersed 48-h mature biofilms by affecting cell viability at 16 µg/mL. The antifungal efficacy of IBC was further validated through microscopic observations using specific dyes and in vitro assays, which confirmed the disruption of cell wall/membrane integrity. RNA-Seq analysis was employed to decipher the effect of IBC on the C. neoformans H99 transcriptomic profiles. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis was performed to validate the transcriptomic data and identify the differentially expressed genes. The results showed that IBC exhibited various mechanisms to impede the growth, biofilm formation, and virulence of C. neoformans H99 by modulating multiple dysregulated pathways related to cell wall/membrane, drug resistance, apoptosis, and mitochondrial homeostasis. The transcriptomic findings were corroborated by the antioxidant analyses, antifungal drug sensitivity, molecular docking, capsule, and melanin assays. In vivo antifungal activity analysis demonstrated that IBC extended the lifespan of C. neoformans-infected Caenorhabditis elegans. Overall, the current study unveiled that IBC targeted multiple pathways simultaneously to inhibit growth significantly, biofilm formation, and virulence, as well as to disperse mature biofilms of C. neoformans H99 and induce cell death.


Assuntos
Chalconas , Criptococose , Cryptococcus neoformans , Animais , Cryptococcus neoformans/genética , Antifúngicos/farmacologia , RNA-Seq , Simulação de Acoplamento Molecular , Biofilmes , Caenorhabditis elegans
7.
Inorg Chem ; 63(2): 1046-1053, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38170680

RESUMO

Metal chalcogenide nanoparticles play a vital role in a wide range of applications and are typically stabilized by organic derivatives containing thiol, amine, or carboxyl moieties, where the nonconjugated particle-ligand interfaces limit the electronic interactions between the inorganic cores and organic ligands. Herein, a wet-chemistry method is developed for the facile preparation of stable platinum chalcogenide (S, Se) nanoparticles capped with acetylene derivatives (e.g., 4-ethylphenylacetylene, EPA). The formation of Pt-C≡ conjugated bonds at the nanoparticle interfaces, which is confirmed by optical and X-ray spectroscopic measurements, leads to markedly enhanced electronic interactions between the d electrons of the nanoparticle cores and π electrons of the acetylene moiety, in stark contrast to the mercapto-capped counterparts with only nonconjugated Pt-S- interfacial bonds, as manifested in spectroscopic measurements and density functional theory calculations. This study underscores the significance of conjugated anchoring linkages in the stabilization and functionalization of metal chalcogenides, a unique strategy for diverse applications.

8.
BMC Cardiovasc Disord ; 24(1): 175, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515032

RESUMO

BACKGROUND: Approximately 90% of intracardial thrombi originate from the left atrial appendage in non-valvular atrial fibrillation patients. Even with anticoagulant therapy, left atrial appendage thrombus (LAAT) still occurs in 8% of patients. While left atrial appendage closure (LAAC) could be a promising alternative, the current consensus considers LAAT a contraindication to LAAC. However, the feasibility and safety of LAAC in patients with LAAT have yet to be determined. METHODS: This systematic review synthesizes published data to explore the feasibility and safety of LAAC for patients with LAAT. RESULTS: This study included a total of 136 patients with LAATs who underwent successful LAAC. The Amulet Amplatzer device was the most frequently utilized device (48.5%). Among these patients, 77 (56.6%) had absolute contraindications to anticoagulation therapy. Cerebral protection devices were utilized by 47 patients (34.6%). Transesophageal echocardiography (TEE) is the primary imaging technique used during the procedure. Warfarin and novel oral anticoagulants were the main anticoagulant medications used prior to the procedure, while dual antiplatelet therapy was primarily used post-procedure. During a mean follow-up period of 13.2 ± 11.5 months, there was 1 case of fatality, 1 case of stroke, 3 major bleeding events, 3 instances of device-related thrombus, and 8 cases of peri-device leakage. CONCLUSIONS: This review highlights the preliminary effectiveness and safety of the LAAC procedure in patients with persistent LAAT. Future large-scale RCTs with varied LAAT characteristics and LAAC device types are essential for evidence-based decision-making in clinical practice.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Trombose , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Oclusão do Apêndice Atrial Esquerdo , Apêndice Atrial/diagnóstico por imagem , Anticoagulantes/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/prevenção & controle , Resultado do Tratamento
9.
Nutr Metab Cardiovasc Dis ; 34(6): 1538-1545, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38644080

RESUMO

BACKGROUND AND AIMS: The role of fractional flow reserve (FFR) in coronary intermediate lesions is widely recommended by guidelines. The effect of uric acid (UA) on cardiovascular events is also well known. However, the relationship between UA and long-term cardiovascular outcomes in patients who received FFR with intermediate lesions remains unknown. METHODS AND RESULTS: We retrospectively included 428 patients who underwent both coronary angiography (CAG) and FFR. Participants were stratified into two groups based on the median UA. The primary endpoint was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including repeat revascularization, nonfatal stroke, nonfatal myocardial infarction, and all-cause death. A Cox proportional hazards model was utilized to analyze the association between UA and the prevalence of MACCEs. During a median follow-up of 5.8 years, a higher MACCEs rate occurred in the high UA group compared to the low UA group (16.8% vs. 5.1%, p log-rank<0.01). Elevated UA was independently linked to a higher incidence of MACCEs, whether UA was treated as a categorical or continuous variable (hazard ratio [HR] 2.76, 95% confidence interval [CI] 1.27-6.03 or HR 1.01, 95% CI 1.01-1.02). The restricted cubic spline (RCS) analysis illustrated that the HR for MACCEs increased with increasing UA. CONCLUSION: The present study demonstrates that UA is associated with MACCEs risk and suggests that UA is a reliable predictor of long-term cardiovascular events in coronary intermediate stenosis patients.


Assuntos
Biomarcadores , Angiografia Coronária , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Hiperuricemia , Ácido Úrico , Humanos , Masculino , Feminino , Ácido Úrico/sangue , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Fatores de Tempo , Fatores de Risco , Estenose Coronária/fisiopatologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/diagnóstico , Estenose Coronária/sangue , Medição de Risco , Hiperuricemia/diagnóstico , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Hiperuricemia/fisiopatologia , Biomarcadores/sangue , Regulação para Cima , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/sangue , Valor Preditivo dos Testes , Cateterismo Cardíaco/efeitos adversos
10.
Ann Noninvasive Electrocardiol ; 29(1): e13100, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38115789

RESUMO

BACKGROUND: Posteroseptal accessory pathways (APs) associated with coronary sinus (CS) diverticulum present a rare and challenge for ablation. This study aimed to compare the safety and efficacy of conventional approach and three-dimensional (3D) mapping system in the catheter ablation. METHODS AND RESULTS: This was a retrospective study of all patients (from January 2013 to July 2022) who underwent catheter ablation of posteroseptal AP associated with CS diverticula in our center. Patients who underwent catheter ablation using the traditional fluoroscopy method were included in the conventional method group (n = 13). Patients who underwent catheter ablation using the 3D mapping method were included in the 3D mapping group (n = 11). Clinical characteristics, ablation procedure, and outcomes were recorded and analyzed between the two groups. Out of 669 patients with posteroseptal APs, 24 of them (3.6%) were associated with CS diverticula. All patients in both groups successfully completed the electrophysiological study. In the conventional method group, two patients experienced complications (one patient with pericardial effusion and the other patient with femoral arterial hematoma), and two patients had recurrence. However, no patients suffered from complications or recurrence during follow-up. The procedure time and fluoroscopy time in the conventional method group were significantly longer than those in the 3D mapping method group. CONCLUSIONS: The utilization of 3D mapping led to reduced fluoroscopy time, shorter procedure duration, enhanced acute success rates, and decreased incidence of complications.


Assuntos
Feixe Acessório Atrioventricular , Ablação por Cateter , Seio Coronário , Divertículo , Cardiopatias Congênitas , Humanos , Seio Coronário/diagnóstico por imagem , Seio Coronário/cirurgia , Estudos Retrospectivos , Eletrocardiografia/métodos , Feixe Acessório Atrioventricular/diagnóstico por imagem , Feixe Acessório Atrioventricular/cirurgia , Cardiopatias Congênitas/cirurgia , Ablação por Cateter/métodos , Divertículo/complicações , Divertículo/diagnóstico por imagem , Divertículo/cirurgia
11.
Ann Noninvasive Electrocardiol ; 29(1): e13099, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37997537

RESUMO

BACKGROUND: The temporary pacing lead routinely is placed into right ventricular (RV), which pose a risk of dislocation and cardiac perforation. OBJECTIVE: We aim to evaluate the effectiveness and safety of temporary transvenous cardiac pacing (TTCP) leads placement into the coronary sinus vein (CSV) in patients with sick sinus syndrome (SSS). METHODS: We investigated patients with SSS who underwent TTCP lead placement into the CSV under the guidance of X-ray between January 2013 and May 2023. Patients were randomly divided into two groups: RV group (n = 33) and CSV group (n = 22). The ordinary passive bipolar electrodes were applied in both groups. In RV groups, electrodes were placed into RV. In CSV group, electrodes were placed into CSV. We evaluated the operation duration, fluoroscopic exposure, first-attempt success rate of leads placement, pacing threshold, success rate of leads placement, rate of leads displacement, and complications. RESULTS: Compared with that in RV group, the procedure time, fluoroscopic exposure was significantly prolonged, while the first-attempt success rate of lead placement was obviously increased in CSV group (both p < .05). Compared with that in RV group, the rate of leads displacement is lower in CSV group (both p < .05). There were three patients occurred cardiac perforation in RV group, but no cardiac perforation was reported in CSV group (p > .05). CONCLUSION: TTCP leads placement into the CSV is an effective and safe strategy in patients with SSS. It indicates a high rate of pacing effectiveness with low device replacement and complication rates.


Assuntos
Seio Coronário , Marca-Passo Artificial , Humanos , Seio Coronário/diagnóstico por imagem , Estimulação Cardíaca Artificial/efeitos adversos , Estimulação Cardíaca Artificial/métodos , Síndrome do Nó Sinusal/terapia , Eletrocardiografia
12.
Lipids Health Dis ; 23(1): 96, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566225

RESUMO

BACKGROUND: Guidelines on coronary intermediate lesions strongly recommend deferred revascularization after detecting a normal fractional flow reserve (FFR). Researches about triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) on cardiovascular diseases has also been well conducted. However, the association of TG/HDL-C and long-term adverse clinical outcomes remains unknown for patients deferred revascularization following FFR. METHODS: This study retrospectively included 374 coronary artery disease (CAD) patients with non-significant coronary lesions diagnosed by coronary angiography (CAG) and FFR. The main outcome measure was the combination of major adverse cardiovascular and cerebrovascular events (MACCEs). All patients were categorized into three subgroups in terms of TG/HDL-C tertiles (T1 < 0.96, 0.96 ≤ T2 < 1.58, T3 ≥ 1.58). Three different Cox regression models were utilized to reveal the association between TG/HDL-C and prevalence of MACCEs. RESULTS: 47 MACCEs were recorded throughout a median monitoring period of 6.6 years. The Kaplan-Meier survival curves showed a higher MACCEs rate occurred in the higher TG/HDL-C group (5.6% vs. 12.9% vs. 19.4%, log-rank P < 0.01). After adjustment, patients in T3 suffered a 2.6-fold risk compared to the T1 group (T3 vs. T1: HR 2.55, 95% CI 1.05-6.21, P = 0.038; T2 vs. T1: HR 1.71, 95% CI 0.65-4.49, P = 0.075; P for trend = 0.001). The restricted cubic spline (RCS) analysis demonstrated that the HR for MACCEs rose as TG/HDL-C increased. Both the receiver operating characteristic (ROC) and time-dependent ROC proved the excellent predictive ability of TG/HDL-C. CONCLUSION: The study illustrates that TG/HDL-C correlates with the risk of MACCEs in CAD patients deferred revascularization following FFR. TG/HDL-C could serve as a dependable predictor of cardiovascular events over the long term in this population.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Humanos , Estudos Retrospectivos , HDL-Colesterol , Triglicerídeos , Doença da Artéria Coronariana/cirurgia , Angiografia Coronária
13.
Scand J Med Sci Sports ; 34(2): e14582, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38349064

RESUMO

BACKGROUND: Due to inconclusive evidence from observational studies regarding the impact of physical activity (PA) and sedentary behavior on frailty and falling risk, we conducted a two-sample Mendelian randomization analysis to investigate the causal associations between PA, sedentary behavior, and frailty and falls. METHODS: We extracted summary data from genome-wide association studies conducted among individuals of European ancestry, encompassing PA (n = 90 667-608 595), sedentary behavior (n = 372 609-526 725), frailty index (n = 175 226), and falling risk (n = 451 179). Single nucleotide polymorphisms associated with accelerometer assessed fraction >425 milligravities, self-reported vigorous activity, moderate to vigorous physical acticity (MVPA), leisure screen time (LST), and sedentary behavior at work were taken as instrumental variables. The causal effects were primarily estimated using inverse variance weighted methods, complemented by several sensitivity and validation analyses. RESULTS: Genetically predicted higher levels of PA were significantly associated with a reduction in the frailty index (accelerometer assessed fraction >425 milligravities: ß = -0.25, 95% CI = -0.36 to -0.14, p = 1.27 × 10-5 ; self-reported vigorous activity: ß = -0.13, 95% CI = -0.20 to -0.05, p = 7.9 × 10-4 ; MVPA: ß = -0.28, 95% CI = -0.40 to -0.16, p = 9.9 × 10-6 ). Besides, LST was significantly associated with higher frailty index (ß = 0.18, 95% CI = 0.14-0.22, p = 5.2 × 10-20 ) and higher odds of falling (OR = 1.13, CI = 1.07-1.19, p = 6.9 × 10-6 ). These findings remained consistent throughout sensitivity and validation analyses. CONCLUSIONS: Our study offers evidence supporting a causal relationship between PA and a reduced risk of frailty. Furthermore, it underscores the association between prolonged LST and an elevated risk of frailty and falls. Therefore, promoting PA and reducing sedentary behavior may be an effective strategy in primary frailty and falls prevention.


Assuntos
Fragilidade , Humanos , Fragilidade/genética , Fragilidade/prevenção & controle , Comportamento Sedentário , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Acidentes por Quedas , Exercício Físico
14.
J Electrocardiol ; 84: 52-57, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38518582

RESUMO

INTRODUCTION: There are great differences in ST-segment depression during PSVT episodes. The aim of this study is to investigate the clinical significance of ST segment depression during PSVT. METHODS: The study enrolled 333 consecutive patients who were diagnosed with PSVT by electrophysiological test from Jan 1, 2021 to July 31, 2022. The range, magnitude and morphology of ST-segment depression were described. The correlation between ST-segment depression and symptoms of chest tightness, chest pain or hypotension, the correlation between ST-segment depression and coronary stenosis, and the possible influencing factors were analyzed. In addition, the diagnostic efficacy of ST-segment depression for AVRT was determined. RESULTS: ST-segment depression was present in 85% of patients, in 70% of which the depression range was more than six leads. The magnitude of the depression was more significant in precordial leads (P < 0.001). ST-segment depression of >1 mm in limb leads and precordial leads was found in 36.0% and 49.8% of the patients, respectively, while >3 mm was found in 2.4% and 9.6%, respectively. The morphology of ST-segment depression in limb leads was different from that in precordial leads (P < 0.001). Downsloping ST-segment depression was more common in limb leads (limb vs. precordial: 40.5% vs. 12.6%), whereas upsloping depression was more common in precordial leads (limb vs. precordial: 3.0% vs. 23.1%). Correlation analysis showed that ST-segment depression was not correlated with symptoms of chest tightness and pain, nor was it correlated with coronary artery stenosis. The most important influencing factor is the type of PSVT, especially affecting the morphology of depression in limb leads (OR = 10.27 [5.93-17.79], P < 0.001). The sensitivity and specificity of downsloping ST-segment depression in limb leads for diagnosis of AVRT were 75.5% and 76.7%. CONCLUSION: ST-segment depression is a common ECG change during PSVT episodes, and it's not associated with severe coronary stenosis. The type of PSVT has a significant effect on the manifestation of ST-segment depression. The downslope morphology of ST-segment depression in limb leads is helpful in differentiating AVRT from AVNRT.


Assuntos
Eletrocardiografia , Taquicardia Supraventricular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Taquicardia Supraventricular/fisiopatologia , Taquicardia Paroxística/fisiopatologia , Estenose Coronária/fisiopatologia , Estenose Coronária/complicações , Estenose Coronária/diagnóstico , Idoso , Sensibilidade e Especificidade , Relevância Clínica
15.
Am J Physiol Endocrinol Metab ; 324(4): E330-E338, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36856188

RESUMO

Lactate, which is an end product of glycolysis, has traditionally been considered a metabolic waste. However, numerous studies have demonstrated that lactate serves metabolic and nonmetabolic functions in physiological processes and multiple diseases. Cancer and pulmonary arterial hypertension have been shown to undergo metabolic reprogramming, which is accompanied by increased lactate production. Metabolic reprogramming and epigenetic modifications have been extensively linked; furthermore, posttranslational modifications of histones caused by metabolites play a vital role in epigenetic alterations. In this paper, we reviewed recent research on lactate-induced histone modifications and provided a new vision about the metabolic effect of glycolysis. Based on our review, the cross talk between the metabolome and epigenome induced by glycolysis may indicate novel epigenetic regulatory and therapeutic opportunities. There is a magnificent progress in the interaction between metabolomics and epigenomics in recent decades, but many questions still remained to be investigated. Lactylation is found in different pathophysiological states and leads to diverse biological effects; however, only a few mechanisms of lactylation have been illustrated. Further research on lactylation would provide us with a better understanding of the cross talk between metabolomics and epigenomics.


Assuntos
Epigenômica , Neoplasias , Humanos , Histonas/metabolismo , Epigênese Genética , Ácido Láctico
16.
Small ; : e2308136, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38054773

RESUMO

Nickel sulfides are promising anode candidates in sodium ion batteries (SIBs) due to high capacity and abundant reserves. However, their applications are restricted by poor cycling stability and slow reaction kinetics. Thus, mesoporous nickel sulfide microsphere encapsulated in nitrogen, sulfur dual-doped carbon (MNS@NSC) is prepared. The packaged structure and carbon matrix restrain the volume variation together, the N, S dual-doping improves the electronic conductivity and offers extra active sites for sodium storage. Ex-situ X-ray diffraction  appeals copper collector adsorbs polysulfide to inhibit the polysulfide accumulation and enhance conductivity. Moreover, the large subsurface attributed to C-S-S-C bonding further boosts pseudocapacitive capacity, conducive to charge transfer. As a result, MNS@NSC delivers a high reversible capacity of 640.2 mAh g-1 after 100 cycles at 0.1 A g-1 , an excellent rate capability (569.8 mAh g-1 at 5 A g-1 ), and a remained capacity of 513.8 mAh g-1 after undergoing 10000 circulations at 10 A g-1 . The MNS@NSC|| Na3 V2 (PO4 )3 full cell shows a cycling performance of specific capacity of 230.8 mAh g-1 after 100 cycles at 1 A g-1 . This work puts forward a valid strategy of combing structural design and heteroatom doping to synthesize high-performance nickel sulfide materials in SIBs.

17.
New Phytol ; 240(3): 1066-1081, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37574840

RESUMO

Modifications of plant architecture can increase planting density, regulate photosynthesis, and improve crop yields. Many basic helix-loop-helix (bHLH) transcription factors participate in the brassinosteroid (BR) signaling pathway and are critical for plant architecture morphogenesis in rice. However, the number of identified bHLH genes suitable for improving production value is still limited. In this study, we cloned Lam1, encoding the typical bHLH transcription factor OsbHLH92. OsbHLH92 knockout (KO) lines exhibit erect leaves. Decreases in the number and size of parenchyma cell layers on the adaxial side of the lamina joint in KO lines were the main reason for the decreased leaf angle. Genetic experiments verify that OsBU1 and its homologs are downstream of OsbHLH92, which is involved in the noncanonical RGA1-mediated BR signaling pathway. OsbHLH91, an OsbHLH92 homolog, plays both conserved and differentiated roles relative to OsbHLH92. Notably, OsbHLH92-KO lines show erect leaves without the acquisition of adverse agronomic traits. Moreover, by driving a specific panicle promoter, OsbHLH92 can greatly increase productivity by at least 10%. This study identifies new components of the BR signaling pathway, demonstrates the importance of OsbHLH92 in improving planting density and crop productivity, and broadens our knowledge of typical and atypical bHLH family members in rice.

18.
Analyst ; 148(11): 2544-2552, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37144556

RESUMO

Antibiotic residues pose a serious threat to ecosystems and food safety. Developing convenient, visual, and on-site detection methods is therefore in high demand and has a practical purpose. In this work, a near-infrared (NIR) fluorescent probe with an analysis platform based on a smartphone has been constructed for quantitative and on-site detection of metronidazole (MNZ). CdTe quantum dots with NIR emission at 710 nm (QD710) were prepared by using a simple hydrothermal method and showed good properties. A spectral overlap between absorption of MNZ and excitation of QD710 resulted in an effective inner filter effect (IFE) between QD710 and MNZ. Because of the IFE, the fluorescence of QD710 decreased gradually with increasing concentrations of MNZ. Based on the fluorescence response, quantitative detection and visualization of MNZ was achieved. NIR fluorescence analysis and the special IFE between probe and target can improve sensitivity and selectivity for MNZ. Additionally, these were also utilized for quantitative detection of MNZ in real food samples and the results were reliable and satisfactory. Meanwhile, a portable visual analysis platform in a smartphone was constructed for on-site analysis of MNZ, which can be used as an alternative method for detection of MNZ residues in situations with limited instrumental conditions. Therefore, this work provides a convenient, visual, and real-time analysis method for detection of MNZ and the analysis platform shows great potential for commercialization.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Metronidazol/análise , Corantes Fluorescentes/química , Compostos de Cádmio/química , Ecossistema , Smartphone , Pontos Quânticos/química , Telúrio/química , Carbono/química , Limite de Detecção
19.
Europace ; 25(6)2023 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-37337928

RESUMO

AIMS: Subarachnoid haemorrhage (SAH) is one of the causes of sudden cardiac death (SCD). However, the time course of ventricular arrhythmias and potential mechanisms responsible for this effect after SAH remain unknown. OBJECTIVE: This study aims to investigate the effect of SAH on ventricular electrophysiological changes and its potential mechanisms in long-term phase. METHODS AND RESULTS: We examined the ventricular electrophysiological remodelling and potential mechanisms in a Sprague Dawley rat model of SAH at six time points (baseline, and Days 1, 3, 7, 14 and 28) and explored the potential mechanisms. We measured the ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT) and left stellate ganglion (LSG) activity at different time points before and after SAH. We also detected neuropeptide Y (NPY) levels in plasma and myocardial tissues by enzyme-linked immunosorbent assay, and quantified NPY 1 receptor (NPY1R) protein and mRNA expression levels by western blotting and quantitative real-time reverse transcription-polymerase chain reaction, respectively. Subarachnoid haemorrhage gradually prolonged QTc intervals, shortened ventricular ERP and reduced VFT during the acute phase, peaking at Day 3. However, no significant changes were observed from Days 14 to 28 compared to Day 0. Subarachnoid haemorrhage gradually increased LSG activity, increased NPY concentrations and up-regulated NPY1R expression in the acute phase of SAH, peaking at Day 3. However, no significant variations were found from Days 14 to 28 compared to Day 0. CONCLUSION: Subarachnoid haemorrhage increases the transient susceptibility of VAs in the acute phase, and the underlying mechanisms for this response included increased sympathetic activity and up-regulated NPY1R expression.


Assuntos
Hemorragia Subaracnóidea , Ratos , Animais , Hemorragia Subaracnóidea/complicações , Ratos Sprague-Dawley , Coração , Encéfalo , Fibrilação Ventricular/etiologia , Arritmias Cardíacas/complicações
20.
Artigo em Inglês | MEDLINE | ID: mdl-37212950

RESUMO

PURPOSE: Novel, effective, and safe preventive therapy targets for AF are still needed. Circulating proteins with causal genetic evidence are promising candidates. We aimed to systematically screen circulating proteins for AF drug targets and determine their safety and efficacy using genetic methods. METHODS: The protein quantitative trait loci (pQTL) of up to 1949 circulating proteins were retrieved from nine large genome-proteome-wide association studies. Two-sample Mendelian Randomization (MR) and colocalization analyses were used to estimate the causal effects of proteins on the risk of AF. Furthermore, phenome-wide MR was conducted to depict side effects and the drug-target databases were searched for drug validation and repurposing. RESULTS: Systematic MR screen identified 30 proteins as promising AF drug targets. Genetically predicted 12 proteins increased AF risk (TES, CFL2, MTHFD1, RAB1A, DUSP13, SRL, ANXA4, NEO1, FKBP7, SPON1, LPA, MANBA); 18 proteins decreased AF risk (PMVK, UBE2F, SYT11, CHMP3, PFKM, FBP1, TNFSF12, CTSZ, QSOX2, ALAD, EFEMP1, FLRT2, LRIG1, OLA1, SH3BGRL3, IL6R, B3GNT8, FCGR2A). DUSP13 and TNFSF12 possess strong colocalization evidence. For the proteins that were identified, extended phe-MR analysis was conducted to assess their side-effect profiles, while drug-target databases provided information on their approved or investigated indications. CONCLUSION: We identified 30 circulating proteins as potential preventive targets for AF.

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