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1.
Front Microbiol ; 15: 1444414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104584

RESUMO

Schisandra chinensis, a traditional Chinese medicine known for its antitussive and sedative effects, has shown promise in preventing various viral infections. Bovine herpesvirus-1 (BoHV-1) is an enveloped DNA virus that causes respiratory disease in cattle, leading to significant economic losses in the industry. Because the lack of previous reports on Schisandra chinensis resisting BoHV-1 infection, this study aimed to investigate the specific mechanisms involved. Results from TCID50, qPCR, IFA, and western blot analyses demonstrated that Schisandra chinensis could inhibit BoHV-1 entry into MDBK cells, primarily through its extract Methylgomisin O (Meth O). The specific mechanism involved Meth O blocking BoHV-1 entry into cells via clathrin- and caveolin-mediated endocytosis by suppressing the activation of PI3K-Akt signaling pathway. Additionally, findings from TCID50, qPCR, co-immunoprecipitation and western blot assays revealed that Schisandra chinensis blocked BoHV-1 gD transcription through enhancing m6A methylation of gD after virus entry, thereby hindering gD protein expression and preventing progeny virus entry into cells and ultimately inhibiting BoHV-1 replication. Overall, these results suggest that Schisandra chinensis can resist BoHV-1 infection by targeting the PI3K-Akt signaling pathway and inhibiting gD transcription.

2.
Front Nutr ; 11: 1432973, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104756

RESUMO

Background: Many studies define obesity based on body mass index (BMI) and explore its relationship with adult asthma. However, BMI only considers height and weight, ignoring other factors such as body fat, which may have a greater impact on health. We investigated the relationship between body fat distribution and adult asthma using both a cross-sectional study and bidirectional Mendelian randomization (MR) analysis. Methods: Weighted logistic regression models were used to examine the relationship between body fat distribution measurements and adult asthma in the cross-sectional study from National Health and Nutrition Examination Survey (NHANES) 2011-2018. Restricted cubic spline (RCS) curves were employed to explore the dose-response relationship between them. The inverse-variance weighted (IVW) method was used as the main method of MR analysis to explore the causal effect of exposure on outcome. Results: After adjusting for all covariates, weighted logistic regression analysis indicated that fat mass in the left arm, left leg, right arm, right leg, trunk, and total body is associated with an increased risk of developing adult asthma (p < 0.05). RCS curves showed that all six fat mass indicators exhibit a J-shaped relationship with adult asthma. Forward MR analysis found a causal effect of six fat mass indicators on the increased risk of adult asthma (p < 0.05). However, reverse MR did not reveal any causal effect of adult asthma on these six fat mass indicators (p > 0.05). Conclusion: Our study supports a positive correlation and a unidirectional causality between body fat distribution measurements and the risk of adult asthma. Further studies are needed to validate our findings.

3.
Pest Manag Sci ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39189548

RESUMO

BACKGROUND: Bees (Apis mellifera), as important pollinators of agricultural crops, are at risk when pesticides are used. Sulfoxaflor is a new insecticide which acts on the nicotinic acetylcholine receptor (nAChR) in a similar way to neonicotinoids. The goal of this study is to evaluate the toxicity of sulfoxaflor and its effect on the A. mellifera exposure. RESULTS: Initially, developmental indicators such as larval survival, pupation, and eclosion were inhibited by 5.0 mg/L (field concentration) sulfoxaflor. In the pupal stage, fat content was significantly increased, while the glycogen content decreased. In addition, A. mellifera heads were treated with 2.0 mg/L (sublethal concentration) of sulfoxaflor and analyzed by RNA sequencing. The transcriptome results indicated that 2.0 mg/L amounts of sulfoxaflor have adverse effects on the immune, digestive, and nervous systems. Sulfoxaflor down-regulated the expression of many genes involved in immunity, detoxification, the myosin cytoskeleton, sensory neurons, and odor-binding proteins. CONCLUSION: Field concentration and sublethal concentration were used for the combined analysis of honeybees. The effect of sublethal concentration of sulfoxaflor on honeybees was studied for the first time from the perspective of transcriptome sequencing of honeybee head. A preliminary study was carried out on the stress of sulfoxaflor at sublethal concentration on honeybee workers, which has certain research significance and can provide theoretical basis for the use of sulfoxaflor in the field environment. © 2024 Society of Chemical Industry.

4.
J Am Chem Soc ; 146(32): 22583-22589, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39102645

RESUMO

Circularly polarized (CP) lasers hold tremendous potential for advancing spin information communication and display technologies. Organic materials are emerging candidates for high-performance CP lasers because of their abundant chiral structures and excellent gain characteristics. However, their dissymmetry factor (glum) in CP emission is typically low due to the weak chiral light matter interactions. Here, we presented an effective approach to significantly amplifying glum by leveraging the intrinsic 2D-chiroptical response of an anisotropic organic supramolecular crystal. The organic complex microcrystal was designed to exhibit large 2D-chiroptical activities through strong coupling interactions between their remarkable linear birefringence (LB) and high degree of fluorescence linear polarization. Such 2D-chiroptical response can be further enhanced by the stimulated emission resulted from an increased degree of linear polarization, yielding a nearly pure CP laser with an exceptionally high glum of up to 1.78. Moreover, exploiting the extreme susceptibility of LB to temperature, we demonstrate a prototype of temperature-controlled chiroptical switches. These findings offer valuable insights for harnessing organic crystals to facilitate the development of high-performance CP lasers and other chiroptical devices.

5.
ACS Catal ; 14(15): 11545-11553, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39114089

RESUMO

Amphiphilic Janus silica particles, tunable with oleophobic-oleophilic properties and low fluorine content (8 wt % F), exhibited prominent foamability for a variety of aromatic alcohols at low particle concentrations (<1 wt %) compared to randomly functionalized silica particles. When selectively loaded with Pd nanoparticles on the oleophilic hemisphere, the particles displayed more than a 2-fold increase in catalytic activity for the aerobic oxidation of benzyl alcohol compared to nonfoam bulk catalysis under ambient O2 pressure. The particles were conveniently recycled with high foamability and catalytic activity maintained for at least five consecutive runs.

6.
Anal Chem ; 96(33): 13421-13428, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39109704

RESUMO

Mitochondrial DNA (mtDNA) is pivotal for mitochondrial morphology and function. Upon mtDNA damage, mitochondria undergo quality control mechanisms, including fusion, fission, and mitophagy. Real-time monitoring of mtDNA enables a deeper understanding of its effect on mitochondrial function and morphology. Controllable induction and real-time tracking of mtDNA dynamics and behavior are of paramount significance for studying mitochondrial function and morphology, facilitating a deeper understanding of mitochondria-related diseases. In this work, a fluorescent platinum complex was designed and developed that not only induces mitochondrial DNA (mtDNA) aggregation but also triggers mitochondrial autophagy (mitophagy) through the MDV pathway for damaged mtDNA clearance in living cells. Additionally, this complex allows for the real-time monitoring of these processes. This complex may serve as a valuable tool for studying mitochondrial microautophagy and holds promise for broader applications in cellular imaging and disease research.


Assuntos
DNA Mitocondrial , Corantes Fluorescentes , Mitofagia , DNA Mitocondrial/metabolismo , Humanos , Corantes Fluorescentes/química , Mitocôndrias/metabolismo , Platina/química , Células HeLa
7.
ACS Chem Biol ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39145437

RESUMO

Cyclic peptides, with remarkable stability, cellular permeability, and proteolysis resistance, display promising potential in pharmaceutical applications. Labionin (Lab), a unique bicyclic cross-link containing both C-C and C-S bonds, provides high rigidity and better control of conformation compared to monocyclic cross-links. To discover more Lab-containing scaffolds with highly rigid conformation for cyclic peptide drug development, herein, a cryptic class III lanthipeptide biosynthetic gene cluster (BGC) (i.e., rcs) was identified in the sponge-associated Streptomyces rochei MB037 and expressed in Escherichia coli, incorporating an N-terminal SUMO-tag on the RcsA precursor peptide to prevent proteolysis. Subsequently, a novel class III lanthipeptide, i.e., rochsin A, exhibiting a highly rigid conformation with coupled Lab cross-links crowded by bulky aromatic amino acids, was produced. Three AplP-like proteases outside the rcs BGC were proven to remove the leader peptide of rochsin A through their dual endo- and aminopeptidase activities, resulting in mature rochsin A in vitro. Ala mutation experiments revealed the C to N cyclization direction, like most class III lanthipeptides. However, RcsKC displays a high substrate breadth, enabling various ring topologies that are rarely observed in other class III lanthipeptides. Overall, the established expression system broadens the chemical diversity of cyclic peptides with unique Lab cross-links and offers a highly rigid scaffold for cyclic peptide drug development.

8.
Sci Rep ; 14(1): 18880, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143186

RESUMO

The surrounding rock of tunnels in cold regions are susceptible to the freeze-thaw cycle resulting from the combination of low temperatures and moisture during tunnel service. The phenomenon will not only lead to the expansion of pores and fissures in the surrounding rock of the initial tunnel, but also destroy the integrity of the rock. This destruction will have a serious impact on tunnel structure and rail transit operation safety. At present, the commonly used thermal insulation measures have some problems such as maintenance difficulties, low economic efficiency, and safety hazards. Therefore, it is urgent to develop a kind of tunnel maintenance grouting material with insulation and anti-permeability, which has the characteristics of simple operation, easy preparation and application. We independently developed a composite grouting material composed of polyurethane (PU), epoxy resin (E-51) and acrylic powder (PMMA). Through the material combustion test, magnesium hydroxide was selected as the flame retardant additive. Moreover, we measured the thermal conductivity, water absorption, apparent density, porosity and strength characteristic parameters. The thermal insulation and anti-permeability characteristics of the composites were also analyzed. The results indicated that the thermal conductivity of the new composite grouting material is 6.3% lower than the PU before adding flame retardant. Compared with the PU with flame retardant, the water absorption decreased by 74.4% and the ultimate strength increased by 33.3%. For the area with an average temperature lower than - 10 °C, we recommend the ratio scheme of E-51: 3%; PMMA: 15%. For the area with high water content in the surrounding rock of the tunnel, we recommend the ratio scheme of E-51: 15%; PMMA: 3%. This study provides new ideas for material preparation and tunnel insulation methods for anti-freezing measures in tunnels during their operational period in cold regions.

9.
Int J Low Extrem Wounds ; : 15347346241273156, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39114877

RESUMO

OBJECTIVE: Diabetic foot ulcers are common chronic complications of diabetes mellitus that can lead to amputation and death in severe cases. There is limited research on the relationship between the red cell distribution width/albumin ratio and diabetic lower-extremity ulcers. The few studies that have been conducted have been in single-center inpatient settings and there is limited research in outpatient settings. This study investigated this relationship in adult outpatient clinics in the United States. METHODS: A retrospective cross-sectional study was conducted with 1624 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. Three logistic regression models were developed to assess the association between red cell distribution width/albumin ratio and diabetic lower-extremity ulcers. The ratio was analyzed as a continuous and categorical variable. Stratified analyses were performed based on age, sex, HbA1c level, and body mass index. RESULTS: The study included 1624 adults, with a mean age of 65.0 ± 12.0 years, of whom 58.8% were male. The prevalence of diabetic lower-extremity ulcers was 8.0% (n = 131). Compared with individuals with a lower red cell distribution width/albumin ratio in T1(2.32,2.93), the adjusted OR values for the ratio and ulcers in T2(2.94,3.26), T3(3.27,7.42), and 2.07 (95% CI = 1.19∼3.61), 2.92 (95% CI = 1.63∼5.23). The association between the ratio and ulcers exhibited a non-linear relationship (nonlinear, P = .028). CONCLUSION: These results support the hypothesis of an S-shaped relationship between red cell distribution width/albumin and diabetic lower-extremity ulcers. Monitoring the RDW/Albumin ratio could be crucial for preventing diabetic lower-extremity ulcers in outpatient settings. Regular assessments may help identify high-risk patients early, enabling timely interventions. Future studies should further assess these two factors and their underlying mechanisms.

10.
Apoptosis ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115621

RESUMO

This study aims to investigate the role and prognostic significance of long non-coding RNAs (lncRNAs) associated with disulfidptosis in colon adenocarcinoma (COAD). The TCGA database's clinical data and transcriptome profiles were employed. Analysis of previous studies identified 10 disulfidptosis-related genes (DRGs). We used these genes to construct a signature that could independently and accurately predict the prognosis of patients with COAD. The Kaplan-Meier (K-M) curve analysis showed that the lower-risk group had a better prognosis. With the help of multivariate Cox regression analysis, the risk score produced from the patient's signature might independently predict the outcomes. Utilizing a nomogram, the receiver operating characteristic (ROC) curve, and principal component analysis (PCA), the signature's predictive ability was also confirmed. It's interesting to note that immunotherapy, especially PD-1 immune checkpoint suppression, was more likely to benefit low-risk patients. The IC50 levels for certain anticancer agents were lower in the high-risk group. Finally, qRT-PCR analyses in colon cancer cell lines revealed elevated levels of lncRNAs CASC9, ZEB1-AS1, ATP2A1-AS1, SNHG7, AL683813.1, and AP003555.1, and reduced levels of FAM160A1-DT and AC112220.2, compared to normal cell lines. This signature offers insights into prognosis, tumor microenvironment, and options for immunotherapy and antitumor drugs in patients with COAD.

11.
Nat Commun ; 15(1): 7150, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168967

RESUMO

Despite the prevalent of hexagonal, tetragonal, and triangular pore structures in two-dimensional covalent organic frameworks (2D COFs), the pentagonal pores remain conspicuously absent. We herein present the Cairo pentagonal tessellated COFs, achieved through precisely chosen geometry and metrics of the linkers, resulting in unprecedented mcm topology. In each pentagonal structure, porphyrin units create four uniform sides around 15.5 Å with 90° angles, while tetrabiphenyl unit establish a bottom edge about 11.6 Å with 120° angles, aligning precisely with the criteria of Cairo Pentagon. According to the narrow bandgap and strong near-infrared (NIR) absorbance, as-synthesized COFs exhibit the efficient singlet oxygen (1O2) generation and photothermal conversion, resulting in NIR photothermal combined photodynamic therapy to guide cancer cell apoptosis. Mechanistic studies reveal that the good 1O2 production capability upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. The implementation of pentagonal Cairo tessellations in this work provides a promising strategy for diversifying COFs with new topologies, along with multimodal NIR phototherapy.


Assuntos
Apoptose , Raios Infravermelhos , Fotoquimioterapia , Oxigênio Singlete , Humanos , Oxigênio Singlete/metabolismo , Oxigênio Singlete/química , Fotoquimioterapia/métodos , Estruturas Metalorgânicas/química , Porfirinas/química , Animais , Peroxidação de Lipídeos , Linhagem Celular Tumoral , Ferroptose , Fototerapia/métodos , Camundongos , Glutationa/química , Glutationa/metabolismo , Fármacos Fotossensibilizantes/química , Neoplasias/terapia , Neoplasias/metabolismo
12.
Discov Med ; 36(187): 1715-1720, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39190386

RESUMO

BACKGROUND: Bile duct injury (BDI) is a severe complication following cholecystectomy and is therefore a particularly concerning surgical predicament for hepatobiliary surgeons. Owing to very high medical compensation awarded to patients suffering from BDI, surgeons need to exercise caution during surgery to avoid BDI. Herein, we explored a novel method to identify cystic duct during laparoscopic cholecystectomy (LC), expanding the applicability of this surgical approach. METHODS: Patients receiving LC between April 2021 and October 2022 at the Gaoyou People's Hospital were included in this retrospective clinical study and divided into two groups according to whether the cystic duct was incised (one group with LC alone, while another with laparoscopic cholecystectomy and cystic duct exploration [LCCDE]). Clinical and baseline characteristics of patients were collected, and the preoperative and postoperative biochemical parameters were compared. The surgical outcomes of LCCDE were observed. RESULTS: A total of 114 patients had undergone LC, while 162 patients had received LCCDE as treatment. There were no significant differences in age, gender, common bile duct diameter, preoperative and postoperative biochemical parameters between the two groups. No significant difference in the mean operation time between the LC and LCCDE groups was noted (p = 0.409). In the LCCDE group, white secretions in the cystic duct were observed in 92 patients (56.8%). CONCLUSIONS: The presence of intraoperative white secretions in the cystic duct may further confirm the presence of cystic duct, thereby enabling earlier detection of BDI. Importantly, LCCDE, as the new surgical method explored in this study, does not extend the operation time.


Assuntos
Colecistectomia Laparoscópica , Ducto Cístico , Humanos , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Masculino , Feminino , Ducto Cístico/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Duração da Cirurgia
13.
Nat Commun ; 15(1): 6930, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138172

RESUMO

Plants flower in response to environmental signals. These signals change the shape and developmental identity of the shoot apical meristem (SAM), causing it to form flowers and inflorescences. We show that the increases in SAM width and height during floral transition correlate with changes in size of the central zone (CZ), defined by CLAVATA3 expression, and involve a transient increase in the height of the organizing center (OC), defined by WUSCHEL expression. The APETALA2 (AP2) transcription factor is required for the rapid increases in SAM height and width, by maintaining the width of the OC and increasing the height and width of the CZ. AP2 expression is repressed in the SAM at the end of floral transition, and extending the duration of its expression increases SAM width. Transcriptional repression by SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) represents one of the mechanisms reducing AP2 expression during floral transition. Moreover, AP2 represses SOC1 transcription, and we find that reciprocal repression of SOC1 and AP2 contributes to synchronizing precise changes in meristem shape with floral transition.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Flores , Regulação da Expressão Gênica de Plantas , Proteínas de Homeodomínio , Proteínas de Domínio MADS , Meristema , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Meristema/metabolismo , Meristema/crescimento & desenvolvimento , Meristema/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Domínio MADS/metabolismo , Proteínas de Domínio MADS/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação da Expressão Gênica no Desenvolvimento , Plantas Geneticamente Modificadas
14.
Angew Chem Int Ed Engl ; : e202412890, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39148428

RESUMO

The design of three-dimensional covalent organic frameworks (3D COFs) using linear and trigonal linkers remains challenging due to the difficulty in achieving a specific non-planar spatial arrangement with low-connectivity building units. Here, we report the novel 3D COFs with linear and trigonal linkers, termed TMB-COFs, exhibiting srs topology. The steric hindrance provides an additional force to alter the torsion angles of peripheral triangular units, guiding the linear unit to connect with the trigonal unit into 3D srs frameworks, rather than the more commonly observed two-dimensional (2D) hcb structures. Furthermore, we comprehensively examined the hydrogen peroxide photocatalytic production capacity of the TMB-COFs in comparison with analogous 2D COFs. The experimental results and DFT calculations demonstrate a significant enhancement in photocatalytic hydrogen peroxide production efficacy through framework regulation. This work emphasizes the steric configuration using low connectivity building units, offering a fresh perspective on the design and application of 3D COFs.

15.
J. pediatr. (Rio J.) ; 100(4): 430-437, July-Aug. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1564755

RESUMO

Abstract Objective: Signs and symptoms of osteomyelitis or septic arthritis in neonates and infants are often nonspecific and early-stage bone infections in infants may often go unnoticed. The objective of this study was to analyze the clinical characteristics of newborns and infants with osteomyelitis and septic arthritis to improve understanding of the disorder and to assist clinicians with diagnosis. Methods: A retrospective multicenter study was conducted on neonates (0-28 days old, n = 94) and infants (1-12 months old, n = 415) with osteoarticular infections. Data consisting of clinical characteristics, complications, laboratory outcomes, and the pathogenic microorganisms causing osteomyelitis were tabulated. The statistics were further broken down into two regions and the significant differences between neonates and infants were evaluated and compared to the literature. Results: Compared to infants, neonates had significantly lower incidences of fever (p < 0.0001), higher incidences of localized swelling (p = 0.0021), higher rate of infection at the humerus (p = 0.0016), higher percentage of Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p = 0.0039) infections, lower percentage of Staphylococcus aureus infections (p < 0.0001) and were more likely to develop septic arthritis (p < 0.0001). Conclusion: Distinct differences were found between neonatal and infants with osteoarticular infections. Future studies should focus on improving diagnosis and subsequent treatment regimens for younger age groups.

16.
Artigo em Inglês | MEDLINE | ID: mdl-39001735

RESUMO

Coronary artery disease continues to be the leading cause of death globally. Identifying patients who are at risk of coronary artery disease remains a public health priority. At present, the focus of cardiovascular disease prevention relies heavily on probabilistic risk scoring despite no randomized controlled trials demonstrating their efficacy. The concept of using imaging to guide preventative therapy is not new, but has previously focused on indirect measures such as carotid intima-media thickening or coronary artery calcification. In recent trials, patients found to have coronary artery disease on computed tomography (CT) coronary angiography were more likely to be started on preventative therapy and had lower rates of cardiac events. This led to the design of the SCOT-HEART 2 (Scottish Computed Tomography of the Heart 2) trial, which aims to determine whether screening with the use of CT coronary angiography is more clinically effective than cardiovascular risk scoring to guide the use of primary preventative therapies and reduce the risk of myocardial infarction.

17.
Circ Res ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082138

RESUMO

BACKGROUND: ß-adrenergic receptor (ß-AR) overactivation is a major pathological cue associated with cardiac injury and diseases. AMPK (AMP-activated protein kinase), a conserved energy sensor, regulates energy metabolism and is cardioprotective. However, whether AMPK exerts cardioprotective effects via regulating the signaling pathway downstream of ß-AR remains unclear. METHODS: Using immunoprecipitation, mass spectrometry, site-specific mutation, in vitro kinase assay, and in vivo animal studies, we determined whether AMPK phosphorylates ß-arrestin-1 at serine (Ser) 330. Wild-type mice and mice with site-specific mutagenesis (S330A knock-in [KI]/S330D KI) were subcutaneously injected with the ß-AR agonist isoproterenol (5 mg/kg) to evaluate the causality between ß-adrenergic insult and ß-arrestin-1 Ser330 phosphorylation. Cardiac transcriptomics was used to identify changes in gene expression from ß-arrestin-1-S330A/S330D mutation and ß-adrenergic insult. RESULTS: Metformin could decrease cAMP/PKA (protein kinase A) signaling induced by isoproterenol. AMPK bound to ß-arrestin-1 and phosphorylated Ser330 with the highest phosphorylated mass spectrometry score. AMPK activation promoted ß-arrestin-1 Ser330 phosphorylation in vitro and in vivo. Neonatal mouse cardiomyocytes overexpressing ß-arrestin-1-S330D (active form) inhibited the ß-AR/cAMP/PKA axis by increasing PDE (phosphodiesterase) 4 expression and activity. Cardiac transcriptomics revealed that the differentially expressed genes between isoproterenol-treated S330A KI and S330D KI mice were mainly involved in immune processes and inflammatory response. ß-arrestin-1 Ser330 phosphorylation inhibited isoproterenol-induced reactive oxygen species production and NLRP3 (NOD-like receptor protein 3) inflammasome activation in neonatal mouse cardiomyocytes. In S330D KI mice, the ß-AR-activated cAMP/PKA pathways were attenuated, leading to repressed inflammasome activation, reduced expression of proinflammatory cytokines, and mitigated macrophage infiltration. Compared with S330A KI mice, S330D KI mice showed diminished cardiac fibrosis and improved cardiac function upon isoproterenol exposure. However, the cardiac protection exerted by AMPK was abolished in S330A KI mice. CONCLUSIONS: AMPK phosphorylation of ß-arrestin-1 Ser330 potentiated PDE4 expression and activity, thereby inhibiting ß-AR/cAMP/PKA activation. Subsequently, ß-arrestin-1 Ser330 phosphorylation blocks ß-AR-induced cardiac inflammasome activation and remodeling.

18.
Stat Methods Med Res ; : 9622802241262521, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39053568

RESUMO

This study investigates the heterogeneity of a biomarker's discriminative performance for predicting subsequent time-to-event outcomes across different patient subgroups. While the area under the curve (AUC) for the time-dependent receiver operating characteristic curve is commonly used to assess biomarker performance, the partial time-dependent AUC (PAUC) provides insights that are often more pertinent for population screening and diagnostic testing. To achieve this objective, we propose a regression model tailored for PAUC and develop two distinct estimation procedures for discrete and continuous covariates, employing a pseudo-partial likelihood method. Simulation studies are conducted to assess the performance of these procedures across various scenarios. We apply our model and inference procedure to the Alzheimer's Disease Neuroimaging Initiative data set to evaluate potential heterogeneities in the discriminative performance of biomarkers for early Alzheimer's disease diagnosis based on patients' characteristics.

19.
Chemistry ; : e202401935, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042471

RESUMO

Low temperature has been a major challenge for lithium-ion batteries (LIBs) to maintain satisfied electrochemical performance, and the main reason is the deactivation of electrolyte with the decreasing temperature. To address this point, in present work, we develop a low-temperature resistant electrolyte which includes ethyl acetate (EA) and fluoroethylene carbonate (FEC) as solvent and lithium difluoro(oxalato)borate (LiDFOB) as the primary lithium salt. Due to the preferential decomposition of LiDFOB and FEC, a solid electrolyte interface rich in LiF is formed on the lithium metal anodes (LMAs) and lithium cobalt oxide (LCO) cathodes, contributing to higher stability and rapid desolvation of Li+ ions. The batteries with the optimized electrolyte can undergo cycling tests at -40 °C, with a capacity retention of 83.9 % after 200 cycles. Furthermore, the optimized electrolyte exhibits excellent compatibility with both LCO cathodes and graphite (Gr) anodes, enabling a Gr/LCO battery to maintain a capacity retention of 90.3 % after multiple cycles at -25 °C. This work proposes a cost-effective electrolyte that can activate potential LIBs in practical scenarios, especially in low-temperature environments.

20.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 2346-2356, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39044596

RESUMO

To achieve rapid detection of enramycin in feed, we employed the competitive inhibition method to develop a colloidal gold immunochromatographic test strip based on the anti-enramycin A monoclonal antibody (anti-Er.A-mAb). Colloidal gold probes were prepared with a laboratory-prepared high-purity anti-Er.A-mAb. The effects of pH, antibody titer, and antigen concentration (test line) on the test strip performance were investigated. The colloidal gold test strip prepared with 8 µL potassium carbonate addition, 4 µg/mL antibody, 1.0 mg/mL antigen (test line), and 3 µL gold-labeled antibody showed acceptable specificity and a low limit of detection. The test strip showed the detection limit of 25 ng/mL for enramycin A, with a linear range of 25-300 ng/mL. The experiments on the feed with positive sample addition proved that the test strip had good repeatability and was more sensitive than high-performance liquid chromatography, being applicable for the rapid detection of enramycin in large batches of feed samples.


Assuntos
Ração Animal , Anticorpos Monoclonais , Cromatografia de Afinidade , Coloide de Ouro , Coloide de Ouro/química , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/química , Cromatografia de Afinidade/métodos , Ração Animal/análise , Nebramicina/análise , Nebramicina/análogos & derivados , Contaminação de Alimentos/análise , Resíduos de Drogas/análise
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