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1.
World J Psychiatry ; 14(3): 467-483, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38617982

RESUMO

BACKGROUND: Depression has gradually become a common psychological disorder among children and adolescents. Depression in children and adolescents affects their physical and mental development. Psychotherapy is considered to be one of the main treatment options for depressed children and adolescents. However, our understanding of the global performance and progress of psychological interventions for depression in children and adolescents (PIDCA) research is limited. AIM: To identify collaborative research networks in this field and explore the current research status and hotspots through bibliometrics. METHODS: Articles and reviews related to PIDCA from January 2010 to April 2023 were identified from the Web of Science Core Collection database. The Charticulator website, CiteSpace and VOSviewer software were used to visualize the trends in publications and citations, the collaborative research networks (countries, institutions, and authors), and the current research status and hotspots. RESULTS: Until April 16, 2023, 1482 publications were identified. The number of documents published each year and citations had increased rapidly in this field. The United States had the highest productivity in this field. The most prolific institution was the University of London. Pim Cuijpers was the most prolific author. In the context of research related to PIDCA, both reference co-citation analysis and keywords co-occurrence analysis identified 10 research hotspots, including third-wave cognitive behavior therapy, short-term psychoanalytic psychotherapy, cognitive behavioral analysis system of psychotherapy, family element in psychotherapy, modular treatment, mobile-health, emotion-regulation-based transdiagnostic intervention program, dementia risk in later life, predictors of the efficacy of psychological intervention, and risks of psychological intervention. CONCLUSION: This bibliometric study provides a comprehensive overview of PIDCA from 2010 to present. Psychological intervention characterized as psychological-process-focused, short, family-involved, modular, internet-based, emotion-regulation-based, and personalized may benefit more young people.

2.
Plant Phenomics ; 6: 0159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629083

RESUMO

The root is an important organ for plants to obtain nutrients and water, and its phenotypic characteristics are closely related to its functions. Deep-learning-based high-throughput in situ root senescence feature extraction has not yet been published. In light of this, this paper suggests a technique based on the transformer neural network for retrieving cotton's in situ root senescence properties. High-resolution in situ root pictures with various levels of senescence are the main subject of the investigation. By comparing the semantic segmentation of the root system by general convolutional neural networks and transformer neural networks, SegFormer-UN (large) achieves the optimal evaluation metrics with mIoU, mRecall, mPrecision, and mF1 metric values of 81.52%, 86.87%, 90.98%, and 88.81%, respectively. The segmentation results indicate more accurate predictions at the connections of root systems in the segmented images. In contrast to 2 algorithms for cotton root senescence extraction based on deep learning and image processing, the in situ root senescence recognition algorithm using the SegFormer-UN model has a parameter count of 5.81 million and operates at a fast speed, approximately 4 min per image. It can accurately identify senescence roots in the image. We propose that the SegFormer-UN model can rapidly and nondestructively identify senescence root in in situ root images, providing important methodological support for efficient crop senescence research.

3.
Plant Phenomics ; 6: 0148, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629084

RESUMO

The root system plays a vital role in plants' ability to absorb water and nutrients. In situ root research offers an intuitive approach to exploring root phenotypes and their dynamics. Deep-learning-based root segmentation methods have gained popularity, but they require large labeled datasets for training. This paper presents an expansion method for in situ root datasets using an improved CycleGAN generator. In addition, spatial-coordinate-based target background separation method is proposed, which solves the issue of background pixel variations caused by generator errors. Compared to traditional threshold segmentation methods, this approach demonstrates superior speed, accuracy, and stability. Moreover, through time-division soil image acquisition, diverse culture medium can be replaced in in situ root images, thereby enhancing dataset versatility. After validating the performance of the Improved_UNet network on the augmented dataset, the optimal results show a 0.63% increase in mean intersection over union, 0.41% in F1, and 0.04% in accuracy. In terms of generalization performance, the optimal results show a 33.6% increase in mean intersection over union, 28.11% in F1, and 2.62% in accuracy. The experimental results confirm the feasibility and practicality of the proposed dataset augmentation strategy. In the future, we plan to combine normal mapping with rendering software to achieve more accurate shading simulations of in situ roots. In addition, we aim to create a broader range of images that encompass various crop varieties and soil types.

4.
Magn Reson Chem ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632498

RESUMO

Three new monacolin analogues, 3,6-dihydroxy-monacolin P (1), 6-methoxy monacolin S (2), and 6-methoxy dehydromonacolin S (3), were isolated from a fraction that strongly inhibited 3-hydroxy-3-methylglutaryl-CoA reductase from the ethyl acetate portion of red yeast rice ethanol extract. Their structures were determined through a combination of 1D and 2D NMR experiments, mass spectrometry analysis, and known literature reports.

5.
J Am Chem Soc ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632847

RESUMO

Lithium metal batteries (LMB) have high energy densities and are crucial for clean energy solutions. The characterization of the lithium metal interphase is fundamentally and practically important but technically challenging. Taking advantage of synchrotron X-ray, which has the unique capability of analyzing crystalline/amorphous phases quantitatively with statistical significance, we study the composition and dynamics of the LMB interphase for a newly developed important LMB electrolyte that is based on fluorinated ether. Pair distribution function analysis revealed the sequential roles of the anion and solvent in interphase formation during cycling. The relative ratio between Li2O and LiF first increases and then decreases during cycling, suggesting suppressed Li2O formation in both initial and long extended cycles. Theoretical studies revealed that in initial cycles, this is due to the energy barriers in many-electron transfer. In long extended cycles, the anion decomposition product Li2O encourages solvent decomposition by facilitating solvent adsorption on Li2O which is followed by concurrent depletion of both. This work highlights the important role of Li2O in transitioning from an anion-derived interphase to a solvent-derived one.

6.
Front Cardiovasc Med ; 11: 1369680, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606381

RESUMO

Introduction: Danon disease is an X-linked disorder caused by pathogenic variants in lysosome-associated membrane protein 2 (LAMP2) gene, typically characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. However, many patients may not present the typical presentation, especially in the early stage. Electrocardiogram (ECG) abnormalities can be found in almost all patients, with Wolff-Parkinson-White (WPW) syndrome being the most common. We reported the case of a 51-year-old woman who experienced multiple types of arrhythmias over three decades and was diagnosed with Danon disease late by genetic testing. Case summary: A 51-year-old woman with a 36-year history of intermittent palpitations was admitted due to hemodynamically stable ventricular tachycardia (VT). Her past medical history revealed multiple arrhythmias and ECG abnormalities in her 30s and 40s, including WPW syndrome with paroxysmal supraventricular tachycardia, paroxysmal atrial flutter, atrial fibrillation, ventricular tachycardia, and complete left bundle branch block. She denied any family history of cardiovascular disease or sudden death. Upon arrival, her vital signs were unremarkable. Cardiovascular magnetic resonance (CMR) imaging revealed left ventricular enlargement and late gadolinium enhancement (LGE) in the anterior, inferior, and lateral walls. Subsequent, whole-exome sequencing (WES) gene testing revealed a pathogenic heterozygous variant in LAMP2 gene (c.696T>A; p.Cys232Ter), which confirmed the diagnosis of Danon disease. Conclusion: Genetic testing should be considered in patients who display multiple arrhythmias with LV structural abnormalities of unknown etiology for a possible Danon disease.

7.
Mol Cell ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38614096

RESUMO

Cytokines regulate immune responses by binding to cell surface receptors, including the common subunit beta (ßc), which mediates signaling for GM-CSF, IL-3, and IL-5. Despite known roles in inflammation, the structural basis of IL-5 receptor activation remains unclear. We present the cryo-EM structure of the human IL-5 ternary receptor complex, revealing architectural principles for IL-5, GM-CSF, and IL-3. In mammalian cell culture, single-molecule imaging confirms hexameric IL-5 complex formation on cell surfaces. Engineered chimeric receptors show that IL-5 signaling, as well as IL-3 and GM-CSF, can occur through receptor heterodimerization, obviating the need for higher-order assemblies of ßc dimers. These findings provide insights into IL-5 and ßc receptor family signaling mechanisms, aiding in the development of therapies for diseases involving deranged ßc signaling.

8.
Cancer Genet ; 284-285: 34-42, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626533

RESUMO

Circular RNAs (circRNAs) play an important role in the development of acquired resistance to many anticancer drugs. We developed the Non-Small-Cell Lung Cancer (NSCLC) cell lines with acquired resistance to osimertinib, a third-generation of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and evaluated the different expression profiles of circRNAs in osimertinib-sensitive and -resistant NSCLC cell lines using RNA sequencing (RNA-Seq). The expression of selected differentially expressed circRNAs was verified using quantitative real-time PCR (qRT-PCR) in paired osimertinib-sensitive and -resistant NSCLC cell lines, and in plasma samples of osimertinib-sensitive and -resistant NSCLC patients. We found that circMYBL1(has_circ_0136924) was downregulated after acquired resistance to osimertinib, inhibiting circMYBL1 expression facilitated the proliferation, migration, and invasion in osimertinib-sensitive NSCLC cells. CircMYBL1 may be a novel molecular biomarker and therapeutic target for osimertinib-resistant NSCLC.

9.
Immunopharmacol Immunotoxicol ; : 1-37, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627024

RESUMO

Objective The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. Method By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures. Results A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, P < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, P < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities. Conclusions Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.

10.
ACS Appl Mater Interfaces ; 16(15): 18745-18753, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38573811

RESUMO

Zeolite-catalyzed dimethyl ether (DME) carbonylation provides a novel route to producing methyl acetate (MeOAc). Mordenite (MOR) has drawn significant interest because of its remarkable MeOAc selectivity in DME carbonylation, albeit with limited catalytic stability. Herein, novel MOR-based DME carbonylation catalysts, distinguished by long-term stability and high activity were successfully developed, based on an H2-promoted benign coke strategy. Both the H2 cofeeds and the presence of metal species with hydrogenation capability are demonstrated to be crucial for the regulation of coke depositions. The coke deposits can potentially cover the acid sites in the 12-MR main channels, thereby mitigating the occurrence of undesirable methanol-to-hydrocarbon side reactions. Meanwhile, the elimination of ultralarge coke species under the assistance of H2 and Cu species could ensure smooth mass transfer within the catalyst, contributing to its remarkable catalytic performance. The most highlighted DME carbonylation performance was achieved on coke-mediated CuZn-HMOR with a high MeOAc yield of 0.4-0.5 g·gcat-1·h-1 for over 520 h (over 50× enhancement versus HMOR), exhibiting promising industrial application potential. The current strategy is expected to inspire further research into zeolite-catalyzed reactions, which could be potentially improved by the presence of benign coke.

11.
J Sci Food Agric ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563388

RESUMO

BACKGROUND: Biogenic amines (BA) are hazardous components in Huangjiu (HJ). To ensure the quality of Dangshen Huangjiu, an orthogonal experiment L9 (33) was proposed to optimize the process by the main brewing factors (pre-fermentation temperature, pre-(post-) fermentation time) that may affect BA and functional factors in Dangshen Huangjiu. Dangshen Huangjiu (DSHJ) was produced with low BA and high functional factors. Gas chromatography-ion mobility spectrometry combined with a multivariate statistical method (GC-IMS-MSM) was used to analyze the volatile components in the DSHJ brewing process of DSHJ. RESULTS: The optimum brewing process parameters of DSHJ were as follows: pre-fermentation temperature 28°C, pre-fermentation time 9 days, and post-fermentation time 18 days. The average content of BA in DSHJ was 33.12 mg/L, and the sensory score, total phenol content, and DPPH free radical scavenging rate of DSHJ were significantly higher than HJ. A total of 14 esters, 7 acids, 7 alcohols, 1 ketones, 5 aldehydes, and 1 pyrazine in DSHJ and HJ were identified by GC-IMS. There were no significant differences (P>0.05) in DSHJ and HJ in the soaking rice and saccharification stage. 11 components, such as ethyl acetate, and 12 components, such as acetic acid, were the different components of HJ and DSHJ in pre-fermentation and post-fermentation stages, respectively. In the post-fermentation stage, the content of 8 components of DSHJ such as ethyl acetate were higher than in HJ. CONCLUSION: The preparation process parameters of DSHJ optimized by orthogonal experiments can ensure that DSHJ has the advantages of low BA, high total phenol content, and good antioxidant activity. Sensory score and GC-IMS-MSM analysis found that DSHJ prepared by the optimal process had the characteristics of good taste and rich aroma. This article is protected by copyright. All rights reserved.

12.
Opt Express ; 32(7): 11895-11906, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571027

RESUMO

Pure-quartic solitons (PQSs) have recently received increasing attention due to their energy-width scaling over the traditional soliton, which has expanded our understanding of soliton dynamics with high-order dispersion in nonlinear systems. Here, we numerically reveal the asynchronization and synchronization processes of the sub-pulse within the vector PQS molecule in a mode-locked fiber laser by solving the coupled Ginzburg-Landau equations. During the establishment of a vector PQS molecule, the repulsion, attraction, and finally stabilization processes have been observed. Specifically, sub-pulse disappearance, regeneration, and finally synchronization with the other pulses are also investigated. Our analysis of the pulse energy, time interval, and relative phase evolution dynamics with the round trip indicates that the asynchronization and synchronization within the vector PQS molecule associate tightly with the gain competition and the cross-phase modulation. Our findings provide insights into the internal mutual dynamics within the vector soliton molecule and offer guidance for the applications of PQS.

13.
Int J Parasitol Parasites Wildl ; 23: 100925, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38560661

RESUMO

Red foxes (Vulpes vulpes) have been recognized as natural reservoirs for multiple pathogens and a source of infection for domestic animals, wildlife and humans. To date, no reports are available on the Bartonella rochalimae and Hepatozoon canis infection in red foxes from China. In 2018-2022, a total of 16 red foxes were sampled in two counties and a city in Xinjiang Uygur Autonomous Region (XUAR) in northwest China. Subsequently analyzed by DNA extraction amplified by polymerase chain reaction (PCR). In the present study, based on nucleotide sequence and phylogenetic tree analyses, B. rochalimae and H. canis were molecularly identified in red foxes. Our findings provide the first molecular evidence of B. rochalimae and H. canis in red foxes from China.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38607584

RESUMO

Periodontitis is an inflammatory condition of the oral cavity caused by a mixed infection of various bacteria, which not only severely affects the alveolar bone and connective tissues but also displays potential correlations with distal intestinal inflammation. In this study, we aimed to elucidate the therapeutic effects of Streptococcus cristatus CA119 on experimental periodontitis in rats and its impact on intestinal morphology. The results demonstrate that CA119 is capable of colonizing the oral cavity and exerting antagonistic effects on Porphyromonas gingivalis and Fusobacterium nucleatum, thus leading to a significant reduction in the oral pathogen load. Following CA119 intervention, there was a significant alleviation of weight loss in rats induced by periodontitis (P < 0.001). CA119 also regulated the expression of IL-6 (P < 0.05), IL-1ß (P < 0.001), IL-18 (P < 0.001), COX-2 (P < 0.001), iNOS (P < 0.001), and MCP-1 (P < 0.01) in the gingival tissue. Additionally, CA119 reduced oxidative stress levels in rats and enhanced their antioxidant capacity. Microcomputed tomography (micro-CT) and histological analysis revealed that CA119 significantly reduced alveolar bone loss and reversed the downregulation of OPG/RANKL (P < 0.001). Furthermore, CA119 exhibited a significant protective effect against intestinal inflammation induced by periodontal disease and improved the colonic morphology in rats. In conclusion, this study demonstrates the role of CA119 as a potential oral probiotic in the prevention and treatment of experimental periodontitis, underscoring the potential of probiotics as a complementary approach to traditional periodontal care.

15.
Top Curr Chem (Cham) ; 382(2): 11, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589726

RESUMO

Silicone surfactants have garnered significant research attention owing to their superior properties, such as wettability, ductility, and permeability. Small-molecular silicone surfactants with simple molecular structures outperform polymeric silicone surfactants in terms of surface activity, emulsification, wetting, foaming, and other areas. Moreover, silicone surfactants with small molecules exhibit a diverse and rich molecular structure. This review discusses various synthetic routes for the synthesis of different classes of surfactants, including single-chain, "umbrella" structure, double chain, bolaform, Gemini, and stimulus-responsive surfactants. The fundamental surface/interface properties of the synthesized surfactants are also highlighted. Additionally, these surfactants have demonstrated enormous potential in agricultural synergism, drug delivery, mineral flotation, enhanced oil recovery, separation, and extraction, and foam fire-fighting.


Assuntos
Silicones , Tensoativos , Tensoativos/química , Propriedades de Superfície , Estrutura Molecular
16.
Front Med (Lausanne) ; 11: 1356225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590315

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)), and lobular inflammation and hepatocyte damage (which characterize nonalcoholic steatohepatitis (NASH) are found in most patients). A subset of patients will gradually develop liver fibrosis, cirrhosis, and eventually hepatocellular carcinoma, which is a deadly disease that threatens human life worldwide. Ferroptosis, a novel nonapoptotic form of programmed cell death (PCD) characterized by iron-dependent accumulation of reactive oxygen radicals and lipid peroxides, is closely related to NAFLD. Traditional Chinese medicine (TCM) has unique advantages in the prevention and treatment of NAFLD due to its multicomponent, multipathway and multitarget characteristics. In this review, we discuss the effect of TCM on NAFLD by regulating ferroptosis, in order to provide reference for the further development and application of therapeutic drugs to treat NAFLD.

17.
Biotechnol Bioeng ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38595326

RESUMO

Pathogenic bacterial membrane proteins (MPs) are a class of vaccine and antibiotic development targets with widespread clinical application. However, the inherent hydrophobicity of MPs poses a challenge to fold correctly in living cells. Herein, we present a comprehensive method to improve the soluble form of MP antigen by rationally designing multi-epitope chimeric antigen (ChA) and screening two classes of protein-assisting folding element. The study uses a homologous protein antigen as a functional scaffold to generate a ChA possessing four epitopes from transferrin-binding protein A of Glaesserella parasuis. Our engineered strain, which co-expresses P17 tagged-ChA and endogenous chaperones groEL-ES, yields a 0.346 g/L highly soluble ChA with the property of HPS-positive serum reaction. Moreover, the protein titer of ChA reaches 4.27 g/L with >90% soluble proportion in 5-L bioreactor, which is the highest titer reported so far. The results highlight a timely approach to design and improve the soluble expression of MP antigen in industrially viable applications.

18.
Lipids Health Dis ; 23(1): 97, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566047

RESUMO

BACKGROUND: Observational studies have suggested an association between birth weight and type 2 diabetes mellitus, but the causality between them has not been established. We aimed to obtain the causal relationship between birth weight with T2DM and quantify the mediating effects of potential modifiable risk factors. METHODS: Two-step, two-sample Mendelian randomization (MR) techniques were applied using SNPs as genetic instruments for exposure and mediators. Summary data from genome-wide association studies (GWAS) for birth weight, T2DM, and a series of fatty acids traits and their ratios were leveraged. The inverse variance weighted (IVW) method was the main analysis approach. In addition, the heterogeneity test, horizontal pleiotropy test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out analysis were carried out to assess the robustness. RESULTS: The IVW method showed that lower birth weight raised the risk of T2DM (ß: -1.113, 95% CI: -1.573 ∼ -0.652). Two-step MR identified 4 of 17 candidate mediators partially mediating the effect of lower birth weight on T2DM, including ratio of polyunsaturated fatty acids to monounsaturated fatty acids (proportion mediated: 7.9%), ratio of polyunsaturated fatty acids to total fatty acids (7.2%), ratio of omega-6 fatty acids to total fatty acids (8.1%) and ratio of linoleic acid to total fatty acids ratio (6.0%). CONCLUSIONS: Our findings supported a potentially causal effect of birth weight against T2DM with considerable mediation by modifiable risk factors. Interventions that target these factors have the potential to reduce the burden of T2DM attributable to low birth weight.


Assuntos
Diabetes Mellitus Tipo 2 , Ácidos Graxos , Humanos , Diabetes Mellitus Tipo 2/genética , Peso ao Nascer/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Ácidos Graxos Monoinsaturados
19.
Diabetes Metab Res Rev ; 40(2): e3773, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38598767

RESUMO

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Taiwan/epidemiologia , Estudos Retrospectivos , Glucose , Sódio , Hipoglicemiantes
20.
mSphere ; : e0006124, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564709

RESUMO

Mycobacterium tuberculosis (Mtb), the pathogenic bacterium that causes tuberculosis, has evolved sophisticated defense mechanisms to counteract the cytotoxicity of reactive oxygen species (ROS) generated within host macrophages during infection. The melH gene in Mtb and Mycobacterium marinum (Mm) plays a crucial role in defense mechanisms against ROS generated during infection. We demonstrate that melH encodes an epoxide hydrolase and contributes to ROS detoxification. Deletion of melH in Mm resulted in a mutant with increased sensitivity to oxidative stress, increased accumulation of aldehyde species, and decreased production of mycothiol and ergothioneine. This heightened vulnerability is attributed to the increased expression of whiB3, a universal stress sensor. The absence of melH also resulted in reduced intracellular levels of NAD+, NADH, and ATP. Bacterial growth was impaired, even in the absence of external stressors, and the impairment was carbon source dependent. Initial MelH substrate specificity studies demonstrate a preference for epoxides with a single aromatic substituent. Taken together, these results highlight the role of melH in mycobacterial bioenergetic metabolism and provide new insights into the complex interplay between redox homeostasis and generation of reactive aldehyde species in mycobacteria. IMPORTANCE: This study unveils the pivotal role played by the melH gene in Mycobacterium tuberculosis and in Mycobacterium marinum in combatting the detrimental impact of oxidative conditions during infection. This investigation revealed notable alterations in the level of cytokinin-associated aldehyde, para-hydroxybenzaldehyde, as well as the redox buffer ergothioneine, upon deletion of melH. Moreover, changes in crucial cofactors responsible for electron transfer highlighted melH's crucial function in maintaining a delicate equilibrium of redox and bioenergetic processes. MelH prefers epoxide small substrates with a phenyl substituted substrate. These findings collectively emphasize the potential of melH as an attractive target for the development of novel antitubercular therapies that sensitize mycobacteria to host stress, offering new avenues for combating tuberculosis.

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