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1.
Biochem Pharmacol ; 225: 116256, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729448

RESUMO

Endocrine treatment, particularly tamoxifen, has shown significant improvement in the prognosis of patients with estrogen receptor-positive (ER-positive) breast cancer. However, the clinical utility of this treatment is often hindered by the development of endocrine resistance. Therefore, a comprehensive understanding of the underlying mechanisms driving ER-positive breast cancer carcinogenesis and endocrine resistance is crucial to overcome this clinical challenge. In this study, we investigated the expression of MICAL-L2 in ER-positive breast cancer and its impact on patient prognosis. We observed a significant upregulation of MICAL-L2 expression in ER-positive breast cancer, which correlated with a poorer prognosis in these patients. Furthermore, we found that estrogen-ERß signaling promoted the expression of MICAL-L2. Functionally, our study demonstrated that MICAL-L2 not only played an oncogenic role in ER-positive breast cancer tumorigenesis but also influenced the sensitivity of ER-positive breast cancer cells to tamoxifen. Mechanistically, as an estrogen-responsive gene, MICAL-L2 facilitated the activation of the AKT/mTOR signaling pathway in ER-positive breast cancer cells. Collectively, our findings suggest that MICAL-L2 could serve as a potential prognostic marker for ER-positive breast cancer and represent a promising molecular target for improving endocrine treatment and developing therapeutic approaches for this subtype of breast cancer.

2.
Eur J Med Chem ; 271: 116437, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38701712

RESUMO

As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions but also in immune system, including cell growth, apoptosis and cancer development and progression. Based on its T-cell targeting profile, PNP is a potential target for the treatment of some malignant T-cell proliferative cancers including lymphoma and leukemia, and some specific immunological diseases. Numerous small-molecule PNP inhibitors have been developed so far. However, only Peldesine, Forodesine and Ulodesine have entered clinical trials and exhibited some potential for the treatment of T-cell leukemia and gout. The most recent direction in PNP inhibitor development has been focused on PNP small-molecule inhibitors with better potency, selectivity, and pharmacokinetic property. In this perspective, considering the structure, biological functions, and disease relevance of PNP, we highlight the recent research progress in PNP small-molecule inhibitor development and discuss prospective strategies for designing additional PNP therapeutic agents.


Assuntos
Inibidores Enzimáticos , Purina-Núcleosídeo Fosforilase , Bibliotecas de Moléculas Pequenas , Purina-Núcleosídeo Fosforilase/antagonistas & inibidores , Purina-Núcleosídeo Fosforilase/metabolismo , Humanos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Estrutura Molecular , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Relação Estrutura-Atividade , Desenvolvimento de Medicamentos
3.
Gut Microbes ; 16(1): 2351532, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38727248

RESUMO

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.


Assuntos
Microbioma Gastrointestinal , Lipopolissacarídeos , NF-kappa B , Prevotella , Insuficiência Renal Crônica , Transdução de Sinais , Receptor 4 Toll-Like , Calcificação Vascular , Animais , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia , NF-kappa B/metabolismo , Lipopolissacarídeos/metabolismo , Ratos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Humanos , Masculino , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Prevotella/metabolismo , Ratos Sprague-Dawley , Miócitos de Músculo Liso/metabolismo , Osteogênese/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fezes/microbiologia , Inflamassomos/metabolismo
5.
Food Chem X ; 22: 101427, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38736982

RESUMO

Flowery-like aroma are positive contributors to green tea. Here, the optimal processing conditions for green tea with flowery-like aroma were designed using spreading time, fixation time and drying temperature as three factors designed by response surface methodology (RSM), and the response value of aroma sensory evaluation score. The volatiles in batches of tea samples were analyzed by GC-MS. The optimal quality was obtained with a flowery-like aroma by RSM under a spreading time of 8.97 h, fixation time of 162.3 s, and drying temperature of 103.32 °C. GC-O and odor activity values further revealed floral-like volatiles, including decanal, linalool oxide, ß-lonone, geraniol, (Z)-jasmone, linalool, nonanal, and benzeneacetaldehyde. The recombination of these floral volatiles confirmed the consistency with the floral green tea. Furthermore, the extending spreading duration (8-10 h), reducing fixation duration (160-190 s), and increasing drying temperature (100-115 °C) promote their accumulation in green tea. This study provides new perspectives for the precise enhancement of floral odorants for green tea.

6.
Chem Commun (Camb) ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738578

RESUMO

A collaborative manipulation strategy of proper heat treatment and self-customized hydrofluoroether-based electrolyte design has been proposed for boosting the sodium-ion storage kinetics of Prussian white cathodes. Improved monoclinic phase stability and electrolyte-cathode compatibility are responsible for an impressive discharge capacity of 148.4 mA h g-1 and excellent electrode reversibility.

7.
J Hazard Mater ; 471: 134380, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38657514

RESUMO

Health of honey bees is threatened by a variety of stressors, including pesticides and parasites. Here, we investigated effects of acetamiprid, Varroa destructor, and Nosema ceranae, which act either alone or in combination. Our results suggested that interaction between the three factors was additive, with survival risk increasing as the number of stressors increased. Although exposure to 150 µg/L acetamiprid alone did not negatively impact honey bee survival, it caused severe damage to midgut tissue. Among the three stressors, V. destructor posed the greatest threat to honey bee survival, and N. ceranae exacerbated intestinal damage and increased thickness of the midgut wall. Transcriptomic analysis indicated that different combinations of stressors elicited specific gene expression responses in honey bees, and genes involved in energy metabolism, immunity, and detoxification were altered in response to multiple stressor combinations. Additionally, genes associated with Toll and Imd signalling, tyrosine metabolism, and phototransduction pathway were significantly suppressed in response to different combinations of multiple stressors. This study enhances our understanding of the adaptation mechanisms to multiple stressors and aids in development of suitable protective measures for honey bees. ENVIRONMENTAL IMPLICATION: We believe our study is environmentally relevant for the following reasons: This study investigates combined effects of pesticide, Varroa destructor, and Nosema ceranae. These stressors are known to pose a threat to long-term survival of honey bees (Apis mellifera) and stability of the ecosystems. The research provides valuable insights into the adaptive mechanisms of honey bees in response to multiple stressors and developing effective conservation strategies. Further research can identify traits that promote honey bee survival in the face of future challenges from multiple stressors to maintain the overall stability of environment.


Assuntos
Neonicotinoides , Nosema , Varroidae , Animais , Abelhas/efeitos dos fármacos , Nosema/efeitos dos fármacos , Neonicotinoides/toxicidade , Varroidae/efeitos dos fármacos , Inseticidas/toxicidade
8.
World J Diabetes ; 15(4): 735-757, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38680704

RESUMO

BACKGROUND: The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neuroinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease. AIM: To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment. METHODS: To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both in vivo and in vitro. To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro, consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with RAC3 and TFRC were identified based on the CTD. CONCLUSION: Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both in vivo and in vitro, consistent with our bioinformatics results. We discovered 11 compounds associated with RAC3 and TFRC. These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

9.
Eur J Med Chem ; 271: 116427, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38657479

RESUMO

Glucocorticoids (GCs) have been used in the treatment of sepsis because of their potent anti-inflammatory effects. However, their clinical efficacy against sepsis remains controversial because of glucocorticoid receptor (GR) downregulation and side effects. Herein, we designed and synthesized 30 ocotillol derivatives and evaluated their anti-inflammatory activities. Ocotillol 24(R/S) differential isomers were stereoselective in their pharmacological action. Specifically, 24(S) derivatives had better anti-inflammatory activity than their corresponding 24(R) derivatives. Compound 20 most effectively inhibited NO release (85.97% reduction), and it exerted dose-dependent inhibitory effects on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels. Mechanistic studies revealed that compound 20 reduces the degradation of GR mRNA and GR protein. Meanwhile, compound 20 inhibited the activation of nuclear factor-κB (NF-κB) signaling, thereby inhibiting the nuclear translocation of p65 and attenuating the inflammatory response. In vivo studies revealed that compound 20 attenuated hepatic, pulmonary, and renal pathology damage in mice with sepsis and suppressed the production of inflammatory mediators. These results indicated that compound 20 is a promising lead compound for designing and developing anti-sepsis drugs.


Assuntos
NF-kappa B , Receptores de Glucocorticoides , Sepse , Transdução de Sinais , Receptores de Glucocorticoides/metabolismo , Receptores de Glucocorticoides/antagonistas & inibidores , Sepse/tratamento farmacológico , Animais , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Camundongos , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Humanos , Estrutura Molecular , Células RAW 264.7 , Descoberta de Drogas , Masculino , Relação Dose-Resposta a Droga , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese química
10.
J Inflamm Res ; 17: 2383-2397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660574

RESUMO

Objective: Keratoconus is a commonly progressive and blinding corneal disorder. Iron metabolism and oxidative stress play crucial roles in both keratoconus and ferroptosis. However, the association between keratoconus and ferroptosis is currently unclear. This study aimed to analyze and verify the role of ferroptosis-related genes (FRGs) in the pathogenesis of keratoconus through bioinformatics. Methods: We first obtained keratoconus-related datasets and FRGs. Then, the differentially expressed FRGs (DE-FRGs) associated with keratoconus were screened through analysis, followed by analysis of their biological functions. Subsequently, the LASSO and SVM-RFE algorithms were used to screen for diagnostic biomarkers. GSEA was performed to explore the potential functions of the marker genes. Finally, the associations between these biomarkers and immune cells were analyzed. qRT‒PCR was used to detect the expression of these biomarkers in corneal tissues. Results: A total of 39 DE-FRGs were screened, and functional enrichment analysis revealed that the DE-FRGs were closely related to apoptosis, oxidative stress, and the immune response. Then, using multiple algorithms, 6 diagnostic biomarkers were selected, and the ROC curve was used to verify their risk prediction ability. In addition, based on CIBERSORT analysis, alterations in the immune microenvironment of keratoconus patients might be associated with H19, GCH1, CHAC1, and CDKN1A. Finally, qRT‒PCR confirmed that the expression of H19 and CHAC1 was elevated in the keratoconus group. Conclusion: This study identified 6 DE-FRGs, 4 of which were associated with immune infiltrating cells, and established a diagnostic model with predictive value for keratoconus.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38664127

RESUMO

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

12.
Adv Sci (Weinh) ; : e2400730, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654621

RESUMO

Metal-enzyme integrated catalysts (MEICs) that combine metal and enzyme offer great potential for sustainable chemoenzymatic cascade catalysis. However, rational design and construction of optimal microenvironments and accessible active sites for metal and enzyme in individual nanostructures are necessary but still challenging. Herein, Pd nanoparticles (NPs) and Candida antarctica lipase B (CALB) are co-immobilized into the pores and surfaces of covalent organic frameworks (COFs) with tunable functional groups, affording Pd/COF-X/CALB (X = ONa, OH, OMe) MEICs. This strategy can regulate the microenvironment around Pd NPs and CALB, and their interactions with substrates. As a result, the activity of the COF-based MEICs in catalyzing dynamic kinetic resolution of primary amines is enhanced and followed COF-OMe > COF-OH > COF-ONa. The experimental and simulation results demonstrated that functional groups of COFs modulated the conformation of CALB, the electronic states of Pd NPs, and the affinity of the integrated catalysts to the substrate, which contributed to the improvement of the catalytic activity of MEICs. Further, the MEICs are prepared using COF with hollow structure as support material, which increased accessible active sites and mass transfer efficiency, thus improving catalytic performance. This work provides a blueprint for rational design and preparation of highly active MEICs.

13.
J Med Imaging Radiat Oncol ; 68(3): 250-256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38563291

RESUMO

INTRODUCTION: The purpose of the study was to determine the usefulness of Ga-68 DOTATATE PET/MR in the identification of tumours in individuals with multiple endocrine neoplasia type 1 (MEN1). METHODS: In this retrospective investigation, five individuals who had tested positive for a hereditary MEN1 variant underwent Ga-68 DOTATATE PET/MR between May 2020 and January 2023. Several types of tumours associated with MEN1 were studied. MEN1-related tumours included pituitary, parathyroid, gastroenteropancreatic, and adrenal. The rates of lesion identification between MRI, Ga-68 DOTATATE PET, and Ga-68 DOTATATE PET/MRI were examined. The maximum and mean standard uptake values (SUVmax and SUVmean) were evaluated in carefully delineated volumes of interest (VOI) for the relevant tumours. RESULTS: Of the 24 primary lesions, 14 were identified by Ga-68 DOTATATE PET, 18 by MRI, and 20 by Ga-68 DOTATATE PET/MRI. Two pituitary tumours were detected by all three techniques. All parathyroid tumours that were not detected by Ga-68 DOTATATE PET and MRI were found by Tc-99m MIBI SPECT/CT or/and EUS. Ga-68 DOTATATE PET/MR detected more gastroenteropancreatic lesions. All adrenal tumours not identified by Ga-68 DOTATATE PET were found by MRI or CT. The median SUVmax for lesions identified on Ga-68 DOTATATE PET/MRI was 18.4 (range, 3.8-85.2), and the median SUVmean was 12.0 (range, 2.3-49.8). CONCLUSION: The combination of Ga-68 DOTATATE PET and MRI demonstrated a higher detection rate and may be more useful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. To increase the identification of MEN1-associated neuroendocrine lesions in the parathyroid gland, approaches other than Ga-68 DOTATATE PET/MRI should be used.


Assuntos
Imageamento por Ressonância Magnética , Neoplasia Endócrina Múltipla Tipo 1 , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Humanos , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Adulto , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Imagem Multimodal/métodos , Idoso , Neoplasias das Paratireoides/diagnóstico por imagem , Adulto Jovem
14.
Transl Oncol ; 45: 101926, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615437

RESUMO

BACKGROUND: Lung cancer stands as the foremost cause of cancer-related fatalities globally. The presence of cancer stem cells (CSCs) poses a challenge, rendering current targeted tumor therapies ineffective. This study endeavors to investigate a novel therapeutic approach focusing on ferroptosis and delves into the expression of ferroptosis-related genes within lung CSCs. METHODS: We systematically examined RNA-seq datasets derived from lung tumor cells (LTCs) and lung cancer stem cells (LSCs), as previously investigated in our research. Our focus was on analyzing differentially expressed genes (DEGs) related to ferroptosis. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), we conducted functional analysis of these ferroptosis-related DEGs. Additionally, we employed protein‒protein interaction networks to identify hub genes. LC‒MS/MS analysis of LTCs and LSCs was conducted to pinpoint the crucial ferroptosis-related gene-thioredoxin-interacting protein (TXNIP).Further, we delved into the immune cell infiltration landscape of LTCs and LSCs, examining the correlation between TXNIP and lung adenocarcinoma (LUAD) using data from The Cancer Genome Atlas (TCGA) database. To complement these findings, we measured the expression levels of TXNIP, glutathione peroxidase 4(GPX4), nuclear receptor coactivator 4 (NCOA4) in LUAD tissues through immunohistochemistry (IHC) staining. RESULTS: A total of 651 DEGs were identified, with 17 of them being ferroptosis-related DEGs. These seventeen genes were categorized into four groups: driver genes, suppressor genes, unclassified genes, and inducer genes. Enrichment analysis revealed significant associations with oxidative stress, cell differentiation, tissue development, and cell death processes. The RNA-seq analysis demonstrated consistent gene expression patterns with protein expression, as evidenced by mass spectrometry analysis. Among the identified genes, SFN and TXNIP were singled out as hub genes, with TXNIP showing particularly noteworthy expression. The expression of the ferroptosis-related gene TXNIP exhibited correlations with the presence of an immunosuppressive microenvironment, TNM stages, and the degree of histological differentiation.Also, the ferroptosis-markers GPX4 and NCOA4 displayed correlations with LUAD. This comprehensive analysis underscores the significance of TXNIP in the context of ferroptosis-related processes and their potential implications in cancer development and progression. CONCLUSION: The investigation conducted in this study systematically delved into the role of the ferroptosis-related gene TXNIP in Lung CSCs. The identification of TXNIP as a potentially valuable biomarker in this context could have significant implications for refining prognostic assessments and optimizing therapeutic strategies for advanced lung cancer.

15.
Cytokine ; 179: 156597, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643631

RESUMO

OBJECTIVES: To analyze the relationship between IL and 6 572C/G polymorphism with sepsis. METHODS: Searching 8 databases the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), Chongqing VIP, Embase, PubMed, WanFang Data, and Web of Science from inception to October 1, 2023. Meta-analysis was performed by using Review Manager 5.4 and STATA 15.0. RESULTS: 9 studies were included, 1 study was excluded from the previous meta-analysis, and 6 studies were added. Sensitivity analysis suggested that the results were relatively robust. The P values of Egger test indicated that no conspicuous publication bias was found. CONCLUSION: According to the meta-analysis results of existing studies, the IL-6 572C/G GG genotype and G allele are risk factors for sepsis, this result changes the previous conclusion that the IL-6 572 polymorphism is not related to sepsis. However, the results still need to be conservatively treated due to the sample size was not large enough.

16.
ACS Appl Mater Interfaces ; 16(15): 18843-18854, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38586920

RESUMO

Sulfide solid-state electrolytes have garnered considerable attention owing to their notable ionic conductivity and mechanical properties. However, achieving an electrolyte characterized by both high ionic conductivity and a stable interface between the electrode and electrolyte remains challenging, impeding its widespread application. In this work, we present a novel sulfide solid-state electrolyte, Li3.04P0.96Zn0.04S3.92F0.08, prepared through a solid-phase reaction, and explore its usage in all-solid-state lithium sulfur batteries (ASSLSBs). The findings reveal that the Zn, F co-doped solid-state electrolyte exhibits an ionic conductivity of 1.23 × 10-3 S cm-1 and a low activation energy (Ea) of 9.8 kJ mol-1 at room temperature, illustrating the aliovalent co-doping's facilitation of Li-ion migration. Furthermore, benefiting from the formation of a LiF-rich interfacial layer between the electrolyte and the Li metal anode, the Li/Li3.04P0.96Zn0.04S3.92F0.08/Li symmetrical cell exhibits critical current densities (CCDs) of up to 1 mA cm-2 and maintains excellent cycling stability. Finally, the assembled ASSLSBs exhibit an initial discharge capacity of 1295.7 mAh g-1 at a rate of 0.05 C and at room temperature. The cell maintains a capacity retention of 70.5% for more than 600 cycles at a high rate of 2 C, representing a substantial improvement compared to the cell with Li3PS4. This work provides a new idea for the design of solid-state electrolytes and ASSLSBs.

17.
RSC Chem Biol ; 5(4): 335-343, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38576724

RESUMO

N 6-Methyladenosine (m6A) is the most prevalent mRNA modification and is required for gene regulation in eukaryotes. ALKBH5, an m6A demethylase, is a promising target, particularly for anticancer drug discovery. However, the development of selective and potent inhibitors of ALKBH5 rather than FTO remains challenging. Herein, we used a targeted covalent inhibition strategy and identified a covalent inhibitor, TD19, which selectively inhibits ALKBH5 compared with FTO demethylase in protein-based and tumor cell-based assays. TD19 irreversibly modifies the residues C100 and C267, preventing ALKBH5 from binding to m6A-containing RNA. Moreover, TD19 displays good anticancer efficacy in acute myeloid leukemia and glioblastoma multiforme cell lines. Thus, the ALKBH5 inhibitor developed in this study, which selectively targets ALKBH5 compared with FTO, can potentially be used as a probe for investigating the biological functions of RNA demethylase and as a lead compound in anticancer research.

18.
J Clin Nurs ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558421

RESUMO

BACKGROUND: Fall prevention is crucial for older adults. Enhanced fall risk perception can encourage older adults to participate in fall prevention programs. However, there is still no unified definition of the concept of fall risk perception. OBJECTIVE: To explore the concept of fall risk perception in older adults. DESIGN: A concept analysis. DATA SOURCES: The literature was searched using online databases including PubMed, Cochrane Library, Embase, CINAHL Complete, PsycINFO, Web of Science, China National Knowledge Infrastructure, WangFang and SinoMed. Searches were also conducted in Chinese and English dictionaries. The literature dates from the establishment of the database to April 2023. METHODS: The methods of Walker and Avant were used to identify antecedents, attributes and consequences of the concept of "fall risk perception" in older adults. RESULTS: Eighteen publications were included eventually. The attributes were identified as: (1) dynamic change, with features of continuum and stage; (2) whether falls are taken seriously; (3) a self-assessment of the fall probability, which is driven by individual independence; and (4) involves multiple complex emotional responses. The antecedents were identified as: (1) demographic and disease factors; (2) psychological factors and (3) environmental factors. The consequences were identified as: (1) risk-taking behaviour; (2) risk compensation behaviour; (3) risk transfer behaviour; and (4) emotions. CONCLUSION: A theoretical definition of fall risk perception was identified. A conceptual model was developed to demonstrate the theoretical relationships between antecedents, attributes and consequences. This is helpful for the development of relevant theories and the formulation of fall prevention measures based on fall risk perception as the intervention target.

19.
Diabetes Obes Metab ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558498

RESUMO

AIM: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non-high-density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. RESULTS: During a median follow-up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10-point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47-0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53-0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. CONCLUSION: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38581311

RESUMO

Context: An acute myocardial infarction (AMI) is a serious, life-threatening disease. Practitioners of traditional Chinese medicine (TCM) commonly use the Tongxinluo (TXL) capsule, a Chinese patent medicine, to treat AMIs. The benefits of TXL capsules for AMIs remain unknown. Objective: The systematic review and meta-analysis intended to investigate the effects of TXL capsules for AMI patients. Design: The research team conducted a comprehensive literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023. The team used the search terms acute myocardial infarction, myocardial infarction, TXL Capsule Therapy, and TXL Capsule. The team also performed a meta-analysis and evaluated the features of the included studies using the Cochrane Collaboration tool for assessing the risk of bias. Setting: The study took place at the Second Affiliated Hospital at Heilongjiang University of Chinese Medicine in Harbin City, Heilongjiang Province, China. Outcome Measures: The research team: (1) evaluated the studies' quality using the Cochrane Collaboration tool for assessing the risk of bias; (2) analyzed the curative effect of the TXL capsules for AMI; (3) explored the effects of the TXL capsules on left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), and left ventricular ejection fraction (LVEF); and (4) explored the effects of the TXL capsules on creatine kinase isoenzyme (CK-MB) peak time, CK-MB peak value, and cardiac index. Results: The literature search found ten studies. Compared with routine treatment alone, a combination of routine treatment and TXL capsules significantly improved the curative effects (odds ratio = 3.48; 95% CI: 2.34, 5.17; P < .00001) Compared with the control groups, the TXL capsule groups' LVESD and LVEF were significantly lower, with MD=-0.23; 95% CI: -0.37, -0.10; and P = .0007 and MD=-0.43; 95% CI: -0.61, -0.25; and P < .00001, respectively, and its LVEDD was significantly higher, with MD=5.27; 95% CI: 4.33, 6.21; and P < .00001. For myocardial enzymes, the TXL capsule groups' creatine kinase isoenzyme (CK-MB) peak values and cardiac indexes were significantly lower than those of the control groups, with MD=-53.11; 95% CI: -55.26, -50.97; and P < .00001 and MD=-1.87; 95% CI: -2.03, -1.70; and P < .00001, respectively. Conclusions: The meta-analysis showed that the TXL capsule can bring greater therapeutic benefits for AMI patients in combination with routine treatment. The current study was a meta-analysis, and the field needs more well-designed studies.

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