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1.
J Hazard Mater ; 477: 135408, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39096641

RESUMEN

This study investigates the spatial and temporal dynamics of air quality in Shandong Province from 2016 to 2022. The Air Quality Index (AQI) showed a seasonal pattern, with higher values in winter due to temperature inversions and heating emissions, and lower values in summer aided by favorable dispersion conditions. The AQI improved significantly, decreasing by approximately 39.4 % from 6.44 to 3.90. Coastal cities exhibited better air quality than inland areas, influenced by industrial activities and geographical features. For instance, Zibo's geography restricts pollutant dispersion, resulting in poor air quality. CO levels remained stable, while O3 increased seasonally due to photochemical reactions in summer, with correlation coefficients indicating a strong positive correlation with temperature (r = 0.65). Winter saw elevated NO2 levels linked to heating and vehicular emissions, with an observed increase in correlation with AQI (r = 0.78). PM2.5 and PM10 concentrations were higher in colder months due to heating and atmospheric dust, showing a significant decrease of 45 % and 40 %, respectively, over the study period. Predictive modeling forecasts continued air quality improvements, contingent on sustained policy enforcement and technological advancements. This approach provides a comprehensive framework for future air quality management and improvement.

2.
Eur Urol ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39155193

RESUMEN

BACKGROUND AND OBJECTIVE: Predicting response to therapy for each patient's tumor is critical to improving long-term outcomes for muscle-invasive bladder cancer. This study aims to establish ex vivo bladder cancer patient-derived organoid (PDO) models that are representative of patients' tumors and determine the potential efficacy of standard of care and curated experimental therapies. METHODS: Tumor material was collected prospectively from consented bladder cancer patients to generate short-term PDO models, which were screened against a panel of clinically relevant drugs in ex vivo three-dimensional culture. Multiomic profiling was utilized to validate the PDO models, establish the molecular characteristics of each tumor, and identify potential biomarkers of drug response. Gene expression (GEX) patterns between paired primary tissue and PDO samples were assessed using Spearman's rank correlation coefficients. Molecular correlates of therapy response were identified using Pearson correlation coefficients and Kruskal-Wallis tests with Dunn's post hoc pairwise comparison testing. KEY FINDINGS AND LIMITATIONS: A total of 106 tumors were collected from 97 patients, with 65 samples yielding sufficient material for complete multiomic molecular characterization and PDO screening with six to 32 drugs/combinations. Short-term PDOs faithfully represent the tumor molecular characteristics, maintain diverse cell types, and avoid shifts in GEX-based subtyping that accompany long-term PDO cultures. Utilizing an integrative approach, novel correlations between ex vivo drug responses and genomic alterations, GEX, and protein expression were identified, including a multiomic signature of gemcitabine response. The positive predictive value of ex vivo drug responses and the novel multiomic gemcitabine response signature need to be validated in future studies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Short-term PDO cultures retain the molecular characteristics of tumor tissue and avoid shifts in expression-based subtyping that have plagued long-term cultures. Integration of multiomic profiling and ex vivo drug screening data identifies potential predictive biomarkers, including a novel signature of gemcitabine response. PATIENT SUMMARY: Better models are needed to predict patient response to therapy in bladder cancer. We developed a platform that uses short-term culture to best mimic each patient's tumor and assess potential sensitivity to therapeutics.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39138982

RESUMEN

Addressing the conflict between achieving elevated mechanical stretchability and environmental adaptability is significant to a breakthrough in the practical application of flexible wearable materials. Therefore, inspired by the perceptive and protective properties of human skin, flexible wearable electronic skins (E-skins) based on deep eutectic solvent (DES) liquid and multiresponse eutectogel have been widely considered to be a promising platform for building a flexible wearable management system to achieve the purpose of "one stone, two birds". In this work, a multifunctional E-skin was designed based on an ultrastretchable, transparent, self-adhesive, and environmentally tolerant eutectogel by first incorporating cationized modified chitin nanocrystals into a covalently cross-linked polymer network comprised of the skeleton formed by a PAA polymerization network structure serving as a stretchable matrix and filled with DESs (ChCl:EG). The obtained eutectogel exhibits superhigh stretchability (up to 6707%), high toughness (17.7 MJ/m3), mechanical strength (0.48 MPa), self-adhesive, and high transparency (91.2%). Simultaneously, the multisignal sensor based on the above comprehensive properties and thermosensitive capacity exhibits a wide monitoring range, high strain/compression/temperature sensitivity, and good reproducibility. Remarkably, the sensor could be attached to rat hearts without glue or stickers for long-term monitoring of high-quality in vivo heartbeat signals. In this way, it is believed that the designed E-skin system based on eutectogel has great potential to serve as a promising platform for the next generation of flexible multisignal monitoring integrated wearable management systems.

4.
Food Funct ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39114922

RESUMEN

Probiotics can alleviate alcoholic liver disease. However, whether inactive counterparts can produce similar outcomes requires further investigation. We investigated the effects of viable (V) and dead (D) Lactobacillus paracasei CCFM1120 on alcohol-induced ALD mice. The results showed that CCFM1120V and D ameliorated the disease symptoms and intestinal injury. Specifically, these interventions strengthened the intestinal barrier, as evidenced by the increased expression of ZO-1 (zonula occludens 1), occludin, and claudin-1 in the colon and the restored ileal microstructure, including the villi and crypts. In addition, they enhanced the antioxidant capacity of the liver by reducing the production of malondialdehyde and increasing the levels of glutathione and superoxide dismutase. The activation of Nrf2 and HO-1 may be responsible for recovering the antioxidant capacity. Interventions can decrease mouse TNF-α, IL-6 and IL-1ß content in serum, probably through the TLR4/MyD88/NF-κB pathway. Furthermore, they possess the ability to restore the quantities of bacteria responsible for producing butyric acid, such as Lactobacillus, Blautia, Bifidobacterium, Ruminococcaceae, Faecalibaculum and Lachnospiraceae. Taken together, CCFM1120V and D apparently can modify the composition of the gut microbiota, foster the gastrointestinal equilibrium, fortify the intestinal barrier, augment the antioxidant capacity of the liver, and effectively shield it from ethanol-induced injury.

5.
J Colloid Interface Sci ; 677(Pt A): 665-676, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39116564

RESUMEN

The microstructure of the electrocatalyst plays a critical role in the reaction efficiency and stability during electrochemical water splitting. Designing an efficient and stable electrocatalyst, further clarifying the synthesis mechanism, is still an important problem to be solved urgently. Inspired by the copper pyrometallurgy theory, an exceptionally active NiMo/CF(N) electrode, consisting of an ant-nest-like copper foam substrate (defined as CF(N)) and deposited NiMo layer, was fabricated for the alkaline hydrogen evolution reaction (HER). Our findings expounded the structure construction mechanism and highlighted the pivotal role of the spatial occupancy of sulfur atoms in the construction of the ant-nest-like structure. The NiMo/CF(N) composite, characterized by channels with a 2 µm diameter, showcases strong electronic interactions, increased catalytic active sites, enhanced electron/ion transport, and facilitated gas release during HER. Remarkably, NiMo/CF(N) demonstrates ultralow overpotentials of 21 mV to deliver a current density of 10 mA cm-2 in 1 M KOH. This electrode also exhibits outstanding durability, maintaining a current density of 200 mA cm-2 for 110 h, attributed to the chemical and structural integrity of its catalytic surface and the excellent mechanical properties of the electrode. This work advances the fundamental understanding of constructing micro/nano-structured electrocatalysts for highly efficient water splitting.

7.
Biometals ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023790

RESUMEN

Selenium (Se) is a beneficial trace element for plants, while zinc (Zn) is a vital micronutrient. Bletilla striata (Thunb.) Reichb. F. is widely recognized as a medicinal herb. In this study, Se and Zn were introduced to determine the medicinal properties of B. striata. The plant's biomass, polysaccharides, Se and Zn contents, and the antioxidant properties of polysaccharide solutions were all examined. A notable increase in polysaccharide synthesis in B. striata tubers was observed following the application of 0.2 kg ha-1 of Se, and 1.0 kg ha-1 of Zn, either individually or in combination. Se and Zn content in polysaccharides were 3.33 to 3.77 mg kg-1 and 82.82 to 121.78 mg kg-1, at 1.0 kg ha-1 Se and 10.0 kg ha-1 Zn treatments, respectively. These values were 2.1-3.1 times and 1.8-2.8 times higher than those observed in control samples. Polysaccharide antioxidation has resulted in an increase in antioxidant activity as the concentration of polysaccharide solutions increased. The largest scavenging of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals and the most excellent reducing power of the polysaccharide solutions were observed when a mixture of Se and Zn was applied at a rate of 1.0 kg ha-1 and 10.0 kg ha-1. The individual application of Se at 1.0 kg ha-1 and Zn at 10.0 kg ha-1 also resulted in significant DPPH radicals scavenging and reduced power. These data suggested that Se-Zn enriched B. striata is a new source of Se and Zn supplementation and an antioxidant resource.

8.
Sci Rep ; 14(1): 16536, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39019970

RESUMEN

This paper propose a wide gain single-bridge interleaved three-level LLC resonant converter with current sharing capability. This novel converter offers numerous advantages, including low cost, low current ripple, reduced voltage and current stress, widely gain range, high efficiency, good current sharing capability and versatile application scalability. Utilizing the three-level inverter + full-wave rectifier LLC converter as a representative case, the paper conducts an in-depth analysis and research on the proposed method. Finality, a 600 W experimental prototype was constructed and tested. Experimental results reveal that the proposed converter exhibits lower current ripple and a broader gain range. Moreover, the converter shows good current sharing capability (with a resonant element tolerance of 10%, the current error between the two phases does not exceed 12%) and high efficiency (peaking at 95.8%).

9.
Biotechnol J ; 19(7): e2400286, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39014927

RESUMEN

22(R)-hydroxycholesterol (22(R)-HCHO) is a crucial precursor of steroids biosynthesis with various biological functions. However, the production of 22(R)-HCHO is expensive and unsustainable due to chemical synthesis and extraction from plants or animals. This study aimed to construct a microbial cell factory to efficiently produce 22(R)-HCHO through systems metabolic engineering. First, we tested 7-dehydrocholesterol reductase (Dhcr7s) and cholesterol C22-hydroxylases from different sources in Saccharomyces cerevisiae, and the titer of 22(R)-HCHO reached 128.30 mg L-1 in the engineered strain expressing Dhcr7 from Columba livia (ClDhcr7) and cholesterol 22-hydroxylase from Veratrum californicum (VcCyp90b27). Subsequently, the 22(R)-HCHO titer was significantly increased to 427.78 mg L-1 by optimizing the critical genes involved in 22(R)-HCHO biosynthesis. Furthermore, hybrid diploids were constructed to balance cell growth and 22(R)-HCHO production and to improve stress tolerance. Finally, the engineered strain produced 2.03 g L-1 of 22(R)-HCHO in a 5-L fermenter, representing the highest 22(R)-HCHO titer reported to date in engineered microbial cell factories. The results of this study provide a foundation for further applications of 22(R)-HCHO in various industrially valuable steroids.


Asunto(s)
Hidroxicolesteroles , Ingeniería Metabólica , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ingeniería Metabólica/métodos , Hidroxicolesteroles/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Fermentación
10.
PeerJ ; 12: e17747, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39035164

RESUMEN

Trichosanthes kirilowii (T. kirilowii) is a valuable plant used for both medicinal and edible purposes. It belongs to the Cucurbitaceae family. However, its phylogenetic position and relatives have been difficult to accurately determine due to the lack of mitochondrial genomic information. This limitation has been an obstacle to the potential applications of T. kirilowii in various fields. To address this issue, Illumina and Nanopore HiFi sequencing were used to assemble the mitogenome of T. kirilowii into two circular molecules with sizes of 245,700 bp and 107,049 bp, forming a unique multi-branched structure. The mitogenome contains 61 genes, including 38 protein-coding genes (PCGs), 20 tRNAs, and three rRNAs. Within the 38 PCGs of the T. kirilowii mitochondrial genome, 518 potential RNA editing sites were identified. The study also revealed the presence of 15 homologous fragments that span both the chloroplast and mitochondrial genomes. The phylogenetic analysis strongly supports that T. kirilowii belongs to the Cucurbitaceae family and is closely related to Luffa. Collinearity analysis of five Cucurbitaceae mitogenomes shows a high degree of structural variability. Interestingly, four genes, namely atp1, ccmFC, ccmFN, and matR, played significant roles in the evolution of T. kirilowii through selection pressure analysis. The comparative analysis of the T. kirilowii mitogenome not only sheds light on its functional and structural features but also provides essential information for genetic studies of the genus of Cucurbitaceae.


Asunto(s)
Genoma Mitocondrial , Filogenia , Plantas Medicinales , Trichosanthes , Trichosanthes/genética , Trichosanthes/química , Genoma Mitocondrial/genética , Plantas Medicinales/genética , Evolución Molecular , Medicina Tradicional China
11.
Transl Oncol ; 48: 102004, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39053344

RESUMEN

Circular RNAs (circRNAs) have been reported to be associated with the malignant phenotypes of cancer. However, the role and underlying mechanism of hsa_Circ_0008035 in colorectal cancer (CRC) remains unclear. In this study, we elucidated the pivotal role of hsa_circ_0008035 in gastric cancer progression and immune evasion. Elevated hsa_circ_0008035 levels in gastric cancer patient serum correlated positively with disease advancement, including tumor stages and lymph node metastasis. Functional analyses revealed a negative association between hsa_circ_0008035 and CD8+ T cell number and function. Mechanistically, hsa_circ_0008035 encoded the novel protein EXT1-219aa, suppressing EXT1 phosphorylation and expression. Additionally, hsa_circ_0008035 regulated pyruvate metabolism by influencing the nucleus localization of PKM2. The identified EXT1/PKM2 axis further underscored the intricate regulatory mechanisms orchestrated by hsa_circ_0008035 in gastric cancer, offering potential diagnostic and therapeutic implications in the ongoing pursuit of targeted therapies for gastric cancer patients.

12.
Water Res ; 262: 122085, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39042968

RESUMEN

Sustainable urban water management is crucial for meeting the growing demands of urban populations. This study presents a novel approach that combines time series clustering, seasonal analysis, and entropy analysis to uncover residential water consumption patterns and their drivers. Using a three-year dataset from the SmartH2o project, encompassing 374 households, we identify nine distinct water consumption patterns through time series clustering, leveraging Dynamic Time Warping (DTW) as the optimal similarity measure. Multiple linear regression reveals key household characteristics influencing water usage behaviors, such as the number of bathrooms and appliance efficiency ratings. Seasonal analysis uncovers temporal dynamics, highlighting shifts towards lower consumption during summer months and increased variability in transitional seasons. Entropy analysis quantifies the diversity and complexity of water consumption at both cluster and household levels, informing targeted interventions. This comprehensive, granular approach enables the development of personalized water conservation strategies and policies, empowering water utilities to optimize resource management and contribute to sustainable urban water practices.


Asunto(s)
Entropía , Análisis por Conglomerados , Abastecimiento de Agua , Humanos , Población Urbana , Estaciones del Año , Composición Familiar , Conservación de los Recursos Hídricos , Ciudades
13.
Plants (Basel) ; 13(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38999563

RESUMEN

Molecular hydrogen (H2) is crucial for agricultural microbial systems. However, the mechanisms underlying its influence on crop yields is yet to be fully elucidated. This study observed that H2-based irrigation significantly increased strawberry (Fragaria × ananassa Duch.) yield with/without nutrient fertilization. The reduction in soil available nitrogen (N), phosphorus (P), potassium (K), and organic matter was consistent with the increased expression levels of N/P/K-absorption-related genes in root tissues at the fruiting stage. Metagenomics profiling showed the alterations in rhizosphere microbial community composition achieved by H2, particularly under the conditions without fertilizers. These included the enrichment of plant-growth-promoting rhizobacteria, such as Burkholderia, Pseudomonas, and Cupriavidus genera. Rhizobacteria with the capability to oxidize H2 (group 2a [NiFe] hydrogenase) were also enriched. Consistently, genes related to soil carbon (C) fixation (i.e., rbcL, porD, frdAB, etc.), dissimilar nitrate reduction (i.e., napAB and nrfAH), and P solublization, mineralization, and transportation (i.e., ppx-gppA, appA, and ugpABCE) exhibited higher abundance. Contrary tendencies were observed in the soil C degradation and N denitrification genes. Together, these results clearly indicate that microbe-mediated soil C, N, and P cycles might be functionally altered by H2, thus increasing plant nutrient uptake capacity and horticultural crop yield.

14.
Sci Total Environ ; 946: 174069, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38908586

RESUMEN

BACKGROUND: Rapid kidney function decline (RKFD) is a main clinical feature of early chronic kidney disease (CKD) in type 2 diabetes (T2D). Environmental and genetic factors influencing RKFD remain inadequately elucidated. OBJECTIVES: This study aimed to examine the associations of metals with RKFD among T2D and to further investigate the effect of metal mixtures on RKFD with the modifying effect of genetic susceptibility. METHODS: This study included 2209 people with T2D (1942 had genotyping data) free of CKD at baseline from the Dongfeng-Tongji cohort. We used inductively coupled plasma-mass spectrometry (ICP-MS) to measure 23 metals in baseline plasma. Using elastic net (ENET), multivariate logistic regression, and Bayesian kernel machine regression (BKMR) model, we examined independent associations of multiple metals with RKFD. We calculated the environmental risk score (ERS) to assess the effects of metal mixtures on RKFD and the genetic risk score (GRS) to assess genetic susceptibility. RKFD was defined as estimated glomerular filtration rate (eGFR) loss > 3 mL/min/1.73 m2/year. RESULTS: During a median of 9.8 years follow-up, 262 participants developed RKFD. Aluminum, vanadium, zinc, selenium, rubidium, tin, barium, and tungsten were screened from ENET. In multivariate logistic models, vanadium, selenium, and tungsten were negatively associated with RKFD, while zinc, tin, and rubidium were positively associated. The BKMR showed a nonlinear association of vanadium and rubidium with RKFD and interactions between metals (barium­vanadium, barium­rubidium). The ERS was positive associated with RKFD (per SD increase in ERS, OR = 1.94, 95% CI: 1.66, 2.27). No significant interaction between ERS and GRS was observed on RKFD, however, participants in the highest ERS and GRS group had the highest RKFD risk. CONCLUSION: Vanadium and rubidium were associated with RKFD in T2D. Metal mixtures was associated with an increased risk of RKFD in T2D, particularly in those at high genetic risk.


Asunto(s)
Diabetes Mellitus Tipo 2 , Predisposición Genética a la Enfermedad , Metales , Diabetes Mellitus Tipo 2/genética , Humanos , Persona de Mediana Edad , Masculino , Femenino , Metales/sangre , Insuficiencia Renal Crónica , Factores de Riesgo , Anciano , Tasa de Filtración Glomerular , China , Exposición a Riesgos Ambientales/estadística & datos numéricos
15.
Anal Chim Acta ; 1315: 342797, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38879209

RESUMEN

BACKGROUND: Harmful algal blooms (HABs), caused by the rapid proliferation or aggregation of microorganisms, are catastrophic for the environment. The Prymnesium parvum is a haptophyte algal species that is found worldwide and is responsible for extensive blooms and death of larval amphibians and bivalves, causing serious negative impacts on the ecological environment. For the prevention and management of environmental pollution, it is crucial to explore and develop early detection strategies for HABs on-site using simple methods. The major challenge related to early detection is the accurate and sensitive detection of algae present in low abundance. RESULTS: Herein, recombinase polymerase amplification (RPA) was combined with clustered regularly interspaced short palindromic repeats and Cas12a protein (CRISPR-LbaCas12a) systems, and the lateral flow dipstick (LFD) was used for the first time for early detection of P. parvum. The internal transcribed spacer (ITS) of P. parvum was selected as the target sequence, and the concentration of single-strand DNA reporters, buffer liquid system, reaction time, and amount of gold particles were optimized. The RPA-CRISPR-LbaCas12a-LFD approach demonstrated highly specificity during experimental testing, with no cross-reaction against different microalgae used as controls. In addition, the lowest detection limit was 10,000 times better than the lowest detection limit of the standalone RPA approach. The feasibility and robustness of this approach were further verified by using the different environmental samples. It also observed that P. parvum are widely distributed in Chinese Sea, but the cell density of P. parvum is relatively low (<0.1 cells/mL). SIGNIFICANCE: The developed approach has an excellent specificity and offers 10,000 times better sensitivity than the standalone RPA approach. These advantages make this approach suitable for early warning detection and prevention of HAB events in environmental water. Also, the outcomes of this study could promote a shift from traditional laboratory-based detection to on-site monitoring, facilitating early warning against HABs.


Asunto(s)
Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico/métodos , Recombinasas/metabolismo , Floraciones de Algas Nocivas , Oro/química , Proteínas Asociadas a CRISPR/genética , Endodesoxirribonucleasas/genética , Proteínas Bacterianas/genética
16.
Cell Death Dis ; 15(6): 450, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926347

RESUMEN

Pathological cardiac hypertrophy is one of the major risk factors of heart failure and other cardiovascular diseases. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. Here, we identified the first evidence that TNFAIP3 interacting protein 3 (TNIP3) was a negative regulator of pathological cardiac hypertrophy. We observed a significant upregulation of TNIP3 in mouse hearts subjected to transverse aortic constriction (TAC) surgery and in primary neonatal rat cardiomyocytes stimulated by phenylephrine (PE). In Tnip3-deficient mice, cardiac hypertrophy was aggravated after TAC surgery. Conversely, cardiac-specific Tnip3 transgenic (TG) mice showed a notable reversal of the same phenotype. Accordingly, TNIP3 alleviated PE-induced cardiomyocyte enlargement in vitro. Mechanistically, RNA-sequencing and interactome analysis were combined to identify the signal transducer and activator of transcription 1 (STAT1) as a potential target to clarify the molecular mechanism of TNIP3 in pathological cardiac hypertrophy. Via immunoprecipitation and Glutathione S-transferase assay, we found that TNIP3 could interact with STAT1 directly and suppress its degradation by suppressing K48-type ubiquitination in response to hypertrophic stimulation. Remarkably, preservation effect of TNIP3 on cardiac hypertrophy was blocked by STAT1 inhibitor Fludaradbine or STAT1 knockdown. Our study found that TNIP3 serves as a novel suppressor of pathological cardiac hypertrophy by promoting STAT1 stability, which suggests that TNIP3 could be a promising therapeutic target of pathological cardiac hypertrophy and heart failure.


Asunto(s)
Cardiomegalia , Miocitos Cardíacos , Factor de Transcripción STAT1 , Animales , Humanos , Masculino , Ratones , Ratas , Cardiomegalia/metabolismo , Cardiomegalia/patología , Cardiomegalia/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/efectos de los fármacos , Fenilefrina/farmacología , Estabilidad Proteica/efectos de los fármacos , Factor de Transcripción STAT1/metabolismo , Ubiquitinación , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo
17.
NPJ Breast Cancer ; 10(1): 43, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858374

RESUMEN

Fatty acid synthesis (FAS) has been shown to play a key role in the survival of brain-metastatic (BM) breast cancer. We demonstrate that the fatty acid synthase inhibitor TVB-2640 synergizes with the topoisomerase inhibitor SN-38 in triple-negative breast cancer (TNBC) BM cell lines, upregulates FAS and downregulates cell cycle progression gene expression, and slows the motility of TNBC BM cell lines. The combination of SN-38 and TVB-2640 warrants further consideration as a potential therapeutic option in TNBC BMs.

18.
PLoS One ; 19(6): e0304108, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38857294

RESUMEN

To stimulate the regional tourism economy, local governments often seek to increase the number of 5A-rated tourist attractions. However, there have been few analyses examining the economic benefits and influence mechanisms of 5A-rated attraction selection. Using the quality signaling theory and data from 282 prefecture-level cities spanning 2002 to 2019, this study examines the impact of 5A-rated attraction selection on the local tourism economy with the difference-in-differences method. This study's results demonstrate that the selection of 5A-rated attractions significantly contributes to the growth of the local tourism economy. The robustness test results confirm the validity of this conclusion. A mechanism analysis reveals that 5A-rated attractions positively impact the tourism economy via investments in infrastructure, popularization of informatization, and increased external openness. Furthermore, the study suggests that the effect of 5A-rated attractions is more pronounced in economically underdeveloped regions and low-level cities. The results of this study contribute to the sustainable development of China's tourism economy and may provide guidance for the establishment of tourism evaluation systems in other international locations in order to foster economic growth.


Asunto(s)
Turismo , China , Humanos , Ciudades , Desarrollo Económico , Desarrollo Sostenible/economía , Viaje/economía
19.
Imeta ; 3(2): e182, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38882487

RESUMEN

The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.

20.
BMC Neurol ; 24(1): 207, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886670

RESUMEN

OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.


Asunto(s)
Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/terapia , Anciano , Procedimientos Endovasculares/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Inutilidad Médica , Trombectomía/métodos , Estudios Prospectivos , Pronóstico
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