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1.
J Phys Chem Lett ; 15(28): 7147-7153, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38959446

RESUMEN

The effect of ionic association on the structure and property of confined electrolytes is investigated using the classical density functional theory. We find that ionic association strongly affects the ion distribution, surface force, and screening behavior of confined electrolytes. The decay length ξ, which can describe the screening effect of high-concentration electrolytes, satisfies a scaling relationship ξ/λD ∼ (σ/λD)n, with λD being the Debye length and σ representing the ion diameter. We find that n = 1.5 in the nonassociation model, which is contributed by the charge correlation, but n = 3 in the association model, which is contributed by the density correlation. The ion association changes the concentration-dependent characteristics of the screening length by promoting the shift of the decay behavior from the charge-dominated regime to the density-dominated regime. Our result reveals the importance of ion association for electrolyte structure and screening behaviors.

2.
Angew Chem Int Ed Engl ; : e202412103, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979667

RESUMEN

7-Aminoindoles are important synthetic intermediates to a broad range of bioactive molecules. Transition metal-catalyzed directed C-H amination is among the most straightforward route for their synthesis, whereas methods that could directly incorporate an NH2 group in a highly selective manner remains elusive. Moreover, there is still high demand for the development of earth-abundant metal catalysis for such attractive reactivity. We present here the first C-7 selective NH2 amination of indoles through a directed homolytic aromatic substitution (HAS) with iron-aminyl radical. The reaction exhibits broad substrate scope, tolerates variety of functional groups, and is readily scalable with catalyst loading down to 0.1 mol% and turnover number (TON) up to 4500.

3.
Mar Genomics ; 76: 101112, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39009493

RESUMEN

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur molecule in marine environments with important roles in stress tolerance, global carbon and sulfur cycling, and chemotaxis. It is the main precursor of the climate active gas dimethyl sulfide (DMS), which is the greatest natural source of bio­sulfur transferred from ocean to atmosphere. Alteromonas sp. M12, a Gram-negative and aerobic bacterium, was isolated from the seawater samples collected from the Mariana Trench at the depth of 2500 m. Here, we report the complete genome sequence of strain M12 and its genomic characteristics to import and utilize DMSP. The genome of strain M12 contains one circular chromosome (5,012,782 bp) with the GC content of 40.88%. Alteromonas sp. M12 can grow with DMSP as a sole carbon source, and produced DMS with DMSP as a precursor. Genomic analysis showed that strain M12 contained a set of genes involved in the downstream steps of DMSP cleavage, but no known genes encoding DMSP transporters or DMSP lyases. The results indicated that this strain contained novel DMSP transport and cleavage genes in its genome which warrants further investigation. The import of DMSP into cells may be a strategy of strain M12 to adapt the hydrostatic pressure environment in the Mariana Trench, as DMSP can be used as a hydrostatic pressure protectant. This study sheds light on the catabolism of DMSP by deep-sea bacteria.


Asunto(s)
Alteromonas , Genoma Bacteriano , Compuestos de Sulfonio , Compuestos de Sulfonio/metabolismo , Alteromonas/genética , Agua de Mar/microbiología , Sulfuros
4.
Opt Lett ; 49(11): 2886-2889, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824284

RESUMEN

Light field (LF) imaging has gained significant attention in the field of computational imaging due to its unique capability to capture both spatial and angular information of a scene. In recent years, super-resolution (SR) techniques based on deep learning have shown considerable advantages in enhancing LF image resolution. However, the inherent challenges of obtaining rich structural information and reconstructing complex texture details persist, particularly in scenarios where spatial and angular information are intricately interwoven. This Letter introduces a novel, to the best of our knowledge, approach for Disentangling LF Image SR Network (DLISN) by leveraging the synergy of dual learning and Fourier channel attention (FCA) mechanisms. Dual learning strategies are employed to enhance reconstruction results, addressing limitations in model generalization caused by the difficulty in acquiring paired datasets in real-world LF scenarios. The integration of FCA facilitates the extraction of high-frequency information associated with different structures, contributing to improved spatial resolution. Experimental results consistently demonstrate superior performance in enhancing the resolution of LF images.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38864839

RESUMEN

A Gram-stain-positive, strictly anaerobic, endospore-forming and rod-shaped (0.6-0.8×2.7-13.1 µm) bacterium, designated as 5 N-1T, was isolated from a yellow water sample collected from the manufacturing process of Nongxiangxing baijiu in the Yibin region of Sichuan, PR China. Growth occurred at 15-40 °C (optimum growth at 37 °C), at pH 6.0-9.0 (optimum growth at pH 7.0) and in NaCl concentrations of 0-1 % (w/v) and ethanol concentrations of 0-2 % (v/v). The major fatty acids in strain 5 N-1T were C16 : 0, C18 : 0 and C14 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids and one unidentified lipid. Phylogenetic analysis of its 16S rRNA gene sequence indicated that strain 5 N-1T was most closely related to Clostridium weizhouense YB-6T (97.70 %) and Clostridium uliginosum DSM 12992T (97.56 %). The average nucleotide identity and digital DNA‒DNA hybridization values between strain 5 N-1T and the above two type strains were 80.89 and 80.05 % and 25.80 and 25.30 %, respectively, which were all below the species thresholds. The genome size of strain 5 N-1T was 3.5 Mbp and the DNA G+C content was 27.5 mol%. Based on the results of phenotypic and genotypic analyses, strain 5 N-1T represents a novel species of the genus Clostridium, for which the name Clostridium aquiflavi sp. nov. is proposed. The type strain is Clostridium aquiflavi 5 N-1T (=CICC 24886T=JCM 35355T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , Clostridium , ADN Bacteriano , Ácidos Grasos , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , China , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , ADN Bacteriano/genética , Clostridium/genética , Clostridium/aislamiento & purificación , Clostridium/clasificación , Microbiología del Agua , Fosfolípidos/análisis
6.
J Bone Miner Res ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896028

RESUMEN

In previous studies, we have demonstrated that stress response-induced high glucocorticoid levels could be the underlying cause of traumatic heterotopic ossification (HO), and we have developed a glucocorticoid-induced ectopic mineralization (EM) mouse model by systemic administration of a high dose of dexamethasone (DEX) to animals with muscle injury induced by cardiotoxin injection. In this model, dystrophic calcification (DC) developed into HO in a cell autonomous manner. However, it is not clear how DC is formed after DEX treatment. Therefore, in this study, we aimed to explore how glucocorticoids initiate muscle EM at a cellular and molecular level. We showed that DEX treatment inhibited inflammatory cell infiltration into injured muscle but inflammatory cytokine production in the muscle was significantly increased, suggesting that other non-inflammatory muscle cell types may regulate the inflammatory response and the muscle repair process. Accompanying this phenotype, transforming growth factor ß1 (TGF-ß1) expression in fibro-adipogenic progenitors (FAPs) was greatly down-regulated. Since TGF-ß1 is a strong immune suppressor and FAP's regulatory role has a large impact on muscle repair, we hypothesized that down-regulation of TGF-ß1 in FAPs after DEX treatment resulted in this hyperinflammatory state and subsequent failed muscle repair and EM formation. To test our hypothesis, we utilized a transgenic mouse model to specifically knock out Tgfb1 gene in PDGFRα positive FAPs to investigate if the transgenic mice could recapitulate the phenotype that was induced by DEX treatment. Our results showed that the transgenic mice completely phenocopied this hyperinflammatory state and spontaneously developed EM following muscle injury. On the contrary, therapeutics that enhanced TGF-ß1 signaling in FAPs inhibited the inflammatory response and attenuated muscle EM. In summary, these results indicate that FAPs-derived TGF-ß1 is a key molecule in regulating muscle inflammatory response and subsequent EM, and that glucocorticoids exert their effect via down-regulating TGF-ß1 in FAPs.


Heterotopic ossification (HO) is abnormal bone formation in soft tissue. Glucocorticoids, which have strong anti-inflammatory properties, have usually been used as HO therapeutics. However, our findings suggest that glucocorticoids can also promote HO formation. In this study, we tried to explain the underlying reason for these seemingly contradictory observations. We showed that glucocorticoids, in addition to exerting an anti-inflammatory effect on inflammatory cells, can also target another type of muscle cell to exert a pro-inflammatory effect. These cells are called fibro-adipogenic progenitors (FAPs), and we demonstrated that FAPs played a master regulatory role in the muscle inflammatory response by modulating the expression of transforming growth factor ß1 (TGF-ß1), a well-known immune suppressor. In summary, our findings highlighted the importance of FAP TGF-ß1 levels in affecting the progression and regression of muscle HO, and provided new treatment options for HO based on their ability to elevate TGF-ß1 levels in FAPs.

7.
Molecules ; 29(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38893354

RESUMEN

Metal halide perovskites have attracted considerable attention as novel optoelectronic materials for their excellent optical and electrical properties. Inorganic perovskites (CsPbX3, X = Cl, Br, I) are now viable alternative candidates for third-generation photovoltaic technology because of their high photoelectric conversion efficiency, high carrier mobility, good defect tolerance, simple preparation method and many other advantages. However, the toxicity of lead is problematic for practical implementation. Thus, the fabrication of lead-free perovskite materials and devices has been actively conducted. In this work, the energy band and photoelectric properties of inorganic perovskites CsBX3 (B = Pb, Sn, Ge, X = Cl, Br, I) have been investigated with the first principles calculation, and the possible defect energy levels and their formation energies in different components, in particular, have been systematically studied. The advantages and disadvantages of Sn and Ge as replacement elements for Pb have been demonstrated from the perspective of defects. This study provides an important basis for the study of the properties and applications of lead-free perovskites.

8.
Materials (Basel) ; 17(11)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38893958

RESUMEN

Poly(9,9-di-n-octylfluorene) (PFO) is a promising material for polymer light-emitting diodes (PLEDs) due to its advantageous properties. To enhance its electron transporting capabilities, diblock polymers were synthesized by attaching polystyrene (PSt) chains of varying lengths to one end of the PFO molecule. In a comparative study with PFO homopolymer, the diblock polymers maintained similar thermal properties, absorption spectra, and photoluminescent stability, while exhibiting slightly deeper lowest unoccupied molecular orbital (LUMO) levels and higher crystallinity. Notably, diblock polymers with shorter polystyrene blocks demonstrated higher electron mobility than the PFO homopolymer and diblock polymers with excessively long polystyrene blocks. These findings suggest that the optimal chain length of the polystyrene block is crucial for maximizing electron mobility, thus offering valuable insights for designing high-performance PLED materials.

9.
Nat Commun ; 15(1): 5221, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890329

RESUMEN

Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.


Asunto(s)
Aminoácidos , Tiorredoxinas , Aminoácidos/metabolismo , Aminoácidos/química , Humanos , Tiorredoxinas/metabolismo , Tiorredoxinas/genética , Tiorredoxinas/química , Reactivos de Enlaces Cruzados/química , Unión Proteica , Péptidos/metabolismo , Péptidos/química , Selenoproteínas/metabolismo , Selenoproteínas/genética , Selenoproteínas/química , Programas Informáticos , Proteínas/metabolismo , Proteínas/química , Células HEK293
10.
Eur J Radiol ; 177: 111543, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38905800

RESUMEN

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) in leukemia patients progresses rapidly with high mortality. Limited data are available on imaging studies in this population. The study aims to develop prediction models for 7-day and short-term mortality risk based on the non-contrast computed tomography (NCCT) image features. METHODS: The NCCT image features of ICH in 135 leukemia patients between 2007-2023 were retrospectively extracted using manual assessment and radiomics methods. After multiple imputation of missing laboratory data, univariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Random forest models were built with comprehensive evaluation and ranking of feature importance. RESULT: 135 and 129 patients were included in the studies for 7-day and short-term prognostic models, respectively. The median age of all enrolled patients was 35 years, and there were 86 male patients (63.7 %). Clinical models (validation: AUC [area under the curve] = 0.78, AUPRC [area under the precision-recall curve] = 0.73; AUC = 0.84, AUPRC = 0.86), radiomics models (validation: AUC = 0.82, AUPRC = 0.78; AUC = 0.75, AUPRC = 0.77), and the combined models (validation: AUC = 0.84, AUPRC = 0.83; AUC = 0.87, AUPRC = 0.89) predicted 7-day and short-term mortality with good predictive efficacy. Clinical decision curve analysis showed that the combined models predicted 7-day and 30-day risk of death would be more beneficial than other models. Shape features contributed significantly more than semantic features in both radiomics models and combined models (93.3 %, 52.1 %, as well as 85.2 %,37.4 %, respectively) for 7-day and 30-day mortality. CONCLUSIONS: Combined models constructed based on NCCT perform well in predicting the risk of 7-day and short-term mortality in ICH patients with leukemia. Shape features extracted by radiomics are important markers for modeling the prognosis.


Asunto(s)
Hemorragia Cerebral , Leucemia , Aprendizaje Automático , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Adulto , Tomografía Computarizada por Rayos X/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/complicaciones , Leucemia/complicaciones , Leucemia/diagnóstico por imagen , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Anciano , Adolescente
11.
J Cancer ; 15(11): 3427-3440, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817863

RESUMEN

Purpose: Platinum-based chemotherapy is effective but limited by resistance in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) can reveal tumour cell heterogeneity and subclonal differentiation. We aimed to analyze resistance mechanisms and potential targets in HGSOC using scRNA-seq. Methods: We performed 10× genomics scRNA-seq sequencing on tumour tissues from 3 platinum-sensitive and 3 platinum-resistant HGSOC patients. We analyzed cell subcluster communication networks and spatial distribution using cellchat. We performed RNA-seq analysis on TACSTD2, a representative resistance gene in the E0 subcluster, to explore its molecular mechanism. Results: Epithelial cells, characterized by distinct chemotherapy resistance traits and highest gene copy number variations, revealed a specific cisplatin-resistant cluster (E0) associated with poor prognosis. E0 exhibited malignant features related to resistance, fostering growth through communication with fibroblasts and endothelial cells. Spatially, E0 promoted fibroblasts to protect tumour cells and impede immune cells infiltration. Furthermore, TACSTD2 was identified as a representative gene of the E0 subcluster, elucidating its role in platinum resistance through the Rap1/PI3K/AKT pathway. Conclusions: Our study reveals a platinum-resistant epithelial cell subcluster E0 and its association with TACSTD2 in HGSOC, uncovers new insights and evidence for the platinum resistance mechanism, and provides new ideas and targets for the development of therapeutic strategies against TACSTD2+ epithelial cancer cells.

12.
BMC Public Health ; 24(1): 1411, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802825

RESUMEN

BACKGROUND: Preterm birth (PTB) is an important predictor of perinatal morbidity and mortality. Previous researches have reported a correlation between air pollution and an increased risk of preterm birth. However, the specific relationship between short-term and long-term exposure to carbon monoxide (CO) and preterm birth remains less explored. METHODS: A population-based study was conducted among 515,498 pregnant women in Chongqing, China, to assess short-term and long-term effects of CO on preterm and very preterm births. Generalized additive models (GAM) were applied to evaluate short-term effects, and exposure-response correlation curves were plotted after adjusting for confounding factors. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using COX proportional hazard models to estimate the long-term effect. RESULTS: The daily incidence of preterm and very preterm birth was 5.99% and 0.41%, respectively. A positive association between a 100 µg/m³ increase in CO and PTB was observed at lag 0-3 days and 12-21 days, with a maximum relative risk (RR) of 1.021(95%CI: 1.001-1.043). The exposure-response curves (lag 0 day) revealed a rapid increase in PTB due to CO. Regarding long-term exposure, positive associations were found between a 100 µg/m3 CO increase for each trimester(Model 2 for trimester 1: HR = 1.054, 95%CI: 1.048-1.060; Model 2 for trimester 2: HR = 1.066, 95%CI: 1.060-1.073; Model 2 for trimester 3: HR = 1.007, 95%CI: 1.001-1.013; Model 2 for entire pregnancy: HR = 1.080, 95%CI: 1.073-1.088) and higher HRs of very preterm birth. Multiplicative interactions between air pollution and CO on the risk of preterm and very preterm birth were detected (P- interaction<0.05). CONCLUSIONS: Our findings suggest that short-term exposure to low levels of CO may have protective effects against preterm birth, while long-term exposure to low concentrations of CO may reduce the risk of both preterm and very preterm birth. Moreover, our study indicated that very preterm birth is more susceptible to the influence of long-term exposure to CO during pregnancy, with acute CO exposure exhibiting a greater impact on preterm birth. It is imperative for pregnant women to minimize exposure to ambient air pollutants.


Asunto(s)
Contaminantes Atmosféricos , Monóxido de Carbono , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Nacimiento Prematuro/epidemiología , China/epidemiología , Monóxido de Carbono/análisis , Adulto , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Recién Nacido , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricos , Factores de Tiempo , Adulto Joven , Factores de Riesgo
13.
World J Stem Cells ; 16(4): 444-458, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38690512

RESUMEN

BACKGROUND: Leukemia stem cells (LSCs) are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia (AML), as they are protected by the bone marrow microenvironment (BMM) against conventional therapies. Gossypol acetic acid (GAA), which is extracted from the seeds of cotton plants, exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2. AIM: To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism. METHODS: In this study, LSCs were magnetically sorted from AML cell lines and the CD34+CD38- population was obtained. The expression of leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) and forkhead box M1 (FOXM1) was evaluated in LSCs, and the effects of GAA on malignancies and mitochondrial function were measured. RESULTS: LRPPRC was found to be upregulated, and GAA inhibited cell proliferation by degrading LRPPRC. GAA induced LRPPRC degradation and inhibited the activation of interleukin 6 (IL-6)/janus kinase (JAK) 1/signal transducer and activator of transcription (STAT) 3 signaling, enhancing chemosensitivity in LSCs against conventional chemotherapies, including L-Asparaginase, Dexamethasone, and cytarabine. GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC. Furthermore, GAA induced reactive oxygen species accumulation, disturbed mitochondrial homeostasis, and caused mitochondrial dysfunction. By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC, GAA resulted in the elimination of LSCs. Meanwhile, GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage. CONCLUSION: Taken together, the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

14.
J Asian Nat Prod Res ; 26(8): 892-899, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38600044

RESUMEN

Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.


Asunto(s)
Antiinflamatorios , Cirsium , Ésteres , Lipopolisacáridos , Óxido Nítrico , Triterpenos , Animales , Ratones , Cirsium/química , Triterpenos/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Estructura Molecular , Óxido Nítrico/biosíntesis , Óxido Nítrico/antagonistas & inhibidores , Células RAW 264.7 , Antiinflamatorios/farmacología , Antiinflamatorios/química , Lipopolisacáridos/farmacología , Ésteres/farmacología , Ésteres/química , Macrófagos/efectos de los fármacos
15.
Chemistry ; 30(33): e202400995, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38600034

RESUMEN

Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp2)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

16.
Clin Mol Hepatol ; 30(3): 468-486, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38637957

RESUMEN

BACKGROUND/AIMS: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. METHODS: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development. RESULTS: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. CONCLUSION: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.


Asunto(s)
Antivirales , Carcinoma Hepatocelular , Hepatitis C Crónica , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Neoplasias Hepáticas , Metformina , Humanos , Carcinoma Hepatocelular/prevención & control , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Masculino , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Metformina/uso terapéutico , Femenino , Persona de Mediana Edad , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Antivirales/uso terapéutico , Taiwán/epidemiología , Incidencia , Anciano , Adulto , Factores de Riesgo , Modelos de Riesgos Proporcionales , Diabetes Mellitus
17.
Drug Discov Today ; 29(6): 103984, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38642702

RESUMEN

Given their high affinity and specificity for a range of macromolecules, antibodies are widely used in the treatment of autoimmune diseases, cancers, inflammatory diseases, and Alzheimer's disease (AD). Traditional experimental methods are time-consuming, expensive, and labor-intensive. Recent advances in artificial intelligence (AI) technologies provide complementary methods that can reduce the time and costs required for antibody design by minimizing failures and increasing the success rate of experimental tests. In this review, we scrutinize the plethora of AI-driven methodologies that have been deployed over the past 4 years for modeling antibody structures, predicting antibody-antigen interactions, optimizing antibody affinity, and generating novel antibody candidates. We also briefly address the challenges faced in integrating AI-based models with traditional antibody discovery pipelines and highlight the potential future directions in this burgeoning field.


Asunto(s)
Anticuerpos , Inteligencia Artificial , Descubrimiento de Drogas , Humanos , Descubrimiento de Drogas/métodos , Anticuerpos/inmunología , Animales
18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 41(2): 228-236, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38686402

RESUMEN

Conventional maximum intensity projection (MIP) images tend to ignore some morphological features in the detection of intracranial aneurysms, resulting in missed detection and misdetection. To solve this problem, a new method for intracranial aneurysm detection based on omni-directional MIP image is proposed in this paper. Firstly, the three-dimensional magnetic resonance angiography (MRA) images were projected with the maximum density in all directions to obtain the MIP images. Then, the region of intracranial aneurysm was prepositioned by matching filter. Finally, the Squeeze and Excitation (SE) module was used to improve the CaraNet model. Excitation and the improved model were used to detect the predetermined location in the omni-directional MIP image to determine whether there was intracranial aneurysm. In this paper, 245 cases of images were collected to test the proposed method. The results showed that the accuracy and specificity of the proposed method could reach 93.75% and 93.86%, respectively, significantly improved the detection performance of intracranial aneurysms in MIP images.


Asunto(s)
Algoritmos , Imagenología Tridimensional , Aneurisma Intracraneal , Angiografía por Resonancia Magnética , Aneurisma Intracraneal/diagnóstico por imagen , Humanos , Angiografía por Resonancia Magnética/métodos , Imagenología Tridimensional/métodos , Sensibilidad y Especificidad , Procesamiento de Imagen Asistido por Computador/métodos
19.
Int Wound J ; 21(4): e14867, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38597295

RESUMEN

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.


Asunto(s)
Diabetes Mellitus Experimental , Oxigenoterapia Hiperbárica , Humanos , Animales , Ratones , Cicatrización de Heridas/fisiología , Diabetes Mellitus Experimental/terapia , Células Endoteliales de la Vena Umbilical Humana , Tejido Adiposo Blanco
20.
J Am Chem Soc ; 146(13): 9335-9346, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38501695

RESUMEN

Controlling product selectivity in successive reactions of the same type is challenging owing to the comparable thermodynamic and kinetic properties of the reactions involved. Here, the synergistic interaction of the two phosphoryl groups in bisphosphine dioxides (BPDOs) with a bromo-phosphonium cation was studied experimentally to provide a practical tool for substrate-catalyst recognition. As the eventual result, we have developed a phosphonium-catalyzed monoreduction of chiral BPDOs to access an array of synthetically useful bisphosphine monoxides (BPMOs) with axial, spiro, and planar chirality, which are otherwise challenging to synthesize before. The reaction features excellent selectivity and impressive reactivity. It proceeds under mild conditions, avoiding the use of superstoichiometric amounts of additives and metal catalysts to simplify the synthetic procedure. The accessibility and scalability of the reaction allowed for the rapid construction of a ligand library for optimization of asymmetric Heck-type cyclization, laying the foundation for a broad range of applications of chiral BPMOs in catalysis.

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