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1.
Int J Biol Sci ; 20(10): 4077-4097, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39113710

RESUMEN

Triptolide (TP), known for its effectiveness in treating various rheumatoid diseases, is also associated with significant hepatotoxicity risks. This study explored Catalpol (CAT), an iridoid glycoside with antioxidative and anti-inflammatory effects, as a potential defense against TP-induced liver damage. In vivo and in vitro models of liver injury were established using TP in combination with different concentrations of CAT. Metabolomics analyses were conducted to assess energy metabolism in mouse livers. Additionally, a Seahorse XF Analyzer was employed to measure glycolysis rate, mitochondrial respiratory functionality, and real-time ATP generation rate in AML12 cells. The study also examined the expression of proteins related to glycogenolysis and gluconeogenesis. Using both in vitro SIRT1 knockout/overexpression and in vivo liver-specific SIRT1 knockout models, we confirmed SIRT1 as a mechanism of action for CAT. Our findings revealed that CAT could alleviate TP-induced liver injury by activating SIRT1, which inhibited lysine acetylation of hypoxia-inducible factor-1α (HIF-1α), thereby restoring the balance between glycolysis and oxidative phosphorylation. This action improved mitochondrial dysfunction and reduced glucose metabolism disorder and oxidative stress caused by TP. Taken together, these insights unveil a hitherto undocumented mechanism by which CAT ameliorates TP-induced liver injury, positioning it as a potential therapeutic agent for managing TP-induced hepatotoxicity.


Asunto(s)
Diterpenos , Compuestos Epoxi , Glucosa , Subunidad alfa del Factor 1 Inducible por Hipoxia , Glucósidos Iridoides , Hígado , Estrés Oxidativo , Fenantrenos , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Diterpenos/farmacología , Diterpenos/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Compuestos Epoxi/farmacología , Compuestos Epoxi/uso terapéutico , Fenantrenos/farmacología , Glucósidos Iridoides/farmacología , Glucósidos Iridoides/uso terapéutico , Ratones , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Glucosa/metabolismo , Masculino , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Ratones Endogámicos C57BL
2.
BMC Bioinformatics ; 25(1): 264, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39127625

RESUMEN

Circular RNA (CircRNA)-microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.


Asunto(s)
Biología Computacional , MicroARNs , ARN Circular , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/química , ARN Circular/genética , ARN Circular/metabolismo , Humanos , Biología Computacional/métodos , ARN/química , ARN/genética , ARN/metabolismo , Algoritmos , Redes Reguladoras de Genes
3.
Foods ; 13(15)2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39123508

RESUMEN

The aim of this study was to assess the advantages of an industry-scale microfluidizer system (ISMS) to prepare whole-grain highland barley pulp (WHBP) compared with colloid milling. Storage stability was evaluated by particle size, gravity separation stability, and rheological properties, as well as the microstructure observation by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLMS). The results showed that colloid milling failed to effectively homogenize the material, while ISMS sample surfaces were compact and smooth at higher pressures according to visual observation and SEM. The Turbiscan stability index of WHBP by ISMS was much lower as a result of colloid milling, demonstrating ISMS can improve WHBP stability. WHBP by colloid milling displayed a three-peak particle size distribution pattern, while a single-peak pattern was evident after ISMS treatment. A higher shear rate decreased the apparent viscosity, suggesting that WHBP was a shear-thinning fluid. According to CLMS, ISMS can successfully improve homogenization by disrupting the structures of oil bodies, proteins, and starches. The WHBP prepared by ISMS exhibited a higher ß-glucan level than that prepared by colloid milling, and showed a significant increase in ß-glucan level with ISMS pressure. These findings indicate that using ISMS to produce WHBP is viable for enhancing its storage stability and nutritional value.

4.
Technol Cancer Res Treat ; 23: 15330338241273160, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099463

RESUMEN

Introduction: The independent diagnostic value of inflammatory markers neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the diagnostic efficacy of NLR, derived neutrophil to lymphocyte ratio (dNLR), PLR, and lymphocyte-to-monocyte ratio (LMR) in glioma cases remain unclear. We investigated the correlation of preoperative peripheral blood inflammatory markers with pathological grade, Ki-67 Proliferation Index, and IDH-1 gene phenotype in patients with glioma, focusing on tumor grade and prognosis. Methods: We retrospectively analyzed the clinical, pathological, and laboratory data of 334 patients with glioma with varying grades and 345 with World Health Organization (WHO I) meningioma who underwent initial surgery at the Affiliated Hospital of Jining Medical University from December 2019 to December 2021. The diagnostic value of peripheral blood inflammatory markers for glioma was investigated. Results: The proportion of men smoking and drinking was significantly higher in the glioma group than in the meningioma group (P < .05); in contrast, the age and body mass index (Kg/m2) were significantly lower in the glioma group (P = .01). Significant differences were noted in the pathological grade (WHO II, III, and IV), Ki-67 Proliferation Index, and peripheral blood inflammatory markers such as lymphocyte median, NLR, dNLR, and PLR between the groups (P < .05). No significant correlation existed between peripheral blood inflammatory factors and IDH-1 gene mutation status or tumor location in patients with glioma (P > .05). LMR, NLR, dNLR, and PLR, varied significantly among different glioma types (P < .05). White blood cell (WBC) count, neutrophil, NLR, and dNLR correlated positively with glioma risk. Further, WBC, neutrophil, NLR, dNLR, and LMR had a high diagnostic efficiency. Conclusion: Peripheral blood inflammatory markers, serving as noninvasive biomarkers, offer high sensitivity and specificity for diagnosing glioma, differentiating it from meningioma, diagnosing GBM, and distinguishing GBM from low-grade glioma. These markers may be implemented as routine screening tools.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas , Glioma , Clasificación del Tumor , Neutrófilos , Humanos , Glioma/patología , Glioma/sangre , Glioma/cirugía , Glioma/diagnóstico , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Neutrófilos/patología , Adulto , Estudios Retrospectivos , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico , Anciano , Linfocitos/patología , Periodo Preoperatorio , Inflamación/patología , Inflamación/sangre , Plaquetas/patología , Curva ROC
5.
Genome Biol ; 25(1): 207, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103856

RESUMEN

Cell type identification is an indispensable analytical step in single-cell data analyses. To address the high noise stemming from gene expression data, existing computational methods often overlook the biologically meaningful relationships between genes, opting to reduce all genes to a unified data space. We assume that such relationships can aid in characterizing cell type features and improving cell type recognition accuracy. To this end, we introduce scPriorGraph, a dual-channel graph neural network that integrates multi-level gene biosemantics. Experimental results demonstrate that scPriorGraph effectively aggregates feature values of similar cells using high-quality graphs, achieving state-of-the-art performance in cell type identification.


Asunto(s)
Análisis de la Célula Individual , Análisis de la Célula Individual/métodos , Humanos , Redes Neurales de la Computación , RNA-Seq/métodos , Biología Computacional/métodos , Algoritmos , Programas Informáticos , Análisis de Expresión Génica de una Sola Célula
6.
Front Nutr ; 11: 1395083, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119466

RESUMEN

Introduction: Weizmannia coagulans has emerged as a promising candidate for the management of gastrointestinal ailments. The novel strain of Weizmannia coagulans, Weizmannia coagulans BC99 (BC99), displays robust pathogen-inhibiting capabilities, susceptibility to various antibiotics, and a high level of biosafety. Nevertheless, additional research is necessary to fully understand its effectiveness in managing chronic constipation. Methods: This study investigates the role of BC99 in alleviating chronic constipation in a double-blind, placebo-controlled, randomized trial, and participants were divided into BC99 (2 billion CFU/d) or placebo (maltodextrin) groups for a 4-week period. Results and discussion: Results showed that significant improvements were noted in the BC99 group, with an increase in complete spontaneous bowel movements (CSBM) after 4-week treatment compared to the placebo (p = 0.002). The BC99 group also showed significantly lower Quality of Life (PAC-QOL) scores and reduced Constipation Symptoms (PAC-SYM) scores after 4 weeks of treatment (p < 0.001), indicating symptomatic relief. Notably, BC99 effectively modulated key gut microbiota such as Bifidobacterium and Ruminococcus, linked to crucial metabolic pathways like glutathione metabolism. In all, BC99 is confirmed to be an effective and safe therapeutic option for the relief of adult chronic constipation, enhancing gut microbiota balance and influencing critical metabolic pathways. Clinical trial registration: ChiCTR2200065493.

7.
Nat Commun ; 15(1): 6704, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39112454

RESUMEN

Body heat, a clean and ubiquitous energy source, is promising as a renewable resource to supply wearable electronics. Emerging tough thermogalvanic device could be a sustainable platform to convert body heat energy into electricity for powering wearable electronics if its Carnot-relative efficiency (ηr) reaches ~5%. However, maximizing both the ηr and mechanical strength of the device are mutually exclusive. Here, we develop a rational strategy to construct a flexible thermogalvanic armor (FTGA) with a ηr over 8% near room temperature, yet preserving mechanical robustness. The key to our design lies in simultaneously realizing the thermosensitive-crystallization and salting-out effect in the elaborately designed ion-transport highway to boost ηr and improve mechanical strength. The FTGA achieves an ultrahigh ηr of 8.53%, coupling with impressive mechanical toughness of 70.65 MJ m-3 and substantial elongation (~900%) together. Our strategy holds sustainable potential for harvesting body heat and powering wearable electronics without recharging.

8.
Environ Sci Technol ; 58(33): 14940-14948, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39105779

RESUMEN

Low concentrations of nitrate (NO3-) widely exist in wastewater, post-treated wastewater, and natural environments; its further disposal is a challenge but meaningful for its discharge goals. Electroreduction of NO3- is a promising method that allows to eliminate NO3- and even generate higher-value NH3. However, the massive side reaction of hydrogen evolution has raised great obstacles in the electroreduction of low concentrations of NO3-. Herein, we present an efficient electroreduction method for low or even ultralow concentrations of NO3- via NO3- self-enrichment and active hydrogen (H*) inducement on the Ce(IV)-Co3O4 cathode. The key mechanism is that the strong oxytropism of Ce(IV) in Co3O4 resulted in two changes in structures, including loose nanoporous structures with copious dual adsorption sites of Ce-Co showing strong self-enrichment of NO3- and abundant oxygen vacancies (Ovs) inducing substantial H*. Ultimately, the bifunctional role synergistically promoted the selective conversion of NH3 rather than H2. As a result, Ce(IV)-Co3O4 demonstrated a NO3- self-enrichment with a 4.3-fold up-adsorption, a 7.5-fold enhancement of NH3 Faradic efficiency, and a 93.1% diminution of energy consumption when compared to Co3O4, substantially exceeding other reported electroreduction cathodes for NO3- concentrations lower than 100 mg·L-1. This work provides an effective treatment method for low or even ultralow concentrations of NO3-.


Asunto(s)
Electrodos , Nitratos , Nitratos/química , Hidrógeno/química , Cerio/química
9.
Exp Ther Med ; 28(4): 371, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39091632

RESUMEN

Although telitacicept is a promising drug for treating systemic lupus erythematosus, there are limited studies on its efficacy and safety in patients with lupus nephritis in China. This lack of research data restricts its potential for broader application and acceptance on a global scale. The present study aimed to determine the efficacy and safety of telitacicept in patients with lupus nephritis (LN) in China. Using a self-controlled before-after comparison method, patients with LN were recruited at Lishui Central Hospital between February 2022 and April 2023, who received telitacicept weekly as part of the standard treatment. Data on the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), glucocorticoid dosing and the quantity of immunosuppressive medicines prescribed was collected. Additionally, serum complements, erythrocyte sedimentation rate (ESR), urinary protein levels, immunoglobulin concentrations, serum creatinine levels, plasma albumin concentrations, platelet counts and renal function parameters were documented throughout the study. A total of 13 patients were enrolled in the trial, comprising 11 women and two men. Following 12-48 weeks of treatment with telitacicept (80 or 160 mg per week), 84.6% (n=11) of all patients experienced symptom relief and their SLEDAI-2K score was reduced by more than four points. By the observation endpoint, the median glucocorticoid dosage of the 13 patients was decreased from 15 to 2.5 mg/d, and six patients discontinued their glucocorticoids. Furthermore, 46.1% of patients (n=6) reduced their dose and number of immunosuppressive medicines, while 15.4% (n=2) stopped their immunosuppressive medicines. Minimal changes were observed in serum creatinine, platelet count, C3 levels and C4 levels among patients. Immunoglobulin levels (IgG, IgA and IgM) remained stable or showed an upward trend. Plasma albumin levels remained within the normal range in three patients and increased in ten patients. It increased to the normal range in three of these ten patients. At the endpoint, ESR levels decreased in all patients. Additionally, three patients displayed varying degrees of renal function improvement, and their estimated glomerular filtration rate (ml/min/l.73 m2) increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively. Urinary protein levels decreased in all patients. It decreased >0.5 g/l in seven patients and reached the normal levels in three patients. The adverse events of telitacicept were manageable. Among the patients infected with COVID-19, three patients had fever, 10 patients remained asymptomatic and none of them exhibited severe respiratory syndromes. In this study, telitacicept effectively stabilized LN activity and alleviated the clinical symptoms of most patients. Furthermore, it reduced the dose of glucocorticoid and immunosuppressive medicines. Therefore, telitacicept may be a promising treatment option for individuals with lupus nephritis.

10.
J Environ Manage ; 368: 122173, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39128355

RESUMEN

To address shortages in construction materials for island engineering, tackle the accumulation of solid waste, and inhibit the shrinkage of geopolymers, coral waste was utilized as the internal curing material to prepare high-performance marine geopolymer concrete (MGC) with seawater, sea-sand, and normal limestone aggregate (LsA). The coral coarse aggregate (CorA) used in this investigation has a total porosity ranging from 50% to 58.3% with internal pore diameters spanning 50-400 µm. The water desorption of CorA followed a two-stage pattern within a relative humidity (RH) range of 75%-85%, becoming nonlinear above 90% RH, which released about 85% of its moisture within 200 h at 97% RH, demonstrating potential for internal curing. Adding a small amount of CorA to MGC increased slump and setting time by providing internal curing water. However, as CorA content exceeded 30%, the slump significantly decreased due to reduced mixing water and elevated activator concentration, while the initial setting time slightly decreased. Furthermore, the inclusion of saturated CorA in MGC significantly reduced autogenous shrinkage, with higher CorA contents (exceeding 30%) leading to slight expansion in the early stages and nearly eliminating shrinkage at contents above 40%. The greater drying shrinkage in geopolymer systems compared to ordinary Portland cement is due to capillary pressure compressing the product framework, converting larger gel pores into smaller ones. Additionally, the layered calcium aluminosilicate hydrate (C-A-S-H) gel exhibits more pronounced creep characteristics under low internal humidity conditions. The higher CorA content in MGC promoted the formation of hybrid C, N-A-S-H gel and hydrotalcite-like phases, and reduced carbonation issues. The interfacial transition zone (ITZ) between CorA and the geopolymer matrix formed a robust mechanical interlock, enhancing tensile strength and minimizing shrinkage-induced cracks. Based on overall performance and marine material utilization, an optimal substitution rate of CorA between 40% and 50% is recommended.

11.
Cancer Med ; 13(15): e70051, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39082888

RESUMEN

BACKGROUND: There was limited research data on large-scale locally advanced non-small cell lung cancer (LA-NSCLC) radical radiotherapy (RT) reported in China. This study examined overall survival (OS), progression-free survival (PFS), treatment effectiveness, and toxicity in patients with LA-NSCLC treated with definitive RT in the pre-durvalumab era. METHODS: A retrospective analysis of demographic information, clinical characteristics, treatment patterns, and clinical outcomes of 789 patients with LA-NSCLC who underwent radical RT at our center between January 2005 and December 2015 was performed. The Kaplan-Meier method and log-rank test were used for survival comparisons, and Cox regression was used for multivariate analysis. RESULTS: There were 328 patients with stage IIIA disease and 461 with stage IIIB disease. By the last follow-up, there were 365 overall deaths and 576 cases of recurrence, metastasis, or death. The median survival time was 31 months. The OS rates at 1, 2, 5, and 10 years were 83.7%, 59.5%, 28.8%, and 18.9%, respectively. PFS rates at 1, 2, 5, and 10 years were 48%, 24.5%, 11.9%, and 5.5%, respectively. Rates of ≥grade 3 acute radiation pneumonitis or esophagitis were 7.6% and 1.9%, respectively. Rates of ≥grade 3 chronic radiation pneumonitis and esophagitis were 11% and 0.4%, respectively. Multivariate analysis showed that the Karnofsky Performance Status (KPS) score, smoking status, and combined chemotherapy were prognostic factors for OS (p < 0.05). Multivariate analysis revealed that combined chemotherapy and radiation dose were prognostic factors for PFS (p < 0.05). CONCLUSIONS: Our center's data showed that the survival prognosis of locally advanced patients receiving RT and chemotherapy in China was consistent with international levels during the same period. Patients with a KPS score of 80 or higher, who had never smoked or received combined RT, had a more favorable prognosis than those with a KPS of less than 80, who had smoked, or only received RT. The combination of RT and chemotherapy, with a reasonable radiation dose, was the key to improving the therapeutic effect.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Femenino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Resultado del Tratamiento , Anciano de 80 o más Años , China/epidemiología , Estimación de Kaplan-Meier
12.
iScience ; 27(7): 110219, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39021795

RESUMEN

The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

13.
Front Cell Infect Microbiol ; 14: 1371543, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39040602

RESUMEN

Acupuncture, an important green and side effect-free therapy in traditional Chinese medicine, is widely use both domestically and internationally. Acupuncture can interact with the gut microbiota and influence various diseases, including metabolic diseases, gastrointestinal diseases, mental disorders, nervous system diseases, and other diseases. This review presents a thorough analysis of these interactions and their impacts and examines the alterations in the gut microbiota and the potential clinical outcomes following acupuncture intervention to establish a basis for the future utilization of acupuncture in clinical treatments.


Asunto(s)
Terapia por Acupuntura , Enfermedades Gastrointestinales , Microbioma Gastrointestinal , Humanos , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/terapia , Trastornos Mentales/terapia , Trastornos Mentales/microbiología , Enfermedades del Sistema Nervioso/terapia , Enfermedades del Sistema Nervioso/microbiología , Animales , Enfermedades Metabólicas/microbiología , Enfermedades Metabólicas/terapia
14.
Small ; : e2400201, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031757

RESUMEN

Water electrolysis has become an attractive hydrogen production method. Oxygen evolution reaction (OER) is a bottleneck of water splitting as its four-electron transfer procedure presents sluggish reaction kinetics. Designing composite catalysts with high performance for efficient OER still remains a huge challenge. Here, the P-doped cobalt oxide/NiFe layered double hydroxides (P-CoOX/NiFe LDHs) composite catalysts with amorphous/crystalline interfaces are successfully prepared for OER by hydrothermal-electrodeposition combined method. The results of electrochemical characterizations, operando Raman spectra, and DFT theoretical calculations have demonstrated the electrons in the P-CoOX/NiFe LDHs heterointerfaces are easily transferred from Ni2+ to Co3+ because that the amorphous configuration of P-CoOX can well induce Ni-O-Co orbital coupling. The electron transfer of Ni2+ to the surrounding Fe3+ and Co3+ will lead to the unoccupied eg orbitals of Ni3+ that can promote water dissociation and accelerate *OOH migration to improve OER catalytic performance. The optimized P-CoOX/NiFe LDHs exhibit superior catalytic performance for OER with a very low overpotential of 265 mV at 300 mA cm-2 and excellent long-term stability of 500 h with almost no attenuation at 100 mA cm-2. This work will provide a new method to design high-performance NiFe LDHs-based catalysts for OER.

15.
Blood ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39046762

RESUMEN

Atypical acute promyelocytic leukemia (aAPL) presents a complex landscape of retinoic acid receptor (RAR) fusion genes beyond the well-known PML::RARA fusion. Among these, 31 individually rare RARA and RARG fusion genes have been documented, often reported in the canonical X::RAR bipartite fusion form. Intriguingly, some artificially mimicked bipartite X::RAR fusions respond well to all-trans retinoic acid (ATRA) in vitro, contrasting with the ATRA resistance observed in patients. To unravel the underlying mechanisms, we conducted a comprehensive molecular investigation into the fusion transcripts in 27 RARA fusion gene-positive aAPL (RARA-aAPL) and 21 RARG-aAPL cases. Our analysis revealed an unexpected novel form of X::RAR::X or X::RAR::Y-type tripartite fusions in certain RARA- and all RARG-aAPL cases, with shared features and notable differences between these two disease subgroups. In RARA-aAPL cases, the occurrence of RARA 3' splices was associated with their 5' fusion partner genes, mapping across the coding region of helix 11_12 (H11_12) within the ligand-binding domain (LBD), resulting in LBD-H12 or H11_12 truncation. In RARG-aAPL cases, RARG 3' splices were consistently localized to the terminus of exon 9, leading to LBD-H11_12 truncation. Significant differences were also observed between RARA and RARG 5' splice patterns. Our analysis also revealed extensive involvement of transposable elements in constructing RARA and RARG 3' fusions, suggesting transposition mechanisms for fusion gene ontogeny. Both protein structural analysis and experimental results highlighted the pivotal role of LBD-H11_12/H12 truncation in driving ATRA unresponsiveness and leukemogenesis in tripartite fusion-positive aAPL, through a protein allosteric dysfunction mechanism.

16.
J Orthop Surg Res ; 19(1): 414, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030606

RESUMEN

BACKGROUND: To explore and compare the values of 3.0T magnetic resonance imaging (MRI) T2 mapping in evaluating the degree of acetabular cartilage degeneration in hip replacement surgery. METHODS: A total of 26 elderly patients with femoral neck fractures who were scanned in 3.0T MRI T2 mapping quantification technique were included. Basing on MRI images, the degree of acetabular cartilage degeneration was classified into Grade 0, 1, 2, 3 and 4, according to the International Cartilage Repair Society (ICRS) scores. In addition, 8 healthy volunteers were included for control group. RESULTS: By comparison with health population, T2 relaxation values in the anterior, superior, and posterior regions of acetabular cartilage in patients with femoral neck fracture were obviously increased (P < 0.001). Among the patients with femoral neck fractures, there were 16 hip joint with Grade 1-2 (mild degeneration subgroup) and 10 hip joints with Grade 3-4 (severe degeneration subgroup), accounting for 61.54% and 38.46%, respectively. Additionally, T2 relaxation values in the anterior and superior bands of articular cartilage were positively related to the MRI-based grading (P < 0.05); while there was no significant difference of T2 relaxation values in the posterior areas of articular cartilage between severe degeneration subgroup and mild degeneration subgroup (P > 0.05). Importantly, acetabular cartilage degeneration can be detected through signal changes of T2 mapping pseudo-color images. CONCLUSION: 3.0T MRI T2 mapping technology can be used to determine the degree of acetabular cartilage degeneration, which can effectively monitor the disease course.


Asunto(s)
Acetábulo , Artroplastia de Reemplazo de Cadera , Cartílago Articular , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Acetábulo/diagnóstico por imagen , Acetábulo/patología , Anciano , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Artroplastia de Reemplazo de Cadera/métodos , Persona de Mediana Edad , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Anciano de 80 o más Años , Enfermedades de los Cartílagos/diagnóstico por imagen , Enfermedades de los Cartílagos/patología , Índice de Severidad de la Enfermedad
17.
Front Pharmacol ; 15: 1423684, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045048

RESUMEN

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.

18.
J Chem Phys ; 161(2)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-38980094

RESUMEN

Methanol steam reforming (MSR) is an attractive route for producing clean energy hydrogen. PdZn alloys are extensively studied as potential MSR catalysts for their stability and high CO2 selectivity. Here, we investigated the reaction mechanism using density functional calculations, mean-field microkinetic modeling (MF-MKM), and kinetic Monte Carlo (kMC) simulations. To overcome the over-underestimation of CO2 selectivity by log-kMC, an ads-kMC algorithm is proposed in which the adsorption/desorption rate constants were reduced under certain requirements and the diffusion process was treated by redistributing surface species each time an event occured. The simulations show that the dominant pathway to CO2 at low temperatures is CH3OH → CH3O → CH2O → H2COOH → H2COO → HCOO → CO2. The ads-kMC predicted OH coverage is 2-3 times that of MF-MKM, while they produce similar coverage for other species. Analyses indicate that surface OH promotes the dehydrogenation of CH3OH, CH3O, and H2COOH significantly and plays a key role in the MSR process. The dissociation of water/methanol is the most important rate-limiting/rate-inhibiting step. The CO2 selectivity obtained by the two methods is close to each other and consistent with the experimental trend with temperature. Generally, the ads-kMC results agree with the MF-MKM ones, supporting the previous finding that kMC and MF-MKM predict similar results if the diffusion is very fast and adsorbate interactions are neglected. The present study sheds light on the MSR process on PdZn alloys, and the proposed scheme to overcome the stiff problems in kMC simulations is worthy of being extended to other systems.

19.
Front Pharmacol ; 15: 1281095, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011501

RESUMEN

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.

20.
Nanoscale ; 16(28): 13654-13662, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38963285

RESUMEN

I-III-VI quantum dots (QDs) have gained widespread attention owing to their significant advantages of non-toxicity, large structural tolerance, and efficient photoluminescence potential. However, the disbalance of reactivity between the elements will result in undesired products and compromised optical properties. Reducing the activity of highly reactive group IB elements is the most common approach, but it will reduce the overall reactivity and lead to a wide dispersion of QD sizes. In this study, we propose a method to improve the overall reactivity of the reaction system using the highly active IIIA precursor InI3, which triggers rapid nucleation and promotes the formation of Ag(In,Ga)S2 (AIGS) QDs, resulting in monodisperse particle size distributions and a significantly improved photoluminescence quantum yield (PLQY) (from 12% to 72%). Furthermore, narrow band edge emission is realized by coating a gallium sulfide (GaSx) shell on the basis of obtaining high-quality AIGS QDs. The core/shell QDs exhibit a 90% PLQY with a full width at half maximum (FWHM) of only 31 nm at 530 nm. This study provides a viable design strategy to synthesize monodisperse AIGS QDs with a narrow peak width and efficient luminescence, promoting the application of AIGS QDs in the field of luminescent displays.

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