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1.
Genes Dis ; 11(5): 101150, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38947742

RESUMEN

The advent of tyrosine kinase inhibitors (TKI) targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia (CML), greatly prolonged the life of CML patients, and improved their prognosis. However, TKI resistance is still a major problem with CML patients, reducing the efficacy of treatment and their quality of life. TKI resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent resistance. Now, the main clinical strategy addressing TKI resistance is to switch to newly developed TKIs. However, data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance mutations. Therefore, finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system (UPS) has emerged as a focus. The UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological processes. In recent years, the study of UPS in hematological malignant tumors has resulted in effective treatments, such as bortezomib in the treatment of multiple myeloma and mantle cell lymphoma. In CML, the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL, interfering with CML-related signaling pathways, and negatively or positively affecting leukemia stem cells. Some of these molecules may help overcome TKI resistance and treat CML. In this review, the mechanism of TKI resistance is briefly described, the components of UPS are introduced, existing studies on UPS participating in TKI resistance are listed, and UPS as the therapeutic target and strategies are discussed.

2.
ACS Nano ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950337

RESUMEN

Therapy-induced modulation of the tumor microenvironment (TME) to overcome the immunosuppressive TME is considered to be an opportunity for cancer treatment. However, monitoring of TME modulation during the therapeutic process to accurately determine immune responses and adjust treatment plans in a timely manner remains to be challenging. Herein, we report a carrier-free nanotheranostic system (CANPs) assembled by two boron dipyrromethene (BODIPY) dyes, a sonophotosensitizer C-BDP, and a nitric oxide (NO) probe amino-BODIPY (A-BDP). CANPs can exert combined sonophototherapeutic effects of C-BDP under ultrasound and light irradiation and simultaneously induce inflammatory TME, as well as emit bright fluorescence via A-BDP by monitoring tumor-associated macrophages (TAMs) repolarization through the released NO in vitro and in vivo. Of note, transforming growth factor-ß (TGF-ß) could be the key cytokine involved in the sonophototherapy-induced TME reprogramming. By virtue of high physiological stability, good biocompatibility, and effective tumor targetability, CANPs could be a potential nanotheranostic system for the simultaneous induction and detection of TME reprogramming triggered by sonophototherapy.

3.
Sci Rep ; 14(1): 15175, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956251

RESUMEN

In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin-eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia-reperfusion injury.


Asunto(s)
Cobre , Disulfiram , Homeostasis , Inflamación , Ratones Endogámicos C57BL , Daño por Reperfusión , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Disulfiram/farmacología , Ratones , Cobre/metabolismo , Homeostasis/efectos de los fármacos , Masculino , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Regulación hacia Abajo/efectos de los fármacos , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Modelos Animales de Enfermedad , Proteínas Hierro-Azufre/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/patología , Apoptosis/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Receptor Toll-Like 4/metabolismo
4.
Nat Commun ; 15(1): 5811, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987310

RESUMEN

Extraintestinal Pathogenic Escherichia coli (ExPEC) pose a significant threat to human and animal health. However, the diversity and antibiotic resistance of animal ExPEC, and their connection to human infections, remain largely unexplored. The study performs large-scale genome sequencing and antibiotic resistance testing of 499 swine-derived ExPEC isolates from China. Results show swine ExPEC are phylogenetically diverse, with over 80% belonging to phylogroups B1 and A. Importantly, 15 swine ExPEC isolates exhibit genetic relatedness to human-origin E. coli strains. Additionally, 49 strains harbor toxins typical of enteric E. coli pathotypes, implying hybrid pathotypes. Notably, 97% of the total strains are multidrug resistant, including resistance to critical human drugs like third- and fourth-generation cephalosporins. Correspondingly, genomic analysis unveils prevalent antibiotic resistance genes (ARGs), often associated with co-transfer mechanisms. Furthermore, analysis of 20 complete genomes illuminates the transmission pathways of ARGs within swine ExPEC and to human pathogens. For example, the transmission of plasmids co-harboring fosA3, blaCTX-M-14, and mcr-1 genes between swine ExPEC and human-origin Salmonella enterica is observed. These findings underscore the importance of monitoring and controlling ExPEC infections in animals, as they can serve as a reservoir of ARGs with the potential to affect human health or even be the origin of pathogens infecting humans.


Asunto(s)
Antibacterianos , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli Patógena Extraintestinal , Filogenia , Enfermedades de los Porcinos , Animales , Porcinos , China/epidemiología , Escherichia coli Patógena Extraintestinal/genética , Escherichia coli Patógena Extraintestinal/efectos de los fármacos , Escherichia coli Patógena Extraintestinal/aislamiento & purificación , Escherichia coli Patógena Extraintestinal/patogenicidad , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/veterinaria , Enfermedades de los Porcinos/microbiología , Proteínas de Escherichia coli/genética , Antibacterianos/farmacología , Humanos , Farmacorresistencia Bacteriana Múltiple/genética , Plásmidos/genética , Genoma Bacteriano/genética , Secuenciación Completa del Genoma , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana/genética , beta-Lactamasas/genética
5.
J Inflamm Res ; 17: 3771-3784, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38882186

RESUMEN

Purpose: Red blood cell distribution width to albumin ratio (RAR) is a novel inflammatory biomarker that independently predicts adverse cardiovascular events and acute kidney injury. This study aimed to assess the predictive value of RAR for cardio-renal syndrome type I (CRS-I) risk in acute myocardial infarction (AMI) patients. Patients and methods: This study retrospectively enrolled 551 patients who were definitively diagnosed as AMI between October 2021 and October 2022 at the Affiliated Zhongda Hospital of Southeast University. Participants were divided into two and four groups based on the occurrence of CRS-I and the quartiles of RAR, respectively. Demographic data, laboratory findings, coronary angiography data, and drug utilization were compared among the groups. Logistic regression and receiver operating characteristic curve (ROC) analysis were performed to identify independent risk factors for CRS-I and evaluated the predictive value of RAR for CRS-I. Results: Among the cohort of 551 patients, 103 (18.7%) developed CRS-I. Patients with CRS-I exhibited significantly elevated RAR levels compared to those without the condition, and the incidence of CRS-I correlated with escalating RAR. Univariate and multivariate logistic regression analyses identified RAR as an independent risk factor for CRS-I. ROC curves analysis demonstrated that RAR alone predicted CRS-I with an area under the curve (AUC) of 0.683 (95% CI=0.642-0.741), which was superior to the traditional inflammatory marker C-reactive protein (CRP). Adding the variable RAR to the model for predicting the risk of CRS-I further improved the predictive value of the model from 0.808 (95% CI=0.781-0.834) to 0.825 (95% CI=0.799-0.850). Conclusion: RAR is an independent risk factor for CRS-I, and high levels of RAR are associated with an increased incidence of CRS-I in patients with AMI. RAR emerges as a valuable and readily accessible inflammatory biomarker that may play a pivotal role in risk stratification in clinical practice.

6.
Inorg Chem ; 63(24): 11393-11405, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38842044

RESUMEN

In this research, a range of Pt/CeO2 catalysts featuring varying Pt-O-Ce bond contents were developed by modulating the oxygen vacancies of the CeO2 support for toluene abatement. The Pt/CeO2-HA catalyst generated a maximum quantity of Pt-O-Ce bonds (possessed the strongest metal-support interaction), as evidenced by the visible Raman results, which demonstrated outstanding toluene catalytic performance. Additionally, the UV Raman results revealed that the strong metal-support interaction stimulated a substantial increase in oxygen vacancies, which could facilitate the activation of gaseous oxygen to generate abundant reactive oxygen species accumulated on the Pt/CeO2-HA catalyst surface, a conclusion supported by the H2-TPR, XPS, and toluene-TPSR results. Furthermore, the results from quasi-in situ XPS, in situ DRIFTS, and DFT indicated that the Pt/CeO2-HA catalyst with a strong metal-support interaction led to improved mobility of reactive oxygen species and lower oxygen activation energies, which could transfer a large number of activated reactive oxygen species to the reaction interface to participate in the toluene oxidation, resulting in the relatively superior catalytic performance. The approach of tuning the metal-support interaction of catalysts offers a promising avenue to develop highly active catalysts for toluene degradation.

7.
Mol Nutr Food Res ; 68(12): e2300833, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38850176

RESUMEN

SCOPE: Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD. METHODS AND RESULTS: This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1flox/flox and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1flox/flox mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1flox/flox mice. Nobiletin antagonizes the expression of these genes in Bmal1flox/flox mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner. CONCLUSION: Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.


Asunto(s)
Factores de Transcripción ARNTL , Flavonas , Lipogénesis , Hepatopatías Alcohólicas , Ratones Noqueados , Proteínas Proto-Oncogénicas c-akt , Animales , Flavonas/farmacología , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Hepatopatías Alcohólicas/prevención & control , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Lipogénesis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Masculino , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones Endogámicos C57BL , Ratones , Sustancias Protectoras/farmacología , Etanol , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos
8.
Biomed Mater ; 19(4)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38838694

RESUMEN

Tantalum and porous tantalum are ideal materials for making orthopedic implants due to their stable chemical properties and excellent biocompatibility. However, their utilization is still affected by loosening, infection, and peripheral inflammatory reactions, which sometimes ultimately lead to implant removal. An ideal bone implant should have exceptional biological activity, which can improve the surrounding biological microenvironment to enhance bone repair. Recent advances in surface functionalization have produced various strategies for developing compatibility between either of the two materials and their respective microenvironments. This review provides a systematic overview of state-of-the-art strategies for conferring biological functions to tantalum and porous tantalum implants. Furthermore, the review describes methods for preparing active surfaces and different bioactive substances that are used, summarizing their functions. Finally, this review discusses current challenges in the development of optimal bone implant materials.


Asunto(s)
Sustitutos de Huesos , Huesos , Propiedades de Superficie , Tantalio , Ingeniería de Tejidos , Tantalio/química , Ingeniería de Tejidos/métodos , Humanos , Porosidad , Animales , Huesos/metabolismo , Sustitutos de Huesos/química , Materiales Biocompatibles/química , Ensayo de Materiales , Prótesis e Implantes , Andamios del Tejido/química
9.
Front Oncol ; 14: 1361527, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699645

RESUMEN

Aim: To investigate whether age at first sexual intercourse could lead to any changes in the risk of oral cavity cancer. Methods: A two-sample mendelian randomization was conducted using genetic variants associated with age at first sexual intercourse in UK biobank as instrumental variables. Summary data of Northern American from a previous genome-wide association study aimed at oral cavity cancer was served as outcome. Three analytical methods: inverse variance-weighted, mendelian randomization Egger, and weighted median were used to perform the analysis, among which inverse variance-weighted was set as the primary method. Robustness of the results was assessed through Cochran Q test, mendelian randomization Egger intercept tests, MR PRESSO, leave one out analysis and funnel plot. Results: The primary analysis provided substantial evidence of a positive causal relationship age at first sexual intercourse and the risk of oral cavity cancer (p = 0.0002), while a delayed age at first sexual intercourse would lead to a decreased risk of suffering oral cavity cancer (ß = -1.013). The secondary outcomes confirmed the results (all ß < 0) and all assessments supported the robustness, too (all p > 0.05). Conclusion: The study demonstrates that a delayed sexual debut would provide protection against OCC, thus education on delaying sexual intercourse should be recommended.

10.
ACS Appl Mater Interfaces ; 16(22): 28537-28549, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38781051

RESUMEN

The structural and interfacial instability of Ni-rich layered cathodes LiNi0.9Co0.05Mn0.05O2 (NCM9055) severely hinders their commercial application. In this work, straightforward high-temperature solid-state methods are utilized to successfully synthesize Nb-doped and Li3PO4-coated LiNi0.9Co0.05Mn0.05O2 by combining two niobium sources, NbOPO4·3H2O and Nb2O5, for the first time. Studies indicate that Nb doping enhanced the integrity of the layered structure, and the Li3PO4 coating reduced water absorption on the surface and considerably boosted the durability of the interface. The dual-modified cathode Li(Ni0.9Co0.05Mn0.05)0.985Nb0.015O2@Li3PO4 (NCM-2) exhibits remarkable cycling and rate performance. The initial discharge specific capacity of NCM-2 is 203.33 mAh g-1 at 0.1 C and 196.04 mAh g-1 at 1 C, while the capacity retention after 200 cycles is 91.38% at 1 C, which is much higher than that of pristine NCM9055 (49.96%). In addition, it also provides a superior discharge specific capacity of about 175.63 mAh g-1 even at 5 C. This study emphasizes a feasible approach to enhancing the stability of Ni-rich cathodes at the interfaces and bulk structures.

11.
Int J Biol Macromol ; 270(Pt 2): 132458, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38772458

RESUMEN

The salient gelling feature of alginate via forming the egg-box structure with calcium ions has received extensive interests for different applications. Owing to the interfacial incompatibility of rigid inorganic solids with soft polymers, the requirement of overall stereocomplexation with calcium released from uniformly distributed solids in alginate remains a challenge. In this study, a novel alginate-incorporated calcium source was proposed to tackle the intractable dispersion for the preparation of injectable alginate hydrogels. Calcium phosphate synthesis in alginate solution yielded CaP-alginate hybrids as a calcium source. The physicochemical characterization confirmed the CaP-alginate hybrid was a nano-scale alginate-hydroxyapatite complex. The colloidally stable CaP-alginate hybrids were uniformly dispersed in alginate solutions even under centrifugation. The calcium-induced gelling of the CaP-alginate hybrids-loaded alginate solutions formed soft yet tough hydrogels including transparent sheets and knittable threads, confirming the homogeneous gelation of the hydrogel. The gelation time, injectability and mechanical properties of the hydrogels could be adjusted by changing preparation parameters. The prepared hydrogels showed uniform porous structure, excellent swelling, wetting properties and cytocompatibility, showing a great potential for applications in different fields. The present strategy with organic/inorganic hybridization could be exemplarily followed in the future development of functional hydrogels especially associated with the interface integration.


Asunto(s)
Alginatos , Durapatita , Hidrogeles , Hidrogeles/química , Alginatos/química , Durapatita/química , Materiales Biocompatibles/química , Inyecciones , Animales , Fenómenos Mecánicos , Ratones
12.
Gels ; 10(5)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38786254

RESUMEN

In order to improve the plugging performance of high-temperature and high-salt oil reservoir plugging agents, this paper utilizes a copolymer composed of acrylamide and 2-acrylamide-2-methylpropanesulfonic acid (AM/AMPS) as the polymer, polyethyleneimine as the cross-linking agent, and nylon fiber as the stabilizer to develop a high-temperature- and high-salt-resistant gel system. This study analyzed and evaluated the temperature resistance, salt resistance and blocking performance of the gel system. The evaluation results show that the gel-forming strength of this gel system can reach an H level, and it has good thermal stability at the high temperature of 130 °C. At the high salinity of 240,720 mg/L, the syneresis rate remains below 2.5%, and the gel-forming time is greater than 15 h; the higher the temperature, the shorter the gelling time. The results of our sand-filled pipe-plugging experiment show that the gel system can adapt to sand-filled pipes with different levels of permeability, and reaching a plugging rate of 94%.

13.
Materials (Basel) ; 17(10)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38793316

RESUMEN

The application potential of additive manufacturing nickel-based superalloys in aeroengines and gas turbines is extensive, and evaluating their mechanical properties is crucial for promoting the engineering application in load-bearing components. In this study, Hastelloy X alloy was prepared using the laser powder bed fusion process combined with solution heat treatment. The tensile and high cycle fatigue properties were experimentally investigated at room temperature as well as two typical elevated temperatures, 650 °C and 815 °C. It was found that, during elevated-temperature tensile deformation, the alloy exhibits significant serrated flow behavior, primarily observed during the initial stage of plastic deformation at 650 °C but occurring throughout the entire plastic deformation process at 815 °C. Notably, when deformation is small, sawtooth fluctuations are significantly higher at 815 °C compared to 650 °C. Irregular subsurface lack of fusion defects serve as primary sources for fatigue crack initiation in this alloy including both single-source and multi-source initiation mechanisms; moreover, oxidation on fracture surfaces is more prone to occur at elevated temperatures, particularly at 815 °C.

14.
J Nutr Biochem ; 130: 109648, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38631512

RESUMEN

Insulin resistance (IR) is a global health challenge, often initiated by dysfunctional adipose tissue. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have different effects on IR, but the mechanisms are unknown. This study aims to evaluate the protective effect of EPA and DHA against IR in a high-fat diet (HFD) mice model and investigate whether EPA and DHA alter IR modulate the G-protein-poupled receptor 120/peroxisome proliferator-activated receptor γ (GPR120/PPARγ) pathway in macrophages and adipocytes, which may affect IR in adipocytes. The findings of this study show that 4% DHA had a better effect in improving IR and reducing inflammatory cytokines in adipose tissue of mice. Additionally, in the cell experiment, the use of AH7614 (a GPR120 antagonist) inhibited the glucose consumption increase and the increasable expression of PPARγ and insulin signaling molecules mediated by DHA in adipocytes. Furthermore, GW9662 (a PPARγ antagonist) hindered the upregulation of glucose consumption and insulin signaling molecule expression induced by EPA and DHA in adipocytes. DHA exhibited significant effects in reducing the number of migrated cells and inflammation. The compounds AH7614 and GW9662 hindered the suppressive effects of EPA and DHA on macrophage-induced IR in adipocytes. These findings suggest that DHA has a stronger potential in improving IR in adipocytes through the GPR120/PPARγ pathway in macrophages, when compared to EPA.


Asunto(s)
Tejido Adiposo , Dieta Alta en Grasa , Ácidos Docosahexaenoicos , Ácido Eicosapentaenoico , Inflamación , Resistencia a la Insulina , Ratones Endogámicos C57BL , PPAR gamma , Receptores Acoplados a Proteínas G , Transducción de Señal , Animales , Ácidos Docosahexaenoicos/farmacología , PPAR gamma/metabolismo , Ácido Eicosapentaenoico/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Ratones , Masculino , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Inflamación/metabolismo , Transducción de Señal/efectos de los fármacos , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Células 3T3-L1 , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Células RAW 264.7 , Anilidas/farmacología , Compuestos de Bifenilo , Fenilpropionatos
15.
Sci Rep ; 14(1): 5380, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38438497

RESUMEN

The damage to the back of the target plate is a phenomenon that occurs when concrete is subjected to high-speed impact. In order to study the motion parameters of prefabricated spherical fragments penetrating finite thickness concrete targets at high speeds and the occurrence rules of concrete damage, as well as the impact of target back damage on the motion of fragments, experiments were conducted on 100 mm finite thickness concrete targets with prefabricated spherical fragments. The concrete model parameters in LS-DYNA were modified based on the residual velocity of fragments, and numerical simulations were conducted on the penetration of prefabricated fragments with different impact velocities and concrete target plates with different thicknesses. By analyzing the location of concrete target plate damage, the relationship between concrete thickness and concrete damage was obtained; Combining the motion parameters of fragment penetration process, the phenomenon of concrete collapse was linked to fragment motion, and the influence of concrete thickness on fragment motion parameters was analyzed. The results indicate that the thickness of the finite thickness concrete target plate and the penetration speed of fragments have a significant impact on the damage state of the target back, and further affect the motion change response stage during the penetration process of prefabricated fragments.

16.
Clin Exp Med ; 24(1): 64, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38554186

RESUMEN

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and ß2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.


Asunto(s)
Linfoma de Células B Grandes Difuso , Nomogramas , Humanos , Pronóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Análisis Multivariante
17.
Clin Epigenetics ; 16(1): 42, 2024 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491513

RESUMEN

BACKGROUND: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. METHODS AND RESULTS: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. CONCLUSIONS: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.


Asunto(s)
Dioxigenasas , MicroARNs , Humanos , Diferenciación Celular , Dioxigenasas/genética , ADN/metabolismo , Metilación de ADN , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , MicroARNs/genética , MicroARNs/metabolismo
18.
Clin Transplant ; 38(4): e15300, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38555576

RESUMEN

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Humanos , Citomegalovirus , Inmunoglobulinas Intravenosas/uso terapéutico , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/tratamiento farmacológico , Estudios Retrospectivos , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anticuerpos Antivirales
19.
Nat Commun ; 15(1): 2601, 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38521765

RESUMEN

Complex entangled states are the key resources for measurement-based quantum computations, which is realised by performing a sequence of measurements on initially entangled qubits. Executable quantum algorithms in the graph-state quantum computing model are determined by the entanglement structure and the connectivity of entangled qubits. By generalisation from graph-type entanglement in which only the nearest qubits interact to a new type of hypergraph entanglement in which any subset of qubits can be arbitrarily entangled via hyperedges, hypergraph states represent more general resource states that allow arbitrary quantum computation with Pauli universality. Here we report experimental preparation, certification and processing of complete categories of four-qubit hypergraph states under the principle of local unitary equivalence, on a fully reprogrammable silicon-photonic quantum chip. Genuine multipartite entanglement for hypergraph states is certificated by the characterisation of entanglement witness, and the observation of violations of Mermin inequalities without any closure of distance or detection loopholes. A basic measurement-based protocol and an efficient resource state verification by color-encoding stabilizers are implemented with local Pauli measurement to benchmark the building blocks for hypergraph-state quantum computation. Our work prototypes hypergraph entanglement as a general resource for quantum information processing.

20.
Pharmaceuticals (Basel) ; 17(2)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38399465

RESUMEN

Hydroxyapatite (HAP) has garnered considerable interest in biomedical engineering for its diverse applications. Yet, the synthesis of HAP integrated with functional natural organic components remains an area ripe for exploration. This study innovatively utilizes the versatile properties of tea polyphenol (TP) to synthesize HAP nanomaterials with superior crystallinity and distinct morphologies, notably rod-like structures, via a chemical deposition process in a nitrogen atmosphere. This method ensures an enhanced integration of TP, as confirmed by thermogravimetric (TGA) analysis and a variety of microscopy techniques, which also reveal the dependence of TP content and crystallinity on the synthesis method employed. The research significantly impacts the field by demonstrating how synthesis conditions can alter material properties. It leads the way in employing TP-modified nano-HAP particles for biomedical applications. The findings of this study are crucial as they open avenues for the future development of tailored HAP nanomaterials, aiming at specific medical applications and advancements in nanotechnology.

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