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1.
Mol Med Rep ; 30(6)2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39392044

RESUMEN

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the Transwell migration and invasion assay data shown in Fig. 4A and B on p. 1418 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports  14: 1714­1720, 2016; DOI: 10.3892/mmr.2016.5409].

2.
Nutr Metab (Lond) ; 21(1): 81, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39402528

RESUMEN

BACKGROUND: Despite the exploration of the connections between serum low-density lipoprotein cholesterol (LDL-C) levels and aneurisms in epidemiological studies, causality remains unclear. Therefore, this study aimed to assess the causal impact of LDL-C-lowering targets (HMGCR, PCSK9, NPC1L1, CETP, APOB, and LDLR) on various forms of aneurisms using Mendelian Randomization (MR) analysis. METHODS: Two genetic instruments acted as proxies for exposure to LDL-C-lowering drugs: expression quantitative trait loci of drug target genes and genetic variants linked to LDL-C near drug target genes. Summary-data-based MR (SMR), inverse-variance-weighted MR (IVW-MR), and multivariable MR (MVMR) methods were employed to compute the effect estimates. RESULTS: The SMR analysis revealed substantial associations between increased HMGCR expression and a heightened risk of aortic aneurism (odds ratio [OR] = 1.603, 95% confidence interval [CI] = 1.209-2.124), thoracic aortic aneurism (OR = 1.666, 95% CI = 1.122-2.475), and abdominal aortic aneurism (OR = 1.910, 95% CI = 1.278-2.856). Likewise, IVW-MR analysis demonstrated positive correlations between HMGCR-mediated LDL-C and aortic aneurism (OR = 2.228, 95% CI = 1.702-2.918), thoracic aortic aneurism (OR = 1.751, 95% CI = 1.191-2.575), abdominal aortic aneurism (OR = 4.784, 95% CI = 3.257-7.028), and cerebral aneurism (OR = 1.993, 95% CI = 1.277-3.110). Furthermore, in the MVMR analysis, accounting for body mass index, smoking, and hypertension, a significant positive relationship was established between HMGCR-mediated LDL-C levels and the development of aortic aneurisms, encompassing both thoracic and abdominal subtypes. Similarly, consistent positive associations were observed for PCSK9 and CETP genes, as well as PCSK9-mediated and CETP-mediated LDL-C levels, with the occurrence of aortic aneurism and abdominal aortic aneurism. Nonetheless, the evidence for potential associations between APOB, NPC1L1 and LDLR with specific subtypes of aortic aneurisms lacked consistent support from both SMR and IVW-MR analyses. CONCLUSIONS: Our MR analysis offered compelling evidence of a plausible causal link between HMGCR and an increased risk of aortic aneurism, encompassing both thoracic and abdominal types. These groundbreaking findings further bolster the case for the deployment of HMGCR inhibitors in the treatment of aortic aneurisms, including both thoracic and abdominal variants.

3.
Biochem Pharmacol ; 230(Pt 1): 116564, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39366431

RESUMEN

As a biological variable, sex influences the metabolism of and/or response to certain drugs. Vicagrel is being developed as an investigational new drug in China; however, it is unknown whether sex could affect its metabolic activation and platelet responsiveness. This study aimed to determine whether such differences could exist, and to elucidate the mechanisms involved. Orchiectomized (ORX) or ovariectomized (OVX) mouse models were used to investigate the effects of androgens or estrogens on the metabolic activation of and platelet response to vicagrel. Plasma vicagrel active metabolite H4 concentrations, platelet inhibition of vicagrel, and protein levels of intestinal hydrolases Aadac and Ces2 were measured, respectively. Further, p38-MAPK signaling pathway was enriched, whose role was determined using SB202190. Results showed that female mice exhibited significantly elevated systemic exposure of H4 and enhanced platelet responses to vicagrel than males, and that protein expression levels of Aadac and Ces2 differed by sex. OVX mice exhibited less changes than sham mice. ORX mice exhibited increases in protein levels of intestinal hydrolases, systemic exposure of H4, and platelet inhibition of vicagrel, but dihydrotestosterone (DHT) reversed these changes in ORX mice and suppressed these changes in OVX mice. Phosphorylated p38 levels were reduced in female or ORX mice but increased in ORX mice by DHT. SB202190 reversed DHT-induced changes observed in ORX mice. We concluded that sex differences exist in metabolic activation of and platelet response to vicagrel in mice through elevation of p38 phosphorylation by androgens, suggesting sex-based vicagrel dosage adjustments for patient care.

4.
Parasit Vectors ; 17(1): 403, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334398

RESUMEN

BACKGROUND: Insecticide resistance poses a significant challenge in the implementation of vector-borne disease control strategies. We have assessed the resistance levels of Aedes albopictus to deltamethrin and pyriproxyfen (PPF) in Fujian Province (China) and investigated the correlation between these resistance levels and mutations in the voltage-gated sodium channel (VGSC). METHODS: The WHO bioassay protocol was used to evaluate the resistance coefficient of Ae. albopictus to deltamethrin and PPF, comparing a susceptible population from the Foshan (FS) area with wild populations from the Sanming (SM), Quanzhou (QZ), Zhangzhou (ZZ), Putian (PT) and Fuzhou (FZ) areas in Fujian Province. Genomic DNA was analyzed by PCR and sequencing to detect knockdown resistance (kdr) in the VGSC, specifically at the pyrethroid resistance alleles V1016V, I1532I and F1534F. Molecular docking was also performed to analyze the binding interactions of PPF and its metabolite 4'-OH-PPF to cytochrome P450 (CYP) 2C19, 2C9 and 3A4 and Ae. albopictus methoprene-tolerant receptors (AeMet), respectively. RESULTS: The analysis of resistance to deltamethrin and PPF among Ae. albopictus populations from the various regions revealed that except for the sensitive population in FS and the SM population, the remaining four regional populations demonstrated resistance levels ranging from 4.31- to 18.87-fold for deltamethrin and from 2.85- to 3.62-fold for PPF. Specifically, the FZ and PT populations exhibited high resistance to deltamethrin, whereas the ZZ and QZ populations approached moderate resistance levels. Also, the resistance of the FZ, PT and ZZ populations to PPF increased slowly but consistently with the increasing trend of deltamethrin resistance. Genomic analysis identified multiple non-synonymous mutations within the VGSC gene; the F1534S and F1534L mutations showed significant resistance to deltamethrin in Ae. albopictus. Molecular docking results revealed that PPF and its metabolite 4'-OH-PPF bind to the Ae. albopictus AeMet receptor and CYP2C19. CONCLUSIONS: The wild Ae. albopictus populations of Fujian Province showed varying degrees of resistance to deltamethrin and PPF and a trend of cross-resistance to deltamethrin and PPF. Increased vigilance is needed for potential higher levels of cross-resistance, especially in the PT and FZ regions.


Asunto(s)
Aedes , Resistencia a los Insecticidas , Insecticidas , Simulación del Acoplamiento Molecular , Nitrilos , Piretrinas , Piridinas , Canales de Sodio Activados por Voltaje , Animales , Piretrinas/farmacología , Nitrilos/farmacología , Aedes/genética , Aedes/efectos de los fármacos , Resistencia a los Insecticidas/genética , Insecticidas/farmacología , Canales de Sodio Activados por Voltaje/genética , Canales de Sodio Activados por Voltaje/metabolismo , China , Piridinas/farmacología , Mutación , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Mosquitos Vectores/genética , Mosquitos Vectores/efectos de los fármacos , Femenino , Bioensayo
5.
Polymers (Basel) ; 16(18)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39339065

RESUMEN

Carbon fiber-reinforced polymer (CFRP), known for its light weight, high strength, and corrosion-resistant properties, is extensively used in the lightweight design of satellite components, the optimization of electronic device casings, and the processing of high-performance composite materials in the defense sector. This study employs picosecond laser drilling technology for the precision machining of CFRP, demonstrating its advantages over traditional mechanical drilling and other unconventional methods in significantly reducing the heat-affected zone (HAZ) and enhancing hole wall quality. The optimization of laser power, scanning speed, and fill times via response surface methodology (RSM) significantly reduced the hole wall taper to 4.160° and confined the HAZ to within 18.577 µm, thereby enhancing machining precision. The actual test results show that the deviations in the hole taper and HAZ width were 5.0% and 2.2%, respectively, further verifying the effectiveness of the optimization method. This technique not only improves processing quality but also offers significant industrial application value in the machining of materials for related high-tech fields.

6.
Sci Rep ; 14(1): 20890, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39244628

RESUMEN

The construction of large reservoirs has modified the process of water and sediment transport downstream, resulting in changes in the morphology of the river cross-section. Changes in water and sand transport and cross-sectional morphology are reflected in the rating curve at the cross-section. This study analyzed the variations in the rating curve at the Huayuankou (HYK) section and their influencing factors, and conducted water level predictions based on this relationship. The findings revealed that while the annual mean water level has shown a declining tendency over the past 20 years, the annual mean discharge has shown a constant pattern. The rating curve at this stretch narrowed from a rope-loop type curve in its natural condition to a more stable single curve as a result of the construction of the dam upstream of the HYK section. The effect of pre-flood section morphology and the water-sediment process on the scattering degree of the rating curve is inverse; increasing roughness and hydraulic radius decreases scattering degree, while increasing sand content and sand transport rate increases scattering degree. Using the measured data from 2020 as an example, the feasibility of predicting cross-sectional water levels using the rating curve was verified. The prediction results were accurate when the flow was between 1000 and 2800 m3/s; However, when the flow was between 2800 and 4000 m3/s, the forecast results were typically slightly lower than the measured values. Overall, the method demonstrates good predictive accuracy. Insight from the method can be used to predict water levels to better inform decision making about water resources management, and flood emergency response in the lower Yellow River.

7.
Xenobiotica ; : 1-11, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39126503

RESUMEN

This study aimed to determine changes in the hydrolysis of vicagrel, a substrate drug of arylacetamide deacetylase (Aadac) and carboxylesterase 2 (Ces2), in P-glycoprotein (P-gp)-deficient or P-gp-inhibited mice and to elucidate the mechanisms involved.Male wild-type (WT) and P-gp knock-out (KO) mice were used to investigate the systemic exposure of vicagrel thiol active metabolite H4 and platelet response to vicagrel, and the mRNA and protein expression levels of intestinal Aadac and Ces2. Moreover, WT mice were administered vicagrel alone or in combination with elacridar (a potent P-gp inhibitor) to determine drug-drug interactions.Compared with WT mice, P-gp KO mice exhibited significant increases in the systemic exposure of H4, the protein expression levels of intestinal Aadac and Ces2, and inhibition of ADP-induced platelet aggregation by vicagrel. Further, the H4 exposure was positively correlated with intestinal Aadac protein expression levels but did not vary with short-term inhibition of P-gp efflux activity by elacridar.P-gp-deficient mice, rather than elacridar-treated mice, exhibited significant upregulation of intestinal Aadac and Ces2 and thus, enhanced metabolic activation of and platelet response to vicagrel, suggesting that the metabolic activation of vicagrel may vary with P-gp deficiency, not P-gp inhibition, in mice.

8.
Plast Reconstr Surg Glob Open ; 12(8): e6049, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39148506

RESUMEN

Background: After tumor resection, lymphadenectomy, and radiotherapy, recurrent lymphatic fluid leakage and infection can occur in the inguinal region, contributing to severe localized tissue fibrosis. When wounds form in this region, they tend to heal slowly over extended periods, and no optimal approach for treating these complex wounds has yet been established. Methods: Groin wound debridement and dissection of the vessels in the wound recipient site were performed by the burn surgeon. A general surgeon performed the laparoscopic partial omentum excision. One portion of the omentum was used to fill the large inguinal space, whereas the other portion was laid flat on the wound sites in the groin and anterior perineum to facilitate the restoration of appropriate lymphatic fluid reflux. The vessels of the omentum were microsurgically anastomosed with the vessels in the recipient site. Thin split-thickness slices of skin were then taken from this donor site based on the size of the wound. Results: After the successful establishment of revascularization between the flap and recipient sites, lymphatic fluid leakage was not observed in this patient. No inguinal wounding or lymphatic exudate were evident in the patient during follow-up, and significant improvements in lymphedema of the lower extremities were evident. Conclusions: In this article, we discuss the advantages and disadvantages of vascularized omentum lymphatic transplantation. Overall, this procedure represents a promising new approach for the treatment of refractory wounds caused by lymphatic fistulas.

9.
Spinal Cord ; 62(8): 429-439, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38849489

RESUMEN

STUDY DESIGN: Animal studies OBJECTIVES: To evaluate the therapeutic effect of olfactory mucosa mesenchymal stem cell (OM-MSCs) transplantation in mice with spinal cord injury (SCI) and to explore the mechanism by which OM-MSCs inhibit neuroinflammation and improve SCI. SETTING: Xiangya Hospital, Central South University; Affiliated Hospital of Guangdong Medical University. METHODS: Mice (C57BL/6, female, 6-week-old) were randomly divided into sham, SCI, and SCI + OM-MSC groups. The SCI mouse model was generated using Allen's method. OM-MSCs were immediately delivered to the lateral ventricle after SCI using stereotaxic brain injections. One day prior to injury and on days 1, 5, 7, 14, 21, and 28 post-injury, the Basso Mouse Scale and Rivlin inclined plate tests were performed. Inflammation and microglial polarization were evaluated using histological staining, immunofluorescence, and qRT-PCR. RESULTS: OM-MSCs originating from the neuroectoderm have great potential in the management of SCI owing to their immunomodulatory effects. OM-MSCs administration improved motor function, alleviated inflammation, promoted the transformation of the M1 phenotype of microglia into the M2 phenotype, facilitated axonal regeneration, and relieved spinal cord injury in SCI mice. CONCLUSIONS: OM-MSCs reduced the level of inflammation in the spinal cord tissue, protected neurons, and repaired spinal cord injury by regulating the M1/M2 polarization of microglia.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Microglía , Mucosa Olfatoria , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Mucosa Olfatoria/citología , Microglía/fisiología , Ratones , Femenino , Modelos Animales de Enfermedad , Células Madre Mesenquimatosas/fisiología , Recuperación de la Función/fisiología , Polaridad Celular/fisiología
10.
Chemosphere ; 361: 142517, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38830464

RESUMEN

Indoor volatile formaldehyde is a serious health hazard. The development of low-temperature and efficient nonhomogeneous oxidation catalysts is crucial for protecting human health and the environment but is also quite challenging. Single-atom catalysts (SACs) with active centers and coordination environments that are precisely tunable at the atomic level exhibit excellent catalytic activity in many catalytic fields. Among two-dimensional materials, the nonmagnetic monolayer material g-C3N4 may be a good platform for loading single atoms. In this study, the effect of nitrogen defect formation on the charge distribution of g-C3N4 is discussed in detail using density functional theory (DFT) calculations. The effect of nitrogen defects on the activated molecular oxygen of Pt/C3N4 was systematically revealed by DFT calculations in combination with molecular orbital theory. Two typical reaction mechanisms for the catalytic oxidation of formaldehyde were proposed based on the Eley-Rideal (E-R) mechanism. Pt/C3N4-V3N was more advantageous for path 1, as determined by the activation energy barrier of the rate-determining step and product desorption. Finally, the active centers and chemical structures of Pt/C3N4 and Pt/C3N4-V3N were verified to have good stability at 375 K by determination of the migration energy barriers and ab initio molecular dynamics simulations. Therefore, the formation of N defects can effectively anchor single-atom Pt and provide additional active sites, which in turn activate molecular oxygen to efficiently catalyze the oxidation of formaldehyde. This study provides a better understanding of the mechanism of formaldehyde oxidation by single-atom Pt catalysts and a new idea for the development of Pt as well as other metal-based single-atom oxidation catalysts.


Asunto(s)
Teoría Funcional de la Densidad , Formaldehído , Oxidación-Reducción , Platino (Metal) , Formaldehído/química , Catálisis , Platino (Metal)/química , Compuestos de Nitrógeno/química , Simulación de Dinámica Molecular , Oxígeno/química , Grafito
11.
J Hazard Mater ; 474: 134710, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38820758

RESUMEN

Indoor formaldehyde pollution seriously jeopardizes human health. The development of efficient and stable non-precious metal catalysts for low-temperature catalytic degradation of formaldehyde is a promising approach. In this study, TiO2 {001} and {101} supports were loaded with different ratios of Mn and Ce active components, and the effects of the ratios of the active components on the catalytic activity were investigated. The elemental oxidation states, redox capacities, active oxygen mobilities and acid site distributions of the catalysts were determined using characterization techniques such as XPS, H2-TPR, O2-TPD, and NH3-TPD. In situ infrared spectroscopy was utilized to reveal the differences in the two-step dehydrogenation reactions of dioxymethylene (DOM) in 5Mn1Ce/Ti-NS and 5Mn1Ce/Ti-NP. Density-functional theory was used to investigate the differences in the catalytic steps and maximum energy barriers of Mn-Ce/Ti-NS and Mn-Ce/Ti-NP for HCHO. The differences in catalytic activity due to the influence of the manganese and cerium active components on the {001} and {101} crystal faces of anatase titanium dioxide are comprehensively revealed. Exposure of the supported crystalline surfaces alters the catalytic activity centers and reaction pathways at the molecular level. This study provides experimental and theoretical guidance for the selection of exposed crystalline surfaces for loaded catalysts.

12.
J Hazard Mater ; 472: 134466, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38718507

RESUMEN

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. ß-amyloid (Aß) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aß and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.


Asunto(s)
Cloruro de Cadmio , Senescencia Celular , Degradación Asociada con el Retículo Endoplásmico , Neuronas , Receptores sigma , Animales , Senescencia Celular/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Cloruro de Cadmio/toxicidad , Receptores sigma/metabolismo , Degradación Asociada con el Retículo Endoplásmico/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Ratones , Proteínas tau/metabolismo , Masculino , Enfermedad de Alzheimer/metabolismo , Humanos , Melatonina/farmacología , Ratones Endogámicos C57BL
13.
Acta Pharmacol Sin ; 45(8): 1618-1631, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38641745

RESUMEN

Hypertension is a prominent contributor to vascular injury. Deubiquinatase has been implicated in the regulation of hypertension-induced vascular injury. In the present study we investigated the specific role of deubiquinatase YOD1 in hypertension-induced vascular injury. Vascular endothelial endothelial-mesenchymal transition (EndMT) was induced in male WT and YOD1-/- mice by administration of Ang II (1 µg/kg per minute) via osmotic pump for four weeks. We showed a significantly increased expression of YOD1 in mouse vascular endothelial cells upon Ang II stimulation. Knockout of YOD1 resulted in a notable reduction in EndMT in vascular endothelial cells of Ang II-treated mouse; a similar result was observed in Ang II-treated human umbilical vein endothelial cells (HUVECs). We then conducted LC-MS/MS and co-immunoprecipitation (Co-IP) analyses to verify the binding between YOD1 and EndMT-related proteins, and found that YOD1 directly bound to ß-catenin in HUVECs via its ovarian tumor-associated protease (OTU) domain, and histidine at 262 performing deubiquitination to maintain ß-catenin protein stability by removing the K48 ubiquitin chain from ß-catenin and preventing its proteasome degradation, thereby promoting EndMT of vascular endothelial cells. Oral administration of ß-catenin inhibitor MSAB (20 mg/kg, every other day for four weeks) eliminated the protective effect of YOD1 deletion on vascular endothelial injury. In conclusion, we demonstrate a new YOD1-ß-catenin axis in regulating Ang II-induced vascular endothelial injury and reveal YOD1 as a deubiquitinating enzyme for ß-catenin, suggesting that targeting YOD1 holds promise as a potential therapeutic strategy for treating ß-catenin-mediated vascular diseases.


Asunto(s)
Angiotensina II , Células Endoteliales de la Vena Umbilical Humana , Ratones Endogámicos C57BL , Ratones Noqueados , beta Catenina , Animales , beta Catenina/metabolismo , Humanos , Angiotensina II/farmacología , Angiotensina II/metabolismo , Masculino , Ratones , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Endotelial-Mesenquimatosa
14.
Chemosphere ; 356: 142024, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38614396

RESUMEN

Indoor formaldehyde (HCHO) pollution poses a major risk to human health. Low-temperature catalytic oxidation is an effective method for HCHO removal. The high activity and selectivity of single atomic catalysts provide a possibility for the development of efficient non-precious metal catalysts. In this study, the most stable single-atom catalyst Ti-Ti4C3O2 was screened by density functional theory among many single atomic catalysts with two-dimensional (2D) monolayer Ti4C3O2 as the support. The computational results show that Ti-Ti4C3O2 is highly selective to HCHO and O2 in complex environments. The HCHO oxidation reaction pathways are proposed based on the Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) mechanisms. According to the reaction energy and energy span models, the E-R mechanism has a lower maximum energy barrier and higher catalytic efficiency than the L-H mechanism. In addition, the stability of the Ti-Ti4C3O2 structure and active center was verified by diffusion energy barrier and ab initio molecular dynamics simulations. The above results indicate that Ti-Ti4C3O2 is a promising non-precious metal catalyst. The present study provides detailed theoretical insights into the catalytic oxidation of HCHO by Ti-Ti4C3O2, as well as an idea for the development of efficient non-precious metal catalysts based on 2D materials.


Asunto(s)
Teoría Funcional de la Densidad , Formaldehído , Oxidación-Reducción , Titanio , Formaldehído/química , Catálisis , Titanio/química , Contaminación del Aire Interior , Contaminantes Atmosféricos/química , Simulación de Dinámica Molecular
15.
J Nanobiotechnology ; 22(1): 208, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664789

RESUMEN

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.


Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , Osteocitos , Osteogénesis , Tropomiosina , Animales , Masculino , Ratones , Adipogénesis , Diferenciación Celular , Células Cultivadas , Vesículas Extracelulares/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ratones Endogámicos C57BL , Ratones Transgénicos , Osteoclastos/metabolismo , Osteocitos/metabolismo , Osteoporosis/metabolismo , Tropomiosina/metabolismo , Tropomiosina/genética
16.
Clin Chem ; 70(6): 820-829, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38517460

RESUMEN

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.


Asunto(s)
Diagnóstico Prenatal , Humanos , Femenino , Embarazo , Estudios Prospectivos , Diagnóstico Prenatal/métodos , Adulto , Cariotipificación , Mapeo Cromosómico , Líquido Amniótico/química , Líquido Amniótico/citología
17.
Pathol Res Pract ; 256: 155230, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38461693

RESUMEN

Papillary thyroid carcinoma (PTC) is generally recognized as a slow-growing tumor. However, a small subset of patients may still experience relapse or metastasis shortly after therapy, leading to a poor prognosis and raising concerns about excessive medical treatment. One major challenge lies in the inadequacy of effective biomarkers for accurate risk stratification. Long non-coding RNAs (lncRNAs), which are closely related to malignant characteristics and poor prognosis, play a significant role in the genesis and development of PTC through various pathways. The objective of this review is to provide a comprehensive summary of the biological functions of lncRNAs in PTC, identify prognosis-relevant lncRNAs, and explore their potential mechanisms in drug resistance to BRAF kinase inhibitors, tumor dedifferentiation, and lymph node metastasis. By doing so, this review aims to offer valuable references for both basic research and the prediction of PTC prognosis.


Asunto(s)
Carcinoma Papilar , ARN Largo no Codificante , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Pronóstico , Neoplasias de la Tiroides/patología , ARN Largo no Codificante/genética , Carcinoma Papilar/patología , Recurrencia Local de Neoplasia , Proteínas Proto-Oncogénicas B-raf/metabolismo
18.
Arch Biochem Biophys ; 753: 109893, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38309681

RESUMEN

Adipose tissue-derived stem cells (ADSCs) are a kind of stem cells with multi-directional differentiation potential, which mainly restore tissue repair function and promote cell regeneration. It can be directionally differentiated into Schwann-like cells to promote the repair of peripheral nerve injury. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the repair of nerve injury, but the underlying mechanism remains unclear, which seriously limits its further application.The study aimed to identify the molecular mechanism by which overexpression of glial cell line-derived neurotrophic factor (GDNF) facilitates the differentiation of ADSCs into Schwann cells, enhancing nerve regeneration after injury. In vitro, ADSCs overexpressing GDNF for 48 h exhibited changes in their morphology, with 80% of the cells having two or more prominences. Compared with that of ADSCs, GDNF-ADSCs exhibited increased expression of the Schwann cell marker S100, nerve damage repair-related factors.ADSC cells in normal culture and ADSC cells were overexpressing GDNF(GDNF-ADSCs) were analysed using TMT-Based Proteomic Analysis and revealed a significantly higher expression of MTA1 in GDNF-ADSCs than in control ADSCs. Hes1 expression was significantly higher in GDNF-ADSCs than in ADSCs and decreased by MTA1 silencing, along with a simultaneous decrease in the expression of S100 and nerve damage repair factors. These findings indicate that GDNF promotes the differentiation of ADSCs into Schwann cells and induces factors that accelerate peripheral nerve damage repair.


Asunto(s)
Factor Neurotrófico Derivado de la Línea Celular Glial , Proteómica , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Regeneración Nerviosa , Tejido Adiposo , Diferenciación Celular , Células de Schwann
19.
Sci Rep ; 14(1): 5034, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38424211

RESUMEN

A large number of burnt rocks in some open-pit mines in Xinjiang, Inner Mongolia and Ningxia have a great influence on the blasting effect. For this kind of rock, through the analysis of physical and chemical changes, combined with ANSYS/LS-DYNA and PFC 2D numerical simulation software, a burnt rock model with multiple joint cracks and irregular distribution is constructed to simulate the blasting process of burnt rock under the combined action of stress wave and detonation gas. The results show that the fracture of rock mass affects the propagation of blasting cracks in the fracture area, resulting in stress concentration and stress hindrance. The action time of stress wave is reduced, and the energy of blasting gas is partially absorbed by the fracture, resulting in uneven stress on the burnt rock bench and seriously affecting the bench blasting effect.

20.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(1): 56-61, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38404273

RESUMEN

OBJECTIVE: To analyze the changes rule of serum procalcitonin (PCT) levels in patients with traumatic brain injury in plateau areas, and to evaluate its value in assessing the severity and prognosis of the patients. METHODS: A prospective cohort study was conducted. The patients with traumatic brain injury admitted to the critical care medicine departments of Xining Third People's Hospital (at an altitude of 2 260 metres) and Golmud City People's Hospital (at an altitude of 2 780 metres) from May 2018 to September 2022 were enrolled. According to the Glasgow coma scale (GCS) score at admission, the patients were divided into mild injury group (GCS score 13-15), severe injury group (GCS score 9-12), and critical injury group (GCS score 3-8). All patients received active treatment. Chemiluminescence immunoassay was used to measure the serum PCT levels of patients on the 1st, 3rd, 5th, and 7th day of admission. The Kendall tau-b correlation method was used to analyze the correlation between serum PCT levels at different time points and the severity of the disease. The patients were followed up until October 30, 2022. The prognosis of the patients was collected. The baseline data of patients with different prognosis were compared. The Cox regression method was used to analyze the relationship between baseline data, serum PCT levels at different time points and prognosis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of serum PCT levels at different time points for death during follow-up. RESULTS: Finally, a total of 120 patients with traumatic brain injury were enrolled, including 52 cases in the mild injury group, 40 cases in the severe injury group, and 28 cases in the critical injury group. The serum PCT levels of patients in the mild injury group showed a continuous downward trend with the prolongation of admission time. The serum PCT levels in the severe injury and critical injury groups reached their peak at 3 days after admission, and were significantly higher than those in the mild injury group (µg/L: 3.53±0.68, 4.47±0.63 vs. 0.40±0.14, both P < 0.05), gradually decreasing thereafter, but still significantly higher than the mild injured group at 7 days. Kendall tau-b correlation analysis showed that there was a significant positive correlation between serum PCT levels on days 1, 3, 5, and 7 of admission and the severity of disease (r value was 0.801, 0.808, 0.766, 0.528, respectively, all P < 0.01). As of October 30, 2022, 92 out of 120 patients with traumatic brain injury survived and 28 died, with a mortality of 23.33%. Compared with the survival group, the GCS score, serum interleukin-6 (IL-6) levels, white blood cell count (WBC) in peripheral blood, and PCT levels in cerebrospinal fluid at admission in the death group were significantly increased [GCS score: 5.20±0.82 vs. 4.35±0.93, IL-6 (ng/L): 1.63±0.45 vs. 0.95±0.27, blood WBC (×109/L): 14.31±2.03 vs. 11.95±1.98, PCT in cerebrospinal fluid (µg/L): 11.30±1.21 vs. 3.02±0.68, all P < 0.01]. The serum PCT levels of patients in the survival group showed a continuous downward trend with prolonged admission time. The serum PCT level in the death group peaked at 3 days after admission and was significantly higher than that in the survival group (µg/L: 4.11±0.62 vs. 0.52±0.13, P < 0.01), gradually decreasing thereafter, but still significantly higher than the survival group at 7 days. Cox regression analysis showed that serum IL-6 levels [hazard ratio (HR) = 17.347, 95% confidence interval (95%CI) was 5.874-51.232], WBC in peripheral blood (HR = 1.383, 95%CI was 1.125-1.700), PCT levels in cerebrospinal fluid (HR = 1.952, 95%CI was 1.535-2.482) at admission and serum PCT levels on admission days 1, 3, 5, and 7 [HR (95%CI) was 6.776 (1.844-24.906), 1.840 (1.069-3.165), 3.447 (1.284-9.254), and 6.666 (1.214-36.618), respectively] were independent risk factors for death during follow-up in patients with traumatic brain injury (all P < 0.05). ROC curve analysis showed that the AUC of serum PCT levels on days 1, 3, 5, and 7 for predicting death during follow-up in patients with traumatic brain injury was all > 0.8 [AUC (95%CI) was 0.898 (0.821-0.975), 0.800 (0.701-0.899), 0.899 (0.828-0.970), 0.865 (0.773-0.958), respectively], indicating ideal predictive value. The optimal cut-off value for serum PCT level at 3 days of admission was 1.88 µg/L, with the sensitivity of 78.6% and specificity of 88.0% for predicting death during follow-up. CONCLUSIONS: Abnormal expression of serum PCT levels in patients with traumatic brain injury on the 3rd day of admission was found. The serum PCT levels greater than 3 µg/L may be related to severe illness. The serum PCT levels greater than 1.88 µg/L can predict the poor prognosis of patients. Dynamic observation of changes in serum PCT levels has good evaluation value for the severity and prognosis of patients with traumatic brain injury in plateau areas.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Sepsis , Humanos , Polipéptido alfa Relacionado con Calcitonina , Estudios Prospectivos , Interleucina-6 , Pronóstico , Lesiones Traumáticas del Encéfalo/diagnóstico , Curva ROC , Estudios Retrospectivos , Sepsis/metabolismo
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