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1.
J Hazard Mater ; 480: 135930, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307021

RESUMEN

Oxygenation of pyrite (Py) is known to mediate generation of reactive oxygen species (ROS) with these species capable of inducing contaminants degradation, whereas the possible participation of coexisting Fe(III) minerals in these processes is still unclear. This study finds that freshly formed ferrihydrite (Fh) significantly enhances the Py-mediated sulfamethoxazole (SMX) degradation process. Through the 56Fe isotope tracer experiment and a series of control experiments, Fh is found to be reduced by Py to form secondary solid-phase Fe(II) species (Fe(II)RF) which in turn facilitates generation of H2O2 from the O2 reduction pathway. However, Py was found to mediate rapid structural transformation of Fh to form more thermodynamically stable goethite and hematite with these less redox active minerals unable to sustainably promote the Py-mediated SMX degradation process. Therefore, the improvement of Fh on Py-mediated SMX degradation process is not readily observable in reaction systems with low concentrations of coexisting Fh. In comparison, continuing input of 10 mM Fh increased the degradation efficiency of SMX by 60 % over three days. Our results demonstrate that the oxidative degradation of organic contaminants over the oxygenation of Py when coexisting with Fh can be more significant but currently underestimated.

2.
AAPS J ; 26(5): 102, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266802

RESUMEN

Oral administration of peptide represents a promising delivery route, however, it is hindered by the harsh gastrointestinal environment, leading to low in vivo absorption. In this study, auto-adaptive protein corona-AT 1002-cationic liposomes (Pc-AT-CLs) are constructed with the characteristic of hydrophilic and electrically neutral surface properties for the encapsulation of liraglutide. BSA protein corona is used to coat AT-CLs reducing the adherence of mucus, and may fall off after penetrating the mucus layer. Transmucus transport experiment demonstrated that the mucus penetration amount of Pc-AT-CLs are 1.45 times that of AT-CLs. After penetrating the mucus layer, AT-CLs complete transmembrane transport by the dual action of AT and cationic surface properties. Transmembrane transport experiment demonstrated that the apparent permeability coefficient (Papp) of AT-CLs is 2.03 times that of CLs. In vivo tests demonstrated that Pc-AT-CLs exhibited a significant hypoglycemic effect and enhanced the relative bioavailability comparing to free liraglutide. Pc-AT-CLs protect liraglutide from degradation, facilitate its absorption, and ultimately improve its oral bioavailability.


Asunto(s)
Sistemas de Liberación de Medicamentos , Hipoglucemiantes , Liposomas , Liraglutida , Moco , Animales , Liraglutida/administración & dosificación , Liraglutida/farmacocinética , Liraglutida/farmacología , Moco/metabolismo , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/química , Humanos , Disponibilidad Biológica , Administración Oral , Masculino , Ratas Sprague-Dawley , Ratas , Absorción Intestinal/efectos de los fármacos
3.
Sci Total Environ ; 952: 175833, 2024 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-39214359

RESUMEN

Pyrite-based Fenton-like processes have been extensively studied for wastewater decontamination; however, most relevant studies placed excessive emphasis on the homogeneous Fenton reaction mediated by aqueous Fe2+, resulting in the proposed technologies facing issues such as additional acid requirements for pH adjustment and excessive iron sludge production. Herein, through in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS), custom dual-chamber reactor experiments, and a series of control experiments, significant hydroxyl radical generation was identified during the pyrite/H2O2 process, while the dominant reactive iron species was verified to the structural Fe sites on the pyrite surface, rather than structural Fe(II) in secondary iron minerals and surface adsorbed Fe2+. Consequently, even with significant suppression of the homogeneous Fenton pathway, the pyrite/H2O2 process exhibited significant degradation efficiency for sulfamethoxazole (SMX) at pH 4. Moreover, the pyrite/H2O2 process was found to selectively remove 50 µM of pollutants with high affinity for pyrite (bisphenol A, carbamazepine, nitrobenzene, and SMX), even in the presence of 50-100 mM methanol. Compared to the typical iron-based reductive catalyst (zero-valent iron, ZVI), pyrite mediated a Fenton process with greater potential for practical applications at pH 4, achieving a 43.75-fold reduction in iron sludge production and almost doubling the H2O2 utilization efficiency. Additionally, in contrast to ZVI, minimal iron oxide formed on the pyrite surface during the oxidation process. Thus, after seven cycles of degradation experiments, the decontamination efficiency of the pyrite/H2O2 process remained stable. These findings are crucial for understanding the complex environmental behavior of pyrite in both natural and engineering processes and provide a new perspective for the efficient utilization of pyrite resources as well.

4.
Talanta ; 280: 126745, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39180874

RESUMEN

The effective method for trypsin purification should be established because trypsin has important economic value. In this work, a novel and simple strategy was proposed for fabricating micron-sized magnetic Fe3O4@agarose-benzamidine beads (MABB) with benzamidine as a ligand, which can efficiently and selectively capture trypsin. The micro-sized MABB, with clear spherical core-shell structure and average particle size of 6.6 µm, showed excellent suspension ability and magnetic responsiveness in aqueous solution. The adsorption capacity and selectivity of MABB towards target trypsin were significantly better than those of non-target lysozyme. According to the Langmuir equation, the maximum adsorption capacity of MABB for trypsin was 1946 mg g-1 at 25 °C, and the adsorption should be a physical sorption process. Furthermore, the initial adsorption rate and half equilibrium time of MABB toward trypsin were 787.4 mg g-1 min-1 and 0.71 min, respectively. To prove the practicability, MABB-based magnetic solid-phase extraction (MSPE) was proposed, and the related parameters were optimized in detail to improve the purification efficiency. With Tris-HCl buffer (50 mM, 10 mM CaCl2, pH 8.0) as extraction buffer, Tris-HCl buffer (50 mM, 100 mM CaCl2, pH 8.0) as rinsing buffer, acidic eluent (0.01 M HCl, 0.5 M NaCl, pH 2.0) as eluent buffer and alkaline buffer (1 M Tris-HCl buffer, pH 10.0) as neutralization solution, the MABB-based MSPE was successfully used for trypsin purification from the viscera of grass carp (Ctenopharyngodon idella). The molecular weight of purified trypsin was determined as approximate 23 kDa through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified trypsin was highly active from 30 °C to 60 °C, with an optimum temperature of 50 °C, and was tolerant to pH variation, exhibiting 85 % of maximum enzyme activity from pH 7.0 to 10.0. The results demonstrated that the proposed MABB-based MSPE could effectively purify trypsin and ensure the biological activity of purified trypsin. Therefore, we believe that the novel MABB could be applicable for efficient purification of trypsin from complex biological systems.


Asunto(s)
Benzamidinas , Sefarosa , Tripsina , Animales , Tripsina/química , Tripsina/metabolismo , Sefarosa/química , Benzamidinas/química , Benzamidinas/aislamiento & purificación , Adsorción , Peces , Tamaño de la Partícula , Extracción en Fase Sólida/métodos , Concentración de Iones de Hidrógeno
5.
J Nanobiotechnology ; 22(1): 434, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044233

RESUMEN

Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-ß1 (TGF-ß1) is a fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-ß1 (MsiTGF-ß1), and their therapeutic potential for bleomycin (BLM)-induced PF was investigated. M-siTGF-ß1 was introduced into the lungs of mice with PF through nebulization. The collagen penetration effect and lysosomal escape ability were verified in vitro. Inhaled MsiTGF-ß1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, and increased the survival rate of PF mice by 4.7-fold. M-siTGF-ß1 protected lung tissue from BLM toxicity by efficiently delivering specific siRNA to the lungs, leading to TGF-ß1 mRNA silencing and epithelial mesenchymal transition pathway inhibition. Therefore, M-siTGF-ß1 offers a promising avenue for therapeutic intervention in fibrosis-related disorders.


Asunto(s)
Bleomicina , Colágeno , Transición Epitelial-Mesenquimal , Exosomas , Pulmón , Leche , Fibrosis Pulmonar , ARN Interferente Pequeño , Factor de Crecimiento Transformador beta1 , Animales , Exosomas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Ratones , Colágeno/metabolismo , Bleomicina/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Pulmón/efectos de los fármacos , Leche/química , Ratones Endogámicos C57BL , Humanos , Permeabilidad , Masculino , Nebulizadores y Vaporizadores
6.
Blood ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39046786

RESUMEN

Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20-30% of people still experienced therapy failure. Data from 1,955 consecutive subjects with chronic-phase CML diagnosed by the European LeukemiaNet (ELN) recommendations from 1 center receiving initial TKI imatinib or a second-generation (2G-) TKI therapy were interrogated to develop a clinical prediction model for TKI therapy failure. This model was subsequently validated in 3,454 subjects from 76 other centers. Using the predictive clinical co-variates associated with TKI therapy failure, we developed a model that stratified subjects into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (p < 0.001). There was good discrimination and calibration in the external validation dataset, and the performance was consistent with that of the training dataset. Our model had the better prediction discrimination than the Sokal and ELTS scores did, with the greater time-dependent area under the receiver-operator characteristic curve (AUROC) values and a better ability to re-defined the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G-TKI therapy failure in people with chronic-phase CML.

7.
Front Pharmacol ; 15: 1412300, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38966553

RESUMEN

Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The "gut-heart" axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg-1·d-1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis.

8.
Transl Lung Cancer Res ; 13(6): 1277-1295, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38973963

RESUMEN

Background: Immune therapy has become first-line treatment option for patients with lung cancer, but some patients respond poorly to immune therapy, especially among patients with lung adenocarcinoma (LUAD). Novel tools are needed to screen potential responders to immune therapy in LUAD patients, to better predict the prognosis and guide clinical decision-making. Although many efforts have been made to predict the responsiveness of LUAD patients, the results were limited. During the era of immunotherapy, this study attempts to construct a novel prognostic model for LUAD by utilizing differentially expressed genes (DEGs) among patients with differential immune therapy responses. Methods: Transcriptome data of 598 patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) database, which included 539 tumor samples and 59 normal control samples, with a mean follow-up time of 29.69 months (63.1% of patients remained alive by the end of follow-up). Other data sources including three datasets from the Gene Expression Omnibus (GEO) database were analyzed, and the DEGs between immunotherapy responders and nonresponders were identified and screened. Univariate Cox regression analysis was applied with the TCGA cohort as the training set and GSE72094 cohort as the validation set, and least absolute shrinkage and selection operator (LASSO) Cox regression were applied in the prognostic-related genes which fulfilled the filter criteria to establish a prognostic formula, which was then tested with time-dependent receiver operating characteristic (ROC) analysis. Enriched pathways of the prognostic-related genes were analyzed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and tumor immune microenvironment (TIME), tumor mutational burden, and drug sensitivity tests were completed with appropriate packages in R (The R Foundation of Statistical Computing). Finally, a nomogram incorporating the prognostic formula was established. Results: A total of 1,636 DEGs were identified, 1,163 prognostic-related DEGs were extracted, and 34 DEGs were selected and incorporated into the immunotherapy responsiveness-related risk score (IRRS) formula. The IRRS formula had good performance in predicting the overall prognoses in patients with LUAD and had excellent performance in prognosis prediction in all LUAD subgroups. Moreover, the IRRS formula could predict anticancer drug sensitivity and immunotherapy responsiveness in patients with LUAD. Mechanistically, immune microenvironments varied profoundly between the two IRRS groups; the most significantly varied pathway between the high-IRRS and low-IRRS groups was ribonucleoprotein complex biogenesis, which correlated closely with the TP53 and TTN mutation burdens. In addition, we established a nomogram incorporating the IRRS, age, sex, clinical stage, T-stage, N-stage, and M-stage as predictors that could predict the prognoses of 1-year, 3-year, and 5-year survival in patients with LUAD, with an area under curve (AUC) of 0.718, 0.702, and 0.68, respectively. Conclusions: The model we established in the present study could predict the prognosis of LUAD patients, help to identify patients with good responses to anticancer drugs and immunotherapy, and serve as a valuable tool to guide clinical decision-making.

9.
Front Psychol ; 15: 1414736, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38984283

RESUMEN

Objective: To explore the relationship among boredom proneness, the behavioral inhibition system, and anxiety among college students based on variable-centered and person-centered analytic approaches. Methods: A questionnaire survey was conducted on 1,102 college students from a university in Hebei Province using the Boredom Proneness Questionnaire (BPQ) for College Students, the Behavioral Inhibition System Scale (BIS), and the General Anxiety Disorder-7 scale (GAD-7). Results: The results reveal that boredom proneness was negatively correlated with scores on the behavioral inhibition system (r = -0.100, p < 0.01), and positively correlated with anxiety (r = 0.457, p < 0.001), while the behavioral inhibition system was positively correlated with anxiety (r = 0.086, p < 0.01). In the variable-centered analyses study, it was found that the behavioral inhibition system partially mediated the association between boredom proneness and anxiety. In the person-centered analyses study, three subtypes were identified: the high boredom-low inhibition group (9.35%), the moderate boredom-inhibition group (66.70%), and the low boredom-high inhibition group (23.95%). Individuals in these subtypes showed significant differences in anxiety scores (F = 4.538, p < 0.05), with the low boredom-high inhibition group scoring the highest. Conclusion: The results showed that the behavioral inhibition system partially mediates the relationship between boredom proneness and anxiety in college students; boredom proneness and the behavioral inhibition system exhibit group heterogeneity, with distinct classification features closely related to anxiety.

10.
J Hazard Mater ; 477: 135289, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39053061

RESUMEN

Heterogeneous catalytic ozonation (HCO) holds promise in water purification but suffers from limited accessible metal sites, metal leaching, and unclear structure-activity relationships. This work reported M-NC (M=Co, Ni, Fe, and Mn) single-atom catalysts (SACs) with high atomic efficiency and minimal metal release. The new HCO systems, especially the Co-based system, exhibited impressive performance in various refractory contaminant removal, involving various reactive species generation, such as •OHads, •OHfree, *O, and 1O2. For sulfamethoxazole removal, the normalized kobs for Co-NC, Ni-NC, Fe-NC, and Mn-NC were determined as 13.53, 3.94, 3.55, and 4.13 min-1·mMmetal-1·g·m-2 correspondingly, attributed to the abundant acid sites, faster electron transfer, and lower energy required for O3 decomposition and conversion. The metal atoms and hydroxyl groups, individually serving as Lewis and Bronsted acid sites (LAS and BAS), were the primary centers for •OH generation and O3 adsorption. The relationships between active sites and both O3 utilization and •OH generation were found. LAS and BAS were responsible for O3 adsorption, while strong LAS facilitated O3 conversion into •OH. Theoretical calculations revealed the catalytic mechanisms involved O3→ *O→ *OO→ O3•-→ •OH. This work highlights the significance of SAC design for HCO and advances the understanding of atomic-level HCO behavior.

11.
J Hazard Mater ; 477: 135251, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39068885

RESUMEN

Organic pollutants polymerization in advanced oxidation processes or environmental matrices has attracted increasing attention, but little is known about stabilization of the polymerization products. The results in this work revealed the contribution of Fe(Ⅱ) oxygenation to stabilization of the products from norfloxacin (NOR) humification. It was found that upon oxygenation of Fe(Ⅱ) complexed by catechol (CT), NOR polymerized into the products with larger molecular weight through nucleophilic addition. Around 83.9-89.7 % organic carbon (OC) can be retained in the reaction solution and the precipitates at different Fe(II)/CT molar ratio. In this system with humification potential, the produced hydroxyl radical (HO•) dominantly modified, instead of decomposed, the structure of transformation products (TPs). TPs with diversified side chains were formed through hydroxylation and ring-opening, leading to the more humified products. In the subsequent Fe(Ⅱ) oxidative precipitation, Fe-TPs composites were formed as spherical particle clusters, which could steadily incorporate OC species with molecular fractionation. Specifically, lignin-like, tannins-like, condensed aromatic and high-molecular-weight TPs were preferentially preserved in the precipitates, while the recalcitrant aliphatic products mainly retained in the solution. These findings shed light on the role of Fe(Ⅱ) oxygenation in stabilizing the products from pollutants humification, which could strengthen both decontamination and organics sequestration.

12.
Int J Biol Macromol ; 274(Pt 2): 133153, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38897500

RESUMEN

Titanium and titanium alloys are widely favored materials for orthopedic implants due to their exceptional mechanical properties and biological inertness. The additional benefit of sustained local release of bioactive substances further promotes bone tissue formation, thereby augmenting the osseointegration capacity of titanium implants and attracting increasing attention in bone tissue engineering. Among these bioactive substances, growth factors have shown remarkable osteogenic and angiogenic induction capabilities. Consequently, researchers have developed various physical, chemical, and biological loading techniques to incorporate growth factors into titanium implants, ensuring controlled release kinetics. In contrast to conventional treatment modalities, the localized release of growth factors from functionalized titanium implants not only enhances osseointegration but also reduces the risk of complications. This review provides a comprehensive examination of the types and mechanisms of growth factors, along with a detailed exploration of the methodologies used to load growth factors onto the surface of titanium implants. Moreover, it highlights recent advancements in the application of growth factors to the surface of titanium implants (Scheme 1). Finally, the review discusses current limitations and future prospects for growth factor-functionalized titanium implants. In summary, this paper presents cutting-edge design strategies aimed at enhancing the bone regenerative capacity of growth factor-functionalized titanium implants-a significant advancement in the field of enhanced bone regeneration.


Asunto(s)
Regeneración Ósea , Péptidos y Proteínas de Señalización Intercelular , Prótesis e Implantes , Titanio , Titanio/química , Humanos , Regeneración Ósea/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Animales , Oseointegración/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ingeniería de Tejidos/métodos , Propiedades de Superficie
13.
Front Oncol ; 14: 1378095, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939337

RESUMEN

Background: Clear cell renal cell carcinoma (ccRCC) is a metabolic disorder characterized by abnormal lipid accumulation in the cytoplasm. Lipid metabolism-related genes may have important clinical significance for prognosis prediction and individualized treatment. Methods: We collected bulk and single-cell transcriptomic data of ccRCC and normal samples to identify key lipid metabolism-related prognostic signatures. qPCR was used to confirm the expression of signatures in cancer cell lines. Based on the identified signatures, we developed a lipid metabolism risk score (LMRS) as a risk index. We explored the potential application value of prognostic signatures and LMRS in precise treatment from multiple perspectives. Results: Through comprehensive analysis, we identified five lipid metabolism-related prognostic signatures (ACADM, ACAT1, ECHS1, HPGD, DGKZ). We developed a risk index LMRS, which was significantly associated with poor prognosis in patients. There was a significant correlation between LMRS and the infiltration levels of multiple immune cells. Patients with high LMRS may be more likely to respond to immunotherapy. The different LMRS groups were suitable for different anticancer drug treatment regimens. Conclusion: Prognostic signatures and LMRS we developed may be applied to the risk assessment of ccRCC patients, which may have potential guiding significance in the diagnosis and precise treatment of ccRCC patients.

14.
Blood Sci ; 6(3): e00190, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38779304

RESUMEN

Engraftment syndrome (ES) is one of the most common complications in the early phase after autologous hematopoietic stem cell transplantation (ASCT), and we aimed to evaluate the incidence and risk factors for ES patients receiving ASCT in the era of plerixafor-based mobilization. A total of 294 were enrolled, and 16.0% (n = 47) experienced ES after ASCT. The main clinical manifestations were fever (100%), diarrhea (78.7%), skin rash (23.4%), and hypoxemia/pulmonary edema (12.8%). Plerixafor-based mobilization was associated with higher counts of CD3+ cells, CD4+ cells, and CD8+ cells in grafts. In univariate analysis of the total cohort, age ≥60 years, receiving ASCT at complete remission (CR), higher number of mononuclear cell (MNC), CD3+ cell counts, CD4+ cells as well as CD8+ cells transfused and plerixafor-based mobilization were associated with ES after ASCT. Multivariate analysis showed that age ≥60 years (P = .0014), receiving ASCT at CR (P = .002), and higher number of MNC transfused (P = .026) were associated with ES in total cohort. In plasma cell disease subgroup, age ≥60 years (P = .013), plerixafor-based mobilization (P = .036), and receiving ASCT at CR (P = .002) were associated with ES. Patients with more risk factors had a higher risk of ES. The 1-year probabilities of relapse, non-relapse mortality, and survival were comparable between patients with and without ES. Thus, plerixafor-based mobilization may influence the composition of T lymphocytes in grafts and increase the risk of ES, particularly in patients with plasma cell disease.

15.
Carcinogenesis ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38795009

RESUMEN

STIP1 homology and U-box protein 1 (STUB1), a crucial member of the RING family E3 ubiquitin ligase, serves dual roles as an oncogene and a tumor suppressor in various human cancers. However, the role and mechanism of STUB1 in clear cell renal cell carcinoma (ccRCC) remain poorly defined. Here, we identified YTHDF1 as a novel STUB1 interaction partner using affinity purification mass spectrometry (AP-MS). Furthermore, we revealed that STUB1 promotes the ubiquitination and degradation of YTHDF1. Consequently, STUB1 depletion leads to YTHDF1 up-regulation in renal cancer cells. Functionally, STUB1 depletion promoted migration and invasion of ccRCC cells in a YTHDF1-dependent manner. Additionally, depletion of STUB1 also increased the tumorigenic potential of ccRCC in a xenograft model. Importantly, STUB1 expression is down-regulated in ccRCC tissues, and its low expression level correlates with advanced tumor stage and poor overall survival in ccRCC patients. Taken together, these findings reveal that STUB1 inhibits the tumorigenicity of ccRCC by regulating YTHDF1 stability.

16.
Adv Sci (Weinh) ; 11(23): e2401368, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38600702

RESUMEN

The microvascular network plays an important role in providing nutrients to the injured tissue and exchanging various metabolites. However, how to achieve efficient penetration of the injured tissue is an important bottleneck restricting the reconstruction of microvascular network. Herein, the hydrogel precursor solution can efficiently penetrate the damaged tissue area, and ultrasound triggers the release of thrombin from liposomes in the solution to hydrolyze fibrinogen, forming a fibrin solid hydrogel network in situ with calcium ions and transglutaminase as catalysts, effectively solving the penetration impedance bottleneck of damaged tissues and ultimately significantly promoting the formation of microvascular networks within tissues. First, the fibrinogen complex solution is effectively permeated into the injured tissue. Second, ultrasound triggered the release of calcium ions and thrombin, activates transglutaminase, and hydrolyzes fibrinogen. Third, fibrin monomers are catalyzed to form fibrin hydrogels in situ in the damaged tissue area. In vitro studies have shown that the fibrinogen complex solution effectively penetrated the artificial bone tissue within 15 s after ultrasonic triggering, and formed a hydrogel after continuous triggering for 30 s. Overall, this innovative strategy effectively solved the problem of penetration resistance of ultrasound-triggered hydrogels in the injured tissues, and finally activates in situ microvascular networks regeneration.


Asunto(s)
Hidrogeles , Hidrogeles/química , Animales , Fibrinógeno/metabolismo , Fibrinógeno/química , Microvasos/metabolismo , Fibrina/metabolismo , Fibrina/química , Ratones , Ondas Ultrasónicas , Trombina/metabolismo , Calcio/metabolismo
17.
J Chromatogr A ; 1724: 464923, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38653039

RESUMEN

Efficient separation of deoxyribonucleic acid (DNA) through magnetic nanoparticles (MN) is a widely used biotechnology. Hedgehog-inspired MNs (HMN) possess a high-surface-area due to the distinct burr-like structure of hedgehog, but there is no report about the usage of HMN for DNA extraction. Herein, to improve the selection of MN and illustrate the performance of HMN for DNA separation, HMN and silica-coated Fe3O4 nanoparticles (Fe3O4@SiO2) were fabricated and compared for the high-efficient separation of pathogenic bacteria of DNA. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical Gram-negative and Gram-positive bacteria and are selected as model pathogenic bacteria. To enhance the extraction efficiency of two kinds of MNs, various parameters, including pretreatment, lysis, binding and elution conditions, have been optimized in detail. In most separation experiments, the DNA yield of HMN was higher than that of Fe3O4@SiO2. Therefore, a HMN-based magnetic solid-phase microextraction (MSPE) and quantitative real-time PCR (qPCR) were integrated and used to detect pathogenic bacteria in real samples. Interestingly, the HMN-based MSPE combined qPCR strategy exhibited high sensitivity with a limit of detection of 2.0 × 101 CFU mL-1 for E. coli and 4.0 × 101 CFU mL-1 for S. aureus in orange juice, and 2.8 × 102 CFU mL-1 for E. coli and 1.1 × 102 CFU mL-1 for S. aureus in milk, respectively. The performance of the proposed strategy was significantly better than that of commercial kit. This work could prove that the novel HMN could be applicable for the efficient separation of DNA from complex biological samples.


Asunto(s)
ADN Bacteriano , Escherichia coli , Nanopartículas de Magnetita , Microextracción en Fase Sólida , Staphylococcus aureus , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/química , Escherichia coli/química , Escherichia coli/aislamiento & purificación , Nanopartículas de Magnetita/química , ADN Bacteriano/aislamiento & purificación , ADN Bacteriano/análisis , Microextracción en Fase Sólida/métodos , Dióxido de Silicio/química , Reacción en Cadena en Tiempo Real de la Polimerasa , Límite de Detección , Erizos/microbiología
18.
Chemosphere ; 356: 141857, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38570045

RESUMEN

Palladized iron (Pd/Fe) represents one of the most common modification strategies for nanoscale zero-valent iron (nZVI). Most studies prepared Pd/Fe by reducing iron salts and depositing Pd species on the surface of pre-synthesized nZVI, which can be called the two-step method. In this study, we proposed a one-step method to obtain Pd/Fe by the concurrent formation of Fe0 and Pd0 and investigated the effects of these two methods on 4-chlorophenol (4-CP) removal, with carboxymethylcellulose (CMC) coated as a surface modifier. Results indicated that the one-step method, not only streamlined the synthesis process, but also Pd/Fe-CMCone-step, synthesized by it, exhibited a higher 4-CP removal rate (97.9%) compared to the two-step method material Pd/Fe-CMCtwo-step (82.4%). Electrochemical analyses revealed that the enhanced activity of Pd/Fe-CMCone-step was attributed to its higher electron transfer efficiency and more available reactive species, active adsorbed hydrogen species (Hads*). Detection of intermediate products demonstrated that, under the influence of Pd/Fe-CMCone-step, the main route of 4-CP was through hydrodechlorination (HDC) to form phenol and H* was the main active specie, supported by EPR tests, quenching experiments and product analysis. Additionally, the effects of initial 4-CP concentration, initial pH, O2 concentration, anions such as Cl-, SO42-, HCO3-, and humic acid (HA) were also investigated. In conclusion, the results of this study suggest that Pd/Fe-CMCone-step, synthesized through the one-step method, is a convenient and efficient nZVI-modifying material suitable for the HDC of chlorinated organic compounds.


Asunto(s)
Carboximetilcelulosa de Sodio , Clorofenoles , Hierro , Paladio , Clorofenoles/química , Carboximetilcelulosa de Sodio/química , Hierro/química , Paladio/química , Contaminantes Químicos del Agua/química , Halogenación , Adsorción , Nanopartículas del Metal/química , Suspensiones
19.
Clin Lymphoma Myeloma Leuk ; 24(6): e257-e266, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38461040

RESUMEN

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.


Asunto(s)
Dasatinib , Mesilato de Imatinib , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Dasatinib/uso terapéutico , Dasatinib/farmacología , Mesilato de Imatinib/uso terapéutico , Mesilato de Imatinib/farmacología , Adulto , Anciano , Pirimidinas/uso terapéutico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Resultado del Tratamiento , Adulto Joven , Adolescente , Benzamidas/uso terapéutico , Anciano de 80 o más Años , Aminopiridinas
20.
Micromachines (Basel) ; 15(3)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38542583

RESUMEN

Laser-based additive manufacturing has garnered significant attention in recent years as a promising 3D-printing method for fabricating metallic components. However, the surface roughness of additive manufactured components has been considered a challenge to achieving high performance. At present, the average surface roughness (Sa) of AM parts can reach high levels, greater than 50 µm, and a maximum distance between the high peaks and the low valleys of more than 300 µm, which requires post machining. Therefore, laser polishing is increasingly being utilized as a method of surface treatment for metal alloys, wherein the rapid remelting and resolidification during the process significantly alter both the surface quality and subsurface material properties. In this paper, the surface roughness, microstructures, microhardness, and wear resistance of the as-received, continuous wave laser polishing (CWLP), and pulsed laser polishing (PLP) processed samples were investigated systematically. The results revealed that the surface roughness (Sa) of the as-received sample was 6.29 µm, which was reduced to 0.94 µm and 0.84 µm by CWLP and PLP processing, respectively. It was also found that a hardened layer, about 200 µm, was produced on the Ti6Al4V alloy surface after laser polishing, which can improve the mechanical properties of the component. The microhardness of the laser-polished samples was increased to about 482 HV with an improvement of about 25.2% compared with the as-received Ti6Al4V alloy. Moreover, the coefficient of friction (COF) was slightly reduced by both CWLP and LPL processing, and the wear rate of the surface layer was improved to 0.790 mm3/(N∙m) and 0.714 mm3/(N∙m), respectively, under dry fraction conditions.

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