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1.
Biomaterials ; 313: 122800, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39241551

RESUMO

The (002) crystallographic plane-oriented hydroxyapatite (HA) and anatase TiO2 enable favorable hydrophilicity, osteogenesis, and biocorrosion resistance. Thus, the crystallographic plane control in HA coating and crystalline phase control in TiO2 is vital to affect the surface and interface bioactivity and biocorrosion resistance of titanium (Ti) implants. However, a corresponding facile and efficient fabrication method is absent to realize the HA(002) mineralization and anatase TiO2 formation on Ti. Herein, we utilized the predominant Ti(0002) plane of the fibrous-grained titanium (FG Ti) to naturally form anatase TiO2 and further achieve a (002) basal plane oriented nanoHA (nHA) film through an in situ mild hydrothermal growth strategy. The formed FG Ti-nHA(002) remarkably improved hydrophilicity, mineralization, and biocorrosion resistance. Moreover, the nHA(002) film reserved the microgroove-like topological structure on FG Ti. It could enhance osteogenic differentiation through promoted contact guidance, showing one order of magnitude higher expression of osteogenic-related genes. On the other hand, the nHA(002) film restrained the osteoclast activity by blocking actin ring formation. Based on these capacities, FG Ti-nHA(002) improved new bone growth and binding strength in rabbit femur implantation, achieving satisfactory osseointegration within 2 weeks.


Assuntos
Durapatita , Osseointegração , Titânio , Titânio/química , Durapatita/química , Animais , Osseointegração/efeitos dos fármacos , Coelhos , Osteogênese/efeitos dos fármacos , Corrosão , Camundongos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos
2.
Food Chem ; 462: 140847, 2025 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-39226647

RESUMO

Effects of varying degree of milling (DOM) (0-22%) on the bran layer structure, physicochemical properties, and cooking quality of brown rice were explored. As the DOM increased, bran degree, protein, lipid, dietary fiber, amylose, mineral elements, and color parameters (a* and b* values) of milled rice decreased while starch and L* value increased. Microscopic fluorescence images showed that the pericarp, combined seed coat-nucellus layer, and aleurone layer were removed in rice processed at DOM of 6.6%, 9.2%, and 15.4%, respectively. The pasting properties, thermal properties, and palatability of rice increased as the DOM increased. Principal component and correlation analysis indicated that excessive milling lead to a decline in nutritional value of rice with limited impact on enhancing palatability. Notably, when parts of aleurone cell wall were retained, rice samples exhibited high cooking and sensory properties. It serves as a potential guide to the production of moderately milled rice.


Assuntos
Culinária , Fibras na Dieta , Oryza , Sementes , Oryza/química , Fibras na Dieta/análise , Sementes/química , Valor Nutritivo , Paladar , Humanos , Manipulação de Alimentos , Amido/química , Amilose/química , Amilose/análise
3.
World J Gastroenterol ; 30(33): 3791-3798, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39351426

RESUMO

In this editorial, we comment on the article published in the recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a fatal disease that causes uncontrolled massive hepatocyte death and rapid loss of liver function. Ferroptosis and pyroptosis, cell death forms that can be initiated or blocked concurrently, can play significant roles in developing inflammation and various malignancies. However, their roles in ALF remain unclear. The article discovered the positive feedback between ferroptosis and pyroptosis in the progression of ALF, and revealed that the silent information regulator sirtuin 1 (SIRT1) inhibits both pathways through p53, dramatically reducing inflammation and protecting hepatocytes. This suggests the potential use of SIRT1 and its downstream molecules as therapeutics for ALF. Thus, we will discuss the role of ferroptosis and pyroptosis in ALF and the crosstalk between these cell death mechanisms. Additionally, we address potential treatments that could alleviate ALF by simultaneously inhibiting both cell death pathways, as well as examples of SIRT1 activators being used as disease treatment strategies, providing new insights into the therapy of ALF.


Assuntos
Ferroptose , Hepatócitos , Falência Hepática Aguda , Piroptose , Sirtuína 1 , Humanos , Piroptose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Falência Hepática Aguda/metabolismo , Falência Hepática Aguda/patologia , Sirtuína 1/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatócitos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Fígado/patologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Terapia de Alvo Molecular/métodos , Proteína Supressora de Tumor p53/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-39353177

RESUMO

Fabrication of well-dispersed thin graphene oxide (GO) films (GOFs) has always been a challenge. Herein, a quick preparation method for GOFs was developed using our homemade GO with a large lateral size. The film can be prepared in less than 2 h via a metal framework-induced self-assembly process. The thickness of the films can be as thin as ∼15.5 µm, which will be thinner with compression. When it is used as a flexible modification layer on the Zn metal for aqueous Zn-ion batteries, Zn can grow along the [010] direction in plane and stack orderly along the [002] direction even on the Cu substrate with GOF through epitaxial plating owing to negligible lattice mismatch between the (002) plane of Zn and the hexagonal ring [also (002) plane for graphite] of GO. Meanwhile, the rich O groups on the GO film can provide abundant zincophilic points and promote uniform distribution of Zn2+ around the anode. Finally, dendrite-free and dense Zn stripping/plating can be achieved and well remained. The GOF@Zn symmetric cell reveals long cyclic stability of 1300 h at 1 mA cm-2 and 1 mA h cm-2. It still can remain at 350 h even at a very high current density of 10 mA cm-2 accompanied by a high areal capacity of 10 mA h cm-2. With the same plating amount of 5 mA h cm-2, the thickness of the plated Zn is only ∼10 µm with GOF modification, very close to the theoretical value of 8.54 µm, much thinner than that without GOF (∼18 µm), indicating very dense deposition. Full cells assembled with the GOF@Zn anode and the MnO2 cathode exhibit a capacity retention rate of 71% over 1000 cycles at 0.7 A g-1, showing much better cycling performance than that using bare Zn.

5.
Front Public Health ; 12: 1454998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39354994

RESUMO

Background: The relationship between secondary traumatic stress (STS), empathy, and vicarious post-traumatic growth (VPTG) in oncology nurses is unclear. Understanding these links is crucial for improving nurse well-being and patient care quality. Objective: This study aimed to investigate the relationships between STS, empathy, and VPTG among oncology nurses. Methods: This cross-sectional study was conducted in a multicentric setting. Data collection involved oncology nurses completing questionnaires assessing STS, empathy, and VPTG levels. Data analysis included correlation analyses, multiple stepwise regression analysis, and structural equation modeling (SEM) to examine the interrelationships between these variables. The study adhered to the STROBE checklist. Results: A total of 391 oncology nurses participated in the study. They showed moderate to low levels of VPTG and high levels of STS. STS exhibited a negative association with VPTG, while empathy demonstrated a positive direct association with both VPTG and STS. Moreover, SEM indicated that empathy mediated the relationship between STS and VPTG, with a partial mediating effect of 0.127. Factors such as receiving psychological training, educational attainment, STS, and empathy collectively explained 24% of the variance in VPTG. Conclusion: Our findings highlighted the negative correlation between STS and VPTG among oncology nurses. Additionally, empathy was found to mediate the relationship between STS and VPTG, suggesting it plays a significant role in influencing VPTG. Implications for practice: To aid oncology nurses, interventions should focus on reducing STS and enhancing empathy. Strategies like resilience workshops, peer support, and stress management can foster VPTG. Creating a supportive work environment is crucial for nurses' well-being and quality patient care.


Assuntos
Empatia , Enfermagem Oncológica , Crescimento Psicológico Pós-Traumático , Humanos , Estudos Transversais , Feminino , Masculino , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/psicologia
6.
Int J Surg ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352118

RESUMO

BACKGROUND: Early diagnosis remains an obstacle for improving the outcome of lung adenocarcinoma (LUAD). DNA methylation changes in peripheral blood mononuclear cells (PBMCs) could reflect immune response to tumorigenesis, providing the theoretical basis for early cancer diagnosis based on immune cell profiling. METHODS: This multi-center study evaluated the DNA methylation patterns based on PBMCs samples from 1115 individuals at nine medical centers. Genome-wide DNA methylation profiling of PBMCs in a discovery cohort (35 LUAD patients and 50 healthy controls) was performed using Illumina 850K microarray. Candidate differentially methylated CpG positions (DMPs) were selected and validated in a two-step DMPs screening cohort (65 LUAD patients and 80 healthy controls) by pyrosequencing and multiple target region methylation enrichment sequencing (MTRMES). Then, an early LUAD Diagnostic Panel (LDP score) based on multi-site methylation-specific chip-based digital PCR was constructed in a training set and then confirmed in a validation set from the LDP score development cohort (389 AIS/stage I LUAD patients and 293 healthy controls). Besides, we included 157 other cancer patients, including 52 gastric cancer (GC) patients, 50 breast cancer (BC) patients, and 55 colorectal cancer (CRC) patients to assess the specificity of LDP score. In addition, we also evaluated the early warning ability of LDP score for LUAD in a prospective cohort (46 people who were at high-risk of developing LC). RESULTS: A total of 1415 LUAD-specific DMPs were identified. Then, six DMPs were selected for validation and three DMPs were finally verified. The LDP score was constructed by combining the three DMPs, age, and gender, and showed an AUC of 0.916, sensitivity of 88.17%, and specificity of 80.20% in combined set, outperforming traditional methods, such as CEA and CT (detection rate: 87.79% vs. 4.69%; 87.79% vs. 35.21%). This diagnostic performance was confirmed in sub-types of LUAD with clinical challenges, such as 6-20 mm LUAD (AUC: 0.914, 95%CI: 0.889-0.934) and ground-glass nodules (AUC: 0.916, 95%CI: 0.889-0.938). Importantly, our LDP score had significant improvement in terms of selecting high-risk individuals who should receive low-dose computed tomography (87.80% vs. 9.28%). Remarkably, LDP score could predict LUAD around two years before clinical diagnosis in our prospective cohort. CONCLUSIONS: The novel developed LDP score represented a convenient and effective assay for the detection of AIS/stage I LUAD with high sensitivity and specificity, and had demonstrated unique advantages over traditional detection methods.

8.
Curr Med Imaging ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39360543

RESUMO

OBJECTIVE: This study aims to optimize the downgrading of BI-RADS class 4a nodules by combining various sectional elastography techniques with age. MATERIALS AND METHODS: We performed conventional ultrasonography, strain elastography (SE), and shear wave elastography (SWE) on patients. Quantitative parameters recorded included age, cross-sectional and longitudinal area ratios (C-EI/B, L-EI/B), strain rate ratios (C-SR, L-SR), overall average elastic modulus values (C-Emean1, L-Emean1), five-point average elastic modulus values (C-Emean2, L-Emean2), and maximum elastic modulus values (C-Emax, L-Emax). RESULTS: Histopathological evaluations showed that out of 230 lesions, 45 were malignant, and 185 were benign. The sensitivity and specificity of conventional ultrasonography were 100% and 0%, respectively. In contrast, SE and SWE exhibited higher specificity but lower sensitivity. Crosssectional parameters (C-EI/B, C-SR, C-Emean1, C-Emean2, and C-Emax) outperformed their longitudinal counterparts, with C-SR and C-Emax showing the highest specificity (72.43% and 73.51%) and satisfactory sensitivity (80.00% and 88.89%). Combining age with C-SR and C-Emax significantly improved diagnostic efficiency, achieving a sensitivity of 97.78% and a specificity of 77.30%. CONCLUSION: Integrating age with C-SR and C-Emax effectively reduces unnecessary biopsies for most BI-RADS 4a benign lesions while maintaining a very low misdiagnosis rate.

9.
Brain Behav ; 14(10): e70071, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39378277

RESUMO

AIM: This cross-sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. RESULTS: Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.


Assuntos
Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Córtex Motor , Córtex Pré-Frontal , Espectroscopia de Luz Próxima ao Infravermelho , Tai Chi Chuan , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Masculino , Tai Chi Chuan/métodos , Feminino , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/diagnóstico por imagem , Idoso , Estudos Transversais , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Córtex Motor/diagnóstico por imagem
10.
Front Cell Dev Biol ; 12: 1460616, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39381372

RESUMO

Macroautophagy/autophagy is an intracellular degradation pathway that has an important effect on both healthy and diseased pancreases. It protects the structure and function of the pancreas by maintaining organelle homeostasis and removing damaged organelles. A variety of pancreas-related diseases, such as diabetes, pancreatitis, and pancreatic cancer, are closely associated with autophagy. Genetic studies that address autophagy confirm this view. Loss of autophagy homeostasis (lack or overactivation) can lead to a series of adverse reactions, such as oxidative accumulation, increased inflammation, and cell death. There is growing evidence that stimulating or inhibiting autophagy is a potential therapeutic strategy for various pancreatic diseases. In this review, we discuss the multiple roles of autophagy in physiological and pathological conditions of the pancreas, including its role as a protective or pathogenic factor.

11.
Clin Ther ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39384437

RESUMO

PURPOSE: The purpose of this study was to assess the effectiveness and tolerability of 0.05% cyclosporine A (CsA) eye drops for neurotrophic keratopathy (NK) secondary to herpes simplex keratitis (HSK). METHODS: Fifteen patients (15 eyes) with prior HSK and secondary NK, classified as stage 2 or 3 on the basis of the Mackie classification, were enrolled. All patients received a combined treatment regimen of 0.05% CsA eye drops (1 drop 4 times daily), a silicone hydrogel bandage contact lens, and 0.15% ganciclovir ophthalmic gel (1 drop 3 times daily). For patients achieving corneal healing, CsA was continued at a reduced dosage of twice daily for an additional 2 months and other treatments were discontinued. Follow-ups were scheduled at weeks 1, 2, 3, and 4 and at months 2 and 3 after treatment initiation, followed by a 3-month follow-up period. Key outcomes, including best-corrected visual acuity, Schirmer I test, and corneal sensitivity, were assessed at each visit before and after treatment. FINDINGS: Significant reductions were observed in the area of corneal defects, expressed as proportion of total corneal area, throughout follow-up period. Complete corneal healing was achieved by 13.3% of patients by week 2, 60.0% by week 3, 86.7% by week 4, and 100.0% by week 8, with the mean (SD) time to healing being 3.8 (1.8) weeks (range, 2-8 weeks). Additionally, significant improvements were noted in diseased eyes for best-corrected visual acuity, tear secretion (Schirmer I test values), and corneal sensitivity after treatment. IMPLICATIONS: CsA eye drops, with bandage lenses and ganciclovir, effectively resolve NK from HSK, without adverse effects. This combination therapy shows promise for future clinical use and research. CLINICAL TRIAL REGISTRATION: Our study is a retrospective observational study because it involves the analysis of previously collected data, so the study was not registered prior to its commencement. However, if it is necessary for publication, we are willing to proceed with retrospective registration.

12.
Phys Chem Chem Phys ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39387127

RESUMO

The issue of energy scarcity has become more prominent due to the recent scientific and technological advancements. Consequently, there is an urgent need for research on sustainable and renewable resources. Solar energy, in particular, has emerged as a highly promising option because of its pollution-free and environment-friendly characteristics. Among the various solar energy technologies, perovskite solar cells have attracted much attention due to their lower cost and higher photoelectric conversion efficiency (PCE). However, the inherent instability of perovskite materials hinders the commercialization of such devices. The utilization of scanning tunneling microscopy/spectroscopy (STM/STS) can provide valuable insights into the fundamental properties of different perovskite materials at the atomic scale, which is crucial for addressing this challenge. In this review, we present the recent research progress of STM/STS analysis applied to various perovskites for solar cells, including halide perovskites, two-dimensional Ruddlesden-Popper perovskites, and oxide perovskites. This comprehensive overview aims to inspire new ideas and strategies for optimizing solar cells.

13.
Ther Adv Neurol Disord ; 17: 17562864241276202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39371640

RESUMO

Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures that significantly impact patients' quality of life. Identifying predictors is crucial for early intervention. Objective: Electroencephalography (EEG) microstates effectively describe the resting state activity of the human brain using multichannel EEG. This study aims to develop a comprehensive prediction model that integrates clinical features with EEG microstates to predict drug-refractory epilepsy (DRE). Design: Retrospective study. Methods: This study encompassed 226 patients with epilepsy treated at the epilepsy center of a tertiary hospital between October 2020 and May 2023. Patients were categorized into DRE and non-DRE groups. All patients were randomly divided into training and testing sets. Lasso regression combined with Stepglm [both] algorithms was used to screen independent risk factors for DRE. These risk factors were used to construct models to predict the DRE. Three models were constructed: a clinical feature model, an EEG microstate model, and a comprehensive prediction model (combining clinical-EEG microstates). A series of evaluation methods was used to validate the accuracy and reliability of the prediction models. Finally, these models were visualized for display. Results: In the training and testing sets, the comprehensive prediction model achieved the highest area under the curve values, registering 0.99 and 0.969, respectively. It was significantly superior to other models in terms of the C-index, with scores of 0.990 and 0.969, respectively. Additionally, the model recorded the lowest Brier scores of 0.034 and 0.071, respectively, and the calibration curve demonstrated good consistency between the predicted probabilities and observed outcomes. Decision curve analysis revealed that the model provided significant clinical net benefit across the threshold range, underscoring its strong clinical applicability. We visualized the comprehensive prediction model by developing a nomogram and established a user-friendly website to enable easy application of this model (https://fydxh.shinyapps.io/CE_model_of_DRE/). Conclusion: A comprehensive prediction model for DRE was developed, showing excellent discrimination and calibration in both the training and testing sets. This model provided an intuitive approach for assessing the risk of developing DRE in patients with epilepsy.

14.
Blood Adv ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39374575

RESUMO

Adult haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells, a process regulated by extracellular cues including cytokines. Many cytokines signal through the conserved JAK/STAT pathway, in which tyrosine-phosphorylated STATs (pSTATs) function as transcription factors. STAT5 is a pivotal downstream mediator of several cytokines known to regulate haematopoiesis but its function in the HSC compartment remains poorly understood. Here, we show that STAT5-deficient HSCs exhibit an unusual phenotype: reduced multi-lineage repopulation and self-renewal, combined with reduced exit from quiescence and increased differentiation. This was driven not only by loss of canonical pSTAT5 signalling, but also by loss of distinct transcriptional functions mediated by STAT5 lacking canonical tyrosine phosphorylation (uSTAT5). Consistent with this concept, expression of an unphosphorylatable STAT5 mutant constrained wild-type HSC differentiation, promoted their maintenance and upregulated transcriptional programs associated with quiescence and stemness. The JAK1/2 inhibitor, ruxolitinib, which increased the uSTAT5:pSTAT5 ratio, had similar effects on murine HSC function: it constrained HSC differentiation and proliferation, promoted HSC maintenance and upregulated transcriptional programs associated with stemness. Ruxolitinib also enhanced serial replating of normal human HSPCs, CALR-mutant murine HSCs and HSPCs obtained from patients with myelofibrosis. Our results therefore reveal a previously unrecognized interplay between pSTAT5 and uSTAT5 in the control of HSC function and highlight JAK inhibition as a potential strategy for enhancing HSC function during ex vivo culture. Increased levels of uSTAT5 may also contribute to the failure of JAK inhibitors to eradicate myeloproliferative neoplasms.

15.
Med ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39389055

RESUMO

BACKGROUND: Zorifertinib (AZD3759), an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with high blood-brain barrier penetration capability, demonstrated promising intracranial and systemic antitumor activity in phase 1 and 2 studies in central nervous system (CNS)-metastatic patients. METHODS: In this phase 3 EVEREST trial (ClinicalTrials.gov: NCT03653546), patients with EGFR-sensitizing mutations, advanced treatment-naive non-small cell lung cancer (NSCLC), and non-irradiated symptomatic or asymptomatic CNS metastases were randomized (1:1) to zorifertinib or first-generation EGFR-TKI (gefitinib or erlotinib; control). The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival (PFS) per RECIST1.1. FINDINGS: Overall, 439 patients were randomized (zorifertinib n = 220; control n = 219). Most patients had the EGFR L858R mutation (55%) or >3 CNS lesions (54%). Median PFS was significantly longer with zorifertinib versus control (9.6 versus 6.9 months; hazard ratio [HR], 0.719; 95% confidence interval [CI], 0.580-0.893; p = 0.0024). Zorifertinib significantly prolonged intracranial PFS versus control (BICR per modified RECIST1.1: HR, 0.467; 95% CI, 0.352-0.619; investigator per RANO-BM: HR, 0.627; 95% CI, 0.466-0.844). Overall survival (OS) was immature; the estimated median OS was 37.3 months with zorifertinib and 31.8 months with control (HR, 0.833; 95% CI, 0.524-1.283) in patients subsequently treated with third-generation EGFR-TKIs. Safety profiles were consistent with previously reported data for zorifertinib. CONCLUSIONS: Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC. FUNDING: This work was funded by Alpha Biopharma (Jiangsu) Co., Ltd., China.

18.
Biol Trace Elem Res ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39370454

RESUMO

In recent years, the concentration of PM2.5 in China has decreased, while the concentration of ozone remains rising. Exposure to ozone contributes to respiratory illnesses; however, little is known about the underlying molecular mechanisms. The present study established an ozone-induced lung injury mice model to investigate potential molecular biomarkers and toxic mechanisms. Collected and analyzed the ozone pollution data in Xinxiang city from 2015 to 2022. At the same time, 24 male C57BL/6 mice were randomly assigned to control group and ozone exposure group. The ozone exposure concentration is 1 ppm, with 4 h of daily exposure for 33 consecutive days. HE staining was used to assess lung histological alterations and lung injury. High-throughput sequencing performed on the lung tissues of mice was used to analyze the differential expressed genes and signal transduction pathways. Xinxiang city is suffering from ozone pollution, especially in summer. HE staining showed that the ozone exposure could induce obvious inflammatory cell infiltration, alveolar wall thickening, or fracture. Transcriptome data revealed that there is a 145 differentially expressed genes between two groups and the genes enriched in PPAR signaling pathway, ferroptosis. The pivotal genes in the PPAR pathway including Adipoq, Lpl, Pck1, and Plin1 expression were significantly reduced. Additionally, the expression of Acsl6 and Scl7a11, which are close to PPAR pathway and ferroptosis has decreased. Ozone exposure could disrupt the lipid metabolism balance via downregulating lipid peroxidation-related genes through the PPAR signaling pathway, which further induced lung cell ferroptosis and aggravated lung injury in mice.

19.
Future Oncol ; : 1-12, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39360943

RESUMO

Aim: We investigated association between skin adverse events (AEs) and efficacy with dacomitinib in patients with EGFR-positive non-small-cell lung cancer (NSCLC).Methods: Post hoc analyses from ARCHER 1050 evaluated efficacy in patients who did and did not experience grade ≥2 skin AEs with dacomitinib. Landmark analyses were performed at 3 and 6 months.Results: In patients who had skin AEs (72.2%) vs. those who did not (27.7%), median progression-free survival was 16.0 vs. 9.2 months, median overall survival (OS) was 37.7 vs. 21.6 months, and objective response rate was 80.2 vs. 61.5%; OS was improved at 3 and 6 months landmark analyses.Conclusion: Presence of grade ≥2 skin AEs was associated with numerically improved efficacy and represents a valuable biomarker of treatment outcome with dacomitinib in patients with advanced NSCLC.Clinical Trial Registration: NCT01774721 (ClinicalTrials.gov).


The ARCHER 1050 study assessed how the drugs called dacomitinib and gefitinib affected people with non-small-cell lung cancer (NSCLC) who had mutations in the EGFR gene. In this study, people who were treated with dacomitinib lived longer without their cancer getting worse than people who were treated with gefitinib. Skin adverse reactions were higher in people who were treated with dacomitinib than gefitinib. In this follow-up analysis, researchers wanted to see if the treatment effect of dacomitinib was different between people who had skin adverse reactions and people who did not have skin adverse reactions after treatment with dacomitinib. The results from this analysis showed that after treatment with dacomitinib, half of the people who had skin adverse reactions lived for 16.0 months, and half of the people who did not have skin adverse reactions lived for 9.2 months without their cancer getting worse. This study also showed that half of the people who had skin adverse reactions lived for 37.7 months, and half of the people who did not have skin adverse reactions lived for 21.6 months. In summary, the results from this study showed that the treatment effect of dacomitinib was better in people who had skin adverse reactions after treatment with dacomitinib. Therefore, skin adverse reactions can be a marker of better treatment effect in people with NSCLC who had mutations in the EGFR gene when treated with dacomitinib.

20.
Nano Lett ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361835

RESUMO

Drawing inspiration from dynamic biological ion channels, researchers have developed various artificial membranes featuring responsive nanochannels. Typically, these membranes modify mass transport behaviors by manipulating the responsive layer on the inner surfaces of the intrinsic layer. In this study, we build two-dimensional lamellar membranes composed of titanium carbide MXene and poly(N-isopropylacrylamide), endowed with dual-level regulatable nanochannels, achieved through adjustments of nanochannel microenvironments. The size of these two-dimensional nanochannels can be altered by both the thermoresponsive polymer layer and the intrinsic MXene layer that could undergo spontaneous oxidation. The multilevel regulation strategy substantially enhances the molecular selectivity of MXene separation membranes, which is further applied for precise gradient separation toward multiple molecules. This advancement showcases the versatility and transformative capabilities of responsive nanochannel technology, setting the stage for innovative developments in diverse fields.

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