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1.
BMC Public Health ; 24(1): 2744, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379902

RESUMO

BACKGROUND AND OBJECTIVE: Childhood psychological abuse (CPA) is highly associated with depression among college students. However, the underlying mechanisms between these variables need further exploration. This study aims to investigate internet addiction as a mediating factor and alexithymia and its different dimensions as moderating factors, to further complement the psychological mechanisms between CPA and depression among college students. METHODS: A self-report survey was conducted on 625 college students from two universities in Hunan Province, China. The survey included CPA, internet addiction, alexithymia, and depression. Descriptive and correlational analyses were performed on these variables, and a moderated mediation model was constructed. RESULTS: CPA is positively correlated with depression, internet addiction, and alexithymia among college students. Internet addiction partially mediates the relationship between CPA and depression among college students, while alexithymia enhances the relationship between CPA and internet addiction as well as depression among college students. The moderating effect of the different dimensions of alexithymia is inconsistent, with the modulation effect of difficulty in identifying feelings being the strongest. CONCLUSION: This study further elucidates the psychological mechanisms between CPA and depression among college students. Internet addiction serves as a mediating factor, while alexithymia may strengthen the relationship between CPA and internet addiction, as well as between CPA and depression.


Assuntos
Sintomas Afetivos , Depressão , Transtorno de Adição à Internet , Estudantes , Humanos , Masculino , Feminino , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Sintomas Afetivos/psicologia , Sintomas Afetivos/epidemiologia , China/epidemiologia , Adulto Jovem , Universidades , Transtorno de Adição à Internet/psicologia , Transtorno de Adição à Internet/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Adolescente , Autorrelato , Adulto , Inquéritos e Questionários , Internet
2.
Microb Cell Fact ; 23(1): 269, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39379932

RESUMO

BACKGROUND: Inorganic polyphosphate (polyP)-targeted polyphosphate kinase 1 (PPK1) has attracted much attention by virtue of its importance in bacterial pathogenicity and persistence, as well as its exclusive presence in microorganisms. However, only very few drugs have been found to be efficacious in inhibiting the Acinetobacter baumannii (A. baumannii) PPK1 protein. RESULTS: In this study, we identified Scutellarein (Scu), a potent PPK1 inhibitor that could significantly influence PPK1-regulated motility, biofilm formation, and bacterial persistence, which was further validated by the results of transcriptome analysis. Mechanistic explorations revealed that Scu achieved its enzyme inhibitory activity predominantly through direct engagement with the active center of PPK1. Moreover, the survival rate of Galleria mellonella larvae was increased by about 35% with 20 mg/kg of Scu treatment. The remarkable therapeutic benefits of Scu were also observed in the mouse pneumonia model, shown mainly by reduced bacterial colonization, pathological lesions, and inflammatory factors. CONCLUSION: Our results revealed that Scu could attenuate the pathogenicity and persistence of A. baumannii by interfering with its important kinase PPK1.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Fosfotransferases (Aceptor do Grupo Fosfato) , Acinetobacter baumannii/efeitos dos fármacos , Animais , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/antagonistas & inibidores , Camundongos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Mariposas/microbiologia , Feminino , Modelos Animais de Doenças
3.
Chin Med ; 19(1): 140, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39380087

RESUMO

Plants such as herbs, vegetables, fruits, and cereals are closely related to human life. Developing effective testing methods to ensure their safety and quantify their active components are of significant importance. Recently, nanomaterials with enzyme-like activity (known as nanozymes) have been widely developed in various assays, including colorimetric, fluorescence, chemiluminescence, and electrochemical analysis. This review presents the latest advances in analyzing phytochemicals and hazardous substances in plant samples based on nanozymes, including some active ingredients, organophosphorus pesticides, heavy metal ions, and mycotoxins. Additionally, the current shortcomings and challenges of the actual sample analysis were discussed.

4.
Biochem Pharmacol ; 230(Pt 1): 116563, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39362501

RESUMO

Progressive cardiac fibrosis, a hallmark of heart failure, remains poorly understood regarding Proprotein convertase subtilisin/kexin type 9 (PCSK9) 's role. This study aims to elucidate PCSK9's involvement in cardiac fibrosis. After ischemia/reperfusion (I/R) injury surgery in rats, PCSK9 inhibitors were used to examine their effects on the transforming growth factor-ß1 (TGF-ß1)/small mother against decapentaplegic 3 (Smad3) pathway and inflammation. Elevated PCSK9, TGF-ß1, and Smad3 levels were observed in cardiac tissues post-I/R injury, indicating fibrosis. PCSK9 inhibition reduced pro-fibrotic protein expression, protecting the heart and mitigating I/R-induced damage and fibrosis. Additionally, it ameliorated cardiac inflammation and reduced post-myocardial infarction (MI) size, improving cardiac function and slowing heart failure progression. PCSK9 inhibitors significantly attenuate myocardial fibrosis induced by I/R via the TGF-ß1/Smad3 pathway.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39383073

RESUMO

Generating high-quality and drug-like molecules from scratch within the expansive chemical space presents a significant challenge in the field of drug discovery. In prior research, value-based reinforcement learning algorithms have been employed to generate molecules with multiple desired properties iteratively. The immediate reward was defined as the evaluation of intermediate-state molecules at each step, and the learning objective would be maximizing the expected cumulative evaluation scores for all molecules along the generative path. However, this definition of the reward was misleading, as in reality, the optimization target should be the evaluation score of only the final generated molecule. Furthermore, in previous works, randomness was introduced into the decision-making process, enabling the generation of diverse molecules but no longer pursuing the maximum future rewards. In this paper, immediate reward is defined as the improvement achieved through the modification of the molecule to maximize the evaluation score of the final generated molecule exclusively. Originating from the A ∗ search, path consistency (PC), i.e., f values on one optimal path should be identical, is employed as the objective function in the update of the f value estimator to train a multi-objective de novo drug designer. By incorporating the f value into the decision-making process of beam search, the DrugBA∗ algorithm is proposed to enable the large-scale generation of molecules that exhibit both high quality and diversity. Experimental results demonstrate a substantial enhancement over the state-of-theart algorithm QADD in multiple molecular properties of the generated molecules.

6.
World J Surg Oncol ; 22(1): 261, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350287

RESUMO

To date, there have been no reports on tertiary lymphoid structures (TLS) in primary adenocarcinoma of jejunum and ileum. In this study, we employed digital pathology image analysis software to classify and quantify TLS, and evaluated the maturity of TLS using immunohistochemistry. Molecular genetics and immunotherapy biomarker detection were performed using next-generation sequencing technology, such as tumor mutational burden (TMB) and microsatellite instability (MSI). The aim of this study was to investigate the presence, location, maturity, association with immunotherapy biomarkers, and prognostic value of TLS in primary adenocarcinoma of jejunum and ileum. Compared to secondary follicle-like TLS (SFL-TLS), intra-tumoral TLS (IT-TLS) were more likely to manifest as early TLS (E-TLS) (P = 0.007). Compared to IT-TLS, SFL-TLS had a higher propensity to occur at the invasive margin (IM) (P = 0.032) and showed a trend towards being more prevalent at the tumor periphery (P = 0.057). In terms of immunotherapy biomarkers, there was a higher trend of IM-TLS density in PD-L1(22C3) score CPS < 1 group compared to PD-L1(22C3) score CPS ≥ 1 group (P = 0.071). TMB-H was significantly associated with MSI-H (P = 0.040). Univariate survival analysis demonstrated a correlation between high SFL-TLS group and prolonged disease free survival (DFS) (P = 0.047). There was also a trend towards prolonged DFS in the E-TLS-high group compared to the E-TLS-low group (P = 0.069). The peri-tumoral TLS (PT-TLS)-high group showed a trend of prolonged overall survival (OS) compared to the PT-TLS-low group (P = 0.090). In conclusion, the majority of TLS were located at the invasive margin and tumor periphery, predominantly consisting of mature TLS, while IT-TLS were mainly immature. Notably, TMB was closely associated with MSI and PD-L1, indicating potential predictive value for immunotherapy in primary adenocarcinoma of jejunum and ileum.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias do Íleo , Neoplasias do Jejuno , Estruturas Linfoides Terciárias , Humanos , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/imunologia , Prognóstico , Masculino , Feminino , Estruturas Linfoides Terciárias/patologia , Estruturas Linfoides Terciárias/imunologia , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias do Íleo/patologia , Neoplasias do Íleo/mortalidade , Neoplasias do Jejuno/patologia , Taxa de Sobrevida , Seguimentos , Instabilidade de Microssatélites , Adulto , Estudos Retrospectivos
7.
Acta Psychol (Amst) ; 250: 104506, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39353340

RESUMO

Obesity has become a prominent public health concern worldwide and is associated with adverse cognitive function. Exercise, particularly aerobic exercise, is known to benefit for weight loss and cognitive function. However, whether acute aerobic exercise could yield benefits to obese individuals and the precise brain mechanisms of action remain poorly understood. The study aimed to investigate whether acute aerobic exercise could improve inhibitory control among obese individuals and what neuroelectric mechanisms are implicated. A 3 (session: control, low-intensity exercise, moderate-intensity exercise) × 2 (congruency: congruent, incongruent) within-subject design was conducted. 18 obese young male adults underwent three sessions of 30-min interventions in a counterbalanced order seperated by five days: moderate-intensity aerobic exercise (MIE), low-intensity aerobic exercise (LIE) and a control session (a sedentary period of seated rest). The Flanker task and EEG recordings (N2 and P3 amplitude) were investigated following exercise and the control treatment. Results showed that the N2 amplitude following MIE was larger than the control session, whereas a larger N2 and reduced congruent P3 amplitude was observed following MIE than LIE. However, no main effect of the session was found for reaction time and accuracy, but a significant main effect of congruency was observed. These findings suggest acute moderate-intensity aerobic exercise may modulate brain activity through enhanced recruitment of attentional resources for cognitive control and conflict monitoring in adults with obesity.

8.
Int J Biol Macromol ; 280(Pt 4): 136091, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39353519

RESUMO

Vitamin K2 (VK2) has been shown to have potential benefits in improving intestinal integrity, but its potential and mechanisms for alleviating intestinal inflammation are still unclear. The present results showed that VK2 supplementation significantly alleviated the symptoms of colitis and maintained the intestinal barrier integrity. In addition, VK2 significantly down-regulated the mRNA expression levels of pro-inflammatory cytokines including IL-1ß, IL-6, and TNF-α, while up-regulated the mRNA expression level of anti-inflammatory cytokines such as IL-10. Moreover, VK2 significantly alleviated DSS-induced intestinal epithelial barrier dysfunction by maintaining the tight junction function. Furthermore, VK2 also regulated DSS-induced gut microbiota dysbiosis by reshaping the structure of gut microbiota, such as increasing the relative abundance of Firmicutes, Euryarchaeota, Prevotellaceae, and Prevotella and reducing the relative abundance of Proteobacteria, Rikenellaceae, Enterobacteriaceae, Acetatifactor, and Alistioes. In conclusion, these results indicated that VK2 effectively alleviates DSS-induced colitis in mice by modulating the gut microbiota.

9.
Rev Cardiovasc Med ; 25(9): 322, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39355606

RESUMO

Rheumatic mitral valve disease often requires surgical interventions, such as percutaneous mitral commissurotomy, surgical mitral valve repair, or replacement, especially in severe cases. This necessitates a precise preoperative assessment of the extent of mitral valve disease. Currently, transthoracic echocardiography, the gold standard for preoperative assessment, has limitations, such as restricted acoustic windows and dependence on the operator, which can affect the evaluation of subvalvular structures and calcification of the mitral valve. Previous studies have shown that cardiac computed tomography (CT), with its high resolution, strong multiplanar reconstruction capabilities, and sensitivity to calcifications, can effectively overcome these limitations. Therefore, this study aims to summarize and evaluate the effectiveness of cardiac CT in examining mitral valve leaflets, annulus, and subvalvular structures. It also reviews the feasibility and guiding significance of using cardiac CT to assess characteristic rheumatic mitral valve lesions.

11.
J Transl Med ; 22(1): 914, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39380010

RESUMO

The heterogeneous nuclear ribonucleoprotein C (HNRNPC) plays a crucial role in tumorigenesis, yet its role in papillary thyroid carcinoma (PTC) remains elusive. Herein, we elucidated the function and molecular mechanism of HNRNPC in PTC tumorigenesis and progression. Our study unveiled a significant upregulation of HNRNPC in PTC, and knockdown of HNRNPC markedly inhibited the proliferation, invasion, and metastasis of BCPAP cells. Furthermore, HNRNPC modulated PKM alternative splicing in BCPAP cells primarily through m6A modification. Additionally, by upregulating PKM2 expression, HNRNPC promoted aerobic glycolysis in BCPAP cells, thereby facilitating malignant progression in PTC. In summary, our findings demonstrate that HNRNPC regulates PKM alternative splicing through m6A methylation modification and promotes the proliferation, invasion and metastasis of PTC through glucose metabolism pathways mediated by PKM2. These discoveries provide new biomarkers for screening and diagnosing PTC patients and offer novel therapeutic targets for personalized treatment strategies.


Assuntos
Processamento Alternativo , Proteínas de Transporte , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glicólise , Ribonucleoproteínas Nucleares Heterogêneas Grupo C , Proteínas de Membrana , Câncer Papilífero da Tireoide , Proteínas de Ligação a Hormônio da Tireoide , Hormônios Tireóideos , Neoplasias da Glândula Tireoide , Regulação para Cima , Humanos , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/metabolismo , Regulação para Cima/genética , Linhagem Celular Tumoral , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Processamento Alternativo/genética , Hormônios Tireóideos/metabolismo , Glicólise/genética , Metilação , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Animais , Invasividade Neoplásica , Metástase Neoplásica , Piruvato Quinase/metabolismo , Piruvato Quinase/genética , Camundongos Nus , Adenosina/análogos & derivados , Adenosina/metabolismo
12.
Br J Cancer ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39369055

RESUMO

BACKGROUND: Ovarian cancer (OvCa) is the most lethal of the gynecologic malignancies. Immune checkpoint inhibitors, which have revolutionized the treatment of multiple malignancies, have had limited efficacy in OvCa patients. This lack of effectiveness is partly due to the abnormal ovarian tumor microenvironment (TME), displaying a desmoplastic, highly fibrotic extracellular matrix. High extracellular matrix deposition leads to a buildup of compressive forces that cause tumor blood vessel collapse, reduced vessel perfusion, poor delivery of drugs, and compromised trafficking of cytotoxic T-cells to these tumors. METHODS: Using two syngeneic OvCa models, we tested the effect of losartan, a widely prescribed anti-hypertensive drug, on reprogramming the TME and chemosensitizing the cancer cells. RESULTS: Losartan treatment (i) reprograms the TME leading to increased vascular perfusion, and thus enhances drug delivery and immune effector cell intratumoral infiltration and function; and (ii) rewires the OvCa cells by suppressing the IGF-1 signaling, resulting in enhanced chemosensitivity. As a result of the combined tumor and stromal effects, losartan treatment enhances the efficacy of chemo-immunotherapy in OvCa models. CONCLUSION: The safety and low cost ( < $1-2/day) of losartan warrant rapid translation of our findings to patients with OvCa.

13.
J Cardiothorac Surg ; 19(1): 578, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354615

RESUMO

BACKGROUND: The incidence of secondary tracheal tumours following lung cancer surgery is notably low. Patients with tracheal tumours typically present with symptoms such as coughing, sputum production, haemoptysis, wheezing, stridor, and dyspnoea. In cases of peripheral structure invasion, symptoms may further extend to hoarseness and dysphagia. Initial symptoms may be notably non-distinct. However, the development of pronounced airway symptoms often signifies a critical condition. CASE PRESENTATION: A 70-year-old male with severe chest tightness and asthma was transferred to our hospital for emergency treatment. He had undergone left pneumonectomy for non-small cell carcinoma of the left upper lobe of the lung 3 years prior. The examination confirmed that a secondary tumour originated from the left main bronchus and extended to the carina, occupying 90% of the diameter of the tracheal lumen. To relieve the patient's emergency airway, we chose right thoracoscopic resection of the tracheal tumour assisted by cardiopulmonary bypass (CPB), which provides extracorporeal lung support and a good surgical field. CONCLUSION: In patients with secondary tracheal tumours after left pneumonectomy for lung cancer, perioperative airway management is challenging for anaesthesiologists, and patients' oxygenation should receive close attention. This article describes the airway management process of this patient for reference.


Assuntos
Ponte Cardiopulmonar , Pneumonectomia , Neoplasias da Traqueia , Humanos , Masculino , Idoso , Pneumonectomia/métodos , Ponte Cardiopulmonar/métodos , Neoplasias da Traqueia/cirurgia , Manuseio das Vias Aéreas/métodos , Neoplasias Pulmonares/cirurgia , Toracoscopia/métodos
15.
Cell ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39305902

RESUMO

m6A modification is best known for its critical role in controlling multiple post-transcriptional processes of the mRNAs. Here, we discovered elevated levels of m6A modification on centromeric RNA (cenRNA) in cancerous cells compared with non-cancerous cells. We then identified CENPA, an H3 variant, as an m6A reader of cenRNA. CENPA is localized at centromeres and is essential in preserving centromere integrity and function during mitosis. The m6A-modified cenRNA stabilizes centromeric localization of CENPA in cancer cells during the S phase of the cell cycle. Mutations of CENPA at the Leu61 and the Arg63 or removal of cenRNA m6A modification lead to loss of centromere-bound CENPA during S phase. This in turn results in compromised centromere integrity and abnormal chromosome separation and hinders cancer cell proliferation and tumor growth. Our findings unveil an m6A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potential targets for cancer therapy.

16.
Front Immunol ; 15: 1451742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224586

RESUMO

Background: Numerous studies have investigated the relationship between gut microbiota (GM) and multiple sclerosis(MS), highlighting the significant role of GM in MS. However, there is a lack of systematic Scientometric analyses published in this specific research area to provide an overall understanding of the current research status. Methods: Perform a scientometric analysis on research conducted between 2010 and 2023 concerning the link between GM and MS using quantitative and visual analysis software (CiteSpace and VOSviewer.). Results: From January 1, 2010, and December 31, 2023, a total of 1019 records about GM and MS were retrieved. The number of publications exhibited a consistent upward trend annually. The United States led in publications, showed the strongest level of collaboration among countries. The University of California, San Francisco stands as the top institution in terms of output, and the most prolific and cited authors were Lloyd H. Kasper and Javier Ochoa-Reparaz from the USA. The research in this field primarily centers on investigating the alterations and associations of GM in MS or EAE, the molecular immunological mechanisms, and the potential of GM-based interventions to provide beneficial effects in MS or EAE. The Keywords co-occurrence network reveals five primary research directions in this field. The most frequently occurring keywords are inflammation, probiotics, diet, dysbiosis, and tryptophan. In recent years, neurodegeneration and neuropsychiatric disorders have been prominent, indicating that the investigation of the mechanisms and practical applications of GM in MS has emerged as a current research focus. Moreover, GM research is progressively extending into the realm of neurodegenerative and psychiatric diseases, potentially becoming future research hotspots. Conclusions: This study revealed a data-driven systematic comprehension of research in the field of GM in MS over the past 13 years, highlighted noteworthy research within the field, provided us with a clear understanding of the current research status and future trends, providing a valuable reference for researchers venturing into this domain.


Assuntos
Microbioma Gastrointestinal , Esclerose Múltipla , Esclerose Múltipla/microbiologia , Humanos , Bibliometria , Animais
17.
bioRxiv ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39229071

RESUMO

Extracellular vesicles (EVs) hold potential as effective carriers for drug delivery, providing a promising approach to resolving challenges in lung cancer treatment. Traditional treatments, such as with the chemotherapy drug cisplatin, encounter resistance in standard cell death pathways like apoptosis, prompting the need to explore alternative approaches. This study investigates the potential of iron oxide nanoparticles (IONP) and EVs to induce ferroptosis-a regulated cell death mechanism-in lung cancer cells. We formulated a novel EV and IONP-based system, namely 'ExoFeR', and observed that ExoFeR demonstrated efficient ferroptosis induction, evidenced by downregulation of ferroptosis markers (xCT/SLC7A11 and GPX4), increased intracellular and mitochondrial ferrous iron levels, and morphological changes in mitochondria. To enhance efficacy, tumor-targeting transferrin (TF)-conjugated ExoFeR (ExoFeR TF ) was developed. ExoFeR TF outperformed ExoFeR, exhibiting higher uptake and cell death in lung cancer cells. Mechanistically, nuclear factor erythroid 2-related factor 2 (Nrf2)-a key regulator of genes involved in glutathione biosynthesis, antioxidant responses, lipid metabolism, and iron metabolism-was found downregulated in the ferroptotic cells. Inhibition of Nrf2 intracellular translocation in ExoFeR TF -treated cells was also observed, emphasizing the role of Nrf2 in modulating ferroptosis-dependent cell death. Furthermore, ExoFeR and ExoFeR TF demonstrated the ability to sensitize chemo-resistant cancer cells, including cisplatin-resistant lung cancer patient-derived tumoroid organoids. In summary, ExoFeR TF presents a promising and multifaceted therapeutic approach for combating lung cancer by intrinsically inducing ferroptosis and sensitizing chemo-resistant cells.

18.
Small ; : e2404207, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240059

RESUMO

Highly efficient electromagnetic wave (EMW)-absorbing multicomposites can be fabricated by constructing particular structures using suitable components. Expanded graphite (EG) has a 3D, low-density porous structure; however, it suffers from poor impedance matching and EMW absorption properties. Based on this information, in the present study, NiCo2S4 components with different morphologies are successfully loaded onto a 3D EG surface using a facile microwave solvothermal method to achieve a synergistic effect between the different components. The NiCo2S4 content is adjusted to alter the compositional morphology and electromagnetic parameters of the composites to achieve impedance-matching and obtain excellent EMW absorption properties. The heterogeneous interface between EG and NiCo2S4 induces an inhomogeneous spatial charge distribution and enhances interfacial polarization. The defects in the material and oxygen-containing groups induce dipole polarization, which enhances the polarization-relaxation process of the composites. The 3D porous heterostructure of the "Fibonacci cauliflower"-shaped NiCo2S4/EG composites results in an optimal reflection loss of -64.93 dB at a filler rate of only 14 wt.%. Analysis of the synergistic conduction loss and polarization loss mechanisms in carbon-based materials with heterogeneous interfaces has led to the development of excellent EMW absorption materials.

19.
Front Immunol ; 15: 1409302, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221255

RESUMO

Introduction: The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen. Methods: Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT. Results: Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality, and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group. Conclusion: The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.


Assuntos
Aclarubicina , Protocolos de Quimioterapia Combinada Antineoplásica , Doença Enxerto-Hospedeiro , Fator Estimulador de Colônias de Granulócitos , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transplante Homólogo , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Aclarubicina/uso terapêutico , Aclarubicina/administração & dosagem , Adulto Jovem , Citarabina/uso terapêutico , Citarabina/administração & dosagem , Idarubicina/administração & dosagem , Idarubicina/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Adolescente , Resultado do Tratamento , Recidiva , Idoso
20.
Transl Pediatr ; 13(8): 1439-1456, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39263286

RESUMO

Background: Kawasaki disease (KD) is a systemic vasculitis primarily affecting the coronary arteries in children. Despite growing attention to its symptoms and pathogenesis, the exact mechanisms of KD remain unclear. Mitophagy plays a critical role in inflammation regulation, however, its significance in KD has only been minimally explored. This study sought to identify crucial mitophagy-related biomarkers and their mechanisms in KD, focusing on their association with immune cells in peripheral blood. Methods: This research used four datasets from the Gene Expression Omnibus (GEO) database that were categorized as the merged and validation datasets. Screening for differentially expressed mitophagy-related genes (DE-MRGs) was conducted, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A weighted gene co-expression network analysis (WGCNA) identified the hub module, while machine-learning algorithms [random forest-recursive feature elimination (RF-RFE) and support vector machine-recursive feature elimination (SVM-RFE)] pinpointed the hub genes. Receiver operating characteristic (ROC) curves were generated for these genes. Additionally, the CIBERSORT algorithm was used to assess the infiltration of 22 immune cell types to explore their correlations with hub genes. Interactions between transcription factors (TFs), genes, and Gene-microRNAs (miRNAs) of hub genes were mapped using the NetworkAnalyst platform. The expression difference of the hub genes was validated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: Initially, 306 DE-MRGs were identified between the KD patients and healthy controls. The enrichment analysis linked these MRGs to autophagy, mitochondrial function, and inflammation. The WGCNA revealed a hub module of 47 KD-associated DE-MRGs. The machine-learning algorithms identified cytoskeleton-associated protein 4 (CKAP4) and serine-arginine protein kinase 1 (SRPK1) as critical hub genes. In the merged dataset, the area under the curve (AUC) values for CKAP4 and SRPK1 were 0.933 [95% confidence interval (CI): 0.901 to 0.964] and 0.936 (95% CI: 0.906 to 0.966), respectively, indicating high diagnostic potential. The validation dataset results corroborated these findings with AUC values of 0.872 (95% CI: 0.741 to 1.000) for CKAP4 and 0.878 (95% CI: 0.750 to 1.000) for SRPK1. The CIBERSORT analysis connected CKAP4 and SRPK1 with specific immune cells, including activated cluster of differentiation 4 (CD4) memory T cells. TFs such as MAZ, SAP30, PHF8, KDM5B, miRNAs like hsa-mir-7-5p play essential roles in regulating these hub genes. The qRT-PCR results confirmed the differential expression of these genes between the KD patients and healthy controls. Conclusions: CKAP4 and SRPK1 emerged as promising diagnostic biomarkers for KD. These genes potentially influence the progression of KD through mitophagy regulation.

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