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1.
Hum Genomics ; 18(1): 80, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014455

RESUMO

BACKGROUND: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. METHOD: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. RESULTS: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. CONCLUSION: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment.


Assuntos
Queloide , RNA-Seq , Queloide/genética , Queloide/diagnóstico , Queloide/patologia , Queloide/imunologia , Queloide/tratamento farmacológico , Humanos , Transcriptoma/genética , Perfilação da Expressão Gênica , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibroblastos/imunologia , Redes Reguladoras de Genes , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Análise de Célula Única/métodos , Diferenciação Celular/genética , Análise de Sequência de RNA/métodos , Aprendizado de Máquina , Análise da Expressão Gênica de Célula Única
2.
Small ; 20(5): e2305533, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37786306

RESUMO

CO2 capture and conversion technology are highly promising technologies that definitely play a part in the journey towards carbon neutrality. Releasing CO2 by mild stimulation and the development of high efficiency catalytic processes are urgently needed. The magnetic field, as a thermodynamic parameter independent of temperature and pressure, is vital in the enhancement of CO2 capture and conversion process. In this review, the recent progress of magnetic field-enhanced CO2 capture and conversion is comprehensively summarized. The theoretical fundamentals of magnetic field on CO2 adsorption, release and catalytic reduction process are discussed, including the magnetothermal, magnetohydrodynamic, spin selection, Lorentz forces, magnetoresistance and spin relaxation effects. Additionally, a thorough review of the current progress of the enhancement strategies of magnetic field coupled with a variety of fields (including thermal, electricity, and light) is summarized in the aspect of CO2 related process. Finally, the challenges and prospects associated with the utilization of magnetic field-assisted techniques in the construction of CO2 capture and conversion systems are proposed. This review offers a reference value for the future design of catalysts, mechanistic investigations, and practical implementation for magnetic field enhanced CO2 capture and conversion.

3.
Ophthalmic Res ; 67(1): 248-256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38527448

RESUMO

INTRODUCTION: This study aimed to determine the interchangeability of bilateral anterior chamber depth (ACD) in intraocular lens (IOL) power calculations for cataractous eyes and refractive outcomes using the unaffected fellow eye's ACD in subluxated crystalline lenses. METHODS: The predicted postoperative spherical equivalent (SE) calculated using the Kane formula with and without fellow eye's ACD in 202 cataract patients was compared. Refractive outcomes of the newer formulas (the Kane, Barrett Universal II [BUII], and Pearl-DGS formulas) with affected eye's ACD and with unaffected fellow eye's ACD were compared in 33 eyes with lens subluxation (the affected eye) undergoing in-the-bag IOL implantation. The SD of the prediction error (PE) was assessed using the heteroscedastic method. RESULTS: In 202 paired cataractous eyes, no marked ACD difference was found bilaterally; the predicted SE obtained without the fellow eye's ACD was comparable with that calculated with the fellow eye one (p = 0.90), with a mean absolute difference of 0.03 ± 0.03 D. With the affected eye AL, keratometry, and ACD, the median absolute error (MedAE) was 0.38-0.64 D, and the percentage of PE within ±0.50 D was 30.30-57.58%. The unaffected eye's ACD improved the results (MedAE, 0.35-0.49 D; the percentage of PE within ±0.50 D, 54.55-63.64%). The SDs of the BUII (0.82 D) and Pearl-DGS formulas (0.87 D) with the affected eye's ACD were significantly larger than those of the Kane and Pearl-DGS formulas (both 0.69 D) with the unaffected eye's ACD. CONCLUSION: Bilateral ACD was interchangeable in IOL power calculation for cataractous eyes when using the Kane formula. Unaffected eye's ACD in lieu of affected eye's ACD can enhance the accuracy of newer formulas in patients with unilateral subluxated lenses undergoing in-the-bag IOL implantation.


Assuntos
Câmara Anterior , Subluxação do Cristalino , Lentes Intraoculares , Refração Ocular , Humanos , Masculino , Feminino , Idoso , Refração Ocular/fisiologia , Pessoa de Meia-Idade , Subluxação do Cristalino/cirurgia , Subluxação do Cristalino/diagnóstico , Subluxação do Cristalino/fisiopatologia , Adulto , Acuidade Visual , Estudos Retrospectivos , Óptica e Fotônica , Implante de Lente Intraocular/métodos , Biometria/métodos , Idoso de 80 Anos ou mais
4.
Cancer Sci ; 114(11): 4157-4171, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37702269

RESUMO

Metastasis is an important factor affecting the prognosis of hormone receptor-positive breast cancer (BC). However, the molecular basis for migration and invasion of tumor cells remains poorly understood. Here, we identify that bactericidal/permeability-increasing-fold-containing family B member 1 (BPIFB1), which plays an important role in innate immunity, is significantly elevated in breast cancer and associated with lymph node metastasis. High expression of BPIFB1 and its coding mRNA are significantly associated with poor prognosis of hormone receptor-positive BC. Using enrichment analysis and constructing immune infiltration evaluation, we predict the potential ability of BPIFB1 to promote macrophage M2 polarization. Finally, we demonstrate that BPIFB1 promotes the metastasis of hormone receptor-positive BC by stimulating the M2-like polarization of macrophages via the establishment of BC tumor cells/THP1 co-culture system, qPCR, Transwell assay, and animal experiments. To our knowledge, this is the first report on the role of BPIFB1 as a tumor promoter by activating the macrophage M2 polarization in hormone receptor-positive breast carcinoma. Together, these results provide novel insights into the mechanism of BPIFB1 in BC.


Assuntos
Macrófagos , Microambiente Tumoral , Animais , Macrófagos/metabolismo , Metástase Linfática/patologia , Prognóstico , Técnicas de Cocultura , Linhagem Celular Tumoral
5.
Phys Chem Chem Phys ; 25(11): 8064-8073, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36876717

RESUMO

The purification of carbon monoxide in H2-rich streams is an urgent problem for the practical application of fuel cells, and requires the development of efficient and economical catalysts for the preferential oxidation of CO (CO-PROX). In the present work, a facile solid phase synthesis method followed by an impregnation method were adopted to prepare a ternary CuCoMnOx spinel oxide, which shows superior catalytic performance with CO conversion of 90% for photothermal CO-PROX at 250 mW cm-2. The dopant of copper species leads to the incorporation of Cu ions into the CoMnOx spinel lattice forming a ternary CuCoMnOx spinel oxide. The appropriate calcination temperature (300 °C) contributes to the generation of abundant oxygen vacancies and strong synergetic Cu-Co-Mn interactions, which are conducive to the mobility of oxygen species to participate in CO oxidation reactions. On the other hand, the highest photocurrent response of CuCoMnOx-300 also promotes the photo-oxidation activity of CO due to the high carrier concentration and efficient carrier separation. In addition, the in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) confirmed that doping copper species could enhance the CO adsorption capacity of the catalyst due to the generation of Cu+ species, which significantly increased the CO oxidation activity of the CuCoMnOx spinel oxide. The present work provides a promising and eco-friendly solution to remove the trace CO in H2-rich gas over CuCoMnOx ternary spinel oxide with solar light as the only energy source.

6.
Breast J ; 2022: 5325556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101863

RESUMO

Purpose: This study aims to analyze the survival outcomes of breast cancer (BC) patients, especially centrally located breast cancer (CLBC) patients undergoing breast-conserving therapy (BCT) or mastectomy. Methods: Surveillance, epidemiology, and end results (SEER) data of patients with T1-T2 invasive ductal or lobular breast cancer receiving BCT or mastectomy were reviewed. We used X-tile software to convert continuous variables to categorical variables. Chi-square tests were utilized to compare baseline information. The multivariate logistic regression model was performed to evaluate the relationship between predictive variables and treatment choice. Survival outcomes were visualized by Kaplan-Meier curves and cumulative incidence function curves and compared using multivariate analyses, including the Cox proportional hazards model and competing risks model. Propensity score matching was performed to alleviate the effects of baseline differences on survival outcomes. Result: A total of 180,495 patients were enrolled in this study. The breast preservation rates fluctuated around 60% from 2000 to 2015. Clinical features including invasive ductal carcinoma (IDC), lower histologic grade, smaller tumor size, fewer lymph node metastases, positive ER and PR status, and chemotherapy use were independently correlated with BCT in both BC and CLBC cohorts. In all the classic Cox models and competing risks models, BCT was an independent favorable prognostic factor for BC, including CLBC patients in most subgroups. In addition, despite the low breast-conserving rate compared with tumors located in the other areas, CLBC did not impair the prognosis of BCT patients. Conclusion: BCT is optional and preferable for most early-stage BC, including CLBC patients.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Neoplasias da Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Metástase Linfática , Mastectomia , Mastectomia Segmentar
7.
Sensors (Basel) ; 22(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36559975

RESUMO

As a typical sequence to sequence task, sign language production (SLP) aims to automatically translate spoken language sentences into the corresponding sign language sequences. The existing SLP methods can be classified into two categories: autoregressive and non-autoregressive SLP. The autoregressive methods suffer from high latency and error accumulation caused by the long-term dependence between current output and the previous poses. And non-autoregressive methods suffer from repetition and omission during the parallel decoding process. To remedy these issues in SLP, we propose a novel method named Pyramid Semi-Autoregressive Transformer with Rich Semantics (PSAT-RS) in this paper. In PSAT-RS, we first introduce a pyramid Semi-Autoregressive mechanism with dividing target sequence into groups in a coarse-to-fine manner, which globally keeps the autoregressive property while locally generating target frames. Meanwhile, the relaxed masked attention mechanism is adopted to make the decoder not only capture the pose sequences in the previous groups, but also pay attention to the current group. Finally, considering the importance of spatial-temporal information, we also design a Rich Semantics embedding (RS) module to encode the sequential information both on time dimension and spatial displacement into the same high-dimensional space. This significantly improves the coordination of joints motion, making the generated sign language videos more natural. Results of our experiments conducted on RWTH-PHOENIX-Weather-2014T and CSL datasets show that the proposed PSAT-RS is competitive to the state-of-the-art autoregressive and non-autoregressive SLP models, achieving a better trade-off between speed and accuracy.


Assuntos
Semântica , Língua de Sinais , Humanos , Idioma
8.
Analyst ; 145(24): 8097-8103, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33084628

RESUMO

A CoNi-based metal-organic framework (CoNi-MOF) nanosheet array is synthesized by the treatment of a CoNi layered double hydroxide nanosheet array on Ni foam with 3,5-diaminobenzoic acid. The CoNi-MOF nanosheet array with amino and carboxyl groups can be used to capture the human chorionic gonadotropin (HCG) primary antibody (HCG Ab1). Nile Blue decorated ZnNi-MOF (NB@ZnNi-MOF) spheres immobilized with HCG secondary antibodies (HCG Ab2) are used for signal amplification. When HCG exists in an analytical sample, a sandwich structure is formed and an electrochemical signal is produced. The analytical signal generated during the detection is caused by the conversion of Co(ii) and Co(iii) in the CoNi-MOF nanosheet array. The Nile Blue of the NB@ZnNi-MOF sphere, as a kind of redox-active species, is responsible for the electrochemical signal amplification in the immunosensor. On the basis of the above advantages, the HCG immunosensor exhibits a lower limit of detection (1.85 × 10-3 mIU mL-1) and a wide linear range from 0.005 mIU mL-1 to 250 mIU mL-1. Additionally, this immunosensor is used to quantitatively detect HCG in human blood serum and shows good correlations with the standard enzyme-linked immunosorbent assay (ELISA), providing a high value on clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Gonadotropina Coriônica/análise , Estruturas Metalorgânicas , Anticorpos Imobilizados , Técnicas Eletroquímicas , Humanos , Imunoensaio , Oxazinas
9.
Mikrochim Acta ; 186(12): 758, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31707617

RESUMO

Nanowires of copper(II)-based metal-organic frameworks (Cu-MOFs) of type Cu(II)(1,4-naphthalenedicarboxylic acid) (1,4-NDC) were deposited on the surface of a copper foam by immersion of Cu(OH)2 nanowires in a solution of 1,4-NDC. An electrochemical immunosensor for the prostate specific antigen (PSA) is obtained by using the nanowire arrays as a redox signal probe. The signal is generated by the conversion of Cu(I) and Cu(II) of Cu-MOFs nanowires. Cu(1,4-NDC) nanowires contain many uncoordinated carboxyl groups which can bind to the amino groups of the PSA antibody. When PSA antibody binds to PSA antigen during an immune response, the current signal will decrease due to the electrical insulation of PSA antigen. The decrease of current is directly proportional to the increase of PSA concentration. The immunosensor, best operated at a voltage of typically -0.08 V (vs. Ag/AgCl), has a low limit of detection (4.4 fg·mL-1) and a wide linear range (0.1 pg·mL-1 to 20 ng·mL-1). This meets the demands of clinical diagnosis (with values <4 ng·mL-1) in serum. The method was applied to the determination of PSA in spiked serum. Graphical abstractSchematic representation of the in-situ growth of ordered Cu-MOFs wrapped with Cu(OH)2 nanowires, building the core-shell structure as the 3D electrode. A novel electrochemical immunosensor for PSA detection has been exploited, using the Cu-MOFs nanowire arrays on Cu foam as a redox signal probe for the first time.


Assuntos
Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , Estruturas Metalorgânicas/química , Nanofios/química , Antígeno Prostático Específico/sangue , Anticorpos Imobilizados/imunologia , Cobre/química , Técnicas Eletroquímicas/instrumentação , Eletrodos , Humanos , Limite de Detecção , Naftalenos/química , Antígeno Prostático Específico/imunologia , Reprodutibilidade dos Testes
10.
Heliyon ; 10(1): e23398, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38226271

RESUMO

Objective: To systematically evaluate the effectiveness and safety of integrated Chinese and Western medicine in the treatment of acute myeloid leukaemia (AML) in elderly people. Method: The Cochrane Library, PubMed, Web of Science, Excerpta Medica Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang Data and VIP Data databases were systematically searched from database inception to 30 June 2023 to identify cases of AML treatment with and without integrated Chinese and Western medicine. Fixed- and random-effect models were used to pool the main results, and the pooled risk ratio (RR) with a 95 % confidence interval (CI) was used as the effect indicator. Results: Eleven randomized controlled trial (RCT) involving 828 patients were finally included. The meta-analysis results showed that the overall response efficiency of integrated Chinese and Western medicine in treating myeloid leukaemia in elderly people was better than that of Western medicine alone (RR = 1.23, 95 % CI: 1.13, 1.33, p < 0.001). There was significant difference in the complete remission rate between the two groups (RR = 1.38, 95 % CI: 1.15, 1.65, p < 0.001). The incidence of myelosuppression (RR = 0.49, 95 % CI: 0.32, 0.75, p = 0.001), hepatic and renal insufficiency (RR = 0.43, 95 % CI: 0.29, 0.66, p < 0.001), infection (RR = 0.26, 95 % CI: 0.17, 0.40, p < 0.001) and gastrointestinal discomfort (RR = 0.31, 95 % CI: 0.22, 0.46, p < 0.001) of integrated Chinese and Western medicine were significantly lower than that of Western medicine alone. Conclusion: Compared with Western medicine alone, the application of integrated traditional Chinese and Western medicine can improve the total clinical remission rate and reduce adverse effects following chemotherapy. However, more high-quality results of randomised controlled trials and analysis are needed to confirm the findings.

11.
J Cancer Res Clin Oncol ; 150(5): 264, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767747

RESUMO

BACKGROUND: Bladder cancer (BCa) is among the most prevalent malignant tumors affecting the urinary system. Due to its highly recurrent nature, standard treatments such as surgery often fail to significantly improve patient prognosis. Our research aims to predict prognosis and identify precise therapeutic targets for novel treatment interventions. METHODS: We collected and screened genes related to the TGF-ß signaling pathway and performed unsupervised clustering analysis on TCGA-BLCA samples based on these genes. Our analysis revealed two novel subtypes of bladder cancer with completely different biological characteristics, including immune microenvironment, drug sensitivity, and more. Using machine learning classifiers, we identified SMAD6 as a hub gene contributing to these differences and further investigated the role of SMAD6 in bladder cancer in the single-cell transcriptome data. Additionally, we analyzed the relationship between SMAD6 and immune checkpoint genes. Finally, we performed a series of in vitro assays to verify the function of SMAD6 in bladder cancer cell lines. RESULTS: We have revealed two novel subtypes of bladder cancer, among which C1 exhibits a worse prognosis, lower drug sensitivity, a more complex tumor microenvironment, and a 'colder' immune microenvironment compared to C2. We identified SMAD6 as a key gene responsible for the differences and further explored its impact on the molecular characteristics of bladder cancer. Through in vitro experiments, we found that SMAD6 promoted the prognosis of BCa patients by inhibiting the proliferation and migration of BCa cells. CONCLUSION: Our study reveals two novel subtypes of BCa and identifies SMAD6 as a highly promising therapeutic target.


Assuntos
Aprendizado de Máquina , Proteína Smad6 , Microambiente Tumoral , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Prognóstico , Proteína Smad6/genética , Proteína Smad6/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Proliferação de Células , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica
12.
Sci Total Environ ; 914: 169582, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38154646

RESUMO

Metals are rarely found as free ions in natural and anthropogenic environments, but they are often associated with organic matter and minerals. Under the context of circular economy, metals should be recycled, yet they are difficult to extract for their complex forms in real situations. Based on the protocols of review methodology and the analysis of VOS viewer, there are few reviews on the properties of metal-organic complexes, decomplexation methods, the effect of coexisting ions, the pH influence, and metal recovery methods for the increasingly complicated metal-organic complexes wastewater. Conventional treatment methods such as flocculation, adsorption, biological degradation, and ion exchange fail to decompose metal-organic complexes completely without causing secondary pollution in wastewater. To enhance comprehension of the behavior and morphology exhibited by metal-organic complexes within aqueous solutions, we presented the molecular structure and properties of metal-organic complexes, the decomplexation mechanisms that encompassed both radical and non-radical oxidizing species, including hydroxyl radical (OH), sulfate radical (SO˙4-), superoxide radical (O˙2-), hydrogen peroxide (H2O2), ozone (O3), and singlet oxygen (1O2). More importantly, we reviewed novel aspects that have not been covered by previous reviews considering the impact of operational parameters and coexisting ions. Finally, the potential avenues and challenges were proposed for future research.

13.
Cell Death Discov ; 10(1): 391, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223162

RESUMO

Bladder cancer (BC) represents a prevalent and formidable malignancy necessitating innovative diagnostic and therapeutic strategies. Circular RNAs (circRNAs) have emerged as crucial regulators in cancer biology. In this study, we comprehensively evaluated ferroptosis levels in BC cells utilizing techniques encompassing lipid peroxidation assessment, transmission electron microscopy, and malondialdehyde (MDA) measurement. Additionally, we probed into the mechanistic intricacies by which circRNAs govern BC, employing RNA pull-down, RNA immunoprecipitation (RIP), and immunoprecipitation (IP) assays. Our investigation unveiled circSIRT5, which displayed significant downregulation in BC. Notably, circSIRT5 emerged as a promising prognostic marker, with diminished expression correlating with unfavorable clinical outcomes. Functionally, circSIRT5 was identified as an inhibitor of BC progression both in vitro and in vivo. Mechanistically, circSIRT5 exerted its tumor-suppressive activities through the formation of a ternary complex involving circSIRT5, SYVN1, and PHGDH. This complex enhanced the ubiquitination and subsequent degradation of PHGDH, ultimately promoting ferroptosis in BC cells. This ferroptotic process contributed significantly to the inhibition of tumor growth and metastasis in BC. In addition, FUS was found to accelerate the biogenesis of circSIRT5 in BC. These findings provide valuable insights into the pivotal role of circSIRT5 in BC pathogenesis, underscoring its potential as a diagnostic biomarker and therapeutic target for this malignancy.

14.
Front Immunol ; 15: 1427124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39238647

RESUMO

Background: Ferroptosis, as a novel form of programmed cell death, plays a crucial role in the occurrence and development of bladder cancer (BCa). However, the regulatory mechanisms of ferroptosis in the tumor microenvironment (TME) of BCa remain to be elucidated. Methods: Based on single-cell RNA (scRNA) transcriptomic data of BCa, we employed non-negative matrix factorization (NMF) dimensionality reduction clustering to identify novel ferroptosis-related cell subtypes within the BCa TME, aiming to explore the biological characteristics of these TME cell subtypes. Subsequently, we conducted survival analysis and univariate Cox regression analysis to explore the prognostic significance of these cell subtypes. We investigated the relationship between specific subtypes and immune infiltration, as well as their implications for immunotherapy. Finally, we discovered a valuable and novel biomarker for BCa, supported by a series of in vitro experiments. Results: We subdivided cancer-associated fibroblasts (CAFs), macrophages, and T cells into 3-5 small subpopulations through NMF and further explored the biological features. We found that ferroptosis played an important role in the BCa TME. Through bulk RNA-seq analysis, we further verified that ferroptosis affected the progression, prognosis, and immunotherapy response of BCa by regulating the TME. Especially ACSL4+CAFs, we found that high-level infiltration of this CAF subtype predicted worse prognosis, more complex immune infiltration, and less response for immunotherapy. Additionally, we found that this type of CAF was associated with cancer cells through the PTN-SDC1 axis, suggesting that SDC1 may be crucial in regulating CAFs in cancer cells. A series of in vitro experiments confirmed these inferences: SDC1 promoted the progression of BCa. Interestingly, we also discovered FTH1+ macrophages, which were closely related to SPP1+ macrophages and may also be involved in the regulation of BCa TME. Conclusion: This study revealed the significant impact of ferroptosis on bladder cancer TME and identified novel ferroptosis-related TME cell subpopulations, ACSL4+CAFs, and important BCa biomarker SDC1.


Assuntos
Progressão da Doença , Ferroptose , Imunoterapia , Análise de Célula Única , Transcriptoma , Microambiente Tumoral , Neoplasias da Bexiga Urinária , Ferroptose/genética , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Imunoterapia/métodos , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Prognóstico , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia
15.
Int J Pharm ; 649: 123665, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38048889

RESUMO

Recently, cylindrical granules have been applied in pharmaceutical fields and their aspect ratio (AR) is considered an important factor in the manufacturing process. However, the relationships between AR and the tableting process were seldom reported. This study aims to clarify the role of AR in the tableting process of cylindrical granules. First, mesalazine cylindrical granules with different AR were extruded, and their physical attributes were then comprehensively characterized. Subsequently, their compression behaviors and tableting performances were systematically assessed. Notably, it was found that the cylindrical granules with high AR possessed good anti-deformation capacity and favorable tabletability. Finally, the dissolution test suggested that tablets compressed from cylindrical granules with higher AR showed lower dissolution rates. Collectively, findings in this study identified that the AR of cylindrical granules was a critical factor in the tableting process and provided valuable guidance for the application of these granules in oral solid formulations.


Assuntos
Mesalamina , Composição de Medicamentos/métodos , Comprimidos , Tamanho da Partícula , Resistência à Tração
16.
J Colloid Interface Sci ; 663: 577-590, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38428115

RESUMO

Photodynamic therapy (PDT) is limited in tumor therapy due to the mature antioxidant barrier of tumor microenvironment (TME) and phototoxicity/easy-degradation characteristics of photosensitizers. Therefore, we prepared Cu2+-doped hollow carbon nanoparticles (CHC) to protect the loaded photosensitizers and sensitize TME by glutathione-depletion and peroxidase (POD)-like activity for enhanced PDT. CHC significantly increased the maximum speed of POD-like reaction (Vm) of 8.4 times. By coating with hyaluronic acid (HA), the active sites on CHC were temporarily masked with low catalytic property, and restored in response to the overexpressed hyaluronidase in TME. Meanwhile, due to the excellent photothermal conversion efficiency (32.5 %) and hollow structure of CHC, the loaded photosensitizers were well protected from sunlight activation-induced unwanted phototoxicity and rapid degradation under the near-infrared light irradiation. In-vivo anti-tumor experiments demonstrated that the combination of photothermal-photodynamic effect achieved the best anti-tumor effect (tumor inhibition rate at 87.8 %) compared with any monotherapy. In addition, the combination of photothermal and photodynamic effect could efficiently suppress the cell migration, manifesting the reduced number of lung metastasized nodules by 74 %. This work provides an integrated platform for photosensitizers protection and TME sensitization for enhanced PDT.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Carbono/farmacologia , Microambiente Tumoral , Neoplasias/tratamento farmacológico , Catálise , Linhagem Celular Tumoral , Nanopartículas/química , Peróxido de Hidrogênio
17.
Adv Drug Deliv Rev ; 213: 115445, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39222795

RESUMO

Deformability is one of the critical attributes of nanoparticle (NP) drug carriers, along with size, shape, and surface properties. It affects various aspects of NP biotransport, ranging from circulation and biodistribution to interactions with biological barriers and target cells. Recent studies report additional roles of NP deformability in biotransport processes, including protein corona formation, intracellular trafficking, and organelle distribution. This review focuses on the literature published in the past five years to update our understanding of NP deformability and its effect on NP biotransport. We introduce different methods of modulating and evaluating NP deformability and showcase recent studies that compare a series of NPs in their performance in biotransport events at all levels, highlighting the consensus and disagreement of the findings. It concludes with a perspective on the intricacy of systematic investigation of NP deformability and future opportunities to advance its control toward optimal drug delivery.


Assuntos
Nanopartículas , Nanopartículas/química , Humanos , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Distribuição Tecidual , Transporte Biológico , Propriedades de Superfície
18.
ACS Nano ; 18(15): 10642-10652, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38560784

RESUMO

Considerable attention has been by far paid to stabilizing metallic Zn anodes, where side reactions and dendrite formation still remain detrimental to their practical advancement. Electrolyte modification or protected layer design is widely reported; nonetheless, an effective maneuver to synergize both tactics has been rarely explored. Herein, we propose a localized electrolyte optimization via the introduction of a dual-functional biomass modificator over the Zn anode. Instrumental characterization in conjunction with molecular dynamics simulation indicates local solvation structure transformation owing to the limitation of bound water with intermolecular hydrogen bonds, effectively suppressing hydrogen evolutions. Meanwhile, the optimized nucleation throughout the protein membrane allows uniform Zn deposition. Accordingly, the symmetric cell exhibits an elongated lifespan of 3280 h at 1.0 mA cm-2/1.0 mAh cm-2, while the capacity retention of the full cell sustains 91.1% after 2000 cycles at 5.0 A g-1. The localized electrolyte tailoring via protein membrane introduction might offer insights into operational metal anode protection.

19.
Adv Mater ; 36(9): e2306992, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37917072

RESUMO

Potassium metal battery is an appealing candidate for future energy storage. However, its application is plagued by the notorious dendrite proliferation at the anode side, which entails the formation of vulnerable solid electrolyte interphase (SEI) and non-uniform potassium deposition on the current collector. Here, this work reports a dual-modification design of aluminum current collector to render dendrite-free potassium anodes with favorable reversibility. This work achieves to modulate the electronic structure of the designed current collector and accordingly attain an SEI architecture with robust inorganic-rich constituents, which is evidenced by detailed cryo-EM inspection and X-ray depth profiling. The thus-produced SEI manages to expedite ionic conductivity and guide homogeneous potassium deposition. Compared to the potassium metal cells assembled using typical aluminum current collector, cells based on the designed current collector realize improved rate capability (maintaining 400 h under 50 mA cm-2 ) and low-temperature durability (stable operation at -50 °C). Moreover, scalable production of the current collector allows for the sustainable construction of high-safety potassium metal batteries, with the potential for reducing the manufacturing cost.

20.
Cancer Lett ; 582: 216515, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38056687

RESUMO

Bladder cancer (BC) is a common malignancy in males, and currently lacks ideal therapeutic approaches. Exploring emerging therapeutic targets from the perspective of endogenous peptides to improve the prognosis of bladder cancer patients holds promise. In this study, we have identified CTSGDP-13, a novel endogenous peptide, which demonstrates potential anti-cancer effects in BC. Our findings reveal that CTSGDP-13 can promote ferroptosis in BC cells, both in vitro and in vivo, leading to the inhibition of BC progression. Furthermore, we have identified TRIM25 as a downstream regulatory target of CTSGDP-13. The expression of TRIM25 is significantly upregulated in BC, and its inhibition of ferroptosis promotes BC progression. Mechanistic studies have shown that CTSGDP-13 promotes the ubiquitination and subsequent degradation of TRIM25 by disrupting its interaction with the deubiquitinase USP7. Further investigations indicate that CTSGDP-13 promotes ferroptosis in BC by regulating the USP7/TRIM25/KEAP1 axis. The elucidation of the functional mechanisms of natural CTSGDP-13 and TRIM25 holds promise in providing valuable therapeutic targets for BC diagnosis and treatment.


Assuntos
Ferroptose , Neoplasias da Bexiga Urinária , Masculino , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch , Micropeptídeos , Peptidase 7 Específica de Ubiquitina , Fator 2 Relacionado a NF-E2 , Neoplasias da Bexiga Urinária/patologia
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