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1.
Anal Chem ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39263740

RESUMO

Dynamic detection of multiple C5F10O decomposition gases can more comprehensively and effectively evaluate the operating status of eco-friendly gas-insulated power equipment (GIPE), which is a technical support for promoting the construction of eco-friendly, low-carbon energy power systems. In this article, we propose a silicon noise suppression fiber-enhanced Raman spectroscopy (FERS) technique and design a FERS sensing system for the dynamic detection of multiple C5F10O decomposition gases. Benefiting from the effective hybrid silicon noise filtering technology, the spectrum noise of FERS can be suppressed by 90% and the system detection sensitivity can be improved by 4.22 times. Utilizing a 2 m-long antiresonant hollow-core fiber, the system achieved detection limits of 1.34 and 1.44 ppmv for CF4 and CO2, respectively, under the conditions of a laser power of 200 mW, a pressure of 0.5 MPa, and a measurement time of 120 s. Afterward, combining sample gas and density functional theory simulation, the characteristic peak positions for quantitative analysis of C5F10O decomposition gas were determined as follows: CF4: 906 cm-1, CO2: 1388 cm-1, C5F10O: 759 cm-1, CF2O: 965 cm-1, CF3H: 1117 cm-1, C2F4: 517 cm-1, C2F6: 807 cm-1, C3F6: 767 cm-1, C3F8: 780 cm-1, C3F7H: 857 cm-1, and C4F10: 770 cm-1. Finally, the sensing system conducted dynamic measurements of the partial discharge decomposition gases of the C5F10O GIPE for 5 days with a 2 h measurement interval. The content trends of C5F10O and decomposition gases CF4, CO2, C3F6, and C3F7H were obtained. These results fully demonstrate the capability of FERS technology for dynamically detecting the decomposition gases of the C5F10O GIPE.

2.
Small ; : e2403354, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101616

RESUMO

Defect engineering is an effective strategy to enhance the enzyme-like activity of nanozymes. However, previous efforts have primarily focused on introducing defects via de novo synthesis and post-synthetic treatment, overlooking the dynamic evolution of defects during the catalytic process involving highly reactive oxygen species. Herein, a defect-engineered metal-organic framework (MOF) nanozyme with mixed linkers is reported. Over twofold peroxidase (POD)-like activity enhancement compared with unmodified nanozyme highlights the critical role of in situ defect formation in enhancing the catalytic performance of nanozyme. Experimental results reveal that highly active hydroxyl radical (•OH) generated in the catalytic process etches the 2,5-dihydroxyterephthalic acid ligands, contributing to electronic structure modulation of metal sites and enlarged pore sizes in the framework. The self-enhanced POD-like activity induced by in situ defect engineering promotes the generation of •OH, holding promise in colorimetric sensing for detecting dichlorvos. Utilizing smartphone photography for RGB value extraction, the resultant sensing platform achieves the detection for dichlorvos ranging from 5 to 300 ng mL-1 with a low detection limit of 2.06 ng mL-1. This pioneering work in creating in situ defects in MOFs to improve catalytic activity offers a novel perspective on traditional defect engineering.

3.
Acta Biomater ; 185: 396-409, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39053815

RESUMO

Near-infrared-II (NIR-II) photothermal therapy is emerging as a cutting-edge modality for tumor ablation due to its good biosafety, high penetration ability and spatiotemporal controllability. Despite efforts, establishing a link between cellular metabolic regulation and photothermal performance is still promising in synergistic cancer therapy. Herein, we developed a core-shell semiconducting polymer@metal-phenolic network (SP@GFP) nanomotor by assembling diphenol-terminated cisplatin prodrug ligand (cPt-DA) and iron (III) (Fe3+) through metal coordination on SP particles in the presence of GOx and DSPE-PEG-cRGD, for NIR-II-propelled self-propulsion and synergistic cancer therapy. Remotely driving the SP@GFP nanomotor with an NIR-II laser through a thermophoresis mechanism would allow for in-depth penetration and accumulation. The synergistic photothermal effect and continuous Fe2+-mediated ROS generation of SP@GFP nanomotor could activate photothermal, chemotherapeutic effects and ferroptosis pathway for cancer cells through reshaping cellular metabolic pathways (HSP and GPX4). By combining the concepts of chemotherapeutic prodrugs, catalytic ROS generation, photothermal response and cellular metabolic regulation, the NIR-II laser-controlled core-shell SP@GFP nanomotor displayed improved outcomes for enhanced cancer therapy through synergistic oxidative stress-photothermo modulation. STATEMENT OF SIGNIFICANCE.


Assuntos
Raios Infravermelhos , Estresse Oxidativo , Pró-Fármacos , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Humanos , Estresse Oxidativo/efeitos dos fármacos , Animais , Camundongos , Neoplasias/patologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Nanopartículas/química , Terapia Fototérmica , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Feminino , Camundongos Nus
4.
Nano Lett ; 24(32): 9974-9982, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39083237

RESUMO

Various applications related to glucose catalysis have led to the development of functional nanozymes with glucose oxidase (GOX)-like activity. However, the unsatisfactory catalytic activity of nanozymes is a major challenge for their practical applications due to their inefficient hydrogen and electron transfer. Herein, we present the synthesis of AuFe/polydopamine (PDA) superparticles that exhibit photothermal-enhanced GOX-like activity. Experimental investigations and theoretical calculations reveal that the glucose oxidation process catalyzed by AuFe/PDA follows an artificial-cofactor-mediated hydrogen atom transfer mechanism, which facilitates the generation of carbon-centered radical intermediates. Rather than depending on charged Au surfaces for thermodynamically unstable hydride transfer, Fe(III)-coordinated PDA with abundant amino and phenolic hydroxyl groups serves as cofactor mimics, facilitating both hydrogen atom and electron transfer in the catalytic process. Finally, leveraging the photothermal-enhanced GOX-like and catalase-like activities of AuFe/PDA, we establish a highly sensitive and accurate point-of-care testing blood glucose determination with exceptional anti-jamming capabilities.


Assuntos
Glucose Oxidase , Ouro , Hidrogênio , Indóis , Polímeros , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Ouro/química , Hidrogênio/química , Transporte de Elétrons , Indóis/química , Polímeros/química , Glucose/química , Catálise , Oxirredução , Glicemia/análise , Ferro/química , Humanos
5.
Acta Biomater ; 181: 176-187, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719158

RESUMO

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.


Assuntos
Hidrogéis , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Infecções Bacterianas/tratamento farmacológico , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Lacase/química , Porfirinas/química , Porfirinas/farmacologia , Escherichia coli/efeitos dos fármacos
6.
Opt Express ; 32(7): 12428-12437, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571065

RESUMO

The challenges presented by the directly reflected field in optical feedback cavity-enhanced spectroscopy systems serve as substantial obstacles, introducing additional complexity to existing systems and compromising their sensitivity, as the underlying mechanisms of its adverse effects remain not fully understood. This study aims to address this issue by introducing a comprehensive analytical model. Additionally, frequency locking can be achieved by decreasing the feedback rate, the laser's linewidth enhancement factor, and the directly reflected field, and by increasing the refractive index of the gain medium, the length of the laser's resonant cavity, the electric field reflectivity of the laser's output facet, and the resonant field. These parameters can affect the feedback coupling rate pre-factor, and for a resonant cavity with a length of 0.394 m, optical feedback can only be established when the feedback coupling rate pre-factor is less than 1.05 × 109. Through experimental validation, we successfully confirm the effectiveness of the proposed solution in eliminating the detrimental effects of the directly reflected field. Importantly, this suppression is achieved without compromising other aspects of the system's performance. The research findings not only offer the potential to optimize various cavity-enhanced spectroscopy systems that rely on optical feedback but also show promising applications in advancing the development of high-purity spectrum diode lasers utilizing optical feedback from an external high-finesse cavity.

7.
Adv Sci (Weinh) ; 11(22): e2400097, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38572522

RESUMO

Plant chloroplasts have a highly compartmentalized interior, essential for executing photocatalytic functions. However, the construction of a photocatalytic reaction compartment similar to chloroplasts in inorganic-biological hybrid systems (IBS) has not been reported. Drawing inspiration from the compartmentalized chloroplast and the phenomenon of liquid-liquid phase separation, herein, a new strategy is first developed for constructing a photocatalytic subcellular hybrid system through liquid-liquid phase separation technology in living cells. Photosensitizers and in vivo expressed hydrogenases are designed to coassemble within the cell to create subcellular compartments for synergetic photocatalysis. This compartmentalization facilitates efficient electron transfer and light energy utilization, resulting in highly effective H2 production. The subcellular compartments hybrid system (HM/IBSCS) exhibits a nearly 87-fold increase in H2 production compared to the bare bacteria/hybrid system. Furthermore, the intracellular compartments of the photocatalytic reactor enhance the system's stability obviously, with the bacteria maintaining approximately 81% of their H2 production activity even after undergoing five cycles of photocatalytic hydrogen production. The research brings forward visionary prospects for the field of semi-artificial photosynthesis, offering new possibilities for advancements in areas such as renewable energy, biomanufacturing, and genetic engineering.


Assuntos
Hidrogênio , Fotossíntese , Hidrogênio/metabolismo , Cloroplastos/metabolismo , Catálise , Processos Fotoquímicos , Separação de Fases
8.
Heliyon ; 10(6): e27302, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38509889

RESUMO

Background: The involvement of molecules associated with PANoptosis in hepatocellular carcinoma (HCC) is still not well understood. Methods: Various R packages were utilized to analyze within the R software. Data that was freely accessible was obtained from the databases of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Results: Here, we comprehensively explored the role of PANoptosis-related genes in HCC. The caspase 2 (CASP2) was identified as the interest gene for further analysis. We found that CASP2 is related to the poor prognosis and worse clinical features of HCC patients. Moreover, we explored the biological pathway CASP2 is involved in and found that CASP2 is associated with multiple carcinogenic pathways. Also, we noticed that CASP2 can significantly reshape the HCC immune microenvironment and affect the response rate of immunotherapy. Analysis of drug sensitivity suggested that individuals exhibiting elevated CASP2 levels may display increased susceptibility to doxorubicin and vorinostat while demonstrating resistance towards erlotinib, lapatinib, sunitinib, and temsirolimus. Meanwhile, we explored the single-cell distribution of CASP2 in the HCC microenvironment. To enhance the clinical application of CASP2 in HCC, we constructed a prognosis model using the molecules derived from CASP2, which demonstrated good efficiency in predicting patients prognosis. Moreover, in vitro experiments indicated that CASP2 can significantly inhibits cell proliferation, invasion and migration ability of HCC cells. Conclusions: Our study comprehensively explored the role of PANoptosis-related molecule CASP2 in HCC, which can provide directions for future studies.

9.
J Clin Med ; 13(2)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38256485

RESUMO

BACKGROUND: The study aimed to investigate the clinical value and prognostic patterns of the neutrophil-to-lymphocyte ratio (NLR) and imaging tumor capsule (ITC) in solitary hepatocellular carcinoma (HCC) patients undergoing narrow-margin hepatectomy. METHODS: Data for solitary HCC patients treated with narrow-margin surgery were extracted from Shanghai General Hospital. Clinical features of recurrence-free survival (RFS), overall survival (OS), and early recurrence were investigated by Cox/logistic regression. The significant variables were subsequently incorporated into the nomogram pattern. Survival analysis stratified by NLR and ITC was also performed. RESULTS: The study included a cohort of 222 patients, with median RFS and OS of 24.083 and 32.283 months, respectively. Both an NLR ≥ 2.80 and incomplete ITC had a significant impact on prognosis. NLR and ITC independently affected RFS and OS, whereas alpha-fetoprotein (AFP) and ITC were identified as independent factors for early relapse. The RFS and OS nomogram, generated based on the Cox model, demonstrated good performance in validation. The combination of NLR and ITC showed greater predictive accuracy for 5-year RFS and OS. Subgroups with an NLR ≥ 2.80 and incomplete ITC had the worst prognosis. CONCLUSIONS: Both NLR and ITC significantly affected RFS, OS, and early recurrence among solitary HCC patients who underwent narrow-margin hepatectomy. The combination of NLR and ITC has the potential to guide rational clinical treatment and determine the prognosis.

10.
Anal Chem ; 96(5): 2100-2106, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38262931

RESUMO

Improving the sensitivity in electrochemiluminescence (ECL) detection systems necessitates the integration of robust ECL luminophores and efficient signal transduction. In this study, we report a novel ECL nanoprobe (Zr-MOF) that exhibits strong and stable emission by incorporating aggregation-induced emission ligands into Zr-based metal-organic frameworks (MOFs). Meanwhile, we designed a high-performance signal modulator through the implementation of a well-designed controlled release system with a self-on/off function. ZnS quantum dots (QDs) encapsulated within the cavities of aminated mesoporous silica nanoparticles (NH2-SiO2) serve as the ECL quenchers, while adenosine triphosphate (ATP) aptamers adsorbed on the surface of NH2-SiO2 through electrostatic interaction act as "gatekeepers." Based on the target-triggered ECL resonance energy transfer between Zr-MOF and ZnS QDs, we establish a coreactant-free ECL aptasensor for the sensitive detection of ATP, achieving an impressive low detection limit of 0.033 nM. This study not only demonstrates the successful combination of ECL with controlled release strategies but also opens new avenues for developing highly efficient MOFs-based ECL systems.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Dióxido de Silício , Trifosfato de Adenosina , Preparações de Ação Retardada , Medições Luminescentes , Técnicas Eletroquímicas
12.
Int J Mol Sci ; 24(12)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37373430

RESUMO

Aberrant transmembrane protein (TMEM) expression is implicated in tumor progression, but its functional role in hepatocellular carcinoma (HCC) is unclear. Thus, we aim to characterize the functional contributions of TMEM in HCC. In this study, four novel TMEM-family genes (TMEMs), TMEM106C, TMEM201, TMEM164, and TMEM45A, were screened to create a TMEMs signature. These candidate genes are distinguished between patients with varying survival statuses. High-risk HCC patients had a significantly worse prognosis and more advanced clinicopathological characteristics in both the training and validation groups. The GO and KEGG analyses unveiled that the TMEMs signature might play a crucial role in cell-cycle-relevant and immune-related pathways. We found that the high-risk patients had lower stromal scores and a more immunosuppressive tumor microenvironment with massive infiltration of macrophages and Treg cells, whereas the low-risk group had higher stromal scores and gamma delta T-cell infiltration. Moreover, the expression level of suppressive immune checkpoints increased as the TMEM-signature scores increased. Furthermore, the in vitro experiments validated TMEM201, one feature of the TMEMs signature, and facilitated HCC proliferation, survival, and migration. The TMEMs signature provided a more precise prognostic evaluation of HCC and reflected the immunological status of HCC. Of the TMEMs signature studied, TMEM201 was found to significantly promote HCC progression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Membrana , Humanos , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Ciclo Celular , Relevância Clínica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Microambiente Tumoral/genética , Proteínas de Membrana/genética
13.
Acta Biomater ; 167: 182-194, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37339693

RESUMO

Glutathione (GSH) consumption-enhanced cancer therapies represent important potential cancer treatment strategies. Herein, we developed a new multifunctional diselenide-crosslinked hydrogel with glutathione peroxidase (GPx)-like catalytic activity for GSH depletion-enhanced glucose oxidase (GOx)-mediated tumor starvation and hypoxia-activated chemotherapy. By increasing acid and H2O2 during GOx-induced tumor starvation, the degradation of the multiresponsive scaffold could be promoted, which led to accelerated release of the loaded drugs. Meanwhile, the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment. Following the GOx-induced amplification of hypoxia, tirapazamine (TPZ) was transformed into the highly toxic benzotriazinyl radical (BTZ·), exhibiting enhanced antitumor activity. This GSH depletion-augmented cancer treatment strategy effectively boosted GOx-mediated tumor starvation and activated the hypoxia drug, leading to significantly enhanced local anticancer efficacy. STATEMENT OF SIGNIFICANCE: There has been a growing interest in depleting intracellular GSH as a potential strategy for improving ROS-based cancer therapy. Herein, a bioresponsive diselenide-functionalized dextran-based hydrogel with GPx-like catalytic activity was developed for GSH consumption-enhanced local starvation- and hypoxia-activated melanoma therapy. Results showed that the overproduced H2O2 led to accelerated intracellular GSH consumption under the cascade catalysis of small molecular selenides released from the degraded hydrogel, further enhancing the curative effect of in situ H2O2 and subsequent multimodal cancer treatment.


Assuntos
Melanoma , Neoplasias , Humanos , Peróxido de Hidrogênio , Hidrogéis/uso terapêutico , Neoplasias/patologia , Melanoma/tratamento farmacológico , Terapia Combinada , Hipóxia , Linhagem Celular Tumoral , Microambiente Tumoral
14.
Adv Sci (Weinh) ; 10(22): e2301919, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37189219

RESUMO

Self-propelled nanomotors, which can autonomous propelled by harnessing others type of energy, have shown tremendous potential as drug delivery systems for cancer therapy. However, it remains challenging for nanomotors in tumor theranostics because of their structural complexity and deficient therapeutic model. Herein, glucose-fueled enzymatic nanomotors (GC6@cPt ZIFs) are developed through encapsulation of glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) using cisplatin-skeletal zeolitic imidazolate frameworks (cPt ZIFs) for synergetic photochemotherapy. The GC6@cPt ZIFs nanomotors can produce O2 through enzymatic cascade reactions for propelling the self-propulsion. Trans-well chamber and multicellular tumor spheroids experiments demonstrate the deep penetration and high accumulation of GC6@cPt nanomotors. Importantly, the glucose-fueled nanomotor can release the chemotherapeutic cPt and generate reactive oxygen species under laser irradiation, and simultaneously consume intratumoral over-expressed glutathione. Mechanistically, such processes can inhibit cancer cell energy and destroy intratumoral redox balance to synergistically damage DNA and induce tumor cell apoptosis. Collectively, this work demonstrates that the self-propelled prodrug-skeleton nanomotors with oxidative stress activation can highlight a robust therapeutic capability of oxidants amplification and glutathione depletion to boost the synergetic cancer therapy efficiency.


Assuntos
Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Glucose Oxidase , Glucose
15.
Front Genet ; 14: 1106952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936440

RESUMO

Introduction: Although the molecular mechanisms of Krüpple-like factor 4 (KLF4) as a tumor suppressor in HCC tumorigenesis have been thoroughly examined, its clinical application in terms of precise prognostication and its influence on tumor immune microenvironment in patients with HCC require further investigation. Methods: Bioinformatics and immunohistochemistry (IHC) were used to validate KLF4 expressions in a tissue microarray (TMA) containing HCC samples. Using Cox regression models, independent prognostic factors were identified and employed in the development of nomograms. Decision curve analysis (DCA) demonstrated the superiority of the nomograms. GO and KEGG pathway analyses were applied to the functional study of KLF4. The GSVA program explored the link between KLF4 expression and tumor-infiltrating immune cells, and CAMOIP was used to construct KLF4 expression immune scores. Changes in immune-related gene markers were also investigated in relation to KLF4 expression. The association between immune cell infiltration and KLF4 expression was validated by IHC in TMA. Results: HCC was reported to have a notable depletion of KLF4. The absence of KLF4 was associated with advanced clinicopathological characteristics of HCC and predicted a bad prognosis for patients. Nomograms constructed using KLF4 expression, tumor differentiation, and TNM stage provided a more accurate prognostic assessment of HCC patients than TNM stage alone. KLF4 expression was associated with immunological-related functions, infiltration of macrophages, CD8+ T cells, and other immune cells, and elevation of immune checkpoints. Higher levels of CD8+ T cells and macrophage infiltration are associated with increased KLF4 expression in HCC TMA. Conclusion: KLF4 loss in HCC is a prognostic biomarker that influences the tumor immune microenvironment (TIME).

16.
J Gastrointest Surg ; 27(6): 1130-1140, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36759386

RESUMO

PURPOSE: Splenectomy is an effective treatment for correcting cytopenia caused by hypersplenism secondary to cirrhosis. However, other potential benefits have not been well characterized. In this study, we investigated the value of splenectomy as it relates to improvement in hepatic function, liver regeneration, and health-related quality of life, and their association with baseline characteristics to clarify which patients may benefit the most from splenectomy. METHODS: Patients with hypersplenism secondary to cirrhosis treated by splenectomy were retrospectively reviewed. Hepatic function was reflected by hematologic indices and albumin-bilirubin score. Liver volume was measured by imaging software, and quality-of-life was assessed by a 36-question short-form questionnaire. The changes in these three aspects after splenectomy were evaluated in the whole cohort and compared between subgroups. RESULTS: The hepatic function of the patients significantly improved after splenectomy, and this was reflected by elevated serum albumin, shortened prothrombin time, and decreased albumin-bilirubin score. Patients with baseline albumin-bilirubin grade 2 or 3 and age < 56 years showed significantly decreased albumin-bilirubin score after splenectomy, whereas other subgroups did not. Moreover, liver volume increased remarkably after splenectomy in patients with baseline albumin-bilirubin grade 1, but not in those with grade 2 or 3. Significant improvement in quality-of-life occurred in the entire cohort after splenectomy, but more profound improvement was found in patients with albumin-bilirubin grade 2 or 3. CONCLUSIONS: Splenectomy improves hepatic function, increases liver volume, and also improves quality-of-life in different subsets of patients with cirrhosis and hypersplenism. Baseline characteristics, such as albumin-bilirubin grade and age, are helpful in estimating the potential benefits of splenectomy for patients before surgery.


Assuntos
Carcinoma Hepatocelular , Hiperesplenismo , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Hiperesplenismo/complicações , Hiperesplenismo/cirurgia , Esplenectomia/métodos , Estudos Retrospectivos , Qualidade de Vida , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Bilirrubina , Albumina Sérica , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/cirurgia
17.
IEEE Trans Med Imaging ; 42(1): 91-102, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063521

RESUMO

Automated medical image segmentation for organs or lesions plays an essential role in clinical diagnoses and treatment plannings. However, training an accurate and robust segmentation model is still a long-standing challenge due to the time-consuming and expertise-intensive annotations for training data, especially 3-D medical images. Recently, self-supervised learning emerges as a promising approach for unsupervised visual representation learning, showing great potential to alleviate the expertise annotations for medical images. Although global representation learning has attained remarkable results on iconic datasets, such as ImageNet, it can not be applied directly to medical image segmentation, because the segmentation task is non-iconic, and the targets always vary in physical scales. To address these problems, we propose a Multi-scale Visual Representation self-supervised Learning (MsVRL) model, to perform finer-grained representation and deal with different target scales. Specifically, a multi-scale representation conception, a canvas matching method, an embedding pre-sampling module, a center-ness branch, and a cross-level consistent loss are introduced to improve the performance. After pre-trained on unlabeled datasets (RibFrac and part of MSD), MsVRL performs downstream segmentation tasks on labeled datasets (BCV, spleen of MSD, and KiTS). Results of the experiments show that MsVRL outperforms other state-of-the-art works on these medical image segmentation tasks.


Assuntos
Processamento de Imagem Assistida por Computador , Baço , Aprendizado de Máquina Supervisionado
18.
Front Pharmacol ; 14: 1288492, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38178862

RESUMO

Background: ARLs, which are a class of small GTP-binding proteins, play a crucial role in facilitating tumor tumorigenesis and development. ARL4C, a vital member of the ARLs family, has been implicated in the progression of tumors, metastatic dissemination, and development of resistance to therapeutic drugs. Nevertheless, the precise functional mechanisms of ARL4C concerning tumor prognosis and immunotherapy drug susceptibility remain elusive. Methods: By combining the GTEx and TCGA databases, the presence of ARL4C was examined in 33 various types of cancer. Immunohistochemistry and immunofluorescence staining techniques were utilized to confirm the expression of ARL4C in particular tumor tissues. Furthermore, the ESTIMATE algorithm and TIMER2.0 database were utilized to analyze the tumor microenvironment and immune infiltration associated with ARL4C. The TISCH platform facilitated the utilization of single-cell RNA-seq datasets for further analysis. ARL4C-related immune escape was investigated using the TISMO tool. Lastly, drug sensitivity analysis was conducted to assess the sensitivity of different types of tumors to compounds based on the varying levels of ARL4C expression. Results: The study found that ARL4C was highly expressed in 23 different types of cancer. Moreover, the presence of high ARL4C expression was found to be associated with a poor prognosis in BLCA, COAD, KIRP, LGG, and UCEC. Notably, ARL4C was also expressed in immune cells, and its high expression was found to be correlated with cancer immune activation. Most importantly, the drug sensitivity analysis revealed a positive correlation between ARL4C expression and the heightened sensitivity of tumors to Staurosporine, Midostaurin, and Nelarabine. Conclusion: The findings from our study indicate that the expression level of ARL4C may exert an influence on cancer development, prognosis, and susceptibility to immunotherapy drugs. In addition, the involvement of ARL4C in the tumor immune microenvironment has expanded the concept of ARL4C-targeted immunotherapy.

19.
Nanomaterials (Basel) ; 12(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36432310

RESUMO

In this work, highly fluorescent gold nanowire arrays (Au NWs) are successfully synthesized by assembling Zn2+ ions and non-emissive oligomeric gold-thiolate clusters using mercaptopropionic acid both as a reducing agent and a growth ligand. The synthesized Au NWs exhibited strong bluish green fluorescence with an absolute quantum yield up to 32% and possessed ultrasensitive pH stimuli-responsive performance in the range of 7.0-7.8. Based on the excellent properties of the as-prepared nanowire arrays, we developed a facile, sensitive, and selective fluorescent method for quantitative detection of urea and urease. The fabricated nanoprobe showed superior biosensing response characteristics with good linearities in the range of 0-100 µM for urea concentration and 0-12 U/L for urease activity. In addition, this fluorescent probe afforded relatively high sensitivity with the detection limit as low as 2.1 µM and 0.13 U/L for urea and urease, respectively. Urea in human urine and urease in human serum were detected with satisfied results, exhibiting a promising potential for biomedical application.

20.
Mater Today Bio ; 16: 100435, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36164505

RESUMO

The idea of using engineered bacteria as prospective living therapeutic agents for the treatment of different diseases has been raised. Nevertheless, the development of safe and effective treatment strategies remains essential to the success of living bacteria-mediated therapy. Hydrogels have presented great promise for the delivery of living bacterial therapeutics due to their tunable physicochemical properties, good bioactivities, and excellent protection of labile payloads. In this review, we summarize the hydrogel design strategies for living bacteria-mediated therapy and review the recent advances in hydrogel-based living bacterial agent delivery for the treatment of typical diseases, including those for digestive health, skin fungal infections, wound healing, vaccines, and cancer, and discuss the current challenges and future perspectives of these strategies in the field. It is believed that the importance of hydrogel-based living bacteria-mediated therapy is expected to further increase with the development of both synthetic biology and biomaterials science in the future.

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