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1.
Molecules ; 29(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38931000

RESUMO

Microbial fuel cells (MFCs) have the potential to directly convert the chemical energy in organic matter into electrical energy, making them a promising technology for achieving sustainable energy production alongside wastewater treatment. However, the low extracellular electron transfer (EET) rates and limited bacteria loading capacity of MFCs anode materials present challenges in achieving high power output. In this study, three-dimensionally heteroatom-doped carbonized grape (CG) monoliths with a macroporous structure were successfully fabricated using a facile and low-cost route and employed as independent anodes in MFCs for treating brewery wastewater. The CG obtained at 900 °C (CG-900) exhibited excellent biocompatibility. When integrated into MFCs, these units initiated electricity generation a mere 1.8 days after inoculation and swiftly reached a peak output voltage of 658 mV, demonstrating an exceptional areal power density of 3.71 W m-2. The porous structure of the CG-900 anode facilitated efficient ion transport and microbial community succession, ensuring sustained operational excellence. Remarkably, even when nutrition was interrupted for 30 days, the voltage swiftly returned to its original level. Moreover, the CG-900 anode exhibited a superior capacity for accommodating electricigens, boasting a notably higher abundance of Geobacter spp. (87.1%) compared to carbon cloth (CC, 63.0%). Most notably, when treating brewery wastewater, the CG-900 anode achieved a maximum power density of 3.52 W m-2, accompanied by remarkable treatment efficiency, with a COD removal rate of 85.5%. This study provides a facile and low-cost synthesis technique for fabricating high-performance MFC anodes for use in microbial energy harvesting.


Assuntos
Fontes de Energia Bioelétrica , Eletrodos , Vitis , Águas Residuárias , Fontes de Energia Bioelétrica/microbiologia , Águas Residuárias/química , Águas Residuárias/microbiologia , Vitis/química , Purificação da Água/métodos , Porosidade , Eletricidade
2.
Adv Mater ; 36(29): e2400248, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38742698

RESUMO

Single-crystal metal foils with high-index facets are currently being investigated owing to their potential application in the epitaxial growth of high-quality van der Waals film materials, electrochemical catalysis, gas sensing, and other fields. However, the controllable synthesis of large single-crystal metal foils with high-index facets remains a great challenge because high-index facets with high surface energy are not preferentially formed thermodynamically and kinetically. Herein, single-crystal nickel foils with a series of high-index facets are efficiently prepared by applying prestrain energy engineering technique, with the largest single-crystal foil exceeding 5×8 cm2 in size. In terms of thermodynamics, the internal mechanism of prestrain regulation on the formation of high-index facets is proposed. Molecular dynamics simulation is utilized to replicate and explain the phenomenon of multiple crystallographic orientations resulting from prestrain regulation. Additionally, large-sized and high-quality graphite films are successfully fabricated on single-crystal Ni(012) foils. Compared to the polycrystalline nickel, the graphite/single-crystal Ni(012) foil composites show more than five-fold increase in thermal conductivity, thereby showing great potential applications in thermal management. This study hence presents a novel approach for the preparation of single-crystal nickel foils with high-index facets, which is beneficial for the epitaxial growth of certain two-dimensional materials.

3.
Opt Lett ; 49(10): 2853-2856, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748176

RESUMO

Because of their ultra-light, ultra-thin, and flexible design, metalenses exhibit significant potential in the development of highly integrated cameras. However, the performances of metalens-integrated camera are constrained by their fixed architectures. Here we proposed a high-quality imaging method based on deep learning to overcome this constraint. We employed a multi-scale convolutional neural network (MSCNN) to train an extensive pair of high-quality and low-quality images obtained from a convolutional imaging model. Through our method, the imaging resolution, contrast, and distortion have all been improved, resulting in a noticeable overall image quality with SSIM over 0.9 and an improvement in PSNR over 3 dB. Our approach enables cameras to combine the advantages of high integration with enhanced imaging performances, revealing tremendous potential for a future groundbreaking imaging technology.

5.
Sci Rep ; 13(1): 18893, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919381

RESUMO

History courses are an essential part of a national education. The application of traditional courseware's media forms in education still requires further development and refinement. Herein, we report on a history courseware mode that integrates various historical teaching media, including 360-degree VR, paintings, maps, infographics, text, audio, and videos, based on the SCORM standard. These media elements are used to provide learners with a multimodal learning experience in history courses. We monitor the learning effects using EEG and questionnaires. The results show a significant improvement in our multimodal courseware technology compared to traditional courseware.

6.
Cancer Med ; 12(17): 18394-18404, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37610374

RESUMO

BACKGROUND: Pathogenic germline variants (PGVs) can play a vital role in the oncogenesis process in carriers. Previous studies have recognized that PGVs contribute to early onset of tumorigenesis in certain cancer types, for example, colorectal cancer and breast cancer. However, the reported prevalence data of cancer-associated PGVs were highly inconsistent due to nonuniform patient cohorts, sequencing methods, and prominent difficulties in pathogenicity interpretation of variants. In addition to the above difficulties, due to the rarity of cases, the prevalence of cancer PGV carriers in young cancer patients affected by late-onset cancer types has not been comprehensively evaluated to date. METHODS: A total of 131 young cancer patients (1-29 years old at diagnosis) were enrolled in this study. The patients were affected by six common late-onset cancer types, namely, lung cancer, liver cancer, colorectal cancer, gastric cancer, renal cancer, and head-neck cancer. Cancer PGVs were identified and analyzed. based on NGS-based targeted sequencing followed by bioinformatic screening and strict further evaluations of variant pathogenicity. RESULTS: Twenty-three cancer PGVs in 21 patients were identified, resulting in an overall PGV prevalence of 16.0% across the six included cancer types, which was approximately double the prevalence reported in a previous pancancer study. Nine of the 23 PGVs are novel, thus expanding the cancer PGV spectrum. Seven of the 23 (30.4%) PGVs are potential therapeutic targets of olaparib, with potential implications for clinical manipulation. Additionally, a small prevalence of somatic mutations of some classic cancer hallmark genes in young patients, in contrast to all-age patients, was revealed. CONCLUSION: This study demonstrates the high prevalence of PGVs in young cancer patients with the common late-onset cancers and the potentially significant clinical implications of cancer PGVs, the findings highlight the value of PGV screening in young patients across lung cancer, liver cancer, colorectal cancer, gastric cancer, renal cancer, or head-neck cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Colorretais , Neoplasias Renais , Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Prevalência , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética
7.
Small ; 19(46): e2304425, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37475500

RESUMO

Nanostructured anodes generate massive reaction sites to oxidize fuels in solid oxide fuel cells (SOFCs); however, the nonexistence of a practically viable approach for the construction of nanostructures and the retention of these nanostructures under the harsh operating conditions of SOFCs poses a significant challenge. Herein, a simple procedure is reported for the construction of a nanostructured Ni-Gd-doped CeO2 anode based on the direct assembly of pre-formed nanocomposite powder with strong metal-oxide interaction. The directly assembled anode forms heterointerfaces with the electrolyte owing to the electrochemical polarization current and exhibits excellent structural robustness against thermal ripening. An electrolyte-supported cell with the directly assembled anode produces a peak power density of 0.73 W cm-2 at 800 °C, while maintaining stability for 100 h, which is in contrast to the drastic degradation of the cermet anode prepared using the conventional method. These findings provide clarity on the design and construction of durable nanostructured anodes and other electrodes for SOFCs.

8.
J Environ Manage ; 344: 118459, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37399623

RESUMO

Anaerobic digestion (AD) of antibiotic manufacturing wastewater to degrade residual antibiotics and produce mixture of combustible gases has been investigated actively in the past decades. However, detrimental effect of residual antibiotic to microbial activities is commonly faced in AD process, leading to the reduction of treatment efficiency and energy recovery. Herein, the present study systematically evaluated the detoxification effect and mechanism of Fe3O4-modified biochar in AD of erythromycin manufacturing wastewater. Results showed that Fe3O4-modified biochar had stimulatory effect on AD at 0.5 g/L erythromycin existence. A maximum methane yield of 327.7 ± 8.0 mL/g COD was achieved at 3.0 g/L Fe3O4-modified biochar, leading to the increase of 55.7% compared to control group. Mechanistic investigation demonstrated that different levels of Fe3O4-modified biochar could improve methane yield via different metabolic pathways involved in specific bacteria and archaea. Low levels of Fe3O4-modified biochar (i.e., 0.5-1.0 g/L) led to the enrichment of Methanothermobacter sp., strengthening the hydrogenotrophic pathway. On the contrary, high levels of Fe3O4-modified biochar (2.0-3.0 g/L) favored the proliferation of acetogens (e.g., Lentimicrobium sp.) and methanogen (Methanosarcina sp.) and their syntrophic relations played vital role on the simulated AD performance at erythromycin stress. Additionally, the addition of Fe3O4-modified biochar significantly decreased the abundance of representative antibiotic resistant genes (ARGs), benefiting the reduction of environmental risk. The results of this study verified that the application of Fe3O4-modified biochar could be an efficient approach to detoxify erythromycin on AD system, which brings high impacts and positive implications for biological antibiotic wastewater treatment.


Assuntos
Eritromicina , Águas Residuárias , Eritromicina/farmacologia , Anaerobiose , Carvão Vegetal , Antibacterianos/farmacologia , Metano , Reatores Biológicos
9.
Biomaterials ; 300: 122202, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37336116

RESUMO

The effectiveness of mesenchymal stem cells (MSCs) on inflammation-related disease is limited and the pharmaceutical preparation that was used to enhance the efficacy of MSCs cannot reach the diseased tissue in large quantities. Herein, antioxidant liposome (Lipo-OPC) is designed to anchor onto the surface of MSCs membrane via click chemical reaction (MSC-Lipo-OPC) without affecting the viability and physiological characteristics of MSCs, thus allowing efficient accumulation of MSC-Lipo-OPC in X-ray irradiated lung sites. More importantly, MSC-Lipo-OPC promotes the change of the quantity and polarity of innate immunocytes, mainly including neutrophils, macrophages and Tregs, in favor of anti-inflammatory, finally preventing the formation of radioactive pulmonary fibrosis. Therefore, it could enhance the treatment outcome of both of MSCs and drugs to radiation-induced lung injury via modifying the drug-loaded nanoparticle on the surface of MSCs membrane, further promoting the application of MSCs in radiation damage and protection.


Assuntos
Lesão Pulmonar , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fibrose Pulmonar , Pneumonite por Radiação , Humanos , Fibrose Pulmonar/terapia , Lipossomos , Pneumonite por Radiação/terapia
10.
Adv Healthc Mater ; 12(26): e2300944, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37235739

RESUMO

Brachytherapy, including radioactive seed implantation (RSI) and transarterial radiation therapy embolization (TARE), is an important treatment modality for advanced hepatocellular carcinoma (HCC), but the inability of RSI and TARE to treat tumor metastasis and recurrence limits their benefits for patients in the clinic. Herein, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors-loaded alginate microspheres (IMs) are developed as radionuclide carriers with immunomodulatory functions to achieve effective radio-immunotherapy. The size and swelling properties of IMs can be facilely tailored by adjusting the calcium source during emulsification. Small/large IMs(SIMs/LIMs) are biocompatible and available for RSI and TARE, respectively, after 177 Lu labeling. Among them, 177 Lu-SIMs completely eliminated subcutaneous HCC in mice after intratumoral RSI. Moreover, in combination with anti-PD-L1, 177 Lu-SIMs not only eradicate primary tumors by RSI but also effectively inhibit the growth of distant tumors, wherein the potent abscopal effect can be ascribed to the immune stimulation of RSI and the modulation of the tumor immune microenvironment (TIME) by IDO1 inhibitors. In parallel, LIMs demonstrate excellent embolization efficiency, resulting in visible necrotic lesions in the central auricular artery of rabbits, which are promising for TARE in future studies. Collectively, a versatile therapeutic agent is provided to synchronously modulate the TIME during brachytherapy for efficient radio-immunotherapy of advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Coelhos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Microesferas , Radioisótopos/uso terapêutico , Imunoterapia , Microambiente Tumoral
11.
Molecules ; 28(8)2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37110522

RESUMO

Chloroquine phosphate (CQP) is effective in treating coronavirus disease 2019 (COVID-19); thus, its usage is rapidly increasing, which may pose a potential hazard to the environment and living organisms. However, there are limited findings on the removal of CQP in water. Herein, iron and magnesium co-modified rape straw biochar (Fe/Mg-RSB) was prepared to remove CQP from the aqueous solution. The results showed that Fe and Mg co-modification enhanced the adsorption efficiency of rape straw biochar (RSB) for CQP with the maximum adsorption capacity of 42.93 mg/g (at 308 K), which was about two times higher than that of RSB. The adsorption kinetics and isotherms analysis, as well as the physicochemical characterization analysis, demonstrated that the adsorption of CQP onto Fe/Mg-RSB was caused by the synergistic effect of pore filling, π-π interaction, hydrogen bonding, surface complexation, and electrostatic interaction. In addition, although solution pH and ionic strength affected the adsorption performance of CQP, Fe/Mg-RSB still had a high adsorption capability for CQP. Column adsorption experiments revealed that the Yoon-Nelson model better described the dynamic adsorption behavior of Fe/Mg-RSB. Furthermore, Fe/Mg-RSB had the potential for repeated use. Therefore, Fe and Mg co-modified biochar could be used for the remediation of CQP from contaminated water.


Assuntos
COVID-19 , Poluentes Ambientais , Poluentes Químicos da Água , Humanos , Ferro/química , Magnésio , Poluentes Ambientais/análise , Água , Tratamento Farmacológico da COVID-19 , Carvão Vegetal/química , Adsorção , Poluentes Químicos da Água/química , Cinética
12.
ACS Nano ; 17(8): 7475-7486, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37057972

RESUMO

The therapy of solid tumors is always hampered by the intrinsic tumor physical microenvironment (TPME) featured with compact and rigid extracellular matrix (ECM) microstructures. Herein, we introduce nattokinase (NKase), a thrombolytic healthcare drug, to comprehensively regulate the TPME for versatile enhancement of various therapy modalities. Intratumoral injection of NKase not only degrades the major ECM component fibronectin but also inhibits cancer-associated fibroblasts (CAFs) in generating fibrosis, resulting in decreased tumor stiffness, enhanced perfusion, and hypoxia alleviation. The NKase-mediated regulation of the TPME significantly promotes the tumoral accumulation of therapeutic agents, leading to efficient chemotherapy without inducing side effects. Additionally, the enhancement of tumor radiotherapy based on radiosensitizers was also achieved by the pretreatment of intratumorally injected NKase, which could be ascribed to the elevated oxygen saturation level in NKase-treated tumors. Moreover, a xenografted human breast MDB-MA-231 tumor model is established to evaluate the influence of NKase on chimeric antigen receptor (CAR)-T cell therapy, illustrating that the pretreatment of NKase could boost the infiltration of CAR-T cells into tumors and thus be a benefit for tumor inhibition. These findings demonstrate the great promise of the NKase-regulated TPME as a translational strategy for universal enhancement of therapeutic efficacy in solid tumors by various treatments.


Assuntos
Neoplasias da Mama , Neoplasias , Receptores de Antígenos Quiméricos , Animais , Humanos , Feminino , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T , Neoplasias/terapia , Imunoterapia Adotiva/métodos , Neoplasias da Mama/metabolismo , Modelos Animais de Doenças , Microambiente Tumoral
13.
Molecules ; 28(6)2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36985840

RESUMO

To remove typical herbicide diuron effectively, a novel sludge-derived modified biochar (SDMBC600) was prepared using sludge-derived biochar (SDBC600) as raw material and Fe-Zn as an activator and modifier in this study. The physico-chemical properties of SDMBC600 and the adsorption behavior of diuron on the SDMBC600 were studied systematically. The adsorption mechanisms as well as practical applications of SDMBC600 were also investigated and examined. The results showed that the SDMBC600 was chemically loaded with Fe-Zn and SDMBC600 had a larger specific surface area (204 m2/g) and pore volume (0.0985 cm3/g). The adsorption of diuron on SDMBC600 followed pseudo-second-order kinetics and the Langmuir isotherm model, with a maximum diuron adsorption capacity of 17.7 mg/g. The biochar could maintain a good adsorption performance (8.88-12.9 mg/g) under wide water quality conditions, in the pH of 2-10 and with the presence of humic acid and six typical metallic ions of 0-20 mg/L. The adsorption mechanisms of SDMBC600 for diuron were found to include surface complexation, π-π binding, hydrogen bonding, as well as pore filling. Additionally, the SDMBC600 was tested to be very stable with very low Fe and Zn leaching concentration ≤0.203 mg/L in the wide pH range. In addition, the SDMBC600 could maintain a high adsorption capacity (99.6%) after four times of regeneration and therefore, SDMBC600 could have a promising application for diuron removal in water treatment.


Assuntos
Esgotos , Poluentes Químicos da Água , Esgotos/química , Diurona , Cinética , Poluentes Químicos da Água/análise , Carvão Vegetal , Adsorção , Zinco
14.
Front Bioeng Biotechnol ; 11: 1107633, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923457

RESUMO

Introduction: The proper operation of wastewater treatment plants is a key factor in maintaining a stable river and lake environment. Low purification efficiency in winter is a common problem in high-altitude wastewater treatment plants (WWTPs), and analysis of the microbial community involved in the sewage treatment process at high-altitude can provide valuable references for improving this problem. Methods: In this study, the bacterial communities of high- and low-altitude WWTPs were investigated using Illumina high-throughput sequencing (HTS). The interaction between microbial community and environmental variables were explored by co-occurrence correlation network. Results: At genus level, Thauera (5.2%), unclassified_Rhodocyclaceae (3.0%), Dokdonella (2.5%), and Ferribacterium (2.5%) were the dominant genera in high-altitude group. The abundance of nitrogen and phosphorus removal bacteria were higher in high-altitude group (10.2% and 1.3%, respectively) than in low-altitude group (5.4% and 0.6%, respectively). Redundancy analysis (RDA) and co-occurrence network analysis showed that altitude, ultraviolet index (UVI), pH, dissolved oxygen (DO) and total nitrogen (TN) were the dominated environmental factors (p < 0.05) affecting microbial community assembly, and these five variables explained 21.4%, 20.3%, 16.9%, 11.5%, and 8.2% of the bacterial assembly of AS communities. Discussion: The community diversity of high-altitude group was lower than that of low-altitude group, and WWTPs of high-altitude aeras had a unique microbial community structure. Low temperature and strong UVI are pivotal factors contributing to the reduced diversity of activated sludge microbial communities at high-altitudes.

15.
Int J Cancer ; 152(6): 1259-1268, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36408924

RESUMO

MET amplification and exon 14 skipping are well known as oncogenic drivers in multiple cancer types. However, MET fusions in most cancer types are poorly defined. To explore the profile and analyze the characteristics of MET fusions, a large-cohort study was conducted to screen MET fusions in clinical samples (n = 10 882) using DNA-based NGS. A total of 37 potentially functional MET fusions containing the intact tyrosine kinase domain (TKD) of MET were identified in 36 samples. Further, 15 novel MET fusions were identified in five cancer types, and the incidence of novel MET fusions accounted for 40.5% (15/37). Brain cancer had the highest incidence of MET fusion, with PTPRZ1-MET as the most common fusion (37.0%). All MET breakpoints in brain cancer (n = 27) were also located in intron 1, while those in lung cancer (n = 4) occurred in intron 1, intron 11, intron 14 and exon 14, respectively. The positive consistency of the common fusion group was 100% (11/11), while that of the rare fusion group was 53.8% (7/13). In conclusion, we provided a comprehensive genomic landscape of MET rearrangement and updated the MET fusions database for clinical test. In addition, we revealed that DNA-based NGS might serve as the clinical test for common MET fusions; however, rare MET fusions must be validated by both DNA-based NGS and RNA-based NGS. Prospective trials are necessary to confirm the treatment efficacy of MET inhibitors.


Assuntos
Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Neoplasias Encefálicas/genética , Estudos de Coortes , Neoplasias Pulmonares/genética , Proteínas de Fusão Oncogênica/genética , Estudos Prospectivos , Proteínas Tirosina Fosfatases Classe 5 Semelhantes a Receptores/genética
16.
Environ Sci Pollut Res Int ; 30(8): 20547-20557, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36255578

RESUMO

Erythromycin fermentation residue (EFR) after spray drying could be reused as a soil amendment. However, the effects of spray-dried EFR on antibiotic resistance genes (ARGs), nitrogen cycling, and microbial community structure in soil are rarely reported. In this study, a pot experiment was conducted by adding spray-dried EFR to soil. For the application of 1.0% spray-dried EFR, the residual erythromycin (ERY) could be rapidly removed with the half-life of 22.2 d; the total relative abundance of ARGs increased at first, but decreased to the initial level of the control group in the end; genes related to ammonium assimilation (glnA, gltB, gltD), ammonification (gdhA, gudB, cynT, cynS, ncd2), denitrification (narI, narG, narH), assimilatory nitrate reduction (nirA, nasA), and dissimilatory nitrate reduction (nirD) were enriched; soil microbial community structure presented temporary variation. Network analysis showed significant negative correlations between ARGs and nitrogen cycling genes. The addition of 6.0% spray-dried EFR resulted in the amplification of ARGs and inhibition of nitrogen cycling. This work provides new insights into the effects of spray-dried EFR on ARGs, nitrogen cycling, and microbial community structure within the fertilized soil.


Assuntos
Antibacterianos , Eritromicina , Antibacterianos/farmacologia , Antibacterianos/análise , Eritromicina/farmacologia , Solo , Fermentação , Nitratos/análise , Ciclo do Nitrogênio , Genes Bacterianos , Resistência Microbiana a Medicamentos/genética , Nitrogênio/análise , Microbiologia do Solo
18.
JAMA Netw Open ; 5(11): e2243457, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36416825

RESUMO

Importance: Synchronous multiple primary colorectal cancer (sMPCC) is clinically rare, but its incidence has increased over the past decade. However, little is known about the molecular and clinical features of sMPCC, which may differ from those of single primary colorectal cancer (SPCRC). Objective: To evaluate the clinical characteristics and pathogenic variations in lesions and the molecular typing of sMPCC. Design, Setting, and Participants: From November 2012 to April 2021, patients with colorectal cancer (CRC) treated at the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this cohort study. Follow-up ended on January 31, 2022. Main Outcomes and Measures: The primary outcome was mismatch repair (MMR) status of each lesion in all patients examined using immunohistochemistry (IHC). Microsatellite instability (MSI) and tumor mutation burden (TMB) were also calculated. Results: A total of 13 276 patients with CRC were enrolled, and 239 patients with sMPCC (mean [SD] age, 63.3 [12.2] years; 173 men [72.4%]) with available clinical data were evaluated. Seventy-eight patients with sMPCC and 94 with SPCRC also underwent next-generation sequencing (NGS)-based molecular testing. The deficient MMR (dMMR)/MSI-H frequencies in sMPCC were significantly higher than those in SPCRC, which was confirmed by both IHC (50 of 239 patients vs 872 of 13 037 patients) and NGS (17 of 78 patients vs 5 of 94 patients). According to the MMR/MSI status of different lesions in patients with sMPCC, they were further divided into 3 subgroups: all dMMR/MSI-H, dMMR/MSI-H and proficient MMR (pMMR)/microsatellite stability (MSS), and all pMMR/MSS. The EGFR and PIK3CA variants were more common, whereas TP53 variants were less prevalent in patients with sMPCC than in those with SPCRC. Moreover, higher tumor mutation burden was associated with higher MSI in patients with sMPCC rather than in those with SPCRC. Conclusions and Relevance: In this cohort study of sMPCC, the incidence of dMMR/MSI-H in patients with sMPCC was significantly higher than that in patients with SPCRC. These findings suggest that sMPCC can be classified into 3 subgroups according to the MMR/MSI status of each lesion, which might be applied to guide personalized therapies for better disease management.


Assuntos
Neoplasias Colorretais , Neoplasias Primárias Múltiplas , Masculino , Humanos , Pessoa de Meia-Idade , Estudos de Coortes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Tipagem Molecular , Neoplasias Primárias Múltiplas/genética
19.
Adv Mater ; 34(51): e2207343, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36222379

RESUMO

The special metabolic traits of cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) are promising targets for developing novel cancer therapy strategies, especially the glycolysis and mitochondrial energy metabolism. However, therapies targeting a singular metabolic pathway are always counteracted by the metabolic reprogramming of cancer, resulting in unsatisfactory therapeutic effect. Herein, this work employs poly(ethylene glycol)-coated (PEGylated) liposomes as the drug delivery system for both mannose and levamisole hydrochloride to simultaneously inhibit glycolysis and restrain mitochondrial energy metabolism and thus inhibit tumor growth. In combination with radiotherapy, the liposomes can not only modulate the immunosuppressive TME by cellular metabolism regulation to achieve potent therapeutic effect for local tumors, but also suppress the M2 macrophage proliferation triggered by X-ray irradiation and thus enhance the immune response to inhibit metastatic lesions. In brief, this work provides a new therapeutic strategy targeting the special metabolic traits of cancer cells and immunosuppressive TAMs to enhance the abscopal effect of radiotherapy for cancer.


Assuntos
Nanopartículas , Neoplasias , Humanos , Lipossomos/metabolismo , Macrófagos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Anticorpos/farmacologia , Imunoterapia/métodos , Homeostase , Microambiente Tumoral
20.
Mol Biochem Parasitol ; 252: 111523, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36195241

RESUMO

Schistosomiasis is a common parasitic disease. Hepatosplenic schistosomiasis, caused by Schistosoma japonicum and Schistosoma mansoni, involves pathological changes, including worm egg-induced hepatic granuloma and fibrosis, which can markedly affect the liver's physiological functions. Although the drug praziquantel (PZQ) is used to treat schistosomiasis, drugs against schistosomiasis-induced liver fibrosis are rare in the clinical setting. Therefore, developing effective strategies to prevent and treat schistosomiasis-induced liver fibrosis is crucial. Previous studies have shown that miRNAs are involved in various liver diseases. In this study, we found a gradual increase in miR-181b expression in the murine liver as S. japonicum infection progressed, while the expression of Smad7 decreased. Down-regulating miR-181b significantly alleviated S. japonicum-induced hepatic granuloma and liver fibrosis. In vitro experiments showed that treatment with TGF-ß1 upregulated miR-181b levels in the hepatic stellate cell (HSC) line LX2 in a concentration- and time-dependent manner. Downregulation of miR-181b significantly decreased collagen type I alpha 1 chain (COL1A1) expression in TGF-ß1-stimulated LX2 cells. These findings indicate that miR-181b promotes HSC activation by down-regulating Smad7 expression, activating the TGF-ß1/Smad signaling pathway, and leading to excess collagen expression and deposition. Our findings suggest that miR-181b might be a potentially novel therapeutic target for schistosomiasis-induced liver fibrosis.


Assuntos
Cirrose Hepática , MicroRNAs , Esquistossomose , Proteína Smad7 , Animais , Camundongos , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fígado , Cirrose Hepática/genética , Cirrose Hepática/parasitologia , MicroRNAs/genética , Esquistossomose/complicações , Esquistossomose/patologia , Fator de Crescimento Transformador beta1/farmacologia , Proteína Smad7/genética , Proteína Smad7/metabolismo
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