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1.
Adv Sci (Weinh) ; : e2308892, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38682485

RESUMO

Heterogeneous organ-specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single-cell profiling using formalin-fixed paraffin-embedded (FFPE) materials. In this study, single-cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ-specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single-cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ-specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4+ T cells at immunogenic sites. Various organ-specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM-3. This study originally deciphers the single-cell landscape of the organ-specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ-specific treatment approaches.

2.
Cancer Lett ; 585: 216663, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38246221

RESUMO

Colorectal melanoma (CRM) is a rare malignant tumor with severe complications, and there is currently a lack of systematic research. We conducted a study that combined proteomics and mutation data of CRM from a cohort of three centers over a 16-years period (2005-2021). The patients were divided into a training set consisting of two centers and a testing set comprising the other center. Unsupervised clustering was conducted on the training set to form two molecular subtypes for clinical characterization and functional analysis. The testing set was used to validate the survival differences between the two subtypes. The comprehensive analysis identified two subtypes of CRM: immune exhausted C1 cluster and DNA repair C2 cluster. The former subtype exhibited characteristics of metabolic disturbance, immune suppression, and poor prognosis, along with APC mutations. A machine learning algorithm named Support Vector Machine (SVM) was applied to predict the classification of CRM patients based on protein expression in the external testing cohort. Two subtypes of primary CRM with clinical and proteomic characteristics provides a reference for subsequent diagnosis and treatments.


Assuntos
Neoplasias Colorretais , Melanoma , Humanos , Melanoma/genética , Multiômica , Estudos Prospectivos , Proteômica , Prognóstico
3.
Mil Med Res ; 10(1): 15, 2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36949519

RESUMO

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.


Assuntos
Adesivos , Adesivos Teciduais , Ratos , Humanos , Suínos , Coelhos , Animais , Criogéis , Células CACO-2 , Inflamação
4.
ACS Appl Mater Interfaces ; 12(45): 50397-50405, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33108720

RESUMO

Solar steam generation is receiving considerable interest because of its potential application in wastewater treatment and desalination. Many devices with various photothermal materials and structures have been demonstrated to be solar steam evaporators by improving their light absorption, heat loss, water transportation, and vapor escape. However, developing a biomass-based evaporator with heat localization and rapid water transportation is highly desired yet still challenging. Here, corncobs, a kind of agricultural waste with vascular bundle and "vesiculose" structures, are used to fabricate solar steam-generation devices. After high-temperature treatment, the carbonized corncobs maintain the highly anisotropic porous framework and favorable hydrophilicity and thereby have excellent thermal management and water transportation. With efficient solar absorption, heat localization, and rapid water transportation, the lightweight carbonized corncobs can float on water and generate water vapor with a high steam generation efficiency of 86.7% under 1 sun.

5.
Nature ; 586(7829): 390-394, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33057223

RESUMO

Owing to its high thermal and electrical conductivities, its ductility and its overall non-toxicity1-3, copper is widely used in daily applications and in industry, particularly in anti-oxidation technologies. However, many widespread anti-oxidation techniques, such as alloying and electroplating1,2, often degrade some physical properties (for example, thermal and electrical conductivities and colour) and introduce harmful elements such as chromium and nickel. Although efforts have been made to develop surface passivation technologies using organic molecules, inorganic materials or carbon-based materials as oxidation inhibitors4-12, their large-scale application has had limited success. We have previously reported the solvothermal synthesis of highly air-stable copper nanosheets using formate as a reducing agent13. Here we report that a solvothermal treatment of copper in the presence of sodium formate leads to crystallographic reconstruction of the copper surface and formation of an ultrathin surface coordination layer. We reveal that the surface modification does not affect the electrical or thermal conductivities of the bulk copper, but introduces high oxidation resistance in air, salt spray and alkaline conditions. We also develop a rapid room-temperature electrochemical synthesis protocol, with the resulting materials demonstrating similarly strong passivation performance. We further improve the oxidation resistance of the copper surfaces by introducing alkanethiol ligands to coordinate with steps or defect sites that are not protected by the passivation layer. We demonstrate that the mild treatment conditions make this technology applicable to the preparation of air-stable copper materials in different forms, including foils, nanowires, nanoparticles and bulk pastes. We expect that the technology developed in this work will help to expand the industrial applications of copper.

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