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1.
Angew Chem Int Ed Engl ; : e202407748, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38818639

RESUMEN

Selective producing ethanol from CO2 electroreduction is highly demanded, yet the competing ethylene generation route is commonly more thermodynamically preferred. Herein, we reported an efficient CO2-to-ethanol conversion (53.5% faradaic efficiency at -0.75 V versus reversible hydrogen electrode (vs. RHE)) over an oxide-derived nanocubic catalyst featured with abundant "embossment-like" structured grain-boundaries. The catalyst also attains a 23.2% energy efficiency to ethanol within a flow cell reactor. In situ spectroscopy and electrochemical analysis identified that these dualphase Cu(I) and Cu(0) sites stabilized by grain-boundaries are very robust over the operating potential window, which maintains a high concentration of co-adsorbed *CO and hydroxyl (*OH) species. Theoretical calculations revealed that the presence of *OHad not only promote the easier dimerization of *CO to form *OCCO (ΔG ~ 0.20 eV) at low overpotentials but also preferentially favor the key *CHCOH intermediate hydrogenation to *CHCHOH (ethanol pathway) while suppressing its dehydration to *CCH (ethylene pathway), which is believed to determine the remarkable ethanol selectivity. Such imperative intermediates associated with the bifurcation pathway were directly distinguished by isotope labelling in situ infrared spectroscopy. Our work promotes the understanding of bifurcating mechanism of CO2ER-to-hydrocarbons more deeply, providing a feasible strategy for the design of efficient ethanol-targeted catalysts.

2.
Adv Healthc Mater ; : e2400303, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38647150

RESUMEN

Renal cell carcinoma (RCC) is a hot tumor infiltrated by large numbers of CD8+ T cells and is highly sensitive to immunotherapy. However, tumor-associated macrophages (TAMs), mainly M2 macrophages, tend to undermine the efficacy of immunotherapy and promote the progression of RCC. Here, macrophage-derived nanosponges are fabricated by M2 macrophage membrane-coated poly(lactic-co-glycolic acid)(PLGA), which could chemotaxis to the CXC and CC chemokine subfamily-enriched RCC microenvironment via corresponding membrane chemokine receptors. Subsequently, the nanosponges act like cytokine decoys to adsorb and neutralize broad-spectrum immunosuppressive cytokines such as colony stimulating factor-1(CSF-1), transforming growth factor-ß(TGF-ß), and Lnterleukin-10(IL-10), thereby reversing the polarization of M2-TAMs toward the pro-inflammatory M1 phenotype, and enhancing the anti-tumor effect of CD8+ T cells. To further enhance the polarization reprogramming efficiency of TAMs, DSPE-PEG-M2pep is conjugated on the surface of macrophage-derived nanosponges for specific recognition of M2-TAMs, and the toll like receptors 7/8(TLR7/8) agonist, R848, is encapsulated in these nanosponges to induce M1 polarization, which result in significant efficacy against RCC. In addition, these nanosponges exhibit undetectable biotoxicity, making them suitable for clinical applications. In summary, a promising and facile strategy is provided for immunomodulatory therapies, which are expected to be used in the treatment of tumors, autoimmune diseases, and inflammatory diseases.

3.
Fitoterapia ; 175: 105938, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38565379

RESUMEN

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.


Asunto(s)
Antineoplásicos Fitogénicos , Limoninas , Fitoquímicos , Hojas de la Planta , Toona , Humanos , Estructura Molecular , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Hojas de la Planta/química , Limoninas/aislamiento & purificación , Limoninas/farmacología , Limoninas/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , China , Toona/química , Tallos de la Planta/química
4.
J Colloid Interface Sci ; 662: 149-159, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38340514

RESUMEN

Efficient and stable oxygen reduction reaction (ORR) catalysts are essential for constructing reliable energy conversion and storage devices. Herein, we prepared noble metal-free FeCoNiMnV high-entropy alloy supported on nitrogen-doped carbon nanotubes (FeCoNiMnV HEA/N-CNTs) by a one-step pyrolysis at 800 °C, as certificated by a set of characterizations. The graphitization degree of the N-CHTs was optimized by tuning the pyrolysis temperature in the control groups. The resultant catalyst greatly enhanced the ORR characteristics in the alkaline media, showing the positive onset potential (Eonset) of 0.99 V and half-wave potential (E1/2) of 0.85 V. More importantly, the above FeCoNiMnV HEA/N-CNTs assembled Zn-air battery exhibited a greater open-circuit voltage (1.482 V), larger power density (185.12 mW cm-2), and outstanding cycle stability (1698 cycles, 566 h). This study provides some valuable insights on developing sustainable ORR catalysts in Zn-air batteries.

5.
Theranostics ; 14(1): 379-391, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38164138

RESUMEN

Endosialin, also known as tumor endothelial marker 1 (TEM1) or CD248, is a single transmembrane glycoprotein with a C-type lectin-like domain. Endosialin is mainly expressed in the stroma, especially in cancer-associated fibroblasts and pericytes, in most solid tumors. Endosialin is also expressed in tumor cells of most sarcomas. Endosialin can promote tumor progression through different mechanisms, such as promoting tumor cell proliferation, adhesion and migration, stimulating tumor angiogenesis, and inducing an immunosuppressive tumor microenvironment. Thus, it is considered an ideal target for cancer treatment. Several endosialin-targeted antibodies and therapeutic strategies have been developed and have shown preliminary antitumor effects. Here, we reviewed the endosialin expression pattern in different cancer types, discussed the mechanisms by which endosialin promotes tumor progression, and summarized current therapeutic strategies targeting endosialin.


Asunto(s)
Antígenos de Neoplasias , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neovascularización Patológica/patología , Pericitos/metabolismo , Microambiente Tumoral , Antígenos CD/metabolismo
6.
Plant Commun ; 5(2): 100717, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-37715446

RESUMEN

The plant genome produces an extremely large collection of long noncoding RNAs (lncRNAs) that are generally expressed in a context-specific manner and have pivotal roles in regulation of diverse biological processes. Here, we mapped the transcriptional heterogeneity of lncRNAs and their associated gene regulatory networks at single-cell resolution. We generated a comprehensive cell atlas at the whole-organism level by integrative analysis of 28 published single-cell RNA sequencing (scRNA-seq) datasets from juvenile Arabidopsis seedlings. We then provided an in-depth analysis of cell-type-related lncRNA signatures that show expression patterns consistent with canonical protein-coding gene markers. We further demonstrated that the cell-type-specific expression of lncRNAs largely explains their tissue specificity. In addition, we predicted gene regulatory networks on the basis of motif enrichment and co-expression analysis of lncRNAs and mRNAs, and we identified putative transcription factors orchestrating cell-type-specific expression of lncRNAs. The analysis results are available at the single-cell-based plant lncRNA atlas database (scPLAD; https://biobigdata.nju.edu.cn/scPLAD/). Overall, this work demonstrates the power of integrative single-cell data analysis applied to plant lncRNA biology and provides fundamental insights into lncRNA expression specificity and associated gene regulation.


Asunto(s)
Arabidopsis , ARN Largo no Codificante , Redes Reguladoras de Genes , ARN Largo no Codificante/genética , Arabidopsis/genética , Análisis de Expresión Génica de una Sola Célula , Regulación de la Expresión Génica
7.
J Nucl Med ; 64(11): 1750-1757, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37652543

RESUMEN

The preoperative Gleason grade group (GG) from transrectal ultrasound-guided prostate biopsy is crucial for treatment decisions but may underestimate the postoperative GG and miss clinically significant prostate cancer (csPCa), particularly in patients with biopsy GG1. In such patients, an SUVmax of at least 12 has 100% specificity for detecting csPCa. In patients with an SUVmax of less than 12, we aimed to develop a model to improve the diagnostic accuracy of csPCa. Methods: The study retrospectively included 56 prostate cancer patients with transrectal ultrasound-guided biopsy GG1 and an SUVmax of less than 12 from 2 tertiary hospitals. All [68Ga]Ga-PSMA-HBED-CC PET scans were centrally reviewed in Xijing Hospital. A deep learning model was used to evaluate the overlap of SUVmax (size scale, 3 cm) and the level of Gleason pattern (size scale, 500 µm). A diagnostic model was developed using the PRIMARY score and SUVmax, and its discriminative performance and clinical utility were compared with other methods. The 5-fold cross-validation (repeated 1,000 times) was used for internal validation. Results: In patients with GG1 and an SUVmax of less than 12, significant prostate-specific membrane antigen (PSMA) histochemical score (H-score) H-score overlap occurred among benign gland, Gleason pattern 3, and Gleason pattern 4 lesions, causing SUVmax overlap between csPCa and non-csPCa. The model of 10 × PRIMARY score + 2 × SUVmax exhibited a higher area under the curve (AUC, 0.8359; 95% CI, 0.7233-0.9484) than that found using only the SUVmax (AUC, 0.7353; P = 0.048) or PRIMARY score (AUC, 0.7257; P = 0.009) for the cohort and a higher AUC (0.8364; 95% CI, 0.7114-0.9614) than that found using only the Prostate Imaging Reporting and Data System (PI-RADS) score of 5-4 versus 3-1 (AUC, 0.7036; P = 0.149) and the PI-RADS score of 5-3 versus 2-1 (AUC, 0.6373; P = 0.014) for a subgroup. The model reduced the misdiagnosis of the PI-RADS score of 5-4 versus 3-1 by 78.57% (11/14) and the PI-RADS score of 5-3 versus 2-1 by 77.78% (14/18). The internal validation showed that the mean 5-fold cross-validated AUC was 0.8357 (95% CI, 0.8357-0.8358). Conclusion: We preliminarily suggest that the model of 10 × PRIMARY score + 2 × SUVmax may enhance the diagnostic accuracy of csPCa in patients with biopsy GG1 and an SUVmax of less than 12 by maximizing PSMA information use, reducing the misdiagnosis of the PI-RADS score, and thereby aiding in making appropriate treatment decisions.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Próstata/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Antígeno Prostático Específico/análisis , Biopsia Guiada por Imagen/métodos
8.
Nat Commun ; 14(1): 5123, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612267

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we present the single-cell transcriptomic landscape of synchronously resected PDAC primary tumors and matched liver metastases. We perform comparative analysis on both cellular composition and functional phenotype between primary and metastatic tumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from cancer cells in primary tumor. We also identify specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5+ cancer-associated fibroblasts, CCL18+ lipid-associated macrophages, S100A8+ neutrophils and FOXP3+ regulatory T cells. Cellular interactome analysis further reveals that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment. Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Transcriptoma , Microambiente Tumoral/genética , Neoplasias Pancreáticas/genética , Neoplasias Hepáticas/genética , Carcinoma Ductal Pancreático/genética , Inmunosupresores , Neoplasias Pancreáticas
9.
Proc Natl Acad Sci U S A ; 120(25): e2301011120, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37307468

RESUMEN

As a sustainable approach for N2 fixation, electrocatalytic N2 reduction reaction (N2RR) to produce ammonia (NH3) is highly desirable with a precise understanding to the structure-activity relationship of electrocatalysts. Here, firstly, we obtain a novel carbon-supported oxygen-coordinated single-Fe-atom catalyst for highly efficient production of ammonia from electrocatalytic N2RR. Based on such new type of N2RR electrocatalyst, by combining operando X-ray absorption spectra (XAS) with density function theory calculation, we reveal significantly that the as-prepared active coordination structure undergoes a potential-driven two-step restructuring, firstly from FeSAO4(OH)1a to FeSAO4(OH)1a'(OH)1b with the adsorption of another -OH on FeSA at open-circuit potential (OCP) of 0.58 VRHE, and subsequently restructuring from FeSAO4(OH)1a'(OH)1b to FeSAO3(OH)1a″ due to the breaking of one Fe-O bond and the dissociation of one -OH at working potentials for final electrocatalytic process of N2RR, thus revealing the first potential-induced in situ formation of the real electrocatalytic active sites to boost the conversion of N2 to NH3. Moreover, the key intermediate of Fe-NNHx was detected experimentally by both operando XAS and in situ attenuated total reflection-surface-enhanced infrared absorption spectra (ATR-SEIRAS), indicating the alternating mechanism followed by N2RR on such catalyst. The results indicate the necessity of considering the potential-induced restructuring of the active sites on all kinds of electrocatalysts for such as highly efficient ammonia production from N2RR. It also paves a new way for a precise understanding to the structure-activity relationship of a catalyst and helps the design of highly efficient catalysts.

10.
Chemistry ; 29(46): e202301455, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37283568

RESUMEN

Electrochemical CO2 reduction reaction (CO2 RR) provides a promising approach for sustainable chemical fuel production of carbon neutrality. Neutral and alkaline electrolytes are predominantly employed in the current electrolysis system, but with striking drawbacks of (bi)carbonate (CO3 2- /HCO3 - ) formation and crossover due to the rapid and thermodynamically favourable reaction between hydroxide (OH- ) with CO2 , resulting in low carbon utilization efficiency and short-lived catalysis. Very recently, CO2 RR in acidic media can effectively address the (bi)carbonate issue; however, the competing hydrogen evolution reaction (HER) is more kinetically favourable in acidic electrolytes, which dramatically reduces CO2 conversion efficiency. Thus, it is a big challenge to effectively suppress HER and accelerate acidic CO2 RR. In this review, we begin by summarizing the recent progress of acidic CO2 electrolysis, discussing the key factors limiting the application of acidic electrolytes. We then systematically discuss addressing strategies for acidic CO2 electrolysis, including electrolyte microenvironment modulation, alkali cations adjusting, surface/interface functionalization, nanoconfinement structural design, and novel electrolyzer exploitation. Finally, the new challenges and perspectives of acidic CO2 electrolysis are suggested. We believe this timely review can arouse researchers' attention to CO2 crossover, inspire new insights to solve the "alkalinity problem" and enable CO2 RR as a more sustainable technology.

11.
Schizophr Res ; 255: 213-221, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37012184

RESUMEN

The present study explored whether acceptance and commitment therapy (ACT), a cognitive behavioral therapy approach, could improve the symptoms of schizophrenia spectrum disorders among patients with schizophrenia in remission. A pre- and post-treatment design with two evaluation time points was employed. Sixty outpatients with schizophrenia in remission were randomly divided into two groups: the ACT plus treatment as usual (ACT+TAU) and treatment as usual (TAU) groups. The ACT+TAU group participated in 10 group-based ACT interventions and TAU in the hospital, and the TAU group only received TAU interventions. General psycho-pathological symptoms, self-esteem, and psychological flexibility were assessed before intervention (baseline; pre-test) and after intervention (five weeks; post-test). Results indicated that, compared to the TAU group, the ACT+TAU group exhibited a more significant improvement in general psychopathological symptoms, self-esteem, cognitive fusion, and acceptance and action at post-test. ACT intervention could effectively decrease the general psycho-pathological symptoms and increase self-esteem level and psychological flexibility in people with schizophrenia in remission.


Asunto(s)
Terapia de Aceptación y Compromiso , Terapia Cognitivo-Conductual , Esquizofrenia , Humanos , Terapia Cognitivo-Conductual/métodos , Esquizofrenia/terapia , Resultado del Tratamiento
13.
Pharmacol Res ; 191: 106773, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37068531

RESUMEN

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.


Asunto(s)
Ataxia Cerebelosa , Ratones , Animales , Ataxia Cerebelosa/inducido químicamente , Células de Purkinje/fisiología , Microglía , Factor de Necrosis Tumoral alfa/farmacología , Cerebelo , Citocinas
14.
BMC Cancer ; 23(1): 290, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36997926

RESUMEN

BACKGROUND: Osteosarcoma (OS) is the most common malignant bone tumor with a high incidence in children and adolescents. Frequent tumor metastasis and high postoperative recurrence are the most common challenges in OS. However, detailed mechanism is largely unknown. METHODS: We examined the expression of CD248 in OS tissue microarrays by immunohistochemistry (IHC) staining. We studied the biological function of CD248 in cell proliferation, invasion and migration of OS cells by CCK8 assay, transwell and wound healing assay. We also studied its function in the metastasis of OS in vivo. At last, we explored the potential mechanism how CD248 promotes OS metastasis by using RNA-seq, western blot, immunofluorescence staining and co-immunoprecipitation using CD248 knockdown OS cells. RESULTS: CD248 was highly expressed in OS tissues and its high expression was correlated with pulmonary metastasis of OS. Knockdown of CD248 in OS cells significantly inhibited cell migration, invasion and metastasis, while had no obvious effect on cell proliferation. Lung metastasis in nude mice was significantly inhibited when CD248 was knocked down. Mechanistically, we found that CD248 could promote the interaction between ITGB1 and extracellular matrix (ECM) proteins like CYR61 and FN, which activated the FAK-paxillin pathway to promote the formation of focal adhesion and metastasis of OS. CONCLUSION: Our data showed that high CD248 expression is correlated with the metastatic potential of OS. CD248 may promote migration and metastasis through enhancing the interaction between ITGB1 and certain ECM proteins. Therefore, CD248 is a potential marker for diagnosis and effective target for the treatment of metastatic OS.


Asunto(s)
Neoplasias Óseas , Neoplasias Pulmonares , Osteosarcoma , Animales , Ratones , Antígenos CD , Antígenos de Neoplasias , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Ratones Desnudos , Osteosarcoma/genética , Osteosarcoma/patología , Paxillin/genética , Paxillin/metabolismo , Integrina beta1/metabolismo
15.
Front Pharmacol ; 14: 1121586, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36744260

RESUMEN

Background: Cancer-associated fibroblasts (CAFs) promote tumor progression through extracellular matrix (ECM) remodeling and extensive communication with other cells in tumor microenvironment. However, most CAF-targeting strategies failed in clinical trials due to the heterogeneity of CAFs. Hence, we aimed to identify the cluster of tumor-promoting CAFs, elucidate their function and determine their specific membrane markers to ensure precise targeting. Methods: We integrated multiple single-cell RNA sequencing (scRNA-seq) datasets across different tumors and adjacent normal tissues to identify the tumor-promoting CAF cluster. We analyzed the origin of these CAFs by pseudotime analysis, and tried to elucidate the function of these CAFs by gene regulatory network analysis and cell-cell communication analysis. We also performed cell-type deconvolution analysis to examine the association between the proportion of these CAFs and patients' prognosis in TCGA cancer cohorts, and validated that through IHC staining in clinical tumor tissues. In addition, we analyzed the membrane molecules in different fibroblast clusters, trying to identify the membrane molecules that were specifically expressed on these CAFs. Results: We found that COL11A1+ fibroblasts specifically exist in tumor tissues but not in normal tissues and named them cancer-specific fibroblasts (CSFs). We revealed that these CSFs were transformed from normal fibroblasts. CSFs represented a more activated CAF cluster and may promote tumor progression through the regulation on ECM remodeling and antitumor immune responses. High CSF proportion was associated with poor prognosis in bladder cancer (BCa) and lung adenocarcinoma (LUAD), and IHC staining of COL11A1 confirmed their specific expression in tumor stroma in clinical BCa samples. We also identified that CSFs specifically express the membrane molecules LRRC15, ITGA11, SPHK1 and FAP, which could distinguish CSFs from other fibroblasts. Conclusion: We identified that CSFs is a tumor specific cluster of fibroblasts, which are in active state, may promote tumor progression through the regulation on ECM remodeling and antitumor immune responses. Membrane molecules LRRC15, ITGA11, SPHK1 and FAP could be used as therapeutic targets for CSF-targeting cancer treatment.

16.
Cancer Immunol Immunother ; 72(6): 1739-1750, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36646951

RESUMEN

BACKGROUND: Immune checkpoint blockade (ICB) therapy can be effective against clear cell renal cell carcinoma (ccRCC), but many patients show no benefit. Tumor-derived pericytes (TDPs) may promote tumor progression by influencing T cells and are an immunotherapy target; however, they may comprise functionally distinct subtypes. We aimed to identify markers of tumor-promoting TDPs and develop TDP-targeting strategies to enhance ICB therapy effectiveness against ccRCC. METHODS: We analyzed the relationship between endosialin (EN) expression and cytotoxic T-lymphocyte (CTL) infiltration in ccRCC tumor samples using flow cytometry and in a ccRCC-bearing mice inhibited for EN via knockout or antibody-mediated blockade. The function of ENhigh TDPs in CTL infiltration and tumor progression was analyzed using RNA-sequencing (RNA-seq) data from ccRCC tissue-derived TDPs and single-cell RNA-seq (scRNA-seq) data from an online database. The role of EN in TDP proliferation and migration and in CTL infiltration was examined in vitro. Finally, we examined the anti-tumor effect of combined anti-EN and anti-programmed death 1 (PD-1) antibodies in ccRCC-bearing mice. RESULTS: High EN expression was associated with low CTL infiltration in ccRCC tissues, and inhibition of EN significantly increased CTL infiltration in ccRCC-bearing mice. RNA-seq and scRNA-seq analyses indicated that high EN expression represented the TDP activation state. EN promoted TDP proliferation and migration and impeded CTL infiltration in vitro. Finally, combined treatment with anti-EN and anti-PD-1 antibodies synergistically enhanced anti-tumor efficacy. CONCLUSION: ENhigh TDPs are in an activated state and inhibit CTL infiltration into ccRCC tissues. Combined treatment with anti-EN and anti-PD-1 antibodies may improve ICB therapy effectiveness against ccRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Animales , Ratones , Linfocitos T CD8-positivos , Proteínas de Unión al ADN/metabolismo , Pericitos/metabolismo , Pericitos/patología , Microambiente Tumoral
17.
Comput Struct Biotechnol J ; 21: 665-676, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36659929

RESUMEN

Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.

18.
Front Med (Lausanne) ; 9: 844964, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36203778

RESUMEN

Objectives: This study aimed to investigate the associations between several dimensions of self-reported satisfaction and the risk of depressive symptoms among Chinese middle-aged and older adults. Methods: The China Health and Retirement Longitudinal Study (CHARLS) conducted a nationwide cross-sectional study of middle-aged and older adults. Depressive status was evaluated using the 10-item center for epidemiological studies depression scale (CESD-10), and self-reported life, health, marital status, parent-child relationship, and air quality satisfaction were adopted using Likert 5-point evaluation methods. A generalized linear model (GLM) was applied to explore the association between satisfaction and depression risk. Results: A total of 13,978 Chinese people aged over 45 years old were included in this study, and 35.7% of the participants had depressive symptoms. The GLM analysis indicated that all dimensions of satisfaction were negatively associated with the risk of depressive symptoms. For each 1-point increase in life, health, marital status, parent-child relationship, and air quality satisfaction, the incidence of depressive symptoms decreased by 60.8% (odds ratio (OR) = 0.392; 95% confidence interval (CI): 0.370, 0.414), 56.3% (OR = 0.437; 95% CI: 0.418, 0.458), 41.8% (OR = 0.582; 95% CI: 0.555, 0.610), 37.2% (OR = 0.628; 95% CI: 0.596, 0.662), and 25.6% (OR = 0.744; 95% CI: 0.711, 0.778), respectively. Conclusion: Higher satisfaction levels with life, health, marital status, parent-child relationship, and air quality are associated with a lower risk of depressive symptoms among middle-aged and older adults. Given the aging society and the increasing mental health problems of middle-aged and older adults in China, our study provides a comprehensive perspective for depression prevention and mental health improvement.

19.
Chemistry ; 28(58): e202201832, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-35853829

RESUMEN

Metal halide perovskites, primarily used as optoelectronic devices, have not been applied for electrochemical conversion due to their insufficient stability in moisture. Herein, two bismuth-based perovskites are introduced as novel electrocatalysts to convert CO2 into HCOOH in aqueous acidic media (pH 2.5), exhibiting a high Faradaic efficiency for HCOOH of >80 % in a wide potential range from -0.75 to -1.25 V. Their structural evolution against water was dynamically monitored by in situ spectra. Theoretical calculations further reveal that the formation of intermediate OCHO* on bismuth sites of Cs3 Bi2 Br9 (111) play a pivotal role toward HCOOH production, which has a lower energy barrier than that on Cs2 AgBiBr6 (001) surfaces. Significantly, CO2 reacts with protons instead of water which can enhance CO2 reduction rate and suppress hydrogen evolution by avoiding carbonate formation in acidic electrolytes. This work paves the way for the extensive investigation of halide perovskites in aqueous systems.

20.
Nat Commun ; 13(1): 4069, 2022 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-35831300

RESUMEN

Non-human primates are attractive laboratory animal models that accurately reflect both developmental and pathological features of humans. Here we present a compendium of cell types across multiple organs in cynomolgus monkeys (Macaca fascicularis) using both single-cell chromatin accessibility and RNA sequencing data. The integrated cell map enables in-depth dissection and comparison of molecular dynamics, cell-type compositions and cellular heterogeneity across multiple tissues and organs. Using single-cell transcriptomic data, we infer pseudotime cell trajectories and cell-cell communications to uncover key molecular signatures underlying their cellular processes. Furthermore, we identify various cell-specific cis-regulatory elements and construct organ-specific gene regulatory networks at the single-cell level. Finally, we perform comparative analyses of single-cell landscapes among mouse, monkey and human. We show that cynomolgus monkey has strikingly higher degree of similarities in terms of immune-associated gene expression patterns and cellular communications to human than mouse. Taken together, our study provides a valuable resource for non-human primate cell biology.


Asunto(s)
Transcriptoma , Animales , Macaca fascicularis/genética , Ratones , Modelos Animales , Transcriptoma/genética
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