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1.
Front Immunol ; 15: 1379742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596670

RESUMO

Background: Kidney transplantation is considered the most effective treatment for end-stage renal failure. Recent studies have shown that the significance of the immune microenvironment after kidney transplantation in determining prognosis of patients. Therefore, this study aimed to conduct a bibliometric analysis to provide an overview of the knowledge structure and research trends regarding the immune microenvironment and survival in kidney transplantation. Methods: Our search included relevant publications from 2013 to 2023 retrieved from the Web of Science core repository and finally included 865 articles. To perform the bibliometric analysis, we utilized tools such as VOSviewer, CiteSpace, and the R package "bibliometrix". The analysis focused on various aspects, including country, author, year, topic, reference, and keyword clustering. Results: Based on the inclusion criteria, a total of 865 articles were found, with a trend of steady increase. China and the United States were the countries with the most publications. Nanjing Medical University was the most productive institution. High-frequency keywords were clustered into 6 areas, including kidney transplantation, transforming growth factor ß, macrophage, antibody-mediated rejection, necrosis factor alpha, and dysfunction. Antibody mediated rejection (2019-2023) was the main area of research in recent years. Conclusion: This groundbreaking bibliometric study comprehensively summarizes the research trends and advances related to the immune microenvironment and survival after kidney transplantation. It identifies recent frontiers of research and highlights promising directions for future studies, potentially offering fresh perspectives to scholars in the field.


Assuntos
Transplante de Rim , Humanos , Anticorpos , Bibliometria , China , Análise por Conglomerados
2.
J Hazard Mater ; 471: 134322, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636238

RESUMO

This study focused on the effects of urea humate-based porous materials (UHPM) on soil aggregates, plant physiological characteristics, and microbial diversity to explore the effects of UHPM on the phytoremediation of petroleum-contaminated soil. The compositions of soil aggregates, ryegrass (Lolium perenne) biomass, plant petroleum enrichment capacity, and bacterial communities in soils with and without UHPM were investigated. The results showed that UHPM significantly increased soil aggregate content by 0.25 mm-5 mm, resulting in higher fertilizer holding capacity, erosion resistance capacity, and plant biomass and microbial number than the soil without UHPM mixed. In addition, UHPM decreased the absorption of petroleum by plants in the soil while increasing the abundance of degrading bacteria and petroleum-degrading-related genes in the soil, thereby promoting the removal of hard-to-degrade petroleum components. RDA showed that, compared with the unimproved soil, each soil indicator was positively correlated with a high abundance of degrading bacteria in the improved soil and was significant. UHPM can be regarded as a petroleum-contaminated soil remediation agent that combines slow nutrient release with soil improvement effects.

3.
J Med Chem ; 67(7): 5783-5799, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38526960

RESUMO

Neutrophil-mediated immunotherapy is a promising strategy for treating Candida albicans infection due to its potential in dealing with drug-resistant events. Our previous study found that ACT001 exhibited good antifungal immunotherapeutic activity by inhibiting PD-L1 expression in neutrophils, but its strong cytotoxicity and high BBB permeability hindered its antifungal application. To address these deficiencies, a series of novel sulfide derivatives were designed and synthesized based on a slow-release prodrug strategy. Among these derivatives, compound 16 exhibited stronger inhibition of PD-L1 expression, less cytotoxicity to neutrophils, and lower BBB permeability than ACT001. Compound 16 also significantly enhanced neutrophil-mediated antifungal immunity in C. albicans infected mice, with acceptable pharmacokinetic properties and good oral safety. Moreover, pharmacological mechanism studies demonstrated that ACT001 and compound 16 reduced PD-L1 expression in neutrophils by directly targeting STAT3. Briefly, this study provided a novel prototype compound 16 which exhibited great potential in neutrophil-mediated antifungal immunotherapy.


Assuntos
Antifúngicos , Furanos , Neutrófilos , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Neutrófilos/metabolismo , Antígeno B7-H1 , Reposicionamento de Medicamentos , Candida albicans/metabolismo
4.
Sci Total Environ ; 926: 171937, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38527534

RESUMO

The tremendous application potentiality of transitional metal dichalcogenides (TMDs), such as molybdenum disulfide (MoS2) nanosheets, will unavoidably lead to increasing release into the environment, which could influence the fate and toxicity of co-existed contaminants. The present study discovered that 59.8 % of trivalent antimony [Sb(III)] was transformed by MoS2 to pentavalent Sb [Sb(V)] in aqueous solutions under light illumination, which was due to hole oxidation on the nanosheet surfaces. A synergistic toxicity between MoS2 and Sb(III, V) to algae (Chlorella vulgaris) was observed, as demonstrated by the lower median-effect concentrations of MoS2 + Sb(III)/Sb(V) (13.1 and 20.9 mg/L, respectively) than Sb(III)/Sb(V) (38.8 and 92.5 mg/L, respectively) alone. Particularly, MoS2 at noncytotoxic doses notably increased the bioaccumulation of Sb(III, V) in algae, causing aggravated oxidative damage, photosynthetic inhibition, and structural alterations. Metabolomics indicated that oxidative stress and membrane permeabilization were primarily associated with down-regulated amino acids involved in glutathione biosynthesis and unsaturated fatty acids. MoS2 co-exposure remarkably decreased the levels of thiol antidotes (glutathione and phytochelatins) and aggravated the inhibition on energy metabolism and ATP synthesis, compromising the Sb(III, V) detoxification and efflux. Additionally, extracellular P was captured by the nanosheets, also contributing to the uptake of Sb(V). Our findings emphasized the nonignorability of TMDs even at environmental levels in affecting the ecological hazard of metalloids, providing insight into comprehensive safety assessment of TMDs.


Assuntos
Chlorella vulgaris , Dissulfetos , Metaloides , Antimônio/metabolismo , Molibdênio/toxicidade , Adsorção , Chlorella vulgaris/metabolismo , Glutationa
5.
Sensors (Basel) ; 24(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38474929

RESUMO

An exhaust gas recirculation (EGR) valve is used to quickly and dynamically adjust the amount of recirculated exhaust gas, which is critical for improving engine fuel economy and reducing emissions. To address problems relating to the precise positioning of an electromotive (EM) valve under slowly varying plant dynamics and uncertain disturbances, we propose a servo control system design based on linear active disturbance rejection control (LADRC) for the EGR EM valve driven by a limited angle torque motor (LATM). By analyzing the structure of the LATM and the transmission, the dynamic model of the system is derived. In addition, to solve the problems caused by slowly varying plant dynamics and uncertain disturbances, we combine the effects of uncertain model parameters and external disturbances as the total disturbance, which is estimated in real time by an extended state observer (ESO) and then compensated. In addition, accurate angular information is obtained using a non-contact magnetic angle measurement method, and a high-speed digital communication channel is established to help implement a closed-loop position control system with improved responsiveness and accuracy. Simulation and experimental results show that the proposed servo system design can effectively ensure the precision and real-time performance of the EM valve under slowly changing plant dynamics and uncertain disturbances. The proposed servo system design achieves a full-stroke valve control accuracy of better than 0.05 mm and a full-stroke response time of less than 100 ms. The controlled valve also has good robustness under shock-type external disturbances and excellent airflow control capability. The repeatability of the airflow control is generally within 5%, and the standard deviation is less than 0.2 m3/h.

6.
Cell Death Dis ; 15(3): 207, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472183

RESUMO

The pathogenesis of psoriasis, a chronic inflammatory autoimmune skin disease with a high global prevalence, remains unclear. We performed a high-resolution single-cell RNA sequencing analysis of 94,759 cells from 13 samples, including those from psoriasis model mice and wild-type mice. We presented a single-cell atlas of the skin of imiquimod-induced mice with psoriasis and WT mice, especially the heterogeneity of keratinocytes and fibroblasts. More interestingly, we discovered that special keratinocyte subtypes and fibroblast subtypes could interact with each other through epithelial-mesenchymal transition and validated the results with drug verification. Moreover, we conducted a tentative exploration of the potential pathways involved and revealed that the IL-17 signalling pathway may be the most relevant pathway. Collectively, we revealed the full-cycle landscape of key cells associated with psoriasis and provided a more comprehensive understanding of the pathogenesis of psoriasis.


Assuntos
Psoríase , Análise da Expressão Gênica de Célula Única , Animais , Camundongos , Queratinócitos/metabolismo , Psoríase/patologia , Pele/patologia , Transição Epitelial-Mesenquimal , Fibroblastos/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
7.
Bioact Mater ; 34: 64-79, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38186961

RESUMO

Given post-operative aseptic loosening in orthopedic disease treatment, osteointegration occurs at the bone-implant interface as a holistic process, including immunoregulation (e.g., macrophage polarization), angiogenesis and osteogenesis in sequence. In order to achieve early rapid and satisfactory osseointegration, different nano-shaped (nanocone, nanopolyhedron and nanoflower abbr. NC, NP & NF) cerium oxide (CeO2-x) coatings, endowed with "nanozyme-like" activities for multiple free radical elimination and osteoimmunology regulation, were hydrothermally synthesized on titanium alloy (TC4). In vitro cell experiments showed that nano-CeO2-x coated TC4 not only induced polarization of RAW264.7 cells toward M2 phenotype, but also promoted angiogenesis and vascularization of endothelial cells along with differentiation and mineralization of osteogenic precursor cells. Improvements in M2-polarized macrophage, angiogenesis, and bone regeneration were further confirmed in a rat femoral condyle model. Among the above three nano-morphologies, NF exhibited the best osseoinetegration. RNA sequencing and mechanism exploration suggested that the inhibition of PI3K-AKT signaling pathway was essential for immunomodulatory capacity of NF. In conclusion, it provided promising insights into the immunomodulatory exploitation of orthopedic implants.

8.
J Hazard Mater ; 465: 133204, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38103293

RESUMO

Hexagonal boron nitride (h-BN) nanomaterials have attracted numerous attentions for application in various fields, including environmental governance. Understanding the environmental implications of h-BN is a prerequisite for its safe and sustainable use; nevertheless, information on the negative effect of h-BN on aquatic organisms and the underlying toxicity mechanisms is scarce. The present study found that low exposure doses (0.1-1 µg/mL) of micron-sized h-BN lamella apparently suppressed (maximally 45.3%) the growth of Chlorella vulgaris (a freshwater alga) via membrane damages and metabolic reprogramming. Experimental and simulation results verified that h-BN can penetrate into and then extract phospholipids from the cell membrane of algae due to the strong hydrophobic interactions between h-BN nanosheets and lipids, resulting in membrane permeabilization and integrity reduction. Oxidative stress-triggered lipid peroxidation also contributes to membrane destruction of algae. Metabolomics assay demonstrated that h-BN down-regulated the CO2-fixation associated Calvin cycle and glycolysis/gluconeogenesis pathways in algae, thereby inhibiting energy synthesis and antioxidation process. Despite releasing soluble B inside cells, the B species exhibited negligible toxicity. These findings highlight the phenomena and mechanisms of h-BN toxicity in photosynthetic algae, which have great implications for guiding their safe use under the scenarios of global carbon neutrality.


Assuntos
Compostos de Boro , Carbono , Chlorella vulgaris , Conservação dos Recursos Naturais , Política Ambiental , Água Doce
9.
Adv Healthc Mater ; 13(7): e2302901, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38102773

RESUMO

Bone metastases severely threaten the lives of patients. Although surgical treatment combined with adjuvant chemotherapy significantly improves the survival rate of patients, tumor recurrence, or metastasis after surgical resection and bone defects caused by surgical treatment remain major challenges for clinicians. Given the abovementioned clinical requirements, barium titanate-containing iron-coated porous titanium alloy scaffolds have been proposed to promote bone defect repair and inhibit tumor recurrence. Fortunately, in vitro and in vivo experimental research confirms that barium titanate containing iron-coated porous titanium alloy scaffolds promote osteogenesis and bone reconstruction in defect repair via mechanoelectric conversion and inhibit tumor recurrence via photothermal effects. Furthermore, the underlying and intricate mechanisms of bone defect repair and tumor recurrence prevention of barium titanate-containing iron-coated porous titanium alloy scaffolds are explored. A win-win strategy for mechanoelectrical conversion and photothermal functionalization provides promising insights into bone reconstruction of tumor-resected defects.


Assuntos
Tecidos Suporte , Titânio , Humanos , Titânio/farmacologia , Porosidade , Bário , Recidiva Local de Neoplasia , Osteogênese , Ligas , Ferro
10.
Environ Geochem Health ; 46(1): 16, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38147141

RESUMO

Soil organic matter can protect plants and microorganisms from toxic substances. Beyond the tolerance limit, the toxicity of petroleum pollution to soil organisms may increase rapidly with the increase of petroleum content. However, the method for evaluating the petroleum tolerance limit of soil organic matter (SOM) is still lacking. In this study, the petroleum saturation limit in SOM was first evaluated by the sorption coefficient (Kd) of 1,2-dichlorobenzene (DCB) from water to soils containing different petroleum levels. The sorption isotherm of dichlorobenzene in several petroleum-contaminated soils with different organic matter content and the microbial toxicity test of several petroleum-contaminated soils were determined. It is found that when the petroleum content is about 5% of the soil organic matter content, the sorption of petroleum to organic matter reached saturation limit. When organic matter reaches petroleum saturation limit, the sorption coefficient of DCB by soil particles increased linearly with the increase of petroleum content (R2 > 0.991). The results provided important insights into the understanding the fate of petroleum pollutants in soil and the analysis of soil toxicity.


Assuntos
Poluentes Ambientais , Petróleo , Poluição Ambiental , Solo
11.
One Health ; 17: 100631, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38024253

RESUMO

Emerging and re-emerging infectious diseases have been on the rise, with a significant proportion being zoonotic. Rodents, as the natural reservoirs of numerous diverse zoonotic viruses, pose a substantial threat to human health. To investigate the diversity of known and unknown viruses harbored by rodents in Guangdong (southern province of China), we conducted a comprehensive analysis of viral genomes through metagenomic sequencing of organs from 194 rodents. Our analysis yielded 2163 viral contigs that were assigned to 25 families known to infect a wide range of hosts, including vertebrates, invertebrates, amoebas, and plants. The viral compositions vary considerably among different organs, but not in rodent species. We also assessed and prioritized zoonotic potential of those detected viruses. Ninety-two viral species that are either known to infect vertebrates and invertebrates or only vertebrates were identified, among which 21 are considered high-risk to humans. The high-risk viruses included members of the Hantavirus, Picobirnaviruses, Astroviruses and Pestivirus. The phylogenetic trees of four zoonotic viruses revealed features of novel viral genomes that seem to fit evolutionarily into a zone of viruses that potentially pose a risk of transmission to humans. Recognizing that zoonotic diseases are a One Health issue, we approached the problem of identifying the zoonotic risk from rodent-transmitted disease in the Guangdong province by performing next-generation sequencing to look for potentially zoonotic viruses in these animals.

12.
Quant Imaging Med Surg ; 13(10): 6887-6898, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869304

RESUMO

Background: Axillary lymph node (ALN) metastasis is seen in encapsulated papillary carcinoma (EPC), mostly with an invasive component (INV). Radiomics can offer more information beyond subjective grayscale and color Doppler ultrasound (US) image interpretation. This study aimed to develop radiomics models for predicting an INV of EPC in the breast based on US images. Methods: This study retrospectively enrolled 105 patients (107 masses) with a pathological diagnosis of EPC from January 2016 to April 2021, and all masses had preoperative US images. Of the 107 masses, 64 were randomized to a training set and 43 to a test set. US and clinical features were analyzed to identify features associated with INVs. Then, based on the manually segmented US images to obtain radiomics features, the models to predict INVs were built with 5 ensemble machine learning classifiers. We estimated the performance of the predictive models using accuracy, the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity. Results: The mean age was 63.71 years (range, 31 to 85 years); the mean size of tumors was 23.40 mm (range, 9 to 120 mm). Among all clinical and US features, only shape was statistically different between EPC with INVs and those without (P<0.05). In this study, the models based on Random Under Sampling (RUS) Boost, Random Forest, XGBoost, AdaBoost, and Easy Ensemble methods had good performance, among which RUS Boost had the best performance with an AUC of 0.875 [95% confidence interval (CI): 0.750-0.974] in the test set. Conclusions: Radiomics prediction models were effective in predicting the INV of EPC, whereas clinical and US features demonstrated relatively decreased predictive utility.

13.
Plants (Basel) ; 12(19)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37836146

RESUMO

Nocturnal moths (Lepidoptera) are important pollinators of a wide range of plant species. Understanding the foraging preferences of these insects is essential for their scientific management. However, this information is lacking for most moth species. The present study was therefore conducted to delineate the host plant feeding and pollination ranges of an agriculturally important nocturnal moth species Athetis lepigone by identifying the pollen species adhering to their bodies during long-distance migration. Pollen grains were dislodged from 1871 A. lepigone migrants captured on Beihuang Island in the Bohai Strait between 2020 and 2021. This region is a key seasonal migration pathway for A. lepigone in northern China. Almost 20% of all moths sampled harbored pollens, providing direct evidences that this moth species may serve as pollinators. Moreover, at least 39 pollen taxa spanning 21 plant families and 31 genera were identified, with a preference for Asteraceae, Amaranthaceae, and Pinaceae. Additionally, the pollen adherence ratios and taxa varied with moth sex, inter-annual changes, and seasonal fluctuations. Most importantly, the pollen taxa were correlated with insect migration stages and indicated that A. lepigone bidirectionally migrates between central China (Shandong, Hebei, and Henan Provinces) and northeastern China (Liaoning Province). Overall, the findings of the present work provide valuable information on the pollination behavior, geographical origins, and pollination regions of A. lepigone moths and could facilitate the design and optimization of efficacious local and regional management strategies for this important insect.

14.
Nanomaterials (Basel) ; 13(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37686924

RESUMO

Porous C nanosheet/Cu2S composites were prepared using a simple self-template method and vulcanization process. The Cu2S nanoparticles with an average diameter of 140 nm are uniformly distributed on porous carbon nanosheets. When used as the anode of a potassium-ion battery, porous C nanosheet/Cu2S composites exhibit good rate performance and cycle performance (363 mAh g-1 at 0.1 A g-1 after 100 cycles; 120 mAh g-1 at 5 A g-1 after 1000 cycles). The excellent electrochemical performance of porous C nanosheet/Cu2S composites can be ascribed to their unique structure, which can restrain the volume change of Cu2S during the charge/discharge processes, increase the contact area between the electrode and the electrolyte, and improve the electron/ionic conductivity of the electrode material.

15.
Bioresour Technol ; 388: 129777, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37722543

RESUMO

Constructed wetlands (CWs) are widely used to polish the effluent of wastewater treatment plants and micro-polluted river or lake water. However, the impact of large-scale applications of CWs on carbon emissions is unclear. In this study, the carbon footprints of two full-scale hybrid CWs were determined based on life cycle assessment (LCA). Results showed that the carbon emission of CW ranged from 0.10 to 0.14 kg CO2-eq/m3, and was significantly correlated with the influent chemical oxygen demand loads and electricity consumption. However, CW would approach carbon neutrality during the service period when taking plant carbon sequestration into consideration. Compared with other advanced wastewater treatment technologies, CWs showed significant low-carbon emission and cost-effective benefits. This study clarified the role of CWs in the carbon cycle and would provide guidance for the construction and management of CWs.

16.
iScience ; 26(9): 107691, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37694154

RESUMO

The liver has long been deemed a tolerogenic organ. We employed high-dimensional mass cytometry and immunohistochemistry to depict the temporal and spatial dynamics of immune cells in the spleen and liver in a murine model of spontaneous liver allograft acceptance. We depicted the immune landscape of spontaneous liver tolerance throughout the rejection and acceptance stages after liver transplantation and highlighted several points of importance. Of note, the CD4+/CD8+ T cell ratio remained low, even in the tolerance phase. Furthermore, a PhenoGraph clustering analysis revealed that exhausted CD8+ T cells were the most dominant metacluster in graft-infiltrating lymphocytes (GILs), which highly expressed the costimulatory molecule CD86. The temporal and spatial dynamics of immune cells revealed by high-dimensional analyses enable a fine-grained analysis of GIL subsets, contribute to new insights for the discovery of immunological mechanisms of liver tolerance, and provide potential ways to achieve clinical operational tolerance after liver transplantation.

17.
Front Genet ; 14: 1165648, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576555

RESUMO

Background: The tumor microenvironment (TME) of breast cancer (BRCA) is a complex and dynamic micro-ecosystem that influences BRCA occurrence, progression, and prognosis through its cellular and molecular components. However, as the tumor progresses, the dynamic changes of stromal and immune cells in TME become unclear. Objective: The aim of this study was to identify differentially co-expressed genes (DCGs) associated with the proportion of stromal cells in TME of BRCA, to explore the patterns of cell proportion changes, and ultimately, their impact on prognosis. Methods: A new heuristic feature selection strategy (CorDelSFS) was combined with differential co-expression analysis to identify TME-key DCGs. The expression pattern and co-expression network of TME-key DCGs were analyzed across different TMEs. A prognostic model was constructed using six TME-key DCGs, and the correlation between the risk score and the proportion of stromal cells and immune cells in TME was evaluated. Results: TME-key DCGs mimicked the dynamic trend of BRCA TME and formed cell type-specific subnetworks. The IG gene-related subnetwork, plasmablast-specific expression, played a vital role in the BRCA TME through its adaptive immune function and tumor progression inhibition. The prognostic model showed that the risk score was significantly correlated with the proportion of stromal cells and immune cells in TME, and low-risk patients had stronger adaptive immune function. IGKV1D-39 was identified as a novel BRCA prognostic marker specifically expressed in plasmablasts and involved in adaptive immune responses. Conclusions: This study explores the role of proportionate-related genes in the tumor microenvironment using a machine learning approach and provides new insights for discovering the key biological processes in tumor progression and clinical prognosis.

18.
Front Oncol ; 13: 1194232, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529690

RESUMO

Background: Lynch syndrome (LS)-associated glioblastoma (GBM) is rare in clinical practice, and simultaneous occurrence with cutaneous porokeratosis is even rarer. In this study, we analyzed the clinicopathological and genetic characteristics of LS-associated GBMs and concurrent porokeratosis, as well as evaluated the tumor immune microenvironment (TIME) of LS-associated GBMs. Methods: Immunohistochemical staining was used to confirm the histopathological diagnosis, assess MMR and PD-1/PD-L1 status, and identify immune cell subsets. FISH was used to detect amplification of EGFR and PDGFRA, and deletion of 1p/19q and CDKN2A. Targeted NGS assay analyzed somatic variants, MSI, and TMB status, while whole-exome sequencing and Sanger sequencing were carried out to analyze the germline mutations. Results: In the LS family, three members (I:1, II:1 and II:4) were affected by GBM. GBMs with loss of MSH2 and MSH6 expression displayed giant and multinucleated bizarre cells, along with mutations in ARID1A, TP53, ATM, and NF1 genes. All GBMs had TMB-H but not MSI-H. CD8+ T cells and CD163+ macrophages were abundant in each GBM tissue. The primary and recurrent GBMs of II:1 showed mesenchymal characteristics with high PD-L1 expression. The family members harbored a novel heterozygous germline mutation in MSH2 and FDPS genes, confirming the diagnosis of LS and disseminated superficial actinic porokeratosis. Conclusion: LS-associated GBM exhibits heterogeneity in clinicopathologic and molecular genetic features, as well as a suppressive TIME. The presence of MMR deficiency and TMB-H may serve as predictive factors for the response to immune checkpoint inhibitor therapy in GBMs. The identification of LS-associated GBM can provide significant benefits to both patients and their family members, including accurate diagnosis, genetic counseling, and appropriate screening or surveillance protocols. Our study serves as a reminder to clinicians and pathologists to consider the possibility of concurrent genetic syndromes in individuals or families.

19.
Cell Rep Methods ; 3(6): 100479, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37426762

RESUMO

Mass spectrometry (MS)-based immunopeptidomics is an attractive antigen discovery method with growing clinical implications. However, the current experimental approach to extract HLA-restricted peptides requires a bulky sample source, which remains a challenge for obtaining clinical specimens. We present an innovative workflow that requires a low sample volume, which streamlines the immunoaffinity purification (IP) and C18 peptide cleanup on a single microfluidics platform with automated liquid handling and minimal sample transfers, resulting in higher assay sensitivity. We also demonstrate how the state-of-the-art data-independent acquisition (DIA) method further enhances the depth of tandem MS spectra-based peptide sequencing. Consequently, over 4,000 and 5,000 HLA-I-restricted peptides were identified from as few as 0.2 million RA957 cells and a melanoma tissue of merely 5 mg, respectively. We also identified multiple immunogenic tumor-associated antigens and hundreds of peptides derived from non-canonical protein sources. This workflow represents a powerful tool for identifying the immunopeptidome of sparse samples.


Assuntos
Microfluídica , Proteômica , Fluxo de Trabalho , Proteômica/métodos , Espectrometria de Massas em Tandem , Peptídeos/química
20.
J Org Chem ; 88(14): 10282-10286, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37431757

RESUMO

The decarboxylative coupling using carboxylic acid and potassium metabisulfite, promoted by a palladium catalyst, is reported for the generation of sulfides. The coupling is performed using the easily available carboxylic acid and environmentally friendly inorganic sulfides as a divalent inorganic sulfur source. Not only aromatic acids but also aliphatic carboxylic acids are workable during the couplings. The method is applicable and practical to a scope of 20 examples and drug molecules.

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