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1.
Sci Total Environ ; 929: 172572, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38641113

RESUMO

Carbonate bound arsenic act as an important reservoir for arsenic (As) in nature aquifers. Sulfate-reducing bacteria (SRB), one of the dominant bacterial species in reductive groundwater, profoundly affects the biogeochemical cycling of As. However, whether and how SRB act on the migration and transformation of carbonate bound arsenic remains to be elucidated. Batch culture experiment was employed using filed collected arsenic bearing calcite to investigate the release and species transformation of As by SRB. We found that arsenic in the carbonate samples mostly exist as inorganic As(V) (93.92 %) and As(III). The present of SRB significantly facilitated arsenic release from carbonates with a maximum of 22.3 µg/L. The main release mechanisms of As by SRB include 1) calcite dissolution and the liberate of arsenic in calcite lattices, and 2) the break of H-bonds frees arsenic absorbed on carbonate surface. A redistribution of arsenic during culture incubation took place which may due to the precipitation of As2Sx or secondary FeAl minerals. To our best knowledge, it is the first experimental study focusing on the release of carbonate bound arsenic by SRB. This study provides new insights into the fate and transport of arsenic mediated by microorganism within high arsenic groundwater-sediment system.


Assuntos
Arsênio , Carbonatos , Água Subterrânea , Sulfatos , Poluentes Químicos da Água , Arsênio/metabolismo , Água Subterrânea/química , Água Subterrânea/microbiologia , Poluentes Químicos da Água/metabolismo , Carbonatos/metabolismo , Sulfatos/metabolismo , Bactérias/metabolismo , Carbonato de Cálcio/metabolismo , Carbonato de Cálcio/química
2.
Heliyon ; 10(5): e27340, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495188

RESUMO

Objectives: The prospect of extended reality (XR) being integrated with surgical training curriculum has attracted scholars. However, there is a lack of bibliometric analysis to help them better understand this field. Our aim is to analyze relevant literature focusing on development trajectory and research directions since the 21st century to provide valuable insights. Methods: Papers were retrieved from the Web of Science Core Collection. Microsoft Excel, VOSviewer, and CiteSpace were used for bibliometric analysis. Results: Of the 3337 papers published worldwide, China contributed 204, ranking fifth. The world's enthusiasm for this field has been growing since 2000, whereas China has been gradually entering since 2001. Although China had a late start, its growth has accelerated since around 2016 due to the reform of the medical postgraduate education system and the rapid development of Chinese information technology, despite no research explosive period has been yet noted. International institutions, notably the University of Toronto, worked closely with others, while Chinese institutions lacked of international and domestic cooperation. Sixteen stable cooperation clusters of international scholars were formed, while the collaboration between Chinese scholars was not yet stable. XR has been primarily applied in orthopedic surgery, cataract surgery, laparoscopic training and intraoperative use in neurosurgery worldwide. Conclusions: There is strong enthusiasm and cooperation in the international research on the XR-based surgical training. Chinese scholars are making steady progress and have great potential in this area. There has not been noted an explosive research phase yet in the Chinese pace. The research on several surgical specialties has been summarized at the very first time. AR will gradually to be more involved and take important role of the research.

3.
Nat Immunol ; 25(4): 703-715, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38514887

RESUMO

Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.


Assuntos
Células-Tronco Hematopoéticas , Transcriptoma , Humanos , Medula Óssea , Perfilação da Expressão Gênica , Células da Medula Óssea
4.
Nat Prod Res ; : 1-8, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551108

RESUMO

A new naphtho-γ-pyrone dimer, asperosperma A, and a new methyl nicotinate derivative, asperosperma B, with 12 known compounds were isolated from the endophytic fungus Aspergillus niger from the stem of Camellia flavida. Their structure was elucidated by NMR, ECD spectrum, and HR-ESI-MS data. Asperosperma A exhibited a highly cytotoxicity against H460 and 4T1 cancer cells with the IC50 values were 0.37 ± 0.06 and 2.04 ± 0.79 µM, respectively. Moreover, it showed a highly sensitive against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and methicillin-resistant S. aureus.

6.
J Med Virol ; 96(3): e29546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38516804

RESUMO

Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.


Assuntos
Células Dendríticas , Hepatite B , Proteínas de Membrana Transportadoras , Humanos , Autofagia/genética , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/metabolismo , Regulação para Baixo , Hepatite B/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/genética , Vírus da Hepatite B , Hepatócitos/metabolismo , Células-Tronco Pluripotentes Induzidas , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , RNA Interferente Pequeno/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Organoides/metabolismo , Organoides/virologia
7.
Sensors (Basel) ; 24(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38400469

RESUMO

The construction of large-diameter shield tunnels underwater involves complex variations in water and earth load outside the tunnel segment, as well as intricate mechanical responses. This study analyzes the variation laws of external loads, axial forces, and bending moments acting on the segment ring during the shield assembly and removal from the shield tail. It accomplishes this through the establishment of an on-site monitoring system based on the Internet of Things (IoT) and proposes a Bayesian-genetic algorithm model to estimate the water and earth pressure. The fluctuation section exhibits a peak load twice as high as that in the stable section. These variations are influenced by Jack thrust, shield shell force, and grouting pressure. The peak load observed in the fluctuation section is twice as high as the load observed in the stable section. During the shield tail removal process, the internal forces undergo significant fluctuations due to changes in both load and boundary conditions, and the peak value of the axial force during the fluctuation section is eight times higher than that during the stable section, while the peak value of the bending moment during the fluctuation section is five times higher than that during the stable section. The earth and water pressure calculated using the inversion analysis method, which relies on the measured internal forces, closely matches the actual measured values. The results demonstrate that the accuracy of the water and earth pressure obtained through inversion analysis is twice as high as that obtained using the full coverage pressure method. These results can serve as a valuable reference for similar projects.

8.
Biotechnol J ; 19(2): e2300628, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38403450

RESUMO

Bioconversion of Rebaudioside D faces high-cost obstacles. Herein, a novel glycosyltransferase StUGT converting Rebaudioside A to Rebaudioside D was screened and characterized, which exhibits stronger affinity and substrate specificity for Rebaudioside A than previously reported enzymes. A whole-cell catalytic system was thus developed using the StUGT strain. The production of Rebaudioside D was enhanced significantly by enhancing cell permeability, and the maximum production of 6.12 g/L and the highest yield of 98.08% by cell catalyst was obtained by statistical-based optimization. A new cascade process utilizing this recombinant strain and E. coli expressing sucrose synthase was further established to reduce cost through replacing expensive UDPG with sucrose. A StUGT-GsSUS1 system exhibited high catalytic capability, and 5.27 g L-1 Rebaudioside D was achieved finally without UDPG addition by systematic optimization. This is the best performance reported in cell-cascaded biosynthesis, which paves a new cost-effective strategy for sustainable synthesis of scarce premium sweeteners from biomass.


Assuntos
Diterpenos do Tipo Caurano , Glicosídeos , Solanum tuberosum , Stevia , Solanum tuberosum/genética , Stevia/química , Uridina Difosfato Glucose , Glicosiltransferases/genética , Escherichia coli/genética
9.
Behav Sci (Basel) ; 14(2)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38392493

RESUMO

Two studies were conducted to test the convergence of mass and interpersonal media processes and their effects on YouTube. The first study examined the influence of interpersonal interactions on video enjoyment. The results indicated that positive comment valence affected participants' identification with the content creator, which then affected enjoyment of the video. To investigate the effects of convergence from a macro-level perspective, the second study tracked and recorded data from 32 YouTube videos for 34 days and recorded the following data for each video: number of views, likes, and comments/responses. The results indicated that the more content creators and users interact, the more likes the video receives. However, user-to-user interactions are associated with a decrease in the number of likes a video receives.

10.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38396725

RESUMO

The transcription of glycine-rich RNA-binding protein 2 (PeGRP2) transiently increased in the roots and shoots of Populus euphratica (a salt-resistant poplar) upon initial salt exposure and tended to decrease after long-term NaCl stress (100 mM, 12 days). PeGRP2 overexpression in the hybrid Populus tremula × P. alba '717-1B4' (P. × canescens) increased its salt sensitivity, which was reflected in the plant's growth and photosynthesis. PeGRP2 contains a conserved RNA recognition motif domain at the N-terminus, and RNA affinity purification (RAP) sequencing was developed to enrich the target mRNAs that physically interacted with PeGRP2 in P. × canescens. RAP sequencing combined with RT-qPCR revealed that NaCl decreased the transcripts of PeGRP2-interacting mRNAs encoding photosynthetic proteins, antioxidative enzymes, ATPases, and Na+/H+ antiporters in this transgenic poplar. Specifically, PeGRP2 negatively affected the stability of the target mRNAs encoding the photosynthetic proteins PETC and RBCMT; antioxidant enzymes SOD[Mn], CDSP32, and CYB1-2; ATPases AHA11, ACA8, and ACA9; and the Na+/H+ antiporter NHA1. This resulted in (i) a greater reduction in Fv/Fm, YII, ETR, and Pn; (ii) less pronounced activation of antioxidative enzymes; and (iii) a reduced ability to maintain Na+ homeostasis in the transgenic poplars during long-term salt stress, leading to their lowered ability to tolerate salinity stress.


Assuntos
Populus , Tolerância ao Sal , Tolerância ao Sal/genética , Populus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cloreto de Sódio/metabolismo , Íons/metabolismo , Sódio/metabolismo , Homeostase , Adenosina Trifosfatases/metabolismo , Antiporters/metabolismo , Fotossíntese/genética , Regulação da Expressão Gênica de Plantas
11.
Mutat Res ; 828: 111852, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38368811

RESUMO

OBJECTIVES: Our group previously found that LINC00665 was upregulated in hepatocellular carcinoma (HCC) tissues through database analysis; however, the potential molecular mechanism of LINC00665 in HCC progression still needs further study. METHODS: qRTPCR was performed to determine the differential expression of LINC00665 and let-7i in HCC cells. Dual-luciferase reporter assays were performed to analyze the interaction of LINC00665 and let-7i. CCK-8 assays, scratch assays, Transwell invasion assays, qRTPCR and western blotting were performed to determine the regulatory mechanism of LINC00665/let-7i/HMGA1 in HCC cells. RESULTS: LINC00665 was upregulated in HCC cells compared with normal hepatocytes. A potential binding site between LINC00665 and let-7i was confirmed by dual-luciferase reporter assay. In HCC cells, inhibition of LINC00665 significantly reduced cell proliferation, migration and invasion ability via the let-7i/HMGA1 signaling axis. CONCLUSION: LINC00665 promotes the proliferation and invasion of HCC cells via the let-7i/HMGA1 signaling axis.


Assuntos
Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a , Neoplasias Hepáticas , MicroRNAs , Invasividade Neoplásica , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína HMGA1a/genética , Proteína HMGA1a/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais
12.
Heliyon ; 10(1): e23056, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163170

RESUMO

Objectives: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype. Methods: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity. Results: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules. Conclusion: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.

13.
Sci Transl Med ; 16(730): eade2886, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38232136

RESUMO

Immunotherapy has emerged as a crucial strategy to combat cancer by "reprogramming" a patient's own immune system. Although immunotherapy is typically reserved for patients with a high mutational burden, neoantigens produced from posttranscriptional regulation may provide an untapped reservoir of common immunogenic targets for new targeted therapies. To comprehensively define tumor-specific and likely immunogenic neoantigens from patient RNA-Seq, we developed Splicing Neo Antigen Finder (SNAF), an easy-to-use and open-source computational workflow to predict splicing-derived immunogenic MHC-bound peptides (T cell antigen) and unannotated transmembrane proteins with altered extracellular epitopes (B cell antigen). This workflow uses a highly accurate deep learning strategy for immunogenicity prediction (DeepImmuno) in conjunction with new algorithms to rank the tumor specificity of neoantigens (BayesTS) and to predict regulators of mis-splicing (RNA-SPRINT). T cell antigens from SNAF were frequently evidenced as HLA-presented peptides from mass spectrometry (MS) and predict response to immunotherapy in melanoma. Splicing neoantigen burden was attributed to coordinated splicing factor dysregulation. Shared splicing neoantigens were found in up to 90% of patients with melanoma, correlated to overall survival in multiple cancer cohorts, induced T cell reactivity, and were characterized by distinct cells of origin and amino acid preferences. In addition to T cell neoantigens, our B cell focused pipeline (SNAF-B) identified a new class of tumor-specific extracellular neoepitopes, which we termed ExNeoEpitopes. ExNeoEpitope full-length mRNA predictions were tumor specific and were validated using long-read isoform sequencing and in vitro transmembrane localization assays. Therefore, our systematic identification of splicing neoantigens revealed potential shared targets for therapy in heterogeneous cancers.


Assuntos
Melanoma , Neoplasias , Humanos , Antígenos de Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/terapia , Linfócitos T , Peptídeos/química , Imunoterapia/métodos
14.
ACS Appl Mater Interfaces ; 16(3): 3576-3585, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38215344

RESUMO

The perovskite material has demonstrated conceivable potential as an absorbing material of solar cells. Although the power conversion efficiency of the device based on perovskite has rapidly come to 26%, there are still many factors that affect the further improvement of the photoelectric conversion efficiency. Interface defects are the dominating concern that influence carrier transportation and stability. Here, we report a novel strategy where B2O3 is deposited on the fresh perovskite film by atomic layer deposition technology. The organic atmosphere during atomic layer deposition can effectively regulate the crystallization kinetics of perovskites and promote crystal growth. The B2O3 adsorbed on the perovskite light-absorption layer can effectively reduce the electropositive defects on the surface of the perovskite, such as uncoordinated Pb2+ and I vacancies due to the electron-donating properties of the side O atoms in B2O3. Consequently, the power conversion efficiency of the perovskite solar cell after B2O3 treatment increases to 21.78% from 18.89%. Simultaneously, B2O3 can improve the stability of devices.

15.
BMC Oral Health ; 24(1): 136, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280992

RESUMO

BACKGROUND: The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing. METHODS: The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2. RESULTS: Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and ß-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed. CONCLUSIONS: Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.


Assuntos
Anodontia , Displasia Ectodérmica Anidrótica Tipo 1 , Displasia Ectodérmica , Dente , Masculino , Humanos , Displasia Ectodérmica Anidrótica Tipo 1/complicações , Displasia Ectodérmica Anidrótica Tipo 1/genética , Displasia Ectodérmica/genética , Fenótipo , Anodontia/genética , Mutação , Proteínas Wnt/genética
16.
Int J Surg ; 110(2): 766-776, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016292

RESUMO

BACKGROUND: Ischemic stroke (IS) is more common every year, the condition is serious, and have a poor prognosis. New, efficient, and safe therapeutic targets are desperately needed as early treatment especially prevention and reperfusion is the key to lowering the occurrence of poorer prognosis. Generally circulating proteins are attractive therapeutic targets, this study aims to identify potential pharmacological targets among plasma and cerebrospinal fluid (CSF) proteins for the prevention and treatment of IS using a multicenter Mendelian randomization (MR) approach. METHODS: First, the genetic instruments of 734 plasma and 151 CSF proteins were assessed for causative connections with IS from MEGASTROKE consortium by MR to identify prospective therapeutic targets. Then, for additional validation, plasma proteins from the deCODE consortium and the Fenland consortium, as well as IS GWAS data from the FinnGen cohort, the ISGC consortium and UK biobank, were employed. A thorough evaluation of the aforementioned possible pharmacological targets was carried out using meta-analysis. The robustness of MR results was then confirmed through sensitivity analysis using several techniques, such as bidirectional MR analysis, Steiger filtering, and Bayesian colocalization. Finally, methods like Protein-Protein Interaction (PPI) Networking were utilized to investigate the relationship between putative drug targets and therapeutic agents. RESULTS: The authors discovered three proteins that may function as promising therapeutic targets for IS and meet the Bonferroni correction ( P <0.05/885=5.65×10 -5 ). Prekallikrein (OR=0.41, 95% CI: 0.27-0.63, P =3.61×10 -5 ), a protein found in CSF, has a 10-fold protective impact in IS, while the plasma proteins SWAP70 (OR=0.85, 95% CI: 0.80-0.91, P =1.64×10 -6 ) and MMP-12 (OR=0.92, 95% CI: 0.89-0.95, P =4.49×10 -6 ) of each SD play a protective role in IS. Prekallikrein, MMP-12, SWAP70 was replicated in the FinnGen cohort and ISGC database. MMP-12 (OR=0.93, 95% CI: 0.91-0.94, P <0.001), SWAP70 (OR=0.92, 95% CI: 0.90-0.94, P <0.001), and prekallikrein (OR=0.53, 95% CI: 0.33-0.72, P <0.001) may all be viable targets for IS, according to the combined meta-analysis results. Additionally, no evidence of reverse causality was identified, and Bayesian colocalization revealed MMP-12 (PPH 4 =0.995), SWAP70 (PPH 4 =0.987), and prekallikrein (PPH 4 =0.894) shared the same variant with IS, supporting the robustness of the aforementioned causation. Prekallikrein and MMP-12 were associated with the target protein of the current treatment of IS. Among them, Lanadelumab, a new drug whose target protein is a prekallikrein, may be a promising new drug for the treatment of IS. CONCLUSION: The prekallikrein, MMP-12, and SWAP70 are causally associated with the risk of IS. Moreover, MMP-12 and prekallikrein may be treated as promising therapeutic targets for medical intervention of IS.


Assuntos
AVC Isquêmico , Proteoma , Humanos , Teorema de Bayes , Metaloproteinase 12 da Matriz , Análise da Randomização Mendeliana , Pré-Calicreína , Estudos Multicêntricos como Assunto
17.
Pac Symp Biocomput ; 29: 654-660, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38160315

RESUMO

Immune modulation is considered a hallmark of cancer initiation and progression, with immune cell density being consistently associated with clinical outcomes of individuals with cancer. Multiplex immunofluorescence (mIF) microscopy combined with automated image analysis is a novel and increasingly used technique that allows for the assessment and visualization of the tumor microenvironment (TME). Recently, application of this new technology to tissue microarrays (TMAs) or whole tissue sections from large cancer studies has been used to characterize different cell populations in the TME with enhanced reproducibility and accuracy. Generally, mIF data has been used to examine the presence and abundance of immune cells in the tumor and stroma compartments; however, this aggregate measure assumes uniform patterns of immune cells throughout the TME and overlooks spatial heterogeneity. Recently, the spatial contexture of the TME has been explored with a variety of statistical methods. In this PSB workshop, speakers will present some of the state-of-the-art statistical methods for assessing the TIME from mIF data.


Assuntos
Biologia Computacional , Neoplasias , Humanos , Reprodutibilidade dos Testes , Microambiente Tumoral
18.
Asia Pac Allergy ; 13(4): 164-174, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38094094

RESUMO

Background: Eosinophilic chronic rhinosinusitis (CRS) has been widely studied for its intractability and high recurrence rate. It can be divided into pure and mixed type 2 CRS subtypes. Mouse models that reflect pure type 2 inflammation of CRS are lacking. Objective: This study aims to establish a relatively pure type 2 CRS mouse model and compare it with 2 mixed type 2 CRS models. Methods: Three mouse CRS models were constructed: (1) aerosol ovalbumin (OVA) + aspergillus oryzae-derived protease (AP); (2) intranasal OVA + AP; (3) Intraperitoneal then intranasal OVA + AP (n = 10 per group). Nasal, lung symptoms, IgE, inflammatory cells, cytokines, and remodeling factors were evaluated. Results: Histological and micro-computed tomography showed inflammation, polyps, and opacification in all 3 experimental groups. The aerosol group had significantly increased local eosinophils and type 2 cytokines, while other types of cytokines showed no noticeable change. The nasal instillation groups also showed elevated other inflammatory factors and tissue polypoid changes were more pronounced. More severe pulmonary inflammation was observed with aerosol delivery. Conclusion: Aerosol inhalation mouse model is superior for studying nasal relatively pure type 2 inflammation and lower airway comorbidities.

19.
J Adv Res ; 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38043608

RESUMO

INTRODUCTION: Surgical ventricular reconstruction (SVR) is an alternative therapeutic approach in patients with refractory heart failure (HF), but residual remodeling after SVR limits the improvement of HF. Recently, we reported that SVR may act as an environmental cue to reactivate endogenous proliferation of cardiomyocytes; however, it is unclear whether enhancing endogenous cardiomyocyte regeneration further improves HF after SVR. OBJECTIVES: We aimed to explore whether circular RNAs (circRNAs) would involved in SVR and their mechanisms. METHODS: Male C57BL/6 mice were subjected to myocardial infarction (MI) or sham surgery. Four weeks later, MI mice with a large ventricular aneurysm underwent SVR or a second open-chest operation only. Echocardiography and histological analysis were used to evaluate heart function, cardiac remodeling, and myocardial regeneration. Sequencing of circular RNAs, RNA immunoprecipitation, RNA pulldown, and luciferase reporter assay were used to explore the underlying mechanisms. RESULTS: SVR markedly attenuated cardiac remodeling and induced cardiomyocyte regeneration, as evidenced by positive staining of Ki-67, phospho-histone H3 (pH3), and Aurora B in the plication zone, but significant residual remodeling still existed in comparison with the sham group. Sequencing results showed that SVR altered the expression profile of cardiac circRNAs, and circMap4k2 was identified as the most upregulated one. After characterizing circMap4k2, we noted that overexpression of circMap4k2 significantly promoted proliferation of cardiomyocytes in cultured neonatal rat cardiomyocytes and silencing of circMap4k2 significantly inhibited it; similar results were obtained in SVR-treated MI mice but not in MI mice without SVR treatment. Residual cardiac remodeling after SVR was further attenuated by circMap4k2 overexpression. CircMap4k2 bound with miR-106a-3p and inhibited cardiomyocyte proliferation by targeting a downstream effector of the antizyme inhibitor 1 (Azin1) gene. CONCLUSIONS: CircMap4k2 acts as an environmental cue and targets the miR-106a-3p/Azin1 pathway to increase cardiac regeneration in the plication zone and attenuate residual remodeling after SVR.

20.
Infect Drug Resist ; 16: 7735-7741, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38144220

RESUMO

Background: This study aimed to investigate the risk factors for persistent viral shedding in cancer patients after Omicron infection. Methods: Patients with asymptomatic or mild Omicron infection (≥18 years) who were treated in a makeshift hospital in Shanghai were enrolled from 9 Apr to 11 May, 2022. Deidentified information of all patients were collected retrospectively. Logistic regression model was used to identify risk factors associated with prolonged duration of viral shedding (defined as the time from the day of first positive SARS-CoV-2 RNA test to the first day of two consecutive negative SARS-CoV-2 RNA tests). Results: A total of 1442 Omicron-infected patients were enrolled, including 129 cancer patients and 1313 non-cancer patients. The baseline clinical characteristics of cancer and non-cancer patients were balanced by propensity score matching (1:4). Compared with non-cancer patients, a higher odds ratio ([OR] 1.84, 95% CI 1.24-2.76, P = 0.003) of lasting viral shedding for ≥7 days was found in cancer patients. Further subgroup analyses found that cancer patients were at higher risk for prolonged viral shedding in a subgroup of patients without hypertension (OR 1.89), diabetes (OR 1.80), or other chronic disease (OR 2.13), unvaccinated (OR 1.97), and asymptomatic (OR 2.36). In addition, 29 patients with active cancer and 19 patients with inactive cancer were identified. The median duration of viral shedding in the active cancer group was longer than that in the inactive cancer group (10 vs 6 days, P = 0.002). The risk of persistent viral shedding ≥7 days was also increased in the active cancer group (OR 5.33, 95% CI 1.49-21.51, P = 0.013). Conclusion: Cancer disease is an independent risk factor for prolonged viral shedding in Omicron infected patients, especially in patients with active cancer.

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