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1.
Transl Pediatr ; 13(4): 596-609, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38715675

RESUMO

Background: Infantile fibrosarcoma (IFS) is the most prevalent soft tissue sarcoma in children under 1 year old and is known for its rapid growth. The tumor lacks specific immunohistochemical tumor marker and a general view of tumor microenvironment (TME). Its primary therapeutic intervention places patients at a risk of disability or mutilation. This study aimed to elucidate the universal transcriptional characteristics of IFS and explore novel targets for diagnosis and therapy using single-cell RNA sequencing (scRNA-seq). Methods: Fresh tissue samples of IFS for scRNA-seq were collected from four patients before other treatments were administered. We conducted cell clustering, inferring copy number variation from scRNA-seq (InferCNV) analysis, gene differential expression analysis, cell function evaluation, Pearson correlation analysis, and cell-cell and ligand-receptor interaction analysis to investigate the distinct ecosystem of IFS. Results: According to the single-cell resolution data, we depicted the cell atlas of IFS, which comprised 14 cell populations. Through comparison with normal cells, the malignant cells were distinguished, and potential novel markers (POSTN, IGFBP2 and CTHRC1) were identified. We also found four various functional malignant cell subtypes, three of which exhibited cancer stem cells (CSCs) phenotypes, and investigated the interplay between these subtypes and nonmalignant cells in the TME of IFS. Endothelial cells and macrophages were found to dominate the cell-cell communication landscape within the microenvironment, promoting tumorigenesis via multiple receptor-ligand interactions. Conclusions: This study provides a comprehensive characterization of the tumor transcriptome and TME of IFS at the cellular level, offering valuable insights for clinically significant advancements in the immunohistochemical diagnosis and treatment of IFS.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38652738

RESUMO

Drug abuse is a severe social problem worldwide. Particularly, the issue of new psychoactive substances (NPSs) have increasingly emerged. NPSs are structural or functional analogs of traditional illicit drugs, such as cocaine, cannabis, and amphetamine; these molecules provide the same or more severe neurological effects. Usually, immunoassays are utilized in the preliminary screening method. However, NPSs have poor detectability in commercially available immunoassay kits. Meanwhile, various chromatography combined with the mass spectrometry platform have been developed to quantify NPSs. Still, a significant amount of time and resources are required during these procedures. Therefore, we established a rapid analytical platform for NPSs employing paper-loaded direct analysis in real time triple quadrupole mass spectrometry (pDART-QqQ-MS). We implemented this platform for the semiquantitative analysis of forensic drug tests in urine. This platform significantly shrinks the analytical time of a single sample within 30 s and requires a low volume of the specimen. The platform can detect 21 NPSs in urine mixtures at a lower limit of qualification of concentration ranging from 20 to 75 nanograms per milliliter (ng mL-1) and is lower than the cutoff value of currently available immune-based devices for detecting multiple drugs (1000 ng mL-1). Urine samples from drug addicts have been collected to verify the platform's effectiveness. By combining efficiency and accuracy, our platform offers a promising solution for addressing the challenges posed by NPSs in drug abuse detection.

3.
J Biol Chem ; : 107309, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38657867

RESUMO

Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that SAM and SH3 domain containing protein 1 (SASH1) expression is negatively correlated with mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) expression in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1 and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC.

4.
Huan Jing Ke Xue ; 45(5): 2983-2994, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629559

RESUMO

Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω(As), ω(Hg), ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Ni), and ω(Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg-1, respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.


Assuntos
Metais Pesados , Poluentes do Solo , Criança , Adulto , Humanos , Monitoramento Ambiental , Solo , Cádmio/análise , Poluentes do Solo/análise , Metais Pesados/análise , Medição de Risco , China
5.
Chin Med J (Engl) ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38613216

RESUMO

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

6.
Heliyon ; 10(7): e28952, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596098

RESUMO

Amino acid variants in protein may result in deleterious effects on enzymatic activity. In this study we investigate the DNA variants on activity of CYP2B6 gene in a Chinese Han population for potential use in precision medicine. All exons in CYP2B6 gene from 1483 Chinese Han adults (Zhejiang province) were sequenced using Sanger sequencing. The effects of nonsynonymous variants on recombinant protein catalytic activity were investigated in vitro with Sf12 system. The haplotype of novel nonsynonymous variants with other single nucleotide variants in the same allele was determined using Nanopore sequencing. Of 38 alleles listed on the Pharmacogene Variation Consortium, we detected 7 previously reported alleles and 18 novel variants, of which 11 nonsynonymous variants showed lower catalytic activity (0.00-0.60) on bupropion compared to CYP2B6*1. Further, these 11 novel star-alleles (CYP2B6*39-49) were assigned by the Pharmacogene Variation Consortium, which may be valuable for pharmacogenetic research and personalized medicine.

7.
Dalton Trans ; 53(17): 7315-7320, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38590209

RESUMO

In recent years, organic-inorganic hybrid materials have demonstrated exceptional performance in nonlinear optics, attracting widespread attention. However, there are relatively few examples of coordination compounds synthesized with Cu as the metal center that exhibit excellent nonlinear optical properties. In this study, we successfully synthesized a pair of enantiomers named R/S-Cu2I2 by reacting chiral ligands with CuI. The crystal structure reveals a one-dimensional copper-iodide chain structure built by Cu2I2 clusters, and its ordered arrangement in space provides not only a strong second harmonic generation (SHG) signal (1.24 × KDP) but also a large birefringence (0.15@1064 nm). Under excitation at 395 nm, the crystals exhibit red fluorescence peaked at 675 nm. The CD spectra of R/S-Cu2I2 show a distinct mirror-symmetric Cotton effect, and their CPL signals are corresponding and opposite in the emission range, with a maximum glum of approximately ±2.5 × 10-3. Theoretical calculations using density functional theory were also carried out to enhance our understanding of the correlation between their structures and optical properties.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38450723

RESUMO

BACKGROUND: The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. METHODS: We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. RESULTS: Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5-6, patients with multimorbidity and a lifestyle score of 0-1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5-6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5-6 to 0-1. And we observed more pronounced association between them among people younger than 60 years old. CONCLUSIONS: Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity.


Assuntos
Demência , Multimorbidade , Humanos , Estudos Prospectivos , Fatores de Risco , Estilo de Vida , Estilo de Vida Saudável , Demência/epidemiologia , Demência/etiologia
10.
J Thorac Dis ; 16(2): 1450-1462, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505060

RESUMO

Background: Bilateral synchronous multiple primary lung cancer (BSMPLC) presents significant clinical challenges due to its unique characteristics and prognosis. Understanding the risk factors that influence overall survival (OS) and recurrence-free survival (RFS) is crucial for optimizing therapeutic strategies for BSMPLC patients. Methods: We retrospectively analyzed clinical characteristics and treatment outcomes of 293 patients with BSMPLC who underwent surgical treatment between January 2010 and July 2017. Results: The 10-year OS and RFS rates were 96.1% and 92.8%, respectively. Preoperative forced expiratory volume in 1 second (FEV1) ≥70% [hazard ratio (HR), 0.214; 95% confidence interval (CI): 0.053 to 0.857], identical pathology types (HR, 9.726; 95% CI: 1.886 to 50.151), largest pT1 (HR, 7.123; 95% CI: 2.663 to 19.055), and absence of lymphovascular invasion (LVI; HR, 7.021; 95% CI: 1.448 to 34.032) emerged as independent predictors of improved OS. Moreover, the sum of tumor sizes less than or equal to 3 cm (HR, 6.229; 95% CI: 1.411 to 27.502) and absence of pleural invasion (HR, 3.442; 95% CI: 1.352 to 8.759) were identified as independent predictors of enhanced RFS. The presence or absence of residual nodules after bilateral surgery did not influence patients' OS (P=0.987) and RFS (P=0.054). Conclusions: Patients with BSMPLC who underwent surgery generally had a favorable prognosis. Whether or not to remove all nodules bilaterally does not affect the patient's long-term prognosis, suggesting the need for an individualized surgical approach.

11.
Huan Jing Ke Xue ; 45(2): 1015-1025, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471939

RESUMO

In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons (PAHs) in soils of Guangzhou, 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method (ERL/ERM) and the (BaP) toxicity equivalent method, and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that: the content of surface soil (∑16PAHs) in Guangzhou was 38-11 115 µg·kg-1, with an average of 526 µg·kg-1, and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou, and there was already a significant ecological risk of PAHs pollution in individual sampling points, which were generally in a state of mild pollution. Based on the results of the health risk assessment, the contribution rates of total cancer risk in both adults and children were presented as follows: skin contact > ingestion of soil > respiratory intake. The health risk of children was greater than that of adults, and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal (37.1%); diesel (32%); coking (17.3%); and mixed sources of traffic emissions, biomass combustion, and petrochemical product volatilization (13.6%). The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.


Assuntos
Neoplasias , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Criança , Adulto , Humanos , Solo/química , Monitoramento Ambiental/métodos , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes do Solo/análise , Poluição Ambiental/análise , Medição de Risco , China
12.
Implement Sci ; 19(1): 18, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389082

RESUMO

BACKGROUND: Given the steady decline in patient numbers at methadone maintenance treatment (MMT) clinics in Taiwan since 2013, the government initiated Patients' Medical Expenditure Supplements (PMES) in January 2019 and the MMT Clinics Accessibility Maintenance Program (MCAM) in September 2019. This study aims to evaluate the impact of the PMES and MCAM on the enrollment and retention of patients attending MMT clinics and whether there are differential impacts on MMT clinics with different capacities. METHODS: The monthly average number of daily participants and 3-month retention rate from 2013 to 2019 were extracted from MMT databases and subjected to single interrupted time series analysis. Pre-PMES (from February 2013 to December 2018) was contrasted with post-PMES, either from January 2019 to December 2019 for clinics funded solely by the PMES or from January 2019 to August 2019 for clinics with additional MCAM. Pre-MCAM (from January 2019 to August 2019) was contrasted with post-MCAM (from September 2019 to December 2019). Based on the monthly average number of daily patients in 2018, each MMT clinic was categorized as tiny (1-50), small (51-100), medium (101-150), or large (151-700) for subsequent stratification analysis. RESULTS: In terms of participant numbers after the PMES intervention, a level elevation and slope increase were detected in the clinics at every scale except medium in MMT clinics funded solely by PMES. In MMT clinics with subsequent MCAM, a level elevation was only detected in small-scale clinics, and a slope increase in the participant numbers was detected in tiny- and small-scale clinics. The slope decrease was also detected in medium-scale clinics. In terms of the 3-month retention rate, a post-PMES level elevation was detected at almost every scale of the clinics, and a slope decrease was detected in the overall and tiny-scale clinics for both types of clinics. CONCLUSIONS: Supplementing the cost of a broad treatment repertoire enhances the enrollment of people with heroin use in MMTs. Further funding of human resources is vital for MMT clinics to keep up with the increasing numbers of participants and their retention.


Assuntos
Metadona , Tratamento de Substituição de Opiáceos , Humanos , Metadona/uso terapêutico , Taiwan , Análise de Séries Temporais Interrompida , China
13.
Front Immunol ; 15: 1325938, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38390334

RESUMO

Background: Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear. Methods: Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed. Results: MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04). Conclusions: This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.


Assuntos
Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Gravidade do Paciente , Linfócitos T CD8-Positivos , Causalidade , Contagem de Células
14.
Plant Physiol ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38345866

RESUMO

Brassinosteroids (BRs) are phytohormones that regulate stomatal development BRASSINAZOLE RESISTANT 1. In this study, we report that BR represses stomatal development in etiolated Arabidopsis (Arabidopsis thaliana) cotyledons via transcription factors BRASSINAZOLE RESISTANT 1 (BZR1) and bri1-EMS SUPPRESSOR1 (BES1), which directly target MITOGEN-ACTIVATED PROTEIN KINASE KINASE 9 (MKK9) and FAMA, two important genes for stomatal development. BZR1/BES1 bind MKK9 and FAMA promoters in vitro and in vivo, and mutation of the BZR1/BES1 binding motif in MKK9/FAMA promoters abolishes their transcription regulation by BZR1/BES1 in plants. Expression of a constitutively active MKK9 (MKK9DD) suppressed overproduction of stomata induced by BR deficiency, while expression of a constitutively inactive MKK9 (MKK9KR) induced high-density stomata in bzr1-1D. In addition, bzr-h, a sextuple mutant of the BZR1 family of proteins, produced overabundant stomata, and the dominant bzr1-1D and bes1-D mutants effectively suppressed the stomata-overproducing phenotype of brassinosteroid insensitive 1-116 (bri1-116) and brassinosteroid insensitive 2-1 (bin2-1). In conclusion, our results revealed important roles of BZR1/BES1 in stomatal development, and their transcriptional regulation of MKK9 and FAMA expression may contribute to BR-regulated stomatal development in etiolated Arabidopsis cotyledons.

15.
Nat Plants ; 10(2): 228-239, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38278952

RESUMO

Rapid advances in DNA synthesis techniques have enabled the assembly and engineering of viral and microbial genomes, presenting new opportunities for synthetic genomics in multicellular eukaryotic organisms. These organisms, characterized by larger genomes, abundant transposons and extensive epigenetic regulation, pose unique challenges. Here we report the in vivo assembly of chromosomal fragments in the moss Physcomitrium patens, producing phenotypically virtually wild-type lines in which one-third of the coding region of a chromosomal arm is replaced by redesigned, chemically synthesized fragments. By eliminating 55.8% of a 155 kb endogenous chromosomal region, we substantially simplified the genome without discernible phenotypic effects, implying that many transposable elements may minimally impact growth. We also introduced other sequence modifications, such as PCRTag incorporation, gene locus swapping and stop codon substitution. Despite these substantial changes, the complex epigenetic landscape was normally established, albeit with some three-dimensional conformation alterations. The synthesis of a partial multicellular eukaryotic chromosome arm lays the foundation for the synthetic moss genome project (SynMoss) and paves the way for genome synthesis in multicellular organisms.


Assuntos
Bryopsida , Epigênese Genética , Cromossomos , Genômica/métodos , Bryopsida/genética , Elementos de DNA Transponíveis
17.
Rev Sci Instrum ; 95(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38214590

RESUMO

In a laser inertial confinement fusion (ICF) facility, an x-ray diode (XRD) detector is mainly used for precise measurement of black cavity radiation flow. The rapid rising time of the XRD detector and the intricate radiation environment of the ICF facility have posed new requirements for the bandwidth and anti-interference performance of signal digitization technologies. The standards are tough for the current recording system to meet. In this paper, based on the anti-interference of digital signals in the radiation field of the ICF facility, we have designed an XRD detector specific transient front-end signal digitizer (TFSD). The digitizer may be put together for consistent shielding in the radiation field since its size matches that of the XRD detector. The test results show that the TFSD has a higher signal input bandwidth than the existing recording method, considerably reduces the effect of pulse radiation field on signal recording, and significantly boosts the accuracy of recording and diagnosis.

18.
Nat Chem Biol ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200110

RESUMO

Biomolecular condensates have been proposed to mediate cellular signaling transduction. However, the mechanism and functional consequences of signal condensates are not well understood. Here we report that LATS2, the core kinase of the Hippo pathway, responds to F-actin cytoskeleton reduction and forms condensates. The proline-rich motif (PRM) of LATS2 mediates its condensation. LATS2 partitions with the main components of the Hippo pathway to assemble a signalosome for LATS2 activation and for its stability by physically compartmentalizing from E3 ligase FBXL16 complex-dependent degradation, which in turn mediates yes-associated protein (YAP)-transcriptional coactivator with PDZ-binding motif (TAZ) recruitment and inactivation. This oncogenic FBXL16 complex blocks LATS2 condensation by binding to the PRM region to promote its degradation. Disruption of LATS2 condensation leads to tumor progression. Thus, our study uncovers that the signalosomes assembled by LATS2 condensation provide a compartmentalized and reversible platform for Hippo signaling transduction and protein stability, which have potential implications in cancer diagnosis and therapeutics.

19.
Chem Asian J ; 19(2): e202300775, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38059381

RESUMO

The development of high-intensity fluorescent materials is always the focuses and forefront projects because of their important applications in displays, sensing and detection fields. In recent years, the detection of explosives has attracted increasing attention due to security and counterterrorism issues. Herein, two diphenyl-anthracene (DPA) derivatives were designed and synthesized by introducing strong electron withdrawing fluorine atoms and cyano-groups to DPA, which exhibited strong fluorescence both in the solution and solid phase with the absolute quantum yields up to 70.4 % and 45.9 % respectively. The detection behavior of nitroaromatic explosives such as picric acid (PA), 2,4,6-trinitrotoluene (TNT) and 3-Nitropropionic acid (3-NP) also shows good sensitivity with the quenching constant as high as 6.3×104  L mol-1 . Theoretical calculation demonstrates that the fluorescence quenching behavior of the two DPA derivatives is caused by the behavior of photoinduced electron transfer (PET) and the resonance energy transfer (RET) studies explained the higher sensitivity and selectivity of both compounds towards PA than other nitro-containing explosives. Furthermore, the strong solid-state fluorescence of the DPA derivatives also shows excellent advantages in enhancing latent fingerprint recognition.

20.
J Magn Reson Imaging ; 59(2): 510-521, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37851581

RESUMO

BACKGROUND: Preoperative assessment of adverse outcomes risk in placenta accreta spectrum (PAS) disorders is of high clinical relevance for perioperative management and prognosis. PURPOSE: To investigate the association of preoperative MRI multisequence images and adverse pregnancy outcomes by establishing a deep learning model in patients with PAS. STUDY TYPE: Retrospective. POPULATION: 323 pregnant women (age from 20 to 46, the median age is 33), suspected of PAS, underwent MRI to assess the PAS, divided into the training (N = 227) and validation datasets (N = 96). FIELD STRENGTH/SEQUENCE: 1.5T scanner/fast imaging employing steady-state acquisition sequence and single shot fast spin echo sequence. ASSESSMENT: Different deep learning models (i.e., with single MRI input sequence/two sequences/multisequence) were compared to assess the risk of adverse pregnancy outcomes, which defined as intraoperative bleeding ≥1500 mL and/or hysterectomy. Net reclassification improvement (NRI) was used for quantitative comparison of assessing adverse pregnancy outcome between different models. STATISTICAL TESTS: The AUC, sensitivity, specificity, and accuracy were used for evaluation. The Shapiro-Wilk test and t-test were used. A P value of <0.05 was considered statistically significant. RESULTS: 215 cases were invasive placenta accreta (67.44% of them with adverse outcomes) and 108 cases were non-invasive placenta accreta (9.25% of them with adverse outcomes). The model with four sequences assessed adverse pregnancy outcomes with AUC of 0.8792 (95% CI, 0.8645-0.8939), with ACC of 85.93% (95%, 84.43%-87.43%), with SEN of 86.24% (95% CI, 82.46%-90.02%), and with SPC of 85.62% (95%, 82.00%-89.23%) on the test cohort. The performance of model with four sequences improved above 0.10 comparing with that of model with two sequences and above 0.20 comparing with that of model with single sequence in terms of NRI. DATA CONCLUSION: The proposed model showed good diagnostic performance for assessing adverse pregnancy outcomes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.


Assuntos
Aprendizado Profundo , Placenta Acreta , Gravidez , Feminino , Humanos , Placenta Acreta/diagnóstico por imagem , Resultado da Gravidez , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Placenta
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