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1.
Soft Matter ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38978461

RESUMEN

Thioctic acid (TA) has been widely used to construct soft materials via supramolecular copolymerization with organic chemicals. In this study, TA and the inorganic compound MoS2 are used to fabricate poly[TA-MoS2] via dynamic covalent and supramolecular interactions. Poly[TA-MoS2] exhibits good and long-lasting adhesion performance on various artificial surfaces, with an adhesion strength up to 3.72 MPa (15 days). Further, it exhibits tough adhesion effects in an aqueous environment. Moreover, poly[TA-MoS2] displays good thermal processing behavior, thus enabling its molding through 3D printing.

2.
NPJ Breast Cancer ; 10(1): 60, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030225

RESUMEN

Triple-negative breast cancers (TNBCs) are a subset of breast cancers that have remained difficult to treat. A proportion of TNBCs arising in non-carriers of BRCA pathogenic variants have genomic features that are similar to BRCA carriers and may also benefit from PARP inhibitor treatment. Using genomic data from 129 TNBC samples from the Malaysian Breast Cancer (MyBrCa) cohort, we developed a gene expression-based machine learning classifier for homologous recombination deficiency (HRD) in TNBCs. The classifier identified samples with HRD mutational signature at an AUROC of 0.93 in MyBrCa validation datasets and 0.84 in TCGA TNBCs. Additionally, the classifier strongly segregated HRD-associated genomic features in TNBCs from TCGA, METABRIC, and ICGC. Thus, our gene expression classifier may identify triple-negative breast cancer patients with homologous recombination deficiency, suggesting an alternative method to identify individuals who may benefit from treatment with PARP inhibitors or platinum chemotherapy.

3.
Eur J Med Res ; 29(1): 366, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014466

RESUMEN

PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.


Asunto(s)
Algoritmos , Antraciclinas , Neoplasias de la Mama , Terapia Neoadyuvante , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Antraciclinas/uso terapéutico , Antraciclinas/administración & dosificación , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , China/epidemiología , Adulto , Recombinación Homóloga , Mutación , Anciano , Variaciones en el Número de Copia de ADN , Proteína BRCA1/genética
4.
Cancer Res Commun ; 4(6): 1597-1608, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38836758

RESUMEN

In breast tumors, somatic mutation frequencies in TP53 and PIK3CA vary by tumor subtype and ancestry. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somatic TP53 or PIK3CA mutation status in breast tumors. A genome-wide association study was conducted in 2,850 women of European ancestry with breast cancer using TP53 and PIK3CA mutation status (positive or negative) as well as specific functional categories [e.g., TP53 gain-of-function (GOF) and loss-of-function, PIK3CA activating] as phenotypes. Germline variants showing evidence of association were selected for validation analyses and tested in multiple independent datasets. Discovery association analyses found five variants associated with TP53 mutation status with P values <1 × 10-6 and 33 variants with P values <1 × 10-5. Forty-four variants were associated with PIK3CA mutation status with P values <1 × 10-5. In validation analyses, only variants at the ESR1 locus were associated with TP53 mutation status after multiple comparisons corrections. Combined analyses in European and Malaysian populations found ESR1 locus variants rs9383938 and rs9479090 associated with the presence of TP53 mutations overall (P values 2 × 10-11 and 4.6 × 10-10, respectively). rs9383938 also showed association with TP53 GOF mutations (P value 6.1 × 10-7). rs9479090 showed suggestive evidence (P value 0.02) for association with TP53 mutation status in African ancestry populations. No other variants were significantly associated with TP53 or PIK3CA mutation status. Larger studies are needed to confirm these findings and determine if additional variants contribute to ancestry-specific differences in mutation frequency. SIGNIFICANCE: Emerging data show ancestry-specific differences in TP53 and PIK3CA mutation frequency in breast tumors suggesting that germline variants may influence somatic mutational processes. This study identified variants near ESR1 associated with TP53 mutation status and identified additional loci with suggestive association which may provide biological insight into observed differences.


Asunto(s)
Neoplasias de la Mama , Fosfatidilinositol 3-Quinasa Clase I , Receptor alfa de Estrógeno , Estudio de Asociación del Genoma Completo , Mutación de Línea Germinal , Proteína p53 Supresora de Tumor , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/etnología , Receptor alfa de Estrógeno/genética , Proteína p53 Supresora de Tumor/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Persona de Mediana Edad , Población Blanca/genética , Predisposición Genética a la Enfermedad/genética , Adulto , Polimorfismo de Nucleótido Simple
5.
Nat Commun ; 15(1): 4793, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839767

RESUMEN

Chiral amides are important structure in many natural products and pharmaceuticals, yet their efficient synthesis from simple amide feedstock remains challenge due to its weak Lewis basicity. Herein, we describe our study of the enantioselective synthesis of chiral amides by N-alkylation of primary amides taking advantage of an achiral rhodium and chiral squaramide co-catalyzed carbene N-H insertion reaction. This method features mild condition, rapid reaction rate (in all cases 1 min) and a wide substrate scope with high yield and excellent enantioselectivity. Further product transformations show the synthetic potential of this reaction. Mechanistic studies reveal that the non-covalent interactions between the catalyst and reaction intermediate play a critical role in enantiocontrol.

6.
World J Gastroenterol ; 30(19): 2575-2602, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38817665

RESUMEN

BACKGROUND: Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further investigations confirmed that lactate is a primary regulator, introducing recently described post-translational modifications of histone and non-histone proteins, termed lysine lactylation. Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation. However, our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited. AIM: To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer. METHODS: RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases via Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package "DESeq2" in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further analyses, including functional enrichment, ESTIMATE, and CIBERSORT, were performed to analyze immune status and treatment responses in patients with pancreatic cancer. PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention; two PDAC cell lines with the most pronounced lactylation were selected. Subsequently, RT-PCR was employed to assess the expression of LRGs genes; SLC16A1, which showed the highest expression, was selected for further investigation. SLC16A1-mediated lactylation was analyzed by immunofluorescence, lactate production analysis, colony formation, transwell, and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells. In vivo validation was performed using an established tumor model. RESULTS: In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes (SLC16A1, HLA-DRB1, KCNN4, KIF23, and HPDL) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma. CONCLUSION: We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/metabolismo , Pronóstico , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Procesamiento Proteico-Postraduccional , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/inmunología , Adenocarcinoma/metabolismo , Ácido Láctico/metabolismo , Simportadores/genética , Simportadores/metabolismo , Proliferación Celular/genética , Perfilación de la Expresión Génica , Masculino , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/terapia , Femenino , Animales , Transcriptoma
7.
Cancer Lett ; 590: 216826, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38574881

RESUMEN

Ferroptosis, an iron-dependent regulated cell death caused by excessive lipid peroxide accumulation, has emerged as a promising therapeutic target in various cancers, including non-small cell lung cancer (NSCLC). In this study, we identified the long non-coding RNA RGMB-AS1 as a key regulator of ferroptosis in NSCLC. Mechanistically, RGMB-AS1 interacted with heme oxygenase 1 (HMOX1) and prevented its ubiquitination by the E3 ligase TRC8, leading to increased HMOX1 stability and enhanced ferroptosis. Additionally, RGMB-AS1 bound to the 82-87 amino acid region of N-alpha-acetyltransferase 10 (NAA10), stimulating its acetyltransferase activity and promoting the conversion of acetyl-CoA to HMG-CoA, further contributing to ferroptosis. The RGMB-AS1-HMOX1 and RGMB-AS1-NAA10 axes synergistically inhibited NSCLC growth both in vitro and in vivo. Clinically, low RGMB-AS1 expression was associated with advanced tumor stage and poor overall survival in NSCLC patients. Furthermore, adeno-associated virus-mediated RGMB-AS1 overexpression significantly suppressed tumor growth in mouse xenograft models. Our findings uncover a novel lncRNA-mediated regulatory mechanism of ferroptosis and highlight the potential of RGMB-AS1 as a prognostic biomarker and therapeutic target in NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Ferroptosis , Hemo-Oxigenasa 1 , Neoplasias Pulmonares , ARN Largo no Codificante , Ubiquitinación , Ferroptosis/genética , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Ratones , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino , Ratones Desnudos , Células A549 , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular
8.
Ultrason Sonochem ; 106: 106884, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38677267

RESUMEN

The purpose of this study was to investigate ferroptosis in Escherichia coli O157:H7 caused by ferrous sulfate (FeSO4) and to examine the synergistic effectiveness of FeSO4 combined with ultrasound-emulsified cinnamaldehyde nanoemulsion (CALNO) on inactivation of E. coli O157:H7 in vitro and in vivo. The results showed that FeSO4 could cause ferroptosis in E. coli O157:H7 via generating reactive oxygen species (ROS) and exacerbating lipid peroxidation. In addition, the results indicated that FeSO4 combined with CALNO had synergistic bactericidal effect against E. coli O157:H7 and the combined treatment could lead considerable nucleic acids and protein to release by damaging the cell membrane of E. coli O157:H7. Besides, FeSO4 combined with CALNO had a strong antibiofilm ability to inhibit E. coli O157:H7 biofilm formation by reducing the expression of genes related on biofilm formation. Finally, FeSO4 combined with CALNO exhibited the significant antibacterial activity against E. coli O157:H7 in hami melon and cherry tomato.


Asunto(s)
Acroleína , Emulsiones , Escherichia coli O157 , Ferroptosis , Compuestos Ferrosos , Escherichia coli O157/efectos de los fármacos , Acroleína/análogos & derivados , Acroleína/farmacología , Acroleína/química , Compuestos Ferrosos/farmacología , Compuestos Ferrosos/química , Ferroptosis/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Ondas Ultrasónicas , Especies Reactivas de Oxígeno/metabolismo
9.
Chem Sci ; 15(16): 6122-6129, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38665530

RESUMEN

Macrocyclization has positioned itself as a powerful method for engineering potent peptide drug candidates. Introducing one or multiple cyclizations is a common strategy to improve properties such as affinity, bioavailability and proteolytic stability. Consequently, methodologies to create large libraries of polycyclic peptides by phage or mRNA display have emerged, allowing the rapid identification of binders to virtually any target. Yet, within those libraries, the performance of linear vs. mono- or bicyclic peptides has rarely been studied. Indeed, a key parameter to perform such a comparison is to use a display protocol and cyclization chemistry that enables the formation of all 3 formats in equal quality and diversity. Here, we developed a simple, efficient and fast mRNA display protocol which meets these criteria and can be used to generate highly diverse libraries of thioether cyclized polycyclic peptides. As a proof of concept, we selected peptides against fibroblast growth factor receptor 3c (FGFR3c) and compared the different formats regarding affinity, specificity, and human plasma stability. The peptides with the best KD's and stability were identified among bicyclic peptide hits, further strengthening the body of evidence pointing at the superiority of this class of molecules and providing functional and selective inhibitors of FGFR3c.

10.
Mar Drugs ; 22(4)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38667800

RESUMEN

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.


Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Poríferos , Terpenos , Humanos , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Poríferos/química , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Terpenos/farmacología , Terpenos/aislamiento & purificación , Terpenos/química , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células HCT116 , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Vimentina/metabolismo , Línea Celular Tumoral , China
11.
Int Urol Nephrol ; 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38642210

RESUMEN

PURPOSE: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method. METHODS: The Emax model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with Emax model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml. RESULTS: In machine learning model, the Emax from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET50 was 0.43 months, and the time to achieving 25% Emax, 50% Emax, 75% Emax, and 80% (plateau) Emax of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively. CONCLUSION: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months.

12.
Ther Adv Med Oncol ; 16: 17588359241242613, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606163

RESUMEN

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers (p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

13.
J Multidiscip Healthc ; 17: 1791-1801, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38686130

RESUMEN

Objective: Sensorineural Hearing Loss (SNHL) is a representative human sensory impairment, few studies have paid attention to the correlation between the Triglyceride-Glucose (TyG) index and SNHL to date. We conducted this analysis to elucidate the correlation between the TyG index and pure tone hearing thresholds among US adults. Methods: Our analysis included 1226 adults (age range: 20 to 69 years old) from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) data. TyG index was scored into three quartiles. Weighted univariate analysis, weighted multivariate linear regression analyses as well as smooth curve fittings evaluated the associations between TyG index and pure tone hearing thresholds. Results: In the multiple regression analysis, the second tertile of TyG index was negatively associated with high-frequency hearing thresholds shifts. Furthermore, the non-linear relationships between TyG index and speech-frequency and high-frequency hearing thresholds were identified by smooth curve fittings. After adjusting for potential confounders, the fitted smooth curves were approximately U-shaped, and the two-segment linear regression models were constructed to calculate their inflection points. Conclusion: Our findings suggested that the TyG index was nearly U-shaped association with speech-frequency and high-frequency hearing thresholds. These results may imply the importance of maintaining a balanced TyG index in health management.

14.
Breast Cancer Res ; 26(1): 67, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649964

RESUMEN

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR + /HER2- breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.


Asunto(s)
Neoplasias de la Mama , Mutación , Fenotipo , Receptor ErbB-2 , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Pueblo Asiatico/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Análisis por Conglomerados , Estudios de Cohortes , Variaciones en el Número de Copia de ADN , Secuenciación del Exoma , Perfilación de la Expresión Génica , Malasia/epidemiología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Receptores de Progesterona/metabolismo , Receptores de Progesterona/genética , Transcriptoma
15.
ChemSusChem ; : e202301911, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477175

RESUMEN

The multifunctional derivatization of alcohols has been achieved by the bipyridinium-based conjugated small molecule photocatalysts with redox center and Lewis acid site. Besides exhibiting high activity in the selective generation of aldehydes/ketones, acids from alcohols through solvent modulation, this system renders the first selective synthesis of esters via an attractive cross-coupling pattern, whose reaction route is significantly different from the traditional condensation of alcohols and acids or esterification from hemiacetals. Following the oxidization of alcohol to aldehyde via bipyridinium-mediated electron and energy transfer, the Lewis acid site of bipyridinium then activates the aldehyde and methanol to obtain the acetal, which further reacts with methanol to generate ester. This method not only demonstrates a clear advantage of bipyridinium in diverse catalytic activities, but also paves the way for designing efficient multifunctional small molecule photocatalysts. This metal- and additive-free photocatalytic esterification reaction marks a significant advancement towards a more environmentally friendly, cost-effective and green sustainable approach, attributed to the utilization of renewable substrate alcohol and the abundant, low-cost air as the oxidant. The mildness of this esterification reaction condition provides a more suitable alternative for large-scale industrial production of esters.

16.
J Org Chem ; 89(7): 5142-5147, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38545874

RESUMEN

A mild and efficient approach for the diastereoselective synthesis of dihydrobenzofuran spirooxindoles using 3-chlorooxindoles and imines is presented. This process involves a formal [4 + 1] annulation, yielding the product with excellent diastereoselectivity. Furthermore, a novel method for constructing benzofuroquinolinone scaffolds through the ring expansion of oxindoles has been established. This method involves a lactam ring expansion to the quinolinone skeleton. Besides, a one-pot procedure for creating benzofuroquinolinone scaffolds from 3-chlorooxindoles and imines is also provided.

17.
J Am Chem Soc ; 146(11): 7487-7497, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38466925

RESUMEN

Upconverting nanoparticles (UCNPs) exhibit unique nonlinear optical properties that can be harnessed in microscopy, sensing, and photonics. However, forming high-resolution nano- and micropatterns of UCNPs with large packing fractions is still challenging. Additionally, there is limited understanding of how nanoparticle patterning chemistries are affected by the particle size. Here, we explore direct patterning chemistries for 6-18 nm Tm3+-, Yb3+/Tm3+-, and Yb3+/Er3+-based UCNPs using ligands that form either new ionic linkages or covalent bonds between UCNPs under ultraviolet (UV), electron-beam (e-beam), and near-infrared (NIR) exposure. We study the effect of UCNP size on these patterning approaches and find that 6 nm UCNPs can be patterned with compact ionic-based ligands. In contrast, patterning larger UCNPs requires long-chain, cross-linkable ligands that provide sufficient interparticle spacing to prevent irreversible aggregation upon film casting. Compared to approaches that use a cross-linkable liquid monomer, our patterning method limits the cross-linking reaction to the ligands bound on UCNPs deposited as a thin film. This highly localized photo-/electron-initiated chemistry enables the fabrication of densely packed UCNP patterns with high resolutions (∼1 µm with UV and NIR exposure; <100 nm with e-beam). Our upconversion NIR lithography approach demonstrates the potential to use inexpensive continuous-wave lasers for high-resolution 2D and 3D lithography of colloidal materials. The deposited UCNP patterns retain their upconverting, avalanching, and photoswitching behaviors, which can be exploited in patterned optical devices for next-generation UCNP applications.

18.
Artículo en Inglés | MEDLINE | ID: mdl-38498754

RESUMEN

HD map reconstruction is crucial for autonomous driving. LiDAR-based methods are limited due to expensive sensors and time-consuming computation. Camera-based methods usually need to perform road segmentation and view transformation separately, which often causes distortion and missing content. To push the limits of the technology, we present a novel framework that reconstructs a local map formed by road layout and vehicle occupancy in the bird's-eye view given a front-view monocular image only. We propose a front-to-top view projection (FTVP) module, which takes the constraint of cycle consistency between views into account and makes full use of their correlation to strengthen the view transformation and scene understanding. In addition, we apply multi-scale FTVP modules to propagate the rich spatial information of low-level features to mitigate spatial deviation of the predicted object location. Experiments on public benchmarks show that our method achieves various tasks on road layout estimation, vehicle occupancy estimation, and multi-class semantic estimation, at a performance level comparable to the state-of-the-arts, while maintaining superior efficiency.

19.
IEEE Trans Image Process ; 33: 1403-1418, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38358873

RESUMEN

Bimodal objects, such as the checkerboard pattern used in camera calibration, markers for object tracking, and text on road signs, to name a few, are prevalent in our daily lives and serve as a visual form to embed information that can be easily recognized by vision systems. While binarization from intensity images is crucial for extracting the embedded information in the bimodal objects, few previous works consider the task of binarization of blurry images due to the relative motion between the vision sensor and the environment. The blurry images can result in a loss in the binarization quality and thus degrade the downstream applications where the vision system is in motion. Recently, neuromorphic cameras offer new capabilities for alleviating motion blur, but it is non-trivial to first deblur and then binarize the images in a real-time manner. In this work, we propose an event-based binary reconstruction method that leverages the prior knowledge of the bimodal target's properties to perform inference independently in both event space and image space and merge the results from both domains to generate a sharp binary image. We also develop an efficient integration method to propagate this binary image to high frame rate binary video. Finally, we develop a novel method to naturally fuse events and images for unsupervised threshold identification. The proposed method is evaluated in publicly available and our collected data sequence, and shows the proposed method can outperform the SOTA methods to generate high frame rate binary video in real-time on CPU-only devices.

20.
Phytochemistry ; 220: 114017, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38342290

RESUMEN

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.


Asunto(s)
Alcaloides , Antineoplásicos , Poríferos , Animales , Espectroscopía de Resonancia Magnética , Antineoplásicos/química , Alcaloides/química , China , Estructura Molecular
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