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1.
Neuroimage ; 291: 120586, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548039

RESUMO

Creativity, a high-order cognitive ability, has received wide attention from researchers and educators who are dedicated to promoting its development throughout one's lifespan. Currently, creativity is commonly assessed with divergent thinking tasks, such as the Alternative Uses Task. Recent advancements in neuroimaging techniques have enabled the identification of brain markers for high-order cognitive abilities. One such brain structure of interest in this regard is the hippocampus, which has been found to play an important role in generating creative thoughts in adulthood. However, such role of the hippocampus in childhood is not clear. Thus, this study aimed to investigate the associations between creativity, as measured by divergent thinking, and both the volume of the hippocampus and its resting-state functional connectivity in 116 children aged 8-12 years. The results indicate significant relations between divergent thinking and the volume of the hippocampal head and the hippocampal tail, as well as the volume of a subfield comprising cornu ammonis 2-4 and dentate gyrus within the hippocampal body. Additionally, divergent thinking was significantly related to the differences between the anterior and the posterior hippocampus in their functional connectivity to other brain regions during rest. These results suggest that these two subregions may collaborate with different brain regions to support diverse cognitive processes involved in the generation of creative thoughts. In summary, these findings indicate that divergent thinking is significantly related to the structural and functional characteristics of the hippocampus, offering potential insights into the brain markers for creativity during the developmental stage.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Criatividade , Cognição , Mapeamento Encefálico/métodos , Hipocampo/diagnóstico por imagem
2.
Curr Issues Mol Biol ; 46(5): 4021-4034, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38785516

RESUMO

The demand for high-precision CRISPR/Cas9 systems in biomedicine is experiencing a notable upsurge. The editing system fdCas9 employs a dual-sgRNA strategy to enhance editing accuracy. However, the application of fdCas9 is constrained by the stringent requirement for two protospacer adjacent motifs (PAMs) of Cas9. Here, we devised an optimized editor, fRYdCas9, by merging FokI with the nearly PAM-less RYdCas9 variant, and two fRYdCas9 systems formed a dimer in a proper spacer length to accomplish DNA cleavage. In comparison to fdCas9, fRYdCas9 demonstrates a substantial increase in the number of editable genomic sites, approximately 330-fold, while maintaining a comparable level of editing efficiency. Through meticulous experimental validation, we determined that the optimal spacer length between two FokI guided by RYdCas9 is 16 base pairs. Moreover, fRYdCas9 exhibits a near PAM-less feature, along with no on-target motif preference via the library screening. Meanwhile, fRYdCas9 effectively addresses the potential risks of off-targets, as analyzed through whole genome sequencing (WGS). Mouse embryonic editing shows fRYdCas9 has robust editing capabilities. This study introduces a potentially beneficial alternative for accurate gene editing in therapeutic applications and fundamental research.

3.
J Magn Reson Imaging ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400805

RESUMO

BACKGROUND: Arterial spin labeling (ASL) derived cerebral blood flow (CBF) maps are prone to artifacts and noise that can degrade image quality. PURPOSE: To develop an automated and objective quality evaluation index (QEI) for ASL CBF maps. STUDY TYPE: Retrospective. POPULATION: Data from N = 221 adults, including patients with Alzheimer's disease (AD), Parkinson's disease, and traumatic brain injury. FIELD STRENGTH/SEQUENCE: Pulsed or pseudocontinuous ASL acquired at 3 T using non-background suppressed 2D gradient-echo echoplanar imaging or background suppressed 3D spiral spin-echo readouts. ASSESSMENT: The QEI was developed using N = 101 2D CBF maps rated as unacceptable, poor, average, or excellent by two neuroradiologists and validated by 1) leave-one-out cross validation, 2) assessing if CBF reproducibility in N = 53 cognitively normal adults correlates inversely with QEI, 3) if iterative discarding of low QEI data improves the Cohen's d effect size for CBF differences between preclinical AD (N = 27) and controls (N = 53), 4) comparing the QEI with manual ratings for N = 50 3D CBF maps, and 5) comparing the QEI with another automated quality metric. STATISTICAL TESTS: Inter-rater reliability and manual vs. automated QEI were quantified using Pearson's correlation. P < 0.05 was considered significant. RESULTS: The correlation between QEI and manual ratings (R = 0.83, CI: 0.76-0.88) was similar (P = 0.56) to inter-rater correlation (R = 0.81, CI: 0.73-0.87) for the 2D data. CBF reproducibility correlated negatively (R = -0.74, CI: -0.84 to -0.59) with QEI. The effect size comparing patients and controls improved (R = 0.72, CI: 0.59-0.82) as low QEI data was discarded iteratively. The correlation between QEI and manual ratings (R = 0.86, CI: 0.77-0.92) of 3D ASL was similar (P = 0.09) to inter-rater correlation (R = 0.78, CI: 0.64-0.87). The QEI correlated (R = 0.87, CI: 0.77-0.92) significantly better with manual ratings than did an existing approach (R = 0.54, CI: 0.30-0.72). DATA CONCLUSION: Automated QEI performed similarly to manual ratings and can provide scalable ASL quality control. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

4.
J Org Chem ; 89(8): 5560-5572, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38564232

RESUMO

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

5.
Infection ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884858

RESUMO

BACKGROUND: Escalating cases of multidrug-resistant tuberculosis (MDR-TB) pose a major challenge to global TB control efforts, necessitating innovative diagnostics to empower decentralized detection of gene mutations associated with resistance to rifampicin (RIF) and isoniazid (INH) in Mycobacterium tuberculosis (M. tuberculosis) in resource-constrained settings. METHODS: Combining multiplex fluorescent PCR and Multiple Probes Melting Analysis, we identified mutations in the rpoB, katG, ahpC and inhA genes from sputum specimens. We first constructed a reference plasmid library comprising 40 prevalent mutations in the target genes' resistance determining regions and promoters, serving as positive controls. Our assay utilizes a four-tube asymmetric PCR method with specifically designed molecular beacon probes, enabling simultaneous detection of all 40 mutations. We evaluated the assay's effectiveness using DNA isolated from 50 clinically confirmed M. tuberculosis sputum specimens, comparing our results with those obtained from Sanger sequencing and retrospective validation involving bacteriological culture and phenotypic drug susceptibility testing (pDST). We also included the commercial Xpert MTB/RIF assay for accuracy comparison. RESULTS: Our data demonstrated remarkable sensitivity in detecting resistance to RIF and INH, achieving values of 93.33% and 95.24%, respectively, with a specificity of 100%. The concordance between our assay and pDST was 98.00%. Furthermore, the accuracy of our assay was comparable to both Sanger sequencing and the Xpert assay. Importantly, our assay boasts a 4.2-h turnaround time and costs only $10 per test, making it an optimal choice for peripheral healthcare settings. CONCLUSION: These findings highlight our assay's potential as a promising tool for rapidly, accurately, and affordably detecting MDR-TB.

6.
Org Biomol Chem ; 22(12): 2409-2413, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38411219

RESUMO

A convenient, efficient and practical approach for the synthesis of S-quinolyl phosphorothioates via cheap TsCl promoted deoxygenative C2-H phosphorothiolation of quinoline N-oxides with readily available triethylammonium O,O-dialkylphosphorothioates was developed. The reaction performed well under transition-metal-free conditions at room temperature with a very short reaction time (10-20 min). Preliminary studies showed that the current transformation underwent a nucleophilic substitution process.

7.
Org Biomol Chem ; 22(18): 3740-3745, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38651658

RESUMO

An efficient and practical method for the synthesis of 3-alkenylquinoxalinones containing the SCF3 group has been readily developed through a three-component radical cascade reaction involving quinoxalinones, alkynes and AgSCF3. The reaction was found to be compatible with a variety of substrates and exhibited a high functional group tolerance and complete E-selectivity. The preliminary study suggests the involvement of a SCF3 radical in the transformation.

8.
Alzheimers Dement ; 20(6): 4147-4158, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38747539

RESUMO

INTRODUCTION: Typical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages. METHODS: Participants had dMRI and either beta-amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was measured in portions of the medial temporal lobe (MTL) with high neurofibrillary tangle (NFT) burden based on a previously developed post mortem 3D-map. Regressions examined relationships between microstructure and markers of Alzheimer's pathology in preclinical disease and then across disease stages. RESULTS: There was higher isometric volume fraction in amyloid-positive compared to amyloid-negative cognitively unimpaired individuals in high tangle MTL regions. Similarly, plasma biomarkers and 18F-flortaucipir were associated with microstructural changes in preclinical disease. Additional microstructural effects were seen across disease stages. DISCUSSION: Combining a post mortem atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease. Highlights Typical markers of neurodegeneration are not sensitive in preclinical Alzheimer's. dMRI measured microstructure in regions with high NFT. Microstructural changes occur in medial temporal regions in preclinical disease. Microstructural changes occur in other typical Alzheimer's regions in later stages. Combining post mortem pathology atlases with in vivo MRI is a powerful framework.


Assuntos
Doença de Alzheimer , Biomarcadores , Substância Cinzenta , Tomografia por Emissão de Pósitrons , Lobo Temporal , Humanos , Doença de Alzheimer/patologia , Doença de Alzheimer/diagnóstico por imagem , Lobo Temporal/patologia , Lobo Temporal/diagnóstico por imagem , Masculino , Feminino , Idoso , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Biomarcadores/sangue , Peptídeos beta-Amiloides/metabolismo , Emaranhados Neurofibrilares/patologia , Imagem de Difusão por Ressonância Magnética
9.
Alzheimers Dement ; 20(3): 1586-1600, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38050662

RESUMO

INTRODUCTION: Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors. METHODS: We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were compared with groups from 159 non-AD (amyloid "negative") patients partitioned using cortical thickness, and groups in 98 patients with ante mortem MRI and post mortem tissue for measuring N and T, respectively. We applied the initial T-N residual model to classify 71 patients in an independent cohort into predefined groups. RESULTS: AD groups displayed spatial T-N mismatch patterns resembling neurodegeneration patterns in non-AD groups, similarly associated with non-AD factors and diverging cognitive outcomes. In the autopsy cohort, limbic T-N mismatch correlated with TDP-43 co-pathology. DISCUSSION: T-N mismatch may provide a personalized approach for determining non-AD factors associated with resilience/vulnerability in AD.


Assuntos
Doença de Alzheimer , Resiliência Psicológica , Humanos , Doença de Alzheimer/patologia , Proteínas tau , Emaranhados Neurofibrilares/patologia , Imageamento por Ressonância Magnética , Peptídeos beta-Amiloides
10.
Molecules ; 29(12)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38930928

RESUMO

A mild, efficient and practical protocol for the preparation of 2-sulfonylquinolines through CS2/Et2NH-induced deoxygenative C2-H sulfonylation of quinoline N-oxides with readily available RSO2Cl was developed. The reaction proceeded well under transition-metal-free conditions and exhibited a wide substrate scope and functional group tolerance. The preliminary studies suggested that the nucleophilic sulfonyl sources were generated in situ via the reaction of CS2, Et2NH and sulfonyl chlorides.

11.
Molecules ; 29(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38474508

RESUMO

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

12.
BMC Oral Health ; 24(1): 282, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418992

RESUMO

BACKGROUND: The incidence of facial fractures has undergone tremendous changes in recent years as a result of socio-economic development and aging populations. Currently, there is a lack of updated and comprehensive analyses of global trends and causes of facial fractures. The Global Burden of Disease (GBD) database is a product of a global research organization used to quantify the global impact of hundreds of diseases, injuries, and risk factors. The aim of this study was to update global burden of facial fractures from 1990 to 2019 by using the GBD2019. MATERIALS AND METHODS: The present study extracted the global incidence, prevalence, and years lived with disability (YLDs) for facial fractures, as well as the age-standardized rates (ASRs) of these variables using the Global Burden of Disease (GBD) 2019 database. The estimated annual percentage change (EAPC) was used to assess the trends of ASRs. RESULTS: Between 1990 and 2019, the incidence of facial fractures increased from 8,943,707 to 10,676,340, but the age-standardized incidence rate (ASIR) decreased from 161.5 to 138.8 per 100,000. Prevalence and YLDs exhibited the same trend as incidence. Over the 30 years, the incidence of facial fractures was consistently greater in males than in females. However, females aged ˃ 75 years had higher fracture incidence rates than males aged ˃ 75 years in 2019. The leading cause of facial fractures was falls, and both the age-standardized prevalence rate (ASPR) and age-standardized years lived with disability rate (ASYR) of falls increased with age. CONCLUSION: Facial fractures still represent a significant burden to the world. Incidence, prevalence and YLDs all showed increasing trends, while ASRs decreased gradually from 1990 to 2019. Enhancing the quality of facial fractures data is helpful for monitoring the burden of facial fractures.


Assuntos
Pessoas com Deficiência , Carga Global da Doença , Masculino , Feminino , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Incidência , Prevalência , Saúde Global
13.
J Neurosci ; 42(10): 2131-2141, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35086906

RESUMO

The medial temporal lobe (MTL) is connected to the rest of the brain through two main networks: the anterior-temporal (AT) and the posterior-medial (PM) systems. Given the crucial role of the MTL and networks in the physiopathology of Alzheimer's disease (AD), the present study aimed at (1) investigating whether MTL atrophy propagates specifically within the AT and PM networks, and (2) evaluating the vulnerability of these networks to AD proteinopathies. To do that, we used neuroimaging data acquired in human male and female in three distinct cohorts: (1) resting-state functional MRI (rs-fMRI) from the aging brain cohort (ABC) to define the AT and PM networks (n = 68); (2) longitudinal structural MRI from Alzheimer's disease neuroimaging initiative (ADNI)GO/2 to highlight structural covariance patterns (n = 349); and (3) positron emission tomography (PET) data from ADNI3 to evaluate the networks' vulnerability to amyloid and tau (n = 186). Our results suggest that the atrophy of distinct MTL subregions propagates within the AT and PM networks in a dissociable manner. Brodmann area (BA)35 structurally covaried within the AT network while the parahippocampal cortex (PHC) covaried within the PM network. In addition, these networks are differentially associated with relative tau and amyloid burden, with higher tau levels in AT than in PM and higher amyloid levels in PM than in AT. Our results also suggest differences in the relative burden of tau species. The current results provide further support for the notion that two distinct MTL networks display differential alterations in the context of AD. These findings have important implications for disease spread and the cognitive manifestations of AD.SIGNIFICANCE STATEMENT The current study provides further support for the notion that two distinct medial temporal lobe (MTL) networks, i.e., anterior-temporal (AT) and the posterior-medial (PM), display differential alterations in the context of Alzheimer's disease (AD). Importantly, neurodegeneration appears to occur within these networks in a dissociable manner marked by their covariance patterns. In addition, the AT and PM networks are also differentially associated with relative tau and amyloid burden, and perhaps differences in the relative burden of tau species [e.g., neurofibriliary tangles (NFTs) vs tau in neuritic plaques]. These findings, in the context of a growing literature consistent with the present results, have important implications for disease spread and the cognitive manifestations of AD in light of the differential cognitive processes ascribed to them.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/patologia , Amiloide , Peptídeos beta-Amiloides/metabolismo , Atrofia/patologia , Disfunção Cognitiva/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Lobo Temporal/metabolismo , Proteínas tau/metabolismo
14.
Biochem Biophys Res Commun ; 639: 106-116, 2023 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-36476950

RESUMO

PURPOSE: To investigate the possible functions of TERT in pan-cancer and OS. METHODS: First, differential TERT gene expression analysis was conducted using multi-omics data integrative analyses, including differential expression, prognosis, the correlation between infiltrating inflammatory immune cells, and mutation in pan-cancer. Furthermore, differential TERT gene expression analysis was conducted using mRNA expression profiles related to OS based on the GEO Datasets. Various differentially expressed genes were chosen based on a fitness threshold for further investigations. Finally, the function of the TERT gene was assessed in OS cells, including cellular proliferation, migration, and metastasis. RESULTS: Pan-cancer research demonstrated that variable expression of TERT was not only associated with numerous types of human cancer but was also intimately linked to DNA methylation. Bioinformatic investigation revealed a link between the differential expression of TERT with immune cell infiltration in the tumor microenvironment (TME). In vitro studies indicated that inhibition of TERT decreased OS cell proliferation, motility, and metastasis. CONCLUSION: TERT may serve as a useful genomic biomarker for the diagnosis and prediction of pan-cancer and as a prospective therapeutic target for the treatment of OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Telomerase , Humanos , Hiperplasia , Linhagem Celular , Proliferação de Células/genética , Microambiente Tumoral/genética , Telomerase/genética
15.
Small ; 19(40): e2302834, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37264710

RESUMO

Immunotherapy gains increasing focus in treating triple-negative breast cancer (TNBC), while its efficacy is greatly restricted owing to low tumor immunogenicity and immunosuppressive tumor microenvironment (ITM). Herein, a LyP-1 and chondroitin sulfate (CS) dual-modified liposome co-loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS/LyP-1-PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript-3 (STAT3) activation. CS/LyP-1-PC Lip enhances cellular uptake through p32 and CD44 dual receptor-mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2-type tumor-associated macrophage, and myeloid-derived suppressor cell, thus reversing ITM. Markedly, the dual-targeting liposome shows superior anti-tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.


Assuntos
Lipossomos , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Morte Celular Imunogênica , Linhagem Celular Tumoral , Paclitaxel/farmacologia , Imunoterapia , Microambiente Tumoral , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/uso terapêutico
16.
Small ; 19(52): e2304321, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37658503

RESUMO

Buildings account for ≈40% of the total energy consumption. In addition, it is challenging to control the indoor temperature in extreme weather. Therefore, energy-saving smart windows with light regulation have gained increasing attention. However, most emerging base materials for smart windows have disadvantages, including low transparency at low temperatures, ultra-high phase transition temperature, and scarce applications. Herein, a self-adaptive multi-response thermochromic hydrogel (PHC-Gel) with dual temperature and pH response is engineered through "one-pot" integration tactics. The PHC-Gel exhibits excellent mechanical, adhesion, and electrical conductivity properties. Notably, the low critical solubility temperature (LCST) of PHC-Gel can be regulated over a wide temperature range (20-35 °C). The outdoor practical testing reveals that PHC-Gel has excellent light transmittance at low temperatures and radiation cooling performances at high temperatures, indicating that PHC-Gel can be used for developing energy-saving windows. Actually, PHC-Gel-based thermochromic windows show remarkable visible light transparency (Tlum ≈ 95.2%) and solar modulation (△Tsol ≈ 57.2%). Interestingly, PHC-Gel has superior electrical conductivity, suggesting that PHC-Gel can be utilized to fabricate wearable signal-response and temperature sensors. In summary, PHC-Gel has broad application prospects in energy-saving smart windows, smart wearable sensors, temperature monitors, infant temperature detection, and thermal management.

17.
Small ; 19(26): e2207602, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36995034

RESUMO

Natural skin-derived products, as traditional wearable materials are widely used in people's daily life due to the products' excellent origins. Herein, a versatile daytime-radiation cooling wearable natural skin (RC-skin) consisting of the collagen micro-nano fibers with the on-demand double-layer radiation cooling structure is nano-engineered through the proposed facile "synergistic inner-outer activation" strategy. The bottom layer (inner strategy) of the RC-skin is fabricated by filling the skin with the Mg11 (HPO3 )8 (OH)6 nanoparticles by soaking. The superstratum (outer strategy) is constituted by a composite coating with an irregular microporous structure. The RC-skin harvests the inherent advantages of natural building blocks including sufficient hydrophobicity, excellent mechanical properties, and friction resistance. Owing to the subtle double-layer structure design, the solar reflectance and the average emissivity in the mid-infrared band of RC-skin are ≈92.7% and ≈95%, respectively. Therefore, the RC-skin's temperature in the sub-ambient is reduced by ≈7.5 °C. Various outdoor practical application experiments further substantiate that RC-skin has superior radiation cooling performances. Collectively, RC-skin has broad-application prospects for intelligent wearing, low-carbon travel, building materials, and intelligent thermoelectric power generation, and this study also provides novel strategies for developing natural-skin-derived functional materials.

18.
Chemistry ; 29(46): e202301390, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37280159

RESUMO

Chemodivergent tandem radical cyclization offers exciting possibilities for the synthesis of structurally diverse cyclic compounds. Herein, we revealed a chemodivergent tandem cyclization of alkene-substituted quinazolinones under metal- and base-free conditions, this transformation is initiated by alkyl radicals produced from oxidant-induced α-C(sp3 )-H functionalization of alkyl nitriles or esters. The reaction resulted in the selective synthesis of a series of mono- and di-alkylated ring-fused quinazolinones by modulating the loading of oxidant, reaction temperature, and reaction time. Mechanistic investigations show that the mono-alkylated ring-fused quinazolinones is constructed by the key process of 1,2-hydrogen shift, whereas the di-alkylated ring-fused quinazolinones is mainly achieved through crucial steps of resonance and proton transfer. This protocol is the first example of remote second alkylation on the aromatic ring via α-C(sp3 )-H functionalization and difunctionalization achieved by association of two unsaturated bonds in radical cyclization.

19.
BMC Cancer ; 23(1): 181, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36814224

RESUMO

BACKGROUND: This study aimed to get a deeper insight into new osteosarcoma (OS) signature based on bone morphogenetic proteins (BMPs)-related genes and to confirm the prognostic pattern to speculate on the overall survival among OS patients. METHODS: Firstly, pathway analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were managed to search for possible prognostic mechanisms attached to the OS-specific differentially expressed BMPs-related genes (DEBRGs). Secondly, univariate and multivariate Cox analysis was executed to filter the prognostic DEBRGs and establish the polygenic model for risk prediction in OS patients with the least absolute shrinkage and selection operator (LASSO) regression analysis. The receiver operating characteristic (ROC) curve weighed the model's accuracy. Thirdly, the GEO database (GSE21257) was operated for independent validation. The nomogram was initiated using multivariable Cox regression. Immune infiltration of the OS sample was calculated. Finally, the three discovered hallmark genes' mRNA and protein expressions were verified. RESULTS: A total of 46 DEBRGs were found in the OS and control samples, and three prognostic DEBRGs (DLX2, TERT, and EVX1) were screened under the LASSO regression analyses. Multivariate and univariate Cox regression analysis were devised to forge the OS risk model. Both the TARGET training and validation sets indicated that the prognostic biomarker-based risk score model performed well based on ROC curves. In high- and low-risk groups, immune cells, including memory B, activated mast, resting mast, plasma, and activated memory CD4 + T cells, and the immune, stromal, and ESTIMATE scores showed significant differences. The nomogram that predicts survival was established with good performance according to clinical features of OS patients and risk scores. Finally, the expression of three crucial BMP-related genes in OS cell lines was investigated using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). CONCLUSION: The new BMP-related prognostic signature linked to OS can be a new tool to identify biomarkers to detect the disease early and a potential candidate to better treat OS in the future.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Prognóstico , Nomogramas , Western Blotting
20.
Org Biomol Chem ; 21(19): 4109-4113, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37128965

RESUMO

A photocatalytic three-component cascade reaction of quinoxalin-2(1H)-ones, alkenes, and sulfinic acids under metal-, strong oxidant-, and external photocatalyst-free conditions was developed. The reaction was performed at room temperature using air as a green oxidant. Various sulfonated quinoxalin-2(1H)-ones were obtained in satisfactory yields with good functional group compatibility. The preliminary study showed that the current transformation was enabled by the formation of an electron donor-acceptor (EDA) complex between quinoxalin-2(1H)-ones and sulfinic acids.

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