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1.
Nature ; 618(7964): 294-300, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36940729

RESUMO

Chiral amines are commonly used in the pharmaceutical and agrochemical industries1. The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods1,2. Although the N-alkylation of aliphatic amines with alkyl halides has been widely adopted for over 100 years, catalyst poisoning and unfettered reactivity have been preventing the development of a catalyst-controlled enantioselective version3-5. Here we report the use of chiral tridentate anionic ligands to enable the copper-catalysed chemoselective and enantioconvergent N-alkylation of aliphatic amines with α-carbonyl alkyl chlorides. This method can directly convert feedstock chemicals, including ammonia and pharmaceutically relevant amines, into unnatural chiral α-amino amides under mild and robust conditions. Excellent enantioselectivity and functional-group tolerance were observed. The power of the method is demonstrated in a number of complex settings, including late-stage functionalization and in the expedited synthesis of diverse amine drug molecules. The current method indicates that multidentate anionic ligands are a general solution for overcoming transition-metal-catalyst poisoning.


Assuntos
Alquilação , Aminas , Catálise , Cobre , Amidas/química , Aminas/química , Cobre/química , Ligantes , Preparações Farmacêuticas/química
2.
Nature ; 598(7881): 451-456, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34464959

RESUMO

Metal-catalysed cross-couplings are a mainstay of organic synthesis and are widely used for the formation of C-C bonds, particularly in the production of unsaturated scaffolds1. However, alkyl cross-couplings using native sp3-hybridized functional groups such as alcohols remain relatively underdeveloped2. In particular, a robust and general method for the direct deoxygenative coupling of alcohols would have major implications for the field of organic synthesis. A general method for the direct deoxygenative cross-coupling of free alcohols must overcome several challenges, most notably the in situ cleavage of strong C-O bonds3, but would allow access to the vast collection of commercially available, structurally diverse alcohols as coupling partners4. We report herein a metallaphotoredox-based cross-coupling platform in which free alcohols are activated in situ by N-heterocyclic carbene salts for carbon-carbon bond formation with aryl halide coupling partners. This method is mild, robust, selective and most importantly, capable of accommodating a wide range of primary, secondary and tertiary alcohols as well as pharmaceutically relevant aryl and heteroaryl bromides and chlorides. The power of the transformation has been demonstrated in a number of complex settings, including the late-stage functionalization of Taxol and a modular synthesis of Januvia, an antidiabetic medication. This technology represents a general strategy for the merger of in situ alcohol activation with transition metal catalysis.


Assuntos
Álcoois/química , Brometos/química , Carbono/química , Cloretos/química , Metais/química , Oxigênio/química , Fotoquímica , Catálise , Metano/análogos & derivados , Metano/química , Nitrogênio/química , Oxirredução , Paclitaxel/química , Sinvastatina/síntese química , Sinvastatina/química
3.
J Cell Biochem ; 125(3): e30527, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38332574

RESUMO

The presence of Helicobacter pylori (H. pylori) infection poses a substantial risk for the development of gastric adenocarcinoma. The primary mechanism through which H. pylori exerts its bacterial virulence is the cytotoxin CagA. This cytotoxin has the potential to induce inter-epithelial mesenchymal transition, proliferation, metastasis, and the acquisition of stem cell-like properties in gastric cancer (GC) cells infected with CagA-positive H. pylori. Cancer stem cells (CSCs) represent a distinct population of cells capable of self-renewal and generating heterogeneous tumor cells. Despite evidence showing that CagA can induce CSCs-like characteristics in GC cells, the precise mechanism through which CagA triggers the development of GC stem cells (GCSCs) remains uncertain. This study reveals that CagA-positive GC cells infected with H. pylori exhibit CSCs-like properties, such as heightened expression of CD44, a specific surface marker for CSCs, and increased ability to form tumor spheroids. Furthermore, we have observed that H. pylori activates the PI3K/Akt signaling pathway in a CagA-dependent manner, and our findings suggest that this activation is associated with the CSCs-like characteristics induced by H. pylori. The cytotoxin CagA, which is released during H. pylori infection, triggers the activation of the PI3K/Akt signaling pathway in a CagA-dependent manner. Additionally, CagA inhibits the transcription of FOXO3a and relocates it from the nucleus to the cytoplasm by activating the PI3K/Akt pathway. Furthermore, the regulatory function of the Akt/FOXO3a axis in the transformation of GC cells into a stemness state was successfully demonstrated.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Citotoxinas/metabolismo , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/patologia , Células-Tronco Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo
4.
Anal Chem ; 96(19): 7697-7705, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38697043

RESUMO

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.


Assuntos
Elementos da Série dos Lantanídeos , Imageamento por Ressonância Magnética , Nanopartículas , Polímeros , Semicondutores , Imageamento por Ressonância Magnética/métodos , Animais , Elementos da Série dos Lantanídeos/química , Polímeros/química , Nanopartículas/química , Camundongos , Humanos , Gadolínio/química , Luminescência , Oxigênio Singlete/química , Ítrio/química , Fluoretos/química , Camundongos Nus
5.
J Transl Med ; 22(1): 297, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38515161

RESUMO

BACKGROUND: The aberrant secretion and excessive deposition of type I collagen (Col1) are important factors in the pathogenesis of myocardial fibrosis in dilated cardiomyopathy (DCM). However, the precise molecular mechanisms underlying the synthesis and secretion of Col1 remain unclear. METHODS AND RESULTS: RNA-sequencing analysis revealed an increased HtrA serine peptidase 1 (HTRA1) expression in patients with DCM, which is strongly correlated with myocardial fibrosis. Consistent findings were observed in both human and mouse tissues by immunoblotting, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, and immunofluorescence analyses. Pearson's analysis showed a markedly positive correlation between HTRA1 level and myocardial fibrosis indicators, including extracellular volume fraction (ECV), native T1, and late gadolinium enhancement (LGE), in patients with DCM. In vitro experiments showed that the suppression of HTRA1 inhibited the conversion of cardiac fibroblasts into myofibroblasts and decreased Col1 secretion. Further investigations identified the role of HTRA1 in promoting the formation of endoplasmic reticulum (ER) exit sites, which facilitated the transportation of Col1 from the ER to the Golgi apparatus, thereby increasing its secretion. Conversely, HTRA1 knockdown impeded the retention of Col1 in the ER, triggering ER stress and subsequent induction of ER autophagy to degrade misfolded Col1 and maintain ER homeostasis. In vivo experiments using adeno-associated virus-serotype 9-shHTRA1-green fluorescent protein (AAV9-shHTRA1-GFP) showed that HTRA1 knockdown effectively suppressed myocardial fibrosis and improved left ventricular function in mice with DCM. CONCLUSIONS: The findings of this study provide valuable insights regarding the treatment of DCM-associated myocardial fibrosis and highlight the therapeutic potential of targeting HTRA1-mediated collagen secretion.


Assuntos
Cardiomiopatias , Cardiomiopatia Dilatada , Animais , Humanos , Camundongos , Colágeno Tipo I , Meios de Contraste , Fibrose , Gadolínio , Miocárdio/patologia
6.
BMC Cancer ; 24(1): 466, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622555

RESUMO

BACKGROUND: [18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC). METHODS: A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI). RESULTS: In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036). CONCLUSION: The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging.


Assuntos
Neoplasias Nasofaríngeas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Prognóstico , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Estadiamento de Neoplasias
7.
J Magn Reson Imaging ; 59(5): 1593-1602, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37610209

RESUMO

BACKGROUND: Identification of non-diabetic renal disease (NDRD) in patients with type 2 diabetes mellitus (T2DM) may help tailor treatment. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising tool to evaluate renal function but its potential role in the clinical differentiation between diabetic nephropathy (DN) and NDRD remains unclear. PURPOSE: To investigate the added role of IVIM-DWI in the differential diagnosis between DN and NDRD in patients with T2DM. STUDY TYPE: Prospective. POPULATION: Sixty-three patients with T2DM (ages: 22-69 years, 17 females) confirmed by renal biopsy divided into two subgroups (28 DN and 35 NDRD). FIELD STRENGTH/SEQUENCE: 3 T/ T2 weighted imaging (T2WI), and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT: The parameters derived from IVIM-DWI (true diffusion coefficient [D], pseudo-diffusion coefficient [D*], and pseudo-diffusion fraction [f]) were calculated for the cortex and medulla, respectively. The clinical indexes related to renal function (eg cystatin C, etc.) and diabetes (eg diabetic retinopathy [DR], fasting blood glucose, etc.) were measured and calculated within 1 week before MRI scanning. The clinical model based on clinical indexes and the IVIM-based model based on IVIM parameters and clinical indexes were established and evaluated, respectively. STATISTICAL TESTS: Student's t-test; Mann-Whitney U test; Fisher's exact test; Chi-squared test; Intraclass correlation coefficient; Receiver operating characteristic analysis; Hosmer-Lemeshow test; DeLong's test. P < 0.05 was considered statistically significant. RESULTS: The cortex D*, DR, and cystatin C values were identified as independent predictors of NDRD in multivariable analysis. The IVIM-based model, comprising DR, cystatin C, and cortex D*, significantly outperformed the clinical model containing only DR, and cystatin C (AUC = 0.934, 0.845, respectively). DATA CONCLUSION: The IVIM parameters, especially the renal cortex D* value, might serve as novel indicators in the differential diagnosis between DN and NDRD in patients with T2DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Nefropatias Diabéticas/diagnóstico por imagem , Cistatina C , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Estudos Prospectivos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Movimento (Física)
8.
J Org Chem ; 89(13): 9641-9646, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38910296

RESUMO

A novel copper-catalyzed cyclization/chalcogenation of o-alkynylphenols with epoxides and elemental S8/Se was developed for the synthesis of a 3-chalcogen-benzofuran architecture in a domino process with no intermediate isolation or purification. Various sensitive functional groups were compatible at room temperature and furnished chalcogenation derivatives in moderate to good yields.

9.
J Nanobiotechnology ; 22(1): 409, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992688

RESUMO

OBJECTIVE: This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination. METHODS: Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses. RESULTS: CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors. CONCLUSION: CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications.


Assuntos
Neoplasias Colorretais , Células Supressoras Mieloides , RNA Interferente Pequeno , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos , Fator de Transcrição STAT3 , Animais , Células Supressoras Mieloides/metabolismo , Camundongos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Fator de Transcrição STAT3/metabolismo , Linhagem Celular Tumoral , Humanos , Transdução de Sinais/efeitos dos fármacos , Receptor de Morte Celular Programada 1/metabolismo , Feminino , Camundongos Endogâmicos BALB C , Janus Quinases/metabolismo , Imunomodulação/efeitos dos fármacos , Receptor de Fator Estimulador de Colônias de Macrófagos
10.
Respiration ; 103(2): 105-110, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38316120

RESUMO

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration is increasingly used as a minimally invasive procedure in clinical settings. It is generally regarded as a safe procedure with high diagnostic accuracy. However, a complication involving a needle fracture that penetrated a nearby artery has not been reported during this procedure. CASE PRESENTATION: A male patient, 58 years of age, underwent endobronchial ultrasound-guided transbronchial needle aspiration for a mediastinal lymph node biopsy at a local hospital. The aspiration needle fractured and penetrated from the right middle segmental bronchus into the right pulmonary artery. The patient was then transferred to our hospital. After conducting repeated chest imaging examinations to confirm the presence of the foreign body and holding multidisciplinary team consultations, we first inserted a deflated balloon catheter near the puncture site in the right middle segmental bronchus. Following the needle retrieval through a flexible bronchoscope, the balloon catheter was inflated to ensure local hemostasis. Follow-up evaluations revealed no further complications for this patient. CONCLUSION: Intragenic vascular injury can occur during endobronchial ultrasound-guided transbronchial needle aspiration. Careful pre-procedure preparations should be planned to minimize complications. In patients experiencing complications due to needle penetration, consultation and coordination with a multidisciplinary team are essential to ensure the safe retrieval of the broken needle.


Assuntos
Neoplasias Pulmonares , Artéria Pulmonar , Humanos , Masculino , Artéria Pulmonar/diagnóstico por imagem , Linfonodos/patologia , Pulmão/patologia , Neoplasias Pulmonares/patologia , Broncoscopia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos
11.
Appl Opt ; 63(3): 757-761, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38294388

RESUMO

A helical structural support scheme is proposed to mechanically support dielectric layers in a hollow-core terahertz Bragg waveguide by means of an axially rotating wrap-around strip structure. The helical-strip supported waveguide samples are fabricated using 3D printing technology, and the waveguide samples are experimentally tested using a terahertz time-domain spectroscopy system. The results show that choosing a suitable helix period can obtain loss characteristics close to those of an ideal Bragg waveguide, with a low transmission loss of less than 0.097 dB/m in the range of 0.57-0.58 THz.

12.
Molecules ; 29(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38398664

RESUMO

Medium- and long-chain triacylglycerol (MLCT), as a novel functional lipid, is valuable due to its special nutritional properties. Its low content in natural resources and inefficient synthesis during preparation have limited its practical applications. In this study, we developed an effective Pickering emulsion interfacial catalysis system (PE system) for the enzymatic synthesis of MLCT by trans-esterification. Lipase NS 40086 served simultaneously as a catalyst and a solid emulsifier to stabilize the Pickering emulsion. Benefitting from the sufficient oil-water interface, the obtained PE system exhibited outstanding catalytic efficiency, achieving 77.5% of MLCT content within 30 min, 26% higher than that of a water-free system. The Km value (0.259 mM) and activation energy (14.45 kJ mol-1) were 6.8-fold and 1.6-fold lower than those of the water-free system, respectively. The kinetic parameters as well as the molecular dynamics simulation and the tunnel analysis implied that the oil-water interface enhanced the binding between substrate and lipase and thus boosted catalytic efficiency. The conformational changes in the lipase were further explored by FT-IR. This method could give a novel strategy for enhancing lipase activity and the design of efficient catalytic systems to produce added-value lipids. This work will open a new methodology for the enzymatic synthesis of structured lipids.

13.
J Youth Adolesc ; 53(3): 550-562, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38183532

RESUMO

Positive and negative leadership styles may influence classroom norms and be related to the school and psychological adjustment of children in general, and victims in particular. This study tested the relation between leadership styles and children's adjustment, and the moderating effects of leadership on the association between self-reported victimization and school and psychological adjustment (self-esteem, social anxiety, and depressive symptoms); and it tested for potential gender differences. Classrooms were classified into those with only positive leaders, only negative leaders, both positive and negative leaders, and without leaders. The sample contained 8748 children (Mage = 10.05, SD = 1.22; 51.2% girls) from 392 classrooms, in grades three to six, in 98 Dutch schools. Multilevel analysis revealed that, in general, children in negative leader classrooms experienced lower school well-being than children in other classrooms. In positive leader classrooms, male and female victims had lower school well-being. For psychological well-being, female victims had lower self-esteem and more depressive symptoms in positive leader classrooms. Male and female victims in negative leader classrooms did not suffer from additional maladjustment. These results demonstrate that negative leadership styles are related to lower school well-being of all children, whereas victimization in classrooms with positive leaders is negatively related to male and female victims' school well-being and girls' psychological adjustment (depressive symptoms); this is in line with the 'healthy context paradox'.


Assuntos
Bullying , Vítimas de Crime , Criança , Humanos , Masculino , Feminino , Ajustamento Emocional , Grupo Associado , Instituições Acadêmicas , Estudantes/psicologia , Bullying/psicologia , Vítimas de Crime/psicologia
14.
J Environ Sci (China) ; 142: 155-168, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38527881

RESUMO

We conducted a simultaneous field study of PM2.5-bound particulate polycyclic aromatic hydrocarbons (PAHs) and aromatic acids (AAs) in a polluted city Zhengzhou to explore the concentration, sources and potential conversion pathways between PAHs and AAs in different seasons. The average concentrations of PM2.5, 28PAHs and 8AAs during the sampling period were 77 µg/m3, 75 ng/m3, and 283 ng/m3, respectively. The concentration of both 28PAHs and 8AAs were highest in winter and lowest in summer with ratios of 6.3 and 2.3, respectively. PAHs with 5-7 rings were the main components of PAHs (52%), followed by 4 rings PAHs (30%) and 2-3 rings PAHs (18%). According to the source appointment results obtained by positive matrix factorization, the main sources of PAHs were combustion and vehicle emissions, which account for 37% and 34%, respectively. 8AAs were divided into three groups, including four benzene dicarboxylic acids (B2CAs), three benzene tricarboxylic acids (B3CAs) and one benzene tetracarboxylic acid (B4CA). And interspecies correlation analysis with PM2.5 source markers were used to investigate potential sources. Phthalic acid (o-Ph) was the most abundant specie of 8AAs (157 ng/m3, 55% of 8AAs), which was well correlated with sulfate. Meanwhile, B3CAs and B4CA were highly correlated with sulfate and weakly correlated with levoglucosan, suggesting that secondary formation was their main source. As logical oxidation products of PAHs, o-Ph and B3CAs showed good correlations with a number of PAHs, indicating possible photochemical oxidation pathway by PAHs. In addition, O3, NO2, temperature and relative humidity have positive effects on the secondary formation of B3CAs.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Benzeno , Monitoramento Ambiental/métodos , China , Emissões de Veículos/análise , Estações do Ano , Poeira/análise , Carvão Mineral/análise , Sulfatos/análise
15.
J Am Chem Soc ; 145(44): 24386-24400, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37883689

RESUMO

Chemotherapeutic resistance poses a significant challenge in cancer treatment, resulting in the reduced efficacy of standard chemotherapeutic agents. Abnormal metabolism, particularly increased anaerobic glycolysis, has been identified as a major contributing factor to chemotherapeutic resistance. To address this issue, noninvasive imaging techniques capable of visualizing tumor glycolysis are crucial. However, the currently available methods (such as PET, MRI, and fluorescence) possess limitations in terms of sensitivity, safety, dynamic imaging capability, and autofluorescence. Here, we present the de novo design of a unique afterglow molecular scaffold based on hemicyanine and rhodamine dyes, which holds promise for low-background optical imaging. In contrast to previous designs, this scaffold exhibits responsive "OFF-ON" afterglow signals through spirocyclization, thus enabling simultaneous control of photodynamic effects and luminescence efficacy. This leads to a larger dynamic range, broader detection range, higher signal enhancement ratio, and higher sensitivity. Furthermore, the integration of multiple functionalities simplifies probe design, eliminates the need for spectral overlap, and enhances reliability. Moreover, we have expanded the applications of this afterglow molecular scaffold by developing various probes for different molecular targets. Notably, we developed a water-soluble pH-responsive afterglow nanoprobe for visualizing glycolysis in living mice. This nanoprobe monitors the effects of glycolytic inhibitors or oxidative phosphorylation inhibitors on tumor glycolysis, providing a valuable tool for evaluating the tumor cell sensitivity to these inhibitors. Therefore, the new afterglow molecular scaffold presents a promising approach for understanding tumor metabolism, monitoring chemotherapeutic resistance, and guiding precision medicine in the future.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Animais , Camundongos , Reprodutibilidade dos Testes , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Glicólise
16.
Hepatology ; 75(6): 1507-1522, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34689362

RESUMO

BACKGROUND AND AIMS: NAFLD is a progressive disease without known effective drug treatments. Switch-associated protein 70 (SWAP70) is a guanine nucleotide exchange factor that participates in the regulation of many cellular processes. However, the role of SWAP70 in NAFLD remains unclear. This study aimed to identify the function and mechanism of SWAP70 in NAFLD. APPROACH AND RESULTS: The results showed that the expression of SWAP70 was significantly increased in mice and hepatocytes after metabolic stimulation. Overexpression of SWAP70 in hepatocytes suppressed lipid deposition and inflammation, and SWAP70 knockdown created the inverse effect. Using hepatocyte-specific Swap70 knockout and overexpression mice fed a high-fat, high-cholesterol diet, we demonstrated that SWAP70 suppressed the progression of nonalcoholic steatohepatitis by inhibiting lipid accumulation, inflammatory response, and fibrosis. Mechanically, RNA sequencing analysis and immunoprecipitation assays revealed that SWAP70 inhibited the interaction between transforming growth factor ß-activated kinase 1 (TAK1) binding protein 1 and TAK1 and sequentially suppressed the phosphorylation of TAK1 and subsequent c-Jun N-terminal kinase/P38 signaling. Inhibition of TAK1 activation blocked hepatocyte lipid deposition and inflammation caused by SWAP70 knockdown. CONCLUSIONS: SWAP70 is a protective molecule that can suppress the progression of NAFLD by inhibiting hepatic steatosis and inflammation. SWAP70 may be important for mitigating the progression of NAFLD.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica/efeitos adversos , Hepatócitos/metabolismo , Inflamação/metabolismo , Resistência à Insulina/genética , Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia
17.
Gastric Cancer ; 26(6): 947-957, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37691031

RESUMO

BACKGROUND: Lymph node (LN) status is vital to evaluate the curative potential of relatively early gastric cancer (GC; T1-T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify LN metastasis before therapeutic decision-making. METHODS: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify lncRNA expression signature capable of detecting LN metastasis of GC and establish a 10-lncRNA risk-prediction model based on deep learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. RESULTS: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (AUC = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1 + T2, AUC = 0.764). Notably, the panel demonstrated significantly better performance compared with CT and traditional tumor markers. CONCLUSIONS: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1-T2), with promising clinical potential.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Metástase Linfática/patologia , RNA Longo não Codificante/genética , Transcriptoma , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfonodos/patologia
18.
Phys Chem Chem Phys ; 25(27): 17850-17859, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37378864

RESUMO

We report a type of micro-electro-mechanical system (MEMS) H2S gas sensors with excellent sensing performance at the ppb level (lowest detection limit is 5 ppb). The sensors were fabricated with ZnO/Co3O4 sensing materials derived from Zn/Co-MOFs by annealing at a suitable temperature of 500 °C. ZnO/Co3O4-500 exhibits the highest response when exposed to 10 ppb H2S gas at 120 °C, and the response/recovery times are 10 s/21 s. Moreover, it exhibits outstanding selectivity, long-term stability (retained 95% response after 45 days), and moisture resistance (only a minor fluctuation of 2% even at 90% RH). This can be ascribed to the fact that ZnO/Co3O4-500 has regular morphology, abundant oxygen vacancies (52.8%) and high specific surface area (96.5 m2 g-1). This work provides not only a high performance H2S MEMS gas sensor but also a systematic study of the effect of the annealing temperature on the sensing performance of ZnO/Co3O4 sensing materials derived from bimetal organic frameworks.

19.
Phys Chem Chem Phys ; 25(4): 3485-3493, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36637146

RESUMO

Although NO2 detection based on metal oxide semiconductors (MOSs) has received continuous attention, the sensing properties of MOSs still need to be further improved for practical application. Carbon nanocoils (CNCs) exhibit excellent physicochemical properties due to their unique polycrystalline amorphous structure and helical morphology. Herein, CNCs composited with NiO nanosheets were developed for room temperature NO2 sensing, in which highly dispersed mesoporous NiO nanosheets on CNCs was achieved with extremely higher sensitivity. Due to a large number of exposed active sites and the efficient conductive network of CNCs, this particular scale-like nanocomposite exhibits a nearly 8 times higher response to 60 ppm NO2 than bare NiO nanosheets at room temperature, outperforming the majority of previously reported NO2 sensors at room temperature. Moreover, the nanocomposite-based gas sensor has a detection concentration limit of 60.3 ppb, which is advantageous for the sensing of NO2 at low concentrations. We believe that this work will provide the direction for the research and development of highly sensitive smart sensors, as well as encourage further investigation of multifunctional sensing applications utilizing CNCs as the primary frame support material.

20.
J Nanobiotechnology ; 21(1): 434, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980476

RESUMO

Manganese-based nanomaterials (Mn-nanomaterials) hold immense potential in cancer diagnosis and therapies. However, most Mn-nanomaterials are limited by the low sensitivity and low efficiency toward mild weak acidity (pH 6.4-6.8) of the tumor microenvironment, resulting in unsatisfactory therapeutic effect and poor magnetic resonance imaging (MRI) performance. This study introduces pH-ultrasensitive PtMn nanoparticles as a novel platform for enhanced ferroptosis-based cancer theranostics. The PtMn nanoparticles were synthesized with different diameters from 5.3 to 2.7 nm with size-dominant catalytic activity and magnetic relaxation, and modified with an acidity-responsive polymer to create pH-sensitive agents. Importantly, R-PtMn-1 (3 nm core) presents "turn-on" oxidase-like activity, affording a significant enhancement ratio (pH 6.0/pH 7.4) in catalytic activity (6.7 folds), compared with R-PtMn-2 (4.2 nm core, 3.7 folds) or R-PtMn-3 (5.3 nm core, 2.1 folds), respectively. Moreover, R-PtMn-1 exhibits dual-mode contrast in high-field MRI. R-PtMn-1 possesses a good enhancement ratio (pH 6.4/pH 7.4) that is 3 or 3.2 folds for T1- or T2-MRI, respectively, which is higher than that of R-PtMn-2 (1.4 or 1.5 folds) or R-PtMn-3 (1.1 or 1.2 folds). Moreover, their pH-ultrasensitivity enabled activation specifically within the tumor microenvironment, avoiding off-target toxicity in normal tissues during delivery. In vitro studies demonstrated elevated intracellular reactive oxygen species production, lipid peroxidation, mitochondrial membrane potential changes, malondialdehyde content, and glutathione depletion, leading to enhanced ferroptosis in cancer cells. Meanwhile, normal cells remained unaffected by the nanoparticles. Overall, the pH-ultrasensitive PtMn nanoparticles offer a promising strategy for accurate cancer diagnosis and ferroptosis-based therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Manganês/química , Medicina de Precisão , Meios de Contraste/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral
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