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1.
ACS Nano ; 18(18): 11753-11768, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38649866

RESUMO

The association between dysfunctional microglia and amyloid-ß (Aß) is a fundamental pathological event and increases the speed of Alzheimer's disease (AD). Additionally, the pathogenesis of AD is intricate and a single drug may not be enough to achieve a satisfactory therapeutic outcome. Herein, we reported a facile and effective gene therapy strategy for the modulation of microglia function and intervention of Aß anabolism by ROS-responsive biomimetic exosome-liposome hybrid nanovesicles (designated as TSEL). The biomimetic nanovesicles codelivery ß-site amyloid precursor protein cleaving enzyme-1 (BACE1) siRNA (siBACE1) and TREM2 plasmid (pTREM2) gene drug efficiently penetrate the blood-brain barrier and enhance the drug accumulation at AD lesions with the help of exosomes homing ability and angiopep-2 peptides. Specifically, an upregulation of TREM2 expression can reprogram microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype while also restoring its capacity to phagocytose Aß and its nerve repair function. In addition, siRNA reduces the production of Aß plaques at the source by knocking out the BACE1 gene, which is expected to further enhance the therapeutic effect of AD. The in vivo study suggests that TSEL through the synergistic effect of two gene drugs can ameliorate APP/PS1 mice cognitive impairment by regulating the activated microglial phenotype, reducing the accumulation of Aß, and preventing the retriggering of neuroinflammation. This strategy employs biomimetic nanovesicles for the delivery of dual nucleic acids, achieving synergistic gene therapy for AD, thus offering more options for the treatment of AD.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Ácido Aspártico Endopeptidases , Materiais Biomiméticos , Terapia Genética , Doença de Alzheimer/terapia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Animais , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Camundongos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Técnicas de Transferência de Genes , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Humanos , Lipossomos/química , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Biomimética , Exossomos/metabolismo , Exossomos/química , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética
2.
Chemistry ; : e202401150, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639722

RESUMO

In this study, a series of H-bonded arylamide foldamers bearing benzoselenadiazole ends with solvent-responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV-vis spectroscopy experiments show that the absorption wavelength of H-bonded arylamide foldamers are significantly red-shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se···N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se···N interactions beyond the crystalline state.

3.
Biol Chem ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38465853

RESUMO

The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate both apoptosis and mitophagy. However, whether similar pathways exist in lower eukaryotes where conical Bcl-2 members are absent remained unclear. Here, a specific inhibitor of the Hsp70-Bim PPI, S1g-10 and its analogs were used as chemical tools to explore the role of yeast Bxi1/Ybh3 in regulating mitophagy and apoptosis. Using Om45-GFP processing assay, we illustrated that yeast Ybh3 mediates a ubiquitin-related mitophagy pathway in both yeast and mammalian cells through association with Hsp70, which is in the same manner with Bim. Moreover, by using Bax/Bak double knockout MEF cells, Ybh3 was identified to induce apoptosis through forming oligomerization to trigger mitochondrial outer membrane permeabilization (MOMP) like Bax. We not only illustrated a conserved ubiquitin-related mitophagy pathway in yeast but also revealed the multi-function of Ybh3 which combines the function of BH3-only protein and multi-domain Bax protein as one.

4.
Oncologist ; 29(4): 364-e578, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38366886

RESUMO

BACKGROUND: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC). METHODS: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints. RESULTS: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group. CONCLUSION: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745).


Assuntos
Anticorpos Monoclonais Humanizados , Piridinas , Neoplasias Gástricas , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Junção Esofagogástrica , Neoplasias Gástricas/tratamento farmacológico
5.
Breast Cancer Res ; 26(1): 33, 2024 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409088

RESUMO

INTRODUCTION: Estrogen receptor (ER) positive patients compromise about 70% of breast cancers. Tamoxifen, an antagonist of ERα66 (the classic ER), is the most effective and the standard first-line drug. However, its efficacy is limited by the development of acquired resistance. METHODS: A specific inhibitor of Hsp70-Bim protein-protein interaction (PPI), S1g-2, together with an inhibitor of Hsp70-Bag3 PPI, MKT-077 and an ATP-competitive inhibitor VER155008, were used as chemical tools. Cell viability assays, co-immunoprecipitation and gene knockdown were used to investigate the role of Hsp70 in tamoxifen resistance. A xenograft model was established in which tamoxifen-resistant breast cancer (MCF-7/TAM-R) cells maintained in the presence of 5 µM tamoxifen were subcutaneously inoculated. The anti-tumor efficiency of S1g-2 was measured after a daily injection of 0.8 mg/kg for 14 days. RESULTS: It was revealed that Hsp70-Bim PPI protects ERα-positive breast cancer from tamoxifen-induced apoptosis through binding and stabilizing ERα36, rather than ERα66, resulting in sustained EGFR mRNA and protein expression. Disruption of Hsp70-Bim PPI and downregulation of ERα36 expression in tumor samples are consistent with the in vitro functions of S1g-2, resulting in about a three-fold reduction in tumor volume. CONCLUSIONS: The in vivo activity and safety of S1g-2 illustrated that it is a potential strategy for Hsp70-Bim disruption to overcome tamoxifen-resistant ER-positive breast cancer.


Assuntos
Neoplasias da Mama , Tamoxifeno , Humanos , Feminino , Tamoxifeno/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica
6.
ACS Omega ; 9(4): 4513-4527, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38313479

RESUMO

Wall impingement, particularly liquid-wall impingement, has been demonstrated to be one of the critical causes of combustion deterioration in plateau diesel engines. Obviously, the complexity of wall impingement is exacerbated by the plateau scenario. However, fundamental studies specifically dedicated to this phenomenon are still inconclusive and insufficiently detailed, obviating the feasibility of the targeted design and optimization of diesel engines operating in regions with different altitudes. Consequently, the second part of this investigation, presented in this work, focused on the detailed physical and chemical processes of impinging spray combustion under different altitude conditions. A wall impingement system was designed to generate an impinging spray flame. The impingement distance was varied from 77 to 37 mm to cover different situations of wall impingement. The liquid spray, ignition, and combustion processes were visualized in detail by using different optical diagnostics. The results showed that the variation of the liquid length with the impingement distance was mainly dependent on the liquid impingement under the same altitude condition. The effect of the impingement distance on the ignition distance was more sensitive to the altitude. The quantitative analysis of the flame natural luminosity confirmed the decisive effect of the impinging flame morphology on the ambient entrainment and fuel-air mixing under different altitude conditions, and it also revealed that there was an optimal impingement distance under identical altitude conditions to achieve minimum soot emissions. And interestingly, the optimal impingement distance increased with altitude. Finally, the spray combustion processes of an impinging diesel jet were determined to occur in four typical regions, upon which a schematic diagram depicting the flame structure of an impinging diesel jet was proposed to phenomenologically describe the role of altitude in impinging spray combustion processes. Based on this, an attempt was made to explore some new perspectives beyond the popular solutions to recover and improve the performance of plateau diesel engines.

7.
Nano Lett ; 24(7): 2226-2233, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38251911

RESUMO

Atomically precise doping of metal nanoclusters provides excellent opportunities not only for subtly tailoring their properties but also for in-depth understanding of composition (structure)-property correlation of metal nanoclusters and has attracted increasing interest partly due to its significance for fundamental research and practical applications. Although single and multiple metal atom doping of metal nanoclusters (NCs) has been achieved, sequential single-to-multiple metal atom doping is still a big challenge and has not yet been reported. Herein, by introducing a second ligand, a novel multistep synthesis method was developed, controlled sequential single-to-multiple metal atom doping was successfully achieved for the first time, and three doped NCs Au25Cd1(p-MBT)17(PPh3)2, Au18Cd2(p-MBT)14(PPh3)2, and [Au19Cd3(p-MBT)18]- (p-MBTH: para-methylbenzenethiol) were obtained, including two novel NCs that were precisely characterized via mass spectrometry, single-crystal X-ray crystallography, and so forth. Furthermore, sequential doping-induced evolutions in the atomic and crystallographic structures and optical and catalytic properties of NCs were revealed.

8.
Mol Pharm ; 21(1): 245-254, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38096423

RESUMO

Assessing CD38 expression in vivo has become a significant element in multiple myeloma (MM) therapy, as it can be used to detect lesions and forecast the effectiveness of treatment. Accurate diagnosis requires a multifunctional, high-throughput probe screening platform to develop molecular probes for tumor-targeted multimodal imaging and treatment. Here, we investigated a microarray chip-based strategy for high-throughput screening of peptide probes for CD38. We obtained two new target peptides, CA-1 and CA-2, from a 105 peptide library with a dissociation constant (KD) of 10-7 M. The specificity and affinity of the target peptides were confirmed at the molecular and cellular levels. Peptide probes were labeled with indocyanine green (ICG) dye and 68Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.


Assuntos
Mieloma Múltiplo , Camundongos , Animais , Mieloma Múltiplo/diagnóstico por imagem , Linhagem Celular Tumoral , Tomografia por Emissão de Pósitrons/métodos , Peptídeos/química , Imagem Multimodal/métodos , Radioisótopos de Gálio/química
9.
Nat Nanotechnol ; 19(1): 124-130, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37696994

RESUMO

In vivo quantitative assessment of oxyhaemoglobin saturation (sO2) status in tumour-associated vessels could provide insights into cancer metabolism and behaviour. Here we develop a non-invasive in vivo sO2 imaging technique to visualize the sO2 levels of healthy and tumour tissue based on photoluminescence bioimaging in the near-infrared IIb (NIR-IIb; 1,500-1,700 nm) window. Real-time dynamic sO2 imaging with a high frame rate (33 Hz) reveals the cerebral arteries and veins through intact mouse scalp/skull, and this imaging is consistent with the haemodynamic analysis results. Utilizing our non-invasive sO2 imaging, the tumour-associated-vessel sO2 levels of various cancer models are evaluated. A positive correlation between the tumour-associated-vessel sO2 levels and the basal oxygen consumption rate of corresponding cancer cells at the early stages of tumorigenesis suggests that cancer cells modulate the tumour metabolic microenvironment. We also find that a positive therapeutic response to the checkpoint blockade cancer immunotherapy could lead to a dramatic decrease of the tumour-associated-vessel sO2 levels. Two-plex dynamic NIR-IIb imaging can be used to simultaneously observe tumour-vessel sO2 and PD-L1, allowing a more accurate prediction of immunotherapy response.


Assuntos
Neoplasias , Oxiemoglobinas , Animais , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Diagnóstico por Imagem , Imunoterapia , Microambiente Tumoral
10.
Hum Resour Health ; 21(1): 94, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053064

RESUMO

Human resource management (HRM) in healthcare is an important component in relation to the quality and efficiency of healthcare delivery. However, a comprehensive overview is lacking to assess and track the current status and trends of HRM research in healthcare. This study aims to describe the current situation and global trends in HRM research in healthcare as well as to indicate the frontiers and future directions of research. The research methodology is based on bibliometric mapping using scientific visualization software (VOSviewer). The data were collected from the Web of Science(WoS) core citation database. After applying the search criteria, we retrieved 833 publications, which have steadily increased over the last 30 years. In addition, 93 countries and regions have published relevant research. The United States and Australia have made significant contributions in this area. Current research articles focus on topics clustered into performance, hospital/COVID-19, job satisfaction, human resource management, occupational/mental health, and quality of care. The most frequently co-occurring keywords are human resource management, job satisfaction, nurses, hospitals, health services, quality of care, COVID-19, and nursing. There is limited research on compensation management and employee relations management, so the current HRM research field still has not been able to present a complete and systematic roadmap. We propose that our colleagues should consider focusing on these research gaps in the future.


Assuntos
Big Data , COVID-19 , Humanos , Bibliometria , COVID-19/epidemiologia , Atenção à Saúde , Recursos Humanos
11.
Cell Rep ; 42(11): 113354, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37917586

RESUMO

The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitro models of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/ß-catenin signaling and engineer endogenous WNT/ß-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/ß-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease.


Assuntos
Tubas Uterinas , beta Catenina , Feminino , Humanos , beta Catenina/metabolismo , Tubas Uterinas/metabolismo , Transcriptoma/genética , Células-Tronco/metabolismo , Via de Sinalização Wnt , Organoides/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Receptores Frizzled/metabolismo
12.
J Med Chem ; 66(23): 16377-16387, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38011535

RESUMO

Selectively targeting the cancer-specific protein-protein interaction (PPI) between Hsp70 and Bim has been discovered as a promising strategy for treating chronic myeloid leukemia (CML). The first Hsp70-Bim PPI inhibitor, S1g-2, has been identified to overcome the on-target toxicity of known Hsp70 inhibitors when it induces apoptosis of CML cells. Herein, we carried out a hit-to-lead optimization of S1g-2, yielding S1g-10, which exhibited a 10-fold increase in Hsp70/Bim suppressing potency. Furthermore, S1g-10 not only exhibited a 5- to 10-fold stronger antitumor activity in the sub-µM range against CML cells than S1g-2 in vitro, but it also overcame BCR-ABL-independent tyrosine kinase inhibitor resistance in CML in vivo depending on the Hsp70-Bim signaling pathway. Moreover, through structure-activity relationship analysis, TROSY-HSQC NMR, molecular dynamics simulation, and point mutation validation, two hydrophobic pockets composed of eight key residues were demonstrated to produce predominant interactions with either Bim or S1g-10, regarded as the "hot-spots" in the Hsp70-Bim PPI interface.


Assuntos
Proteínas de Fusão bcr-abl , Transdução de Sinais , Apoptose , Proteína 11 Semelhante a Bcl-2/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/metabolismo , Mesilato de Imatinib/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas de Choque Térmico HSP70/química , Proteínas de Choque Térmico HSP70/metabolismo
13.
ACS Omega ; 8(39): 36292-36301, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37810671

RESUMO

Due to the inherent combustion characteristics of diesel engines, particulate matter (PM) and nitrogen oxides (NOx) are the main pollutants of diesel engines. NOx emissions under low load and low temperature are the focus of future regulation. Selective catalytic reduction coated on diesel particulate filter (SDPF) can reduce NOx and PM emissions of diesel engines at the same time, especially improving the emission characteristics of NOx under low load and low temperature. In this paper, a light-duty diesel engine with diesel oxidation catalyst (DOC) and SDPF was studied, and emission of particulate and gaseous pollutants of the engine before DOC, after DOC, and after SDPF was measured under 10 steady-state operating conditions. The effects of SDPF on particulate size distribution, the filtration efficiency of particulate, and the conversion efficiency of gaseous pollutants were analyzed. The results show that DOC + SDPF can trap PM with particle sizes between 10 and 23 nm by 1-2 orders of magnitude, and the conversion and filtration efficiency of DOC + SDPF for both gaseous pollutants and PM exceeds 90% under low-temperature and low-load conditions. The filtration efficiency of SDPF is 94.37% for PM and 90.36% for PN, and the conversion efficiency is 91.43% for NOx.

14.
Water Res ; 246: 120711, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37844339

RESUMO

The accumulation of volatile fatty acids (VFAs) in anaerobic digestion (AD) systems resulting from food waste overload poses a risk of system collapse. However, limited understanding exists regarding the inhibitory mechanisms and effective strategies to address VFAs-induced stress. This study found that accumulated VFAs exert reactive oxygen species (ROS) stress on indigenous microbiota, particularly impacting methanogens due to their lower antioxidant capability compared to bacteria, which is supposed to be the primary reason for methanogenesis failure. To enhance the VFAs-stressed AD process, microbiome re-assembly using customized propionate-degrading consortia and bioaugmentation with concentrated digestate were implemented. Microbiome re-assembly demonstrated superior efficiency, yielding an average methane yield of 563.6±159.8 mL/L·d and reducing VFAs to undetectable levels for a minimum of 80 days. This strategy improved the abundance of Syntrophomonas, Syntrophobacter and Methanothrix, alleviating ROS stress. Conversely, microbial community in reactor with other strategy experienced an escalating intracellular damage, as indicated by the increase of ROS generation-related genes. This study fills knowledge gaps in stress-related metabolic mechanisms of anaerobic microbiomes exposed to VFAs and microbiome re-assembly to boost methanogenesis process.


Assuntos
Microbiota , Eliminação de Resíduos , Anaerobiose , Espécies Reativas de Oxigênio , Alimentos , Reatores Biológicos/microbiologia , Ácidos Graxos Voláteis/metabolismo , Metano/metabolismo
15.
Chem Commun (Camb) ; 59(77): 11580-11583, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37691557

RESUMO

In this paper, two types of solid phase 2D and 3D XBOFs were selectively constructed from identical building blocks of tetraphenylmethane tetrapyridine derivative and 1,4-diiodotetrafluorobenzene by changing the crystallization solvent. This 3D XBOF is a novel hybrid supramolecular organic framework with the synergistic control of hydrogen and halogen bonds.

16.
Micromachines (Basel) ; 14(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37763842

RESUMO

In this work, the effects of total dose irradiation on the parasitic bipolar junction transistor (BTJ) in 130 nm PDSOI MOSFETs were investigated. The experimental results demonstrate that irradiation-induced oxide-trap charges can modify the E-B junction barrier, and thereby make the common-emitter gain ß0 of the parasitic BJT in NMOS device increase, while decreasing it in a PMOS device. Additionally, irradiation-generated oxide-trap charges in shallow trench isolation (STI) elevate the surface electrostatic potential of the gate above the STI sidewall, thus providing an additional channel from the emitter to the collector. Moreover, these charges may generate parasitic reverse conductive paths at the STI/Si interface under high dose irradiation, thereby enhancing the leakage current in the front gate channel and diminishing the significance of the parasitic BJT. Under irradiation, the electric field intensity difference between two biases leads to higher ß0 of the parasitic BJT in PG-biased devices than in ON-biased ones. Furthermore, the lifting effect of irradiation on ß0 increases in wide or short channel irradiated devices, which can be explained using simulations and an emitter current crowding effect model.

17.
J Clin Oncol ; 41(26): 4192-4199, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37672882

RESUMO

PURPOSE: To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression-based "intrinsic" subtypes luminal A, luminal B, HER2-enriched, and basal-like. METHODS: A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen. RESULTS: The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%. CONCLUSION: Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.

18.
Sci Total Environ ; 901: 165890, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-37541499

RESUMO

In recent decades, the Beijing-Tianjin-Hebei city cluster is experiencing rapid urbanization along with economic booming. Meanwhile, these cities are suffering the influence of extreme precipitation and dust storms. In this study, the impact of dust aerosol on extreme precipitation that occurred in Beijing during 19-21 July 2016 is investigated using both satellite retrievals and Weather Research and Forecasting model coupled to Chemistry (WRF-Chem) model simulations. Results reveal that the dust particles can increase extreme precipitation by promoting the formation of ice clouds and enhancing convections. The dust is lifted into the upper troposphere (>10 km) via strong convection and affects the physical process of precipitation after long-range transport. It further transforms the supercooled water into the middle and high levels of ice nuclei (IN). These promote the formation of ice clouds according to the decreased effective radius of IN and increased ice water path, respectively. Along with sufficient water vapor transport and strong convergence, the formation of IN could release more latent heat and further strengthen convection development. Thus, the precipitation amount in southern Beijing is almost enhanced by 40 % (>80 mm). This study will provide a deep insight into understanding the causes of urban extreme precipitation.

19.
Mikrochim Acta ; 190(8): 335, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37507622

RESUMO

The preparation of nitrogen and sulfur co-doped carbon dots (N, S-CDs) with highly bright orange-red fluorescence is reported through a facile solvothermal approach with naphthalenetetracarboxylic dianhydride as starting material. The N, S-CDs exhibited superior properties, including intense long-wavelength emission with a narrow full width at half maxima (FWHM) of 33 nm, high fluorescence quantum yield (QY) of 60.5% in aqueous solution, excitation-independent emission behavior, and excellent water dispersibility. In addition, sulfide ions (S2-) could selectively recover the fluorescence of N, S-CDs quenched by Sn2+. The selective experiment suggested that the N, S-CDs/Sn2+ complex could be used as a fluorescence-enhancement sensor for sulfide ions (S2-), with the linear range of 5-50 µM and the LOD of 0.35 µM. The practicality and feasibility of this sensor for the determination of sulfide ions in tap and lake water were verified with good recoveries. Furthermore, because of their highly bright fluorescence and strong water solubility, the N, S-CDs could be easily fabricated into fluorescent ink and transparent films, demonstrating the promising application in anti-counterfeiting. Therefore, the designed N, S-CDs exhibited the advantages of facile preparation, intense fluorescence, high stability, easy processing, and selective fluorescence change for specific analytes, which showed high potential in fluorescence detection and anti-counterfeiting.

20.
Food Chem ; 429: 136957, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37499505

RESUMO

In this study, we reported the eco-responsible synthesis of iron-doped carbon quantum dots (Fe-CQDs) from waste coffee grounds through a simple hydrothermal method. The Fe-CQDs exhibited high peroxidase-like activity, which could convert 3,3',5,5'-tetramethylbenzidine (TMB) into blue ox-TMB in the presence of H2O2. After adding ascorbic acid (AA) to above system, the blue solution faded. Based on this phenomenon, a colorimetric method for visual monitoring of H2O2 and AA was developed. Meanwhile, the fluorescence of Fe-CQDs can be quenched by the formed ox-TMB via inner filter effect (IFE), followed by the recovery upon the addition of AA. Therefore, Fe-CQDs can be acted as a fluorescent probe to detect H2O2 and AA through the "on-off-on" mode. Furthermore, the dual-recognition methods based on Fe-CQDs were used to measure AA content in beverage samples. Thus, this work would shed much light on converting waste into biomass CQDs and their potential applications in biomolecular detection.


Assuntos
Ácido Ascórbico , Pontos Quânticos , Ácido Ascórbico/análise , Café , Peroxidase , Carbono , Colorimetria/métodos , Peróxido de Hidrogênio , Antioxidantes
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