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1.
J Cell Mol Med ; 28(8): e18294, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38652109

RESUMO

Forkhead box protein 1 (FOXP1) serves as a tumour promoter or suppressor depending on different cancers, but its effect in oesophageal squamous cell carcinoma has not been fully elucidated. This study investigated the role of FOXP1 in oesophageal squamous cell carcinoma through bioinformatics analysis and experimental verification. We determined through public databases that FOXP1 expresses low in oesophageal squamous cell carcinoma compared with normal tissues, while high expression of FOXP1 indicates a better prognosis. We identified potential target genes regulated by FOXP1, and explored the potential biological processes and signalling pathways involved in FOXP1 in oesophageal squamous cell carcinoma through GO and KEGG enrichment, gene co-expression analysis, and protein interaction network construction. We also analysed the correlation between FOXP1 and tumour immune infiltration levels. We further validated the inhibitory effect of FOXP1 on the proliferation of oesophageal squamous cell carcinoma cells through CCK-8, colony formation and subcutaneous tumour formation assays. This study revealed the anticarcinogenic effect of FOXP1 in oesophageal squamous cell carcinoma, which may serve as a novel biological target for the treatment of tumour.


Assuntos
Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fatores de Transcrição Forkhead , Regulação Neoplásica da Expressão Gênica , Proteínas Repressoras , Humanos , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Linhagem Celular Tumoral , Animais , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Biologia Computacional/métodos , Camundongos , Prognóstico , Mapas de Interação de Proteínas/genética , Transdução de Sinais , Redes Reguladoras de Genes , Camundongos Nus
2.
J Am Chem Soc ; 146(19): 13546-13557, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38690842

RESUMO

Glycidic esters represent pivotal constituents in synthetic chemistry, offering enhanced versatility for tailoring toward a diverse array of molecular targets in comparison with simple epoxides. While considerable progress has been made in the asymmetric synthesis of trans- and trisubstituted glycidic esters, achieving enantioselective preparation of cis-glycidic esters has remained a long-standing challenge. Here, we demonstrate a selectivity-predictable modular platform for the asymmetric synthesis of cis-glycidic esters via a novel dinuclear (salen)titanium(III)-catalyzed radical-type kinetic resolution (KR) approach. This radical KR protocol operates under mild conditions and demonstrates a wide substrate scope, facilitating the synthesis of alkyl- and aryl-substituted cis-glycidic esters with high levels of regioselectivity and enantioselectivity, along with hydroxy ester byproducts representing synthetically valuable motifs as well. This study presents a unique exploration of radical-type KR applied to epoxides, effectively overcoming the steric challenges inherent in conventional nucleophilic-type methodologies typically employed in epoxide chemistry.

3.
J Am Chem Soc ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584396

RESUMO

Because of their innate chemical stability, the ubiquitous perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been dubbed "forever chemicals" and have attracted considerable attention. However, their stability under environmental conditions has not been widely verified. Herein, perfluorooctanoic acid (PFOA), a widely used and detected PFAS, was found to be spontaneously degraded in aqueous microdroplets under room temperature and atmospheric pressure conditions. This unexpected fast degradation occurred via a unique multicycle redox reaction of PFOA with interfacial reactive species on the droplet surface. Similar degradation was observed for other PFASs. This study extends the current understanding of the environmental fate and chemistry of PFASs and provides insight into aid in the development of effective methods for removing PFASs.

4.
Int J Cancer ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863244

RESUMO

There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.

5.
Anal Chem ; 96(11): 4514-4520, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38447135

RESUMO

Nanoplastics have attracted much attention due to their potential hazards. However, analysis of nanoplastics remains challenging. In this study, ionic liquid-assisted cloud-point extraction (IL-assisted CPE) was developed to enrich nanoplastics in the aqueous environment and further coupled with electromagnetic heating pyrolysis mass spectrometry. The use of trace ILs improves the extraction efficiency of CPE for nanoplastics. The effects of ILs (types, contents), nanoplastic properties (type, size), and environmental factors (aging time, humic acid content) were systematically investigated to evaluate the applicability. The limits of detection of poly(methyl methacrylate) (PMMA) and polystyrene (PS) were determined to be 1.78 and 2.67 µg/L, respectively. Real environmental samples including lake water, rainwater, and influent and effluent from wastewater treatment plant were analyzed with good accuracy (79.58-116.87%) and satisfactory precision (RSD ≤ 11.99%). A possible mechanism for ILs being absorbed into the ordered surfactant micellar and generating larger micelles to synergically enclose hydrophobic nanoplastics was proposed. This work provides a simple and efficient approach to the extraction and analysis of nanoplastics in aqueous environments.

6.
Plant Cell Environ ; 47(4): 1141-1159, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38098148

RESUMO

Intercropping is a widely recognised technique that contributes to agricultural sustainability. While intercropping leguminous green manure offers advantages for soil health and tea plants growth, the impact on the accumulation of theanine and soil nitrogen cycle are largely unknown. The levels of theanine, epigallocatechin gallate and soluble sugar in tea leaves increased by 52.87% and 40.98%, 22.80% and 6.17%, 22.22% and 29.04% in intercropping with soybean-Chinese milk vetch rotation and soybean alone, respectively. Additionally, intercropping significantly increased soil amino acidnitrogen content, enhanced extracellular enzyme activities, particularly ß-glucosidase and N-acetyl-glucosaminidase, as well as soil multifunctionality. Metagenomics analysis revealed that intercropping positively influenced the relative abundances of several potentially beneficial microorganisms, including Burkholderia, Mycolicibacterium and Paraburkholderia. Intercropping resulted in lower expression levels of nitrification genes, reducing soil mineral nitrogen loss and N2 O emissions. The expression of nrfA/H significantly increased in intercropping with soybean-Chinese milk vetch rotation. Structural equation model analysis demonstrated that the accumulation of theanine in tea leaves was directly influenced by the number of intercropping leguminous green manure species, soil ammonium nitrogen and amino acid nitrogen. In summary, the intercropping strategy, particularly intercropping with soybean-Chinese milk vetch rotation, could be a novel way for theanine accumulation.


Assuntos
Camellia sinensis , Fabaceae , Glutamatos , Fabaceae/metabolismo , Esterco , Leguminas , Solo/química , Camellia sinensis/metabolismo , Glycine max , Chá , Nitrogênio/metabolismo
7.
Opt Express ; 32(9): 15645-15657, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38859210

RESUMO

The spectral emission of laser-induced plasma in water has a broadband continuum containing ultraviolet light, which can be used as a novel light source for the degradation of organic compounds. We studied the degradation process of the organic dye Rhodamine B (RhB) using plasma light source excited by the "Laser + Fe" mode. Spectral analysis and reaction kinetics modelling were used to study the degradation mechanism. The degradation process using this light source could be divided into two stages. The initial stage was mainly photocatalytic degradation, where ultraviolet light broke the chemical bond of RhB, and then RhB was degraded by the strong oxidising ability of ·OH. As the iron and hydrogen ion concentrations increased, the synergistic effect of photocatalysis and the Fenton reaction further enhanced the degradation rate in the later stage. The plasma excited by the "Laser + Fe" mode achieved photodegradation by effectively enhancing the ultraviolet wavelength ratio of the emission spectrum and triggered the Fenton reaction to achieve rapid organic matter degradation. Our findings indicate that the participation of the Fenton reaction can increase the degradation rate by approximately 10 times. Besides, the impact of pH on degradation efficiency demonstrates that both acidic and alkaline environments have better degradation effects than neutral conditions; this is because acidic environments can enhance the Fenton reaction, while alkaline environments can provide more ·OH.

8.
Opt Lett ; 49(15): 4262-4265, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090909

RESUMO

Topological edge state, a unique mode for manipulating electromagnetic waves (EMs), has been extensively studied in both fundamental and applied physics. Up to now, the work on topological edge states has focused on manipulating linearly polarized waves. Here, we realize chirality-dependent topological edge states in one-dimensional photonic crystals (1DPCs) to manipulate circularly polarized waves. By introducing the magneto-electric coupling term (chirality), the degeneracy Dirac point (DP) is opened in PCs with symmetric unit cells. The topological properties of the upper and lower bands are different in the cases of left circularly polarized (LCP) and right circularly polarized (RCP) waves by calculating the Zak phase. Moreover, mapping explicitly 1D Maxwell's equations to the Dirac equation, we demonstrate that the introduction of chirality can lead to different topological properties of bandgaps for RCP and LCP waves. Based on this chirality-dependent topology, we can further realize chirality-dependent topological edge states in photonic heterostructures composed of two kinds of PCs. Finally, we propose a realistic structure for the chirality-dependent topological edge states by placing metallic helixes in host media. Our work provides a method for manipulating topological edge states for circularly polarized waves, which has a broad range of potential applications in designing optical devices including polarizers, filters, and sensors with robustness against disorder.

9.
Chemphyschem ; 25(12): e202400078, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38526528

RESUMO

Interactions between oxygen molecules play an important role in atmospheric chemistry and hypersonic flow chemistry in atmospheric entries. Recently, high-quality ab initio potential energy surface (PES) of the quintet O4 was reported by Paukku et al. [J. Chem. Phys. 147, 034301 (2017)]. 10543 configurations were sampled and calculated at the level of MS-CASPT2/maug-cc-pVTZ with scaled external correlation. The PES was fitted to a many-body (MB) form with the many-body part described by the permutationally invariant polynomial approach (MB-PIP). In this work, the PIP-Neural Network (PIP-NN) and MB-PIP-NN methods were used to refit the PES based on the same data by Paukku et al. Three PESs were compared. It was found that the performances differ significantly in the O+O3 region as well as in the long-range region. Therefore, additional 1300 points were sampled, and the efficient compressed-state multistate pair-density functional theory (CMS-PDFT) was used to calculate the electronic structure of these 1300 points and 10543 points by Paukku et al. Then, a completely new quintet PES was fitted using the MB-PIP-NN method. Based on this PES, the quasi-classical trajectory (QCT) approach was used to reveal all possible reaction channels for hyperthermal O2-O2 collisions.

10.
Langmuir ; 40(23): 12097-12106, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38814133

RESUMO

Antimony sulfide (Sb2S3) has been recognized as a catalytic material for splitting water by solar energy because of its suitable narrow band gap, high absorption coefficient, and abundance of elements. However, many deep-level defects in Sb2S3 result in a significant recombination of photoexcited electron-hole pairs, weakening its photoelectrochemical performance. Here, by using a simple hydrothermal and spin-coating method, we fabricated a step-scheme heterojunction of Sb2S3/α-Fe2O3 to improve the photoelectrochemical performance of pure Sb2S3. Our Sb2S3/α-Fe2O3 photoanode has a photocurrent density of 1.18 mA/cm2 at 1.23 V vs reversible hydrogen electrode, 1.39 times higher than that of Sb2S3 (0.84 mA/cm2). In addition, our heterojunction has a lower onset potential, a higher absorbance intensity, a higher incident photon-to-current conversion efficiency, a higher applied bias photon-to-current efficiency, and a lower charge transfer resistance compared to pure Sb2S3. Based on ultraviolet photoelectron spectroscopy, we constructed a step-scheme band structure of Sb2S3/α-Fe2O3 to explain its photoelectrochemical enhancement. This work offers a promising strategy to optimize the performance of Sb2S3 photoelectrodes for solar-driven photoelectrochemical water splitting.

11.
Nutr Cancer ; 76(4): 335-344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379140

RESUMO

AIM: Malnutrition is prevalent in hepatocellular carcinoma (HCC) patients, linked to poor outcomes, necessitating early intervention. This study aimed to investigate malnutrition in HCC patients, assess Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA) vs. Global Leadership Initiative on Malnutrition (GLIM) criteria, and identify independent risk factors. METHOD: A cross-sectional retrospective study was conducted on 207 patients with HCC. Nutritional screening/assessment results and blood samples were collected within 72 h of admission. This study assessed the prevalence of malnutrition using the NRS-2002 and PG-SGA and retrospectively using the GLIM criteria. The performance of the screening tools was evaluated using kappa (K) values. Logistic regression analyses were performed to determine whether laboratory parameters were associated with malnutrition as identified by the GLIM criteria. RESULTS: Of the participants, 30.4% were at risk of malnutrition according to NRS-2002. The agreement between the NRS-2002 and GLIM criteria was substantial. The GLIM criteria and PG-SGA diagnosed malnutrition in 43 and 54.6% of the participants, respectively. Age, anemia, and ascites correlated with malnutrition in regression. CONCLUSION: The GLIM criteria, along with NRS-2002 and PG-SGA, aid in diagnosing malnutrition in HCC patients. Recognizing risk factors improves accuracy, enabling timely interventions for better outcomes.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Desnutrição , Humanos , Estado Nutricional , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/epidemiologia , Prevalência , Estudos Retrospectivos , Estudos Transversais , Liderança , Avaliação Nutricional , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/epidemiologia , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/etiologia , Fatores de Risco
12.
J Theor Biol ; 581: 111739, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38280542

RESUMO

Elucidating the mechanism of effect of phosphate (PO43-) uptake on the growth of algal cells helps understand the frequent outbreaks of algal blooms caused by eutrophication. In this study, we develop a comprehensive mathematical model that incorporates two stages of PO43- uptake and accounts for transport time delay. The model parameter values are determined by fitting experimental data of Prorocentrum donghaiense and the model is validated using experimental data of Karenia mikimotoi. The numerical results demonstrate that the model successfully captures the general characteristics of algal growth and PO43- uptake under PO43- sufficient conditions. Significantly, the experimental and mathematical findings suggest that the time delay associated with the transfer of PO43- from the surface-adsorbed PO43- (Ps) pool to the intracellular PO43- (Pi) pool may serve as a physiologically plausible mechanism leading to oscillations of algal cell quota. These results have important implications for resource managers, enabling them to predict and deepen their understanding of harmful algal blooms.


Assuntos
Dinoflagellida , Fosfatos , Proliferação Nociva de Algas , Cinética , Modelos Teóricos
13.
Analyst ; 149(5): 1496-1501, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38315553

RESUMO

Cathodic electrochemiluminescence (ECL) of a luminol (or its analogues)-dissolved oxygen (O2) system is an ideal alternative to ECL of the traditional luminol-hydrogen peroxide (H2O2) system, which can efficiently avoid the self-decomposition of H2O2 at room temperature. However, the mechanism for the generation of cathodic ECL by the luminol (or its analogues)-O2 system is still ambiguous. Herein, we report the study of cathodic ECL generation by the L012-O2 system at a glassy carbon electrode (GCE). The types of reactive oxygen species (ROS) involved generated during ECL reactions were verified. A possible reaction mechanism for the system was proposed and the rate constants of related reactions were estimated. Furthermore, several intermediates of L012 involved in the proposed pathways were validated by electrochemistry-coupled mass spectrometry. Finally, the cathodic ECL system was successfully used for measuring the antioxidant capacity of commercial juice with Trolox as a standard.


Assuntos
Antioxidantes , Técnicas Biossensoriais , Luminol/química , Peróxido de Hidrogênio/química , Medições Luminescentes/métodos , Eletrodos , Oxigênio/química , Técnicas Eletroquímicas , Limite de Detecção
14.
Inorg Chem ; 63(4): 2174-2184, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38235735

RESUMO

Recently, all-inorganic copper(I) metal halides have emerged as promising optical materials due to their high light emission efficiencies. This work details the crystal structure of the two hybrid organic-inorganic metal halides [(CH3)3SO]M2I3 (M = Cu and Ag) and their alloyed derivatives [(CH3)3SO]Cu2-xAgxI3 (x = 0.2; 1.25), which were obtained by incorporating trimethylsulfoxonium organic cation (CH3)3SO+ in place of Cs+ in the yellow-emitting all-inorganic CsCu2I3. These compounds are isostructural and centrosymmetric with the space group Pnma, featuring one-dimensional edge-sharing [M2I3]- anionic double chains separated by rows of (CH3)3SO+ cations. Based on density functional theory calculations, the highest occupied molecular orbitals (HOMOs) of [(CH3)3SO]M2I3 (M = Cu and Ag) are dominated by the Cu or Ag d and I p orbitals, while the lowest unoccupied molecular orbitals (LUMOs) are Cu or Ag s and I p orbitals. [(CH3)3SO]Cu2I3 single crystals exhibit a semiconductor resistivity of 9.94 × 109 Ω·cm. Furthermore, a prototype [(CH3)3SO]Cu2I3 single-crystal-based X-ray detector with a detection sensitivity of 200.54 uCGy-1 cm-2 (at electrical field E = 41.67 V/mm) was fabricated, indicating the potential use of [(CH3)3SO]Cu2I3 for radiation detection applications.

15.
Cell Biol Toxicol ; 40(1): 1, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252352

RESUMO

Acetaminophen (APAP) stands as the predominant contributor to drug-induced liver injury (DILI), and limited options are available. ß-Arrestin1 (ARRB1) is involved in numerous liver diseases. However, the role of ARRB1 in APAP-induced liver injury remained uncertain. Wild-type (WT) and ARRB1 knockout (KO) mice were injected with APAP and sacrificed at the indicated times. The histological changes, inflammation, endoplasmic reticulum (ER) stress, and apoptosis were then evaluated. Hepatic cell lines AML-12 and primary hepatocytes were used for in vitro analyses. Systemic ARRB1-KO mice were susceptible to APAP-induced hepatotoxicity, as indicated by larger areas of centrilobular necrosis area and higher levels of ALT, AST, and inflammation level. Moreover, ARRB1-KO mice exhibited increased ER stress (indicated by phosphorylated α subunit of eukaryotic initiation factor 2 (p-eIF2α)-activating transcription factor 4 (ATF4)-CCAAT-enhancer-binding protein homologous protein (CHOP)) and apoptosis (indicated by cleaved caspase 3). Further rescue experiments demonstrated that the induction of apoptosis was partially mediated by ER stress. Overexpression of ARRB1 alleviated APAP-induced ER stress and apoptosis. Moreover, co-IP analysis revealed that ARRB1 directly bound to p-eIF2α and eIF2α. ARRB1 protected against APAP-induced hepatoxicity through targeting ER stress and apoptosis. ARRB1 is a prospective target for treating APAP-induced DILI.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Estresse do Retículo Endoplasmático , beta-Arrestina 1 , Animais , Camundongos , Acetaminofen/toxicidade , Fator 4 Ativador da Transcrição , Apoptose , Inflamação , Camundongos Knockout , Necrose , beta-Arrestina 1/genética , Fator de Iniciação 2 em Eucariotos
16.
Environ Sci Technol ; 58(20): 8643-8653, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38676641

RESUMO

Antimicrobial nanomaterials frequently induce inflammatory reactions within lung tissues and prompt apoptosis in lung cells, yielding a paradox due to the inherent anti-inflammatory character of apoptosis. This paradox accentuates the elusive nature of the signaling cascade underlying nanoparticle (NP)-induced pulmonary inflammation. In this study, we unveil the pivotal role of nano-microflora interactions, serving as the crucial instigator in the signaling axis of NP-induced lung inflammation. Employing pulmonary microflora-deficient mice, we provide compelling evidence that a representative antimicrobial nanomaterial, silver (Ag) NPs, triggers substantial motility impairment, disrupts quorum sensing, and incites DNA leakage from pulmonary microflora. Subsequently, the liberated DNA molecules recruit caspase-1, precipitating the release of proinflammatory cytokines and activating N-terminal gasdermin D (GSDMD) to initiate pyroptosis in macrophages. This pyroptotic cascade culminates in the emergence of severe pulmonary inflammation. Our exploration establishes a comprehensive mechanistic axis that interlinks the antimicrobial activity of Ag NPs, perturbations in pulmonary microflora, bacterial DNA release, macrophage pyroptosis, and consequent lung inflammation, which helps to gain an in-depth understanding of the toxic effects triggered by environmental NPs.


Assuntos
Pneumonia , Piroptose , Piroptose/efeitos dos fármacos , Camundongos , Animais , Pneumonia/induzido quimicamente , Pneumonia/patologia , Prata/toxicidade , Nanopartículas Metálicas/toxicidade , Macrófagos/efeitos dos fármacos , Inflamação
17.
Int J Gynecol Cancer ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38658024

RESUMO

BACKGROUND: Platinum-resistant, recurrent ovarian cancer has an abysmal prognosis with limited treatment options. Poly-(ADP-ribose)-polymerase (PARP), angiogenesis, and immune checkpoint inhibitors might improve the outcomes of platinum-resistant, recurrent ovarian cancer, but accurate patient selections for those therapies remain a significant clinical challenge. PRIMARY OBJECTIVE: To evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer. STUDY HYPOTHESIS: A precision medicine combination of PARP inhibitors, anti-angiogenic therapy, immunotherapy, and chemotherapy will improve disease outcomes of platinum-resistant, recurrent ovarian cancer by accounting for genomic and immunologic features. TRIAL DESIGN: The BRIGHT Trial is a prospective, open-label, multicenter, phase II, umbrella study planning to enroll 160 patients with serous, endometrioid, or clear cell platinum-resistant, recurrent ovarian cancer from 11 clinical centers in China. Patients are assigned to one of three experimental arms based on biomarkers. Patients with BRCA1/2 mutations will receive pamiparib plus bevacizumab (arm 1, n=40) regardless of CD8+ tumor-infiltrating lymphocytes count. Patients with wild-type BRCA1/2 (BRCAwt) and ≥3 CD8+ tumor-infiltrating lymphocytes count will receive the combination of tislelizumab, bevacizumab, and nab-paclitaxel (arm 2, n=50), while BRCAwt patients with <3 CD8+ tumor-infiltrating lymphocytes count will receive bevacizumab plus dose-dense nab-paclitaxel (arm 3, n=50). After completing patient enrollment in arm 2, another 20 BRCAwt patients with ≥3 CD8+ tumor-infiltrating lymphocytes count will be included as an arm 2 expansion. Treatment will continue until disease progression or intolerable toxicity, and all adverse events will be recorded. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients include those aged ≥18 with serous, endometrioid, or clear cell ovarian cancer, platinum-resistant recurrence, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. PRIMARY ENDPOINT: Objective response rate (ORR) assessed by the investigators by the RECIST 1.1 criteria. SAMPLE SIZE: 160 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Recruitment is estimated to be completed by 2024 and results may be published by 2027. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05044871.

18.
J Chem Phys ; 160(17)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38748014

RESUMO

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air-water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system.


Assuntos
Poluição do Ar em Ambientes Fechados , Ácidos Graxos , Ácidos Graxos/química , Ácido Hipocloroso/química , Culinária , Fosfolipídeos/química
19.
Cell Biochem Funct ; 42(4): e4078, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38898665

RESUMO

Zinc finger proteins (ZNFs) play a significant role in the initiation and progression of tumors. Nevertheless, the specific contribution of ZNF610 to lung adenocarcinoma (LUAD) remains poorly understood. This study sought is to elucidate the role of ZNF610 in LUAD. Transcript data of LUAD were obtained from The Cancer Genome Atlas Program (TCGA) database and processed via R program. The expression of ZNF610 was assessed in various cell lines. To compare the proliferative capacity of cells with or without ZNF610 silencing, CCK8, cell colony formation assay, and Celigo label-free cell counting assay were employed. Furthermore, transwell migration and invasion assays were conducted to evaluate the migratory and invasive abilities of the cells. The expression levels of genes and proteins were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot techniques. In different LUAD cells, the expression level of ZNF610 was found to be significantly higher in LUAD cells compared to MRC-5 and BASE-2B cells. Moreover, the silencing of ZNF610 resulted in a decrease in cell proliferation and migration abilities. Additionally, the apoptosis rate of cells increased upon silencing ZNF610. Notably, the proportion of cells in the G0/G1 phase increased, while the proportion of cells in the S phase decreased following ZNF610 silencing. Finally, ß-catenin and snail were identified as downstream targets of ZNF610 in cells. Our findings suggest that silencing ZNF610 could inhibit LUAD cell proliferation and migration, possibly through the downregulation of ß-catenin and snail.


Assuntos
Adenocarcinoma de Pulmão , Movimento Celular , Proliferação de Células , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Inativação Gênica , Linhagem Celular Tumoral , Apoptose
20.
Clin Lab ; 70(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38965969

RESUMO

BACKGROUND: This study aimed to understand the clinical characteristics of pulmonary abscess caused by Streptococcus constellatus infection. METHODS: The clinical manifestations, laboratory examination, drug sensitivity, chest CT manifestations, and treatment and prognosis of patients with pulmonary abscess caused by Streptococcus constellatus infection were retrospectively collected and analyzed. RESULTS: A total of 9 cases of pulmonary abscess caused by Streptococcus constellatus infection were confirmed; one case was confirmed by traditional cultures, while metagenomic next-generation sequencing (mNGS) confirmed the other 8 cases. All of the 9 patients had different degrees of cough, sputum, fever, chest pain, and/or dyspnea, and the physical examination showed fast breathing, reduced respiratory sound, or moist rales on the affected side. In laboratory tests, 8 patients had elevated white blood cells and hypoproteinemia upon admission. Blood gas analysis showed an oxygenation index < 300. The antimicrobial susceptibility testing results in 1 patient with culture-confirmed pathogen diagnosis showed that Streptococcus constellatus was susceptible to ampicillin, penicillin G, cefotaxime, ceftriaxone, cefepime, meropenem, chloramphenicol, linezolid, levofloxacin, and vancomycin and resistant to tetracycline and clindamycin. Relevant antibiotic resistance genes were not detected by mNGS in the 8 patients with negative culture and positive mNGS results. A chest CT showed lung consolidation or cavity formation in 9 patients admitted to the hospital, and 5 patients had pleural effusion. 3 cases were admitted to the respiratory intensive care unit (RICU) and 6 cases were admitted to the general ward. There were 3 cases of nasal catheter oxygen inhalation, 1 case of mask oxygen inhalation, and 5 cases of non-invasive ventilator assisted ventilation. All patients received penicillin or respiratory quinolones anti-infection therapy, and 3 cases were treated with a thoracic closed drainage tube. All patients were discharged from the hospital after improvement, and the hospital stay was 15 - 23 days. CONCLUSIONS: Patients with pulmonary abscess caused by Streptococcus constellatus infection have an urgent condition and rapid progression. It is helpful to use mNGS combined with traditional culture as soon as possible to identify the pathogenic bacteria. Penicillin antibiotics should be the first choice for pulmonary abscess caused by a suspected Streptococcus constellatus infection. If a patient´s condition worsens during the treatment, especially for patients who have lesions involving the interlobar fissure or pleura, compressive atelectasis caused by pleural fluid formation or an increase in the amount of pleural effusion needs to be highly suspected.


Assuntos
Antibacterianos , Abscesso Pulmonar , Infecções Estreptocócicas , Streptococcus constellatus , Humanos , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Abscesso Pulmonar/microbiologia , Abscesso Pulmonar/diagnóstico , Abscesso Pulmonar/tratamento farmacológico , Streptococcus constellatus/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Idoso , Adulto , Testes de Sensibilidade Microbiana , Tomografia Computadorizada por Raios X , Sequenciamento de Nucleotídeos em Larga Escala
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