RESUMO

The metastasis of hepatocellular carcinoma (HCC) poses a significant threat to the survival of patients. G protein-coupled receptor 56 (GPR56) has garnered extensive attention within malignant tumor research and plays a crucial role in cellular surface signal transmission. Nonetheless, its precise function in HCC remains ambiguous. Our investigation reveals a notable rise in GPR56 expression levels in human HCC cases, with heightened GPR56 levels correlating with unfavorable prognoses. GPR56 regulates TGF-ß pathway by interacting with TGFBR1, thereby promoting HCC metastasis. At the same time, GPR56 is subject to regulation by the canonical cascade of TGF-ß signaling, thereby establishing a positive feedback loop. Furthermore, the combination application of TGFBR1 inhibitor galunisertib (GAL) and GPR56 inhibitor Dihydromunduletone (DHM), significantly inhibits HCC metastasis. Interventions towards this signaling pathway could offer a promising therapeutic approach to effectively impede the metastasis of GPR56-mediated HCC.

Assuntos

Carcinoma Hepatocelular , Neoplasias Hepáticas , Metástase Neoplásica , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores Acoplados a Proteínas G , Transdução de Sinais , Fator de Crescimento Transformador beta , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Fator de Crescimento Transformador beta/metabolismo , Animais , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Linhagem Celular Tumoral , Camundongos , Camundongos Nus , Quinolinas/farmacologia , Regulação Neoplásica da Expressão Gênica , Masculino , Pirazóis

RESUMO

To investigate the effects of antibiotic exposure on the prognosis of patients with advanced metastatic non-small cell lung cancer (m-NSCLC) who received immune checkpoint inhibitors (ICIs). This study retrospectively included 199 patients diagnosed with m-NSCLC in Shandong Cancer Hospital and Institute from December 2017 to October 2021, all patients received ICIs for the first time. The basic clinical characteristics of patients before the first treatment of ICIs, whether antibiotics were used during treatment, progression-free survival (PFS), and overall survival (OS) were collected. The survival among different groups was compared by the Kaplan-Meier method. The median follow-up time of m-NSCLC patients was 33.79 months, mPFS was 11.67 months, and mOS was 21.55 months. Univariate analysis showed that antibiotic use, radiotherapy, and targeted drug resistance influenced PFS and OS (P < 0.05). Multivariate analysis showed that antibiotic use, radiotherapy, and targeted resistance remained independent factors of PFS, and targeted resistance was an independent factor of OS (P < 0.05). Subgroup analysis found that antibiotic use within 30 days before and after immunotherapy could decrease the PFS and OS (P < 0.05). Kaplan-Meier analysis showed that patients without radiotherapy had shorter PFS (mPFS, 12.89 vs. 8.13 months; P = 0.0258) and OS (mOS, 26.94 vs. 16.43 months; P = 0.0465). The mPFS (16.17 vs. 9.19 months; P = 0.0151) and mOS (27.27 vs. 18.65 months; P = 0.0437) of patients in the antibiotic group were shorter. Patients in the targeted drug-resistant group had shorter PFS (mPFS, 40.66 vs. 7.77 months, P < 0.001) and OS (mOS, 41.98 vs. 16.89 months, P < 0.001) compared with patients who did not receive targeted treatment. Antibiotics and radiation therapy are associated with the prognosis of m-NSCLC who are newly treated with ICIs. Effectively reducing antibiotic use in 1 month before and after ICIs treatment may help improve the immunotherapy efficacy of patients with m-NSCLC.

RESUMO

In this work, a highly efficient rongalite/iodine-mediated oxime formation reaction for the preparation of thiohydroximic acids from methyl ketones by employing copper nitrate as the [NO] reagent has been developed. Notably, copper nitrate participated as both a catalyst and the mild oximation reagent in the transformation. This reaction is highly efficient and facile, with a broad substrate scope, especially for fused ring skeleton substrates, heterocyclic skeleton substrates, and acetyl-substituted natural products. Mechanistic studies revealed that copper nitrate might be converted into a NO2 radical or the NO2 radical dimeric forms as an ion-pair equivalent to participate in the transformation.

RESUMO

Parabens are preservatives used in personal care products, cosmetics, and pharmaceuticals. Steroid 5α-reductase 1 (SRD5A1) catalyzes the conversion of testosterone to dihydrotestosterone and is present in the brain, contributing to neurosteroid production. This study aimed to assess the effects of nine paraben preservatives on SRD5A1 in human SF126 glioblastoma cell and rat brain microsomes, particularly focusing on dihydrotestosterone production in SF126 cells. The results showed that methyl, ethyl, propyl, butyl, hexyl, heptyl, nonyl, phenyl, and benzyl paraben inhibited human SRD5A1, with nonylparaben having the strongest effect (7.59 µM). Additionally, kinetic analysis indicated that parabens acted as mixed/noncompetitive inhibitors, leading to a significant decrease in dihydrotestosterone production in SF126 cells. While rat SRD5A1 exhibited lower sensitivity to parabens, docking analysis revealed that parabens bind to the NADPH-binding site of both human and rat SRD5A1. In conclusion, these results highlight the inhibitory effects of paraben preservatives on SRD5A1 and elucidate their binding mechanisms, underscoring their role in hormone production.

RESUMO

Both the transforming growth factor beta (TGF-ß) signaling pathway and N6-methyladenosine (m6A) modification for mRNA play an important role in hepatocellular carcinoma (HCC) progression. However, the relationship between TGF-ß and m6A in hepatocellular carcinoma (HCC) remains unclear. Here, it is found that TGF-ß can promote the liquid phase separation of METTL3, which further leads to the reduction of mRNA stability of ITIH1. As a secreted protein, ITIH1 can act as a ligand of integrin α5ß1 to antagonize fibronectin, induce the inhibition of focal adhesion kinase signaling pathway, and inhibit the progression of HCC. In the preclinical model (mouse model, patient-derived organoid, patient-derived xenografts), purified recombinant ITIH1 (r-ITIH1) protein can be targeted for HCC. More importantly, r-ITIH1 can play a synergistic role in targeting HCC with TGF-ß inhibitor. The downstream ITIH1 regulatory mechanism of TGF-ß and m6A modification is revealed, and ITIH1 can be translational as a potential target for HCC.

RESUMO

The development of electrocatalysts is of vital importance to the OER. In this work, an optimized MOF electrode, Ir-NiFe-btz/NF, was synthesized by incorporating ultralow levels of Ir nanoparticles into an ionic bimetallic MOF. Under alkaline conditions, the prepared MOF electrode demonstrated outstanding OER activity and stability with a low overpotential of 182 mV to reach 10 mA cm-2 and no obvious increase of overpotential in a chronovoltammetry test over 100 hours at 100 mA cm-2.

RESUMO

Pulmonary hypertension (PH) is a serious pulmonary vascular disease characterized by vascular remodeling. Circular RNAs (CircRNAs) play important roles in pulmonary hypertension, but the mechanism of PH is not fully understood, particularly the roles of circRNAs located in the nucleus. Circ-calmodulin 4 (circ-calm4) is expressed in both the cytoplasm and the nucleus of pulmonary arterial smooth muscle cells (PASMCs). This study aimed to investigate the role of endonuclear circ-calm4 in PH and elucidate its underlying signaling pathway in ferroptosis. Immunoblotting, quantitative real-time polymerase chain reaction (PCR), malondialdehyde (MDA) assay, immunofluorescence, iron assay, dot blot, and chromatin immunoprecipitation (ChIP) were performed to investigate the role of endonuclear circ-calm4 in PASMC ferroptosis. Increased endonuclear circ-calm4 facilitated ferroptosis in PASMCs under hypoxic conditions. We further identified the cartilage oligomeric matrix protein (COMP) as a downstream effector of circ-calm4 that contributed to the occurrence of hypoxia-induced ferroptosis in PASMCs. Importantly, we confirmed that endonuclear circ-calm4 formed circR-loops with the promoter region of the COMP gene and negatively regulated its expression. Inhibition of COMP restored the phenotypes related to ferroptosis under hypoxia stimulation combined with antisense oligonucleotide (ASO)-circ-calm4 treatment. We conclude that the circ-calm4/COMP axis contributed to hypoxia-induced ferroptosis in PASMCs and that circ-calm4 formed circR-loops with the COMP promoter in the nucleus and negatively regulated its expression. The circ-calm4/COMP axis may be useful for the design of therapeutic strategies for protecting cellular functionality against ferroptosis and pulmonary hypertension.

Assuntos

Ferroptose , Miócitos de Músculo Liso , Artéria Pulmonar , RNA Circular , Animais , Masculino , Camundongos , Proteína de Matriz Oligomérica de Cartilagem/genética , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Hipóxia Celular/genética , Núcleo Celular/metabolismo , Células Cultivadas , Ferroptose/genética , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Transdução de Sinais

RESUMO

BACKGROUND: Small airway dysfunction not only affects asthma control, but also has adverse effects on the psychological and/or social activities of asthma patients. However, few long-term observational studies have explored the complex relationship between small airway dysfunction and asthma control and health-related quality of life in patients with asthma exacerbations. METHODS: The study recruited 223 patients with exacerbations of asthma (i.e. those with at least one asthma attack over the past year) and 228 patients without exacerbations of asthma (i.e. those without asthma attacks over the past year). We evaluated SAD in patients with asthma exacerbations using impulse oscillometry method. At each evaluation time point within one year of follow-up, the attending physician conducts a case investigation of the patients. We analyzed the correlation between SAD and general characteristics (age, obesity, smoking history), type 2 inflammation (blood eosinophils, exhaled nitric oxide), FEV1, as well as asthma control (ACT) and health-related quality of life (mini-AQLQ) in patients with asthma exacerbations, and constructed a structural equation model to evaluate the causality of these clinical variables. RESULTS: The SAD prevalence in patients with asthma exacerbation is as high as 75%. SAD is connected with poor asthma control and poor health-related quality of life. The structural equation model indicates that age, obesity, FeNO, and FEV1 are independent predictive factors of SAD. SAD is the main determinant factor of asthma control, which in turn affected health-related quality of life. FEV1 and age directly affect asthma control and affect health-related quality of life through asthma control. In addition, there is a bidirectional relationship between FEV1 and small airway dysfunction and between asthma control and health-related quality of life. CONCLUSIONS: Small airways are involved from an early stage in asthma. Abnormal function of the small airways can significantly increase airway resistance in asthma patients, while worsening their clinical symptoms. In addition, aging is also a key risk factor for asthma control. Especially, small airway dysfunction links asthma control with health-related quality of life.

Assuntos

Asma , Qualidade de Vida , Humanos , Asma/epidemiologia , Asma/fisiopatologia , Asma/diagnóstico , Asma/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Progressão da Doença , Idoso , Seguimentos

RESUMO

Background and Aims Abnormalities in tryptophan (TRP) metabolism induce abdominal pain and intestinal motility disorders. The study of TRP metabolism in diarrhea-predominant-irritable bowel syndrome (IBS-D) is important for the prevention, diagnosis, and treatment of this disease. In this study, a rapid and reliable ultra performance liquid chromatography-mass spectrometry (UPLC-MS) method was established to quantify tryptophan-kynurenine (TRP-Kyn) metabolism in the colon of a rat model with IBS-D. Methods The proteins were precipitated by methanol, chromatographically separated on a Welch Ultimate® Polar RP column with a gradient elution for 12 min, and detected by high-resolution tandem mass spectrometry. Pure water were used as an alternative mechanism for standard calibration, and the stable structural analog 2-Cl-Phe was used as an internal standard. Results Within a certain range, the r of TRP, kynurenine (Kyn) and quinolinic acid (QA), kynurenic acid (KA) are greater than 0.99, were found to be accurate and precise. The metabolism of TRP was significantly up-regulated along the Kyn pathway in the IBS-D model rats and normalized after treatment with pivacurium bromide. Conclusion This study investigates the mechanisms of IBS-D gastrointestinal dysfunction from the perspective of colonic TRP metabolism, and also provides new directions for the diagnosis and therapeutic approach of this disease.

Assuntos

Modelos Animais de Doenças , Síndrome do Intestino Irritável , Cinurenina , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Triptofano , Animais , Triptofano/metabolismo , Cinurenina/metabolismo , Cinurenina/análogos & derivados , Ratos , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Espectrometria de Massas em Tandem/métodos , Diarreia/metabolismo , Diarreia/tratamento farmacológico , Colo/metabolismo , Ácido Cinurênico/metabolismo , Ácido Quinolínico/metabolismo , Espectrometria de Massa com Cromatografia Líquida

RESUMO

To address severe soil Pb and Cd contamination from anthropogenic activities, governments have implemented various environmental management measures. However, the extent to which these measures have constrained Pb and Cd accumulation in industrial and mining city soils remains unclear. Here, we investigated Pb and Cd accumulation patterns in soils of Panzhihua City, Southwest China, and determined their dominant anthropogenic drivers using Pb and Cd isotopes. Pb accumulation initially slowed and then increased, while Cd showed a continuous acceleration. Traffic and coal-burning power generation were the dominant anthropogenic forcings for Pb and Cd accumulation in the soils, respectively. Environmental protection measures, particularly the ban on leaded gasoline, significantly reduced Pb accumulation by decreasing traffic-related Pb contributions to soils from 1980 to 2008. However, environmental management measures could not practically mitigate Cd accumulation in the soils owing to the high Cd content in consumed coal, poor efficiency of air pollutant control measures, and steep rise in coal-burning power generation. This study thus indicates the criticality of controlling Cd emissions from thermal power generation. Additionally, the challenges faced by small industrial and mining cities during economic transformation and environmental policy implementation warrant more attention.

RESUMO

Microorganisms are pivotal in sustaining soil functions, yet the specific contributions of bacterial and fungal succession on the functions during vegetation restoration in metallic tailing reservoirs remains elusive. Here, we explored bacterial and fungal succession and their impacts on soil multifunctionality along a ∼50-year vegetation restoration chronosequence in China's largest vanadium titano-magnetite tailing reservoir. We found a significant increase in soil multifunctionality, an index comprising factors pertinent to soil fertility and microbially mediated nutrient cycling, along the chronosequence. Despite increasing heavy metal levels, both bacterial and fungal communities exhibited significant increase in richness and network complexity over time. However, fungi demonstrated a slower succession rate and more consistent composition than bacteria, indicating their relatively higher resilience to environmental changes. Soil multifunctionality was intimately linked to bacterial and fungal richness or complexity. Nevertheless, when scrutinizing both richness and complexity concurrently, the correlations disappeared for bacteria but remained robust for fungi. This persistence reveals the critical role of the fungal community resilience in sustaining soil multifunctionality, particularly through their stable interactions with powerful core taxa. Our findings highlight the importance of fungal succession in enhancing soil multifunctionality during vegetation restoration in metallic tailing reservoirs, and manipulating fungal community may expedite ecological recovery of areas polluted with heavy metals.

Assuntos

Bactérias , Fungos , Microbiologia do Solo , Fungos/metabolismo , Bactérias/metabolismo , China , Metais Pesados , Poluentes do Solo/metabolismo , Solo/química , Recuperação e Remediação Ambiental

RESUMO

The complexity of the multielement interaction in high-entropy alloys (HEAs) may provide more active sites to adapt different catalytic reaction steps in oxygen evolution reaction (OER). Investigating the correlation between structure and performance of HEAs electrocatalysts is both essential and challenging. In this work, FeCoNiCrMox HEA nanoparticles are successfully fabricated utilizing a unique nanofabrication method called inert gas condensation. With the increase of high-valence metal component Mo, the atomic structure amorphization and electronic structure reconstruction are unveiled. According to the X-ray photoelectron spectroscopy valence spectra, the d-band center of FeCoNiCrMox is ascending, and thus enhancing the adsorption energy. Synchrotron pair distribution function analysis reflects the degree of structural disorder and reveals a robust correlation with the intrinsic OER activities of the electrocatalysts. FeCoNiCrMo1.0 high-entropy metallic glass nanoparticles exhibit an outstanding OER performance with an ultralow overpotential of 294.5 mV at a high current density of 100 mA cm-2. This work brings fundamental and practical insights into the modulation mechanism of metal components of HEAs catalysts for developing OER.

RESUMO

Protein glycosylation is a highly heterogeneous post-translational modification that has been demonstrated to exhibit significant variations in various diseases. Due to the differential patterns observed in disease and healthy populations, the glycosylated proteins hold promise as early indicators for multiple diseases. With the continuous development of liquid chromatography-mass spectrometry (LC-MS) technology and spectrum analysis software, the sensitivity for the decipher of the tandem mass spectra of the glycopeptides carrying intact glycans, i.e., intact glycopeptides, enzymatic hydrolyzed from glycoproteins has been significantly improved. From quantified intact glycopeptides, the difference of protein glycosylation at multiple levels, e.g., glycoprotein, glycan, glycosite, and site-specific glycans, could be obtained for different samples. However, the manual analysis of the intact glycopeptide quantitative data at multiple levels is tedious and time consuming. In this study, we have developed a software tool named "GP-Marker" to facilitate large-scale data mining of spectra dataset of intact N-glycopeptide at multiple levels. This software provides a user-friendly and interactive interface, offering operational tools for machine learning to researchers without programming backgrounds. It includes a range of visualization plots displaying differential glycosylation and provides the ability to extract multi-level data analysis from intact glycopeptide data quantified by Glyco-Decipher.

RESUMO

In view of the cracking, sag, and damage of sheath caused by the load effect and external force impact of power cable, the echo parameters of cable sheath damage detection based on the characteristics of torsional guided wave propagation are studied in this work. According to the Navier displacement equilibrium equation, the dispersion curve of a magnetostrictive guided wave of the cable sheath was solved, and the T(0,1) mode with a group velocity of 1198.8 m/s and no dispersion was selected. Furthermore, while considering the excitation frequency, loss rate, and direction of the damaged section, the displacement field and the echo characteristic parameters of guided wave in the cable sheath were solved. Moreover, by analyzing the time-domain signals of damaged section echo, the cubic fitting function for the loss rate of the damaged section and the damaged section echo coefficient were obtained, which can effectively characterize the quantitative relationship between the damaged location, size, and guided wave echo of the cable sheath.

RESUMO

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC. METHODS: A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed. RESULTS: Among the 63 patients with high-risk UTUC, the median age was 66 years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26 months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers. CONCLUSIONS: The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.

RESUMO

Untethered magnetic soft robots capable of performing adaptive locomotion and shape reconfiguration open up possibilities for various applications owing to their flexibility. However, magnetic soft robots are typically composed of soft materials with fixed modulus, making them unable to exert or withstand substantial forces, which limits the exploration of their new functionalities. Here, water-induced, shape-locking magnetic robots with magnetically controlled shape change and water-induced shape-locking are introduced. The water-induced phase separation enables these robots to undergo a modulus transition from 1.78 MPa in the dry state to 410 MPa after hydration. Moreover, the body material's inherent self-healing property enables the direct assembly of morphing structures and magnetic soft robots with complicated structures and magnetization profiles. These robots can be delivered through magnetic actuation and perform programmed tasks including supporting, blocking, and grasping by on-demand deformation and subsequent water-induced stiffening. Moreover, a water-stiffening magnetic stent is developed, and its precise delivery and water-induced shape-locking are demonstrated in a vascular phantom. The combination of untethered delivery, on-demand shape change, and water-induced stiffening properties makes the proposed magnetic robots promising for biomedical applications.

RESUMO

Vegetation restoration in metallic tailing reservoirs is imperative to restore the post-mining degraded ecosystems. Extracellular enzymes determine microbial resource acquisition in soils, yet the mechanisms controlling the enzyme activity and stoichiometry during vegetation restoration in metallic tailing reservoirs remain elusive. Here, we investigated the variations and drivers of C-, N- and P-acquiring enzymes together with microbial community along a 50-year vegetation restoration chronosequence in the China's largest vanadium titano-magnetite tailing reservoir. We found a parabolic pattern in the enzyme activity and efficiency along the chronosequence, peaking at the middle restoration stage (∼30 years) with approximately six-fold increase relative to the initial 1-year site. The enzyme ratios of C:P and N:P decreased by 33 % and 68 % along the chronosequence, respectively, indicating a higher microbial demand of C and N at the early stage and a higher demand of P at the later stage. Soil nutrients directly determined the enzyme activities and stoichiometry, whereas microbial biomass and community structure regulated the temporal pattern of the enzyme efficiency. Surprisingly, increased heavy metal pollution imposed a positive effect on the enzyme efficiency indirectly by altering microbial community structure. This was evidenced by the increased microbial diversity and the conversion of copiotrophic to oligotrophic and stress-tolerant taxa along the chronosequence. Our findings provide new insights into microbial functioning in soil nutrient dynamics during vegetation restoration under increasing heavy metal pollution.

Assuntos

Metais Pesados , Microbiota , Mineração , Microbiologia do Solo , Poluentes do Solo , Solo , Metais Pesados/análise , China , Solo/química , Recuperação e Remediação Ambiental/métodos , Biodegradação Ambiental

RESUMO

RATIONALE: Epithelioid trophoblastic tumor (ETT) is an extremely rare variant of gestational trophoblastic neoplasms (GTNs). The biological behavior and therapeutic schedule of ETT remains to be defined which frequently poses diagnostic and therapeutic challenges. Although ETT is a relatively indolent malignancy tumor, the therapeutic efficacy and survival rate decrease significantly when presented with metastases. The lung is the most common site of ETT metastasis. PATIENT CONCERNS: A 39-year-old female patient presented with irregular vaginal bleeding and slight distention pain in lower abdomen. DIAGNOSES: The patient was diagnosed ETT with lung metastasis after surgery and immunohistochemical staining. INTERVENTIONS: A total abdominal hysterectomy plus bilateral salpingectomy and histopathology were performed. The patient received 3 cycles of etoposide, methotrexate, actinomycin-D/etoposide, cisplatin (EMA/EP) regimen chemotherapy after surgery. Due to the presence of lung metastasis, she received pulmonary lesion resection and another cycle of postoperative chemotherapy. OUTCOMES: The patients showed a good response to treatment initially. However, the patient did not complete the full initial treatment for family reasons and had signs of recurrence after 2.5 months. The serum ß-hCG level gradually elevated and the lung imaging showed that the lesion area gradually expanded. After 15 months of follow-up, the patient declined further treatment due to a lack of presenting symptoms. LESSONS: The diagnosis of ETT should be taken into consideration in patients with abnormal vaginal bleeding and low levels of ß-hCG. Patients with metastatic disease should be treated with complete surgical resection and intensive combination chemotherapy to maximize the opportunity for cure. Targeted biological agents might be potential therapeutic strategies for chemotherapy-resistant or recurrent patients.

Assuntos

Neoplasias Pulmonares , Neoplasias Uterinas , Humanos , Feminino , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Adulto , Neoplasias Uterinas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Trofoblásticas/secundário , Neoplasias Trofoblásticas/patologia , Gravidez , Histerectomia/métodos

RESUMO

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.

Assuntos

Glutationa , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Glutationa/análise , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Homocisteína/análise , Cisteína/análise , Ácido Pirrolidonocarboxílico/análise , Ácido Pirrolidonocarboxílico/química , Ácido Pirrolidonocarboxílico/metabolismo , Dipeptídeos/análise , Acetilcisteína/análise , Acetilcisteína/química , Cistina/análise

RESUMO

Improving the slow redox kinetics of sulfur species and shuttling issues of soluble intermediates induced from the multiphase sulfur redox reactions are crucial factors for developing the next-generation high-energy-density lithium-sulfur (Li-S) batteries. In this study, we successfully constructed a novel molecular electrocatalyst through in situ polymerization of bis(3,4-dibromobenzene)-18-crown-6 (BD18C6) with polysulfide anions on the cathode interface. The crown ether (CE)-based polymer acts as a spatial "fence" to precisely control the unique redox characteristics of sulfur species, which could confine sulfur substance within its interior and interact with lithium polysulfides (LiPSs) to optimize the reaction barrier of sulfur species. The "fence" structure and the double-sided Li+ penetrability of the CE molecule may also prevent the CE catalytic sites from being covered by sulfur during cycling. This new fence-type electrocatalyst mitigates the "shuttle effect", enhances the redox activity of sulfur species, and promotes the formation of three-dimensional stacked lithium sulfide (Li2S) simultaneously. It thus enables lithium-sulfur batteries to exhibit superior rate performance and cycle stability, which may also inspire development facing analogous multiphase electrochemical energy-efficient conversion process.