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1.
Lancet Oncol ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35576956

RESUMO

BACKGROUND: Extensive-stage small-cell lung cancer (ES-SCLC) is associated with poor prognosis and treatment options are scarce. Immunotherapy has shown robust clinical activity in ES-SCLC in previous phase 3 trials. We aimed to assess the efficacy and safety of adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, with standard chemotherapy as a first-line treatment for ES-SCLC. METHODS: The CAPSTONE-1 study was a randomised, double-blind, placebo-controlled, phase 3 trial, done in 47 tertiary hospitals in China. Key inclusion criteria were patients aged 18-75 years, with previously untreated histologically or cytologically confirmed ES-SCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Eligible patients were randomly assigned (1:1) to receive four to six cycles of carboplatin (area under the curve of 5 mg/mL per min, day 1 of each cycle) and etoposide (100 mg/m2 of body-surface area, on days 1-3 of each cycle) with either adebrelimab (20 mg/kg, day 1 of each cycle) or matching placebo, followed by maintenance therapy with adebrelimab or placebo. All treatments were given intravenously in 21-day cycles. Randomisation was done using a centralised interactive web response system with a block size of four, stratified by liver metastases, brain metastases, and lactate dehydrogenase concentration. The primary endpoint was overall survival in patients who received at least one dose of study medication. Safety was analysed in the as-treated population. This study is complete and registered with ClinicalTrials.gov, NCT03711305. FINDINGS: Between Dec 26, 2018, and Sept 4, 2020, 462 eligible patients were enrolled and randomly assigned: 230 (50%) patients received adebrelimab plus chemotherapy (adebrelimab group) and 232 (50%) patients received placebo plus chemotherapy (placebo group). At data cutoff (Oct 8, 2021), median follow-up was 13·5 months (IQR 8·9-20·1). Median overall survival was significantly improved in the adebrelimab group (median 15·3 months [95% CI 13·2-17·5]) compared with the placebo group (12·8 months [11·3-13·7]; hazard ratio 0·72 [95% CI 0·58-0·90]; one-sided p=0·0017). The most common treatment-related grade 3 or 4 adverse events were decreased neutrophil count (174 [76%] patients in the adebrelimab group and 175 [75%] patients in the placebo group), decreased white blood cell count (106 [46%] and 88 [38%]), decreased platelet count (88 [38%] and 78 [34%]), and anaemia (64 [28%] and 66 [28%]). Treatment-related serious adverse events occurred in 89 (39%) patients in the adebrelimab group and 66 (28%) patients in the placebo group. Four treatment-related deaths were reported: two each in the adebrelimab group (respiratory failure and interstitial lung disease and pneumonia) and placebo group (multiple organ dysfunction and unknown cause of death). INTERPRETATION: Adding adebrelimab to chemotherapy significantly improved overall survival with an acceptable safety profile in patients with ES-SCLC, supporting this combination as a new first-line treatment option for this population. FUNDING: Jiangsu Hengrui Pharmaceuticals.

2.
Langmuir ; 38(14): 4287-4294, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35363495

RESUMO

Two-dimensional (2D) nanostructured catalysts have attracted great attention in many important fields, including energy applications and chemical industry. In this study, PdCu nanosheet assemblies (NSAs) have been synthesized and investigated as electrocatalysts for direct ethanol fuel cells in an alkaline medium. A great number of active sites on the nanosheets of PdCu NSAs for ethanol electro-oxidation are exposed, where the electron structures are optimized combined with the second element copper. Electrochemical measurements show that PdCu NSA1 exhibits excellent catalytic activity (2536 mA mg-1) and cyclic stability compared to PdCu NSA2 (1700 mA mg-1) and PdCu NSA3 (1436 mA mg-1), much higher than commercial Pd/C. Kinetics studies on the electrolysis of ethanol suggest that PdCu NSAs should be more favorable at higher catalytic temperatures, higher concentrations of ethanol, and low pH value environments. The unique composition and structures PdCu NSA1 would result in the lowest energy barrier in the rate-controlling step of the ethanol oxidation reaction (EOR), confirmed by density functional theory (DFT). The formation mechanism of PdCu NSAs and their excellent electrocatalytic activity toward EOR have been discussed and analyzed.

3.
J Clin Oncol ; : JCO2101511, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35404684

RESUMO

PURPOSE: This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS: Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS: Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION: Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

4.
J Am Chem Soc ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35469397

RESUMO

Solution processable flexible transparent electrodes (FTEs) are urgently needed to boost the efficiency and mechanical stability of flexible organic solar cells (OSCs) on a large scale. However, how to balance the optoelectronic properties and meanwhile achieve robust mechanical behavior of FTEs is still a huge challenge. Silver nanowire (AgNW) electrodes, exhibiting easily tuned optoelectronic/mechanical properties, are attracting considerable attention, but their poor contacts at the junction site of the AgNWs increase the sheet resistance and reduce mechanical stability. In this study, an ionic liquid (IL)-type reducing agent containing Cl- and a dihydroxyl group was employed to control the reduction process of silver (Ag) in AgNW-based FTEs precisely. The Cl- in the IL regulates the Ag+ concentration through the formation and dissolution of AgCl, whereas the dihydroxyl group slowly reduces the released Ag+ to form metal Ag. The reduced Ag grew in situ at the junction site of the AgNWs in a twin-crystal growth mode, facilitating an atomic-level contact between the AgNWs and the reduced Ag. This enforced atomic-level contact decreased the sheet resistance, and enhanced the mechanical stability of the FTEs. As a result, the single-junction flexible OSCs based on this chemically welded FTE achieved record power conversion efficiencies of 17.52% (active area: 0.062 cm2) and 15.82% (active area: 1.0 cm2). These flexible devices also displayed robust bending and peeling durability even under extreme test conditions.

5.
J Environ Sci (China) ; 118: 171-180, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35305766

RESUMO

Surfactants are widely used to improve the solubility of oil in water in petrochemical, making it more difficult to remove oil-water emulsions during the water treatment process. Electrocoagulation (EC) is an appropriate method for treating oily wastewater and destabilizing emulsions. However, the demulsification mechanism of oil-water droplets emulsified by surfactants with different charges have not been investigated systematically. The demulsification performance of electrocoagulation on emulsions wastewater containing cationic, non-ionic, and anionic surfactants was studied. The results showed that the removal rate of total organic carbon (TOC) in oily wastewater with anionic surfactant by EC reached 92.98% ± 0.40% at a current density of 1 mA/cm2, while that of the non-ionic surfactant was 84.88% ± 0.63%. The characterization of flocs showed that EC has the highest coagulation and demulsification of oil droplets with a negative charge on the surface (-70.50 ± 10.25 mV), which indicated that the charge neutralization of oil droplets was beneficial for the destabilization of the formed oily flocs. However, when the zeta potential of the oil droplets reached 75.50 ± 1.25 mV, the TOC removal efficiency was only 11.80% ± 1.43%. The TOC removal could achieve 33.23% ± 3.21% when the current density improved from 1 mA/cm2 to 10 mA/cm2. The enhanced removal was due to the sweep coagulation rather than charge neutralization. This study provides a fundamental basis for the electrochemical treatment of oily wastewater.


Assuntos
Surfactantes Pulmonares , Purificação da Água , Eletrocoagulação , Emulsões/química , Tensoativos/química , Purificação da Água/métodos
6.
Molecules ; 27(5)2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35268807

RESUMO

Oxytropis falcata Bunge is a plant used in traditional Tibetan medicine, with reported anti-inflammatory and antioxidants effects and alleviation of myocardial ischemia reperfusion injury (MIRI). However, the underlying mechanism against MIRI and the phytochemical composition of O. falcata are vague. One fraction named OFF1 with anti-MIRI activity was obtained from O. falcata, and the chemical constituents were identified by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS). The potential targets and signaling pathways involved in the action of O. falcata against MIRI were predicted by network pharmacology analysis, and its molecular mechanism on MIRI was determined by in vitro assays. The results revealed that flavonoids are the dominant constituents of OFF1. A total of 92 flavonoids reported in O. falcata targeted 213 potential MIRI-associated factors, including tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2), and the NF-κB signaling pathway. The in vitro assay on H9c2 cardiomyocytes subjected to hypoxia/reoxygenation injury confirmed that the flavonoids in OFF1 reduced myocardial marker levels, apoptotic rate, and the inflammatory response triggered by oxidative stress. Moreover, OFF1 attenuated MIRI by downregulating the ROS-mediated JNK/p38MAPK/NF-κB pathway. Collectively, these findings provide novel insights into the molecular mechanism of O. falcata in alleviating MIRI, being a potential therapeutic candidate.


Assuntos
Traumatismo por Reperfusão Miocárdica , Oxytropis , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Traumatismo por Reperfusão Miocárdica/metabolismo , NF-kappa B/metabolismo , Oxytropis/química , Transdução de Sinais
7.
Cell Rep ; 38(9): 110460, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35235781

RESUMO

We report a comprehensive proteomic study of a 90-case cohort of paired samples of triple-negative breast cancer (TNBC) in quantification, phosphorylation, and DNA-binding capacity. Four integrative subtypes (iP-1-4) are stratified on the basis of global proteome and phosphoproteome, each of which exhibits distinct molecular and pathway features. Scaffold and co-expression network analyses of three proteomic datasets, integrated with those from genome and transcriptome of the same cohort, reveal key pathways and master regulators that, characteristic of TNBC subtypes, play important regulatory roles within and between scaffold sub-structures and co-expression communities. We find that NAE1 is a potential drug target for subtype iP-1, and a series of key molecules in fatty acid metabolism, such as AKT1/FASN, are plausible targets for subtype iP-2. Libraries of proteins, pathways and networks of TNBC provide a valuable molecular infrastructure for further clinical exploration and in-depth studies of the molecular mechanisms of the disease.


Assuntos
Neoplasias de Mama Triplo Negativas , Genoma , Humanos , Proteoma/genética , Proteômica , Transcriptoma , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
8.
Int Immunopharmacol ; 107: 108705, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35338960

RESUMO

Progranulin (PGRN) is a secreted factor involved in inflammatory diseases. However, the function of PGRN in silica-induced lung inflammation has not been elucidated. In this study, we demonstrated that PGRN in serum and lung tissues was markedly increased in silicosis mouse model. And immunohistochemistry results showed that PGRN was mainly expressed in alveolar macrophages, which was further confirmed in silica-treated alvelar macrophages cell line (MH-S) in vitro. PGRN promoted pro-inflammatory cytokines transcription such as interleukin (Il)-6, tumor necrosis factor-α (Tnf-α) and Il-1ß in MH-S cells, and the increasing of Il-6 was most obvious. Knockdown of PGRN blocked the silica-induced elevation of intracellular Il-6 in MH-S cells. Furthermore, we also found that PGRN could increase the phosphorylation of Cyclic AMP-responsive element-binding protein 1 (Creb1), a transcriptional regulator of Il-6. Inhibition of p-Creb1 by the phosphorylation inhibitor of Creb1 (666-15) decreased PGRN-induced intracellular Il-6 production in MH-S cells. In conclusion, PGRN was highly increased in silicosis mouse model and upregulated inflammatory cytokines expression. These findings suggested that PGRN might be a key mediator in silica-induced inflammation and provided a new clue for the diagnosis and drug therapy of silicosis.


Assuntos
Macrófagos Alveolares , Silicose , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Interleucina-6/metabolismo , Macrófagos Alveolares/metabolismo , Camundongos , Progranulinas/metabolismo , Dióxido de Silício , Silicose/metabolismo
9.
Front Oncol ; 12: 829248, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237523

RESUMO

BACKGROUND: Prostate cancer is the second most common cancer in males worldwide, and multitudes of factors have been reported to be associated with prostate cancer risk. OBJECTIVES: We aim to conduct the phenome-wide exposed-omics analysis of the risk factors for prostate cancer and verify the causal associations between them. METHODS: We comprehensively searched published systematic reviews and meta-analyses of cohort studies and conducted another systematic review and meta-analysis of the Mendelian randomization studies investigating the associations between extrinsic exposures and prostate cancer, thus to find all of the potential risk factors for prostate cancer. Then, we launched a phenome-wide two-sample Mendelian randomization analysis to validate the potentially causal relationships using the PRACTICAL consortium and UK Biobank. RESULTS: We found a total of 55 extrinsic exposures for prostate cancer risk. The causal effect of 30 potential extrinsic exposures on prostate cancer were assessed, and the results showed docosahexaenoic acid (DHA) [odds ratio (OR)=0.806, 95% confidence interval (CI): 0.661-0.984, p=0.034], insulin-like growth factor binding protein 3 (IGFBP-3) (OR=1.0002, 95%CI: 1.00004-1.0004, p=0.016), systemic lupus erythematosus (SLE) (OR=0.9993, 95%CI: 0.9986-0.99997, p=0.039), and body mass index (BMI) (OR=0.995, 95%CI: 0.990-0.9999, p=0.046) were associated with prostate cancer risk. However, no association was found between the other 26 factors and prostate cancer risk. CONCLUSIONS: Our study discovered the phenome-wide exposed-omics risk factors profile of prostate cancer, and verified that the IGFBP-3, DHA, BMI, and SLE were causally related to prostate cancer risk. The results may provide new insight into the study of the pathogenesis of prostate cancer.

10.
Head Neck ; 44(5): 1114-1123, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35170140

RESUMO

BACKGROUND: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients. METHODS: The clinical data of 284 NPC patients, who received intensity-modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed. RESULTS: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease-free survival (DFS) (p = 0.002) and relapse-free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05). CONCLUSIONS: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required.


Assuntos
Hipotireoidismo , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos
11.
World J Pediatr ; 18(3): 206-213, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35066802

RESUMO

BACKGROUND: This study aimed to investigate the performance of handmade tri-leaflet expanded polytetrafluoroethylene (ePTFE) conduits in the absence of a suitable homograft. METHODS: Patients who underwent right ventricular outflow tract reconstruction with tri-leaflet ePTFE conduits or homografts between December 2016 and August 2020 were included. The primary endpoint was the incidence of moderate or severe conduit stenosis (≥ 36 mmHg) and/or moderate or severe insufficiency. The secondary endpoint was the incidence of severe conduit stenosis (≥ 64 mmHg) and/or severe insufficiency. RESULTS: There were 102 patients in the ePTFE group and 52 patients in the homograft group. The median age was younger [34.5 (interquartile range: 20.8-62.8) vs. 60.0 (interquartile range: 39.3-81.0) months, P = 0.001] and the median weight was lower [13.5 (10.0-19.0) vs. 17.8 (13.6-25.8) kg, P = 0.003] in the ePTFE group. The conduit size was smaller (17.9 ± 2.2 vs. 20.5 ± 3.0 mm, P < 0.001) and the conduit Z score was lower (1.48 ± 1.04 vs. 1.83 ± 1.05, P = 0.048) in the ePTFE group. There was no significant difference in the primary endpoints (log rank, P = 0.33) and secondary endpoints (log rank, P = 0.35). Multivariate analysis identified lower weight at surgery [P = 0.01; hazard ratio: 0.75; 95% confidence interval (CI) 0.59-0.94] and homograft conduit use (P = 0.04; hazard ratio: 8.43; 95% CI 1.14-62.29) to be risk factors for moderate or severe conduit insufficiency. No risk factors were found for moderate or severe conduit stenosis or conduit dysfunction on multivariate analysis. CONCLUSION: Handmade tri-leaflet ePTFE conduits showed acceptable early and midterm outcomes in the absence of a suitable homograft, but a longer follow-up is needed.


Assuntos
Cardiopatias Congênitas , Politetrafluoretileno , Aloenxertos , Constrição Patológica , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Estudos Retrospectivos , Resultado do Tratamento
12.
Int J Hyperthermia ; 39(1): 190-199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35042449

RESUMO

PURPOSE: To investigate the long-term efficacy of radiofrequency ablation (RFA) with a multiple-electrode switching system (MESS) in the treatment of early hepatocellular carcinoma (HCC) and evaluate the patterns and risk factors of intrahepatic recurrence of HCC after RFA. METHODS: In total, 139 patients with early HCC who underwent RFA with MESS as primary treatment at multiple centers were prospectively enrolled according to the inclusion criteria. We evaluated the local tumor progression (LTP), intrahepatic distant recurrence (IDR), the incidence of cumulative disease-free survival (DFS), LTP-free survival, IDR-free survival, and overall survival. We also analyzed the associated risk factors. RESULTS: A total of 139 patients were included in the study and the median follow-up time was 64 months, ranging from 11 to 72 months. The complete ablation rate was 98.56%. Sixty-nine (49.64%) were found to have intrahepatic recurrence (LTP, n = 15; IDR, n = 55) during follow-up. The 1-year, 3-year and 5-year cumulative DFS, LTP-free survival, and IDR-free survival rates were 74.82, 94.46 and 78.75%; 54.68, 88.03 and 61.79%; and 51.80, 85.67 and 60.17%, respectively. In the multivariable analysis, tumor size > 4 cm was the only important risk factor for LTP. The alkaline phosphatase (ALP) level and the number of tumors were independent risk factors for IDR; α-fetoprotein (AFP) level > 400 µg/L and recurrence interval were risk factors for the overall survival period. CONCLUSIONS: The MESS-RFA is an effective method for local control of tumors in early HCC. Early HCC with multiple high-ALP tumors has a higher rate of recurrence, which mainly occurs in an IDR pattern. Early HCC with high AFP levels and a shorter initial recurrence interval resulted in a poorer prognosis. Thus, treatments such as liver transplantation or surgical resection may be a good strategy in those cases. CLINICALTRIALS.GOV ID: NCT02046356.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Carcinoma Hepatocelular/patologia , Ablação por Cateter/métodos , Eletrodos , Humanos , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
13.
Angew Chem Int Ed Engl ; 61(13): e202115331, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-34936185

RESUMO

Developing low-cost electrocatalysts for efficient and robust oxygen evolution reaction (OER) is the key for scalable water electrolysis, for instance, NiFe-based materials. Decorating NiFe catalysts with other transition metals offers a new path to boost their catalytic activities but often suffers from the low controllability of the electronic structures of the NiFe catalytic centers. Here, we report an interfacial atom-substitution strategy to synthesize an electrocatalytic oxygen-evolving NiFeV nanofiber to boost the activity of NiFe centers. The electronic structure analyses suggest that the NiFeV nanofiber exhibits abundant high-valence Fe via a charge transfer from Fe to V. The NiFeV nanofiber supported on a carbon cloth shows a low overpotential of 181 mV at 10 mA cm-2 , along with long-term stability (>20 h) at 100 mA cm-2 . The reported substitutional growth strategy offers an effective and new pathway for the design of efficient and durable non-noble metal-based OER catalysts.

14.
Langmuir ; 37(50): 14571-14581, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34894696

RESUMO

In this study, the wetting and dewetting behaviors of water nanodroplets containing various molecule numbers on nanopillar-arrayed surfaces in the presence or absence of an external electric field are investigated via molecular dynamics (MD) simulations, aiming to examine whether there is a scale effect. The results show that, in the absence of an electric field, nanodroplets on coexisting Cassie/Wenzel surfaces may be in the Cassie or the Wenzel state depending on their initial states, and apparent contact angles of the Cassie or Wenzel nanodroplets increase monotonously with increasing the droplet size. Energy analysis shows that on the same coexisting Cassie/Wenzel surface, when an electric field is imposed, a small nanodroplet possesses a lower energy barrier separating the Cassie state from the Wenzel state. Therefore, the small nanodroplet is easier to collapse into the Wenzel state. Moreover, the spontaneous Wenzel-to-Cassie dewetting transition is not observed for the nanodroplets after the removal of the electric field because the Wenzel state is a globally stable energetic state. With the same pillar geometry, both the wetting transition and the dewetting transition are significantly modified for liquids with higher intrinsic contact angles. The energy barrier of the wetting transition increases for both the large and small nanodroplets, meaning that the Cassie state becomes more robust. The energy curve shows that the Wenzel state of the large nanodroplet has higher energy so that the droplet can return to the Cassie state when removing the electric field. Intriguingly, although the small Wenzel nanodroplet has lower energy in the presence of the electric field, the dewetting transition still occurs. The increased solid-liquid interfacial tension when removing the electric field is responsible for this abnormal result. The wetting and dewetting transitions follow different energy pathways, leading to a hysteresis energy loop. There exists a critical water molecule number separating the unstable/stable Wenzel configurations, above which the Cassie state is energetically favorable and the dewetting transition can occur spontaneously after removing the electric field.

15.
J Immunother Cancer ; 9(12)2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34933967

RESUMO

BACKGROUND: This study aimed to evaluate the antitumor activity of camrelizumab, an antiprogrammed cell death-1 antibody, in pretreated recurrent or metastatic nasopharyngeal carcinoma (NPC) and to explore predictive biomarkers. METHODS: Patients with recurrent (not amenable to locally curative treatment) or metastatic NPC who had failed at least two lines of chemotherapy were eligible to receive camrelizumab (200 mg intravenously every 2 weeks) for 2 years or until disease progression, intolerable adverse events, withdrawal of consents, or investigator decision. The primary endpoint was objective response rate (ORR) assessed by an independent review committee (IRC). Programmed cell death-ligand 1 (PD-L1) expression was assessed by immunohistochemistry. Other immune-related biomarkers including major histocompatibility complex class I and major histocompatibility complex class II (MHC-II) were assessed by multiplex immunofluorescence staining. RESULTS: Between August 14, 2018, and December 30, 2019, a total of 156 patients were enrolled. The IRC-assessed ORR was 28.2% (95% CI 21.3% to 36.0%). The median progression-free survival was 3.7 months (95% CI 2.0 to 4.1) per IRC, and the median overall survival was 17.4 months (95% CI 15.2 to 21.9). The ORRs were 35.2% (95% CI 25.3% to 46.1%) vs 19.4% (95% CI 10.4% to 31.4%) in patients with tumor PD-L1 expression of ≥10% and<10%, respectively. Patients with durable clinical benefit (DCB), which was defined as complete response, partial response or stable disease of ≥18 weeks, had higher density of MHC-II+ cell in stroma than patients without DCB (median 868.1 (IQR 413.4-2854.0) cells/mm2 vs median 552.4 (IQR 258.4 to 1242.1) cells/mm2). MHC-II+ cell density did not correlate with PD-L1 expression, and a composite of high stromal MHC-II+ cell density and tumor PD-L1 expression further enriched patients who could benefit from camrelizumab. CONCLUSIONS: Camrelizumab had clinically meaningful antitumor activity in patients with recurrent or metastatic NPC. The composition of both MHC-II+ cell density and PD-L1 expression could result in better patient selection.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
16.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5270-5277, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738429

RESUMO

Dirigent(DIR) proteins are involved in the biosynthesis of lignin, lignans, and gossypol in plants and respond to biotic and abiotic stresses. Based on the full-length transcriptome of Schisandra chinensis, bioinformatics methods were used to preliminarily identify the DIR gene family and analyze the physico-chemical properties, subcellular localization, conserved motifs, phylogeny, and expression patterns of the proteins. The results showed that a total of 34 DIR genes were screened and the encoded proteins were 156-387 aa. The physico-chemical properties of the proteins were different and the secondary structure was mainly random coil. Half of the DIR proteins were located in chloroplast, while the others in extracellular region, endoplasmic reticulum, cytoplasm, etc. Phylogenetic analysis of DIR proteins from S. chinensis and the other 8 species such as Arabidopsis thaliana, Oryza sativa, and Glycine max demonstrated that all DIR proteins were clustered into 5 subfamilies and that DIR proteins from S. chinensis were in 4 subfamilies. DIR-a subfamily has the unique structure of 8 ß-sheets, as verified by multiple sequence alignment. Finally, through the analysis of the transcriptome of S. chinensis fruit at different development stages, the expression pattern of DIR was clarified. Combined with the accumulation of lignans in fruits at different stages, DIR might be related to the synthesis of lignans in S. chinensis. This study lays a theoretical basis for exploring the biological functions of DIR genes and elucidating the biosynthesis pathway of lignans in S. chinensis.


Assuntos
Lignanas , Schisandra , Frutas/química , Frutas/genética , Lignanas/análise , Filogenia , Alinhamento de Sequência
17.
Langmuir ; 37(44): 13132-13140, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34714658

RESUMO

Although many researchers have made great efforts to pursue promising high-efficiency electrocatalysts, a formidable challenge remains for designing excellent palladium-based electrocatalysts for commercializing direct liquid fuel cells. This study reports the synthesis of bimetallic PdPb nanoparticles (NPs) via a mixed solution containing cetyl trimethyl ammonium bromide as the capping agent. Alloyed PdPb NPs are formed, where the size of the NPs increases as Pb atoms are introduced gradually. However, Pd3Pb NPs are obtained with the same molar ratio of Pd and Pb in the raw systems. Among all of the as-made NPs, Pd9Pb1 NPs exhibit superior catalytic activity (2620 mA mg-1) toward ethanol electrooxidation, 4.3 times higher than commercial Pd/C catalysts (613 mA mg-1). The overall rate of the EOR for PdPb NPs is determined, demonstrating that the electrocatalytic activity of the PdPb NPs increases at high catalytic temperatures, in high pH environments, and/or at high ethanol concentrations.

18.
J Biol Chem ; 297(5): 101315, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34678311

RESUMO

Coagulopathy is associated with both inflammation and infection, including infections with novel severe acute respiratory syndrome coronavirus-2, the causative agent Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19. Clot formation is promoted via cAMP-mediated secretion of von Willebrand factor (vWF), which fine-tunes the process of hemostasis. The exchange protein directly activated by cAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a regulatory role in suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1-null mouse model and revealed increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1-/- phenotype. In addition, EPAC1 regulated tumor necrosis factor-α-triggered vWF secretion from human umbilical vein endothelial cells in a manner dependent upon inflammatory effector molecules PI3K and endothelial nitric oxide synthase. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro. Our data delineate a novel regulatory role for EPAC1 in vWF secretion and shed light on the potential development of new strategies to control thrombosis during inflammation.


Assuntos
Células Endoteliais/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator de von Willebrand/metabolismo , Animais , COVID-19/metabolismo , Modelos Animais de Doenças , Fatores de Troca do Nucleotídeo Guanina/deficiência , Fatores de Troca do Nucleotídeo Guanina/genética , Inflamação/metabolismo , Camundongos , Camundongos Knockout
19.
J Cell Mol Med ; 25(19): 9447-9459, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34498380

RESUMO

Oestradiol (E2) is a critical factor for multiple systems' development during the embryonic period. Here, we aimed to investigate the effects of oestradiol on intrahepatic bile duct development, which may allow a better understanding of congenital bile duct dysplasia. DLK+ hepatoblasts were extracted from the C57BL/6CrSlc foetal mice and randomly divided into control group, oestradiol groups (1, 10, 100 nM) and oestradiol (10 nM) + DAPT (inhibitor of Notch signalling; 40 µM) group for in vitro experiments. For in vivo analysis, pregnant mice were divided into control group, oestradiol (intraperitoneal injection of 0.6 mg/kg/day) ± DAPT (subcutaneous injection of 10 mg/kg/day) groups and tamoxifen (gavage administration of 0.4 mg/kg/day) group. The results showed that oestradiol promoted hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development during the embryonic period. Tamoxifen, an antioestrogenic drug, inhibited the above processes. Moreover, oestradiol promoted the expression of Notch signalling pathway-associated proteins and genes both in vitro and in vivo. Notably, DAPT addition inhibited the oestradiol-mediated effects. In conclusion, oestradiol can promote hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via the Notch signalling pathway.


Assuntos
Ductos Biliares Intra-Hepáticos/embriologia , Ductos Biliares Intra-Hepáticos/metabolismo , Estradiol/metabolismo , Organogênese , Receptores Notch/metabolismo , Transdução de Sinais , Animais , Biomarcadores , Diferenciação Celular , Células Cultivadas , Estradiol/farmacologia , Expressão Gênica , Hepatócitos/metabolismo , Imuno-Histoquímica , Imunofenotipagem , Camundongos , Camundongos Endogâmicos C57BL , Organogênese/efeitos dos fármacos , Células-Tronco/metabolismo
20.
Plast Reconstr Surg ; 148(5): 720e-726e, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34529592

RESUMO

BACKGROUND: Osseous genioplasty is a powerful procedure that can correct chin dysmorphology; however, traditional techniques may result in chin ptosis or a "witch's chin" deformity. Iatrogenic chin ptosis is thought to be caused by excessive degloving of soft tissue with a failure to reattach the mentalis muscle. In the authors' study, they compared the "no-degloving" technique (using a 90-degree plate with lag-screw fixation) to the "traditional" technique, for minimization of chin ptosis. METHODS: The authors compared genioplasty techniques for consecutive patients: group 1 (traditional) underwent degloving for fixation of a stair-step plate, whereas group 2 (no-degloving) underwent lag-screw fixation (n = 50; 25 patients per group). The authors compared operating room time, advancement, complications, preoperative-to-postoperative vertical height change of the pogonion and menton (obtained through cone beam computed tomographic scans), surgeons' assessment of witch's chin, and FACE-Q surveys. RESULTS: No-degloving versus traditional groups had similar age and sex distributions, horizontal/vertical change (5 mm/2 mm versus 6 mm/2 mm), length of surgery, and complication rate (5 percent). The traditional group had more deviation from expected position for both the pogonion (3.4 mm versus 1.2 mm; p ≤ 0.05) and menton (2.9 mm versus 0.8 mm; p ≤ 0.05), and more occurrences of witch's chin (six versus zero). No-degloving was superior for several FACE-Q scales, including Chin Appearance, Quality of Life, Satisfaction with Decision to Undergo Procedure, and Satisfaction with Outcome. CONCLUSION: No-degloving osseous genioplasty is a safe, reproducible technique that results in decreased soft-tissue ptosis and increased patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Queixo/cirurgia , Mentoplastia/métodos , Procedimentos Cirúrgicos Ortognáticos/métodos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Parafusos Ósseos , Cefalometria , Queixo/anatomia & histologia , Estética , Feminino , Mentoplastia/efeitos adversos , Mentoplastia/instrumentação , Humanos , Masculino , Procedimentos Cirúrgicos Ortognáticos/efeitos adversos , Procedimentos Cirúrgicos Ortognáticos/instrumentação , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
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