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1.
Water Res ; 267: 122521, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39357159

RESUMO

Heterogeneous activation of peracetic acid (PAA) process is a promising method for removing organic pollutants from water. Nevertheless, this process is constrained by several complex factors, such as the selection of catalysts, optimization of reaction conditions, and identification of mechanism. In this study, a task decomposition strategy was adopted by combining a catalyst and reaction condition optimization machine learning (CRCO-ML) model and a mechanism identification machine learning (MI-ML) model to address these issues. The Categorical Boosting (CatBoost) model was identified as the best-performing model for the dataset (1024 sets and 7122 data points) in this study, achieving an R2 of 0.92 and an RMSE of 1.28. Catalyst composition, PAA dosage, and catalyst dosage were identified as the three most important features through SHAP analysis in the CRCO-ML model. The HCO3- is considered the most influential water matrix affecting the k value. The errors between all reverse experiment results and the predictions of the CRCO-ML and MI-ML models were <10 % and 15 %, respectively. This interdisciplinary work provides novel insights into the design and application of the heterogeneous activation of PAA process, significantly contributing to the rapid development of this technology.

2.
BMC Gastroenterol ; 24(1): 383, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39468442

RESUMO

BACKGROUND: T-tube cholangiography and choledochoscopy are commonly used techniques for detecting residual bile duct stones after biliary surgery. However, the utility of routine cholangiography before T-tube removal needs further investigation. This study aims to evaluate the diagnostic efficacy of various methods for detecting residual calculi following biliary surgery. METHODS: We retrospectively analyzed the clinical data of 287 adult patients who underwent common bile duct exploration with T-tube drainage, followed by T-tube cholangiography and choledochoscopy, at the Department of General Surgery, Xuanwu Hospital, Capital Medical University, between 2017 and 2022. Exclusion criteria were patients with bile duct tumors, incomplete medical records or loss to follow-up, and patients with contraindications to T-tube or choledochoscopy. McNemanr test and Kappa test were used to compare the results and consistency between choledochoscopy and T-tube cholangiography. All patients underwent both cholangiography and choledochoscopy six to eight weeks after laparoscopic cholecystectomy combined with common bile duct exploration and T-tube drainage. The results of T-tube cholangiography and choledochoscopy for each patient were recorded, analyzed, and compared. RESULTS: Among the 287 patients, T-tube cholangiography detected residual stones in 38 cases, which were confirmed by choledochoscopy in 29 cases. Conversely, of the 249 patients without evidence of residual stones on T-tube angiography, 11 patient was later found to have retained stones through choledochoscopy. There was no significant difference between the results of T-tube cholangiography and choledochoscopy (P = 0.82), indicating a high level of agreement between the two methods (Kappa value: 0.70) (95% CI, 0.65-0.76). CONCLUSION: There is no significant difference in the diagnostic accuracy between T-tube cholangiography and choledochoscopy for detecting residual bile duct stones after surgery (P = 0.82). The two methods demonstrated a high level of consistency (Kappa value: 0.70) (95% CI, 0.65-0.76). The choice of diagnostic method for postoperative residual bile duct stones should be based on the specific condition of the patient.


Assuntos
Colangiografia , Endoscopia do Sistema Digestório , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Colangiografia/métodos , Endoscopia do Sistema Digestório/métodos , Idoso , Adulto , Drenagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico , Cálculos Biliares/cirurgia , Cálculos Biliares/diagnóstico por imagem , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia , Colecistectomia Laparoscópica , Procedimentos Cirúrgicos do Sistema Biliar
3.
Environ Res ; 262(Pt 1): 119780, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39142460

RESUMO

Antimicrobial resistance (AMR) poses a global health threat to aquatic environments and its propagation is a hot topic. Therefore, deactivating antibiotic-resistant bacteria (ARB) and removing antibiotic resistance genes (ARGs) from water is crucial for controlling AMR transmission. Peracetic acid (PAA), which is known for its potent oxidizing properties and limited by-product formation, is emerging as a favorable disinfectant for water treatment. In this study, we aimed to assess the efficacy of pre-exposure to PAA followed by UV treatment (PAA-UV/PAA) compared with the simultaneous application of UV and PAA (UV/PAA). The focus was on deactivating vancomycin-resistant Enterococcus faecalis (VREfs), a typical ARB in water. Pre-exposure to PAA significantly enhanced the efficacy of subsequent UV/PAA treatment. At a UV fluence of 7.2 mJ cm-2, the PAA-UV/PAA method achieved a 6.21 log reduction in VREfs, surpassing the 1.29 log reduction observed with UV/PAA. Moreover, compared to UV/PAA, PAA-UV/PAA showed increased efficacy with longer pre-exposure times and higher PAA concentrations, maintaining superior performance across a broad pH range and in the presence of humic acid. Flow cytometry analysis indicated minimal cellular membrane damage using both methods. However, the assessments of superoxide dismutase (SOD) activity and adenosine triphosphate content revealed that PAA-UV/PAA induced greater oxidative stress under similar UV irradiation conditions, leading to slower bacterial regrowth. Specifically, SOD activity in PAA-UV/PAA surged to 3.06 times its baseline, exceeding the 1.73-fold increase under UV/PAA conditions. Additionally, pre-exposure to PAA amplified ARGs degradation and reduced resistance gene leakage, effectively mitigating the spread of AMR. Pre-exposure to 200 µM PAA for 10 and 20 min enhanced vanB gene removal efficiency by 0.14 log and 1.29 log, respectively. Our study provides a feasible approach for optimizing UV/PAA disinfection for efficient removal of ARB and ARGs.

4.
Oncol Lett ; 27(6): 265, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38659422

RESUMO

Hepatocellular carcinoma (HCC) is a malignancy associated with high morbidity and mortality rates. Conversion therapy provides patients with unresectable HCC (uHCC) the opportunity to undergo radical treatment and achieve long-term survival. Despite accumulating evidence regarding the efficacy of conversion therapy, the optimal treatment approach for such therapy remains uncertain. Lenvatinib (LEN) has shown efficacy and tolerable rates of adverse events (AEs) when applied in combination with immune checkpoint inhibitors (ICIs) or locoregional therapy (LRT) over the past decade. Therefore, the present meta-analysis was performed to systematically assess the safety and efficacy of LEN-based treatment regimens in conversion therapies for uHCC. Data on outcomes, including the conversion rate, objective response rate (ORR), disease control rate (DCR) and AE incidence in patients with uHCC, were collected. A systematic literature search was performed using MEDLINE, Embase, Web of Science and Cochrane Library databases, up to the date of September 1, 2023. In total, 16 studies, encompassing a total of 1,650 cases of uHCC, were included in the final meta-analysis. The pooled conversion rates for LEN alone, LEN + ICI, LEN + LRT and LEN + ICI + LRT were calculated to be 0.04 (95% CI, 0.00-0.07; I2=77%), 0.23 (95% CI, 0.16-0.30; I2=66%), 0.14 (95% CI, 0.10-0.18; I2=0%) and 0.35 (95% CI, 0.23-0.47; I2=88%), respectively. The pooled ORRs for LEN alone, LEN + ICI, LEN + LRT and LEN + ICI + LRT were found to be 0.45 (95% CI, 0.23-0.67; I2=96%), 0.49 (95% CI, 0.39-0.60; I2=78%), 0.43 (95% CI, 0.24-0.62; I2=88%) and 0.69 (95% CI, 0.56-0.82; I2=92%), respectively. The pooled DCRs for LEN alone, LEN + ICI, LEN + LRT and LEN + ICI + LRT were observed to be 0.77 (95% CI, 0.73-0.81; I2=23%), 0.82 (95% CI, 0.69-0.95; I2=90%), 0.67 (95% CI, 0.39-0.94; I2=94%) and 0.87 (95% CI, 0.82-0.93; I2=67%), respectively. The pooled grade ≥3 AEs for LEN alone, LEN + ICI, LEN + LRT and LEN + ICI + LRT were 0.25 (95% CI, 0.14-0.36; I2=89%), 0.43 (95% CI, 0.34-0.53; I2=23%), 0.42 (95% CI, 0.19-0.66; I2=81%) and 0.35 (95% CI, 0.17-0.54; I2=94%), respectively. These findings suggested that LEN-based combination strategies may confer efficacy and acceptable tolerability for patients with uHCC. In particular, LEN + ICI, with or without LRT, appears to represent a highly effective conversion regimen, with an acceptable conversion rate and well-characterized safety profile.

5.
Sci Total Environ ; 920: 170818, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38342461

RESUMO

In this study, we synthesized nano zero-valent iron incorporated with a multifunctional molybdenum disulfide film (MoS2@nZVI). The material exhibited a 100.00 % removal efficiency for sulfamethoxazole (SMX) and achieved a kobs of 0.4485 min-1 within 10 min. The excellent degradation performance can be attributed to the incorporation of the MoS2 film, which facilitated Fe2+ regeneration. Simultaneously, the MoS2 film assisted in proton accumulation and electron transfer, thereby amplifying the efficiency of SMX degradation across a wide pH range. Comprehensive experimental examinations and characterizations confirmed the selectivity and stability of the MoS2@nZVI catalysts, encompassing both degradation efficiency and structural stability. Interestingly, the MoS2@nZVI/PMS system for SMX degradation significantly involved a non-radical mechanism (1O2), along with radicals (SO4·-, ·OH, and O2·-). The direct oxidation of PMS by Fe2+ not only facilitated the generation of ·OH and SO4·- but also actively engaged in a reaction with O2, leading to the production of O2·-. The primary pathway for 1O2 production was established through the interplay between Mo6+ and O2·-, in conjunction with the direct electron transfer (DET) mechanism between PMS and SMX. The contributions of these active species to SMX degradation occurred in the following precedence: SO4·- > 1O2 > ·OH > O2·-. Notably, the primary pathways for radicals and non-radicals were studied during separate reaction periods. This investigation proposed a promising approach for mitigating pharmaceutical pollutants using a transition metal sulfide-modified nZVI catalyst.

6.
Angew Chem Int Ed Engl ; 63(12): e202318784, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38291557

RESUMO

Plitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75 mg/L. Next, we developed two straightforward chemical strategies to convert didemnin B into plitidepsin, one of which involved a one-step synthetic route giving over 90 % overall yield. Furthermore, we synthesized 13 new didemnin derivatives and three didemnin probes, enabling research into structure-activity relationships and interactions between didemnin and proteins. Our study highlights the synergistic potential of biosynthesis and chemical synthesis in overcoming the challenge of producing complex natural products sustainably and at scale.


Assuntos
Antineoplásicos , Depsipeptídeos , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/metabolismo , Depsipeptídeos/farmacologia , Antineoplásicos/farmacologia , Relação Estrutura-Atividade
7.
J Hazard Mater ; 458: 131968, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37429190

RESUMO

Both molybdenum disulfide (MoS2) and nano zero-valent iron (nZVI) exhibit excellent adsorption abilities. However, the constrained conductivity of MoS2 and the lack of selectivity of nZVI for electron transfer still pose challenges. In this study, we designed a series of novel nano zero-valent iron supported by molybdenum disulfide composites (nZVI@MD) with multiple electron-rich active sites, including iron dopant replacement, iron atom intercalation and exposed Mo4+, for effective removal of Cr(VI). Results showed that preparation temperature and the amount of MoS2 added were identified as the two most significant factors affecting the reduction properties of nZVI@MD. Systematic experiments revealed that the nZVI@MD exhibited good anti-interference performance, stability and reusability due to its excellent electron selectivity. Characterization results exhibited that iron atoms replaced the sulfur vacancies in MoS2 and inserted into an intercalation of MoS2 during the preparation process. The mechanisms underlying the uptake of Cr(VI) by nZVI@MD can be proposed as follows: (i) electrostatic interactions, (ii) reduction reaction, and (iii) co-precipitation involving Fe-O-Cr. Furthermore, nZVI@MD exhibited excellent electron activity, hydrophilicity and oxidation resistance, confirmed by density functional theory (DFT) calculations. This work provided new strategies and mechanistic insights for the rational design of adsorbents.

8.
J Environ Manage ; 340: 117962, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37086557

RESUMO

Disinfection is widely applied in water and wastewater treatment to inactivate viruses. However, the inactivation mechanism associated with viral structural alteration during disinfection is still not clear. In this work, inactivation of bacteriophage phiX174 by ultraviolet radiation (UV254) and free chlorine (FC), two most commonly used disinfection processes, was studied at the molecular level to investigate the relationship between phiX174 genome impairment and virus inactivation, and the correlation between protein impairment and function loss. Double-layer agar technique, quantitative real-time polymerase chain reaction (qPCR), real-time reverse transcription-polymerase chain reaction (RT-qPCR), and liquid chromatography-tandem mass spectrometry techniques (LC-MS/MS), together with structure impairment and function experiments were implemented to quantitatively analyze the inactivation and damage to genome and proteins of phiX174. Results showed that UV254 and FC could effectively inactivate phiX174 at the practical doses (UV254 dose of 30 mJ/cm2, and FC of 1-3 mg/L) used in water treatment plants, accompanied with the damage to viral genome and proteins. Specifically, a UV254 irradiation dose of 9.6 mJ/cm2, and FC at an initial concentration of 1 mg/L at 4 min could lead to a 4-log10 inactivation. Nevertheless, the combination of these two methods at selected doses played no significant synergistic disinfection effect. During UV254 disinfection, the proportion of phiX174 with damaged genome was similar with that of the inactivated phiX174. In addition, UV254 and FC could disrupt proteins of phiX174 such as H protein, thereby hindering the physiological function associated with these proteins. With these findings, it is suggested that UV254 and FC disinfection could hinder the injection of the viral genome into host cells, thus resulting in the inactivation of phiX174. This work provides a comprehensive study of the inactivation mechanism of phiX174, which can enhance the applicability of UV254 and FC in water treatment plants, and facilitate the design and optimization of disinfection technologies for virus control in drinking water and wastewater worldwide to ensure the biosafety.


Assuntos
Bacteriófagos , Vírus , Purificação da Água , Raios Ultravioleta , Cloro/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Desinfecção/métodos , Cloretos
9.
Front Oncol ; 12: 985281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330502

RESUMO

Background: Intraoperative blood salvage autotransfusion(IBSA) has been widely used in a variety of surgeries, but the use of IBSA in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT) is controversial. Numerous studies have reported that IBSA used during LT for HCC is not associated with adverse oncologic outcomes. This systematic review and meta-analysis aims to estimate the clinical prognosis of IBSA for patients with H+CC undergoing LT. Methods: MEDLINE, Embase, Web of Science, and Cochrane Library were searched for articles describing IBSA in HCC patients undergoing LT from the date of inception until May 1, 2022, and a meta-analysis was performed. Study heterogeneity was assessed by I2 test. Publication bias was evaluated by funnel plots, Egger's and Begg's test. Results: 12 studies enrolling a total of 2253 cases (1374 IBSA and 879 non-IBSA cases) are included in this meta-analysis. The recurrence rate(RR) at 5-year(OR=0.75; 95%CI, 0.59-0.95; P=0.02) and 7-year(OR=0.65; 95%CI, 0.55-0.97; P=0.03) in the IBSA group is slightly lower than non-IBSA group. There are no significant differences in the 1-year RR(OR=0.77; 95% CI, 0.56-1.06; P=0.10), 3-years RR (OR=0.79; 95% CI, 0.62-1.01; P=0.06),1-year overall survival outcome(OS) (OR=0.90; 95% CI, 0.63-1.28; P=0.57), 3-year OS(OR=1.16; 95% CI, 0.83-1.62; P=0.38), 5-year OS(OR=1.04; 95% CI, 0.76-1.40; P=0.82),1-year disease-free survival rate(DFS) (OR=0.80; 95%CI, 0.49-1.30; P=0.36), 3-year DFS(OR=0.99; 95%CI, 0.64-1.55; P=0.98), and 5-year DFS(OR=0.88; 95%CI, 0.60-1.28; P=0.50). Subgroup analysis shows a difference in the use of leukocyte depletion filters group of 5-year RR(OR=0.73; 95%CI, 0.55-0.96; P=0.03). No significant differences are found in other subgroups. Conclusions: IBSA provides comparable survival outcomes relative to allogeneic blood transfusion and does not increase the tumor recurrence for HCC patients after LT. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022295479.

10.
Chem Biodivers ; 19(9): e202200473, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35931661

RESUMO

An undescribed tigliane diterpenoid, 13-acetyl-12,17-di-O-tiglylphorbol (1), along with thirty-three known components, were isolated from the stems of Croton tiglium L. var. xiaopadou (Euphorbiaceae). Their structures were established based on spectroscopic data and ECD spectra. Their anti-neuroinflammatory effects were evaluated in LPS-induced BV-2 microglia. Thirteen tested compounds showed significant inhibitory activities, especially compounds 10, 16, 18 and 21 exhibited an inhibitory effect with IC50 values in the range of 12.39 to 17.80 µM, which are comparable with that of the positive control (minocycline, IC50 13.92 µM).


Assuntos
Croton , Diterpenos , Forbóis , Croton/química , Diterpenos/química , Diterpenos/farmacologia , Lipopolissacarídeos/farmacologia , Minociclina , Estrutura Molecular , Doenças Neuroinflamatórias
12.
Environ Sci Process Impacts ; 22(2): 418-429, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32002526

RESUMO

The emergence of vancomycin-resistant Enterococcus faecalis (E. faecalis) in water is threatening the health of human beings. The effect of ultraviolet disinfection on vancomycin-resistant E. faecalis, including the effectiveness, photoreactivation and dark repair of E. faecalis, and the deactivation mechanism were investigated in this work. Ultraviolet disinfection could quickly inactivate the target antibiotic resistant bacterium (ARB), E. faecalis, and it caused damage to the cell membrane and induced the decrease of the total adenosine triphosphate (ATP) content and the superoxide dismutase (SOD) activity significantly (p < 0.05). E. faecalis could reactivate after ultraviolet disinfection especially under light conditions. Furthermore, the removal of the selected antibiotic resistance gene (ARG), vanB, by ultraviolet radiation and the effect on the vancomycin resistance of E. faecalis were investigated, which showed that ultraviolet disinfection had no significant effect on the vancomycin resistance of E. faecalis (p > 0.05).


Assuntos
Antibacterianos , Resistência Microbiana a Medicamentos , Enterococcus faecalis , Raios Ultravioleta , Vancomicina , Desinfecção , Enterococcus faecalis/efeitos dos fármacos , Humanos
13.
Gastroenterol Res Pract ; 2019: 6160783, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781194

RESUMO

PURPOSE: As we all know, curative resection remains the only effective treatment for hepatocellular cancer (HCC). However, systemic inflammatory response syndrome always correlates with surgery, which may impose an impact on the clinical outcome of HCC patients who had undergone curative treatment. The present study is aimed at exploring the correlation between perioperative inflammatory mediators and recurrence risk of HCC. METHODS: This study retrospectively included 157 histologically confirmed single HCC patients (88 patients developed HCC again) who had received radical hepatectomy between January 2016 and May 2018 at the Department of Hepatobiliary Surgery, the People's Liberation Army General Hospital (PLAGH), China. The cut-off values for predicting recurrence were determined by receiver operating characteristic (ROC) curve analysis with estimation of the Youden index. Recurrence-free survival (RFS) was assessed using the Kaplan-Meier method, and the difference was compared between groups by the log-rank test. Univariate/multivariate analysis was performed to identify independent risk factors of postoperative tumor recurrence. RESULTS: The perioperative serum IL1, IL2, and IL10 levels showed no difference between groups, whereas the serum IL6, IL8, and TNF-α levels showed significant differences between groups. High preoperative serum IL6, IL8, and TNF-α levels were significantly associated with shorter RFS. Multivariate analysis revealed that preoperative serum IL6 > 8.45 pg/ml, preoperative serum IL8 > 68 pg/ml, preoperative serum TNF - α > 14.9 pg/ml, microvascular invasion (MVI), and maximum tumor size > 6 cm were independent predictors of RFS. CONCLUSIONS: The present study confirmed that high preoperative serum IL6, IL8, and TNF-α levels were distinctly correlated with the postoperative tumor recurrence risk of HCC patients.

14.
Med Sci Monit ; 25: 6755-6766, 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31494663

RESUMO

BACKGROUND Matricellular proteins of the extracellular matrix (ECM) include tenascin-C (TNC) and cellular communication network factor 3 (CCN3). This study aimed to investigate the role of TNC and CCN3 as prognostic factors for post hepatectomy liver failure (PHLF) in a rat model of partial hepatectomy and 50 patients following partial hepatectomy. MATERIAL AND METHODS Sprague-Dawley rats underwent 85% (n=53) or 90% hepatectomy (n=53) in the partial hepatectomy (PHx) model. TNC and CCN3 mRNA expression in residual liver tissue was evaluated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and enzyme-linked immunoassay (ELISA) determined the serum levels of TNC and CCN3. In 50 patients who underwent partial hepatectomy, TNC and CCN3 serum levels were measured on postoperative day 1 and day 3. RESULTS In the rat partial hepatectomy model, mRNA and serum levels of TNC and CCN3 were significantly increased within the first 24 h, and were higher in the 90% PHx group compared with the 85% PHx group. Fifty patients who underwent partial hepatectomy, included patients with PHLF (n=12) and patients without PHLF (n=38). Multivariate analysis confirmed that serum levels on postoperative day 3 TNChigh+CCN3high was a significant predictor of PHLF, which was associated with more than twice the risk of severe morbidity when compared with the low-risk patients (80% vs. 30%) and a significantly longer hospital stay (17 days vs. 8 days). CONCLUSIONS Further studies are needed to evaluate the potential role of the matricellular proteins, TNC and CCN3 as early clinical predictors for PHLF.


Assuntos
Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Tenascina/metabolismo , Adulto , Idoso , Animais , Área Sob a Curva , Bilirrubina/sangue , Modelos Animais de Doenças , Feminino , Humanos , Tempo de Internação , Falência Hepática/sangue , Falência Hepática/genética , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Morbidade , Análise Multivariada , Proteína Sobre-Expressa em Nefroblastoma/sangue , Proteína Sobre-Expressa em Nefroblastoma/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Ratos Sprague-Dawley , Fatores de Risco , Análise de Sobrevida , Tenascina/sangue , Tenascina/genética
15.
J Immunother Cancer ; 7(1): 125, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064408

RESUMO

BACKGROUND: Insertion-deletion mutations (indels) may generate more tumour-specific neoantigens with high affinity to major histocompatibility complex class I. A high indel ratio is also related to a good response to programmed death-1 (PD-1) checkpoint blockade in melanoma and renal cell carcinoma. However, the correlation between a high indel ratio and the immunotherapy response in intrahepatic cholangiocarcinoma (ICC) is unknown. CASE PRESENTATION: Two patients with relapsed ICC at stage IIIb were treated with PD-1 blockade combined with chemotherapy. After 7 and 4 months of chemotherapy and PD-1 blockade (3 and 15 cycles, and 5 and 6 cycles, respectively), magnetic resonance imaging and positron emission tomography with computed tomography imaging showed that both patients achieved a complete response (CR), which has lasted up to nearly 16 and 13 months to date, respectively. Whole-exome sequencing and immunohistochemistry analysis showed that both patients had cancers with microsatellite stability (MSS) and mismatch repair (MMR) proficiency, weak PD-L1 expression, and a tumour mutation burden (TMB) of 2.95 and 7.09 mutations/Mb, respectively. Patient 2 had mutations of TP53 and PTEN that are known to confer sensitivity to immunotherapy, and the immunotherapy-resistant mutation JAK2, whereas patient 1 had no known immunotherapy response-related mutations. However, the indel ratios of the two patients (48 and 66.87%) were higher than the median of 12.77% determined in a study of 71 ICC patients. Moreover, comparison to six additional ICC patients who showed a partial response, stable disease, or progressive disease after PD-1 blockade treatment alone or in combination with chemotherapy demonstrated no difference in PD-L1 expression, TMB, MSI, and MMR status from those of the two CR patients, whereas the indel frequency was significantly higher in the CR patients. CONCLUSIONS: These two cases suggest that indels might be a new predictor of PD-1 blockade response for ICC patients beside PD-L1 expression, TMB, MSI, and dMMR, warranting further clinical investigation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Mutação INDEL , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Colangiocarcinoma/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do Tratamento
16.
J Colloid Interface Sci ; 539: 297-305, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30590237

RESUMO

Understanding the interaction between silver nanoparticles (Ag NPs) and substances in aquatic systems enables Ag NPs to be better applied in science and industry. Moreover, it also could help us to determine the fate of Ag NPs and assess their hazards in aquatic environment. In this work, the interaction of Ag NPs with HCO3-, ubiquitous ligand in aquatic systems, during long-term incubation was firstly studied and the possible mechanism was proposed. Results showed that the long-term incubation with HCO3- led to the red-shifting of UV-vis spectra, the increasing of particles zeta potential (more negative), and the declining of the aqueous Ag+ concentration, as well as the decreasing in the toxicity of Ag NPs suspensions. Furthermore, the ambient temperature was found to have a great impact on the interaction of Ag NPs with HCO3-. The reaction process between Ag NPs and HCO3- was revealed by H2O2 mediated oxidation experiments. An ultrathin Ag2CO3 layer was proved to form on the surface of Ag NPs, which should be the reason for the evolution of various properties of Ag NPs described above.


Assuntos
Antibacterianos/farmacologia , Bicarbonatos/farmacologia , Escherichia coli/efeitos dos fármacos , Nanopartículas Metálicas/química , Viabilidade Microbiana/efeitos dos fármacos , Prata/farmacologia , Antibacterianos/química , Bicarbonatos/química , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Prata/química , Propriedades de Superfície , Temperatura
17.
Sci Total Environ ; 648: 271-284, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30118940

RESUMO

Chlorination is one of the most widely used disinfection techniques, and the problem of "chlorine-resistant bacteria" (CRB) has attracted more attention recently. In this study, the deactivation of typical CRB in water, Mycobacterium fortuitum (M. fortuitum) and Mycobacterium mucogenicum (M. mucogenicum), by free chlorine was investigated with Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) as the reference. The chlorination effectiveness of chlorine on M. fortuitum and M. mucogenicum and the effect of chlorine concentration, pH, and humic acid were studied. It was found that M. mucogenicum was more resistant to chlorine than M. fortuitum, both of which were much more resistant than E. coli and B. subtilis. The effect of disinfectant concentration on the inactivation efficiency was positive, whereas the influence of pH and humic acid was negative. The inactivation mechanisms were explored by analyzing the bacteria morphology, the destruction of cell membrane, the cell hydrophobicity, as well as total adenosine triphosphate (ATP), superoxide dismutase (SOD) activity. The slight destruction of the cell membrane was observed after deactivation with chlorine, and high hydrophobicity of the cell membrane combined with metabolic changes might lead to the chlorine tolerance of Mycobacteria.


Assuntos
Cloro/farmacologia , Desinfetantes/farmacologia , Desinfecção/métodos , Mycobacterium/efeitos dos fármacos , Substâncias Húmicas/análise , Concentração de Íons de Hidrogênio
18.
RSC Adv ; 10(1): 228-235, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-35492535

RESUMO

Understanding the effect of various environmental factors on the transformation of silver nanoparticles (Ag NPs) is crucial to determine their toxicity and fate in the environment. Ag NPs are inevitably exposed to sunlight and will be in contact with chloride (Cl-), a ubiquitous ligand in natural water, once released into the environment. In this study, the combined effect of Cl- and light on various physicochemical properties (optical property, dissolution, morphology, surface charge) of different sizes Ag NPs was studied. The results showed that light irradiation, in the presence of Cl-, led to a great decrease in the concentration of dissolved Ag and a remarkable increase in the zeta potential of Ag NPs, as well as the generation of some tiny Ag NPs and fusion aggregates. AgCl was suggested to rapidly coat onto Ag NPs after exposure to Cl-. And the AgCl layer was obviously destroyed by photoreduction under light irradiation. Meanwhile, the Ag NP size exhibited a great impact on the destruction of the AgCl layer. It was further observed that the AgCl layer gradually re-formed when the light was removed, which suggested that Ag NPs might present different states during the daytime and at night in aquatic environments.

19.
RSC Adv ; 9(44): 25667-25676, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35530077

RESUMO

In this study, we prepared polymer quaternary ammonium salt-capped silver nanoparticles (PQAS-AgNPs) and investigated their antimicrobial activities. The antimicrobial effectiveness of PQAS-AgNPs on Bacillus subtilis (B. subtilis), and the effect of dose, pH, chloride ion and humic acid (HA) were studied. It was found that PQAS-AgNPs revealed excellent antimicrobial activity to B. subtilis, compared with polyvinylpyrrolidone-capped silver nanoparticles (PVP-AgNPs), which was the reference antimicrobial material. The positive surface, the antimicrobial activity of PQAS, and the synergistic antibacterial effect between PQAS and AgNPs contributed to the significant antibacterial superiority of PQAS-AgNPs. This study demonstrated that the impact of the dose of the material was positive and the microbiocidal efficacy of PQAS-AgNPs was stronger at lower pH. In addition, the antibacterial performance of PQAS-AgNPs decreased in the presence of Cl- and HA. Finally, in combination with the results of FCM and adenosine triphosphate (ATP) content, it was found that PQAS-AgNPs destroyed the respiratory chain of bacterial cells, reduced the synthesis of ATP, and destroyed the cell wall and cell membrane function.

20.
Sci Total Environ ; 619-620: 1618-1627, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29103649

RESUMO

To investigate the fate of metal-based nanoparticles in water oxidation treatment processes, the decay of Ag-NPs in the presence of three kinds of water treatment preoxidants, sodium hypochlorite (NaClO), hydrogen peroxide (H2O2) and potassium permanganate (KMnO4), was investigated in this work. Dissolution of Ag-NPs into silver ions (Ag+) was found to occur under exposure to NaClO, H2O2 and KMnO4. The morphology of Ag-NPs changed after reacting with NaClO, H2O2 and KMnO4. Factors affecting the decay of Ag-NPs, i.e., the dosage of oxidants, pH, the presence of humic acid, typical ions in water, and the size of the nanoparticles, were investigated. A higher dosage of oxidants, the presence of calcium ions, and lower size of Ag-NPs promoted the decay of Ag-NPs. The presence of humic acid and sulfide ions inhibited the decay of Ag-NPs. The decay of Ag-NPs under exposure to oxidants was significantly affected by the pH. The mechanism of the Ag-NPs in the presence of oxidants under different environmental conditions is also discussed.

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