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1.
Sci Total Environ ; 750: 141415, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32846251

RESUMO

Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.


Assuntos
Colistina , Microbioma Gastrointestinal , Amoxicilina , Antibacterianos , Disbiose , Humanos
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118832, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32871391

RESUMO

The assignment of experimental optical absorption spectra of protonated anthracene has been under debate for years. It is complicated by the presence of rich vibronic spectral features and the possible co-occurrence of two isomers, 9H-An+ and 1H-An+. In this study, the vibrationally resolved absorption spectra of 9H-An+ and 1H-An+ have been calculated using time-dependent density functional theory. The calculated vibronic spectra profiles of 9H-An+ and 1H-An+ are in excellent agreement with the corresponding experimental results and provide unambiguously spectra assignments. It shows that the previously reported assignments based on vertical excitation energy are largely wrong. The onset located at 493.8 nm of the experimental spectrum can be assigned to the S0 â†’ S1 transition of 9H-An+, while the origin band located at 453.5 nm corresponds to the S0 â†’ S2 transition of 1H-An+.

3.
Cell Biol Toxicol ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33130971

RESUMO

Inflammatory bowel disease (IBD) is a chronic idiopathic disorder causing inflammation in the gastro-intestinal tract, which is lack of effective drug targets and medications. To identify novel therapeutic agents against consistent targets, we exploited a systems pharmacology-driven framework that incorporates drug-target networks of natural product and IBD disease genes. Our in silico approach found that Ligustilide (LIG), one of the major active components of Angelica acutiloba and Cnidium Officinale, potently attenuated IBD. The following in vivo and in vitro results demonstrated that LIG prevented experimental mice colitis induced by dextran sulfate sodium (DSS) via suppressing inflammatory cell infiltration, the activity of MPO and iNOS, and the expression and production of IL-1ß, IL-6, and TNF-α. Subsequently, the network analysis helped to validate that LIG alleviated colitis by inhibiting NF-κB and MAPK/AP-1 pathway through activating PPARγ, which were further confirmed in RAW 264.7 cells and bone marrow-derived macrophages in vitro. In summary, this study reveals that LIG activated PPARγ to inhibit the activation of NF-κB and AP-1 signaling thus eventually alleviated DSS-induced colitis, which has promising activities and may serve as a candidate for the treatment of IBD.Graphical abstract This study suggested novel computational and experimental pharmacology approaches to identify potential IBD therapeutic agents by exploiting polypharmacology of natural products. We demonstrated that LIG could attenuate inflammation in IBD by inhibiting NF-κB and AP-1 pathways via PPARγ activation to reduce the expression of pro-inflammatory cytokines in macrophages. These findings offer comprehensive pre-clinical evidence that LIG may serve as a promising candidate for IBD therapy in the future. Graphical headlights: 1. Systems pharmacology uncovered Ligustilide attenuates experimental colitis in mice. 2. Network-based analysis predicted the mechanism of Ligustilide against IBD, which was validated by inhibiting PPARγ-mediated inflammation pathways. 3. Ligustilide activated PPARγ to inhibit NF-κB and AP-1 activation thus eventually alleviated DSS-induced colitis.4. Ligustilide has promising activities and may serve as a candidate for the treatment of IBD.

4.
Int J Biol Macromol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33157130

RESUMO

The aim of this study was to investigate the effect of a polysaccharide from Scutellaria baicalensis Georgi on UC. Gut microbiota dysbiosis is a worldwide problem associating with ulcerative colitis. One homogeneous polysaccharide, named SP2-1, was isolated from Scutellaria baicalensis Georgi. SP2-1 comprised mannose, ribose, rhamnose, glucuronic acid, glucose, xylose, arabinose, fucose in the molar ratio of 5.06:21.24:1.00:20.25:3.49:50.90:228.77:2.40, with Mw of 3.72 × 106 Da. SP2-1 treatment attenuated body weight loss, reduced DAI, ameliorated colonic pathological damage, and decreased MPO activity of UC mice induced by DSS. SP2-1 also suppressed the levels of proinflammatory cytokines. Additionally, the intestinal barrier was repaired due to the up-regulated expressions of ZO-1, Occludin and Claudin-5. SP2-1 remarkably enhanced the levels of acetic acid, propionic acid, and butyric acid in DSS-treated mice. Furthermore, as compared with model group, the abundance of Firmicutes, Bifidobacterium, Lactobacillus, and Roseburia were significantly increased with SP2-1 treatment. And SP2-1 could significantly inhibit the levels of Bacteroides, Proteobacteria and Staphylococcus. In conclusion, SP2-1 might serve as a novel drug candidate against UC.

5.
Adv Mater ; : e2004059, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33174328

RESUMO

The practical utilization of plasmon-based technology relies on the ability to find high-performance plasmonic materials other than noble metals. A key scientific challenge is to significantly increase the intrinsically low concentration of free carriers in metal-oxide materials. Here, a novel electron-proton co-doping strategy is developed to achieve uniform hydrogen doping in metal-oxide MoO3 at mild conditions, which creates a metal-like ultrahigh free-carrier concentration approaching that of noble metals (1021 cm-3 in H1.68 MoO3 versus 1022 cm-3 in Au/Ag). This bestows giant and tunable plasmonic resonances in the visible region to this originally semiconductive material. Using ultrafast spectroscopy characterizations and first-principle simulations, the formation of a quasi-metallic energy band structure that leads to long-lived and strong plasmonic field is revealed. As verified by the surface-enhanced Raman spectra (SERS) of rhodamine 6G molecules on Hx MoO3 , the SERS enhancement factor reaches as high as 1.1 × 107 with a detection limit at concentration as low as 1 × 10-9  mol L-1 , representing the best among the hitherto reported non-metal systems. The findings not only provide a set of metal-like semiconductor materials with merits of low cost, tunable electronic structure, and plasmonic resonance, but also a general strategy to induce tunable ultrahigh free-carrier concentration in non-metal systems.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33174426

RESUMO

Dioxygen (O2) activation is a vital step in many oxidation reactions, and a graphitic carbon nitride (g-C3N4) sheet is known as a famous semiconductor catalytic material. Here, we report that the atomic boron (B)-doped g-C3N4 (B/g-C3N4) can be used as a highly efficient catalyst for O2 activation. Our first-principles results show that O2 can be easily chemisorbed at the B site and thus can be highly activated, featured by an elongated O-O bond (∼1.52 Å). Interestingly, the O-O cleavage is almost barrier free at room temperatures, independent of the doping concentration. It is revealed that the B atom can induce considerable spin polarization on B/g-C3N4, which accounts for O2 activation. The doping concentration determines the coupling configuration of net-spin and thus the magnitude of the magnetism. However, the distribution of net-spin at the active site is independent of the doping concentration, giving rise to the doping concentration-independent catalytic capacity. The unique monolayer geometry and the existing multiple active sites may facilitate the adsorption and activation of O2 from two sides, and the newly generated surface oxygen-containing groups can catalyze the oxidation coupling of methane to ethane. The present findings pave a new way to design g-C3N4-based metal-free catalysts for oxidation reactions.

7.
Am J Otolaryngol ; 42(1): 102790, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33137674

RESUMO

PURPOSES: To improve the lymph node dissection as well as protect parathyroid gland and recurrent laryngeal nerve, the carbon nanoparticles and intraoperative neuromonitoring were applied in papillary thyroid microcarcinoma surgery. METHODS: Carbon nanoparticles and intraoperative neuromonitoring were used in the experimental group, whereas the control group were not. Routine pathological examination was performed. RESULTS: The lymph nodes dissected was significantly higher in the experimental group, but the metastatic lymph nodes were not. The number of mistakenly dissected parathyroid gland and postoperative hypoparathyroidism were 3 and 13 in the experimental group respectively, significantly less than 10 and 25 in the control group. The incidences of overall, transient and persistent recurrent laryngeal nerve palsy in the experimental group were 5.5%, 5.5% and 0% respectively, whereas in the control group were 8.6%, 6.9% and 1.7%. CONCLUSIONS: Carbon nanoparticles can improve lymph node dissection in papillary thyroid microcarcinoma surgery, and the combination of carbon nanoparticles with intraoperative neuromonitoring can reduce surgical complications and improve patient quality of life.

9.
Rev Esp Enferm Dig ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33222482

RESUMO

BACKGROUND: Endoscopic submucosal dissection has been widely recognized by patients and doctors for its advantages for early gastric cancer. The accurate prediction of the risk of lymph node metastasis in early gastric cancer is important to select patients suitable treatments for this procedure. Unfortunately, the accuracy of endoscopic ultrasound and computed tomography in the diagnosis of early gastric cancer lymph node status is extremely limited. PURPOSE: This study was aimed to identify the risk factors of lymph node metastasis in early gastric cancer. Based on which, a nomogram risk prediction model was then constructed to accurately determine the possibility of lymph node metastasis in early gastric cancer for guiding further treatment of clinicians. METHODS: A retrospective examination of records of early gastric cancer patients undergoing radical gastrectomy from August 2012 to August 2019 in the Gastrointestinal Center of Subei people's Hospital was conducted. The clinicopathological data were classified into the training set and validation set according to the time. Univariate and multivariate analyses were carried out to identify risk factors related to lymph node metastasis. A nomogram model for predicting the occurrence of lymph node metastasis in early gastric cancer was established and validated. RESULTS: Of the 503 early gastric cancer patients, 15.5% had lymph node metastasis. Logistic stepwise regression analysis showed that the predictive factors included sex, tumor location, tumor diameter, differentiation, ulcer, and lymphatic vascular invasion. The discrimination of lymph node metastasis prediction model was satisfactory with area under curve of 0.8033 (internal validation) and 0.7353 (external validation). The correction effect of the calibration was satisfactory, and the decision curve analysis showed strong clinical practicability. CONCLUSION: The nomogram risk prediction model of lymph node metastasis has been established for early gastric cancer patients to assist in formulating personalized treatment plans.

11.
Virulence ; 11(1): 1569-1581, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33172355

RESUMO

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Área Sob a Curva , Betacoronavirus/genética , Biomarcadores , Sedimentação Sanguínea , Proteína C-Reativa/análise , China , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Laringe/virologia , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Valor Preditivo dos Testes , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Proteína Amiloide A Sérica/análise
12.
Nat Mater ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230325

RESUMO

Electrically conducting 2D metal-organic frameworks (MOFs) have attracted considerable interest, as their hexagonal 2D lattices mimic graphite and other 2D van der Waals stacked materials. However, understanding their intrinsic properties remains a challenge because their crystals are too small or of too poor quality for crystal structure determination. Here, we report atomically precise structures of a family of 2D π-conjugated MOFs derived from large single crystals of sizes up to 200 µm, allowing atomic-resolution analysis by a battery of high-resolution diffraction techniques. A designed ligand core rebalances the in-plane and out-of-plane interactions that define anisotropic crystal growth. We report two crystal structure types exhibiting analogous 2D honeycomb-like sheets but distinct packing modes and pore contents. Single-crystal electrical transport measurements distinctively demonstrate anisotropic transport normal and parallel to the π-conjugated sheets, revealing a clear correlation between absolute conductivity and the nature of the metal cation and 2D sheet packing motif.

13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(10): 1241-1246, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33198872

RESUMO

OBJECTIVE: To established the diagnostic criteria for venomous snakebite of Trimeresurus stejnegeri in Guangxi by ourselves, and explore the clinical effect and mechanism of covered vacuum sealing drainage (VSD) in the treatment for venomous snakebite of Trimeresurus stejnegeri in Guangxi. METHODS: According to the Chinese emergency medicine for snakebite and the Chinese snake, the diagnostic criteria for venomous snakebite of Trimeresurus stejnegeri in Guangxi were formulated: (1) the responsible venomous snake was identified as Trimeresurus stejnegeri in Guangxi; (2) the appearance and morphology of the venomous snake described by the patient basically conformed to the characteristics of Trimeresurus stejnegeri in Guangxi; (3) clinical manifestations of hematotoxin included local swelling, severe wound pain, and subcutaneous ecchymosis in some patients; having (1) or both (2) and (3) could be diagnosed. The patients with venomous snakebite of Trimeresurus stejnegeri in Guangxi admitted to Snake Injury Treatment Base in Central and Northern Guangxi/Liuzhou Integrated Chinese and Western Medicine Snake Injury Treatment Center from January 2016 to January 2020 were enrolled. The patients were divided into the general treatment group and the covered VSD technology group, with 60 patients in each group. The general treatment group was treated with antivenom, anti-tetanus, closed injection around the wound, anti-inflammatory, magnesium sulfate gauze applied on the affected limb, symptomatic support treatment. The covered VSD technique was used in the covered VSD technology group based on the treatment options of the general treatment group. Treatment cycle of both groups were calculated from the next day of admission and lasted for 7 days. In the treatment cycle, blood was collected at 08:00 every day. The red blood cell count (RBC) and hemoglobin (Hb) were detected by automatic blood cell analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (Fib) were detected by automatic blood coagulation analyzer, and the affected limb swelling degree and the appearance of subcutaneous ecchymosis were recorded. RESULTS: At different time points in the treatment cycle, the dynamic change trends of PT, APTT and Fib in the covered VSD technology group and the general treatment group were significantly different. Fib in both groups decreased on the 1-4 days, and gradually rose on the 5th day, and the lowest Fib value in the covered VSD technology group on the 4th day was higher than that in the general treatment group (g/L: 0.70±0.03 vs. 0.41±0.01, P < 0.05). In the treatment cycle, PT of both groups increased in the early and middle stage, but decreased in the later stage. The peak value of PT of the covered VSD technology group on the 5th day was significantly lower than that of the general treatment group (s: 25.2±0.1 vs. 35.4±0.2, P < 0.05), and the PT of the covered VSD technology group returned to the normal range on the 7th day, while the PT of the general treatment group was still abnormal. APTT in both groups increased at the beginning of the treatment cycle and gradually decreased. The peak value of APTT of the covered VSD technology group on the 3th day was lower than that in the general treatment group (s: 47.3±0.1 vs. 55.7±0.2, P < 0.05), and the rate of increase and decline was also more gradual than that in the general treatment group. There was no significant difference in RBC or Hb between the two groups. With the passage of time, the degree of affected limb swelling was relieved to different degrees in both groups, and the remission degree in the covered VSD technology group was more obvious than that in the general treatment group, and there was significant difference between the two groups (χ 2 = 86.060, P = 0.000). The occurrence rate of subcutaneous ecchymosis in the covered VSD technology group was significantly lower than that in the general treatment group (13.3% vs. 40.0%, χ 2 = 10.909, P = 0.002). CONCLUSIONS: The application of covered VSD technology to the venomous snakebite of Trimeresurus stejnegeri in Guangxi does not aggravate the bleeding. It is beneficial to the reduction of the swelling of the affected limb, and also promotes the recovery of coagulation function, which can better control the occurrence of adverse events caused by coagulation dysfunction.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Mordeduras de Serpentes , Trimeresurus , Animais , China , Drenagem , Humanos , Mordeduras de Serpentes/terapia
14.
Chem Commun (Camb) ; 56(91): 14287-14290, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33130834

RESUMO

A palladium-catalyzed cross-coupling reaction of sulfoxonium ylides and benzyl bromides has been developed, which has potential safety advantages over previous carbene coupling reactions using either diazo compounds or their in situ precursors. This reaction affords polysubstituted olefins, and features good substrate tolerance and is suitable for late-stage modification of biologically active molecules. Pd-carbene migratory insertion is supposed to be involved in this coupling reaction.

15.
Int J Mol Sci ; 21(21)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147881

RESUMO

Accumulation of amyloid fibrils in organisms accompanies many diseases. Natural extracts offer an alternative strategy to control the process with potentially fewer side effects. In this study, the inhibition of C-phycocyanin from Spirulina sp. on amyloid formation of bovine serum albumin (BSA) during a 21-day incubation was investigated using fluorescence and circular dichroism (CD), and mechanisms were explored via kinetic fitting and molecular docking. C-phycocyanin (0-50 µg/mL) hindered the amyloid formation process of BSA with increased half-lives (12.43-17.73 days) based on fluorescence intensity. A kinetic model was built and showed that the k1 decreased from 1.820 × 10-2 d-1 to 2.62 × 10-3 d-1 with the increase of C-phycocyanin, while k2 showed no changes, indicating that the inhibition of BSA fibrillation by C-phycocyanin occurred in a spontaneous process instead of self-catalyzed one. CD results show that C-phycocyanin inhibited conformational conversion (α-helices and ß-sheets) of BSA from day 6 to day 18. Molecular docking suggested that C-phycocyanin may hinder BSA fibrillation by hydrogen-bonding > 6 of 27 α-helices of BSA in a gomphosis-like structure, but the unblocked BSA α-helices might follow the self-catalytic process subsequently.

16.
Int J Mol Sci ; 21(21)2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33172177

RESUMO

Claudin-4 (CLDN4) is a tight junction protein to maintain the cancer microenvironment. We recently reported the role of the CLDN4 not forming tight junction in the induction of epithelial-mesenchymal transition (EMT). Herein, we investigated the role of CLDN4 in renal cell carcinoma (RCC), focusing on CLDN4. CLDN4 expression in 202 RCCs was examined by immunostaining. CLDN4 phosphorylation and subcellular localization were examined using high metastatic human RCC SN12L1 and low metastatic SN12C cell lines. In 202 RCC cases, the CLDN4 expression decreased in the cell membrane and had no correlation with clinicopathological factors. However, CLDN4 was localized in the nucleus in 5 cases (2%), all of which were pT3. Contrastingly, only 6 of 198 nuclear CLDN4-negative cases were pT3. CLDN4 was found in the nuclear fraction of a highly metastatic human RCC cell line, SN12L1, but not in the low metastatic SN12C cells. In SN12L1 cells, phosphorylation of tyrosine and serine residues was observed in cytoplasmic CLDN4, but not in membranous CLDN4. In contrast, phosphorylation of serine residues was observed in nuclear CLDN4. In SN12L1 cells, CLDN4 tyrosine phosphorylation by EphA2/Ephrin A1 resulted in the release of CLDN4 from tight junction and cytoplasmic translocation. Furthermore, protein kinase C (PKC)-ε phosphorylated the CLDN4 serine residue, resulting in nuclear import. Contrarily, in SN12C cells that showed decreased expression of EphA2/Ephrin A1 and PKCε, the activation of EphA2/EphrinA1 and PKCε induced cytoplasmic and nuclear translocation of CLDN4, respectively. Furthermore, the nuclear translocation of CLDN4 promoted the nuclear translocation of Yes-associated protein (YAP) bound to CLDN4, which induced the EMT phenotype. These findings suggest that the release of CLDN4 by impaired tight junction might be a mechanism underlying the malignant properties of RCC. These findings suggest that the release of CLDN4 by impaired tight junction might be one of the mechanisms of malignant properties of RCC.

17.
PLoS One ; 15(11): e0242321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33232337

RESUMO

Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.

18.
Environ Sci Technol ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236898

RESUMO

1,1,1-Trichloroethane (1,1,1-TCA) and trichloroethene (TCE) are common recalcitrant contaminants that coexist in groundwater. H2-induced reduction over precious-metal catalysts has proven advantageous, but its application to long-term continuous treatment has been limited due to poor H2-transfer efficiency and catalyst loss. Furthermore, catalytic reductions of aqueous 1,1,1-TCA alone or concomitant with TCE catalytic co-reductions are unstudied. Here, we investigated 1,1,1-TCA and TCE co-reduction using palladium nanoparticle (PdNP) catalysts spontaneously deposited on H2-transfer membranes that allow efficient H2 supply on demand in a bubble-free form. The catalytic activities for 1,1,1-TCA and TCE reductions reached 9.9 and 11 L/g-Pd/min, values significantly greater than that reported for other immobilized-PdNP systems. During 90 day continuous operation, removals were up to 95% for 1,1,1-TCA and 99% for TCE. The highest steady-state removal fluxes were 1.5 g/m2/day for 1,1,1-TCA and 1.7 g/m2/day for TCE. The major product was nontoxic ethane (94% selectivity). Only 4% of the originally deposited PdNPs were lost over 90 days of continuous operation. Documenting long-term continuous Pd-catalyzed dechlorination at high surface loading with minimal loss of the catalyst mass or activity, this work expands understanding of and provides a foundation for sustainable catalytic removal of co-existing chlorinated solvents.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33077902

RESUMO

Both haploidentical hematopoietic stem cell transplantation (HSCT) and donor lymphocyte infusion (DLI) exhibit strong graft-versus-leukemia (GVL) effect. However, the role of prophylactic DLI following haploidentical HSCT remains unclear. Here, 34 patients with high-risk acute leukemia who underwent low-dose anti-T-lymphocyte globulin-Fresenius (ATG-F)-based myeloablative haploidentical HSCT and prophylactic modified DLI (pro-DLI) were well-matched with patients without pro-DLI. The 5-year overall survival (OS) (67.8% versus 41.3%, P < 0.01) and leukemia-free survival (LFS) (64.6% versus 33.9%, P < 0.01) of pro-DLI cohort were superior to the control cohort. A slightly higher GVHD-free/relapse-free survival was found in the pro-DLI cohort (32.8% versus 16.3%, P = 0.32). The 5-year cumulative incidence of relapse of the pro-DLI recipients was significantly lower than that of the control cohort (14.7% versus 49.3%, P = 0.01). The cumulative incidence of grades II-IV and III-IV acute GVHD at 100 days after pro-DLI was 17.6% and 9.1%, respectively. There was no difference between the two cohorts in terms of the cumulative incidence of chronic GVHD and non-relapse mortality. Data from the multivariate analysis demonstrated that pro-DLI was an independent protective variable for LFS (P = 0.01, hazard ratio {HR} = 0.35), OS (P = 0.01, HR = 0.32), and relapse (P = 0.02, HR = 0.33). Taken together, we demonstrate that pro-DLI after ATG-F-based HSCT effectively decreases the risk of relapse and improves long-term survival of patients with high-risk acute leukemia without increasing treatment toxicity.

20.
Drug Des Devel Ther ; 14: 3941-3950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061299

RESUMO

Purpose: Desmoid fibromatosis (DF) is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Although multiple therapeutic modalities seem effective for DF, the standard systemic treatment for symptomatic and progressive DF remains controversial. As targeted therapy, tyrosine kinase inhibitors have been recently reported to contribute to the treatment of DF. Thus, the purpose of this study was to assess the efficacy and safety of anlotinib, a novel multi-kinase angiogenesis inhibitor, in patients with DF. Patients and Methods: We retrospectively collected the clinical medical records of patients with extremity DF who received anlotinib between January 2019 and January 2020 in our center. Anlotinib was started with a dose of 8 mg daily and adjusted according to the drug-related toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival (PFS) was identified as the primary endpoint and analyzed using the Kaplan-Meier method. Results: In total, 21 (6 male, 15 female) consecutive patients with DF were enrolled. The median medication time was nine months (Q1, Q3: 7.5, 10.5). None of the patients achieved a complete response, but eight (38.1%) patients achieved a partial response and ten patients (47.6%) achieved disease stability. Three (14%) patients developed progressive disease and the 3-, 6-, and 12-month PFS rates were 95.2%, 90.5%, and 84.0%, respectively. The disease control rate was 86.0% (18/21) and the objective response rate was 38.1% (8/21). Moreover, 15/21 (71.4%) patients achieved a reduction in tumor size, accompanied with a decrease in T2-weighted signal intensity on magnetic resonance imaging and clinical benefit. Conclusion: Anlotinib was effective against DF with an acceptable safety profile, and significantly slowed the disease progression. Further, multicenter studies with a longer follow-up time are needed to characterize fully the clinical application of anlotinib in DF.

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