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1.
Artigo em Inglês | MEDLINE | ID: mdl-33565700

RESUMO

Despite tremendous success of chimeric antigen receptor (CAR) T cell therapy in clinical oncology, the dose-exposure-response relationship of CAR-T cells in patients is poorly understood. Moreover, the key drug- and system-specific determinants leading to favourable clinical outcomes are also unknown. Here, we have developed a multiscale mechanistic PK-PD model for anti-BCMA (bb2121) CAR-T cell therapy to characterize 1) in vitro target cell killing in multiple BCMA expressing tumor cell lines at varying E:T ratios, 2) preclinical in vivo tumor growth inhibition (TGI) and blood CAR-T cell expansion in xenograft mice, and 3) clinical PK and PD biomarkers in multiple myeloma (MM) patients. Our translational PK-PD relationship was able to effectively describe the commonly observed multiphasic CAR-T cell PK profile in clinic, consisting of rapid distribution, expansion, contraction and persistent phases, as well as accounted for the categorical individual responses in multiple myeloma to effectively calculate progression-free survival rates. Preclinical and clinical data analysis revealed comparable parameter estimates pertaining to CAR-T cell functionality and suggested that patient baseline tumor burden could be more sensitive than dose levels towards overall extent of exposure (Cmax) after CAR-T cell infusion. Virtual patient simulations also suggested a very steep dose-exposure-response relationship with CAR-T cell therapy and indicated presence of a 'threshold' dose, beyond which a flat dose-response curve could be observed. Our simulations were concordant with multiple clinical observations discussed within this paper. Moving forward, this framework could be leveraged a priori, to explore multiple infusions and support preclinical/clinical development of future CAR-T cell therapies.

2.
Biomaterials ; 271: 120714, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33610048

RESUMO

Rotator cuff repair is a common surgery in sports medicine. During the surgery, torn tendon was re-fixed onto the bony surface. The majority of patients gain good results. However, re-tear occurs in some patients. The reason under this phenomenon is that the normal tendon-bone enthesis cannot be reconstructed. In order to strengthen the tendon-bone healing and promote enthesis regeneration, numerous manners are tested, among which stem cell related therapies are preferred. Stem cells, due to the ability of multi-lineage differentiation, are widely used in regenerative medicine. However, safety and ethics concerns limit its clinical use. Recent studies found that it is the secretome of stem cells that is biologically effective. On ground of this, we, in the current study, collected the conditioned medium of human bone marrow-derived stem cells (hBMSC-CM) and tested whether this acellular method could promote tendon-bone healing in a rat model of rotator cuff repair. By using histological, radiological, and biomechanical methods, we found that hBMSC-CM promoted tendon-bone healing of the rat rotator cuff. Then, we noticed that hBMSC-CM exerted an impact on macrophage polarization both in vivo and in vitro by inhibiting M1 phenotype and promoting M2 phenotype. Further, we proved that the benefit of hBMSC-CM on tendon-bone healing was related to its regulation on macrophage. Finally, we proved that, hBMSC-CM influenced macrophage polarization, which was, at least partially, related to Smad2/3 signaling pathway. Based on the experiments above, we confirmed the benefit of hBMSC-CM on tendon-bone healing, which relied on its immune-regulative property. Considering the accessibility and safety of acellular hBMSC-CM, we believe it is a promising candidate clinically for tendon-bone healing.

3.
IEEE Trans Cybern ; PP2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33400669

RESUMO

The robust iterative learning control (RILC) can deal with the systems with unknown time-varying uncertainty to track a repeated reference signal. However, the existing robust designs consider all the possibilities of uncertainty, which makes the design conservative and causes the controlled process converging to the reference trajectory slowly. To eliminate this weakness, a data-driven method is proposed. The new design intends to employ more information from the past input-output data to compensate for the robust control law and then to improve performance. The proposed control law is proved to guarantee convergence and accelerate the convergence rate. Ultimately, the experiments on a robot manipulator have been conducted to verify the good convergence of the trajectory errors under the control of the proposed method.

4.
Inflammation ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398542

RESUMO

Inflammation theory has suggested that the pathogenesis of postoperative ileus (POI) involves the steroid receptor coactivator-3 (SRC-3). Therefore, we investigated the role of SRC-3 in the muscles of the small intestine using a mouse POI model. Here, we reported that intestinal manipulation (IM) significantly reduced the extent of phenol red migration in the entire gastrointestinal tract, and the calculated geometric center (GC) value in wild-type (WT) mice at 24 h after surgery was higher than that in the knockout (KO) mice and in the sham-operated control group. The expression of SRC-3 was upregulated in the mouse intestinal muscularis at 24 h after surgical manipulation, and the mRNA and protein levels of inflammatory cytokines were upregulated compared with those in the control group. At 24 h after IM, the number of neutrophils in the experimental group was significantly higher than that in the control group; in the IM group, the number of neutrophils in the SRC-3-/- mice was markedly higher than that in the WT mice. At 24 h after IM, the myeloperoxidase (MPO) activity in the experimental group was significantly higher than that in the control group. In the IM group, the MPO activity of the SRC-3-/- mice was markedly higher than that of the WT mice. In summary, proinflammatory cytokines, the number of neutrophils, and the MPO activity were significantly increased in the muscularis of the jejunum and ileum of KO mice after IM compared with those of the WT mice, indicating that SRC-3 might play a protective role in POI.

5.
mSphere ; 6(1)2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408234

RESUMO

Apoptosis, a type of programmed cell death, plays crucial roles in various physiological processes, from development to adaptive responses. Key features of apoptosis have been verified in various fungal microbes but not yet in Fusarium species. Here, we identified 19 apoptosis-related genes in Fusarium pseudograminearum using a genome-wide survey. Expression profile analysis revealed that several apoptosis-related genes were significantly increased during conidiation and infection stages. Among these is FpBIR1, with two BIR (baculovirus inhibitor-of-apoptosis protein repeat) domains at the N-terminal end of the protein, a homolog of Saccharomyces cerevisiae BIR1, which is a unique apoptosis inhibitor. FpNUC1 is the ortholog of S. cerevisiae NUC1, which triggers AIF1- or YCA1-independent apoptosis. The functions of these two proteins were assessed by creating Δfpbir1 and Δfpnuc1 mutants via targeted gene deletion. The Δfpbir1 mutant had more cells with nuclear fragmentation and exhibited reduced conidiation, conidial formation, and infectivity. Correspondingly, the Δfpnuc1 mutant contained multiple nuclei, produced thicker and more branched hyphae, was reduced in conidiation, and exhibited faster conidial formation and higher infection rates. Taken together, our results indicate that the apoptosis-related genes FpBIR1 and FpNUC1 function in conidiation, conidial germination, and infection by F. pseudograminearum IMPORTANCE The plant-pathogenic fungus F. pseudograminearum is the causal agent of Fusarium crown rot (FCR) in wheat and barley, resulting in substantial yield losses worldwide. Particularly, in the Huanghuai wheat-growing region of China, F. pseudograminearum was reported as the dominant Fusarium species in FCR infections. Apoptosis is an evolutionarily conserved mechanism in eukaryotes, playing crucial roles in development and cell responses to biotic and abiotic stresses. However, few reports on apoptosis in plant fungal pathogens have been published. In this study, we identified 19 conserved apoptosis-related genes in F. pseudograminearum, several of which were significantly increased during conidiation and infection stages. Potential apoptosis functions were assessed by deletion of the putative apoptosis inhibitor gene FpBIR1 and apoptosis trigger gene FpNUC1 in F. pseudograminearum The FpBIR1 deletion mutant exhibited defects in conidial germination and pathogenicity, whereas the FpNUC1 deletion mutant experienced faster conidial formation and higher infection rates. Apoptosis appears to negatively regulate the conidial germination and pathogenicity of F. pseudograminearum To our knowledge, this study is the first report of apoptosis contributing to infection-related morphogenesis and pathogenesis in F. pseudograminearum.

6.
New Phytol ; 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33469925

RESUMO

The patterning of adaxial-abaxial tissues plays a vital role in the morphology of lateral organs, which is maintained by antagonism between the genes that specify adaxial and abaxial tissue identity. The homeo-domain leucine zipper class III (HD-ZIP III) family genes regulate adaxial identity; however, little information is known about the physical interactions or transcriptionally regulated downstream genes of HD-ZIP III. In this study, we identified a dominant rice mutant, lateral floret 1 (lf1), which has defects in lateral organ polarity. LF1 encodes the HD-ZIP III transcription factor, which expressed in the adaxial area of lateral organs. LF1 can activate directly the expression of LITTLE ZIPPER family gene OsZPR4 and HD-ZIP II family gene OsHOX1, and OsZPR4 and OsHOX1 respectively interact with LF1 to form a heterodimer to repress the transcriptional activity of LF1. LF1 influences indole-3-acetic acid (IAA) content by directly regulating the expression of OsYUCCA6. Therefore, LF1 forms negative feedback loops between OsZPR4 and OsHOX1 to affect IAA content, leading to the regulation of lateral organs polarity development. These results reveal the cross-talk among HD-ZIP III, LITTLE ZIPPER, and HD-ZIP II proteins and provide new insights into the molecular mechanisms underlying the polarity development of lateral organs.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 248: 119247, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33302216

RESUMO

In order to explore diverse luminescence properties of Eu3+ in inorganic phosphors, a series of novel deep-red-emitting Ca2Ga2GeO7 phosphors were successfully synthesized by solid-state reactions. The phase formation was verified by the X-ray diffraction patterns and Rietveld refinement and there is only one kind of Ca2+ site in Ca2Ga2GeO7. The excitation spectrum shows typical excitation peaks of Eu3+ and the broad band ranging from 200 nm to 300 nm was composed of the charge transfer band of O2--Eu3+ and Ga3+-O2- transition band. The emission spectrum depicts that the intensity of the peak located at 704 nm (5D0 â†’ 7F4) is higher than that of 618 nm (5D0 â†’ 7F2), which finally leads to the deep-red emission of the phosphor with high color saturation. The coordination dodecahedron of EuO8 distorted from a cubic geometry to the square antiprism is responsible for the unusual emission of Eu3+. The research of the concentration quenching behavior, lifetime and luminescence decay curves imply that the energy transfer between Eu3+ ions finally leads to the concentration quenching, and the interaction type is d-d interaction. The charge compensation, quantum efficiency and the thermal stability of Ca2Ga2GeO7:Eu3+ were also studied.

8.
AAPS J ; 22(6): 143, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-33156437

RESUMO

The ability to predict the incidence of chemotherapy-induced neutropenia in early drug development can inform risk monitoring and mitigation strategies, as well as decisions on advancing compounds to clinical trials. In this report, a physiological model of granulopoiesis that incorporates the drug's mechanism of action on cell cycle proliferation of bone marrow progenitor cells was extended to include the action of the cytotoxic agents paclitaxel, carboplatin, doxorubicin, and gemcitabine. In vitro bone marrow studies were conducted with each compound, and results were used to determine the model's drug effect parameters. Population simulations were performed to predict the absolute neutrophil count (ANC) and incidence of neutropenia for each compound, which were compared to results reported in the literature. In addition, using the single agent in vitro study results, the model was able to predict ANC time course in response to paclitaxel plus carboplatin in combination, which compared favorably to the results reported in a phase 1 clinical trial of 46 patients (r2 = 0.70). Model simulations were used to compare the relative risk (RR) of neutropenia in patients with high baseline ANCs for five chemotherapeutic regimens: doxorubicin (RR = 0.59), paclitaxel plus carboplatin combination (RR = 0.079), carboplatin (RR = 0.047), paclitaxel (RR = 0.031), and gemcitabine (RR = 0.013). Finally, the model was applied to quantify the reduced incidence of neutropenia with coadministration of pegfilgrastim or filgrastim, for both paclitaxel and the combination of paclitaxel plus carboplatin. The model provides a framework for predicting clinical neutropenia using in vitro bone marrow studies of anticancer agents that may guide drug development decisions.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33085912

RESUMO

Studies on health effects of engineered nanomaterials (ENM) in the lung has provided information on ENM toxicity and translocation across airway and alveolar epithelial barriers. Various inhaled ENM (e.g., gold and iridium nanoparticles) have been reported to partially cross the air-blood barrier in the lung, enter the vasculature and distribute in several end organs including heart, liver, spleen and kidney. Using an in vitro primary rat alveolar epithelial cell (AEC) monolayer model, we reported transport rates of relatively non-toxic polystyrene nanoparticles (PNP), which appear to be taken up via non-endocytic processes into AEC. PNP internalized into cytoplasm then trigger autophagy, followed by delivery of PNP from autophagosomes into lysosomes, from where PNP are exocytosed. We utilized the data from these experiments to perform biokinetic modeling that incorporates the processes associated with internalization and intracellular distribution of PNP, autophagy, lysosomal exocytosis of PNP, and several putative mechanisms of action that extend our previous understanding of AEC processing of PNP. Results suggest that entry of PNP into AEC, subsequent activation of autophagy by cytosolic PNP, accumulation of PNP in lysosomes, and lysosomal exocytosis are interwoven by proposed regulatory mechanisms.

10.
Clin Pharmacol Ther ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002189

RESUMO

Chimeric antigen receptor (CAR)-T cell therapy has achieved considerable success in treating B-cell hematologic malignancies. However, the challenges of extending CAR-T therapy to other tumor types, particularly solid tumors, remain appreciable. There are substantial variabilities in CAR-T cellular kinetics across CAR-designs, CAR-T products, dosing regimens, patient responses, disease types, tumor burdens, and lymphodepletion conditions. As a "living drug," CAR-T cellular kinetics typically exhibit four distinct phases: distribution, expansion, contraction, and persistence. The cellular kinetics of CAR-T may correlate with patient responses, but which factors determine CAR-T cellular kinetics remain poorly defined. Herein, we developed a cellular kinetic model to retrospectively characterize CAR-T kinetics in 217 patients from 7 trials and compared CAR-T kinetics across response status, patient populations, and tumor types. Based on our analysis results, CAR-T cells exhibited a significantly higher cell proliferation rate and capacity but a lower contraction rate in patients who responded to treatment. CAR-T cells proliferate to a higher degree in hematologic malignancies than in solid tumors. Within the assessed dose ranges (107 -109 cells), CAR-T doses were weakly correlated with CAR-T cellular kinetics and patient response status. In conclusion, the developed CAR-T cellular kinetic model adequately characterized the multiphasic CAR-T cellular kinetics and supported systematic evaluations of the potential influencing factors, which can have significant implications for the development of more effective CAR-T therapies.

11.
Food Chem Toxicol ; 146: 111803, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33035629

RESUMO

This study aimed to investigate the therapeutic effect of curcumin on type 2 diabetes and its underlying mechanisms. A type 2 diabetes mellitus rat model was established by providing high-fat diet and low doses of streptozotocin. Type 2 diabetes mellitus rats were treated with low dose and high dose of curcumin for 8 weeks. The results showed that high-dose curcumin significantly reduced fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase, liver coefficient, and malondialdehyde levels, and BCL2-Associated X expression in the type 2 diabetes mellitus rats. High-dose curcumin increased the levels of liver superoxide dismutase, catalase, and glutathione; as well as the expression of liver B-cell lymphoma-2, phosphatidylinositol 3-kinase, phosphorylated phosphatidylinositol 3-kinase, protein kinase B, and phosphorylated protein kinase B in type 2 diabetes mellitus rats. Furthermore, it ameliorated the histological structure of the liver and pancreas in diabetes mellitus model rats. However, low-dose curcumin had no significant effect on diabetes mellitus model rats. The results suggest that adequate doses of curcumin controls type 2 diabetes mellitus development as well as the mechanism involved in its anti-apoptotic actions and phosphatidylinositol 3-hydroxy kinase/protein kinase B signal pathway regulation in the liver.

12.
Orthop J Sports Med ; 8(9): 2325967120948491, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32974410

RESUMO

Background: Suture tape (ST) augmented repair, an alternative to traditional Broström repair (BR), may protect the repaired anterior talofibular ligament during ligament healing. No systematic review of cohort studies has been conducted to compare traditional BR with ST-augmented repair for chronic lateral ankle instability. Purpose: To review the current evidence in the literature to ascertain whether ST-augmented repair is superior to traditional BR in managing chronic lateral ankle instability. Study Design: Systematic review; Level of evidence, 3. Methods: A literature search was performed to identify relevant articles published in PubMed, Embase, and Cochrane Library databases in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search included cohort studies comparing the efficacy of BR and ST-augmented repair procedures in terms of incidence of instability recurrence, functional scores, talar tilt angle (TTA), anterior talar translation (ATT), and complication rate. Methodological quality was assessed using the Jadad scale for randomized studies and the Newcastle-Ottawa Scale for nonrandomized studies. Results: A total of 4 clinical trials with 254 patients were included. No significant differences were detected between BR and ST-augmented repair procedures in terms of incidence of recurrent instability, American Orthopaedic Foot & Ankle Society score, Foot and Ankle Outcome Score, Foot and Ankle Ability Measure, TTA, ATT, or complication rate. The ST group appeared to have a shorter operation time compared with the BR group. Conclusion: No significant differences were found between ST-augmented repair and BR surgery regarding incidence of recurrent instability, functional outcome scores, or complication rates. Although technically challenging, the ST-augmented repair procedure appears to be a safe and fast option.

13.
Carbohydr Polym ; 246: 116551, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32747236

RESUMO

Chinese water chestnut peels are a kind of vegetable processing waste containing many active components such as polysaccharides, the structure of which remains unknown. To elucidate the structure of polysaccharides from Chinese water chestnut peels, two polysaccharides named WVP-1 and WVP-2 were isolated. WVP-1 (3.16 kDa) consisted of mannose (1.75 %), glucose (84.69 %), galactose (6.32 %), and arabinose (7.24 %), while WVP-2 (56.97 kDa) was composed of mannose (3.18 %), rhamnose (1.52 %), glucuronic acid (1.42 %), galacturonic acid (4.83 %), glucose (11.51 %), galactose (36.02 %), and arabinose (41.53 %). Linkage and NMR data indicated that WVP-1 was composed mainly of →4)-α-d-Glcp(1→ and a certain proportion of →3)-ß-d-Glcp-(1→, including linear and branched polysaccharides simultaneously. WVP-2 was a pectin-like polysaccharide with →4)-α-d-GalpA6Me-(1→ units and the branch points of →3,4)-α-l-Arap-(1→, →3,6)-ß-d-Galp-(1→. WVP-2 exhibited stronger potential antioxidant and immunomodulatory activities than WVP-1 in vitro. These results provide a foundation for the further study of polysaccharides from Chinese water chestnut peels.

14.
Mol Cancer ; 19(1): 128, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838810

RESUMO

BACKGROUND: Deregulated circular RNAs (circRNAs) are associated with the development of cancer and therapy resistance. However, functional research of circRNAs mostly focus on potential miRNA or protein binding and more potential regulation of circRNA on host gene DNA in cancers are yet to be inspected. METHOD: We performed total RNA sequencing on clinical breast cancer samples and identified the expression patterns of circRNAs and corresponding host genes in patient blood, tumor and adjacent normal tissues. qPCR, northern blot and in situ hybridization were used to validate the dysregulation of circRNA circSMARCA5. A series of procedures including R-loop dot-blotting, DNA-RNA immunoprecipitation and mass spectrum, etc. were conducted to explore the regulation of circSMARCA5 on the transcription of exon 15 of SMARCA5. Moreover, immunofluorescence and in vivo experiments were executed to investigate the overexpression of circSMARCA5 with drug sensitivities. RESULTS: We found that circRNAs has average higher expression over its host linear genes in peripheral blood. Compared to adjacent normal tissues, circSMARCA5 is decreased in breast cancer tissues, contrary to host gene SMARCA5. The enforced expression of circSMARCA5 induced drug sensitivity of breast cancer cell lines in vitro and in vivo. Furthermore, we demonstrated that circSMARCA5 can bind to its parent gene locus, forming an R-loop, which results in transcriptional pausing at exon 15 of SMARCA5. CircSMARCA5 expression resulted in the downregulation of SMARCA5 and the production of a truncated nonfunctional protein, and the overexpression of circSMARCA5 was sufficient to improve sensitivity to cytotoxic drugs. CONCLUSION: Our results revealed a new regulatory mechanism for circRNA on its host gene and provided evidence that circSMARCA5 may serve as a therapeutic target for drug-resistant breast cancer patients.

15.
Insects ; 11(9)2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-32842525

RESUMO

The whitefly Bemisia tabaci (Gennadius) is a notorious insect vector that transmits hundreds of plant viruses, affecting food and fiber crops worldwide, and results in the equivalent of billions of U.S. dollars in crop loss annually. To gain a better understanding of the mechanism in virus transmission, we conducted deep sequencing of small RNAs on the whitefly B. tabaci MEAM1 (Middle East-Asia Minor 1) that fed on tomato plants infected with tomato yellow leaf curl virus (TYLCV). Overall, 160 miRNAs were identified, 66 of which were conserved and 94 were B. tabaci-specific. Among the B. tabaci-specific miRNAs, 67 were newly described in the present study. Two miRNAs, with predicted targets encoding a nuclear receptor (Bta05482) and a very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 2 (Bta10702), respectively, were differentially expressed in whiteflies that fed on TYLCV-infected versus uninfected plants. To better understand the regulatory effects of identified miRNAs and their target genes, we correlated expression profiles of miRNAs and their target transcripts and found that, interestingly, miRNA expression was inversely correlated with the expression of ~50% of the predicted target genes. These analyses could serve as a model to study gene regulation in other systems involving arthropod transmission of viruses to plants and animals.

16.
Immunotherapy ; 12(12): 891-901, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32693660

RESUMO

Aim: To evaluate the long-term efficacy of sublingual immunotherapy (SLIT) in treating mite-sensitized allergic rhinitis (AR). Materials & methods: 150 AR children were randomly divided into SLIT and pharmacotherapy (PT) groups, receiving a 3-year course of SLIT along with PT or PT only. Results: The symptom and medication scores at the 3- and 6-year follow-up were significantly lower compared with the baseline levels in both groups, while the values were significantly lower in SLIT group than in PT group. No significant differences were observed between 3- and 6-year follow-up in SLIT group. Conclusion: 3-year SLIT along with PT appeared more effective compared with PT only for mite-induced AR in children, and the treatment was effective for at least 3 consecutive years even after SLIT ceased.

17.
Chemosphere ; 261: 127755, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32721696

RESUMO

Deep cement mixing (DCM) method is a widely used geotechnical technique for increasing ground stabilization before construction works. However, the environmental influence of stabilized ground on the surrounding area remains a concern. A physical model experiment of DCM-treated sediment column was conducted to investigate both geotechnical and environmental effects on the surrounding sediment. The DCM column contained the cement-stabilized contaminated sediment and surrounded by uncontaminated sediment. The physical behaviour, including settlement, pore water pressure, and total pressure were measured under different loadings. Simultaneously, the migration of the major ions into seawater, and leaching of potentially toxic elements into the surrounding sediment were evaluated. The results revealed that the leaching of major ions from the DCM column followed the dissipation of excess pore water and migrated to the seawater above the sediment surface. Nevertheless, the leaching behaviour of potentially toxic elements into the surrounding sediment and variation of pH value after the DCM treatment were within an acceptable level. Therefore, the contaminated marine sediment could be effectively stabilized and solidified by in-situ remediation with minimal secondary pollution to the surrounding environment.


Assuntos
Materiais de Construção , Recuperação e Remediação Ambiental/métodos , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Poluição da Água/prevenção & controle , Hong Kong , Água do Mar/química
18.
Nat Commun ; 11(1): 3709, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709843

RESUMO

Cryo-electron tomography combined with subtomogram averaging (StA) has yielded high-resolution structures of macromolecules in their native context. However, high-resolution StA is not commonplace due to beam-induced sample drift, images with poor signal-to-noise ratios (SNR), challenges in CTF correction, and limited particle number. Here we address these issues by collecting tilt series with a higher electron dose at the zero-degree tilt. Particles of interest are then located within reconstructed tomograms, processed by conventional StA, and then re-extracted from the high-dose images in 2D. Single particle analysis tools are then applied to refine the 2D particle alignment and generate a reconstruction. Use of our hybrid StA (hStA) workflow improved the resolution for tobacco mosaic virus from 7.2 to 4.4 Å and for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. These resolution gains make hStA a promising approach for other StA projects aimed at achieving subnanometer resolution.


Assuntos
Canais de Cálcio/química , Microscopia Crioeletrônica/métodos , Processamento de Imagem Assistida por Computador/métodos , Tomografia com Microscopia Eletrônica/métodos , Substâncias Macromoleculares/química , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Razão Sinal-Ruído , Imagem Individual de Molécula , Fluxo de Trabalho
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 240: 118567, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32526398

RESUMO

In this thesis, a novel ultraviolet-activated Li2ZnTi3O8:Mn4+ red emitting phosphor is prepared by the traditional high-temperature solid-state reaction method in air. The crystal structure, luminescence properties and decay curves of the phosphor are studied in detail. The sample belongs to spinel cubic crystal structure and there are abundant [TiO6]8- octahedron sites can be occupied by Mn4+. The Li2ZnTi3O8:Mn4+ phosphor shows the red emission in region of 600-800 nm with a maximum at ~681 nm under 330 nm excitation, which can promote the plant growth. The optimal Mn4+ doping concentration is ~0.3 mol%, which is higher than that of other hosts. By calculating the crystal field strength (Dq) and Racah parameter B, we can evaluate that there is a strong crystal environment of Mn4+ in the Li2ZnTi3O8 host lattice, which major comes from the 2Eg â†’ 4A2g transition of Mn4+ ion. Furthermore, the characteristics of thermal quenching are also studied, poor thermal quenching performance may be due to high doping concentration of Mn4+. All data suggest that Li2ZnTi3O8:Mn4+ phosphor can be a potential application in plant-cultivation.

20.
Exp Physiol ; 105(8): 1360-1372, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32592428

RESUMO

NEW FINDINGS: What is the central question of this study? The aim was to investigate the function of microRNA-188 in the biological characteristics of lung cancer stem cells and the molecular mechanisms involved. What is the main finding and its importance? This study highlights a new molecular mechanism involving microRNA-188, MDK and the Hippo signalling pathway that plays a suppressive role in biological activity of lung cancer stem cells. This finding might offer new insights into gene-based therapy for lung cancer. ABSTRACT: MicroRNAs (miRNAs) have been implicated in lung cancer and reported as new promising diagnostic and therapeutic tools for cancer control. Here, we investigated the action of microRNA-188 (miR-188) in lung cancer stem cells. We first tested miR-188 expression in clinical samples of lung cancer patients, and a low expression profile of miR-188 was found. Next, we analysed the role of miR-188 in lung cancer stem cells with cell growth assays. To verify the in vitro results, we used a xenograft model to validate the capability of miR-188 in tumorigenesis. Overexpression of miR-188 reduced viability and metastasis of cancer stem cells. Similar results were reproduced in vivo, where overexpression of miR-188 retarded tumour growth in mice. We also identified MDK as a target of miR-188, and overexpression of MDK was found in lung cancer samples. Overexpressed MDK promoted the malignant behaviours of lung cancer stem cells. In addition, the Hippo pathway was found to be inactivated in lung cancer tissues, presenting as increased levels of YAP and TAZ. Suppression of the Hippo pathway also enhanced lung cancer stem cell activity and promoted the growth of xenograft tumours. To sum up, our results reveal that miR-188 inhibits the malignant behaviours of lung cancer stem cells and the growth of xenograft tumours. This study might offer new insights into gene-based therapies for cancer.

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