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1.
Environ Sci Technol ; 56(23): 17288-17297, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36214751

RESUMO

Desulfurization sorbent with a high active component utilization is of importance for the removal of H2S from coal gas at high temperatures. Thus, the hypothesis for producing ZnxCo3-xO4/carbon nanofiber sorbents via the combinations of electrospinning, in situ hydrothermal growth, and carbonization technique has been rationally constructed in this study. ZnxCo3-xO4 nanoparticles derived from metal-organic frameworks are uniformly loaded on the electrospun carbon nanofibers (CNFs) with high dispersion. ZnxCo3-xO4/CNFs sorbents possess the highest breakthrough sulfur adsorption capacity (12.4 g S/100 g sorbent) and an excellent utilization rate of the active component (83.2%). The excellent performance of ZnxCo3-xO4/CNFs can be attributed to the synergetic effect of the hierarchical structure and widely distributed ZnxCo3-xO4 on the CNFs supporter. The decomposition of Zn/Co-ZIFs not only generates the nucleus of oxides but also realizes their physical isolation through the formation of carbon grids on the surface of CNFs, avoiding the aggregation of oxides. Furthermore, ZnxCo3-xO4/CNFs sorbents show an overwhelming superiority over the ZnO/CNFs sorbent, which is attributed to the introduction of Co and then the promotion of the stability of Zn at high temperatures. The presence of Co also accelerates the adsorption of H2S on the active site of the oxide surface. The presented method is beneficial for promoting desulfurization performances and producing sorbents with high utilization of active components.

2.
J Sep Sci ; 43(11): 2162-2171, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32134171

RESUMO

Saponin is an important class of natural products with various pharmacological activities. The selective separation of saponins is an essential step before further analysis. Molecular imprinting has been an effective strategy for preparing antibody mimics. However, a facile and efficient imprinting strategy for saponins is still lacking owing to their amphiphilic nature. Herein, we have prepared the saponins imprinted nanoparticles via cooperative imprinting strategy. This new strategy relies on the combination of various non-covalent interactions (hydrophobic and hydrogen bonding) and covalent boronate affinity interactions. The obtained imprinted nanoparticles could rebind specific saponins from complex matrices with good selectivity, superb tolerance to interference, and fast binding equilibrium. This method was verified to be versatile and facile. Thus, this strategy could greatly facilitate the preparation of imprinted nanoparticles for the specific recognition of saponins.


Assuntos
Produtos Biológicos/isolamento & purificação , Impressão Molecular , Nanopartículas/química , Saponinas/isolamento & purificação , Produtos Biológicos/síntese química , Produtos Biológicos/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Saponinas/síntese química , Saponinas/química
3.
J Cell Biochem ; 120(10): 17337-17344, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31209945

RESUMO

Transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo pathway downstream effector, promotes tumor progression by serving as a transcriptional coactivator with TEAD. Here, we introduced a new construct which can express the TEAD-binding domain of TAZ protein (TAZBD), and determined its antitumor effect in malignant glioma both in vitro and in vivo. We first observed that TAZ was upregulated in glioma tissues and related to malignant clinicopathologic characteristic, indicating the crucial role of TAZ during glioma progression. In U87 and U251 cells, TAZBD expression increased the proportion of apoptotic cells, and suppressed the colony formation and tumorigenicity. Further, TAZBD also decreased cell metastasis through the repression of epithelial-mesenchymal transition. The mechanistic study showed that TAZBD suppression of glioma cells was predominantly through blocking the TAZ-TEAD complex formation by competing with endogenous TAZ. Thus, the gene therapy of malignant glioma through blocking TAZ-TEAD complex by TAZBD may provide a new way for the targeted therapy of glioma.


Assuntos
Apoptose , Neoplasias Encefálicas/secundário , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal , Glioma/patologia , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Animais , Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Proteínas Nucleares/genética , Prognóstico , Fatores de Transcrição de Domínio TEA , Transativadores/genética , Fatores de Transcrição/genética , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Biochem Biophys Res Commun ; 515(1): 85-91, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31128917

RESUMO

Aerobic glycolysis is a hallmark of cancer. Sine oculis homeobox 1 (SIX1), a key transcription factor in terms of regulating aerobic glycolysis (the Warburg Effect), plays a critical role in tumorigenesis of various cancer types, including breast cancer, liver cancer, and lung cancer. However, the upstream regulating mechanisms of SIX1 in melanoma remain to be determined. MicroRNAs (miRNAs) have emerged as key regulators in tumorigenesis and progression. Here, we initially showed that microRNA-150-5p (miR-150-5p) inhibits SIX1 expression by directly targeting its 3'-UTR in melanoma cells. miR-150-5p suppressed melanoma cell proliferation, migration, and invasion through inhibition of SIX1. Mechanistically, miR-150-5p dampens glycolysis by decreasing the glucose uptake, lactate production, ATP generation, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) by targeting SIX1. Importantly, glycolysis regulated by miR-150-5p/SIX1 axis is critical for its regulation of melanoma growth and metastasis both in vitro and in vivo. Collectively, our study demonstrates the importance of miR-150-5p/SIX1 axis in melanoma, which could be a promising therapeutic target in melanoma.


Assuntos
Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Proteínas de Homeodomínio/genética , Melanoma/genética , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Trifosfato de Adenosina/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Glucose/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Ácido Láctico/metabolismo , Melanoma/metabolismo , Melanoma/patologia , Invasividade Neoplásica , Homologia de Sequência do Ácido Nucleico
5.
BMC Cancer ; 19(1): 1126, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747895

RESUMO

BACKGROUND: TAE-gene therapy for hepatoma, incorporating the tumor-targeted therapeutic efficacy of trans-arterial embolization, hydroxyapatite nanoparticles (nHAP) and anti-cancer wild-type p53 gene (wt-p53), was presented in our former studies (Int J Nanomedicine 8:3757-68, 2013, Liver Int 32:998-1007, 2012). However, the incompletely antitumoral effect entails defined guidelines on searching properer materials for this novel therapy. METHODS: Unmodified nHAP, Ca(2+) modified nHAP, poly-lysine modified nHAP and liposome were separately used to form U-nanoplex, Ca-nanoplex, Pll-nanoplex, L-nanoplex respectively with wt-p53 expressing plasmid. The four nanoplexs were then applied in vitro for human normal hepacyte L02 and hepatoma HePG2 cell line, and in vivo for rabbits with hepatic VX2 tumor by injection of nanoplexs/lipiodol emulsion into the hepatic artery in a tumor target manner. The distribution, superficial potential, physical structure, morphology and chemical compositions of nanoplexs were evaluated by TEM, SEM, EDS etc., with the objective of understanding their roles in hepatoma TAE-gene therapy. RESULTS: In vitro, L-nanoplex managed the highest gene transferring efficiency. Though with the second highest transfection activity, Pll-nanoplex showed the strongest tumor inhibition activity while maintaining safe to the normal hepacyte L02. In fact, only Pll-nanoplex can combine both the antitumoral effect to HePG2 and safe procedure to L02 among the four systems above. In vivo, being the only one with successful gene transference to hepatic VX2 tumor, Pll-nanoplex/lipiodol emulsion can target the tumor more specifically, which may explain its best therapeutic effect and hepatic biologic response. Further physical characterizations of the four nanoplexs suggested particle size and proper electronic organic surface may be crucial for nano-TAE gene therapy. CONCLUSION: Pll-nanoplex is the most proper system for the combined therapy due to its selectively retention in liver cancer cells, secondary to its morphological and physico-chemical properties of nanometric particle size, steady emulsion, proper organic and electronic surface.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Terapia Genética , Neoplasias Hepáticas/terapia , Proteína Supressora de Tumor p53/genética , Animais , Carcinoma Hepatocelular/diagnóstico , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Emulsões , Óleo Etiodado/administração & dosagem , Feminino , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Nanopartículas , Coelhos , Nanomedicina Teranóstica
6.
Med Sci Monit ; 24: 8422-8429, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30465552

RESUMO

BACKGROUND The present study examined the feasibility and safety of allogeneic uterus transplantation (UTx) from a living donor and assessed long-term graft survival and the resumption of reproductive function in a swine model. MATERIAL AND METHODS Ten female miniature swine with regular menstrual cycles were used; the animals were either donors or recipients (n=5) depending on the sibling. Retrieval surgery included uterus and uterine arteries together with the anterior branches of the internal iliacs from the living donor; the vaginal canal was cut. After the back-table had been prepared, bilateral internal iliac arteries were anastomosed end-to-side with the external iliac arteries. The transplanted uterus was evaluated based on the arterial blood flow by transabdominal ultrasonography and observed by secondary laparotomy after surgery; estrus recovery was stimulated by mating with a male, and artificial embryo transfer was performed in healing swine. RESULTS All 5 pigs revealed successful surgery without any surgical complications, injuries to other organs, or unanticipated vascular injury. All recipients survived for >3 months after the surgery, except pig 5, which died due to uterus necrosis 3 days post-surgery. A 100% surgical success rate and 80% long-term survival rate of the receptor were observed. Pig 2 had temporary estrus resumed, and the artificial embryo was transplanted 3 months after surgery; however, apparent gestation was not found by ultrasonography. CONCLUSIONS This study evaluated the safety and feasibility of the technology of allogeneic UTx, which was performed only by transplant uterine artery system from living-donor surgery in a swine model. Laboratory animals can show long-term survival and resumed estrous after UTx, which can be monitored by ultrasonography to assess the arterial blood flow of the grafted uterus.


Assuntos
Transplante Homólogo/métodos , Útero/transplante , Animais , Artérias/transplante , Feminino , Sobrevivência de Enxerto , Doadores Vivos , Ovário/transplante , Suínos
7.
Mol Cell Biochem ; 407(1-2): 69-76, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26002288

RESUMO

MicroRNAs (miRNAs) play vital roles in the regulation of cell cycle, cell growth, apoptosis, and tumorigenesis. Our previous studies showed that miR-526a positively regulated innate immune response by suppressing CYLD expression, however, the functional relevance of miR-526a expression and cell growth remains to be evaluated. In this study, miR-526a overexpression was found to promote cancer cell proliferation, migration, and anchor-independent colony formation. The molecular mechanism(s) of miR-526a-mediated growth stimulation is associated with rapid cell cycle progression and inhibition of cell apoptosis by targeting CYLD. Taken together, these results provide evidence to show the stimulatory role of miR-526a in tumor migration and invasion through modulation of the canonical NF-κB signaling pathway.


Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Apoptose , Movimento Celular , Proliferação de Células , Enzima Desubiquitinante CYLD , Células HEK293 , Células Hep G2 , Humanos , Células MCF-7 , NF-kappa B/metabolismo , Invasividade Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais , Proteínas Supressoras de Tumor/genética
8.
Zhonghua Fu Chan Ke Za Zhi ; 50(8): 603-7, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26675184

RESUMO

OBJECTIVE: To apply robotic surgery of early ovarian malignancy tumors clinically and evaluate its feasibility in management for early ovarian cancer. METHODS: Using the da Vinci robotic surgical system, seven patients with early ovarian malignancy tumors (stage I) underwent robotic surgery from April 2012 to September 2013. The average age was 45.7 years. Robotic surgeries approaches contained salpingo-oophorectomy, para-aortic lymphadenectomy, pelvic lymphadenectomy, omentectomy and appendectomy. Perioperative and follow-up clinical data were recorded. RESULTS: All robotic surgeries were successfully completed without the conversion to laparotomy. The mean operative time was 225 minutes (100-330 minutes). The average estimated blood loss was 171 ml (20-600 ml). No patients received blood transfusions. No intraoperative and postoperative complications were observed. The average number of pelvic lymph node dissected were 18.3 (11-34). The average number of para-aortic lymph node dissected were 3.7 (3-4). The mean follow-up time was 26.0 months after surgery (20-36 months). Currently, all patients had no tumor recurrence and survived. CONCLUSION: Robotic surgery is feasible as a novel alternative approach in the treatment of early ovarian malignancy tumors.


Assuntos
Excisão de Linfonodo , Linfonodos/cirurgia , Neoplasias Ovarianas/cirurgia , Robótica/métodos , Feminino , Humanos , Recidiva Local de Neoplasia , Duração da Cirurgia , Neoplasias Ovarianas/patologia , Pelve , Resultado do Tratamento
9.
Bull Math Biol ; 76(10): 2449-75, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25223537

RESUMO

Bacterial chemotaxis can enhance the bioremediation of contaminants in aqueous and subsurface environments if the contaminant is a chemoattractant that the bacteria degrade. The process can be promoted by traveling bands of chemotactic bacteria that form due to metabolism-generated gradients in chemoattractant concentration. We developed a multiple-relaxation-time (MRT) lattice-Boltzmann method (LBM) to model chemotaxis, because LBMs are well suited to model reactive transport in the complex geometries that are typical for subsurface porous media. This MRT-LBM can attain a better numerical stability than its corresponding single-relaxation-time LBM. We performed simulations to investigate the effects of substrate diffusion, initial bacterial concentration, and hydrodynamic dispersion on the formation, shape, and propagation of bacterial bands. Band formation requires a sufficiently high initial number of bacteria and a small substrate diffusion coefficient. Uniform flow does not affect the bands while shear flow does. Bacterial bands can move both upstream and downstream when the flow velocity is small. However, the bands disappear once the velocity becomes too large due to hydrodynamic dispersion. Generally bands can only be observed if the dimensionless ratio between the chemotactic sensitivity coefficient and the effective diffusion coefficient of the bacteria exceeds a critical value, that is, when the biased movement due to chemotaxis overcomes the diffusion-like movement due to the random motility and hydrodynamic dispersion.


Assuntos
Fenômenos Fisiológicos Bacterianos , Modelos Biológicos , Biodegradação Ambiental , Quimiotaxia/fisiologia , Simulação por Computador , Difusão , Hidrodinâmica , Conceitos Matemáticos , Porosidade
10.
Int J Gynecol Cancer ; 24(3): 437-43, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24476894

RESUMO

OBJECTIVE: ARHI is a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence of ARHI on epithelial ovarian cancer cell death and the underlying mechanisms behind how ARHI regulates cancer cells still require further studies. METHODS: Epithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected with ARHI vectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy. RESULTS: ARHI expression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). Overexpressed ARHI inhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response to ARHI overexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2-Beclin 1 complex were observed in ARHI overexpressing cells. Moreover, modulation of ARHI to Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation. CONCLUSIONS: The silence of ARHI expression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressed ARHI in TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.


Assuntos
Adenocarcinoma/metabolismo , Apoptose , Autofagia , Neoplasias Ovarianas/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
11.
Sci Total Environ ; 919: 170912, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38354794

RESUMO

Agricultural ditches are significant methane (CH4) sources since substantial nutrient inputs stimulate CH4 production and emission. However, few studies have quantified the role of diffusion and ebullition pathways in total CH4 emission from agricultural ditches. This study measured the spatiotemporal variations of diffusive and ebullitive CH4 fluxes from a multi-level ditch system in a typical temperate agriculture area, and assessed their contributions to the total CH4 emission. Results illustrated that the mean annual CH4 flux in the ditch system reached 1475.1 mg m-2 d-1, among which 1376.7 mg m-2 d-1 was emitted via diffusion and 98.5 mg m-2 d-1 via ebullition. Both diffusive and ebullitive fluxes varied significantly across different types of ditches and seasons, with diffusion dominating CH4 emission in middle-size ditches and ebullition dominating in large-size ditches. Diffusion was primarily driven by large nutrient inputs from adjacent farmlands, while hydrological factors like water temperature and depth controlled ebullition. Overall, CH4 emission accounted for 86 % of the global warming potential across the ditch system, with 81 % attributed to diffusion and 5 % to ebullition. This study highlights the importance of agricultural ditches as hotspots for CH4 emissions, particularly the dominant role of the diffusion pathway.

12.
Sci Total Environ ; 923: 171417, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447725

RESUMO

The water-level fluctuations zones (WLFZs) are crucial transitional interfaces within river-reservoir systems, serving as hotspots for N2O emission. However, the comprehension of response patterns and mechanisms governing N2O emission under hydrological fluctuation remains limited, especially in karstic canyon reservoirs, which introduces significant uncertainty to N2O flux assessments. Soil samples were collected from the WLFZs of the Hongjiadu (HJD) Reservoir along the water flow direction from transition zone (T1 and T2) to lacustrine zone (T3, T4 and T5) at three elevations for each site. These soil columns were used to conduct simulation experiments under various water-filled pore space gradients (WFPSs) to investigate the potential N2O flux pattern and elucidate the underlying mechanism. Our results showed that nutrient distribution and N2O flux pattern differed significantly between two zones, with the highest N2O fluxes in the transition zone sites and lacustrine zone sites were found at 75 % and 95 % WFPS, respectively. Soil nutrient loss in lower elevation areas is influenced by prolonged impoundment durations. The higher N2O fluxes in the lacustrine zone can be attributed to increased nutrient levels resulting from anthropogenic activities. Furthermore, correlation analysis revealed that soil bulk density significantly impacted N2O fluxes across all sites, while NO3-and SOC facilitated N2O emissions in T1-T2 and T4-T5, respectively. It was evident that N2O production primarily contributed to nitrification in the transition zone and was constrained by the mineralization process, whereas denitrification dominated in the lacustrine zone. Notably, the annual N2O efflux from WLFZs accounted for 27 % of that from the water-air interface in HJD Reservoir, indicating a considerably lower contribution than anticipated. Nevertheless, this study highlights the significance of WLFZs as a vital potential source of N2O emission, particularly under the influence of anthropogenic activities and high WFPS gradient.

13.
Bioresour Technol ; 395: 130399, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286165

RESUMO

The utilization of biomass char was hindered by the low gasification activity due to thick ring structures and unclear gasification mechanism. Herein, the mechanism was elucidated by experimental and DFT to improve the activity. The results demonstrated that temperature increased the gasification activity but did not changed the order of gasification activity of samples. Pressure dominated the position of the highest point of instantaneous CH4 yield, and high pressure enhanced carbon conversion by 81.72 % and 7.32 times. Moreover, KNi exhibited an uppermost catalytic activity with the instantaneous CH4 yield 1.89 times higher than that of raw char at 750 °C. The formation of the CxNi structure lowered the activation barrier for the ring opening reaction. Possible transformation pathways of Ni species were as follows: Ni(NO3)2·6H2O â†’ NiO â†’ Ni. KNi changed the reaction pathways and the most energy-consuming step. The study could shed light on the hydrogasification reaction mechanism.


Assuntos
Dióxido de Carbono , Elementos de Transição , Dióxido de Carbono/química , Carbono , Temperatura , Catálise , Biomassa
14.
Sci Total Environ ; 947: 174608, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38997040

RESUMO

Climate change and human interference, notably nutrient input, affect the water quality. Nitrogen (N) and phosphorus (P) are pivotal in managing eutrophication. This study investigated the effects of water dynamics and chemical constituents on water quality in Hongfeng Lake, a typical weakly stratified reservoir suffering from algae blooms in Southwest China, using the Environmental Fluid Dynamics Code. Leveraging climate, hydrological, and water quality data, we constructed, calibrated, and validated the temperature-hydrodynamics-water quality-sediment model. Various scenarios were analyzed, including wind speed, air temperature, solar radiation, rainfall, water discharge, N and P external input, and internal release. The findings revealed that no rain and warming increased trophic state index (TSI) and chlorophyll-a (Chl-a) concentration, and no solar radiation initially elevated nitrate concentration, followed by an increase in ammonium concentration. Besides, no solar radiation and changes in rainfall significantly increased total phosphate concentration. The management scenarios of N and P reduction, halving tributary, and mainstream flow scenarios improved water quality and reduced eutrophication. The wind speed under the N and P reduced scenarios showed that a doubling in wind led to increased concentrations of the particulate organic matter, Chl-a, and dissolved oxygen, alongside decreased ammonium and nitrate, while TSI exhibited minimal change. However, 5- and 10-times wind speed scenarios amplified TSI in shallow water, potentially due to a substantial rise in internal nutrient release. The degradation trend observed in drinking water quality amid climate change (warming and flooding) raises concerns regarding health-related risks. These simulations provided the quantified influence of climate change and environmental management strategies on water quality in the weakly stratified reservoir, notably highlighting the looming threat of exacerbated eutrophication due to warming, necessitating more stringent N and P reduction measures compared to current practices.

15.
Cell Oncol (Dordr) ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008193

RESUMO

BACKGROUND: Immunotherapies, including chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs), encounter several challenges in the management of acute myeloid leukemia (AML), including limited persistence of these treatments, antigen loss and resistance of leukemia stem cells (LSCs) to therapy. METHODS: Here, we proposed a novel dual-targeting approach utilizing engineered anti-IL10R CAR-T cells to secrete bispecific antibodies targeting CD33. This innovative strategy, rooted in our previous research which established a connection between IL-10 and the stemness of AML cells, designed to improve targeting efficiency and eradicate both LSCs and AML blasts. RESULTS: We first demonstrated the superior efficacy of this synergistic approach in eliminating AML cell lines and primary cells expressing different levels of the target antigens, even in cases of low CD33 or IL10R expression. Furthermore, the IL10R CAR-T cells that secret anti-CD33 bsAbs (CAR.BsAb-T), exhibited an enhanced activation and induction of cytotoxicity not only in IL10R CAR-T cells but also in bystander T cells, thereby more effectively targeting CD33-positive tumor cells. Our in vivo experiments provided additional evidence that CAR.BsAb-T cells could efficiently redirect T cells, reduce tumor burden, and demonstrate no significant toxicity. Additionally, delivering bsAbs locally to the tumor sites through this strategy helps mitigate the pharmacokinetic challenges typically associated with the rapid clearance of prototypical bsAbs. CONCLUSIONS: Overall, the engineering of a single-vector targeting IL10R CAR, which subsequently secretes CD33-targeted bsAb, addresses the issue of immune escape due to the heterogeneous expression of IL10R and CD33, and represents a promising progress in AML therapy aimed at improving treatment outcomes.

16.
Int J Biol Macromol ; 252: 126093, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37573910

RESUMO

Inspired by recent advances on functional modification of cellulosic materials, the crosslinking behaviors of epoxide with cellulose under the catalysis of different homogeneous catalysts including H2O, Brønsted acid, Brønsted base, Lewis acid and neutral salt were systematically investigated using density functional theory (DFT) methods with hybrid micro-solvation-continuum approach. The results showed that catalytic activity, reaction mechanism and regioselectivity are determined by the combined effect of catalyst type, electronic effect and steric hindrance. All the homogeneous catalysts have catalytic activity for the crosslinking reaction, which decreases in the order of NaOH > HCl > NCl3 > MCl2 > CH3COOH > NaCl (N = Fe3+, Al3+; M = Zn2+, Ca2+). Upon the catalysis of NaOH, hydroxyl group of cellulose is firstly deprotonated to form a carbanion-like intermediate which will further attack the less sterically hindered C atom of epoxide showing excellent regioselectivity. Acidic catalysts readily cause epoxide protonated, which suffers from nucleophilic attack of cellulose and forms the carbocation-like intermediate. Brønsted acid exhibits poor regioselectivity, however, Lewis acid shows an interesting balance between catalytic activity and regioselectivity for the crosslinking reaction, which may be attributed to the unique catalysis and stabilization effects of its coordinated H2O on the transition state structure.


Assuntos
Celulose , Compostos de Epóxi , Compostos de Epóxi/química , Solventes/química , Hidróxido de Sódio , Catálise , Ácidos de Lewis
17.
Water Res ; 242: 120271, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37399689

RESUMO

Agricultural ditches are pervasive in agricultural areas and are potential greenhouse gas (GHG) hotspots, since they directly receive abundant nutrients from neighboring farmlands. However, few studies measure GHG concentrations or fluxes in this particular water course, likely resulting in underestimations of GHG emissions from agricultural regions. Here we conducted a one-year field study to investigate the GHG concentrations and fluxes from typical agricultural ditch systems, which included four different types of ditches in an irrigation district located in the North China Plain. The results showed that almost all the ditches were large GHG sources. The mean fluxes were 333 µmol m-2 h-1 for CH4, 7.1 mmol m-2 h-1 for CO2, and 2.4 µmol m-2 h-1 for N2O, which were approximately 12, 5, and 2 times higher, respectively, than that in the river connecting to the ditch systems. Nutrient input was the primary driver stimulating GHG production and emissions, resulting in GHG concentrations and fluxes increasing from the river to ditches adjacent to farmlands, which potentially received more nutrients. Nevertheless, the ditches directly connected to farmlands showed lower GHG concentrations and fluxes compared to the ditches adjacent to farmlands, possibly due to seasonal dryness and occasional drainage. All the ditches covered approximately 3.3% of the 312 km2 farmland area in the study district, and the total GHG emission from the ditches in this area was estimated to be 26.6 Gg CO2-eq yr-1, with 17.5 Gg CO2, 0.27 Gg CH4, and 0.006 Gg N2O emitted annually. Overall, this study demonstrated that agricultural ditches were hotspots of GHG emissions, and future GHG estimations should incorporate this ubiquitous but underrepresented water course.


Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Dióxido de Carbono , Metano/análise , Óxido Nitroso/análise , Água , Efeito Estufa
18.
J Mater Chem B ; 11(27): 6372-6382, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37334568

RESUMO

Although NIR-II laser-mediated photothermal therapy (PTT) is considered as an emerging strategy for tumor therapy, its therapeutic effects are still seriously hampered by low photothermal conversion efficacy, limited tissue penetration depth, and inevitable damage to adjoining healthy tissues. Herein, we report a mild second-near-infrared (NIR-II) photothermal-augmented nanocatalytic therapy (NCT) nanoplatform based on CD@Co3O4 heterojunctions by depositing NIR-II-responsive carbon dots (CDs) onto the surface of Co3O4 nanozymes. The as-prepared Co3O4 nanozymes possess multi-enzyme-mimicking catalytic activity including peroxidase, catalase, and glutathione-peroxidase to realize the cascade amplification of ROS levels owing to the presence of multivalent Co2+ and Co3+. CDs with a high NIR-II photothermal conversion efficiency (PCE) (51.1%) enable the realization of mild PTT (∼43 °C), which could not only avoid damage to adjoining healthy tissues but also enhance the multi-enzyme-mimic catalytic activity of Co3O4 nanozymes. More importantly, the NIR-II photothermal properties of CDs and the multi-enzyme-mimicking catalytic activity of Co3O4 nanozymes are greatly augmented by the fabrication of heterojunctions due to the induced localized surface plasmonic resonance (LSPR) and accelerated carrier transfer. On the basis of these advantages, satisfactory mild PTT-amplified NCT is accomplished. Our work presents a promising approach for mild NIR-II photothermal-amplified NCT based on semiconductor heterojunctions.


Assuntos
Carbono , Terapia Fototérmica , Linhagem Celular Tumoral , Peroxidases
19.
Sci Total Environ ; 895: 165099, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37379928

RESUMO

Forest soils cover about 30 % of the Earth's land surface and play a fundamental role in the global cycle of organic matter. Dissolved organic matter (DOM), the largest active pool of terrestrial carbon, is essential for soil development, microbial metabolism and nutrient cycling. However, forest soil DOM is a highly complex mixture of tens of thousands of individual compounds, which is largely composed of organic matter from primary producers, residues from microbial process and the corresponding chemical reactions. Therefore, we need a detailed picture of molecular composition in forest soil, especially the pattern of large-scale spatial distribution, which can help us understand the role of DOM in the carbon cycle. To explore the spatial and molecular variations of DOM in forest soil, we choose six major forest reserves located in different latitudes ranging in China, which were investigated by Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). Results show that aromatic-like molecules are preferentially enriched in DOM at high latitude forest soils, while aliphatic/peptide-like, carbohydrate-like, and unsaturated hydrocarbon molecules are preferentially enriched in DOM at low latitude forest soils, besides, lignin-like compounds account for the highest proportion in all forest soil DOM. High latitude forest soils have higher aromatic equivalents and aromatic indices than low latitude forest soils, which suggest that organic matter at higher latitude forest soils preferentially contain plant-derived ingredients and are refractory to degradation while microbially derived carbon is dominant in organic matter at low latitudes. Besides, we found that CHO and CHON compounds make up the majority in all forest soil samples. Finally, we visualized the complexity and diversity of soil organic matter molecules through network analysis. Our study provides a molecular-level understanding of forest soil organic matter at large scales, which may contribute to the conservation and utilization of forest resources.

20.
Genes Genomics ; 44(4): 455-465, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34860317

RESUMO

BACKGROUND: Tripartite Motif Containing 3 (TRIM3) has been reported to be downregulated in several malignancies. However, its prognostic significance in thyroid cancer remains unknown. OBJECTIVE: Here we aimed to investigate TRIM3's expression and its involvement in papillary thyroid carcinoma (PTC). METHODS: Clinicopathological analyses were performed in patients with PTC. Expression of TRIM3 protein was evaluated by IHC. The prognostic role of TRIM3 in PTC patients was assessed by univariate and multivariate analyses. Cell proliferation and invasion were tested in two PTC cell lines following overexpression or knockdown. RESULTS: TRIM3 was decreased in PTC tissues compared to adjacent thyroid tissues on both mRNA and protein levels. Additionally, low expression of TRIM3 was significantly related to tumor size, lymph node metastasis and TNM stage. Moreover, TRIM3 was identified as an independent prognosis factor by multivariate analysis. Cellular data revealed that TRIM3 can inhibit the proliferation and invasion of PTC cells. Consistently, TRIM3 can upregulate the expression level of E-cadherin, while downregulate N-cadherin, Vimentin, and cyclin D1 expression. CONCLUSIONS: TRIM3 expression was downregulated in PTC tissues comparing with that in adjacent nontumorous thyroid tissues. Lower TRIM3 expression in PTC can contribute independently to a poorer prognosis by enhancing PTC proliferation and invasion, highlighting its potential as a novel therapeutic target and prognostic biomarker.


Assuntos
Neoplasias da Glândula Tireoide , Proliferação de Células/genética , Humanos , Prognóstico , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
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