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The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body's immune potential, providing an eutherapeutic strategy for the treatment of OC.
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Antígenos de Neoplasias , Antígeno B7-H1 , Vacinas Anticâncer , Nanopartículas , Neoplasias Ovarianas , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Animais , Camundongos , Vacinas Anticâncer/uso terapêutico , Nanopartículas/química , Linhagem Celular Tumoral , Antígenos de Neoplasias/imunologia , Humanos , Células Dendríticas/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Lipídeo A/análogos & derivados , Lipídeo A/química , Lipídeo A/farmacologia , Imunoterapia/métodos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Endogâmicos BALB C , Inibidores de Checkpoint Imunológico/farmacologia , NanovacinasRESUMO
BACKGROUND: TMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging. RESULTS: In this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine. CONCLUSION: TMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis.
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Linfonodo Sentinela , Animais , Camundongos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Receptor 3 de Fatores de Crescimento do Endotélio Vascular , Terapia Fototérmica , Fator A de Crescimento do Endotélio Vascular , Verde de Indocianina/química , Imagem Óptica/métodos , Imagem Molecular/métodosRESUMO
Dendritic cell (DC)-targeted vaccines based on nanotechnology are a promising strategy to efficiently induce potent immune responses. We synthesized and manufactured a mannose-modified poly (ß-amino ester) (PBAE) nano-vaccines with easily tuneable and pH-sensitive characteristics to co-deliver the tumor-associated antigen polypeptide Trp-2 and the TLR4 agonist monophosphoryl lipid A (MPLA). To reduce immunosuppression in the tumor microenvironment, an immune checkpoint inhibitor, PD-L1 antagonist, was administrated along with PBAE nano-vaccines to delay melanoma development. We found that mannosylated Trp-2 and MPLA-loaded PBAE nano-vaccines can target and mature DCs, consequently boosting antigen-specific cytotoxic T lymphocyte activity against melanoma. The prophylactic study indicates that combination therapy with PD-L1 antagonist further enhanced anti-tumor efficacy by 3.7-fold and prolonged median survival time by 1.6-fold more than free Trp-2/MPLA inoculation. DC-targeting PBAE polymers have a great potential as a nanotechnology platform to design vaccines and achieve synergistic anti-tumor effects with immune checkpoint therapy.
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Vacinas Anticâncer/imunologia , Sistemas de Liberação de Medicamentos , Lipídeo A/análogos & derivados , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Nanopartículas/química , Peptídeos/administração & dosagem , Polímeros/química , Animais , Vacinas Anticâncer/efeitos adversos , Citocinas/metabolismo , Células Dendríticas/imunologia , Feminino , Concentração de Íons de Hidrogênio , Imunização , Lipídeo A/administração & dosagem , Linfonodos/metabolismo , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/ultraestrutura , Resultado do TratamentoRESUMO
Molecular imaging agents are considered to be promising tracers for tumor imaging and guided therapy. TMTP1 was screened through the FliTrx bacterial peptide display system in our laboratory previously and shown to specifically target to primary tumors and metastatic foci. In this study, small peptide TMTP1 was designed to conjugate to a near-infrared fluorescent agent ICG derivative ICG-OSu through PEG4, forming the novel probe TMTP1-PEG4-ICG. It was successfully synthesized and certified. CCK-8 assay showed that it was nontoxic to normal cells and cancerous cells. Dynamics study indicated that the probe was cleared through the liver-intestine and kidney-bladder pathway. Tumor targeting capability of this probe in vitro was evaluated on 4T1, SiHa, HeLa, S12, and HaCaT cells by flow cytometry. In vivo imaging of 4T1 and HeLa tumor-bearing mice further identified the tumor homing ability. As we had expected, the probe showed excellent affinity to cancer cells not only in vitro but also in vivo, whether in murine tumor or humanized tumor. In conclusion, TMTP1-PEG4-ICG demonstrated ideal imaging effects on tumor-bearing mice model, providing new opportunities for tumor diagnostic or guiding resection.
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Corantes Fluorescentes/química , Oligopeptídeos/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Linhagem Celular , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
XPNPEP2 is a proline hydrolytic enzyme that hydrolyzes several biologically active peptides and causes a loss of substrate activity. However, its function in cancer is still unknown. Our study showed that XPNPEP2 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and cervical intraepithelial neoplasm tissues. Statistical analysis showed that XPNPEP2 expression was associated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Overexpression of XPNPEP2 in SiHa and HeLa cells promoted cell invasion and migration without affecting cell proliferation and apoptosis. Mechanistically, we found that XPNPEP2 facilitated cervical cancer cell invasion and migration by inducing epithelial-mesenchymal transition. Furthermore, we demonstrated that XPNPEP2 had significant effects on the metastasis of xenografted tumors in vivo. Collectively, our findings identify the novel function of XPNPEP2 in the metastasis of cervical cancer and suggest that XPNPEP2 could be a novel potential therapeutic target for the treatment of cervical cancer.
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Aminopeptidases/biossíntese , Proliferação de Células/genética , Prognóstico , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Aminopeptidases/genética , Animais , Apoptose/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Metástase Linfática/genética , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The main objective of this study was to develop a nondestructive method for monitoring cotton growth and N status using a digital camera. Digital images were taken of the cotton canopies between emergence and full bloom. The green and red values were extracted from the digital images and then used to calculate canopy cover. The values of canopy cover were closely correlated with the normalized difference vegetation index and the ratio vegetation index and were measured using a GreenSeeker handheld sensor. Models were calibrated to describe the relationship between canopy cover and three growth properties of the cotton crop (i.e., aboveground total N content, LAI, and aboveground biomass). There were close, exponential relationships between canopy cover and three growth properties. And the relationships for estimating cotton aboveground total N content were most precise, the coefficients of determination (R(2)) value was 0.978, and the root mean square error (RMSE) value was 1.479 g m(-2). Moreover, the models were validated in three fields of high-yield cotton. The result indicated that the best relationship between canopy cover and aboveground total N content had an R(2) value of 0.926 and an RMSE value of 1.631 g m(-2). In conclusion, as a near-ground remote assessment tool, digital cameras have good potential for monitoring cotton growth and N status.
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Gossypium/crescimento & desenvolvimento , Gossypium/metabolismo , Nitrogênio/metabolismo , Fotografação , Biomassa , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismoRESUMO
Objective: Online social support provides a way to positively influence depression sufferers. In the present study, we aim to analyze how social support in Chinese online depression communities is communicated through the lens of deliberate metaphor theory (DMT) to deepen the understanding of the under-researched complicated, emotionally laden, and culture-related concepts of this experience. Methods: We collected data (n = 3546 comments) from the Warm Supporting section of the Depression Super Topic, a major Chinese online depression community on Weibo. The data were analyzed using a metaphorical analysis with the Metaphor Identification Procedure Vrije Universiteit and a thematic analysis. Results: Our findings identify two themes: deliberate metaphors (DMs) of depression and DMs of social environment for depression sufferers. The former conceptualizes future expectations without depression (as rosy images; victorious battles; the beaten black dog); disorder (as subtle objects; subjective initiative events); depression sufferers (as valuable objects; important roles); and present life with depression (as optional events; spiritual practices; fragile objects). The latter conceptualizes social connection (as solid objects; nonessentials); individuals in the social environment (as energetic objects; vicious roles); and prejudice (as colored objects). Conclusions: The findings suggest that DMs as important online social support resources, helping to express empathy and normalize depression with more common-sense, and non-judgmental concepts. Additionally, in DMs, Chinese netizens navigate the intricate intersection of medical and moral perspectives on depression and its recovery, leveraging both aspects to offer comprehensive social support. "Confucian-based" elements are embedded in culture-related social support expressions in DMs. In practice, our findings contribute to tailored and appropriate health interventions for depression.
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A simple all-optical power equalization scheme based on a single two-section reflective semiconductor optical amplifier (RSOA) is presented. Double optical path and non-uniform injection current density in the two sections easily saturate the RSOA and suppress pattern effect, thereby significantly reducing packet-to-packet power fluctuation while maintaining better signal quality. The mechanism of the two-section RSOA-based power equalizer is investigated and it is indicated that the two-section RSOA biased at proper current density functions as three cascaded SOAs, including a preamplifying SOA, a gain-saturated SOA and a third SOA. The performance dependence on driven current and structural parameters is also studied.
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Amplificadores Eletrônicos , Lasers , Refratometria/instrumentação , Transferência de Energia , Desenho de Equipamento , Análise de Falha de EquipamentoRESUMO
Cross-linguistic features of light verb constructions (LVCs) profile a major facet of the typological difference between Chinese and English. By adopting a theory-driven, context-based interpreting task, this study explores the effectiveness and variability of translation strategies in dealing with 12 target LVCs extracted from a Chinese-English Consecutive Interpreting test to capture effective translation strategies fit for Chinese English-as-foreign-language (EFL) learners (N = 66). Appropriate rates and entropy values denoting variability of strategy selection are calculated by using 12 LVC segments and nine strategies, respectively. A correlation test is also carried out for vocabulary knowledge and the appropriate rates of LVCs to assess the efficacy of learners' vocabulary knowledge in interpreting performance. Results show the general preferences for strategy selection among Chinese EFL learners as well as typical structural patterns in LVC translation. The degree of lightness of the light verbs exerts a reverse effect on the appropriate rates and consistency of strategy selection, and the positive correlation between vocabulary knowledge and LVCs' appropriate rates suggests the need to incorporate the constructional teaching into the EFL learning curriculum. Thus felicitous conditions of applying the strategies have been proposed.
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The smiling emoji has been claimed to be a marker of sarcastic intention among young Chinese users in computer-mediated communication. However, it is not well understood whether people interpret the emoji differently based on the characteristics or traits of the sender, as conveyed by occupation stereotypes. We investigated the effect of sender occupation on emoji-based sarcasm interpretation in both unambiguous (Experiment 1) and ambiguous (Experiment 2) contexts. The results showed that contextual incongruity was privileged over sender occupation in cueing sarcastic intention. In unambiguous contexts, sender occupation exerted no significant influence on the interpretation of emoji-based sarcastic statements. In contrast, sender occupation played an important role in the interpretation of emoji-based statements in ambiguous contexts. Specifically, emoji-based ambiguous statements delivered by senders in highirony occupations were more likely to be perceived as sarcastic than by those in low-irony occupations. However, sender occupation did not affect the interpretation of the emoji; instead, it biased the judgment of emoji in sarcasm interpretation. In a follow-up experiment (Experiment 3), we investigated the perceived characteristics of both high- and low-irony occupations. The results demonstrated that individuals in high-irony occupations were stereotyped with characteristics, including being humorous, insincere, easy to setting up close relationships, and of a lower social status. Taken together, our study suggests that stereotypical information about the sender could drive the interpretation of potentially sarcastic statements, and the contextual information modulates the effect of sender occupation on sarcasm interpretation.
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Sinais (Psicologia) , Julgamento , Humanos , Comunicação , Estereotipagem , SorrisoRESUMO
Microplastics (MPs), an emerging pollutant of concern, widely cooccurred with heavy metals in soil, however, little is known about the combined effects of the interactions of MPs and cadmium (Cd) on the soil-plant system. In this study, the combined effects of several types of MPs and soil Cd contamination on Brassica juncea growth, Cd uptake, and soil microbial carbon metabolism were investigated in a 50-day pot experiment. Aged polyethylene (PE), aged polypropylene (PP), biodegradable polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA) displayed moderate phytotoxicity, with reductions in leaf chlorophyll content and shoot biomass. Compared with the control treatment without MPs or B. juncea, B. juncea growth significantly increased the soil pH by 0.3 pH units, and the growth of B. juncea in the presence of biodegradable PBAT or PLA MPs increased the soil pH by an additional 0.4 or 0.6 pH units, respectively. The presence of PBAT or PLA MPs greatly reduced soil diethylenetriamine pentaacetic acid (DTPA)-extractable Cd concentrations and plant Cd accumulation. The Cd bioconcentration factor was higher in roots than shoots in all treatments except the treatment containing PBAT MPs. The average well color development (AWCD), an indicator of metabolic activity, was highest in the treatment with B. juncea alone and was reduced by both biodegradable and conventional MPs. The microbial utilization efficiency of esters and alcohols was enhanced in the treatment with PBAT MPs, whereas carboxylic acids were preferentially utilized in the treatment with PLA MPs. These findings indicate that co-exposure to MPs and Cd may alter soil microenvironmental characteristics such as soil pH, leading to changes in Cd bioavailability, plant growth and Cd accumulation, and the microbial community's capacity to metabolize carbon. These effects of MPs in soil warrant further exploration.
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Microplásticos , Poluentes do Solo , Solo/química , Plásticos/toxicidade , Cádmio/análise , Poliésteres , Carbono , Poluentes do Solo/análiseRESUMO
Nitrogen is a vital element for soil fertility and crop productivity. The transformation of nitrogen is directly affected by tillage practices for the disturbing soil. The characteristics of different nitrogen forms under different tillage modes are still unclear. A 3-year cycle tillage experiment was carried out to assess the combination of rotary tillage (RT), deep tillage (DT), and shallow rotary tillage (SRT) on nitrogen transformation and distribution, wheat yield and nitrogen balance in fluvo-aquic soil from Huang-Huai-Hai Plain in China. The results showed the rotation tillage cycle with deep tillage in the first year increased the total nitrogen (TN), and the main nitrogen form content in 0-30 cm compared with continued rotary tillage (RT-RT-RT). Moreover, the nitrate (NO3--N) and ammonium nitrogen (NH4+-N) content were improved in 20-40 cm by deep tillage practice with the highest value as 39.88 mg kg-1 under DT-SRT-RT. The time, tillage, and depth significantly affected the different nitrogen forms, but there was no effect on dissolved organic carbon (DON) and soil microbial biomass nitrogen (SMBN) by the interaction of time and tillage. Moreover, compared with RT-RT-RT, the rotation tillage promoted the spike number and kernels per spike of wheat, further increasing the wheat yield and nitrogen partial productivity, and with a better effect under DT-SRT-RT. The NO3--N and NH4+-N trended closer and positively correlated with wheat yield in 0-40 cm in 2019. The rotation tillage with deep tillage improved the different forms of nitrogen in 0-30 cm, wheat yield, and nitrogen partial productivity, and decreased the apparent nitrogen loss. It was suggested as the efficiency tillage practice to improve nitrogen use efficiency and crop yield in this area.
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Optimum tillage practices can create a suitable soil environment, and they improve the soil nutrient status to ensure crop development and yield. In this study, we evaluated the influences of six tillage practices on soil nutrients and maize yields from 2017 to 2019 in fluvo-aquic soil in the North China Plain. The field experiment was carried out by a split design with rotary tillage (RT) and deep tillage (DT) in wheat season in the main plot and no-tillage (NT), subsoiling between the row (SBR), and subsoiling in the row (SIR) in maize season in the subplot. The results showed that the soil nutrient content was higher under the treatments with rotary tillage in the wheat season in the 0-20 cm soil layer, while in the 20-40 cm soil layer, the soil nutrient content was higher under the treatments with deep tillage in the wheat season. The integrated principal component scores indicated that the soil nutrients had improved in the second year. The ecosystem multifunctionality (EMF) index was higher with the treatments with rotary tillage in wheat season in the 0-20 cm soil layer, while it was the highest under DT-SIR at 20-40 cm. Correlation analysis showed that the soil EMF index correlated significantly (p < 0.05) with the soil nutrient content mainly in the 0-40 cm soil layer. The higher maize yield was under the treatments with deep tillage compared to that under the treatments with rotary tillage in the wheat season. The yield-increasing effect was higher under the treatments with subsoiling than those utilizing no-till in the maize season, with the highest average yield of 13,910 kg hm-2 in the DT-SIR during the three years. Maize yield was strongly correlated with nutrients in the subsoil layer. The higher yield stability was found under RT-NT. To sum up, during the three-year experiment, rotary tillage in the wheat season combined with subsoiling in the maize season improved the soil nutrient content and the EMF index in the 0-20 cm layer, while the combination of deep tillage in the wheat season and subsoiling in the maize season improved those indices in the 20-40 cm soil layer, and increased the maize yield, the best one was under DT-SIR.
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TMTP1 is a polypeptide independently screened in our laboratory, which can target tumors in situ and metastases. In previous work, we have successfully developed a near-infrared (NIR) probe TMTP1-PEG4-ICG for tumor imaging. However, the limited ability to target tumor micrometastases hinders its further clinical application. Multimerization of peptides has been extensively demonstrated as an effective strategy to increase receptor binding affinity due to "multivalent effect" or "apparent cooperative affinity". In this study, a novel TMTP1 homodimer-directed NIR probe (TMTP1-PEG4)2-ICG was successfully constructed and synthesized. The cyclic TMTP1 peptides were bridged by two PEG4 linkers and then labeled with ICG-NHS for tumor imaging and photothermal therapy. In vivo biodistribution were assessed in normal BALB/c mice, and tumor targeting abilities of (TMTP1-PEG4)2-ICG and its monomer were evaluated and compared in 4T1-bearing subcutaneous tumor and lymph node metastasis model mice. Biodistribution analysis in vivo revealed that (TMTP1-PEG4)2-ICG was cleared mainly in both liver and kidney dependent way. Comparing with free ICG dye or TMTP1-PEG4-ICG probe, this improved (TMTP1-PEG4)2-ICG dimer showed more sensitive tumor imaging and could clearly identify tumors at a minimum volume of 10 mm3. Additionally, when compared to its monomer, lymph node (LN) metastases could also be apparently visualized and easily distinguished from normal LN by the novel dimer at 24 h post-injection. The blocking study revealed that the tumor accumulation of this probe was specifically medicated by receptor-ligand interaction. Furthermore, with the increase in stability and tumor targeting ability of ICG in vivo, the probe could also be an attractive photothermal agent to significantly inhibit tumor growth under 808 nm NIR laser irradiation. In conclusion, our work revealed that the novel (TMTP1-PEG4)2-ICG dimer could be a promising theranostic agent for sensitive tumor imaging and imaging-guided photothermal therapy, indicating its broad prospects for further clinical transformation.
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Neoplasias da Mama/diagnóstico por imagem , Verde de Indocianina/química , Oligopeptídeos/química , Terapia Fototérmica , Animais , Células Cultivadas , Feminino , Humanos , Verde de Indocianina/farmacocinética , Camundongos , Estrutura Molecular , Oligopeptídeos/farmacocinética , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Distribuição TecidualRESUMO
LIM homeobox 6 (LHX6) has been reported to be downregulated and inhibits cell proliferation in various cancers. Alternative splicing of LHX6 leads to six annotated isoforms, which can be found in the NCBI database. However, the expression patterns and potential roles of these isoforms remain poorly characterized in cervical cancer. Here, we demonstrated that the LHX6 isoforms containing exon 12 (LHX6EX(+12) group) and isoforms lacking exon 12 (LHX6EX(-12) group) were differentially expressed in cervical tissue by qRT-PCR. The mRNA expression level of LHX6EX(+12) group was higher than that of LHX6EX(-12) group in cervical cancer tissue. Knockdown of LHX6EX(+12) group and all LHX6 isoforms (LHX6All group) inhibited cell growth, increased cell apoptosis, and induced cell cycle arrest from G0/G1 phase to S phase in vitro. Consistently, overexpression of the LHX6EX(+12) group promoted cervical cancer cell proliferation in vitro. In contrast, no significant differences in cell proliferation were found between LHX6EX(-12) isoform knockdown group and its control. RNA-sequencing suggested that the LHX6EX(+12) isoform group might exert its cancer-promoting effects in cervical cancer via regulating MAPK signaling pathway. Downregulation of the LHX6EX(+12) group significantly suppressed the phosphorylation of MRK, ERK, JNK, and P38 at the protein level. We also identified some unique biological processes and signaling pathways in which each isoform group might be involved. In summary, our results indicated that LHX6EX(+12) isoform group was the dominant oncogenic type of LHX6 in cervical cancer, which may be a new biomarker and a potential precise therapeutic target for cervical cancer in the future.
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Neoplasias do Colo do Útero , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Éxons , Feminino , Humanos , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Proteínas do Tecido Nervoso/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA , RNA Mensageiro , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias do Colo do Útero/genéticaRESUMO
Cadmium (Cd) contamination seriously threatens the soil health and food safety. Combination of amendment and accumulator plant is a green and effective technique to improve phytoremediation of Cd-contaminated alkaline soil. In this study, a potting experiment was conducted to investigate the effect of sulfur on Cd phytoextraction by Cichorium intybus (chicory). Soil chemical and microbial properties were determined to reveal the mechanism of sulfur-assisting Cd phytoremediation by chicory. Soil pH decreased from 7.77 to the lowest 7.30 with sulfur addition (0.6, 0.9 and 1.2 g kg-1, LS, MS and HS treatment); Electric conductivity, sulfate anion and available cadmium concentration increased gradually with increasing sulfur doses. Cd concentration of shoot and root significantly increased from 1.47 to 4.43 mg kg-1, 6.15 to 20.16 mg kg-1 by sulfur treatment relative to CK, which were attributed to increased available Cd concentration induced by decreased pH. Sulfur treatments significantly increased the Cd bioconcentration factor by 64.1%, 118.6%, 201.0% for shoot, 76.3%, 145.6% and 227.7% for root under LS, MS and HS relative to CK treatment, respectively (P < 0.05). However, only MS treatment significantly improved the Cd removal efficiency by 82.9% in comparison of CK treatment (P < 0.05). Microbial community diversity measured by 16SrRNA showed that Thiobacillus and Actinobacteria were the key and dominant strains of soil microbial communities after sulfur addition, which played a pivotal role in the process of sulfur oxidation involved in decrease of soil pH and the transformation of Cd forms. Correlation analysis and path analysis by structural equation model indicated that soil sulfate anion and Thiobacillus directly affected Cd removal efficiency by chicory in Cd-contaminated alkaline soil. This suggests that combination of sulfur and chicory may provide a way to promote Cd bioaccumulation for phytoremediation of Cd-contaminated alkaline soil.
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Cichorium intybus , Metais Pesados , Microbiota , Poluentes do Solo , Thiobacillus , Bioacumulação , Biodegradação Ambiental , Cádmio/análise , Metais Pesados/análise , Solo/química , Poluentes do Solo/análise , Sulfatos/análise , EnxofreRESUMO
The present study examines the emotional experience and expression of Chinese tertiary-level English as a foreign language (EFL) teachers and their interaction with their students. Data were drawn from semi-structured in-depth interviews with 10 EFL teachers recruited from seven universities of different levels in China and were analyzed in light of Emotional Geography Theory. The results reveal that Chinese tertiary-level EFL teachers experience more negative emotions than positive ones. The emotions most frequently reported by them are anger, enjoyment, anxiety, disappointment, and ambivalence. When it comes to emotional expressions, Chinese tertiary-level EFL teachers tend to display positive emotions by following the emotional rules of school settings. This study also uncovers that EFL teaching in Chinese universities is characterized by EFL teachers' physical and moral distance from but political closeness to students, all of which are the sources of EFL teachers' negative emotions. The need for providing positive psychology intervention for EFL teachers is then suggested.
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Foreign Language Enjoyment (FLE) plays a facilitative role in FL learning and its contributing factors have been the object of scholarly attention in the Positive Psychology approach to second language acquisition (SLA). The present study examined the predictive effects of gender and academic discipline on overall FLE and each of its subcomponents in a specific Chinese EFL context. Statistical analyses based on a sample of 1,718 high school students showed that: (1) female students scored significantly higher in overall FLE, FLE-Private, and FLE-Atmosphere than their male counterparts, but no significant difference was found in their FLE-Teacher; (2) students of Humanities and Social Sciences scored significantly higher in overall FLE, FLE-Teacher and FLE-Atmosphere than students of Natural Science, though no significant difference was identified for FLE-Private. Reasons for the statistical variations and their implications were also discussed.
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BACKGROUND AND PURPOSE: Cisplatin-paclitaxel (TP) combination chemotherapy as the first-line therapy for numerous cancers is hindered by its inadequate accumulation in tumors and severe side effects resulting from non-specific distribution. The aim of this study is to explore whether TMTP1-modified, cisplatin and paclitaxel prodrugs co-loaded nanodrug could improve cervical cancer chemotherapy and relieve its side effects through active and passive tumor targeting accumulation and controlled drug release. METHODS: TDNP, with capacities of active targeting for tumors and controlled drug release, was prepared to co-deliver cisplatin and paclitaxel prodrugs. The characteristics were investigated, including the diameter, surface zeta potential, stability and tumor microenvironment (TME) dependent drug release profiles. Cellular uptake, cytotoxicity, drug accumulation in tumors, antitumor effects and safety analysis were evaluated in vitro and in vivo. RESULTS: The oxidized cisplatin and the paclitaxel linked to the polymer achieved a high loading effciency of over 80% and TME-dependent sustained drug release. Moreover, TMTP1 modification enhanced cellular uptake of TDNP and further improved the cytotoxicity of TDNP in vitro. In vivo, TDNP showed an extended blood circulation and increased accumulation in SiHa xenograft models with the aid of TMTP1. More importantly, TDNP controlled tumor growth without life-threatening side effects. CONCLUSION: Our study provided a novel TP co-delivery platform for targeted chemotherapy of cervical cancer, which was promising to improve the therapeutic effcacy of TP and may also have application in other tumors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Pró-Fármacos/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/metabolismo , Cisplatino/farmacologia , Feminino , Humanos , Paclitaxel/administração & dosagem , Paclitaxel/metabolismo , Paclitaxel/farmacologia , Polímeros/química , Neoplasias do Colo do Útero/tratamento farmacológico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
It has been reported recently that bradykinin (BK) is involved in the regulation of various processes in cancer cells. However, its role and underlying mechanism of action in cervical cancer (CC) are still unknown. In the present study, it was revealed that BK promoted proliferation, migration, and invasion of CC cells, whereas bradykinin B2 receptor antagonist HOE140 had the inverse effect. Furthermore, it was confirmed that overexpression of bradykinin B2 receptor (B2R) facilitated the proliferation, migration, and invasion of BKtreated CC cells, while knockdown of B2R had the opposite effect. Mechanistically, the present results revealed that the BK/B2Rinduced biological function of CC cells occured by activating STAT3 signaling pathways, and that knockdown of B2R or B2R antagonist had the opposite effects. Moreover, it was demonstrated that BK/B2R facilitated CC cell migration and invasion by upregulating the expression of the STAT3regulated products MMP2 and MMP9, while downregulating the expression of the proapoptotic protein cleaved caspase9. Thus, the present findings revealed that BK promoted CC cell proliferation, migration, and invasion by binding to B2R via STAT3 signaling pathways.