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1.
Sci Total Environ ; 806(Pt 2): 150430, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34852427

RESUMO

This study aims to provide a comprehensive understanding of the role of urban waterbodies in avian ecology, which is instructive for both biodiversity conservation and urban planning. Based on bird surveys conducted in 41 urban parks in Beijing during the breeding and wintering seasons of 2018-2019, and using standardized regression analyses, we identified the specific effects of waterbody attributes on the full avian community and forest bird guilds. We assessed this at multiple spatial scales, first within the focal parks, and then within buffer zones with radius of 200 m and 1000 m. We found that waterbodies can serve as avian diversity "hotspots" in the urban landscape. More specifically, they support avian diversity in the following ways: (1) Parks with waterbodies maintain a higher number of bird species than parks without waterbodies during the breeding season and attract resident forest birds during the wintering season. (2) When not frozen, waterbodies inside and outside parks contribute equally to resident forest bird species richness, while more individuals were attracted by waterbodies within neighborhoods. (3) In parks without waterbodies, the number of forest bird species significantly increases with the number of waterbody patches within neighborhoods, while the corresponding relationship for parks with waterbodies is insignificant. These findings suggest a preference for habitats nearby waterbodies among forest birds residing highly urbanized areas. This study provides new insights into avian ecology in urban landscapes and scientific support for the idea that creating and maintaining urban waterbodies can conserve biodiversity.

2.
Genome Biol ; 22(1): 326, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847934

RESUMO

BACKGROUND: Polyploidy, especially allopolyploidy, which entails merging divergent genomes via hybridization and whole-genome duplication (WGD), is a major route to speciation in plants. The duplication among the parental genomes (subgenomes) often leads to one subgenome becoming dominant over the other(s), resulting in subgenome asymmetry in gene content and expression. Polyploid wheats are allopolyploids with most genes present in two (tetraploid) or three (hexaploid) functional copies, which commonly show subgenome expression asymmetry. It is unknown whether a similar subgenome asymmetry exists during translation. We aim to address this key biological question and explore the major contributing factors to subgenome translation asymmetry. RESULTS: Here, we obtain the first tetraploid wheat translatome and reveal that subgenome expression asymmetry exists at the translational level. We further perform in vivo RNA structure profiling to obtain the wheat RNA structure landscape and find that mRNA structure has a strong impact on translation, independent of GC content. We discover a previously uncharacterized contribution of RNA structure in subgenome translation asymmetry. We identify 3564 single-nucleotide variations (SNVs) across the transcriptomes between the two tetraploid wheat subgenomes, which induce large RNA structure disparities. These SNVs are highly conserved within durum wheat cultivars but are divergent in both domesticated and wild emmer wheat. CONCLUSIONS: We successfully determine both the translatome and in vivo RNA structurome in tetraploid wheat. We reveal that RNA structure serves as an important modulator of translational subgenome expression asymmetry in polyploids. Our work provides a new perspective for molecular breeding of major polyploid crops.

3.
Chem Commun (Camb) ; 57(92): 12301-12304, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34730575

RESUMO

Herein, we developed a triple-line lateral flow strip-based platform combined with an miRNA-initiated cyclic chain displacement reaction for the rapid and simultaneous dual-miRNA detection of lung cancer in a single strip test. The simultaneous dual-miRNA detection platform was used for the analysis of clinical serum samples, and distinguished non-small cell lung cancer patients from heathy individuals.

4.
Soft Matter ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811559

RESUMO

Gel electrolytes have aroused extensive interest for diverse flexible electronics due to their high ionic conductivity and inherent stretchability. However, gel electrolytes still face challenges in terms of mechanical properties, fatigue resistance, and environmental adaptation, which severely limit the practical application of gel-based electronics. In this paper, we have synthesized a novel polymerizable ionic liquid [SBMA][AA] by mixing zwitterionic sulfobetaine methacrylate with acrylic acid. Then a dually cross-linked single network poly(ionic liquid)/ionic liquid (DCSN PIL/IL) ionogel was prepared by a simple one-step photopolymerization of the [SBMA][AA] in another IL 1-ethyl-3-methylimidazolium dicyanoamide ([EmIm][DCA]). The synergistic effect between covalent crosslinking and dynamic physical crosslinking points endows the ionogel with good mechanical properties as well as outstanding fatigue resistance. Gratifyingly, the entrapment of [EmIm][DCA] in the ionogel matrix yields excellent environmental adaptability and high ionic conductivity. Meanwhile, the DCSN PIL/IL ionogel also exhibited strong adhesive capacity due to the abundance of carboxyl and sulphonic acid groups. The outstanding electromechanical properties make the DCSN PIL/IL ionogel a perfect candidate for strain sensors to monitor diverse human body activities, such as the movement of the thumb knuckle and handwriting. Interestingly, the DCSN PIL/IL ionogel also displayed high responsiveness to humidity. Therefore, it is believed that this DCSN PIL/IL ionogel offers a broad prospect in flexible strain-humidity bimodal sensors.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34751881

RESUMO

Carbon emission trading policy is of great importance for addressing climate change and reducing carbon emissions. Reducing carbon emissions could further affect energy efficiency (EE). Based on the data from 30 provinces in China from 2006 to 2017, this paper first calculated EE by using the super slack-based model (Super-SBM) and then analysed the theoretical mechanism of the impact of carbon emission trading policy on EE. We also used a difference-in-difference (DID) model and mediation effect model for empirical analysis. Finally, we established the spatial difference-in-difference (SDID) model to test the policy spillover effects of carbon emission trading policy. The results showed that the high EE areas have gradually shifted to the central and eastern regions during 2006-2017 in China. The EE value in the pilot area of the carbon emission trading policy was obviously higher than that in the non-pilot area. Carbon emission trading policy had a significant positive effect on improving EE overall. In particular, green technology innovation and energy structure both had positive mediation effects on carbon emission trading policy affecting EE. However, the industrial structuring adjustment had no significant mediation effect in its influencing mechanism. Additionally, the spatial spillover effects test showed that the carbon emission trading policy had a positive effect on the EE of the pilot areas but a negative effect on that of the non-pilot areas.

6.
Biomater Sci ; 9(22): 7343-7378, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34672315

RESUMO

Traumatic hemorrhage can be a fatal event, particularly when large quantities of blood are lost in a short period of time. Therefore, hemostasis has become a crucial part of emergency treatment. For small wounds, hemostasis can be achieved intrinsically depending on the body's own blood coagulation mechanism; however, for large-area wounds, particularly battlefield and complex wounds, materials delivering rapid and effective hemostasis are required. In parallel with the constant progress in science, technology, and society, advances in hemostatic materials have also undergone various iterations by integrating new ideas with old concepts. There are various natural and synthetic hemostatic materials, including hemostatic powders, adhesives, hydrogels, and tourniquets, for the treatment of severe external trauma. This review covers the differences among the currently available hemostatic materials and comprehensively describes the hemostatic effects of different materials based on the underlying mechanisms. Finally, solutions for current issues related to trauma bleeding are discussed, and the prospects of hemostatic materials are proposed.


Assuntos
Hemostáticos , Coagulação Sanguínea , Hemorragia/terapia , Hemostasia , Hemostáticos/farmacologia , Humanos , Hidrogéis/farmacologia
7.
Theor Appl Genet ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34661697

RESUMO

KEY MESSAGE: Two read depth methods were jointly used in next-generation sequencing data to identify deletions in maize population. GWAS by deletions were analyzed for gene expression pattern and classical traits, respectively. Many studies have confirmed that structural variation (SV) is pervasive throughout the maize genome. Deletion is one type of SV that may impact gene expression and cause phenotypic changes in quantitative traits. In this study, two read count approaches were used to analyze the deletions in the whole-genome sequencing data of 270 maize inbred lines. A total of 19,754 deletion windows overlapped 12,751 genes, which were unevenly distributed across the genome. The deletions explained population structure well and correlated with genomic features. The deletion proportion of genes was determined to be negatively correlated with its expression. The detection of gene expression quantitative trait loci (eQTL) indicated that local eQTL were fewer but had larger effects than distant ones. The common associated genes were related to basic metabolic processes, whereas unique associated genes with eQTL played a role in the stress or stimulus responses in multiple tissues. Compared with the eQTL detected by SNPs derived from the same sequencing data, 89.4% of the associated genes could be detected by both markers. The effect of top eQTL detected by SNPs was usually larger than that detected by deletions for the same gene. A genome-wide association study (GWAS) on flowering time and plant height illustrated that only a few loci could be consistently captured by SNPs, suggesting that combining deletion and SNP for GWAS was an excellent strategy to dissect trait architecture. Our findings will provide insights into characteristic and biological function of genome-wide deletions in maize.

8.
Nanotechnology ; 33(4)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34649234

RESUMO

A novel plasmonic structure is demonstrated by combining graphene with a planar LiNbO3thin layer, which is simple and easy to fabricate compared to the complex design of general graphene surface plasmons devices. Graphene from the chemical vapor deposition is investigated and characterized to be a continuous and uniform monolayer or fewlayer. LiNbO3capped by graphene layer show an extraordinary absorption enhancement in an attenuated total reflection (ATR) measurement at a wide bandwidth of 500-4000 cm-1, which can be explained by resonance absorption resulting from the coupling of graphene surface plasmons with optical modes of LiNbO3-SiO2Fabry-Perot cavity and LiNbO3planar waveguide. The simulation results are generally consistent with the ATR experimental results. The absorption spectra versus temperature of this plasmonic configuration is also investigated, which show that increasing the testing temperature not only highlights the atomic vibrational peaks of graphene, but also enhances the absorption at several characteristic absorption frequencies due to the enhanced coupling between the surface plamons excitations and the optical modes.

9.
Front Pharmacol ; 12: 734040, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707499

RESUMO

Objective: To investigate the immunological mechanism of bone marrow-derived mesenchymal stem cells (BM-MSCs) in inflammatory bowel disease (IBD). Methods: Mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were intraperitoneally injected with phosphate-buffered saline, BM-MSCs, BM-MSCs with tumor necrosis factor-induced protein 6 (Tnfaip6) knockdown mediated by RNA interference recombinant adenovirus, and BM-MSCs-infected with control adenovirus or recombinant mouse Tnfaip6. The disease activity index, weight loss, and histological scores were recorded. Serum levels of Tnfaip6 and pro- and anti-inflammatory cytokines, including interleukin (IL)-21, tumor necrosis factor-alpha (TNF-α), IL-10 were measured by enzyme-linked immunosorbent assay. The relative expression levels of these cytokines, B-cell lymphoma 6 (BCL-6) and fork-like transcription factor p3 (Foxp3) in the colon were determined by real-time quantitative PCR (RT-qPCR). BCL-6 and Foxp3 are the master regulators of follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr), respectively. The infiltration of Tfh and Tfr in mesenteric lymph nodes (MLNs) and spleens was analyzed by flow cytometry. Results: Compared to the normal control group, the expression levels of BCL-6 and IL-21 in the colon, Tfh infiltration, and ratios of Tfh/Tfr in the MLNs and spleen, and the serum concentrations of IL-21 and TNF-α increased significantly in the colitis model group (p < 0.05). Intraperitoneal injection of BM-MSCs or Tnfaip6 ameliorated weight loss and clinical and histological severity of colitis, downregulated the expression of BCL-6, IL-21, and TNF-α, upregulated the expression of Foxp3, IL-10, and Tnfaip6 (p < 0.05), increased Tfr and reduced the infiltration of Tfh in the MLNs and spleen, and downregulated the Tfh/Tfr ratio (p < 0.05). On the other hand, BM-MSCs lost the therapeutic effect and immune regulatory functions on Tfh and Tfr after Tnfaip6 knockdown. Conclusion: Tfh increase in the inflamed colon, Tfh decrease and Tfr increase during the colitis remission phase, and the imbalance of the Tfh/Tfr ratio is closely related to the progression of IBD. Tnfaip6 secreted by BM-MSCs alleviates IBD by inhibiting Tfh differentiation, promoting Tfr differentiation, and improving the imbalance of Tfh/Tfr in mice.

10.
Materials (Basel) ; 14(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34640062

RESUMO

The preservation and restoration of heritage sites have always been of key focus in the field of cultural relics. Current restoration methods mainly involve physical or chemical techniques, which are in many cases intrusive, destructive, and irreversible. Hereby, we introduce a novel biological strategy (microbial-induced carbonate precipitation (MICP)) to repair natural and simulated surface cracks on six hundred years' old wall bricks (part of the Nanjing City Min Dynasty ancient wall, China). X-ray micro computed tomography (X-ray micro-CT) was employed to non-destructively visualize the internal structure of the MICP-treated brick cubes. The results showed that MICP can effectively repair both natural and simulated cracks present on the brick's surface. The compressive strength of the MICP-treated brick cubes was significantly higher than that of the untreated control cubes (33.56 ± 9.07 vs. 19.00 ± 1.98 kN, respectively). MICP significantly increased the softening coefficient and decreased the water absorption rate (p < 0.05), indicating that the water resistance of the wall bricks can be improved after treatment. The 3D images from X-ray micro-CT, a method that could non-destructively assess the internals of such cultural structures, showed that MICP can effectively repair ancient relics, promoting durability and limiting degradation without affecting the structure. X-ray diffraction analyses showed that MICP generates the same calcite form as that of original bricks, indicating that MICP filler is compatible with the ancient city wall brick. These findings are in line with the concept of contemporary heritage preservation.

11.
J Hematol Oncol ; 14(1): 152, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556152

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70+ renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.


Assuntos
Ligante CD27/antagonistas & inibidores , Carcinoma de Células Renais/terapia , Imunoterapia Adotiva/métodos , Neoplasias Renais/terapia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Anticorpos de Cadeia Única/uso terapêutico , Animais , Ligante CD27/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Proteínas de Membrana/imunologia , Camundongos , Nucleotidiltransferases/imunologia , Transdução de Sinais
12.
Biomedicines ; 9(9)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34572430

RESUMO

Up to now, the chemotherapy approaches for glioblastoma were limited. 1-[2-Thiazolylazo]-2-naphthol (named as NSC139021) was shown to significantly inhibit the proliferation of prostate cancer cells by targeting the atypical protein kinase RIOK2. It is documented that RIOK2 overexpressed in glioblastoma. However, whether NSC139021 can inhibit the growth of glioblastoma cells and be a potential drug for glioblastoma treatment need to be clarified. In this study, we investigated the effects of NSC139021 on human U118MG, LN-18, and mouse GL261 glioblastoma cells and the mouse models of glioblastoma. We verified that NSC139021 effectively inhibited glioblastoma cells proliferation, but it is independent of RIOK2. Our data showed that NSC139021 induced cell cycle arrest at G0/G1 phase via the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway in G1/S checkpoint regulation. In addition, NSC139021 also increased the apoptosis of glioblastoma cells by activating the p53 signaling pathway and increasing the levels of Bax and cleaved caspase 3. Furthermore, intraperitoneal administration of 150 mg/kg NSC139021 significantly suppressed the growth of human and mouse glioblastoma in vivo. Our study suggests that NSC139021 may be a potential chemotherapy drug for the treatment of glioblastoma by targeting the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway.

13.
Plant Biotechnol J ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510693

RESUMO

Recent advances in plant genomics are scaling up gene expression profiling from the individual level to the population level, making transcriptomics a more powerful tool while deciphering the genome function. This study developed an efficient 3'RNA-seq method, Simplified Poly(A) Anchored Sequencing (SiPAS), to perform large-scale experiments of gene expression quantification. Aside from being cost-effective, by conducting a comprehensive performance assessment of SiPAS in hexaploid wheat, we demonstrated that SiPAS is highly sensitive, accurate, and reproducible while quantifying gene expression. Our method is anticipated to boost studies of population transcriptomics in plants and improve our understanding of genome biology.

14.
World J Diabetes ; 12(8): 1292-1303, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34512894

RESUMO

BACKGROUND: In addition to insulin resistance, impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Scarce clinical data exist for pediatric T2DM. AIM: To investigate the association of ß-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study. METHODS: This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019. Children with normal glycemic levels (n = 1935) were included as healthy control subjects. The homeostasis models (HOMAs) were used to assess the ß-cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) levels. The HOMA index was standardized by sex and age. We performed logistic regression analysis to obtain odds ratios (ORs) for T2DM risk using the standardized HOMA index, adjusted for confounding factors including sex, Tanner stage, T2DM family history, body mass index z-score, and lipid profile. RESULTS: The male-female ratio of newly diagnosed T2DM patients was 1.37:1 (OR = 2.20, P = 0.011), and the mean ages of onset for boys and girls were 12.5 ± 1.9 years and 12.3 ± 1.7 years, respectively. The prevalence of related comorbidities including obesity, elevated blood pressure, and dyslipidemia was 58.2%, 53.2%, and 80.0%, respectively. The T2DM group had lower HOMA2-%B levels (P < 0.001) and higher HOMA2-IR levels (P < 0.001) than the control group. Both the decrease in HOMA2-%B z-score (OR = 8.40, 95%CI: 6.40-11.02, P < 0.001) and the increase in HOMA2-IR z-score (OR = 1.79, 95%CI: 1.60-2.02, P < 0.001) were associated with a higher risk of T2DM, and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors. CONCLUSION: Besides insulin resistance, ß-cell function impairment is also strongly associated with Chinese pediatric T2DM. Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.

15.
Lipids Health Dis ; 20(1): 109, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544437

RESUMO

BACKGROUND: Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. METHODS: NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. RESULTS: Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). CONCLUSIONS: Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

16.
Front Nutr ; 8: 717640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527690

RESUMO

Background: China has a large emerging economy that illustrates how dietary patterns can affect food-source nitrogen (N) cycling. The indicator of food nitrogen footprint (NF) reflects the amount of reactive nitrogen (Nr) emissions and impacts of these emissions on the environment. It is a result of food production and consumption to satisfy basic dietary demands of a given population. Different from urban food consumption with improved waste treatment, rural food consumption significantly affects the environment from food production to waste disposal. We therefore, performed a nationwide case study to link dietary patterns to environmental degradation based on rural food NF accounting. Methods: The N-Calculator model was adopted to reveal the spatiotemporal characteristics of food NFs per capita, and regional food NFs related to rural diets in China from 2000 to 2019. Then, food-source Nr emissions to regional environment were quantified based on food NF accounting and relevant inventory of regional Nr emissions. Results: (i) The average annual food NF per-capita in rural regions was lower than that of its national counterpart, but exhibited regional differences, mainly attributed to the dietary role of cereals. (ii) There existed significant spatiotemporal characteristics among regional food NFs that were mainly contributed by plant-derived food consumptions (73%). Sichuan, Henan, Shandong, and Hunan exhibited larger regional food NFs, and Beijing, Shanghai, and Tibet showed a growth in NFs, wherein rural diets were dominated by animal-derived food. (iii) Rural diets affected the environment by the pathways of ammonia and nitrous oxide volatilization processes, as well as Nr loss to water, accounting for a 33, 5, and 62% average of food NFs across regions. (iv) Although current rural dietary patterns suggest reliance on cereal and vegetable consumptions, more animal-derived types of food would be consumed as urbanization continues, especially in developed regions, creating a barrier for further reduction in national food NF. Conclusion: The findings of this study highlight the importance of changing dietary patterns to the human health-environment dilemma. Strategies that include improvements in N recycling rates, adjustments in dietary patterns, and reductions in food wastes could mitigate regional N pollution with rural dietary shifts.

17.
Cell Death Dis ; 12(8): 772, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354046

RESUMO

Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis, with an unfavorable response to palliative chemotherapy. Unfortunately, there are few effective therapeutic regimens. Therefore, we require novel treatment strategies with enhanced efficacy. The present study aimed to investigate the antitumor efficacy of APG-1252-M1, a dual inhibitor of BCL-2/BCL-XL, as a single agent and combined with gemcitabine. We applied various apoptotic assays and used subcutaneous transplanted NPC model to assess the in vitro and in vivo antitumor activity. Moreover, phospho-tyrosine kinase array was used to investigate the combined therapy's potential synergistic mechanism. In addition, further validation was performed using immunohistochemistry and western blotting. In vitro, we observed that APG-1252-M1 had moderate antitumor activity toward NPC cells; however, it markedly improved gemcitabine's ability to promote NPC cell apoptosis and suppress invasion, migration, and proliferation. Specifically, APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo. Mechanistically, the drug combination synergistically suppressed NPC by activating caspase-dependent pathways, blocking the phospho (p)-JAK-2/STAT3/MCL-1 signaling pathway, and inhibiting epithelial-mesenchymal transition. In conclusion, the results indicated that the combination of APG-1252 and gemcitabine has synergistic anticancer activities against NPC, providing a promising treatment modality for patients with NPC.

18.
Theranostics ; 11(16): 7869-7878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335969

RESUMO

Goals: Chemotherapy, the most conventional modality for cancer therapy, usually brings serious side effects because of the low cancer-therapeutic specificity and bioavailability. It is of great significance for cancer treatment to develop new effective strategies to regulate biochemical reactions in organelles, enhance the specificity of chemotherapeutic drugs and reduce their side effects. Methods: We report herein a zeolitic imidazole framework-90 (ZIF-90) based nanoplatform, which was used to initiate a series of mitochondrial cascade reactions using ATP as a molecular switch for cancer therapy. The thioketal linked camptothecin (camptothecin prodrug, TK-CPT) and 2-Methoxyestradiol (2-ME) were encapsulated into the pores of ZIF-90 nanoparticles using a simple one-pot method, and the nanoplatform was finally coated with a layer of homologous cell membrane. Results: Mitochondrial ATP can efficiently degrade ZIF-90 and then release the loaded 2-ME and CPT prodrugs. 2-ME can inhibit the activity of superoxide dismutase (SOD), which induces the up-regulation of reactive oxygen species (ROS) in situ. The thioketal linkers in CPT prodrug can respond to ROS, thereby achieving subsequent release of parent CPT drug. This cascade of reactions can lead to prolonged high oxidative stress and cause continuous cancer cell apoptosis, due to the increased ROS level and the liberation of CPT. Conclusion: We constructed an ATP-triggered strategy using nanoscale ZIF-90 to initiate mitochondrial cascade reactions for cancer therapy. The ZIF-90 based nanoplatform exhibited low cytotoxicity, good mitochondria-targeting ability, and excellent therapeutic effect. In vivo experiments demonstrated that the growth of tumor can be efficiently inhibited in a mouse model. This ATP-triggered strategy to induce mitochondrial biochemical reactions offers more possibilities for developing organelle-targeted therapeutic platforms.


Assuntos
Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Zeolitas/química , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Animais , Antineoplásicos/farmacologia , Disponibilidade Biológica , Linhagem Celular Tumoral , China , Liberação Controlada de Fármacos/fisiologia , Imidazóis/química , Imidazóis/metabolismo , Imidazóis/farmacologia , Camundongos , Mitocôndrias/metabolismo , Nanopartículas/administração & dosagem , Neoplasias/metabolismo , Pró-Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Zeolitas/metabolismo , Zeolitas/farmacologia
19.
Anal Chem ; 93(35): 11899-11909, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34427091

RESUMO

Timely diagnosis is of great benefit to improve the survival rate of cancer patients. Body fluid cancer biomarker detection is a critical kind of noninvasive method for cancer diagnosis. Nevertheless, traditional methods for cancer biomarker detection always rely on a large-scale instrument and involve sophisticated operation. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-based in vitro diagnosis can simplify the detection procedures and improve sensitivity and specificity, holding great promise as the next-generation molecular diagnostic technology. In this Feature, we introduce the working mechanisms of different kinds of CRISPR/Cas systems for biosensing and CRISPR/Cas-mediated detection strategies for different kinds of cancer biomarkers including nucleic acids, proteins, and extracellular vesicles. In addition, the perspective and challenges of CRISPR/Cas-based strategies for cancer biomarkers are discussed.


Assuntos
Neoplasias , Ácidos Nucleicos , Biomarcadores Tumorais/genética , Sistemas CRISPR-Cas/genética , Humanos , Neoplasias/diagnóstico , Neoplasias/genética
20.
Eur Arch Otorhinolaryngol ; 278(12): 4909-4916, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34374843

RESUMO

PURPOSE: Observational study to determine if the voice-related self-concept as measured via the Fragebogen zur Erfassung des Stimmlichen Selbstkonzepts FESS (questionnaire for the assessment of the voice self-concept) can be improved through in-patient voice therapy. METHODS: 234 female and 80 male patients that underwent an intensive 3- to 4-week in-patient voice treatment due to varying types of dysphonia. After imputation of missing items but not missing questionnaires, 255 patients were eligible for FESS evaluation, 313 for VHI-12 evaluation. The German questionnaire for the assessment of the voice self-concept (FESS) and the German 12-item short-form of the Voice Handicap Index (VHI-12) were administered at the beginning and at the end of the hospital stay. Before-after comparisons are made visually and via t test. RESULTS: The Voice Handicap was significantly reduced, demonstrating the effectiveness of the administered therapy. Of the three scales of the FESS, the relationship with one's own voice and the awareness of the use of one's own voice was increased and thus improved. The connection between voice and emotional changes decreased significantly but only slightly. CONCLUSION: Conservative voice rehabilitation can not only reduce the voice handicap, but also improve the voice self-concept and the results can be measured.


Assuntos
Disfonia , Voz , Tratamento Conservador , Avaliação da Deficiência , Disfonia/etiologia , Disfonia/terapia , Feminino , Humanos , Masculino , Autoimagem , Índice de Gravidade de Doença , Inquéritos e Questionários
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