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1.
Plant Biotechnol J ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949081

RESUMO

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a widely occurring foliar diseases of wheat worldwide. Wild emmer wheat (WEW, Triticum dicoccoides) (AABB, 2n=4x=28), the progenitor of the cultivated tetraploid and hexaploid wheat, is highly resistant to powdery mildew and many resistance alleles were identified in this wild species.

2.
J Hazard Mater ; 413: 125462, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930973

RESUMO

Photocatalytic water disinfection has emerged as a promising approach for water purification. However, exploring efficient and rapid visible light driven materials for photocatalytic bacterial inactivation is still a challenging problem. Herein, red phosphorus/titanium oxide (TiO2@RP) nanofibers were developed for effective water disinfection by a vacuum ampoule strategy. The complete E. coli and S. aureus (7-log CFU mL-1) could be rapidly killed within 25 min and 30 min over the optimized TiO2@RP heterostructure under the white LED irradiation. The efficient photocatalytic antibacterial activity should be mainly ascribed to the synergetic enhancement in light absorption by RP decoration and charge migration and separation by the interface between TiO2 and RP. And then more unpaired photo-carriers would be transferred to the surface to facilitate the generation of photo-holes, •O2- radicals, and H2O2 species, which could destroy the bacterial cells efficiently.

3.
J Am Chem Soc ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871997

RESUMO

It is highly desirable to achieve solar-driven conversion of CO2 to valuable fuels with controlled selectivity. The existing catalysts are mainly explored for CO production but rarely for formate generation. Herein, highly selective photoreduction of CO2 to formate (99.7%) was achieved with a high yield of 3040 µmol g-1 in 10 h by hierarchical integration of photosensitizers and monometallic [bpy-Cu/ClX] (X = Cl or adenine) catalysts into a stable Eu-bpy metal-organic framework. However, replacing X with pyridine in [bpy-CuCl/X] significantly reduced formate production while increasing the CO yield to 960 µmol g-1. Systematic investigations revealed that the catalytic process is mediated by the H-bond synergy between Cu-bound X and CO2-derived species, and the selectivity of HCOO- can be controlled by simply replacing the coordination ligands. This work provides a molecularly precise structural model to provide mechanistic insights for selectivity control of CO2 photoreduction.

4.
Huan Jing Ke Xue ; 42(5): 2541-2549, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884825

RESUMO

The widespread use of antibiotics in the aquaculture industry has caused antibiotic resistance genes (ARGs) pollution. Metagenomics technology was used to detect and analyze the relative abundance of ARGs and microbial community structure in a fishery reclamation mining subsidence area. A total of 29 ARGs were detected, and bacA had the highest relative abundance in all the samples, reaching 1.96×10-5-1.19×10-4. The relative abundance of sulfonamide and tetracycline ARGs in sediments was relatively high and the relative abundance of multidrug ARGs in well water was relatively high. Proteobacteria was the most dominant bacterial phylum in all the samples, and Chloroflexi and Euryarchaeota were relatively abundant in the sediments. Thiobacillus was the most dominant bacterial genus in the sediments, and Acinetobacter and Pseudomonas were the dominant bacterial genera in the well water. The correlation analysis between the ARGs and microorganisms showed that the genera and ARGs were mainly correlated to a moderate degree, and multiple genera had significant positive correlations with ARGs. The distribution of ARGs was affected by the structure of the microbial community. The sediments and well water in the fishery reclamation mining subsidence area were both contaminated by ARGs, and corresponding control measures should be strengthened to protect the regional environment.


Assuntos
Antibacterianos , Microbiota , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Pesqueiros , Genes Bacterianos/genética , Microbiota/genética
5.
Proc Natl Acad Sci U S A ; 118(17)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33883281

RESUMO

Modern dune fields are valuable sources of information for the large-scale analysis of terrestrial and planetary environments and atmospheres, but their study relies on understanding the small-scale dynamics that constantly generate new dunes and reshape older ones. Here, we designed a landscape-scale experiment at the edge of the Gobi desert, China, to quantify the development of incipient dunes under the natural action of winds. High-resolution topographic data documenting 42 mo of bedform dynamics are examined to provide a spectral analysis of dune pattern formation. We identified two successive phases in the process of dune growth, from the initial flat sand bed to a meter-high periodic pattern. We focus on the initial phase, when the linear regime of dune instability applies, and measure the growth rate of dunes of different wavelengths. We identify the existence of a maximum growth rate, which readily explains the mechanism by which dunes select their size, leading to the prevalence of a 15-m wavelength pattern. We quantitatively compare our experimental results with the prediction of the dune instability theory using transport and flow parameters independently measured in the field. The remarkable agreement between theory and observations demonstrates that the linear regime of dune growth is permanently expressed on low-amplitude bed topography, before larger regular patterns and slip faces eventually emerge. Our experiment underpins existing theoretical models for the early development of eolian dunes, which can now be used to provide reliable insights into atmospheric and surface processes on Earth and other planetary bodies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33844491

RESUMO

In this work, we report the presence of surface-densified phases (ß-Ni5O8, γ-Ni3O4, and δ-Ni7O8) in LiNiO2 (LNO)- and LiNi0.8Al0.2O2 (LNA)-layered compounds by combined atomic level scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS). These surface phases form upon electrochemical aging at high state of charge corresponding to a fully delithiated state. A unique feature of these phases is the periodic occupancy by Ni2+ in the Li layer. This periodic Ni occupancy gives rise to extra diffraction reflections, which are qualitatively similar to those of the LiNi2O4 spinel structure, but these surface phases have a lower Ni valence state and cation content than spinel. These experimental results confirm the presence of thermodynamically stable surface phases and provide new insights into the phenomena of surface phase formation in Ni-rich layered structures.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33907083

RESUMO

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare the accuracy of pedicle screw placement and proximal facet joint violation (FJV) in single-level degenerative lumbar diseases using Cortical bone trajectory (CBT) and traditional trajectory (TT) techniques, and analyzed their possible risk factors. SUMMARY OF BACKGROUND DATA: CBT screws have been utilized increasingly to improve cortical bone contact to prevent screw pullout and reduce approach-related morbidity. However, the studies on intra-pedicular accuracy and proximal FJV between the two methods are rare. METHODS: A total of 40 patients who required single-level instruments were included in the retrospective study treated with the CBT-TLIF and the TT-TLIF at a 1:1 ratio from March 2019 to August 2020. The radiographic outcomes were the intra-pedicular accuracy and proximal FJV. Moreover, the possible risk factors were assessed using bivariate and multivariate analyses. RESULTS: As for the intra-pedicular accuracy, 73 screws (91.3%) were classified as grade A, 7 screws (8.7%) classified as grade B in the CBT group. A total of 71 screws (88.8%) were graded A with remaining 8 screws (10.0%) graded B and 1 screw (1.2%) graded C in the TT group. The proportion of optimal and clinically acceptable screw positions in the two groups were not significantly different (P > 0.05). In addition, the rate of proximal FJV in CBT approach (8.3%) was significantly lower than that in the TT approach (35.0%) (P < 0.001). Multivariate analysis showed the TT insertion approach and facet angle ≥45° were the independent risk factors for proximal FJV, but no factors above affected intra-pedicular accuracy. CONCLUSION: Compared with the TT approach in TLIF, the CBT approach showed similar intra-pedicular accuracy and remarkable superiority in proximal facet joint protection. Facet angle ≥45° is the independent risk factors for proximal FJV.Level of Evidence: 2.

8.
Neural Regen Res ; 16(11): 2316-2323, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33818518

RESUMO

Although the transcriptional alterations inside the facial nucleus after facial nerve injury have been well studied, the gene expression changes in the facial nerve trunk after injury are still unknown. In this study, we established an adult rat model of facial nerve crush injury by compressing the right lateral extracranial nerve trunk. Transcriptome sequencing, differential gene expression analysis, and cluster analysis of the injured facial nerve trunk were performed, and 39 intersecting genes with significant variance in expression were identified. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the 39 intersecting genes revealed that these genes are mostly involved in leukocyte cell-cell adhesion and phagocytosis and have essential roles in regulating nerve repair. Quantitative real-time polymerase chain reaction assays were used to validate the expression of pivotal genes. Finally, nine pivotal genes that contribute to facial nerve recovery were identified, including Arhgap30, Akr1b8, C5ar1, Csf2ra, Dock2, Hcls1, Inpp5d, Sla, and Spi1. Primary Schwann cells were isolated from the sciatic nerve of neonatal rats. After knocking down Akr1b8 in Schwann cells with an Akr1b8-specific small interfering RNA plasmid, expression levels of monocyte chemoattractant protein-1 and interleukin-6 were decreased, while cell proliferation and migration were not obviously altered. These findings suggest that Akr1b8 likely regulates the interaction between Schwann cells and macrophages through regulation of cytokine expression to promote facial nerve regeneration. This study is the first to reveal a transcriptome change in the facial nerve trunk after facial nerve injury, thereby revealing the potential mechanism underlying repair of facial nerve injury. This study was approved by the Animal Ethics Committee of Nantong University, China in 2018 (approval No. S20180923-007).

9.
Cytokine ; : 155522, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33849765

RESUMO

Complement is an important branch of innate immunity; however, its biological significance goes far beyond the scope of simple nonspecific defense and involves a variety of physiological functions, including the adaptive immune response. In this review, to unravel the complex relationship between complement and tumors, we reviewed the high diversity of complement components in cancer and the heterogeneity of their production and activation pathways. In the tumor microenvironment, complement plays a dual regulatory role in the occurrence and development of tumors, affecting the outcomes of the immune response. We explored the differential expression levels of various complement components in human cancers via the Oncomine database. The gene expression profiling interactive analysis (GEPIA) tool and Kaplan-Meier plotter (K-M plotter) confirmed the correlation between differentially expressed complement genes and tumor prognosis. The tumor immune estimation resource (TIMER) database was used to statistically analyze the effect of complement on tumor immune infiltration. Finally, with a view to the role of complement in regulating T cell metabolism, complement could be a potential target for immunotherapies. Targeting complement to regulate the antitumor immune response seems to have potential for future treatment strategies. However, there are still many complex problems, such as who will benefit from this therapy and how to select the right therapeutic target and determine the appropriate drug concentration. The solutions to these problems depend on a deeper understanding of complement generation, activation, and regulatory and control mechanisms.

10.
Pharmazie ; 76(4): 172-174, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33849703

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancers. Chemotherapy is the most important therapeutic option for TNBC, and chemotherapy-induced nausea and vomiting (CINV) is inevitable. Metoclopramide is a good and cost-effective therapeutic option for chemotherapy-induced nausea and vomiting. However, it is not commonly used in breast cancer because it can increase serum prolactin levels by blocking dopamine D2 receptor. This study aimed at elucidating the effect of metoclopramide on triple-negative breast cancer, MDA-MB-231 cells were treated with various concentrations of metoclopramide, the cell proliferation was detected by MTT method, the apoptosis rate was detected by Annexin V/PI double staining method, the expression change of death-related protein was detected by Western Blot. We found that metoclopramide inhibits cell proliferation and induces cell apoptosis of MDA-MB-231 in a concentration-dependent manner, and the Bcl family was involved in this process.

11.
J Transl Med ; 19(1): 150, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858440

RESUMO

BACKGROUND: Sidedness (right/left) of colorectal cancer (CRC) is essential for treatment. Whether carcinogenesis of tobacco varies by sidedness remains unclear. The present study aims to evaluate the sidedness tendency of cigarette smoking and to explore its impact on prognosis. METHODS: In the multi-center retrospective study, data on 46 166 Chinese CRC patients were extracted from a big-data platform. Logistic regression analyses were performed to evaluate qualitative and quantitative associations between smoking and tumor sidedness. Survival analyses were conducted in metastatic CRC. RESULTS: History of smoking was associated with left-sided CRC (LSCRC; Adjusted odds ratio, 1.25; 95% CI, 1.16 - 1.34; P < .001). The sidedness tendency towards LSCRC increased from non-smokers, to ex-smokers, and to current smokers (P for trend < .001). Longer duration (P for trend < .001) and larger total amount of cigarette smoking (P for trend < .001) were more associated with LSCRC, respectively. The association was confirmed in both left-sided colon cancer and rectal cancer, but was stronger for rectal cancer (P = .016). Alcoholism significantly enhanced the association by 7% (P = .027). Furthermore, prognostic advantage of metastatic LSCRC diminished among ever-smokers, with contrary survival impacts of smoking on either side of CRC. CONCLUSIONS: History of smoking was associated with LSCRC in a positive dose-response relationship, and presented opposite prognostic impacts on right- and left-sided tumors. Smoking potentially plays an instrumental role in the mechanism for sidedness heterogeneity in CRC.

12.
Sensors (Basel) ; 21(6)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809575

RESUMO

A vibration fiber sensor based on a fiber ring cavity laser and an interferometer based single-mode-multimode-single-mode (SMS) fiber structure is proposed and experimentally demonstrated. The SMS fiber sensor is positioned within the laser cavity, where the ring laser lasing wavelength can be swept to an optimized wavelength using a simple fiber loop design. To obtain a better signal-to-noise ratio, the ring laser lasing wavelength is tuned to the maximum gain region biasing point of the SMS transmission spectrum. A wide range of vibration frequencies from 10 Hz to 400 kHz are experimentally demonstrated. In addition, the proposed highly sensitive vibration sensor system was deployed in a field-test scenario for pipeline acoustic emission monitoring. An SMS fiber sensor is mounted on an 18" diameter pipeline, and vibrations were induced at different locations using a piezoelectric transducer. The proposed method was shown to be capable of real-time pipeline vibration monitoring.

14.
Asia Pac J Clin Nutr ; 30(1): 7-14, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787035

RESUMO

BACKGROUND AND OBJECTIVES: Little is known about nutritional status in patients with hepatocellular carcinoma (HCC) after multiple rounds of transarterial chemoembolization (TACE). We established a comprehensive nutritional index (CNI) and evaluated its prognostic value for overall survival (OS) and time to progression (TTP). METHODS AND STUDY DESIGN: HCC patients (N=282) who underwent multiple TACE treatments were enrolled. CNI was established by principal component analysis based on body mass index, usual body weight percentage, hemoglobin, total lymphocyte count, and albumin; the cutoff value was determined by receiver operating characteristic curve and Youden index analysis. The correlation between CNI and treatment-related complications was analyzed with Spearman's method. The Kaplan-Meier method with log-rank test and Cox proportional hazards model were used to compare the prognostic values of CNI, prognostic nutritional index (PNI), and nutrition risk index (NRI) for OS and TTP. RESULTS: Nutritional status declined after repeated TACE (p<0.001). CNI (cutoff= 0.251) varied according to albumin-bilirubin grade, tumor size, and number of TACE treatments (p<0.001 or 0.025) and was negatively correlated with rate of serious complications (r=-0.185, p=0.002). Patients with low CNI had shorter OS (p=0.014) and TTP (p=0.007); high CNI predicted longer OS (hazard ratio [HR], 0.72; 95% confidence interval [CI]: 0.52-1.00, p=0.048) and TTP (HR, 0.69; 95% CI: 0.50-0.94, p=0.019). Post-treatment PNI and NRI were unrelated to prognosis (p>0.05). CONCLUSIONS: HCC patients have poor nutritional status after multiple TACE treatments, which predicts shorter OS and TTP. The prognostic performance of CNI is superior to those of PNI and NRI.

15.
Cancer Biol Med ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724741

RESUMO

OBJECTIVE: In this post-hoc analysis, we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma (ESCC) patients. METHODS: A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included. The tumor response was assessed by computed tomography at week 3, week 6, and then every 6 weeks until progressive disease was observed. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints included overall survival (OS) and objective response rate (ORR). RESULTS: In all patients, the median PFS was 3.02 months [95% confidence interval (CI): 2.63-3.65 months] and the OS was 6.11 months (95% CI: 4.40-7.79 months). The ORR was 7.34% (95% CI: 3.22%-13.95%). A total of 59 (54%) patients were diagnosed with treatment-induced hypertension (Group A), and the remaining patients (n = 50, 46%) were in Group B. Baseline prognostic factors were similar between the 2 groups. Patients in Group A had a longer PFS and OS and higher ORR. When stratifying patients using a previously known history of hypertension, treatment-induced hypertension was a predictor only for patients without previous hypertension, who had longer PFS [hazard ratio (HR): 0.40, 95% CI: 0.24-0.68] and OS (HR: 0.37, 95% CI: 0.21-0.67). CONCLUSIONS: We showed, for the first time, a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib, without a previously known history of hypertension. Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients, which may also reflect the intended target inhibition.

16.
Sensors (Basel) ; 21(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669717

RESUMO

A review of recent progress in the use of infrared femtosecond lasers to fabricate optical fiber sensors that incorporate fiber Bragg gratings (FBG) and random fiber gratings (RFG) is presented. The important advancements in femtosecond laser writing based on the phase mask technique now allow through-the-coating (TTC) fabrication of Bragg gratings in ultra-thin fiber filaments, tilted fiber Bragg gratings, and 1000 °C-resistant fiber Bragg gratings with very strong cladding modes. As an example, through-the-coating femtosecond laser writing is used to manufacture distributed fiber Bragg grating sensor arrays for oil pipeline leak detection. The plane-by-plane femtosecond laser writing technique used for the inscription of random fiber gratings is also reviewed and novel applications of the resultant devices in distributed temperature sensing, fiber lasers and fiber laser sensors are discussed.

17.
Poult Sci ; 100(5): 101030, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33752066

RESUMO

Heat stress can decrease poultry performance indices, immune function, and intestinal development, which can reduce birds' innate protective mechanisms and may be more susceptible for pathogens. Ma chickens heat-stressed with 41°C for 12 h and recovered for 7 d had extremely low immunity. In this study, a susceptible chicken model induced by heat stress and then infected with Escherichia coli O157:H7 was established to explore the mechanisms of birds' intestinal immune function changes. Ma chickens in heat stress + E. coli (HS + E. coli) group were stressed at 41°C for 12 h and recovered for 7 d, then chickens in E. coli group and HS + E. coli group were orally administered with 1 mL E. coli O157:H7 (1 × 109 cfu/mL). Chickens were sacrificed at the fourth day after E. coli administration. Results showed that the HS + E. coli group had increased intestinal length and weight, had higher E. coli counts in cecum contents than the E. coli group. Heat stress also enhanced serum diamine oxidase and decreased IgA level in chickens infected by E. coli. Heat stress had protective effects in small intestinal morphology except for duodenum by using hematoxylin and eosin staining. Compared with the E. coli group birds, IL-1ß, TNF-α, and caspase-1 protein levels in the duodenum and ileum were significantly increased. Heat stress also can significantly enhance the gene and protein expression of Hsp70, TLR4, and NF-κB in the duodenum and ileum, respectively. The gene expression of Hsp70, TLR4, and NF-κB in the jejunum was not influenced, but the protein expression of Hsp70 and NF-κB was inhibited by heat stress. The results indicated heat stress can amplify the effect of E. coli on intestinal inflammatory injury of Ma chickens through increasing TLR4-NF-κB signaling pathway.

18.
Cancer Lett ; 508: 47-58, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33766751

RESUMO

Perineural invasion (PNI) is a common feature of pancreatic ductal adenocarcinoma (PDAC) and is one of the important causes of local recurrence in resected pancreatic cancer, but the molecular mechanism remains largely unexplored. Here, we used immunohistochemistry staining to determine the expression of CD74. Then the in vivo PNI model, in vitro neuroplasticity assay, cell proliferation assay, wound healing and Transwell-based invasion assay were performed to examine the function of CD74 in pancreatic cancer cell lines. ChIP assay and Luciferase reporter assay were used to illustrate the mechanism underlying CD74 induced GDNF expression. We confirmed that the expression level of CD74 was an independent predictor of PNI and poor prognosis for PDAC. Moreover, we found that upregulation of CD74 on PDAC enhanced its migration and invasive capabilities and potentiated the secretion of neurotrophic factor GDNF to promote the neuroplasticity. Mechanistically, CD74 promoted GDNF production via the AKT/EGR-1/GDNF axis in PDAC. Taken together, our findings suggest a supportive role of CD74 in the PNI of PDAC, and deepen our understanding of how cancer cells promote neuroplasticity in the microenvironment of PDAC.

19.
Eur J Cancer ; 148: 1-13, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33691262

RESUMO

BACKGROUND: GLS-010, a novel engineered fully human immunoglobin G4 monoclonal antibody, can specially block the PD-1/PD-L1/2 axis and reactivate the antitumor immunity. AIM: This phase Ia/Ib study was carried out to evaluate the safety, recommended phase II dose (R2PD), and primary antitumor effects of GLS-010 in patients with advanced, refractory lymphoma and solid tumors. METHODS: In phase Ia study, patients with refractory solid tumors and lymphoma enrolled and received GLS-010 at a dose of 1, 4, or 10 mg/kg Q2W; 240 mg Q3W or Q2W. The primary objective was to assess the dose-limiting toxicity (DLT). In phase Ib study, doses were expanded in 9 specific tumors to ensure the R2PD and explore the efficacy. Tumor mutation burden level and PD-L1 expression were also assessed with whole-exome sequencing and immunohistochemistry (SP263), respectively. RESULTS: Up to April 18, 2020, a total of 289 patients (n = 24, phase Ia; n = 265, phase Ib) were enrolled. DLT was not observed in phase Ia part. The T1/2, CLss, and Vd were similar among all dose groups and different tumors. The most common treatment-emergent adverse events (TEAEs) were anemia, leukopenia, elevated alanine aminotransaminase/asparate aminotransferase (ALT/AST), and elevated bilirubin. And hypothyroidism was the most common immune-related adverse event (irAE). The incidence of grade ≥3 TEAE was 39.8%, while grade ≥3 irAE was only 4.5%. Based on safety studies, pharmacokinetics/pharmacodynamics, and preclinical data, 240-mg Q2W was recommended as the expansion dose. The overall objective response rate was 23.6%, with 10 patients achieving complete response. Patients with a high PD-L1 expression level (31.3% Versus. 13.7%, p = 0.012) or t-issue tumor mutation burden level (31.3% Versus. 5.6%, p = 0.009) showed a significantly better response. CONCLUSION: GLS-010 showed acceptable safety profile and favorable clinical response. The dose of 240 mg Q2W was an optimal recommended dose as monotherapy.

20.
J Cell Physiol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559206

RESUMO

Bitter taste receptors (TAS2Rs) and their signaling elements are detected throughout the body, and bitter tastants induce a wide variety of biological responses in tissues and organs outside the mouth. However, the roles of TAS2Rs in these responses remain to be tested and established genetically. Here, we employed the CRISPR/Cas9 gene-editing technique to delete three bitter taste receptors-Tas2r143/Tas2r135/Tas2r126 (i.e., Tas2r triple knockout [TKO]) in mice. The fidelity and effectiveness of the Tas2r deletions were validated genetically at DNA and messenger RNA levels and functionally based on the tasting of TAS2R135 and TAS2R126 agonists. Bitter tastants are known to relax airways completely. However, TAS2R135 or TAS2R126 agonists either failed to induce relaxation of pre-contracted airways in wild-type mice and Tas2r TKO mice or relaxed them dose-dependently, but to the same extent in both types of mice. These results indicate that TAS2Rs are not required for bitter tastant-induced bronchodilation. The Tas2r TKO mice also provide a valuable model to resolve whether TAS2Rs mediate bitter tastant-induced responses in many other extraoral tissues.

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