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1.
Chemosphere ; 262: 127861, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32791368

RESUMO

In this study, goethiete (α-FeOOH) -biochar (BC) composites were successfully developed from a co-precipitation reaction under alkaline conditions (pH = 11.93) and used as the adsorbent for phosphate recovery from urine. The morphology and crystallinity of α-FeOOH-BC composites were characterized by scanning electron microscopy and X-ray diffraction. α-FeOOH loaded BC was found to be amorphous. This may be caused by the Si residue in BC. The Elovich model and the Langmuir model fit better to the kinetic and isotherm results of α-FeOOH-600BC, respectively, indicating that phosphate adsorption is mainly a chemisorption and monolayer adsorption process. The α-FeOOH-600BC with amorphous structure showed higher adsorption capacity than crystalline α-FeOOH, and the maximum phosphate sorption capacity reached 57.39 mg g-1. Additionally, the extractable phosphate of this material was approximately 967.5 mg P·kg-1 suggesting the α-FeOOH-600BC after adsorption could be a promising alternative as a slow-phosphate-release fertilizer. Fourier-transform infrared and X-ray induced photoelectron spectroscopy results showed that the active sites of the adsorption of phosphate were the Fe-OH bonds that formed inner-sphere complexes (Fe-O-P).


Assuntos
Fertilizantes , Compostos de Ferro/química , Minerais/química , Fosfatos/química , Poluentes Químicos da Água/química , Adsorção , Carvão Vegetal , Cinética , Organofosfatos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Zea mays
2.
Skeletal Radiol ; 50(1): 159-169, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32691127

RESUMO

PURPOSE: To assess the accuracy of craniocervical measurements for identifying craniocervical injuries and the frequency of subjective findings of craniocervical injuries on CT in pediatric patients. METHODS: Case-controlled retrospective review of patients ≤ 16 years old with craniocervical junction injuries. Receiver operator curves were created for common craniocervical measurements on CT comparing patients with complete and partial craniocervical injuries to uninjured cohort. Frequency of subjective CT findings of craniocervical injury was assessed in the injured cohort. RESULTS: For complete disruption injuries (CD) (n = 27), C1-C2 distance (AUC = 0.90, 95%CI = 0.83-0.97), atlanto-occipital distance (AUC = 0.95-0.98, 95%CI = 0.90-1.00), and basion-dens distance (AUC = 0.90, 95%CI = 0.82-0.98) had excellent accuracy diagnosing injury. Powers ratio (AUC = 0.85, 95%CI = 0.76-0.94) had good, basion-posterior axial line (AUC = 0.74, 95%CI = 0.61-0.86) fair, and atlanto-dental distance (AUC = 0.69, 95%CI = 0.57-0.82) poor accuracy. For partial disruption injuries (PD) (n = 21), basion-dens distance (AUC = 0.75, 95%CI = 0.62-0.88) had fair accuracy diagnosing injury. Powers ratio (AUC = 0.63, 95%CI = 0.47-0.79), C1-C2 distance (AUC = 0.60, 95%CI = 0.45-0.75), atlanto-dental distance (AUC = 0.55, 95%CI = 0.39 = 0.71), atlanto-occipital distance (AUC = 0.63-0.65, 95%CI = 0.47-0.81), and basion-posterior axial line (AUC = 0.60, 95%CI = 0.44-0.76) all had poor accuracy. Eighty-one percent (n = 22) of CD and 38% (n = 8) of PD patients had non-concentric atlanto-occipital joints. One hundred percent of CD patients had ≥ 1 soft tissue finding and eighty-one percent (n = 22) had ≥ 2 findings. Seventy-three percent (n = 16) of PD patients had ≥ 1 soft tissue finding. Eighty-six percent (n = 18) of PD patients had non-concentric atlanto-occipital joints and/or soft tissue findings. CONCLUSION: Craniocervical measurements have poor accuracy for identifying craniocervical injuries in pediatric patients with incomplete craniocervical ligament disruption. Subjective findings of craniocervical injury are frequently present on CT in pediatric patients and can help increase sensitivity for identifying injury.

3.
Bioresour Technol ; 319: 124121, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32957045

RESUMO

The study aimed to identify the preference of pathways of humus formation. Five lab-scale composting experiments were established: the control (CK), montmorillonite addition (M), illite addition (I), thermal treatment montmorillonite addition (M-) and thermal treatment illite addition (I-). Results showed humus content was increased by 11.5%, 39.3%, 37.2%, 30.9% and 27.6% during CK, M-, M, I- and I composting. Meanwhile, Redundancy analysis indicated the bands of bacteria community related to humic acid (HA) were more abundant in the M- and I- treatments. Furthermore, structural equation model and variance partitioning analysis demonstrated that M- and I- treatments promoted precursors to synthesize HA by coordinated regulation of biotic pathway and abiotic pathway, the increase of HA in the M and I treatments mainly through the abiotic pathway. In summary, an effective method was proposed to improve humus production by adjusting the preference of biotic and abiotic pathways of humus formation.


Assuntos
Compostagem , Animais , Bentonita , Galinhas , Substâncias Húmicas , Esterco , Minerais , Solo
4.
Bioresour Technol ; 319: 124142, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32987278

RESUMO

This study investigated oxytetracycline (OTC) effects on nitrogen (N) transformation and bacterial community diversity during chicken manure composting. The addition of OTC inhibited nitrifying bacteria, resulted in a decrease in the transformation of NH4+-N to NO3--N during composting, and affected in the order T3 (32.76%) > T2 (28.76%) > T1 (17.02%) > CK. The OTC could act as an inhibitor against core microbial growth, leading to a delay effect during composting. 16S rRNA sequencing was employed for the functional prediction, and results indicated the bacterial community related to N transformation reconstructed under OTC stress. The core microorganisms were changed after OTC addition, with the emergence of Bacillus and Thermobifida, which could inhibit the N transformation by network analysis. Therefore, core microorganisms could be regulated to reduce the negative of OTC impacts on N transformation and thus reduce N loss during composting.


Assuntos
Compostagem , Microbiota , Oxitetraciclina , Animais , Esterco , Nitrogênio , RNA Ribossômico 16S/genética , Solo
5.
Sci Total Environ ; 751: 141869, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32882542

RESUMO

Black bloom occurs frequently in eutrophic waters. We investigated the conditions promoted the formation of black bloom via in-situ measurement in two aquatic microcosms and the effects of black bloom on the bacterial community composition. Although larger changes in dissolved oxygen (DO) were detected in the Hydrilla verticillata-dominated microcosm over the 90-day simulation, black bloom occurred more readily in the phytoplankton-dominated than macrophyte-dominated microcosm under conditions of O2 depletion and temperature above 30 °C. The sediment bacterial community composition shifted after black bloom; the relative abundance of Thiobacillus and Sideroxydans, which oxidize iron (Fe) and sulfur (S), decreased by 47% and 48%, respectively, in the phytoplankton-dominated microcosm and by 18% and 20% in the macrophyte-dominated microcosm. By contrast, Desulfatiglans increased by 13% and 19%, respectively, after black bloom. Furthermore, inter-taxa correlations remarkably changed according to co-occurrence network analysis. Thirty-six different taxa from the phylum to the genus level were identified as biomarkers of sediments collected before and after the black bloom event. Most of these biomarkers are related to Fe/S cycling in aquatic ecosystems.


Assuntos
Sedimentos Geológicos , Ferro , Bactérias , Ecossistema , Eutrofização , Ferro/análise , Lagos , Enxofre
6.
HLA ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33258295

RESUMO

HLA-B*55:71 has one nucleotide change from HLA-B*55:02:01:01 where Histidine (3) is changed to Tyrosine. This article is protected by copyright. All rights reserved.

7.
Ann Surg Oncol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259043

RESUMO

INTRODUCTION: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined. METHODS: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally. RESULTS: Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p < 0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p < 0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR = 1.40, 95% CI 1.14-1.71; high TB: HR = 1.89, 95% CI 1.46-2.45) and DFS (medium TB, HR = 1.61, 95% CI 1.33-1.96; high TB: HR = 2.03, 95% CI 1.56-2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p = 0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p < 0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p = 0.02). CONCLUSION: Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.

8.
Environ Int ; 146: 106252, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33242729

RESUMO

OBJECTIVE: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository. METHODS: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017-2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle's completion. RESULTS: In 2017-2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites. CONCLUSIONS: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity.

9.
BMC Ophthalmol ; 20(1): 465, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243174

RESUMO

BACKGROUND: This study investigated the characteristics of corneal higher-order aberrations (HOAs) of the anterior surface, posterior surface, and total cornea in adolescents with mild to moderate myopia. METHODS: A total of 183 patients with myopia (183 eyes) aged 8 to 18 years were enrolled in this study. The axial length (AL) of the eyes was measured by an IOL-Master, and corneal curvatures (K-values) and HOAs were measured by a Pentacam anterior segment diagnostic analyzer. RESULTS: Results of this study showed that the anterior, posterior and total corneal horizontal coma Z31 were - 0.1249 ± 0.105 µm, 0.0009 ± 0.001 µm, and - 0.1331 ± 0.116 µm, respectively; the anterior, posterior and total corneal vertical coma Z3- 1 were - 0.0212 ± 0.164 µm, 0.0003 ± 0.043 µm, and - 0.0216 ± 0.168 µm, respectively; and spherical aberration (SA) Z40 values were 0.2244 ± 0.091 µm, 0.1437 ± 0.029 um, and 0.1889 ± 0.090 µm, respectively. Total corneal Z31 was statistically correlated with posterior corneal astigmatism (K2b - K1b) (p = 0.038). Total corneal Z3- 1 was correlated with anterior corneal astigmatism (K2f - K1f) (p = 0.027). Anterior, posterior, and total corneal Z40 were correlated with anterior and posterior corneal curvature (K1f, K2f, K1b, K2b) (p = 0.001). Posterior corneal Z40b was also significantly correlated with AL. CONCLUSIONS: In adolescents with mild to moderate myopia, the posterior corneal surface shape may play a compensatory role in the balance of corneal aberrations, and the posterior corneal SA tended to become less negative as the AL increased. The corneal coma may also play a compensatory role in posterior corneal surface astigmatism, which was valuable for the treatment for improving visual quality. This conclusion still needs to be verified.

10.
Int J Equity Health ; 19(1): 211, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246458

RESUMO

BACKGROUND: Jiangsu was one of the first four pilot provinces to engage in comprehensive health care reform in China, which has been on-going for the past 5 years. This study aims to evaluate the equity, efficiency and productivity of health care resource allocation in Jiangsu Province using the most recent data, analyse the causes of deficiencies, and discuss measures to solve these problems. METHODS: Data were extracted from the Jiangsu Health/Family Planning Statistical Yearbook (2015-2019) and Jiangsu Statistical Yearbook (2015-2019). The Gini coefficient (G), Theil index (T) and health resource density index (HRDI) were chosen to study the fairness of health resource allocation in Jiangsu Province. Data envelopment analysis (DEA) and the Malmquist productivity index (MPI) were used to analyse the efficiency and productivity of this allocation. RESULTS: From 2014 to 2018, the total amount of health resources in Jiangsu Province increased. The G of primary resource allocation by population remained below 0.15, and that by geographical area was between 0.14 and 0.28; additionally, the G of health financial resources was below 0.26, and that by geographical area was above 0.39. T was consistent with the results for G and Lorenz curves. The HRDI shows that the allocated amounts of health care resources were the highest in southern Jiangsu, except for the number of health institutions. The average value of TE was above 0.93, and the DEA results were invalid for only two cities. From 2014 to 2018, the mean TFPC in Jiangsu was less than 1, and the values exceeded 1 for only five cities. CONCLUSION: The equity of basic medical resources was better than that of financial resources, and the equity of geographical allocation was better than that of population allocation. The overall efficiency of health care resource allocation was high; however, the total factor productivity of the whole province has declined due to technological regression. Jiangsu Province needs to further optimize the allocation and increase the utilization efficiency of health care resources.

11.
Anal Chem ; 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33253538

RESUMO

The gut microbiome and its metabolic processes are dynamic systems. Surprisingly, our understanding of gut microbiome dynamics is limited. Here, we report a metaproteomic workflow that involves protein stable isotope probing (protein-SIP) and identification/quantification of partially labeled peptides. We also developed a package, which we call MetaProfiler, that corrects for false identifications and performs phylogenetic and time series analysis for the study of microbiome dynamics. From the stool sample of five mice that were fed with 15N hydrolysate from Ralstonia eutropha, we identified 12 326 nonredundant unlabeled peptides, of which 8256 of their heavy counterparts were quantified. These peptides revealed incorporation profiles over time that were different between and within taxa, as well as between and within clusters of orthologous groups (COGs). Our study helps unravel the complex dynamics of protein synthesis and bacterial dynamics in the mouse microbiome. MetaProfiler and the bioinformatic pipeline are available at https://github.com/northomics/MetaProfiler.git.

12.
Rev Sci Instrum ; 91(10): 104706, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33138585

RESUMO

Contact welding is considered the major failure mechanism for electromechanical switch applications. There has been increasing demand to research the measurement method to characterize the anti-welding ability of metal electrode materials. In this paper, the contact welding phenomenon of closed electrodes is made to reoccur by using our novel designed test rig. The welding strength and welding area of typical electrode materials, including silver, copper, silver tin oxide, and silver nickel alloy, are explicitly measured and compared. In addition, the effects of electrical current and mechanical load force on welding strength and welding trace are presented. The calculation method of the threshold welding current is introduced for elastic contact situation in low current switching devices.

13.
Rev Sci Instrum ; 91(10): 103109, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33138613

RESUMO

Light shift produced by the AC Stark effect is one of the major factors limiting the accuracy and long-term stability of a cold atom interferometer. The first order light shift can be canceled by fixing the power ratio of the Raman beams at a specified value. We report here a new method to stabilize the power ratio of the two Raman lasers with ∼100 kHz locking bandwidth, suppressing the effect of the first order light shift. We first mixed the two Raman lasers (at different optical frequencies) with a reference beam and then used two Schottky diode detectors to extract the corresponding beat note signals for each beam, which are much easier to be manipulated and processed as they are in the microwave band. The stability of the power ratio is improved by three orders of magnitude from 5.84 × 10-3 to 3.51 × 10-6 at 1 s averaging time and reaches 1.59 × 10-7 at 10 000 s integrating time when the servo loop is engaged. This method can be used in other precise quantum measurement based on the stimulated Raman transition and can be applied to compact inertial sensors.

14.
Adv Mater ; : e1906070, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33150693

RESUMO

Li-rich layered oxides (LLOs) are fascinating high-energy cathodes for lithium-ion batteries (LIBs), but still suffer from critical drawbacks that retard their practical applications. Although surface modification is effective to protect LLOs from structural deterioration, the delicate design of structures on a grain surface with promising scalability for industrial application is still challenging. Herein, using the atomic layer deposition (ALD) technique, a composite nanostructure comprising a uniform LiTaO3 coating layer (≈3 nm) and a spinel interlayer structure (≈1 nm) is constructed on the grain surface of industrial LLO (Li1.13 Mn0.517 Ni0.256 Co0.097 O2 ) agglomerated spheres. The surface composite nanostructure can not only enhance the structural/interfacial stability of the LLO, but also facilitates Li+ diffusion, thereby significantly improving its cycle stability, rate performance, thermal stability, and voltage maintenance. Specifically, the LLO coated with 10 ALD cycles exhibits a small voltage decay rate of 0.9 mV per cycle, a reversible capacity of 272.8 mAh g-1 at 0.1 C, and a capacity retention of 85% after 200 cycles at 1 C, suggesting the important role of surface composite nanostructure for improving the electrochemical performance. This work provides new insights into the composite nanostructure design on the grain surface of cathode materials for high-performance LIBs.

15.
Biomed Res Int ; 2020: 1712723, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178818

RESUMO

Background: Cyclin-dependent kinase-like 2 (CDKL2) is a member of the CDKL family and recognized as a novel regulator of epithelial-mesenchymal transition of breast cancer cells, but its role has not been explored in gastric cancer (GC). This study was to characterize the CDKL2 protein expression and gene copy number in relation to human epidermal growth factor receptor 2 (HER2) status, clinicopathological features, and overall survival (OS) in GC. Methods: This study detected the CDKL2 protein expression and gene copy number by immunochemistry (IHC) and fluorescent in situ hybridization (FISH), respectively, in 334 GC samples. HER2 status was determined according to established criteria. Associations of the CDKL2 protein expression and gene copy number with OS in GC were evaluated, and the association between CDKL2 mRNA expression and OS in GC was also analyzed using TCGA data. Results: The detection results suggested that 34.1% cases showed high CDKL2 protein expression; 11.4% cases had ≥5 copies of CDKL2 gene or a ratio of CDKL2 to chromosome of ≥2. The CDKL2 protein expression was markedly correlated with its gene copy number. High protein expression and high gene copy number were both significantly associated with positive HER2 status, and they both could predicted a shorter OS, although not as independent markers suggested by the multivariate Cox proportional hazard regression analysis. The TCGA data indicated that higher CDKL2 mRNA level also predicted a shorter OS in GC. Conclusions: The combined detection of the CDKL2 protein level and gene copy number could be of important value in predicting HER2 status and prognosis of patients with GC.

16.
Chem Commun (Camb) ; 56(92): 14427-14430, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33146184

RESUMO

A new non-encapsulated fluorinated liposome (TSL) was developed, which showed instantaneous temperature-induced 19F MR signal enhancement and excellent stability under reversible signal transition at different conditions.

17.
J Cell Physiol ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222224

RESUMO

Long noncoding RNAs (lncRNAs) have been found to play essential roles in the occurrence and development of multiple human cancers. Accumulating evidence has shown that LINC00473, an oncogenic lncRNA, is upregulated in various human malignancies and related to poor clinical outcomes. Besides, LINC00473 overexpression can promote cell proliferation, migration, and invasion through multiple potential mechanisms, indicating that it may serve as a novel prognostic biomarker and therapeutic target for human cancers. Here, we reviewed the biological functions, molecular mechanisms, and clinical implications of LINC00473 in human cancers.

18.
Water Res ; 188: 116560, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33137526

RESUMO

In the absence of an effective vaccine to prevent COVID-19 it is important to be able to track community infections to inform public health interventions aimed at reducing the spread and therefore reduce pressures on health-care, improve health outcomes and reduce economic uncertainty. Wastewater surveillance has rapidly emerged as a potential tool to effectively monitor community infections through measuring trends of RNA signal in wastewater systems. In this study SARS-CoV-2 viral RNA N1 and N2 gene regions are quantified in solids collected from influent post grit solids (PGS) and primary clarified sludge (PCS) in two water resource recovery facilities (WRRF) serving Canada's national capital region, i.e., the City of Ottawa, ON (pop. ≈ 1.1M) and the City of Gatineau, QC (pop. ≈ 280K). PCS samples show signal inhibition using RT-ddPCR compared to RT-qPCR, with PGS samples showing similar quantifiable concentrations of RNA using both assays. RT-qPCR shows higher frequency of detection of N1 and N2 gene regions in PCS (92.7, 90.6%, n = 6) as compared to PGS samples (79.2, 82.3%, n = 5). Sampling of PCS may therefore be an effective approach for SARS-CoV-2 viral quantification, especially during periods of declining and low COVID-19 incidence in the community. The pepper mild mottle virus (PMMoV) is determined to have a less variable RNA signal in PCS over a three month period for two WRRFs, regardless of environmental conditions, compared to Bacteroides 16S rRNA or human 18S rRNA, making PMMoV a potentially useful biomarker for normalization of SARS-CoV-2 signal. PMMoV-normalized PCS RNA signal from WRRFs of two cities correlated with the regional public health epidemiological metrics, identifying PCS normalized to a fecal indicator (PMMoV) as a potentially effective tool for monitoring trends during decreasing and low-incidence of infection of SARS-Cov-2 in communities.

19.
Bioorg Chem ; 105: 104453, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33197849

RESUMO

CD147 is a transmembrane glycoprotein and a member of immunoglobulin superfamily, is strongly expressed in melanoma cells. CD147 has a pivotal role in tumor development. Therefore, it is a potential drug target for melanoma. In this article, we report the discovery of the first CD147 protein proteolysis targeting chimeras (PROTACs) derived from the natural product pseudolaric acid B (PAB). The representative compound 6a effectively induced degradation of CD147 and inhibited melanoma cells in vitro and in vivo. 6a could be used as the novel type of anticancer agent or as a part of the molecular biology research toolkit used in the gain-of-function study of the dynamic roles of CD147 in cancer networks.

20.
J Hazard Mater ; : 124502, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33229260

RESUMO

The biological safety of mesoporous silica nanoparticles (MSNs) has gradually attracted attention. However, few studies of their toxicity to the intestine and mechanism are available. In this study, their primary structures were characterized, and their subacute toxicity to mice was investigated. After 2 weeks of intragastric administration of MSNs, they significantly enhanced serum ALP, ALT, AST and TNF-α levels and caused infiltration of inflammatory cells in the spleen and intestines. MSNs induced intestinal oxidative stress and colonic epithelial cell apoptosis in mice. Intestinal epithelial cells exhibited mitochondrial ridge rupture and membrane potential decrease after MSN treatment. Additionally, MSNs increased ROS and NLRP3 levels and inhibited expression of the autophagy proteins LC3-II and Beclin1. MSNs significantly changed the intestinal flora diversity in mice, especially for harmful bacteria, leading to intestinal microecology imbalance. Meanwhile, MSNs influenced the expression of metabolites, which were involved in a range of metabolic pathways, including pyrimidine metabolism, central carbon metabolism in cancer, protein digestion and absorption, mineral absorption, ABC transport and purine metabolism. These results indicated that the subacute toxicity of mesoporous silicon was mainly caused by intestinal damage. Thus, our research provides additional evidence about the safe dosage of MSNs in the clinical and food industries.

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