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1.
J Hazard Mater ; 421: 126628, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34343879

RESUMO

Electroreduction of nitrate (NO3-) to value-added ammonia (NH3) provides an alternative to NH3 production industry and remediation of NO3--containing wastewater. This study reports a series of Cu-Ni catalysts with component-controllable CuxNiy nanoparticles encapsulated in N-doped carbon film (CuxNiy/NC), and disclosure of the associated mechanism for NO3- reduction reaction (NO3-RR). Cu0.43Ni0.57/NC achieves a better NO3--N removal proportion of 89% in comparison with the reference catalysts, including Cu/NC (73%) and CuxNiy/NC with other compositions (Cu0.79Ni0.21/NC, 83%; Cu0.26Ni0.74/NC, 62%; Ni/NC, 20%). The experimental results and density functional theory calculations demonstrate that the lowered energy barriers of *NO2-to-*NO derived from appropriate Ni atom alloying plays a key role in the enhanced catalytic activity. Auxiliary porous substrate further contributes to the exposure of active sites and the durability of catalyst structure. These findings offer a mechanistic understanding of catalyst structure on the NO3-RR activity and valuable insights toward rational design of other catalysts for enhanced NO3-RR.

2.
Front Chem ; 9: 789249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900946

RESUMO

Analysis, purification, and characterization of AFB1 degraded products are vital steps for elucidation of the photocatalytic mechanism. In this report, the UPLC-Q-TOF-MS/MS technique was first coupled with purification and NMR spectral approaches to analyze and characterize degraded products of AFB1 photocatalyzed under UV irradiation. A total of seventeen degraded products were characterized based on the UPLC-Q-TOF-MS/MS analysis, in which seven ones (1-7) including four (stereo) isomers (1,2, 5, and 6) were purified and elucidated by NMR experiments. According to the structural features of AFB1 and degraded products (1-7), the possible photocatalytic mechanisms were suggested. Furthermore, AFB1 and degraded products (1-7) were evaluated against different cell lines. The results indicated that the UPLC-Q-TOF-MS/MS technique combined with purification, NMR spectral experiments, and biological tests was an applicable integrated approach for analysis, characterization, and toxic evaluation of degraded products of AFB1, which could be used to evaluate other mycotoxin degradation processes.

3.
Infect Dis Poverty ; 10(1): 140, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963481

RESUMO

BACKGROUND: Reaching optimal vaccination rates is an essential public health strategy to control the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to simulate the optimal vaccination strategy to control the disease by developing an age-specific model based on the current transmission patterns of COVID-19 in Wuhan City, China. METHODS: We collected two indicators of COVID-19, including illness onset data and age of confirmed case in Wuhan City, from December 2, 2019, to March 16, 2020. The reported cases were divided into four age groups: group 1, ≤ 14 years old; group 2, 15 to 44 years old; group 3, 44 to 64 years old; and group 4, ≥ 65 years old. An age-specific susceptible-exposed-symptomatic-asymptomatic-recovered/removed model was developed to estimate the transmissibility and simulate the optimal vaccination strategy. The effective reproduction number (Reff) was used to estimate the transmission interaction in different age groups. RESULTS: A total of 47 722 new cases were reported in Wuhan City from December 2, 2019, to March 16, 2020. Before the travel ban of Wuhan City, the highest transmissibility was observed among age group 2 (Reff = 4.28), followed by group 2 to 3 (Reff = 2.61), and group 2 to 4 (Reff = 1.69). China should vaccinate at least 85% of the total population to interrupt transmission. The priority for controlling transmission should be to vaccinate 5% to 8% of individuals in age group 2 per day (ultimately vaccinated 90% of age group 2), followed by 10% of age group 3 per day (ultimately vaccinated 90% age group 3). However, the optimal vaccination strategy for reducing the disease severity identified individuals ≥ 65 years old as a priority group, followed by those 45-64 years old. CONCLUSIONS: Approximately 85% of the total population (nearly 1.2 billion people) should be vaccinated to build an immune barrier in China to safely consider removing border restrictions. Based on these results, we concluded that 90% of adults aged 15-64 years should first be vaccinated to prevent transmission in China.


Assuntos
COVID-19 , Adolescente , Adulto , Idoso , China , Cidades , Humanos , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinação , Adulto Jovem
4.
Chin J Integr Med ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826043

RESUMO

OBJECTIVE: To explore the effect and mechanism of action of bufalin in triple-negative breast cancer (TNBC) drug-resistant cell lines. METHODS: The normal human mammary epithelial cell line, TNBC cell line, TNBC adriamycin-resistant cell line, and TNBC docetaxel-resistant cell line were treated with different doses of bufalin (0-1,000 nmol/L) at different time points (0-72 h). Propidium iodide staining, AV-FITC/PI double staining, Hoechst 33342/PI double staining and transmission electron microscopy (TEM) were used to evaluate the death patterns of the cell lines. RESULTS: Bufalin killed the TNBC cell line and its drug-resistant cell lines in a dose/time-dependent manner (all P<0.01). After treatment with bufalin for 24 h, the adriamycin-resistant cell line showed a co-existing pattern of necroptosis and apoptosis. However, at 48 h, necroptosis was the main manifestation. After treatment with bufalin, the expressions of tumor necrosis factor α, phospho-tumor necrosis factor receptor 1, phospho-receptor interacting protein 1 and c-caspase 3 increased (all P<0.01), the killing effect of bufalin could be mostly inhibited by NEC-1, and by z-VAD-fmk (both P<0.01). Besides, the intracellular reactive oxygen species (ROS) levels increased considerably (P<0.01), the antioxidant N-acetyl cysteine or Nec-1 could inhibit the increase of ROS level and the killing effect of bufalin (all P<0.01). The adriamycin-resistant cell line exhibited necroptosis characteristic after 48 h of bufalin treatment under TEM. CONCLUSIONS: Bufalin could induce necroptosis through RIP1/ROS-mediated pathway to kill the drug-resistant TNBC cell lines. This finding provides critical experimental data and theoretical basis for the clinical application of bufalin to overcome the difficulties in the treatment of TNBC.

5.
Nat Commun ; 12(1): 6524, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764284

RESUMO

Out-of-plane spin polarization σz has attracted increasing interests of researchers recently, due to its potential in high-density and low-power spintronic devices. Noncollinear antiferromagnet (AFM), which has unique 120° triangular spin configuration, has been discovered to possess σz. However, the physical origin of σz in noncollinear AFM is still not clear, and the external magnetic field-free switching of perpendicular magnetic layer using the corresponding σz has not been reported yet. Here, we use the cluster magnetic octupole in antiperovskite AFM Mn3SnN to demonstrate the generation of σz. σz is induced by the precession of carrier spins when currents flow through the cluster magnetic octupole, which also relies on the direction of the cluster magnetic octupole in conjunction with the applied current. With the aid of σz, current induced spin-orbit torque (SOT) switching of adjacent perpendicular ferromagnet is realized without external magnetic field. Our findings present a new perspective to the generation of out-of-plane spin polarizations via noncollinear AFM spin structure, and provide a potential path to realize ultrafast high-density applications.

6.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3079-3088, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658192

RESUMO

In July 2019-July 2020, we conducted a field trial to examine the effects of nitrogen addition (60 kg N·hm-2·a-1), biochar application (10 t·hm-2), and their combination on soil N2O emission and the relationship between soil N2O emission and environmental factors in a typical Moso bamboo (Phyllostachys edulis) plantation in Hangzhou City of Zhejiang Province. Soil N2O flux of Moso bamboo plantation was measured by the static chamber-gas chromatography technique. The results showed that nitrogen addition treatment increased the annual cumulative N2O emission by 14.6%, while biochar application and the combination treatment reduced it by 20.8% and 10.6%, respectively. Soil N2O flux rate was significantly correlated with soil temperature, NO3--N concentration, urease and protease activities, and soil NH4+-N concentration across all treatments. In conclusion, under the background of nitrogen deposition, the application of biochar would have a significant reduction effect on soil N2O fluxes in Moso bamboo plantations.


Assuntos
Nitrogênio , Solo , Carvão Vegetal , Poaceae
7.
Nanoscale ; 13(43): 18256-18266, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34713881

RESUMO

Oxygen ion migration in strongly correlated oxides can cause dramatic changes in the crystal structure, chemical and magnetoelectric properties, which holds promising for a wide variety of applications in catalysis, energy conversion, and electronics. However, the high strength and stability of metal-oxygen (M-O) bonds cause a large thermodynamic barrier for oxygen migration. Here, we designed Co-O bond activation in cobaltite (SrCoOx) films by Au-nanodot-decoration. Charge transfer from Au to SrCoOx effectively weakens the Co-O bond, meanwhile Co-O-Au synergistic bonding remarkably decreases the migration barrier of oxygen ions. Fast oxygen evolution occurs at the perimeter of the Au/SrCoOx interface, and the chemical potential gradient of O2- drives inner ion diffusion to the surface. Consequently, bias-free topotactic phase reduction from perovskite SrCoO3-δ to brownmillerite SrCoO2.5 has been achieved at room temperature. Our finding explores a new dimension to accelerate oxygen ion kinetics in transition-metal oxides from the aspect of interfacial bond activation, which is significant for developing oxide/noble-metal interfaces for high-efficiency ion migration and redox catalysis at low temperature.

8.
Front Surg ; 8: 726067, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568419

RESUMO

Objective: The present study aimed to explore the application value of magnetic resonance imaging (MRI) histograms with multiple sequences in the preoperative differential diagnosis of endometrial stromal sarcoma (ESS) and degenerative hysteromyoma (DH). Methods: The clinical and preoperative MRI data of 20 patients with pathologically confirmed ESS and 24 patients with pathologically confirmed DH were retrospectively analyzed, forming the two study groups. Mazda software was used to select the MRI layer with the largest tumor diameter in T2WI, the apparent diffusion coefficient (ADC), and enhanced T1WI (T1CE) images. The region of interest (ROI) was outlined for gray-scale histogram analysis. Nine parameters-the mean, variance, kurtosis, skewness, 1st percentile, 10th percentile, 50th percentile, 90th percentile, and 99th percentile-were obtained for intergroup analysis, and the receiver operating curves (ROCs) were plotted to analyze the differential diagnostic efficacy for each parameter. Results: In the T2WI histogram, the differences between the two groups in seven of the parameters (mean, skewness, 1st percentile, 10th percentile, 50th percentile, 90th percentile, and 99th percentile) were statistically significant (P < 0.05). In the ADC histogram, the differences between the two groups in three of the parameters (skewness, 10th percentile, and 50th percentile) were statistically significant (P < 0.05). In the T1CE histogram, no significant differences were found between the two groups in any of the parameters (all P > 0.05). Of the nine parameters, the 50th percentile was found to have the best diagnostic efficacy. In the T2WI histogram, ROC curve analysis of the 50th percentile yielded the best area under the ROC curve (AUC; 0.742), sensitivity of 70%, and specificity of 83.3%. In the ADC histogram, ROC curve analysis of the 50th percentile yielded the best area under the ROC curve (AUC; 0.783), sensitivity of 81%, and specificity of 76.9%. Conclusion: The parameters of the mean, 10th percentile and 50th percentile in the T2WI histogram have good diagnostic efficacy, providing new methods and ideas for clinical diagnosis.

9.
Hepatology ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34543483

RESUMO

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is aggressive and has high rates of relapse, conferring poor long-term survival after curative resection. Little is known about the genomic evolution that occurs during ICC relapse. APPROACH AND RESULTS: We conducted whole-exome sequencing of 30 paired primary and relapsed tumors from 10 patients with ICC who received curative resection. We sought to identify frequently altered genes, infer tumor subclonal architectures, and track genomic evolution from primary to relapsed tumors. We examined functional effects and the mechanism of action of SLIT2, a gene specifically mutated in relapsed tumors, on tumor growth and metastasis and the tumor microenvironment. Our results indicated that relapsed ICCs were genetically derived from intrahepatic dissemination of primary tumors. However, they acquired additional mutations while maintaining most drivers, such as TP53 and IDH1. Multiregion sequencing suggested polyclonal seeding of ICC dissemination. Four of 10 relapsed ICCs acquired SLIT2 mutations that were not present in the corresponding primary tumors. Validation in an expanded sample revealed SLIT2 mutations in 2.3% (1/44) of primary ICCs and 29.5% (13/44) of relapsed ICCs. Biofunctional investigations revealed that inactivating mutation of SLIT2 resulted in activation of PI3K-Akt signaling in ICC cells, directly enhanced neutrophil chemotaxis, mediated tumor-associated neutrophil infiltration, and contributed to ICC growth and metastasis. CONCLUSIONS: We characterized genomic evolution during ICC relapse and identified SLIT2 as a driver of tumor dissemination and tumor-associated neutrophil infiltration.

10.
Chem Commun (Camb) ; 57(79): 10198-10201, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34522932

RESUMO

By introducing 8-arylselenium as the active group, a BODIPY fluorescent probe ASeBD was constructed for rapid and sensitive detection and dual-channel discrimination of GSH and Cys/Hcy in solution and in living cells, and its mechanism was demonstrated.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Compostos de Selênio/química , Compostos de Sulfidrila/análise , Células Hep G2 , Humanos , Estrutura Molecular
11.
Huan Jing Ke Xue ; 42(9): 4366-4373, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414735

RESUMO

In order to understand the characteristics and interactions of the microbial community during the anaerobic ferric ammonium oxidation (FEAMMOX) process, this study investigated the effects of various forms of chelated iron on nitrogen removal efficiency and microbial community structure. After 77 days of reactor operation, the removal efficiency of total nitrogen was 83.32% for the ferric humate group, 43.67% for the ferric citrate group, 55.07% for the ferric sodium ethylene diamine tetraacetate group, and 12.65% for the ferric ammonium triacetate group. After the experiment, the abundance of denitrifying bacteria Comamonadaceae in ferric humate group was 17.57%, the abundance of Clostridium in ferric citrate group was 47.70%; and the abundance of denitrifying bacteria Thermomonas in the ferric sodium ethylene diamine tetraacetate group was 20.11%. This indicates that ferric humate is a more effective electron acceptor for the FEAMMOX process. The result of function prediction shows that the iron, sulfur, and nitrogen cycles are all closely related, with iron and sulfur metabolism playing an important role in nitrogen removal. In the humate group, iron respiration and the nitrogen cycle are more strongly correlated than other groups. Co-occurrence network analysis showed that the keystone species in the FEAMMOX process is Tessaracoccus.


Assuntos
Compostos de Amônio , Microbiota , Anaerobiose , Desnitrificação , Ferro , Nitrogênio
13.
Angew Chem Int Ed Engl ; 60(44): 23578-23583, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34423529

RESUMO

Chiral Pb(Sn)-I hybrid organic-inorganic perovskites exhibit outstanding chiral-induced spin selectivity (CISS) performance, but the nontoxic lead-free hybrid materials with high stability are still greatly desired for spin filtering in spintronic applications. We synthesize chiral hybrid copper halides (R/S-MBA)2 CuX4 (MBA=methylbenzylammonium; X=Cl, Br) with characteristic 0D CuX4 tetrahedral structural motifs, combining the low toxicity of Cu2+ and air stability of halide ions (Cl- and Br- ). Despite similar structural and electronic features, (R/S-MBA)2 CuBr4 shows much smaller chiroptical activity than the chloride counterpart. Magnetically conductive atomic force microscopy measurements display a typical spin-polarized charge-transport property with high efficiency up to 90 % for both copper halides. Our work expands the CISS effect into eco-friendly and stable metal-organic halides, which is promising for applications in spintronics based on transition-metal hybrid systems.

14.
Front Genet ; 12: 687689, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306028

RESUMO

Dendrobium is a semi-shade epiphytic Orchidaceae herb with important ornamental and medicinal value. Parts of the cultivation of Dendrobium germplasm resources, as well as the identification of medicinal components, are more studied, but the functional characterization of the flowering regulation in Dendrobium plants is less reported. Here, six PEBP family genes (DhFT3, DhFT1, DhMFT, DhTFL1b, DhFT2, and DhTFL1a) were identified from the Dendrobium huoshanense genome. The chromosome-level mapping showed that these genes were sequentially distributed on chromosomes 6, 9, 15, and 17. The paralogous gene DhTFL1b corresponded to DhTFL1a, which was determined through tandem duplication. The gene structure and conserved motif of DhPEBP indicated five PEBP genes apart from DhMFT contained four exons and three introns entirely. The phylogeny analysis showed that the PEBP gene family in A. thaliana, O. sativa, Z. mays, S. lycopersicum, and P. equestris were classified into three subclades, FT, TFL, and MFT, which maintained a high homology with D. huoshanense. The conserved domain of the amino acid demonstrated that two highly conserved short motifs (DPDXP and GXHR) embed in DhPEBPs, which may contribute to the conformation of the ligand binding bag. The 86th position of DhFTs was tyrosine (Y), while the 83th and 87th of DhTFL1s belonged to histidine (H), suggesting they should have distinct functions in flowering regulation. The promoter of six DhPEBPs contained several cis-elements related to hormone induction, light response, and abiotic stress, which indicated they could be regulated by the environmental stress and endogenous signaling pathways. The qRT-PCR analysis of DhPEBPs in short-term days induced by GA indicated the gene expressions of all DhFTs were gradually increased, whereas the expression of DhTFL1 was decreased. The results implied that DhPEBPs have various regulatory functions in modulating flowering, which will provide a scientific reference for the flowering regulation of Dendrobium plants.

15.
Neurosci Lett ; 760: 136088, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34233203

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) played critical roles in the survival and repair of dopaminergic (DA) neurons. Transcription factor Six2 could repair injured DA cells by promoting the expression of GDNF, however, the underlying molecular mechanisms remain largely unknown. In this study, we screened forty-three proteins that interacted with Six2 in MES23.5 DA cells treated with 6-OHDA by liquid chromatography - electrospray - ionization tandem mass spectrometry (LC-ESI-ITMS/MS). Among these proteins, Smarcd1 is a member of SWI/SNF chromatin-remodeling complex family. Our results confirmed that Smarcd1 formed a transcription complex with Six2, and Smarcd1 mainly binded to the 2840 bp-2933 bp region of the GDNF promoter. Furthermore, knockdown of Smarcd1 inhibited the effect of Six2 on GDNF expression, and resulted in decreased cell viability and increased the apoptosis of injured DA neurons, and the result of overexpression of Smarcd1 is opposite to knockdown. Taken together, our results indicate that smarcd1 can be recruited to the promoter region of GDNF by transcription factor Six2 to promote the effect of Six2 on GDNF expression and protect injured MES23.5 DA cells, which could be useful in identifying potential drug targets for promoting endogenous GDNF expression.

16.
World J Gastrointest Oncol ; 13(7): 693-705, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34322198

RESUMO

BACKGROUND: Approximately 90% of new cases of noncardiac gastric cancer (GC) are related to Helicobacter pylori (H. pylori), and cytotoxin-associated gene A (CagA) is one of the main pathogenic factors. Recent studies have shown that the pharmacological effects of cryptotanshinone (CTS) can be used to treat a variety of tumors. However, the effects of CTS on H. pylori, especially CagA+ strain-induced gastric mucosal lesions, on the development of GC is unknown. AIM: To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells, and determine if CagA+ H. pylori strains causes pathological changes in the gastric mucosa of mice. METHODS: The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8 (CCK-8) assay, and the abnormal growth, migration and invasion caused by CagA were detected by CCK-8 and transwell assays. After transfection with pSR-HA-CagA and treatment with CTS, proliferation and metastasis were evaluated by CCK-8 and transwell assays, respectively, and the expression of Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) and phosphorylated SHP2 (p-SHP2) was detected using western blotting in AGS cells. The enzyme-linked immunosorbent assay was used to determine the immunoglobulin G (IgG) level against CagA in patient serum. Mice were divided into four groups and administered H. pylori strains (CagA+ or CagA-) and CTS (or PBS) intragastrically, and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains. Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney. RESULTS: CTS inhibited the growth of GC cells in dose- and time-dependent manners. Overexpression of CagA promoted the growth, migration, and invasion of GC cells. Importantly, we demonstrated that CTS significantly inhibited the CagA-induced abnormal proliferation, migration, and invasion of GC cells. Moreover, the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients. Additionally, CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells. CTS suppressed CagA+ H. pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA- H. pylori strain group. CONCLUSION: CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro, and CagA+ H. pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.

17.
Front Genet ; 12: 683037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194480

RESUMO

Peucedanum praeruptorum Dunn is a perennial and one-off flowering plant of the Peucedanum genus in Umbelliferae. The cultivated P. praeruptorum Dunn usually grows nutritionally in the first year and then moves into the reproductive growth in the second year. The lignification of the roots caused by bolting leads to the quality decline of crude materials. Since most of the previous studies have dealt with coumarin biosynthesis and identification of functional genes in P. praeruptorum, the scientific connotation of the inability that the bolted P. praeruptorum cannot be used medically is still unclear. Here, we employed a transcriptome sequencing combined with coexpression analysis to unearth the regulation mechanism of key genes related to coumarin synthesis in pre- and postbolting period, and to explore the mechanisms underlying the effects of bolting on the formation and transport of coumarins between the annual and biennial plants. Six cDNA libraries were constructed, and the transcripts were sequenced and assembled by Illumina Hiseq platform. A total of 336,505 unigenes were obtained from 824,129 non-redundant spliced transcripts. Unigenes (114,488) were annotated to the NCBI nr database, 119,017 and 10,475 unigenes were aligned to Gene Ontology (GO) functional groups and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. Differential expression analysis screened out a series of upregulated and downregulated genes related to the phenylpropanoid pathway. The heatmap clustering showed that the similar expression patterns were both observed in groups C vs. D and groups C vs. F. The WGCNA-based coexpression was performed to elucidate the module and trait relationship to unearth important genes related to the bolting process. Seven pivotal modules on the KEGG functional annotations suggested these genes were mainly enriched in the process of plant-pathogen interaction, plant hormone signal transduction, MAPK signaling pathway, α-linolenic acid metabolism, circadian rhythm, and phenylpropanoid pathway. Further analysis provided clues that the key genes of the phenylpropanoid pathway, the ABC transporters, the apoptosis-related and circadian rhythm regulatory genes may play pivotal roles in regulating bolting signaling, biosynthesis, and transportation of coumarins.

18.
Nat Commun ; 12(1): 4215, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244506

RESUMO

Negative capacitance effect in ferroelectric materials provides a solution to the energy dissipation problem induced by Boltzmann distribution of electrons in conventional electronics. Here, we discover that besides ferroelectrics, the antiferroelectrics based on Landau switches also have intrinsic negative capacitance effect. We report both the static and transient negative capacitance effect in antiferroelectric PbZrO3 films and reveal its possible physical origin. The capacitance of the capacitor of the PbZrO3 and paraelectric heterostructure is demonstrated to be larger than that of the isolated paraelectric capacitor at room temperature, indicating the existence of the static negative capacitance. The opposite variation trends of the voltage and charge transients in a circuit of the PbZrO3 capacitor in series with an external resistor demonstrate the existence of transient negative capacitance effect. Strikingly, four negative capacitance effects are observed in the antiferroelectric system during one cycle scan of voltage pulses, different from the ferroelectric counterpart with two negative capacitance effects. The polarization vector mapping, electric field and free energy analysis reveal the rich local regions of negative capacitance effect with the negative dP/dE and (δ2G)/(δD2), producing stronger negative capacitance effect. The observation of negative capacitance effect in antiferroelectric films significantly extends the range of its potential application and reduces the power dissipation further.

19.
Mol Med Rep ; 24(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34165157

RESUMO

Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present study investigated the effects of excessive mechanically stretched osteoblasts on the metabolism and apoptosis of chondrocytes, and also assessed the involvement of the Wnt/ß­catenin signaling pathway. In the present study, rat chondrocytes and osteoblasts were subjected to mechanical tensile strain, and an indirect chondrocyte­osteoblast co­culture model was established. Reverse transcription­quantitative PCR and western blotting were performed to determine the expression levels of genes and proteins of interest. An ELISA was performed to investigate the levels of cytokines, including matrix metalloproteinase (MMP) 13, MMP 3, interleukin­6 (IL­6) and prostaglandin E2 (PG E2), released from osteoblasts. Flow cytometry was performed to detect the apoptosis of chondrocytes exposed to stretched osteoblast conditioned culture medium. The levels of MMP 13, IL­6 and PG E2 increased significantly in the supernatants of stretched osteoblasts compared with the un­stretched group. By contrast, the mRNA expression levels of Collagen 1a and alkaline phosphatase were significantly decreased in osteoblasts subjected to mechanical stretch compared with the un­stretched group. The mRNA expression level of Collagen 2a was significantly decreased, whereas the expression levels of MMP 13 and a disintegrin and metalloproteinase with thrombospondin­like motifs 5 were significantly increased in chondrocytes subjected to mechanical stretch compared with the un­stretched group. In the co­culture model, the results indicated that excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes, which was partly inhibited by Wnt inhibitor XAV­939. The results of the present study demonstrated that excessive mechanical stretch led to chondrocyte degradation and inhibited osteoblast osteogenic differentiation; furthermore, excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes via the Wnt/ß­catenin signaling pathway.


Assuntos
Apoptose , Condrócitos/metabolismo , Osteoblastos/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Interleucina-6/metabolismo , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Osteoartrite/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Commun Biol ; 4(1): 736, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127790

RESUMO

Aggregates of hyperphosphorylated tau protein are a pathological hallmark of more than 20 distinct neurodegenerative diseases, including Alzheimer's disease, progressive supranuclear palsy, and frontotemporal dementia. While the exact mechanism of tau aggregation is unknown, the accumulation of aggregates correlates with disease progression. Here we report a genome-wide CRISPR screen to identify modulators of endogenous tau protein for the first time. Primary screens performed in SH-SY5Y cells, identified positive and negative regulators of tau protein levels. Hit validation of the top 43 candidate genes was performed using Ngn2-induced human cortical excitatory neurons. Using this approach, genes and pathways involved in modulation of endogenous tau levels were identified, including chromatin modifying enzymes, neddylation and ubiquitin pathway members, and components of the mTOR pathway. TSC1, a critical component of the mTOR pathway, was further validated in vivo, demonstrating the relevance of this screening strategy. These findings may have implications for treating neurodegenerative diseases in the future.


Assuntos
Redes e Vias Metabólicas/genética , Neurônios/metabolismo , Proteínas tau/metabolismo , Animais , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Edição de Genes , Genes/genética , Genes/fisiologia , Testes Genéticos/métodos , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Neuroblastoma/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo
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