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Mixed-matrix membranes (MMMs) have the potential for energy-efficient gas separation by matching the superior mass transfer and anti-plasticization properties of the fillers with processability and scaling up features of the polymers. However, construction of high-performance MMMs has been prohibited due to low filler-loading and the existence of interfacial defects. Here, high MOF-loaded, i.e., 55â wt %, MMMs are developed by a 'dormancy and double-activation' (DDA) strategy. High MOF precursor concentration suppresses crystallization in the membrane casting solution, realizing molecular level mixing of all components. Then, the polymeric matrix was formed with uniform encapsulation of MOF nutrients. Subsequently, double-activation was employed to induce MOF crystallization: the alkali promotes MOFs nucleation to harvest small porous nanocrystals while excessive ligands activate the metal ions to enhance the MOFs conversion. As such, quasi-semi-continuous mass transfer channels can be formed in the MMMs by the connected MOFs nanocrystals to boost the gas permeability. The optimized MMM shows significantly ameliorated CO2 permeability, i.e., 2841 Barrer, five-fold enhancement compared with pristine polymer membrane, with a good CO2 /N2 selectivity of 36. Besides, the nanosized MOFs intensify their interaction with polymer chains, endowing the MMMs with good anti-plasticization behaviour and stability, which advances practical application of MMMs in carbon capture.
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Determining the pairing symmetry of single-layer FeSe on SrTiO3 is the key to understanding the enhanced pairing mechanism. It also guides the search for superconductors with high transition temperatures. Despite considerable efforts, it remains controversial whether the symmetry is the sign-preserving s- or the sign-changing s±-wave. Here, we investigate the pairing symmetry of single-layer FeSe from a topological point of view. Using low-temperature scanning tunneling microscopy/spectroscopy, we systematically characterize the superconducting states at edges and corners of single-layer FeSe. The tunneling spectra collected at edges and corners show a full energy gap and a substantial dip, respectively, suggesting the absence of topologically non-trivial edge and corner modes. According to our theoretical calculations, these spectroscopic features can be considered as strong evidence for the sign-preserving s-wave pairing in single-layer FeSe.
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Background: Skin cutaneous melanoma (SKCM) is the deadliest dermatology tumor. Ongoing researches have confirmed that the NOD-like receptors (NLRs) family are crucial in driving carcinogenesis. However, the function of NLRs signaling pathway-related genes in SKCM remains unclear. Objective: To establish and identify an NLRs-related prognostic signature and to explore its predictive power for heterogeneous immune response in SKCM patients. Methods: Establishment of the predictive signature using the NLRs-related genes by least absolute shrinkage and selection operator-Cox regression analysis (LASSO-COX algorithm). Through univariate and multivariate COX analyses, NLRs signature's independent predictive effectiveness was proven. CIBERSORT examined the comparative infiltration ratios of 22 distinct types of immune cells. RT-qPCR and immunohistochemistry implemented expression validation for critical NLRs-related prognostic genes in clinical samples. Results: The prognostic signature, including 7 genes, was obtained by the LASSO-Cox algorithm. In TCGA and validation cohorts, SKCM patients with higher risk scores had remarkably poorer overall survival. The independent predictive role of this signature was confirmed by multivariate Cox analysis. Additionally, a graphic nomogram demonstrated that the risk score of the NLRs signature has high predictive accuracy. SKCM patients in the low-risk group revealed a distinct immune microenvironment characterized by the significantly activated inflammatory response, interferon-α/γ response, and complement pathways. Indeed, several anti-tumor immune cell types were significantly accumulated in the low-risk group, including M1 macrophage, CD8 T cell, and activated NK cell. It is worth noting that our NLRs prognostic signature could serve as one of the promising biomarkers for predicting response rates to immune checkpoint blockade (ICB) therapy. Furthermore, the results of expression validation (RT-qPCR and IHC) were consistent with the previous analysis. Conclusion: A promising NLRs signature with excellent predictive efficacy for SKCM was developed.
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OBJECTIVE: Intrauterine growth restriction followed by postnatal catch-up growth (CG-IUGR) increases the risk of insulin resistance-related diseases. Low-density lipoprotein receptor-related protein 6 (LRP6) plays a substantial role in glucose metabolism. However, whether LRP6 is involved in the insulin resistance of CG-IUGR is unclear. This study aimed to explore the role of LRP6 in insulin signaling in response to CG-IUGR. METHODS: The CG-IUGR rat model was established via a maternal gestational nutritional restriction followed by postnatal litter size reduction. The mRNA and protein expression of the components in the insulin pathway, LRP6/ß-catenin and mammalian target of rapamycin (mTOR)/S6 kinase (S6K) signaling, was determined. Liver tissues were immunostained for the expression of LRP6 and ß-catenin. LRP6 was overexpressed or silenced in primary hepatocytes to explore its role in insulin signaling. RESULTS: Compared with the control rats, CG-IUGR rats showed higher homeostasis model assessment for insulin resistance (HOMA-IR) index and fasting insulin level, decreased insulin signaling, reduced mTOR/S6K/ insulin receptor substrate-1 (IRS-1) serine307 activity, and decreased LRP6/ß-catenin in the liver tissue. The knockdown of LRP6 in hepatocytes from appropriate-for-gestational-age (AGA) rats led to reductions in insulin receptor (IR) signaling and mTOR/S6K/IRS-1 serine307 activity. In contrast, LRP6 overexpression in hepatocytes of CG-IUGR rats resulted in elevated IR signaling and mTOR/S6K/IRS-1 serine307 activity. CONCLUSION: LRP6 regulated the insulin signaling in the CG-IUGR rats via two distinct pathways, IR and mTOR-S6K signaling. LRP6 may be a potential therapeutic target for insulin resistance in CG-IUGR individuals.
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Retardo do Crescimento Fetal , Resistência à Insulina , Insulina , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Proteínas Quinases S6 Ribossômicas , Animais , Feminino , Humanos , Ratos , beta Catenina/genética , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/metabolismo , Insulina/metabolismo , Resistência à Insulina/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Receptor de Insulina/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Topological boundary states emerged at the spatial boundary between topological non-trivial and trivial phases, are usually gapless, or commonly referred as metallic states. For example, the surface state of a topological insulator is a gapless Dirac state. These metallic topological boundary states are typically well described by non-interacting fermions. However, the behavior of topological boundary states with significant electron-electron interactions, which could turn the gapless boundary states into gapped ordered states, e.g., density wave states or superconducting states, is of great interest theoretically, but is still lacking evidence experimentally. Here, we report the observation of incommensurable charge density wave (CDW) formed on the topological boundary states driven by the electron-electron interactions on the (001) surface of CoSi. The wavevector of CDW varies as the temperature changes, which coincides with the evolution of topological surface Fermi arcs with temperature. The orientation of the CDW phase is determined by the chirality of the Fermi arcs, which indicates a direct association between CDW and Fermi arcs. Our finding will stimulate the search of more interactions-driven ordered states, such as superconductivity and magnetism, on the boundaries of topological materials.
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Hospital wastewater treatment system (HWTS) is an important source and environmental reservoir of clinically relevant antibiotic resistance genes (ARGs). However, how antibiotic resistome of clinical wastewater changed in HWTS is poorly understood. Herein, the basic quantitative traits (i.e., diversity and abundance) of ARGs in three HWTSs were profiled by metagenomics. In total, 709 ARG subtypes belonging to 20 ARG types were detected with relative abundance ranging from 1.12 × 10-5 to 7.33 × 10-1 copies/cell. Notably, most ARGs could not be significantly removed by chlorination treatment in the HWTS. These ARGs were identified to confer resistance to almost all major classes of antibiotics and include ARGs of last-resort antibiotics, such as blaNDM, mcr and tet(X) which were abundantly occurred in HWTS with 19, 5 and 7 variants, respectively. Moreover, qualitative analysis based on metagenome-assembled genome (MAG) analysis revealed that the putative hosts of the identified ARGs were broadly distributed into at least 8 dominant bacterial phyla. Of the 107 ARG-carrying MAGs recovered, 39 encoded multi-antibiotic resistance and 16 belonged to antibiotic resistant pathogens. Further analysis of co-occurrence patterns of ARGs with mobile genetic elements suggested their potential mobility. These key qualitative traits of ARGs provided further information about their phylogeny and genetic context. This study sheds light on the key traits of ARGs associated with resistance dissemination and pathogenicity and health risks of clinical wastewater.
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Antibacterianos , Purificação da Água , Antibacterianos/farmacologia , Águas Residuárias , Genes Bacterianos , HospitaisRESUMO
Mixed matrix membranes (MMMs), conjugating the advantages of flexible processing-ability of polymers and high-speed mass transfer of porous fillers, are recognized as the next-generation high-performance CO2 capture membranes for solving the current global climate challenge. However, controlling the crystallization of porous metal-organic frameworks (MOFs) and thus the close stacking of MOF nanocrystals in the confined polymer matrix is still undoable, which thus cannot fully utilize the superior transport attribute of MOF channels. In this study, the "confined swelling coupled solvent-controlled crystallization" strategy is employed for well-tailoring the in-situ crystallization of MOF nanocrystals, realizing rapid (<5 min) construction of defect-free freeway channels for CO2 transportation in MMMs due to the close stacking of MOF nanocrystals. Consequently, the fabricated MMMs exhibit approximately fourfold enhancement in CO2 permeability, i.e., 2490 Barrer with a CO2 /N2 selectivity of 37, distinctive antiplasticization merit, as well as long-term running stability, which is at top-tier level, enabling the large-scale manufacture of high-performance MMMs for gas separation.
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OBJECTIVE: The ataxia telangiectasia mutated (ATM) gene is a master regulator in cellular DNA damage response. The dysregulation of ATM expression is frequent in breast cancer, and is known to be involved in the carcinogenesis and prognosis of cancer. However, the underlying mechanism remains unclear. The bioinformatic analysis predicted a potential antisense transcript ATM-antisense (AS) from the opposite strand of the ATM gene. The purpose of this study was to identify ATM-AS and investigate the possible effect of ATM-AS on the ATM gene regulation. METHODS: Single strand-specific RT-PCR was performed to verify the predicted antisense transcript ATM-AS within the ATM gene locus. qRT-PCR and Western blotting were used to detect the expression levels of ATM-AS and ATM in normal and breast cancer cell lines as well as in tissue samples. Luciferase reporter gene assays, biological mass spectrometry, ChIP-qPCR and RIP were used to explore the function of ATM-AS in regulating the ATM expression. Immunofluorescence and host-cell reactivation (HCR) assay were performed to evaluate the biological significance of ATM-AS in ATM-mediated DNA damage repair. Breast cancer tissue samples were used for evaluating the correlation of the ATM-AS level with the ATM expression as well as prognosis of the patients. RESULTS: The ATM-AS significantly upregulated the ATM gene activity by recruiting KAT5 histone acetyltransferase to the gene promoter. The reduced ATM-AS level led to the abnormal downregulation of ATM expression, and impaired the ATM-mediated DNA damage repair in normal breast cells in vitro. The ATM-AS level was positively correlated with the ATM expression in the examined breast cancer tissue samples, and the patient prognosis. CONCLUSION: The present study demonstrated that ATM-AS, an antisense transcript located within the ATM gene body, is an essential positive regulator of ATM expression, and functions by mediating the binding of KAT5 to the ATM promoter. These findings uncover the novel mechanism underlying the dysregulation of the ATM gene in breast cancer, and enrich our understanding of how an antisense transcript regulates its host gene.
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Neoplasias da Mama , Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Regulação para Baixo , Feminino , Humanos , Prognóstico , RNA AntissensoRESUMO
The significant rise in the number of antibiotic resistance genes (ARGs) that resulted from our abuse of antibiotics could do severe harm to public health as well as to the environment. We investigated removal efficiency and removal mechanism of electrochemical (EC) treatment based on 6 different bacteria isolated from hospital wastewater carrying 3 last resort ARGs including NDM-1, mcr-1 and tetX respectively. We found that the removal efficiency of ARGs increased with the increase of both voltage and electrolysis time while the maximum removal efficiency can reach 90%. The optimal treatment voltage and treatment time were 3 V and 120 min, respectively. Temperature, pH and other factors had little influence on the EC treatment process. The mechanism of EC treatment was explored from the macroscopic and microscopic levels by scanning electron microscopy (SEM) and flow cytometry. Our results showed that EC treatment significantly changed the permeability of cell membrane and caused cells successively experience early cell apoptosis, late cell apoptosis and cell necrosis. Moreover, compared with traditional disinfection methods, EC treatment had less potential risks. The conjugative transfer frequencies of cells were significantly reduced after treatment. Less than 1% of bacteria entered the viable but nonculturable (VBNC) state and less than 5% of intracellular ARGs (iARGs) turned into extracellular ARGs (eARGs). Our findings provide new insights into as well as important reference for future electrochemical treatment in removing ARB from hospital wastewater.
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Antagonistas de Receptores de Angiotensina , Antibacterianos , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Águas ResiduáriasRESUMO
Hospital wastewater contains abundant antibiotics, antibiotic resistance genes (ARGs), and pathogens. Last-resort antibiotic resistance genes (LARGs) include the New Delhi metallo-ß-lactamase gene blaNDM, mobile colistin resistance gene mcr and tigecycline resistance gene tet(X) which confers resistance to carbapenems, colistin and tigecycline. The presence and significance of LARGs in hospital wastewater treatment systems (HWTS) have not yet been systematically explored. Here, LARG variants were shown to be prevalent both influents and effluents of HWTS. A total of 989 Enterobacteriaceae isolates that confer resistance to last-resort antibiotics were collected from effluents and multiple genetic contexts of LARGs were analyzed. LARGs-carrying plasmids were confirmed to show high multidrug phenotypes and transferability. We also discovered the co-occurrence of plasmids harboring blaNDM-1 and mcr-1 in single Escherichia coli, as well as E. coli HM016 containing two unique mcr-1-carrying plasmids. This result might accelerate co-dissemination of LARGs under environmental selection pressure. Different core genetic arrangements in these strains suggest several evolutionary pathways in HWTS. The resistance functions of LARGs were confirmed in vitro and in vivo by mass spectrometry. This study provides novel insights into the diversity, genetic context and function of critical ARGs in HWTS. The results raise the concern that LARGs may further spread into the environment, thus, more stringent discharge standards and regulations for hospital wastewater are urgently needed.
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Antimicrobial resistance is an increasingly serious threat to public health worldwide. The presence of antibiotic resistance genes (ARGs) in human airways and relevant environments has not received significant attention. In this study, abundances of ARGs and microbes from airborne particulate matter, dust, and human airways in a hospital were profiled using high-throughput qPCR and 16S rRNA gene sequencing. More diverse ARGs and microbes in indoor dust and higher levels of ARGs in particulate matter PM10 and PM2.5 were observed. Macrolides and aminoglycoside resistance genes were the most abundant ARGs in the airway and environmental samples, respectively. Moreover, the co-occurrences of priority pathogens, ARGs, and mobile genetic elements (MGEs) were shown by the Network analysis. Campylobacter spp. and Staphylococcus spp. positively correlated with fluoroquinolone (vatC-02, mexD) and ß-lactams (blaZ, mecA) resistance genes, respectively. In this regard, based on SourceTracker analysis, inhalable particles contributed to 4.0% to 5.5% of ARGs in human airway samples, suggesting an important exchange between airborne inhalable particles and human commensals. This study may advance knowledge about ARGs in airborne particulate matter and dust associated environments, reveal their potential link between environments and humans, and provide a new sight and fundamental data for ARG risk assessment.
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Antibacterianos , Microbiota , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Poeira , Genes Bacterianos , Hospitais Urbanos , Humanos , Microbiota/genética , Material Particulado/toxicidade , RNA Ribossômico 16S/genéticaRESUMO
Antibiotic resistance genes (ARGs) as emergence contaminations have spread widely in the water environment. Wild fish may be recipients and communicators of ARGs in the water environment, however, the distribution and transmission of ARGs in the wild fish and relevant water environment were rarely reported. Here, we have profiled ARGs and bacterial communities in wild freshwater fish and relevant water in a peri-urban river using high-throughput qPCR and 16S rRNA gene sequence. A total of 80 and 220 unique ARG subtypes were identified in fish and water samples. Fish and water both showed significant ARG seasonal variations (P < 0.05). The highest absolute abundance of ARGs in fish and water occurred in summer (1.32 × 109 copies per g, on average) and autumn (9.04 × 106 copies per mL), respectively. In addition, the bipartite network analysis showed that 9 ARGs and 1 mobile genetic element continuously shared in fish and water. Furthermore, bacteria shared in fish and water were found to significantly correlate with shard ARGs. The findings demonstrate that bacteria and ARGs in fish and water could interconnect and ARGs might transfer between fish and water using bacteria as a spreading medium.
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Microbioma Gastrointestinal , Rios , Animais , Antibacterianos/análise , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , RNA Ribossômico 16S/genética , ÁguaRESUMO
Abuse of antibiotics in aquaculture have been alarming and might aggravate spread of resistance genes in the environment. Holistic ARGs proliferation checks require deeper analyses of coupled absolute abundances in 16S rRNA bacteria communities at the phylum level to detect biomarkers. Sulfanilamide (sul) and copper II sulfate (CuSO4 II) were, therefore, designed and added as separate or combined treatments in 9 replicate engineered goldfish tanks comprising 3 individual sul, 3 CuSO4 II, 3 (sul + CuSO4 II) combinations, and 3 controls within 180 days. The DNA from water and fish guts was sequenced under qPCR to determine 16S rRNA bacteria biomarkers co-occurring with the correspondent ARGs. Combined chemical addition at 0.8-1.5 mg sul + 0.5-1.0 mg CuSO4 II/3 L of tank waters reduced sequenced 16S rRNA bacteria absolute abundances in fish gut and water samples while portraying the biomarkers. Absolute abundances of the entire 16S rRNA bacteria was higher in fish guts (3.4 × 1014-4.9 × 108 copies/g) than water samples (1.5 × 109-2.6 × 1015 copies/L), respectively. Much as sul 1(log) were dominant over intl 1(log) genes, and their fundamental profiles were also higher in the fish guts than water samples; the Spearman's correlation analyses revealed positive relationship (p < 0.01 and r = 0.873) among the biomarkers of both ARG pairs at the phylum level and the physicochemical parameters. In the fish gut and water samples ratios, Bacteroidetes (10-85:12-85%) > Proteobacteria (10-50:15-65%) > Planktomycetes (10-52:8-25%) featured prominently based on LEfSe use as the hot-spotted biomarkers, hence justifying its higher prospects towards innovative environmental microbiological and biotechnological studies.
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Cobre , Genes Bacterianos , Animais , Antibacterianos , Bactérias/genética , Resistência Microbiana a Medicamentos , Carpa Dourada , RNA Ribossômico 16S/genética , SulfanilamidaRESUMO
Wastewater treatment plants (WWTPs) in China have been upgraded or renovated with a variety of emerging processes, but a comprehensive understanding of the behavior of antibiotic resistance genes (ARGs) in these WWTPs is still lacking. Here, the distribution of ARGs and bacterial community were investigated in a wastewater treatment plant with upgrading processes (WWTP-UP). 238 unique ARGs were detected in all samples. During the study period, the average ARGs concentration decreased by 98.4% along the entire treatment process. The removal efficiency of A2/O-membrane bioreactor (MBR) process was significantly higher than that of A2/O-high efficiency flocculent settling/cloth media filter (HEFS/CMF) process (p < 0.05), which corresponded to 3.5 and 2.1 log values on average, respectively. Notably, 35 ARGs and 14 mobile genetic elements (MGEs) were persistent in all samples. Based on the co-occurrence pattern revealed by network analysis, persistent ARGs possibly spread through the transfer of persistent MGEs among persistent bacteria. Using multiple linear regression analysis, we obtained 3 to 5 possible indicators for major ARG types, which might be served to evaluate the general distribution of ARGs or even predict the abundance of different ARG types. Our findings provide new insights into the impacts of upgrading process on ARGs and highlight the need for better strategies to improve ARGs elimination in WWTPs.
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Antibacterianos , Purificação da Água , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Águas ResiduáriasRESUMO
The transcription of eukaryotic genes is regulated by both proximal promoters and distal enhancers. Some promoters also have enhancer activity. NOXA and BCL2 are pro-apoptotic and anti-apoptotic members of the BCL2 family of protein, respectively. Our previous study has found that the NOXA gene promoter and the BCL2 gene promoter interact at the level of three-dimensional chromatin structure. Moreover, the NOXA gene promoter region displays histone modifications characteristic of both promoters and enhancers. This study aimed to explore whether and when the NOXA promoter could act as an active enhancer to regulate BCL2 expression. Based on the apoptosis model of MCF-7 cells induced by camptothecin, we used chromosome conformation capture (3C), quantitative real-time PCR (qRT-PCR) and the luciferase reporter gene technology to demonstrate that the NOXA promoter could function as an active enhancer and physically interact with the BCL2 promoter through chromatin looping. The regulatory properties of the NOXA promoter were closely related to the strength of the apoptosis stimulation. Under weak apoptotic stimulation (1 µmol/L camptothecin treatment), the NOXA promoter mainly functioned as an enhancer; with the enhancement of apoptotic stimulation (10 µmol/L camptothecin treatment), the NOXA promoter activity increased and mainly regulated the expression of the gene itself to promote apoptosis. Chromatin immunoprecipitation (ChIP) confirmed that the dynamic changes of the promoter activity and enhancer activity in the NOXA promoter region are consistent with its histone modification marks. This study provides new clues for further exploring the mechanism underlying cooperative response of BCL2 family member to apoptosis stimuli.
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Apoptose , Regulação da Expressão Gênica no Desenvolvimento , Regiões Promotoras Genéticas , Apoptose/genética , Imunoprecipitação da Cromatina , Humanos , Células MCF-7 , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
The activation of long interspersed nuclear element-1 (LINE-1) leads to genomic instability, which promotes carcinogenesis and drug resistant. Therefore, exploring the mechanism underlying LINE-1 abnormal activation has the theoretical and clinical significance. DNA methylation is an important way to regulate gene expression. DNMT3a, one member of the DNA methyltransferase family, not only inhibits gene expression by inducing promoter hypermethylation, but also activates gene expression by increasing the intragenic DNA methylation. Our previous studies found that the expression of LINE-1 did not increase significantly in the promoter methylation in breast cancer cells treated with paclitaxel (PTX), a first-line chemotherapeutic drug for breast cancer. Here we explored whether DMNMT3a could directly mediate the drug-induced activation of LINE-1 in breast cancer cells through increasing the LINE-1 intragenic methylation. Our ChIP experiments and methyl analysis showed that treatment of breast cancer cells with PTX not only induced DNMT3a expression, but also promoted the binding of DNMT3a to the inner region of the LINE-1 gene to increase its methylation, resulting in upregulation of LINE-1 expression. Using expression vectors or RNA interference to alter the DNMT3a expression levels in the cells significantly changed the intragenic methylation degree and LINE-1 expression. Moreover, down-regulation of DNMT3a expression effectively inhibited the expression of LINE-1. These results indicate that DNMT3a-mediated intragenic methylation plays an important role in drug-induced abnormal activation of LINE-1, which provides a new idea for understanding the mechanism of abnormal activation of Line-1 induced by chemotherapy drug stress in breast cancer cells.
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DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Elementos Nucleotídeos Longos e Dispersos , Paclitaxel/farmacologia , Linhagem Celular Tumoral , DNA Metiltransferase 3A , Regulação Neoplásica da Expressão Gênica , HumanosRESUMO
BACKGROUND: Cartilaginous endplate (CEP), a thin layer of hyaline cartilage located between the vertebral endplate and nucleus pulposus, transports the nutrient into the disc. The objective of this study was to evaluate the influence of T140 (polyphemusin II-derived peptide) on the CEP cell growth, apoptosis, and the matrix formation via the stromal cell-derived factor-1 (SDF-1)/cysteine X cysteine (CXC) receptor-4 (CXCR4) signaling pathway. METHODS: Sprague-Dawley rats were euthanized by cervical dislocation and dissected for the isolation and the appraisal of CEP cells that were extracted from the endplate in rat intervertebral discs and were then added with different concentrations of reagents (SDF-1 and T140). The effect of T140 on CEP cell proliferation and apoptosis were analyzed. The messenger RNA (mRNA) and protein expressions of CXCR4, prominin-1, proteoglycans, type II collagen, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein were analyzed by reverse transcription quantitative polymerase chain reaction and Western blot analysis. RESULTS: T140 promoted the proliferation of CEP cells and inhibited the apoptosis of CEP cells. Additionally, T140 suppressed the mRNA and protein expression of CXCR4, prominin-1, and Bcl-2 associated X protein, and increased the mRNA and protein expression of proteoglycans, type II collagen, and Bcl-2. CONCLUSIONS: T140 promotes the proliferation and matrix formation and inhibits the apoptosis of CEP cells by blocking the SDF-1/CXCR4 signaling pathway in vitro, which provides a certain therapeutic effect on the degeneration of intervertebral discs.
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Apoptose/efeitos dos fármacos , Quimiocina CXCL12/fisiologia , Condrócitos/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Cartilagem Hialina/citologia , Disco Intervertebral/citologia , Oligopeptídeos/farmacologia , Receptores CXCR4/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Proteínas da Matriz Extracelular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Disco Intervertebral/efeitos dos fármacos , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
In materials chiral fermions such as Weyl fermions are characterized by nonzero chiral charges, which are singular points of Berry curvature in momentum space. Recently, new types of chiral fermions beyond Weyl fermions have been discovered in structurally chiral crystals CoSi, RhSi and PtAl. Here, we have synthesized RhSn single crystals, which have opposite structural chirality to the CoSi crystals we previously studied. Using angle-resolved photoemission spectroscopy, we show that the bulk electronic structures of RhSn are consistent with the band calculations and observe evident surface Fermi arcs and helical surface bands, confirming the existence of chiral fermions in RhSn. It is noteworthy that the helical surface bands of the RhSn and CoSi crystals have opposite handedness, meaning that the chiral fermions are reversed in the crystals of opposite structural chirality. Our discovery establishes a direct connection between chiral fermions in momentum space and chiral lattices in real space.
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BACKGROUND: An adductor canal block (ACB) provides recognized analgesia following total knee arthroplasty (TKA). This meta-analysis compared the single-injection ACB (SACB) with the continuous-injection ACB (CACB). METHOD: Relevant studies were searched from PubMed (1996-October 2018), Embase (1980-October 2018), and Cochrane Library (CENTRAL, October 2018). Four randomized controlled trials (RCTs), which compared SACB with CACB, were included in our meta-analysis. RESULTS: Four RCTs met the inclusion criteria. Our pooled data indicated that the SACB group had similar efficacy compared with the CACB group in terms of morphine consumption (Pâ=â.19), time to first opioid request (Pâ=â.32), range of motion (Pâ=â.97), and visual analogue scale (VAS) scores at 24âhours at rest (Pâ=â.12) and movement (Pâ=â.24), without increasing the risk of complications (Pâ=â.97) and length of stay (Pâ=â.54). CONCLUSION: The SACB technique provides similar analgesia in the 24âhours following TKA compared with CACB, while the CACB method was better over 48âhours.
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Artroplastia do Joelho/métodos , Bloqueio Nervoso/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Esquema de Medicação , Humanos , Tempo de Internação , Medição da Dor , Complicações Pós-Operatórias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Fatores de TempoRESUMO
Connate topological superconductor (TSC) combines topological surface states with nodeless superconductivity in a single material, achieving effective p-wave pairing without interface complication. By combining angle-resolved photoemission spectroscopy and in-situ molecular beam epitaxy, we studied the momentum-resolved superconductivity in ß-Bi2Pd film. We found that the superconducting gap of topological surface state (ΔTSSâ¯â¼â¯3.8â¯meV) is anomalously enhanced from its bulk value (Δbâ¯â¼â¯0.8â¯meV). The ratio of 2ΔTSS/kBTcâ¯â¼â¯16.3, is substantially larger than the BCS value. By measuring ß-Bi2Pd bulk single crystal as a comparison, we clearly observed the upward-shift of chemical potential in the film. In addition, a concomitant increasing of surface weight on the topological surface state was revealed by our first principle calculation, suggesting that the Dirac-fermion-mediated parity mixing may cause this anomalous superconducting enhancement. Our results establish ß-Bi2Pd film as a unique case of connate TSCs with a highly enhanced topological superconducting gap, which may stabilize Majorana zero modes at a higher temperature.