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1.
Nat Commun ; 12(1): 5755, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599172

RESUMO

Strain glass is a glassy state with frozen ferroelastic/martensitic nanodomains in shape memory alloys, yet its nature remains unclear. Here, we report a glassy feature in strain glass that was thought to be only present in structural glasses. An abnormal hump is observed in strain glass around 10 K upon normalizing the specific heat by cubed temperature, similar to the boson peak in metallic glass. The simulation studies show that this boson-peak-like anomaly is caused by the phonon softening of the non-transforming matrix surrounding martensitic domains, which occurs in a transverse acoustic branch not associated with the martensitic transformation displacements. Therefore, this anomaly neither is a relic of van Hove singularity nor can be explained by other theories relying on structural disorder, while it verifies a recent theoretical model without any assumptions of disorder. This work might provide fresh insights in understanding the nature of glassy states and associated vibrational properties.

2.
Sci Total Environ ; 806(Pt 1): 150370, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34562760

RESUMO

Predicting the migration behavior of volatile organic compounds (VOCs) vapor is essential for the remediation of subsurface contamination such as soil vapor extraction. Previous analytical prediction models of VOCs migration are mostly limited to constant-concentration nonpoint sources in homogeneous soil. Thus, this study presents a novel analytical model for two-dimensional transport of VOCs vapor subjected to multiple time-dependent point sources involving transient diffusion, sorption and degradation in layered unsaturated soils. Two representative time-dependent sources, i.e., an instantaneous source and a finite pulse source, are used to describe the short-term and long-term leakage. Results reveal that soil heterogeneity can cause pollution accumulation, especially in low-diffusivity capillary fringe. The assumption of an equivalent plane source from multiple point sources would significantly overestimate the vapor concentration and the contaminated range. The previous single point source model is no longer inapplicable when the relative distance and/or the release interval between sources is small, giving a strong interaction between multiple sources. Moreover, a faster vapor degradation rate or a higher groundwater level will reduce the area of vapor plume linearly. Hence, close attention should be paid to the time-variation characteristics of multiple sources, the vapor degradation and the groundwater level fluctuation in practice to facilitate soil remediation. The proposed model is a promising tool for addressing the above issue.

3.
Sci Rep ; 11(1): 18591, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545152

RESUMO

Environmental exposures interact with genetic factors has been thought to influence susceptibility of systemic lupus erythematosus (SLE) development. To evaluate the effects of environmental exposures on SLE, we conducted a population-based cohort study across Jiangsu Province, China, to examine the associations between the living environment including air and water pollution, population density, economic income level, etc. and the prevalence and mortality of hospitalized SLE (h-SLE) patients. A total of 2231 h-SLE patients were retrieved from a longitudinal SLE database collected by the Jiangsu Lupus Collaborative Group from 1999 to 2009. The results showed that: It existed regional differences on the prevalence of h-SLE patients in 96 administrative districts; The distribution of NO2 air concentration monitored by atmospheric remote sensors showed that three of the ultra-high-prevalence districts were located in the concentrated chemical industry emission area; h-SLE patient prevalence was positively correlated with the excessive levels of nitrogen in drinking water; The positive ratio of pericarditis and proteinuria was positively correlated with the prevalence of h-SLE patients and pollution not only induced a high h-SLE patient prevalence but also a higher mortality rate, which might be attributed to NOx pollution in the air and drinking water. In summary, our data suggested that NOx in air and drinking water may be one of the important predispositions of SLE, especially for patients with renal involvement.

4.
ACS Appl Mater Interfaces ; 13(36): 43449-43457, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34472846

RESUMO

Composites based on a shape-memory polymer doped with conductive particles are considered as soft actuators for artificial muscles and robots. Low-voltage actuating is expected to reduce equipment requirement and safety hazards, which requires a highly conductive particle content but weakens the reversible deformation. The spatial distribution of the conductive particle is key to decreasing the actuating voltage and maintaining the reversible deformation. Herein, an approach of fabricating a low-voltage actuator that can perform various biomimetic locomotions by spraying and hot pressing is reported. Carbon nanotubes (CNTs) are enriched inside the surface layer of poly(ethylene-co-vinyl acetate) (EVA) to form a high-density conductive network without degradation of the reversible deformation. The bilayer CNT/EVA actuator exhibits a reversible transformation of more than 10% even with 100 cycles, which requires an applied voltage of just 15 V. Taking advantage of the reprogrammability of the CNT/EVA actuator and reversible shift between the different shapes, different biomimetic locomotions (sample actuator, gripper, and walking robot) are demonstrated without any additional mechanical components. A scheme combining the electrical properties and the shape-memory effect provides a versatile strategy to fabricate low-voltage-actuated polymeric actuators, providing inspiration in the development of electrical soft actuators and biomimetic devices.

5.
Materials (Basel) ; 14(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500938

RESUMO

The deformation of a thick-walled cylinder under pressure is a classic elastic mechanics problem with various engineering applications. In this study, the displacement of a viscoelastic thick-walled cylinder under internal pressure is investigated via analytical as well as numerical modelling. The fractional Maxwell model is initially introduced to describe the creep deformation of high-strength Q460 steel. Subsequently, an analytical solution to the creep deformation of the thick-walled cylinder under both internal and external pressures is deduced with the corresponding principle. The analytical solution is examined with a numerical simulation that incorporates the fractional Maxwell model by a user-defined subroutine. The numerical simulation agrees well with the analytical solution. The limitations of the current study are also discussed.

6.
Nanomicro Lett ; 13(1): 162, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338928

RESUMO

HIGHLIGHTS: The cationic waterborne polyurethanes microspheres with Diels-Alder bonds were synthesized for the first time. The electrostatic attraction not only endows the composite with segregated structure to gain high electromagnetic-interference shielding effectiveness, but also greatly enhances mechanical properties. Efficient healing property was realized under heating environment. It is still challenging for conductive polymer composite-based electromagnetic interference (EMI) shielding materials to achieve long-term stability while maintaining high EMI shielding effectiveness (EMI SE), especially undergoing external mechanical stimuli, such as scratches or large deformations. Herein, an electrostatic assembly strategy is adopted to design a healable and segregated carbon nanotube (CNT)/graphene oxide (GO)/polyurethane (PU) composite with excellent and reliable EMI SE, even bearing complex mechanical condition. The negatively charged CNT/GO hybrid is facilely adsorbed on the surface of positively charged PU microsphere to motivate formation of segregated conductive networks in CNT/GO/PU composite, establishing a high EMI SE of 52.7 dB at only 10 wt% CNT/GO loading. The Diels-Alder bonds in PU microsphere endow the CNT/GO/PU composite suffering three cutting/healing cycles with EMI SE retention up to 90%. Additionally, the electrostatic attraction between CNT/GO hybrid and PU microsphere helps to strong interfacial bonding in the composite, resulting in high tensile strength of 43.1 MPa and elongation at break of 626%. The healing efficiency of elongation at break achieves 95% when the composite endured three cutting/healing cycles. This work demonstrates a novel strategy for developing segregated EMI shielding composite with healable features and excellent mechanical performance and shows great potential in the durable and high precision electrical instruments.

7.
Cell Death Discov ; 7(1): 202, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349099

RESUMO

Cancer is one of the most fatal diseases that threaten human health, whereas more than 90% mortality of cancer patients is caused by tumor metastasis, rather than the growth of primary tumors. Thus, how to effectively control or even reverse the migration of tumor cells is of great significance for cancer therapy. CtBP, a transcriptional cofactor displaying high expression in a variety of human cancers, has become one of the main targets for cancer prediction, diagnosis, and treatment. The roles of CtBP in promoting tumorigenesis have been well studied in vitro, mostly based on gain-of-function, while its physiological functions in tumor invasion and the underlying mechanism remain largely elusive. Snail (Sna) is a well-known transcription factor involved in epithelial-to-mesenchymal transition (EMT) and tumor invasion, yet the mechanism that regulates Sna activity has not been fully understood. Using Drosophila as a model organism, we found that depletion of CtBP or snail (sna) suppressed RasV12/lgl-/--triggered tumor growth and invasion, and disrupted cell polarity-induced invasive cell migration. In addition, loss of CtBP inhibits RasV12/Sna-induced tumor invasion and Sna-mediated invasive cell migration. Furthermore, both CtBP and Sna are physiologically required for developmental cell migration during thorax closure. Finally, Sna activates the JNK signaling and promotes JNK-dependent cell invasion. Given that CtBP physically interacts with Sna, our data suggest that CtBP and Sna may form a transcriptional complex that regulates JNK-dependent tumor invasion and cell migration in vivo.

8.
Nanomicro Lett ; 13(1): 165, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351515

RESUMO

Nonlayered two-dimensional (2D) materials have attracted increasing attention, due to novel physical properties, unique surface structure, and high compatibility with microfabrication technique. However, owing to the inherent strong covalent bonds, the direct synthesis of 2D planar structure from nonlayered materials, especially for the realization of large-size ultrathin 2D nonlayered materials, is still a huge challenge. Here, a general atomic substitution conversion strategy is proposed to synthesize large-size, ultrathin nonlayered 2D materials. Taking nonlayered CdS as a typical example, large-size ultrathin nonlayered CdS single-crystalline flakes are successfully achieved via a facile low-temperature chemical sulfurization method, where pre-grown layered CdI2 flakes are employed as the precursor via a simple hot plate assisted vertical vapor deposition method. The size and thickness of CdS flakes can be controlled by the CdI2 precursor. The growth mechanism is ascribed to the chemical substitution reaction from I to S atoms between CdI2 and CdS, which has been evidenced by experiments and theoretical calculations. The atomic substitution conversion strategy demonstrates that the existing 2D layered materials can serve as the precursor for difficult-to-synthesize nonlayered 2D materials, providing a bridge between layered and nonlayered materials, meanwhile realizing the fabrication of large-size ultrathin nonlayered 2D materials.

9.
ACS Omega ; 6(31): 20398-20407, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34395988

RESUMO

Hydraulic fracturing is often used to exploit unconventional hydrocarbons, and proppants are usually added during hydraulic fracturing to keep the fractures induced open. Nevertheless, time-dependent proppant embedment has often been neglected in previous studies. In this survey, the fractional Maxwell model is first proposed to describe the viscoelastic deformation of tight sandstones. Then, the fractional rheological model is incorporated into the finite element framework in ABAQUS to establish a numerical model to investigate the time-dependent embedment of proppants in viscoelastic formations. Parameter sensitivity studies are also performed to investigate the influences of the mechanical characteristics of proppants and formation on the embedment depth. Several factors that influence proppant embedment are also discussed.

10.
Ann Rheum Dis ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226187

RESUMO

OBJECTIVES: Osteoarthritis (OA) is the most common joint disease; however, the indeterminate nature of mechanisms by which OA develops has restrained advancement of therapeutic targets. TNF signalling has been implicated in the pathogenesis of OA. TNFR1 primarily mediates inflammation, whereas emerging evidences demonstrate that TNFR2 plays an anti-inflammatory and protective role in several diseases and conditions. This study aims to decipher TNFR2 signalling in chondrocytes and OA. METHODS: Biochemical copurification and proteomics screen were performed to isolate the intracellular cofactors of TNFR2 complex. Bulk and single cell RNA-seq were employed to determine 14-3-3 epsilon (14-3-3ε) expression in human normal and OA cartilage. Transcription factor activity screen was used to isolate the transcription factors downstream of TNFR2/14-3-3ε. Various cell-based assays and genetically modified mice with naturally occurring and surgically induced OA were performed to examine the importance of this pathway in chondrocytes and OA. RESULTS: Signalling molecule 14-3-3ε was identified as an intracellular component of TNFR2 complexes in chondrocytes in response to progranulin (PGRN), a growth factor known to protect against OA primarily through activating TNFR2. 14-3-3ε was downregulated in OA and its deficiency deteriorated OA. 14-3-3ε was required for PGRN regulation of chondrocyte metabolism. In addition, both global and chondrocyte-specific deletion of 14-3-3ε largely abolished PGRN's therapeutic effects against OA. Furthermore, PGRN/TNFR2/14-3-3ε signalled through activating extracellular signal-regulated kinase (ERK)-dependent Elk-1 while suppressing nuclear factor kappa B (NF-κB) in chondrocytes. CONCLUSIONS: This study identifies 14-3-3ε as an inducible component of TNFR2 receptor complex in response to PGRN in chondrocytes and presents a previously unrecognised TNFR2 pathway in the pathogenesis of OA.

11.
J Extracell Vesicles ; 10(9): e12123, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34276900

RESUMO

Advancements in omics-based technologies over the past few years have led to the discovery of numerous biologically relevant peptides encoded by small open reading frames (smORFs) embedded in long noncoding RNA (lncRNA) transcripts (referred to as microproteins here) in a variety of species. However, the mechanisms and modes of action that underlie the roles of microproteins have yet to be fully characterized. Herein, we provide the first experimental evidence of abundant microproteins in extracellular vesicles (EVs) derived from glioma cancer cells, indicating that the EV-mediated transfer of microproteins may represent a novel mechanism for intercellular communication. Intriguingly, when examining human plasma, 48, 11 and 3 microproteins were identified from purified EVs, whole plasma and EV-free plasma, respectively, suggesting that circulating microproteins are primarily enriched in EVs. Most importantly, the preliminary data showed that the expression profile of EV microproteins in glioma patient diverged from the health donors, suggesting that the circulating microproteins in EVs might have potential diagnostic application in identifying patients with glioma.

12.
Front Pediatr ; 9: 693583, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262890

RESUMO

Background: Neonatal mortality rates remain high in Sub-Saharan African countries. Improving the newborn resuscitation skills of healthcare professionals is important in addressing this challenge. The aim of this study was to evaluate a neonatal resuscitation training programme delivered over a two-year period for healthcare professionals in Zanzibar, Tanzania. Methods: A pre- and post-intervention study was designed. We delivered neonatal resuscitation training over a 2-day period in 2017 and 2 days of refresher training in 2018. Knowledge was evaluated by a self-designed survey (11 items with a total score of 22) before and after the two training periods, and skills were evaluated by a skills checklist (six domains with 25 items with a total score of 50) completed by the trainers based on their observations. Statistical analysis included differences in the knowledge and skills scores before and after the training sessions and between the two periods. Results: A total of 23 healthcare professionals participated and completed both neonatal resuscitation training sessions. The knowledge mean scores before and after the training in 2017 increased from 9.60 to 13.60 (95% CI: -5.900; -2.099, p < 0.001), and in 2018, the scores increased from 10.80 to 15.44 (95% CI: -6.062; -3.217, p < 0.001). The mean knowledge scores post-training over time were 13.60 in 2017 and 15.44 in 2018 (95% CI: -3.489; 0.190, p = 0.030). The resuscitation skills performance between the two time periods increased from a mean of 32.26 (SD = 2.35) to a mean of 42.43 (SD = 1.73) (95% CI: -11.402; -8.945, p < 0.001). Conclusion: The neonatal resuscitation training programme increased the theoretical knowledge and resuscitation skills before and after the two training sessions and over time after a 9-month period. Continuous neonatal resuscitation training based on the local needs in resource-limited countries is essential to provide confidence in healthcare professionals to initiate resuscitation and to improve newborn outcomes.

13.
Huan Jing Ke Xue ; 42(8): 3837-3846, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309270

RESUMO

The adsorption of heavy metals by suspended sediment particles is a key process in the migration of heavy metals in lakes and is affected by various environmental conditions. To reveal the effects and mechanisms of dissolved organic matter (DOM) on the adsorption of copper ions by suspended sediment particles, a Cu(Ⅱ) adsorption test was conducted through a laboratory simulation test. The results showed that DOM promoted the adsorption of Cu(Ⅱ) onto the suspended particles. Under the respective influences of fulvic acid and DOM extracted from the sediment of the Xiangjiang River, the adsorption percentage of Cu(Ⅱ) increased from 71.51% to 75.31% and 85.69%. Scanning electron microscope-energy spectroscopy results showed that under the influence of DOM, Cu(Ⅱ) existed inside the sediment particles after being adsorbed. The results of UV-visible (UV-Vis) spectroscopy showed that Cu(Ⅱ) and DOM were first complexed and then dissociated during the adsorption reaction. The results of fluorescent excitation-emission matrix spectroscopy combined with parallel factor analysis and synchronous fluorescence spectroscopy combined with two-dimensional correlation analysis indicate that protein-like components promoted the adsorption of Cu(Ⅱ) onto the sediment suspended particles. In particular, tyrosine-like components played a critical role in promoting adsorption. However, humic-like components hardly promote this adsorption. This study has improved the theory of heavy metal migration in lakes and can be used as a basis for the prevention and control of heavy metal pollution in sediments.


Assuntos
Cobre , Substâncias Húmicas , Adsorção , Sedimentos Geológicos , Substâncias Húmicas/análise , Espectrometria de Fluorescência
14.
J Contam Hydrol ; 242: 103845, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34139441

RESUMO

A one-dimensional analytical model is proposed to analyze contaminant diffusion through a composite geomembrane cut-off wall (CGCW) composed of a geomembrane (GMB) and a bentonite cut-off wall (BCW). The model considers degradation process of contaminant and time-dependent inlet boundary condition which are common in engineering practices. Moreover, two limiting scenarios of the exit boundary condition (EBC) of CGCW for field conditions are taken into account, including the flushing and non-advective semi-infinite aquifer EBCs. The influence of boundary conditions and performance of CGCW are comprehensively investigated. The results show that the upper and lower limits of the mass flux of the exit face of CGCW can be obtained by the models with flushing EBC and the model with non-advective semi-infinite aquifer EBC, respectively. In addition, degradation has substantial influence on the contaminant migration, and smaller half-life in BCW results in smaller contaminant leakage. The performance of CGCW can be improved by embedding GMB at a proper location which is related to the type of contaminant and EBC. Furthermore, thickening HDPE GMB or adopting a coextruded EVOH GMB is efficient to improve the performance of CGCW. The present model can be used as an applicable tool for rational design of CGCW.

15.
Front Immunol ; 12: 683330, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135910

RESUMO

Idiopathic membranous nephropathy (IMN) is an organ-specific autoimmune disease of the kidney glomerulus. It may gradually progress to end-stage renal disease (ESRD) characterized by increased proteinuria, which leads to serious consequences. Although substantial advances have been made in the understanding of the molecular bases of IMN in the last 10 years, certain questions remain largely unanswered. To define the transcriptomic landscape at single-cell resolution, we analyzed kidney samples from 6 patients with anti-PLA2R positive IMN and 2 healthy control subjects using single-cell RNA sequencing. We then identified distinct cell clusters through unsupervised clustering analysis of kidney specimens. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. Based on transcriptional expression patterns, we identified all previously described cell types in the kidney. The DEGs in most kidney parenchymal cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling, and MAPK signaling. Moreover, cell-cell crosstalk highlighted the extensive communication of mesangial cells, which infers great importance in IMN. IMN with massive proteinuria displayed elevated expression of genes participating in inflammatory signaling pathways that may be involved in the pathogenesis of the progression of IMN. Overall, we applied single-cell RNA sequencing to IMN to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis, and identify novel therapeutic targets of anti-PLA2R positive IMN.

16.
Int J Mol Sci ; 22(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073283

RESUMO

Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and IL-6. Although they facilitate local antiviral immunity, their excessive release leads to life-threatening cytokine release syndrome, exemplified by the severe cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we investigated the roles of the integrated stress response (ISR) and activator protein-1 (AP-1) family proteins in regulating coronavirus-induced IL-8 and IL-6 upregulation. The mRNA expression of IL-8 and IL-6 was significantly induced in cells infected with infectious bronchitis virus (IBV), a gammacoronavirus, and porcine epidemic diarrhea virus, an alphacoronavirus. Overexpression of a constitutively active phosphomimetic mutant of eukaryotic translation initiation factor 2α (eIF2α), chemical inhibition of its dephosphorylation, or overexpression of its upstream double-stranded RNA-dependent protein kinase (PKR) significantly enhanced IL-8 mRNA expression in IBV-infected cells. Overexpression of the AP-1 protein cJUN or its upstream kinase also increased the IBV-induced IL-8 mRNA expression, which was synergistically enhanced by overexpression of cFOS. Taken together, this study demonstrated the important regulatory roles of ISR and AP-1 proteins in IL-8 production during coronavirus infection, highlighting the complex interactions between cellular stress pathways and the innate immune response.


Assuntos
Infecções por Coronavirus/metabolismo , Estresse do Retículo Endoplasmático/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Interleucina-8/metabolismo , Resposta a Proteínas não Dobradas/genética , Alphacoronavirus/metabolismo , Alphacoronavirus/patogenicidade , Animais , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/genética , Gammacoronavirus/metabolismo , Gammacoronavirus/patogenicidade , Regulação da Expressão Gênica , Humanos , Imunidade Inata , Vírus da Bronquite Infecciosa/metabolismo , Vírus da Bronquite Infecciosa/patogenicidade , Interleucina-8/genética , Fosforilação , Vírus da Diarreia Epidêmica Suína/metabolismo , Vírus da Diarreia Epidêmica Suína/patogenicidade , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Transdução de Sinais/genética , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Regulação para Cima , Células Vero , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo
17.
Front Immunol ; 12: 645988, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936064

RESUMO

The molecular mechanisms underlying renal damage of IgA nephropathy (IgAN) remain incompletely defined. Here, single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from IgAN and control subjects to define the transcriptomic landscape at single-cell resolution. We presented a comprehensive scRNA-seq analysis of human renal biopsies from IgAN. We showed for the first time that IgAN mesangial cells displayed increased expression of several novel genes including MALAT1, GADD45B, SOX4, and EDIL3, which were related to cell proliferation and matrix accumulation. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. Furthermore, we compared the results of 4 IgAN patients with the published scRNA-Seq data of healthy kidney tissues of three human donors in order to further validate the findings in our study. The results also verified that the overexpressed genes in tubule cells from IgAN patients were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, and NOD-like receptor signaling. The receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. IgAN patients with overt proteinuria displayed elevated genes participating in several signaling pathways compared with microproteinuria group. It needs to be mentioned that based on number of mesangial cells and other kidney cells analyzed in this study, the results of our study are preliminary and needs to be confirmed on larger number of cells from larger number of patients and controls in future studies. Therefore, these results offer new insight into pathogenesis and identify new therapeutic targets for IgAN.


Assuntos
Glomerulonefrite por IGA/metabolismo , Análise de Célula Única/métodos , Transcriptoma , Comunicação Celular , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/patologia , Humanos , Interleucina-17/fisiologia , Proteinúria/metabolismo , Análise de Sequência de RNA , Transdução de Sinais/fisiologia
18.
Sci Adv ; 7(19)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952527

RESUMO

The checkpoint kinase ATR [ATM (ataxia-telangiectasia mutated) and rad3-related] is a master regulator of DNA damage response. Yet, how ATR activity is regulated remains to be investigated. We report here that histone demethylase PHF8 (plant homeodomain finger protein 8) plays a key role in ATR activation and replication stress response. Mechanistically, PHF8 interacts with and demethylates TOPBP1 (DNA topoisomerase 2-binding protein 1), an essential allosteric activator of ATR, under unperturbed conditions, but replication stress results in PHF8 phosphorylation and dissociation from TOPBP1. Consequently, hypomethylated TOPBP1 facilitates RAD9 (RADiation sensitive 9) binding and chromatin loading of the TOPBP1-RAD9 complex to fully activate ATR and thus safeguard the genome and protect cells against replication stress. Our study uncovers a demethylation and phosphorylation code that controls the assembly of TOPBP1-scaffolded protein complex, and provides molecular insight into non-histone methylation switch in ATR activation.

19.
Zhongguo Gu Shang ; 34(5): 400-5, 2021 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-34032040

RESUMO

OBJECTIVE: To explore clinical effect of locking plate external fixation combined with membrane induction technology in treating open and comminuted tibial fractures with bone defects. METHODS: Totally 92 patients of open and comminuted tibial fractures with bone defects were chosen form January 2018 to July 2019, and randomly divided into external fixation group and internal fixation group, 46 patients in each group. In external fixation group, there were 29 males and 17 females, aged from 25 to 62 years old, with an average of (37.45±10.92) years old;according to AO classification, 15 patients were type A, 22 patients were type B and 9 patients were type C;according to Gustilo classification, 21 patients were typeⅡ, 10 patients were type ⅢA, 10 patients were type ⅢB, 5 patients were type Ⅲ C;treated by fracture reduction with locking plate external fixation. In internal fixation group, there were 31 males and 15 females, aged from 23 to 60 years old, with an average of(36.88±10.64) years old;according to AO classification, 18 patients were type A, 20 patients were type B and 8 patients were type C; according to Gustilo classification, 22 patients were typeⅡ, 11 patients were type ⅢA, 7 patients were type ⅢB, 6 patients were type Ⅲ C;treated by traditional open reduction with plate internal fixation. Operation time, intraoperative blood loss, incision length, hospital stay, fracture healing time and lower limb full weight-bearing time and postoperative complications between two groups were observed and compared, bone mineral density, osteocalcin, blood calcium and phosphorus before operation and 1 month after operation. RESULTS: All patients were followed up from 12 to 18 months with an average of (14.92±2.46) months. Operation time, intraoperative blood loss, incision length, hospital stay, fracture healing time and lower limb full weight-bearing time of external fixation group were significantly better than that of internal fixation group(P<0.05). Postoperative bone mineral density, osteocalcin, blood calcium and phosphorus at 1 month in external group were higher than that of internal fixation group (P<0.05). Four patients in external fixation group occurred complications, 13 patients in internal fixtaion group, and occurrence rate of complications in external fixation group (8.70%) was lower than that of internal fixtaion group (28.26%)(χ2=4.618, P=0.032). CONCLUSION: Locking plate external fixation combined with membrane induction technology in treating open and comminuted tibial fractures with severe post-traumatic bone defects has advantages of less trauma, reliable fixation, shorter fracture healing time, and could improve bone metabolic activity with less postoperative complications.


Assuntos
Fraturas Cominutivas , Fraturas da Tíbia , Adulto , Placas Ósseas , Fixadores Externos , Feminino , Fixação de Fratura , Fixação Interna de Fraturas , Fraturas Cominutivas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tecnologia , Fraturas da Tíbia/cirurgia , Resultado do Tratamento , Adulto Jovem
20.
Phys Rev Lett ; 126(17): 176401, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33988439

RESUMO

Improving the efficiency of charge separation (CS) and charge transport (CT) is essential for almost all optoelectronic applications, yet its maximization remains a big challenge. Here we propose a conceptual strategy to achieve CS efficiency close to unity and simultaneously avoid charge recombination (CR) during CT in a ferroelectric polar-discontinuity (PD) superlattice structure, as demonstrated in (BaTiO_{3})_{m}/(BiFeO_{3})_{n}, which is fundamentally different from the existing mechanisms. The competition of interfacial dipole and ferroelectric PD induces opposite band bending in BiFeO_{3} and BaTiO_{3} sublattices. Consequently, the photoexcited electrons (e) and holes (h) in individual sublattices move forward to the opposite interfaces forming electrically isolated e and h channels, leading to a CS efficiency close to unity. Importantly, the spatial isolation of conduction channels in (BaTiO_{3})_{m}/(BiFeO_{3})_{n} enable suppression of CR during CT, thus realizing a unique band diagram for spatially orthogonal CS and CT. Remarkably, (BaTiO_{3})_{m}/(BiFeO_{3})_{n} can maintain a high photocurrent and large band gap simultaneously. Our results provide a fascinating illumination for designing artificial heterostructures toward ideal CS and CT in optoelectronic applications.

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