Advances in microfluidic-based DNA methylation analysis

DNA methylation has been extensively investigated in recent years,not least because of its known relationship with various diseases.Progress in analytical methods can greatly increase the relevance of DNA methylation studies to both clinical medicine and scientific research.Microflu-idic chips are excellent carriers for molecular analysis,and their use can provide improvements from multiple aspects.On-chip molecular analysis has received extensive attention owing to its advantages of portability,high throughput,low cost,and high efficiency.In recent years,the use of novel microfluidic chips for DNA methylation analysis has been widely reported and has shown obvious superiority to conventional methods.In this review,wefirst focus on DNA methylation and its applications.Then,we discuss advanced microfluidic-based methods for DNA methylation analysis and describe the great progress that has been made in recent years.Finally,we summarize the advantages that microfluidic technology brings to DNA methylation analysis and describe several challenges and perspectives for on-chip DNA methylation analysis.This review should help researchers improve their understanding and make progress in developing microfluidic-based methods for DNA methylation analysis.

Thoracoscopic resection of giant left atrial appendage aneurysm: A case report

Left atrial appendage aneurysm(LAAA)was first reported in the 1960s.1 LAAA is a rare condition,with just over 100 congenital or acquired cases reported to date.2 LAAA is frequently diagnosed incidentally during echocardiography or computed tomography(CT)scans.Most patients with LAAA are asymptomatic,while a few exhibit nonspecific symptoms,such as dyspnea,palpitation,and chest tightness.Patients with LAAA frequently present with atrial arrhythmias and systemic thromboembolism,such as stroke or multiorgan infarctions,due to the formation of a left atrial appendage thrombus.3 The lesion may be cured using aneurysm resection.Considering it as the potential cause of atrial arrhythmias and thromboembolism,the lesion must be identified on time and cured using a suitable treatment approach.

The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation

Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation （XLMR） and cleft lip/cleft palate. However, the underlying mechanism is unknown. Here we show that PHF8 is a histone demethylase and coactivator for retinoic acid receptor （RAR）. Although activities for both H3K4me3/2/1 and H3K9me2/1 demethylation were detected in cellularbased assays, reeombinant PHF8 exhibited only H3K9me2/1 demethylase activity in vitro, suggesting that PHF8 is an H3K9me2/1 demethylase whose specificity may be modulated in vivo. Importantly, a mutant PHF8 （phenylalanine at position 279 to serine） identified in the XLMR patients is defective in enzymatie activity, indicating that the loss of histone demethylase activity is causally linked with the onset of disease. In addition, we show that PHF8 binds specifically to H3K4me3/2 peptides via an N-terminal PHD finger domain. Consistent with a role for PHF8 in neuronal differentiation, knockdown of PHF8 in mouse embryonic carcinoma P19 cells impairs RA-induced neuronal differentiation, whereas overexpression of the wild-type but not the F279S mutant PHF8 drives PI9 cells toward neuronal differentiation. Furthermore, we show that PHF8 interacts with RAR~ and functions as a coactivator for RARa. Taken together, our results suggest that histone methylation modulated by PHF8 plays a critical role in neuronal differentiation.

The in-situ Ti alloying of aluminum alloys and its application in A356 alloys

This research has investigated the in-situ Ti alloying of aluminum alloys and its application to A356 alloys and wheels through the evaluation of microstructure and mechanical properties. The results showed that stable titanium content can be obtained by adding a small quantity of TiO2 into electrolyte of pure aluminum. Under this approach, a greater than 95% absorptivity of titanium was achieved, and the microstructure of the specimens was changed to fine equiaxed grains from coarse columnar grains in the pure aluminum. In comparison with the tradition A356 alloys and wheels, the corresponding microstructure in the testing A356 alloys and wheels was finer. Although the tensile strength was similar between the testing and the tradition A356 alloys and wheels, the ductility of the former (testing) is superior to that of the later (tradition), leading to an excellent combination of strength and ductility from the testing alloys and wheels.

AOF1 is a histone H3K4 demethylase possessing demethylase activity-independent repression function

LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclature）, a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4mel and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.

The biomimetic design provides efficient self-healing of ultrahightough and damage-warning bio-based elastomer for protective clothing of metals

Facing the ubiquitous corrosion threat,the great significance of developing high-performance protective materials with the dual function of self-healing defects and self-warning damage is extremely challenging.Herein,inspired by the biological skin and pearls,we proposed that the biological polyurethanes(PU)embedded with multiple dynamic bonds(reversible hydrogen bonds and aromatic disulfide bonds)were combined with polydopamine(PDA)/1,10-phenanthroline(Phen)/graphene oxide(GO)(PPG)nanosheets(PDA encapsulated GO with Phen)to obtain a versatile nacre structure polymer with the interface hydrogen bond between PPG and PU matrix.The biomimetic polymer not only guarantees ultrahigh toughness(116.1 MJ·m^(-3))and abnormal elongation(2320%)but shows satisfactory repair performance(81%under 25℃ for 3 h),and the coating can accelerate damage recovery(87%)under near-infrared light(NIR)irradiation for 1 h due to the photothermal properties of PPG.The warning of damages in the coating can be enabled through the Phen chelation Fe^(2+)ions that bring in the corrosion reaction to produce a conspicuous red color,thereby achieving the active warning function of the bionic coating on defects for the first time.In addition,the electrochemical tests exhibit that the repair performance and protection effect of the biomimetic coating in 3.5 wt.%NaCl solution are also trustworthy,and this highly reliable bio-based bionic coating brings a revolutionary program to inaugurate multifunctional and high-performance intelligent materials under harsh environments.

MYC promotes global transcription in part by controlling P-TEFb complex formation via DNA-binding independent inhibition of CDK9 SUMOylation

MYC is an oncogenic transcription factor with a novel role in enhancing global transcription when overexpressed. However, how MYC promotes global transcription remains controversial. Here, we used a series of MYC mutants to dissect the molecular basis for MYC-driven global transcription. We found that MYC mutants deficient in DNA binding or known transcriptional activation activities can still promote global transcription and enhance serine 2 phosphorylation(Ser2P) of the RNA polymerase(Pol) II Cterminal domain(CTD), a hallmark of active elongating RNA Pol II. Two distinct regions within MYC can promote global transcription and Ser2P of Pol II CTD. The ability of various MYC mutants to promote global transcription and Ser2P correlates with their ability to suppress CDK9 SUMOylation and enhance positive transcription elongation factor b(P-TEFb) complex formation. We showed that MYC suppresses CDK9 SUMOylation by inhibiting the interaction between CDK9 and SUMO enzymes including UBC9 and PIAS1. Furthermore, MYC's activity in enhancing global transcription positively contributes to its activity in promoting cell proliferation and transformation. Together, our study demonstrates that MYC promotes global transcription, at least in part, by promoting the formation of the active P-TEFb complex via a sequence-specific DNA-binding activity-independent manner.

Protective Coatings Containing ZnMOF-BTA Metal–Organic Framework for Active Protection of AA2024-T3

ZnMOF-BTA,a new metal–organic framework with excellent anti-corrosion properties was prepared and characterized.Polarization and immersion tests in 3.5 wt%NaCl were performed on AA2024-T3 alloy to assess the corrosion inhibition ability of ZnMOF-BTA.It showed an inhibition efficiency of more than 90%,indicating excellent corrosion inhibition of ZnMOF-BTA on AA 2024-T3 in NaCl.Moreover,ZnMOF-BTA particles were incorporated into polyurethane coatings to create corrosion-resistant coatings.Electrochemical tests and neutral salt spray analysis were used to assess the corrosion protection ability of ZnMOF-BTA-laden polyurethane coatings.The results of electrochemical impedance spectra clearly showed the outstanding corrosion resistance and durability of ZnMOF-BTA coatings after 1440 h of immersion with a high pore resistance(Rpo)of 1.76×10^(10)Ωcm^(2).In addition,during the cross-cut adhesion test,the coating did not detach from the substrate,and after the impact test,there was scarcely any indication of a fracture,which further supports the notion that the coating has strong adhesion to the substrate.

Influence of Different Al Contents on Microstructure, Tensile and Wear Properties of Zn-based Alloy

The influence of different Al contents on the microstructure, hardness, tensile and wear behavior of Zn-based alloys was investigated in the present study. The test results show that alloy with 27% Al content shows the higher ultimate strength and elongation percent at room and elevated temperatures. It also exhibits the higher wear resistance at all loads in view of the higher tightness of Zn-27Al alloy. Increasing Al content from 33% to 48% results in improvement of ultimate strength and elongation percent at room and elevated temperatures. However, the ultimate strength and elongation percent of the ZA48 alloy are still lower than that of Zn-27Al alloys. The reason can be attributed to the increasing segregation and voids with increasing Al contents.

Acidic domains differentially read histone H3 lysine 4 methylation status and are widely present in chromatin-associated proteins

Histone methylation is believed to provide binding sites for specific reader proteins, which translate histone code into biological function. Here we show that a family of acidic domain-containing proteins including nucleophosmin （NPM 1）, pp32, SET/TAF 113, nucleolin （NCL） and upstream binding factor （UBF） are novel H3K4me2-binding proteins. These proteins exhibit a unique pattern of interaction with methylated H3K4, as their binding is stimulated by H3K4me2 and inhibited by H3K4mel and H3K4me3. These proteins contain one or more acidic domains consisting mainly of aspartic and/or glutamic residues that are necessary for preferential binding of H3K4me2. Furthermore, we demonstrate that the acidic domain with sufficient length alone is capable of binding H3K4me2 in vitro and in vivo. NPM1, NCL and UBF require their acidic domains for association with and transcriptional activation ofrDNA genes. Interestingly, by defining acidic domain as a sequence with at least 20 acidic residues in 50 continuous amino acids, we identified 655 acidic domain-containing protein coding genes in the human genome and Gene Ontology （GO） analysis showed that many of the acidic domain proteins have chromatin-related functions. Our data suggest that acidic domain is a novel histone binding motif that can differentially read the status of H3K4 methylation and is broadly present in chromatin-associated proteins.