Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

Prospects and challenges of dynamic DNA nanostructures in biomedical applications

The physicochemical nature of DNA allows the assembly of highly predictable structures via several fabrication strategies, which have been applied to make breakthroughs in various fields. Moreover, DNA nanostructures are regarded as materials with excellent editability and biocompatibility for biomedical applications. The ongoing maintenance and release of new DNA structure design tools ease the work and make large and arbitrary DNA structures feasible for different applications. However, the nature of DNA nanostructures endows them with several stimulus-responsive mechanisms capable of responding to biomolecules, such as nucleic acids and proteins, as well as biophysical environmental parameters, such as temperature and p H. Via these mechanisms, stimulus-responsive dynamic DNA nanostructures have been applied in several biomedical settings, including basic research, active drug delivery, biosensor development, and tissue engineering. These applications have shown the versatility of dynamic DNA nanostructures, with unignorable merits that exceed those of their traditional counterparts, such as polymers and metal particles.However, there are stability, yield, exogenous DNA, and ethical considerations regarding their clinical translation. In this review, we first introduce the recent efforts and discoveries in DNA nanotechnology, highlighting the uses of dynamic DNA nanostructures in biomedical applications. Then, several dynamic DNA nanostructures are presented, and their typical biomedical applications,including their use as DNA aptamers, ion concentration/p H-sensitive DNA molecules, DNA nanostructures capable of strand displacement reactions, and protein-based dynamic DNA nanostructures, are discussed. Finally, the challenges regarding the biomedical applications of dynamic DNA nanostructures are discussed.

The extraction of aromatics using N-methylpyrrolidone: Liquid-liquidequilibrium determination and mechanism exploration

LLE data of cyclooctane/3-methylpentane + benzene/toluene + N-methylpyrrolidone (NMP) at 298.15 Kand 313.15 K under a pressure of 101.3 kPa were measured in this work. The Othmer-Tobias and Handequations were adopted to validate the reliability of LLE data, where the correlation coefficients (R2) wereclose to unity, indicating the high reliability of the experimental data. The experimental data were analyzed using the distribution coefficient (D) and separation factor (S), and the effect of NMP extracting benzene and toluene from aromatics was explored. Meanwhile, the reason for the different extractionefficiencies of benzene and toluene using NMP was analyzed by quantum chemical calculations. TheNRTL and UNIQUAC thermodynamic models were used to correlate the liquid–liquid equilibrium data,and the relevant binary interaction parameters were obtained. The calculated root mean square deviation(RMSD) were all less than 0.0063, indicating that the obtained binary interaction parameters can be usedto simulate and calculate the extraction of aromatics using NMP.

Correction to:Tetrahedral Framework Nucleic Acid‑Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

Correction to:Nano‑Micro Lett.(2021)13:86 https://doi.org/10.1007/s40820-021-00614-6 The Nano-Micro Letters(2021)13:86,article by Li et al.,entitled“Tetrahedral Framework Nucleic Acid‐Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity”(Nano-Micro Lett.https://doi.org/10.1007/s40820-021-00614-6),was published online 06 March,2020,with errors.

Development, Application and Prospect of Dissolving Microneedles

In recent years, as a new transdermal drug delivery method, microneedle transdermal drug delivery technology accelerates the absorption of drugs through micron pores, which has been widely used in the field of medicine and cosmetics. Dissolving microneedles have the characteristics of good biocompatibility and fast dissolution speed, which attract more and more researchers’ attention and research. In this paper, the concept, properties and preparation methods of dissolving microneedles as well as the research status of dissolving microneedles in the field of medicine and cosmetics in recent years were summarized and prospected, so as to enable researchers to have a clearer and comprehensive understanding of dissolving microneedles and prospect the application and development prospects of dissolving microneedles in the industry.

Evaluation of sweet spots and horizontal-well-design technology for shale gas in the basin-margin transition zone of southeastern Chongqing,SW China

The shale gas accumulation conditions in the basin-margin transition zone of southeastern Chongqing in SW China are complex.In order to improve single-well productivity in this area,the geologic characteristics,major factors controlling the occurrence of sweet spots,and drilling/fracturing optimization were investigated in this study.The sweet spot evaluation system and criteria were established,and the horizontal-well-design technology was developed.The following three conclusions were drawn.First,the accumulation and high-productivity-oriented approaches for sweet spot evaluation are proposed and the criteria are established based on screened key indicators.Second,the horizontal well was designed based on:(1)the“six-map”method,to identify both the geology and engineering sweet spots for well locations;and(2)seismic attributes,to predict the development of fractures and cavities,and thus,avoid mud loss and improve the drilling efficiency.The target window,well-azimuth optimization,and the curvature were forecasted to improve the fracturing performances.Third,the Pingqiao anticline,Dongsheng anticline,Jinfo slope,and Wulong syncline were selected as Type I sweet spots.Currently,shale gas has been successfully discovered in the basin-margin transition zone and is being commercially developed.

The Hardness and Corrosion Properties of Trivalent Chromium Hard Chromium

The formulation of hard chromium plating from trivalent chromium electrolyte and its related process have been intensively studied in this work. Through optimized conditions, the coating hardness can achieve more than HV0.1900 without any treatment and HV0.11700 after heat treatment for five minutes at 300°C, and the thickness of hard chromium coating was about 100 μm. The hard chromium coatings show good adhesion on the carbon steel and low alloy structural steel. The corrosion resistance of hard chromium coatings was enhanced by the adding nanometer materials into trivalent chromium plating coatings. More than 120 hours salt spray corrosion resistance can be achieved with 40 to 50 microns thickness of trivalent chromium plating coatings.

Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell

Diabetes mellitus considerably affects bone marrow mesenchymal stem cells(BMSCs),for example,by inhibiting their proliferation and differentiation potential,which enhances the difficulty in endogenous bone regeneration.Hence,effective strategies for enhancing the functions of BMSCs in diabetes have farreaching consequences for bone healing and regeneration in diabetes patients.Tetrahedral framework nucleic acids(tFNAs)are nucleic acid nanomaterials that can autonomously enter cells and regulate their behaviors.In this study,we evaluated the effects of tFNAs on BMSCs from diabetic rats.We found that tFNAs could promote the proliferation,migration,and osteogenic differentiation of BMSCs from rats with type 2 diabetes mellitus,and inhibited cell senescence and apoptosis.Furthermore,tFNAs effectively scavenged the accumulated reactive oxygen species and activated the suppressed protein kinase B(Akt)signaling pathway.Overall,we show that tFNAs can recover the proliferation and osteogenic potential of diabetic BMSCs by alleviating oxidative stress and activating Akt signaling.The study provides a strategy for endogenous bone regeneration in diabetes and also paves the way for exploiting DNA-based nanomaterials in regenerative medicine.

Online Learning Behavior Analysis and Prediction Based on Spiking Neural Networks

The vast amount of data generated by large-scale open online course platforms provide a solid foundation for the analysis of learning behavior in the field of education.This study utilizes the historical and final learning behavior data of over 300000 learners from 17 courses offered on the edX platform by Harvard University and the Massachusetts Institute of Technology during the 2012-2013 academic year.We have developed a spike neural network to predict learning outcomes,and analyzed the correlation between learning behavior and outcomes,aiming to identify key learning behaviors that significantly impact these outcomes.Our goal is to monitor learning progress,provide targeted references for evaluating and improving learning effectiveness,and implement intervention measures promptly.Experimental results demonstrate that the prediction model based on online learning behavior using spiking neural network achieves an impressive accuracy of 99.80%.The learning behaviors that predominantly affect learning effectiveness are found to be students’academic performance and level of participation.

The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications

Histone lysine methyltransferases(HKMTs)deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression.The structures and functions of HKMTs have been extensively investigated in recent decades,significantly advancing our understanding of the dynamic regulation of histone methylation.Here,we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes(H3K4,H3K27,H3K36,H3K79,and H4K20 methyltransferases),with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs.These structural studies inform HKMTs'roles in tumorigenesis and provide the foundations for developing new therapeutic approachestargetingHKMTs incancers.

Serum lipid profiles and aggressive prostate cancer

The introduction of widespread prostate specific antigen （PSA） screening in western countries led to a sharp increase in prostate biopsies and the subsequent diagnosis of prostate cancer. This phenomenon appears to be repeating itself in countries such as China where economic development in recent decades has resulted in increased access to healthcare and more frequent screening tests. It is now recognized that the majority of prostate cancers diagnosed in PSA-screened men is of the indolent nature that does not impact patients＇ quality of life or life expectancy. Unfortunately, due to our inability to image prostate cancer accurately,

Tetrahedral framework nucleic acids regulate osteogenic differentiation potential of osteoporotic adipose-derived stem cells

Osteoporosis(OP)is a noncommunicable bone disease caused by a shift in the balance between os-teoblasts and osteoclasts,and can severely affect the health of elderly persons.Autologous stem-cell transplantation can improve reduced bone density and weakened fracture healing abilities in patients with OP.However,OP can adversely affect the osteogenesis and proliferation abilities of autologous adipose-derived stem cells(ASCs).Therefore,an effective drug is required to facilitate autologous ASCs to recover their osteogenic and proliferative potential.Tetrahedral framework nucleic acid(tFNA)is a new type of nanomaterial that has ability to regulate the biological behavior of cells effectively and en-hance the bioactivity of stem cells.In this study,we examine the effects of tFNAs on the osteogenic differentiation and proliferation abilities of ASCs in rats with OP.The results indicate that the 250 nmol/L tFNAs can considerably increase the expression of osteogenesis-related markers,effectively promote the proliferation and osteogenic differentiation of osteoporotic ASCs(OP-ASCs),and help them to regain their osteogenic and proliferative potential.In short,tFNAs can enable OP-ACSs to recover their osteogenic po-tential and promote their proliferation and,therefore,can play a key regulatory role in autologous ASC transplantation.