Chemical Approaches to Emerging Advancements in Deformable Bioelectronics:Synthesis,Device Concepts,Performance,and Applications

This mini review examines the current advances and future prospects of chemical approaches in deformable bioelectronics,emphasizing their transformative potential in healthcare and other sectors.The mini review outlines novel fabrication strategies that rely on chemical principles to create adaptable,comfortable,and durable bioelectronic devices that are capable of seamlessly integrating into the dynamic biological environment.The discussion also extends to the integration of innovative device concepts that enhance the outcomes in both sensing and modulation functionalities.Performance-enhancing strategies that use chemistry to refine the sensitivity and precision of these devices are also highlighted.Moreover,the mini review explores the emerging applications of chemically enhanced bioelectronic devices in healthcare,reflecting the potential of this field to revolutionize patient care and improve health monitoring.In the outlook section,this mini review investigates the promising future of transient and living bioelectronics,emphasizing the pivotal role of chemical approaches in their development.It additionally covers the potential of chemical techniques in powering bioelectronic devices using biological systems and discusses the prospective applications of chemically synthesized bioelectronic devices outside of healthcare.While the field has made substantial progress,this mini review also identifies challenges that must be addressed,thus underlining the necessity for continued research and chemical innovation in bioelectronics.

拟南芥m6A甲基化组的系统鉴定和功能分析

作为mRNA上最丰富的一种甲基化修饰,N6-甲基腺苷（N6-methyl-adenosine,m6A）广泛存在于酵母以及动植物中。然而多年来由于缺乏有效的技术手段,这些甲基化修饰发生在mRNA的什么位置,以及如何行使其生物学功能,却长时间没有定论。近年来,随着mRNA去甲基酶FTO和ALKBH5的发现,

The dual-action mechanism of Arabidopsis cryptochromes

Photoreceptor cryptochromes (CRYs) mediate blue-light regulation of plant growth and development. It has been reported that Arabidopsis CRY1and CRY2 function by physically interacting with at least 84 proteins, including transcription factors or co-factors, chromatin regulators, splicing factors, messenger RNA methyltransferases, DNA repair proteins, E3 ubiquitin ligases, protein kinases and so on. Of these 84 proteins, 47 have been reported to exhibit altered binding affinity to CRYs in response to blue light, and 41 have been shown to exhibit condensation to CRY photobodies. The blue light-regulated composition or condensation of CRY complexes results in changes of gene expression and developmental programs. In this mini-review, we analyzed recent studies of the photoregulatory mechanisms of Arabidopsis CRY complexes and proposed the dual mechanisms of action, including the “Lock-and-Key” and the “Liquid-Liquid Phase Separation (LLPS)” mechanisms. The dual CRY action mechanisms explain, at least partially, the structural diversity of CRY-interacting proteins and the functional diversity of the CRY photoreceptors.

Nano-enabled cellular engineering for bioelectric studies

Engineered cells have opened up a new avenue for scientists and engineers to achieve specialized biological functions.Nanomaterials,such as silicon nanowires and quantum dots,can establish tight interfaces with cells either extra-or intracellularly,and they have already been widely used to control cellular functions.The future exploration of nanomaterials in cellular engineering may reveal numerous opportunities in both fundamental bioelectric studies and clinic applications.In this review,we highlight several nanomaterials-enabled non-genetic approaches to fabricating engineered cells.First,we briefly review the latest progress in engineered or synthetic cells,such as protocells that create cell-like behaviors from nonliving building blocks,and cells made by genetic or chemical modifications.Next,we illustrate the need for non-genetic cellular engineering with semiconductors and present some examples where chemical synthesis yields complex morphology or functions needed for biointerfaces.We then provide discussions in detail about the semiconductor nanostructure-enabled neural,cardiac,and microbial modulations.We also suggest the need to integrate tissue engineering with semiconductor devices to carry out more complex functions.We end this review by providing our perspectives for future development in non-genetic cellular engineering.

New horizons of regulatory RNA

Genetic information flows from DNA to protein through RNA in the central dogma.Different RNA species are known to accomplish essential tasks of protein encoding(mRNAs),amino acid loading(tRNAs),and translation machinery assembly(rRNAs).However,on top of these well-known roles,RNAs are central to various cellular regulatory pathways.Here we summarize newly emerging regulatory functions of RNA,specifically focusing on regulations through RNA modifications,RNP granules,and chromatin-associated regulatory RNA.In addition to being an essential building block of the central dogma,RNA can be critical to the regulation of many cellular processes.

Systematic identification of CRISPR off-target effects by CROss-seq

DearEditor,The CRISPR-mediated genome editing tools,including nucleases,base editors(ABE/CBE),transposases/recombinases,and prime editor(PE),have been extensively applied in basic and clinical researches,although the off-target effect remains a major concern(Anzalone et al.,2020).Recently,various methods have been developed to assess the specificity and accuracy of different tools(Zhang et al.,2021),yet each method is designed for limited editing systems,and none of them can simultaneously detect off-target sites in vivo and in vitro.A versatile method for profiling genome-wide off-target effects of various tools remains lacking.

METTL14 is a chromatin regulator independent of its RNA N^(6)-methyladenosine methyltransferase activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m^(6)A methyltransferase complex(MTC)that installs m^(6)A.Surprisingly,depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell(mESC).While comparable global hypo-methylation in RNA m^(6)A was observed in Mettl3 or Mettl14 knockout mESCs,respectively.Mettl14 knockout led to a globally decreased nascent RNA synthesis,whereas Mettl3 depletion resulted in transcription upregulation,suggesting that METTL14 might possess an mA-independent role in gene regulation.We found that METTL14 colocalizes with the repressive H3K27me3 modification.Mechanistically,METTL14,but not METTL3,binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3.Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression.The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs.This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m^(6)A,and critically impacts transcriptional regulation,stemness maintenance,and differentiation ofmESCs.

Nuclear m^(6)A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells(ESCs),which highly depends on the m^(6)A-binding ability.Ythdcl is required for sufficient rRNA synthesis and repression of the 2-cell(2C)transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 scaffold.Detailed analyses revealed that YTHDC1 recognizes m^(6)A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdcl-depleted ESCs and inner cell mass(ICM)cells,which consequently increases the transcriptional activities.Our study reveals a role of m^(6)A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.

E]iomimetic approaches toward smart bio-hybric systems

Bio-integrated materials and devices can blur the interfaces between living and artificial systems. Microfluidics, bioelectronics, and engineered nanostructures, with close interactions with biology at the cellular or tissue levels, have already yielded a spectrum of new applications. Many new designs emerge, including of organ-on-a-chip systems, biodegradable implants, electroceutical devices, minimally invasive neuro-prosthetic tools, and soft robotics. In this review, we highlight a few recent advances of the fabrication and application of smart bio-hybrid systems, with a particular emphasis on the three-dimensional （3D） bio-integrated devices that mimic the 3D feature of tissue scaffolds. Moreover, neurons integrated with engineered nanostructures for wireless neuromodulation and dynamic neural output are briefly discussed. We also discuss the progress in the construction of cell-enabled soft robotics, where a tight coupling of the synthetic and biological parts is crucial for efficient function. Finally, we summarize the approaches for enhancing bio-integration with biomimetic micro- and nanostructures.

Nanoenabled Bioelectrical Modulation

CONSPECTUS:Studying the formation and interactions between biological systems and artificial materials is significant for probing complex biophysical behaviors and addressing challenging biomedical problems.Bioelectrical interfaces,especially nanostructure-based,have improved compatibility with cells and tissues and enabled new approaches to biological modulation.In particular,free-standing and remotely activated bioelectrical devices demonstrate potential for precise biophysical investigation and efficient clinical therapies.Interacting with single cells or organelles requires devices of sufficiently small size for high resolution probing.Nanoscale semiconductors,given their diverse functionalities,are promising device platforms for subcellular modulation.

Decoding the transcriptome and DNA methylome of human primordial germ cells

Primordial germ cells(PGCs)are the embryonic founder cells of the gametes—the oocytes and sperms that are vital for transmitting genetic information faithfully and efficiently from one generation to the next and for maintaining the continuation of a species[1].It is therefore critical to understand the crucial epigenetic processes during the de-

Did the Nationalist Government Manipulate the Chinese Bond Market？ A Quantitative Perspective on Short-Term Price Fluctuations of Domestic Government Bonds, 1932-1934

Based on a newly constructed set of data, this paper offers a quantitative perspective on the Nationalist Government＇s relations with China＇s domestic bond markets during the period 1932-34. For all the recent revisionist scholarship on the achievements of Nationalist state-building, the perception of the Nationalist elite as corrupt is still widely accepted. In order to demonstrate the empirical potential of quantitative financial history, this paper tests one particular assertion： that members of the Nationalist elite manipulated the issue price of domestic government bonds in order to enrich themselves and their associates. We test this by calculating two price data correlations： that of a first sample of government bonds, all of them issued before 1932, and that of a second sample of government bonds, which includes bonds issued during the period under review. The price fluctuations of the first sample are correlated with each other to a much higher degree than those of the second sample. This indicates that the prices of bonds in the first sample were reacting similarly to the same range of influences, while the bonds issued during the period under review and included in the second sample were displaying individual price fluctuations. One possible explanation for this is that members of the Nationalist elite enriched themselves or their associates by issuing domestic government bonds at artificially low prices. In sum, the article illustrates both the potential and the limitations of quantitative history： it allows us to test and dismiss a precisely formulated hypothesis about Nationalist corruption, but it is only one possible way in which statistical analysis can be applied and does not cover the wholeDid the Nationalist Government Manipulate the Chinese Bond Market？ realm of state practices

RNA m^(6)A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications

N^(6)-Methyladenosine(m^(6)A)RNA modification brings a new dawn for RNA modification researches in recent years.This posttranscriptional RNA modification is dynamic and reversible,and is regulated by methylases(“writers”),demethylases(“erasers”),and proteins that preferentially recognize m^(6)A modifications(“readers”).The change of RNA m^(6)A modification regulates RNA metabolism in eucaryon,including translation,splicing,exporting,decay,and processing.Thereby the dysregulation ofm^(6)A may lead to tumorigenesis and progression.Given the tumorigenic role of abnormalm^(6)A expression,m^(6)A regulators may function as potential clinical therapeutic targets for cancers.In this review,we emphasize on the underlying mechanisms of m^(6)A modifications in tumorigenesis and further introduce the potential m^(6)A regulators-associated therapeutic targets for tumor therapy.

Correction to:Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

CORRECTION TO:PROTEIN CELL(2021)HTTPS://DOI.ORG/10.1007/S13238-021-00837-8 In the original publication of the article figure 1 is incorrectly published.The correct Figure 1 is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit https://creativecommons.org/licenses/by/4.0/.

Revealing the nature of Pt-based immunotherapy through the lens of neoantigens in cancer

Metal elements play an important role in immune modulation[1,2], Pt-based drugs are broadly applied in the clinical treatment of different human tumors due to their superior clinical efficacy[3,4]. In recent years, the combination therapy of Pt-based chemotherapy and immunotherapy has demonstrated improved clinical outcomes in several types of cancer [5].