Discovering Cathodic Biocompatibility for Aqueous Zn–MnO_(2) Battery:An Integrating Biomass Carbon Strategy

Developing high-performance aqueous Zn-ion batteries from sustainable biomass becomes increasingly vital for large-scale energy storage in the foreseeable future.Therefore,γ-MnO_(2) uniformly loaded on N-doped carbon derived from grapefruit peel is successfully fabricated in this work,and particularly the composite cathode with carbon carrier quality percentage of 20 wt%delivers the specific capacity of 391.2 mAh g^(−1)at 0.1 A g^(−1),outstanding cyclic stability of 92.17%after 3000 cycles at 5 A g^(−1),and remarkable energy density of 553.12 Wh kg^(−1) together with superior coulombic efficiency of~100%.Additionally,the cathodic biosafety is further explored specifically through in vitro cell toxicity experiments,which verifies its tremendous potential in the application of clinical medicine.Besides,Zinc ion energy storage mechanism of the cathode is mainly discussed from the aspects of Jahn–Teller effect and Mn domains distribution combined with theoretical analysis and experimental data.Thus,a novel perspective of the conversion from biomass waste to biocompatible Mn-based cathode is successfully developed.

REDH:A database of RNA editome in hematopoietic differentiation and malignancy

Background:The conversion of adenosine(A)to inosine(I)through deamination is the prevailing form of RNA editing,impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species.Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases,providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets.However,the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking.Methods:We downloaded RNA sequencing(RNA-seq)data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information(NCBI)Gene Expression Omnibus(GEO)database,and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used.We performed sequence alignment,identified RNA editing sites,and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases.Results:We established a new database,"REDH",represents RNA editome in hematopoietic differentiation and malignancy.REDH is a curated database of associations between RNA editome and hematopoiesis.REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts(human).Through the Differentiation,Disease,Enrichment,and knowledge modules,each A-to-I editing site is systematically integrated,including its distribution throughout the genome,its clinical information(human sample),and functional editing sites under physiological and pathological conditions.Furthermore,REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control.Conclusions:REDH is accessible at http://www.redhdatabase.com/.This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies.It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Micro RNAs as lung cancer biomarkers

Lung cancer is the leading cause of cancer mortality worldwide. Its high mortality is due to the poor prognosis of the disease caused by a late disease presentation, tumor heterogeneities within histological subtypes, and the relatively limited understanding of tumor biology. Importantly, lung cancer histological subgroups respond differently to some chemotherapeutic substances and side effects of some therapies appear to vary between subgroups. Biomarkers able to stratify for the subtype of lung cancer, prognosticate the course of disease, or predict the response to treatment are in high demand. In the last decade, microR NAs(miR NAs), measured in resected tumor samples or in fine needle aspirate samples have emerged as biomarkers for tumor diagnosis, prognosis and prediction of response to treatment, due to the ease of their detection and in their extreme specificity. Moreover, miR NAs present in sputum, in plasma, in serum or in whole blood have increasingly been explored in the last five years as less invasive biomarkers for the early detection of cancers. In this review we cover the increasing amounts of datathat have accumulated in the last ten years on the use of miR NAs as lung cancer biomarkers.

Extending the spatiotemporal resolution of super-resolution microscopies using photomodulatable °uorescent proteins

In the past two decades,various super-resolution(SR)microscopy techniques have been developed to break the di®raction limit using subdi®raction excitation to spatially modulate the°uorescence emission.Photomodulatable°uorescent proteins(FPs)can be activated by light of speci¯c wavelengths to produce either stochastic or patterned subdi®raction excitation,resulting in improved optical resolution.In this review,we focus on the recently developed photomodulatable FPs or commonly used SR microscopies and discuss the concepts and strategies for optimizing and selecting the biochemical and photophysical properties of PMFPs to improve the spatiotemporal resolution of SR techniques,especially time-lapse live-cell SR techniques.

Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

Complicated target recognition by archaeal box C/D guide RNAs

Box C/D RNAs guide the site-specific formation of 2′-O-methylated nucleotides(Nm)of RNAs in eukaryotes and archaea.Although C/D RNAs have been profiled in several archaea,their targets have not been experimentally determined.Here,we mapped Nm in r RNAs,t RNAs,and abundant small RNAs(s RNAs)and profiled C/D RNAs in the crenarchaeon Sulfolobus islandicus.The targets of C/D RNAs were assigned by analysis of base-pairing interactions,in vitro modification assays,and gene deletion experiments,revealing a complicated landscape of C/D RNA-target interactions.C/D RNAs widely use dual antisense elements to target adjacent sites in r RNAs,enhancing modification at weakly bound sites.Two consecutive sites can be guided with the same antisense element upstream of box D or D′,a phenomenon known as doublespecificity that is exclusive to internal box D′in eukaryotic C/D RNAs.Several C/D RNAs guide modification at a single non-canonical site.This study reveals the global landscape of RNA-guided 2′-O-methylation in an archaeon and unexpected targeting rules employed by C/D RNA.

Defining two subpopulations of marginal zone B cells

Marginal zone(MZ)B cells,which are composed of heterogeneous subpopulations,are participate in the rapid response to antigens.Lee et al.showed that MZ B cells can be divided into two distinct subpopulations based on CD80 expression.These two subpopulations of MZ B cells exhibit differential autoreactivity,radiosensitivity,and functional capacities.

Steering Against Wind： A New Network of NamiRNAs and Enhancers

MicroRNAs （miRNAs） are a class of endogenous non-coding RNAs with regulatory functions. Traditionally, miRNAs are thought to play a negative regulatory role in the cytoplasm by binding to the YUTR of target genes to degrade mRNA or inhibit translation. However, it remains a challenge to interpret the potential function of many miRNAs located in the nucleus. Recently, we reported a new type of miRNAs present in the nucleus, which can activate gene expres- sion by binding to the enhancer, and named them nuclear activating miRNAs （NamiRNAs）. The discovery of NamiRNAs showcases a complementary regulatory mechanism of miRNA, demon- strating their differential roles in the nucleus and cytoplasm. Here, we reviewed miRNAs in nucleus to better understand the function of NamiRNAs in their interactions with the enhancers. Accord- ingly, we propose a NamiRNA--enhancer-target gene activation network model to better under- stand the crosstalk between NamiRNAs and enhancers in regulating gene transcription. Moreover, we hypothesize that NamiRNAs may be involved in cell identity or cell fate determina- tion during development, although further study is needed to elucidate the underlying mechanisms in detail.

Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent m6A demethylation of Nr4a1 mRNA

Group 3 innate lymphoid cells(ILC3s)play critical roles in innate immunity and gut homeostasis.However,how ILC3 homeostasis is regulated remains elusive.Here,we identified a novel circular RNA,circZbtb20,that is highly expressed in ILC3s and required for their maintenance and function.CircZbtb20 deletion causes reduced ILC3 numbers,increasing susceptibility to C.rodentium infection.Mechanistically,circZbtb20 enhances the interaction of Alkbh5 with Nr4a1 mRNA,leading to ablation of the m6A modification of Nr4a1 mRNA to promote its stability.Nr4a1 initiates Notch2 signaling activation,which contributes to the maintenance of ILC3 homeostasis.Deletion of Alkbh5 or Nr4a1 also impairs ILC3 homeostasis and increases susceptibilities to bacterial infection.Thus,our findings reveal an important role of circular RNA in the regulation of innate lymphoid cell homeostasis.

Role of Long Non-coding RNAs in Reprogramming to Induced Pluripotency

The generation of induced pluripotent stem cells through somatic cell reprogramming requires a global reorganization of cellular functions.This reorganization occurs in a multi-phased manner and involves a gradual revision of both the epigenome and transcriptome.Recent studies have shown that the large-scale transcriptional changes observed during reprogramming also apply to long noncoding RNAs(lncR NAs),a type of traditionally neglected RNA species that are increasingly viewed as critical regulators of cellular function.Deeper understanding of lncR NAs in reprogramming may not only help to improve this process but also have implications for studying cell plasticity in other contexts,such as development,aging,and cancer.In this review,we summarize the current progress made in profiling and analyzing the role of lncR NAs in various phases of somatic cell reprogramming,with emphasis on the re-establishment of the pluripotency gene network and X chromosome reactivation.

Viral miRNA-mediated activation of hyaluronan production as a drug target against COVID-19

The global coronavirus disease 2019(COVID-19)pandemic has caused more than 6.1 million deaths until March 24,2022,as reported by the World Health Organization(WHO).Recently,breakthrough infections have appeared in individuals fully vaccinated against SARS-Co V-2^(1),which could be attributed to the rapid mutation of the RNA virus2.Currently,following the Delta variant,the Omicron variant of SARS-Co V-2 is increasingly becoming the dominant epidemic strain in the world.

Anti-CRISPRs: The natural inhibitors for CRISPR-Cas systems

CRISPR (clustered regularly interspaced short palindromic repeats)‐Cas (CRISPR associated protein) systems serve as the adaptive immune system by which prokaryotes defend themselves against phages. It has also been developed into a series of powerful gene‐editing tools. As the natural inhibitors of CRISPR‐Cas systems, anti‐CRISPRs (Acrs) can be used as the “off‐switch” for CRISPR‐Cas systems to limit the off‐target effects caused by Cas9. Since the discovery of CRISPR‐Cas systems, much research has focused on the identification, mechanisms and applications of Acrs. In light of the rapid development and scientific significance of this field, this review summarizes the history and research status of Acrs, and considers future applications.

AlphaFold2 and its applications in the fields of biology and medicine

AlphaFold2(AF2)is an artificial intelligence(AI)system developed by DeepMind that can predict three-dimensional(3D)structures of proteins from amino acid sequences with atomic-level accuracy.Protein structure prediction is one of the most challenging problems in computational biology and chemistry,and has puzzled scientists for 50 years.The advent of AF2 presents an unprecedented progress in protein structure prediction and has attracted much attention.Subsequent release of structures of more than 200 million proteins predicted by AF2 further aroused great enthusiasm in the science community,especially in the fields of biology and medicine.AF2 is thought to have a significant impact on structural biology and research areas that need protein structure information,such as drug discovery,protein design,prediction of protein function,et al.Though the time is not long since AF2 was developed,there are already quite a few application studies of AF2 in the fields of biology and medicine,with many of them having preliminarily proved the potential of AF2.To better understand AF2 and promote its applications,we will in this article summarize the principle and system architecture of AF2 as well as the recipe of its success,and particularly focus on reviewing its applications in the fields of biology and medicine.Limitations of current AF2 prediction will also be discussed.

Structural insights reveal the specific recognition of meiRNA by the Mei2 protein

In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sme2 gene locus,which encodes meiRNA.Previous research has shown that the Mei2 C-terminal RNA recognition motif(RRM3)physically interacts with the meiRNA 5'region in vitro and stimulates meiosis in vivo.However,the underlying mechanisms still remain elusive.We first employed an in vitro crosslinking and immunoprecipitation sequencing(CLIP-seq)assay and demonstrated a preference for U-rich motifs of meiRNA by Mei2 RRM3.We then solved the crystal structures of Mei2 RRM3 in the apo form and complex with an 8 mer RNA fragment,derived from meiRNA,as detected by in vitro CLIP-seq.These results provide structural insights into the Mei2 RRM3-meiRNA complex and reveal that Mei2 RRM3 binds specifically to the Uuc(U)sequence.Furthermore,a structure-based Mei2 mutation,Mei2F644A causes defective karyogamy,suggesting an essential role of the RNA-binding ability of Mei2 in regulating meiosis.

Mechanosensing via Immunereceptors

The immune response is orchestrated by a variety of immune cells,the function of which then is determined by the collective signals from different immunoreceptors.Recent studies have highlighted the presence of mechanical force on these receptor-ligand pairs and its important role in regulating antigen recognition/discrimination and function.In this perspective,we use the T cell receptor as an example to review the current understanding of the mechanosensing properties of immunoreceptors.We discuss the types of forces that immunoreceptors may encounter,the effects on ligand recognition,conformational changes and mechanosensing mechanisms,as well as the consequences in downstream signal transduction and function.

Identification and analysis of intermediate-size noncoding RNAs in the rhesus macaque fetal brain

Although only about 2%of the human genome has proved to be protein-coding genes,recent advances in genome wide analysis have revealed that the majority of the genome is transcribed,mainly from noncoding segments that were once considered＂junk sequences＂or＂dark matters＂（Liu et al.,2011a;Zhang et al.,2014b）. In addition to the well-characterized housekeeping non- coding RNAs （ncRNAs） （tRNA, rRNA, small nuclear RNA and small nucleolar RNAs） and some small regulatory ncRNAs （microRNAs and small interfering RNAs）, the transcriptome of mammals could also pervasively have been transcribed long noncoding RNAs （lncRNAs, at least 200 nt） （Rinn and Chang, 2012; Xie et al., 2012）.

NP-23 Cascade Events for Delayed Postoperative Cognitive Dysfunction

Background:Postoperative cognitive dysfunction(POCD)can occur in patients with cardiac and non-cardiac surgeries.About 20%to 40%patients develop POCD at hospital discharge(a few days after surgery,acute POCD)and 10%elderly patients(>60 years old)have POCD at 3 months after surgery(delayed POCD).Age and degree of education are risk factors for delayed POCD.It has been shown that POCD is associated with increased mortality.Patients with POCD have a longer hospital stay and an increased rate of leaving job market.Thus,POCD is a very significant clinical syndrome during the perioperative period,which is recognized only in recent years.We and others have shown that neuroinflammation is a critical neuropathological process for POCD.However,neuroinflammation lasts for a few days after surgery.It is not known how such a short-lived neuropathological process lead to POCD a few months after surgery.To address this issue,a series of experiments were performed in my laboratory.Methods:Rats or mice were subjected to common carotid arterial exposure,a surgical component of carotid endarterectomy that is often performed in elderly patients.Their learning and memory were assessed at least one week after surgery.Their blood and brain tissues were harvested at various time after surgery for biochemical and structural analyses.Results:The surgery induced an increase of proinflammatory cytokines in the blood.The surgery also increased the expression of active matrix metallopeptidase 9(MMP-9)and its activity in the brain.This surgery induced POCD and neuroinflammation in wild-type mice but not in the MMP-9 knockout mice.P2X7 receptors and inflammasome were activated by the surgery.Inhibition of P2X7 receptors and P2X7 receptor knockout abolished POCD and neuroinflammation after surgery.The surgery decreased growth factor production and inhibition of neuroinflammation attenuated this decrease.The decreased growth factor expression occurred at 3 to 5 days after the surgery.Surgery increased histone deacetylase activity and inhibition of histone deacetylase attenuated the decrease of growth factor expression and the development of POCD.The surgery decreased neurogenesis in the hippocampus and application of growth factors to the brain attenuated this decrease and POCD.This decreased neurogenesis was observed 3 weeks after surgery.Finally,surgery impaired dendritic arborization that was assessed 3 weeks after surgery.Inhibition of histone deacetylases attenuated this impairment and POCD.Conclusion:Surgery induces a delayed POCD in rodents.Surgery results in systemic inflammation,which then activates MMP-9 to damage the brain-blood barrier to facilitate the systemic inflammation to be transmitted to the brain.Proinflammatory signals in the blood activate P2X7 receptors to induce neuroinflammation that inhibits growth factor expression through epigenetic regulation.Reduced growth factor expression results in decreased neurogenesis and dendritic arborization that then ultimately lead to the delayed POCD.Thus,surgery activates a series of cascade events to induce the delayed POCD.

ADAR1:a mast regulator of aging and immunity

Recently,Nature and Nature Cell Biology published five papers on the function and molecular mechanism of ADAR1(adenosine deaminases acting on RNA)in aging,cancer,and autoimmune diseases.1,2,3,4,5 Among them,four papers published in Nature revealed that ADAR1 regulates autoimmune disease and cancer immunotherapy through canonical adenosine-to-inosine(A-to-I)RNA editing.

秀丽隐杆线虫RNA结合蛋白复合物AMG-1/SLRP-1通过线粒体稳态维持实现调控生殖腺发育和精子发生

RNA结合蛋白(mtRBP)介导的mRNA转录后调节对精子发生必不可少但却鲜有报道.在本文中,我们鉴定到一个在生殖腺中特异性表达的线粒体RNA结合蛋白AMG-1,它是秀丽隐杆线虫精子发生过程中必需的蛋白,同时与哺乳动物LRPPRC蛋白同源.amg-1突变会阻碍生殖腺的发育,最终导致生殖细胞的线粒体形态和结构异常以及线粒体功能障碍.通过测序鉴定RNA结合蛋白的靶点发现,AMG-1更倾向于与mtDNA编码的参与线粒体核糖体组装的12S和16S核糖体RNA(rRNA)结合,12S rRNA对于维持生殖细胞线粒体蛋白稳态至关重要,而12S rRNA的表达却受AMG-1蛋白调节.此外,哺乳动物SLIRP在秀丽线虫中的同源蛋白SLRP-1蛋白与AMG-1在遗传上存在互作关系,它们可共同调节秀丽线虫的精子发生和育性.综上所述,这些发现揭示了mtRBP蛋白AMG-1在线粒体调控中的新机制,这可能为由线粒体功能障碍引发的男性不育治疗提供新的理论基础.

RNA biology and therapeutics

Eukaryotic genomes undergo pervasive transcription,generating vast amounts of noncoding RNAs alongside protein-coding mRNAs[1].These noncoding RNAs,including small noncoding RNAs,long noncoding RNAs(lncRNAs),and circular RNAs,have been shown to play critical roles in gene regulation,chromatin remodeling,assembly of membraneless organelles,and other essential biological processes.They function through a diverse range of mechanisms[2],[3],[4],[5].Dysregulation of noncoding RNAs contributes to human disease pathogenesis and affects plant development and stress response[6],[7],[8].Over the past decade,significant progress has been made in unraveling the functions of noncoding RNAs and elucidating the molecular mechanisms by which they operate.The involvement of noncoding RNAs in human disease pathogenesis and agronomic trait regulation has garnered increasing attention.