The avascular nature of cartilage and the hostile post-injury microenvironment severely limit its intrinsic regenerative capacity. Tissue engineering technology based on three-dimensional bioprinting offers a promising strategy. However, the development of functional bioinks capable of spatiotemporally regulating cellular behaviors and the regenerative microenvironment remains a significant challenge. Here, we reported a multifunctional bioink integrating magnetic responsiveness, antioxidant activity, and pro-chondrogenic capability, constructed by incorporating tannic acid-modified iron oxide nanoparticles (TIO NPs) into a hyaluronic acid/gelatin-based biomimetic matrix. Excellent shear-thinning behavior and rapid photo-crosslinking characteristic enabled the bioink to achieve high-resolution bioprinting. Moreover, the incorporation of TIO NPs enhanced the mechanical properties of hydrogels by forming dynamic hydrogen-bonding networks and endowed them with potent antioxidant capability, effectively protecting the encapsulated cells from oxidative stress. In vitro results demonstrated that the printed hydrogels significantly promoted cell adhesion, proliferation, and chondrogenic differentiation under external magnetic stimulation. In vivo studies further confirmed that the combination of cell-laden printed hydrogels with magnetic stimulation markedly enhanced the deposition of glycosaminoglycan and type II collagen, while suppressing the expression of type I collagen and inflammatory factor, thereby accelerating the repair of rabbit cartilage defects. This work presents a remote physical field-regulated strategy for intelligent cartilage regeneration.

As a critical stage in chronic liver disease, liver fibrosis can progress to irreversible damage without timely intervention. Stem cell therapy offers significant therapeutic potential owing to its potent regenerative and immunomodulatory properties. However, its clinical application is challenged by low cell survival, poor targeting, and inadequate paracrine regulation. Here, we present a magnetic hydrogel patch laden with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) to enhance their antifibrotic efficacy via synergistic magneto-mechanical stimulation. The patch is fabricated through thiol-ene "click" chemistry using multi-thiol-functionalized magnetic nanoparticles as crosslinkers. Molecular dynamics simulations reveal the regulatory mechanism of nanoparticle concentration on the crosslinking topology of the hydrogel network, thereby identifying the optimal formulation with favorable mechanical properties and magnetic responsiveness. Under magneto-mechanical stimulation, the resulting patch significantly enhances the secretion of key antifibrotic factors from hUC-MSCs by activating the PI3K/Akt/mTOR signaling pathway. Moreover, in vitro and in vivo results demonstrate that, under magnetic stimulation, the hUC-MSC-laden magnetic patch significantly inhibits hepatic stellate cell activation, promotes anti-inflammatory macrophage polarization, reduces collagen deposition, and ameliorates the inflammatory microenvironment, thereby effectively reversing liver fibrosis. This study offers a versatile stem cell-based platform for spatiotemporally controlled therapy of liver fibrosis and potentially other fibrotic diseases.

Motivation Editome Disease Knowledgebase (EDK) is a curated resource of knowledge between RNA editome and human diseases. Since its first release in 2018, a number of studies have discovered previously uncharacterized editome-disease associations and generated an abundance of RNA editing datasets. Thus, it is desirable to make significant updates for EDK by incorporating more editome-disease associations as well as their related editing profiles. Results Here, we present EDK v2.0, an updated version of editome-disease associations based on both literature curation and integrative analysis. EDK v2.0 incorporates a curated collection of 1,097 editome-disease associations involving 115 diseases from 321 publications. Meanwhile, based on a standardized pipeline, EDK v2.0 provides RNA editing profiles from 48 datasets covering 2,536 samples across 55 diseases. Through differential analysis on RNA editing, it further identifies a total of 7,190 differential edited genes and 86,242 differential editing sites (DESs), leading to 266,339 DES-disease associations. Moreover, a curated list of 28,160 cis-RNA editing QTL associations, 458,187 DES-RNA binding protein associations, and 21 DES-RNA secondary structure associations are annotated and added to EDK v2.0. Additionally, it is equipped with a series of user-friendly tools to facilitate RNA-editing online analysis. Availability and implementation https://ngdc.cncb.ac.cn/edk/.

Persistent inflammatory episodes driven by immune cell dysregulation pose a formidable clinical challenge in diabetic wound healing. Sustained and coordinated regulation of the immune niche within diabetic wounds is critical for tissue regeneration. Here, we develop a programmed therapeutic strategy based on arginine-lysine-methionine third-generation dendrimeric polypeptides whose dopamine-coated surfaces contain ferrous ions (G3D-Pmet25@PDA) to reprogram the immune niche. G3D-Pmet25@PDA exhibits a core-shell structure: ferrous ions on the surface are rapidly released under near-infrared (NIR) laser irradiation, while methionine chains encapsulated within the dopamine shell undergo a reactive oxygen species (ROS) triggered hydrophilic transition that liberates arginine for cascade release. Under NIR laser irradiation, G3D-Pmet25@PDA initiates a clearance program targeting dysregulated immune cells and concurrently reprograms the energy metabolism of newly recruited immune cells, thereby reshaping the immune niche to alleviate inflammation and activate tissue-regenerative programs for accelerated healing. Moreover, sustained low-dose nitric oxide release caused by arginine accelerates angiogenesis, which is beneficial for tissue regeneration. These findings expand the perspective on the intricate coordination of the immune system in diabetic wound repair and reveal new strategies for novel immunomodulatory biomaterials.

Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Cuyo (FCA-UNCuyo), Almirante Brown 500, M5528AHB, Chacras de Coria 5507, Mendoza, Argentina Most classes of nascent plant primary RNAs must be modified or processed in various ways to be converted to their mature forms. RNA processing is the term collectively used to describe the series of events required to produce functional RNAs. During co-and post-transcriptional regulatory stages, RNA processing such as splicing, editing, 5' capping, 3'-end polyadenylation, nucleolytic To present an overview of the fundamental discoveries related to the processing and modification of various classes of plant RNAs, which can generate new insights into the biological roles and underlying regulatory mechanisms of RNA processing in plant biological systems, the research topic of Frontiers in Plant Science on "Biological Roles of RNA Processing and its Regulations in Plants" presents 3 original research articles and 1 review report.The first article was on the roles of RNA splicing in the development of maize seed, the second one reported RNA editing's impacts on rice drought tolerance, the third one identified lncRNAs that may be involved in rose floral scent synthesis, and the fourth one reviewed the production and regulation of miRNA in Arabidopsis thaliana.Maturases regulating RNA splicing play key roles in plant development.

Abnormal cardiac development has been observed in individuals with Cornelia de Lange syndrome (CdLS) due to mutations in genes encoding members of the cohesin complex. However, the precise role of cohesin in heart development remains elusive. In this study, we aimed to elucidate the indispensable role of SMC3, a component of the cohesin complex, in cardiac development and its underlying mechanism. Our investigation revealed that CdLS patients with SMC3 mutations have high rates of congenital heart disease (CHD). We utilized heart-specific Smc3-knockout (SMC3-cKO) mice, which exhibit varying degrees of outflow tract (OFT) abnormalities, to further explore this relationship. Additionally, we identified 16 rare SMC3 variants with potential pathogenicity in individuals with isolated CHD. By employing single-nucleus RNA sequencing and chromosome conformation capture high-throughput genome-wide translocation sequencing, we revealed that Smc3 deletion downregulates the expression of key genes, including Ets2, in OFT cardiac muscle cells by specifically decreasing interactions between super-enhancers (SEs) and promoters. Notably, Ets2-SE-null mice also exhibit delayed OFT development in the heart. Our research revealed a novel role for SMC3 in heart development via the regulation of SE-associated genes, suggesting its potential relevance as a CHD-related gene and providing crucial insights into the molecular basis of cardiac development. Understanding heart development is vital as defects in this process are a major cause of birth abnormalities. This study focuses on a protein, SMC3, and its role in heart development. Experiments were conducted on mice genetically altered to lack SMC3 in heart cells. Researchers found that mice without SMC3 had various heart defects, like those seen in humans with congenital heart disease. They also found mutations in the SMC3 gene in patients with congenital heart disease, suggesting a link between SMC3 and heart development in humans. The findings reveal that SMC3 plays a crucial role in heart development, with its absence leading to significant heart defects in mice. These results suggest a potential genetic cause for some forms of congenital heart disease in humans.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.Introduction

The rapid advancement of sequencing technologies poses challenges in managing the large volume and exponential growth of sequence data efficiently and on time. To address this issue, we present GenBase (https://ngdc.cncb.ac.cn/genbase), an open-access data repository that follows the International Nucleotide Sequence Database Collaboration (INSDC) data standards and structures, for efficient nucleotide sequence archiving, searching, and sharing. As a core resource within the National Genomics Data Center (NGDC), of the China National Center for Bioinformation (CNCB; https://ngdc.cncb.ac.cn), GenBase offers bilingual submission pipeline and services, as well as local submission assistance in China. GenBase also provides a unique Excel format for metadata description and feature annotation of nucleotide sequences, along with a real-time data validation system to streamline sequence submissions. As of April 23, 2024, GenBase received 68,251 nucleotide sequences and 689,574 annotated protein sequences across 414 species from 2319 submissions. Out of these, 63,614 (93%) nucleotide sequences and 620,640 (90%) annotated protein sequences have been released and are publicly accessible through GenBase’s web search system, File Transfer Protocol (FTP), and Application Programming Interface (API). Additionally, in collaboration with INSDC, GenBase has constructed an effective data exchange mechanism with GenBank and started sharing released nucleotide sequences. Furthermore, GenBase integrates all sequences from GenBank with daily updates, demonstrating its commitment to actively contributing to global sequence data management and sharing.

AbstractBiomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals’ biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein–protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA–miRNA–mRNA associations, lncRNA–miRNA associations and protein–protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.

Genomic data serve as an invaluable resource for unraveling the intricacies of the higher plant systems, including the constituent elements within and among species. Through various efforts in genomic data archiving, integrative analysis and value-added curation, the National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), has successfully established and currently maintains a vast amount of database resources. This dedicated initiative of the NGDC facilitates a data-rich ecosystem that greatly strengthens and supports genomic research efforts. Here, we present a comprehensive overview of central repositories dedicated to archiving, presenting, and sharing plant omics data, introduce knowledgebases focused on variants or gene-based functional insights, highlight species-specific multiple omics database resources, and briefly review the online application tools. We intend that this review can be used as a guide map for plant researchers wishing to select effective data resources from the NGDC for their specific areas of study.

The number of patients with non-healing wounds continuously increases, and has become a prominent societal issue that imposes a heavy burden on both patients and the entire healthcare system. Although traditional dressings play an important role in wound healing, the complexity and diversity of the healing process pose serious challenges in this field. Magneto-responsive biocomposites, with their excellent biocompatibility, remote spatiotemporal controllability, and unique convenience, demonstrate enticing advantages in the field of wound dressings. However, current research on magneto-responsive biocomposites as wound dressings lacks comprehensive and in-depth reviews, which to some extent, restricts the deeper understanding and further development of this field. Based on this, this paper reviews the latest advances in magnetic responsive wound dressings for wound healing. First, we review the process of skin wound healing and parameters for assessing repair progress. Then, we systematically discuss the preparation strategies and unique characteristics of magneto-responsive biocomposites, focusing on magneto-induced orientation, magneto-induced mechanical stimulation, and magnetocaloric effect. Subsequently, this review elaborates the multiple mechanisms of magneto-responsive biocomposites in promoting wound healing, including regulating cell behavior, enhancing electrical signal, controlling drug release, and accelerating tissue reconstruction. Finally, we further propose the development direction and future challenges of magnetic responsive biomaterials as wound dressings in clinical application. Schematic illustrations of the pathways through which magneto-responsive biocomposites promote wound healing.

Homology is fundamental to infer genes' evolutionary processes and relationships with shared ancestry. Existing homolog gene resources vary in terms of inferring methods, homologous relationship and identifiers, posing inevitable difficulties for choosing and mapping homology results from one to another. Here, we present HGD (Homologous Gene Database, https://ngdc.cncb.ac.cn/hgd), a comprehensive homologs resource integrating multi-species, multi-resources and multi-omics, as a complement to existing resources providing public and one-stop data service. Currently, HGD houses a total of 112 383 644 homologous pairs for 37 species, including 19 animals, 16 plants and 2 microorganisms. Meanwhile, HGD integrates various annotations from public resources, including 16 909 homologs with traits, 276 670 homologs with variants, 398 573 homologs with expression and 536 852 homologs with gene ontology (GO) annotations. HGD provides a wide range of omics gene function annotations to help users gain a deeper understanding of gene function.

Many soft tissues of the human body possess hierarchically anisotropic structures, exhibiting orientation-specific mechanical properties and biological functionality. Hydrogels have been proposed as promising scaffold materials for tissue engineering applications due to their water-rich composition, excellent biocompatibility, and tunable physico-chemical properties. However, conventional hydrogels with homogeneous structures often exhibit isotropic properties that differ from those of biological tissues, limiting their further application. Recently, magnetically anisotropic hydrogels containing long-range ordered magneto-structures have attracted widespread interest owing to their highly controllable assembly strategy, rapid magnetic responsiveness and remote spatiotemporal regulation. In this review, we summarize the latest progress of magnetically anisotropic hydrogels for tissue engineering. The fabrication strategy of magnetically anisotropic hydrogels from magnetic nanofillers with different dimensions is systemically introduced. Then, the effects of magnetically anisotropic cues on the physicochemical properties of hydrogels and the cellular biological behavior are discussed. And the applications of magnetically anisotropic hydrogels in the engineering of different tissues are emphasized. Finally, the current challenges and the future perspectives for magnetically anisotropic hydrogels are presented.

Magnetically actuated mechanical stimulation, as a novel form of intelligent responsive force stimulation, has a great potential for remote spatiotemporal regulation of a variety of life processes. Hence, the optimal design of magnetic nanomaterials for generating magneto-mechanical stimuli becomes an important driving force in the development of magneto-controlled biotherapy. This study aims to clarify the general rule that the surface modification amount of magnetic nanoparticles (NPs) affects the biological behavior (e.g., cell adhesion, proliferation and differentiation) of pre-osteoblast cells. First of all, course-grained molecular dynamics simulations predict that 23.3% graft modification of the NPs can maximize the heterogeneity of the dynamics of the polymer matrix, which may generate enhanced mechanical stimuli. Then, experimentally, iron oxide (IO) NPs grafted with different amounts of poly(γ-benzyl-L-glutamate) (PBLG) were prepared to obtain homogeneous magnetic nanocomposites with improved mechanical properties. Further in vitro cell experiments demonstrate that the grafting amounts of 21.46% and 32.34% of PBLG on IO NPs are the most beneficial for the adhesion and osteogenic differentiation of cells. Simultaneously, the maximized upregulation of the Piezo1 gene indicates that the cells receive the strongest magneto-mechanical stimuli. The consistent conclusion of the experiments and simulations indicates that 20-30% PBLG grafted on the IO surface could maximize the ability of magnetic stimuli to regulate the biological behavior of the cells, which validates the feasibility of simulation auxiliary material design and is of great importance for promoting the application of magneto-controlled biotherapy in bioengineering and biomedicine.

The emergence and innovation of three-dimensional (3D) bioprinting provide new development opportunities for tissue engineering and regenerative medicine. However, how to obtain bioinks with both biomimicry and manufacturability remains a great issue in 3D bioprinting. Developing intelligent responsive biomaterials is conducive to break through the current dilemma. Herein, a stepwise multi-cross-linking strategy concerning thermosensitive thiolated Pluronic F127 (PF127-SH) and hyaluronic acid methacrylate (HAMA) is proposed to achieve temperature-controlled 3D embedded bioprinting, specifically pre-cross-linking (Michael addition reaction) at low temperatures (4-20 °C) and subsequently self-assembly (hydrophobic interaction) in a high-temperature (30-37 °C) suspension bath as well as final photo-cross-linking (mainly thiol-ene "click" reaction). The unique stepwise cross-linking mechanism promises the thermosensitive bioink appropriate viscosity at different printing stages, making it possible to print complex structures with excellent shape fidelity and simultaneously maintain the biological activity of cells. In vitro studies reveal that 3D-printed hydrogels are beneficial for enhancing cell viability. Further, in vivo experiments demonstrate that cell-laden printed hydrogels significantly promote wound healing and re-epithelialization by modulating inflammation and accelerating collagen deposition and angiogenesis. Therefore, the proposed stepwise multi-cross-linking strategy is expected to accelerate the development of novel bioinks and promote the clinical applications of 3D bioprinting.

Thermodynamic behavior of polymer chains out of equilibrium is a fundamental problem in both polymer physics and biological physics. By using molecular dynamics simulation, we discover a general non-equilibrium mechanism that controls the conformation and dynamics of polar active polymer, i.e., head activity commands the overall chain activity, resulting in re-entrant swelling of active chains and non-monotonic variation of Flory exponent $\nu$. These intriguing phenomena lie in the head-controlled railway motion of polar active polymer, from which two oppose non-equilibrium effects emerge, i.e., dynamic chain rigidity and the involution of chain conformation characterized by the negative bond vector correlation. The competition between these two effects determines the polymer configuration. Moreover, we identify several generic dynamic features of polar active polymers, i.e., linear decay of the end-to-end vector correlation function, polymer-size dependent crossover from ballistic to diffusive dynamics, and a polymer-length independent diffusion coefficient that is sensitive to head activity. A simple dynamic theory is proposed to faithfully explain these interesting dynamic phenomena. This sensitive structural and dynamical response of active polymer to its head activity provides us a practical way to control active-agents with applications in biomedical engineering.

Excessive inflammation, bacterial infection, and blocked angiogenesis make diabetic wound healing challenging. Multifunctional wound dressings have several advantages in diabetic wound healing. In addition, the pH regulation of the microenvironment is shown to be a key factor that promotes skin regeneration through cellular immune regulation. However, few reports have focused on the development of functional dressings with the ability to regulate the pH microenvironment and promote diabetic wound healing. This study presents a novel approach for regulating the pH microenvironment of diabetic wound sites using a glycopeptide‐based hydrogel consisting of modified hyaluronic acid and poly(6‐aminocaproic acid). This hydrogel forms a network through Schiff base interactions and metal complexation, which suppresses inflammation and accelerates angiogenesis during wound healing. Hydrogels not only have adequate mechanical properties and self‐healing ability but can also support tissue adhesion. They can also promote the secretion of inducible cAMP early repressor, which promotes the polarization of macrophages toward the M2 type. The in vivo results confirm that hydrogel promotes diabetic wound repair and skin regeneration by exerting rapid anti‐inflammatory effects and promoting angiogenesis. Therefore, this hydrogel system represents an effective strategy for treating diabetic wounds.

Viruses rely on hosts for life and reproduction, cause a variety of symptoms from common cold to AIDS to COVID-19 and provoke public health threats claiming millions of lives around the globe. RNA editing, as a crucial co-/post-transcriptional modification inducing nucleotide alterations on both endogenous and exogenous RNA sequences, exerts significant influences on virus replication, protein synthesis, infectivity and toxicity. Hitherto, a number of host-mediated RNA editing sites have been identified in diverse viruses, yet lacking a full picture of RNA editing-associated mechanisms and effects in different classes of viruses. Here we synthesize the current knowledge of host-mediated RNA editing in a variety of viruses by considering two enzyme families, viz., ADARs and APOBECs, thereby presenting a landscape of diverse editing mechanisms and effects between viruses and hosts. In the ongoing pandemic, our study promises to provide potentially valuable insights for better understanding host-mediated RNA editing on ever-reported and newly-emerging viruses.

Three-dimensional (3D) bioprinting is a promising technique to construct heterogeneous architectures that mimic cell microenvironment. However, the current bioinks for 3D bioprinting usually show some limitations, such as low printing accuracy, unsatisfactory mechanical properties and compromised cytocompatibility. Herein, a novel bioink comprising hydroxyphenyl propionic acid-conjugated gelatin and tyramine-modified alginate is developed for printing 3D constructs. The bioink takes advantage of an ionic/covalent intertwined network that combines covalent bonds formed by photo-mediated redox reaction and ionic bonds formed by chelate effect. Benefiting from the thermosensitivity of gelatin and the double-crosslinking mechanism, the developed bioink shows controllable rheological behaviors, enhanced mechanical behavior, improved printing accuracy and structure stability. Moreover, the printed cell-laden hydrogels exhibit a homogeneous cell distribution and considerable cell survival because the pre-crosslinking of the bioink prevents cellular sedimentation and the visible light crosslinking mechanism preserves cell viability. Further in vivo studies demonstrate that resulting cell-laden hydrogels are beneficial for the reduction of inflammation response and the promotion of collagen deposition and angiogenesis, thereby improving the quality of skin wound healing. This convenient and effective strategy is of great significance for accelerating the development of multifunctional bioinks and broadening the biomedical applications of 3D bioprinting.