Endogenous Signals Research Articles

Effect of Octamer-Binding Transcription Factor 4 Overexpression on the Neural Induction of Human Dental Pulp Stem Cells

Stem cell-based therapy is a potential alternative strategy for brain repair, with neural stem cells (NSC) presenting as the most promising candidates. Obtaining sufficient quantities of NSC for clinical applications is challenging, therefore alternative cell types, such as neural crest-derived dental pulp stem cells (DPSC), may be considered. Human DPSC possess neurogenic potential, exerting positive effects in the damaged brain through paracrine effects. However, a method for conversion of DPSC into NSC has yet to be developed. Here, overexpression of octamer-binding transcription factor 4 (OCT4) in combination with neural inductive conditions was used to reprogram human DPSC along the neural lineage. The reprogrammed DPSC demonstrated a neuronal-like phenotype, with increased expression levels of neural markers, limited capacity for sphere formation, and enhanced neuronal but not glial differentiation. Transcriptomic analysis further highlighted the expression of genes associated with neural and neuronal functions. In vivo analysis using a developmental avian model showed that implanted DPSC survived in the developing central nervous system and respond to endogenous signals, displaying neuronal phenotypes. Therefore, OCT4 enhances the neural potential of DPSC, which exhibited characteristics aligning with neuronal progenitors. This method can be used to standardise DPSC neural induction and provide an alternative source of neural cell types.Graphical

Role of Potential Plant Hormones for Activation and Enhancing Physiological Processes, Growth and Development

Plant hormones are chemicals that are present in small amounts, influence and promote the division, growth, and maturation of cells and tissues. Salicylic acid is a phenolic phytohormone and has a function in growth/development, photosynthesis, transpiration, ion absorption, and transport. By interfering with endogenous signals, SA mediates plant defense against pathogens. It strengthens the body's defenses against infections by promoting the production of pathogenesis-related proteins. It affects the systemic acquired resistance (SAR) pathway, wherein a pathogenic assault on one. Water deficiency affects during tillering, head emergence, filling of grain and maturity water deficiency of wheat. Concentration of carotenoids more during drought stress and that produced for drought tolerance enhancement in bread wheat. Water shortage on pigment contents of photosynthesis, relative water amount, shot weight in dried form, flag leaf area specific mass, parameters for gas exchange, physiological parameters and yield. Drought there more significant reduction in tillers/plant, fertile tillers/plant, length of spike, yield/spike and thousand kernel weight of wheat cultivars during drought conditions as compared with normal irrigation conditions. Polyamine exogenously via spray during grain filling condition. The water deficiency spermidine and spermine reduced the inhibition caused by water deficiency when polyamine had applied.

Abstract WP162: Myelin Suppresses Macrophage Responses to Diverse Stimuli

Introduction: In intracerebral hemorrhage (ICH), blood-derived macrophages initially contribute to a neurotoxic inflammatory response. Understanding the endogenous signals that control this response could help limit these effects. Uptake of myelin debris limits macrophage inflammatory cytokine production in response to LPS, possibly due to the cholesterol present in myelin. However, the pathways by which myelin suppresses macrophage responses and the broader impacts of myelin on macrophage phenotype are poorly understood. Methods and Results: RNA sequencing was used to examine impacts of myelin in diverse conditions. BMDMs were pretreated with myelin, cholesterol or T0901317, an agonist of the cholesterol-response transcription factor LXR. The cells were stimulated with Type I cytokines, Type II cytokines, and different TLR agonists to mimic the diverse stimuli encountered in the inflamed brain (Fig 1A). Myelin suppressed responses to all stimulations, as did T0901317. Cholesterol suppressed the response to LPS and had little effect on other stimulations, including the ICH-relevant alarmin S100A9 (Fig 2). Gene Ontology Enrichment showed that many of the inflammatory gene pathways suppressed by myelin were unique for each stimulation although lipid metabolism pathways were shared across stimulations. Conclusions: Myelin broadly limits macrophage responses to diverse stimulations, partially though not completely through cholesterol and activation of LXR. Cholesterol does not suppress the response to S100A9, suggesting that other components of myelin or activation of phagocytic receptors contribute to suppression of the macrophage response during ICH.

SUPPRESSOR OF MAX2 1-LIKE (SMXL) homologs are MAX2-dependent repressors of Physcomitrium patens growth.

SUPPRESSOR OF MAX2 (SMAX)1-LIKE (SMXL) proteins are a plant-specific clade of type I HSP100/Clp-ATPases. SMXL genes are present in virtually all land plant genomes. However, they have mainly been studied in angiosperms. In Arabidopsis (Arabidopsis thaliana), 3 functional SMXL subclades have been identified: SMAX1/SMXL2, SMXL345, and SMXL678. Of these, 2 subclades ensure endogenous phytohormone signal transduction. SMAX1/SMXL2 proteins are involved in KAI2 ligand (KL) signaling, while SMXL678 proteins are involved in strigolactone (SL) signaling. Many questions remain regarding the mode of action of these proteins, as well as their ancestral roles. We addressed these questions by investigating the functions of the 4 SMXL genes in the moss Physcomitrium patens. We demonstrate that PpSMXL proteins are involved in the conserved ancestral MAX2-dependent KL signaling pathway and negatively regulate growth. However, PpSMXL proteins expressed in Arabidopsis cannot replace SMAX1 or SMXL2 function in KL signaling, whereas they can functionally replace SMXL4 and SMXL5 and restore root growth. Therefore, the molecular functions of SMXL proteins are conserved, but their interaction networks are not. Moreover, the PpSMXLC/D clade positively regulates SL signal transduction in P. patens. Overall, our data reveal that SMXL proteins in moss mediate crosstalk between the SL and KL signaling pathways.

A Less-is-More Strategy for Mitochondria-Targeted Photodynamic Therapy of Rheumatoid Arthritis.

Conventional photodynamic therapy (PDT) of rheumatoid arthritis (RA) faces a dilemma: low-power is insufficient to kill pro-inflammatory cells while high-power exacerbates inflammation. Herein, mitochondrial targeting is introduced in PDT of RA to implement a "less-is-more" strategy, where higher apoptosis in pro-inflammatory cells are achieved with lower laser power. In arthritic rats, chlorine 6-loaded and mitochondria-targeting liposomes (Ce6@M-Lip) passively accumulated in inflamed joints, entered pro-inflammatory macrophages, and actively localized to mitochondria, leading to enhanced mitochondrial dysfunction under laser irradiation. By effectively disrupting mitochondria, pro-inflammatory macrophages are more susceptible to PDT, resulting in increased apoptosis initiation. Additionally, it identifies that high-power irradiation caused cell rupture and release of endogenous danger signals that recruited and activated additional macrophages. In contrast, under low-power irradiation, mitochondria-targeting Ce6@M-Lip not only prevented inflammation but also reduced pro-inflammatory macrophage infiltration and pro-inflammatory cytokine secretion. Overall, targeting mitochondria reconciled therapeutic efficacy and inflammation, thus enabling efficacious yet inflammation-sparing PDT for RA. This highlights the promise of mitochondrial targeting to resolve the dilemma between anti-inflammatory efficacy and inflammatory exacerbation in PDT by implementing a "less-is-more" strategy.

Increased expression of NLRP3 associated with elevated levels of HMGB1 in children with febrile seizures: a case–control study

BackgroundHigh mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS.MethodsThirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1β, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The Mann‒Whitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman’s rank correlation coefficient was calculated to detect significant correlations between cytokine levels.ResultsSerum levels of HMGB1, NLRP3, caspase-1, IL-1β, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1β (p < 0.05). Serum levels of IL-1β were significantly correlated with levels of IL-6 and TNF-α (p < 0.05).ConclusionsHMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1β. Given that activated Caspase-1 directly regulates the expression of mature IL-1β and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1β secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.

COL2-dependent photoperiodic floral induction in Nicotiana sylvestris seems to be lost in the N. sylvestris × N. tomentosiformis hybrid N. tabacum.

Plants are sessile organisms that maximize reproductive success by adapting to their environment. One of the key steps in the reproductive phase of angiosperms is flower development, requiring the perception of multiple endogenous and exogenous signals integrated via a complex regulatory network. Key floral regulators, including the main transcription factor of the photoperiodic pathway (CONSTANS, CO) and the central floral pathway integrator (FLOWERING LOCUS T, FT), are known in many species. We identified several CO-like (COL) proteins in tobacco (Nicotiana tabacum). The NtCOL2a/b proteins in the day-neutral plant N.tabacum were most closely related to Arabidopsis CO. We characterized the diurnal expression profiles of corresponding genes in leaves under short-day (SD) and long-day (LD) conditions and confirmed their expression in phloem companion cells. Furthermore, we analyzed the orthologs of NtCOL2a/b in the maternal LD ancestor (N. sylvestris) and paternal, facultative SD ancestor (N.tomentosiformis) of N. tabacum and found that they were expressed in the same diurnal manner. NtCOL2a/b overexpression or knock-out using the CRISPR/Cas9 system did not support a substantial role for the CO homologs in the control of floral transition in N. tabacum. However, NsCOL2 overexpression induced flowering in N. sylvestris under typically non-inductive SD conditions, correlating with the upregulation of the endogenous NsFTd gene. Our results suggest that NsFTd is transcriptionally regulated by NsCOL2 and that this COL2-dependent photoperiodic floral induction seems to be lost in N. tabacum, providing insight into the diverse genetics of photoperiod-dependent flowering in different Nicotiana species.

The genetic architecture of flowering in the Arabidopsis accession colonising southern Patagonia

AbstractFlowering is a critical developmental step impacting the survival of plant species, and a plethora of complex interdependent regulatory pathways have evolved to sense and integrate environmental with endogenous signals. Extensive explorations in Arabidopsis thaliana revealed some key genes controlling flowering time and associated phenotypic traits. However, quantitative and population genetics suggest that other less explored flowering players may also have relevant impact on the natural variability, explaining adaptive developmental responses to local environments. Here, we report on the flowering time genetic architecture in A. thaliana, using a Recombinant‐Inbred‐Line (RIL) population constructed with accessions bearing contrasting flowering phenotypes, such as the laboratory standard Col‐0 and the anthropically introduced southern Patagonia accession (Pat). Informative Quantitative‐Trait‐Loci (QTLs) mapping resulted in the recognition of a most significant QTL under vernalisation, localised at the end of chromosome V, and independently confirmed genetically by Heterogeneous‐Inbred‐Family lines (HIFs) and Near‐Isogenic‐Lines (NILs). Importantly, classical genes controlling flowering time and vernalisation, such as FLOWERING LOCUS T (FT), FLOWERING LOCUS C (FLC) and FRIGIDA (FRI) do not occur in this QTL. Furthermore, the associated Col‐0 allele contributed to delayed flowering with an increased number of leaves and correlated increase in leaf length; however, this was counterintuitive, as Col‐0 presented the contrary phenotypes when compared to Pat. We conclude that vernalisation contributing to local adaptation may be more diversely influenced across natural species variants than previously thought, with causative alleles having both positive and negative effects depending on genetic background.

Utilizing Plant Protein Secretion System for Pharmaceutical Protein Production.

Molecular farming, also known as plant molecular farming (PMF), is a technique that involves using plants and plant cells as bioreactors to produce recombinant proteins. This is a cost-effective and sustainable way of producing large quantities of proteins for various applications, including pharmaceuticals, vaccines, and industrial enzymes. An endogenous or exogenous signal peptide (SP) is flanked at the N-terminal for recombinant protein targeting and storage. These SPs are responsible for guiding the recombinant protein products to the correct destination within the plant cell or facilitating their secretion into the extracellular space. In this chapter, we will give a brief introduction of the current PMF research outcomes supported by the basic study of vesicle trafficking and protein secretion, mainly introducing the bright yellow 2 (BY-2) cell-based secretion pathway and its associated protocols according to our study of recombinant human iduronidase.

Physiological and transcriptomic analyses of leaves from Gardenia jasminoides Ellis under waterlogging stress.

Gardenia jasminoides Ellis is a Chinese herbal medicine with medicinal and economic value, but its mechanism of response to waterlogging stress remains unclear. In this study, the "double pots method" was used to simulate the waterlogging stress of Gardenia jasminoides Ellis to explore its physiological and transcriptomic response mechanism. We found no significant damage to Gardenia jasminoides Ellis membrane lipid during stress. POD played a vital antioxidant role, KEGG enrichment showed that secondary metabolites such as flavonoids might also play an antioxidant role, and PRO played a significant osmotic adjustment. Endogenous hormones regulate the Gardenia jasminoides Ellis's growth and development and play a role in signal transduction. Among them, light waterlogging stress is delayed. At the same time, there were 19631, 23693, and 15045 differentially expressed genes on the 5th, 10d, and 15d of Gardenia jasminoides Ellis under waterlogging stress. These genes were closely associated with the proteasome, endopeptidase, ribosome, MAPK signal transduction, and endogenous hormone signal transduction, plant-pathogen interaction and phenylpropanoid biosynthesis and other physiological and metabolic pathways, which regulate the turnover and transportation of protein, the reinforcement and adhesion of cell walls, the induction of stomatal closure, allergic reactions, defense reactions, leaf movements and others. It also can absorb ultraviolet rays to reduce the generation of oxygen free radicals, change the way of energy utilization and adjust the osmotic pressure of plant cells.

FLAG-KRAS4B as a Model System for KRAS4B Proteoform and PTM Evaluation by Mass Spectrometry.

Prior analysis of intact and modified protein forms (proteoforms) of KRAS4B isolated from cell lines and tumor samples by top-down mass spectrometry revealed the presence of novel posttranslational modifications (PTMs) and potential evidence of context-specific KRAS4B modifications. However, low endogenous proteoform signal resulted in ineffective characterization, making it difficult to visualize less abundant PTMs or perform follow-up PTM validation using standard proteomic workflows. The NCI RAS Initiative has developed a model system, whereby KRAS4B bearing an N-terminal FLAG tag can be stably expressed within a panel of cancer cell lines. Herein, we present a method for combining immunoprecipitation with complementary proteomic methods to directly analyze N-terminally FLAG-tagged KRAS4B proteoforms and PTMs. We provide detailed protocols for FLAG-KRAS4B purification, proteoform analysis by targeted top-down LC-MS/MS, and validation of abundant PTMs by bottom-up LC-MS/MS with example results.

Analysis on morphological characteristics and identification of candidate genes during the flowering development of alfalfa.

Flower development is a crucial and complex process in the reproductive stage of plants, which involves the interaction of multiple endogenous signals and environmental factors. However, regulatory mechanism of flower development was unknown in alfalfa (Medicago sativa). In this study, the three stages of flower development of 'M. sativa cv. Gannong No. 5' (G5) and its early flowering and multi flowering mutant (MG5) were comparatively analyzed by transcriptomics. The results showed that compared with late bud stage (S1), 14287 and 8351 differentially expressed genes (DEGs) were identified at early flower stage (S2) in G5 and MG5, and 19941 and 19469 DEGs were identified at late flower stage (S3). Compared with S2, 9574 and 10870 DEGs were identified at S3 in G5 and MG5, respectively. Venn analysis revealed that 547 DEGs were identified among the three comparison groups. KEGG pathway enrichment analysis showed that these genes were involved in the development of alfalfa flowers through redox pathways and plant hormone signaling pathways. Key candidate genes including SnRK2, BSK, GID1, DELLA and CRE1, for regulating the development from buds to mature flowers in alfalfa were screened. In addition, differential expression of transcription factors such as MYB, AP2, bHLH, C2C2, MADS-box, NAC, bZIP, B3 and AUX/IAA also played an important role in this process. The results laid a theoretical foundation for studying the molecular mechanisms of the development process from buds to mature flowers in alfalfa.

Sequential Clearing of Network-Aware Local Energy and Flexibility Markets in Community-Based Grids

In this paper, network-aware clearing algorithms for local energy markets (LEMs) and local flexibility markets (LFM) are proposed to be sequentially run and coordinate assets and flexible resources of energy communities (ECs) in distribution networks. In the proposed LEM clearing algorithm, EC managers run a two-stage stochastic programming while considering random events by scenario generation and network constraints using linearized DistFlow. As one of outcomes, maximum available up-and down-regulations provided by ECs are estimated in LEM and communicated to LFM. In the distributed LFM clearing algorithm, an iterative auction is designed using a dual-decomposition technique (Augmented Lagrangian) which is solved by consensus alternating direction method of multipliers. The LFM algorithm efficiently dispatches the flexibility provided by ECs in operating time while considering flexibility local marginal price as pricing method. Network constraints are included in the algorithm with an AC distribution optimal power flow for dynamic network topology in which branches and buses are decomposed to solve the problem in distributed fashion. The designed LFM algorithm can respond to exogenous and endogenous signals for flexibility requests. The simulation results in a test case display effectiveness of two proposed LEM and LFM algorithms for an efficient provision of flexibility.

Liver macrophages as the key regulators of tissue homeostasis in organ

Introduction. View about hepatic macrophages as key regulators of tissue homeostasis, acting via innate and adaptive immune reactions, stimulated by exogenous and/or endogenous alarm signals of tissue injury or cell stress is substantiated in the review. From one hand, environmental signals determine macrophage polarization and production, but, on the other hand, macrophages affect tissue microenvironment and cells and tissue function at whole. The review was aimed to provide recent evidence of macrophage role in maintenance of tissue homeostasis in liver. Materials and Methods. Review is based on the 67 scientific articles, devoted to the study and analysis of macrophage role in the maintenance of tissue homeostasis in liver, found in PubMed database. Most of the analyzed articles (40 from 67) were published in 2017-2023. Results and Discussion. Information of origin and morpho-functional heterogeneity of hepatic macrophages was summarized in the review. Conclusion. The information presented in the review allow to conclude that macrophages are key regulators of homeostasis in the liver due to their ability to perceive many endogenous and exogenous signals in tissues and quickly respond to them in the direction of stabilizing the tissue microenvironment.

Characterization of Inflammasomes and Their Regulation in the Red Fox.

Inflammasomes recognize endogenous and exogenous danger signals, and subsequently induce the secretion of IL-1β. Studying inflammasomes in the red fox (Vulpes vulpes) is crucial for wildlife veterinary medicine, as it can help control inflammatory diseases in foxes. We investigated the activation and intracellular mechanisms of three inflammasomes (NLRP3, AIM2, and NLRC4) in fox peripheral blood mononuclear cells (PBMCs), using established triggers and inhibitors derived from humans and mice. Fox PBMCs exhibited normal activation and induction of IL-1β secretion in response to representative inflammasome triggers (ATP and nigericin for NLRP3, dsDNA for AIM2, flagellin for NLRC4). Additionally, PBMCs showed normal IL-1β secretion when inoculated with inflammasome-activating bacteria. In inhibitors of the inflammasome signaling pathway, fox inflammasome activation was compared with mouse inflammasomes. MCC950, a selective NLRP3 inhibitor, suppressed the secretion of dsDNA- and flagellin-mediated IL-1β in foxes, unlike mice. These findings suggest that NLRP3 may have a common role in dsDNA- and flagellin-mediated inflammasome activation in the red fox. It implies that this fox inflammasome biology can be applied to the treatment of inflammasome-mediated diseases in the red fox.

RNA Aptamer-Mediated Gene Activation Systems for Inducible Transgene Expression in Animal Cells.

RNA expression analyses can be used to obtain various information from inside cells, such as physical conditions, the chemical environment, and endogenous signals. For detecting RNA, the system regulating intracellular gene expression has the potential for monitoring RNA expression levels in real time within living cells. Synthetic biology provides powerful tools for detecting and analyzing RNA inside cells. Here, we devised an RNA aptamer-mediated gene activation system, RAMGA, to induce RNA-triggered gene expression activation by employing an inducible complex formation strategy grounded in synthetic biology. This methodology connects DNA-binding domains and transactivators through target RNA using RNA-binding domains, including phage coat proteins. MS2 bacteriophage coat protein fused with a transcriptional activator and PP7 bacteriophage coat protein fused with the tetracycline repressor (tetR) can be bridged by target RNA encoding MS2 and PP7 stem-loops, resulting in transcriptional activation. We generated recombinant CHO cells containing an inducible GFP expression module governed by a minimal promoter with a tetR-responsive element. Cells carrying the trigger RNA exhibited robust reporter gene expression, whereas cells lacking it exhibited no expression. GFP expression was upregulated over 200-fold compared with that in cells without a target RNA expression vector. Moreover, this system can detect the expression of mRNA tagged with aptamer tags and modulate reporter gene expression based on the target mRNA level without affecting the expression of the original mRNA-encoding gene. The RNA-triggered gene expression systems developed in this study have potential as a new platform for establishing gene circuits, evaluating endogenous gene expression, and developing novel RNA detectors.

Elucidation of the Mechanism of Rapid Growth Recovery in Rice Seedlings after Exposure to Low-Temperature Low-Light Stress: Analysis of Rice Root Transcriptome, Metabolome, and Physiology.

Late spring cold is a disastrous weather condition that often affects early rice seedlings in southern China, limiting the promotion of direct seeding cultivation. However, there are few reports on the effect of these events and on the growth recovery mechanism of rice root systems after rice seedlings are exposed to this stress. This study selected the strong-growth-recovery variety B116 (R310/R974, F17) and the slow-recovery variety B811 (Zhonghui 286) for direct seeding cultivation and exposed them to low temperature and low-light stress to simulate a late spring cold event in an artificial climate chamber. The treatment consisted of 4 days of exposure to a day/night temperature of 14/10 °C and a light intensity of 266 µmol m-2s-1 while the control group was kept at a day/night temperature of 27/25 °C and light intensity of 533 µmol m-2s-1. The results showed that 6 days after stress, the total length, surface area, and volume of B116 roots increased by 335.5%, 290.1%, and 298.5%, respectively, while those of B811 increased by 228.8%, 262.0%, and 289.1%, respectively. In B116, the increase in root fresh weight was 223.1%, and that in B811 was 165.6%, demonstrating rapid root recovery after stress and significant differences among genotypes. The content of H2O2 and MDA in the B116 roots decreased faster than that in the B811 roots after normal light intensity and temperature conditions were restored, and the activity of ROS metabolism enzymes was stronger in B116 roots than in B811 roots. The correlation analysis between the transcriptome and metabolome showed that endogenous signal transduction and starch and sucrose metabolism were the main metabolic pathways affecting the rapid growth of rice seedling roots after exposure to combined stress from low temperature and low light intensities. The levels of auxin and sucrose in the roots of the strong-recovery variety B116 were higher, and this variety's metabolism was downregulated significantly faster than that of B811. The auxin response factor and sucrose synthesis-related genes SPS1 and SUS4 were significantly upregulated. This study contributes to an understanding of the rapid growth recovery mechanism in rice after exposure to combined stress from low-temperature and low-light conditions.

Cover Image:

The BAP module, comprising BRASSINAZOLE RESISTANT 1 (BZR1), AUXIN RESPONSE FACTOR 6 (ARF6), and PHYTOCHROME‐INTERACTING FACTOR 4 (PIF4), is an important hub in plant signaling networks. Diao et al. (pages 2631‐2644) determined that the prototype BAP module arose in Marchantia polymorpha, underwent stepwise evolution and became established as a mature regulatory system in seed plants. This work elucidates the evolutionary trajectory of the BAP module and provides insight into the mechanisms by which plants to integrate environmental and endogenous signals. The cover image depicts the key players in the BAP module in bryophytes and seed plants.

Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration.

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.

Moving beyond the arabidopsis-centric view of G-protein signaling in plants.

Heterotrimeric G-protein-mediated signaling is a key mechanism to transduce a multitude of endogenous and environmental signals in diverse organisms. The scope and expectations of plant G-protein research were set by pioneering work in metazoans. Given the similarity of the core constituents, G-protein-signaling mechanisms were presumed to be universally conserved. However, because of the enormous diversity of survival strategies and endless forms among eukaryotes, the signal, its interpretation, and responses vary even among different plant groups. Earlier G-protein research in arabidopsis (Arabidopsis thaliana) has emphasized its divergence from Metazoa. Here, we compare recent evidence from diverse plant lineages with the available arabidopsis G-protein model and discuss the conserved and novel protein components, signaling mechanisms, and response regulation.