Subfunctionalisation and self-repression of duplicated E1 homologues finetunes soybean flowering and adaptation.

Soybean is a photoperiod-sensitive staple crop. Its photoperiodic flowering has major consequences for latitudinal adaptation and grain yield. Here, we identify and characterise a flowering locus named Time of flower 4b (Tof4b), which encodes E1-Like b (E1Lb), a homologue of the key soybean floral repressor E1. Tof4b protein physically associates with the promoters of two FLOWERING LOCUS T (FT) genes to repress their transcription and delay flowering to impart soybean adaptation to high latitudes. Three E1 homologues undergo subfunctionalisation and show differential subcellular localisation. Moreover, they all possess self-repression capability and each suppresses the two homologous counterparts. Subfunctionalisation and the transcriptional regulation of E1 genes collectively finetune flowering time and high-latitude adaptation in soybean. We propose a model for the functional fate of the three E1 genes after the soybean whole-genome duplication events, refine the molecular mechanisms underlying high-latitude adaption, and provide a potential molecular-breeding resource.

Soybean hypocotyl elongation is regulated by a MYB33-SWEET11/21-GA2ox8c module involving long-distance sucrose transport.

The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.

Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

A critical suppression feedback loop determines soybean photoperiod sensitivity.

Photoperiod sensitivity is crucial for soybean flowering, adaptation, and yield. In soybean, photoperiod sensitivity centers around the evening complex (EC) that regulates the transcriptional level of the core transcription factor E1, thereby regulating flowering. However, little is known about the regulation of the activity of EC. Our study identifies how E2/GIGANTEA (GI) and its homologs modulate photoperiod sensitivity through interactions with the EC. During long days, E2 interacts with the blue-light receptor flavin-binding, kelch repeat, F box 1 (FKF1), leading to the degradation of J/ELF3, an EC component. EC also suppresses E2 expression by binding to its promoter. This interplay forms a photoperiod regulatory loop, maintaining sensitivity to photoperiod. Disruption of this loop leads to losing sensitivity, affecting soybean's adaptability and yield. Understanding this loop's dynamics is vital for molecular breeding to reduce soybean's photoperiod sensitivity and develop cultivars with better adaptability and higher yields, potentially leading to the creation of photoperiod-insensitive varieties for broader agricultural applications.

Synthesis and Properties of Injectable Hydrogel for Tissue Filling.

Hydrogels with injectability have emerged as the focal point in tissue filling, owing to their unique properties, such as minimal adverse effects, faster recovery, good results, and negligible disruption to daily activities. These hydrogels could attain their injectability through chemical covalent crosslinking, physical crosslinking, or biological crosslinking. These reactions allow for the formation of reversible bonds or delayed gelatinization, ensuring a minimally invasive approach for tissue filling. Injectable hydrogels facilitate tissue augmentation and tissue regeneration by offering slow degradation, mechanical support, and the modulation of biological functions in host cells. This review summarizes the recent advancements in synthetic strategies for injectable hydrogels and introduces their application in tissue filling. Ultimately, we discuss the prospects and prevailing challenges in developing optimal injectable hydrogels for tissue augmentation, aiming to chart a course for future investigations.

Tissue adhesives based on chitosan for skin wound healing: Where do we stand in this era? A review.

Chitosan has been commonly used as an adhesive dressing material due to its excellent biocompatibility, degradability, and renewability. Tissue adhesives are outstanding among wound dressings because they can close the wound, absorb excess tissue exudate from the wound site, provide a moist environment, and act as a carrier for loading various bioactive molecules. They have been widely used in both preclinical and clinical treatment of skin wounds. This review summarizes recent research progresses in the application of chitosan and its derivatives for tissue adhesives. We also introduce their biomedical effects on wound adhesion, contamination isolation, antibacterial, immune regulation, and wound healing, and the strategies to achieve these functions when used as wound dressings. Finally, challenges and future perspectives of chitosan-based tissue adhesives are discussed for wound healing.

Mechanisms underlying key agronomic traits and implications for molecular breeding in soybean.

Soybean (Glycine max [L.] Merr.) is an important crop that provides protein and vegetable oil for human consumption. As soybean is a photoperiod-sensitive crop, its cultivation and yield are limited by the photoperiodic conditions in the field. In contrast to other major crops, soybean has a special plant architecture and a special symbiotic nitrogen fixation system, representing two unique breeding directions. Thus, flowering time, plant architecture, and symbiotic nitrogen fixation are three critical or unique yield-determining factors. This review summarizes the progress made in our understanding of these three critical yield-determining factors in soybean. Meanwhile, we propose potential research directions to increase soybean production, discuss the application of genomics and genomic-assisted breeding, and explore research directions to address future challenges, particularly those posed by global climate changes.

Transparent silk fibroin film-facilitated infected-wound healing through antibacterial, improved fibroblast adhesion and immune modulation.

The clinical application of regenerated silk fibroin (RSF) films for wound treatment is restricted by its undesirable mechanical properties and lack of antibacterial activity. Herein, different pluronic polymers were introduced to optimize their mechanical properties and the RSF film with 2.5% pluronic F127 (RSFPF127) stood out to address the above issues owing to its satisfactory mechanical properties, hydrophilicity, and transmittance. Diverse antibacterial agents (curcumin, Ag nanoparticles, and antimicrobial peptide KR-12) were separately encapsulated in RSFPF127 to endow it with antibacterial activity. In vitro experiments revealed that the medicated RSFPF127 could persistently release drugs and had desirable bioactivities toward killing bacteria, promoting fibroblast adhesion, and modulating macrophage polarization. In vivo experiments revealed that medicated RSFPF127 not only eradicated methicillin-resistant Staphylococcus aureus in the wound area and inhibited inflammatory responses, but also facilitated angiogenesis and re-epithelialization, regardless of the types of antibacterial agents, thus accelerating the recovery of infected wounds. These results demonstrate that RSFPF127 is an ideal matrix platform to load different types of drugs for application as wound dressings.

CaO2-Cu2O micromotors accelerate infected wound healing through antibacterial functions, hemostasis, improved cell migration, and inflammatory regulation.

During the wound tissue healing process, the relatively weak driving forces of tissue barriers and concentration gradients lead to a slow and inefficient penetration of bioactive substances into the wound area, consequently showing an impact on the effectiveness of deep wound healing. To overcome these challenges, we constructed biocompatible CaO2-Cu2O "micromotors". These micromotors reacted with the fluids at the wound site, releasing oxygen bubbles and propelling particles deep into the wound tissue. In vitro experimental results revealed that these micromotors not only exhibited antibacterial and hemostatic functions but also facilitated the migration of dermal fibroblasts and vascular endothelial cells, while modulating the inflammatory microenvironment. A methicillin-resistant Staphylococcus aureus infected full-thickness-wound model was created in rats, in which CaO2-Cu2O micromotors markedly expedited the wound healing process. Specifically, CaO2-Cu2O provided a sterile microenvironment for wounds and increased the amounts of M1-type macrophages during infection and inflammation. During the proliferation and remodeling stages, the amount of M1 macrophages gradually decreased, while the amount of M2 macrophages increased, and CaO2-Cu2O did not prolong the inflammatory period. Furthermore, the introduction of a regenerated silk fibroin (RSF) film on the wound surface successfully enhanced the therapeutic effects of CaO2-Cu2O against the infected wound. The combined application of oxygen-producing CaO2-Cu2O micromotors and a RSF film demonstrates significant therapeutic potential and emerges as a promising candidate for the treatment of infected wounds.

Soybean reduced internode 1 determines internode length and improves grain yield at dense planting.

Major cereal crops have benefitted from Green Revolution traits such as shorter and more compact plants that permit high-density planting, but soybean has remained relatively overlooked. To balance ideal soybean yield with plant height under dense planting, shortening of internodes without reducing the number of nodes and pods is desired. Here, we characterized a short-internode soybean mutant, reduced internode 1 (rin1). Partial loss of SUPPRESSOR OF PHYA 105 3a (SPA3a) underlies rin1. RIN1 physically interacts with two homologs of ELONGATED HYPOCOTYL 5 (HY5), STF1 and STF2, to promote their degradation. RIN1 regulates gibberellin metabolism to control internode development through a STF1/STF2-GA2ox7 regulatory module. In field trials, rin1 significantly enhances grain yield under high-density planting conditions comparing to its wild type of elite cultivar. rin1 mutants therefore could serve as valuable resources for improving grain yield under high-density cultivation and in soybean-maize intercropping systems.

Bioinspired Polyacrylic Acid-Based Dressing: Wet Adhesive, Self-Healing, and Multi-Biofunctional Coacervate Hydrogel Accelerates Wound Healing.

Polyacrylic acid (PAA) and its derivatives are commonly used as essential matrices in wound dressings, but their weak wet adhesion restricts the clinical application. To address this issue, a PAA-based coacervate hydrogel with strong wet adhesion capability is fabricated through a facile mixture of PAA copolymers with isoprenyl oxy poly(ethylene glycol) ether and tannic acid (TA). The poly(ethylene glycol) segments on PAA prevent the electrostatic repulsion among the ionized carboxyl groups and absorbed TA to form coacervates. The absorbed TA provides solid adhesion to dry and wet substrates via multifarious interactions, which endows the coacervate with an adhesive strength to skin of 23.4 kPa and 70% adhesion underwater. This coacervate achieves desirable self-healing and extensible properties suitable for frequently moving joints. These investigations prove that the coacervate has strong antibacterial activity, facilitates fibroblast migration, and modulates M1/M2 polarization of macrophages. In vivo hemorrhage experiments further confirm that the coacervate dramatically shortens the hemostatic time from hundreds to tens of seconds. In addition, full-thickness skin defect experiments demonstrate that the coacervate achieves the best therapeutic effect by significantly promoting collagen deposition, angiogenesis, and epithelialization. These results demonstrate that a PAA-based coacervate hydrogel is a promising wound dressing for medical translation.

A retrotransposon insertion in the Mao1 promoter results in erect pubescence and higher yield in soybean.

Adaptive changes in crops contribute to the diversity of agronomic traits, which directly or indirectly affect yield. The change of pubescence form from appressed to erect is a notable feature during soybean domestication. However, the biological significance and regulatory mechanism underlying this transformation remain largely unknown. Here, we identified a major-effect locus, PUBESCENCE FORM 1 (PF1), the upstream region of Mao1, that regulates pubescence form in soybean. The insertion of a Ty3/Gypsy retrotransposon in PF1 can recruit the transcription factor GAGA-binding protein to a GA-rich region, which up-regulates Mao1 expression, underpinning soybean pubescence evolution. Interestingly, the proportion of improved cultivars with erect pubescence increases gradually with increasing latitude, and erect-pubescence cultivars have a higher yield possibly through a higher photosynthetic rate and photosynthetic stability. These findings open an avenue for molecular breeding through either natural introgression or genome editing toward yield improvement and productivity.

The genetic basis of high-latitude adaptation in wild soybean.

In many plants, flowering time is influenced by daylength as an adaptive response. In soybean (Glycine max) cultivars, however, photoperiodic flowering reduces crop yield and quality in high-latitude regions. Understanding the genetic basis of wild soybean (Glycine soja) adaptation to high latitudes could aid breeding of improved cultivars. Here, we identify the Tof4 (Time of flowering 4) locus, which encodes by an E1-like protein, E1La, that represses flowering and enhances adaptation to high latitudes in wild soybean. Moreover, we found that Tof4 physically associates with the promoters of two important FLOWERING LOCUS T (FT2a and FT5a) and with Tof5 to inhibit their transcription under long photoperiods. The effect of Tof4 on flowering and maturity is mediated by FT2a and FT5a proteins. Intriguingly, Tof4 and the key flowering repressor E1 independently but additively regulate flowering time, maturity, and grain yield in soybean. We determined that weak alleles of Tof4 have undergone natural selection, facilitating adaptation to high latitudes in wild soybean. Notably, over 71.5% of wild soybean accessions harbor the mutated alleles of Tof4 or a previously reported gain-of-function allele Tof5H2, suggesting that these two loci are the genetic basis of wild soybean adaptation to high latitudes. Almost no cultivated soybean carries the mutated tof4 allele. Introgression of the tof4-1 and Tof5H2 alleles into modern soybean or editing E1 family genes thus represents promising avenues to obtain early-maturity soybean, thereby improving productivity in high latitudes.

Diverse flowering responses subjecting to ambient high temperature in soybean under short-day conditions.

Flowering time is one of important agronomic traits determining the crop yield and affected by high temperature. When facing high ambient temperature, plants often initiate early flowering as an adaptive strategy to escape the stress and ensure successful reproduction. However, here we find opposing ways in the short-day crop soybean to respond to different levels of high temperatures, in which flowering accelerates when temperature changes from 25 to 30 °C, but delays when temperature reaches 35 °C under short day. phyA-E1, possibly photoperiodic pathway, is crucial for 35 °C-mediated late flowering, however, does not contribute to promoting flowering at 30 °C. 30 °C-induced up-regulation of FT2a and FT5a leads to early flowering, independent of E1. Therefore, distinct responsive mechanisms are adopted by soybean when facing different levels of high temperatures for successful flowering and reproduction.

GIGANTEA orthologs, E2 members, redundantly determine photoperiodic flowering and yield in soybean.

Soybean (Glycine max L.) is a typical photoperiod-sensitive crop, such that photoperiod determines its flowering time, maturity, grain yield, and phenological adaptability. During evolution, the soybean genome has undergone two duplication events, resulting in about 75% of all genes being represented by multiple copies, which is associated with rampant gene redundancy. Among duplicated genes, the important soybean maturity gene E2 has two homologs, E2-Like a (E2La) and E2-Like b (E2Lb), which encode orthologs of Arabidopsis GIGANTEA (GI). Although E2 was cloned a decade ago, we still know very little about its contribution to flowering time and even less about the function of its homologs. Here, we generated single and double mutants in E2, E2La, and E2Lb by genome editing and determined that E2 plays major roles in the regulation of flowering time and yield, with the two E2 homologs depending on E2 function. At high latitude regions, e2 single mutants showed earlier flowering and high grain yield. Remarkably, in terms of genetic relationship, genes from the legume-specific transcription factor family E1 were epistatic to E2. We established that E2 and E2-like proteins form homodimers or heterodimers to regulate the transcription of E1 family genes, with the homodimer exerting a greater function than the heterodimers. In addition, we established that the H3 haplotype of E2 is the ancestral allele and is mainly restricted to low latitude regions, from which the loss-of-function alleles of the H1 and H2 haplotypes were derived. Furthermore, we demonstrated that the function of the H3 allele is stronger than that of the H1 haplotype in the regulation of flowering time, which has not been shown before. Our findings provide excellent allelic combinations for classical breeding and targeted gene disruption or editing.

Identification of two quantitative genes controlling soybean flowering using bulked-segregant analysis and genetic mapping.

Photoperiod responsiveness is important to soybean production potential and adaptation to local environments. Varieties from temperate regions generally mature early and exhibit extremely low yield when grown under inductive short-day (SD) conditions. The long-juvenile (LJ) trait is essentially a reduction and has been introduced into soybean cultivars to improve yield in tropical environments. In this study, we used next-generation sequencing (NGS)-based bulked segregant analysis (BSA) to simultaneously map qualitative genes controlling the LJ trait in soybean. We identified two genomic regions on scaffold_32 and chromosome 18 harboring loci LJ32 and LJ18, respectively. Further, we identified LJ32 on the 228.7-kb scaffold_32 as the soybean pseudo-response-regulator gene Tof11 and LJ18 on a 301-kb region of chromosome 18 as a novel PROTEIN FLOWERING LOCUS T-RELATED gene, Glyma.18G298800. Natural variants of both genes contribute to LJ trait regulation in tropical regions. The molecular identification and functional characterization of Tof11 and LJ18 will enhance understanding of the molecular mechanisms underlying the LJ trait and provide useful genetic resources for soybean molecular breeding in tropical regions.

Agronomical selection on loss-of-function of GIGANTEA simultaneously facilitates soybean salt tolerance and early maturity.

Salt stress and flowering time are major factors limiting geographic adaptation and yield productivity in soybean (Glycine max). Although improving crop salt tolerance and latitude adaptation are essential for efficient agricultural production, whether and how these two traits are integrated remains largely unknown. Here, we used a genome-wide association study to identify a major salt-tolerance locus controlled by E2, an ortholog of Arabidopsis thaliana GIGANTEA (GI). Loss of E2 function not only shortened flowering time and maturity, but also enhanced salt-tolerance in soybean. E2 delayed soybean flowering by enhancing the transcription of the core flowering suppressor gene E1, thereby repressing Flowering Locus T (FT) expression. An E2 knockout mutant e2CR displayed reduced accumulation of reactive oxygen species (ROS) during the response to salt stress by releasing peroxidase, which functions in ROS scavenging to avoid cytotoxicity. Evolutionary and population genetic analyses also suggested that loss-of-function e2 alleles have been artificially selected during breeding for soybean adaptation to high-latitude regions with greater salt stress. Our findings provide insights into the coupled selection for adaptation to both latitude and salt stress in soybean; and offer an ideal target for molecular breeding of early-maturing and salt-tolerant cultivars.

A functionally divergent SOC1 homolog improves soybean yield and latitudinal adaptation.

Soybean (Glycine max) grows in a wide range of latitudes, but it is extremely sensitive to photoperiod, which reduces its yield and ability to adapt to different environments. Therefore, understanding of the genetic basis of soybean adaptation is of great significance for breeding and improvement. Here, we characterized Tof18 (SOC1a) that conditions early flowering and growth habit under both short-day and long-day conditions. Molecular analysis confirmed that the two SOC1 homologs present in soybeans (SOC1a and SOC1b) underwent evolutionary functional divergence, with SOC1a having stronger effects on flowering time and stem node number than SOC1b due to transcriptional differences. soc1a soc1b double mutants showed stronger functional effects than either of the single mutants, perhaps due to the formation of SOC1a and SOC1b homodimers or heterodimers. Additionally, Tof18/SOC1a improves the latitudinal adaptation of cultivated soybeans, highlighting the functional importance of SOC1a. The Tof18G allele facilitates adaptation to high latitudes, whereas Tof18A facilitates adaptation to low latitudes. We demonstrated that SOC1s contribute to floral induction in both leaves and shoot apex through inter-regulation with FTs. The SOC1a-SOC1b-Dt2 complex plays essential roles in stem growth habit by directly binding to the regulatory sequence of Dt1, making the genes encoding these proteins potential targets for genome editing to improve soybean yield via molecular breeding. Since the natural Tof18A allele increases node number, introgressing this allele into modern cultivars could improve yields, which would help optimize land use for food production in the face of population growth and global warming.

Identification of ST1 reveals a selection involving hitchhiking of seed morphology and oil content during soybean domestication.

Seed morphology and quality of cultivated soybean (Glycine max) have changed dramatically during domestication from their wild relatives, but their relationship to selection is poorly understood. Here, we describe a semi-dominant locus, ST1 (Seed Thickness 1), affecting seed thickness and encoding a UDP-D-glucuronate 4-epimerase, which catalyses UDP-galacturonic acid production and promotes pectin biosynthesis. Interestingly, this morphological change concurrently boosted seed oil content, which, along with up-regulation of glycolysis biosynthesis modulated by ST1, enabled soybean to become a staple oil crop. Strikingly, ST1 and an inversion controlling seed coat colour formed part of a single selective sweep. Structural variation analysis of the region surrounding ST1 shows that the critical mutation in ST1 existed in earlier wild relatives of soybean and the region containing ST1 subsequently underwent an inversion, which was followed by successive selection for both traits through hitchhiking during selection for seed coat colour. Together, these results provide direct evidence that simultaneously variation for seed morphology and quality occurred earlier than variation for seed coat colour during soybean domestication. The identification of ST1 thus sheds light on a crucial phase of human empirical selection in soybeans and provides evidence that our ancestors improved soybean based on taste.

Parallel selection of distinct Tof5 alleles drove the adaptation of cultivated and wild soybean to high latitudes.

Photoperiod responsiveness is a key factor limiting the geographic distribution of cultivated soybean and its wild ancestor. In particular, the genetic basis of the adaptation in wild soybean remains poorly understood. In this study, by combining whole-genome resequencing and genome-wide association studies we identified a novel locus, Time of Flowering 5 (Tof5), which promotes flowering and enhances adaptation to high latitudes in both wild and cultivated soybean. By genomic, genetic and transgenic analyses we showed that Tof5 encodes a homolog of Arabidopsis thaliana FRUITFULL (FUL). Importantly, further analyses suggested that different alleles of Tof5 have undergone parallel selection. The Tof5H1 allele was strongly selected by humans after the early domestication of cultivated soybean, while Tof5H2 allele was naturally selected in wild soybean, and in each case facilitating adaptation to high latitudes. Moreover, we found that the key flowering repressor E1 suppresses the transcription of Tof5 by binding to its promoter. In turn, Tof5 physically associates with the promoters of two important FLOWERING LOCUS T (FT), FT2a and FT5a, to upregulate their transcription and promote flowering under long photoperiods. Collectively, our findings provide insights into how wild soybean adapted to high latitudes through natural selection and indicate that cultivated soybean underwent changes in the same gene but evolved a distinct allele that was artificially selected after domestication.