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Cotton provides the most abundant natural fiber for the textile industry. The mature cotton fiber largely consists of secondary cell walls with the highest proportion of cellulose and a small amount of hemicellulose and lignin. To dissect the roles of hemicellulosic polysaccharides during fiber development, four IRREGULAR XYLEM 15 (IRX15) genes, GhIRX15-1/-2/-3/-4, were functionally characterized in cotton. These genes encode DUF579 domain-containing proteins, which are homologs of AtIRX15 involved in xylan biosynthesis. The four GhIRX15 genes were predominantly expressed during fiber secondary wall thickening, and the encoded proteins were localized to the Golgi apparatus. Each GhIRX15 gene could restore the xylan deficient phenotype in the Arabidopsis irx15irx15l double mutant. Silencing of GhIRX15s in cotton resulted in shorter mature fibers with a thinner cell wall and reduced cellulose content as compared to the wild type. Intriguingly, GhIRX15-2 and GhIRX15-4 formed homodimers and heterodimers. In addition, the GhIRX15s showed physical interaction with glycosyltransferases GhGT43C, GhGT47A and GhGT47B, which are responsible for synthesis of the xylan backbone and reducing end sequence. Moreover, the GhIRX15s can form heterocomplexes with enzymes involved in xylan modification and side chain synthesis, such as GhGUX1/2, GhGXM1/2 and GhTBL1. These findings suggest that GhIRX15s participate in fiber xylan biosynthesis and modulate fiber development via forming large multiprotein complexes. [ABSTRACT FROM AUTHOR]

Repairing skin wounds has always been challenging in clinical practice. The new skin tissue engineering scaffold provides innovative ways to address these challenges with a good chance of success because of its stable mechanical properties, biodegradability, and antibacterial properties. This paper presents the fabrication and evaluation of a three-dimensional composite scaffold made with sulfated silk fibroin, chitosan, and hydroxyapatite (SSF/CS/HAP). An electron microscope shows that the scaffold has an aperture of 15–20 μm, while an absorption performance test shows that its expansion index reaches 779%. The co-culture of L929 cells and the CCK-8 experiments demonstrated good cell compatibility and low scaffold cytotoxicity, respectively. Meanwhile, in vivo experiments demonstrate that rats with SSF/CS/HAP scaffold-treated neck wounds heal faster. In the wound skin tissue of the SSF/CS/HAP scaffold group, immunohistochemistry indicates a more rapid and mature development of hair follicles. This study successfully developed a novel skin tissue engineering scaffold material with high moisture retention, high tissue compatibility, and low cytotoxicity, demonstrating its ability to improve wound repair with promising potential for tissue engineering applications. • Sulfation of silk fibroin improved the hydrophilicity and biocompatibility of silk fibroin. • Innovatively constructed a three-dimensional composite scaffold and verified its porous structure and good expansibility. • This new composite scaffold could significantly promote cell proliferation and wound healing in rats. [ABSTRACT FROM AUTHOR]

To investigate the effects of kinetin (Kn) on thymus and immune function in a rat model of D-galactose (D-gal)-induced aging, fifty SD rats were randomly divided into five groups: young control group, aging model group, low-dose Kn-treated group, middle-dose Kn-treated group and a high-dose Kn-treated group. Rats in the aging model group were subcutaneously injected with D-gal (125 mg/kg BW/day) in the back of the neck. Rats in the Kn-treated groups were intraperitoneally injected with 5, 10 or 20 mg/kg BW/day Kn solution. Changes in the thymus index, activity of antioxidant enzymes such as superoxide dismutase (SOD), the content of metabolic products such as malondialdehyde (MDA), the content of serum immunoglobulins and Interleukin-2 (IL-2), as well as histological changes in the thymus were recorded and analyzed. Results showed that the thymus index, antioxidant enzyme activity and the immunoglobulin contents of experimental animals in the aging model group decreased significantly compared with the young control group. The contents of metabolic products increased significantly compared with the young control group. The thymus index, content of immunoglobulin and IL-2, as well as antioxidant enzyme activity of the rats in the Kn-treatment groups significantly increased compared with the aging model control group, while the contents of Interleukin-6 (IL-6) and MDA decreased significantly. The structure and substructure of thymus cells were protected by Kn treatment. Therefore, we conclude that Kn can protect the tissue structure of the thymus and effectively antagonize oxidative damage in the thymus of aging rats induced by D-gal, and thereby improve the body's immune ability and delay aging of the thymus. [ABSTRACT FROM AUTHOR]

The molecular mechanisms specifying anti-oxidative and anti-aging action of kinetin (Kn) on the splenic oxidative damage of aging rats are poorly understood. Here, the Sprague Dawley (SD) rats (Rattus norregicus) aging model was proposed by napes subcutaneous injection of D-galactose, and anti-aging group were subsequently dealt with doses of 5, 10, 20 mg/kg⋅BW of Kn. Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX), catalase (CAT), lipid peroxide (LPO), spleen indexes and histopathology were evaluated. Our results showed that Kinetin significantly decreased the MDA and LPO activity, while spleen indexes, SOD, GSH-PX and CAT were higher than aging model group; histopathological studies for spleen confirmed the rescue from the aging rats. These results demonstrate that kinetin recovers the splenic cell structure and could effectively protect the spleen cells from oxidative damage and aging. [ABSTRACT FROM AUTHOR]

Sexual dimorphism is a widespread phenomenon throughout the animal kingdom and a key topic in evolutionary biology. In this study, we quantified patterns of sexual dimorphism in two hynobiid salamanders (Hynobius leechii and Salamandrella keyserlingii) from Chinese populations. Sexual size dimorphism did not occur in either species, despite differences in body shape traits. Likely related to fecundity selection, females have relatively longer trunks in both species. Female S. keyserlingii have larger heads likely due to reproductive investment and ecological selection, whereas larger forelimb and hindlimb width in male H. leechii may be related to reproductive behaviour. [ABSTRACT FROM AUTHOR]

Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNAencoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNPbased mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types. [ABSTRACT FROM AUTHOR]

Checkpoint blockade antibodies have been approved as immunotherapy for multiple types of cancer, but the response rate and efficacy are still limited. There are few immunogenic cell death (ICD)-inducing drugs available that can kill cancer cells, enhance tumor immunogenicity, increase the in vivo immune infiltration, and thereby boosting a tumor response to immunotherapy. So far, the ICD markers have been identified as the few immuno-stimulating characteristics of dead cells, but whether the presence of such ICD markers on tumor cells translates into enhanced antitumor immunity in vivo is still investigational. To identify anticancer drugs that could induce tumor cell death and boost T cell response, we performed drug screenings based on both an ICD reporter assay and T cell activation assay. We identified that teniposide, a DNA topoisomerase II inhibitor, could induce high mobility group box 1 (HMGB1) release and type I interferon signaling in tumor cells, and teniposide-treated tumor cells could activate antitumor T cell response both in vitro and in vivo. Mechanistically, teniposide induced tumor cell DNA damage and innate immune signaling including NF-κB activation and STING-dependent type I interferon signaling, both of which contribute to the activation of dendritic cells and subsequent T cells. Furthermore, teniposide potentiated the antitumor efficacy of anti-PD1 on multiple types of mouse tumor models. Our findings showed that teniposide could trigger tumor immunogenicity, and enabled a potential chemo-immunotherapeutic approach to potentiate the therapeutic efficacy of anti-PD1 immunotherapy. [ABSTRACT FROM AUTHOR]

Adaptation to osmotic stress is crucial for bacterial growth and survival in changing environments. Although a large number of osmotic stress response genes have been identified in various bacterial species, how osmotic changes affect bacterial motility, biofilm formation, and colonization of host niches remains largely unknown. In this study, we report that the LrhA regulator is an osmoregulated transcription factor that directly binds to the promoters of the flhDC, eps, and opgGH operons and differentially regulates their expression, thus inhibiting motility and promoting exopolysaccharide (EPS) production, synthesis of osmoregulated periplasmic glucans (OPGs), biofilm formation, and root colonization of the plant growth-promoting bacterium Pantoea alhagi LTYR-11Z. Further, we observed that the LrhA-regulated OPGs control RcsCD-RcsB activation in a concentration-dependent manner, and a high concentration of OPGs induced by increased medium osmolarity is maintained to achieve the high level of activation of the Rcs phosphorelay, which results in enhanced EPS synthesis and decreased motility in P. alhagi. Moreover, we showed that the osmosensing regulator OmpR directly binds to the promoter of lrhA and promotes its expression, while lrhA expression is feedback inhibited by the activated Rcs phosphorelay system. Overall, our data support a model whereby P. alhagi senses environmental osmolarity changes through the EnvZ-OmpR two-component system and LrhA to regulate the synthesis of OPGs, EPS production, and flagellum-dependent motility, thereby employing a hierarchical signaling cascade to control the transition between a motile lifestyle and a biofilm lifestyle. IMPORTANCE Many motile bacterial populations form surface-attached biofilms in response to specific environmental cues, including osmotic stress in a range of natural and host-related systems. However, cross talk between bacterial osmosensing, swimming, and biofilm formation regulatory networks is not fully understood. Here, we report that the pleiotropic regulator LrhA in Pantoea alhagi is involved in the regulation of flagellar motility, biofilm formation, and host colonization and responds to osmotic upshift. We further show that this sensing relies on the EnvZ-OmpR two-component system that was known to detect changes in external osmotic stress. The EnvZ-OmpR-LrhA osmosensing signal transduction cascade is proposed to increase bacterial fitness under hyperosmotic conditions inside the host. Our work proposes a novel regulatory mechanism that links osmosensing and motile-sessile lifestyle transitions, which may provide new approaches to prevent or promote the formation of biofilms and host colonization in P. alhagi and other bacteria possessing a similar osmoregulatory mechanism. [ABSTRACT FROM AUTHOR]

Efficient root colonization is a prerequisite for application of plant growthpromoting (PGP) bacteria in improving health and yield of agricultural crops. We have recently identified an endophytic bacterium, Pantoea alhagi LTYR-11Z, with multiple PGP properties that effectively colonizes the root system of wheat and improves its growth and drought tolerance. To identify novel regulatory genes required for wheat colonization, we screened an LTYR-11Z transposon (Tn) insertion library and found cra to be a colonization-related gene. By using transcriptome (RNA-seq) analysis, we found that transcriptional levels of an eps operon, the ydiV gene encoding an anti-FlhD4C2 factor, and the yedQ gene encoding an enzyme for synthesis of cyclic dimeric GMP (c-di-GMP) were significantly downregulated in the Δcra mutant. Further studies demonstrated that Cra directly binds to the promoters of the eps operon, ydiV, and yedQ and activates their expression, thus inhibiting motility and promoting exopolysaccharide (EPS) production and biofilm formation. Consistent with previous findings that Cra plays a role in transcriptional regulation in response to carbon source availability, the activating effects of Cra were much more pronounced when LTYR-11Z was grown within a gluconeogenic environment than when it was grown within a glycolytic environment. We further demonstrate that the ability of LTYR-11Z to colonize wheat roots is modulated by the availability of carbon sources. Altogether, these results uncover a novel strategy utilized by LTYR-11Z to achieve host colonization in response to carbon nutrition in the environment, in which Cra bridges a connection between carbon metabolism and colonization capacity of LTYR-11Z. IMPORTANCE Rapid and appropriate response to environmental signals is crucial for bacteria to adapt to competitive environments and to establish interactions with their hosts. Efficient colonization and persistence within the host are controlled by various regulatory factors that respond to specific environmental cues. The most common is nutrient availability. In this work, we unraveled the pivotal role of Cra in regulation of colonization ability of Pantoea alhagi LTYR-11Z in response to carbon source availability. Moreover, we identified three novel members of the Cra regulon involved in EPS synthesis, regulation of flagellar biosynthesis, and synthesis of c-di-GMP and propose a working model to explain the Cra-mediated regulatory mechanism that links carbon metabolism to host colonization. This study elucidates the regulatory role of Cra in bacterial attachment and colonization of plants, which raises the possibility of extending our studies to other bacteria associated with plant and human health. [ABSTRACT FROM AUTHOR]