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Rice (Oryza sativa), the staple food for almost half of the world's population, prefers ammonium (NH4 +) as the major nitrogen resource, and while NH4 + has profound effects on rice growth and yields, the underlying regulatory mechanisms remain largely unknown. Brassinosteroids (BRs) are a class of steroidal hormones playing key roles in plant growth and development. In this study, we show that NH4 + promotes BR biosynthesis through miR444 to regulate rice root growth. miR444 targeted five homologous MADS-box transcription repressors potentially forming homologous or heterogeneous complexes in rice. miR444 positively regulated BR biosynthesis through its MADS-box targets, which directly repress the transcription of BR-deficient dwarf 1 (OsBRD1), a key BR biosynthetic gene. NH4 + induced the miR444-OsBRD1 signaling cascade in roots, thereby increasing the amount of BRs, whose biosynthesis and signaling were required for NH4 +-dependent root elongation inhibition. Consistently, miR444-overexpressing rice roots were hypersensitive to NH4 + depending on BR biosynthesis, and overexpression of miR444's target, OsMADS57, resulted in rice hyposensitivity to NH4 + in root elongation, which was associated with a reduction of BR content. In summary, our findings reveal a cross talk mechanism between NH4 + and BR in which NH4 + activates miR444-OsBRD1, an undescribed BR biosynthesis-promoting signaling cascade, to increase BR content, inhibiting root elongation in rice.

As a by product of higher value cotton fibre, cotton seed has been increasingly recognised to have excellent potential as a source of additional food, feed, biofuel stock and even a renewable platform for the production of many diverse biological molecules for agriculture and industrial enterprises. The large size difference between cotyledon and embryo axis that make up a cotton seed results in the under-representation of embryo axis gene transcript levels in whole seed embryo samples. Therefore, the determination of gene transcript levels in the cotyledons and embryo axes separately should lead to a better understanding of metabolism in these two developmentally diverse tissues. A comparative study of transcriptome changes between cotton developing cotyledon and embryo axis has been carried out. 17,384 unigenes (20.74% of all the unigenes) were differentially expressed in the two adjacent embryo tissues, and among them, 7,727 unigenes (44.45%) were down-regulated and 9,657 unigenes (55.55%) were up-regulated in cotyledon. Our study has provided a comprehensive dataset that documents the dynamics of the transcriptome at the mid-maturity of cotton seed development and in discrete seed tissues, including embryo axis and cotyledon tissues. The results showed that cotton seed is subject to many transcriptome variations in these two tissue types and the differential gene expression between cotton embryo axis and cotyledon uncovered in our study should provide an important starting point for understanding how gene activity is coordinated during seed development to make a seed. Further, the identification of genes involved in rapid metabolite accumulation stage of seed development will extend our understanding of the complex molecular and cellular events in these developmental processes and provide a foundation for future studies on the metabolism, embryo differentiation of cotton and other dicot oilseed crops.

Vegetable oils high in oleic acid are considered to be advantageous because of their better nutritional value and potential industrial applications. The oleic acid content in the classic safflower oil is normally 10-15% while a natural mutant (ol) accumulates elevated oleic acid up to 70% in seed oil. As a part of our investigation into the molecular features of the high oleic (HO) trait in safflower we have profiled the microRNA (miRNA) populations in developing safflower seeds expressing the ol allele in comparison to the wild type high linoleic (HL) safflower using deep sequencing technology. The small RNA populations of the mid-maturity developing embryos of homozygous ol HO and wild type HL safflower had a very similar size distribution pattern, however, only ~16.5% of the unique small RNAs were overlapping in these two genotypes. From these two small RNA populations we have found 55 known miRNAs and identified two candidate novel miRNA families to be likely unique to the developing safflower seeds. Target genes with conserved as well as novel functions were predicted for the conserved miRNAs. We have also identified 13 miRNAs differentially expressed between the HO and HL safflower genotypes. The results may lay a foundation for unraveling the miRNA-mediated molecular processes that regulate oleic acid accumulation in the HO safflower mutant and developmental processes in safflower embryos in general.

Plant RNA-DEPENDENT RNA POLYMERASE1 (RDR1) is a key component of the antiviral RNA-silencing pathway, contributing to the biogenesis of virus-derived small interfering RNAs. This enzyme also is responsible for producing virus-activated endogenous small interfering RNAs to stimulate the broad-spectrum antiviral activity through silencing host genes. The expression of RDR1 orthologs in various plants is usually induced by virus infection. However, the molecular mechanisms of activation of RDR1 expression in response to virus infection remain unknown. Here, we show that a monocot-specific microRNA, miR444, is a key factor in relaying the antiviral signaling from virus infection to OsRDR1 expression. The expression of miR444 is enhanced by infection with Rice stripe virus (RSV), and overexpression of miR444 improves rice (Oryza sativa) resistance against RSV infection accompanied by the up-regulation of OsRDR1 expression. We further show that three miR444 targets, the MIKCC-type MADS box proteins OsMADS23, OsMADS27a, and OsMADS57, form homodimers and heterodimers between them to repress the expression of OsRDR1 by directly binding to the CArG motifs of its promoter. Consequently, an increased level of miR444 diminishes the repressive roles of OsMADS23, OsMADS27a, and OsMADS57 on OsRDR1 transcription, thus activating the OsRDR1-dependent antiviral RNA-silencing pathway. We also show that overexpression of miR444-resistant OsMADS57 reduced OsRDR1 expression and rice resistance against RSV infection, and knockout of OsRDR1 reduced rice resistance against RSV infection. In conclusion, our results reveal a molecular cascade in the rice antiviral pathway in which miR444 and its MADS box targets directly control OsRDR1 transcription.

Background As a by product of higher value cotton fibre, cotton seed has been increasingly recognised to have excellent potential as a source of additional food, feed, biofuel stock and even a renewable platform for the production of many diverse biological molecules for agriculture and industrial enterprises. The large size difference between cotyledon and embryo axis that make up a cotton seed results in the under-representation of embryo axis gene transcript levels in whole seed embryo samples. Therefore, the determination of gene transcript levels in the cotyledons and embryo axes separately should lead to a better understanding of metabolism in these two developmentally diverse tissues. Results A comparative study of transcriptome changes between cotton developing cotyledon and embryo axis has been carried out. 17,384 unigenes (20.74% of all the unigenes) were differentially expressed in the two adjacent embryo tissues, and among them, 7,727 unigenes (44.45%) were down-regulated and 9,657 unigenes (55.55%) were up-regulated in cotyledon. Conclusions Our study has provided a comprehensive dataset that documents the dynamics of the transcriptome at the mid-maturity of cotton seed development and in discrete seed tissues, including embryo axis and cotyledon tissues. The results showed that cotton seed is subject to many transcriptome variations in these two tissue types and the differential gene expression between cotton embryo axis and cotyledon uncovered in our study should provide an important starting point for understanding how gene activity is coordinated during seed development to make a seed. Further, the identification of genes involved in rapid metabolite accumulation stage of seed development will extend our understanding of the complex molecular and cellular events in these developmental processes and provide a foundation for future studies on the metabolism, embryo differentiation of cotton and other dicot oilseed crops.

Immuno-oncology has witnessed remarkable advancements in the past decade, revolutionizing the landscape of cancer therapeutics in an encouraging manner. Among the diverse immunotherapy strategies, mRNA vaccines have ushered in a new era for the therapeutic management of malignant diseases, primarily due to their impressive impact on the COVID-19 pandemic. In this comprehensive review, we offer a systematic overview of mRNA vaccines, focusing on the optimization of structural design, the crucial role of delivery materials, and the administration route. Additionally, we summarize preclinical studies and clinical trials to provide valuable insights into the current status of mRNA vaccines in cancer treatment. Furthermore, we delve into a systematic discussion on the significant challenges facing the current development of mRNA tumor vaccines. These challenges encompass both intrinsic and external factors that are closely intertwined with the successful application of this innovative approach. To pave the way for a more promising future in cancer treatments, a deeper understanding of immunological mechanisms, an increasing number of high-quality clinical trials, and a well-established manufacturing platform are crucial. Collaborative efforts between scientists, clinicians, and industry engineers are essential to achieving these goals.

Rates of photosynthesis can be lower in plants grown under conditions of high leaf-to-air vapour pressure difference (VPD) than under low VPD. Leaf phenotype plasticity is a primary factor determining photosynthetic responses to environmental stimuli. However, it remains unclear how changes in leaf anatomical traits drive photosynthetic acclimation to high VPD. Here, we examined the role of leaf anatomy in the differing photosynthetic responses of two tomato cultivars (Jinpeng and Zhongza) to long-term growth under high and low VPD. Photosynthesis was not affected by VPD in Jinpeng. This was attributed to homeostasis in stomatal conductance (g s) and, to a lesser extent, mesophyll conductance (g m). Disruption of synchronized changes to cell size in the epidermis and mesophyll meant that growth under high VPD reduced stomatal density in Jinpeng, but minor vein density remained unchanged. Thus, water supplied by the veins could support the increased transpirational demand, preventing stomatal closure. Variation in VPD did not affect mesophyll cell structures, and therefore g m, in Jinpeng. By contrast, photosynthesis in Zhongza was reduced under high VPD, which was primarily attributed to decreased g s and g m. The former was mainly induced by decreased stomatal aperture. Thus, transpirational demand exceeded water supply in Zhongza. This was likely due to coordinated decreases in stomatal and minor vein density driven by synchronized increases in epidermal and mesophyll cell size under high VPD. Liquid-phase limitation was primarily responsible for the reduced g m in Zhongza under high VPD. High VPD induced an increase in liquid-phase resistance by reducing the mesophyll surface area exposed to intercellular air spaces and increasing cytosolic resistance. These results suggest that plasticity in epidermal and mesophyll cell size provides an efficient means of regulating photosynthesis during acclimation to long-term high VPD.

Particle size reduction inevitably occurs inside ironmaking blast furnaces (BFs) but is not studied under BF conditions due to the lack of an effective tool. This paper simulates this phenomenon inside a 5000-m3 commercial BF using a recently developed three-dimensional computational fluid dynamics (CFD) process model. In particular, the sinter reduction degradation and coke gasification are modeled for considering the size reduction. By incorporating this information in the BF model, the in-furnace states and global performance are evaluated with respect to sinter reduction degradation index (RDI) under different conditions, e.g., keeping a constant blast rate or gas pressure drop. The results show that with increasing RDI, the bed permeability deteriorates, and there exists a critical value of RDI beyond which the decreased bed permeability leads to a significant drop in productivity for a given gas pressure drop. However, this problem can be mitigated substantially by charging more coke particles at the furnace periphery under the conditions considered. The proposed approach offers an extended capability to model and control BF operations.

The aim of this study was to investigate the effect of quercetin on hepatic fibrosis, a characteristic response to acute or chronic liver injury. Mice were randomized to bile duct ligation (BDL) or carbon tetrachloride (CCl 4 ) cirrhosis models. Quercetin (100 mg/kg or 200 mg/kg daily) was administered by gavage for 2 or 4 weeks. Liver tissue and blood samples were collected for histological and molecular analysis. The results of our experiments showed that quercetin reduced BDL or CCl 4 liver fibrosis, inhibited extracellular matrix formation, and regulated matrix metallopeptidase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1. Quercetin attenuated liver damage by suppressing the TGF-β1/Smads signaling pathway and activating the PI3K/Akt signaling pathway to inhibit autophagy in BDL- or CCl 4 - induced liver fibrosis. Quercetin prevented hepatic fibrosis by attenuating hepatic stellate cell activation and reducing autophagy through regulating crosstalk between the TGF-β1/Smads and PI3K/Akt pathways.

Yak has been subject to natural selection, human domestication and interspecific introgression during its evolution. However, genetic variants favored by each of these processes have not been distinguished previously. We constructed a graph-genome for 47 genomes of 7 cross-fertile bovine species. This allowed detection of 57,432 high-resolution structural variants (SVs) within and across the species, which were genotyped in 386 individuals. We distinguished the evolutionary origins of diverse SVs in domestic yaks by phylogenetic analyses. We further identified 334 genes overlapping with SVs in domestic yaks that bore potential signals of selection from wild yaks, plus an additional 686 genes introgressed from cattle. Nearly 90% of the domestic yaks were introgressed by cattle. Introgression of an SV spanning the KIT gene triggered the breeding of white domestic yaks. We validated a significant association of the selected stratified SVs with gene expression, which contributes to phenotypic variations. Our results highlight that SVs of different origins contribute to the phenotypic diversity of domestic yaks. Yaks have been subject to natural selection, human domestication and interspecific introgression during their evolution. Here, the authors have identified genomic structural variations and the linked genes involved in these processes in domestic yaks, to reveal new insight into genetic basis of phenotypic diversity.