Dissecting the molecular basis of the ultra-large grain formation in rice.

The shape of rice grains not only determines the thousand-grain weight but also correlates closely with the grain quality. Here we identified an ultra-large grain accession (ULG) with a thousand-grain weight exceeding 60 g. The integrated analysis of QTL, BSA, de novo genome assembled, transcription sequencing, and gene editing was conducted to dissect the molecular basis of the ULG formation. The ULG pyramided advantageous alleles from at least four known grain-shaping genes, OsLG3, OsMADS1, GS3, GL3.1, and one novel locus, qULG2-b, which encoded a leucine-rich repeat receptor-like kinase. The collective impacts of OsLG3, OsMADS1, GS3, and GL3.1 on grain size were confirmed in transgenic plants and near-isogenic lines. The transcriptome analysis identified 112 genes cooperatively regulated by these four genes that were prominently involved in photosynthesis and carbon metabolism. By leveraging the pleiotropy of these genes, we enhanced the grain yield, appearance, and stress tolerance of rice var. SN265. Beyond showcasing the pyramiding of multiple grain size regulation genes that can produce ULG, our study provides a theoretical framework and valuable genomic resources for improving rice variety by leveraging the pleiotropy of grain size regulated genes.

Modulation of ER-mitochondria tethering complex VAPB-PTPIP51: Novel therapeutic targets for aging-associated diseases.

Aging is a gradual and irreversible natural process. With aging, the body experiences a functional decline, and the effects amplify the vulnerability to a range of age-related diseases, including neurodegenerative, cardiovascular, and metabolic diseases. Within the aging process, the morphology and function of mitochondria and the endoplasmic reticulum (ER) undergo alterations, particularly in the structure connecting these organelles known as mitochondria-associated membranes (MAMs). MAMs serve as vital intracellular signaling hubs, facilitating communication between the ER and mitochondria when regulating various cellular events, including calcium homeostasis, lipid metabolism, mitochondrial function, and apoptosis. The formation of MAMs is partly dependent on the interaction between the vesicle-associated membrane protein-associated protein-B (VAPB) and protein tyrosine phosphatase-interacting protein-51 (PTPIP51). Accumulating evidence has begun to elucidate the pivotal role of the VAPB-PTPIP51 tether in the initiation and progression of age-related diseases. In this study, we delineate the intricate structure and multifunctional role of the VAPB-PTPIP51 tether and discuss its profound implications in aging-associated diseases. Moreover, we provide a comprehensive overview of potential therapeutic interventions and pharmacological agents targeting the VAPB-PTPIP51-mediated MAMs, thereby offering a glimmer of hope in mitigating aging processes and treating age-related disorders.

The DEP1 Mutation Improves Stem Lodging Resistance and Biomass Saccharification by Affecting Cell Wall Biosynthesis in Rice.

BACKGROUND: Plant cell walls have evolved precise plasticity in response to environmental stimuli. The plant heterotrimeric G protein complexes could sense and transmit extracellular signals to intracellular signaling systems, and activate a series of downstream responses. dep1 (Dense and Erect Panicles 1), the gain-of-function mutation of DEP1 encoding a G protein γ subunit, confers rice multiple improved agronomic traits. However, the effects of DEP1 on cell wall biosynthesis and wall-related agronomic traits remain largely unknown. RESULTS: In this study, we showed that the DEP1 mutation affects cell wall biosynthesis, leading to improved lodging resistance and biomass saccharification. The DEP1 is ubiquitously expressed with a relatively higher expression level in tissues rich in cell walls. The CRISPR/Cas9 editing mutants of DEP1 (dep1-cs) displayed a significant enhancement in stem mechanical properties relative to the wild-type, leading to a substantial improvement in lodging resistance. Cell wall analyses showed that the DEP1 mutation increased the contents of cellulose, hemicelluloses, and pectin, and reduced lignin content and cellulose crystallinity (CrI). Additionally, the dep1-cs seedlings exhibited higher sensitivity to cellulose biosynthesis inhibitors, 2,6-Dichlorobenzonitrile (DCB) and isoxaben, compared with the wild-type, confirming the role of DEP1 in cellulose deposition. Moreover, the DEP1 mutation-mediated alterations of cell walls lead to increased enzymatic saccharification of biomass after the alkali pretreatment. Furthermore, the comparative transcriptome analysis revealed that the DEP1 mutation substantially altered expression of genes involved in carbohydrate metabolism, and cell wall biosynthesis. CONCLUSIONS: Our findings revealed the roles of DEP1 in cell wall biosynthesis, lodging resistance, and biomass saccharification in rice and suggested genetic modification of DEP1 as a potential strategy to develop energy rice varieties with high lodging resistance.

Ferroptosis in age-related vascular diseases: Molecular mechanisms and innovative therapeutic strategies.

Aging, an inevitable aspect of human existence, serves as one of the predominant risk factors for vascular diseases. Delving into the mystery of vascular disease's pathophysiology, the profound involvement of programmed cell death (PCD) has been extensively demonstrated. PCD is a fundamental biological process that plays a crucial role in both normal physiology and pathology, including a recently discovered form, ferroptosis. Ferroptosis is characterized by its reliance on iron and lipid peroxidation, and its significant involvement in vascular disease pathophysiology has been increasingly acknowledged. This phenomenon not only offers a promising therapeutic target but also deepens our understanding of the complex relationship between ferroptosis and age-related vascular diseases. Consequently, this article aims to thoroughly review the mechanisms that enable the effective control and inhibition of ferroptosis. It focuses on genetic and pharmacological interventions, with the goal of developing innovative therapeutic strategies to combat age-related vascular diseases.

Mapping the knowledge domains of medical textiles: A review.

As the world's textile industry shifts towards manufacturing high value-added textile structures and products, medical textiles have drawn extensive attention from researchers and the related research field is rapidly developing in recent years. To provide readers a systematic overview of this research field, a comprehensive bibliometric analysis of scientific publications related to the field in performed and visually presented using the software CiteSpace and VOSviewer in this paper. Totally 2839 papers have been retrieved and collected from the core database of Web of Science™. First, the papers are divided into several groups and quantitatively analyzed based on the year of publication, the citations in each year, and the disciplines involved in the papers. VOSviewer is adopted to analyze the collaboration among countries, organizations, and authors in the research community as well as their research output and influence in terms of citation. Then the major journals in the field are identified through performing co-citation analysis on source journals of all references cited in the retrieved papers. In addition, the highly cited papers and their references are listed in this paper. They offer researchers a glimpse of the internal relationship of scientific literature and the dynamic structure of scientific evolution. Finally, the co-occurrence analysis of keywords is also performed using VOSviewer and CiteSpace. The connection between various disciplines in the research field is revealed, so that the scientific development history, the research hotspots, and main research directions in the field can be traced.

The Fragile culm19 (FC19) mutation largely improves plant lodging resistance, biomass saccharification, and cadmium resistance by remodeling cell walls in rice.

Cell wall is essential for plant upright growth, biomass saccharification, and stress resistance. Although cell wall modification is suggested as an effective means to increase biomass saccharification, it is a challenge to maintain normal plant growth with improved mechanical strength and stress resistance. Here, we reported two independent fragile culm mutants, fc19-1 and fc19-2, resulting from novel mutations of OsIRX10, produced by the CRISPR/Cas9 system. Compared to wild-type, the two mutants exhibited reduced contents of xylose, hemicellulose, and cellulose, and increased arabinose and lignin without significant alteration in levels of pectin and uronic acids. Despite brittleness, the mutants displayed increased breaking force, leading to improved lodging resistance. Furthermore, the altered cell wall and increased biomass porosity in fc19 largely increased biomass saccharification. Notably, the mutants showed enhanced cadmium (Cd) resistance with lower Cd accumulation in roots and shoots. The FC19 mutation impacts transcriptional levels of key genes contributing to Cd uptake, sequestration, and translocation. Moreover, transcriptome analysis revealed that the FC19 mutation resulted in alterations of genes mainly involved in carbohydrate and phenylpropanoid metabolism. Therefore, a hypothetic model was proposed to elucidate that the FC19 mutation-mediated cell wall remodeling leads to improvements in lodging resistance, biomass saccharification, and Cd resistance.

Textile waste water treatment: analysis of mapping knowledge domains.

Textile waste water contains dyes and chemicals that produce harmful vapors and exhaust gases, which is hazardous to the environment and public health. Therefore, it must be carefully treated before discharged. To understand the research evolution in the research area of textile waste water treatment, based on bibliometrics, an in-depth analysis of the publications and hotspots in this area was presented in this paper. For the analysis, totally 6774 papers related to the research area that are published between the year 1964 and 2023 were collected from the Web of Science Core Collection. Using CiteSpace and VOSviewer as bibliometric analysis tools, the collaboration of countries, regions, and organizations was investigated. Besides, an analysis for citation and co-citation of journals, authors, references, and co-occurrence of keywords was performed. The evolution of research hotspots in the three major research directions related to degradation, oxidation, and adsorption is also analyzed in this paper. The analysis results show that researches related to oxidation and adsorption are active in recent years, while nanocomposite adsorbents and graphene oxide are the current research hotspots.

Cloning and function analysis of a Saussurea involucrata LEA4 gene.

Late embryogenesis abundant proteins (LEA) help adapt to adverse low-temperature environments. The Saussurea involucrate SiLEA4, which encodes a membrane protein, was significantly up-regulated in response to low temperature stress. Escherichia coli expressing SiLEA4 showed enhanced low-temperature tolerance, as evident from the significantly higher survival numbers and growth rates at low temperatures. Moreover, tomato strains expressing SiLEA4 had significantly greater freezing resistance, due to a significant increase in the antioxidase activities and proline content. Furthermore, they had higher yields due to higher water utilization and photosynthetic efficiency under the same water and fertilizer conditions. Thus, expressing SiLEA4 has multiple advantages: (1) mitigating chilling injury, (2) increasing yields, and (3) water-saving, which also indicates the great potential of the SiLEA4 for breeding applications.

OsUGE3-mediated cell wall polysaccharides accumulation improves biomass production, mechanical strength, and salt tolerance.

Cell walls constitute the majority of plant biomass and are essential for plant resistance to environmental stresses. It is promising to improve both plant biomass production and stress resistance simultaneously by genetic modification of cell walls. Here, we report the functions of a UDP-galactose/glucose epimerase 3 (OsUGE3) in rice growth and salt tolerance by characterizing its overexpressing plants (OsUGE3-OX) and loss-of-function mutants (uge3). The OsUGE3-OX plants showed improvements in biomass production and mechanical strength, whereas uge3 mutants displayed growth defects. The OsUGE3 exhibits UDP-galactose/glucose epimerase activity that provides substrates for polysaccharides polymerization, consistent with the increased biosynthesis of cellulose and hemicelluloses and strengthened walls in OsUGE3-OX plants. Notably, the OsUGE3 is ubiquitously expressed and induced by salt treatment. The uge3 mutants were hypersensitive to salt and osmotic stresses, whereas the OsUGE3-OX plants showed improved tolerance to salt and osmotic stresses. Moreover, OsUGE3 overexpression improves the homeostasis of Na+ and K+ and induces a higher accumulation of hemicelluloses and soluble sugars during salt stress. Our results suggest that OsUGE3 improves biomass production, mechanical strength, and salt stress tolerance by reinforcement of cell walls with polysaccharides and it could be targeted for genetic modification to improve rice growth under salt stress.

FRAGILE CULM 18 encodes a UDP-glucuronic acid decarboxylase required for xylan biosynthesis and plant growth in rice.

Although UDP-glucuronic acid decarboxylases (UXSs) have been well studied with regard to catalysing the conversion of UDP-glucuronic acid into UDP-xylose, their biological roles in grasses remain largely unknown. The rice (Oryza sativa) genome contains six UXSs, but none of them has been genetically characterized. Here, we reported on the characterization of a novel rice fragile culm mutant, fc18, which exhibited brittleness with altered cell wall and pleiotropic defects in growth. Map-based cloning and transgenic analyses revealed that the FC18 gene encodes a cytosol-localized OsUXS3 and is widely expressed with higher expression in xylan-rich tissues. Monosaccharide analysis showed that the xylose level was decreased in fc18, and cell wall fraction determinations confirmed that the xylan content in fc18 was lower, suggesting that UDP-xylose from FC18 participates in xylan biosynthesis. Moreover, the fc18 mutant displayed defective cellulose properties, which led to an enhancement in biomass saccharification. Furthermore, expression of genes involved in sugar metabolism and phytohormone signal transduction was largely altered in fc18. Consistent with this, the fc18 mutant exhibited significantly reduced free auxin (indole-3-acetic acid) content and lower expression levels of PIN family genes compared with wild type. Our work reveals the physiological roles of FC18/UXS3 in xylan biosynthesis, cellulose deposition, and plant growth in rice.

The Rice BZ1 Locus Is Required for Glycosylation of Arabinogalactan Proteins and Galactolipid and Plays a Role in both Mechanical Strength and Leaf Color.

BACKGROUND: The cell wall and chloroplast are two fundamental structures determining plant mechanical strength and grain yield. Therefore, understanding mechanisms that improve plants' ability to develop a robust cell wall and well-developed chloroplast is of utmost importance for agricultural activities. RESULTS: In this study, we report the functional characterization of a novel rice mutant, brittle stem and zebra leaf (bz1), which displays altered cell wall composition and collapsed chloroplast membrane. Molecular and biochemical analysis revealed that BZ1 encodes a functional UDP-galactose/glucose epimerase (UGE) and is ubiquitously expressed with higher expression in stem and leaf tissues. Multiple techniques analyses, including immunoblots, immuno-gold, and cryogenic scanning electron microscopy, demonstrated a significantly impaired glycosylation of arabinogalactan proteins (AGPs) and disordered cellulose microfibril deposition in bz1. Lipid profiling assay showed that the amount of monogalactosyldiacylglycerols (MGDG), a major chloroplast membrane glycolipid, was significantly decreased in bz1. Taken together, these results strongly demonstrate that BZ1 participates in UDP-galactose supply for the sugar chains biosynthesis of AGPs and MGDG, which thereby, respectively, results in altered cell wall and abnormal chloroplast development. Due to inferior mechanical strength and reduced photosynthesis, bz1 plants displayed detrimental agronomic traits, whereas BZ1 overexpressing lines showed enhanced plant growth. Transcriptome analysis of stems and leaves further showed that numerous key genes involved in AGPs biosynthesis and photosynthesis metabolism were substantially suppressed in bz1. CONCLUSIONS: Our finding identifies BZ1 as a dual-targeting UGE protein for glycosylation of AGPs and MGDG and suggests a strategy for breeding robust elite crops.

Dopamine D2 receptor-mediated Akt/PKB signalling: initiation by the D2S receptor and role in quinpirole-induced behavioural activation.

The short and long isoforms of the dopamine D2 receptor (D2S and D2L respectively) are highly expressed in the striatum. Functional D2 receptors activate an intracellular signalling pathway that includes a cAMP-independent route involving Akt/GSK3 (glycogen synthase kinase 3). To investigate the Akt/GSK3 response to the seldom-studied D2S receptor, we established a rat D2S receptor-expressing cell line [HEK (human embryonic kidney)-293/rD2S]. We found that in HEK-293/rD2S cells, the D2/D3 agonists bromocriptine and quinpirole significantly induced Akt and GSK3 phosphorylation, as well as ERK1/2 (extracellular-signal-regulated kinase 1/2) activation. The D2S receptor-induced Akt signals were profoundly inhibited by the internalization blockers monodansyl cadaverine and concanavalin A. Activation of the D2S receptor in HEK-293/rD2S cells appeared to trigger Akt/phospho-Akt translocation to the cell membrane. In addition to our cell culture experiments, we studied D2 receptor-dependent Akt in vivo by systemic administration of the D2/D3 agonist quinpirole. The results show that quinpirole evoked Akt-Ser473 phosphorylation in the ventral striatum. Furthermore, intra-accumbens administration of wortmannin, a PI3K (phosphoinositide 3-kinase) inhibitor, significantly suppressed the quinpirole-evoked behavioural activation. Overall, we demonstrate that activation of the dopamine D2S receptor stimulates Akt/GSK3 signalling. In addition, in vivo Akt activity in the ventral striatum appears to play an important role in systemic D2/D3 agonist-induced behavioural activation.

Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction.

The dynamic interaction between positive and negative signals is necessary for remodeling of postsynaptic structures at the neuromuscular junction. Here we report that Wnt3a negatively regulates acetylcholine receptor (AChR) clustering by repressing the expression of Rapsyn, an AChR-associated protein essential for AChR clustering. In cultured myotubes, treatment with Wnt3a or overexpression of beta-catenin, the condition mimicking the activation of the Wnt canonical pathway, inhibited Agrin-induced formation of AChR clusters. Moreover, Wnt3a treatment promoted dispersion of AChR clusters, and this effect was prevented by DKK1, an antagonist of the Wnt canonical pathway. Next, we investigated possible mechanisms underlying Wnt3a regulation of AChR clustering in cultured muscle cells. Interestingly, we found that Wnt3a treatment caused a decrease in the protein level of Rapsyn. In addition, Rapsyn promoter activity in cultured muscle cells was inhibited by the treatment with Wnt3a or beta-catenin overexpression. Forced expression of Rapsyn driven by a promoter that is not responsive to Wnt3a prevented the dispersing effect of Wnt3a on AChR clusters, suggesting that Wnt3a indeed acts to disperse AChR clusters by down-regulating the expression of Rapsyn. The role of Wnt/beta-catenin signaling in dispersing AChR clusters was also investigated in vivo by electroporation of Wnt3a or beta-catenin into mouse limb muscles, where ectopic Wnt3a or beta-catenin caused disassembly of postsynaptic apparatus. Together, these results suggest that Wnt/beta-catenin signaling plays a negative role for postsynaptic differentiation at the neuromuscular junction, probably by regulating the expression of synaptic proteins, such as Rapsyn.

Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction.

Agrin induces, whereas acetylcholine (ACh) disperses, ACh receptor (AChR) clusters during neuromuscular synaptogenesis. Such counteractive interaction leads to eventual dispersal of nonsynaptic AChR-rich sites and formation of receptor clusters at the postjunctional membrane. However, the underlying mechanisms are not well understood. Here we show that calpain, a calcium-dependent protease, is activated by the cholinergic stimulation and is required for induced dispersion of AChR clusters. Interestingly, the AChR-associated protein rapsyn interacted with calpain in an agrin-dependent manner, and this interaction inhibited the protease activity of calpain. Disrupting the endogenous rapsyn/calpain interaction enhanced CCh-induced dispersion of AChR clusters. Moreover, the loss of AChR clusters in agrin mutant mice was partially rescued by the inhibition of calpain via overexpressing calpastatin, an endogenous calpain inhibitor, or injecting calpeptin, a cell-permeable calpain inhibitor. These results demonstrate that calpain participates in ACh-induced dispersion of AChR clusters, and rapsyn stabilizes AChR clusters by suppressing calpain activity.