Network pharmacology and molecular docking reveal the immunomodulatory mechanism of rhubarb peony decoction for the treatment of ulcerative colitis and irritable bowel syndrome.

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) share various similarities in clinical symptoms, pathogenesis, and treatment. UC concurrent IBS tends toward more severe symptoms and worse prognosis, and promising feasible therapies for the overlapping symptoms remains a challenge. Rhubarb peony decoction (RPD) is a well-known traditional Chinese medicine that has been widely applied in treating UC.

Ligand-induced activation and G protein coupling of prostaglandin F receptor.

Prostaglandin F (PGF), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled receptor (GPCR), the PGF receptor (FP), which also is the primary therapeutic target for glaucoma and several other diseases. Here, we report cryo-electron microscopy (cryo-EM) structures of the human FP bound to endogenous ligand PGF and anti-glaucoma drugs LTPA and TFPA at global resolutions of 2.67 Å, 2.

Improving diameter measurement from Fraunhofer diffraction with fringe segment splicing.

Fraunhofer diffraction is an easy but powerful method for measuring the diameter of a thin filament. In practice, however, the diffraction pattern attainable is always subject to limits imposed by various imperfections in real systems, such as small angle approximation and sensor threshold, thus degrading the measurement resolution. In this Letter, we propose a method of fringe segment splicing for improving the diameter measurement from Fraunhofer diffraction.

Estimating divergent forest carbon stocks and sinks via a knife set approach.

Forest carbon stocks and sinks (CSSs) have been widely estimated using climate classification tables and linear regression (LR) models with common independent variables (IVs) such as the average diameter at breast height (DBH) of stems and root shoot ratio. However, this approach is relatively ineffective when the explanatory power of IVs is lower than that of unobservable variables. Various environmental and anthropogenic factors affect target variables that cause the correlation between them to be chaotic.

Structure of PDE3A-SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells.

Molecular glues are a class of small molecular drugs that mediate protein-protein interactions, that induce either the degradation or stabilization of target protein. A structurally diverse group of chemicals, including 17-β-estradiol (E2), anagrelide, nauclefine, and DNMDP, induces apoptosis by forming complexes with phosphodiesterase 3A (PDE3A) and Schlafen 12 protein (SLFN12). They do so by binding to the PDE3A enzymatic pocket that allows the compound-bound PDE3A to recruit and stabilize SLFN12, which in turn blocks protein translation, leading to apoptosis.

A phosphorylation of RIPK3 kinase initiates an intracellular apoptotic pathway that promotes prostaglandin-induced corpus luteum regression.

Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) normally signals to necroptosis by phosphorylating MLKL. We report here that when the cellular RIPK3 chaperone Hsp90/CDC37 level is low, RIPK3 also signals to apoptosis. The apoptotic function of RIPK3 requires phosphorylation of the serine 165/threonine 166 sites on its kinase activation loop, resulting in inactivation of RIPK3 kinase activity while gaining the ability to recruit RIPK1, FADD, and caspase-8 to form a cytosolic caspase-activating complex, thereby triggering apoptosis.

Casein kinase 1G2 suppresses necroptosis-promoted testis aging by inhibiting receptor-interacting kinase 3.

Casein kinases are a large family of intracellular serine/threonine kinases that control a variety of cellular signaling functions. Here we report that a member of casein kinase 1 family, casein kinase 1G2, CSNK1G2, binds and inhibits the activation of receptor-interacting kinase 3, RIPK3, thereby attenuating RIPK3-mediated necroptosis. The binding of CSNK1G2 to RIPK3 is triggered by auto-phosphorylation at serine 211/threonine 215 sites in its C-terminal domain.

Genome-wide identification of the restorer-of-fertility-like (RFL) gene family in Brassica napus and expression analysis in Shaan2A cytoplasmic male sterility.

Background: Cytoplasmic male sterility (CMS) is very important in hybrid breeding. The restorer-of-fertility (Rf) nuclear genes rescue the sterile phenotype. Most of the Rf genes encode pentatricopeptide repeat (PPR) proteins.

An alkaloid initiates phosphodiesterase 3A-schlafen 12 dependent apoptosis without affecting the phosphodiesterase activity.

The promotion of apoptosis in tumor cells is a popular strategy for developing anti-cancer drugs. Here, we demonstrate that the plant indole alkaloid natural product nauclefine induces apoptosis of diverse cancer cells via a PDE3A-SLFN12 dependent death pathway. Nauclefine binds PDE3A but does not inhibit the PDE3A's phosphodiesterase activity, thus representing a previously unknown type of PDE3A modulator that can initiate apoptosis without affecting PDE3A's canonical function.

Estrogen-Related Hormones Induce Apoptosis by Stabilizing Schlafen-12 Protein Turnover.

The mitochondrial pathway of apoptosis is controlled by the ratio of anti- and pro-apoptotic members of the Bcl-2 family of proteins. The molecular events underlying how a given physiological stimulus changes this ratio to trigger apoptosis remains unclear. We report here that human 17-β-estradiol (E2) and its related steroid hormones induce apoptosis by binding directly to phosphodiesterase 3A, which in turn recruits and stabilizes an otherwise fast-turnover protein Schlafen 12 (SLFN12).

Transcriptomic and Proteomic Analysis of Shaan2A Cytoplasmic Male Sterility and Its Maintainer Line in .

Cytoplasmic male sterility (CMS) lines are widely used for hybrid production in . The Shaan2A CMS system is one of the most important in China and has been used for decades; however, the male sterility mechanism underlying Shaan2A CMS remains unknown. Here, we performed transcriptomic and proteomic analysis, combined with additional morphological observation, in the Shaan2A CMS.

Genetic dissection of the mechanism of flowering time based on an environmentally stable and specific QTL in Brassica napus.

Flowering time is an important agronomic trait that is highly influenced by the environment. To elucidate the genetic mechanism of flowering time in rapeseed (Brassica napus L.), a genome-wide QTL analysis was performed in a doubled haploid population grown in winter, semi-winter and spring ecological conditions.

RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system.

A pair of kinases, RIPK1 and RIPK3, as well as the RIPK3 substrate MLKL cause a form of programmed necrotic cell death in mammals termed necroptosis. We report here that male reproductive organs of both 3- and -knockout mice retain 'youthful' morphology and function into advanced age, while those of age-matched wild-type mice deteriorate. The RIPK3 phosphorylation of MLKL, the activation marker of necroptosis, is detected in spermatogonial stem cells in the testes of old but not in young wild-type mice.

Identification of the Relationship between Oil Body Morphology and Oil Content by Microstructure Comparison Combining with QTL Analysis in .

Oil bodies (OBs) are relatively simple but very important organelles comprising a matrix of triacylglycerol (TAG) surrounded by a phospholipid monolayer embedded and covered with unique proteins. The OB structure in with different oil content and the relationship between the oil content and the OB structure needs to be better understood. In this paper, the characteristics of OBs in the embryo of a series of materials with different oil content ranging from 34% to over 60% were studied.

Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis.

RIP3-dependent necroptosis has recently garnered significant interest because of the unique signaling mechanisms and pathologic functions involved in this process. Accordingly, a number of chemical screens have identified several effective small-molecule inhibitors that specifically block necroptosis. Here, we report the discovery that kongensin A (KA), a natural product isolated from Croton kongensis, is a potent inhibitor of necroptosis and an inducer of apoptosis.

A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis.

Receptor-interacting protein kinase 3, RIP3, and a pseudokinase mixed lineage kinase-domain like protein, MLKL, constitute the core components of the necroptosis pathway, which causes programmed necrotic death in mammalian cells. Latent RIP3 in the cytosol is activated by several upstream signals including the related kinase RIP1, which transduces signals from the tumor necrosis factor (TNF) family of cytokines. We report here that RIP3 activation following the induction of necroptosis requires the activity of an HSP90 and CDC37 cochaperone complex.

Quantitative trait loci that control the oil content variation of rapeseed (Brassica napus L.).

This report describes an integrative analysis of seed-oil-content quantitative trait loci (QTL) in Brassica napus , using a high-density genetic map to align QTL among different populations. Rapeseed (Brassica napus) is an important source of edible oil and sustainable energy. Given the challenge involved in using only a few genes to substantially increase the oil content of rapeseed without affecting the fatty acid composition, exploitation of a greater number of genetic loci that regulate the oil content variation among rapeseed germplasm is of fundamental importance.

Identification of QTLs associated with oil content in a high-oil Brassica napus cultivar and construction of a high-density consensus map for QTLs comparison in B. napus.

Increasing seed oil content is one of the most important goals in breeding of rapeseed (B. napus L.).

Proteomic and comparative genomic analysis of two Brassica napus lines differing in oil content.

Ultrastructural observations, combined with proteomic and comparative genomic analyses, were applied to interpret the differences in protein composition and oil-body characteristics of mature seed of two Brassica napus lines with high and low oil contents of 55.19% and 36.49%, respectively.

Involvement of alternative oxidase in the regulation of sensitivity of Sclerotinia sclerotiorum to the fungicides azoxystrobin and procymidone.

Sclerotinia sclerotiorum is a filamentous fungal pathogen that can infect many economically important crops and vegetables. Alternative oxidase is the terminal oxidase of the alternative respiratory pathway in fungal mitochondria. The function of alternative oxidase was investigated in the regulation of sensitivity of S.

Involvement of alternative oxidase in the regulation of growth, development, and resistance to oxidative stress of Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum is a cosmopolitan, filamentous, fungal pathogen that can cause serious disease in many kinds of crops. Alternative oxidase is the terminal oxidase of the alternative mitochondrial respiratory pathway in fungi and higher plants. We report the presence of this alternative pathway respiration and demonstrate its expression in two isolates of S.

Molecular mapping of Arabidopsis thaliana lipid-related orthologous genes in Brassica napus.

Quantitative Trait Loci (QTL) for oil content has been previously analyzed in a SG-DH population from a cross between a Chinese cultivar and a European cultivar of Brassica napus. Eight QTL with additive and epistatic effects, and with environmental interactions were evaluated. Here we present an integrated linkage map of this population predominantly based on informative markers derived from Brassica sequences, including 249 orthologous A.

Functional analysis of the two Brassica AP3 genes involved in apetalous and stamen carpelloid phenotypes.

The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes which encode MADS-box transcription factors and specify petal and stamen identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and AMS, of B. rapa and B.

Δ6-Desaturase from Mortierella alpina: cDNA cloning, expression, and phylogenetic analysis.

The open reading frame of the Δ(6)-desaturase gene was isolated from Mortierella alpina W15 and the gene was cloned into a pPIC3.5K vector. The vector was transformed into Pichia pastoris GS115 and expression was induced with methanol.

Sequence analysis and expression of orf224 gene associated with two types of cytoplasmic male sterility in Brassica napus L.

Polima and Shaan 2A are the two most widely used forms of cytoplasmic male sterility (CMS) in the utilization of heterosis of rapeseed (Brassica napus) in China. A previous study indicated that the mitochondrial gene, orf224, was the only gene with a differential expression pattern among the normal, sterile and fertility-restored lines in rapeseed. DNA sequences of orf224, including coding sequences from Shaan 2A and Polima CMS, were then amplified and analyzed.