Effector MoSDT1 enhances Magnaporthe oryzae virulence and plays a dual role in regulating rice defense.

C2H2 zinc effectors are a class of pathogen proteins that play a dual role in plant-pathogen interactions, promoting pathogenicity and enhancing plant defense. In our previous research, we identified Magnaporthe oryzae Systemic Defense Trigger 1 (MoSDT1) as a C2H2 zinc effector that activates rice (Oryza sativa) defense when overexpressed in rice. However, its regulatory roles in pathogenicity and defense require further investigation. In this study, we generated an MoSDT1 overexpressing strain and 2 knockout strains of M. oryzae to assess the impact of MoSDT1 on pathogenicity, rice defense, and phenotypic characteristics. Our analyses revealed that MoSDT1 substantially influenced vegetative growth, conidia size, and conidiation, and was crucial for the virulence of M. oryzae while suppressing rice defense. MoSDT1 localized to the nucleus and cytoplasm of rice, either dependent or independent of M. oryzae delivery. Through RNA-seq, scRNA-seq, and ChIP-seq, we identified that MoSDT1 modulates rice defense by regulating the phosphorylation and ubiquitination of various rice signaling proteins, including transcription factors, transcription repressors, kinases, phosphatases, and the ubiquitin system. These findings provide valuable insights into the regulatory mechanisms of C2H2 zinc finger effector proteins and offer important foundational information for utilizing their target genes in disease resistance breeding and the design of targets for disease management.

Characterization of Firmiana danxiaensis plastomes and comparative analysis of Firmiana: insight into its phylogeny and evolution.

BACKGROUND: Firmiana danxiaensis is a critically endangered and ecologically important tree currently only found in four locations in Danxia or Karst habitats in northern Guangdong Province, China. The specialized habitat preference makes it an ideal model species for study of adaptive evolution. Meanwhile, the phylogenetic relationships of F. danxiaensis in four locations under two landforms are unclear. Therefore, we sequenced its complete chloroplast (cp.) genomes and conducted comprehensive interspecific and intrageneric plastome studies. RESULTS: The F. danxiaensis plastomes in four locations showed a typical quadripartite and circular structure that ranged from 160,832 to 161,206 bp in size, with 112 unique genes encoded. Comparative genomics showed that the plastomes of F. danxiaensis were relatively conserved with high similarity of genome organization, gene number, GC content and SSRs. While the genomes revealed higher biased codon preferences in Karst habitat than those in Danxia habitats. Eighteen and 11 divergent hotpots were identified at interspecific and intrageneric levels for species identification and further phylogenetic studies. Seven genes (clpP, accD, ccsA, ndhH, rpl20, rpoC2, and rps4) were under positive selection and may be related to adaptation. Phylogenetic analysis revealed that F. danxiaensis is sister to F. major and F. simplex. However, the interspecific relationships are not consistent with the habitat types. CONCLUSIONS: The characteristics and interspecific relationship of F. danxiaensis plastomes provide new insights into further integration of geographical factors, environmental factors, and genetic variations on the genomic study of F. danxiaensis. Together, our study will contribute to the study of species identification, population genetics, and conservation biology of F. danxiaensis.

Comparative Analysis of Intramedullary Nail versus Plate Fixation for Fibula Fracture in Supination External Rotation Type IV Ankle Injury.

BACKGROUND Lateral malleolus fractures, typically from trauma, sports, or accidents, are common, with supination external rotation (SER) injuries being most prevalent. SER injuries involve complex joint mechanics and often necessitate surgical intervention for instability. This study compares intramedullary nail and plate fixation for fibula fractures in SER type IV ankle injuries, considering their biomechanical properties and influence on fracture healing. MATERIAL AND METHODS A prospective, randomized study was conducted between January 2021 and December 2021. A total of 81 patients with SER injuries were included in the study. Surgical procedures were performed using either intramedullary nails or plates. The following parameters were recorded and analyzed: postoperative complications, operation times, bone healing times, American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS) scores for pain, and ankle range of motion. RESULTS Out of the 81 cases, 42 were treated with intramedullary nails, while 39 received plate fixation. Statistical analysis revealed a significantly lower rate of postoperative complications in the intramedullary nail group than in the the plate fixation group (9.52% vs 30.77%, P<0.0164). However, there were no significant differences between the 2 groups in terms of operation time, bone healing time, AOFAS scores, VAS scores, and functional evaluations (P>0.05). CONCLUSIONS Plate fixation and intramedullary nail fixation are effective techniques for treating fibula fractures in SER type IV injuries. However, intramedullary nail fixation demonstrates a lower rate of complications. Therefore, intramedullary nails may be preferable to plate fixation for the management of fibula fractures in SER type IV ankle injuries.

Phylogeny, character evolution, and biogeography of the fern genus Bolbitis (Dryopteridaceae).

Bolbitis is a pantropical fern genus of Dryopteridaceae with ca. 80 species mainly in tropical Asia. Earlier studies confirmed the monophyly of Bolbitis when Mickelia is excluded and identified three major clades in Bolbitis. However, earlier studies are based on relatively small sampling and the majority of Asian species are not sampled. In this study, DNA sequences of three plastid markers of 169 accessions representing ca. 68 (85 % of total) species of Bolbitis in nine out of the 10 series recognized by Hennipman (1977), and 54 accessions representing the five remaining bolbitidoid genera are used to infer a global phylogeny with a focus on Asian species. The major results include: (1) Bolbitis is strongly supported as monophyletic; (2) species of Bolbitis are resolved into four major clades and their relationships are: the Malagasy/Mascarene clade is sister to the rest, followed by the African clade which is sister to the American clade + the Asian clade; (3) six well-supported subclades are identified in the most speciose Asian clade; (4) the free-veined Egenolfia is embedded in Bolbitis and is paraphyletic in relation to species with anastomosing venation; (5) three series sensu Hennipman (1977), B. ser. Alienae, B. ser. Egenolfianae, and B. ser. Heteroclitae, are paraphyletic or polyphyletic; (6) evolution of six morphological characters is analyzed and free venation is found to have evolved from anastomosing venation and reversed to free venation in Bolbitis; and (7) biogeographical implications are drawn and it is shown that a single recent dispersal from Asia resulted in continental disjunction of closely related ferns of Bolbitis between Africa and America.

Directly Using Paraffin as the Toughening Agent of Epoxy Composites: An Experimental and Molecular Dynamics Simulation Study.

It is still a challenge in studying the toughening mechanism by well combining the experimental and atomistic molecular dynamics (MD) simulation study. This article directly introduced eicosane (C20, model compound of paraffin) into the epoxy matrix (DGEBA) by using a special epoxy resin with alkyl side chains (D12) as a compatibilizer, which was synthesized through thiol-ene click chemistry. The toughening mechanism of the ternary DGEBA/D12/C20 (EPDA-X) systems was systematically investigated by experimental and MD simulation methods. Though C20 can be well dispersed in the curing mixture, the huge polarity difference between C20 and DGEBA can be the driving force for C20 to stay away from DGEBA, demonstrating the self-assembly effect of C20 around the alkyl side chains of D12 because of the good compatibility of D12 and C20. The soft alkyl chains of D12 and C20 as well as the self-assembly effect of C20 around the D12 molecules can simultaneously improve the strength, modulus, and toughness of the EPDA-2.5 system. This article not only provides a brand new toughening strategy by directly using nonfunctional alkyl derivatives as the toughening agent of epoxy composites with superior mechanical properties but also provides a systematic MD simulation method to evaluate whether there is the interaction or not and the strength of interaction between different molecular chains so as to provide a theoretical basis for the cause of the microphase separation structure and related toughening mechanism in cross-linking networks on the atomic and molecular levels.

The Ccr4-Not complex regulates TORC1 signaling and mitochondrial metabolism by promoting vacuole V-ATPase activity.

The Ccr4-Not complex functions as an effector of multiple signaling pathways that control gene transcription and mRNA turnover. Consequently, Ccr4-Not contributes to a diverse array of processes, which includes a significant role in cell metabolism. Yet a mechanistic understanding of how it contributes to metabolism is lacking. Herein, we provide evidence that Ccr4-Not activates nutrient signaling through the essential target of rapamycin complex 1 (TORC1) pathway. Ccr4-Not disruption reduces global TORC1 signaling, and it also upregulates expression of the cell wall integrity (CWI) pathway terminal kinase Mpk1. Although CWI signaling represses TORC1 signaling, we find that Ccr4-Not loss inhibits TORC1 independently of CWI activation. Instead, we demonstrate that Ccr4-Not promotes the function of the vacuole V-ATPase, which interacts with the Gtr1 GTPase-containing EGO complex to stimulate TORC1 in response to nutrient sufficiency. Bypassing the V-ATPase requirement in TORC1 activation using a constitutively active Gtr1 mutant fully restores TORC1 signaling in Ccr4-Not deficient cells. Transcriptome analysis and functional studies revealed that loss of the Ccr4 subunit activates the TORC1 repressed retrograde signaling pathway to upregulate mitochondrial activity. Blocking this mitochondrial upregulation in Ccr4-Not deficient cells further represses TORC1 signaling, and it causes synergistic deficiencies in mitochondrial-dependent metabolism. These data support a model whereby Ccr4-Not loss impairs V-ATPase dependent TORC1 activation that forces cells to enhance mitochondrial metabolism to sustain a minimal level of TORC1 signaling necessary for cell growth and proliferation. Therefore, Ccr4-Not plays an integral role in nutrient signaling and cell metabolism by promoting V-ATPase dependent TORC1 activation.

Characterization of infected process and primary mechanism in rice Acuce defense against rice blast fungus, Magnaporthe oryzae.

KEY MESSAGE: Identification of infection process and defense response during M. oryzae infecting Acuce. Magnaporthe oryzae is a destructive rice pathogen. Recent studies have focused on the initial infectious stage, with a few studies conducted to elucidate the characteristics of the late infectious stages. This study aims to decipher the characteristics at different stages (biotrophic, biotrophy-necrotrophy switch (BNS), and necrotrophic) between the interaction of two M. oryzae-rice combinations and investigate the resistance mechanisms of rice to M. oryzae using cytological and molecular methods. The biotrophic phase of M. oryzae-LTH compatible interaction was found to be longer than that of M. oryzae-Acuce incompatible interaction. We also found that jasmonic acid (JA) signaling plays an important role in defense by regulating antimicrobial compound accumulation in infected Acuce via a synergistic interaction of JA-salicylic acid (SA) and JA-ethylene (ET). In infected LTH, JA-ET/JA-SA showed antagonistic interaction. Ibuprofen (IBU) is a JA inhibitor. Despite the above findings, we found that exogenous JA-Ile and IBU significantly alleviated blast symptoms in infected LTH at 36 hpi (biotrophic) and 72 hpi (BNS), indicating these two-time points may be critical for managing blast disease in the compatible interaction. Conversely, IBU significantly increased blast symptoms on the infected Acuce at 36 hpi, confirming that the JA signal plays a central role in the defense response in infected Acuce. According to transcriptional analysis, the number of genes enriched in the plant hormone signal pathway was significantly higher than in other pathways. Our findings suggested that JA-mediated defense mechanism is essential in regulating Acuce resistance, particularly during the biotrophic and BNS phases.

MoSDT1 triggers defense response through modulating phosphorylated proteins in rice.

KEY MESSAGE: MoSDT1, a rice blast fungus transcription factor, is as an inducer to activate defense response through mainly mediating phosphorylated proteins in rice. Pathogen effector proteins play a dual role in infecting the host or triggering a defense response. Our previous research found a Magnaporthe oryzae effector, MoSDT1, which could activate the rice defense response when it was overexpressed in rice. However, we still know little about the mechanisms on how MoSDT1 in vivo or in vitro influences the resistance ability of rice. Our results showed that decreased ROS and increased lignin contents appeared along with significant upregulation of defense-related genes, raffinose synthesis gene, and phenylalanine ammonialyase gene. Moreover, we revealed that the contents of lignin were increased, which was in accordance with the upregulation of its precursor phenylalanine gene despite the fact that the glutamate-/thiamine-responsive genes were inhibited in MoSDT1 transgenic rice, and these indicated that MoSDT1 triggered the defense system of rice in vivo. Interestingly, in vitro studies, we further found that MoSDT1 induced the defense system by ROS synthesis, callose deposition, PR gene expression and SA/JA synthesis/signal genes using the purified prokaryotic expression system in rice plants. In addition, this defense response was confirmed to be activated by the zinc finger domain of MoSDT1 via prokaryotic expression of MoSDT1 truncated mutants in rice plants. To elucidate the regulative effects of MoSDT1 on protein phosphorylation in rice, phosphoproteome analysis was performed in both MoSDT1-transgenic and wild type  rice. We found that MoSDT1 specifically up-regulated the expression levels of a few phosphorylated proteins, which were involved in multiple functions, such as biotic/abiotic stress and growth. In addition, the motifs in these specific proteins ranked the top among the top-five conserved motifs in the MoSDT1-transgenic rice. MoSDT1 played a crucial role in enhancing rice resistance by modulating several genes and signaling pathways.

Phylogenomic framework of the IRLC legumes (Leguminosae subfamily Papilionoideae) and intercontinental biogeography of tribe Wisterieae.

The inverted repeat-lacking clade (IRLC) is one of the most derived clades within the subfamily Papilionoideae of the legume family, and includes various economically important plants, e.g., chickpeas, peas, liquorice, and the largest genus of angiosperms, Astragalus. Tribe Wisterieae is one of the earliest diverged groups of the IRLC, and its generic delimitation and spatiotemporal diversification needs further clarifications. Based on genome skimming data, we herein reconstruct the phylogenomic framework of the IRLC, and infer the inter-generic relationships and historical biogeography of Wisterieae. We redefine tribe Caraganeae to contain Caragana only, and tribe Astragaleae is reduced to the Erophaca-Astragalean clade. The chloroplast capture scenario was hypothesized as the most plausible explanation of the topological incongruences between the chloroplast CDSs and nuclear ribosomal DNA trees in both the Glycyrrhizinae-Adinobotrys-Wisterieae clade and the Chesneyeae-Caraganeae-Hedysareae clade. A new name, Caragana lidou L. Duan & Z.Y. Chang, is proposed within Caraganeae. Thirteen genera are herein supported within Wisterieae, including a new genus, Villosocallerya L. Duan, J. Compton & Schrire, segregated from Callerya. Our biogeographic analyses suggest that Wisterieae originated in the late Eocene and its most recent common ancestor (MRCA) was distributed in continental southeastern Asia. Lineages of Wisterieae remained in the ancestral area from the early Oligocene to the early Miocene. By the middle Miocene, Whitfordiodendron and the MRCA of Callerya-Kanburia-Villosocallerya Clade became disjunct between the Sunda area and continental southeastern Asia, respectively; the MRCA of Wisteria migrated to North America via the Bering land bridge. The ancestor of Austrocallerya and Padbruggea migrated to the Wallacea-Oceania area, which split in the early Pliocene. In the Pleistocene, Wisteria brachybotrys, W. floribunda and Wisteriopsis japonica reached Japan, and Callerya cinerea dispersed to South Asia. This study provides a solid phylogenomic for further evolutionary/biogeographic/systematic investigations on the ecologically diverse and economically important IRLC legumes.

Structures and catalytic performances of Me/SAPO-34 (Me = Mn, Ni, Co) catalysts for low-tem perature SCR of NOx by ammonia.

Me/SAPO-34 (Me = Mn, Ni, Co) series of catalysts were prepared by a wetness impregnation method and investigated for the selective catalytic reduction of nitrogen oxides with ammonia (NH3-SCR). Among them, Mn/SAPO-34 catalyst was found as the most promising candidate based on its superior low-temperature activity. The catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy images (TEM), nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), temperature programmed reduction and desorption (TPR and TPD), and diffuse reflectance infrared Fourier transformed spectroscopy (DRIFTS) of NH3/NOx adsorption. Mn/SAPO-34 is obviously different from Ni/SAPO-34 and Co/SAPO-34 in the active species state and distribution. Surface MnOx species which play an essential role in NO oxidation and NO2 adsorption, act as better active sites than nickel and cobalt mostly in the form of the aluminates and silicates.

A fossil-calibrated phylogeny reveals the biogeographic history of the Cladrastis clade, an amphi-Pacific early-branching group in papilionoid legumes.

The early-branching Cladrastis clade of papilionoid legumes (Leguminosae, Papilionoideae) has an intriguing amphi-Pacific disjunct distribution in eastern Asia and temperate-tropical Americas. Here we used nuclear and three plastid regions to reconstruct the phylogenetic relationships and divergence times in the Cladrastis clade, as well as the evolution of morphological characters that might have been key in its biogeographic history. The ancestral character state estimation revealed that the most recent common ancestor of the Cladrastis clade was deciduous trees possessing compressed, winged fruits. The Cladrastis clade was inferred to have originated in the mid-latitude thermophilic forests of North America in the early Eocene, followed by the split between ancestors of wing-fruited Platyosprion and the non-wing-fruited group, and later the divergence of Cladrastis s.s. from the non-wing-fruited group in middle Eocene. Platyosprion and Cladrastis s.s. display an "out-of-North-America" biogeographic pattern and might have migrated to Asia via the Bering land bridge (BLB) or the North Atlantic land bridges (NALB) during middle to late Eocene. Our results, coupled with the relatively well documented fossil record for the clade, suggest that Platyosprion experienced an extinction event in North America caused by climatic cooling around the Eocene-Oligocene transition, which drove a major vegetation shift in western North America, in turn serving as a barrier for the vicariance of Pickeringia and Styphnolobium. The evolution of shrubby habit and sclerophyllous leaves in the former might be adaption to the chaparral vegetation in southwestern North America; the latter gained the trait of moniliform, succulent fruit. Styphnolobium further dispersed southward to tropical North America in the Oligocene, and eastward to Asia through BLB during middle Miocene. Subsequent sundering of BLB facilitated the vicariance of St. affine and St. japonicum.

Characterization and subcellular localization of histone deacetylases and their roles in response to abiotic stresses in soybean.

BACKGROUND: Histone deacetylases (HDACs) function as key epigenetic factors in repressing the expression of genes in multiple aspects of plant growth, development and plant response to abiotic or biotic stresses. To date, the molecular function of HDACs is well described in Arabidopsis thaliana, but no systematic analysis of this gene family in soybean (Glycine max) has been reported. RESULTS: In this study, 28 HDAC genes from soybean genome were identified, which were asymmetrically distributed on 12 chromosomes. Phylogenetic analysis demonstrated that GmHDACs fall into three major groups previously named RPD3/HDA1, SIR2, and HD2. Subcellular localization analysis revealed that YFP-tagged GmSRT4, GmHDT2 and GmHDT4 were predominantly localized in the nucleus, whereas GmHDA6, GmHDA13, GmHDA14 and GmHDA16 were found in both the cytoplasm and nucleus. Real-time quantitative PCR showed that GmHDA6, GmHDA13, GmHDA14, GmHDA16 and GmHDT4 were broadly expressed across plant tissues, while GmHDA8, GmSRT2, GmSRT4 and GmHDT2 showed differential expression across various tissues. Interestingly, we measured differential changes in GmHDACs transcripts accumulation in response to several abiotic cues, indicating that these epigenetic modifiers could potentially be part of a dynamic transcriptional response to stress in soybean. Finally, we show that the levels of histone marks previously reported to be associated with plant HDACs are modulated by cold and heat in this legume. CONCLUSION: We have identified and classified 28 HDAC genes in soybean. Our data provides insights into the evolution of the HDAC gene family and further support the hypothesis that these genes are important for the plant responses to environmental stress.

ETS1 is associated with cisplatin resistance through IKKα/NF-κB pathway in cell line MDA-MB-231.

BACKGROUND: Platinum-based drugs are used extensively in neoadjuvant chemotherapy for triple-negative breast cancer (TNBC), but their use can be limited by resistance. In this study, we established cisplatin (DDP) resistant TNBC cells to investigate the potential relationship among ETS1, IKKα/NF-κB and resistance. METHODS: The sensitivity was evaluated by MTT, apoptosis analysis. The intracellular DDP concentration difference was tested by inductively coupled plasma mass spectrometry (ICP-MS) method. Molecular pathological mechanism of DDP resistance was explored by microarray analysis and PPI network analysis. The ETS1, NF-κB signaling change were assessed by western blot and q-PCR in vitro and vivo. The existing binds between ETS1 and the core IKKα promoter were found by luciferase assay and chromatin immunoprecipitation technique (ChIP). RESULTS: MDA-MB-231/DDP (231/DDP) cell had a higher IC50 value of cisplatin, lower intracellular DDP concentration, and lower apoptosis ratio than MDA-MB-231 (231/wt) cell line treated with DDP. Increased ABC transporters were induced by the activation of NF-κB pathway in 231/DDP cells. ETS1, RPL6, RBBP8, BIRC2, PIK3A and RARS were six important genes for DDP-resistance based on PPI network and expression validation. Protein expression of ETS1 and IKKα were significantly up-regulated in 231/DDP cells. However, inhibition of ETS1 expression enhances chemo-sensitivity to DDP and reversed the activation of NF-κB pathway in 231/DDP cells and subcutaneous transplantation tumor in vivo. Moreover, there is existing binds between ETS1 and the core IKKα promoter though luciferase assay and ChIP. CONCLUSION: This study enables us to understand the functions of ETS1 in TNBC chemotherapy and suggests that ETS1 could be used as a novel marker of poor response to DDP and a potential therapeutic target for TNBC chemotherapy.

Ccr4-not regulates RNA polymerase I transcription and couples nutrient signaling to the control of ribosomal RNA biogenesis.

Ribosomal RNA synthesis is controlled by nutrient signaling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. mTORC1 regulates ribosomal RNA expression by affecting RNA Polymerase I (Pol I)-dependent transcription of the ribosomal DNA (rDNA) but the mechanisms involved remain obscure. This study provides evidence that the Ccr4-Not complex, which regulates RNA Polymerase II (Pol II) transcription, also functions downstream of mTORC1 to control Pol I activity. Ccr4-Not localizes to the rDNA and physically associates with the Pol I holoenzyme while Ccr4-Not disruption perturbs rDNA binding of multiple Pol I transcriptional regulators including core factor, the high mobility group protein Hmo1, and the SSU processome. Under nutrient rich conditions, Ccr4-Not suppresses Pol I initiation by regulating interactions with the essential transcription factor Rrn3. Additionally, Ccr4-Not disruption prevents reduced Pol I transcription when mTORC1 is inhibited suggesting Ccr4-Not bridges mTORC1 signaling with Pol I regulation. Analysis of the non-essential Pol I subunits demonstrated that the A34.5 subunit promotes, while the A12.2 and A14 subunits repress, Ccr4-Not interactions with Pol I. Furthermore, ccr4Δ is synthetically sick when paired with rpa12Δ and the double mutant has enhanced sensitivity to transcription elongation inhibition suggesting that Ccr4-Not functions to promote Pol I elongation. Intriguingly, while low concentrations of mTORC1 inhibitors completely inhibit growth of ccr4Δ, a ccr4Δ rpa12Δ rescues this growth defect suggesting that the sensitivity of Ccr4-Not mutants to mTORC1 inhibition is at least partially due to Pol I deregulation. Collectively, these data demonstrate a novel role for Ccr4-Not in Pol I transcriptional regulation that is required for bridging mTORC1 signaling to ribosomal RNA synthesis.

Effects of psoralen on the pharmacokinetics of anastrozole in rats.

CONTEXT: Psoralen and anastrozole are always used together for breast cancer patients in Chinese clinics. OBJECTIVE: This study investigates the effects of psoralen on the pharmacokinetics of anastrozole in rats and its potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of orally administered anastrozole (0.5 mg/kg) with (test group) or without (Control group) psoralen pretreatment (20 mg/kg/day for 10 days) in male Sprague-Dawley rats (six rats in each group) were investigated. The plasma concentration of anastrozole was determined using a sensitive and reliable LC-MS/MS method. Additionally, the effects of psoralen on the intestine transport and metabolic stability of anastrozole (1 µM) were investigated using a Caco-2 cell transwell model and rat liver microsome incubation systems. RESULTS: The results indicated that psoralen could significantly increase the Cmax (from 56.74 ± 3.17 ng/mL to 83.26 ± 6.87 ng/mL), and t1/2 (from 10.80 ± 1.05 to 14.29 ± 1.38 h) of anastrozole (p < 0.05). Psoralen could also significantly decrease the efflux ratio of anastrozole from 1.88 to 1.32 (p < 0.05). Additionally, the intrinsic clearance rates of anastrozole decreased significantly (from 62.83 to 43.97 µL/min/mg protein) (p < 0.05) with psoralen pretreatment in rat liver microsome incubation systems. DISCUSSION AND CONCLUSIONS: This study indicates that when the rats were pretreated with psoralen, the system exposure of anastrozole would be increased significantly. The results showed that the herb-drug interaction between psoralen and anastrozole might occur when they were co-administered, and future studies in humans also need to investigate its herb-drug interaction potential.

[Correlation Study between Syndrome Types of Chinese Medicine and Molecular Subtyping of Breast Cancer in Consolidate Period].

Objective To observe the correlation between syndrome types of Chinese medicine (CM) and molecular subtyping of breast cancer in consolidation period. Methods Multivariate statistical analysis was applied in this research. Totally 612 breast cancer patients in consolidation period were as- signed to 4 syndrome types of CM [qi deficiency syndrome (22. 22% , 136/612) , Gan-qi stagnation syn- drome (21.73%, 133/612), Gan-Shen yin deficiency syndrome (20.10%, 123/612), Shen deficiency blood stasis syndrome (35. 95%, 220/612) ]. The correlation between each syndrome type and each molecular subtyping was respectively analyzed using Χ² (R x C table) test. Results Through statistical a- nalysis and expert consultation, results showed that cluster four types in consolidate period of breast cancer were compatible. Each syndrome type was correlated with each molecular subtyping in 612 breast cancer patients in consolidation period. Luminal type A was correlated with Gan-qi stagnation syndrome (P <0. 05). Luminal type B and triple negative type were correlated with qi deficiency syndrome and Gan- Shen yin deficiency syndrome (P <0. 05). But each syndrome type was not obviously correlated with dis- ease course. There was no obvious correlation between molecular subtyping and age/disease course (P >0. 05). Conclusion Luminal type A occupied the highest ratio in Gan-qi stagnation syndrome, with relatively better prognosis.

Regulation of directional cell migration by membrane-induced actin bundling.

During embryonic development and in metastatic cancers, cells detach from the epithelium and migrate with persistent directionality. Directional cell migration is also crucial for the regeneration and maintenance of the epithelium and impaired directional migration is linked to chronic inflammatory diseases. Despite its significance, the mechanisms controlling epithelial cell migration remain poorly understood. Villin is an epithelial-cell-specific actin modifying protein that regulates epithelial cell plasticity and motility. In motile cells villin is associated with the highly branched and the unbranched actin filaments of lamellipodia and filopodia, respectively. In this study we demonstrate for the first time that villin regulates directionally persistent epithelial cell migration. Functional characterization of wild-type and mutant villin proteins revealed that the ability of villin to self-associate and bundle actin as well as its direct interaction with phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] regulates villin-induced filopodial assembly and directional cell migration. Our findings suggest that convergence of different signaling cascades could spatially restrict villin activity to areas of high PtdIns(4,5)P(2) and F-actin concentration to assemble filopodia. Furthermore, our data reveal the ability of villin to undergo actin- and PtdIns(4,5)P(2)-induced self-association, which may be particularly suited to coalesce and reorganize actin bundles within the filopodia.

Identification of the relationship between Chinese Adiantum reniforme var. sinense and Canary Adiantum reniforme.

BACKGROUND: There are different opinions about the relationship of two disjunctively distributed varieties Adiantum reniforme L. var. sinense Y.X.Lin and Adiantum reniforme L. Adiantum reniforme var. sinense is an endangered fern only distributed in a narrowed region of Chongqing city in China, while Adiantum reniforme var. reniforme just distributed in Canary Islands and Madeira off the north-western African coast. To verify the relationship of these two taxa, relative phylogenetic analyses, karyotype analyses, microscopic spore observations and morphological studies were performed in this study. Besides, divergence time between A. reniforme var. sinense and A. reniforme var. reniforme was estimated using GTR model according to a phylogeny tree constructed with the three cpDNA markers atpA, atpB, and rbcL. RESULTS: Phylogenetic results and divergence time analyses--all individuals of A. reniforme var. sinense from 4 different populations (representing all biogeographic distributions) were clustered into one clade and all individuals of A. reniforme var. reniforme from 7 different populations (all biogeographic distributions are included) were clustered into another clade. The divergence between A. reniforme var. reniforme and A. reniforme var. sinense was estimated to be 4.94 (2.26-8.66) Myr. Based on karyotype analyses, A. reniforme var. reniforme was deduced to be hexaploidy with 2n = 180, X = 30, while A. reniforme var. sinense was known as tetraploidy. Microscopic spore observations suggested that surface ornamentation of A. reniforme var. reniforme is psilate, but that of A. reniforme var. sinense is rugate. Leaf blades of A. reniforme var. sinense are membranous and reniform and with several obvious concentric rings, and leaves of A. reniforme var. reniforme are pachyphyllous and coriaceous and are much rounder and similar to palm. CONCLUSION: Adiantum reniforme var. sinense is an independent species rather than the variety of Adiantum reniforme var. reniforme. As a result, we approve Adiantum nelumboides X. C. Zhang, nom. & stat. nov. as a legal name instead of the former Adiantum reniforme var. sinense. China was determined to be the most probable evolution centre based on the results of phylogenetic analyses, divergence estimation, relative palaeogeography and palaeoclimate materials.