Search

Developing stable and highly efficient thick-film organic solar cells (OSCs) is crucial for the large-scale commercial application of organic photovoltaics. A novel synergistic dilution strategy to address this issue, using Polymethyl Methacrylate (PMMA) -modified zinc oxide (ZnO) as the interfacial layer, is introduced. This strategy effectively mitigates oxygen defects in ZnO while also regulating the self-assembly process of the active layer to achieve an ordered distribution of donors and acceptors. In synergistic diluted devices, the dynamic disorder is reduced owing to the suppression of electron-phonon coupling, while the static disorder is suppressed by improved molecular stacking and enhanced intermolecular interactions. Consequently, the 300 nm PM6:L8-BO device post-synergistic dilution manifests a marked enhancement in device performance, achieving a photovoltaic power conversion efficiency (PCE) >17% with excellent thermal stability. A typical ternary system is selected to explore the general applicability of synergistic dilution strategy, the PCE has been enhanced significantly from 17.89% to 18.72%, which falls within the range of the highest values among inverted single junction OSCs. As a practical application that depends on the pivotal synergy between high efficiency and stability, this approach paves the way for large-scale implementation of OSCs and ensures cost-effectiveness., (© 2024 Wiley‐VCH GmbH.)

ABC transporters are a highly conserved membrane protein class that promote the transport of substances across membranes. Under drought conditions, insects primarily regulate the content of cuticular hydrocarbon (CHC) to retain water and prevent evaporative loss. Involvement of ABC transporter protein G (ABCG) subfamily genes in insect CHC transport has been relatively understudied. In this study, we demonstrated that ABCG4 gene in Acyrthosiphon pisum (ApABCG4) is involved in CHC transport and affects drought tolerance by regulating CHC accumulation. ApABCG4 is strongly expressed in the abdominal cuticle and embryonic stages of A. pisum. Effective silencing of ApABCG4 was achieved using RNAi, and the silencing duration was analyzed. ApABCG4 silencing resulted in a significant decrease in the total and component contents of the CHC and cuticular waxy coatings of A. pisum. Nevertheless, the internal hydrocarbon content remained unchanged. The lack of cuticular hydrocarbons significantly reduced the drought tolerance of A. pisum, shortening its survival time under drought stress. Drought stress caused significant upregulation of ApABCG4. Molecular docking showed that ApABCG4 has a high binding affinity for nine n-alkanes of CHC through electrostatic interactions. These results indicate that ApABCG4 is a novel RNAi target with key applications in aphid biological control., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

A phytochemical investigation of the tuber of Bletilla striata afforded eight stilbene derivatives, including a new bibenzyl ( 1 ) and two new phenanthrene ( 2 and 3 ). The structures of these compounds were elucidated using a combination of spectroscopic analyses. Further, the anti-inflammatory activity of all the compounds was evaluated to assess their capability to inhibit nitric oxide (NO) production by RAW 264.7 macrophages. The bioactive screening revealed that compounds 4 and 7 exhibited moderate inhibitory effects against NO production with the IC 50 values 38.7 and 16.7 μM, respectively.

Developing efficient organic solar cells (OSCs) with thick active layers is crucial for roll-to-roll printing. However, thicker layers often result in lower efficiency. This study tackles this challenge using a polymer adsorption strategy combined with a layer-by-layer approach. Incorporating insulator polystyrene (PS) into the PM6:L8-BO system creates PM6+PS:L8-BO blends, effectively suppressing trap states and extending exciton diffusion length in the mixed donor domain. Adding insulating polymers with benzene rings to the donor enhances π-π stacking of donors, boosting intermolecular interactions and electron wave function overlap. This results in more orderly molecular stacking, longer exciton lifetimes, and higher diffusion lengths. The promoted long-range exciton diffusion leads to high power conversion efficiencies of 19.05% and 18.15% for PM6+PS:L8-BO blend films with 100 and 300 nm thickness, respectively, as well as a respectable 16.00% for 500 nm. These insights guide material selection for better exciton diffusion, and offer a method for thick-film OSC fabrication, promoting a prosperous future for practical OSC mass production., (© 2024 Wiley‐VCH GmbH.)

The use of physical plasma to treat cancer is an emerging field, and interest in its applications in oncology is increasing rapidly. Physical plasma can be used directly by aiming the plasma jet onto cells or tissue, or indirectly, where a plasma-treated solution is applied. A key scientific question is the mechanism by which physical plasma achieves selective killing of cancer over normal cells. Many studies have focused on specific pathways and mechanisms, such as apoptosis and oxidative stress, and the role of redox biology. However, over the past two decades, there has been a rise in omics, the systematic analysis of entire collections of molecules in a biological entity, enabling the discovery of the so-called "unknown unknowns." For example, transcriptomics, epigenomics, proteomics, and metabolomics have helped to uncover molecular mechanisms behind the action of physical plasma, revealing critical pathways beyond those traditionally associated with cancer treatments. This review showcases a selection of omics and then summarizes the insights gained from these studies toward understanding the biological pathways and molecular mechanisms implicated in physical plasma treatment. Omics studies have revealed how reactive species generated by plasma treatment preferentially affect several critical cellular pathways in cancer cells, resulting in epigenetic, transcriptional, and post-translational changes that promote cell death. Finally, this review considers the outlook for omics in uncovering both synergies and antagonisms with other common cancer therapies, as well as in overcoming challenges in the clinical translation of physical plasma., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

The charge transfer between the donor and acceptor determines the photogenerated carrier density in organic solar cells. However, a fundamental understanding regarding the charge transfer at donor/acceptor interfaces with high-density traps has not been fully addressed. Herein, a general correlation between trap densities and charge transfer dynamics is established by adopting a series of high-efficiency organic photovoltaic blends. It is found that the electron transfer rates are reduced with increased trap densities, while the hole transfer rates are independent of trap states. The local charges captured by traps can induce potential barrier formation around recombination centers, leading to the suppression of electron transfer. For the hole transfer process, the thermal energy provides a sufficient driving force, which ensures an efficient transfer rate. As a result, a 17.18% efficiency is obtained for PM6:BTP-eC9-based devices with the lowest interfacial trap densities. This work highlights the importance of interfacial traps in charge transfer processes and proposes an underlying insight into the charge transfer mechanism at nonideal interfaces in organic heterostructures.

We aimed to confirm whether transmembrane serine protease 2 (TMPRSS2) regulates nidogen 1 (NID1) expression in extracellular vesicles (EVs) and metastatic hepatocellular carcinoma (HCC) cells. HCC cells, HUVEC cells, MRC-5 cells, HLE cells, MHCCLM3 cells, MHCC97L cells, H2P cells, H2M cells, as well as LO2 cells were cultured according to providers' instruction and EV models were established by using BALB/cAnN-nu mice to facilitate the verifications. We found that TMPRSS2 expression was inversely correlated with the metastatic potential of HCC cell lines. The expression of TMPRSS2 decreased in a time-dependent manner in tumor-bearing model mice implanted with MHCCLM3 cells compared with uninoculated mice. TMPRSS2 overexpression in MHCCLM3 and MHCC97L cells led to the significant downregulation of NID1 expression in total cell lysates and isolated EVs. In contrast, TMPRSS2 silencing resulted in the elevation of NID1 expression in cells and EVs. Administration of EVs from MHCCLM3 and MHCC97L cells with overexpressed or silenced TMPRSS2 inhibited or strengthened, respectively, the invasion, proliferation, and migration of LO2 tumor cells. EVs derived from MHCCLM3 and MHCC97L cells with overexpressed or depleted TMPRSS2 also deactivated or activated fibroblasts, respectively. These EVs secrete inflammatory cytokines and phosphorylated p65, facilitate the colonization of fibroblasts, and augment fibroblast growth and motility. These findings provide evidence for a new candidate drug targeting tumorigenic EV-NID1 to treat HCC.

Coronavirus disease (COVID) toes are pernio-like skin lesions associated with severe acute respiratory syndrome coronavirus 2. We observed pernio-like skin findings presenting after a Pfizer BioNTech vaccine, which significantly worsened after an infusion of rituximab. This suggests that the mechanism for COVID toes is interferon activation. Military providers may avoid unnecessary referrals for this self-limiting condition by anticipating this adverse effect., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase (CPR) is involved in the metabolism of endogenous and exogenous substances, and detoxification of insecticides. RNA interference (RNAi) of CPR in certain insects causes developmental defects and enhanced susceptibility to insecticides. However, the CPR of Acyrthosiphon pisum has not been characterized, and its function is still not understood. In this study, we investigated the biochemical functions of A. pisum CPR (ApCPR). ApCPR was found to be transcribed in all developmental stages and was abundant in the embryo stage, and in the gut, head, and abdominal cuticle. After optimizing the dose and silencing duration of RNAi for downregulating ApCPR, we found that ApCPR suppression resulted in a significant decrease in the production of cuticular and internal hydrocarbon contents, and of cuticular waxy coatings. Deficiency in cuticular hydrocarbons (CHCs) decreased the survival rate of A. pisum under desiccation stress and increased its susceptibility to contact insecticides. Moreover, desiccation stress induced a significant increase in ApCPR mRNA levels. We further confirmed that ApCPR participates in CHC production. These results indicate that ApCPR modulates CHC production, desiccation tolerance, and insecticide susceptibility in A. pisum, and presents a novel target for pest control., (© 2021 Institute of Zoology, Chinese Academy of Sciences.)

Cuticular hydrocarbons form a barrier that protects terrestrial insects from water loss via the epicuticle. Lipophorin loads and transports lipids, including hydrocarbons, from one tissue to another. In some insects, the lipophorin receptor (LpR), which binds to lipophorin and accepts its lipid cargo, is essential for female fecundity because it mediates the incorporation of lipophorin by developing oocytes. However, it is unclear whether LpR is involved in the accumulation of cuticular hydrocarbons and its precise role in aphid reproduction remains unknown. We herein present the results of our molecular characterization, phylogenetic analysis, and functional annotation of the pea aphid (Acyrthosiphon pisum) LpR gene (ApLpR). This gene was transcribed throughout the A. pisum life cycle, but especially during the embryonic stage and in the abdominal cuticle. Furthermore, we optimized the RHA interference (RNAi) parameters by determining the ideal dose and duration for gene silencing in the pea aphid. We observed that the RNAi-based ApLpR suppression significantly decreased the internal and cuticular hydrocarbon contents as well as adult fecundity. Additionally, a deficiency in cuticular hydrocarbons increased the susceptibility of aphids to desiccation stress, with decreased survival rates under simulated drought conditions. Moreover, ApLpR expression levels significantly increased in response to the desiccation treatment. These results confirm that ApLpR is involved in transporting hydrocarbons and protecting aphids from desiccation stress. Furthermore, this gene is vital for aphid reproduction. Therefore, the ApLpR gene of A. pisum may be a novel RNAi target relevant for insect pest management., (© 2020 Institute of Zoology, Chinese Academy of Sciences.)

Apolipoprotein D (ApoD) is a lipocalin superfamily member that plays important roles in the transport of small hydrophobic molecules, lipid metabolism, and stress resistance. Cuticular hydrocarbons are the principal components of the epicuticular lipid layer and play a critical role in water retention against environmental desiccation stress; however, the mechanism underlying the role of ApoD in insect desiccation tolerance has not yet been elucidated. Here, we report the molecular constitution, functional analysis, and phylogenetic relationship of the ApoD gene in Acyrthosiphon pisum (ApApoD). We found that ApApoD was transcribed throughout the life cycle of A. pisum, but was prominently expressed in the embryonic period and abdominal cuticle. In addition, we optimized the dose and silencing duration of RNAi, observing that RNAi against ApApoD significantly reduced the levels of both internal and cuticular hydrocarbons and adult fecundity. Moreover, cuticular hydrocarbon deficiency increased the sensitivity of aphids to desiccation stress and reduced their survival time, while desiccation stress significantly increased ApApoD expression. Together, it is confirmed that ApApoD participates in regulating cuticular hydrocarbon content of aphids under desiccation stress and is crucial for aphid reproduction. Therefore, the ApApoD gene of A. pisum may be a potential target for RNAi-based insect pest control due to its involvement in cuticular hydrocarbon accumulation and reproduction., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Eight compounds were isolated from the ethyl acetate extraction of Prunus mume by column chromatography. On the basis of physicochemical properties and spectrum analysis, these compounds were identified as isoquercitrin-6″-O-benzoate(1), pinoresinol(2), naringin(3), ethyl-β-D-glucopyranoside(4), astragalin(5), quercetin(6), hypericin(7), and rutin(8). Among them, compound 1 was a new natural product, and compounds 2-5 were isolated from this plant for the first time. In vitro study, compounds 1, 3, 5-8 could significantly increase the cell survival ratio.

Insect cuticular hydrocarbons (CHCs), the evolutionary products of aquatic hexapod ancestors expanding to terrestrial environment, are deposited on the surface of insect integument and originally functioned primarily as waterproofing agents. CHCs are derived from the conserved fatty acid synthesis pathway in insects. However, the pivotal fatty acid synthase (FAS) involved in hydrocarbon (HC) biosynthesis remains unknown in many insect orders including the primitive Blattodea. Here, we investigated functional FAS genes that modulate cuticular lipid biogenesis in the German cockroach, Blattella germanica (L.). Based on our full-length transcriptomic data and the available genomic data, seven FAS genes (BgFas1-7) were identified from B. germanica. Tissue-specific expression analysis revealed that BgFas1, BgFas3, BgFas4 and BgFas7 were highly expressed in the integument, whereas BgFas2 was dominantly expressed in the fat body. BgFas5/6 mRNA was almost negligible in the tested tissues. Systemic RNAi screen was performed against BgFas1-7, we found that only RNAi knockdown of BgFas1 caused a dramatic reduction of methyl-branched HCs (mbHCs) and a slight decrease of straight-chain HCs (scHCs) for both internal and external HCs. Significant reduction of cuticular free fatty acids (cFFAs) was also detected within BgFas1-repressed cockroaches, while repression of CYP4G19 resulted in dramatic increase of cFFAs. Moreover, we found that BgFas1 mRNA levels were correlated with insect molting cycles, and could be induced by long-term mild dryness treatment. Furthermore, desiccation assay revealed that BgFas1 suppression accelerated water loss and led to early death of cockroaches under desiccation. Our results indicate that BgFas1 is necessary for both HC and cFFA biosynthesis in B. germanica. In addition, our study also confirms that cuticular lipids, particularly mbCHCs, are critical for desiccation resistance in B. germanica., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The breakdown of the Stokes-Einstein relation (SER) in three model metallic liquids is investigated via molecular dynamics simulations. It is found that the breakdown of SER is closely correlated with the clustering behavior of well-packed atoms. When the SER breaks down, many cluster properties have almost the same value in these metallic liquids. At the breakdown temperature of SER, the temperature dependence of the number of clusters begins to deviate from a linear increase and the average number of well-packed atoms in the clusters reaches about 2, which indicates an increase in structure heterogeneity. Moreover, the size of the largest cluster shows a direct correlation with the SER. Therefore, our study provides a possible structural origin for the breakdown of SER in metallic liquids.

The present study demonstrates that Ti-based metallic glass matrix composites (MGMCs) with a normal composition of Ti 43 Zr 32 Ni 6 Ta 5 Be 14 containing ductile dendrites dispersed in the glass matrix has been developed, and deformation mechanisms about the tensile property have been investigated by focusing on twinning-induced plasticity (TWIP) effect. The Ti-based MGMC has excellent tensile properties and pronounced tensile work-hardening capacity, with a yield strength of 1100 MPa and homogeneous elongation of 4%. The distinguished strain hardening is ascribed to the formation of deformation twinning within the dendrites. Twinning generated in the dendrites works as an obstacle for the rapid propagation of shear bands, and then, the localized necking is avoided, which ensures the ductility of such kinds of composites. Besides, a finite-element model (FEM) has been established to explain the TWIP effect which brings out a work-hardening behavior in the present MGMC instead of a localized strain concentration. According to the plasticity theory of traditional crystal materials and some new alloys, TWIP effect is mainly controlled by stacking fault energy (SFE), which has been analyzed intensively in the present MGMC.

Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities.

Remarkable tensile ductility was first obtained in an in-situ Ti-based bulk metallic glass (BMG) composite at cryogenic temperature (77 K). The novel cryogenic tensile plasticity is related to the effective accommodation of ductile body-centered cubic dendrites at 77 K, characteristic of the prevailing slip bands and dislocations, as well as lattice disorder, which can effectively hinder the propagation of critical shear bands. The greatly increased yield strength of dendrites contributes to the high yield strength of composite at 77 K. A trend of stronger softening is observed at low temperature, and a criterion is proposed to understand the softening behavior. The current research could also provide a guidance to the promising cryogenic application of these new advanced BMG composites.

We investigated structural disorder by a new structural parameter, quasi-nearest atom (QNA), in atomistic configurations of eight metallic glass-forming systems generated through molecular dynamics simulations at various temperatures. Structural analysis reveals that the scaled distribution of the number of QNA appears to be an universal property of metallic liquids and the spatial distribution of the number of QNA displays to be clearly heterogeneous. Furthermore, the new parameter can be directly correlated with potential energy and structural relaxation at the atomic level. Some straightforward relationships between QNA and other properties (per-atom potential energy and α-relaxation time) are introduced to reflect structure-property relationship in metallic liquids. We believe that the new structural parameter can well reflect structure disorder in metallic liquids and play an important role in understanding various properties in metallic liquids.

Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon-associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets.

Profiling post-translational modifications represents an alternative dimension to gene expression data in characterizing cellular processes. Many cellular responses to drugs are mediated by changes in cellular phosphosignaling. We sought to develop a common platform on which phosphosignaling responses could be profiled across thousands of samples, and created a targeted MS assay that profiles a reduced-representation set of phosphopeptides that we show to be strong indicators of responses to chemical perturbagens.To develop the assay, we investigated the coordinate regulation of phosphosites in samples derived from three cell lines treated with 26 different bioactive small molecules. Phosphopeptide analytes were selected from these discovery studies by clustering and picking 1 to 2 proxy members from each cluster. A quantitative, targeted parallel reaction monitoring assay was developed to directly measure 96 reduced-representation probes. Sample processing for proteolytic digestion, protein quantification, peptide desalting, and phosphopeptide enrichment have been fully automated, making possible the simultaneous processing of 96 samples in only 3 days, with a plate phosphopeptide enrichment variance of 12%. This highly reproducible process allowed ∼95% of the reduced-representation phosphopeptide probes to be detected in ∼200 samples.The performance of the assay was evaluated by measuring the probes in new samples generated under treatment conditions from discovery experiments, recapitulating the observations of deeper experiments using a fraction of the analytical effort. We measured these probes in new experiments varying the treatments, cell types, and timepoints to demonstrate generalizability. We demonstrated that the assay is sensitive to disruptions in common signaling pathways (e.g. MAPK, PI3K/mTOR, and CDK). The high-throughput, reduced-representation phosphoproteomics assay provides a platform for the comparison of perturbations across a range of biological conditions, suitable for profiling thousands of samples. We believe the assay will prove highly useful for classification of known and novel drug and genetic mechanisms through comparison of phosphoproteomic signatures., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

To establish an HPLC-ELSD method for the quantification of triterpenoids in the fruits of Buddleja lindleyana. The RP-HPLC-ELSD method was used for the determination of triterpenoids in B. lindleyana fruits, which were collected from different habitats. The column used was a packed with 5 μm stationary phase Waters SunFireTM C₁₈ (4.6 mm×150 mm, 5 μm). The mobile phase consisted of Methanol-water(82∶18) at a flow rate of 1 mL•min⁻¹. Column temperature： 30 ℃. ELSD conditions： drift tube temperature： 106 ℃; carrier gas (nitrogen) flow rate： 1.5 L•min⁻¹; amplification factor： 1. The calibration curves showed good linear relationship on a range from 0.702 to 28.08 μg(r=0.999 2) for Clinoposaponin III, 0.390 to 15.60 μg(r=0.998 9) for Desrhamnoverbascosaponin and 0.192 to 7.68μg(r=0.999 0) for Mimengoside I. The average recovery rate(n=6) were 99.41%, 99.08% and 98.67% and it's RSD were 0.86%, 1.56% and 1.80%. This method can be used to determine the contents of triterpenoids in the fruits of Buddleja lindleyana for its simplicity, accurateness and reliability., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

We report simulations on the local structural evolution in the liquid-bcc transition of a model iron. Fourteen main Voronoi polyhedra are chosen as the representatives of short-range orders (SROs) and their transformations during crystallization are also investigated. Thus, the crystallization pathways for the main SROs are drawn. Our results also show that the transformations between two SROs in the crystallization pathways can be classified into two categories, first the enlargement of coordination number, second the transformation of local symmetry from five-fold to four-fold. The former reduces the potential energy while the latter increases it. It is found that the potential energy cannot decease monotonously whatever crystallization pathway is chosen to transform the icosahedral SRO to bcc SRO. Therefore, the latter transformation might provide the energy barrier of crystallization. We propose two transformation styles among SROs. All the transformations in the crystallization pathways can be achieved according to the styles. Moreover, the two transformation styles indicates that the bcc structure is more similar to liquid than other crystals. That might be the reason why the first phase nucleated during a rapid cooling process should be bcc crystal.

With regard to previous tensile deformation models simulating the tensile behavior of in-situ dendrite-reinforced metallic glass matrix composites (MGMCs) [Qiao et al., Acta Mater. 59 (2011) 4126; Sci. Rep. 3 (2013) 2816], some parameters, such as yielding strength of the dendrites and glass matrix, and the strain-hardening exponent of the dendrites, are estimated based on literatures. Here, Ti48Zr18V12Cu5Be17 MGMCs are investigated in order to improve the tensile deformation model and reveal the tensile deformation mechanisms. The tensile behavior of dendrites is obtained experimentally combining nano-indentation measurements and finite-element-method analysis for the first time, and those of the glass matrix and composites are obtained by tension. Besides, the tensile behavior of the MGMCs is divided into four stages: (1) elastic-elastic, (2) elastic-plastic, (3) plastic-plastic (work-hardening), and (4) plastic-plastic (softening). The respective constitutive relationships at different deformation stages are quantified. The calculated results coincide well with the experimental results. Thus, the improved model can be applied to clarify and predict the tensile behavior of the MGMCs.

Cell-type specific gene silencing by histone H3 lysine 27 and lysine 9 methyltransferase complexes PRC2 and G9A-GLP is crucial both during development and to maintain cell identity. Although studying their interaction partners has yielded valuable insight into their functions, how these factors are regulated on a network level remains incompletely understood. Here, we present a new approach that combines quantitative interaction proteomics with global chromatin profiling to functionally characterize repressive chromatin modifying protein complexes in embryonic stem cells. We define binding stoichiometries of 9 new and 12 known interaction partners of PRC2 and 10 known and 29 new interaction partners of G9A-GLP, respectively. We demonstrate that PRC2 and G9A-GLP interact physically and share several interaction partners, including the zinc finger proteins ZNF518A and ZNF518B. Using global chromatin profiling by targeted mass spectrometry, we discover that even sub-stoichiometric binding partners such as ZNF518B can positively regulate global H3K9me2 levels. Biochemical analysis reveals that ZNF518B directly interacts with EZH2 and G9A. Our systematic analysis suggests that ZNF518B may mediate the structural association between PRC2 and G9A-GLP histone methyltransferases and additionally regulates the activity of G9A-GLP., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing biological insight, informing drug and diagnostic development, and guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact of ischemia, we collected human ovarian tumor and breast cancer xenograft tissue without vascular interruption and performed quantitative proteomics and phosphoproteomics after defined ischemic intervals. Although the global expressed proteome and most of the >25,000 quantified phosphosites were unchanged after 60 min, rapid phosphorylation changes were observed in up to 24% of the phosphoproteome, representing activation of critical cancer pathways related to stress response, transcriptional regulation, and cell death. Both pan-tumor and tissue-specific changes were observed. The demonstrated impact of pre-analytical tissue ischemia on tumor biology mandates caution in interpreting stress-pathway activation in such samples and motivates reexamination of collection protocols for phosphoprotein analysis., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

In-situ dendrite/metallic glass matrix composites (MGMCs) with a composition of Ti₄₆Zr₂₀V₁₂Cu₅Be₁₇ exhibit ultimate tensile strength of 1510 MPa and fracture strain of about 7.6%. A tensile deformation model is established, based on the five-stage classification: (1) elastic-elastic, (2) elastic-plastic, (3) plastic-plastic (yield platform), (4) plastic-plastic (work hardening), and (5) plastic-plastic (softening) stages, analogous to the tensile behavior of common carbon steels. The constitutive relations strongly elucidate the tensile deformation mechanism. In parallel, the simulation results by a finite-element method (FEM) are in good agreement with the experimental findings and theoretical calculations. The present study gives a mathematical model to clarify the work-hardening behavior of dendrites and softening of the amorphous matrix. Furthermore, the model can be employed to simulate the tensile behavior of in-situ dendrite/MGMCs.

Objective: To investigate the effect of 0.1 Gy X-ray irradiation on the gene expression profiles in normal human lymphoblastoid cells using gene microarray and to explore the possible mechanism of the biological effect of low-dose irradiation., Methods: The NimbleGen 12×135 K microarray corresponding to 45033 genes was used to analyze the gene expression profiles in AHH-1 cells cultured for 6 h and 20 h after 0.1 Gy X-ray irradiation. A gene was identified as the differentially expressed gene if the ratio between its expression levels in irradiation group and control group was higher than 2 or lower than 0.5. RT-PCR and real-time PCR were used to confirm some differentially expressed genes., Results: There were 760 up-regulated genes and 1222 down-regulated genes in the cells at 6 h after 0.1 Gy X-ray irradiation, while there were 463 up-regulated genes and 753 down-regulated genes at 20 h after 0.1 Gy X-ray irradiation; there were 92 differentially expressed genes in common. The expression of GADD45A, CDKN2A, and Cx43 measured using gene microarray was confirmed by RT-PCR and real-time PCR., Conclusion: Low-dose irradiation can affect the expression of many functional genes, which provides a basis for the research on the mechanism of radiation damage.

We report a mass spectrometry-based method for the integrated analysis of protein expression, phosphorylation, ubiquitination and acetylation by serial enrichments of different post-translational modifications (SEPTM) from the same biological sample. This technology enabled quantitative analysis of nearly 8,000 proteins and more than 20,000 phosphorylation, 15,000 ubiquitination and 3,000 acetylation sites per experiment, generating a holistic view of cellular signal transduction pathways as exemplified by analysis of bortezomib-treated human leukemia cells.

Detection of endogenous ubiquitination sites by mass spectrometry has dramatically improved with the commercialization of anti-di-glycine remnant (K-ε-GG) antibodies. Here, we describe a number of improvements to the K-ε-GG enrichment workflow, including optimized antibody and peptide input requirements, antibody cross-linking, and improved off-line fractionation prior to enrichment. This refined and practical workflow enables routine identification and quantification of ∼20,000 distinct endogenous ubiquitination sites in a single SILAC experiment using moderate amounts of protein input.

Thimet oligopeptidase (TOP) and prolyl endopeptidase (PEP) are neuropeptidases involved in the hydrolysis of gonadotropin-releasing hormone, a key component of the hypothalamic-pituitary-gonadal axis. GnRH is regulated in part by feedback from steroid hormones such as estradiol. Previously, we demonstrated that TOP levels are down-regulated by estradiol in reproductively-relevant regions of the female rodent brain. The present study supports these findings by showing that TOP enzyme activity, as well as protein levels, in the ventromedial hypothalamic nucleus of female mice is controlled by estradiol. We further demonstrate that PEP levels in this same brain region are down-regulated by estradiol in parallel with those of TOP. These findings provide evidence that these neuropeptidases are part of the fine control of hormone levels in the HPG axis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To establish the dose-effect curve between TCR MF and ionizing radiation., Methods: Peripheral lymphocytes were collected from 8 healthy adults (4 males and 4 females) and cultured in vitro with 12 well culture plates. They were stimulated by PHA-P and IL-2 after exposed to different doses of irradiation (0.00 - 8.00 Gy) and cultured for 7 d. The dose-effect curve was established after measuring TCR MF using flow cytometry. Also, using the same method, we separated and cultured the peripheral lymphocytes collected from 16 radiotherapy cancer patients, whose radiation styles and doses were different, and then measured TCR MF to estimate the whole equivalent dose of radiotherapy patients through the dose-effect curve. Peripheral blood was collected and cultured, chromosome aberration (dicentric and ring) was determined under microscope to estimate irradiation dose., Results: The relationship of dose-effect between the TCR MF and ionizing radiation (0.00 - 8.00 Gy) was well, the curve of large dose group (2.00 - 8.00 Gy), low dose group (0.00 - 1.00 Gy) and 0.00 - 8.00 Gy dose group were met with the quadratic polynomial model, the equation was TCR MF = -32.8579 + 20.5436D + 0.6341D(2), TCR MF = 1.796 + 0.017D + 5.155D(2) and TCR MF = -0.6229 + 6.305D + 0.6919D(2), respectively. D was the radiation dose (Gy). Using the established curve and the chromosome aberration method to estimate the systemic exposure dosage, the average relative deviation was 16.8%., Conclusion: The curve established by the TCR gene mutation analysis technology can be applied to exposure dose estimation of victims in ionization radiation accidents.

The 37-kDa laminin receptor precursor/67-kDa laminin receptor (LRP/LR, also known as ribosomal protein SA, RPSA) has been reported to be involved in cancer development and prion internalization. Previous studies have shown that the LRP/LR is expressed in a wide variety of tissues. In particular, expression of LRP/LR mRNA may be closely related to the degree of PrP(Sc) propagation. This study presents a detailed investigation of the LRP/LR mRNA expression levels in eleven normal ovine tissues. Using real-time quantitative PCR, the highest LRP/LR expression was found in neocortex (p < 0.05). Slightly lower levels were found in the heart and obex. Intermediate levels were seen in hippocampus, cerebellum, spleen, thalamus, mesenteric lymph node, and the lowest levels were present in liver, kidney, and lung. In general, the LRP/LR mRNA levels were much higher in neuronal tissues than in peripheral tissues. The observation that differences in LRP/LR mRNA expression levels are consistent with the corresponding variation in PrP(Sc) accumulation suggests that the 37-kDa/67-kDa laminin receptor may be involved in the regulation of PrP(Sc) propagation.