Comparative theoretical study of CO2 activation on clean and potassium-preadsorbed low index surfaces of transition metals.

CONTEXT: The efficient catalysis of CO2 adsorption and activation presents a formidable challenge due to its pronounced thermodynamic stability and kinetic inertia. Previous experiments have left gaps in understanding the promotional effects and underlying mechanism of potassium. In this study, we systematically investigate CO2 adsorption and activation on clean and potassium-preadsorbed low index surfaces of transition metals. Theoretical results reveal a substantial augmentation in CO2 binding strength when potassium is introduced, concomitant with a general reduction in activation energies. Notably, linear correlations are significant on close-packed metal surfaces without and with potassium additive. Through a comprehensive analysis encompassing geometric parameters, electronic structures, and energy decomposition, we discern the physical underpinnings of the potassium effect. This enhancement is primarily ascribed to direct electron transfer and dipole-dipole interactions. Furthermore, we scrutinize the impact of an external electric field, demonstrating that the application of a negative electric field accelerates CO2 activation, mirroring the effects observed with potassium. METHODS: All the periodic density function theory (DFT) calculations were performed by the Vienna Ab Initio Simulation package (VASP). The interaction between nucleus and valence electron was described using the pseudopotentials found in the projector augmented wave method (PAW). Throughout the entire work, the Bayesian error estimation functional (BEEF) was used.

DORIS: Personalized course recommendation system based on deep learning.

Course recommendation aims at finding proper and attractive courses from massive candidates for students based on their needs, and it plays a significant role in the curricula-variable system. However, nearly all students nowadays need help selecting appropriate courses from abundant ones. The emergence and application of personalized course recommendations can release students from that cognitive overload problem. However, it still needs to mature and improve its scalability, sparsity, and cold start problems resulting in poor quality recommendations. Therefore, this paper proposes a novel personalized course recommendation system based on deep factorization machine (DeepFM), namely Deep PersOnalized couRse RecommendatIon System (DORIS), which selects the most appropriate courses for students according to their basic information, interests and the details of all courses. The experimental results illustrate that our proposed method outperforms other approaches.

Three-Dimensional Cell Co-Culture Liver Models and Their Applications in Pharmaceutical Research.

As the primary site for the biotransformation of drugs, the liver is the most focused on organ type in pharmaceutical research. However, despite being widely used in pharmaceutical research, animal models have inherent species differences, while two-dimensional (2D) liver cell monocultures or co-cultures and three-dimensional (3D) liver cell monoculture in vitro liver models do not sufficiently represent the complexity of the human liver's structure and function, making the evaluation results from these tools less reliable. Therefore, there is a pressing need to develop more representative in vitro liver models for pharmaceutical research. Fortunately, an exciting new development in recent years has been the emergence of 3D liver cell co-culture models. These models hold great promise as in vitro pharmaceutical research tools, because they can reproduce liver structure and function more practically. This review begins by explaining the structure and main cell composition of the liver, before introducing the potential advantages of 3D cell co-culture liver models for pharmaceutical research. We also discuss the main sources of hepatocytes and the 3D cell co-culture methods used in constructing these models. In addition, we explore the applications of 3D cell co-culture liver models with different functional states and suggest prospects for their further development.

Numerical analysis of novel concrete filled K joints with different brace sections.

All over the world, truss structures are commonly used in long-span bridge. Since joint is the weakest part of this structure, this paper proposes a novel type in which different brace members are used in the concrete filled box section K-joints. This novel type is designed as rectangular compression brace with the brace width to chord ratio ß < 0.8 and chord welded tension brace ( ß = 1 ) . That configuration allows to reduce the gap, thus eliminate the secondary moment. Moreover, load transfer and failure modes are not similar to the ordinary. Numerical simulation is the used method of investigation in which validation is carried out through thirty-four models composed of RHS K gap Joint - CFST T Joint - CFST Y Joint - RHS T Integral Joint - CFST K gap Joint. Difference between experiments and Finite Element models are less than 20% thus acceptable. Through the validated numerical simulation model, analysis of suitable boundary conditions and variation of initial stiffness, ultimate strength are presented in accordance with the novel joint parameters. Comparison of the novel joint type to the rectangular hollow section (RHS) and rectangular concrete filled steel tube (RCFST) is carried out in terms of initial stiffness and ultimate strength. Finally, optimization of the novel type of joint is proposed for engineering practice so as to have overview of the strength in practical aspect. Results have shown that most of the proposed types of boundary condition procure the joint deformation while subjected in compression and tension load. Tension brace failure is the typical failure mode of the novel joint in which the chord width, the parameter ß are fundamental and directly proportional to the joint initial stiffness and ultimate strength. For ß = 0.8 and the chord width between 500 and 1000 mm, the initial stiffness can vary from [ 9944.92 k N / m m - 19887.31 k N / m m ] ; ultimate strength varies from [ 29551.76 k N - 117916.20 k N ] . Moreover, the novel joint type is stronger than the RHS and the RCFST in both initial stiffness and ultimate strength. That difference is about 3-6% in the initial stiffness and around 10% for the ultimate strength. These demonstrate that the novel type of joint is acceptable in engineering truss bridge with proposition of joint optimization.

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-I as an Example.

Ion-complementary self-assembling peptides have been studied in many fields for their distinct advantages, mainly due to their self-assembly properties. However, their shortcomings, such as insufficient specific activity and poor mechanical properties, also limited their application. For the better and wider application of these promising biomaterials, ion-complementary self-assembling peptides can be modified with their self-assembly properties not being destroyed to the greatest extent. The modification strategies were reviewed by taking RADA16-I as an example. For insufficient specific activity, RADA16-I can be structurally modified with active motifs derived from the active domain of the extracellular matrix or other related active factors. For weak mechanical properties, materials with strong mechanical properties or that can undergo chemical crosslinking were used to mix with RADA16-I to enhance the mechanical properties of RADA16-I. To improve the performance of RADA16-I as drug carriers, appropriate adjustment of the RADA16-I sequence and/or modification of the RADA16-I-related delivery system with polymer materials or specific molecules can be considered to achieve sustained and controlled release of specific drugs or active factors. The modification strategies reviewed in this paper may provide some references for further basic research and clinical application of ion-complementary self-assembling peptides and their derivatives.

Visualizing Conformational Space of Functional Biomolecular Complexes by Deep Manifold Learning.

The cellular functions are executed by biological macromolecular complexes in nonequilibrium dynamic processes, which exhibit a vast diversity of conformational states. Solving the conformational continuum of important biomolecular complexes at the atomic level is essential to understanding their functional mechanisms and guiding structure-based drug discovery. Here, we introduce a deep manifold learning framework, named AlphaCryo4D, which enables atomic-level cryogenic electron microscopy (cryo-EM) reconstructions that approximately visualize the conformational space of biomolecular complexes of interest. AlphaCryo4D integrates 3D deep residual learning with manifold embedding of pseudo-energy landscapes, which simultaneously improves 3D classification accuracy and reconstruction resolution via an energy-based particle-voting algorithm. In blind assessments using simulated heterogeneous datasets, AlphaCryo4D achieved 3D classification accuracy three times those of alternative methods and reconstructed continuous conformational changes of a 130-kDa protein at sub-3 Å resolution. By applying this approach to analyze several experimental datasets of the proteasome, ribosome and spliceosome, we demonstrate its potential generality in exploring hidden conformational space or transient states of macromolecular complexes that remain hitherto invisible. Integration of this approach with time-resolved cryo-EM further allows visualization of conformational continuum in a nonequilibrium regime at the atomic level, thus potentially enabling therapeutic discovery against highly dynamic biomolecular targets.

A highly potent maytansinoid analogue and its use as a cytotoxic therapeutic agent in gold nanoparticles for the treatment of hepatocellular carcinoma.

Gold nanoparticles are promising drug delivery agents with the potential to deliver chemotherapeutic agents to tumour sites. The highly cytotoxic maytansinoid tubulin inhibitor DM1 has been attached to gold nanoparticles and shows tumour growth inhibition in mouse models of hepatocellular carcinoma. Attempting to improve the stability of the gold-cytotoxin bond led to the design and synthesis of novel maytansinoids with improved potency in cell viability assays and improved in vivo tolerability compared to the DM1 analogues. These novel maytansines may also have applications in other methods of drug delivery, for example as the cytotoxic component of antibody drug conjugates.

Visualization of Ligand-Bound Ectodomain Assembly in the Full-Length Human IGF-1 Receptor by Cryo-EM Single-Particle Analysis.

Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell membrane. However, the complete structure of the receptor and the signal transduction mechanism remains unclear. Here, we report the cryo-EM structure of the ligand-bound ectodomain in the full-length human IGF-1R. We reconstructed the IGF-1R/insulin complex at 4.7 Å and the IGF-1R/IGF-1 complex at 7.7 Å. Our structures reveal that only one insulin or one IGF-1 molecule binds to and activates the full-length human IGF-1R receptor.

Live-cell imaging of the cytoskeleton in elongating cotton fibres.

Cotton (Gossypium hirsutum) fibres consist of single cells that grow in a highly polarized manner, assumed to be controlled by the cytoskeleton1-3. However, how the cytoskeletal organization and dynamics underpin fibre development remains unexplored. Moreover, it is unclear whether cotton fibres expand via tip growth or diffuse growth2-4. We generated stable transgenic cotton plants expressing fluorescent markers of the actin and microtubule cytoskeleton. Live-cell imaging revealed that elongating cotton fibres assemble a cortical filamentous actin network that extends along the cell axis to finally form actin strands with closed loops in the tapered fibre tip. Analyses of F-actin network properties indicate that cotton fibres have a unique actin organization that blends features of both diffuse and tip growth modes. Interestingly, typical actin organization and endosomal vesicle aggregation found in tip-growing cell apices were not observed in fibre tips. Instead, endomembrane compartments were evenly distributed along the elongating fibre cells and moved bi-directionally along the fibre shank to the fibre tip. Moreover, plus-end tracked microtubules transversely encircled elongating fibre shanks, reminiscent of diffusely growing cells. Collectively, our findings indicate that cotton fibres elongate via a unique tip-biased diffuse growth mode.

Towards a better recording of microtubule cytoskeletal spatial organization and dynamics in plant cells.

Numerous fluorescent marker lines are currently available to visualize microtubule (MT) architecture and dynamics in living plant cells, such as markers expressing p35S::GFP-MBD or p35S::GFP-TUB6. However, these MT marker lines display obvious defects that affect plant growth or produce unstable fluorescent signals. Here, a series of new marker lines were developed, including the pTUB6::VisGreen-TUB6-expressing line in which TUB6 is under the control of its endogenous regulatory elements and eGFP is replaced with VisGreen, a brighter fluorescent protein. Moreover, two different markers were combined into one expression vector and developed two dual-marker lines. These marker lines produce bright, stable fluorescent signals in various tissues, and greatly shorten the screening process for generating dual-marker lines. These new marker lines provide a novel resource for MT research.

Augmin Antagonizes Katanin at Microtubule Crossovers to Control the Dynamic Organization of Plant Cortical Arrays.

Plant cells do not possess centrosomes, which serve as the microtubule organizing center in animal cells; how plant cell microtubule arrays are established and maintain their dynamics remain poorly understood [1]. The γ-tubulin complex and the katanin complex play central roles in the organization of plant cortical microtubules [2-6]. Previously, we reported that the augmin complex recruits the γ-tubulin complex to preexisting microtubules and initiates microtubule nucleation [7]. Moreover, we described how an intricate interaction between the katanin p60 subunit KTN1 and the p80 subunit KTN80 confers precise microtubule severing at either microtubule branching nucleation sites or crossovers [8]. Here, we observed that augmin preferentially localizes to microtubule crossovers. Live-cell observations and analyses revealed that, whereas a small portion of crossover-localized augmin complexes act to trigger nascent microtubule nucleation, the majority function in stabilizing the architecture of microtubule crossovers. Finally, genetic analyses and computational modeling confirmed that suppression of augmin activity elevates microtubule severing frequency and facilitates the formation of aligned microtubule arrays. Combined, our findings reveal an unexpected role of augmin and demonstrate that augmin antagonizes katanin-mediated microtubule severing. Furthermore, we propose a novel mechanism for how augmin determines self-organization of plant cortical microtubules by preventing microtubule severing at crossovers in addition to triggering microtubule nucleation.

Ectopic expression of SsPETE2, a plastocyanin from Suaeda salsa, improves plant tolerance to oxidative stress.

Accumulating evidence indicates that plant plastocyanin is involved in copper homeostasis, yet the physiological relevance remains elusive. In this study, we found that a plastocyanin gene (SsPETE2) from euhalophyte Suaeda salsa possessed a novel antioxidant function, which was associated with the copper-chelating activity of SsPETE2. In S. salsa, expression of SsPETE2 increased in response to oxidative stress and ectopic expression of SsPETE2 in Arabidopsis enhanced the antioxidant ability of the transgenic plants. SsPETE2 bound Cu ion and alleviated formation of hydroxyl radicals in vitro. Accordingly, SsPETE2 expression lowered the free Cu content that was associated with reduced H2O2 level under oxidative stress. Arabidopsis pete1 and pete2 mutants showed ROS-sensitive phenotypes that could be restored by expression of SsPETE2 or AtPETEs. In addition, SsPETE2-expressing plants exhibited more potent tolerance to oxidative stress than plants overexpressing AtPETEs, likely owing to the stronger copper-binding activity of SsPETE2 than AtPETEs. Taken together, these results demonstrated that plant PETEs play a novel role in oxidative stress tolerance by regulating Cu homeostasis under stress conditions, and SsPETE2, as an efficient copper-chelating PETE, potentially could be used in crop genetic engineering.

Orchestration of microtubules and the actin cytoskeleton in trichome cell shape determination by a plant-unique kinesin.

Microtubules (MTs) and actin filaments (F-actin) function cooperatively to regulate plant cell morphogenesis. However, the mechanisms underlying the crosstalk between these two cytoskeletal systems, particularly in cell shape control, remain largely unknown. In this study, we show that introduction of the MyTH4-FERM tandem into KCBP (kinesin-like calmodulin-binding protein) during evolution conferred novel functions. The MyTH4 domain and the FERM domain in the N-terminal tail of KCBP physically bind to MTs and F-actin, respectively. During trichome morphogenesis, KCBP distributes in a specific cortical gradient and concentrates at the branching sites and the apexes of elongating branches, which lack MTs but have cortical F-actin. Further, live-cell imaging and genetic analyses revealed that KCBP acts as a hub integrating MTs and actin filaments to assemble the required cytoskeletal configuration for the unique, polarized diffuse growth pattern during trichome cell morphogenesis. Our findings provide significant insights into the mechanisms underlying cytoskeletal regulation of cell shape determination.

GhCFE1A, a dynamic linker between the ER network and actin cytoskeleton, plays an important role in cotton fibre cell initiation and elongation.

Fibre cell initiation and elongation is critical for cotton fibre development. However, little is known about the regulation of initiation and elongation during fibre cell development. Here, the regulatory role of a novel protein GhCFE1A was uncovered. GhCFE1A is preferentially expressed at initiation and rapid elongation stages during fibre development; in addition, much higher expression of GhCFE1A was detected at the fibre initiation stage in fibreless cotton mutants than in the fibre-bearing TM-1 wild-type. Importantly, overexpression of GhCFE1A in cotton not only delayed fibre cell elongation but also significantly reduced the density of lint and fuzz fibre initials and stem trichomes. Yeast two-hybrid assay showed that GhCFE1A interacted with several actin proteins, and the interaction was further confirmed by co-sedimentation assay. Interestingly, a subcellular localization assay showed that GhCFE1A resided on the cortical endoplasmic reticulum (ER) network and co-localized with actin cables. Moreover, the density of F-actin filaments was shown to be reduced in GhCFE1A-overexpressing fibres at the rapid elongation stage compared with the wild-type control. Taken together, the results demonstrate that GhCFE1A probably functions as a dynamic linker between the actin cytoskeleton and the ER network, and plays an important role in fibre cell initiation and elongation during cotton fibre development.

Augmin triggers microtubule-dependent microtubule nucleation in interphase plant cells.

Microtubule (MT)-dependent MT nucleation by γ-tubulin is required for interphase plant cells to establish a highly dynamic cortical MT network underneath the plasma membrane, which influences the deposition of cell wall materials and consequently governs patterns of directional cell expansion. Newly formed MTs either assume 40° angles or are parallel to the extant ones. To date, it has been enigmatic how the γ-tubulin complex is recruited to the sidewall of cortical MTs and initiates MT nucleation. Here, we discovered that the augmin complex was recruited to cortical MTs and initiated MT nucleation in both branching and parallel forms. The augmin complex overwhelmingly colocalized with the γ-tubulin complex. When the function of the augmin complex was compromised, MT nucleation frequency was drastically reduced, most obviously for the branching nucleation. Consequently, the augmin knockdown cells displayed highly parallel and bundled MTs, replacing the fine and mesh-like MT network in the wild-type cells. Our findings uncovered a mechanism by which the augmin complex functions in recruiting the γ-tubulin complex to cortical MTs and initiating MT nucleation, and they shifted the paradigm of the commonly perceived mitotic-specific function of augmin and established its crucial function in MT-dependent MT nucleation in interphase plant cells.

[Cloning and functional analysis of chitinase gene GbCHI from sea-island cotton (Gossypium barbadense)].

Chitinase is one of the important pathogenesis-related (PR) proteins in plants. By comparative proteomics study, a novel pathogen-responsive chitinase (known as GbCHI) has been identified from sea-island cotton (Gossypium barbadense). The GbCHI cDNA was cloned from wilt-resistant sea-island cotton and the anti-fungal activity of the gene product was investigated. qRT-PCR analysis indicated that GbCHI was expressed constitutively in root, stem, leaf, flower, and ovule of cotton plant, and the expression could be induced by Verticillium dahliae and plant hormone SA, ACC, and JA. Subcellular localization analysis using GFP-tagged proteins showed that GbCHI-GFP fusion proteins were targeted mainly to the plasma membrane. Anti-fungal assay demonstrated that GbCHI could inhibit spore germination and hyphae growth of V. dahliae significantly. These results provide important information for understanding the cellular function of GbCHI and for exploring the application potential of this gene in molecular breeding of wilt-tolerant cotton plants.

Exercise-induced galanin release facilitated GLUT4 translocation in adipocytes of type 2 diabetic rats.

Although galanin has been shown to increase insulin sensitivity in skeletal muscle of rats, there is no literature available about the effect of galanin on Glucose Transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of type 2 diabetic rats. In the present study M35, a galanin antagonist was used to elucidate whether exercise-induced galanin release increased GLUT4 translocation in adipocytes of streptozotocin-induced diabetic rats. The present findings showed that plasma galanin levels after swimming training in all four trained groups were higher compared with each sedentary control. M35 treatment had an inhibitory effect on glucose infusion rates in the euglycemic-hyperinsulinemic clamp test and GLUT4 mRNA expression levels in adipocytes. Moreover, M35 treatment reduced GLUT4 concentration in both plasma membranes and total cell membranes. The ratios of GLUT4 contents in plasma membranes to total cell membranes in four drug groups were lower compared with each control. These data demonstrate a beneficial role of endogenous galanin to transfer GLUT4 from internal stores to plasma membranes in adipocytes of type 2 diabetic rats. Galanin plays a significant role in regulation of glucose metabolic homeostasis and is an important hormone relative to diabetes.

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior.

Galanin is a neuropeptide widely expressed in the brain. It is implicated in energy expenditure, feeding, and the regulation of body weight. Numerous studies have revealed that galanin regulates food intake via galanin receptors, 5-HT(1A) receptor and adrenergic α-2 receptor. In this review, we summarize recent findings that reveal the essential role of galanin in increasing food intake as well as body weight and that identify the individual galanin receptor subtypes involved in the brain's modulation of food intake and energy expenditure, to provide a theoretical basis for further studies of different aspects of galanin action.

Proteomic analysis of the sea-island cotton roots infected by wilt pathogen Verticillium dahliae.

Verticillium wilt of cotton is a vascular disease mainly caused by the soil-born filamentous fungus Verticillium dahliae. To study the mechanisms associated with defense responses in wilt-resistant sea-island cotton (Gossypium barbadense) upon V. dahliae infection, a comparative proteomic analysis between infected and mock-inoculated roots of G. barbadense var. Hai 7124 (a cultivar showing resistance against V. dahliae) was performed by 2-DE combined with local EST database-assisted PMF and MS/MS analysis. A total of 51 upregulated and 17 downregulated proteins were identified, and these proteins are mainly involved in defense and stress responses, primary and secondary metabolisms, lipid transport, and cytoskeleton organization. Three novel clues regarding wilt resistance of G. barbadense are gained from this study. First, ethylene signaling was significantly activated in the cotton roots attacked by V. dahliae as shown by the elevated expression of ethylene biosynthesis and signaling components. Second, the Bet v 1 family proteins may play an important role in the defense reaction against Verticillium wilt. Third, wilt resistance may implicate the redirection of carbohydrate flux from glycolysis to pentose phosphate pathway (PPP). To our knowledge, this study is the first root proteomic analysis on cotton wilt resistance and provides important insights for establishing strategies to control this disease.

Beneficial effect of galanin on insulin sensitivity in muscle of type 2 diabetic rats.

The aim of this study was to determine whether enhanced galanin (GAL) release induced by exercise would elevate insulin sensitivity and glucose transporter 4 (GLUT4) concentration in the plasma membranes of skeletal muscle in type 2 diabetic rats. We used M35, a GAL antagonist to antagonize the GAL function and swimming training for four weeks to increase GAL release of rats. The blood samples were analyzed for GAL and insulin concentration. The euglycemic-hyperinsulinemic clamp test was conducted for an index of glucose infusion rates. Additionally, skeletal muscle was collected and processed for GLUT4 mRNA level and GLUT4 concentration. The present findings showed that plasma GAL levels after swimming training in all three trained groups were higher compared with each sedentary control and each preswimming level. The insulin levels after swimming in both M35 treatment groups were elevated compared with each diabetic control and each pretraining level. Moreover, M35 treatment reduced glucose infusion rates compared with each diabetic control, but swimming enhanced the rates in all trained groups compared with each sedentary control. Furthermore, M35 treatment reduced GLUT4 concentration and GLUT4 mRNA levels compared with each diabetic control. The ratio of GLUT4 contents in plasma membranes to total cell membranes in both drug groups were lower compared with each diabetic control. These results suggest that endogenous GAL may enhance GLUT4 contents and promote GLUT4 transportation from intracellular membrane pools to plasma membranes. GAL is an important hormone to regulate insulin sensitivity in skeletal muscle from type 2 diabetic rats.