Search

Hylurgus ligniperdainvaded Shandong, China, through imported forest timber, posing a threat to China’s forest health. Exotic insects with broad environmental tolerance, including low temperatures, may have a better chance of surviving the winters and becoming invasive. Understanding the cold-tolerance strategies of H. ligniperdamay help to design sustainable pest management approaches. In this study, we aim to investigate the cold-tolerance ability and relevant physiological indicators in overwintering H. ligniperdaadults to determine any possible overwintering strategies. Supercooling points (SCPs) for adults H. ligniperdadiffered significantly across months and reached the lowest level in the mid- and post-overwintering period, the minimum SCPs −6.45 ± 0.18 °C. As the cold exposure temperature decreased, the survival rate of adults gradually decreased, and no adult survived more than 1 day at −15 °C, and the LLT50for 1 day was −7.1 °C. Since H. ligniperdaadults can survive internal ice formation, they are freeze-tolerant insects. Throughout the overwintering period, the SCPs and the water, protein, sorbitol, and glycerol content in adults decreased initially and then increased. We reported significant correlations between total protein, sorbitol, trehalose, and glycerol content in the beetles and SCPs. Glycogen, lipid, protein, trehalose, and sorbitol content in adult beetles may directly affect their cold-tolerance capacity and survival during winter. This study provides a physiological and biochemical basis for further study of metabolism and cold-tolerance strategies in H. ligniperdaadults, which may help predict population dynamics and distribution potential of pests.

Graphene as a typical conductive filler was previously introduced to enhance the protective performance of zinc-rich coatings (ZRC). However, it is not completely clear the correlation between shielding and cathodic protection performances under the effect of introduced graphene. Herein, the effects of graphene on the shielding performance and cathodic protection were explored, respectively. Results revealed that the introduced graphene tends to promote the corrosion of zinc particles, building chemical shielding effects by converting H2O and O2, etc. and then enhancing the physical shielding performance through the spontaneous formation of corrosion products. The chemical and physical shielding effects cooperatively enhance the shielding performance of zinc-rich topcoat (ZRT), which is conducive to prolonging the cathodic protection life of zinc-rich primer (ZRP). It clarifies the essence of graphene enhancing the protective performance of ZRC clearly, and provides theoretical guidance for improving the protective performance of zinc-rich protective coatings.

In this article, some convergence conditions are investigated for the multiple tuning parameters iterative algorithm (MIA) and the single tuning parameter iterative algorithm (SIA), which are proposed to solve the discrete periodic Lyapunov matrix equations related to discrete-time linear periodic systems. First, when all the tuning parameters are selected in the interval (0, 1] and the initial conditions are arbitrarily given, it is proven that the MIA is convergent if and only if the discrete-time linear periodic system is asymptotically stable. In particular, when the coefficient matrices of the considered matrix equations are nonnegative, it is shown that the convergence rate of the MIA increases with the tuning parameter increases from 0 to 1. Moreover, the above convergence results derived for the MIA are extended to the SIA. Furthermore, the searching interval of the optimal tuning parameter for the SIA to achieve the fastest convergence rate is narrowed. Finally, two numerical examples are provided to demonstrate the correctiveness of the proposed theoretical results.

ABSTRACTBackgroundDasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia.Research design & methodsWe designed a clinical study to demonstrate that the dasatinib tablet (YiNiShu®) (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Dasatinib (Bristol Myers Squibb) were bioequivalent under fasting and fed conditions. The whole study was structured into the fasting trial and the postprandial trial. Each period, subjects were given 50 mg dasatinib or its generic. The RSABE (reference scale average bioequivalence) and ABE (average bioequivalence) methods were employed to assess bioequivalence by pharmacokinetics (PK) parameters for a highly variable drug.Results32 and 24 eligible volunteers were enrolled in the fasting and postprandial trials, respectively. In the fasting trial, the RSABE method was performed, and point estimates of Cmax, AUC0-t, and AUC0-∞met the bioequivalence criteria. In the postprandial trial, the ABE method was performed, and the 90% CI of the geometric mean ratio (GMR) for PK parameters met the requirements of bioequivalence standards.ConclusionThe results proved that the PK parameters of the two drugs were similar and bioequivalent, indicating that both drugs had a good safety profile.Clinical trial registrationThis trial was registered in ClinicalTrials.gov (Number: NCT05640804) and Drug Clinical Trial Registration and Information Disclosure Platform (Number: CTR20181708)

The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape.

ABSTRACTBackgroundLenvatinib is a tyrosine kinase receptor inhibitor that inhibits vascular and endothelial growth factor receptor kinase activity. This study evaluated the bioequivalence and safety of lenvatinib with Lenvima® .Research design and methodsThe fasting and postprandial groups were two independent trials. Subjects were randomly divided into two sequences at a ratio of 1:1 for two-cycle crossover administration. Subjects took 10 mg lenvatinib or Lenvima® once per cycle. The wash-out period was 14 days. Detected the plasma drug concentrations and assessed the bioequivalence of two drugs. Besides, we evaluated the safety of the drugs throughout the trial.ResultsIn the fasting state, the GMRs of Cmax, AUC0-t, and AUC0-∞were 99.89%, 102.98% and 103.19%, respectively. The 90% CIs were all within 80%-125%. In the postprandial state, the GMRs of Cmax, AUC0-t, and AUC0-∞were 98.96%, 94.25% and 95.27%, respectively. The 90% CIs were all within 80%-125%. All results met the bioequivalence criteria. Both drugs had good safety and tolerance in this trial.ConclusionThis study showed that lenvatinib and Lenvima® had similar bioequivalence and safety in healthy Chinese subjects under fasting and postprandial conditions.Clinical trial registrationThis trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html# CTR20191172)

•We comprehensively analyzed molecular differences between male breast cancer (MBC) and female breast cancer (FBC) after controlling for confounding factors with propensity score matching.•There are distinct differences in transcriptomes, genomes, immune microenvironments, epigenomes, proteomes, responses to sex hormones (estrogen and androgen), and drug sensitivities between MBC and FBC that underlie poor MBC prognoses.•The immunogenicity of MBC is lower than that of FBC and the efficacy of immunotherapy is worse.•The effect of estrogen on MBC is more intense, and anti-estrogen therapy is more important in treating MBC.•Differential expression of FDA-approved therapeutic target genes indicates that MBC differs from FBC in drug responses.

Laser cladding provides a rapid and environmental way for remanufacturing high value engineering components. In this paper, the remanufacturing strategy for broken 45 steel gear using H13 steel powder based on the laser cladding technology is studied systematically. Based on the reverse engineering technology, the 3D model of the broken tooth is constructed. The broken tooth is remanufactured by laser cladding. Optimal cladding parameters including overlapping rate, scanning strategy, Z-axis increment and multi-layer accumulation pattern are investigated. Then the remanufactured tooth is post-processed by machining. Finally, the mechanical properties of the remanufactured tooth are tested. It is indicated that after laser cladding, the remanufactured tooth can basically recover its appearance before breakage. Comparing with the original tooth, the remanufactured one has a lower tensile property, but a higher hardness and better wear resistance.

The purpose of this study is to verify the reliability and effectiveness of an educational psychology scale, which is explored by using the methods of literature, interview, questionnaire survey and mathematical statistics. The research object is the education psychology data of undergraduate students in local undergraduate colleges and universities.The data are collected and analyzed through the scale. The results show that the educational psychology scale contains six dimensions, including self-efficacy, learning motivation, hope trait, psychological resilience, physical self-esteem and emotional management, with a total of 27 items. The kmo sampling appropriateness of the scale is 0.800. The load of six dimensions in the total amount table is between 0.58 and 0.73. The fitting coefficient of each item of the structural model is between 0.45-0.73, and the correlation between each dimension and the total table is between 0.24-0.52. Scale cronbach's α The coefficient was 0.83 and the test-retest reliability was 0.90. The content validity of the scale ranged from 0.554 to 0.775. The scale has good reliability and validity, and can be used to evaluate undergraduate students' educational psychology.

In this paper, a new iterative method is proposed to solve the generalized Hamilton-Jacobi-Bellman &#x0028 GHJB &#x0029 equation through successively approximate it. Firstly, the GHJB equation is converted to an algebraic equation with the vector norm, which is essentially a set of simultaneous nonlinear equations in the case of dynamic systems. Then, the proposed algorithm solves GHJB equation numerically for points near the origin by considering the linearization of the non-linear equations under a good initial control guess. Finally, the procedure is proved to converge to the optimal stabilizing solution with respect to the iteration variable. In addition, it is shown that the result is a closed-loop control based on this iterative approach. Illustrative examples show that the update control laws will converge to optimal control for nonlinear systems.

•Design and Implementation of model reference adaptive controller.•Ability to achieve finite-time stability of piezoelectric actuator.•Design of iterative adjustment rule for automatic parameter regulation.

An effective electrochemical platform was set up for the real-time and simultaneous monitoring of the kinetics of drug release from electrospun nanofibers. The method describes the development and utilization of a 4-phosphatephenyl (4-PP)-modified glassy carbon electrode (GCE). The modified electrode was used to monitor paracetamol (PCT) and/or diclofenac (DCF) release from electrospun nanofibers. The drug-loaded nanofibers were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Using differential pulse voltammetry (DPV), the modified electrode shows good sensitivity and selectivity for the simultaneous determination of PCT (1.87 μM to 170 mΜ) and DCF (0.37s–51.87 μM). The release kinetics study reveals that the drug follows first order kinetics and that the mechanism of drug release was a diffusion-controlled type. No significant drug–polymer interactions were observed in the FTIR studies. The results obtained are promising, which demonstrates that the electrochemical method possesses the capability for the simultaneous detection of multiple molecules in a drug delivery system (DDS).

HIV-1 infected individuals live longer but experience a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND.

Protein-DNA interactions are involved in many essential biological processes such as transcription, splicing, replication and DNA repair. It is of great value to identify DNA-binding proteins as well as their binding sites in order to study the mechanisms of these biological processes. A number of experimental methods have been developed for the identification of DNA-binding proteins, such as DNAase foot printing, EMSA, X-ray crystallography, NMR spectroscopy and CHIP-on-Chip. However, with the increasingly greater number of suspected protein-DNA interactions, identification by experimental methods is expensive, labor-intensive and time-consuming. Hence, in the past decades researchers have developed many computational approaches to predict in silico the interactions of proteins and DNA. Machine learning technology has been widely used and become dominant in this field. In this article, we focus on reviewing recent machine learning–based progresses in DNA-binding protein and binding residue prediction methods, the most commonly used features in these predictions, machine learning classifier comparison and selection, evaluation method comparison, and existing problems and future directions for the field.

The liver is the largest internal organ in mammals, and is important for the maintenance of normal physiological functions of other tissues and organs. Hepatitis, cirrhosis, liver cancer and other chronic liver diseases are serious threats to human health, and these problems are compounded by a scarcity of liver donors for transplantation therapies. Directed differentiation of embryonic stem cells to liver cells is a promising strategy for obtaining hepatocytes that can be used for cell transplantation. In vitrohepatocyte differentiation of embryonic stem cells requires a profound understanding of normal development during embryonic hepatogenesis. Here we provide a simple description of hepatogenesis in vivoand discuss directed differentiation of embryonic stem cells into hepatocytes in vitro.

Interferon gamma induced GTPase (IGTP) (also named Irgm3) and interferon gamma inducible protein 47 (IRG-47) (also named Irgd) are interferon (IFN)-inducible p47 GTPases that have been shown to regulate host resistance to intracellular pathogens. Little knowledge has been known about the role of p47 GTPases in host responses against extracellular pathogens. To investigate possible roles of IGTP and IRG-47 in the course of Schistosoma japonicum infection, IGTP and IRG-47 knockout and wild-type (WT) mice were challenged with cercariae of S. japonicum, and host responses were analyzed. At the acute stage of S. japonicum infection, mice that lacked IGTP displayed similar parasite burden and pathological damage to WT mice. Importantly, S. japonicum-infected IRG-47-deficient mice, in contrast to IGTP-deficient mice and WT mice, showed significantly reduced worms and lower egg-burden, but intense granulomatous reaction evoked by schistosome eggs in peripheral parts of liver lobes. In addition, upregulation of inflammation-related gene expression was observed in the spleen of IRG-47-deficient mice using oligonucleotide microarrays, in which multiple pathways of cytokine–cytokine receptor interaction, T-cell receptor signaling, complement, coagulation cascades and cell adhesion molecules were highlighted. Taken together, these data suggest that IGTP and IRG-47 might have distinct features that were differentially required for resistance to S. japonicum.

The PTHrPgene generates low‐abundance mRNA and protein products that are not easily localized by in situ hybridization histochemistry or immunohistochemistry. We report here a PTHrP‐lacZ knockin mouse in which β‐gal activity seems to provide a simple and sensitive read‐out of PTHrPgene expression.

The PTHrPgene generates low‐abundance mRNA and protein products that are not easily localized by in situ hybridization histochemistry or immunohistochemistry. We report here a PTHrP‐lacZ knockin mouse in which β‐gal activity seems to provide a simple and sensitive read‐out of PTHrPgene expression.Introduction: PTH‐related protein (PTHrP) is widely expressed in fetal and adult tissues, typically as low‐abundance mRNA and protein products that maybe difficult to localize by conventional methods. We created a PTHrP‐lacZ knockin mouse as a means of surveying PTHrPgene expression in general and of identifying previously unrecognized sites of PTHrP expression.Materials and Methods: We created a lacZ reporter construct under the control of endogenous PTHrPgene regulatory sequences. The AU‐rich instability sequences in the PTHrP 3′ untranslated region (UTR) were replaced with SV40 sequences, generating products with lacZ/β gal kinetics rather than those of PTHrP. A nuclear localization sequence was not present in the construct.Results: We characterized β‐galactosidase (β‐gal) activity in embryonic whole mounts and in the skeleton in young and adult animals. In embryos, we confirmed widespread PTHrP expression in many known sites and in several novel epidermal appendages (nail beds and footpads). In costal cartilage, β‐gal activity localized to the perichondrium but not the underlying chondrocytes. In the cartilaginous molds of forming long bones, β‐gal activity was first evident at the proximal and distal ends. Shortly after birth, the developing secondary ossification center formed in the center of this PTHrP‐rich chondrocyte population. As the secondary ossification center developed, it segregated this population into two distinct PTHrP β‐gal+subpopulations: a subarticular subpopulation immediately subjacent to articular chondrocytes and a proliferative chondrocyte subpopulation proximal to the chondrocyte columns in the growth plate. These discrete populations remained into adulthood. β‐gal activity was not identified in osteoblasts but was present in many periosteal sites. These included simple periosteum as well as fibrous tendon insertion sites of the so‐called bony and periosteal types; the β‐gal‐expressing cells in these sites were in the outer fibrous layer of the periosteum or its apparent equivalents at tendon insertion sites. Homozygous PTHrP‐lacZ knockin mice had the expected chondrodysplastic phenotype and a much expanded region of proximal β‐gal activity in long bones, which appeared to reflect in large part the effects of feedback signaling by Indian hedgehog on proximal cell proliferation and PTHrPgene expression.Conclusions: The PTHrP‐lacZ mouse seems to provide a sensitive reporter system that may prove useful as a means of studying PTHrPgene expression.

Gangliosides are endogenous membrane components enriched in neuronal cells. They have been shown to play regulatory roles in many cellular processes. Here, we show for the first time that ganglioside GD1b plays an antiapoptotic role in cultured hippocampal neurons. GD1b inhibited the voltage-dependent outward delayed rectifier current (IK) but not the transient outward A-type current in a dose-dependent manner, with an IC50 value of 15.2 µM. This effect appears to be somehow specific, because GD1b, but not GM1, GM2, GM3, GD1a, GD3, or GT1b, was effective in inhibiting IK. Intracellular application of staurosporine (STS; 0.1 µM) resulted in rapid activation of IK, which was partially reversed upon addition of the K+ channel blocker tetraethylammonium (TEA; 5 mM) and GD1b (10 µM). Furthermore, GD1b (10 µM) attenuated STS-induced neuronal apoptosis by nearly the same amount as 5 mM TEA. In addition, GD1b suppressed the apoptosis-associated caspase 3 activation that was activated by STS. Collectively, these findings suggest that GD1b plays an antiapoptotic role in cultured hippocampal neurons through its inhibitory effect on the IK and caspase activity.

Mechanical forces play a critical role in regulating skeletal mass and structure. We report that mechanical loading induces PTHrP in osteoblast‐like cells and that TREK‐2 stretch‐activated potassium channels seem to be involved in this induction. Our data suggest PTHrP as a candidate endogenous mediator of the anabolic effects of mechanical force on bone.

Mechanical forces play a critical role in regulating skeletal mass and structure. We report that mechanical loading induces PTHrP in osteoblast‐like cells and that TREK‐2 stretch‐activated potassium channels seem to be involved in this induction. Our data suggest PTHrP as a candidate endogenous mediator of the anabolic effects of mechanical force on bone.Introduction:Mechanical force has anabolic effects on bone. The PTH‐related protein (PTHrP) gene is known to be mechanically inducible in smooth muscle cells throughout the organism, and N‐terminal PTH and PTHrP products have been reported to have anabolic effects in bone. We explored the idea that PTHrP might be a candidate mediator of the effects of mechanical force on bone.Materials and Methods:Mechanical loading was applied by swelling osteoblast‐like cells in hypotonic solution and/or by application of cyclical stretch through a FlexerCell apparatus. RNase protection assay and real‐time quantitative PCR analysis were used to assay PTHrPgene expression.Results and Conclusion:Stretching UMR201‐10B osteoblast‐like cells by swelling in hypotonic solutions rapidly increased PTHrP mRNA. This induction was insensitive to gadolinium and nifedipine, to the removal of extracellular calcium, and to depletion of endoplasmic reticulum calcium, indicating that neither stretch‐activated cation channels, L‐type calcium channels, nor ER calcium is involved in the induction of PTHrP. The TREK family potassium channels are activated by both stretch and intracellular acidosis, and we identified these channels in osteoblast‐like cells by PCR. Intracellular acidification increased PTHrP mRNA expression in UMR‐201‐10B cells, and siRNA targeted against the TREK‐2gene reduced endogenous TREK‐2 expression and dampened PTHrP mRNA induction. Cyclical stretch also induced PTHrP in UMR‐201‐10B osteoblast‐like cells and in MLO‐A5 post‐osteoblast‐pre‐osteocyte cells, the latter a stage in the osteoblastic differentiation program that is likely to be a key target of force in vivo. Our evidence suggests PTHrP as a candidate mediator of the anabolic effects of mechanical force on bone.

We identified cellular targets of canonical Wnt signaling within the skeleton, which included chondrocytes, osteoblasts, and osteocytes in growing bone, but only osteocytes and chondrocytes in the mature skeleton. Mechanical deformation induced Wnt signaling in osteoblasts in vitro.

We identified cellular targets of canonical Wnt signaling within the skeleton, which included chondrocytes, osteoblasts, and osteocytes in growing bone, but only osteocytes and chondrocytes in the mature skeleton. Mechanical deformation induced Wnt signaling in osteoblasts in vitro.Introduction:Genetic evidence in mice and humans has implicated the canonical Wnt signaling pathway in the control of skeletal development and bone mass. However, little is known of the details of Wnt signaling in the skeleton in vivo. We used Wnt indicator TOPGAL mice to identify which cells activated this pathway during bone development and in the mature skeleton.Materials and Methods:We examined canonical Wnt signaling during embryonic and neonatal bone development in TOPGAL mice. The TOPGAL transgene consists of a β‐galactosidasegene driven by a T cell factor (TCF)β‐catenin responsive promoter so that canonical Wnt activity can be detected by X‐gal staining. Expression of Wnt signaling components was examined in primary calvarial cell cultures by RT‐PCR. The effect of mechanical deformation on Wnt signaling was examined in primary calvarial cells grown on collagen I and stretched using Flexercell Tension Plus System FX‐4000T. Immunohistochemistry was used to examine the localization of β‐catenin in cartilage, bone, and cultured calvarial cells exposed to physical deformation.Results and Conclusions:Canonical Wnt signaling was active in several cell types in the fetal and neonatal skeleton, including chondrocytes, osteoblasts, and osteocytes. With age, activation of Wnt signaling became less prominent but persisted in chondrocytes and osteocytes. Although osteoblasts in culture expressed many different individual Wnt's and Wnt receptors, the TOPGAL transgene was not active in these cells at baseline. However, Wnt signaling was activated in these cells by physical deformation. Together with the activation of canonical Wnt signaling in osteocytes seen in vivo, these data suggest that Wnt signaling may be involved in the coupling of mechanical force to anabolic activity in the skeleton.

•siRNA-SP1-loaded AuNPs (AuNPs-si-SP1) inhibits SP1 expression in lung cancer cells.•GZMB expression is elevated by silencing SP1 in lung cancer cells.•AuNPs-si-SP1 combined with radiotherapy inhibits lung cancer growth effectively.•AuNPs-si-SP1 enhances radiosensitivity of lung cancer via SP1/GZMB axis.•AuNPs-si-SP1 provides a novel target for radiotherapy of lung cancer.

An intelligent control system of 9-degree-of-freedom full-servo bottle-making robot was developed based on multi-DOF robot controller, with an aim to realize the full-automatic intelligent flexible manufacturing of glass bottles and improve the level of automation and intelligence of bottle-making equipment. Based on TCP/IP technology, the relative function model, such as the system of remote image monitoring, remote network control, fault diagnosis, production correction and other functions of the bottle-making robot is designed to realize the remote control and maintenance development of the bottle making process, then the "Internet +" function of the bottle-making robot is realized.

For Abstract see ChemInform Abstract in Full Text.

For Abstract see ChemInform Abstract in Full Text.