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Evidence is accumulating that pattern recognition receptor (PRR) C‐type lectins (CTL) play essential roles in recognition of pathogens. TcCTL14 (accession no. TC00871) contains the most domains among all CTL of Tribolium castaneum. Yet the biological function of TcCTL14 remains unclear. In this study, TcCTL14 exhibiting typical motif and domain of CTL was cloned from T. castaneum. The expression pattern analysis showed that TcCTL14 was highly expressed in late pupae and central nervous system, and was upregulated after treatment with Escherichia coli and Staphylococcus aureus, respectively. Analysis of binding affinity revealed that recombinant TcCTL14 not only could bind to lipopolysaccharide and peptidoglycan in a dose‐dependent fashion, but possibly could bind to and agglutinate different bacteria in a Ca2+‐dependent fashion. Knockdown of TcCTL14 before injection with bacteria led to the downregulation of nuclear factor‐κB transcription factors of Toll/IMD and 4 antimicrobial peptides. Knockdown of TcCTL14 also caused suppressed metamorphosis, reduced fecundity, and delayed embryogenesis of T. castaneum. Further observation discovered that knockdown of TcCTL14 inhibited the development of ovaries and embryos. The detection of signaling pathways revealed that TcCTL14 may be involved in metamorphosis and fecundity by impacting 20‐hydroxyecdysone and vitellogenin, respectively. Overall, these results indicate that TcCTL14 may contribute to immune response by agglutination or regulating the expression of antimicrobial peptides by the Toll/IMD pathway, and is required for T. castaneum development including metamorphosis, fecundity, and embryogenesis. These findings will improve the functional cognition of PRR CTL in insects and provide the new strategy for pest control. [ABSTRACT FROM AUTHOR]

• The coupling effect is exploited to suppress structural vibration. • The collision avoidance between two arms is achieved with the reactionless motion. • A reactionless trajectory is coordinately planned for two arms to perform capture. This paper presents a coordinated control scheme for two capture tasks via a dual-arm space robot with its base on a flexible space structure. The robot system consists of a base, a mission arm for capture, and a balance arm for removing disturbance forces to the base. To counteract the impact of structural vibration, a two-stage strategy containing a vibration control stage and a target capture stage is proposed. In the first stage, the robot and structure are treated as a mass-spring system in which the coupling effect between the robot and the flexible structure is exploited to suppress structural vibration. Notably, the collision avoidance between two arms is achieved by a velocity inequality constraint, wherein the reactionless motion is utilized. In the second stage, a reactionless trajectory is planned for the mission arm to reach the target location and attitude, as the balance arm remove the coupling disturbance to the base. Afterwards, the balance arm becomes the new mission arm for capture and the other arm is defined as the new balance arm. Finally, numerical simulations are given to validate the efficiency of the proposed coordinated control strategy. [ABSTRACT FROM AUTHOR]

Aldehyde oxidases (AOXs) are a group of metabolic enzymes that play critical roles in the degradation of xenobiotics and chemicals. However, the physiological function of this enzyme in insects remains poorly understood. In this study, three TcAOX genes (TcAOX1 , TcAOX2 , TcAOX3) were identified and characterized from Tribolium castaneum genome. Spatiotemporal expression profiling showed that TcAOX1 expression was most highly expressed at the early pupal stage and was predominantly expressed in the antennae of adults, indicating that TcAOX1 was involved in the degradation of chemical signals; TcAOX2 expression was most highly expressed at the late pupal stage and was mainly expressed in the fat body, epidermis of larvae and adults, respectively; and TcAOX3 expression was in all stages and was primarily expressed in the head of adults. Moreover, the transcripts of TcAOX2 and TcAOX3 were significantly induced after exposure to plant oil, and RNA interference (RNAi) targeting of each of them enhanced the susceptibility of beetles to this plant toxicant, suggesting that these two genes are associated with plant toxicant detoxification. Intriguingly, knockdown of the TcAOX1 led to reductions in female egg-laying but unchanged the hatchability and the development of genital organs, suggesting that this gene may mediate fecundity by effecting the inactivation of chemical signals in T. castaneum. Overall, these results shed new light on the function of AOX genes in insects, and could facilitate the development of research on pest control management. [ABSTRACT FROM AUTHOR]

Objective. To investigate the efficacy of high-volume hemofiltration (HVHF) in the treatment of severe acute respiratory distress syndrome (ARDS) caused by sepsis and its effect on serum levels of miR-126, miR-184, and MAP1-LC3. Methods. From July 1, 2015 to December 31, 2021, patients with severe ARDS caused by sepsis who were admitted to our hospital were retrospectively analyzed. Patients who received conventional treatment were summarized into the control group, and those who received HVHF were summarized into the study group. The treatment effects of the two groups were compared. Results. Ninety-five qualified patients were retrieved, with 42 patients in the control group and 53 patients in the study group. After treatment, the levels of IL-6, IL-10, TNF-α, miR-126, miR-184, and MAP1-LC3 were significantly lower in the study group (P < 0.05 for all), whereas PEF, FRC, TEF25%, heart rate, mean arterial pressure, and blood oxygen were significantly higher in the study group (P < 0.05 for all). Conclusion. HVHF has a good clinical effect on improving patients with severe ARDS caused by sepsis and can improve the pulmonary function of patients. [ABSTRACT FROM AUTHOR]

The control plant model of multiple grid-connected converters is a multivariable coupling model. There is complex coupling interaction between the control loops of the multiple converters, resulting in poor current control quality or interaction oscillation issues when the grid impedance is high or the number of converters is large. This article proposes a novel multivariable decoupling control method based on a summation difference coordinate for eliminating the current control interaction between multiple converters. With a summation difference coordinate transformation matrix, the multivariable model of multiple converters can be transformed to be multiple single-variable models. By designing specific current regulators for the summation current and the difference current loops in the summation difference coordinate, the summation current and each difference current can be regulated independently. Compared with the conventional methods, the proposed method can improve the current control bandwidth and stability without introducing any high-frequency oscillation especially when the grid impedance is high or the number of converters is large. Moreover, based on the proposed approach, the classical single variable control theory is enough to designthe regulator parameters for any number of converters under the new coordinate system. Experimental results of four three-phase 2 kW two-level converters have been presented, which validates the proposed approach. [ABSTRACT FROM AUTHOR]

PD-1/PD-L1 pathway blockade is a promising immunotherapy for the treatment of cancer. In this manuscript, a series of triaryl compounds containing ester chains were designed and synthesized based on the pharmacophore studies of the lead BMS-1. After several SAR iterations, 22 showed the best biochemical activity binding to hPD-L1 with an IC 50 of 1.21 nM in HTRF assay, and a K D value of 5.068 nM in SPR analysis. Cell-based experiments showed that 22 effectively promoted A549 cell death by restoring T-cell immune function. 22 showed significant in vivo antitumor activity in a 4T1 mouse model without obvious toxicity, with a TGI rate of 67.8 % (20 mg/kg, ip). Immunohistochemistry data indicated that 22 activates the immune activity in tumors. These results suggest that 22 is a promising compound for further development of PD-1/PD-L1 inhibitor for cancer therapy. [Display omitted] • Synthesis of a series of novel triaryl derivatives containing ester chains. • 22 Showed the best biochemical activity binding to hPD-L1 with an IC 50 of 1.21 nM. • 22 effectively promoted A549 cell death by restoring T cell immune function. • 22 showed significant in vivo antitumor activity in a 4T1 mouse model. [ABSTRACT FROM AUTHOR]

The vibration isolation system using a pair of oblique springs or a spring-rod mechanism as a negative stiffness mechanism exhibits a high-static low-dynamic stiffness characteristic and a nonlinear jump phenomenon when the system damping is light and the excitation amplitude is large. It is possible to remove the jump via adjusting the end trajectories of the above springs or rods. To realize this idea, the article presents a vibration isolation system with a cam–roller–spring–rod mechanism and gives the detailed numerical and experimental studies on the effects of the above mechanism on the vibration isolation performance. The comparative studies demonstrate that the vibration isolation system proposed works well and outperforms some other vibration isolation systems. [ABSTRACT FROM AUTHOR]

Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2, Isocitrate dehydrogenase, and Cytochrome b-related protein, might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP, UGT, GST, OBP, CSP, and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7, detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum, providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum. These results aid eugenol insecticidal mechanisms and provide the basis of insect control. [ABSTRACT FROM AUTHOR]

C-type lectins (CTLs) play vital roles in invertebrates' innate immunity. Six CTL-X type lectins are identified in Tribolium castaneum. However, their functions and regulating mechanisms remain elusive. Here, TcCTL12 , one CTL-X, was identified and cloned from T. castaneum. Spatiotemporal expression profiling revealed that TcCTL12 highly expressed in late pupa and early adult of T. castaneum in comparison with other developmental stages, and exhibited the highest expression level in the haemolymph and central nervous system (CNS). Then, the expression of TcCTL12 was remarkably induced by the stimulation of Escherichia coli and Staphylococcus aureus. Moreover, the recombinant protein TcCTL12 could bind pathogen-associated molecular patterns (PAMPs) including LPS and PGN, and displayed agglutinative activity to both Gram-positive and Gram-negative bacteria in a calcium-dependent manner in vitro. Furthermore, RNAi of TcCTL12 caused T. castaneum pupation and eclosion defected. The abnormal pupa thinned their epidermal, and appeared the abnormal development of muscle cell compared with the control group. Additionally, depletion of TcCTL12 resulted in reducing fertility of offspring and affected their fecundity. In sum, these results indicated that TcCTL12 had extensive functions in the regulation of development in T. castaneum , in addition to the immune response. It further expanded insights into CTL functions in insects. [ABSTRACT FROM AUTHOR]

Chemical ionization mass spectrometry (CIMS) is a powerful tool for on-line characterization of atmospheric trace species and reveal of new atmospheric oxidation mechanisms. The applications of CIMS promoted understanding of new particle formation and the roles of trace species in air-quality issues. In the past decade or so, various new techniques in ion sources have been applied to improve sensitivity and replace radioactive sources. Moreover, researchers have developed multiple sampling inlets for CIMS to meet the measurement demand of reactive trace species. In this study, we discussed these developments and reviewed a limited number of representative applications of CIMS, including trace highly reactive gaseous pollutants, aerosols and highly oxygenated organic molecules. In particular, we summarized the choice of reagent ions, the influencing factors of the sensitivity, and the strategies in improving instrument sensitivity. This review summarizes CIMS instrument developments and its applications from an appreciation of instrument technology developing perspectives. • The choice of appropriate reagent ions is summarized. • The developments of various new ion sources and sampling inlets are introduced. • The strategies in improving instrument sensitivity are revealed. • The applications of chemical ionization mass spectrometry are discussed. • The future developments of chemical ionization mass spectrometry are proposed. [ABSTRACT FROM AUTHOR]

The algorithm complexity of model predictive control (MPC) for cascaded H-bridge (CHB) static synchronous compensators (STATCOMs) was optimized to a polynomial level in previous studies. However, implementing MPC with conventional approaches still suffers from long execution time, where a low cost digital signal processor (DSP) is used to execute optimization algorithms and a small-sized field-programmable gate array (FPGA) is used to extend gate signals and sampling functions. This paper presents a parallel implementation approach to reduce the execution time of MPC, where the FPGA is configured to be used for accelerating the high-complexity sorting tasks. By running the DSP and FPGA in parallel, the algorithm execution time is only determined by the DSP, and the resource consumption is only determined by the FPGA. To minimize the resource consumption and requirement in FPGA, a parallel comparison-based sorter with multiple comparison and accumulators is proposed. The proposed implementation method can reduce the time and space complexity of the MPC from the polynomial level to a linear level without additional hardware cost, which means the MPC for medium-voltage CHB STATCOMs (e.g., 20 stages) can be implemented online with existing control platforms. Experimental results for various CHB STATCOMs are presented to validate the proposed configuration and algorithm. [ABSTRACT FROM AUTHOR]

One promising solution for future large wind turbine power conversion is to use medium-voltage power conversion systems for high efficiency and high power-density, e.g., by using a cascaded structure presented in this paper. However, a medium-frequency (MF) oscillation issue was observed while testing the experimental prototype of the above system. Given the complex multivariable coupling models of the multiwinding transformer and multiple inverters, conventional single-variable theories are not suitable. Therefore, this paper presents a new decoupling analysis method. Using a proposed linear transformation matrix, the output currents of multiple inverters can be transformed to a summation (grid) current and difference currents, where the former is the summation of inverter currents and the latter are the differences between currents of any two inverters. This transformation has enabled the use of single-variable theories, e.g., Bode diagram to analyze the summation current and difference current separately. It was found that the MF oscillation issue is caused by the equivalent impedance of the summation current being much larger than that of the difference current. Specifically, using small controller parameters cannot ensure the grid current quality and using large parameters may cause oscillation in the difference current. The proposed method can provide guidelines to design the parameters of current regulators and filters in multiple-inverter systems. Experimental results of a downscaled wind energy conversion system are presented to verify the proposed method. [ABSTRACT FROM AUTHOR]

Applying model predictive control (MPC) to cascaded H-bridge multilevel converters, while improving the dynamic performance, suffers from high computation burden due to substantial voltage vectors and switching combinations. In this paper, a simplified branch and bound approach is proposed to reduce the computation of the MPC for a cascaded H-bridge Static Synchronous Compensator (STATCOM). The underlying optimization problem of the current predictive control is a two-variable integer quadratic programming problem. With the proposed approach, the global optimal voltage vector can be selected within linear time instead of polynomial time. This is achieved by selecting the possible values of one variable as the branch, and enumerating the optimal integer results of each branch. The execution time of the proposed approach and conventional methods are compared to demonstrate the effectiveness of the proposed approach. Simulation and experimental results for a seven-level cascaded H-bridge STATCOM system are presented to verify the usability and reliability of the proposed approach. [ABSTRACT FROM PUBLISHER]

C-type lectin S group (CTL-S) plays a variety of roles in invertebrate including pathogen recognition and activation of immune responses. Previous studies have shown that CTL-S subfamily of Tribolium castaneum is mainly divided into two clades, of which only TcCTL1 was separately located in one clade. However, it remains unclear whether TcCTL1 occurs the differentiation of function. Therefore, the CTL-S TcCTL1 gene was cloned and characterized from T. castaneum. Functional analysis revealed that TcCTL1 could recognize and agglutinate pathogens, as well as activate immune signaling pathways to participate in immune response, which was consistent with our previously reported for TcCTL5 and TcCTL6. Differently, RNAi of TcCTL1 discovered that the egg produced by ds TcCTL1- treated adult could not hatch into larvae. Further DAPI-straining embryo indicated that the process of embryogenesis in ds TcCTL1 -treated beetle was defeated, implying that TcCTL1 is required for embryogenesis in T. castaneum except for immune response. These results will aid implications for the understanding of CTL-S in invertebrate. • First report of TcCTL1 involved in embryogenesis except for immune response. [ABSTRACT FROM AUTHOR]

To solve the issue of exponentially increasing computational burden of finite control set model predictive control (FCS-MPC) for multilevel converters, a fast MPC scheme for multilevel cascaded H-bridge STATCOM is presented. The proposed approach consists of three steps. First, with the partially stratified optimization approach, the multiobjective programming of MPC is divided into two suboptimization problems, i.e., current-control MPC and voltage-balancing MPC. Second, a dynamic programming algorithm is proposed for the optimization of current-control MPC. Third, a mixed algorithm, which combines dynamic programming and greedy algorithm (0-1 programing), is proposed to select the optimal switching combination from all the redundant switching combinations for the voltage balancing MPC achieving a global optimization. Through the analysis of the time complexity, with the proposed scheme, the total computation of FCS-MPC can be reduced to polynomial time from exponential time. The proposed approaches will not deteriorate the control performance. The control performance is validated by simulation results and the effectiveness is further demonstrated by implementing the algorithm on a low-cost DSP (TMS320F28335) in real time. [ABSTRACT FROM PUBLISHER]

This research focuses on developing and evaluating a free-flying space robot equipped with a cable-driven manipulator and an adaptive gripper. First, a transmission joint comprising a pair of gears and pulleys is designed and actuated by motors located in the first link of the manipulator. Afterward, based on the kinematics and dynamics models of the robot, a mission distribution control scheme is proposed for the robot to drive its end-effector to achieve the desired position and attitude for capturing space targets. Furthermore, exploiting this strategy, considerable comparison simulations between two space robots equipped with a traditional manipulator and a cable-driven arm are conducted. Wherein, the goal position and attitude are selected through a uniform sampling method. For the same capture mission, energy consumptions of the base and manipulator as well as state errors of the base are taken as cost functions for performance evaluation. Finally, a planar target capture case study using the adaptive gripper and a spatial motion test with the help of an air-bearing simulator are carried out to demonstrate the efficiency of the presented cable-driven space robot. • A space robot equipped with a cable-driven manipulator with an adaptive gripper is developed. • A mission distribution control scheme is proposed for capturing space targets. • Energy consumptions and state errors are selected as cost functions to evaluate the performance of the presented robot. [ABSTRACT FROM AUTHOR]

C-type lectin X (CTL-X) plays critical roles in immune defense, cell adhesion, and developmental regulation. Here, a transmembrane CTL-X of Tribolium castaneum, TcCTL15, with multiple domains was characterized. It was highly expressed in the early and late pupae and early adults and was distributed in all examined tissues. In addition, its expression levels were significantly induced after being challenged with pathogen-associated molecular patterns (PAMPs) and bacteria. In vitro, the recombinant TcCTL15 could recognize bacteria through binding PAMPs and exhibit agglutinating activity against a narrow range of bacteria in the presence of Ca2+. RNAi-mediated TcCTL15-knockdown-larvae infected with Escherichia coli and Staphylococcus aureus showed less survival, had activated immune signaling pathways, and induced the expression of antimicrobial peptide genes. Moreover, silencing TcCTL15 caused eclosion defects by impairing ecdysone and crustacean cardioactive peptide receptors (CCAPRs). Suppression of TcCTL15 in female adults led to defects in ovary development and fecundity, accompanied by concomitant reductions in the mRNA levels of vitellogenin (TcVg) and farnesol dehydrogenase (TcFDH). These findings imply that TcCTL15 has extensive functions in developmental regulation and antibacterial immunity. Uncovering the function of TcCTL15 will enrich the understanding of CTL-X in invertebrates. Its multiple biological functions endow the potential to be an attractive target for pest control. [ABSTRACT FROM AUTHOR]

[Display omitted] Valine-containing protein (VCP) is a member of the adenosine triphosphate family involved in a variety of cellular activities. VCP/p97 is capable of maintaining protein homeostasis and mediating the degradation of misfolded polypeptides by the ubiquitin–proteasome system (UPS). In this manuscript, a series of novel p97 inhibitors with pyrimidine as core structure were designed, synthesized and biologically evaluated. Based on the enzymatic results, a detailed structure–activity relationship discussion of the synthesized compounds was carried out. Furthermore, cellular activities of the compounds with enzymatic potency of less than 200 nM were investigated by using A549 and RPMI8226 cell lines. Among the screened inhibitors, compound 17 (IC 50 , 54.7 nM) showed good enzymatic activity. Investigation of cellular activities with non-small cell lung cancer A549 and multiple myeloma (MM) RPMI8226 further confirmed the potency of 17 with the IC 50 values of 2.80 μM and 0.86 μM, respectively. Compound 17 is now being developed as a candidate. Finally, docking studies were carried out to explore the possible binding mode between the active inhibitor 17 and p97. [ABSTRACT FROM AUTHOR]

The widespread clay minerals on Mars have been detected using orbital data using near-infrared spectroscopy, which is limited by its shallow detection depth, low recognition precision and resolution, and can only be qualitative etc. Terrestrial analogues on the Earth provide valuable guidance to further understand the distribution and occurrence of clay minerals on Mars. In this study, seven detrital samples with clay minerals as coatings (Abbreviated as "clay coatings") were collected from four sites in the western Qaidam Basin, a Martian analogue terrain. We identify the mineralogy of the surface coatings to be illite and chlorite, as confirmed by a combination techniques of X-Ray Diffraction (XRD), Scanning Electron Microscope (SEM), Electron Probe X-ray Microanalysis (EPMA) and Near-infrared spectroscopy (NIR). The NIR results suggested that merely small amounts of clay minerals (~0.5 mg/cm2 and about several micrometers in thickness) masking the surface of sands could lead to well-distinguished characteristic NIR absorption, and their band depth could reach those measured from Martian soil analogues with ~5 wt % to 25 wt % clay minerals at 2.20–2.40 μm. The results of the synthesized samples as coating analogues with clay minerals coated on the surface of quartz grains showed a consistent trend as that of the field samples on the Earth. The further mineralogical analysis indicated that the origin of clay minerals in the coatings of Qaidam Basin is of Aeolian source. Environmental similarities between western Qaidam Basin and Martian surface suggested that various rock coatings potentially exist on Mars and they could affect the mineral detection and the accuracy of mineral identification by remote sensing. • Detrital sand in Qaidam Basin was found coated by Clay minerals of aeolian origin. • NIR band depth of trace clay coating was comparable to that caused by Martian soil. • Clay coatings may also exist on Mars and affect its clay detection and identification. [ABSTRACT FROM AUTHOR]

[Display omitted] • Migration of chalcophile elements and the material source of metallogenesis. • Au and Ag can be leached in an oxidized system, regardless of acidic or alkaline. • Pyrite is the main source of Au, Ag, As in Lower Cambrian black shale. • Highest Au content is up to 0.344 ppm in the black shale of research area. Chalcophile elements hosted by black shales of the Lower Cambrian Niutitang Formation, South China Block, contribute to low-temperature mineralisation in southwest China. To study the mobilisation and migration of ore-forming elements, hydrothermal experiments were performed to simulate leaching of Au, As, Sb and Ag from an Au-rich black shale from the Kaiyang Phosphate Mine (KYPM), China. The experiments were designed to simulate low-temperature mineralisation at 150 °C, with solvent concentrations of ~5%, durations of 15 d and 30 d, and water/rock mass ratios of 13:1 and 26:1. Reagent-grade NaCl, NaHCO 3 and Na 2 S were used to provide the common anions found in hydrothermal systems. The results show that solutions containing Cl− ions in oxidised acidic systems leached Au most effectively. Weakly alkaline systems containing HCO 3 − ions leached Au less effectively. Solutions containing HS− ions did not leach Au effectively, and Au precipitated within the HS−-bearing system. The results for Ag were similar to those for Au, and Ag-leaching was most effective in the oxidised acidic system containing Cl− ions. As-leaching does not occur in the Cl−-bearing system, but As is leached effectively by HS−-bearing and HCO 3 −-bearing solutions. Sb was not leached by our experiments. Oxidised fluids produced by deep-sourced magma during the Indosinian and Yanshanian tectonic events infiltrated black shales affected by extensional deformation through faults, joints and fractures. Fluid–rock interaction leached a range of elements in these structural settings. These experiments provide insights into migration of chalcophile elements, particularly Au and Ag, and the source of large-scale low-temperature mineralisation within the South China Block. [ABSTRACT FROM AUTHOR]

A cascaded H-bridge STATCOM requires large DC filter capacitors to suppress the low-frequency voltage fluctuation in each of the H-bridge cells. Keeping the voltage stress of power device unchanged, increasing the fluctuation of the DC-link voltage is a possible method to significantly reduce the required capacitance for a STATCOM. However, excessive voltage fluctuation greatly degrades the operating range of the inductive conditions. This paper proposes a universal capacitance design method that can significantly reduce the required capacitance when compared with the traditional design method. First, the inductance is constrained in the form normalized by the system impedance. Then a new analysis method between the DC-link capacitance and the operating range is introduced. Experiment results obtained on a low-power 5-level cascaded H-bridge STATCOM prototype are presented to validate the correctness of the proposed design method. [ABSTRACT FROM AUTHOR]

Neuronal cells overexpressing phosphorylated Tau proteins can increase the susceptibility to oxidative stress. Regulation of glycogen synthase-3β (GSK-3β) and reduction of Tau protein hyperphosphorylation, along with alleviation of oxidative stress, may be an effective way to prevent or treat Alzheimer's disease (AD). For this purpose, a series of Oxazole-4-carboxamide/butylated hydroxytoluene hybrids were designed and synthesized to achieve multifunctional effects on AD. The biological evaluation showed that the optimized compound KWLZ-9e displayed potential GSK-3β (IC 50 = 0.25 μM) inhibitory activity and neuroprotective capacity. Tau protein inhibition assays showed that KWLZ-9e reduced the expression of GSK-3β and downstream p-Tau in HEK GSK-3β 293T cells. Meanwhile, KWLZ-9e could alleviate H 2 O 2 -induced ROS damage, mitochondrial membrane potential imbalance, Ca2+ influx and apoptosis. Mechanistic studies suggest that KWLZ-9e activates the Keap1-Nrf2-ARE signaling pathway and enhances the expression of downstream oxidative stress proteins including TrxR1, HO-1, NQO1, GCLM to exert cytoprotective effects. We also confirmed that KWLZ-9e could ameliorate learning and memory impairments in vivo model of AD. The multifunctional properties of KWLZ-9e suggest that it is a promising lead for the treatment of AD. [Display omitted] • The novel agents of GSK3β inhibitory and neuroprotective were synthesized and evaluated. • KWLZ-9e reduced GSK3β and p-Tau proteins overexpression in HEK GSK-3β 293T cells. • KWLZ-9e alleviated H 2 O 2 -induced ROS damage, mitochondrial membrane potential imbalance, Ca2+ influx and apoptosis. • KWLZ-9e activated the Keap1-Nrf2-ARE signaling pathway and upregulate of downstream antioxidant proteins. • KWLZ-9e ameliorates learning and memory deficits in the OA-induced Morris water maze task. [ABSTRACT FROM AUTHOR]

Zinc finger protein (Zelda) of Tribolium castaneum (TcZelda) has been showed to play pivotal roles in embryonic development and metamorphosis. However, the regulatory mechanism of TcZelda associated with these physiology processes is unclear. Herein, the developmental expression profile showed that Zelda of T. castaneum was highly expressed in early eggs. Tissue expression profiling revealed that TcZelda was mainly expressed in the larval head and adult ovary of late adults and late larvae. TcZelda knockdown led to a 95% mortality rate in adults. These results suggested that TcZelda is related to the activation of the zygote genome in early embryonic development. Furthermore, 592 differentially expressed genes were identified from the ds Zelda treated group. Compared with the control group, altered disjunction (ALD) and AGAP005368-PA (GAP) in the ds Zelda group were significantly down-regulated, while TGF-beta, propeptide (TGF) was significantly up-regulated, suggesting that TcZelda may be involved in insect embryonic development. In addition, the expression of Ubx ultrabithorax (UBX), Cx cephalothorax (CX), En engrailed (EN), and two Endocuticle structural glycoprotein sgabd (ABD) genes were significantly down-regulated, suggesting that they may cooperate with TcZelda to regulate the development of insect wings. Additionally, Elongation (ELO), fatty acid synthase (FAS), and fatty acyl-CoA desaturase (FAD) expression was inhibited in ds Zelda insects, which could disturb the lipase signaling pathways, thus, disrupting the insect reproductive system and pheromone synthesis. These results may help reveal the function of TcZelda in insects and the role of certain genes in the gene regulatory network and provide new ideas for the prevention and control of T. castaneum. [ABSTRACT FROM AUTHOR]

Receptor-interacting protein kinase 1 (RIPK1), a vital protein of the necroptosis pathway, plays a pivotal role in various inflammatory diseases. Sibiriline has been reported to be a potent ATP-competitive RIPK1 inhibitor, but its anti-necroptotic effects are limited. A series of structural analogues of Sibiriline were synthesized and evaluated for their anti-necroptotic activity. Comprehensive structure-activity relationship (SAR) was performed to left azaindole and right substituents of benzene of Sibiriline, respectively. The optimal compound KWCN-41 , specifically inhibiting cell necroptosis but not apoptosis, protects cell survival by blocking the necroptotic pathway, which inhibits the phosphorylation of essential proteins of the necroptosis. It also prevented the development of inflammation and reduced the level of inflammatory factors in mice. KWCN-41 is expected to be a lead compound for further studies in inflammatory diseases. [Display omitted] • The SAR of Sibiriline was extended through a series of its analogues being designed, synthesized, evaluated. • KWCN-41 exhibited higher anti-necroptosis activity than Sibiriline. • KWCN-41 prevents necrosome formation by inhibiting phosphorylation of RIPK1, RIPK3 and MLKL. • KWCN-41 blocks hypothermia and death in mice in the TNFα-induced SIRS model. [ABSTRACT FROM AUTHOR]

[Display omitted] • New orthologous cluster of eclosion hormone-like (EHL) was identified in Arthropoda. • 20E up-regulated the expression of TcEHL during pupal-adult development. • RNAi of TcEHL caused lethal phenotypes with un-tanning adult cuticle in T. castaneum. • RNAi of TcEHL affected ecdysis behavior and tanning pathway genes in T. castaneum. Eclosion hormone (EH) is a neurohormone that plays a key role in the regulation of insect pre-ecdysis behavior at the end of each molt. Previous research has reported more than one EH gene was found in certain insects, with their functions and mechanisms still unclear. Here, aside from the classical EH gene orthologous group, we characterized another novel orthologous cluster of eclosion hormone-like (EHL) genes in Arthropoda and investigated the roles of EHL during development in Tribolium castaneum. T. castaneum EHL (TcEHL) shows high expression levels during pupal − adult development, which also positively responded to 20‐hydroxyecdysone (20E) treatment as well as RNA interference (RNAi) of ECR (20E nuclear receptor). Knockdown of TcEHL prevented the tanning of the adult cuticle and caused lethal phenotypes. Further analysis indicated that knockdown of TcEHL could upregulate expression levels of the classical TcEH , and downregulate the ecdysis behavior cascade genes, as well as tanning pathway enzymes. This suggests a critical role for TcEHL in adult eclosion and cuticle tanning. In addition, our data indicated that TcEHL is responsible for the female reproduction process. Taken together, these results suggest that TcEHL has specific roles in adult cuticle tanning during the post-eclosion process and female reproduction. They also suggest that EHL gene is the ancestral copy for the EH family and it is functionally shuffled by synfunctionalization. [ABSTRACT FROM AUTHOR]

Here, we report the complete genome sequence and organization of a novel virus detected in rubber trees (Hevea brasiliensis). Because the infected plants were asymptomatic, this virus was tentatively named "rubber tree latent virus 1" (RTLV1). The full genome of RTLV1 is 9,422 nt in length and contains three open reading frames with a 157-nt 5' untranslated region (UTR) and a 316-nt 3' UTR. The replicase shares the highest amino acid (aa) sequence identity (32.62%), with only 31% query coverage, with the replicase of Hubei virga-like virus 11. Phylogenetic analysis based on the aa sequence of ORF1 showed that RTLV1 clustered with unclassified members of the family Virgaviridae in a clade that was not closely related to any genus in this family. [ABSTRACT FROM AUTHOR]

Tribolium castaneum (T. castaneum) is a worldwide pest of stored grain that mainly harms flour, and not only causes serious loss of flour quality but also leads to deterioration of flour quality. Chemical detection plays a key role in insect behavior, and the role of odorant-binding proteins (OBPs) in insect chemical detection has been widely studied. However, the mechanism of OBPs in insect defense against exogenous toxic substances is still unclear. In this study, biochemical analysis showed that eugenol, the active component of A. vulgaris essential oil, significantly induced the expression of the OBP gene OBPC12 from T. castaneum (TcOBPC12). The mortality of late larvae treated with eugenol was higher than that of the control group after RNA interference (RNAi) against TcOBPC12 , which indicates that the OBP gene is involved in the eugenol defense mechanism and leads to a decrease in sensitivity to eugenol. Tissue expression profiling showed that the expression of TcOBPC12 in the epidermis, hemolymph, and intestine was higher than in other larval tissues, and TcOBPC12 was expressed mainly in the epidermis, head, and fat body of adults. The developmental expression profile showed that the expression of TcOBPC12 in late eggs, early and late larval stages, and late adult stages was higher than in other developmental stages. These data suggest that TcOBPC12 may be involved in the absorption of exogenous toxic substances by the larvae from T. castaneum. Our results provide a theoretical basis for the metabolism and degradation mechanism of exogenous toxic substances and help explore more potential target genes of insect pests. [Display omitted] • The expression of TcOBPC12 was up-regulated at 60 and 72 h after eugenol treatment. • TcOBPC12 was highly expressed in late eggs, early and late larval, and late adult stages. • TcOBPC12 was abundant in the epidermis, hemolymph and intestine of the late larval. • TcOBPC12 was more in the epidermis, head and fat body of the early adult. • RNAi of TcOBPC12 increased the mortality of late larvae after eugenol treatment. [ABSTRACT FROM AUTHOR]

Currently available PARP inhibitors are mainly used for the treatment of BRCA-mutated triple-negative breast cancer (TNBC), with a narrow application range of approximately 15% of patients. Recent studies have shown that EZH2 inhibitors have an obvious effect on breast cancer xenograft models and can promote the sensitivity of ovarian cancer cells to PARP inhibitors. Here, a series of new dual-target PARP1/EZH2 inhibitors for wild-BRCA type TNBC were designed and synthesized. SAR studies helped us identify compound 12e , encoded KWLX-12e , with good inhibitory activity against PARP1 (IC 50 = 6.89 nM) and EZH2 (IC 50 = 27.34 nM). Meanwhile, KWLX-12e showed an optimal cytotoxicity against MDA-MB-231 cells (IC 50 = 2.84 μM) and BT-549 cells (IC 50 = 0.91 μM), with no toxicity on normal breast cell lines. KWLX-12e also exhibited good antitumor activity with the TGI value of 75.94%, more effective than Niraparib plus GSK126 (TGI = 57.24%). Mechanistic studies showed that KWLX-12e achieved synthetic lethality indirectly by inhibiting EZH2 to increase the sensitivity to PARP1, and induced cell death by regulating excessive autophagy. KWLX-12e is expected to be a potential candidate for the treatment of TNBC. [Display omitted] • Novel dual-target PARP1/EZH2 inhibitors were designed and synthesized. • KWLX-12e showed potential inhibitory activity on PARP1/EZH2 and had no toxicity. • KWLX-12e increased sensitivity to PARP1 by inhibiting EZH2. • KWLX-12e could significantly inhibit tumor growth and proliferation. [ABSTRACT FROM AUTHOR]

• Graphene/chitosan/parathion multi-residue electrochemical biosensor was prepared to detect 11 OPs. • The strategy was combined with the conductivity of graphene and ability of OPs to inhibit AChE. • The biosensor indicates wide linear relationship and low detection limit. • The biosensor displays potential applications in detection of real apple sample. A graphene/chitosan/parathion multi-residue electrochemical biosensor was prepared by combining the formation of phosphorylated acetylcholinesterase (AChE) between organophosphorus molecules and AChE as well as the excellent conductivity of graphene, and was used to detect 11 organophosphorus pesticides (OPs) by indirect competitive method. The optical and electrochemical properties of modified electrode were studied by UV–Vis absorption spectroscopy, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The linear detection ranges for 11 organophosphorus molecules are 1–1500 ng⋅mL−1, with detection limits of 0.012–0.23 ng⋅mL−1, which indicates satisfactory repeatability and stability and can realize quantitative detection of organophosphorus molecules with high sensitivity. The accuracy of chlorpyrifos or dichlorvos detection in real apple samples was performed by graphene/chitosan/parathion electrochemical biosensor, which greatly meets the needs of various departments for quantitative detection of organophosphorus pesticides. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC. [ABSTRACT FROM AUTHOR]

Based on the facts that significant synergistic effect existed between PARP inhibitors and DNA damage agents and the DNA damage caused by indirubin's derivatives, we herein adopted the strategy to combine the pharmacophores of PARP inhibitors and the unique scaffold of indirubin to design a series of bifunctional molecules inducing DNA damage and targeting PARP. After SAR studies, the most potent compound 12a , encoded as KWWS-12a , exhibited improved inhibitory effect against PARP1 compared with PARP1 inhibitor Olaparib (IC 50 = 1.89 nM vs 7.48 nM) and enhanced antiproliferative activities than the combination of Olaparib and indirubin-3′-monoxime towards HCT-116 cells (IC 50 = 0.31 μM vs 1.37 μM). In the normal NCM-460 cells, 12a showed low toxicity (IC 50 > 60 μM). The mechanism research indicated that 12a could increase the levels of γH2AX concentration dependently, arrest the cell cycle in S phase and induce apoptosis in HCT-116 cells. In vivo experiments showed that 12a displayed more significant antitumor potential than that of the positive controls. Our studies demonstrated that 12a could be a promising candidate for cancer therapy. [Display omitted] • A series of indirubin derivatives as anticancer agents were designed, synthesized and evaluated. • 12a could inhibit the growth of colonic cancer cells in vitro and in vivo. • 12a could show significant antiproliferative activities against HCT-116 cells and notable inhibitory effect against PARP1. • 12a could accumulate DNA double-strand breaks in HCT-116 cells, arrest the cell cycle in S phase and induce apoptosis in HCT-116 cells. [ABSTRACT FROM AUTHOR]

Hypoxic microenvironment commonly occurred in the solid tumors considerably decreases the chemosensitivity of cancer cells. Salidroside (Sal), the main active ingredient of Rhodiola rosea, was shown to be able of regulating the tumor hypoxia micro-environment and enhancing the chemotherapeutic efficacy of drug-resistant cancer. Therefore, in this study, the Sal was co-loaded with Apatinib (Apa) by the PLGA-based nanoparticles (NPs) to improve the chemosensitivity of gastric cancer cells. Additionally, to improve the drug delivery efficacy, the tumor-homing peptide (iVR1 peptides) was further decorated on the surface of NPs. The tumor targeting ability of the peptides-functionalized nanoparticles (iVR1-NPs-Apa/Sal) was evaluated by in vitro and in vivo experiments. As the obtained results revealed that the iVR1-NPs-Apa/Sal displayed excellent tumor affinity than the unmodified ones (NPs-Apa/Sal), which in turn resulted in more efficient of anti-proliferation of gastric cancer cells and anti-tumor effect in vivo. In addition, compared with the cells or tumor-bearing mice only treaded by monotherapy of Apa, the cells or mice received combinational treatment of Apa and Sal showed obvious lower rate of growth, invasion, and migration or tumor growth and progress. Underlying mechanisms were further investigated and it was revealed that the anti-gastric cancer effect of Apa was signally improved by Sal through down-regulation the proliferation factors and increase the pro-apoptotic genes, as well as reprograming the tumor hypoxia micro-environment. In a word, the study showed that the Sal was able of improving the chemosensitivity of gastric cancer to Apa and the iVR1-NPs-Apa/Sal was capable of realizing highly efficient of tumor-targeting drug delivery. [ABSTRACT FROM AUTHOR]

Background: Current strategies are insufficient to predict pathologically complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) before treatment. Here, we aim to develop a novel long noncoding RNA (lncRNA) signature for pCR and outcome prediction of ESCCs through a multicenter analysis for a Chinese population. Methods: Differentially expressed lncRNAs (DELs) between pCRs and less than pCR (

Multi-level converters are widely used in various industrial applications. Among various space vector modulation (SVM) schemes, the multi-level SVM scheme based on two-level space vector pulse width modulation (SVPWM) is recognised as a simplified multi-level SVM scheme, which can reduce the computation complexity. However, this scheme is still complicated when the number of the voltage levels is large. This paper proposes a modified SVM scheme that can further simplify the multi-level SVM scheme based on two-level SVPWM. The proposed SVM scheme can directly determine the two-level hexagon where the reference voltage vector is located by calculating a simple formula. The whole modulation process can be completed by only three steps. Meanwhile, the proposed method is generic for any n-level converter without adding much calculation, which greatly simplifies the modulation process. Experimental results have been provided, which verify the effectiveness and generality of the proposed SVM scheme for two types of multi-level converters. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts (CAFs) have been intensively studied in recent studies with aims of finding more concrete evidence on their mechanism of involvement in tumor progression, which is currently unknown. CAFs can secrete exosomes which are loaded with proteins, lipids and RNAs, all of which affect tumor microenvironment. The present study identified microRNA-93-5p (miR-93-5p) as a novel exosomal cargo responsible for the pro-tumorigenic effects of CAFs on colorectal cancer (CRC). Methods: CAFs and normal fibroblasts (NFs) were isolated from cancerous tissues and matched with paracancerous tissues that had been surgically resected from CRC patients. The interaction among miR-93-5p, forkhead box A1 (FOXA1) and TGFB3 was identified through ChIP and dual luciferase reporter assays. The proliferation and apoptosis of SW480 cells co-cultured with CAFs-derived exosomes under irradiation were evaluated by CCK-8, colony formation, and flow cytometric assays. Tumorigenesis of SW480 cells in nude mice was assessed under the irradiation. Results: FOXA1 was found to be associated with reduced radioresistance in CRC cells and was verified as a target of miR-93-5p. CAFs-derived exosomes contained higher miR-93-5p than those from NFs, which augmented SW480 cell proliferation and rescued them from radiation-induced apoptosis. miR-93-5p was identified as a mediator of the exosomal effects of CAFs on SW480 cells, possibly through downregulating FOXA1 and upregulating TGFB3. FOXA1 could bind to the promoter of TGFB3, thereby inhibiting nuclear accumulation of TGFB3. Also, CAFs-derived exosomes containing miR-93-5p increased the tumor growth of SW480 cells in irradiated nude mice. Conclusion: The present study identifies miR-93-5p as a specific exosomal cargo that rescues CRC cells against radiation-induced apoptosis. [ABSTRACT FROM AUTHOR]

The present study was aimed to explore the functional role of microRNA (miR)‐29b in colon cancer, as well as underlying mechanisms. Expressions of miR‐29b and folate receptor 1 (FOLR1) were measured in both human colon tumor samples and cell lines. Colon cancer cell lines SW480 and SW620 were transfected with miR‐29b mimic, antisense oligonucleotides (ASO)‐miR‐29b, small interfering (siRNA) against FOLR1 (si‐FOLR1), or corresponding negative controls (NCs), and then were incubated with or without oxaliplatin (L‐OHP). Thereafter, cell viability, cytotoxicity, cell apoptosis, and expression of FOLR1, ATP Binding Cassette Subfamily G Member 2 (ABCG2) and p‐glycoprotein (p‐gp) were analyzed. We found that miR‐29b was significantly decreased, while FOLR1 was statistically elevated in colon cancer samples and cell lines compared to the nontumor samples and nontumourigenic immortalized human colon epithelial cell line FHC. Overexpression of miR‐29b markedly inhibited cell viability, promoted sensitivity to L‐OHP, stimulated cell apoptosis (all p <.05), and decreased the levels of ABCG2 and p‐gp in cancer cells, whereas suppression of miR‐29b showed contrary results. Moreover, we observed that FOLR1 was a direct target of miR‐29b and was negatively regulated by miR‐29b. In addition, the findings revealed that the effects of FOLR1 inhibition on cell viability, sensitivity to L‐OHP, cell apoptosis, and the levels of ABCG2 and p‐gp were similar to overexpression of miR‐29b. Taken together, our study suggests that miR‐29b inhibits cell growth and promotes sensitivity to L‐OHP in colon cancer by targeting FOLR1. Highlights: miR‐29b is decreased, while FOLR1 is elevated in cancer samples and cell lines;miR‐29b inhibits cell growth and promotes sensitivity to L‐OHP in cancer cells;FOLR1 is a direct target of miR‐29b;FOLR1 promotes cell growth and inhibits sensitivity and apoptosis in cancer cells;Effects of miR‐29b on cell growth and sensitivity might be by targeting FOLR1. [ABSTRACT FROM AUTHOR]

Efficiency, power quality, and reliability of SiC MOSFET-based voltage-source converters are significantly affected by the dead-time settings. The conventional fixed dead-time setting can induce large output voltage loss and additional energy loss due to the output capacitance of the SiC MOSFETs and the SiC Schottky barrier diodes or the freewheeling of the diodes, which will be more serious under high switching frequencies. This paper analyzes and models the detailed switching process of the SiC MOSFET half-bridge circuit when various dead-time settings are adopted. Based on the models, an optimal asymmetric variable dead-time (OAVDT) setting is proposed, which can avoid the discharging loss of the output capacitance and redundant freewheeling loss of the diode. The OAVDT setting is realized by adjusting the optimal dead-time in real time after the active device is turned off, which does not require any additional hardware circuits. The OAVDT setting can also reduce the output voltage loss to a certain level compared to the fixed dead-time setting. A three-phase two-level SiC MOSFET inverter has been built in the lab to verify the proposed OAVDT setting. Experimental results show a decrease of power loss by 22.5% with reduced output voltage loss compared to the fixed dead-time setting of 0.28 μs when the output power is 8 kW and the switching frequency is 40 kHz. The proposed OAVDT setting shows clear advantages over that of fixed dead-time setting, especially at light load and high switching frequencies. [ABSTRACT FROM AUTHOR]

[Display omitted] • We designed, synthesized and evaluated a series of highly effective PARP/CDK6 dual inhibitions. • P4i could effectively inhibit the proliferation of the three TNBC cells. • P4i could induce DNA damage in TNBC cells with wild-type BRCA. Inhibition of PARP is synthetic lethal with defects in BRCA, which provide effective targeted therapy strategy for BRCA mutation type of TNBC patients. However, approximately 80% of TNBC patients do not have BRCA mutations. Recent studies have shown that CDK4/6 inhibitors can increase the sensitivity of wild-type BRCA cells to PARP inhibitors. We designed a series of dual PARP and CDK6 inhibitors, and the most promising compound, P4i , showed good inhibitory activity against PARP1 and CDK6 and good inhibitory effects on MDA-MB-231 (IC 50 = 1.96 μM), MDA-MB-468 (IC 50 = 2.81 μM) and BT-549 (IC 50 = 2.37 μM) cells with wild-type BRCA. Compared with Olaparib, the inhibition capacity of the three BRCA wild-type (MDA-MB-231, MDA-MB-468 and BT-549) cells was about 10–20 times higher, and even better than the combination of Olaparib and Palbociclib. As a novel PARP multifunctional molecule, it is a potential compound for the treatment of BRCA wild-type TNBC. [ABSTRACT FROM AUTHOR]

The higher voltage blocking capability and faster switching speed of silicon-carbide (SiC) mosfets have the potential to replace Si insulated gate bipolar transistors (IGBTs) in medium-/low-voltage and high-power applications. In this paper, a state-of-the-art commercially available 325 A, 1700 V SiC mosfet module has been fully characterized under various load currents, bus voltages, and gate resistors to reveal their switching capability. Meanwhile, Si IGBT modules with similar power ratings are also tested under the same conditions. From the test results, several interesting points have been obtained: different to the Si IGBT module, the over-shoot current of the SiC mosfet module increases linearly with the increase of the load current and it has been explained by a model of the over-shoot current proposed in this paper; the induced negative gate voltage due to the complementary device turn-off (crosstalk effect) is more harmful to the SiC mosfet module than the induced positive gate voltage during turn-on when the gate off-voltage is –6 V; the maximum dv/dt and di/dt (electromagnetic interference) during switching transients of the SiC mosfet module are close to those of the Si IGBT module when the gate resistance is larger than 8 Ω but the switching loss of the SiC mosfet module is much smaller; the switching losses of the Si IGBT module are greater than those of the SiC mosfet module even when the gate resistance of the former is reduced to zero. An accurate power loss model, which is suitable for a three-phase two-level converter based on SiC mosfet modules considering the power loss of the parasitic capacitance, has been presented and verified in this paper. From the model, a 96.2% efficiency can be achieved at the switching frequency of 80 kHz and the power of 100 kW. [ABSTRACT FROM AUTHOR]

Nowadays, the widespread existence and potential adverse effects of emerging micropollutants in waters have prompted the search for effective treatment methods. In this study, the feasibility of UV/O 3 /PMS (peroxymonosulfate, HSO 5 −) method for the elimination of Flutamide (FLU) was comprehensively investigated, with focus on transformation behaviors and risk assessment. The results showed that the UV/O 3 /PMS method has excellent oxidation capability to FLU with the elimination efficiency of 83.7% within 40 min. In addition, the radical (·OH and SO 4 −·) oxidation occupies greater advantages in the initiation reaction pathways of FLU compared to non-radical (O 3 and 1O 2) oxidation. With the participation of H 2 O 2 , H 2 O, O 2 , and ·OH, eleven transformation products (TPs) are generated through hydroxylation, demethylation, and decomposition reactions. According to the risk assessment results, the toxicity of most TPs gradually decreased, but the residual developmental toxicity could not be ignored. Further, the environmental persistence of FLU was evaluated with respect to natural water and advanced oxidation processes. These findings could help to advance the fundamental understanding of emerging micropollutants in the aquatic environments, and provide a basis for their practical application in water treatment. [Display omitted] • The transformation mechanisms involved in UV/O 3 /PMS system were elucidated. • ·OH and SO 4 −· are the major contributors to FLU degradation compared to O 3 and 1O 2. • FLU degradation was caused by hydroxylation, demethylation, and decomposition paths. • UV/O 3 /PMS is a promising treatment method for O 3 or UV-refractory micropollutants. [ABSTRACT FROM AUTHOR]

• Chat knockdown severely affected larval development and pupal eclosion, but vacht RNAi only disrupted pupal eclosion. • Parental RNAi of chat or vacht would reduce egg production and completely inhibite egg hatchability in T. castaneum. • Reduction of chat or vacht decreased the resistance to carbofuran and dichlorvos. Choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are essential enzymes for synthesizing and transporting acetylcholine (ACh). But their functions in metamorphosis, reproduction, and the insecticide susceptibility were poorly understood in the insects. To address these issues, we identified the orthologues of chat and vacht in Tribolium castaneum. Spatiotemporal expression profiling showed Chat has the highest expression at the early adult stage, while vacht shows peak expression at the early larval stage. Both of them were highly expressed at the head of late adult. RNA interference (RNAi) of chat and vacht both led to a decrease in ACh content at the late larval stage. It is observed that chat knockdown severely affected larval development and pupal eclosion, but vacht RNAi only disrupted pupal eclosion. Further, parental RNAi of chat or vacht led to 35 % or 30 % reduction in fecundity, respectively, and knockdown of them completely inhibited egg hatchability. Further analysis has confirmed that both the reduction in fecundity and hatchability caused through the maternal specificity in T. castaneum. Moreover, the transcript levels of chat and vacht were elevated after carbofuran or dichlorvos treatment. Reduction of chat or vacht decreased the resistance to carbofuran and dichlorvos. This study provides the evidence for chat and vacht not only involved in development and reproduction of insects but also could as the potential targets of insecticides. [ABSTRACT FROM AUTHOR]

EZH2 is usually overexpressed in TNBC and other tumors, which has a great influence on the occurrence, development and prognosis of tumors. However, current EZH2 inhibitors, including Tazemetostat and GSK126, affect the methyl catalytic capacity of EZH2 and have little effect on the tumorigenic activity of EZH2 itself, resulting in poor efficacy against most solid tumors. Herein, we designed and optimized proteolytic targeting chimeras (PROTACs) precision targeting EZH2. The most active PROTAC molecule U3i has a high affinity for PRC2 complex (K D = 16.19 nM) and show good inhibitory effects on MDA-MB-231 (IC 50 = 0.57 μM) and MDA-MB-468 (IC 50 = 0.38 μM) cells. Compared with that of the GSK126, the growth inhibitory activities of U3i against these two TNBC cells increased by approximately 20- and 30-fold. Further studies showed that U3i can degrade PRC2 complex in TNBC cells, induce apoptosis, and cause little damage to normal cells. Therefore, U3i is a potential anticancer molecule for TNBC treatment. [Display omitted] • We designed, synthesized and evaluated a series of highly effective EZH2 degraders. • U3i could inhibit the proliferation of the two TNBC cells and did little damage to normal cells. • U3i maintained high affinity for EZH2 (K D = 16.19 nM) and could specifically degrade EZH2 in TNBC cells. • U3i can induce apoptosis of TNBC cells. [ABSTRACT FROM AUTHOR]

Tribolium castaneum is an agricultural and stored pest found throughout the world. The cytochrome P450 genes of T. castaneum can encode various detoxification enzymes and catabolize heterologous substances, conferring tolerance to insecticides. Herein, we describe the identification of a P450 gene (CYP9Z6) from T. castaneum and investigated its expression profile and potential role in the detoxification of terpinen-4-ol. TcCYP9Z6 expression was significantly induced after exposure to terpinen-4-ol, and RNA-mediated silencing of TcCYP9Z6 increased terpinen-4-ol-induced larval mortality from 47.75% to 63.92%, showing that TcCYP9Z6 is closely related to the detoxification of terpinen-4-ol. The developmental expression profile revealed that TcCYP9Z6 was mainly expressed in late adults and late larvae. Tissue expression profiling revealed that the highest TcCYP9Z6 expression occurred in the head, in both the adult and the larval tissues, followed by the gut in larvae and the antennae in adults. These developmental stages and tissues with high TcCYP9Z6 expression are closely related to the detoxification of heterologous substances. These results indicated that TcCYP9Z6 may play a pivotal role in the detoxification of terpinen-4-ol, which provides support for using TcCYP9Z6 a potential gene for the RNAi-mediated prevention and control of T. castaneum. [Display omitted] • Expression of TcCYP9Z6 gene was induced with terpinen-4-ol. • Knockdown of TcCYP9Z6 increases sensitivity of T. castaneum to terpinen-4-ol. • The CYP9Z6 of T. castaneum is related to its detoxification. [ABSTRACT FROM AUTHOR]

Protease-activated receptors (PARs) are G protein-coupled receptors of which four members PAR1, PAR2, PAR3, and PAR4 have been identified, characterized by a typical mechanism of activation involving various related proteases. The amino-terminal sequence of PARs is cleaved by a broad array of proteases, leading to specific proteolytic cleavage which forms endogenous tethered ligands to induce agonist-biased PAR activation. The biological effect of PARs activated by coagulation proteases to regulate hemostasis and thrombosis plays an enormous role in the cardiovascular system, while PAR4 can also be activated by trypsin, cathepsin G, the activated factor X of the coagulation cascade, and trypsin IV. Irrespective of its role in thrombin-induced platelet aggregation, PAR4 activation is believed to be involved in inflammatory lesions, as show by investigations that have unmasked the effects of PAR4 on neutrophil recruitment, the regulation of edema, and plasma extravasation. This review summarizes the roles of PAR4 in coagulation and other extracellular protease pathways, which activate PAR4 to participate in normal regulation and disease. [ABSTRACT FROM AUTHOR]

• Many segmental duplications and tandem duplications have been discovered in S. frugiperda , which is the key factor for the expansion of the GPCR superfamily. • There are 40 receptors that had different degrees of expansion in S. frugiperda , among which 23 receptors expanded in biogenic amine receptors and neuropeptide and protein hormone receptors. • 17 members of Mth/Mthls subfamily in S. frugiperda were more than other insects, showing a special expansion pattern. Spodoptera frugiperda (Insecta: Lepidoptera) is a destructive invasive pest feeding on various plants and causing serious damage to several economically-important crops. G protein-coupled receptors (GPCRs) are cellular receptors that coordinate diverse signaling processes, associated with many physiological processes and disease states. However, less information about GPCRs had been reported in S. frugiperda , limiting the recognition of signaling system and in-depth studies of this pest. Here, a total of 167 GPCRs were identified in S. frugiperda. Compared with other insects, the GPCRs of S. frugiperda were significantly expanded. A large of tandem duplication and segmental duplication events were observed, which may be the key factor to increase the size of GPCR family. In detail, these expansion events mainly concentrate on biogenic amine receptors, neuropeptide and protein hormone receptors, which may be involved in feeding, reproduction, life span, and tolerance of S. frugiperda. Additionally, 17 Mth/Mthl members were identified in S. frugiperda , which may be similar to the evolutionary pattern of 16 Mth/Mthl members in Drosophila. Moreover, the expression patterns across different developmental stages of all GPCR genes were also analyzed. Among these, most of the GPCR genes are poorly expressed in S. frugiperda and some highly expressed GPCR genes help S. frugiperda adapt to the environment better, such as Rh6 and AkhR. In this study, all GPCRs in S. frugiperda were identified for the first time, which provided a basis for further revealing the role of these receptors in the physiological and behavioral regulation of this pest. [ABSTRACT FROM AUTHOR]

Abstract: A simple and systematic approach is developed for modeling and neural adaptive backstepping control of an uncertain chaotic system, using only input–output data obtained from the underlying dynamical systems. Gaussian fuzzy membership functions are used in conjunction with the least-squares principle for modeling and control. Based on the dynamic fuzzy neural network (DFNN) modeling, an adaptive backstepping controller is devised, which works through structure and parameter-learning phases for adaptation. The DFNN implements Takagi–Sugeno–Kang fuzzy systems based on extended radial basis function (RBF) neural networks. The design procedure is illustrated by using the multiscroll chaotic attractors as an example, on which simulation results demonstrate the effectiveness of the proposed methodology. [ABSTRACT FROM AUTHOR]

With the increase in the scale and complexity of underwater engineering, safety problems caused by underwater deformation have become increasingly prominent. Although the intensity fiber curvature sensor can be used for curvature monitoring on the ground, its sensing mechanism is still under investigation. This paper establishes the mathematical model of optical power relative loss and bending radius during deformation of the fiber sensitive region and uses the optical power meter to measure light intensity loss in the sensitive region, which verifies the correctness of the model and reveals the sensing mechanism of the intensity fiber curvature sensor, then optimizes the sensor signal conditioning circuit, applies the sensor to the single-point deformation curvature measurement, and analyzes its measurement error and accuracy. It is proved that the linear measurement range of the sensor is improved when compared with existing similar products. [ABSTRACT FROM AUTHOR]

In low and medium voltage power conversion systems, multilevel converters are becoming more and more attractive due to improved power density. However, the complexity of topology and control is a big challenge for the application of multilevel converters. In this paper, a four-level (4L) hybrid flying capacitor (FC) T-type converter has been researched in detail. The topological advantage of the converter is displayed in comparison to existing four-level converters. According to the feature of the topology, the operating status has been analyzed and the reason for the voltage jump is researched in detail during the dead-time period. A strategy to reduce voltage jump by adjusting the switching states has be presented. The FC voltages can be balanced by selecting the appropriate switching states. The relationships between the fluctuations of FC voltages and the modulation index and power factor (PF) have been analyzed by simulation results. The performance of the 4L converter has been investigated in MATLAB/Simulink as well as on a down-scaled laboratory prototype. [ABSTRACT FROM AUTHOR]