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Plant viruses threaten crop yield and quality; thus, efficient and accurate pathogen diagnostics are critical for crop disease management and control. Recent advances in sequencing technology have revolutionized plant virus research. Metagenomics sequencing technology, represented by next-generation sequencing (NGS), has greatly enhanced the development of virus diagnostics research because of its high sensitivity, high throughput and non-sequence dependence. However, NGS-based virus identification protocols are limited by their high cost, labor intensiveness, and bulky equipment. In recent years, Oxford Nanopore Technologies and advances in third-generation sequencing technology have enabled direct, real-time sequencing of long DNA or RNA reads. Oxford Nanopore Technologies exhibit versatility in plant virus detection through their portable sequencers and flexible data analyses, thus are wildly used in plant virus surveillance, identification of new viruses, viral genome assembly, and evolution research. In this review, we discuss the applications of nanopore sequencing in plant virus diagnostics, as well as their limitations.

This paper studies a non-linear energy harvesting (EH) enabled full-duplex (FD) cooperative non-orthogonal multiple access (C-NOMA) system, where the near user acts as an FD relay to assist the transmission from BS to far user with power-splitting (PS) protocol. We derive the close-form expressions of outage probability in this considered system, and also give the asymptotic outage probability under high signal-to-noise ratio (SNR) regime. Additionally, we obtain the optimal power allocation parameter to minimize the outage probability, and discuss the impact of self-interference (SI) on outage performance. Moreover, it is observed from simulation results that the presence of SI improve the outage performance, which is caused by the so-called self-energy recycling.

Diffusion MRI measures of the human brain provide key insight into microstructural variations across individuals and into the impact of central nervous system diseases and disorders. One approach to extract information from diffusion signals has been to use biologically relevant analytical models to link millimetre scale diffusion MRI measures with microscale influences. The other approach has been to represent diffusion as an anomalous transport process and infer microstructural information from the different anomalous diffusion equation parameters. In this study, we investigated how parameters of various anomalous diffusion models vary with age in the human brain white matter, particularly focusing on the corpus callosum. We first unified several established anomalous diffusion models (the super-diffusion, sub-diffusion, quasi-diffusion and fractional Bloch-Torrey models) under the continuous time random walk modelling framework. This unification allows a consistent parameter fitting strategy to be applied from which meaningful model parameter comparisons can be made. We then provided a novel way to derive the diffusional kurtosis imaging (DKI) model, which is shown to be a degree two approximation of the sub-diffusion model. This link between the DKI and sub-diffusion models led to a new robust technique for generating maps of kurtosis and diffusivity using the sub-diffusion parameters βSUB and DSUB. Superior tissue contrast is achieved in kurtosis maps based on the sub-diffusion model. 7T diffusion weighted MRI data for 65 healthy participants in the age range 19–78 years was used in this study. Results revealed that anomalous diffusion model parameters α and β have shown consistent positive correlation with age in the corpus callosum, indicating α and β are sensitive to tissue microstructural changes in ageing.

To obtain an anthropomorphic performance in physical human-robot interaction during a reaching task, a variable impedance control (vIC) algorithm with human-like characteristics is proposed in this article. The damping value of the proposed method is varied with the target position as well as through the tracking error. The proposed control algorithm is compared with the impedance control algorithm with constant parameters (IC) and another vIC algorithm, which is only changed with the tracking error (vIC-e). The different control algorithms are validated through the simulation study, and are experimentally implemented on a cable-driven rehabilitation robot. The results show that the proposed vIC can improve the tracking accuracy and trajectory smoothness, and reduce the interaction force at the same time.

The hydropower system’s water-energy-ecosystem nexus (WEEN) has gained particular focus in the last years. The water-use trade-offs between hydropower and ecosystem maintenance are complex and variable for cascade hydropower systems, leading to challenges in water resources management and sustainable development of hydropower. To understand the trade-off in the WEEN of cascade hydropower systems and their changes, a WEEN model using the multi-objective optimization approach is developed in this study, including maximizing cascade power generation, minimizing reservoir water footprint, and minimizing amended annual proportional flow deviation. These optimization objectives characterize the nexus’s water, energy, and ecosystem sectors. And the Pareto non-inferiority solutions are obtained by the third edition of the Non-dominated Sorting Genetic Algorithm. Also, we novelly propose an evaluation index called the Multi-objective Trade-off Index (MTI), a quantitative method with clear physical meaning to explore the trade-offs as revealed between different objectives by the solutions. A case study of the Yalong River, China, has shown that: 1) the larger the incoming water is, the more beneficial to the power generation and ecological benefits of the hydropower system; and 2) the trade-off degrees of the water sector with respect to energy-ecosystem and energy sector with respect to water-ecosystem decreases when the hydrological condition changes from wet to dry, while the degree of ecosystem sector with respect to water-energy increases. In general, the proposed MTI that quantifies trade-offs in the WEEN of cascade hydropower systems is efficient and feasible. Meanwhile, the MTI is also generic and can be applied to other multi-objective optimization problems.

Glucocorticoids are commonly used to treat anti-GBM crescentic glomerulonephritis, however, the mechanism underlying its therapeutic effectiveness is not completely understood. Since podocyte EGFR/STAT3 signaling is known to mediate the development of anti-GBM glomerulonephritis, we investigated the effect of glucocorticoids on EGFR/STAT3 signaling in podocytes. We found that the levels of phosphorylated (activated) EGFR and STAT3 in podocytes were markedly elevated in anti-GBM patients without glucocorticoids treatment, but were normalized in patients with glucocorticoids treatment. In a rat model of anti-GBM glomerulonephritis, glucocorticoids treatment significantly attenuated the proteinuria, crescent formation, parietal epithelial cell (PEC) activation and proliferation, accompanied by elimination of podocyte EGFR/STAT3 signaling activation. In cultured podocytes, glucocorticoids were found to inhibit HB-EGF-induced EGFR and STAT3 activation. The conditioned medium from podocytes treated with HB-EGF in the absence but not presence of glucocorticoids was capable of activating Notch signaling (which is known to be involved in PEC proliferation and crescent formation) and enhancing proliferative activity in primary PECs, suggesting that glucocorticoids prevent podocytes from producing secreted factors that cause PEC proliferation and crescent formation. Furthermore, we found that glucocorticoids can downregulate the expression of EGFR ligands, EGF and HB-EGF, while upregulate the expression of EGFR inhibitor, Gene 33, explaining how glucocorticoids suppress EGFR signaling. Taken together, glucocorticoids exert therapeutic effect on anti-GBM crescentic glomerulonephritis through inhibiting podocyte EGFR/STAT3 signaling and the downstream pathway that leads to PEC proliferation and crescent formation.

Microbial resources from the human gut may find use in various applications, such as empirical research on the microbiome, the development of probiotic products, and bacteriotherapy. Due to the development of “culturomics”, the number of pure bacterial cultures obtained from the human gut has significantly increased since 2012. However, there is still a considerable number of human gut microbes to be isolated and cultured. Thus, to improve the efficiency of obtaining microbial resources from the human gut, some constraints of the current methods, such as labor burden, culture condition, and microbial targetability, still need to be optimized. Here, we overview the general knowledge and recent development of culturomics for human gut microorganisms. Furthermore, we discuss the optimization of several parts of culturomics including sample collection, sample processing, isolation, and cultivation, which may improve the current strategies.

In winter, many rural people in the coastal areas of northern China burn coal for both cooking and heating. As a result, the rural population is seriously affected by indoor air pollution. To analyze the influence of the location of heating sources on the air quality within rural buildings, 60 buildings with coal heating were surveyed and monitored using an Intelligent Built Environmental Monitor for eight days. In addition, four typical rural buildings with different locations of heating sources were selected for a transient analysis. The peak concentration of CO2 was 2869 ppm in House 1 with a coal-fired stove in the living room. The average particulate matter (PM) levels were 89 μg/m3, 150 μg/m3, and 182 μg/m3 for PM 1.0, PM 2.5, and PM 10, respectively, in House 2 where a stove was situated in a room adjacent to the living room. House 3, where stoves were in separate rooms, had PM 1.0, PM 2.5, and PM 10 values of 25 μg/m3, 39 μg/m3, and 49 μg/m3, respectively, and the lowest CO2 concentration (564 ppm) was found in House 4. The data collected showed that the CO2, PM 1.0, PM 2.5, and PM 10 concentrations within Houses 1 and 2 far exceeded the standard for indoor air quality. The findings suggested that coal-fired stoves, as a heating source, should be situated away from the living room and adjacent rooms, and this change would clearly reduce the concentrations of CO2 and particulate matter. Suitable courtyard ventilation was necessary for houses with two or more heating sources.

CCAAT/enhancer-binding proteins (C/EBPs) are a family of at least six identified transcription factors that contain a highly conserved basic leucine zipper domain and interact selectively with duplex DNA to regulate target gene expression. C/EBPs play important roles in various physiological processes, and their abnormal function can lead to various diseases. Recently, accumulating evidence has demonstrated that aberrant C/EBP expression or activity is closely associated with the onset and progression of fibrosis in several organs and tissues. During fibrosis, various C/EBPs can exert distinct functions in the same organ, while the same C/EBP can exert distinct functions in different organs. Modulating C/EBP expression or activity could regulate various molecular processes to alleviate fibrosis in multiple organs; therefore, novel C/EBPs-based therapeutic methods for treating fibrosis have attracted considerable attention. In this review, we will explore the features of C/EBPs and their critical functions in fibrosis in order to highlight new avenues for the development of novel therapies targeting C/EBPs.

We have developed a migration scheme that can compensate absorption and dispersion with effective Q estimation and Fresnel zone identification based on deep learning. We use the U-Net neural network technology in deep learning to automatically identify Fresnel zones from compensated migrated dip-angle gathers and obtain the optimal aperture for migration, avoiding the tedious task of manually modifying the boundaries of Fresnel zones. Instead of the interval Q factor, we used an effective Q parameter to compensate absorption and dispersion. The effective Q is estimated using VSP well data and surface seismic velocity data. The proposed scheme can be incorporated into conventional seismic data processing workflow. A field data set was employed to validate the proposed scheme. Higher resolution imaging results with low noise levels are obtained.

Diabetic kidney disease (DKD) is currently one of the leading causes of end-stage renal disease (ESRD). Mitochondrial dysfunction in podocyte is involve in DKD development. However, whether early mitochondrial stabilization delays or reverses DKD progression has not been elucidated. SS31 is a novel tetrapeptide compound that targets the inner mitochondrial membrane and protects mitochondria by reducing ROS and inhibiting cardiolipin oxidation. Our study discovered that SS31 might have a long-term podocyte protection in DKD. In this study, we examined the glomerular pathological damage and proteinuria at different stages of diabetes. Results revealed that podocyte mitochondrial injury appeared at the early stage of DKD. Early treatment with SS31 could protect podocyte and alleviate the development of DKD via inhibiting OMA1-mediated hydrolysis of OPA1. Those data indicate that SS31 might be a promising agent in delaying the development of DKD and OMA1-mediated hydrolysis of OPA1 in mitochondria, and SS31 is a novel therapeutic target for the treatment of DKD.

Objective and Background. In order to explore the needs of the elderly for elderly nursing services, this paper studies from this aspect; China’s economic development, scientific, and technological progress and concepts have also changed. Although the living conditions of the Chinese people have improved, the rapid growth of the population has led to an aging society. Therefore, great attention has been paid to the care of the elderly. In addition, with the fast pace of life, many elderly people with chronic diseases, poor physical conditions, and need spiritual comfort are in a state of lack of care for a long time. It has affected the stability and harmony of Chinese society. Methods. 500 inpatients with chronic diseases in a famous tertiary hospital in a city were studied, and the corresponding countermeasures were put forward through the analysis of their needs and influencing factors. Results. The study found that the vast majority of elderly patients have higher requirements for elderly care services, which is related to factors such as family income. Compared with the huge medical demand, there is a large gap in the level of domestic medical and health talents. According to relevant research, the current number of beds in China is 1 : 0.27, but in fact it is 1 : 0.4. Therefore, relevant units should strengthen the health examination of the elderly, provide high-quality medical services, make full use of health resources, and strengthen nursing management, so as to improve the quality of nursing services. Conclusion. The survey results show that the vast majority of elderly patients have high requirements for their elderly care services, which is related to family income and other related factors. Therefore, relevant departments should formulate corresponding measures to improve the quality of life of the elderly.

The Mn3X (where X = Ga, Ge, Sn, etc.) compounds have appealing prospects for spintronic applications due to their various crystal structures and magnetic properties for the design of reliable high-density memories. However, controlled growth of high-quality Mn3X thin films remains challenging in material science. Here, we reported the controlled film growth of Heusler alloy Mn3Ge, which could crystallize in respective tetragonal and hexagonal structures. The tetragonal D022-type Mn3Ge film exhibits strong perpendicular ferromagnetic anisotropy, while the hexagonal D019-type Mn3Ge film indicates non-collinear triangular antiferromagnetic order. From our experimental observations of structure characterizations, magnetic properties, anomalous Hall effect, and magnetoresistance measurements, we realized the manipulation of spin orientations and topological features. Majority/minority spin polarized Fermi surface and density of states of both tetragonal and hexagonal Mn3Ge structures were investigated by density functional theory calculations. Our work not only opens up technology routes toward the development of Mn3X-based devices for applications in topological spintronics and spin-torque memories but also leads to engineer the physical properties for fundamental study.

The rural living environment, especially for thermal environment and air quality, has always been concerned during the heating period. This study conducted a field measurement and questionnaire survey of indoor air quality in five villages in the cold rural coastal region of Qingdao, China. This area experiences the more extreme weather conditions, compared to the inland region. The sixty rural buildings were selected, while the basic characteristics, heating methods, indoor thermal environment, and air quality were recorded. Results showed the main heating method is the coal-fired stove combined with other radiators. The neutral values of indoor air temperature and relative humidity are 13 °C and 40% for local residents, which are much less than the comfortable levels. However, local residents demonstrated the ability to independently regulate temperature and humidity levels to within comfortable levels. And The coal combustion increases the indoor smell intensity and pollute indoor air. The CO2 concentration can be up to 1015.47 ppm and 690.78 ppm in rooms with and without the stove in the activity room respectively, while PM2.5 concentration can reach up to 199.6ug/m3 and 62.9ug/m3 respectively. These concentration values are much higher than the relative standards and the present air quality is very harmful to the human health.

Rehabilitation robots play an increasingly important role in the recovery of motor function for stroke. To ensure a natural physical human-robot interaction (pHRI) and enhance the active participation of subjects, it is necessary for the robots to understand the human intention and cooperate actively with humanlike characteristics. This study proposed a hybrid active control algorithm with human motion intention detection. The motion intention was defined as the desired position and velocity, which were continuously estimated according to the human upper-limb model and minimum jerk model, respectively. The motion intention was then fed into a hybrid force and position controller of an upper-limb cable driven rehabilitation robot (CDRR). And a three-dimensional reaching task without predefined trajectory was employed to validate the effectiveness of the proposed control algorithm. Experimental results showed that the control algorithm could continuously recognize the human motion intention and enabled the robot better movement performance indicated as smaller offset error, smoother trajectory, and lower impact. The proposed method could guarantee a natural pHRI and improve the engagement of the subjects, which has great potential in clinical applications.

Wave energy is a renewable clean and resources for ships. According to the rolling characteristics of merchant ships, this research designs an energy recovery device installed on the ship deck to harvest the energy generated by waves. And a typical 50,000-ton ship is selected as the experimental platform of the device. The mathematical model is established and solved by Newmark- $\beta $ method, and a simulation platform is built in MATLAB. By simulating the movement of the slider in the device, it shows that the slider can realize reciprocating motion when the ship rolls continuously. Then, the relevant parameters in different combinations of natural frequency $\omega _{n}$ and damping ratio $\varepsilon $ are calculated, the power output of the device and the motion law of the slider are analyzed, and parameters’ variable curves are drawn in figures. A reasonable combination of $\omega _{n}=1.225$ Hz, $\varepsilon =0.0612$ and a relatively ideal average power (174.11 W) are found by comparing amounts of simulated results from typical sea conditions. It is indicated that four main factors affecting the power generation of the device include the elasticity coefficient $K$ , effective damping coefficient $C$ in the device, the ship rolling period and rolling angle. Besides, the device can still output power continuously by simulation in complex sea condition. Based on the research, it is proved that the device mentioned in this study has good feasibility in generating electric energy during ship rolling, which can provide valuable ideas for the application of wave energy in ships on voyage.

Abstract Background Silk glands are used by silkworms to spin silk fibers for making their cocoons. These have recently been regarded as bioreactor hosts for the cost-effective production of other valuable exogenous proteins and have drawn wide attention. Results In this study, we established a transgenic silkworm strain which synthesizes the recombinant human lactoferrin (rhLF) in the silk gland and spins them into the cocoon by our previously constructed silk gland based bioreactor system. The yield of the rhLF with the highest expression level was estimated to be 12.07 mg/g cocoon shell weight produced by the transgenic silkworm strain 34. Utilizing a simple purification protocol, 9.24 mg of the rhLF with recovery of 76.55% and purity of 95.45% on average could be purified from 1 g of the cocoons. The purified rhLF was detected with a secondary structure similar with the commercially purchased human lactoferrin. Eight types of N-glycans which dominated by the GlcNAc (4) Man (3) (61.15%) and the GlcNAc (3) Man (3) (17.98%) were identified at the three typical N-glycosylation sites of the rhLF. Biological activities assays showed the significant evidence that the purified rhLF could relief the lipopolysaccharide (LPS)-induced cell inflammation in RAW264.7 cells and exhibit potent antibacterial bioactivities against the Escherichia coli (E. coli) and Bacillus subtilis. Conclusions These results show that the middle silk gland of silkworm can be an efficient bioreactor for the mass production of rhLF and the potential application in anti-inflammation and antibacterial.

Csk, a non-receptor tyrosine kinase, serves as an indispensable negative regulator of the Src family kinases (SFKs). However, little is known about regulation of Csk expression so far. SUMOylation, a reversible post-translational modification, has been shown to regulate many biological processes especially in tumor progression. Here we report that Csk is covalently modified by SUMO1 at lysine 53 (K53) both in vitro and in vivo. Treatment with hydrogen peroxide inhibited this modification to a certain extent, but PIAS3, identified as the main specific SUMO E3 ligase for Csk, could significantly enhance SUMO1-Csk level. In addition, phosphorylation at Ser364, the active site in Csk, had no effect on this modification. Ectopic expression of SUMO-defective mutant, Csk K53R, inhibited tumor cell growth more potentially than Csk wild-type. Consistent with the biological phenotype, the SUMO modification of Csk impaired its activity to interact with Cbp (Csk binding protein) leading to decreased c-Src phosphorylation at Y527. Our results suggest that SUMOylation of Csk mainly at lysine 53 negatively modulates its tumor suppressor function by reducing its binding with Cbp and consequently, inducing c-Src activation.

The growing evidence suggests that circular RNAs (circRNAs) have significant associations with tumor occurrence and progression, yet the regulatory mechanism of circRNAs in lung adenocarcinoma (LUAD) remains unclear. This study clarified the potentially regulatory network and functional mechanism of circRNAs in LUAD. The expression data of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were obtained from the Gene Expression Omnibus (GEO) database. Relying on GSE101586, GSE101684, and GSE112214, we identified differentially expressed circRNAs (DEcircRNAs). Depending on GSE135918 and GSE32863, we screened out differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs), respectively. Then, a novel competing endogenous RNA (ceRNA) regulatory network related to LUAD was constructed. We also revealed biological processes and signal pathways regulated by these DEcircRNAs. Based on gene expression data and survival information of LUAD patients in The Cancer Genome Atlas (TCGA) and GEO, we implemented survival analysis to select DEmRNAs related to prognosis and build a novel circRNA–miRNA–mRNA hub regulatory network. Meanwhile, quantitative real-time PCR (qRT-PCR) was utilized to validate DEcircRNAs in the ceRNA hub regulatory network. As a result, a total of 8 DEcircRNAs, 19 DEmiRNAs, and 85 DEmRNAs were identified. The novel ceRNA regulatory network included 5 circRNAs, 8 miRNAs, and 22 mRNAs. The final ceRNA hub regulatory network contained two circRNAs, two miRNAs, and two mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the five DEcircRNAs may affect LUAD onset and progression through Wnt signaling pathway and Hippo signaling pathway. All in all, this study revealed the regulatory network and functional mechanism of circRNA-related ceRNAs in LUAD.

Soybean [Glycine max (L.) Merri.] is an important oilseed and food crop. In recent years, environmental degradation has accelerated soil alkalization, salinization, and water deficit, which have seriously threatened the soybean quality and yield. Chaperone DNAJ proteins play important roles in plant response to a number of abiotic and biotic stresses. Here, we investigated the function of a soybean DNAJ gene, GmDNAJC7, in plant tolerance to abiotic stresses. GmDNAJC7 gene expression was induced by alkaline-salt, salt, and drought treatments in soybean roots, suggesting its possible role in soybean response to these stresses. GmDNAJC7 overexpression improved the alkaline-salt tolerance of soybean composite plants, which showed a higher SPAD (Soil and Plant Analysis Development) value for chlorophyll content and leaf relative water content than the control plants after NaHCO3 treatment. Moreover, the GmDNAJC7 overexpressing Arabidopsis had a higher germination rate and average root length than the wild type and dnajc7 mutant, under NaHCO3, NaCl, and mannitol stresses, indicating that the ectopic expression of the GmDNAJC7 gene enhanced the alkaline-salt, salt, and drought tolerance in Arabidopsis. These findings suggest that GmDNAJC7 is involved in the alkaline-salt, salt, and drought tolerance in Arabidopsis and soybean. This study provides new insights into the role of DNAJ proteins in plant tolerance to abiotic stress.

A semidiscrete integrable coupled system is obtained by embedding a free function into the discrete zero-curvature equation. Then, explicit solutions of the first two nontrivial equations in this system are derived directly by the Darboux transformation method. Finally, in order to compare the solutions before and after coupling intuitively, their structure figures are presented and analyzed.

Proteasomal deubiquitinase (DUB) inhibition has been found to be effective in experimental cancer therapy by inducing proteasome inhibition and apoptosis. Ferroptosis is a form of regulated cell death characterized by an iron-dependent lipid peroxidation. Antioxidant enzyme glutathione peroxidase 4 (GPX4) plays a key role in blocking ferroptosis through directly reducing phospholipid hydroperoxides production. Since cytoplasmic DUB inhibition can promote protein degradation in the cell, we hypothesize that DUB inhibition induces GPX4 degradation. Here we used palladium pyrithione complex (PdPT), a broad spectrum deubiquitinase inhibitor, to explore its cell death induction and anti-cancer effect in vitro, ex vivo, and in vivo. Mechanically, caspase activation and GPX4 protein degradation are required for PdPT-induced apoptosis and ferroptosis, respectively. Notably, PdPT-induced multiple deubiquitinase inhibition is essential for proteasomal degradation of GPX4. These findings not only identify a novel mechanism of post-translational modification of GPX4 in ferroptosis, but also suggest a potential anti-caner therapeutic strategy using Pan-DUB inhibition.

The study of a metro traction power supply system reliability makes a significant contribution to researching on new power supply principles and configuration, and also providing a reference for system design and operation. According to the power supply structure and operation mode of the metro traction substation power supply system, based on the internal equipment, the reliability evaluation model of the traction substation is established by the block processing fault tree. An improved sequential Monte Carlo method is used to realize the quantitative reliability evaluation of the metro traction substation power supply system. The conclusions show that the reliability model and the sequential Monte Carlo simulation method proposed in this paper can obtain rich reliability indexes. Through visual simulation and theoretical calculation, the reliability of the metro traction power supply system can be effectively evaluated.

Ubiquitin–proteasome system (UPS) and autophagy–lysosome pathway (ALP) are two major systems for protein quality control (PQC) in eukaryotic cells. Interconnectivity between these two pathways has been suggested, but the molecular detail of how they impact each other remains elusive. Proteasomal deubiquitinase (DUB) is an important constituent in the UPS and has proved to be a novel anticancer target. We have previously found that a novel DUB inhibitor, nickel complex NiPT, induces apoptosis in both cultured tumor cell lines and cancer cells from acute myeloid leukemia human patients. In this study, we found that NiPT triggered autophagy both in vitro and in vivo. Mechanistically, NiPT targets two DUBs, USP14, and UCHL5, and increased the total cellular level of polyubiquitination. Deletion of the Ubiquitin Associated (UBA) domain of P62 that is required for polyubiquitin binding prevented NiPT-induced autophagy. NiPT-induced autophagy is through either concomitant activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR) signaling, or eliciting endoplasmic reticulum (ER)-stress by activating activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP). Moreover, NiPT could induce more lung cancer cells undergoing apoptosis if it synergistically uses autophagy inhibitors, suggesting that NiPT-induced autophagy protects cancer cell from death. Collectively, our findings demonstrate that autophagy inhibition enhances the anticancer effects of proteasomal DUB inhibitor and might be an effective treatment strategy for lung cancer.

The use of lead-free ceramic film materials with positive temperature coefficient of resistivity (PTCR) is widespread in temperature heaters and sensors in micro-electromechanical systems. In this research, the out of plane transport properties of the BiFeO3 (BFO) films have been studied. Surprisingly, PTCR was found in the BFO ceramic films due to the strongly correlated interaction between the multiferroic material BFO and the superconductor YBCO perovskite oxides. To our knowledge, this is the first report on the PTCR effect of BFO films. The BFO/YBCO interface and the bulk conductivity of BFO are important for the PTCR effect, as they make it possible to compare the transport properties of Au/BFO/YBCO- and YBCO/BFO/YBCO-type structures. PTCR was observed in Au/BFO/YBCO at a bias voltage of more than 2 V, but not in the YBCO/BFO/YBCO, even with a 40 V bias voltage. PTCR was found after BFO breakdown of a YBCO/BFO/YBCO capacitor. This indicated that the conductivity of BFO is critical for PTCR. The dependence of PTCR on the superconducting transition temperature illustrates that a cooper-pair can be injected into BFO. Our work presents a method by which to produce a lead-free ceramic film material with PTCR.

Background/Aims: The ubiquitin proteasome system (UPS) is responsible for the degradation of most intracellular proteins, and proteasomal deubiquitinases (DUBs) have recently been highlighted as novel anticancer targets. It is well documented that copper complexes can inhibit UPS function through targeting both 20S proteasome and proteasomal DUBs. The antineoplastic activities of silver complexes have received much attention, but the exact mechanisms are not fully elucidated. In this study, we aim to investigate the effects of a novel silver complex [Ag(S2CN(C2H5)2)]6 (AgDT) on UPS function and its anticancer potential in non-small cell lung cancer (NSCLC). Methods: Cell viability assay (i.e., the MTS assay) and flow cytometry assay were used to analyze the cell viability and apoptosis. Proteasome inhibition was measured using 20S proteasome activity assay and 19S proteasomal DUBs activity assay. Western blot analysis and immunohistochemistry were performed to detect protein levels. The in vivo antitumor activity of AgDT was assessed with nude xenografts. Results: Silver ions, alone or in combination with disulfiram (DSF), induced UPS inhibition in NSCLC cells mainly through inhibition of proteasomal DUBs activities. Silver complex AgDT triggered intracellular accumulation of ubiquitinated proteins, and prevented the degradation of surrogate substrate GFPu. Mechanistically, AgDT potently inhibited the activities of proteasomal DUBs USP14 and UCHL5, without altering the 20S proteasome peptidases. Moreover, AgDT induced apoptosis in NSCLC cells and significantly inhibited tumor growth in xenografts. Conclusion: Our findings suggest that silver complex AgDT is a novel metal-based proteasomal DUBs inhibitor, and pharmacologic inhibition of USP14 and UCHL5 could prove to be an effective therapeutic strategy for NSCLC.

The booklouse, Liposcelis bostrychophila is an important storage pest worldwide. The mitochondrial (mt) genome of an asexual strain (Beibei, China) of the L. bostrychophila comprises two chromosomes; each chromosome contains approximate half of the 37 genes typically found in bilateral animals. The mt genomes of two sexual strains of L. bostrychophila, however, comprise five and seven chromosomes, respectively; each chromosome contains one to six genes. To understand mt genome evolution in L. bostrychophila, and whether L. bostrychophila is a cryptic species, we sequenced the mt genomes of six strains of asexual L. bostrychophila collected from different locations in China, Croatia, and the United States. The mt genomes of all six asexual strains of L. bostrychophila have two chromosomes. Phylogenetic analysis of mt genome sequences divided nine strains of L. bostrychophila into four groups. Each group has a distinct mt genome organization and substantial sequence divergence (48.7–87.4%) from other groups. Furthermore, the seven asexual strains of L. bostrychophila, including the published Beibei strain, are more closely related to two other species of booklice, L. paeta and L. sculptilimacula, than to the sexual strains of L. bostrychophila. Our results revealed highly divergent mt genomes in the booklouse, L. bostrychophila, and indicate that L. bostrychophila is a cryptic species.

Isodon diterpenoids, promising anti-cancer agents found in certain tropical plants, are difficult to obtain. Here, the authors developed a synthetic strategy to synthesise several different members of this group, including neolaxiflorin L which emerged from this study as a promising drug candidate.

We assembled and annotated the complete mitochondrial genome of Scatoglyphus polytrematus. It is the first complete mitochondrial genome sequence from the genus Scatoglyphus. The mitogenome was 13,966 bp in length and contains 37 genes (including 13 protein-coding genes, 22 transfer RNA (tRNA), and two ribosomal RNA (rRNA)), and one largest non-coding region. The gene arrangement of S. polytrematus is consistent with the pattern of possible common ancestor of astigmatid mites. In the present study, phylogenetic analysis shows that genus Scatoglyphus was clustered into one branch with other Acaridae species.

Two dinuclear complexes [M2(H2L)2](ClO4)4·2MeCN (M = Co for Co2 and Fe for Fe2) were synthesized using a symmetric hydrazone ligand with the metal ions in an N6 coordination environment. The crystal structures and magnetic properties were determined by single-crystal X-ray diffraction and magnetic susceptibility measurements. The crystal structure study revealed that the spin centers were all in the high-spin state with a distorted octahedron (Oh) geometry. Dynamic magnetic properties measurements revealed that complex Co2 exhibited field-induced single-molecule magnet properties with two-step relaxation in which the fast relaxation path was from QTM and the slow relaxation path from the thermal relaxation under an applied field.

Search for different types of distinguishers are common tasks in symmetrickey cryptanalysis. In this work, we employ the constraint programming (CP) technique to tackle such problems. First, we show that a simple application of the CP approach proposed by Gerault et al. leads to the solution of the open problem of determining the exact lower bound of the number of active S-boxes for 6-round AES-128 in the related-key model. Subsequently, we show that the same approach can be applied in searching for integral distinguishers, impossible differentials, zero-correlation linear approximations, in both the single-key and related-(twea)key model. We implement the method using the open source constraint solver Choco and apply it to the block ciphers PRESENT, SKINNY, and HIGHT (ARX construction). As a result, we find 16 related-tweakey impossible differentials for 12-round SKINNY-64-128 based on which we construct an 18-round attack on SKINNY-64-128 (one target version for the crypto competition https://sites.google.com/site/skinnycipher announced at ASK 2016). Moreover, we show that in some cases, when equipped with proper strategies (ordering heuristic, restart and dynamic branching strategy), the CP approach can be very efficient. Therefore, we suggest that the constraint programming technique should become a convenient tool at hand of the symmetric-key cryptanalysts.

Background and objectiveThe relationship between antimitochondrial antibody (AMA) levels and the severity or prognosis of primary biliary cholangitis (PBC) is unclear. This study explored the clinical significance of serum IgG antimitochondrial M2 antibody (IgG-M2) levels.MethodsFrom 2008 to 2017, a retrospective analysis was conducted with PBC patients who had available quantitative values of serum IgG-M2 levels obtained with ELISA based on triple expression hybrid clones. The patients were divided into two groups based on high and low concentrations of IgG-M2. Baseline parameters, the incidence of adverse events, and prognosis were compared.ResultsAmong the 530 PBC patients, the levels of albumin, cholinesterase, hemoglobin, fibrinogen and triglycerides and the red blood cell count were significantly lower in the high-concentration group than in the low-concentration group (n = 263, 49.6%). The red cell distribution width (RDW) and levels of serum immunoglobulin (Ig) G, IgM and IgA were significantly higher in the high-concentration group than in the low-concentration group. Spearman's correlation analysis suggested that the correlation between the above baseline indicators and IgG-M2 levels was statistically significant but weak (r < 0.2, P < 0.05). In total, 203 patients were followed up, of whom 87 (42.9%) were in the high-concentration group. During the median follow-up period of 52 months (range: 28-75), 121 (59.6%) experienced hepatic decompensation, and 37 (18.2%) died or underwent liver transplantation. There was no significant difference in the incidence of complications or survival (log-rank test: P = 0.079) between the two groups. One year after ursodeoxycholic acid (UDCA) treatment, the two groups had similar responses. In addition, the levels of IgG-M2 did not fluctuate significantly during treatment.ConclusionIgG-M2 levels were not related to the disease severity, prognosis or efficacy of UDCA. The levels of IgG-M2 did not change significantly during treatment.

BcHpt is a core element of the high-osmolarity glycerol (HOG) transduction pathway in Botrytis cinerea. In contrast to other elements of the pathway, which have been characterized and proven to play important roles in vegetative differentiation, fungicide resistance, the multistress response, and virulence in B. cinerea, BcHpt (Histidine-containing phosphotransfer) is essential but uncharacterized in B. cinerea. Our previous study reported the first lysine acetylation site (Lys161) in BcHpt. In this study, the functions of this lysine acetylation site in BcHpt were characterized using site-directed mutagenesis. To mimic Lys161 acetylation, we generated the mutant strain ΔBcHPt + BcHptK161Q-GFP, which exhibited a slower growth rate; lower pathogenicity; higher sensitivity to multiple stresses, including osmotic and oxidative stresses, dicarboximides, and demethylation inhibitors (DMIs); and lower BcSak1 phosphorylation levels than wild-type B. cinerea. Constitutive acetylation of BcHpt Ly161 apparently inhibits hyphal growth, the multistress response, and sensitivity to fungicides in B. cinerea. Moreover, the lysine acetylation site affected phosphorylation of the MAPK BcSak1.

Fluorescence lifetime (FLT) of fluorophores is sensitive to the changes in their surrounding microenvironment, and hence it can quantitatively reveal the physiological characterization of the tissue under investigation. Fluorescence lifetime imaging microscopy (FLIM) provides not only morphological but also functional information of the tissue by producing spatially resolved image of fluorophore lifetime, which can be used as a signature of disorder and/or malignancy in diseased tissues. In this paper, we begin by introducing the basic principle and common detection methods of FLIM. Then the recent advances in the FLIM-based diagnosis of three different skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM) are reviewed. Furthermore, the potential advantages of FLIM in skin cancer diagnosis and the challenges that may be faced in the future are prospected.

High-osmolarity glycerol (HOG) signaling pathway belongs to mitogen-activated protein kinase (MAPK) cascades that regulate responses of organism to diverse extracellular stimuli. The membrane spanning proteins Sho1 and Sln1 serve as biosensors of HOG pathway in Saccharomyces cerevisiae. In this study, we investigated the biological functions of BcSHO1 and BcSLN1 in the gray mold fungus Botrytis cinerea. Target gene deletion demonstrated that both BcSHO1 and BcSLN1 are important for mycelial growth, conidiation and sclerotial formation. The BcSHO1 and BcSLN1 double deletion mutant ΔBcSln1-Sho1 produced much more, but smaller sclerotia than ΔBcSho1 and the wild-type (WT) strain, while ΔBcSln1 failed to develop sclerotia on all tested media, instead, formed a large number of conidia. Infection tests revealed that the virulence of ΔBcSln1-Sho1 decreased significantly, however, ΔBcSho1 or ΔBcSln1 showed no difference with the WT strain. In addition, ΔBcSln1-Sho1 exhibited resistance to osmotic stress by negatively regulating the phosphorylation of BcSak1 (yeast Hog1). All the phenotypic defects of mutants were recovered by target gene complementation. These results suggest that BcSHO1 and BcSLN1 share some functional redundancy in the regulation of fungal development, pathogenesis and osmotic stress response in B. cinerea.

Mathematical models are becoming increasingly important in magnetic resonance imaging (MRI), as they provide a mechanistic approach for making a link between tissue microstructure and signals acquired using the medical imaging instrument. The Bloch equations, which describes spin and relaxation in a magnetic field, are a set of integer order differential equations with a solution exhibiting mono-exponential behaviour in time. Parameters of the model may be estimated using a non-linear solver or by creating a dictionary of model parameters from which MRI signals are simulated and then matched with experiment. We have previously shown the potential efficacy of a magnetic resonance fingerprinting (MRF) approach, i.e., dictionary matching based on the classical Bloch equations for parcellating the human cerebral cortex. However, this classical model is unable to describe in full the mm-scale MRI signal generated based on an heterogenous and complex tissue micro-environment. The time-fractional order Bloch equations have been shown to provide, as a function of time, a good fit of brain MRI signals. The time-fractional model has solutions in the form of Mittag–Leffler functions that generalise conventional exponential relaxation. Such functions have been shown by others to be useful for describing dielectric and viscoelastic relaxation in complex heterogeneous materials. Hence, we replaced the integer order Bloch equations with the previously reported time-fractional counterpart within the MRF framework and performed experiments to parcellate human gray matter, which consists of cortical brain tissue with different cyto-architecture at different spatial locations. Our findings suggest that the time-fractional order parameters, α and β, potentially associate with the effect of interareal architectonic variability, which hypothetically results in more accurate cortical parcellation.

With the rapid development of urban economy and the continuous expansion of urban scale, the limitations of urban carrying capacity begin to appear. For the sustainable development of the city, more and more scholars are paying attention to the research onurban carrying capacity. Basedon the continuous research of the authors’ research group over the past ten years, this paper uses a multiscale geographically weighted regression model and method to explore the impact of geographical location, floor area ratio, public transportation, residents’ consumption level, the density of high-tech enterprises, and the ecological environment on the carrying capacity of the Shanghai metropolis. The results show that (1) the impact of geographical location on the bearing capacity decreases from downtown to the outer areas and from the northeastern area to the southwestern area of Shanghai. (2) On the whole, the elasticity of the average floor area ratio to the urban carrying capacity is 0.52%. In different regions, most of the central urban areas have exceeded the optimal average plot ratio. With an increase in the average plot ratio, the urban carrying capacity presents a downward trend. Other sample areas generally did not reach the average optimal plot ratio, especially the southwestern area of Shanghai. With an increase in the average plot ratio, the urban carrying capacity of this area improved significantly. (3) The elasticity of public transportation convenience to the urban carrying capacity is 0.23%; that is, the average increase in the urban carrying capacity is 0.23% for every 1% increase in public transportation convenience. The elasticity of residents’ consumption level is −0.18%; in other words, every 1% increase in residents’ consumption level will reduce the urban carrying capacity by 0.18% on average. The elasticity of the density of high-tech enterprises is 0.08%; hence, when the density of high-tech enterprises increases by 1%, the urban carrying capacity increases by 0.08% on average. Lastly, the elasticity of the eco-environmental status index is 0.17%; that is, every 1% increase in the eco-environmental status index increases the urban carrying capacity by 0.17% on average.

Hall-effect in semiconductors has wide applications for magnetic field sensing. Yet, a standard Hall sensor retains two problems: its linearity is affected by the non-uniformity of the current distribution; the sensitivity is bias-dependent, with linearity decreasing with increasing bias current. In order to improve the performance, we here propose a novel structure which realizes bias-free, photo-induced Hall sensors. The system consists of a semi-transparent metal Pt and a semiconductor Si or GaAs to form a Schottky contact. We systematically compared the photo-induced Schottky behaviors and Hall effects without net current flowing, depending on various magnetic fields, light intensities and wavelengths of Pt/GaAs and Pt/Si junctions. The electrical characteristics of the Schottky photo-diodes were fitted to obtain the barrier height as a function of light intensity. We show that the open-circuit Hall voltage of Pt/GaAs junction is orders of magnitude lower than that of Pt/Si, and the barrier height of GaAs is smaller. It should be attributed to the surface states in GaAs which block the carrier drifting. This work not only realizes the physical investigations of photo-induced Hall effects in Pt/GaAs and Pt/Si Schottky junctions, but also opens a new pathway for bias-free magnetic sensing with high linearity and sensitivity comparing to commercial Hall-sensors.

It is of great significance to detect faults correctly in continental sandstone reservoirs in the east of China to understand the distribution of remaining structural reservoirs for more efficient development operation. However, the majority of the faults is characterized by small displacements and unclear components, which makes it hard to recognize them in seismic data via traditional methods. We consider fault detection as an end-to-end binary image-segmentation problem of labeling a 3D seismic image with ones as faults and zeros elsewhere. Thus, we developed a fully convolutional network (FCN) based method to fault segmentation and used the synthetic seismic data to generate an accurate and sufficient training data set. The architecture of FCN is a modified version of the VGGNet (A convolutional neural network was named by Visual Geometry Group). Transforming fully connected layers into convolution layers enables a classification net to create a heatmap. Adding the deconvolution layers produces an efficient network for end-to-end dense learning. Herein, we took advantage of the fact that a fault binary image is highly biased with mostly zeros but only very limited ones on the faults. A balanced crossentropy loss function was defined to adjust the imbalance for optimizing the parameters of our FCN model. Ultimately, the FCN model was applied on real field data to propose that our FCN model can outperform conventional methods in fault predictions from seismic images in a more accurate and efficient manner.

Underwater fishing nets represent a danger faced by autonomous underwater vehicles (AUVs). To avoid irreparable damage to the AUV caused by fishing nets, the AUV needs to be able to identify and locate them autonomously and avoid them in advance. Whether the AUV can avoid fishing nets successfully depends on the accuracy and efficiency of detection. In this paper, we propose an object detection multiple receptive field network (MRF-Net), which is used to recognize and locate fishing nets using forward-looking sonar (FLS) images. The proposed architecture is a center-point-based detector, which uses a novel encoder-decoder structure to extract features and predict the center points and bounding box size. In addition, to reduce the interference of reverberation and speckle noises in the FLS image, we used a series of preprocessing operations to reduce the noises. We trained and tested the network with data collected in the sea using a Gemini 720i multi-beam forward-looking sonar and compared it with state-of-the-art networks for object detection. In order to further prove that our detector can be applied to the actual detection task, we also carried out the experiment of detecting and avoiding fishing nets in real-time in the sea with the embedded single board computer (SBC) module and the NVIDIA Jetson AGX Xavier embedded system of the AUV platform in our lab. The experimental results show that in terms of computational complexity, inference time, and prediction accuracy, MRF-Net is better than state-of-the-art networks. In addition, our fishing net avoidance experiment results indicate that the detection results of MRF-Net can support the accurate operation of the later obstacle avoidance algorithm.

Coronavirus disease 2019 (COVID-19) pandemic has led to a rare reduction in human activities. In such a background, data from ground-based environmental stations, satellites, and reanalysis materials are utilized to conduct a comprehensive analysis of the global air quality changes during the COVID-19 outbreak. The results showed that under the impact of the COVID-19 outbreak, a significant decrease in particulate matter (PM _x ) and nitrogen dioxide (NO _2 ) occurred in more than 40% of the world’s land area, with NO _2 (PM _x ) decreasing by ∼30% (∼20%). The mobility, meteorological factors, and the response speed to COVID-19 outbreaks were examined. It was further found that in quick-response cities, lockdowns produced a sharp decline in mobility and had a dominant impact on air quality. In contrast, in slow-response cities, mobility dropped gradually since the confirmation of the first COVID-19 case (FCC) and he impact of the FCC, lockdowns, and meteorological factors were comparable.

This paper developed a new type of disconnect switch contact with high-conductivity, oxidation resistance and wear resistance. Contact material and preparation were researched. The Cu–Cr–Zr alloy was prepared by vacuum induction melting, then the plate was obtained after rolling and aging strengthening. Contact sample was formed by die stamping, at last, a wear-resistant coating/Cu–Cr–Zr alloy switch contact was manufactured, after the silver antimony alloy hard coating was electroplated on the surface. In order to further study the Cu–Cr–Zr alloy and hard silver coating of the contact, microstructure analysis and performance testing are carried out. A large number of nano-sized pure Cr phases were found to exist in the Cu–Cr–Zr alloy matrix, and the material conductivity was 76.3% IACS. Compared with T2 copper, its mechanical properties and oxidation resistance were significantly improved, which helped to delay the corrosion progress of the substrate after the coating disappeared. The hard silver coating contains 1% of the alloy element Sb. Compared with the silver coating, its wear resistance was increased by 135.30%. Cu–Cr–Zr alloy and hard silver plating technology are effective for improving strength, corrosion resistance and wear resistance of contact.

Herein, we report on the growth of Cr4+–Li2CaGeO4 crystals by the flux growth method from the flux of LiCl, as well as on the effect of doping Li2CaGeO4 with Cr4+ ions on the NIR region spectral properties and crystal structure. The results quantified the occupancy of Cr4+ in Ge4+ sites. The emission spectrum presented broad bands in the NIR region, i.e., 1000–1500 nm excited by 980 nm, with maximum peaks at 1200 nm at room temperature caused by the transition of 3T2→3A2 in Cr4+ ions. The lifetime decreased with the Cr4+ ion doping concentration, specifically from 14.038 to 12.224 ms. The chemical composition and the valence state of chromium in Li2CaGeO4 were analyzed using X-ray photoelectron spectroscopy, which showed that the chromium in Li2CaGeO4 was tetravalent and no trivalent chromium was found. Therefore, the Cr4+–Li2CaGeO4 crystal has a great potential and future in optical applications.

An integrable lattice hierarchy is derived on the basis of a new matrix spectral problem. Then, some properties of this hierarchy are shown, such as the Liouville integrability, the bi-Hamiltonian structure, and infinitely many conservation laws. After that, the Darboux transformation of the first integrable lattice equation in this hierarchy is constructed. Eventually, the explicitly exact solutions of the integrable lattice equation are investigated via graphs.

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) is a gatekeeper of mitochondrial quality control. The present study was aimed to examine whether PINK1 possesses a protective function against gentamicin (GM)-induced sensory hair cell (HC) damage in vitro. The formation of parkin particles (a marker revealing the activation of PINK1 pathway which is a substrate of PINK1 and could signal depolarized mitochondria for clearance) and autophagy were determined by immunofluorescence staining. The expressions of PINK1, LC3B, cleaved-caspase 3 and p53 were measured by Western blotting. The levels of reactive oxygen species (ROS) and apoptosis were respectively evaluated by DCFH-DA staining, Annexin V Apoptosis Detection Kit and TUNEL staining. Cell viability was tested by a CCK8 kit. We found that treatment of 400 μM GM elicited the formation of ROS, which, in turn, led to PINK1 degradation, parkin recruitment, autophagy formation, an increase of p53 and cleaved-caspase 3 in HEI-OC1 cells and murine HCs. In contrast, co-treatment with ROS scavenger N-acetyl-L-cysteine (NAC) inhibited parkin recruitment, alleviated autophagy and p53 pathway-related damaged-cell elimination. Moreover, PINK1 interference contributed to a decrease of autophagy but an increase of p53 level in HEI-OC1 cells in response to GM stimulus. Findings from this work indicate that PINK1 alleviates the GM-elicited ototoxicity via induction of autophagy and resistance the increase of p53 in HCs.

CD4+CD25+Foxp3+ regulatory T cells (Tregs) accumulate in bone marrow microenvironment in acute myeloid leukemia (AML). However, little is known about how the tumor environment including tumor cells themselves affects this process. Here we demonstrated that AML cells expressed inducible T-cell costimulator ligand (ICOSL) that can provide costimulation through ICOS for the conversion and expansion of Tregs sustaining high Foxp3 and CD25 expression as well as a suppressive function. TNF-a stimulation up-regulated the expression of ICOSL. Furthermore, both the conversion and expansion of CD4+CD25+Foxp3+ T cells and CD4+ICOS+Foxp3+ T cells were induced by co-culture with AML cells overexpressed ICOSL. CD4+CD25+ICOS+ T cells possessed stronger ability to secrete IL-10 than CD4+CD25+ICOS− T cells. The mechanism by which IL-10 promoted the proliferation of AML cells was dependent on the activation of the Akt, Erk1/2, p38, and Stat3 signaling pathways. Blockade of ICOS signaling using anti-ICOSL antibody impaired the generation of Tregs and retarded the progression of an AML mice model injected with C1498 cells. The expression of ICOSL of patient AML cells and ICOS+ Tregs were found to be predictors for overall survival and disease-free survival in patients with AML, with ICOS+ Treg cell subset being a stronger predictor than total Tregs. These results suggest that ICOSL expression by AML cells may directly drive Treg expansion as a mechanism of immune evasion and ICOS+ Treg cell frequency is a better prognostic predictor in patients with AML.

Yak1, a member of the dual-specificity tyrosine phosphorylation-regulated protein kinases, plays an important role in diverse cellular processes in fungi. However, to date, the role of BcYak1 in Botrytis cinerea, the causal agent of gray mold diseases in various plant species, remains uncharacterized. Our previous study identified one lysine acetylation site (Lys252) in BcYak1, which is the first report of such a site in Yak1. In this study, the function of BcYak1 and its lysine acetylation site were investigated using gene disruption and site-directed mutagenesis. The gene deletion mutant ΔBcYak1 not only exhibits much lower pathogenicity, conidiation and sclerotium formation, but was also much more sensitive to H2O2 and the ergosterol biosynthesis inhibitor (EBI) triadimefon. The Lys252 site-directed mutagenesis mutant strain ΔBcYak1-K252Q (mimicking the acetylation of the site), however, only showed lower sclerotium formation and higher sensitivity to H2O2. These results indicate that BcYAK1 is involved in the vegetative differentiation, adaptation to oxidative stress and triadimefon, and virulence of B. cinerea.

Dexmedetomidine (DEX) is known to provide neuroprotective effect in the central nervous system. However, the detailed mechanism remains far more elusive. This study was designed to investigate the relevant mechanisms of DEX's neuroprotective effect. Sprague-Dawley (SD) rats were injected with dexmedetomidine and/or Lipopolysaccharide (LPS) intraperitoneally, and inflammatory cytokines in serum and in the hippocampus were measured by enzyme linked immunosorbent assay (ELISA). NF-κB in the brain tissue extracts was analyzed with western-blot. Then, we investigated whether NF-κB inhibitor prevents the elevation of inflammatory cytokines in rats injected with LPS. Our results indicated that compared with the control group, the rats exposed to LPS showed significant cognitive dysfunction. When compared to controls, the levels of TNF-α and IL-6 in the serum and hippocampus homogenate were increased in rats treated with LPS. DEX pretreatment inhibited the rats' TNF-α, IL-6 and NF-κB levels induced by LPS. In response to LPS, PDTC pretreatment restrains the production of proinflammatory cytokines (TNF-α and IL-6). Rats treated with PDTC and DEX alongside LPS exhibited less TNF-α and IL-6 than the LPS treated group. In combination, PDTC and DEX showed addictive effects. Our data suggest that DEX exerts a neuroprotective effect through NF-κB in part after LPS-induced cognitive dysfunction.