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Corticosterone (CORT) damages hippocampal neurons as well as induces neuroinflammation. The tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis is a form of programmed cell death, also known as inflammatory cell death. Menin is a multifunctional scaffold protein, which deficiency aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation as well as necroptosis and further investigated the mediatory role of Menin in this protective effect of itaconate by using an exposure of CORT to HT22 cells (a hippocampal neuronal cell line). The viability of HT22 cells was examined by the cell counting kit 8 (CCK-8). The morphology of HT22 cells was observed by transmission electron microscope (TEM). The expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) were evaluated by western blotting. The contents of inflammatory factors were detected by an enzyme-linked immunosorbent assay (ELISA) kit. Our results showed that CORT increases the contents of pro-inflammatory factors (IL-1β, TNF-α) as well as decreases the contents of anti-inflammatory factors (IL-4, IL-10) in HT22 cells. We also found that CORT increases the expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) and decreases the cell viability in HT22 cells, indicating that CORT induces necroptosis in HT22 cells. Itaconate improves CORT-induced neuroinflammation and necroptosis. Furthermore, itaconate upregulates the expression of Menin in CORT-exposed HT22 cells. Importantly, silencing Menin abolishes the antagonistic effect of itaconate on CORT-induced necroptosis and neuroinflammation. In brief, these results indicated that itaconate protects HT22 cells against CORT-induced neuroinflammation and necroptosis via upregulating Menin. [ABSTRACT FROM AUTHOR]

In image reconstruction for fluorescence molecular tomography (FMT), solving matrix equations of large scale can result in high computational costs. In this article, a method based on the wavelet-Schur decomposition is developed. In this method, the reconstruction problem for FMT is solved via the Schur decomposition in the wavelet domain. The proposed method can sufficiently explore the features of wavelet and Schur decomposition. The performance of convergence for reconstruction can be improved based on the proposed method. The results confirm that our method can improve the computational efficiency of reconstruction and achieve the high accuracy of reconstruction. [ABSTRACT FROM AUTHOR]

Sheet-like ZSM-5 zeolites with varied b-axis thicknesses (92, 160, 264 and 407 nm, respectively) and equivalent Si/Al molar ratios (ca. 150) were prepared using urea as additive in the aluminosilicate gels, and studied with respect to their performance in benzene alkylation with methanol. The ZSM-5 samples have similar textural properties and acidic properties. Catalytic tests show that these catalysts exhibit comparable benzene conversions of ca. 64% at 400 °C and WHSV of 2 h−1. The correlation between the selectivity of toluene and xylene and the ZSM-5 crystal size in the b-axis can be established. As the b axis length is decreased from 407 to 92 nm, the selectivity to toluene and xylene increases obviously from 80.3 to 87.4%, which is attributed to enhanced diffusion property of ZSM-5 zeolite. This finding provides an alternative strategy to improve the selectivity of toluene and xylene in the alkylation of benzene with methanol over ZSM-5-based catalysts. [ABSTRACT FROM AUTHOR]

Butyric acid is a volatile saturated monocarboxylic acid, which is widely used in the chemical, food, pharmaceutical, energy, and animal feed industries. This study focuses on producing butyric acid from pre-treated rape straw using simultaneous enzymatic hydrolysis semi-solid fermentation (SEHSF). Clostridium beijerinckii BRM001 screened from pit mud of Chinese nongxiangxing baijiu was used. The genome of C. beijerinckii BRM001 was sequenced and annotated. Using rape straw as the sole carbon source, fermentation optimization was carried out based on the genomic analysis of BRM001. The optimized butyric acid yield was as high as 13.86 ± 0.77 g/L, which was 2.1 times higher than that of the initial screening. Furthermore, under optimal conditions, non-sterile SEHSF was carried out, and the yield of butyric acid was 13.42 ± 0.83 g/L in a 2.5-L fermentor. This study provides a new approach for butyric acid production which eliminates the need for detoxification of straw hydrolysate and makes full use of the value of fermentation waste residue without secondary pollution, making the whole process greener and more economical, which has a certain industrial potential. [ABSTRACT FROM AUTHOR]

Sound source approaching is a typical task for the robot with auditory sensing. Many existing methods are based on sound source localization (SSL), and utilize the explicit location as the control input. To reduce the localization computation cost and improve the robustness against noise and reverberation, we propose a novel auditory feature driven model predictive control (AFD-MPC) method, which directly uses the auditory feature as the control input. First, a new convolution-ternarization based interaural time difference (CT-ITD) estimation method is proposed, which is more robust to noise and reverberation by eliminating signal spikes and irrelevant components. Second, a new system model is derived and established, which directly links the robot motions and the interaural time difference (ITD) feature. Third, AFD-MPC is realized based on the proposed CT-ITD feature estimation and system model. The states at multiple future time steps are predicted based on the system model, and a control objective function considering both target approaching and motion smoothness is designed. By involving the multi-step future states in the control objective function, the control outcome is more smooth on motion trajectory and more robust to instantaneous interferences. A series of experiments such as static and dynamic sound source approaching are conducted on a mobile robot equipped with a small-sized 6-microphone array to validate the effectiveness of our methods. [ABSTRACT FROM AUTHOR]

Spraying trajectory planning is a key and challenging work for intelligent spraying robot. In order to effectively fulfill spraying on complex surfaces without CAD model, a novel spraying trajectory planning method based on segmentation and trajectory sequence optimization is proposed in this paper, which is mainly composed by three steps: surface segmentation, trajectories generation and trajectories connection. In surface segmentation, a method named regional growth with minimum curvature point (RGMCP) is proposed to segment a 3D entity into different subsurfaces by taking normals and curvatures into consideration simultaneously. In trajectories generation step, an intersection of plane and point cloud (IPPC) algorithm is used to generate the optimal spraying trajectory for each segmented subsurface. Finally, for trajectories connection, a sequence optimization algorithm based on swap-evolution particles (SOSP) is proposed to connect all the subsurface trajectories as a complete spraying one in an optimum manner by regarding it as a sequence optimization problem. The effectiveness of the proposed method is validated by simulation and practical experiment simultaneously. Comparatively, our method can improve the efficiency of a spray task with 367 trajectories and 627 s time-consuming to 215 trajectories and 413 s, while the coating thickness variances are lowered from 51.9 µm2 and 30.4 µm2 to 3.64 µm2 and 7.89 µm2 respectively, which shows that the proposed method is more effective and can keep better coating thickness uniformity. [ABSTRACT FROM AUTHOR]

Person re-identification is an image retrieval technique for person in real scenes. Due to factors such as camera angle, lighting, and occlusion, there is a high intra-class variation in the representation of a specific sample. Furthermore, discriminative local regions such as hats and shoes are often ignored, resulting in some useful local information being unable to be used for retrieval. In this paper, a multi-scale feature fusion network model combining global and local features is proposed. The network is built with four stacked building block, where multi-scale features are assigned with different weights and fused according to the output conditions of each branch. In addition, a multi-attention mechanism network is combined with the multi-scale feature fusion in this paper. This method aims to enable the network to model the relation between input images, so as to effectively aggregate the features of neighbour person samples to obtain a more robust image representation. Experimental results show that the retrieval performance can be improved by the proposed method. [ABSTRACT FROM AUTHOR]

Using the linear combination operator method and variational technique improved by Tokuda, we obtain the expression of the effective mass of a strong coupled polaron in an anisotropic quantum dot. Due to the spin–orbit interaction, the effective mass of the polaron splits into two branches. The dependence of effective mass on temperature, electron–phonon coupling strength, transverse and longitudinal confinement lengths, and velocity is discussed by numerical calculation. The theoretical results indicate that the effective mass of the polaron is an increasing function of temperature and electron–phonon coupling strength, but a decreasing function of transverse confinement length, longitudinal confinement length, and velocity. The absolute value of spin splitting effective mass increases with the increase of temperature and spin–orbit coupling parameter, but decreases with the increase of transverse confinement length, longitudinal confinement length, and velocity. Due to the heavy hole characteristic, the spin splitting effective mass is negative. [ABSTRACT FROM AUTHOR]

SiO2 aerogels are widely utilized in the heat insulation industry due to their low density and thermal conductivity. To achieve large-scale preparation and reduce the cost, hydrophobic modification of SiO2 and solvent replacement assisted ambient pressure drying strategies are commonly employed. However, the resultant aerogels have been found to have high density, while the organic solvents used in their preparation are environmentally harmful. This study introduces a novel approach for aerogel-like materials preparation that utilizes a non-organic solvent and ambient pressure drying strategy. Methyltrimethoxysilane (MTMS) is used as the silicon source, with Cetyltrimethylammonium bromide (CTAB) serving as a surfactant to assist in the gelation of the silica sol. Additionally, Polytetrafluoroethylene (PTFE) emulsion, which shares the same charge attribute as the SiO2 sol, is added to prevent sedimentation during the gelation process. The resulting SiO2/PTFE aerogel-like materials exhibits a density of 0.0874 g/cm3, the lower reported value for aerogel-like materials prepared using ambient pressure drying. Furthermore, this aerogel-like materials demonstrates excellent hydrophobic properties and corrosion resistance. Even after high-temperature treatment, it retains its hydrophobicity and excellent thermal insulation performance. The water contact angle remains at 140° even after 1 week of exposure to HCl treatment, and its thermal conductivity is measured at 64.43 mW/m K. Overall, this materials holds great potential for application in the field of thermal insulation. Highlights: The prepared SiO2/PTFE aerogel-like materials can be dried at atmospheric pressure without surface modification and solvent replacement. Through electrostatic repulsion between PTFE emulsion and SiO2 sol, the sedimentation of SiO2 sol during gelation process was avoided. The SiO2/PTFE aerogel-like materials still has excellent hydrophobic properties after high-temperature treatment. [ABSTRACT FROM AUTHOR]

A mathematical morphological filter-based de-noising method is developed in this study for bridge cable force monitoring data. Structure elements, one of the most important parameters in the mathematical morphology, dominate de-noising effects. The de-noising effects subject to single structure element and multi-structure element filters are discussed based on the simulation signals. The results indicate that the de-noising effects by using the spherical structure element are better than using the straight line or rhombic structure element. Moreover, the multi-structure element filter outperforms the single one. Through simulation analysis, the de-noising performance of the low-pass filter, wavelet filter and morphological filter is compared. The results show that the performance of the wavelet and morphological filters is better than that of the low-pass filter. For low signal-to-noise signals, the performance of the wavelet filter is superior. With the increase of signal-to-noise ratio, the morphological filters show more advantages. Taking the cable force monitoring data of the 3rd Nanjing Yangtze River Bridge as an example, the de-noising performance of the wavelet and morphological filters is discussed. The results show that both the wavelet filters and morphological filters have satisfactory de-noising effects. The mathematical morphology method can provide an optional and effective de-nosing choice, which enriches the means of de-noising for bridge monitoring data. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage is a common neurological disease, and its pathological mechanism is complex. As the first recruited leukocyte subtype after intracerebral hemorrhage, neutrophils play an important role in tissue damage. In the past, it was considered that neutrophils performed their functions through phagocytosis, chemotaxis, and degranulation. In recent years, studies have found that neutrophils also have the function of secreting extracellular traps. Extracellular traps are fibrous structure composed of chromatin and granular proteins, which plays an important role in innate immunity. Studies have shown a large number of neutrophil extracellular traps in hematoma samples, plasma samples, and drainage samples after intracerebral hemorrhage. In this paper, we summarized the related mechanisms of neutrophil external traps and injury after intracerebral hemorrhage. Neutrophil extracellular traps are involved in the process of brain injury after intracerebral hemorrhage. The application of related inhibitors to inhibit the formation of neutrophil external traps or promote their dissolution can effectively alleviate the pathological damage caused by intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

The study aimed to assess the biocompatibility and efficacy of a prostatic urethral lift (PUL) for benign prostatic hyperplasia (BPH). Human BPH-1 cells were co-cultured with implant anchors and sutures, and cytotoxicity was measured. Scanning electron microscopy (SEM) was used to observe adhesion and growth of cells and to evaluate implant biocompatibility. Fifteen male beagle dogs were randomly assigned to the surgical (n = 9) or sham-operated (n = 6) groups. The surgical group underwent cystotomy, and PUL was used to insert two implants in each lobe of the prostate to compress the enlarged prostate and dilate the urethra; the sham group underwent cystotomy without implant insertion. Compared with the control group, no significant difference in cell viability among the groups with different co-culture times of implant anchors and sutures (P > 0.05) was observed. SEM revealed good adhesion and growth of prostate cells on the implants. Improvements in urine flow rates remained stable at 7, 28, and 180 days after surgery, and the urethral diameter in the prostate region was significantly increased compared with that before surgery. PUL is a biocompatible and effective treatment for BPH, improving the urine flow rate without causing inflammation, tissue damage, or cytotoxic effects. Here, the basis for further PUL application was provided. [ABSTRACT FROM AUTHOR]

Background: Chimonanthus praecox and Chimonanthus salicifolius are closely related species that diverged approximately six million years ago. While both C. praecox and C. salicifolius could withstand brief periods of low temperatures of – 15 °C. Their flowering times are different, C. praecox blooms in early spring, whereas C. salicifolius blooms in autumn. The SBP-box (SQUAMOSA promoter-binding protein) is a plant-specific gene family that plays a crucial vital role in regulating plant flowering. Although extensively studied in various plants, the SBP gene family remains uncharacterized in Calycanthaceae. Methods and results: We conducted genome-wide identification of SBP genes in both C. praecox and C. salicifolius and comprehensively characterized the chromosomal localization, gene structure, conserved motifs, and domains of the identified SBP genes. In total, 15 and 18 SBP genes were identified in C. praecox and C. salicifolius, respectively. According to phylogenetic analysis, the SBP genes from Arabidopsis, C. praecox, and C. salicifolius were clustered into eight groups. Analysis of the gene structure and conserved protein motifs showed that SBP proteins of the same subfamily have similar motif structures. The expression patterns of SBP genes were analyzed using transcriptome data. The results revealed that more than half of the genes exhibited lower expression levels in leaves than in flowers, suggesting their potential involvement in the flower development process and may be linked to the winter and autumn flowering of C. praecox and C. salicifolius. Conclusion: Thirty-three SBPs were identified in C. praecox and C. salicifolius. The evolutionary characteristics and expression patterns were examined in this study. These results provide valuable information to elucidate the evolutionary relationships of the SBP family and help determine the functional characteristics of the SBP genes in subsequent studies. [ABSTRACT FROM AUTHOR]

The robot-task-sequencing planning problem is investigated in this paper, where multi-robot tasks with resource conflicts and precedence constraints are involved making the problem challenging and complex. An effective approach is proposed to minimize the production cycle time while handling the high complexity effectively. The approach decouples the entire problem into simpler ones and then solves them separately to obtain the final solution. Firstly, given the multi-robot tasks, how to coordinate the operation of each single robot is determined. This is achieved by searching the shortest path in the graph where the tasks are organized in the optimal order without the consideration of resource constraints. Then, the resource allocation is modeled as a constrained assignment problem with the objective of minimal cycle time, which is solved with graph optimization. Consequently, the best-fit robot configurations for task execution are selected according to a heuristic optimality metric, based on which the task execution sequence obtained in previous steps is re-optimized. Finally, the robots involved in the task are regarded as a whole to deduce feasible trajectories. Experimental results demonstrate that the proposed approach can generate solutions where the robot can complete the given tasks effectively with feasible scheduling. Moreover, the proposed approach is successfully implemented in a pragmatic system which tests signals at both ends of components in a circuit board. [ABSTRACT FROM AUTHOR]

Investigating gene function relies on the efficient manipulation of endogenous gene expression. Currently, a limited number of tools are available to robustly manipulate endogenous gene expression between "on" and "off" states. In this study, we insert a 63 bp coding sequence of T3H38 ribozyme into the 3' untranslated region (UTR) of C. elegans endogenous genes using the CRISPR/Cas9 technology, which reduces the endogenous gene expression to a nearly undetectable level and generated loss-of-function phenotypes similar to that of the genetic null animals. To achieve conditional knockout, a cassette of loxP-flanked transcriptional termination signal and ribozyme is inserted into the 3' UTR of endogenous genes, which eliminates gene expression spatially or temporally via the controllable expression of the Cre recombinase. Conditional endogenous gene turn-on can be achieved by either injecting morpholino, which blocks the ribozyme self-cleavage activity or using the Cre recombinase to remove the loxP-flanked ribozyme. Together, our results demonstrate that these ribozyme-based tools can efficiently manipulate endogenous gene expression both in space and time and expand the toolkit for studying the functions of endogenous genes. Manipulation of endogenous genes in space and time in C. elegans is accomplished by inserting a ribozyme sequence into the 3'UTR with CRISPR/Cas9, utilizing self-cleavage of the ribozyme and Cre/loxP system as an "off and "on" switch, respectively. [ABSTRACT FROM AUTHOR]

An accurate assessment of human exposure to pollutants through the ingestion of dust and/or soil particles depends on a thorough understanding their rate of human ingestion. To this end, we investigated the load and size distribution patterns of dust/soil particles on the hands of three typical subpopulations, including preschoolers, college students, and security guards (outdoor workers). The geometric mean diameter of dust/soil particles on hands was observed to be 38.7 ± 11.2, 40.0 ± 12.1, and 36.8 ± 10.4 μm for preschoolers, college students, and security guards, respectively. The particle size distribution differed between subpopulations: Preschoolers were more exposed to fine particles, whereas security guards were exposed to more coarse particles. The geometric means of dust/soil particle loading on the hands were 0.126, 0.0163, and 0.0377 mg/cm2 for preschoolers, college students, and security guards, respectively. Males had statistically higher dust/soil particle loadings on hands than females, notably for preschoolers and college students; preschoolers with frequent hand contact with the bare ground had higher dust/soil particle loadings compared to those of peers in contact with commercial and residential grounds. The mean total dust/soil particle ingestion rate was estimated to be 245, 19.7, and 33.1 mg/day for preschoolers, college students, and security guards, respectively. Our estimates for college students and security guards are close to the consensus central-tendency values recommended by the U.S. EPA's Exposure Factor Handbook for American adults, whereas the estimates for children are much higher than the upper percentile values recommended for American children. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare low-temperature tolerances in different strains of large yellow croaker. Dai Qu (DQ), Min-Yue Dong (MY), and Quan Zhou (NZ) strains of large yellow croaker were subjected to cold stress (8.6 °C) for 12 h, 24 h, 48 h, and 96 h. Survival rate, histological observation, and antioxidant and energy metabolism indicators were determined. The results showed that compared with the DQ group and MY group, NZ group aggravated hepatic structure, enhanced ROS, lactate, and anaerobic metabolism (PK gene expression and activity), while inhibited ATP, GSH, antioxidant enzymes (mRNA levels and activities of SOD, GPx, and CAT), and aerobic metabolism enzymes (mRNA levels and activities of F-ATPase, SDH, and MDH), indicating the reduction of cold tolerance in the NZ group was closely correlated with the decrement of antioxidative capacity and energy metabolism efficiency. Nrf2 and AMPK gene expressions were correlated with antioxidant and energy metabolism mRNA levels, respectively, suggesting Nrf2 and AMPK might participate in the modulation of target genes during the cold-stress adaptation. In conclusion, low temperature tolerance of fish depended on the antioxidant defense and energy metabolism efficiency, which contributes to understanding the underlying mechanisms of cold adaptation in large yellow croaker. [ABSTRACT FROM AUTHOR]

Mutation-based greybox fuzzing has been one of the most prevalent techniques for security vulnerability discovery and a great deal of research work has been proposed to improve both its efficiency and effectiveness. Mutation-based greybox fuzzing generates input cases by mutating the input seed, i.e., applying a sequence of mutation operators to randomly selected mutation positions of the seed. However, existing fruitful research work focuses on scheduling mutation operators, leaving the schedule of mutation positions as an overlooked aspect of fuzzing efficiency. This paper proposes a novel greybox fuzzing method, PosFuzz, that statistically schedules mutation positions based on their historical performance. PosFuzz makes use of a concept of effective position distribution to represent the semantics of the input and to guide the mutations. PosFuzz first utilizes Good-Turing frequency estimation to calculate an effective position distribution for each mutation operator. It then leverages two sampling methods in different mutating stages to select the positions from the distribution. We have implemented PosFuzz on top of AFL, AFLFast and MOPT, called Pos-AFL, -AFLFast and -MOPT respectively, and evaluated them on the UNIFUZZ benchmark (20 widely used open source programs) and LAVA-M dataset. The result shows that, under the same testing time budget, the Pos-AFL, -AFLFast and -MOPT outperform their counterparts in code coverage and vulnerability discovery ability. Compared with AFL, AFLFast, and MOPT, PosFuzz gets 21% more edge coverage and finds 133% more paths on average. It also triggers 275% more unique bugs on average. [ABSTRACT FROM AUTHOR]

An experimental investigation is made for evaluating the long-term creep behavior of a compacted clay under low confining pressure (from 12 to 50 kPa). Specimens compacted at the natural dry density and natural water content were first subjected to consolidated undrained shear tests to determine the shear strength. Undrained triaxial creep tests were thereafter conducted to study the axial strain versus time relationships under different deviatoric stress levels which were determined referencing the shear strength. Mercury intrusion porosimetry tests were performed to track the evolution of the microstructure during the undrained creep. Testing results showed that (i) the diameter of the dominant pores within the clay increases under low confining pressure but decreases under higher confining pressure after undrained creep, (ii) all axial strain versus time relationships show attenuated or transitional characteristics and no creep rupture occurs, and (iii) the proportion of total progressive axial strain in the total axial strain increases with the increasing deviatoric stress level and decreasing confining pressure. Three approaches were used to predict the measured axial strain versus time relationships under low confining pressures. Good agreements have been achieved between the predictions and measurements obtained in this study, which confirms the validity of the proposed approaches. [ABSTRACT FROM AUTHOR]

The photovoltaic performance of mesoscopic perovskite solar cells (PSCs) is strongly dependent on the interface between perovskite and electron transport layer. Herein, an attempt to load facile processed ZnO quantum dots (ZQDs) or TiO2 quantum dots (TQDs) into the mesoporous TiO2 (mp-TiO2) layer via a simple spin coating method was performed. Both of them had huge impact on the morphology of perovskite films, leading to larger perovskite grains. However, the power conversion efficiency (PCE) of these two kinds of QDs modified cells exhibited a different tendency. The champion PCE of ZQDs modified PSCs was remarkably improved from 14.54 to 17.2%, while for that of TQDs modified ones decreased to 11.78%. It was demonstrated that the enhanced PCE and short-circuit current (Jsc) were attributed to the enlarged grain size and enhanced light absorption of perovskite film, faster electron extraction and transport as well as less recombination for ZQDs modified PSCs, which mainly resulted from the increased active specific surface area. On the contrary, the deterioration of TQDs modified PSCs was ascribed to the aggregation of TQDs, which sharply decreased the specific surface area of the electron transport layer. This work provided an efficient and facile way to improve the photovoltaic performance of mesoscopic PSCs. [ABSTRACT FROM AUTHOR]

Infinite volume expansion and uncontrolled lithium dendrite growth are the main bottlenecks that greatly hinder the commercial application of lithium metal anodes. Herein, derived from zeolitic imidazolate framework (ZIF)-67, carbon nanotubes (CNTs)-wrapped and CoP/Co2P uniformly distributed nitrogen-doped hollow porous polyhedron carbon (CNT-CoP@NC) is elaborately designed as lithium metal host. A hybrid of N-doping and metallic phosphides modifications improves the lithiophilicity and reduces the nucleation barrier, consequently leading to homogeneous nucleation and smooth deposition of metallic lithium, thus suppresses the growth of Li dendrites. Meanwhile, self-generated CNTs arrays efficiently reduce the local current density. Moreover, the reduced lithium is preferentially deposited into the hollow structure of CNT-CoP@NC and then filled the voids among the CNT-CoP@NC particles. This all-pervasive Li plating design can not only alleviate the volume effect, but also maximize the anode space utilization. Benefiting from these synergistic modulations, even with an ultra-thin (7.2 µm) anode layer of CNT-CoP@NC host, a high Coulombic efficiency for more than 400 cycles and an extended lifespan of 1,700 h under 1 mA·cm−2 can be achieved. When paired with a competitive high mass loading (17.1 mg·cm−2) LiFePO4 cathode, a superb cycling stability (126.7 mAh·g−1 over 550 cycles) is recorded at 1 C. [ABSTRACT FROM AUTHOR]

The difficulties of injured and degenerated neurons to regenerate neurites and regain functions are more significant than in other body tissues, making neurodegenerative and related diseases hard to cure. Uncovering the secrets of neural regeneration and how this process may be inhibited after injury will provide insights into novel management and potential treatments for these diseases. Caenorhabditis elegans and Drosophila melanogaster are two of the most widely used and well-established model organisms endowed with advantages in genetic manipulation and live imaging to explore this fundamental question about neural regeneration. Here, we review the classical models and techniques, and the involvement and cooperation of subcellular structures during neurite regeneration using these two organisms. Finally, we list several important open questions that we look forward to inspiring future research. [ABSTRACT FROM AUTHOR]

China is actively upgrading its industrial structure through industries transferring between developed and undeveloped areas; however, the overall level of the national value chain is still not high, and the asymmetric competition pattern between the upstream and the downstream has not been broken. Therefore, this paper establishes a competitive equilibrium model for the production of manufacturing enterprises, with factor price distortion, under the condition of constant returns to scale. The authors derive the relative distortion coefficients of each factor price, calculate the misallocation indices of capital and labor, and construct an industry resource misallocation measure. Furthermore, this paper applies the regional value-added decomposition model to calculate the national value chain index and matches the market index of the China Market Index Database with the Chinese Industrial Enterprises Database and the Inter-Regional Input-Output Tables through quantitative analysis. From the perspective of the national value chain, the authors study the improvement effect and mechanism of the business environment on the resource allocation in industry. The study shows that industry resource allocation will be improved by 17.89% if the business environment level is improved by one standard deviation. This effect is most prevalent in the eastern and central regions, not so much in the west; the effect of downstream industries in the national value chain is higher than that of upstream industries; the improvement effect on capital allocation is higher in downstream industries than in the upstream industries; and the improvement effect on labor misallocation is basically the same in both the upstream and the downstream. Compared with labor intensive industries, capital intensive industries are more influenced by the national value chain, while the effect of upstream industries is weaker. At the same time, it is well documented that participation in the global value chain can improve the efficiency of regional resource allocation, and the construction of high-tech zones can improve resource allocation for both upstream and downstream industries. Based on the results of study, the authors propose suggestions for optimizing business environments, suiting the national value chain construction, and improving resource allocation in the future. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). Methods: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. Results: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. Conclusions: ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization. [ABSTRACT FROM AUTHOR]

Cysteinyl aspartate-specific protease 8 (caspase-8) plays a key role in various biological processes by regulating apoptosis. Therefore, this makes accurate detection and intracellular imaging of caspase-8 of great importance for drug screening, disease diagnosis, and prognostication. Here, by designing a reduced graphene oxide (rGO) quenched peptide probe, we constructed a new biosensing system for monitoring in vitro and intracellular caspase-8 activity. In this system, a fluorophore-labeled peptide and rGO were used as the substrate of caspase-8 and the fluorophore quencher, respectively. The hydrolysis of caspase-8 on the polypeptide probe substrate can generate two fragments with different lengths. The release of the short fragment labeled with the fluorophore causes recovery of the fluorescence signal (Ex/Em = 520/576 nm). Under the optimized conditions, the proposed fluorescence method exhibited a linear response range of 0.2 to 5 U·mL−1 for caspase-8 with a limit of detection (LOD) of 0.2 U·mL−1 in vitro. Furthermore, this method has been successfully applied to monitoring the upregulation of intracellular caspase-8 activity caused by tert-butyl hydroperoxide (TBHP) and fluorouracil. Flow cytometry assay indicated the positive relation between the upregulation of intracellular caspase-8 activity and cell apoptosis rate. In summary, the above results demonstrated the practical application of this method for apoptosis-related cell imaging. [ABSTRACT FROM AUTHOR]

Grey-box fuzzing techniques have been widely used in software bug finding. In general, there are many decisions to make in the fuzzing process, including which code block in the target program should be explored first, which bytes of an input seed should be mutated to reach the target code block, and how to mutate the chosen input bytes. However, existing solutions usually rely on random exploration or certain heuristics to choose where and how to fuzz, which limits the efficiency of fuzzing. In this paper, we propose a novel solution CAMFuzz to guide the fuzzing process with explainable decisions in explainable artificial intelligence (XAI). First, we propose a dynamic weight adjustment algorithm, which considers both the difficulty of reaching a block and the number of unvisited blocks nearby, to find code blocks worthy to explore first. Second, we utilize a widely used local interpretation technique, i.e., class activation mapping (CAM), to recognize which part of an input seed should be mutated to reach a given target code block. Therefore, CAMFuzz can distinguish which part of code in the program is more important and which positions in the input file should be mutated first, in order to achieve a better code coverage and bug finding efficiency. Third, to further help the fuzzer increase fuzzing efficiency, we leverage a lightweight static program analysis to help the fuzzer identify magic values. We implement a prototype of CAMFuzz and evaluate it on 13 real-world programs (including 11 open source targets, 2 closed-source commercial products including a Microsoft component and Hancom Office) Results show that CAMFuzz outperforms state-of-the-art fuzzers in both code coverage and bug finding. To detail, CAMFuzz on average achieves 2.07 × more bugs and 1.17 × coverage improvements. In total, it found 19 previously unknown vulnerabilities, of which 6 have been assigned by CVE so far. [ABSTRACT FROM AUTHOR]

Polypropylene (PP) foams have received tremendous attention because of its outstanding performance such as higher tensile modulus, impact resistance and excellent chemical resistance. But the poor pore structure on account of low melt strength leads to poor mechanical properties. In this work, a novel organic silicon-carbon type foam stabilizer was introduced to obtain PP foam with excellent properties. The foam stabilizer contained long carbon chain with good compatibility with the PP melt as well as -Si-O-Si- with good compatibility with the cells. Thus, the surface tension of the system was reduced. The results shown that the foam stabilizer we prepared could significantly reduce the size, size distribution and density of the cells. Besides, when 1.0 wt.% of foam stabilizer was added, the mechanical properties had also been significantly improved: the tensile strength and the elongation at break was 18.7 MPa and 499%, increased by 16.1 and 55%, respectively. [ABSTRACT FROM AUTHOR]

Over the last two decades, thousands of genome-scale metabolic network models (GSMMs) have been constructed. These GSMMs have been widely applied in various fields, ranging from network interaction analysis, to cell phenotype prediction. However, due to the lack of constraints, the prediction accuracy of first-generation GSMMs was limited. To overcome these limitations, the next-generation GSMMs were developed by integrating omics data, adding constrain condition, integrating different biological models, and constructing whole-cell models. Here, we review recent advances of GSMMs from the first generation to the next generation. Then, we discuss the major application of GSMMs in industrial biotechnology, such as predicting phenotypes and guiding metabolic engineering. In addition, human health applications, including understanding biological mechanisms, discovering biomarkers and drug targets, are also summarized. Finally, we address the challenges and propose new trend of GSMMs. Key points: •This mini-review updates the literature on almost all published GSMMs since 1999. •Detailed insights into the development of the first- and next-generation GSMMs. •The application of GSMMs is summarized, and the prospects of integrating machine learning are emphasized. [ABSTRACT FROM AUTHOR]

Water supply reservoirs form one of the critical drinking water resources. Their water quality directly affects human health. However, reservoir sediments have not received adequate attention in antibiotic resistance genes (ARGs) dissemination, though they reflect long-term ARGs contamination of water supply reservoirs. Moreover, the physicochemical parameters in water supply reservoir sediments are generally better than those in the other media. Thus, the main ARGs biotic drivers of the media would demonstrate their unique characteristics. In this study, sediment samples were collected from 10 water supply reservoirs in central China, and the antibiotic resistomes were determined with the metagenomic method. As revealed from the results, 174 ARGs (18 ARG types) were detected in the reservoir sediment. Besides, multidrug-, sulfonamide-, and vancomycin-ARGs were the dominant ARGs in the sediment samples. The macrolide-resistant Microcystis was prevalent (100% detection frequency with 0.35% average percentage) in reservoir sediments and posed potential risks to human health. Furthermore, the results of the Mantel test and VPA demonstrated that mobile genetic elements (MGEs) were the more essential biotic drivers in ARG contents of reservoir sediments rather than the bacteria community. [ABSTRACT FROM AUTHOR]

Robot control based on audition plays an important role in many robot applications, which is generally implemented by three steps: aural features extraction, sound source localization and approaching control strategy. This paper presents a novel and practical auditory perception and control method adoptable to the small-sized microphone array. Firstly, a novel aural feature extraction strategy, namely dynamic signals matching (DSM), is proposed to search for the matching points of the signals with similarity measurement based on gradient and amplitude by dynamic programming. Secondly, a new sound source localization method called steered grid search (SGS) is proposed, which combines the source localization method based on time delay of arrival (TDOA) and spatial search strategy to achieve the robustness and real-time performance. Thirdly, inspired by image-based visual control, the interaction matrix is deduced and applied to transform the spatial information of the sound source into auditory control, based on which a mechanism for robot to approach the sound source is implemented. Finally, we apply our methods to a mobile robot equipped with a small array of six microphones. The experimental results show the feasibility and the suitability of our method under adverse conditions. [ABSTRACT FROM AUTHOR]

Nitrogen and phosphorus stratification is crucial for ecosystem dynamics in deep lakes and reservoirs. It is critical for water quality management to understand the characteristics of nitrogen and phosphorus stratification and its driving forces. In this study, high-frequency total nitrogen (TN) and total phosphorus (TP) from January 2017 to October 2019 were estimated using the datasets of high-frequency buoy parameters, including water temperature, pH, chlorophyll-a, oxidation–reduction potential, dissolved oxygen, and fluorescent dissolved organic matter. The results revealed that both nitrogen and phosphorus in water column were periodically stratified. Specifically, the stratification of nitrogen and phosphorus occurred from April to December or January of the following year. Moreover, indices of TN stratification (IC-TN) and TP stratification (IC-TP) were − 0.29 ~ 0.05 and − 0.78 ~ 0.28, respectively. Significant (P < 0.01) positive correlations were observed between RWCS (an index of thermal stability) and IC-TN (or IC-TP), indicating thermal stratification may be the main driving force of nutrient stratification at inter-month scales. Further analysis indicated that the thermal stratification may affect nitrogen and phosphorus stratification though (1) influencing algal growth and (2) affecting the release of internal sources and the material exchange between water columns. Furthermore, precipitation is also suggested as an important factor affecting the stability of nitrogen and phosphorus vertical profile in the flood season. These findings may provide important information for optimizing water quality management efforts in Qiandaohu and other subtropical deep reservoirs. In addition, the knowledge of the effect of temperature and precipitation on nutrient stratification are essential to understand future ecosystem dynamics of deep reservoirs. [ABSTRACT FROM AUTHOR]

The focus of this paper was directed towards investigating the influence of multiple freeze–thaw (FT) cycles on the mechanical behaviors of an expansive soil under a wide range of confining stresses (σc) from 0 to 300 kPa. Consolidated undrained (CU) shear tests with pore pressure measurement (σc = 10–300 kPa) and unconfined compression (UC) tests (σc = 0 kPa) were conducted on FT impact specimens to derive the shearing stress–strain relationships and the associated mechanical properties including (i) failure strength (qu), elastic modulus (Eu), effective and apparent cohesion (c′ and c), and effective and apparent friction angle (ϕ′ and ϕ) obtained from CU tests and (ii) qu and reloading modulus (E1%) and stress (Su1%) at 1% strain obtained from UC tests. Besides, the influence of FT cycles on the soil structure was investigated using mercury intrusion porosimetry (MIP) and scanning electron microscope (SEM) tests. Testing results show that FT cycles mainly influence the soil's macropores with diameters between 5 and 250 μ. Cracks develop during FT cycles and result in slight swelling which contributes to an increase in the global volume of the soil specimens. There is a significant reduction in the investigated mechanical properties after FT cycles. They typically achieve equilibrium after about six cycles. The shearing stress–strain curves transit from strain-softening to strain-hardening as the confining stress increases. A simple empirical model is developed to well describe the strain-softening behavior of the stress–strain curves under low confining stresses. [ABSTRACT FROM AUTHOR]

Using lightweight networks for facial expression recognition (FER) is becoming an important research topic in recent years. The key to the success of FER with lightweight networks is to explore the potentials of expression features in distinct abstract levels and regions, and design robust features to characterize the facial appearance. This paper proposes a lightweight network called Multi-feature Fusion Based Convolutional Neural Network (MFF-CNN), for image-based FER. The proposed model uses the Image Branch to extract both mid-level and high-level global features from the whole input image and utilizes the Patch Branch to extract local features from sixteen image patches of the original image. In MFF-CNN, feature selection based on L2 norm is performed to obtain more discriminative local features. Joint tuning is employed to integrate the two branches and fuse features. Experiment results on three widely used datasets, CK+, JAFFE and Oulu-CASIA show the proposed MFF-CNN outperforms the state-of-the-art methods in terms of average recognition accuracy. Compared to other competitive models with similar or larger number of parameters, our MFF-CNN improves the average recognition accuracy by 9.80% to 15.05%. [ABSTRACT FROM AUTHOR]

Intracerebral haemorrhage (ICH) can be a catastrophic event; even if the initial stages of the pathology were well-managed, a number of patients experience varied residual neurological deficits following the insult. Ferroptosis is a recently identified type of cell demise which is tightly linked to the neurological impairment associated with ICH. In the current work, the prophylactic impact of scalp acupuncture (SA) therapy on autologous blood injection murine models of ICH was investigated in order to establish whether SA could mitigate the secondary damage arising following ICH by moderating ferroptosis. The pathophysiological mechanisms associated with this process were also explored. Ludmila Belayev tests were utilised for the characterisation of neurological damage. Haematoxylin–eosin staining was employed in order to determine the cerebral impact of the induced ICH. Malondialdehyde (MDA) and iron titres in peri-haemorrhagic cerebral tissues were appraised using purchased assay kits. Transmission electron microscopy delineated mitochondrial appearances within nerve cell bodies from the area of haemorrhage. Western blotting techniques were utilised to assay the degree of protein expression of NeuN, sequestosome 1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1). The frequencies of Nrf2, GPX4 and FTH1 positive cells, respectively, were documented with immunohistochemical staining. The results demonstrated that therapy with SA after ICH mitigated MDA and iron sequestration, diminished the appearance of contracted mitochondria with increased outer mitochondrial membrane diameter within the nerve cell bodies, and suppressed neuronal ferroptosis. The pathways responsible for these effects may encompass amplified p62, Nrf2, GPX4 and FTH1 expression, together with decreased Keap1 expression. Application of SA reduced identified neurobehavioural abnormalities after ICH; no disparities were observed between the consequences of SA therapy and deferoxamine delivery. It can be surmised that intervention with SA enhanced recovery after ICH by triggering the antioxidant pathway, p62/Keap1/Nrf2, and causing FTH1 and GPX4 upregulation, factors that participate in diminishing excess iron and thus in mitigating lipid peroxidation insults arising from ferroptosis following ICH. [ABSTRACT FROM AUTHOR]

Motivated by the increasing demands on complex borehole trajectories in oil and gas directional drilling, an adaptive fault-tolerant control (AFTC) method for drilling trajectory tracking and rectification of rotary steerable system (RSS) is proposed by adopting actor-critic reinforcement learning (RL) and integral sliding mode control (ISMC) in the presence of system uncertainties and fault signals. Considering a discrete delay differential equation (DDE) with distance delays, uncertainties and fault signals, first we design an online learning framework via actor-critic RL and radial basis function neural network (RBFNN) in order to make drill bit can track pre-designed trajectory accurately and smoothly. Then in order to handle the fault signals problem, we utilize ISMC to eliminate it as weak as possible and rectify drilling trajectory which may derivate original direction caused by it. The system stability and convergence have been analyzed to ensure uniformly ultimately boundedness of tracking errors and fault-tolerant control signals. The proposed method would have wide application potentials in realizing the trajectory tracking and rectification with automatic operations of directional drilling. The effectiveness and accuracy of it are validated by simulation results with ramp and sine input signals. [ABSTRACT FROM AUTHOR]

The parallel-coupled double circular mesoscopic Josephson junction devices connecting to two photon reservoirs are investigated, and the time-dependent photonic heat current formula is derived. The time-oscillating structures of heat current are contributed by the superposition of heat current branches with frequencies 0 , ± ω i , ± 2 ω i ( i = 1 , 2 ). The frequency ratio ω 2 / ω 1 of field-induced oscillation branches dominates the current evolution structure. The main oscillation wave package can be superposed by multiple resonant peaks as the two frequencies do not match entirely. As magnetic fluxes Φ i possess the relation Φ 2 = m Φ 1 , the dc photonic heat current versus Φ 1 exhibits maximum values with equal height located at Φ 1 = n Φ 0 , where m, n are integers, and Φ 0 is the flux quantum. The main peaks are split to form multi-peak structure, and the number of split resonant peaks in a period Φ 0 is equal to m. The detailed behavior is intimately ascribed to whether m being odd or even. [ABSTRACT FROM AUTHOR]

This study investigates the influences of moisture content and freeze–thaw (FT) cycles on the compression behaviors of a compacted clay. Compacted specimens were first conditioned to different moisture contents (w) and then subjected to FT cycles. The treated specimens were either (i) directly used for constant water content (CW) compression tests or (ii) saturated and used for conventional consolidation tests to determine the compression curves under unsaturated and saturated conditions, respectively. Mercury intrusion porosimetry (MIP) tests were performed to track the evolution of the soil’s pore structure during moisture and FT conditionings. The compression indexes (including the recompression index Cr, preconsolidation pressure σvp or σ’vp, and compression index Cc of the specimens) derived from the experimental results demonstrate that (i) within the initial elastic compression range, the Cr is independent of moisture content changes but increases after FT conditioning. The variations of Cr are associated with the volume of soil’s large pores (el), which remains constant during moisture conditioning but increases after FT cycles; (ii) within the elastoplastic compression range, the σvp or σ’vp increases, while the Cc decreases as the moisture content decreases. However, the σvp, σ’vp, and Cc decrease after FT cycles. The σvp, σ’vp, and Cc are related to the volume of the soil’s medium pores (em), which decreases after moisture and FT conditionings. A few unique relationships are established to reveal the influences of pore structure changes on compression characteristics. The variations of the soil’s shrinkage curves under different external stress are also analyzed considering the effects of the changes in the pore structure. A model was proposed for the void ratio–moisture content–external stress relationships. This model was demonstrated useful for describing soils’ compression behaviors at different moisture contents and shrinkage characteristics under different external stress. [ABSTRACT FROM AUTHOR]

In visual servoing tasks, it is an important problem to maintain the observability to feature points on objects, which are usually used to calculate the pose between objects and robots. In particular, when the robot's vision has a limited field of view (FOV) and the points on objects are distributed separately, the problem is more serious. In this paper, based on FOV constraint region analysis and path planning, we propose a novel method for a mobile robot equipped with a pan-tilt camera to keep all points on objects in its view. According to the Horizontal-FOV and Vertical-FOV angular aperture of camera, bounding boxes assisting to calculate the regions with FOV constraint are acquired firstly. Then the region where the robot inside it cannot keep all points in its view can be obtained. Finally the mobile robot plans a shortest path from the current position to the destination, which can avoid the region with FOV constraint. The results of simulations and experiments prove that our method can make mobile robot keep all feature points in its view when it is moving. [ABSTRACT FROM AUTHOR]

This paper investigates the volumetric, microstructural, and shear behaviours of an expansive soil during multiple drying-wetting (DW), freeze–thaw (FT), and drying-wetting-freeze–thaw (DWFT) cycles. Specimens compacted at natural moisture content and dry density were subjected to 1, 4, 6, and 10 DW, FT, or DWFT cycles. Volumetric changes were recorded during the treatments and mercury intrusion porosimetry, and scanning electron microscope tests were conducted to observe the soil's microstructure before and after treatments. As compacted specimens and specimens after different numbers of DW, FT, and DWFT cycles were saturated and sheared under consolidated undrained condition to determine their undrained elastic modulus (Eu), shear strength (qu), total cohesion (c), and friction angle (ϕ). Experimental results show that DW, FT, and DWFT cycles mainly influence the soil's macropores with diameters between 5 and 250 μm. Macropores collapse during DW cycles, which lead to collapse in the soil's global volume. Cracks develop during FT cycles and result in slight swelling in the soil's volume. These two effects offset during DWFT cycles and cause an intermediate volumetric behaviour. The Eu, qu, c, and ϕ decline during DW, FT, and DWFT cycles, and the reduction was most significant during DWFT cycles. They reach an equilibrium after approximately 6 cycles of treatment. A simple normalized model was developed to describe the stress–strain curves considering the influence of DW, FT, and DWFT cycles. Good agreements were achieved between the model predictions and measurements for all stress–strain curves obtained in this study. [ABSTRACT FROM AUTHOR]

Baihui-penetrating-Qubin acupuncture is frequently used to treat intracerebral hemorrhage (ICH) in China. Acupuncture affects multiple microRNAs in diseases. MicroRNA-23a-3p (miR-23a-3p) has been demonstrated to be up-regulated in ICH patients. Herein, the effect of Baihui-penetrating-Qubin acupuncture on miR-23a-3p expression after ICH and the role of miR-23a-3p in ICH were discussed. A rat model of ICH was induced by infusing autologous blood into caudate nucleus. Acupuncture was performed after ICH once a day for 30 min. After 3 consecutive days of acupuncture, the neurobehavioral function, brain edema, neuronal cell death, inflammation, ferroptosis, nuclear factor E2-like 2 (NFE2L2) signaling and miR-23a-3p levels in brain tissues were analyzed. Additionally, antagomiR-23a-3p was injected into rats 3 days prior to ICH modeling to analyze the function of miR-23a-3p in neuronal cell death, inflammation, ferroptosis, and NFE2L2 signaling. Acupuncture relieved the ICH-induced neurological function deficits, increases in brain water content and Fluoro-Jade B (FJB)-positive cells and release of proinflammatory cytokines. Acupuncture also alleviated ferroptosis and decreased miR-23a-3p expression, as evidenced by the increased NFE2L2 nuclear translocation and expressions of heme oxygenase-1 and glutathione peroxidase 4 and the decreased iron and malondialdehyde contents and reactive oxygen species accumulation. Additionally, antagomiR-23a-3p inhibited the ICH-induced increases in FJB-positive cells, release of proinflammatory cytokines, ferroptosis, and promoted NFE2L2 activation. Notably, the binding site of miR-23a-3p existed in NFE2L2. Taken together, acupuncture may alleviate the neuronal cell death, inflammation, and ferroptosis after ICH by down-regulating miR-23a-3p. This study provides a potential mechanism underlying the Baihui-penetrating-Qubin acupuncture improving the early injury after ICH. [ABSTRACT FROM AUTHOR]

Bacillus subtilis is a well-characterized Gram-positive bacterium and a valuable host for recombinant protein production because of its efficient secretion ability, high yield, and non-toxicity. Here, we comprehensively review the recent studies on recombinant protein production in B. subtilis to update and supplement other previous reviews. We have focused on several aspects, including optimization of B. subtilis strains, enhancement and regulation of expression, improvement of secretion level, surface display of proteins, and fermentation optimization. Among them, optimization of B. subtilis strains mainly involves undirected chemical/physical mutagenesis and selection and genetic manipulation; enhancement and regulation of expression comprises autonomous plasmid and integrated expression, promoter regulation and engineering, and fine-tuning gene expression based on proteases and molecular chaperones; improvement of secretion level predominantly involves secretion pathway and signal peptide screening and optimization; surface display of proteins includes surface display of proteins on spores or vegetative cells; and fermentation optimization incorporates medium optimization, process condition optimization, and feeding strategy optimization. Furthermore, we propose some novel methods and future challenges for recombinant protein production in B. subtilis. Key points • A comprehensive review on recombinant protein production in Bacillus subtilis. • Novel techniques facilitate recombinant protein expression and secretion. • Surface display of proteins has significant potential for different applications. [ABSTRACT FROM AUTHOR]

Sleep deprivation (SD) is widespread in society causing serious damage to cognitive function. Hydrogen sulfide (H2S), the third gas signal molecule, plays important regulatory role in learning and memory functions. Inhibition of excessive autophagy and upregulation of silent information regulator 1 (Sirt-1) have been reported to prevent cognitive dysfunction. Therefore, this present work was to address whether H2S attenuates the cognitive impairment induced by SD in Wistar rats and whether the underlying mechanisms involve in inhibition of excessive autophagy and upregulation of Sirt-1. After treatment with SD for 72 h, the cognitive function of Wistar rats was evaluated by Y-maze, new object recognition, object location, and Morris water maze tests. The results shown that SD-caused cognitive impairment was reversed by treatment with NaHS (a donor of H2S). NaHS also prevented SD-induced hippocampal excessive autophagy, as evidenced by the decrease in autophagosomes, the down-regulation of Beclin1, and the up-regulation of p62 in the hippocampus of SD-exposed Wistar rats. Furthermore, Sirtinol, an inhibitor of Sirt-1, reversed the inhibitory roles of NaHS in SD-induced cognitive impairment and excessive hippocampal autophagy in Wistar rats. Taken together, our results suggested that H2S improves the cognitive function of SD-exposed rats by inhibiting excessive hippocampal autophagy in a hippocampal Sirt-1-dependent way. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) is a neurotoxicity amino acid that causes cognitive dysfunction. Hydrogen sulfide (H2S) is a neuroprotective gas molecular and can improve cognitive ability in a range of physiological concentrations. Our previous study confirmed that H2S (by its donor, NaHS) ameliorates cognitive impairment in Hcy-exposed rats, but the underlying mechanism has not been well elucidated. Accumulating evidence suggests that k252a, the furanosylated indolocarbazoleas, is usually used as the receptor tyrosine kinase B (TrkB) antagonist and blocks brain-derived neurotrophic factor (BDNF)/TrkB signaling, thus leading to cognitive decline. Interestingly, we previously demonstrated that k252a reversed H2S alleviated Hcy-induced endoplasmic reticulum stress and neuronal apoptosis via inhibiting BDNF-TrkB pathway. Therefore, we assumed that k252a might inhibit the protective effect of H2S on Hcy-induced cognitive dysfunction. We used Hcy to establish a rat model of cognitive impairment. We found that after administration of k252a by intracerebroventricular injection, the beneficial effect of H2S on Hcy-induced cognitive decline is abolished, as reflected by the increasing escape latency and time spent in the target quadrant in the Morris Water Maze (MWM) test as well as decreased spontaneous alternation in Y-maze test and the lower discrimination index in the Novel Object Recognition (NOR) test in rats co-treated with sodium hydrosulfide (NaHS, a donor of H2S), Hcy and k252a. Our findings suggested that k252a antagonized the effect of H2S on preventing Hcy-related cognitive decline. Our finding expands the understanding of the potential mechanism on the resistant role of H2S in Hcy-caused cognitive damage. [ABSTRACT FROM AUTHOR]

Immunologically-cold tumors including glioblastoma (GBM) are refractory to checkpoint blockade therapy, largely due to extensive infiltration of immunosuppressive macrophages (Mϕs). Consistent with a pro-tumor role of IL-6 in alternative Mϕs polarization, we here show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T-cell infiltration into GBM and enhances mouse survival; however, IL-6 inhibition does not synergize PD-1 and CTLA-4 checkpoint blockade. Interestingly, anti-IL-6 therapy reduces CD40 expression in GBM-associated Mϕs. We identify a Stat3/HIF-1α-mediated axis, through which IL-6 executes an anti-tumor role to induce CD40 expression in Mϕs. Combination of IL-6 inhibition with CD40 stimulation reverses Mϕ-mediated tumor immunosuppression, sensitizes tumors to checkpoint blockade, and extends animal survival in two syngeneic GBM models, particularly inducing complete regression of GL261 tumors after checkpoint blockade. Thus, antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting opportunities for GBM and other solid tumors. Glioblastomas are generally resistant to treatment with immune checkpoint inhibitors. Here the authors show that IL6 blockade, in combination with a CD40 agonist, overcomes macrophage-mediated immunosuppression and sensitizes glioblastoma to immune checkpoint blockade in preclinical models. [ABSTRACT FROM AUTHOR]

To have a clear understanding of the interactive relationship between the marine economy and marine environment in China and to further promote the sustainable development of China's oceans, this study evaluates the level of coordinated development between China's marine economy and marine environment by defining and calculating marine eco-efficiency. Next, it uses the Tapio decoupling model to analyze the decoupling relationships among the marine environment, its determinant factors, and the marine economy. This reveals the nature and development trend of the internal relationship between dynamic changes in the marine economy and the marine environment. The results show that, during the study period, there is improvement in the marine eco-efficiencies of 11 Chinese coastal provinces and cities, and there exists a spatial pattern comprising higher marine eco-efficiency in the central regions and lower in the southern and northern ones. Further, the decoupling relationship between the marine economy and marine environment in 11 coastal areas mainly showed a decline from 2006 to 2015. Massive investment of marine resources was not only the major contributor to marine economic growth but also the main factor exerting pressure on the marine environment. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed "variant" due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC. Ling Cai et al. used transcriptomic profiling data of healthy lung, patient-derived small cell lung cancer cell lines, xenografts, and primary tumors to examine a link between neuroendocrine (NE) signatures and immune gene expression. Their findings suggest that cell-autonomous immune gene repression is a shared feature between healthy and tumor cells of NE lineage and may influence tumor-immune cell interaction and response to immunotherapy. [ABSTRACT FROM AUTHOR]

Diabetes-associated cognitive dysfunction (DACD) characterized by hippocampal injury increases the risk of major cerebrovascular events and death. Endoplasmic reticulum (ER) stress and synaptic dysfunction play vital roles in the pathological process. At present, no specific treatment exists for the prevention and/or the therapy of DACD. We have recently reported that hydrogen sulfide (H2S) exhibits therapeutic potential for DACD, but the underlying mechanism has not been fully elucidated. Silent information regulator 1 (SIRT1) has been shown to play a role in regulating the progression of diabetes and is also indispensable for memory formation and cognitive performance. Hence, the present study was performed to explore whether SIRT1 mediates the protective effect of H2S on streptozotocin (STZ)-induced cognitive deficits, an in vivo rat model of DACD, via inhibiting hippocampal ER stress and synaptic dysfunction. The results showed that administration of NaHS (an exogenous H2S donor) increased the expression of SIRT1 in the hippocampus of STZ-induced diabetic rats. Then, results proved that sirtinol, a special blocker of SIRT1, abrogated the inhibition of NaHS on STZ-induced cognitive deficits, as appraised by Morris water maze test, Y-maze test, and Novel object recognition behavioral test. In addition, administration of NaHS eliminated STZ-induced ER stress as evidenced by the decreases in the expressions of ER stress-related proteins including glucose-regulated protein 78, C/EBP homologous protein, and cleaved caspase-12 in the hippocampus, while these effects of NaHS were also reverted by sirtinol. Furthermore, the NaHS-induced up-regulation of hippocampal synapse-related protein (synapsin-1, SYN1) expression in STZ-induced diabetic rats was also abolished by sirtinol. Taken together, these results demonstrated that SIRT1 mediates the protection of H2S against cognitive dysfunction in STZ-diabetic rats partly via inhibiting hippocampal ER stress and synaptic dysfunction. [ABSTRACT FROM AUTHOR]

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