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Protein engineering of enzyme loop regions is an effective strategy to improve enzymatic properties. Previous studies that aimed to boost the activity of PpADI (an arginine deiminase from Pseudomonas plecoglossicida ) under physiological conditions yielded several significantly improved variants that harbor substitutions predominantly located in active-site-decorating loops. A multi-site saturation mutagenesis at four positions in loop 1 (37, 38, 42, and 43) and three positions in loop 4 (402, 403, and 404) was performed to elucidate the importance of these loops in modulating the substrate affinity of PpADI. The identified “best” variant (M6-L1-4) showed a decreased S 0.5 (‘ K M ’) of 0.48 mM compared with the parent M6 (0.81 mM). Subsequently, a rational design to recombine beneficial substitutions within loops 1 and 4 yielded variant L6 with a substantially decreased S 0.5 value (0.17 mM). A comprehensive simulation analysis resulted in a conclusion that high loop flexibility (especially the gating residue Arg400) is beneficial for substrate affinity due to less efficient blocking of the active site. [ABSTRACT FROM AUTHOR]

In this paper, we present a conceptually simple, flexible, and efficient "Combine-and-Conquer" detection framework. The proposed framework is composed of a very simple one-level detection pipeline. We modularized the proposed framework into four parts, Backbone, Neck, Feature Aggregation and Detection Head. To verify the performance of this framework, we design a simple yet strong detector, CC-Det. First CC-Det deploys a backbone network to encode the input image, and then uses a neck network to extract rich features and enlarge the receptive field. Next, a feature aggregation network is deployed to aggregate multi-scale features into one feature map. Finally, only one detection head is deployed on the one-level feature map to output a heatmap and bounding boxes. Compared with existing multi-level detectors such as RetinaNet and FCOS, CC-Det achieves excellent performance with much fewer parameters of model and much lower FLOPs. In addition, CC-Det also achieves better trade-off among speed, accuracy and model size without any elaborate special design, compared to other one-level detectors. Moreover, CC-Det is easy to generalize to other tasks with minor modifications and achieves state-of-the-art performance. Excellent results are presented on COCO, PASCAL VOC, WiderFace and CrowdHuman datasets. • We follow the proposed Combine-and-Conquer to design CC-Det detector with a simple network structure and anchor-free mechanism. Thanks to the one-level feature, the hassle of carefully designing multi-level label assignment like scale range of interest is unnecessary for our framework. • Without any bells and whistles, CC-Det achieves state-of-the-art performance with fewer model's parameters and lower FLOPs, surpassing previous powerful baseline models of multi-level detection framework. • CC-Det is evaluated on multiple datasets, COCO, VOC, WiderFace and CrowdHuman of different detection tasks and achieves excellent performance, demonstrating the versatility of the propose detection framework. • Based on the propose framework, we also design a more efficient yet effective detector, CC-Det-E. Compared with CC-Det, CC-Det-E is almost twice as fast with less than 1% performance loss, achieving better trade-off between precision and speed. • To further demonstrate the powerful potential of Combine-and-Conquer framework, we design a strong yet efficient detector CC-Det-v2. On COCO benchmark, CC-Det-v2 shows excellent trade-off between precision and speed. [ABSTRACT FROM AUTHOR]

• The proposed method solves non-stationary feature extraction of rolling bearing. • The research system parameter control system is in different stable states. • The relationship between potential well depth and pitchfork bifurcation phenomenon. • Simulation and experiments demonstrate the superiority of the proposed method. Stochastic resonance (SR) is mainly produced by the synergistic effect of noise, nonlinear system, and signals. This converts a part of the noise energy into useful signal energy, thereby improving the output of the system. When rotating machinery starts and stops, driving force and load will cause the variation of speed, and thus the produced vibration signal has strong non-stationary characteristics. Furthermore, although SR can be used to process non-stationary signals, its system parameters need to be matched in real-time, and therefore its application and development are limited. This paper mainly studies an adaptive frequency-shift SR of the tri-stable nonlinear system. On the one hand, order analysis can transform non-stationary signals into stationary signals, which shows the advantages of SR in stationary signal processing. On the other hand, the change of system parameters switches the system from tri-stable state to bistable and monostable state, so it loses the advantage of tri-stable weak signal detection. The variation of potential well depth, bifurcation phenomenon, and steady-state switching process caused by system parameters are studied, to help facilitate the control of the system parameters to determine the steady-state situation. Finally, SR is applied to the fault diagnosis of rolling bearing under variable speed conditions and the background of strong noise, which effectively extracts weak fault features. [ABSTRACT FROM AUTHOR]

• Unknown fault feature extraction of rolling bearing is realized under variable speed conditions. • Statistical complexity measuresselects the optimalintrinsic mode function component. • Compared with spectral amplitude modulation have optimal performance. As the main transmission components of rotating machinery, rolling bearings have important research significance for fault diagnosis and state detection. However, the operating environment of mechanical equipment is complex, and the fault characteristic information of rolling bearings is often unknown. Through the complex transmission path, the bearing seat vibration sensor picks up the fault vibration response is weaker, and it is often submerged by strong noise. When the speed and load of rotating mechanical equipment change, the fault characteristic of rolling bearings is more obvious under variable speed conditions. The fault diagnosis problem of rolling bearings needs to be solved urgently under strong noise background, variable speed, and unknown fault characteristics. Therefore, this paper studies an unknown fault feature extraction method of variable speed rolling bearing based on statistical complexity measures (SCM). Order analysis preprocesses the variable speed vibration signal of rolling bearings. It is convenient for subsequent fault feature extraction and analysis. The SCM selects the optimal intrinsic mode function (IMF) component corresponding to the Empirical mode decomposition (EMD) decomposition, and it is also evaluated index for the optimal response of stochastic resonance. Therefore, the adaptive frequency shift stochastic resonance effectively extracts the unknown fault features of rolling bearings under strong noise background. [ABSTRACT FROM AUTHOR]

JPEG steganography is an important branch of information hiding. However, with the development of deep learning-based steganalysis models, steganography is facing great challenges. To better resist these steganalysis models, this paper proposes a deep JPEG steganography framework based on sparse adversarial attacks. According to the vulnerability of deep steganalysis models to adversarial attacks, sparse adversarial attacks are introduced into the deep JPEG steganographic structure to improve the security of stego images. In addition, to resist steganalysis from JPEG and spatial domains, both JPEG and spatial domain steganalysis models are involved in adversarial training. Finally, to further enhance the imperceptibility of adversarial stego images, the visual perception loss is designed from the perspective of human eyes. Experimental results indicate that compared with the existing methods, the proposed method has higher imperceptibility and security and can resist modern deep steganalysis models in both JPEG and spatial domains to a certain extent. The source code is available at https://github.com/imagecbj/SAE-JS. [ABSTRACT FROM AUTHOR]

Changes of macrophage in the local immune microenvironment of periodontitis cause alveolar bone resorption. This study aims to investigate the effect of a new drug delivery method of aspirin on the immune microenvironment of periodontitis to promote alveolar bone repair, and to explore mechanism of aspirin's effect on macrophage. We isolated extracellular vesicles (EVs) from periodontal stem cells (PDLSCs) and loaded with aspirin by sonication, and then evaluated the treatment efficacy of aspirin-loaded vesicles (EVs-ASP) in periodontitis model in mice. In vitro, we explored the role of EVs-ASP in the regulation of LPS-induced macrophages. The underlying mechanism by which EVs-ASP regulates phenotypic remodeling of macrophages in periodontitis was further investigated. EVs-ASP inhibited the inflammatory environment of LPS-induced macrophage, and promoted anti-inflammatory macrophages formation both in vivo and in vitro, and reduced bone loss in periodontitis models. Moreover, EVs-ASP enhanced oxidative phosphorylation and suppressed glycolysis in macrophages. Consequently, EVs-ASP improves the periodontal immune microenvironment by enhancing oxidative phosphorylation (OXPHOS) in macrophages, resulting in a certain degree of regeneration of alveolar bone height. Our study provides a new potential strategy for bone repair in periodontitis therapy. • Macrophages play a key role in regulation of inflammatory response in periodontitis. • Aspirin-loaded extracellular vesicles (EVs-ASP) is a new drug delivery method in periodontitis treatment. • EVs-ASP polarizes macrophages from pro-inflammatory to anti-inflammatory phenotype. • EVs-ASP switches the metabolic process of macrophages from glycolysis to OXPHOS. [ABSTRACT FROM AUTHOR]

It is a challenging task to detect the weak character signal in the noisy background. The stochastic resonance (SR) method has been wildly adopted recently because it can not only reduce the noise, but also enhance the weak feature information simultaneously. However, the traditional bistable model for SR is not perfect. So, this paper presents a new model with periodic potential to induce the adaptive SR. In the new model, based on the adaptive SR theory, the system parameters are simultaneously optimized by the improved artificial fish swarm algorithm. Meanwhile, the improved signal-to-noise ratio (ISNR) is set as the evaluation index. When the ISNR reaches a maximum, the output is optimal. In order to eliminate interference to obtain more useful information, the signals are preprocessed by Hilbert transform and High-pass filter before being input to the adaptive SR system. To verify the effectiveness of the proposed method, both numerical simulation and the vibration signal of the rolling element bearing from the lab experimental are adopted. Both of the results indicate that the adaptive SR model proposed shows better performance in weak character signals detection than the traditional adaptive SR in the bistable model. Meanwhile, the experimental signals with different working conditions are also processed by the new method. The results show that the method proposed could be more widely applied. [ABSTRACT FROM AUTHOR]

• Optical frequency domain reflectometry (OFDR) system has been expected to achieve high spatial resolution and sensitivity. • FPGA is good at data processing and calculation. • The combination of OFDR and FPGA can achieve high real-time performance. This paper presents a novel approach to accelerate the data processing rate in optical frequency-domain reflectometry (OFDR) system. In conventional solution, data is sampled by data acquisition card and then sent to personal computer (PC) for data processing through high-speed interface such as peripheral component interconnect express (PCIE) and so on. But frequently-used general laptop can't provide this interface. What's more, long time is necessary to complete the calculation in PC due to the limitations of serial processing in central processing unit (CPU). To improve the real-time performance of OFDR system, in our work, field-programmable gate array (FPGA) is used as hardware circuit to complete the calculation task and then send the results to PC only to display through universal asynchronous receiver/transmitter (UART) interface in the OFDR system simultaneously. In this way, the refresh rate of output can be accelerated about 50 times, which means the real-time performance of the system is improved a lot. [ABSTRACT FROM AUTHOR]

Abstract: Single-crystal X-ray diffraction (SCD), X-ray fluorescence (XRF), inductively coupled plasma optical emission spectroscopy (ICP-OES) and X-ray excited luminescence (XEL) measurements were performed to investigate structure details and segregation coefficients of (Lu1−x Y x )2SiO5:Ce (x=0at%, 8.7at%, 25.7at%, 44.7at%, 65.7at%, 87.9at% and 100at%). Y3+ cations were found to have a preferential occupation for RE1 site (7-oxygen-coordinated) over RE2 site (6-oxygen-coordinated), which results in a greater increase of cell parameter c than that of a with increase in Y content due to LYSO's microstructure characteristics. Results presented here revealed that the less the difference in electronegativity and effective ionic radius between the two ions, the easier substitution of one ion by the other, and hence the higher segregation coefficients. Besides, the contribution of luminescence of Ce1 and Ce2 in the whole XEL was evaluated, and the location of Ce3+ ion was discussed. [Copyright &y& Elsevier]

Exploring the spatiotemporal variations of vegetation net primary productivity (NPP) and analyzing the relationships between NPP and its influencing factors are vital for ecological protection in the Beijing-Tianjin-Hebei (BTH) region. In this study, we employed the CASA model in conjunction with spatiotemporal analysis techniques to estimate and analyze the spatiotemporal variations of NPP in BTH and different ecological function sub-regions over the past two decades. Subsequently, we established three scenarios (actual, climate-driven and land cover-driven) to assess the influencing factors and quantify their relative contributions. The results indicated that the overall NPP in BTH exhibited a discernible upward trend from 2000 to 2020, with a growth rate of 3.83 gC·m−2a−1. Furthermore, all six sub-regions exhibited an increase. The Bashang Plateau Ecological Protection Zone (BP) exhibited the highest growth rate (5.03 gC·m−2a−1), while the Low Plains Ecological Restoration Zone (LP) exhibited the lowest (2.07 gC·m−2a−1). Geographically, the stability of NPP exhibited a spatial pattern of gradual increase from west to east. Climate and land cover changes collectively increased NPP by 0.04 TgC·a−1 and 0.07 TgC·a−1, respectively, in the BTH region. Climate factors were found to have the greatest influence on NPP variations, contributing 40.49% across the BTH region. This influence exhibited a decreasing trend from northwest to southeast, with precipitation identified as the most influential climatic factor compared to temperature and solar radiation. Land cover change has profound effects on ecosystems, which is an important factor on NPP. From 2000 to 2020, 15.45% area of the BTH region underwent land cover type change, resulting in a total increase in NPP of 1.33 TgC. The conversion of grass into forest brought about the 0.89 TgC increase in NPP, which is the largest of all change types. In the area where land cover had undergone change, the land cover factor has been found to be the dominant factor influencing variations in NPP, with an average contribution of 49.37%. In contrast, in the south-central area where there has been no change in land cover, the residual factor has been identified as the most influential factor influencing variations in NPP. Our study highlights the important role of land cover change in influencing NPP variations in BTH. It also offers a novel approach to elucidating the influences of diverse factors on NPP, which is crucial for the scientific assessment of vegetation productivity and carbon sequestration capacity. [Display omitted] • NPP in the BTH region increased by 3.83 gC·m−2a−1 from 2000 to 2020. • Climate factors contribute 40% of NPP changes, and precipitation is the major. • Land cover change profoundly affect ecosystems and NPP variation. • NPP show heterogeneous among ecological function subregions in the BTH region. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a fatal respiratory disease with no effective medical treatments available. TGF-β/Smads signaling has been implicated to play an essential in the pathogenesis of PF, in which Smad3 act as the integrator of pro-fibrosis signals. In this study, we determined the effect of SIS3, a specific inhibitor of Smad3, in an experimental mouse model of lung fibrosis. We observed that SIS3 treatment significantly reduced bleomycin (BLM)-induced pathological changes and collagen deposition in the lung as indicated by Masson staining, real-time PCR and hydroxyproline content assay. As expected, the levels of Smad3 phosphorylation were decreased in the lung of mice treated with SIS3. Furthermore, SIS3 treatment also suppressed BLM-induced infiltration of inflammatory cells in the lung. Taken together, our results suggest that SIS3 ameliorated BLM-induced PF in mouse lungs. Thus, targeting Smad3 with SIS3 may be an effective approach for treatment of fibrotic disorders. [ABSTRACT FROM AUTHOR]

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used worldwide. It has been associated with a variety of toxicities in rodents. In this study, male mice were orally administered 2,4-D at 50, 100 or 200 mg/kg/day to investigate testicular toxicity and the possible mechanisms of action. Exposure to 2,4-D at high concentrations (100 and 200 mg/kg/day) for 14 consecutive days caused spermatogenic disruption and seminiferous epithelial destruction. Furthermore, 2,4-D administration (100 and 200 mg/kg/day) increased the formation of the lipid peroxidation product malondialdehyde and decreased activities of the antioxidant enzymes superoxide dismutase and catalase in the testis. Moreover, 2,4-D exposure up-regulated the expression of p53 and Bax protein and down-regulated the expression of Bcl-2 protein in the testis. These results demonstrate that oxidative stress and apoptosis may be involved in testicular toxicity induced by high concentrations of 2,4-D in mice. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes is a Gram-positive intracellular bacterium that was transmitted through contaminated food and causes sepsis and even death. IL-37 has been described as an important anti-inflammatory factor, but little is known about the function of IL-37 in host defense against Liseria monocytogenes (Lm) infection. In mice model of systemic infection, we found that mice treated with IL-37 were more sensitive to Lm infection compared with PBS-treated mice. This reduced resistance to Lm in IL-37-treated mice is accompanied with increased bacterial burden and liver damage. Serum levels of colony-stimulating factors were decreased in IL-37-treated mice. IL-37 treatment reduced bactericidal ability of bone marrow derived macrophages (BMDMs) in vitro, which contribute to the inability of IL-37-treated mice to combat Lm infection. Furthermore, increased apoptosis was observed in Lm-infected macrophages treated with IL-37. Increased macrophage apoptosis reduced percentage in liver macrophages was observed in IL-37-treated mice following Lm infection. These results indicate the negative regulatory effect of IL-37 on host resistance during immune defense against Lm. [ABSTRACT FROM AUTHOR]

CecropinXJ is a cationic antimicrobial peptide originally isolated from the larvae of Bombyx mori. In this study, an antibacterial peptide gene of cecropinXJ was cloned into the pYES2/CT/α Factor expression vector and expressed in the Saccharomyces cerevisiae INVSc1 strain. Following an induction of recombinant protein expression in yeast for 120h, the maximum amount of total secreted protein was 1.437g/L. The percentage of recombinant cecropinXJ was estimated to be 79.45% of the total protein. After purification with Ni–NTA agarose column, recombinant cecropinXJ was noted to exert strong antimicrobial activities against a broad-spectrum of microorganisms, including Gram-negative and Gram-positive bacteria. Its minimal inhibitory concentration (MIC) against Escherichia coli ATCC25922 was 0.81μM. In addition, transmission electron microscopy (TEM) analysis indicated that the surfaces of the treated pathogens underwent obvious morphological changes compared with the untreated controls, suggesting that this antimicrobial peptide exerts its action by directly disrupting membranes of microorganisms. CecropinXJ had a small hemolytic effect on red blood cells even with a peptide concentration of 200μM. Thus, cecropinXJ acts selectively on bacterial membranes. Purified recombinant antibacterial peptide, cecropinXJ, retained a high stability against E. coli ATCC25922 over a temperature range from 4°C to 100°C and a pH range from pH 2.0 to 12.0. Taken together, this study demonstrates that recombinant cecropinXJ can be produced in large quantities in yeast with genetic engineering methods, and that it has strong and rapid antimicrobial activities against all of microorganisms tested. Our results suggest that cecropinXJ is a potential candidate for therapy. [ABSTRACT FROM AUTHOR]

Abstract: Sm1−x/3Sc x/3FeAsO1−x F x (x=0.09–0.27) were synthesized by the mechanical alloying and subsequent low temperature rapid sintering (2h at 950°C). The superconducting transition temperature (T c) increased with the doping level of x. The optimal doping achieved a T c up to 53.5K in Sm0.93Sc0.07FeAsO0.79F0.21. The higher T c value was attributed to the increased chemical inner pressure from local lattice distortion induced by smaller-size dopants, which was further confirmed by Sm1−x Sc x FeAsO0.88F0.12 (x=0.04, 0.08, 0.12). Accordingly, larger lattice distortion can enhance the superconductivity below the doping limit. Similar phenomenon was also observed in the La1−x Y x FeAsO0.8F0.2 (x=0.4, 0.5, 0.6). [Copyright &y& Elsevier]

Abstract: Objective.: To evaluate BMI and direct measures of body fat (BF) and lean body mass (LBM) in relation to fasting serum lipid profiles in a large Chinese population based twin sample using a monozygotic (MZ) co-twin analysis. Methods.: Adiposity measures collected 1998–2000 on 987 MZ female 20–60 year old twin pairs (n =1974) included BMI, waist circumference (WC), waist/hip ratio (WHR), LBM, trunk fat (TF), %TF, total BF, and % total BF (measured by DEXA). Serum lipids included total cholesterol (TC), triglycerides (TG), LDL, and HDL. Co-twin analyses and conventional regression analyses were used to assess the association between individual adiposity and LBM measures, and serum lipids. Results.: In this lean population with a mean BMI 21.8 (2.8), we observed considerable variability in adiposity measures and serum lipids. A positive linear association between all adiposity measures with LDL, TC, and TG, and a negative linear association with HDL was observed. A 1-unit z-score increase of adiposity measures, reflecting fat distribution, was associated with increases in (mmol/L) TC (0.063 to 0.164), LDL (0.064 to 0.131), TG (0.049 to 0.164), and a decrease in HDL (0.021 to 0.038) while controlling for matched factors within twin pairs (i.e., age and unmeasured confounders). However, similar associations were not observed for LBM. Conclusion.: It is the BF (not LBM) that appears to be associated with serum lipid profiles. This study underscores that in populations where BMI is highly correlated with BF, BMI can be used as a surrogate for BF in evaluating risk of dyslipidemia. Otherwise, direct measures of BF are needed. [Copyright &y& Elsevier]

Abstract: Intracellular signaling pathways and their relationship to malignant progression have become a major focus of cancer biology. The dual-specificity phosphatase (DSP) family is a more recently identified family of intracellular signaling modulators. We have identified a novel protein phosphatase with a well-conserved DSP catalytic domain containing the DSP catalytic motif, xHCxxGxSRS, and mitogen-activated protein kinase phosphatase (MKP) motif, AYLM. Because of these unique characteristics, the protein was named mitogen-activated protein kinase phosphatase-8 (MKP-8). This protein is approximately 20kDa in size and mainly localizes to the nuclear compartment of the cell. MKP-8 is expressed in embryonal cancers (retinoblastoma, neuroepithelioma, and neuroblastoma) and has limited expression in normal tissues. MKP-8 displays significant phosphatase activity that is inhibited by a cysteine to serine substitution in the catalytic domain. When co-expressed with activated MAPKs, MKP-8 is able to inhibit p38 kinase phosphorylation and downstream activity. [Copyright &y& Elsevier]