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Chimeric antigen receptor (CAR) T cell therapy has emerged as a groundbreaking treatment for hematological cancers, yet it faces significant hurdles, particularly regarding its efficacy in solid tumors and concerning associated adverse effects. This review provides a comprehensive analysis of the advancements and ongoing challenges in CAR-T therapy. We highlight the transformative potential of nanotechnology in enhancing CAR-T therapy by improving targeting precision, modulating the immune-suppressive tumor microenvironment, and overcoming physical barriers. Nanotechnology facilitates efficient CAR gene delivery into T cells, boosting transfection efficiency and potentially reducing therapy costs. Moreover, nanotechnology offers innovative solutions to mitigate cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cutting-edge nanotechnology platforms for real-time monitoring of CAR-T cell activity and cytokine release are also discussed. By integrating these advancements, we aim to provide valuable insights and pave the way for the next generation of CAR-T cell therapies to overcome current limitations and enhance therapeutic outcomes.

Persimmon fruits are brightly colored and nutritious and are fruits that contain large amounts of sugar, vitamins, mineral elements, and phenolic substances. The aim of this study was to explore the differences in fruit-sugar components of different persimmon germplasms and their relationships with phenotypic and flavor indices through the determination of phenotypes and sugar components and through electronic-tongue indices, which provided the basis and inspiration for the selection of different sugar-accumulating types of persimmon fruits and the selection of high-sugar persimmon varieties. Our results showed that persimmon germplasm fruit-sugar components were dominated by sucrose, glucose and fructose and that the remaining sugar components were more diverse but less distributed among the various germplasm types. Based on the proportion of each sugar component in the fruit, persimmon germplasms can be categorized into sucrose-accumulating and reduced-sugar-accumulation types. Sucrose-accumulating types are dominated by sucrose, galactose, fucose and inositol, while reduced-sugar-accumulation types are dominated by glucose, fructose, mannose-6-phosphate, and xylose. The content of sugar components in the germplasm persimmon of fruits of different types and maturity periods of also differed, with significant differences in sugar components between PCNA (pollination-constant non-astringent) and PCA (pollination-constant astringent) fruits. Cluster analysis classified 81 persimmon germplasms into three clusters, including cluster I-A, with low glucose and fructose content, and cluster I-B, with medium glucose, fructose, and sucrose contents. Cluster II was high in sucrose and fructose. Cluster III had high contents of glucose and fructose and low contents of sucrose and inositol.

There are numerous applications of terahertz (THz) imaging in many fields. However, current THz imaging is generally based on scanning technique due to the limited intensity of the THz sources. Thus, it takes a long time to obtain a frame image of the target and cannot meet the requirement of fast THz imaging. Here, we demonstrate a single-shot direct THz imaging strategy based on a broadband intense THz source with a frequency range of 0.1~23 THz and a THz camera with a frequency response range of 1~7 THz. This THz source was generated from the laser-plasma interaction, with its central frequency at ~12 THz. The frame rate of this imaging system was 8.5 frames per second. The imaging resolution reached 146.2 μm. With this imaging system, a single-shot THz image for a target object with a size of more than 7 cm was routinely obtained, showing a potential application for fast THz imaging. Furthermore, we proposed and tested an image enhancement algorithm based on an improved dark channel prior (DCP) theory and multi-scale retinex (MSR) theory to optimize the image brightness, contrast, entropy and peak signal-to-noise ratio (PSNR).

Ultraviolet B (UVB) exposure can contribute to photoaging of skin. Cornus officinalis is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the Cornus officinalis extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of Cornus officinalis . The effect of COE on UVB damage was assessed using Caenorhabditis elegans . The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of C. elegans exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the skn-1 downstream gene and the extension of the lifespan in skn-1 mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in C. elegans via the SKN-1/Nrf2 pathway.

Virtual reality technology brings a new experience to human-computer interaction, while wearable force feedback devices can enhance the immersion of users in interaction. This paper proposes a wearable fingertip force feedback device that uses a tendon drive mechanism, with the aim of simulating the stiffness characteristics of objects within virtual scenes. The device adjusts the rotation angle of the torsion spring through a DC motor, and then uses a wire to convert the torque into a feedback force at the user's index fingertips, with an output force of up to 4 N and a force change rate of up to 10 N/s. This paper introduces the mechanical structure and design process of the force feedback device, and conducts a mechanical analysis of the device to select the appropriate components. Physical and psychological experiments are conducted to comprehensively evaluate the device's performance in conveying object stiffness information. The results show that the device can simulate different stiffness characteristics of objects, and users can distinguish objects with different stiffness characteristics well when wearing the force feedback device and interacting with the three-dimensional virtual environments.

To address the issue of pavement cracking due to brittle concrete in road and bridge engineering, this study explores the use of high-ductility magnesium phosphate cementitious concrete (HD-MPCC) for rapid repairs. The deformation and frost properties of HD-MPCC are analyzed to assess its suitability for this application. Deformation properties were tested for HD-MPCC specimens cured in both air and water. Subsequent tests focused on the frost performance and mechanical properties after freeze-thaw cycles. A mercury penetration technique was utilized to examine the pore structure. The findings reveal that the expansion deformation of HD-MPCC increases with curing age in both air and water conditions, and the quantitative relationship between the expansion deformation and curing age of HD-MPCC was analyzed. Additionally, the freeze-thaw cycles led to a decrease in mass loss, the relative dynamic elastic modulus, the ultimate tensile strength, the ultimate tensile strain, the flexural strength, and the peak deflection. The volume fraction of harmless and less harmful pores gradually decreased as the freeze-thaw cycle increased, while the volume fraction of more harmful pores increased, resulting in a decrease in the strength, ultimate tensile strain, and peak deflection.

Protein-DNA complex interactivity plays a crucial role in biological activities such as gene expression, modification, replication and transcription. Understanding the physiological significance of protein-DNA binding interfacial hot spots, as well as the development of computational biology, depends on the precise identification of these regions. In this paper, a hot spot prediction method called EC-PDH is proposed. First, we extracted features of these hot spots' solid solvent-accessible surface area (ASA) and secondary structure, and then the mean, variance, energy and autocorrelation function values of the first three intrinsic modal components (IMFs) of these conventional features were extracted as new features via the empirical modal decomposition algorithm (EMD). A total of 218 dimensional features were obtained. For feature selection, we used the maximum correlation minimum redundancy sequence forward selection method (mRMR-SFS) to obtain an optimal 11-dimensional-feature subset. To address the issue of data imbalance, we used the SMOTE-Tomek algorithm to balance positive and negative samples and finally used cat gradient boosting (CatBoost) to construct our hot spot prediction model for protein-DNA binding interfaces. Our method performs well on the test set, with AUC, MCC and F1 score values of 0.847, 0.543 and 0.772, respectively. After a comparative evaluation, EC-PDH outperforms the existing state-of-the-art methods in identifying hot spots.

Gastric cancer is ranked as the fifth most prevalent cancer globally and has long been a topic of passionate discussion among numerous individuals. However, the incidence of gastric cancer in society has not decreased, but instead has shown a gradual increase in recent years. For more than a decade, the treatment effect of gastric cancer has not been significantly improved. This is attributed to the heterogeneity of cancer, which makes popular targeted therapies ineffective. Methionine is an essential amino acid, and many studies have shown that it is involved in the development of gastric cancer. Our study aimed to review the literature on methionine and gastric cancer, describing its mechanism of action to show that tumor heterogeneity in gastric cancer does not hinder the effectiveness of methionine-restricted therapies. This research also aimed to provide insight into the inhibition of gastric cancer through metabolic reprogramming with methionine-restricted therapies, thereby demonstrating their potential as adjuvant treatments for gastric cancer.

Chinese cabbage is the most widely consumed vegetable crop due to its high nutritional value and rock-bottom price. Notably, the presence of the physiological disease petiole spot significantly impacts the appearance quality and marketability of Chinese cabbage. It is well known that excessive nitrogen fertilizer is a crucial factor in the occurrence of petiole spots; however, the mechanism by which excessive nitrogen triggers the formation of petiole spots is not yet clear. In this study, we found that petiole spots initially gather in the intercellular or extracellular regions, then gradually extend into intracellular regions, and finally affect adjacent cells, accompanied by cell death. Transcriptomic and proteomic as well as physiology analyses revealed that the genes/proteins involved in nitrogen metabolism exhibited different expression patterns in resistant and susceptible Chinese cabbage lines. The resistant Chinese cabbage line has high assimilation ability of NH 4 + , whereas the susceptible one accumulates excessive NH 4 + , thus inducing a burst of reactive oxygen species (ROS). These results introduce a novel perspective to the investigation of petiole spot induced by the nitrogen metabolism pathway, offering a theoretical foundation for the development of resistant strains in the control of petiole spot.

The tumor microenvironment (TME) is pivotal in tumor growth and metastasis, aligning with the "Seed and Soil" theory. Within the TME, tumor-associated macrophages (TAMs) play a central role, profoundly influencing tumor progression. Strategies targeting TAMs have surfaced as potential therapeutic avenues, encompassing interventions to block TAM recruitment, eliminate TAMs, reprogram M2 TAMs, or bolster their phagocytic capabilities via specific pathways. Nanomaterials including inorganic materials, organic materials for small molecules and large molecules stand at the forefront, presenting significant opportunities for precise targeting and modulation of TAMs to enhance therapeutic efficacy in cancer treatment. This review provides an overview of the progress in designing nanoparticles for interacting with and influencing the TAMs as a significant strategy in cancer therapy. This comprehensive review presents the role of TAMs in the TME and various targeting strategies as a promising frontier in the ever-evolving field of cancer therapy. The current trends and challenges associated with TAM-based therapy in cancer are presented.

The prolonged course of the COVID-19 pandemic necessitates sustained surveillance of emerging variants. This study aimed to develop a multiplex real-time polymerase chain reaction (rt-PCR) suitable for the real-time tracking of Omicron subvariants in clinical and wastewater samples. Plasmids containing variant-specific mutations were used to develop a MeltArray assay. After a comprehensive evaluation of both analytical and clinical performance, the established assay was used to detect Omicron variants in clinical and wastewater samples, and the results were compared with those of next-generation sequencing (NGS) and droplet digital PCR (ddPCR). The MeltArray assay identified 14 variant-specific mutations, enabling the detection of five Omicron sublineages (BA.2*, BA.5.2*, BA.2.75*, BQ.1*, and XBB.1*) and eight subvariants (BF.7, BN.1, BR.2, BQ.1.1, XBB.1.5, XBB.1.16, XBB.1.9, and BA.4.6). The limit of detection (LOD) of the assay was 50 copies/reaction, and no cross-reactivity was observed with 15 other respiratory viruses. Using NGS as the reference method, the clinical evaluation of 232 swab samples exhibited a clinical sensitivity of > 95.12% (95% CI 89.77-97.75%) and a specificity of > 95.21% (95% CI, 91.15-97.46%). When used to evaluate the Omicron outbreak from late 2022 to early 2023, the MeltArray assay performed on 1408 samples revealed that the epidemic was driven by BA.5.2* (883, 62.71%) and BF.7 (525, 37.29%). Additionally, the MeltArray assay demonstrated potential for estimating variant abundance in wastewater samples. The MeltArray assay is a rapid and scalable method for identifying SARS-CoV-2 variants. Integrating this approach with NGS and ddPCR will improve variant surveillance capabilities and ensure preparedness for future variants.

Laminated glass is extensively used in automotive windshields, making it crucial to have a comprehensive understanding of its fracture mechanism to ensure driver and pedestrian safety in various windshield impact scenarios. Current research on the cohesive zone model of glass impact failure has encountered challenges related to accuracy and computational efficiency. This paper addresses these issues by utilizing the finite element software LS-DYNA, which integrates a cohesive zone model and thick shell (Tshell) elements to simulate and analyze the impact failure process of laminated glass. The combination of Tshell and cohesive elements was validated using a DCB example. Subsequently, the proposed method was applied to simulate the impact damage on an automobile's front windshield, providing valuable insights from the obtained results. Finally, the influence of curvature, the number of layers, and the thickness ratio of each layer were investigated, leading to some valuable conclusions. Firstly, an increase in the thickness of the upper glass layer correlates with a decrease in the peak acceleration of the dummy-head model due to the ductility of PVB material. Secondly, when a curvature exists, the arched configuration of the windshield promotes higher resistance against impact, consequently leading to increased peak acceleration.

In order to improve predictive capabilities of numerical simulations, Yld2000-2D yield criterion is used to model the plastic anisotropic behaviors of AA5086 sheets. The parameters of Yld2000-2D yield criterion are identified based on the traditional testing strategy and the inverse identification strategy, respectively. The traditional testing strategy considers uniaxial and equi-biaxial tensile tests. The inverse identification strategy relies on the finite element model update (FEMU) method that couples with a biaxial tensile test using a dedicated cruciform specimen or the Pottier bulging test. The identified parameters are preliminarily evaluated by comparing predicted and experimental yield stresses, r -values, and yield loci. Then, the deep drawing test and simulations are performed. The identified parameter sets of Yld2000-2D yield criterion are further evaluated in terms of practical forming by comparing the predicted earing profile height with the experimental results. The results show that the inverse identification strategy can be an effective alternative to identify the parameters of Yld2000-2D yield criterion, and a well-designed heterogeneous test could lead to a better identification result.

Magnetorheological damper (MRD) has been successfully applied to vehicle suspension systems as an intelligent core component. Most conventional MRDs have closed rectangle-shaped magnetic circuits, resulting in a short effective working length and negligible damping force. To address the above issues, a novel full-channel effective MRD with trapezoidal magnetic rings (FEMRD_TMR) is proposed. The trapezoidal magnetic ring can shunt the magnetic circuit, distributing it evenly along the damping channel and increasing the effective working length. Additionally, which has the same variation trend as the magnetic flux through it, makes the magnetic induction intensity distribution more uniform to reduce the magnetic saturation problem. Theoretically analyzing the damping characteristics of the FEMRD_TMR, a quasi-static model is developed to forecast the output damping force. The structural design of MRD is challenging since conventional quasi-static models rely on the yield stress of magnetorheological fluid (MRF) to reflect the rheological property, which cannot be directly observed and is challenging to calculate. The Takagi-Sugeno (T-S) fuzzy neural network and a unique magnetic circuit computation are offered as a novel quasi-static modeling approach to address the issue. The MRF's yield stress is linearized into magnetic induction intensity functions by the T-S fuzzy neural network and then converted into the MRD's structural size by the special magnetic circuit calculation. Therefore, the proposed quasi-static model can directly reflect the relationship between the damping force and structure size, simplifying MRD's structure design. The novel quasi-static model is shown to be more straightforward and understandable than the conventional Bingham quasi-static model and to have approximately accurate damping force prediction when compared to experimental data.

The yak lives in harsh alpine environments and the rumen plays a crucial role in the digestive system. Rumen-associated cells have unique adaptations and functions. The yak rumen fibroblast cell line (SV40T-YFB) was immortalized by introducing simian virus 40 large T antigen (SV40T) by lentivirus-mediated transfection. Further, we have reported the effects of lipopolysaccharide (LPS) of different concentrations on cell proliferation, extracellular matrix (ECM), and proinflammatory mediators in SV40T-YFB. The results showed that the immortalized yak rumen fibroblast cell lines were identified as fibroblasts that presented oval nuclei, a fusiform shape, and positive vimentin and SV40T staining after stable passage. Chromosome karyotype analysis showed diploid characteristics of yak (n = 60). LPS at different concentrations inhibited cell viability in a dose-dependent manner. SV40T-YFB treated with LPS increased mRNA expression levels of matrix metalloproteinases (MMP-2 and MMP-9), inflammatory cytokines (TNF-α, IL-1β, IL-6), and urokinase-type plasminogen activator system components (uPA, uPAR). LPS inhibits the expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), plasminogen activator inhibitor-2 (PAI-2), fibronectin (FN), anti-inflammatory factor IL-10, and collagen I (COL I) in SV40T-YFB. Overall, these results suggest that LPS inhibits cell proliferation and induces ECM degradation and inflammatory response in SV40T-YFB.

Based on the first-order shear deformation theory (FSDT) and Kelvin-Voigt viscoelastic model, one derives a wave equation of longitudinal guide waves in viscoelastic orthotropic cylindrical shells, which analytically solves the wave equation and explains the intrinsic meaning of the wave propagation. In the numerical examples, the velocity curves of the first few modes for the elastic cylindrical shell are first calculated, and the results of the available literature are compared to verify the derivation and programming. Furthermore, the phase velocity curves and attenuation coefficient curves of the guide waves for a functionally graded (FG) shell are calculated, and the effects of viscoelastic parameters, material gradient patterns, material volume fractions, and size ratios on the phase velocity curves and attenuation curves are studied. This study can be widely used to analytically model the wave propagating in inhomogeneous viscoelastic composite structures and present a theoretical basis for the excellent service performance of composite structures and ultrasonic devices.

Ciphertext-Policy Attribute-Based Encryption (CP-ABE) technology provides a new solution to address the security and fine-grained access control of traffic information in vehicular ad hoc networks (VANETs). However, in most CP-ABE schemes for VANETs, attribute revocation suffers from high system consumption and complex revocation operations, as well as from high computational overhead and low efficiency due to the use of bilinear pairwise operations. Based on this, this paper proposes a lightweight CP-ABE scheme that supports direct attribute revocation in VANETs. The scheme implements an agent-based direct attribute revocation mechanism by separating dynamic and static attributes of vehicle terminals, which reduces system consumption and simplifies the revocation operation process. The scheme uses scalar multiplication on elliptic curves instead of bilinear pairing operations and uses computational outsourcing techniques to reduce the terminal decryption cost and improve the efficiency of the scheme. The security and performance analysis shows that the overall efficiency of our scheme is better than the existing schemes under the premise of ensuring data confidentiality and integrity.

Signal transmission plays an important role in the daily operation of structural health monitoring (SHM) systems. In wireless sensor networks, transmission loss often occurs and threatens reliable data delivery. The massive amount of data monitoring also leads to a high signal transmission and storage cost throughout the system's service life. Compressive Sensing (CS) provides a novel perspective on alleviating these problems. Based on the sparsity of vibration signals in the frequency domain, CS can reconstruct a nearly complete signal from just a few measurements. This can improve the robustness of data loss while facilitating data compression to reduce transmission demands. Extended from CS methods, distributed compressive sensing (DCS) can exploit the correlation across multiple measurement vectors (MMV) to jointly recover the multi-channel signals with similar sparse patterns, which can effectively enhance the reconstruction quality. In this paper, a comprehensive DCS framework for wireless signal transmission in SHM is constructed, incorporating the process of data compression and transmission loss together. Unlike the basic DCS formulation, the proposed framework not only activates the inter-correlation among channels but also provides flexibility and independence to single-channel transmission. To promote signal sparsity, a hierarchical Bayesian model using Laplace priors is built and further improved as the fast iterative DCS-Laplace algorithm for large-scale reconstruction tasks. Vibration signals (e.g., dynamic displacement and accelerations) acquired from real-life SHM systems are used to simulate the whole process of wireless transmission and test the algorithm's performance. The results demonstrate that (1) DCS-Laplace is an adaptative algorithm that can actively adapt to signals with various sparsity by adjusting the penalty term to achieve optimal performance; (2) compared with CS methods, DCS methods can effectively improve the reconstruction quality of multi-channel signals; (3) the Laplace method has advantages over the OMP method in terms of reconstruction performance and applicability, which is a better choice in SHM wireless signal transmission.

With the increasing number of violent terrorist attacks around the world, it is quite a common to improve the anti-blast performance of structures by reinforcing the exterior of the structure. In order to explore the dynamic performance of polyurea reinforced concrete arch structures, a three-dimensional finite element model was established by LS-DYNA software in this paper. Under the condition of ensuring the validity of the simulation model, the dynamic response of the arch structure under the blast load is investigated. Deflection and vibration of the structure under different reinforcement models are discussed. The optimum thickness of reinforcement (approximately 5 mm) and the strengthening method for the model were found by deformation analysis. The vibration analysis shows that the vibration damping effect of the sandwich arch structure is relatively excellent, but increasing the thickness and number of layers of the polyurea does not necessarily achieve a better vibration damping function for the structure. By reasonable design of the polyurea reinforcement layer and concrete arch structure, a protective structure with excellent performance of anti-blast and vibration damping can be created. Polyurea can be used as a new form of reinforcement in practical applications.

Aiming at the problems of Non-Line-of-Sight (NLOS) observation errors and inaccurate kinematic model in ultra-wideband (UWB) systems, this paper proposed an improved robust adaptive cubature Kalman filter (IRACKF). Robust and adaptive filtering can weaken the influence of observed outliers and kinematic model errors on filtering, respectively. However, their application conditions are different, and improper use may reduce positioning accuracy. Therefore, this paper designed a sliding window recognition scheme based on polynomial fitting, which can process the observation data in real-time to identify error types. Simulation and experimental results indicate that compared to the robust CKF, adaptive CKF, and robust adaptive CKF, the IRACKF algorithm reduces the position error by 38.0%, 45.1%, and 25.3%, respectively. The proposed IRACKF algorithm significantly improves the positioning accuracy and stability of the UWB system.

Nephronophthisis (NPHP) is the most prevalent monogenic disease leading to end-stage renal failure in childhood. RhoA activation is involved in NPHP pathogenesis. This study explored the role of the RhoA activator guanine nucleotide exchange factor (GEF)-H1 in NPHP pathogenesis. We analyzed the expression and distribution of GEF-H1 in NPHP1 knockout ( NPHP1 KO ) mice using Western blotting and immunofluorescence, followed by GEF-H1 knockdown. Immunofluorescence and renal histology were used to examine the cysts, inflammation, and fibrosis. A RhoA GTPase activation assay and Western blotting were used to detect the expression of downstream GTP-RhoA and p-MLC2, respectively. In NPHP1 knockdown ( NPHP1 KD ) human kidney proximal tubular cells (HK2 cells), we detected the expressions of E-cadherin and α-smooth muscle actin (α-SMA). In vivo, increased expression and redistribution of GEF-H1, and higher levels of GTP-RhoA and p-MLC2 in renal tissue of NPHP1 KO mice were observed, together with renal cysts, fibrosis, and inflammation. These changes were alleviated by GEF-H1 knockdown. In vitro, the expression of GEF-H1 and activation of RhoA were also increased, with increased expression of α-SMA and decreased E-cadherin. GEF-H1 knockdown reversed these changes in NPHP1 KD HK2 cells. Thus, the GEF-H1/RhoA/MLC2 axis is activated in NPHP1 defects and may play a pivotal role in NPHP pathogenesis.

Abnormal mutations in the microbial structure of early-weaning mammals are an important cause of enteritis. Based on the multiple known beneficial functions of butyrate, we hypothesized that butyrate would alleviate the imbalance of intestinal homeostasis induced by early weaning in animals. However, the mechanisms of action between butyrate and intestinal microbes are still poorly explored. In this study, we aimed to investigate whether butyrate exerts beneficial effects on the structure of the intestinal flora of weanling rabbits and their intestinal homeostasis, growth and development, and we attempted to elucidate the potential mechanisms of action through a combined omics analysis. We found that dietary butyrate upregulated the transcription of tight junction-related proteins in the epithelial barrier and improved the intestinal microbial structure by suppressing harmful bacteria and promoting beneficial ones. Intestinal and plasma metabolomes were also altered. The bile acid secretion, α-linolenic acid, apoptotic, and prostate cancer pathways responded to the positive dietary butyrate-induced metabolic changes in the weanling rabbits, resulting in the inhibition of inflammation, improved antioxidant capacity, increased rates of cell proliferation and survival, and decreased levels of apoptosis. Additionally, dietary butyrate suppressed the release of pro-inflammatory factors and enhanced positive appetite regulation, which increased the average daily gain of the rabbits. These results demonstrated that dietary butyrate can help maintain the integrity of the intestinal epithelial barrier, improve the structural composition of the intestinal microflora, enhance organismal metabolism, inhibit inflammation, reduce post-weaning anorexia, and promote growth and development in early-weaning rabbits. These positive effects of dietary butyrate were exerted via the modulation of the microbe-gut-brain axis.

Type 2 diabetes mellitus (T2DM) has been recognized as one of the most important and independent risk factors for hepatocellular cancer (HCC). However, there is still a lack of ideal tumor markers for HCC detection in the T2DM population. Serum lipids have been revealed as potential tumor markers for HCC. In this study, our objective was to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect several lipids including 8,15-dihydroxy-5,9,11,13-eicosatetraenoic acid (8,15-DiHETE), hexadecanedioic acid (HDA), 15-keto-13,14-dihydroprostaglandin A2 (DHK-PGA2), ricinoleic acid (RCL), octadecanedioic acid (OA) and 16-hydroxy hexadecanoic acid (16OHHA) in serum and explore their diagnostic potential for T2DM-positive [T2DM(+)] HCC. A robust LC-MS/MS method was established for the measurement of 8,15-DiHETE, HDA, DHK-PGA2, RCL, OA, and 16OHHA. The methodology validation was conducted, and the results suggested the reliability of this LC-MS/MS method for targeted lipids. Several serum lipids, including 8,15-DiHETE, HDA, DHK-PGA2, and OA were increased in T2DM(+) HCC patients. A biomarker signature that incorporated HDA, DHK-PGA2, and AFP was established and showed good diagnostic potential for T2DM(+) HCC, and the area under the ROC curve (AUC) was 0.87 for diagnosing T2DM(+) HCC from T2DM individuals. Additionally, the biomarker signature diagnosed small-size (AUC = 0.88) and early-stage (AUC = 0.79) tumors with high efficacy. Moreover, the biomarker signature could differentiate T2DM(+) HCC from other T2DM(+) tumors, including pancreatic, gastric and colorectal cancer (AUC = 0.88) as well. In conclusion, our study develops a novel tool for early diagnosis of T2DM(+) HCC in T2DM patients.

A novel malachite green molecularly imprinted membrane (MG-MIM) with specific selectivity for malachite green (MG) and leucomalachite green (LMG) was prepared using a hydrophobic glass fiber membrane as the polymer substrate, methyl violet as a template analog, 4-vinyl benzoic acid as the functional monomer, and ethyleneglycol dimethacrylate as the crosslinking agent. MG-MIM and non-imprinted membrane (NIM) were structurally characterized using scanning electron microscopy, surface area analyzer, Fourier-transform infrared spectrometer and synchronous thermal analyzer. The results showed that MG-MIM possessed a fluffier surface, porous and looser structure, and had good thermal stability. Adsorption properties of MG-MIM were investigated under optimal conditions, and adsorption equilibrium was reached in 20 min. The saturated adsorption capacities for MG and LMG were 24.25 ng·cm -2 and 13.40 ng·cm -2 , and the maximum imprinting factors were 2.41 and 3.20, respectively. Issues such as "template leakage" and "embedding" were resolved. The specific recognition ability for the targets was good and the adsorption capacity was stable even after five cycles. The proposed method was successfully applied for the detection of MG and LMG in real samples, and it showed good linear correlation in the range of 0 to 10.0 μg·L -1 (R 2 = 0.9991 and 0.9982), and high detection sensitivity (detection limits of MG and LMG of 0.005 μg/kg and 0.02 μg·kg -1 in shrimp, and 0.005 μg/kg and 0.02 μg/kg in fish sample). The recoveries and relative standard deviations were in the range of 76.31-93.26% and 0.73-3.72%, respectively. The proposed method provides a simple, efficient and promising alternative for monitoring MG and LMG in aquatic products.

To develop the full application potential of composite materials, research on the post-buckling behavior of composite stiffened panels is of great significance. In this paper, the impact and compression after impact (CAI) behaviors of four different types of composite stiffened panels were studied by numerical simulation and experimental methods. The low-velocity impact damage simulated dynamically was introduced as the initial state in the compression simulation, and a two-dimensional shell model with Hashin failure criteria and stiffness degradation was adopted to estimate the failure load of composite stiffened panels under impact and CAI. The error between simulation results and test results was less than 10%, showing that the method used in this study achieved considerable accuracy in experimental results. Analysis of the impact test results revealed that the extent of damage is related to many factors, including the cross-sectional size of stiffeners, the spacing of stiffeners, and the material and thickness of the skin. In addition, the influence of fatigue damage on residual strength after impact was also studied experimentally, with results showing that the buckling and failure loads decreased by about 5% under 10 6 flight fatigue loads. However, there were obvious fluctuations in the load-displacement curves, which may have been caused by debonding between the stiffeners and the skin. Experimental results and the simulation matrix show that the post-buckling ratio increased with the increase of the stiffness ratio, then was stable after 2.0. Furthermore, the thinner the skin, the greater the post-buckling ratio. The experimental and simulation results provide an important reference for the structural design and failure-mechanism analysis of composite stiffened panels.

Purpose: To assess the potential added value of Optical Genomic Mapping (OGM) for identifying chromosomal aberrations., Methods: We utilized Optical Genomic Mapping (OGM) to determine chromosomal aberrations in 46 children with B-cell Acute lymphoblastic leukemia ALL (B-ALL) and compared the results of OGM with conventional technologies. Partial detection results were verified by WGS and PCR., Results: OGM showed a good concordance with conventional cytogenetic techniques in identifying the reproducible and pathologically significant genomic SVs. Two new fusion genes ( LMNB1 :: PPP2R2B and TMEM272 :: KDM4B ) were identified by OGM and verified by WGS and RT-PCR for the first time. OGM has a greater ability to detect complex chromosomal aberrations, refine complicated karyotypes, and identify more SVs. Several novel fusion genes and single-gene alterations, associated with definite or potential pathologic significance that had not been detected by traditional methods, were also identified., Conclusion: OGM addresses some of the limitations associated with conventional cytogenomic testing. This all-in-one process allows the detection of most major genomic risk markers in one test, which may have important meanings for the development of leukemia pathogenesis and targeted drugs.

Homeodomain-leucine zipper (HD-ZIP) transcription factors are one of the plant-specific gene families involved in plant growth and response to adverse environmental conditions. However, little information is available on the HD-ZIP gene family in watermelon. In this study, forty ClHDZs were systemically identified in the watermelon genome, which were subsequently divided into four distinctive subfamilies (I-IV) based on the phylogenetic topology. HD-ZIP members in the same subfamily generally shared similar gene structures and conserved motifs. Syntenic analyses revealed that segmental duplications mainly contributed to the expansion of the watermelon HD-ZIP family, especially in subfamilies I and IV. HD-ZIP III was considered the most conserved subfamily during the evolutionary history. Moreover, expression profiling together with stress-related cis -elements in the promoter region unfolded the divergent transcriptional accumulation patterns under abiotic stresses. The majority (13/23) of ClHDZs in subfamilies I and II were downregulated under the drought condition, e.g., ClHDZ4 , ClHDZ13 , ClHDZ18 , ClHDZ19 , ClHDZ20 , and ClHDZ35 . On the contrary, most HD-ZIP genes were induced by cold and salt stimuli with few exceptions, such as ClHDZ3 and ClHDZ23 under cold stress and ClHDZ14 and ClHDZ15 under the salt condition. Notably, the gene ClHDZ14 was predominantly downregulated by three stresses whereas ClHDZ1 was upregulated, suggesting their possible core roles in response to these abiotic stimuli. Collectively, our findings provide promising candidates for the further genetic improvement of abiotic stress tolerance in watermelon.

To address the low Ca-induced growth inhibition of tomato plants, the mitigation effect of exogenous Si on tomato seedlings under low-Ca stress was investigated using different application methods. We specifically analyzed the effects of root application or foliar spraying of 1 mM Si on growth conditions, leaf photosynthetic properties, stomatal status, chlorophyll content, chlorophyll fluorescence, ATP activity and content, Calvin cycle-related enzymatic activity, and gene expression in tomato seedlings under low vs. adequate calcium conditions. We found that the low-Ca environment significantly affected (reduced) these parameters, resulting in growth limitation. Surprisingly, the application of 1 mM Si significantly increased plant height, stem diameter, and biomass accumulation, protected photosynthetic pigments, improved gas exchange, promoted ATP production, enhanced the activity of Calvin cycle key enzymes and expression of related genes, and ensured efficient photosynthesis to occur in plants under low-Ca conditions. Interestingly, when the same amount of Si was applied, the beneficial effects of Si were more pronounced under low-Ca conditions that under adequate Ca. We speculate that Si might promote the absorption and transport of calcium in plants. The effects of Si also differed depending on the application method; foliar spraying was better in alleviating photosynthetic inhibition in plants under low-Ca stress, whereas root application of Si significantly promoted root growth and development. Enhancing the photosynthetic capacity by foliar Si application is an effective strategy for ameliorating the growth inhibition of plants under low-Ca stress.

Background: Despite the enormous changes observed in China since entering the 21st century, little is known about changes in sleep quality among older adults., Aims: The purpose of this study is to explore the changes, features, and influence factors of sleep quality among the elderly in a ten-year period, providing evidence for sleep-quality enhancement., Methods: The data were obtained from the data of epidemiological sampling surveys on mental disorders in Shandong province in 2004 and 2015. A total of 4451 subjects (aged ≥ 60 years) in 2004 and 10,894 subjects (aged ≥ 60 years) in 2015 were selected by the multistage stratified sampling method. The demographic information and Pittsburgh Sleep Quality Index (PSQI) were collected., Results: The adjusted 1-month prevalence of poor sleep in 2015 was 22.5% (95% CI:21.7-23.3), which is lower than that in 2004 (24.8%) (95% CI:23.5-26.0, p = 0.002). The total score of the PSQI in 2015 (4.74 ± 3.96) was lower than that in 2004 (4.97 ± 4.18, p = 0.002). In 2015, a binary multi-factor logistic and stepwise regression analysis showed that being female, living in a rural area, living alone, being older, spending less years in school, and being jobless/unemployed made the participants more likely to develop poor sleep ( p < 0.05, p < 0.01)., Conclusions: In 2015, the overall sleep quality of the elderly (aged ≥ 60) in Shandong province was significantly improved compared to 2004. After more than 10 years, the characteristics of the elderly with sleep disturbances in Shandong province has changed. Therefore, more attention should be paid to gender, location of residence (rural or urban), living arrangement, age, education, occupation, and other factors to improve the sleep quality of the elderly.

Methionine aminopeptidases (MetAPs) catalyze the cleavage of the N-terminal initiator methionine (iMet) in new peptide chains and arylamides, which is essential for protein and peptide synthesis. MetAP is differentially expressed in two diamondback moth (DBM; Plutella xylostella ) strains: the G88 susceptible strain and the Cry1S1000 strain, which are resistant to the Bt toxin Cry1Ac, implicating that MetAP expression might be associated with Bt resistance. In this study, we identified and cloned a MetAP gene from DBMs, named PxMetAP1 , which has a CDS of 1140 bp and encodes a 379 amino acid protein. The relative expression of PxMetAP1 was found to be ~2.2-fold lower in the Cry1S1000 strain compared to that in the G88 strain. PxMetAP1 presents a stage- and tissue-specific expression pattern, with higher levels in the eggs, adults, integument, and fatbody of DBMs. The linkage between PxMetAP1 and Cry1Ac resistance is verified by genetic linkage analysis. The knockout of PxMetAP1 in G88 by CRISPR/Cas9 leads to a ~5.6-fold decrease in sensitivity to the Cry1Ac toxin, further supporting the association between the PxMetAP1 gene and Bt tolerance. Our research sheds light on the role of MetAP genes in the development of Bt tolerance in P. xylostella and enriches the knowledge for the management of such a cosmopolitan pest.

The CRISPR/Cas9 system is an efficient tool for reverse genetics validation, and the application of this system in the cell lines provides a new perspective on target gene analysis for the development of biotechnology tools. However, in the cell lines of diamondback moth, Plutella xylostella , the integrity of the CRISPR/Cas9 system and the utilization of this cell lines still need to be improved to ensure the application of the system. Here, we stabilize the transfection efficiency of the P. xylostella cell lines at different passages at about 60% by trying different transfection reagents and adjusting the transfection method. For Cas9 expression in the CRIPSPR/Cas9 system, we identified a strong endogenous promoter: the 217-2 promoter. The dual-luciferase and EGFP reporter assay demonstrated that it has a driving efficiency close to that of the IE1 promoter. We constructed pB-Cas9-Neo plasmid and pU6-sgRNA plasmid for CRISPR/Cas9 system and subsequent cell screening. The feasibility of the CRISPR/Cas9 system in P. xylostella cell lines was verified by knocking out endogenous and exogenous genes. Finally, we generated a transgenic Cas9 cell line of P. xylostella that would benefit future exploitation, such as knock-in and multi-threaded editing. Our works provides the validity of the CRISPR/Cas9 system in the P. xylostella cell lines and lays the foundation for further genetic and molecular studies on insects, particularly favoring gene function analysis.

Hepatitis B virus (HBV) infection is still one of the most dangerous viral illnesses. HBV infects around 257 million individuals worldwide. Hepatitis B in many individuals ultimately develops hepatocellular carcinoma (HCC), which is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. The innate immunity acts as the first line of defense against HBV infection through activating antiviral genes. Along with the immune responses, pro-inflammatory cytokines are triggered to enhance the antiviral responses, but this may result in acute or chronic liver inflammation, especially when the clearance of virus is unsuccessful. To a degree, the host innate immune and inflammatory responses dominate the HBV infection and liver pathogenesis. Thus, it is crucial to figure out the signaling pathways involved in the activation of antiviral factors and inflammatory cytokines. Here, we review the interplay between HBV and the signal pathways that mediates innate immune responses and inflammation. In addition, we summarize current therapeutic strategies for HBV infection via modulating innate immunity or inflammation. Characterizing the mechanisms that underlie these HBV-host interplays might provide new approaches for the cure of chronic HBV infection.

Automated robots are an important part of realizing sustainable food production in smart agriculture. Agricultural robots require a powerful and precise navigation system to be able to perform tasks in the field. Aiming at the problems of complex image background, as well as weed and light interference factors of the visual navigation system in field and greenhouse environments, a Faster-U-net model that retains the advantages of the U-net model feature jump connection is proposed. Based on the U-net model, pruning and optimization were carried out to predict crop ridges. Firstly, a corn dataset was trained to obtain the weight of the corn dataset. Then, the training weight of the obtained corn dataset was used as the pretraining weight for the cucumber, wheat, and tomato datasets, respectively. The three datasets were trained separately. Finally, the navigation line between ridges and the yaw angle of the robot were generated by B-spline curve fitting. The experimental results showed that the parameters of the improved path segmentation model were reduced by 65.86%, and the mPA was 97.39%. The recognition accuracy MIoU of the Faster-U-net model for maize, tomatoes, cucumbers, and wheat was 93.86%, 94.01%, 93.14%, and 89.10%, respectively. The processing speed of the single-core CPU was 22.32 fps/s. The proposed method had strong robustness in predicting rows of different crops. The average angle difference of the navigation line under a ridge environment such as that for corn, tomatoes, cucumbers, or wheat was 0.624°, 0.556°, 0.526°, and 0.999°, respectively. This research can provide technical support and reference for the research and development of intelligent agricultural robot navigation equipment in the field.

Lysine (Lys) is essential for skeletal muscle growth and protein synthesis in mammals. However, the regulatory network underlying Lys-regulated skeletal muscle development is unknown. To determine whether any cross-talk occurs among mammalian targets of rapamycin complex 1 (mTORC1) and Lys in the regulation of muscle satellite cells (SCs) proliferation, we applied the treatment rapamycin (a mTORC1 inhibitor) and MHY1485 (a mTORC1 activator) on Lys-added or -deficient SCs. The results show Lys deprivation significantly decreases SCs viability, protein synthesis, and cell cycling, increases autophagy and apoptosis, and inhibits the mTORC1 signaling pathway. Restoration of Lys content significantly attenuates this effect. mTORC1 signaling pathway activation during Lys deprivation or mTORC1 signaling pathway inhibition during Lys addition attenuates the effect of Lys deprivation or addition on SCs viability, protein synthesis, cell cycling, autophagy, and apoptosis. In conclusion, Lys could improve SCs proliferation, and inhibit SCs apoptosis and autophagy, via the mTORC1 signaling pathway.

Using behavioral and event-related potential (ERP) measures, the present study examined whether eye gaze triggers a unique form of attentional orienting toward threat-relevant targets. A threatening or neutral target was presented after a non-predictive gaze or an arrow cue. In Experiment 1, reaction times indicated that eye gaze and arrow cues triggered different attention orienting towards threatening targets, which was confirmed by target-elicited P3b latency in Experiment 2. Specifically, for targets preceded by arrow and gaze cues, P3b peak latency was shorter for neutral targets than threatening targets. However, the latency differences were significantly smaller for gaze cues than for arrow cues. Moreover, target-elicited N2 amplitude indicated a significantly stronger cue validity effect of eye gaze than that of arrows. These findings suggest that eye gaze uniquely triggers spatial attention orienting to socially threatening information.

Based on the twin bridge shear specimen, the cyclic shear experiments were performed on 1.2 mm thin plates of 316L metastable austenitic stainless steel with different strain amplitudes from 1 to 5% at ambient temperature. The fatigue behavior of 316L stainless steel under the cyclic shear path was studied, and the microscopic evolution of the material was analyzed. The results show that the cyclic stress response of 316L stainless steel exhibited cyclic hardening, saturation and cyclic softening, and the fatigue life is negatively correlated with the strain amplitude. The microstructure was analyzed by using electron back-scattered diffraction (EBSD). It was found that grain refinement and martensitic transformation during the deformation process led to rapid crack expansion and reduced the fatigue life of 316L.

A multi-mechanism constitutive model is proposed in this paper to better describe the effect of the local hardening behavior of the interface layer on the mechanical heterogeneity of dual-phase (DP) steel. The constitutive equations considering the geometrically necessary dislocations (GNDs) and back stress at grain level and sample level were established. Based on the finite element simulation results, the influences of local hardening and microstructure characteristics on the strain-stress evolution, statistical storage dislocations, GNDs, and back stress of DP steel were studied and discussed. Due to the local hardening effect, the ferrite phase was treated as an inhomogeneous matrix reinforced by some small islands of martensite in the simulation. The simulation results show that the thickness of the interface layer has a significant effect on the macroscopic hardening property of DP steel, while the number of interface layers has little effect. Meanwhile, the GNDs and back stress at the grain level also have little effect on the strengthening of DP steel. The contribution of GNDs at the sample level to the flow stress is about 47%.

The adoption of additive manufacturing (AM) techniques into the medical space has revolutionised tissue engineering. Depending upon the tissue type, specific AM approaches are capable of closely matching the physical and biological tissue attributes, to guide tissue regeneration. For hard tissue such as bone, powder bed fusion (PBF) techniques have significant potential, as they are capable of fabricating materials that can match the mechanical requirements necessary to maintain bone functionality and support regeneration. This review focuses on the PBF techniques that utilize laser sintering for creating scaffolds for bone tissue engineering (BTE) applications. Optimal scaffold requirements are explained, ranging from material biocompatibility and bioactivity, to generating specific architectures to recapitulate the porosity, interconnectivity, and mechanical properties of native human bone. The main objective of the review is to outline the most common materials processed using PBF in the context of BTE; initially outlining the most common polymers, including polyamide, polycaprolactone, polyethylene, and polyetheretherketone. Subsequent sections investigate the use of metals and ceramics in similar systems for BTE applications. The last section explores how composite materials can be used. Within each material section, the benefits and shortcomings are outlined, including their mechanical and biological performance, as well as associated printing parameters. The framework provided can be applied to the development of new, novel materials or laser-based approaches to ultimately generate bone tissue analogues or for guiding bone regeneration.

Copper (Cu) is an important coenzyme factor in cell signaling, such as cytochrome c oxidase (Complex IV). Metabolism plays an important role in regulating the fate of mammalian cells. The aim of this study is to experimentally investigate the effect of copper on cell metabolism in the dermal papilla cells of the Rex rabbit. In this study, Cu promoted proliferation of dermal papilla cells (p = 0.0008) while also increasing levels of cellular CIII, CIV, Complex IV and ATP. Moreover, fifty metabolites that were significantly different between Cu and controls were identified as potential biomarkers of Cu stimulation. Copper-stimulated cells had altered levels of arachidonic acid derivatives, S-glutamic acid, and citric acid, which were primarily linked to two different pathways: arachidonic acid metabolism (p < 0.0001) and alanine, aspartate and glutamate metabolism (p = 0.0003). The addition of Cu can increase the proliferation of Rex rabbit dermal papilla cells. Increased levels of ubiquinol-cytochrome c reductase complex core protein 2 (CIII) and cytochrome c oxidase subunit 1 (CIV) were associated with the increased levels of cellular cytochrome c oxidase (Complex IV) and adenosine triphosphate (ATP). In a word, copper promotes cell proliferation by maintaining the function of the cellular mitochondrial electron transport chain (ETC) pathway.

Collagens from a wide array of animals have been explored for use in tissue engineering in an effort to replicate the native extracellular environment of the body. Marine-derived biomaterials offer promise over their conventional mammalian counterparts due to lower risk of disease transfer as well as being compatible with more religious and ethical groups within society. Here, collagen type I derived from a marine source ( Macruronus novaezelandiae , Blue Grenadier) is compared with the more established porcine collagen type I and its potential in tissue engineering examined. Both collagens were methacrylated, to allow for UV crosslinking during extrusion 3D printing. The materials were shown to be highly cytocompatible with L929 fibroblasts. The mechanical properties of the marine-derived collagen were generally lower than those of the porcine-derived collagen; however, the Young's modulus for both collagens was shown to be tunable over a wide range. The marine-derived collagen was seen to be a potential biomaterial in tissue engineering; however, this may be limited due to its lower thermal stability at which point it degrades to gelatin.

As the most abundant protein in the extracellular matrix, collagen has become widely studied in the fields of tissue engineering and regenerative medicine. Of the various collagen types, collagen type I is the most commonly utilised in laboratory studies. In tissues, collagen type I forms into fibrils that provide an extended fibrillar network. In tissue engineering and regenerative medicine, little emphasis has been placed on the nature of the network that is formed. Various factors could affect the network structure, including the method used to extract collagen from native tissue, since this may remove the telopeptides, and the nature and extent of any chemical modifications and crosslinking moieties. The structure of any fibril network affects cellular proliferation and differentiation, as well as the overall modulus of hydrogels. In this study, the network-forming properties of two distinct forms of collagen (telo- and atelo-collagen) and their methacrylated derivatives were compared. The presence of the telopeptides facilitated fibril formation in the unmodified samples, but this benefit was substantially reduced by subsequent methacrylation, leading to a loss in the native self-assembly potential. Furthermore, the impact of the methacrylation of the collagen, which enables rapid crosslinking and makes it suitable for use in 3D printing, was investigated. The crosslinking of the methacrylated samples (both telo- and atelo-) was seen to improve the fibril-like network compared to the non-crosslinked samples. This contrasted with the samples of methacrylated gelatin, which showed little, if any, fibrillar or ordered network structure, regardless of whether they were crosslinked.

Efficient, high-precision, and automatic measurement of tunnel structural changes is the key to ensuring the safe operation of subways. Conventional manual, static, and discrete measurements cannot meet the requirements of rapid and full-section detection in subway construction and operation. Mobile laser scanning technology is the primary method for tunnel detection. Herein, we propose a method to calculate shield tunnel displacements of a full cross-section tunnel. The point cloud data, obtained via a mobile tunnel deformation detection system, were fitted, projected, and interpolated to generate an orthophoto image. Combined with the cumulative characteristics of the tunnel gray gradient, the longitudinal ring seam of the tunnel was identified, while the Canny algorithm and Hough line detection algorithm identified the transverse seam. The symmetrical vertical foot method and cross-section superposition analysis were used to calculate the circumferential and radial displacements, respectively. The proposed displacement calculation method achieves automatic recognition of a ring seam, reduces human-computer interaction, and is fast, intelligent, and accurate. Furthermore, the description of the tunnel deformation location and deformation amount is more quantitative and specific. These results confirm the significance of shield tunnel displacement monitoring based on mobile monitoring systems in tunnel disease monitoring.

The COVID-19 pandemic has greatly influenced society in the past few years. Park accessibility and social distancing are considered important under the threat of a long-term epidemic. However, measures that can maintain park accessibility and diminish virus spreading synchronously have been seldom studied before, which may threaten public health in all major urban parks globally. This paper proposed a methodology based on an agent-based model to analyze capacities for parks by simulating park visitor behaviors when they all are social distancing. The model was derived from historical visitor data and realistic visitor behaviors in three park settings. Then, park capacities of varied contact conditions, different park policies, and layout adjustments were analyzed. First, congestions caused by social distancing without proper visitor control are found inside all parks. Second, 85 to 3972 square meters per person is predicted as a safe space in different parks. Third, the current results can be easily adjusted according to various concerns regarding infection distance and rate. Finally, it can be inferred that information provisions are more effective than space design adjustments and mandatory measures. The results can guide park managers and those who plan and design park settings. They are also helpful in improving knowledge of the mechanisms behind visitor behaviors. Moreover, these findings can be tested and verified in a variety of public spaces with many other contact-based illnesses.

Grey wolf optimizer (GWO) is a meta-heuristic algorithm inspired by the hierarchy of grey wolves (Canis lupus). Fireworks algorithm (FWA) is a nature-inspired optimization method mimicking the explosion process of fireworks for optimization problems. Both of them have a strong optimal search capability. However, in some cases, GWO converges to the local optimum and FWA converges slowly. In this paper, a new hybrid algorithm (named as FWGWO) is proposed, which fuses the advantages of these two algorithms to achieve global optima effectively. The proposed algorithm combines the exploration ability of the fireworks algorithm with the exploitation ability of the grey wolf optimizer (GWO) by setting a balance coefficient. In order to test the competence of the proposed hybrid FWGWO, 16 well-known benchmark functions having a wide range of dimensions and varied complexities are used in this paper. The results of the proposed FWGWO are compared to nine other algorithms, including the standard FWA, the native GWO, enhanced grey wolf optimizer (EGWO), and augmented grey wolf optimizer (AGWO). The experimental results show that the FWGWO effectively improves the global optimal search capability and convergence speed of the GWO and FWA.

Glucose oxidase (GOx) based biosensors are commercialized and marketed for the high selectivity of GOx. Incorporation nanomaterials with GOx can increase the sensitivity performance. In this work, an enzyme glucose biosensor based on nanotubes was fabricated. By using Ti foil as a carrier, hydrogen titanate nanotubes (HTNTs), which present fine 3D structure with vast pores, were fabricated in-situ by the hydrothermal treatment. The multilayer nanotubes are open-ended with a diameter of 10 nm. Then glucose oxidase (GOx) was loaded on the nanotubes by cross-linking to form an electrode of the amperometric glucose biosensor (GOx/HTNTs/Ti electrode). The fabricated GOx/HTNTs/Ti electrode had a linear response to 1-10 mM glucose, and the response time was 1.5 s. The sensitivity of the biosensor was 1.541 μ A·mM -1 ·cm -2 , and the detection limit (S/N = 3) was 59 μ M. Obtained results indicate that the in-situ fabrication and unique 3D structure of GOx/HTNTs/Ti electrode are beneficial for its sensitivity., Competing Interests: The authors declare no conflict of interest.

Liposomes are extensively used in drug delivery, while alginates are widely used in tissue engineering. However, liposomes are usually thermally unstable and drug-leaking when in liquids, while the drug carriers made of alginates show low loading capacities when used for drug delivery. Herein, we developed a type of thermo-responsible liposome-alginate composite hydrogel (TSPMAH) by grafting thermo-responsive liposomes onto alginates by using Ca2+ mediated bonding between the phosphatidic serine (PS) in the liposome membrane and the alginate. The temperature-sensitivity of the liposomes was actualized by using phospholipids comprising dipalmitoylphosphatidylcholine (DPPC) and PS and the liposomes were prepared by a thin-film dispersion method. The TSPMAH was then successfully prepared by bridge-linking the microcapsules onto the alginate hydrogel via PS-Ca 2+ -Carboxyl-alginate interaction. Characterizations of the TSPMAH were carried out using scanning electron microscopy, transform infrared spectroscopy, and laser scanning confocal microscopy, respectively. Their rheological property was also characterized by using a rheometer. Cytotoxicity evaluations of the TSPMAH showed that the composite hydrogel was biocompatible, safe, and non-toxic. Further, loading and thermos-inducible release of model drugs encapsulated by the TSPMAH as a drug carrier system was also studied by making protamine-siRNA complex-carrying TSPMAH drug carriers. Our results indicated that the TSPMAH described herein has great potentials to be further developed into an intelligent drug delivery system.

Surface coating modification on a polyethylene separator serves as a promising way to meet the high requirements of thermal dimensional stability and excellent electrolyte wettability for lithium ion batteries (LIBs). In this paper, we report a new type of surface modified separator by coating polyvinylidene fluoride (PVDF) organic particles on traditional microporous polyethylene (PE) separators. The PE separator coated by PVDF particles (PE-PVDF separator) has higher porosity (61.4%), better electrolyte wettability (the contact angle to water was 3.28° ± 0.21°) and superior ionic conductivity (1.53 mS/cm) compared with the bare PE separator (51.2%, 111.3° ± 0.12°, 0.55 mS/cm). On one hand, the PVDF organic polymer has excellent organic electrolyte compatibility. On the other hand, the PVDF particles contain sub-micro spheres, of which the separator can possess a large specific surface area to absorb additional electrolyte. As a result, LIBs assembled using the PE-PVDF separator showed better electrochemical performances. For example, the button cell using a PE-PVDF as the separator had a higher capacity retention rate (70.01% capacity retention after 200 cycles at 0.5 C) than the bare PE separator (62.5% capacity retention after 200 cycles at 0.5 C). Moreover, the rate capability of LIBs was greatly improved as well-especially at larger current densities such as 2 C and 5 C.

Diallyl disulfide (DADs), a natural organic compound, is extracted from garlic and scallion and has anti-tumor effects against various tumors. This study investigated the anti-tumor activity of DADs in human osteosarcoma cells and the mechanisms. MG-63 cells were exposed to DADs (0, 20, 40, 60, 80, and 100 μM) for different lengths of time (24, 48, and 72 h). The CCK8 assay results showed that DADs inhibited osteosarcoma cell viability in a dose-and time-dependent manner. FITC-Annexin V/propidium iodide staining and flow cytometry demonstrated that the apoptotic ratio increased and the cell cycle was arrested at the G 2 /M phase as the DADs concentration was increased. A Western blot analysis was employed to detect the levels of caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and p62 as well as suppression of the mTOR pathway. High expression of LC3-II protein revealed that DADs induced formation of autophagosome. Furthermore, DADs-induced apoptosis was weakened after adding 3-methyladenine, demonstrating that the DADs treatment resulted in autophagy-mediated death of MG-63 cells. In addition, DADs depressed p-mTOR kinase activity, and the inhibited PI3K/Akt/mTOR pathway increased DADs-induced apoptosis and autophagy. In conclusion, our results reveal that DADs induced G 2 /M arrest, apoptosis, and autophagic death of human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

As China is now facing the severe challenge of rapid population ageing, the health behaviors in Chinese elderly people are of great significance for realizing the goal of "Healthy Ageing" and the construction of a "Healthy China". Little is known about the evolutionary trends of health behaviors in the Chinese elderly and about the factors influencing these trends; thus, the purposes of this paper are: (1) To describe the classes and evolutionary trends of health behaviors in the Chinese elderly; and (2) to explore the factors that influence the changes in the health behaviors in the elderly in China. Latent class analysis (LCA) is applied in this study to analyze the classes of health behaviors in the Chinese elderly. Growth mixture modelling (GMM) is employed to describe the evolutionary trends of the health behaviors in elderly people in China. In addition, the Bivariate analysis model is adopted to identify the influencing factors of the evolution of health behaviors. The data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2005 to 2014. The results reveal that the health behaviors in the Chinese elderly can be grouped into five classes: Negative, relatively negative, fair, relatively positive, and positive. Approximately 77.2% of the health behaviors in the Chinese elderly have the characteristics of "modified", with a positive tendency. Moreover, approximately 22.8% of the health behaviors in Chinese elderly people have the characteristics of "non-modified", with a negative tendency or remaining unchanged. The evolution of the health behaviors in the elderly in China is more affected by economic factors such as timely medical treatment during childhood, pension, occupations before the age of 60 and family income, as well as by self-rated health (SRH) and demographic characteristics such as household registration, age, and education level. Hence, various possible interventions should be made to improve the health behaviors in elderly people.