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Based on the flexibility of the neck manipulator of the bionic pelican fishing device, the demand for carrying capacity and the consideration of economic benefits, a 3-DOF connecting rod manipulator based on the 5R kinematic chain was designed, and the kinematic characteristics of the 5R five-bar mechanism in two-dimensional space and the mobility of the mechanism under the constraint of the bar length were studied. Through the application of matlab simulation, the movable range of the mechanism is obtained and the data analysis of the predetermined track is realized within the movable range, and the angle change curve chart required for the motor to achieve the predetermined track is obtained. The predetermined movement track is simulated by using the corresponding data and motion characteristics of the curve chart, which verifies the feasibility of achieving the target tracksetting within the movable range of the track.

In order to meet the needs of surface floating objects fishing operations in small areas such as lakes and rivers, a fishing device is developed that can be used for high-intensity operations and is highly adaptable to the environment. In this paper, a water and land type bionic pelican surface floating object fishing device is developed based on the MeArm robotic arm combined with a three-degree-of-freedom linkage robotic arm using bionic principles. In order to meet the needs of the fishing function, the overall structure of the surface floating object fishing device was bionically designed by combining the large beak and flexible neck of the pelican, The innovative design of the mouth lower beak opening and closing mechanism, the lower beak gear rack lever slide mechanism, the mouth throat pouch bottom release mechanism and the neck structure are mainly carried out.The structural strength of the device under the most dangerous operating conditions was simulated using finite element analysis software for statics and dynamics simulation. The research results show that the structure of this design is reliable, and the experimental test of the prototype model verifies the validity and reliability of this design scheme, which provides the theoretical and experimental basis for the further development of the subsequent products.

Effective glucose surveillance provides a strong guarantee for the high-quality development of human health. Au nanomaterials possess compelling applications in nonenzymatic electrochemical glucose biosensors owing to superior catalytic performances and intriguing biocompatibility properties. However, it has been a grand challenge to accurately control the architecture and composition of Au nanomaterials to optimize their optical, electronic, and magnetic properties for further improving the performance of electrocatalytic sensing. Herein, ultra-low content Bi-anchored Au aerogels are synthesized via a one-step reduction strategy. Benefiting from the unique structure of aerogels as well as the synergistic effect between Au and Bi, the optimized Au

Although carbon nanozymes have attracted great interest due to their good biocompatibility, low cost, and high stability, designing high-active carbon nanozymes still faces great challenges. Herein, ultrathin nitrogen-doped carbon nanosheets with rich defects (d-NC) were prepared through a high-temperature annealing process, using potassium chloride and ammonium chloride as templates. Owing to the large specific surface area, rich defects and the high exposure of active sites, the proposed d-NC nanozymes exhibited excellent peroxidase-like activity. The d-NC nanozymes possess maximal reaction velocity and their specific activity is 9.4-fold higher than that of nitrogen-doped carbon nanozymes, indicating that the induced defects can boost the catalytic performance. Benefited from the good peroxidase-like activities of d-NC nanozymes, the colorimetric sensing platforms were constructed for the detection of urease activity and fluoride ion, exhibiting satisfactory stability and selectivity. This study not only offers a way to synthesize carbon nanozymes with improved enzyme-like activities but also broadens their applications in colorimetric biosensing.

Part of the Hang-Tai High-speed Railway (Hangzhou via Shaoxing to Taizhou in Zhejiang Provence) in China passes through the diatomaceous earth area, which is the first time in the history of Chinese high-speed railway construction. This type of soil has significant compressibility, swelling and disintegration. Diatomaceous earth also shows a sharp reduction in strength when exposed to water, which severely impacts the safety of the project. However, no studies have been carried out on the engineering practice of building a high-speed railway in the diatomaceous earth area in China. Moreover, there is limited experience in the construction of ballastless track through the diatomaceous earth area. In order to ensure the stability of the high-speed railway subgrade in diatomaceous earth area, and considering the high level of precipitation in the location of this railway, a kind of waterproof and drainage subgrade (WDS) is proposed to reduce the influence of precipitation on the strength of the diatomaceous earth foundation. The subgrade has a flexible waterproof and drainage layer (WDL) inside, which consists of capillary waterproof and drainage plates and medium-coarse sand. In the present study, field tests including immersion tests and excitation test are carried out on a subgrade test section to verify the subgrade structure. The tests mainly focus on construction technology, waterproof performance and dynamic characteristics. The studies show that the subgrade bed with the WDL can effectively avoid the diatomaceous earth foundation from rainfall interference and maintain the long-term stability of the subgrade. The flexible WDL in WDS has a significant energy dissipation effect in comparison with the traditional subgrade (TS) filler and can play a key role in vibration damping, promoting the attenuation of dynamic response in the downward and cross-sectional directions within the subgrade. The dynamic response of the WDS attenuates along the depth. In comparison with the existing high-speed railway subgrade measured data, its dynamic response attenuation coefficient is within acceptable limits. The laying of the WDL does not change the subgrade dynamic characteristics transfer law. The proposed structure meets the requirements of ballastless track construction for high-speed railways, and the WDL can be used in the design of high-speed railways for enhanced drainage protection in diatomaceous soil areas or other special soil areas.

Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS (including FUSION, PrediXcan, summary-data-based Mendelian randomization (SMR), joint-tissue imputation approach with Mendelian randomization (MR-JTI)), gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNP rs35874192, an eQTL SNP for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA-seq revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse, as well as genes dysregulated in postmortem brains of SCZ patients or in cerebral organoids derived from SCZ patients. The metabolomic and mitochondrial function analyses confirmed the deceased GABA levels resulted from reduced tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics data and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic system, highlighting the mitochondrial function in SCZ.

The high-speed railway (HSR) subgrade has a strict settlement-control standard at the mm level, but its deformation stability is significantly threatened on permafrost with poor thermal stability and in susceptible-to-thawing settlements. Therefore, the filler suitable for permafrost regions needs to be explored and determined. In this study, the frost heaves, permeabilities and static strength characteristics of three coarse fillers were experimentally investigated, and the optimal subgrade filler was determined for the certain HSR, the first HSR in permafrost regions around the world. The test fillers include pure fillers, 5% cement improved fillers and 5% cement + 3% modifier improved fillers, and the effects of curing time, modifier content and freeze–thaw cycles were analyzed. The test results show that: (1) the frost heave rate and permeability coefficient decrease with the increase of curing time and modifier content, while increasing with the freeze-thaw cycles; (2) After six freeze–thaw cycles, the cement + modifier improved filler’s frost heave rate and permeability coefficient are 0.51 and 0.00331 cm/s, a larger decrease in the frost heave rate (more than 50%) and the permeability coefficient (about one order of magnitude) than that of pure filler; (3) The cement + modifier improved filler shares the highest compressive strength under different curing times and freeze-thaw cycles. In summary, the modifier has a more significant influence on the engineering characteristics than the curing time or freeze-thaw cycles, and the cement + modifier improved filler has the best comprehensive performance. This study will provide a technical reference for the foundation-treatment and disease-prevention of HSRs in island permafrost regions.

Effective strategies are needed to prevent the development of neuroinflammation, which is associated with nervous system disease, in patients. A previous study indicated that mitochonic acid 5 (MA‑5) may promote the survival of microglial cells via mitofusin 2 (Mfn2)‑associated mitophagy in response to lipopolysaccharide (LPS)‑induced inflammation. The current study investigated the role and underlying mechanisms of MA‑5 in the migration of BV‑2 cells following LPS‑mediated inflammation. The results of the present study revealed that MA‑5 promoted migration and upregulated the expression of F‑actin, C‑X‑C motif chemokine receptor (CXCR) 4 and CXCR7 in BV‑2 cells in response to LPS‑induced inflammation. The results also indicate that MA‑5 did not promote migration or upregulate the expression of F‑actin, CXCR4 or CXCR7 following the inhibition of Mfn2. Overall, the results of the present study suggest that MA‑5 may promote the migration of microglial cells via Mfn2‑associated mitophagy following LPS‑induced inflammation.

Enzyme cascade reactions in biological systems can effectively improve the catalytic performances owing to their high local concentration, efficient mass transfer and reduced intermediate decomposition. However, the disadvantages of high cost, low stability, and easy inactivation limit their practical applications in harsh environments. Nanozymes as the substitutes for enzymes not only have enzyme-like activities but also possess high stability, tunable catalytic property, and high pH/temperature tolerance, which have been intensively investigated for the establishment of biomimetic catalysis systems. In this review, we first summarized the recent development of the construction and advantage of the nanozyme-involved cascade reaction system. Then, the biomedical applications of the nanozyme-enhanced biomimetic cascade catalytic systems, including biosensing, therapies and antioxidation, were highlighted in detail. Finally, current challenges and future perspectives for nanozyme-activated cascade reactions are discussed and outlooked.

The rational construction of advanced sensing platforms to sensitively detect H2O2 produced by living cells is one of the challenges in both physiological and pathological fields. Owing to the extraordinary catalytic performances and similar metal coordination to natural metalloenzymes, single atomic site catalysts (SASCs) with intrinsic peroxidase (POD)-like activity have shown great promise for H2O2 detection. However, there still exists an obvious gap between them and natural enzymes because of the great challenge in rationally modulating the electronic and geometrical structures of central atoms. Note that the deliberate modulation of the metal-support interaction may give rise to the promising catalytic activity. In this work, an extremely sensitive electrochemical H2O2 biosensor based on single atomic Fe sites coupled with carbon-encapsulated Fe3C crystals (Fe3C@C/Fe-N-C) is proposed. Compared with the conventional Fe SASCs (Fe-N-C), Fe3C@C/Fe-N-C exhibits superior POD-like activity and electrochemical H2O2 sensing performance with a high sensitivity of 1225 μA/mM·cm2, fast response within 2 s, and a low detection limit of 0.26 μM. Significantly, sensitive monitoring of H2O2 released from living cells is also achieved. Moreover, the density functional theory calculations reveal that the incorporated Fe3C nanocrystals donate electrons to single atomic Fe sites, endowing them with improved activation ability of H2O2 and further enhancing the overall activity. This work provides a new design of synergistically enhanced single atomic sites for electrochemical sensing applications.

In order to not only improve the stability of nanomicelles in blood circulation but also promote the cellular uptake in tumors and rapidly release the encapsulated drugs in tumor cells, a kind of acid/reduction dual-sensitive amphiphilic graft polyurethane with folic acid and detachable poly(ethylene glycol) (FA-PUSS-g

Microglia are resident immune cells in the central nervous system, playing critical roles in brain development and homeostasis. Increasing evidence has implicated microglia dysfunction in the pathogenesis of various brain disorders ranging from psychiatric disorders to neurodegenerative diseases. Using a human cell-based model to illuminate the functional mechanisms of microglia will promote pathological studies and drug development. The recently developed microglia-containing human brain organoids (MC-HBOs), in-vitro three-dimensional cell cultures that recapitulate key features of the human brain, have provided a new avenue to model brain development and pathology. However, MC-HBOs generated from different methods differ in the origin, proportion, and fidelity of microglia within the organoids, and may have produced inconsistent results. To help researchers to develop a robust and reproducible model that recapitulates in-vivo signatures of human microglia to study brain development and pathology, this review summarized the current methods used to generate MC-HBOs and provided opinions on the use of MC-HBOs for disease modeling and functional studies.

Design of highly active carbon nanozymes and further establishment of ultrasensitive biosensors remain a challenge. Herein, hierarchically porous carbon nanozymes with sulfur (S)/nitrogen (N) codoping (SNC) were developed. Compared with N-doped carbon (NC) nanozymes, SNC nanozymes have a smaller Michaelis-Menten constant and higher specific activities, demonstrating that the S-doping in SNC nanozymes could not only enhance their affinity toward substrates but also improve their catalytic performance. These results may be caused by the synergistic effect of heteroatoms (S and N). Because of the good enzyme-like activity, the proposed SNC nanozymes were exploited to the colorimetric detection of the total antioxidant capacity (TAC) using ascorbic acid as a typical model with a limit of detection of 0.08 mM. Because of its high sensitivity and selectivity and encouraging performance, the detection method presented practical feasibility for the TAC assay in commercial beverages. This work paves a way to design the highly active carbon nanozymes and expand their applications in the construction of high-performance biosensors.

Despite the breakthroughs of transition-metal catalysts in enzyme mimicking, fundamental investigation on the design of efficient nanozymes at the atomic scale is still required for boosting their ...

In the era of high-speed trains, it is very important to ensure the safety and stability of rail tracks under adverse conditions including seasonal freezing and thawing. Freeze–thaw cycles (FTCs) affecting the engineering performance of coarse-grained soil (CGS) is one of the major reasons for track deterioration. The reported results of a number of static freeze–thaw triaxial tests on the shear behaviour of CGS are analysed herein. It was observed that confining pressure (σ3) and FTCs have a significant influence on the shear behaviour of CGS. In this paper, an empirical mathematical model has been proposed to capture the dilatancy of CGS subjected to FTCs during shearing. The empirical constants a, b, and c proposed in the model are a function of σ3 and FTCs. The results of the model have been compared with the laboratory experiments and are found to be in good agreement.

Although single-atom catalysts with high enzyme-like activities have been found, the rational design of highly active peroxidase (POD)-like nanozymes is still a formidable challenge. Herein, highly active POD-like nanozymes were synthesized through loading Pt clusters on the Fe single-atom (FeSA-PtC) nanozymes. The POD-like activity of FeSA-PtC nanozymes is enhanced 4.5-fold and 7-fold, in comparison to that of FeSA and PtC nanozymes, respectively, which is attributed to the unexpected synergistic effect between Fe single atoms and Pt clusters. Based on the outstanding POD-like activity of FeSA-PtC nanozymes, a cascade signal amplification strategy was constructed by combining glucose oxidase for the colorimetric biosensing of prostate-specific antigens, exhibiting satisfactory sensitivity, high selectivity, a low detection limit of 1.8 pg/mL, and practical feasibility in serum sample detection. This work may serve as a tough foundation to guide the design of superior POD-like nanozymes and expand the application in biosensing.

Nanomaterials with enzyme-like activities, coined nanozymes, have been researched widely as they offer unparalleled advantages in terms of low cost, superior activity, and high stability. The complex structure and composition of nanozymes has led to extensive investigation of their catalytic sites at an atomic scale, and to an in-depth understanding of the biocatalysis occurring. Single-atom catalysts (SACs), characterized by atomically dispersed active sites, have provided opportunities for mimicking metalloprotease and for bridging the gap between natural enzymes and nanozymes. In this Minireview, we illustrate the unique properties of nanozymes and we discuss recent advances in the synthesis, characterization, and applications of SACs. Subsequently, we outline the impressive progress made in single-atom nanozymes and we discuss their applications in sensing, degradation of organic pollutants, and in therapeutic roles. Finally, we present the major challenges and opportunities remaining for a successful marriage of nanozymes and SACs.

Improvement in the sensitivity and portability of enzyme-linked immunosorbent assay (ELISA) still faced huge challenges recently. Inspired by the nanoprecipitation process for the carrier-free nanodrug in drug delivery systems, we developed an self-assembly strategy to prepare a kind of all-inclusive allochroic 3,3',5,5'-tetramethylbenzidine (TMB) nanoparticles for developing improved ELISA (named TLISA). During the self-assembly of TMB molecules, the antibody as signal recognition units and bovine serum albumin as the stabilizing agents could be accommodated simultaneously through hydrogen-bonding and van der Waals interactions to form all-inclusive signal tags, which can avoid the complex cross-linking procedures. Due to the ultrahigh loading capacity (817 mg/g) of TMB molecules, the sensitivity of TLISA toward inflammatory biomarkers interleukin-6 was 11.82 times higher than that of conventional ELISA, which paves an avenue to develop an ultrasensitive colorimetric immunoassay.

Background and purpose Parkinson's disease (PD), a common neurodegenerative disorder with motor and nonmotor symptoms, does not have effective treatments. Dietary tryptophan (Trp) supplementation has potential benefits for the treatment of multiple disorders. However, whether additional Trp in the diet could be beneficial for PD remains to beinvestigated. In the present study, the neuroprotective role of dietary Trp on a rotenone‐induced rat model of PD was determined. Methods The rotenone was injected to build the PD model, and then the rats were treated with Trp in the diet. And then, an open field test, western blot analysis, and enzyme linked immunosorbent assay (ELISA) were performed. Results We observed that dietary Trp significantly ameliorated impaired motor function, upregulated tyrosine hydroxylase expression, inhibited the nuclear transport of Nuclear factor‐kappa B (NF‐κB) in substantia nigra (SN), and downregulated the protein levels of IL‐1β, IL‐6, and TNF‐α in serum in rotenone‐treated rats. However, these patterns were reversed in response to treatment with ampicillin, an agent that can clean intestinal Trp metabolism flora. Moreover, after using CH223191, an inhibitor of the aromatic hydrocarbon receptor (AhR) pathway, dietary Trp could not exert neuroprotective roles in the rotenone‐induced rat model of PD. Conclusion These results suggest that Trp in the diet can protect against rotenone‐induced neurotoxicity to ameliorate motor deficits, which may be mediated through activating AhR pathway., In the present study, the neuroprotective role of dietary Trp on a rotenone‐induced rat model of PD was determined. We revealed that Trp in the diet can protect against rotenone‐induced neurotoxicity to ameliorate motor deficits, which may be mediated through activating AhR pathway.

Enzyme immobilization plays an essential role in solving the problems of the inherently fragile nature of enzymes. Although prominent stability and reuse of enzymes can be achieved by enzyme immobilization, their bioactivity and catalytic efficiency will be adversely affected. Herein, PdCu hydrogel nanozymes with a hierarchically porous structure were used to immobilize horseradish peroxidase (HRP) to obtain PdCu@HRP. In addition to the improvement of stability and reusability, PdCu@HRP displayed synergistically enhanced activities than native HRP and PdCu hydrogels. Not only the specific interactions between PdCu hydrogel nanozymes and enzymes but also the enrichment of substrates around enzymes by electrostatic adsorption of hydrogels was proposed to expound the enhanced catalytic activity. Accordingly, by taking advantage of the excellent catalytic performance of the PdCu@HRP and the glucose oxidase encapsulated in zeolitic imidazolate framework-8, colorimetric biosensing of the carcinoembryonic antigen via catalytic cascade reactions for achieving signal amplification was performed. The obtained biosensor enhanced the detection sensitivity by approximately 6.1-fold as compared to the conventional HRP-based enzyme-linked immunosorbent assay, demonstrating the promising potential in clinical diagnosis.

The rational construction of advanced sensing platforms to sensitively detect H

Benefiting from the maximum atom-utilization efficiency and distinct structural features, single-atom catalysts open a new avenue for the design of more functional catalysts, whereas their bioapplications are still in their infancy. Due to the advantages, platinum single atoms supported by cadmium sulfide nanorods (Pt SAs-CdS) are synthesized to build an ultrasensitive photoelectrochemical (PEC) biosensing platform. With the decoration of Pt SAs, the PEC signal of CdS is significantly boosted. Furthermore, theory calculations indicate the positively charged Pt SAs could change the charge distribution and increase the excited carrier density of CdS. Meanwhile, it also suggests that Cu2+ can severely hinder the photoexcitation and electron-hole separation of CdS. As a proof of concept, prostate-specific antigen is chosen as the target analyte to demonstrate the superiority of the Pt SAs-CdS-based PEC sensing system. As a result, the PEC biosensor based on Pt SAs-CdS exhibits outstanding detection sensitivity and promising applicability.

Development of highly sensitive biosensors has received ever-increasing attention over the years. Due to the unique physicochemical properties, the functional nanomaterial-enabled signal amplification strategy has made some great breakthroughs in biosensing. However, the sensitivity and selectivity still need further improvement. Single-atom catalysts (SACs) containing atomically dispersed metal active sites demonstrate distinctive advantages in catalytic activity and selectivity for various catalytic reactions. As a consequence, the SAC-enabled signal amplification strategy holds great promise in biosensors, demonstrating satisfactory sensitivity and selectivity with the assistance of tunable metal–support interactions, coordination environments and geometric/electronic structures of active sites. In this tutorial review, we briefly discuss the structural advantages of SACs. Then, the catalytic mechanism at the atomic scale and signal amplification effects of SACs in the colorimetric, electrochemical, chemiluminescence, electrochemiluminescence, and photoelectrochemical biosensing applications are highlighted in detail. Finally, opportunities and challenges to be faced in the future development of the SAC-enabled signal amplification strategy for biosensing are discussed and outlooked.

To ensure the safety and stability of train operation, a reasonable evaluation of long-term durability of railway subgrade subjected to large number of cyclic train loads is necessary. With the concept of controlling safety margins against excessive inelastic deformation, shakedown theory provides an effective approach for the analysis of long-term performance of geotechnical structures. In this paper, an improved thermo-parameters method (TPM) is proposed to carry out dynamic shakedown analysis on the railway subgrade. Mathematically, the method is formulated as an optimization problem, in which the objective function is the dynamic shakedown limit and variables are the shakedown residual stresses defined through the distribution of hypothetical thermal stress field and further described by the Non-Uniform Rational B-Splines (NURBS) surface. The presented solution procedure was incorporated to the finite element (FE) model and numerical examples were presented to demonstrate its effectiveness for different cases. An in-situ test conducted in a fill section of railway subgrade was used for numerical modeling and further result validation. The results indicated that the dynamic shakedown limits varied with the loading frequency and showed smaller values than the quasi-static shakedown limit, especially at the natural frequency of structure. The current findings may be beneficial to the further understanding of the long-term durability and stability of subgrade under dynamic loading, and provide useful information for the shakedown design of the railway subgrade.

To improve therapeutic efficacy, we designed novel poly(ethylene glycol) (PEG)-modified oxidized mesoporous carbon nanospheres (OMCNPs) that were loaded with the therapeutic drug doxorubicin (DOX) and targeted with ligand hyaluronic acid (HA) to kill lung cancer cells. ZnO quantum dots (ZnO QDs) were introduced not only to cap OMCNP-based carriers but also to chelate with DOX, which exhibited a high drug-loading capacity. Upon cellular uptake, the pH-sensitive ZnO lids dissolved to Zn2+ in tumor cells, resulting in dissociation of the Zn2+–DOX complex and controlled release of DOX. Moreover, the novel OMCNP-based system could generate hyperthermia and facilitate the release of loaded DOX with near-infrared (NIR) irradiation. The combined chemo-/photothermal-targeted therapy exhibited significant advantages superior to single chemotherapy or photothermal therapy. This technology provided an excellent lung cancer cell-targeted drug delivery system, integrating chemotherapy with photothermal therapy. This ch...