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8-17 DNAzymes (8-17, 17E, Mg5, and 17EV1) are in vitro-selected catalytic DNA molecules that are capable of cleaving complementary RNAs. The conserved residues in their similar catalytic cores, together with the metal ions, were suggested to contribute to the catalytic reaction. Based on the contribution of the less conserved residues in the bulge loop residues (W12, A15, A15.0) and the internal stem, new catalytic cores of 8-17 DNAzymes were programmed. The internal stem CTC-GAG seems to be more favorable for the DNAzymes than CCG-GGC, while an extra W12.0 led to a significant loss of activity of DNAzymes, which is contrary to the positive effect of A15.0, by which a new active DNAzyme 17EM was derived. It conducts a faster reaction than 17E. It is most active in the presence of Pb2+, with the metal ion preference of Pb2+ >> Zn2+ > Mn2+ > Ca2+ ≈ Mg2+. In the Pb2+ and Zn2+-mediated reactions of 17EM and 17E, the same Na+- and pH dependence were also observed as what was observed for 17E and other 8-17 DNAzymes. Therefore, 17EM is another member of the 8-17 DNAzymes, and it could be applied as a potential biosensor for RNA and metal ions. [ABSTRACT FROM AUTHOR]

This paper proposes a new enhanced method based on one-dimensional direct linear transformation for estimating vehicle movement states in video sequences. The proposed method utilizes a contoured structure of target vehicles, and the data collection procedure is found to be relatively stable and effective, providing a better applicability. The movements of vehicles in the video are captured by active calibration regions while the spatial consistency between the vehicle's driving track and the calibration information are in sync. The vehicle movement states in the verification phase are estimated using the proposed method first, and then the estimated states are compared with the actual movement states recorded in the experimental test. The results show that, in the case of camera perspective of 90 degrees, in all driving states of low speed, high speed, or deceleration, the error between estimated speed and recorded speed is less than 1.5%, the error of accelerations is less than 7%, and the error of distances is less than 2%; similarly, in the case of camera perspective of 30 degrees, the errors of speeds, distances, and accelerations are less than 4%, 5%, and 10%, respectively. It is found that the proposed method is superior to other existing methods., 1. Introduction As the video image records the vehicles' motions within the monitoring range and can provide objective raw data for further quantitative analysis, video surveillance equipment has been applied [...]

Cationic polymeric materials and cell-penetrating peptides (CPPs) were often used as the delivery vectors in the evaluation of nucleic acid therapeutics. 10-23 DNAzyme is a kind of potential antisense therapeutics by catalytic cleavage of the disease-related RNAs. Here, lipofectamine 2000 and Tat peptide were evaluated for their effect on the catalytic activity of 10-23 DNAzyme, with the observed rate constant, thermal stability, CD spectra, and PAGE analysis, with a duplex DNA mimicking DNAzyme-substrate as a control. It was shown that the cationic carriers had a negative effect on the catalytic performance of the 10-23 DNAzyme. Significantly, the destabilizing effect of the cationic carriers on the duplex formation was noteworthy, as a duplex formation is an essential prerequisite in the silencing mechanisms of antisense and RNAi. [ABSTRACT FROM AUTHOR]

An active disturbance rejection formation tracking problem is studied herein. Aiming at the time-varying formation tracking problem with external disturbance, a distributed control strategy of formation tracking based on extended state observer is presented. Considering the unknown state and external disturbance of single agent, a special extended state observer is produced which uses the output of neighbors. Subsequently, the extended state observer output–based formation protocol is designed to implement a predetermined formation. In addition, the necessary and sufficient condition of formation tracking control is obtained by taking full advantage of matrix transformation and Lyapunov theory. In the end, there are three simulation instances to verify the validity and feasibility of this method, which is mentioned in this article. [ABSTRACT FROM AUTHOR]

In this article, a robust extended state Kalman filter estimation algorithm for nonlinear complex networks is designed, fully considering the state coupling and colored noise among system nodes. The innovative measurement information subtraction method at adjacent moments deals with colored noise, making it more in line to meet engineering requirements. The states information of system nodes is redundant, and the collected data are processed by the quantizer, which greatly reduces the impact of network bandwidth constraints. Based on the bounds of the dynamic change rate of the nonlinear function rather than the bounds of the procedure itself, the upper bound of the error covariance is obtained, and real-time gain optimization is realized. Finally, the rationality and accuracy of the estimator are verified by simulation. According to the control variable method, the effects of the quantization density and quantization level of the quantizer on the stability of system are briefly demonstrated. [ABSTRACT FROM AUTHOR]

A feasible method in evaluating the protection effect and corrosion state of marine cathodic protection (CP) systems is collecting sufficient electric potential data around a submarine pipeline and then establishing the mapping relations between these data and corrosion states of pipelines. However, it is difficult for scientists and researchers to obtain those data accurately due to the harsh marine environments and absence of dedicated potential measurement device. In this paper, to alleviate these two problems, firstly, the theory of dimension and conductivity scaling (DACS) physical scale modeling of marine impressed current cathodic protection (ICCP) systems is generalized to marine CP systems, secondly, a potential measurement device is developed specially and analogue experiment is designed according to DACS physical scale modeling to verify the feasibility of the measuring system. The experimental results show that 92 percent of the measurement errors are less than 0.25mv, thereby providing an economical and feasible measuring system to get electric potential data around an actual submarine pipeline under CP.

To monitoring the subsea pipeline in real-time, a special potentiometric sensor array and a potential prediction model are presented in this paper. Firstly, to measure the potential of seawater, a special potentiometric sensor array with Ag/AgCl all-solid-state reference electrodes is first developed in this paper. Secondly, according to the obtained distribution law of electric field intensities a prediction model of the pipeline potentials is developed. Finally, the potentiometric sensor array is applied in sink experiment and the prediction model is validated by the sink measurements. The maximum error for pipeline potential prediction model is 1.1 mV. The proposed non-contact monitoring method for subsea pipeline can predict the potential of sea pipeline in real-time, thus providing important information for further subsea pipeline maintenance.

Leech attachment is a common nuisance to outdoor recreationists and farmers in aquatic environments. Consequences include bleeding, infection, and, rarely, death. Methods to prevent leech attachment are anecdotal and individual; effective repellent formulations with universal applicability are needed. In this study, icaridin is demonstrated to be repellent and toxic to aquatic leech, and formulation of icaridin loading nitrocellulose (Icar-Nitr) is proposed as a new leech repellent. The nitrocellulose provided sustained drug release and waterproof properties. One optimal formulation, 10-Icar-Nitr, proved effective for leech repelling in aquatic environment. Using a rat model, the same formulation also showed removal and killing after leech attachment. The nitrocellulose reduced percutaneous absorption of icaridin, and 10-Icar-Nitr showed good biocompatibility. This study provides a potential new and practicable strategy for prevention and removal against leech attachment and bites. [ABSTRACT FROM AUTHOR]

Surface Electromyography (sEMG) based human–robot interaction has been widely studied, where prediction of human voluntary torques is one of the key issues that have not been well addressed. In this article, a torque prediction method based on collaborative neuromusculoskeletal modeling and adaptive learning, is proposed to overcome the limitation of existing methods. First, an sEMG-torque model is designed in comprehensive consideration of the previous research results, the requirement for subject-specific adjustment and the coupling between the muscle or muscle-tendon length and the adjacent joint angles, where the latter two factors have rarely been considered in the literature. Then, by combining the advantages of the stochastic particle swarm optimization and conjugate gradient algorithms, a collaborative optimization method is designed to calibrate simultaneously the undetermined parameters. Moreover, an adaptive learning method based on Gaussian process regression is proposed to learn and predict the estimation errors in real time, by which it is supposed that the torque prediction accuracy can be improved efficiently. Finally, experiments were carried out to validate the performance of the proposed method. [ABSTRACT FROM AUTHOR]

Enhancing patients' engagement is of great benefit for neural rehabilitation. However, physiological and neurological differences among individuals can cause divergent responses to the same task, and the responses can further change considerably during training; both of these factors make engagement enhancement a challenge. This challenge can be overcome by training task optimization based on subjects' responses. To this end, an engagement enhancement method based on human-in-the-loop optimization is proposed in this paper. Firstly, an interactive speed-tracking riding game is designed as the training task in which four reference speed curves (RSCs) are designed to construct the reference trajectory in each generation. Each RSC is modeled using a piecewise function, which is determined by the starting velocity, transient time, and end velocity. Based on the parameterized model, the difficulty of the training task, which is a key factor affecting the engagement, can be optimized. Then, the objective function is designed with consideration to the tracking accuracy and the surface electromyogram (sEMG)-based muscle activation, and the physical and physiological responses of the subjects can consequently be evaluated simultaneously. Moreover, a covariance matrix adaption evolution strategy, which is relatively tolerant of both measurement noises and human adaptation, is used to generate the optimal parameters of the RSCs periodically. By optimization of the RSCs persistently, the objective function can be maximized, and the subjects' engagement can be enhanced. Finally, the performance of the proposed method is demonstrated by the validation and comparison experiments. The results show that both subjects' sEMG-based motor engagement and electroencephalography based neural engagement can be improved significantly and maintained at a high level. [ABSTRACT FROM AUTHOR]

Motor imagery based brain-computer interface (MI-BCI) has been studied for improvement of patients’ motor function in neurorehabilitation and motor assistance. However, the difficulties in performing imagery tasks limit its application. To overcome the limitation, an enhanced MI-BCI based on functional electrical stimulation (FES) and virtual reality (VR) is proposed in this study. On one hand, the FES is used to stimulate the subjects’ lower limbs before their imagination to make them experience the muscles’ contraction and improve their attention on the lower limbs, by which it is supposed that the subjects’ motor imagery (MI) abilities can be enhanced. On the other hand, a ball-kicking movement scenario from the first-person perspective is designed to provide visual guidance for performing MI tasks. The combination of FES and VR can be used to reduce the difficulties in performing MI tasks and improve classification accuracy. Finally, the comparison experiments were conducted on twelve healthy subjects to validate the performance of the enhanced MI-BCI. The results show that the classification performance can be improved significantly by using the proposed MI-BCI in terms of the classification accuracy (ACC), the area under the curve (AUC) and the F1 score (paired t-test, ${p} < 0.05$). [ABSTRACT FROM AUTHOR]

For the treatment of pain, the design of a bifunctional mu-opioid receptor (MOR)/delta-opioid receptor (DOR) agonist is an effective strategy to seek safer opioids with higher antinociceptive efficacy and diminished adverse side effects. Herein, we describe the design, synthesis, and evaluation of a novel bivalent ligand (SW-WL-2) with a methyl 1-(3-methoxy-3-oxopropyl)-4-(phenylamino) piperidine- 4-carboxylate moiety (remifentanil derivative) covalently linked to a dermorphin-like structure (H-Dmt- N -Me- D -Ala-Aba-Gly-NH 2 , BVD03) at the C-terminus. Our results showed that SW-WL-2 behaved as a potent dual agonist of MOR and DOR with significant and prolonged antinociceptive effects in acute pain models in vivo. Furthermore, SW-WL-2 exhibited reduced or no opioid-like side effects such as physical dependence or respiratory depression, in contrast to an equipotent analgesic dose of morphine or BVD03. Thus, SW-WL-2 should be used as a new lead compound for the discovery of safer opioid drugs for the treatment of pain. [ABSTRACT FROM AUTHOR]

CPT-11 (irinotecan) is a derivative of camptothecin which is a natural product derived from the Chinese tree Camptotheca acuminta and widely used in antitumor therapy. Here, the in vitro anti-tumor activity and associated mechanisms of a novel derivative of camptothecin, ZBH-1205, were investigated in a panel of 9 human tumor cell lines, as well as in HEK 293 and SK-OV-3/DPP, a multi-drug resistant (MDR) cell line, and compared to CPT-11 and 7-ethyl-10-hydroxy-camptothecin (SN38). Comparisons between the different compounds were made on the basis of IC 50 values as determined by the MTT assay, and flow cytometry was used to evaluate cell cycle progression, apoptosis, and the levels of pro- and active caspase-3 among different treatment groups. Interaction between the molecules and topoisomerase-1 (Topo-1)-DNA complexes was detected by a DNA relaxation assay. Our results demonstrated that IC 50 values for ZBH-1205 ranged from 0.0009 μmol/L to 2.5671 μmol/L, which were consistently lower than IC 50 values of CPT-11 or SN38 in the panel of cell lines, including SK-OV-3/DPP. Furthermore, ZBH-1205 was more effective than CPT-11 or SN38 at stabilizing Topo-1-DNA complexes and inducing tumor cell apoptosis. Therefore, ZBH-1205 is a promising chemotherapeutic agent to be further assessed in large-scale clinical trials. [ABSTRACT FROM AUTHOR]

Thesmall molecule fusion inhibitors N-(4-carboxy-3-hydroxyphenyl)-2,5-dimethylpyrrole(NB-2) and N-(3-carboxy-4-hydroxyphenyl)-2,5-dimethylpyrrole(A12) target a hydrophobic pocket of HIV-1 gp41 and havemoderate anti-HIV-1 activity. In this paper, we report the design,synthesis, and structure–activity relationship of a group ofhybrid molecules in which the pocket-binding domain segment of theC34 peptide was replaced with NB-2 and A12derivatives.In addition, the synergistic effect between the small molecule andpeptide moieties was analyzed, and lead compounds with a novel scaffoldwere discovered. We found that either the nonpeptide or peptide partalone showed weak activity against HIV-1-mediated cell–cellfusion, but the conjugates properly generated a strong synergisticeffect. Among them, conjugates Aoc−βAla–P26 andNoc−βAla–P26 exhibited a low nanomolar IC50in the cell–cell fusion assay and effectively inhibitedT20-sensitive and -resistant HIV-1 strains. Furthermore, the new moleculesexhibited better stability against proteinase K digestion than T20and C34. [ABSTRACT FROM AUTHOR]

Abstract: The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins. [Copyright &y& Elsevier]

Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Nav1.7 and anti-Nav1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Nav targets, could serve as new leads for the development of analgesic medicines. [ABSTRACT FROM AUTHOR]

'Biased' ligands of G protein-coupled receptors (GPCRs) represent a type of promising analgesic with reduced on-target side effects. PZM21, a potent μ-opioid-receptor (μOR)-biased agonist with a new chemical scaffold compared to classic opioids, has been identified as a therapeutic lead molecule for treating pain. In the current study, novel PZM21 analogues were synthesized and evaluated for their in vitro and in vivo efficacy. Novel compound 7a and PZM21 demonstrated undetectable β-arrestin-2 recruitment, however, their analgesic effects need to be further confirmed. Compounds 7b, 7d, and 7g were stronger analgesics than PZM21 in both the mouse formalin injection assay and the writhing test. Compound 7d was the most potent analogue, requiring a dose that was 1/16th to 1/4th of that of PZM21 for its analgesic activity in the two assays, respectively. Therefore, compound 7d could serve as a lead to develop new biased μOR agonists for treating pain. [ABSTRACT FROM AUTHOR]

The variable residue A15 of 8-17 and 17E DNAzymes could be modified at 6-amino group to obtain more efficient and more Ca2+-specific DNAzymes. A15 is a very important catalytic residue in defining catalytic efficiency and metal ion preference. • New chemical modification approach found for more efficient 8-17DNAzyme and 17E DNAzymes. • More Ca2+-specific DNAzymes obtained. • Importance of catalytic residues were evaluated at the level of functional groups. 8-17 and 17E DNAzyme are being explored as biosensors for metal ions and RNA motifs of interest, more sensitive and efficient DNAzymes are required to meet the practical applications. Their similarity in the catalytic cores and differences in catalytic efficiency and metal ion dependence initiated great interest about the contribution of the catalytic residues. Functionalization of four adenine residues in the catalytic cores of 8-17 DNAzyme and 17E was conducted with amino, guanidinium, and imidazolyl groups. In the bulge loops of 8-17 and 17E, N6-(3-aminopropyl)-2′-deoxyadenosine (residue 1) at A15 led to new DNAzymes 8-17DZ-A15-1 and 17E-A15-1 , with much more efficient cleavage ability in the Ca2+-mediated reaction and the greater preference for Ca2+ over Mg2+ than 8-17 DNAzyme and 17E, respectively, especially with a concentration-dependent increase of the selectivity, which is different from most DNAzymes with the similar dependence on both Mg2+ and Ca2+. With this kind of post-selection modification on 8-17 DNAzymes, for the first time, the catalytic efficiency and metal ion selectivity could be positively modulated. It is also helpful for the catalyic mechanistic studies of these DNAzymes, especially, the role of the unconserved A15 should be emphasized. [ABSTRACT FROM AUTHOR]

This study explored the potential of a series of PZM21 analogues for pain treatment. Specifically, the hydroxyphenyl ring of PZM21 was replaced with a naphthyl ring, the thienyl ring was substituted with either a phenyl ring or furan rings, and the essential dimethylamine and urea groups were retained. These compounds aimed to enhance safety and minimize the adverse effects associated with opioid drugs. The research findings suggest that compound 6a does not induce β-arrestin recruitment at low-nanomolar concentrations but exhibits significant analgesic effects in established mouse models. Compared to morphine, 6a shows advantages in alleviating respiratory depression and minimizing physical dependence. Molecular docking studies underscore the pivotal role of the D147 amino acid residue in the analgesic mechanism of 6a . Consequently, 6a is a compelling candidate for the development of safer opioid analgesics and warrants further attention.

Arctigenin (ARG) has potent antifatigue activity, but its clinical application has been restricted for its poor water solubility. In this study, seven ARG derivatives containing different amino acids coupled via an ethoxy linker were synthesized, and tested for their solubility, as well as activities to improve exercise performance in mice. All of the derivatives showed improved solubility compared to that of ARG. Derivative Z-A-6 exhibited the highest activity, showing that the mice ran a 4.88-fold greater distance in the running wheel test and swam a 2.86-fold greater time in the swimming test than those in the blank control group. Z-A-6 treatment increased the plasma superoxide dismutase and catalase concentrations as well as reduced lactic acid and blood urea nitrogen accumulation during exercise. Z-A-6 treatment enhanced the phosphorylation of adenosine monophosphate-activated protein kinase, and no acute toxicity was observed. The results will contribute to the development of potential antifatigue agents., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Mental state monitoring is a hot topic especially in neurorehabilitation, skill training, etc, for which the functional near-infrared spectroscopy (fNIRS) has been suggested to be used, and fewer detection channels and cross-subject performance are usually required for real-world application. To this goal, we propose a transformer-based method for cross-subject mental workload classification using fewer channels of fNIRS. Firstly, the input fNIRS signals in a window are divided into patches in the temporal order and transformed into embeddings, to which a classification token and learnable position embeddings are added. Then, a transformer encoder is used to learn the long-range dependencies among the embeddings, of which the output classification token is sent to a multilayer perceptron (MLP) head. Mental workload classification results can be represented by the outputs of the MLP head. Finally, comparison experiments were conducted on the open-access fNIRS2MW dataset. The results show that, the proposed method can outperform previous methods in cross-subject classification accuracy, and relatively efficient computation can be obtained.

Leech attachment is a common nuisance to outdoor recreationists and farmers in aquatic environments. Consequences include bleeding, infection, and, rarely, death. Methods to prevent leech attachment are anecdotal and individual; effective repellent formulations with universal applicability are needed. In this study, icaridin is demonstrated to be repellent and toxic to aquatic leech, and formulation of icaridin loading nitrocellulose (Icar-Nitr) is proposed as a new leech repellent. The nitrocellulose provided sustained drug release and waterproof properties. One optimal formulation, 10-Icar-Nitr, proved effective for leech repelling in aquatic environment. Using a rat model, the same formulation also showed removal and killing after leech attachment. The nitrocellulose reduced percutaneous absorption of icaridin, and 10-Icar-Nitr showed good biocompatibility. This study provides a potential new and practicable strategy for prevention and removal against leech attachment and bites.

Active rehabilitation training can improve patients' neural engagement and the rehabilitation effects. A position based impedance control strategy is proposed for implement of active training in this paper. Firstly, it is necessary to accurately estimate patients' active torques during the training process, which can be calculated by using the human-robot dynamic model. A novel friction model is designed, where the influence of the joint coupling factor and viscosity is considered to improve the model accuracy. In order to prevent sudden changes of the interaction force, a virtual tunnel around the reference trajectory is established to limit the motion range to ensure patient safety in case of emergency, such as muscle spasm. Then, a position based impedance control strategy designed in the joint space is used to convert human torques into the required movement. The strategy is implemented by a double closed loop control structure, the outer loop of which converts the interaction force into angular, angular velocity, and angular acceleration deviations by the inverse impedance equation. The regulated trajectory will be used as reference for the inner position control loop. The experimental results show that the proposed system dynamic model can be used to accurately estimate the patients' active torques, and the proposed control strategy can be used to design a compliant human-robot interaction interface, so that patients can complete the training task comfortably and naturally, and also safety of the training can be ensured.

Portal hypertension (PHT) is a common liver disease that is closely related to cirrhosis and has a high morbidity and mortality. The present study aimed to probe the efficacy of a novel nitric oxide (NO)-releasing agent with NO linked to ursodeoxycholic acid (UDCA) through threonine (UDCA-Thr-NO) as a liver-targeted therapy for cirrhosis and PHT. After intraperitoneal treatment of dimethyl nitrosamine-induced cirrhotic rats for 3 or 4 weeks, UDCA-Thr-NO could prevent ascites formation and reduce portal pressure instead of carotid artery pressure, when compared with UDCA or compound embryonic bovine liver extract tablets. Biochemical analysis of the rat sera also revealed that UDCA-Thr-NO improved the levels of alanine aminotransferase and total bilirubin and reduced the level of hydroxyproline (P < 0.05). Colorimetric analysis of the liver tissue by staining hematoxylin-eosin (HE) and Sirius red (SR) showed that UDCA-Thr-NO could improve pathological changes and reduce liver collagen deposition and intrahepatic resistance without affecting systemic circulation. It was concluded that UDCA-Thr-NO had a protective effect on liver injury and could be utilized to improve cirrhosis and PHT., Competing Interests: None.