Unsatisfactory Effect Research Articles

Liraglutide as an innovative and multifunctional drug for patients with obesity – the current state of knowledge and future prospects

Obesity is considered a disease of civilization representing a global health and social problem. Currently, 21% of adult Poles suffer from obesity, so every fifth patient contacted by a doctor is obese. Obesity is a chronic disease, associated with excessive accumulation of adipose tissue, which causes a deterioration in the health and quality of life of an obese patient. It also consequently leads to an increased risk of developing many diseases - including cardiovascular, metabolic and neoplastic diseases. Excessive body weight ranks sixth in importance as a risk factor responsible for the number of deaths worldwide. The mainstay of obesity treatment is lifestyle modification. It includes changing eating habits and increasing physical activity. However, due to the high prevalence of obesity in developed countries, its serious consequences and the unsatisfactory effect of weight loss in some patients with an appropriate diet, pharmacological methods of obesity treatment were searched for. Currently, there are three drugs approved for the treatment of obesity in Poland: orlistat, a combined preparation of naltrexone + bupropion and liraglutide – agonist of a glucagon-like peptide-1 receptor. The effectiveness of one of them - liraglutide - is particularly significant, and the effect of this drug in reducing cardiovascular risk is also promising, which is extremely important in obese patients. For this reason, in the latest recommendations of the Polish Obesity Treatment Association, liraglutide is indicated as the drug of first choice for obese or overweight patients with a BMI ≥27 kg / m2, in whom coexisting: pre-diabetes, type 2 diabetes, arterial hypertension, polycystic ovary syndrome, nonalcoholic fatty liver disease, metabolic syndrome, atherosclerosis or sleep apnea syndrome. Due to the presence of GLP-1 receptors in many organs, the use of liraglutide in the future would probably extend to more diseases than obesity and type 2 diabetes.

Bearing fault diagnosis method based on improved Siamese neural network with small sample

Fault diagnosis of rolling bearings is very important for monitoring the health of rotating machinery. However, in actual industrial production, owing to the constraints of conditions and costs, only a small number of bearing fault samples can be obtained, which leads to an unsatisfactory effect of traditional fault diagnosis models based on data-driven methods. Therefore, this study proposes a small-sample bearing fault diagnosis method based on an improved Siamese neural network (ISNN). This method adds a classification branch to the standard Siamese network and replaces the common Euclidean distance measurement with a network measurement. The model includes three networks: a feature extraction network, a relationship measurement network, and a fault classification network. First, the fault samples were input into the same feature extraction network in pairs, and a long and short-term memory (LSTM) network and convolutional neural network (CNN) were used to map the bearing signal data to the low-dimensional feature space. Then, the extracted sample features were measured for similarity by the relationship measurement network; at the same time, the features were input into the classification network to complete the bearing fault recognition. When the number of training samples was particularly small (training set A, 10 samples), the accuracy of 1D CNN, Prototype net and Siamese net were 49.8%, 60.2% and 58.6% respectively, while the accuracy of the proposed ISNN method was 84.1%. For the 100-sample case of training set D, the accuracy of 1D CNN was improved to 93.4%, which was still higher than that of prototype and Siam network, while the accuracy of ISNN method reached 98.1%.The experimental results show that the method in this study achieved higher fault diagnosis accuracy and better generalization in the case of small samples.

Aggregation-Induced Emission Luminogens for Enhanced Photodynamic Therapy: From Organelle Targeting to Tumor Targeting.

Photodynamic therapy (PDT) has attracted much attention in the field of anticancer treatment. However, PDT has to face challenges, such as aggregation caused by quenching of reactive oxygen species (ROS), and short 1O2 lifetime, which lead to unsatisfactory therapeutic effect. Aggregation-induced emission luminogen (AIEgens)-based photosensitizers (PSs) showed enhanced ROS generation upon aggregation, which showed great potential for hypoxic tumor treatment with enhanced PDT effect. In this review, we summarized the design strategies and applications of AIEgen-based PSs with improved PDT efficacy since 2019. Firstly, we introduce the research background and some basic knowledge in the related field. Secondly, the recent approaches of AIEgen-based PSs for enhanced PDT are summarized in two categories: (1) organelle-targeting PSs that could cause direct damage to organelles to enhance PDT effects, and (2) PSs with tumor-targeting abilities to selectively suppress tumor growth and reduce side effects. Finally, current challenges and future opportunities are discussed. We hope this review can offer new insights and inspirations for the development of AIEgen-based PSs for better PDT effect.

Safety and Effectiveness of Ruxolitinib in Real-World Patients with Myelofibrosis: A 2-Year Observational Study from Taiwan

Introduction Ruxolitinib (RUX) is an approved JAK1/JAK2 inhibitor for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), and post-essential thrombocythemia myelofibrosis (PET-MF), but real-world safety and efficacy of RUX in Taiwan are not well understood. This study was conducted to evaluate the safety and efficacy of treatment with RUX with intermediate-2 or high risk PMF, PPV-MF or PET-MF in routine clinical practice. Method This 2-year, single-arm, multicenter, post-marketing surveillance registry collected data on the safety, tolerability, efficacy, and other clinical information of adult patients (pts) aged ≥20 years with a confirmed diagnosis of intermediate-2 or high-risk PMF, PPV-MF, or PET-MF who either received RUX or starting RUX in accordance with the general clinical practice in Taiwan. Primary endpoint included collection of adverse events (AEs), AE of special interest (AESIs; anemia, thrombocytopenia, leukocytosis, hepatitis B virus (HBV) infection or reactivation, tuberculosis (TB) infection, and other infections), and serious adverse events (SAEs) throughout the study. Key secondary endpoints included treatment duration, discontinuation rates, dosage of prescribed RUX, Myeloproliferative Neoplasm symptom assessment form (MPN-10) score after study entry and change in spleen size, specifically in naïve patients who were eligible for spleen response evaluation. Results A total of 99 (51% PMF, 22.4% PPV-MF, and 26.5% PET-MF) pts were recruited, of which 38 (38.4%) pts discontinued due to consent withdrawal (n=11), death (n=10), discontinued prescription of RUX for 3 months (n=4), AEs (n = 2), unsatisfactory therapeutic effect (n=2), administrative problems (n=1), disease progression (n=1), required immediate stem cell transplantation (n=1), and others (n=6). Median age was 68.1 (range: 38.3-87.2) years and gender ratio was balanced, with 97 Taiwanese pts (98.0%). Median disease duration was 13.9 months (range: 0-967.6 months) and 70.7% and 28.3% of pts were identified with the risk of intermediate-2 or high using IPSS/DIPSS risk assessment, respectively. Majority of the recruited pts were RUX pre-treated (n=75; 75.8%) and 24.2% (n=24) pts were RUX-naïve at baseline. During the study, 88 pts (89.8%) had 673 AEs, and 44 (44.9%) experienced 159 SAEs. Half of the pts (55.1%) had moderate or severe SAEs and 39 pts recovered. Over 80% of SAEs (n=131) were not related to RUX. Major AESIs were anemia (29.6%) and thrombocytopenia (20.4%). There were no HBV infection or reactivation reported; 2% of pts had TB while 3% of pts had herpes zoster infections. The major reported infection was pneumonia (20.4%). Key safety data are summarized in Table 1. Most pts had their AEs resolved (77.6%), while 10 deaths occurred due to AEs (10.2%). Majority of the pts (41.8%) received a daily dose of RUX 20 mg at the enrolment, with an average mean daily dose of 22.7±9.2 mg (Figure 1). For naïve pts, mean initial dose was 18.8 ± 8.50 mg and gradually titrated up to 22.3 ± 8.69 mg at 3 months and to 24.0 ± 9.17 mg at 6 months. Among 98 pts, 13.3% pts whose platelet counts between 100-200×103/μL and 21.4% pts whose platelet counts were >200×103/μL were treated with RUX 5-10 mg twice daily. Among 27 RUX pre-treated patients (mean RUX duration before study entry: 17.0 ± 20.98 months), spleen size by palpation was relatively stable throughout the study period. For the 7 RUX naïve pts, the mean spleen size change from baseline was -15.9 %± 28.72 at 12 weeks, -30.8% ± 31.28 at 24 weeks, -54.2% ± 41.93 at 48 weeks and -52.0% ± 36.41 at 96 weeks. However, it should be interpreted with caution due to the small pt pool. A total of 65 pts (65.7%) had >50% improvement in the symptom response by MPN-10 during 2-year study period. . Conclusion This is the first real-world study in Taiwan to evaluate safety and efficacy with RUX in patients with MF. It was observed that physicians employed a conservative strategy for a lower starting dose with gradual titration resulting in comparable safety profile, but lower incidences of thrombocytopenia compared to published clinical trials. The majority of pts reported continuous symptomatic improvement and a small number of RUX naïve pts had pronounced spleen size reduction. Further investigations are required to evaluate whether optimal dose of RUX or titration speed would improve spleen response. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Hematological Response to Avatrombopag Switch in Thrombopoietin Receptor Agonist-Refractory Aplastic Anemia

ATG combined with CsA is the first-line treatment for patients with SAA who cannot choose HLA-matched HSCT because of various conditions. The HR rate is only approximately 60-80%, and the CR is not high. The lack of residual HSC in patients is an important reason for this unsatisfactory effect. RhTPO/TPO-RA combine with HSC membrane receptors to promote their proliferation and differentiation, expand multipotent hematopoietic progenitor cells in vivo. Studies have found that TPO-RA eltrombopag (EPAG) combined with IST can significantly increase the HR rate and improve the quality of the HR. From 40-50% hematologic improvement can also be obtained with refractory SAA. However, TPO-RA treatment is ineffective in some patients. Avatrombopag (APAG) acts on the transmembrane region of the TPO receptor, has a stronger effect than EPAG, and has no obvious liver toxicity. We analyzed the efficacy and safety of IST combined with rhTPO and/or EPAG in patients with SAA of switching to APAG. We retrospectively analyzed the data of 10 patients who were hospitalized between January and December 2021. All patients have been diagnosed with V/SAA. They received IST combined with rhTPO/TPO-RA treatment, failed to obtain a HR, and were converted to APAG. The patients were treated with IST for at least 6 months, combined with rhTPO and/or EPAG for at least 3 months, and did not get HR. None of the patients included in this study was suitable for undergo allogeneic HSCT. APAG was administered orally at a dose of 40 mg/day once a day for at least 6 months.The efficacy criteria for refractory SAA were defined as follows: one-line response included platelet response (HI-P), neutrophil response (HI-N), and erythroid response (HI-E). The 2-line HR could be a combination of any two of the aforementioned one-line responses. A trilineage response was defined as a patient with simultaneous platelet, erythroid, and neutrophil responses, and the quality of the trilineage response was the same as that of the initial treatment with SAA/TDNSAA. Ten patients were included in the study, with a median age of 54 (14-68) years, including five males and five females. All patients received IST for a median of 8.5 (6-40) months. Four patients received rhTPO for 1-2 months followed by EPAG for 2-8 months. Six patients received only EPAG for 3-4 months. All the patients received rhTPO/TP-RA for a median of 3.5 (3-10) months. Five patients with PNH clones were positive by flow cytometry, and there was no hemolytic or biochemical evidence of hemolysis. Two patients had clonal chromosomal abnormalities: one with 47,XY; +8 [2/20] and the other with 45,XY; -Y [10/20]. Ten patients were converted to APAG treatment for a median of 6 (6-10) months. After 3 months of follow-up , seven patients obtained a HR (7/10, 70%), of which two patients obtained a HI-P and HI-N, and five patients (5/10, 50%) obtained a three-line HR (1-CR, 3-GPR, 1-PR). Seven patients (7/10, 70%) obtained HR after 6 months of follow-up, of which one patient obtained HI-P/N and six patients (6/10, 60%) obtained three-line HR (3-CR, t2-GPR, 1-PR). The patient with two-line HR further improved after 8 months of APAG, reaching a three-line blood cell response to PR. At the end of the last follow-up, the HR rate of all patients with APAG conversion therapy was 70%, and all of them achieved three-line blood cell responses (4-CR, 1-GPR, 2-PR). During the follow-up period, no APAG-related adverse events of grade 2 or above were found in any patient, no thrombotic events occurred, and no fibrous tissue hyperplasia was found in the bone marrow pathology review after 6 months of treatment. Among the five patients with PNH clones before APAG conversion therapy, three patients did not change significantly. Otherwise one patient's granulocyte PNH clone decreased from 16.2% at baseline to 6.3%, and the other patient's PNH clone increased from 9.8% at baseline to 19.6%, whereas there was no symptomatic hemolysis in all patient. One patient (1/10, 10%) with normal chromosomal before therapy get a new clonal chromosomal abnormality after 3 months. It was 46XX, t(X;4 )(p11.4;q21) [4/20]; the HR was assessed as GPR. In conclusion, patients with SAA refractory to TPO-RA, drug conversion therapy can be based on the safety, pharmacological, and pharmacodynamic characteristics of TPO-RA drugs. Therefore, APAG is a better choice for switch therapy in these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Metabolic Homeostasis-Regulated Nanoparticles for Antibody-Independent Cancer Radio-Immunotherapy.

The special metabolic traits of cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) are promising targets for developing novel cancer therapy strategies, especially the glycolysis and mitochondrial energy metabolism. However, therapies targeting a singular metabolic pathway are always counteracted by the metabolic reprogramming of cancer, resulting in unsatisfactory therapeutic effect. Herein, this work employs poly(ethylene glycol)-coated (PEGylated) liposomes as the drug delivery system for both mannose and levamisole hydrochloride to simultaneously inhibit glycolysis and restrain mitochondrial energy metabolism and thus inhibit tumor growth. In combination with radiotherapy, the liposomes can not only modulate the immunosuppressive TME by cellular metabolism regulation to achieve potent therapeutic effect for local tumors, but also suppress the M2 macrophage proliferation triggered by X-ray irradiation and thus enhance the immune response to inhibit metastatic lesions. In brief, this work provides a new therapeutic strategy targeting the special metabolic traits of cancer cells and immunosuppressive TAMs to enhance the abscopal effect of radiotherapy for cancer.

A Novel Biodegradable Nanoplatform for Tumor Microenvironments Responsive Bimodal Magnetic Resonance Imaging and Sonodynamic/Ion Interference Cascade Therapy

The unsatisfactory therapeutic effect and long-term adverse effect markedly prevent inorganic nanomaterials from clinical transformation. In light of this, we developed a novel biodegradable theranostic agent (MnCO3:Ho3+@DOX/Ca3(PO4)2@BSA, HMCDB) based on the sonosensitizer manganese carbonate (MnCO3) coating with calcium phosphate (Ca3(PO4)2) and simultaneously loaded it with the chemotherapeutic drug doxorubicin (DOX). Due to the mild acidity of the tumor microenvironment (TME), the Ca3(PO4)2 shell degraded first, releasing substantial quantities of calcium ions (Ca2+) and DOX. Meanwhile, with the ultrasound (US) irradiation, MnCO3 produced enough reactive oxygen species (ROS) to cause oxidative stress in the cells, resulting in accumulation of Ca2+. Consequently, the cascade effect significantly amplified the therapeutic effect. Importantly, the nanocomposite can be completely degraded and cleared from the body, demonstrating that it was a promising theranostic agent for tumor therapy. Furthermore, the doped holmium ions (Ho3+) and in situ generation of manganese ions (Mn2+) in TME endow the nanoagent with the ability for tumor-specific bimodality T1/T2-weighted magnetic resonance imaging (MRI). This novel nanoplatform with low toxicity and biodegradability holds great potential for cancer diagnosis and treatment.

A Pneumatic Control Method for Commercial Vehicle Electronic Brake System Based on EPV Module

The traditional electronic braking system (EBS) of a commercial vehicle has the problems of sluggish pressure response, large dynamic error and unsatisfactory braking effect during braking. First, a novel EBS system based on electronic pneumatic valves (EPV) module is designed, which integrated the control of each pneumatic valve. Secondly, the hardware of the EBS bottom controller and the air pressure closed-loop control are carried out. A kind of similar to PWM (SPWM) air pressure control method is proposed. By controlling the opening and closing time of the solenoid valves, the brake air pressure could be precisely regulated, and the dynamic response characteristics of the system are improved. Eventually, commercial vehicle air brake hardware in the loop (HIL) test platform based on LabVIEW and NI-PXI system is built to verify the effectiveness of the EBS dynamic response characteristics. The experimental results showed that the continuous control of EBS solenoid valves is realized by using the SPWM control method, and the fine dynamic response characteristics of EBS air pressure closed-loop control are ensured.

Stereoscopic plant-protection system integrating UAVs and autonomous ground sprayers for orchards.

For orchard plant protection, conventional large machines and small sprayers are practically restricted by either narrow planting intervals with dense leaves or their inadequate penetration power, which leads to an unsatisfactory effect of spray. This paper proposes a stereoscopic plant-protection strategy that integrates unmanned air and ground sprayers to spray different parts of canopies to improve uniformity. In order to verify the proposal, a stereoscopic plant-protection system (SPS) was developed, consisting of a small swing-arm sprayer and a T16 plant-protection Unmanned Aerial Vehicle (UAV). Then, optimal operation parameters were determined by Computational Fluid Dynamics (CFD) and orthogonal experiments, and the uniformity was finally quantified by trials. CFD and orthogonal experiments showed that a swing-arm angle of 60° and a forward speed of 0.4 m/s were optimal for the ground sprayer, whilst a height of 2.0 m from the top of canopies and a forward speed of 1.0 m/s were appropriate for the UAV. The trial results showed that the density of vertical droplet deposition varied from 90 to 107 deposits/cm2 in canopies, and the uniformity was 38.3% higher than conventional approaches. The uniformity of top, bottom, inside and outside canopies was significantly improved. Meanwhile, the density of droplet deposition on both sides of leaves in all test points exceeded 25 deposits/cm2, able to meet the standard of spray. This study provides a practical approach for uniform pesticide spray to large-canopy fruit trees. Moreover, the high flexibility of plant-protection UAVs and the significant trafficability of small swing-arm sprayers can solve the problem of large machine entering and leaving orchards.

A Tumor‐Specific Platform of Peroxynitrite Triggering Ferroptosis of Cancer Cells

AbstractPeroxynitrite (ONOO−) is a potent oxidant and nucleophile participating in a variety of pathophysiological processes as well as playing a major role in cancer therapy. However, the intracellular environment of solid tumors severely restricts the production of ONOO−, which leads to an unsatisfactory anticancer effect. Here, a tumor‐specific platform for ONOO− generation, prepared by linking a type I photosensitizer with a GSH‐responsive NO donor, is constructed to overcome the tumor hypoxic microenvironment and enhance treatment efficiency (NBS‐2S‐NO). Responding to the overexpressed glutathione (GSH) within tumors, NBS‐2S‐NO can selectively induce ONOO− generation after a cascade including red light irradiation causing superoxide radical (O2•−) production, GSH‐triggered NO release, and fast reaction between O2•− and NO. The generated ONOO− can cause oxidative damage to tumor cells, induce lipid peroxidation (LPO) during the cell death process and finally cause ferroptosis. Both in vitro and in vivo outcomes demonstrate the notable anticancer ferroptosis efficacy of this platform, suggesting not only an effective ferroptosis strategy for the design of new photosensitizers but also a worthy of reference for antioxidant regulation to enhance the oxidative damage during the tumor treatment process.

Quercetin Alleviates Lipopolysaccharide-Induced Cell Damage and Inflammation via Regulation of the TLR4/NF-κB Pathway in Bovine Intestinal Epithelial Cells.

Acute diarrhoea and intestinal inflammation represent one of the most prevalent clinical disorders of milk production, resulting in enormous annual financial damage for the dairy sector. In the context of an unsatisfactory therapeutic effect of antibiotics, the natural products of plants have been the focus of research. Quercetin is an important flavonoid found in a variety of plants, including fruits and vegetables, and has strong anti-inflammatory effects, so it has received extensive attention as a potential anti-inflammatory antioxidant. However, the underlying basis of quercetin on inflammatory reactions and oxidative tension generated by lipopolysaccharide (LPS) in bovine intestinal epithelial cells (BIECs) is currently unexplained. This research aimed to determine the influence of quercetin on LPS-induced inflammatory reactions, oxidative tension, and the barrier role of BIECs. Our findings demonstrated that BIEC viability was significantly improved in LPS-treated BIEC with 80 μg/mL quercetin compared with the control group. Indicators of oxidative overload and genes involved in barrier role revealed that 80 μg/mL quercetin efficiently rescued BIECs from oxidative and barrier impairment triggered by 5 μg/mL LPS. In addition, the mRNA expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as chemokines CXCL2, CXCL5, CCL5, and CXCL8, was diminished in LPS-treated BIECs with 80 μg/mL quercetin compared with LPS alone. Furthermore, the mRNA expression of toll-like receptor 4 (TLR4), CD14, myeloid differential protein-2 (MD2), and myeloid differentiation primary response protein (MyD88) genes associated with the TLR4 signal mechanism was markedly reduced by the addition of quercetin to LPS-modulated BIECs, indicating that quercetin can suppress the TLR4 signal mechanism. We performed Western blotting on the NF-κB signalling mechanism and compared it with immunofluorescence to further corroborate this conclusion. The LPS treatment enhanced the proportions of p-IκBα/GAPDH and p-p65/GAPDH. Compared with the LPS-treated group, quercetin administration decreased the proportions of p-IκBα/GAPDH and p-p65/GAPDH. In addition, immunofluorescence demonstrated that quercetin greatly reduced the LPS-induced nuclear translocation of NF-κB p65 in BIECs. The benefits of quercetin on inflammatory reactions in LPS-induced BIECs may be a result of its capacity to inhibit the TLR4-mediated NF-κB signalling mechanism. These findings suggest that quercetin can be used as an anti-inflammatory reagent to treat intestinal inflammation induced by LPS release.

Metallocene Polyolefins Reinforced by Low-Entanglement UHMWPE through Interfacial Entanglements

By introducing low-entanglement UHMWPE, the mechanical properties of polyolefins are improved to varying degrees. For polypropylene, the lack of interaction between UHMWPE and polypropylene results in an unsatisfactory reinforcement effect, and the disentangled state makes it easier for the particles to form defects driven by a chain explosion. In contrast, regarding polyethylene and elastomer containing ethylene segments, low-entanglement UHMWPE plays a better role in reinforcement. A series of measurements including scanning electron microscopy (SEM), rheological measurements, differential scanning calorimetry (DSC), and mechanical measurement were used to investigate the mechanisms for the different enhancement effects. It originates from interdiffusion and entanglement forming of polyethylene segments across the interface, endowing the material with different aggregated and defect structures. For instance, EPDM possesses a higher optimal dosage of UHMWPE particles reflected in good interfacial interdiffusion with UHMWPE particles, leading to significant optimized mechanical performance.

Theoretical, numerical, and experimental studies on controlled synchronization strategy of four-axis variable trajectory equal-thickness screen

The four-axis variable trajectory equal-thickness screen (FAVTETS) achieves equal-thickness screening by appropriate excitation force generated by four eccentric rotors in synchronized motion. The forced synchronization exciter is characterized by an unsatisfactory synchronization effect due to the wear of transmission parts. Hence, in this paper, the four-axis controlled synchronization of FAVTETS is investigated, and an intelligent control system is proposed. Firstly, research is conducted on the variable trajectory characteristics of FAVTETS. Next, the sliding mode, fuzzy, and PID controllers are designed and compared to obtain an ideal control effect. Moreover, the influence of torsional stiffness of flexible coupling on control accuracy is considered. The results show that the sliding mode controller has a good control effect. Based on the aforementioned, the simulation model of a four-axis controlled synchronization structure is established via MATLAB/Simulink. Finally, Labview is employed to design the four-axis controlled synchronization software system. Then, the physical experiment is carried out. The four-axis controlled synchronization and vibration trajectory measurement results verify the effectiveness and robustness of the intelligent control system.

Improving the Force Display of Haptic Device Based on Gravity Compensation for Surgical Robotics

Haptic devices are applied as masters to provide force displays for telemedicinal robots. Gravity compensation has been proven to be crucial for the accuracy and capability of force displays, which are critical for haptic devices to assist operators. Therefore, the existing method suffers from an unsatisfactory effect, a complex implementation, and low efficiency. In this paper, an approach combining active and passive gravity compensation is proposed to improve the performance of a force display. The passive compensation is conducted by counterweights fixed with the moving platform and pantographs to offset most of the gravity and reduce the loads of the motors, while the peak capability of the force display is enhanced. The required weight is optimized by a multi-objective genetic algorithm in terms of the maximum torque of the motors in the global workspace. As a supplement, the residual gravity is eliminated by active compensation to extend the accuracy of the force display. The balancing forces in the discretized workspace are entirely calibrated, and the required force for the arbitrary configuration is calculated by interpolations. The decisions regarding the algorithm parameters are also discussed to achieve a compromise between the effect and elapsed time. Finally, the prototype with a compensation mechanism is implemented and experiments are carried out to verify the performance of the proposed method. The results show that the peak capability of the force display is enhanced by 45.43% and the maximum deviation is lowered to 0.6 N.

Tire Defect Detection by Dual-Domain Adaptation-Based Transfer Learning Strategy

In tire defect detection, an X-ray image sensor is utilized to collect samples, upon which automatic defect detection methods are constructed. The performance of existing defect detection methods is reduced significantly when working condition shifts. Fortunately, domain adaptation can address this domain shift problem effectively. However, previous methods only align the marginal distribution or conditional distribution, while ignoring the unified adaptation of the two distributions, and may result in an unsatisfactory transfer effect. To this end, this article proposes a dual-domain adaptation model, which harnesses the adaptation of global marginal distribution and fine-grained conditional distribution simultaneously. Specifically, to learn the feature with the consideration of intraclass compact and interclass discriminative, the relative importance of marginal distribution and conditional distribution is measured by a dynamic adaptive factor. In addition, a multihead self-attention (MSA) mechanism is designed in the feature extractor for global context modeling. To evaluate the effectiveness of the proposed method, the tire defect detection task on five kinds of familiar defects, namely slack, bend, overlap, impurity, and bubble, was constructed. Compared with other existing domain adaptation models, the proposed model can achieve 96.39% detect detection accuracy. The experimental results demonstrate the effectiveness of the proposed method in tire defect detection under the domain shift.

Machine learning for Internet of things anomaly detection under low-quality data

With the popularization of Internet of things, its network security has aroused widespread concern. Anomaly detection is one of the important technologies to protect network security. To meet the needs of automatic and intelligent detection, supervised machine learning is widely used in anomaly detection. However, the existing schemes ignore the problem of data quality, which leads to the unsatisfactory detection effect in practice. Therefore, practitioners may not know which algorithm to choose due to the lack of review and evaluation of anomaly detection methods under low-quality data. To address this problem, we give a detailed review and evaluation of six supervised anomaly detection methods, as well as release the core code of feature extractor for pcap format traffic traces and anomaly detection methods for reuse. We evaluate the methods on two public datasets (one is a simulated network dataset and the other is a real Internet of things dataset). We believe that our work and insights will help practitioners quickly understand and develop anomaly detection schemes for Internet of things and can provide reference for future research.

Design of the Jump Mechanism for a Biomimetic Robotic Frog.

Frogs are vertebrate amphibians with both efficient swimming and jumping abilities due to their well-developed hind legs. They can jump over obstacles that are many or even tens of times their size on land. However, most of the current jumping mechanisms of biomimetic robotic frogs use simple four-bar linkage mechanisms, which has an unsatisfactory biomimetic effect on the appearance and movement characteristics of frogs. At the same time, multi-joint jumping robots with biomimetic characteristics are subject to high drive power requirements for jumping action. In this paper, a novel jumping mechanism of a biomimetic robotic frog is proposed. Firstly, the structural design of the forelimb and hindlimb of the frog is given, and the hindlimb of the robotic frog is optimized based on the design of a single-degree-of-freedom six-bar linkage. A simplified model is established to simulate the jumping motion. Secondly, a spring energy storage and trigger mechanism is designed, including incomplete gear, one-way bearing, torsion spring, and so on, to realize the complete jumping function of the robot, that is, elastic energy storage and regulation, elastic energy release, and rapid leg retraction. Thirdly, the experimental prototype of the biomimetic robotic frog is fabricated. Finally, the rationality and feasibility of the jumping mechanism are verified by a jumping experiment. This work provides a technical and theoretical basis for the design and development of a high-performance amphibious biomimetic robotic frog.

Simulation of Video Image Fault Tolerant Coding Transmission in Digital Multimedia

In order to effectively improve the quality of video image transmission, this paper proposes a method of digital multimedia video image coding. The transmission of digital multimedia video image fault-tolerant coding requires sparse decomposition of a digital multimedia video image to obtain the linear form of the image and complete the transmission of video image fault-tolerant coding. The traditional method of fault-tolerant coding is based on human visual characteristics but ignores the linear form of the digital multimedia video image, which leads to the unsatisfactory effect of coding and transmission. In this paper, a fault-tolerant coding method based on wavelet transform and vector quantization is proposed to decompose and reconstruct digital multimedia video images. The smoothness of wavelet transform can remove visual redundancy; the decomposed image is vector quantized. The mean square deviation method and the similar scalar optimal quantization method are used to select and calculate the image vector, construct the over complete database of a digital multimedia video image, and normalize it; the digital multimedia video image is thinly decomposed by asymmetric atoms, and a linear representation of the image is obtained. According to the above-given operations, we can master the distribution range and law of pixels and realize fault-tolerant coding. The experimental results show that when the number of iterations is 15, the CR index is the same, PSNR increases by 8.7%, coding is 23.7% faster and decoding is 15% faster. Conclusion. The proposed method can not only improve the speed of fault-tolerant coding but also improve the quality of video image transmission.

Self-engineered lipid peroxidation nano-amplifier for ferroptosis-driven antitumor therapy

Ferroptosis has been extensively explored as a promising therapeutic target for cancer. Most ferroptosis inducers promote the intracellular accumulation of lipid peroxidation by depleting glutathione peroxidase 4 (GPX4). However, GPX4 suppression alone is not sufficient to trigger intracellular lipid peroxidation storm, resulting in inefficient ferroptosis induction and unsatisfactory antitumor effect. Herein, we precisely engineer a lipid peroxidation nano-amplifier based on a facile drug-deliver-drug (DDD) engineering strategy. Interestingly, FIN56 (a GPX4 inhibitor) is found to readily co-assemble with arachidonic acid (AA) into stable nanoparticles without the assistance of any excipients. Then, a disulfide bond-containing amphipathic PEG polymer is decorated on the nano-amplifier for long blood circulation and tumor-specific drug release. Notably, AA could not only be converted into abundant lipid reactive oxygen species (ROS) but also elicit membranous lipid peroxidation in tumor cells, synergistically inducing tumor ferroptosis with FIN56-mediated GPX4 depletion. As expected, the nano-amplifier exhibits potent ferroptosis-driven antitumor activity in 4 T1 breast tumor-bearing mice. This study drives a conceptual step forward in ferroptosis-driven nanotherapeutics, and offers a novel DDD co-delivery paradigm for combination cancer therapy.

Experience in the use of prolonged analgesic peripheral nerve blocks as part of multimodal analgesia regimens in the treatment of patients with gunshot wounds of the limbs

The use of regional analgesic techniques as part of multimodal analgesia regimens provides better control of acute pain. Effective anesthesia is one of the key tasks in the treatment of the wounded at all stages of medical care.
 Three clinical cases of the use of prolonged regional analgesic blockades as part of a multimodal analgesia regimen in the treatment of patients with gunshot wounds of the extremities are presented. Catheterizations of the perineural space of the peripheral nerves were performed using ultrasound imaging.
 Clinical case 1 - a patient with a gunshot shrapnel through wound of the left tibia with gunshot comminuted fractures of both bones of the lower third of the left tibia and the upper third of the fibula of the left tibia, was admitted two days after the injury. Performed catheterization of the perineural space of the left sciatic nerve in the popliteal fossa, constant infusion of 0.25 % bupivacaine solution at a rate of 5 ml per hour using a perfusor. A satisfactory analgesic effect was observed, narcotic analgesics were not prescribed.
 Clinical case 2 - a patient with a gunshot shrapnel through wound of the left shoulder with a gunshot comminuted fracture of the left humerus in the middle third and with damage to the neurovascular bundle, was admitted more than 6 weeks after the injury. Performed catheterization of the perineural space of the left brachial plexus interscalene access, continuous infusion of 0.25 % bupivacaine solution at a rate of 5 ml per hour using a perfusor. However, in the absence of complaints of soreness at the fracture sites and postoperative wounds, the patient began to be disturbed by neuropathic pain.Satisfactory analgesic effect was observed sporadically, narcotic analgesics were prescribed. On the second day of observation, dislocation of the catheter was detected.Considering that the patient was more concerned about pain in the distal part of the limb, catheterization of the perineural space of the left brachial plexus was performed by supraclavicular access, and a constant infusion of 0.25 % bupivacaine solution was started at a rate of 5 ml per hour using a perfusor. Satisfactory analgesic effect was observed sporadically, narcotic analgesics were prescribed.
 Clinical case 3 - a patient with a gunshot shrapnel through wound of the left thigh with a gunshot comminuted fracture of the left femur in the lower third and with damage to the popliteal artery, was admitted three weeks after the injury. Performed paravertebral catheterization of the left lumbar plexus, constant infusion of 0.25 % bupivacaine solution at a rate of 5 ml per hour using a perfusor. In combination with oral analgesic adjuvants (effect on neuropathic pain), a satisfactory analgesic effect was observed without the prescription of narcotic analgesics.After repeated surgical treatment with the installation of the VAC-system on the posterior surface of the thigh, an unsatisfactory effect of non-opiate analgesia was observed, and narcotic analgesics were additionally prescribed.