MateJam: Multi-Material Teeth-Clutching Layer Jamming Actuation for Soft Haptic Glove.

Most existing force feedback gloves use rigid exoskeleton with large structural dimensions, making it challenging to meet the future demand of virtual reality (VR) applications for large-scale end users. There is an urgent need to develop soft and ultrathin gloves similar to daily gloves. Different from the idea of regulating the friction between layers, here we propose a multi-material teeth-clutching layer jamming (MateJam) actuator, which can achieve distinctive bending stiffness in free and constrained space. The actuator consists of multi-material layers whose modulus span three orders of magnitude, including flexible substrate layer, limiting layer, rigid micro-teeth clutching structure layer, sliding film boundary layer, and sealed shell layer. In free space, the flexible substrate, and the rigid micro-teeth array structure form flexible hinges, ensuring low resistance. In constrained space, the engagement degree of the rigid micro-teeth array is controlled by vacuum pressure to continuously adjust the output resistance. Reliable switching between free and constrained space is ensured by introducing the sliding film boundary layer and the optimized design of the micro-teeth cross-sectional shape. The force output ratio between free and constrained space reaches over 20 times (0.45N vs. 11.95N). The thickness of the actuator is as low as 3.8mm (clutched state), and the weight of the glove is 44.03g. The ultrathin formfactor and the low cost fabrication process makes the MateJam glove a promising solution for VR applications in home entertainment and social interactions.

From Static to Dynamic: A Review on the Role of Mucus Heterogeneity in Particle and Microbial Transport.

Mucus layers (McLs) are on the front line of the human defense system that protect us from foreign abiotic/biotic particles (e.g., airborne virus SARS-CoV-2) and lubricates our organs. Recently, the impact of McLs on human health (e.g., nutrient absorption and drug delivery) and diseases (e.g., infections and cancers) has been studied extensively, yet their mechanisms are still not fully understood due to their high variety among organs and individuals. We characterize these variances as the heterogeneity of McLs, which lies in the thickness, composition, and physiology, making the systematic research on the roles of McLs in human health and diseases very challenging. To advance mucosal organoids and develop effective drug delivery systems, a comprehensive understanding of McLs' heterogeneity and how it impacts mucus physiology is urgently needed. When the role of airway mucus in the penetration and transmission of coronavirus (CoV) is considered, this understanding may also enable a better explanation and prediction of the CoV's behavior. Hence, in this Review, we summarize the variances of McLs among organs, health conditions, and experimental settings as well as recent advances in experimental measurements, data analysis, and model development for simulations.

CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to Facilitate SOX9 Transcription.

Glioblastoma multiforme (GBM) is the most common cancer in nervous system around the world. Little advancement has been achieved in promoting prognosis of GBM patients. Circular RNAs (circRNAs) are suggested as crucial effectors in modulating GBM development. Hsa_circRNA_092437 (circPOLR2A), an up-regulated circRNA in GBM cells, has not been studied yet. In this study, RT-qPCR and western blot assays were applied to detect RNA and protein levels. Cell proliferation and apoptosis were analyzed via functional assays. Subcellular fractionation assay was carried out to determine circPOLR2A distribution in cells. Bioinformatics analysis and mechanism assays were done for detecting relationships among different factors. Rescue assays were performed to confirm validity of circPOLR2A/SOX9 axis. According to experimental results, circPOLR2A was up-regulated in GBM cells and promoted GBM cell proliferation while inhibiting GBM cell apoptosis. CircPOLR2A mainly existed in cell cytoplasm and sponged miR-2113 to positively regulate POU3F2 expression. POU3F2 activated the transcription of SOX9 through interacting with SOX9 promoter (1-500). Rescue assays validated that circPOLR2A influenced GBM cell proliferation and apoptosis via SOX9. To conclude, circPOLR2A enhanced the transcription of SOX9 through miR-2113/POU3F2 axis, thus exacerbating GBM cells growth.

A Novel Mean-Field-Game-Type Optimal Control for Very Large-Scale Multiagent Systems.

In this article, a decentralized adaptive optimal controller based on the emerging mean-field game (MFG) and self-organizing neural networks (NNs) has been developed for multiagent systems (MASs) with a large population and uncertain dynamics. This design can effectively break the "curse of dimensionality" and reduce the computational complexity by appropriately integrating emerging MFG theory with self-organizing NNs-based reinforcement learning techniques. First, the decentralized optimal control for massive MASs has been formulated into an MFG. To unfold the MFG, the coupled Hamilton-Jacobian-Bellman (HJB) equation and Fokker-Planck-Kolmogorov (FPK) equation needed to be solved simultaneously, which is challenging in real time. Therefore, a novel actor-critic-mass (ACM) structure has been developed along with self-organizing NNs subsequently. In the developed ACM structure, each agent has three NNs, including: 1) mass NN learning the mass MAS's overall behavior via online estimating the solution of the FPK equation; 2) critic NN obtaining the optimal cost function through learning the HJB equation solution along with time; and 3) actor NN estimating the decentralized optimal control by using the critic and mass NNs along with the optimal control theory. To reduce the NNs' computational complexity, a self-organizing NN has been adopted and integrated into a developed ACM structure that can adjust the NNs' architecture based on the NNs' learning performance and the computation cost. Finally, numerical simulation has been provided to demonstrate the effectiveness of the developed schemes.

Large-Scale Multiagent System Tracking Control Using Mean Field Games.

This article studies the tracking control problem with a large-scale group of agents. Unlike traditional control techniques used in multiagent systems (MASs), a new type of intelligent design is needed to handle the intractable "Curse of Dimensionality" caused by the extremely large number of agents. To address this challenge, the mean field game (MFG) theory has been embedded into reinforcement learning to advance intelligent tracking control with large-scale MAS. Specifically, MFG-based control can calculate the optimal strategy based on one unified fix-dimension probability density function (pdf) instead of high-dimensional large-scale MAS information collected from individual agents. Moreover, the approximate dynamic programming technique is adopted to generate a new type of MFG-based algorithm. Each agent has three neural networks (NNs) to approximate the solution of the mean field type control. In addition to the algorithm development, the performance of the NNs is also analyzed using the Lyapunov method. Finally, the linear and nonlinear tracking control simulations are given to evaluate the algorithm's performance.

Decentralized Adaptive Optimal Tracking Control for Massive Autonomous Vehicle Systems With Heterogeneous Dynamics: A Stackelberg Game.

In this article, a decentralized optimal tracking control problem has been studied for a large-scale autonomous vehicle system with heterogeneous system dynamics. Due to the ultralarge number of agents, the notorious "curse of dimension" problem as well as the unrealistic assumption of the existence of reliable very large-scale communication links in uncertain environments have challenged the traditional multiagent system (MAS) algorithms for decades. The emerging mean-field game (MFG) theory has recently been widely adopted to generate a decentralized control method that deals with those challenges by encoding the large scale MASs' information into a novel time-varying probability density functions (PDF) which can be obtained locally. However, the traditional MFG methods assume all agents are homogeneous, which is unrealistic in practical industrial applications, e.g., Internet of Things (IoTs), and so on. Therefore, a novel mean-field Stackelberg game (MFSG) is formulated based on the Stackelberg game, where all the agents have been classified as two different categories where one major leader's decision dominates the other minor agents. Moreover, a hierarchical structure that treats all minor agents as a mean-field group is developed to tackle the assumption of homogeneous agents. Then, the actor-actor-critic-critic-mass ( A2C2M ) algorithm with five neural networks is designed to learn the optimal policies by solving the MFSG. The Lyapunov theory is utilized to prove the convergence of A2C2M neural networks and the closed-loop system's stability. Finally, a series of numerical simulations are conducted to demonstrate the effectiveness of the developed method.

Feasibility and Clinical Value of CT-Guided 125I Brachytherapy for Pain Palliation in Patients With Breast Cancer and Bone Metastases After External Beam Radiotherapy Failure.

Objectives: To evaluate the feasibility and clinical value of CT-guided iodine-125 (125I) brachytherapy for pain palliation in patients with breast cancer and bone metastases after external beam radiotherapy failure. Methods: From January 2014 to July 2016, a total of 90 patients, who had received the standard therapies for bone metastases but still suffered moderate-to-severe pain, were retrospectively studied. About 42 patients were treated with both 125I brachytherapy and bisphosphonates (Group A), and 48 patients were treated with bisphosphonates alone (Group B). Results: In Group A, 45 125I brachytherapy procedures were performed in 42 patients with 69 bone metastases; the primary success rate of 125I seed implantation was 92.9%, without severe complications. Regarding pain progression of the two groups, Group A exhibited significant relief in "worst pain," "least pain," "average pain," and "present pain" 3-day after treatment and could achieve a 12-week-remission for "worst pain," "least pain," "average pain," and "present pain." The morphine-equivalent 24-h analgesic dose at 3 days, 4 weeks, 8 weeks, and 12 weeks was 91 ± 27, 53 ± 13, 31 ± 17, and 34 ± 12 mg for Group A, and 129 ± 21, 61 ± 16, 53 ± 15, and 105 ± 23 mg for Group B. Group A experienced a lower incidence of analgesic-related adverse events and better quality of life than Group B. Conclusion: The CT-guided 125I brachytherapy is a feasible and an effective treatment for the palliation of pain caused by bone metastases from breast cancer after external beam radiotherapy failure.

Predicting hyperprogressive disease in patients with advanced hepatocellular carcinoma treated with anti-programmed cell death 1 therapy.

BACKGROUND: Hyperprogressive disease (HPD) is a new progressive pattern in patients with advanced hepatocellular carcinoma (HCC) treated with programmed cell death 1 (PD-1) inhibitors. We aimed to investigate risk factors associated with HPD in advanced HCC patients undergoing anti-PD-1 therapy. METHODS: A total of 69 patients treated with anti-PD-1 therapy between March 2017 and January 2020 were included. HPD was determined according to the time to treatment failure, tumour growth rate, and tumour growth rate ratio. Univariate and multivariate analyses were performed to identify clinical variables significantly associated with HPD. A risk model was constructed based on clinical variables with prognostic significance for HPD. FINDINGS: Overall, 10 (14·49%) had HPD. Haemoglobin level, portal vein tumour thrombus, and Child-Pugh score were significantly associated with HPD. The risk model had an area under the curve of 0·931 (95% confidence interval, 0·844-1·000). Patients with HPD had a significantly shorter overall survival (OS) than that of the patients with non-HPD (p < 0·001). However, there was no significant difference in OS between PD (progressive disease) patients with and without HPD (p = 0·05). INTERPRETATION: We identified three clinical variables as risk factors for HPD, providing an opportunity to aid the pre-treatment evaluation of the risk of HPD in patients treated with immunotherapy. FUNDING: This study was funded by the National Natural Science Foundation of China (81571664, 81871323, and 81801665); National Natural Science Foundation of Guangdong Province (2018B030311024); Scientific Research General Project of Guangzhou Science Technology and Innovation Commission (201707010,328); and China Postdoctoral Science Foundation (2016M600145).

Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy for advanced biliary tract cancers with biliary obstruction: a multicentre, retrospective, controlled study.

OBJECTIVE: To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). METHODS: We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. RESULTS: Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1-9.3) than in the control group (4.3 months, 95% CI: 3.6-5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1-16.5; control: 8.5 months, 95% CI: 7.6-9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. CONCLUSIONS: Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. KEY POINTS: • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.

[Advances and Challenges of Local Thermal Ablation in Non-small Cell Lung Cancer].

Non-small cell lung cancer (NSCLC) is the most common pathological type of primary lung cancer. Currently, main treatment approaches for NSCLC patients include surgical resection, radiotherapy, chemotherapy, targeted therapy and so on. In recent years, thermal ablation has received increasing attention in the treatment of various stages of NSCLC. As a safe and efficient local treatment, thermal ablation may bring potential clinical benefits to NSCLC patients. However, many issues remain unsolved and further investigation is needed in the clinical application of thermal ablation in NSCLC. In this review, we aim to summarize the applications of thermal ablation in NSCLC and further discuss the emerging controversies as well as future research directions.

Efficacy and safety of sorafenib versus apatinib in the treatment of intermediate and advanced hepatocellular carcinoma: a comparative retrospective study.

OBJECTIVE: To compare the efficacy and safety profiles of sorafenib and apatinib in patients with intermediate- and advanced-stage hepatocellular carcinoma (HCC). METHODS: This was a single-center, retrospective study where we collected the clinical data of 72 patients, diagnosed with intermediate or advanced HCC from January 2014 to December 2016. Depending on the treatment received, 38 patients were categorized into group S (sorafenib group) and 34 into group A (apatinib group). The patients in group A received the initial recommended dose of 750 mg once daily (QD), which was reduced to 250 mg QD in the case of any class 3 or 4 adverse event (AE). Sorafenib was administered orally 400 mg twice daily (BID), and dose was modified to 400 mg or 200 mg QD in the case of grade 3 or 4 AEs. The median overall survival (OS), progression-free survival (PFS), and AEs reported in the two groups were analyzed and compared. RESULTS: Among the 38 patients treated with sorafenib, one patient had complete response (CR), 5 patients had partial response (PR), and 10 patients had stable disease (SD), and among the 34 patients treated with apatinib, 6 patients had PR and 7 patients had SD with no cases of CR. PFS in group S was significantly longer compared with that in group A (7.39 vs 4.79 months, respectively, P=0.031). Similar observations were made for median OS (10.4 months in group S vs 7.18 months in group A, P=0.011). However, there was no significant difference in the objective response rates (ORRs) among the study population (15.7 vs 17.6%, P=0.829). Common AEs in group S included hand and foot syndrome (HFS) and diarrhea, whereas common AEs in group A included hypertension, proteinuria, and increased transaminase. CONCLUSION: Our study showed promising clinical outcome with apatinib, but the sorafenib group exhibited better clinical efficacy with no significant difference in safety profile.

Impact of molecular hydrogen treatments on the innate immune activity and survival of zebrafish (Danio rerio) challenged with Aeromonas hydrophila.

Recently, molecular hydrogen has been reported to have a suppressive effect on inflammation in human and rodent models. The aim of this study was to evaluate the preventive effects of hydrogen-rich water (HRW) on zebrafish challenged by A. hydrophila. We have found an increased survival rate of bacteria-challenged zebrafish subjected to the HRW immersion treatment. Furthermore, we have revealed that HRW was able to block multiplication of A. hydrophila in zebrafish. In addition, treatment of zebrafish infected by A. hydrophila with effective concentrations of HRW strongly affected the expression of genes mediating pro-inflammatory and anti-inflammatory cytokines. There were down-regulation of selected pro-inflammatory immune response genes (IL-1ß, IL-6, and NF-κB), and up-regulation of the anti-inflammatory cytokine gene (IL-10) in the spleen, kidney, and liver. This study is the first one to investigate the effects of HRW on fish infected with bacteria, and might shed new light on hydrogen's antimicrobial effects and further application in aquaculture fish species.

Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells.

Hepatocellular carcinoma is the most common subtype of liver cancer. Protein arginine N-methyltransferase 1 was shown to be upregulated in various cancers. However, the role of protein arginine N-methyltransferase 1 in hepatocellular carcinoma progression remains incompletely understood. We investigated the clinical and functional significance of protein arginine N-methyltransferase 1 in a series of clinical hepatocellular carcinoma samples and a panel of hepatocellular carcinoma cell lines. We performed suppression analysis of protein arginine N-methyltransferase 1 using small interfering RNA to determine the biological roles of protein arginine N-methyltransferase 1 in hepatocellular carcinoma. In addition, the expression of epithelial-mesenchymal transition indicators was verified by western blotting in hepatocellular carcinoma cell lines after small interfering RNA treatment. Protein arginine N-methyltransferase 1 expression was found to be significantly upregulated in hepatocellular carcinoma cell lines and clinical tissues. Moreover, downregulation of protein arginine N-methyltransferase 1 in hepatocellular carcinoma cells by small interfering RNA could inhibit cell proliferation, migration, and invasion in vitro. These results indicate that protein arginine N-methyltransferase 1 may contribute to hepatocellular carcinoma progression and serves as a promising target for the treatment of hepatocellular carcinoma patients.

Microwave ablation versus radiofrequency ablation for the treatment of pulmonary tumors.

To retrospectively compare the efficacy and safety of radiofrequency ablation (RFA) and microwave ablation (MWA) in the treatment of pulmonary tumors, a total of 75 patients with lung tumor who underwent thermal ablation therapy in Guangdong General Hospital into the study from March 2007 to December 2014 were enrolled. Of the patients, 43 received radiofrequency ablation and 32 received microwaves ablation. The response rates, overall survival (OS), and complications rates between the RFA group and MWA group were compared. There were no significant differences in the baseline characteristics between two groups. The overall response rates of in RFA and MWA groups were 79% (34/43) and 69% (22/32), respectively, and there was no statistically significant difference between two groups (P = 0.309). The 1-, 2-, 3-, 5-year overall survival (OS) rates in RFA group and MWA group were 77%, 55%, 42%, 34% and 75%, 44%, 40%, 27%, respectively. No significant differences were found in the OS rates between two groups (P = 0.653). The complication rates were 49% (21/43) in RFA group and 50% (16/32) in MWA group; there was no significant difference between two groups (P = 0.921). No patients died during the perioperative period. Our study shows that no significant differences exist in efficacy and safety between RFA and MWA for the treatment of pulmonary tumors, which indicates that MWA could be a substitute therapy for RFA in terms of effectiveness and safety for treating pulmonary tumors.

[Transarterial oily chemoembolization combined with interstitial laser thermotherapy for treatment of hepatocellular carcinoma].

OBJECTIVE: To evaluate the therapeutic effects and adverse effects of transarterial oily chemoembolization combined with interstitial laser thermotherapy (TOCE+ILT) in the treatment of hepatocellular carcinoma. METHODS: Totally 120 patients with hepatocellular carcinoma were randomized into two groups and received interventions with TOCE+ILT or TOCE combined with percutaneous ethanol injection (TOCE+PEI). The treatment was repeated when necessary until the tumor was completely ablated, after which the therapeutic effects were evaluated and the patients were the followed up for observing long-term clinical outcome. RESULTS: Of the 120 patients enrolled in this observation, 105 were followed up for two years (54 in TOCE+ILT group and 51 in TOCE+PEI group). The complete tumor necrosis rate of TOCE+ILT group was significantly higher than that of the TOCE+PEI group (84.8% vs 73.9%,Chi(2)=4.405, P=0.036), and TOCE+ILT was associated with a significantly higher negative conversion rate of AFP positivity (77.8% vs 56.1%, Chi(2)=4.592, P=0.032). The 1-year survival rate were similar between two groups, but the 2-year survival rate was significantly higher in patients with TOCE+ILT (79.6% vs 60.8%, Chi(2)=4.477, P=0.034). The hepatic function was comparable between the two groups before treatment, and 1 week after treatment, the ALT level in patients undergoing TOCE+ILT was significantly lower than that in patients with TOCE+PEI (95.90-/+56.06 U/L vs 116.31-/+45.27 U/L, t=2.04, P=0.043). Post-embolization syndrome was observed in the patients in two groups, but no severe adverse events were found. CONCLUSION: TOCE+ILT has good therapeutic effects and mild side effects in the treatment of hepatocellular carcinoma.

[Long-term result of combination of transcatheter arterial chemoembolization and percutaneous ethanol injection for treatment of hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Both transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) are the most important and popular procedures of interventional treatment for hepatocellular carcinoma (HCC). Although the improvement of the short-term efficacy of the combination of TACE and PEI has been proved, the long-term efficacy is seldom reported so far. The purpose of this study was to evaluate the long-term efficacy of the combination of TACE and PEI for treatment of HCC. METHODS: Six hundred and seventy-five patients with HCC from 2 cm to 15 cm in the greatest diameter (average 9.6 cm) were enrolled in this study. Among them, 179 were treated by a combination of TACE using the emulsion of lipiodol and anti-cancer drugs and PEI (TACE/PEI group) and 496 patients by TACE alone (TACE group). Ten patients in each group underwent resection after the final interventional treatment and the resected specimens were detected by histopathology method. The unresected patients had been followed up for 5-7 years and the 1-, 3-, 5 -, and 7-year survival rates were evaluated. The clinical data of the patients in two groups before intervention were comparable. RESULTS: Pathological data of two groups showed that remarkable differences were found in the mean necrosis rates (100.0+/-0.0% vs 91.5+/-7.1%, P< 0.05) and the complete necrosis rates of tumors (100% vs 20%, P = 0.0007), while there were no statistical significances in the extent of shrinkage of tumors after treatment between two groups. The results of follow-up showed that the 1-, 3-, 5-, and 7-year survival rates were 80.5%, 58.6%, 29.6%, 16.5% in TACE-PEI group, and 68.5%, 27.8%, 7.2%, 5.2% in TACE group, respectively. Significant differences were found between two groups (P< 0.01). CONCLUSION: The combination of TACE and PEI is a valuable remedy for HCC to prolong long-term survival rate.

[Optimum mode of interventional treatment for hepatocellular carcinoma].

OBJECTIVE: To establish a reasonable protocol for interventional treatment of hepatocellular carcinoma (HCC). METHODS: The data of 1 000 HCC patients treated by different kinds of interventional treatment were reviewed with their results of biochemistry, imaging, pathology and survival rate evaluated. The value as well as the pros and cons of these various kinds of interventional treatment were compared in order to find an optimum protocol. RESULTS: Segmental-transcatheter oil chemoembolization (S-TOCE) was much effective eradicate the tumor yet inflicting less damage on the noncancerous hepatic tissue and giving much higher survival rate than the conventional transcatheter oil chemoembolization (C-TOCE). Percutaneous ethanol injection (PEI) played an important role in eradicating the residual tumor and improving the survival rate without damaging the noncancerous hepatic tissue. The survival quality or survival rate could be improved by choosing different ways of interventional treatments to cut down the complications. CONCLUSION: The selection of different interventional treatments should be done according to the size and type of HCC. Active management is indicated for different complications presenting along with HCC.