Modularized microrobot with lock-and-detachable modules for targeted cell delivery in bile duct.

The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design-based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.

Global Neural Network Potential with Explicit Many-Body Functions for Improved Descriptions of Complex Potential Energy Surface.

The high dimensional machine learning potential (MLP) that has developed rapidly in the past decade represents a giant step forward in large-scale atomic simulation for complex systems. The long-range interaction and the poor description of chemical reactions are typical problems of high dimensional MLP, which are mainly caused by the poor structure discrimination of the atom-centered ML model. Herein, we propose a low-cost neural-network-based MLP architecture for fitting global potential energy surface data, namely, G-MBNN, that can offer improved energy and force resolution on a complex potential energy surface. In G-MBNN, a set of many-body energy terms based on the local atomic environment are explicitly included in computing the total energy─the total energy of the system is written as the sum of atomic energy and many-body energy contributions. These extra many-body energy terms are computationally low-cost and, importantly, can provide easy access to delicate energy terms in complex systems such as very short repulsion, long-range attractions, and sensitive angular-dependent covalent interactions. We implement G-MBNN in the LASP code and demonstrate the improved accuracy of the new framework in representative systems, including ternary-element energy materials LiCoOx, TiO2 with defects, and a series of organic reactions.

Magnetic Continuum Robot with Intraoperative Magnetic Moment Programming.

Magnetic continuum robots (MCRs), which are free of complicated structural designs for transmission, can be miniaturized and are therefore widely used in the medical field. However, the deformation shapes of different segments, including deflection directions and curvatures, are difficult to control simultaneously under an external programmable magnetic field. This is because the latest MCRs have designs with an invariable magnetic moment combination or profile of one or more actuating units. Therefore, the limited dexterity of the deformation shape causes the existing MCRs to collide readily with their surroundings or makes them unable to approach difficult-to-reach regions. These prolonged collisions are unnecessary or even hazardous, especially for catheters or similar medical devices. In this study, a novel magnetic moment intraoperatively programmable continuum robot (MMPCR) is introduced. By applying the proposed magnetic moment programming method, the MMPCR can deform under three modalities, that is, J, C, and S shapes. Additionally, the deflection directions and curvatures of different segments in the MMPCR can be modulated as desired. Furthermore, the magnetic moment programming and MMPCR kinematics are modeled, numerically simulated, and experimentally validated. The experimental results exhibit a mean deflection angle error of 3.3° and correspond well with simulation results. Comparisons between navigation capacities of the MMPCR and MCR demonstrate that the MMPCR has a higher capacity for dexterous deformation.

Wirelessly powered deformable electronic stent for noninvasive electrical stimulation of lower esophageal sphincter.

Electrical stimulation is a promising method to modulate gastrointestinal disorders. However, conventional stimulators need invasive implantation and removal surgeries associated with risks of infection and secondary injuries. Here, we report a battery-free and deformable electronic esophageal stent for wireless stimulation of the lower esophageal sphincter in a noninvasive fashion. The stent consists of an elastic receiver antenna infilled with liquid metal (eutectic gallium-indium), a superelastic nitinol stent skeleton, and a stretchable pulse generator that jointly enables 150% axial elongation and 50% radial compression for transoral delivery through the narrow esophagus. The compliant stent adaptive to the dynamic environment of the esophagus can wirelessly harvest energy through deep tissue. Continuous electrical stimulations delivered by the stent in vivo using pig models significantly increase the pressure of the lower esophageal sphincter. The electronic stent provides a noninvasive platform for bioelectronic therapies in the gastrointestinal tract without the need for open surgery.

Decreased autophagic activity of detrusor cells is involved in the inflammatory response of interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Genome-wide association studies suggest that autophagy plays an important regulatory role in inflammatory and autoimmune diseases. Inflammation and immune regulation disorders are involved in the occurrence and development of interstitial cystitis/bladder pain syndrome (IC/BPS). However, the changes and roles of autophagy in IC/BPS have not been reported. Therefore, this study aimed to investigate bladder autophagy and inflammation changes in patients with IC/BPS. METHODS: Bladder specimens (n = 5) from patients with cystectomy due to end-stage IC/BPS were collected. The bladder samples of the control group (n = 5) were derived from the normal area bladder tissue after radical cystectomy. H&E and toluidine blue staining were used for histological evaluation. The co-location of LC3, alpha-smooth muscle actin (α-SMA), and autophagosome was investigated with double-labeled immunofluorescence and transmission electron microscopy (TEM). The expression of IL-6, TNF-α, Bax, caspase-3, and BCL-2 in the detrusor layer was analyzed using immunohistochemistry (IHC) and Western blot (WB). RESULTS: Compared with the control group, bladder tissue from IC/BPS patients revealed thinner and edematous epithelium with many mast cells (P < 0.05) infiltrating into the muscle layer. By using TEM (P < 0.05), double-labeled immunofluorescence (P < 0.05), and Western blot (P < 0.05) in IC/BPS patients, autophagy was also found and was significantly increased in detrusor myocytes. IHC and WB indicate the expression of BCL-2 (P < 0.05) was decreased, while IL-6, TNF-α, Bax, and caspase-3 expression was elevated (P < 0.05). CONCLUSIONS: The number of autophagosomes in detrusor cells was increased in IC/BPS. However, autophagy of detrusor muscle cells may not have sufficient phagocytic activity to effectively remove damaged proteins and mitochondria, which may lead to the continued deterioration of IC/BPS inflammation and apoptosis.

Dynamic morphological transformations in soft architected materials via buckling instability encoded heterogeneous magnetization.

The geometric reconfigurations in three-dimensional morphable structures have a wide range of applications in flexible electronic devices and smart systems with unusual mechanical, acoustic, and thermal properties. However, achieving the highly controllable anisotropic transformation and dynamic regulation of architected materials crossing different scales remains challenging. Herein, we develop a magnetic regulation approach that provides an enabling technology to achieve the controllable transformation of morphable structures and unveil their dynamic modulation mechanism as well as potential applications. With buckling instability encoded heterogeneous magnetization profiles inside soft architected materials, spatially and temporally programmed magnetic inputs drive the formation of a variety of anisotropic morphological transformations and dynamic geometric reconfiguration. The introduction of magnetic stimulation could help to predetermine the buckling states of soft architected materials, and enable the formation of definite and controllable buckling states without prolonged magnetic stimulation input. The dynamic modulations can be exploited to build systems with switchable fluidic properties and are demonstrated to achieve capabilities of fluidic manipulation, selective particle trapping, sensitivity-enhanced biomedical analysis, and soft robotics. The work provides new insights to harness the programmable and dynamic morphological transformation of soft architected materials and promises benefits in microfluidics, programmable metamaterials, and biomedical applications.

Endoscope-assisted magnetic helical micromachine delivery for biofilm eradication in tympanostomy tube.

Occlusion of the T-tube (tympanostomy tube) is a common postoperative sequela related to bacterial biofilms. Confronting biofilm-related infections of T-tubes, maneuverable and effective treatments are still challenging presently. Here, we propose an endoscopy-assisted treatment procedure based on the wobbling Fe2O3 helical micromachine (HMM) with peroxidase-mimicking activity. Different from the ideal corkscrew motion, the Fe2O3 HMM applies a wobbling motion in the tube, inducing stronger mechanical force and fluid convections, which not only damages the biofilm occlusion into debris quickly but also enhances the catalytic generation and diffusion of reactive oxygen species (ROS) for killing bacteria cells. Moreover, the treatment procedure, which integrated the delivery, actuation, and retrieval of Fe2O3 HMM, was validated in the T-tube implanted in a human cadaver ex vivo. It enables the visual operation with ease and is gentle to the tympanic membrane and ossicles, which is promising in the clinical application.

Highly efficient Ni-Mo-P composite rare earth elements electrode as electrocatalytic cathode for oil-based drill sludge treatment.

It is considered an effective strategy to improve electrochemical performance that introducing rare elements into metal catalysts, which would provide abundant electrochemical active sites and be a benefit for redox reactions. A new Ni-Mo-P composite electrode material modified with rare earth elements (light rare earth Nd and heavy rare earth Yb) was prepared, evaluating the current density of direct current electrodeposition, the doping ratio of Yb and Nd, and the cyclic voltammetry deposition (CVD) cycle numbers on electrode structure and electrochemical performance. The results showed that the electrode has the most obvious amorphous state, the lowest hydrogen evolution overpotential (41.5 mV vs Ag/AgCl) and charge transfer resistance (15.74 Ω/cm2), and remarkable stability when the molar ratio of Yb and Nd was 8:2 and the 20 cycle numbers under the CVD condition. The electrochemical performance and characterization of the electrode showed that there was a good synergistic effect between rare earth elements (Yb, Nd) and Ni-Mo-P alloys. The oil-based drill sludge (OBDS) treatment indicated that the organic matter content is significantly reduced by using the above-modified electrode as the cathode, and the COD and petroleum removal rate can reach up to 85.4 ± 1.2% and 66.2 ± 5.9%. The effect of degradation for aliphatic hydrocarbon was better than aromatic hydrocarbons and no other intermediates are produced during the degradation, which may eventually mineralize the organic matter. This research provided technical support for the preparation of new Ni-Mo-P electrodes modified with rare earth elements and confirmed that electrocatalytic technology was a suitable method for OBDS treatment.

The Diversity and Spatiotemporally Evolutionary Dynamic of Atypical Porcine Pestivirus in China.

The presence of congenital tremor (CT) type A-II in newborn piglets, caused by atypical porcine pestivirus (APPV), has been a focus since 2016. However, the source, evolutionary history, and transmission pattern of APPV in China remain poorly understood. In this study, we undertook phylogenetic analyses based on available complete E2 gene sequences along with 98 newly sequenced E2 genes between 2016 and 2020 in China within the context of global genetic diversity. The phylogenies revealed four distinct lineages of APPV, and interestingly, all lineages could be detected in China with the greatest diversity. Bayesian phylogenetic analyses showed that the E2 gene evolves at a mean rate of 1.22 × 10-3 (8.54 × 10-4-1.60 × 10-3) substitutions/site/year. The most recent common ancestor for APPVs is dated to 1886 (1837-1924) CE, somewhat earlier than the documented emergence of CT (1922 CE). Our phylogeographic analyses suggested that the APPV population possibly originated in the Netherlands, a country with developed livestock husbandry, and was introduced into China during the period 1837-2010. Guangdong, as a primary seeding population together with Central and Southwest China as epidemic linkers, was responsible for the dispersal of APPVs in China. The transmission pattern of "China lineages" (lineage 3 and lineage 4) presented a "south to north" movement tendency, which was likely associated with the implementation of strict environmental policy in China since 2000. Reconstruction of demographic history showed that APPV population size experienced multiple changes, which correlated well with the dynamic of the number of pigs in the past decades in China. Besides, positively selected pressure and geography-driven adaptation were supposed to be key factors for the diversification of APPV lineages. Our findings provide comprehensive insights into the diversity and spatiotemporal dynamic of APPV in China.

Rolling Bearing Fault Diagnosis Based on WOA-VMD-MPE and MPSO-LSSVM.

In order to further improve the accuracy of fault identification of rolling bearings, a fault diagnosis method based on the modified particle swarm optimization (MPSO) algorithm optimized least square support vector machine (LSSVM), combining parameter optimization variational mode decomposition (VMD) and multi-scale permutation entropy (MPE), was proposed. Firstly, to solve the problem of insufficient decomposition and mode mixing caused by the improper selection of mode component K and penalty factor α in VMD algorithm, the whale optimization algorithm (WOA) was used to optimize the penalty factor and mode component number in the VMD algorithm, and the optimal parameter combination (K, α) was obtained. Secondly, the optimal parameter combination (K, α) was used for the VMD of the rolling bearing vibration signal to obtain several intrinsic mode functions (IMFs). According to the Pearson correlation coefficient (PCC) criterion, the optimal IMF component was selected, and its optimal multi-scale permutation entropy was calculated to form the feature set. Finally, K-fold cross-validation was used to train the MPSO-LSSVM model, and the test set was input into the trained model for identification. The experimental results show that compared with PSO-SVM, LSSVM, and PSO-LSSVM, the MPSO-LSSVM fault diagnosis model has higher recognition accuracy. At the same time, compared with VMD-SE, VMD-MPE, and PSO-VMD-MPE, WOA-VMD-MPE can extract more accurate features.

Untethered small-scale magnetic soft robot with programmable magnetization and integrated multifunctional modules.

Intelligent magnetic soft robots capable of programmable structural changes and multifunctionality modalities depend on material architectures and methods for controlling magnetization profiles. While some efforts have been made, there are still key challenges in achieving programmable magnetization profile and creating heterogeneous architectures. Here, we directly embed programmed magnetization patterns (magnetization modules) into the adhesive sticker layers to construct soft robots with programmable magnetization profiles and geometries and then integrate spatially distributed functional modules. Functional modules including temperature and ultraviolet light sensing particles, pH sensing sheets, oil sensing foams, positioning electronic component, circuit foils, and therapy patch films are integrated into soft robots. These test beds are used to explore multimodal robot locomotion and various applications related to environmental sensing and detection, circuit repairing, and gastric ulcer coating, respectively. This proposed approach to engineering modular soft material systems has the potential to expand the functionality, versatility, and adaptability of soft robots.

Decoupling and Reprogramming the Wiggling Motion of Midge Larvae Using a Soft Robotic Platform.

The efficient motility of invertebrates helps them survive under evolutionary pressures. Reconstructing the locomotion of invertebrates and decoupling the influence of individual basic motion are crucial for understanding their underlying mechanisms, which, however, generally remain a challenge due to the complexity of locomotion gaits. Herein, a magnetic soft robot to reproduce midge larva's key natural swimming gaits is developed, and the coupling effect between body curling and rotation on motility is investigated. Through the authors' systematically decoupling studies using programmed magnetic field inputs, the soft robot (named LarvaBot) experiences various coupled gaits, including biomimetic side-to-side flexures, and unveils that the optimal rotation amplitude and the synchronization of curling and rotation greatly enhance its motility. The LarvaBot achieves fast locomotion and upstream capability at the moderate Reynolds number regime. The soft robotics-based platform provides new insight to decouple complex biological locomotion, and design programmed swimming gaits for the fast locomotion of soft-bodied swimmers.

Fault severity assessment of rolling bearing based on optimized multi-dictionaries matching pursuit and Lempel-Ziv complexity.

For the safe working of rolling bearing, this paper presents a fault severity assessment method through optimized multi-dictionaries matching pursuit (OMMP) and Lempel-Ziv (LZ) complexity. To solve the redundancy problem of over-complete dictionary, the OMMP is proposed by introducing the quantum particle swarm optimization into matching pursuit for best representing the original vibration signal. And then, LZ complexity is calculated as an index of fault severity assessment by reconstructed signal. The performance of assessment method is verified through the measured signals of three bearing tests, and the comparisons with various methods are specifically described. The results indicate that the OMMP method averagely takes the shortest running time for the vibration signal decomposition. The assessment method is able to effectively evaluate different fault sizes of rolling bearing, and has a great applicability to in the condition-based maintenance of rotating machineries.

[Effects of SiRNA-EGFR on the expression of hyaluronidase gene EGFR in human breast cancer cells].

OBJECTIVE: To study the effect of SiRNA-EGFR on the expression of hyaluronidase gene in human breast cancer cells. METHODS: Reverse transcription-polymerse chain reaction was used to detect the changes in the expression of EGFR mRNA in human breast cancer cell lines MDA-MB-231, MDA-MB-435S, ZR-75 and ZR-75-30 after transfection by SiRNA-EGFR. RESULTS: After transfection with SiRNA-EGFR, the expression levels of EGFR were significantly inhibited in MDA-MB-231, MDA-MB-435S, ZR-75 and ZR-75-30 cells (P<0.05). CONCLUSION: Transfection by SiRNA-EGFR can inhibit the expression of EGFR mRNA in human breast cancer cells.

[Effects of RNA interference on epidermal growth factor receptor expression in breast cancer cells: a study in tumor-bearing nude mice].

OBJECTIVE: To investigate the effect of cationic liposome-mediated RNA interference (RNAi) in silencing epidermal growth factor (EGF) receptor (EGFR) gene in breast cancer cells in vivo. METHODS: A small interfering RNA (siRNA) targeting EGFR gene was constructed and transfected into human breast cancer cell in vitro via cationic liposome. The transfected cells were inoculated into nude mice, and the tumor growth inhibition rate was calculated. The tumors were then removed for immunohistochemistry and Western blotting to examine the expression of EGFR protein. Quantitative RT-PCR was used to detect the mRNA expression of the EGF receptor gene, and enzyme-linked immunosorbent assay (ELISA) performed to assess the EGF level in both the serum and tumor extraction. RESULTS: In athymic nude mice, MDA-MB-231 cells had obviously lower tumor formation rate than ZR-75 cells (30.00% and 88.89%). Transfection of the cells with EGFR siRNA significantly inhibited tumor formation capacity of the cells in vivo as compared with the cells transfected with empty vector or irrelevant siRNA. The results of ELISA demonstrated that in mice bearing the tumors grown from EGFR siRNA-transfected cells, the EGF levels in the serum and tumor extraction were lowered by 16.77% and 12.59%, respectively. Real-time RT-PCR showed that EGFR siRNA transfection caused a specific downregulation of EGFR mRNA expression by 21.05% in the tumor. CONCLUSION: Chemically synthesized 21-nucleotide siRNA duplexes can be effectively delivered via lipofectamine 2000 into breast cancer cells in vivo to induce a longer-lasting gene silencing effect than in vitro transfection. RNAi of EGFR gene may indicate a promising approach for management of lung cancers, especially those nodular ones with easy access.