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Drug-induced liver injury (DILI) occurs frequently and can be life-threatening. Increasing researches suggest that acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury. Indole-3-carboxaldehyde (I3A) alleviates hepatic inflammation, fibrosis and atherosclerosis, suggesting a potential role in different disease development. However, the question of whether and how I3A protects against acetaminophen-induced liver injury remains unanswered. In this study, we demonstrated that I3A treatment effectively mitigates acetaminophen-induced liver injury. Serum alanine/aspartate aminotransferases (ALT/AST), liver malondialdehyde (MDA) activity, liver glutathione (GSH), and superoxide dismutase (SOD) levels confirmed the protective effect of I3A against APAP-induced liver injury. Liver histological examination provided further evidence of I3A-induced protection. Mechanistically, I3A reduced the expression of apoptosis-related factors and oxidative stress, alleviating disease symptoms. Finally, I3A treatment improved survival in mice receiving a lethal dose of APAP. In conclusion, our study demonstrates that I3A modulates hepatotoxicity and can be used as a potential therapeutic agent for DILI.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Indóis , Animais , Camundongos , Acetaminofen/efeitos adversos , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Estresse Oxidativo , Fígado/metabolismo , Apoptose , Glutationa/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Aspartato Aminotransferases , Alanina TransaminaseRESUMO
BACKGROUND: Minimally invasive lobectomy is the standard treatment for early stage non-small cell lung cancer (NSCLC). The aim of this study is to investigate postoperative recovery in a prospective trial of discharged patients with early stage non-small cell lung cancer undergoing robot-assisted thoracic surgery (RATS) versus uniportal video-assisted thoracic surgery (UVATS). PATIENTS AND METHODS: This is a prospective and observational study. From 9 September 2022 to 1 July 2023, 178 patients diagnosed with NSCLC admitted to the Department of Thoracic Surgery of Shandong Provincial Hospital signed informed consent and underwent lobectomy by RATS and UVATS. The functional recovery index included MD Anderson Symptom Inventory, Christensen Fatigue Scale, EORTC QLQ-C30, and Leicester Cough Questionnaire. RESULTS: After propensity score-matched analysis, each group included 42 cases. For the baseline characteristics of patients, operation time (p = 0.01) and length of stay (p = 0.04) were shorter in the RATS group. The number of lymph nodes resected in the RATS group was much more than in the UVATS group. According to our investigation, appetite loss, nausea, diarrhea, and cough severity after RATS were better than after UVATS. After the first week, pain severity degree of the RATS group was higher than UVATS, while there was no difference during the second and third week. The physical score of the RATS group was higher than the UVATS group (p = 0.04), according to the Leicester Cough Questionnaire. CONCLUSION: RATS was associated with severe short-term postoperative pain but less postoperative complications.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Robótica , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Pontuação de Propensão , Pneumonectomia/métodos , Carcinoma de Pequenas Células do Pulmão/cirurgia , Tosse/cirurgia , Cirurgia Torácica Vídeoassistida/métodosRESUMO
The disorder operator is often designed to reveal the conformal field theory (CFT) information in quantum many-body systems. By using large-scale quantum Monte Carlo simulation, we study the scaling behavior of disorder operators on the boundary in the two-dimensional Heisenberg model on the square-octagon lattice with gapless topological edge state. In the Affleck-Kennedy-Lieb-Tasaki phase, the disorder operator is shown to hold the perimeter scaling with a logarithmic term associated with the Luttinger liquid parameter K. This effective Luttinger liquid parameter K reflects the low-energy physics and CFT for (1+1)D boundary. At bulk critical point, the effective K is suppressed but it keeps finite value, indicating the coupling between the gapless edge state and bulk fluctuation. The logarithmic term numerically captures this coupling picture, which reveals the (1+1)D SU(2)_{1} CFT and (2+1)D O(3) CFT at boundary criticality. Our Letter paves a new way to study the exotic boundary state and boundary criticality.
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We present large-scale quantum Monte Carlo simulation results on a realistic Hamiltonian of kagome-lattice Rydberg atom arrays. Although the system has no intrinsic disorder, intriguingly, our analyses of static and dynamic properties on large system sizes reveal emergent glassy behavior in a region of parameter space located between two valence bond solid phases. The extent of this glassy region is demarcated using the Edwards-Anderson order parameter, and its phase transitions to the two proximate valence bond solids-as well as the crossover towards a trivial paramagnetic phase-are identified. We demonstrate the intrinsically slow (imaginary) time dynamics deep inside the glassy phase and discuss experimental considerations for detecting such a quantum disordered phase with numerous nearly degenerate local minima. Our proposal paves a new route to the study of real-time glassy phenomena and highlights the potential for quantum simulation of a distinct phase of quantum matter beyond solids and liquids in current-generation Rydberg platforms.
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Peptide self-assemblies show intriguing and tunable physicochemical properties, and thus have been attracting increasing interest over the last two decades. However, the micro/nano-scale dimensions of the self-assemblies severely restrict their extensive applications. Inspired by nature, to genuinely realize the practical utilization of the bio-organic super-architectures, it is beneficial to further organize the peptide self-assemblies to integrate the properties of the individual supermolecules and fabricate higher-level organizations for smart functional devices. Therefore, cumulative studies have been reported on peptide microfabrication giving rise to diverse properties. This review summarizes the recent development of the microfabrication of peptide self-assemblies, discussing each methodology along with the diverse properties and practical applications of the engineered peptide large-scale, highly-ordered organizations. Finally, the current limitations of the state-of-the-art microfabrication strategies are critically assessed and alternative solutions are suggested.
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Microtecnologia , Peptídeos , Peptídeos/químicaRESUMO
We develop a nonequilibrium increment method to compute the Rényi entanglement entropy and investigate its scaling behavior at the deconfined critical (DQC) point via large-scale quantum Monte Carlo simulations. To benchmark the method, we first show that, at a conformally invariant critical point of O(3) transition, the entanglement entropy exhibits universal scaling behavior of area law with logarithmic corner corrections, and the obtained correction exponent represents the current central charge of the critical theory. Then we move on to the deconfined quantum critical point, where we still observe similar scaling behavior, but with a very different exponent. Namely, the corner correction exponent is found to be negative. Such a negative exponent is in sharp contrast with the positivity condition of the Rényi entanglement entropy, which holds for unitary conformal field theories (CFTs). Our results unambiguously reveal fundamental differences between DQC and quantum critical points described by unitary CFTs.
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High-throughput automated manipulation of microparticles in complex-shaped environments has been demonstrated with great potential in the field of pharmaceutical microfluidics. Generally, the development of a highly efficient actuation method for functional microparticle manipulation in complex-shaped chamber structures is the key challenge of this technology. Here, we present a novel traveling surface acoustic wave (TSAW)-based manipulation device that allows for automated and high-throughput maze-solving manipulation of microparticles inside complex round-shaped and square-shaped maze chambers. This technology relies on the localized acoustic streaming effects generated by TSAWs, which are capable of automatically trapping microparticles and driving them to move along the determined trajectories based on the topographic features of the maze chamber. Numerical modelling and simulation were conducted to demonstrate the feasibility of our proposed device for targeted microparticle transportation in complex-shaped maze chamber environments. In addition, by configuring the excitation of electric signals of interdigital transducers (IDTs), such as excitation frequency and input voltage, the motion velocity of microparticles can be rapidly adjusted within 0.1 s. Thus, our device enables low-cost, compact, and contactless trajectory manipulation of high-throughput microparticles inside chambers with complex topographical features and would have application in cell-directed transportation, low-volume chemical mixing, and precise drug delivery.
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Acústica , Som , Microfluídica , Transdutores , Simulação por ComputadorRESUMO
The recent discovery of two-dimensional (2D) ferromagnetism in van der Waals materials has opened the door to the control of 2D magnetism by means of electric field. Here we demonstrate the magnetization reversal through switching polarization in a designed 2D multiferroic oxide by combining group theory analysis and first-principles calculation. We show that ferroelectricity can be induced by a specific octahedral rotation in a perovskite bilayer. Ferromagnetism can be introduced simultaneously by extending the guideline to the B-site ordered double-perovskite bilayer. We have found two coupling mechanisms between polarization and magnetization that enable the reversal of the in-plane magnetization by ferroelectric switching. Our work provides guidelines for the design of 2D multiferroics with intrinsic magnetoelectric coupling and helps to control the 2D magnetism by electric field.
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Polymer-based substrate with region-selective microstructures are crucial for many biomedical applications. Here, we explored a novel method based on standing surface acoustic waves (SSAWs) for the fabrication of localized polymer-based microstructures via a predefined waveguide. When the SSAWs are excited, the generated acoustic pressure field can be controlled in a predetermined region of the fluid surface through controlling the size and shape of the waveguide geometry. On the basis of the capillary wave motion, the generated acoustic pressure field can excite microwavy patterned structures on the surface. Then with use of ultraviolet (UV) solidification, the polymer-based substrates with region-selective patterned microstructures can be successfully fabricated. Both finite element modeling and experimental studies demonstrated that the polymer substrate with different region-selective microstructures can be achieved by selecting the pairs of interdigital transducers (IDTs) and shapes of the predefined waveguides. The results showed that the proposed method is effective for fabricating polymer-based substrate with region-selective microstructures and may have potential in cell-laden chips for tissue engineering, cell-cell interactions, and other biomedical applications.
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Employing large-scale quantum Monte Carlo simulations, we study the extended XXZ model on the kagome lattice. A Z_{2} quantum spin liquid phase with effective even Ising gauge field structure emerges from the delicate balance among three symmetry-breaking phases including stripe solid, staggered solid, and ferromagnet. This Z_{2} spin liquid is stabilized by an extended interaction related to the Rokhsar-Kivelson potential in the quantum dimer model limit. The phase transitions from the staggered solid to a spin liquid or ferromagnet are found to be first order and so is the transition between the stripe solid and ferromagnet. However, the transition between a spin liquid and ferromagnet is found to be continuous and belongs to the 3D XY^{*} universality class associated with the condensation of spinons. The transition between a spin liquid and stripe solid appears to be continuous and associated with the condensation of visons.
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The nontriviality of quantum spin liquids (QSLs) typically manifests in the nonlocal observables that signify their existence; however, this fact actually casts a shadow on detecting QSLs with experimentally accessible probes. Here, we provide a solution by unbiasedly demonstrating a dynamical signature of anyonic excitations and symmetry fractionalization in QSLs. Employing large-scale quantum Monte Carlo simulation and stochastic analytic continuation, we investigate the extended XXZ model on the kagome lattice, and find out that, across the phase transitions from Z_{2} QSLs to different symmetry breaking phases, spin spectral functions can reveal the presence and condensation of emergent anyonic spinon and vison excitations, in particular, the translational symmetry fractionalization of the latter, which can be served as the dynamical signature of the seemingly ephemeral QSLs in spectroscopic techniques such as inelastic neutron or resonance (inelastic) x-ray scatterings.
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We present a quantum Monte Carlo study of the "quantum glass" phase of the two-dimensional Bose-Hubbard model with random potentials at filling ρ=1. In the narrow region between the Mott and superfluid phases, the compressibility has the form κâ¼exp(-b/T^{α})+c with α<1 and c vanishing or very small. Thus, at T=0 the system is either incompressible (a Mott glass) or nearly incompressible (a Mott-glass-like anomalous Bose glass). At stronger disorder, where a glass reappears from the superfluid, we find a conventional highly compressible Bose glass. On a path connecting these states, away from the superfluid at larger Hubbard repulsion, a change of the disorder strength by only 10% changes the low-temperature compressibility by more than 4 orders of magnitude, lending support to two types of glass states separated by a phase transition or a sharp crossover.
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This research presents an experimental study evaluating stomach suturing using a precurved nickel-titanium (NiTi) guidewire for an endoscopic minimally invasive obesity treatment. Precise path planning is critical for accurate and effective suturing. A position measurement system utilizing a hand-held magnetic sensor was used to measure the shape of a precurved guidewire and to determine the radius of curvature before and after suturing. Ex vivo stomach suturing experiments using four different guidewire tip designs varying the radius of curvature and bevel angles were conducted. The changes in radius of curvature and suturing force during suturing were measured. A model was developed to predict the guidewire radius of curvature based on the measured suturing force. Results show that a small bevel angle and a large radius of curvature reduce the suturing force and the combination of small bevel angle and small radius of curvature can maintain the shape of guidewire for accurate suturing.
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Fenômenos Mecânicos , Níquel , Suturas , Titânio , Animais , Teste de Materiais , Reprodutibilidade dos Testes , Estômago/cirurgia , SuínosRESUMO
The cellular membrane serves as a pivotal barrier in regulating intra- and extracellular matter exchange. Disruption of this barrier through pulsed electric fields (PEFs) induces the transmembrane transport of ions and molecules, creating a concentration gradient that subsequently results in the imbalance of cellular osmolality. In this study, a multiphysics model was developed to simulate the electromechanical response of cells exposed to microsecond pulsed electric fields (µsPEFs). Within the proposed model, the diffusion coefficient of the cellular membrane for various ions was adjusted based on electropore density. Cellular osmolality was governed and described using Van't Hoff theory, subsequently converted to loop stress to dynamically represent the cell swelling process. Validation of the model was conducted through a hypotonic experiment and simulation at 200 mOsm/kg, revealing a 14.2% increase in the cell's equivalent radius, thereby confirming the feasibility of the cell mechanical model. With the transmembrane transport of ions induced by the applied µsPEF, the hoop stress acting on the cellular membrane reached 179.95 Pa, and the cell equivalent radius increased by 11.0% when the extra-cellular medium was supplied with normal saline. The multiphysics model established in this study accurately predicts the dynamic changes in cell volume resulting from osmotic imbalance induced by PEF action. This model holds theoretical significance, offering valuable references for research on drug delivery and tumor microenvironment modulation.
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Eletricidade , Eletroporação , Eletroporação/métodos , Membrana Celular/metabolismo , Modelos Teóricos , ÍonsRESUMO
Quantum annealing, which involves quantum tunnelling among possible solutions, has state-of-the-art applications not only in quickly finding the lowest-energy configuration of a complex system, but also in quantum computing. Here we report a single-crystal study of the frustrated magnet α-CoV2O6, consisting of a triangular arrangement of ferromagnetic Ising spin chains without evident structural disorder. We observe quantum annealing phenomena resulting from time-reversal symmetry breaking in a tiny transverse field. Below ~ 1 K, the system exhibits no indication of approaching the lowest-energy state for at least 15 hours in zero transverse field, but quickly converges towards that configuration with a nearly temperature-independent relaxation time of ~ 10 seconds in a transverse field of ~ 3.5 mK. Our many-body simulations show qualitative agreement with the experimental results, and suggest that a tiny transverse field can profoundly enhance quantum spin fluctuations, triggering rapid quantum annealing process from topological metastable Kosterlitz-Thouless phases, at low temperatures.
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Long non-coding RNA (lncRNA) is associated with a large number of tumor cellular functions together with chemotherapy resistance in a variety of tumors. LINC00963 was identified to regulate the malignant progression of various cancers. However, whether LINC00963 affects drug resistence in esophageal squamous cell carcinoma (ESCC) and the relevant molecular mechanisms have never been reported. This study aims to investigate the effect of LINC00963 on cisplatin resistance in ESCC. After detecting the level of LINC00963 in human esophageal squamous epithelial cells (HET-1 A), ESCC cells (TE-1) and cisplatin resistant cells of ESCC (TE-1/DDP), TE-1/DDP cell line and nude mouse model that interfered with LINC00963 expression were established. Then, the interaction among LINC00963, miR-10a, and SKA1 was clarified by double luciferase and RNA immunoprecipitation (RIP) assays. Meanwhile, the biological behavior changes of TE-1/DDP cells with miR-10a overexpression or SKA1 silencing were observed by CCK-8, flow cytometry, scratch, Transwell, and colony formation tests. Finally, the biological function of the LINC00963/SKA1 axis was elucidated by rescue experiments. LINC00963 was upregulated in TE-1 and TE-1/DDP cell lines. LINC00963 knockdown inhibited SKA1 expression of both cells and impaired tumorigenicity. Moreover, LINC00963 has a target relationship with miR-10a, and SKA1 is a target gene of miR-10a. MiR-10a overexpression or SKA1 silencing decreased the biological activity of TE-1/DDP cells and the expression of SKA1. Furthermore, SKA1 overexpression reverses the promoting effect of LINC00963 on cisplatin resistance of ESCC. LINC00963 regulates TE-1/DDP cells bioactivity and mediates cisplatin resistance through interacting with miR-10a and upregulating SKA1 expression.
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Irreversible electroporation (IRE) has emerged as a promising modality for tumor ablation, leveraging the controlled application of electrical pulses to induce cell death. However, the associated muscle contractions during the procedure pose challenges. This study introduces a novel approach, termed Synergistic Bipolar Irreversible Electroporation (SBIRE), aimed at achieving tumor ablation without the undesirable side effect of muscle contraction. SBIRE involves the simultaneous application of nanosecond bipolar electrical pulses (±1600 V per 0.2 cm or ±8000 V per 1 cm, ±500 ns, "+" to "-" delay 1 µs, "-" to "+" delay 200 µs, 5 cycles) and microsecond bipolar electrical pulses (±300 V per 0.2 cm or ±1500 V per 1 cm, ±2 µs, "+" to "-" delay 2 µs, "-" to "+" delay 1000 µs, 25 cycles), strategically designed to synergistically target tumor cells while minimizing the impact on adjacent muscle tissue. The experimental setup includes in vitro and in vivo studies utilizing tumor cells and animal models to assess the efficacy of SBIRE. Preliminary results demonstrate the effectiveness of SBIRE in inducing irreversible electroporation within the tumor, leading to cell death, and the ablation effect is better than other parameter forms (24.41±0.23 mm2 (SBIRE group) vs 12.93±0.31 mm2 (ns group), 6.55±0.23 mm2 (µs group), 19.54±0.25 mm2 (ns+µs group), p<0.0001). Notably, muscle contraction is significantly reduced compared to traditional IRE procedures, highlighting the potential of SBIRE to enhance patient comfort and procedural success. The development of SBIRE represents a significant advancement in the field of tumor ablation, addressing a fundamental limitation associated with muscle contraction during IRE. This technique not only offers a valuable and promising approach to tumor treatment but also holds promise for minimizing procedural side effects.
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Seawater-groundwater interactions can enhance the migration process of microplastics to coastal aquifers, posing increased associated environmental risks. Here, we aim to analyze the relationship between seawater intrusion (SWI) and groundwater microplastic pollution in Laizhou Bay (LZB), which is a typical area of sea-land interactions. The results showed that modern seawater intrusion was the main process controlling the migration of microplastics. The detected microplastics in the study area showed a migration pattern from nearshore marine areas to groundwater aquifers along the SWI direction. In addition, the microplastics also reached the brine formed by palaeo-saltwater intrusion through hydraulic exchange between aquifers. By comparing the spatial distributions of different microplastic parameters, we found that nearshore fisheries, commercial, tourism, textile, and agricultural activities were the main sources of microplastics in groundwater in the study area. A risk assessment model of microplastics associated with SWI was further optimized in this study using a three-level classification system by assigning appropriate weights to different potential influencing factors. The results showed moderate comprehensive ecological risks associated with microplastics from seawater intrusion in the study area, with high microplastic enrichment risks. This study provides a scientific basis for future research on seawater-groundwater interactions and microplastic pollution in coastal regions.
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Tactile sensing requires integrated detection platforms with distributed and highly sensitive haptic sensing capabilities along with biocompatibility, aiming to replicate the physiological functions of the human skin and empower industrial robotic and prosthetic wearers to detect tactile information. In this regard, short peptide-based self-assembled hydrogels show promising potential to act as bioinspired supramolecular substrates for developing tactile sensors showing biocompatibility and biodegradability. However, the intrinsic difficulty to modulate the mechanical properties severely restricts their extensive employment. Herein, by controlling the self-assembly of 9-fluorenylmethoxycarbonyl-modifid diphenylalanine (Fmoc-FF) through introduction of polyethylene glycol diacrylate (PEGDA), wider nanoribbons are achieved by untwisting from well-established thinner nanofibers, and the mechanical properties of the supramolecular hydrogels can be enhanced 10-fold, supplying bioinspired supramolecular encapsulating substrate for tactile sensing. Furthermore, by doping with poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) and 9-fluorenylmethoxycarbonyl-modifid 3,4-dihydroxy-l-phenylalanine (Fmoc-DOPA), the Fmoc-FF self-assembled hydrogels can be engineered to be conductive and adhesive, providing bioinspired sensing units and adhesive layer for tactile sensing applications. Therefore, the integration of these modules results in peptide hydrogelation-based tactile sensors, showing high sensitivity and sustainable responses with intrinsic biocompatibility and biodegradability. The findings establish the feasibility of developing programmable peptide self-assembly with adjustable features for tactile sensing applications.
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Fluorenos , Hidrogéis , Hidrogéis/química , Fluorenos/química , Tato , Polietilenoglicóis/química , Humanos , Dipeptídeos/química , Fenilalanina/química , Fenilalanina/análogos & derivados , Nanofibras/química , Nanotubos de Carbono/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Materiais Biocompatíveis/química , Polímeros/químicaRESUMO
Acoustic tweezers based on surface acoustic waves (SAWs) have raised great interest in the fields of tissue engineering, targeted therapy, and drug delivery. Generally, the complex structure and array layout design of interdigital electrodes would restrict the applications of acoustic tweezers. Here, we present a novel approach by using bisymmetric coherent acoustic tweezers to modulate the shape of acoustic pressure fields with high flexibility and accuracy. Experimental tests were conducted to perform the precise, contactless, and biocompatible cluster manipulation of polystyrene microparticles and yeast cells. Stripe, dot, quadratic lattice, hexagonal lattice, interleaved stripe, oblique stripe, and many other complex arrays were achieved by real-time modulation of amplitudes and phase relations of coherent SAWs to demonstrate the capability of the device for the cluster manipulation of particles and cells. Furthermore, rapid switching among various arrays, shape regulation, geometric parameter modulation of array units, and directional translation of microparticles and cells were implemented. This study demonstrated a favorable technique for flexible and versatile manipulation and patterning of cells and biomolecules, and it has the advantages of high manipulation accuracy and adjustability, thus it is expected to be utilized in the fields of targeted cellular assembly, biological 3D printing, and targeted release of drugs.