Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant Klebsiella pneumoniae.

Purpose: Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) co-producing carbapenem-resistant Klebsiella pneumoniae (KPC-NDM-CRKP) isolates have been increasingly reported worldwide but have not yet been systematically studied. Thus, we have conducted a study to compare the risk factors, molecular characteristics, and mortality involved in clinical bloodstream infections (BSIs) caused by KPC-NDM-CRKP and KPC-CRKP strains. Methods: A retrospective study was conducted on 231 patients with BSIs caused by CRKP at Jinling Hospital in China from January 2020 to December 2022. Antimicrobial susceptibility testing, carbapenemase genes detection and whole-genome sequencing were performed subsequently. Results: Overall, 231 patients were included in this study: 25 patients with KPC-NDM-CRKP BSIs and 206 patients with KPC-CRKP BSIs. Multivariate analysis implicated ICU-acquired BSI, surgery within 30 days, and longer stay of hospitalization prior to CRKP isolation as independent risk factors for KPC-NDM-CRKP BSIs. The 30-day mortality rate of the KPC-NDM-CRKP BSIs group was 56% (14/25) compared with 32.5% (67/206) in the KPC-CRKP BSIs control group (P = 0.02). The ICU-acquired BSIs, APACHE II score at BSI onset, and BSIs caused by KPC-NDM-CRKP were independent predictors for 30-day mortality in patients with CRKP bacteremia. The most prevalent ST in KPC-NDM-CRKP isolates was ST11 (23/25, 92%), followed by ST15 (2/25, 8%). Conclusion: In patients with CRKP BSIs, KPC-NDM-CRKP was associated with an excess of mortality. The likelihood that KPC-NDM-CRKP will become the next "superbug" highlights the significance of epidemiologic surveillance and clinical awareness of this pathogen.

Through-polymer, via technology-enabled, flexible, lightweight, and integrated devices for implantable neural probes.

In implantable electrophysiological recording systems, the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing. While advancements in MEMS and CMOS technology have significantly improved these components, their interconnection still relies on conventional printed circuit boards and sophisticated adapters. This conventional approach adds considerable weight and volume to the package, especially for high channel count systems. To address this issue, we developed a through-polymer via (TPV) method inspired by the through-silicon via (TSV) technique in advanced three-dimensional packaging. This innovation enables the vertical integration of flexible probes, amplifier chips, and PCBs, realizing a flexible, lightweight, and integrated device (FLID). The total weight of the FLIDis only 25% that of its conventional counterparts relying on adapters, which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants. Furthermore, by incorporating a platinum-iridium alloy as the top layer material for electrical contact, the FLID realizes exceptional electrical performance, enabling in vivo measurements of both local field potentials and individual neuron action potentials. These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

Ultraflexible PEDOT:PSS/IrOx-Modified Electrodes: Applications in Behavioral Modulation and Neural Signal Recording in Mice.

Recent advancements in neural probe technology have become pivotal in both neuroscience research and the clinical management of neurological disorders. State-of-the-art developments have led to the advent of multichannel, high-density bidirectional neural interfaces that are adept at both recording and modulating neuronal activity within the central nervous system. Despite this progress, extant bidirectional probes designed for simultaneous recording and stimulation are beset with limitations, including elicitation of inflammatory responses and insufficient charge injection capacity. In this paper, we delineate the design and application of an innovative ultraflexible bidirectional neural probe engineered from polyimide. This probe is distinguished by its ability to facilitate high-resolution recordings and precise stimulation control in deep brain regions. Electrodes enhanced with a PEDOT:PSS/IrOx composite exhibit a substantial increase in charge storage capacity, escalating from 0.14 ± 0.01 mC/cm2 to an impressive 24.75 ± 0.18 mC/cm2. This augmentation significantly bolsters the electrodes' charge transfer efficacy. In tandem, we observed a notable reduction in electrode impedance, from 3.47 ± 1.77 MΩ to a mere 41.88 ± 4.04 kΩ, while the phase angle exhibited a positive shift from -72.61 ± 1.84° to -34.17 ± 0.42°. To substantiate the electrodes' functional prowess, we conducted in vivo experiments, where the probes were surgically implanted into the bilateral motor cortex of mice. These experiments involved the synchronous recording and meticulous analysis of neural signal fluctuations during stimulation and an assessment of the probes' proficiency in modulating directional turning behaviors in the subjects. The empirical evidence corroborates that targeted stimulation within the bilateral motor cortex of mice can modulate the intensity of neural signals in the stimulated locale, enabling the directional control of the mice's turning behavior to the contralateral side of the stimulation site.

GCLR: A self-supervised representation learning pretext task for glomerular filtration barrier segmentation in TEM images.

Automatic segmentation of the three substructures of glomerular filtration barrier (GFB) in transmission electron microscopy (TEM) images holds immense potential for aiding pathologists in renal disease diagnosis. However, the labor-intensive nature of manual annotations limits the training data for a fully-supervised deep learning model. Addressing this, our study harnesses self-supervised representation learning (SSRL) to utilize vast unlabeled data and mitigate annotation scarcity. Our innovation, GCLR, is a hybrid pixel-level pretext task tailored for GFB segmentation, integrating two subtasks: global clustering (GC) and local restoration (LR). GC captures the overall GFB by learning global context representations, while LR refines three substructures by learning local detail representations. Experiments on 18,928 unlabeled glomerular TEM images for self-supervised pre-training and 311 labeled ones for fine-tuning demonstrate that our proposed GCLR obtains the state-of-the-art segmentation results for all three substructures of GFB with the Dice similarity coefficient of 86.56 ± 0.16%, 75.56 ± 0.36%, and 79.41 ± 0.16%, respectively, compared with other representative self-supervised pretext tasks. Our proposed GCLR also outperforms the fully-supervised pre-training methods based on the three large-scale public datasets - MitoEM, COCO, and ImageNet - with less training data and time.

Lightweight Soft Robotic Glove with Whole-Hand Finger Motion Tracking for Hand Rehabilitation in Virtual Reality.

Soft robotic gloves have attracted significant interest in hand rehabilitation in the past decade. However, current solutions are still heavy and lack finger-state monitoring and versatile treatment options. To address this, we present a lightweight soft robotic glove actuated by twisted string actuators (TSA) that provides whole-hand finger motion tracking. We have developed a virtual reality environment for hand rehabilitation training, allowing users to interact with various virtual objects. Fifteen small inertial measurement units are placed on the glove to predict finger joint angles and track whole-hand finger motion. We performed TSA experiments to identify design and control rules, by understanding how their response varies with input load and voltages. Grasping experiments were conducted to determine the grasping force and range of motion. Finally, we showcase an application of the rehabilitation glove in a Unity-based VR interface, which can actuate the operator's fingers to grasp different virtual objects.

A mosquito mouthpart-like bionic neural probe.

Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinical applications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, with their mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability and longevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation; however, the protective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels during implantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimetic neuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array. This customizable system achieves distributed and minimally invasive implantation across brain regions. Most importantly, the system's nonvisual monitoring capability provides an early warning detection for intracranial soft tissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstrates exceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperative and chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential for future applications in neuroscience and brain-machine interfaces. A mosquito mouthpart-like bionic neural probe consisting of a highly sensitive tactile sensor module, a flexible microelectrode array, and implanted modules that mimic the structure of mosquito mouthparts. The system enables distributed implantation of electrode arrays across multiple brain regions while making the implantation minimally invasive and avoiding additional dural removal. The tactile sensor array can monitor the implantation process to achieve early warning of vascular damage. The excellent postoperative short-term recording performance and long-term neural activity tracking ability demonstrate that the system is a promising tool in the field of brain-computer interfaces.

Identification of Risk Factors and Phenotypes of Surgical Site Infection in Patients After Abdominal Surgery.

OBJECTIVES: We aimed to determine the current incidence rate and risk factors for surgical site infection (SSI) after abdominal surgery in China and to further demonstrate the clinical features of patients with SSI. BACKGROUND: Contemporary epidemiology and clinical features of SSI after abdominal surgery remain poorly characterized. METHODS: A prospective multicenter cohort study was conducted from March 2021 to February 2022; the study included patients who underwent abdominal surgery at 42 hospitals in China. Multivariable logistic regression analysis was performed to identify risk factors for SSI. Latent class analysis (LCA) was used to explore the population characteristics of SSI. RESULTS: In total, 23,982 patients were included in the study, of whom 1.8% developed SSI. There was a higher SSI incidence in open surgery (5.0%) than in laparoscopic or robotic surgeries (0.9%). Multivariable logistic regression indicated that the independent risk factors for SSI after abdominal surgery were older age, chronic liver disease, mechanical bowel preparation, oral antibiotic bowel preparation, colon or pancreas surgery, contaminated or dirty wounds, open surgery, and colostomy/ileostomy. LCA revealed 4 subphenotypes in patients undergoing abdominal surgery. Types α and ß were mild subclasses with a lower SSI incidence; whereas types γ and δ were the critical subgroups with a higher SSI incidence, but their clinical features were different. CONCLUSIONS: LCA identified 4 subphenotypes in patients who underwent abdominal surgery. Types γ and δ were critical subgroups with a higher SSI incidence. This phenotype classification can be used to predict SSI after abdominal surgery.

A silk-based self-adaptive flexible opto-electro neural probe.

The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits, which provides a promising approach for the study of progressive neurophysiological phenomena. Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance. However, lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness. Herein, we report a hybrid probe (Silk-Optrode) consisting of a silk protein optical fiber and multiple flexible microelectrode arrays. The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals. Silk plays an important role due to its high transparency, excellent biocompatibility, and mechanical controllability. Through the hydration of the silk optical fiber, the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue. The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses, surpassing previous work of a similar type. Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions. A silk optical fiber-based Silk-Optrode probe consisting of a natural silk optical fiber and a flexible micro/nano electrode array is reported. The multifunctional soft probe can modify its own Young's modulus through hydration to achieve accurate implantation into the brain. The low optical loss and single-unit recording abilities allow simultaneous optogenetic stimulation and multichannel readout, which expands the applications in the operation and parsing of neural circuits in behavioral animals.

Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development.

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.

Bioinformatics analysis identified apolipoprotein E as a hub gene regulating neuroinflammation in macrophages and microglia following spinal cord injury.

Macrophages and microglia play important roles in chronic neuroinflammation following spinal cord injury (SCI). Although macrophages and microglia have similar functions, their phagocytic and homeostatic abilities differ. It is difficult to distinguish between these two populations in vivo, but single-cell analysis can improve our understanding of their identity and heterogeneity. We conducted bioinformatics analysis of the single-cell RNA sequencing dataset GSE159638, identifying apolipoprotein E (APOE) as a hub gene in both macrophages and microglia in the subacute and chronic phases of SCI. We then validated these transcriptomic changes in a mouse model of cervical spinal cord hemi-contusion and observed myelin uptake, lipid droplets, and lysosome accumulation in macrophages and microglia following SCI. Finally, we observed that knocking out APOE aggravated neurological dysfunction, increased neuroinflammation, and exacerbated the loss of white matter. Targeting APOE and the related cholesterol efflux represents a promising strategy for reducing neuroinflammation and promoting recovery following SCI.

St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.

BACKGROUND: Early diagnosis and treatment of chronic pancreatitis (CP) are limited. In this study, St13, a co-chaperone protein, was investigated whether it constituted a novel regulatory target in CP. Meanwhile, we evaluated the value of micro-PET/CT in the early diagnosis of CP. METHODS: Data from healthy control individuals and patients with alcoholic CP (ACP) or non-ACP (nACP) were analysed. PRSS1 transgenic mice (PRSS1Tg) were treated with ethanol or caerulein to mimic the development of ACP or nACP, respectively. Pancreatic lipid metabolite profiling was performed in human and PRSS1Tg model mice. The potential functions of St13 were investigated by crossing PRSS1Tg mice with St13-/- mice via immunoprecipitation and lipid metabolomics. Micro-PET/CT was performed to evaluate pancreatic morphology and fibrosis in CP model. RESULTS: The arachidonic acid (AA) pathway ranked the most commonly dysregulated lipid pathway in ACP and nACP in human and mice. Knockout of St13 exacerbated fatty replacement and fibrosis in CP model. Sdf2l1 was identified as a binding partner of St13 as it stabilizes the IRE1α-XBP1s signalling pathway, which regulates COX-2, an important component in AA metabolism. Micro-PET/CT with 68Ga-FAPI-04 was useful for evaluating pancreatic morphology and fibrosis in CP model mice 2 weeks after modelling. CONCLUSION: St13 is functionally activated in acinar cells and protects against the cellular characteristics of CP by binding Sdf2l1, regulating AA pathway. 68Ga-FAPI-04 PET/CT may be a very valuable approach for the early diagnosis of CP. These findings thus provide novel insights into both diagnosis and treatment of CP.

A Hierarchically Encoded Data Storage Device with Controlled Transiency.

In the era of information explosion, high-security and high-capacity data storage technology attracts more and more attention. Physically transient electronics, a form of electronics that can physically disappear with precisely controlled degradation behaviors, paves the way for secure data storage. Herein, the authors report a silk-based hierarchically encoded data storage device (HEDSD) with controlled transiency. The HEDSD can store electronic, photonic, and optical information simultaneously by synergistically integrating a resistive switching memory (ReRAM), a terahertz metamaterial device, and a diffractive optical element, respectively. These three data storage units have shared materials and structures but diverse encoding mechanisms, which increases the degree of complexity and capacity of stored information. Silk plays an important role as a building material in the HEDSD thanks to its excellent mechanical, optical, and electrical properties and controlled transiency as a naturally extracted protein. By controlling the degradation rate of storage units of the silk-based HEDSD, different degradation modes of the HEDSD, and multilevel information encryption/decryption have been realized. Compared with the conventional memory devices, as-reported silk-based HEDSD can store multilevel complex information and realize multilevel information encryption and decryption, which is highly desirable to fulfill the future demands of secure memory systems and implantable storage devices.

Robotic Manipulation under Harsh Conditions Using Self-Healing Silk-Based Iontronics.

Progress toward intelligent human-robotic interactions requires monitoring sensors that are mechanically flexible, facile to implement, and able to harness recognition capability under harsh environments. Conventional sensing methods have been divided for human-side collection or robot-side feedback and are not designed with these criteria in mind. However, the iontronic polymer is an example of a general method that operates properly on both human skin (commonly known as skin electronics or iontronics) and the machine/robotic surface. Here, a unique iontronic composite (silk protein/glycerol/Ca(II) ion) and supportive molecular mechanism are developed to simultaneously achieve high conductivity (around 6 kΩ at 50 kHz), self-healing (within minutes), strong stretchability (around 1000%), high strain sensitivity and transparency, and universal adhesiveness across a broad working temperature range (-40-120 °C). Those merits facilitate the development of iontronic sensing and the implementation of damage-resilient robotic manipulation. Combined with a machine learning algorithm and specified data collection methods, the system is able to classify 1024 types of human and robot hand gestures under challenging scenarios and to offer excellent object recognition with an accuracy of 99.7%.

Lamin A/C-Dependent Translocation of Megakaryoblastic Leukemia-1 and ß-Catenin in Cyclic Strain-Induced Osteogenesis.

Lamins are intermediate filaments that play a crucial role in sensing mechanical strain in the nucleus of cells. ß-catenin and megakaryoblastic leukemia-1 (MKL1) are critical signaling molecules that need to be translocated to the nucleus for their transcription in response to mechanical strain that induces osteogenesis. However, the exact molecular mechanism behind the translocation of these molecules has not been fully investigated. This study used 10% cyclic strain to induce osteogenesis in the murine osteoblast precursor cell line (MC3T3). The translocation of ß-catenin and MKL1 was studied by performing knockdown and overexpression of lamin A/C (LMNA). Cyclic strain increased the expression of osteogenic markers such as alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and enhanced ALP staining after seven days of incubation. Resultantly, MKL1 and ß-catenin were translocated in the nucleus from the cytoplasm during the stress-induced osteogenic process. Knockdown of LMNA decreased the accumulation of MKL1 and ß-catenin in the nucleus, whereas overexpression of LMNA increased the translocation of these molecules. In conclusion, our study indicates that both MKL1 and ß-catenin molecules are dependent on the expression of LMNA during strain-induced osteogenesis.

Single-cell transcriptomic sequencing analyses of cell heterogeneity during osteogenesis of human adipose-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are known for their multilineage differentiation potential with immune-modulatory properties. The molecular underpinnings of differentiation remain largely undefined. In this study, we investigated the cellular and molecular features of chemically induced osteogenesis from MSC isolated from human adipose tissue (human adipose MSCs, hAMSCs) using single-cell RNA-sequencing (scRNA-seq). We found that a near complete differentiation of osteogenic clusters from hAMSCs under a directional induction. Both groups of cells are heterogeneous, and some of the hAMSCs cells are intrinsically prepared for osteogenesis, while variant OS clusters seems in cooperation with a due division of the general function. We identified a set of genes related to cell stress response highly expressed during the differentiation. We also characterized a series of transitional transcriptional waves throughout the process from hAMSCs to osteoblast and specified the unique gene networks and epigenetic status as key markers of osteogenesis.

Actin polymerization state regulates osteogenic differentiation in human adipose-derived stem cells.

BACKGROUND: Actin is an essential cellular protein that assembles into microfilaments and regulates numerous processes such as cell migration, maintenance of cell shape, and material transport. METHODS: In this study, we explored the effect of actin polymerization state on the osteogenic differentiation of human adipose-derived stem cells (hASCs). The hASCs were treated for 7 days with different concentrations (0, 1, 5, 10, 20, and 50 nM) of jasplakinolide (JAS), a reagent that directly polymerizes F-actin. The effects of the actin polymerization state on cell proliferation, apoptosis, migration, and the maturity of focal adhesion-related proteins were assessed. In addition, western blotting and alizarin red staining assays were performed to assess osteogenic differentiation. RESULTS: Cell proliferation and migration in the JAS (0, 1, 5, 10, and 20 nM) groups were higher than in the control group and the JAS (50 nM) group. The FAK, vinculin, paxillin, and talin protein expression levels were highest in the JAS (20 nM) group, while zyxin expression was highest in the JAS (50 nM) group. Western blotting showed that osteogenic differentiation in the JAS (0, 1, 5, 10, 20, and 50 nM) group was enhanced compared with that in the control group, and was strongest in the JAS (50 nM) group. CONCLUSIONS: In summary, our data suggest that the actin polymerization state may promote the osteogenic differentiation of hASCs by regulating the protein expression of focal adhesion-associated proteins in a concentration-dependent manner. Our findings provide valuable information for exploring the mechanism of osteogenic differentiation in hASCs.

Robotic Trajectories and Morphology Manipulation of Single Particle and Granular Materials by a Vibration Tweezer.

Robotic self-assembly of deformable materials holds potential for the automatic construction of complex robots. Current manipulation for deformable manipulation mainly focuses on a soft robot. It still remains a great challenge for morphology manipulation of a swarm of particles. Chladni patterns have raised great interest in the field of self-assembly for different materials. The formation of Chladni patterns is driven by the vibration process that involves the particles moving from disorder to order. Particles bounce randomly on the plate, and gradually accumulate along nodal lines, whereas the instantaneous random effect is inevitable, meaning that the trajectories of particles are uncertain. Here, the vibration tweezer is proposed by programmable two-frequency driving Chladni patterns. Different materials can be precisely and flexibly trapped to the vibration node. The vibration tweezer is further programmed for arbitrary positions by solving the vibration inverse problem. Then, different controllable trajectories "PKU" manipulation of particle can be achieved through switching the tweezer positions. Most importantly, the vibration tweezer exhibits the morphology of granular materials assemblages with collection, motion, and rotation. This work paves the way for the control of complex self-assembly, thereby enabling programmable manipulation of granular materials and micro robots.

Reconfigurable Particle Swarm Robotics Powered by Acoustic Vibration Tweezer.

Inspired by natural swarms such as bees and ants, various types of swarm robotic systems have been developed to work together to complete tasks that transcend individual capabilities. Autonomous robots controlled by collective algorithm and colloidal swarms energized by external field have been designed in an attempt to emulate collective behaviors in nature. However, either sophisticated hardware designs or active agents with special electromagnetic properties and microstructural designs are needed. Here, for the first time, we create a swarm robotic system that can make any granular materials an active swarm robot by acoustic vibration tweezer. It should be noted that the particles energized by only one vibration generator are ordinary sand without any microstructural design. Therefore, it is the simplest and lowest cost swarm robot. Particles can display a solid-like aggregate, which is capable of robustly carrying and transporting an object that is about 1 million times heavier than a single particle. Moreover, through the cooperation of two swarm robots, we can achieve cooperative transport of a stick with a length of 1000 times the diameter of a single particle. The particle robot can move in a fluid-like amorphous group, which can change its own shape to adapt to the surrounding environment, thus having a strong environmental adaptability. Besides, it can move quickly (about 600 times the particle diameter per second) in a discrete state. Within one certain particle system, the particle swarm robot can emulate diverse biomimetic collective behaviors through navigated locomotion, multimode transformation, and cooperative transport.

Spatial organization and crosstalk of vimentin and actin stress fibers regulate the osteogenic differentiation of human adipose-derived stem cells.

Human adipose-derived stem cells (hASCs) are ideal seed cells for tissue engineering due to their multidirectional differentiation potential. Microfilaments, microtubules, and intermediate filaments are responsible for supporting the intracellular space. Vimentin, a type III intermediate filament protein that is specifically expressed in cells of mesenchymal origin, can function as a scaffold and endow cells with tension and shear stress resistance. Actin stress fibers (ASF) act as an important physical device in stress signal transduction, providing stiffness for cells, and promoting osteogenesis. Through direct physical contact, cross-linkers, and spatial interactions, vimentin and actin networks exist as intersecting entities. Spatial interactions occur in the overlapping area of cytoskeleton subsystems, which could affect cell morphology, cell mechanics, and cell fate. However, how does the spatial organization between the cytoskeletal subsystems changed during osteogenesis, especially between vimentin and ASF, is still not understood, and its mechanism effect on cell fate remains unclear. In our study, WB experiment was used to detect the expression changes in Vimentin, ASF, and other proteins. Cells were reconstructed by three-dimensional scanning with fluorescence microscope, and the spatial thickness of vimentin and ASF cytoskeletons and the thickness of the overlapping area between them were calculated, respectively, so as to observe the spatial reorganization of vimentin and ASF in cells. Cytochalasin D (an inhibitor of actin polymerization) and vimentin upregulated/downregulated cells were used to verify the change in the spatial organization between vimentin and ASF and its influence on osteogenesis. Then, heat shock protein 27 (HSP27) was downregulated to illuminate the regulatory mechanisms of spatial organization between vimentin and ASF during osteogenesis. The amounts and the spatial positions of vimentin and actin stress fiber exhibited opposite trends during osteogenesis. Through controlling the anchor sites on the nucleus, intermediate filaments vimentin can reduce the spatial proportion of actin stress fibers, which can be regulated by HSP27. In addition, depolymerization of actin stress fibers lead to lower osteogenic differentiation ability, resulting in osteogenesis and lipogenesis existed simultaneously, that can be resisted by vimentin. Our data indicate that the spatial reorganization of vimentin and actin stress fibers is a key factor in the regulation of the differentiation state of hASCs. And their spatial overlapping area is detrimental to hASCs osteogenesis, providing a new perspective for further exploring the mechanism underlying hASCs osteogenesis.