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Enzymes catalyze almost all material conversion processes within living organisms, yet their natural evolution remains unobserved. Short peptides, derived from proteins and featuring active sites, have emerged as promising building blocks for constructing bioactive supramolecular materials that mimic native proteins through self-assembly. Herein, we employ histidine-containing isomeric tetrapeptides KHFF, HKFF, KFHF, HFKF, FKHF, and FHKF to craft supramolecular self-assemblies, aiming to explore the sequence–activity landscapes of enzyme evolution. Our investigations reveal the profound impact of peptide sequence variations on both assembly behavior and catalytic activity as hydrolytic simulation enzymes. During self-assembly, a delicate balance of multiple intermolecular interactions, particularly hydrogen bonding and aromatic–aromatic interactions, influences nanostructure formation, yielding various morphologies (e.g., nanofibers, nanospheres, and nanodiscs). Furthermore, the analysis of the structure–activity relationship demonstrates a strong correlation between the distribution of the His active site on the nanostructures and the formation of the catalytic microenvironment. This investigation of the sequence–structure–activity paradigm reflects how natural enzymes enhance catalytic activity by adjusting the primary structure during evolution, promoting fundamental research related to enzyme evolutionary processes.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1−/−mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

Grinding is a fundamental operation in craniotomy. Suitable grinding parameters will not only reduce force damage, but also ensure grinding efficiency. In this study, the regression equations of material removal rate and grinding force were obtained based on the theory of cortical bone grinding and full factorial test results, a multi-objective optimization based on the particle swarm algorithm was proposed for optimizing the grinding parameters: spindle speed, feed speed, and grinding depth in the grinding process. Two conflicting objectives, minimum grinding force and maximum material removal rate, were optimized simultaneously. The results revealed that the optimal grinding parameter combination and optimization results were as follows: spindle speed of 5000 rpm, feed rate of 60 mm/min, grinding depth of 0.6 mm, grinding force of 15.1 N, and material removal rate of 113.8 mm3/min. The parameter optimization result can provide theoretical guidance for selecting cortical bone grinding parameters in actual craniotomy.

Studying the anisotropic mechanical properties of cartilage induced by inhomogeneous structure is significant to prevent cartilage damage induced by overloading or fatigue and to develop biomaterials for tissue engineering. The depth-dependent fracture behavior of knee articular cartilage was studied by conducting the fracture tests on the clamped single-edge notched tensile (SENT) samples. The articular cartilage exhibited excellent load bearing capacity and ductility due to its unique depth-dependent matrix structure. The necking length of cartilage decreases through the depth of cartilage, while the peak tensile load first increases, then decreases in depth. The grow of crack in full-thickness cartilage starts in superficial layer at about peak load and the cartilage fails gradually once the crack begins to grow. The fibril network experiences irreversible damage with large area of collagen fibrils yielding before the fracture of full-thickness cartilage. Three fracture parameters, namely the stress intensity factor (K), the critical total work (CTW) and the crack tip opening displacement (CTOD) are calculated to study the fracture properties of cartilage, and CTODΔa = 0.2is employed to evaluate the depth-dependent initiation fracture toughness of cartilage. The fracture toughness of cartilage decreases along depth direction and the fracture toughness of full-thickness cartilage is close to that of deep layer. In addition, the superficial layer with external layer exhibits larger ductility and larger crack-tip blunting degree than the middle and deep layer of cartilage, and plays a vital role in fracture of cartilage. In addition, the fracture toughness of cartilage increases slightly with the increase of loading rate. The study could provide mechanical reference for repairing cartilage defects with artificial cartilage produced by tissue engineering.

During spaceflight, astronauts experience 1–1.5% bone loss per month, especially in the lumbar spine, pelvis and lower limbs. The bone loss leads to osteoporosis and increased the risk of fracture. Current researches focus on anti-osteoporosis under microgravity mainly by inhibiting bone resorption of osteoclasts and / or increasing bone formation of osteoblasts. However, studies on the effects of mass transfer in the bone lacunar-canalicular system (LCS) on osteoporosis are lacking. Osteocytes reside in the lacunae and communicate with other osteocytes, osteoblasts and osteoclasts through the LCS in the bone matrix. Osteocytes are mainly responsible for mechanosensing and signal regulation in bone, and the LCS is the basic structure for signaling, mass transfer and mechanical stimulation. Microgravity causes deficient mass transfer in the LCS, especially in the outer layer of osteon. Osteocytes far away from the Haversian canals are inhibited or accelerated apoptosis to stimulate osteoclasts which result in bone loss. Deficient mass transfer in the LCS may be a determinant of human osteoporosis under microgravity, which will open up a new way to treat osteoporosis in space.

Bone surgery is a complex process involving sustainable and healthy human recuperation, but poor surface quality and loose implant fixtures can affect the recovery time of orthopedic patients. However, it has been demonstrated that the application of ultrasonic vibration during drilling procedures can improve the success of bone remediation procedures. The focus of the present paper was on the investigation of surface quality and pullout strength of drilled holes. After analyzing the special kinematic characteristics of the ultrasonically-assisted drilling (UAD), UAD testing using fresh cortical bone was carried out and compared with the results obtained after conventional drilling (CD) procedures. Surface roughness measurements and microscope examination were used to evaluate surface quality, and an electro-mechanical tensile machine was used to measure pullout resistance. The test findings indicated that surface roughness was reduced by 17–68.7% when using UAD; the axial pullout strength of screws inserted into UAD holes was significantly increased by 4.28–30.1% compared to that of CD. It was found also that low spindle speeds and high feed rates reduced surface quality and the stability of the inserted cortical screws. The findings demonstrated that UAD produced better surface quality and higher pullout strengths, which could provide greater stability for implants and improved post-operative recovery.

Water-responsive materials undergo reversible shape changes upon varying humidity levels. These mechanically robust yet flexible structures can exert substantial forces and hold promise as efficient actuators for energy harvesting, adaptive materials and soft robotics. Here we demonstrate that energy transfer during evaporation-induced actuation of nanoporous tripeptide crystals results from the strengthening of water hydrogen bonding that drives the contraction of the pores. The seamless integration of mobile and structurally bound water inside these pores with a supramolecular network that contains readily deformable aromatic domains translates dehydration-induced mechanical stresses through the crystal lattice, suggesting a general mechanism of efficient water-responsive actuation. The observed strengthening of water bonding complements the accepted understanding of capillary-force-induced reversible contraction for this class of materials. These minimalistic peptide crystals are much simpler in composition compared to natural water-responsive materials, and the insights provided here can be applied more generally for the design of high-energy molecular actuators.

Collagen is a structural protein that is widely present in vertebrates, being usually distributed in tissues in the form of fibers. In living organisms, fibers are organized in different orientations in various tissues. As the structural base in connective tissue and load-bearing tissue, the orientation of collagen fibers plays an extremely important role in the mechanical properties and physiological and biochemical functions. The study on mechanics role in formation of oriented collagen fibers enables us to understand how discrete cells use limited molecular materials to create tissues with different structures, thereby promoting our understanding of the mechanism of tissue formation from scratch, from invisible to tangible. However, the current understanding of the mechanism of fiber orientation is still insufficient. In addition, existing fabrication methods of oriented fibers are varied and involve interdisciplinary study, and the achievements of each experiment are favorable to the construction and improvement of the fiber orientation theory. To this end, this review focuses on the preparation methods of oriented fibers and proposes a model explaining the formation process of oriented fibers in tendons based on the existing fiber theory.Impact statementAs the structural base in connective tissue and load-bearing tissue, the orientation of collagen fibers plays an extremely important role in the mechanical properties and physiological and biochemical functions. However, the current understanding of the mechanism of fiber orientation is still insufficient, which is greatly responsible for the challenge of functional tissue repair and regeneration. Understanding the mechanism of fiber orientation can promote the successful application of fiber orientation scaffolds in tissue repair and regeneration, as well as providing an insight for the mechanism of tissue histomorphology.

In order to feedback the cutting temperature in real time during the operation with the surgical robot, this study established a temperature prediction model to analyze the temperature distribution of the cortex. In this work, a three-dimensional governing equation for heat transfer of bone tissue during drilling is proposed, and the heat transfer of cortical bone is evaluated by a reverse heat transfer method. The prediction model was validated by experimental methods and the heat affected zone (HAZ) of cortical bone was analyzed. The results show that the prediction results are in good agreement with the relevant experimental results. HAZ increases with increasing rate of penetration; the closer the bone hole is, the earlier the temperature rises; and the temperature at which the cortical bone is difficult to measure (radial distance x < 0.5 mm) is predicted. The predictive model can accurately predict the temperature distribution of the cortical bone and prevent the occurrence of thermal damage. Provide technical support for the development of medical rehabilitation robots. And reduce the patient’s secondary injury, which is conducive to rapid recovery after surgery.

The intervertebral disk cushions the load generated by human activity and absorbs energy to keep the spine moving steadily. Vibration condition is one of the important causes of disk degeneration. Creep experiments using the sheep lumbar intervertebral disk were carried out under vibration compression. Regularities of the strain of the disk with time were obtained and compared with those of static load. The influence of vibration frequency and time on the creep properties of the intervertebral disk was analyzed. An intervertebral disk three-parameter solid creep constitutive model considering vibration factors was established and the parameters in the model were identified. The results show that the strain of the lumbar intervertebral disk exhibits an exponential relationship with time and is unrelated to static compression or vibration load. Under the same vibration amplitude, the creep increases with vibration frequency and the relationship between them is nonlinear. The vibration frequency has a significant effect on the strain. The creep rate decreases gradually with time and is obviously influenced by vibration frequency at low vibration amplitudes. The creep prediction results obtained using the constitutive model with the time-varying material parameters are in good agreement with the experimental results. The two elastic moduli in the model decrease with time and the viscosity coefficient increases with time.

Tight sandstone gas reservoirs commonly contain water, so liquid loading often appears near wellbores, leading to production decline and even shutdown of gas wells. Therefore, the study on the change of water saturation near wellbores is of great significance to understanding the water production mechanisms of gas wells. In this paper, a set of physical simulation experiment procedures of identifying the change of water saturation near wellbores was designed according to the principle of radial well seepage of gas wells, and the production performance after vertical well fracturing in gas reservoirs was simulated by connecting tight cores with a diameter of 10.5 cm, 3.8 cm and 2.5 cm in series in a descending order of distance. According to the depressurizing production mode of gas wells, tubes with small diameters of 20, 30, 40 and 50 μm were used to simulate gas well tubing to control the gas production rate. And the change of water saturation near wellbore in the process of depletion production and its influencing factors were investigated. Finally, combined with actual data of production wells, the water saturation and water production of gas wells near wellbores and in different zones were calculated at the above four different small diameters of tubes and the changes thereof were also analyzed. The following results were obtained. First, each gas production rate corresponds to a critical water saturation. When the initial water saturation is lower than the critical value, the formation water flowing near the wellbore and in the middle zone can be carried out along with the production of gas and no liquid loading is formed. Second, when the initial water saturation is higher than the critical value, a large amount of formation water migrating from the far-wellbore zones accumulates near the wellbore, and thus liquid loading occurs at the bottom hole. Third, when the initial water saturation is equal to the critical value, the higher the gas production rate is, the more easily liquid loading tends to form near the wellbore. Fourth, for the same water saturation, water production increases and recovery factor decreases with the increase of gas production rate. In conclusion, the cumulative water production chart of a gas well generated by the physical simulation experiment method proposed in this paper agrees well with the water production behavior of the corresponding gas well. The research results are conducive to the effective prediction of gas well water production and can be used as guidance for the reasonable gas well water control.

Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitrois to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling–sliding–compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers often ignore the importance of biochemical factors to the growth and development of engineered cartilage. In our point of view, only by fully considering synergistic effects of mechanical and biochemical factors can we find appropriate culture conditions for functional cartilage constructs. Once again, rolling–sliding–compression load under appropriate biochemical conditions may be conductive to realize the adaptive development between the structure and function of engineered cartilage in vitro.

Viruses have evolved to be outstandingly efficient at gene delivery, but their use as vectors is limited by safety risks. Inspired by the structure of viruses, we constructed a virus-mimicking vector (denoted as TR4@siRNA@Tf NCs) with virus-like architecture and infection properties. Composed of a hydrophilic peptide, an aggregation-induced emission (AIE) luminogen, and a lipophilic tail, TR4 imitates the viral capsid and endows the vector with AIE properties as well as efficient siRNA compaction. The outer glycoprotein transferrin (Tf) mimics the viral envelope protein and endows the vector with reduced cytotoxicity as well as enhanced targeting capability. Because of the strong interaction between Tf and transferrin receptors on the cell surface, the Tf coating can accelerate the intracellular release of siRNA into the cytosol. Tf and TR4 are eventually cycled back to the cell membrane. Our results confirmed that the constructed siRNA@TR4@Tf NCs show a high siRNA silencing efficiency of 85% with significantly reduced cytotoxicity. These NCs have comparable transfection ability to natural viruses while avoiding the toxicity issues associated with typical nonviral vectors. Therefore, this proposed virus-like siRNA vector, which integrates the advantages of both viral and nonviral vectors, should find many potential applications in gene therapy.

High-efficiency gene transfer and suitably low cytotoxicity are the main goals of gene transfection systems based on nonviral vectors. In addition, it is desirable to track the gene transfer process in order to observe and explain the mechanism. Herein, inspired by viral structures that are optimized for gene delivery, we designed a small-molecule gene vector (TR4) with aggregation-induced emission properties by capping a peptide containing four arginine residues with tetraphenylethene (TPE) and a lipophilic tail. This novel vector can self-assemble with plasmid DNA to form nanofibers in solution with low cytotoxicity, high stability, and high transfection efficiency. pDNA@TR4 complexes were able to transfect a variety of different cell lines, including stem cells. The self-assembly process induces bright fluorescence from TPE, which makes the nanofibers visible by confocal laser scanning microscopy (CLSM). This allows us for the tracking of the gene delivery process.

Multidrug resistance (MDR) of cancer is a challenge to effective chemotherapeutic interventions. The stimulus-responsive drug delivery system (DDS) based on nanotechnology provides a promising approach to overcome MDR. Through the development of a doxorubicin delivery system based on zinc oxide nanomaterials, we have demonstrated that MDR in breast cancer cell line can be significantly circumvented by a combination of efficient cellular uptake and a pH-triggered rapid drug release due to degradation of nanocarriers in acidic environment. Doxorubicin and zinc oxide nanoparticles, compared with free doxorubicin, effectively enhanced the intracellular drug concentration by simultaneously increasing cell uptake and decreasing cell efflux in MDR cancer cells. The acidic environment-triggered release of drug can be tracked real-time by the doxorubicin fluorescence recovery from its quenched state. Therefore, with the combination of therapeutic potential and the capacity to track release of drug in cancer cells, our system holds great potential in nanomedicine by serving dual roles of overcoming drug resistance and tracking intracellular drug release from the DDS.

Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.

In this work, 2-(2-aminoethoxy) ethanol-blocked phenylboronic acid-functionalized magnetic nanoparticles (blocked PMNPs) were fabricated for selective enrichment of different types of saccharides. The phenylboronic acid was designed for capturing the cis-diols moieties on saccharides molecules, and the 2-(2-aminoethoxy) ethanol can deplete the nonspecific absorption of peptides and proteins which always coexisted with saccharides. For mass spectrometry analysis, the PMNPs bound saccharides can be directly applied onto the MALDI plate with matrix without removing the PMNPs. By PMNPs, the simple saccharide (glucose) could be detected in pmol level. The complex saccharides can also be reliably purified and analyzed; 16 different N-glycans were successfully identified from ovalbumin, and the high-abundance N-glycans can be detected even when the ovalbumin was in very low concentration (2 μg). In human milk, ten different oligosaccharides were identified, and the lactose can still be detected when the human milk concentration was low to 0.01 μL.

The versatility of the fluorescent probes inspires us to design fluorescently traceable prodrugs, which enables tracking the drug delivery kinetics in living cells. Herein, we constructed a self-indicating nanoprodrug with two fluorescent moieties, an aggregation-induced emission molecule (tetraphenylethylene, TPE) and a luminant anticancer drug (doxorubicin, DOX), with a pH-responsive linker between them. Except when a low pH environment is encountered, an energy-transfer relay (ETR) occurs and inactivates the fluorescence of both, showing a dark background. Otherwise, the ETR would be interrupted and evoke a dual-color fluorogenic process, giving distinct fluorogenic read out. By observing the dual-color fluorogenic scenario, we captured the kinetics of the drug release process in living cells. Because the separated TPE and DOX are both fluorescent but have a distinct spectrum, by examining the spatiotemporal pattern of TPE and DOX, we were able to precisely disclose the drug-releasing site, the releasing time, the destinations of the carriers, and the executing site of the drugs at subcellular level. Furthermore, different intracellular drug release kinetics between free doxorubicin and its nanoformulations were also observed in a real-time manner.

The fluorescence of tetraphenylethylene (TPE), an archetypal luminogen, is induced by restriction of intramolecular rotation (RIR). TPE was grafted with palmitic acid (PA) onto a hydrophilic peptide to yield a cell membrane tracker named TR4. TR4 was incorporated into liposomes, where it showed significant RIR characteristics. When cells were incubated with TR4, cytoplasmic membranes were specifically labeled. TR4 shows excellent photostability and low cytotoxicity.

Nanoformulations show many therapeutic advantages over conventional formulations. We seek to develop traceable nanoformulations in order to closely monitor delivery. Herein, we developed a new drug delivery system (DDS) using tetraphenylethene (TPE) to fabricate a self-assembly micelle with aggregation-induced emission (AIE micelle). AIE makes the nanocarriers visible for high-quality imaging, and the switching on and off of the AIE is intrinsically controlled by the assembly and disassembly of the micelles. This DDS was tested for doxorubicin (DOX) delivery and intracellular imaging. For the DOX-loaded micelles (TPED), the DOX content reached as much as 15.3% by weight, and the anticancer efficiency was higher than for free DOX. Meanwhile, high-quality imaging was obtained to trace the intracellular delivery of the TPED.

Tetraphenylethylene (TPE), an archetypal luminogen with aggregation-induced emission (AIE), was grafted to a salt-responsive peptide to yield a yet luminescent hydrogelator. After testing different parameters, we found that only in the presence of salt rather than temperature, pH, and solvent, did the monodisperse hydrogelators self-assemble into a hydrogel network with bright emission turned on. The induced luminescence was a dynamic change and enabled real time monitoring of hydrogel formation. Grating AIE molecules to stimuli-responsive peptides is a promising approach for the development of self-revealing soft materials for biological applications.

Toolbox of allosteric catalysts Allosteric regulation that controls the activities of natural enzymes motivates the exploration of expanded toolbox of switchable catalysts for chemical biology research. This review presents prospects of how allosteric scaffolds, ranging from single molecules to self‐assemblies, could be designed into artificial switchable catalysts. The strategy of conformation‐catalysis synergistics provides great inspirations and opportunities for fundamental research and biomedical applications.

Allosteric regulation, in many cases, involves switching the activities of natural enzymes, which further affects the enzymatic network and cell signaling in the living systems. The research on the construction of allosteric switchable catalysts has attracted broad interests, aiming to control the progress and asymmetry of catalytic reactions, expand the chemical biology toolbox, substitute unstable natural enzymes in the biological detection and biosensors, and fabricate the biomimetic cascade reactions. Thus, in this review, we summarize the recent outstanding works in switchable catalysts based on the allosterism of single molecules, supramolecular complexes, and self‐assemblies. The concept of allosterism was extended from natural proteins to polymers, organic molecules, and supramolecular systems. In terms of the difference between these building scaffolds, a variety of design methods that tailor biological and synthetic molecules into controllable catalysts were introduced with emphasis. Allosteric regulation controls the activities of natural enzymes and expands the chemical biology toolbox for the research on switchable catalysts. These rationally designed substitutes for unstable natural enzymes have been applied in areas such as biosensors and biomimetic cascade reactions. This review extended the concept of allosterism to artificial scaffolds and introduced a variety of design methods for controllable catalysts.

Construction of catalytic centers on natural protein aggregates is a challenging topic in biomaterial and biomedicine research. Here we report a novel construction of artificial nanoenzyme with glutathione peroxidase (GPx)-like function. By engineering the surface of tobacco mosaic virus (TMV) coat protein, the main catalytic components of GPx were fabricated on TMV protein monomers. Through direct self-assembly of the functionalized viral coat proteins, the multi-GPx centers were installed on these well-defined nanodisks or nanotubes. With the help of muti-selenoenzyme centers, the resulting organized nanoenzyme exhibited remarkable GPx activity, even approaching the level of natural GPx. The antioxidation study on subcell mitochondrial level demonstrated that virus-based nanoenzyme exerted excellent capacity for protecting cell from oxidative damage. This strategy represents a new way to develop artificial nanoenzymes.

Background: Mesenchymal stem cells (MSCs) known to be sensitive to mechanical stimulus. This type of stimulus plays a role in cellular differentiation, so that it might affect MSCs differentiation toward cardiomyocytes.

Liposomes, especially cationic liposomes, are the most common and well-investigated nanocarriers for biomedical applications, such as drug and gene delivery. Like other types of nanomaterials, once liposomes are incubated in a biological milieu, their surface can be immediately cloaked by biological components to form a protein corona, which confers a new ‘biological identity’ and modulates downstream interactions with cells. However, it remains unclear how the protein corona affects the transportation mechanism after liposomes interact with cells. Here, we employed home-made aggregation-induced-emission-visualized nanoliposomes TR4@Lipo as a model to investigate transportation with or without the protein corona by optical imaging techniques. The results show that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent endocytosis. The protein corona also modulates the intracellular distribution of loaded cargoes. This knowledge furthers our understanding of bio-nano interactions and is important for the efficient use of cationic liposomes.Using home-made AIE-visualized nanoliposomes TR4@Lipo as a model, this work reports that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent endocytosis.

A Correction to this paper has been published: https://doi.org/10.1038/s41563-021-00950-3.

Craniotomy, as a part of neurosurgery, implies a safe opening of the skull with mechanical equipment. Grinding is a traditional machining method that can accurately and efficiently remove bone tissue. Aiming at low-damage and high-efficiency bone grinding, this study analyzed the kinematic law of a single abrasive grain during the grinding process. The theoretical model of grinding force was established based on the calculation of specific energy and friction force. The grinding test platform was set up, and the full factorial experimental design was performed to link the grinding force evolution with different processing parameters. The experimental results obtained on porcine femurs validated the model predictions where the grinding force grew with feed speed and grinding depth; it exhibited a decreasing trend with rotation speed, followed by increasing one.

Cells in organisms are surrounded by fluid environment, and the fluid shear force produced by this fluid affects the morphology and behaviour of cells. The stimulation of cells in a bioreactor is a key area of research in tissue engineering and regenerative medicine. This paper introduces a fluid shear system for cell culture in vitro. The main component of system is a perfusion chamber, which consists of an inoculation room and a perfusion cap. The inoculation room is used for the common laboratory consumables of microorganism or cell culture, such as petri dish, six-well plate and so on. It can realize to six independent experiments of fluid shear; the new type of perfusion cap was designed to obtain a reasonable cavity by hydrodynamic simulation. The cap was produced by casting technology. It not only has the function of cap with nozzles, but also has the function of sealing. With peristaltic pumps, nozzles, liquid storage bottles and so on, the fluid shearing system which can provide uniform, controllable and up to 60 dyn/cm2 shear stress along the bottom surface is constructed, and is easy to operate and can be personalized.

Objective To investigate the effect of fibre periodontal splint restoration on mandibular anterior teeth displacement and periodontal membrane stress. Methods Micro-CT scanning technology, combined with Mimics, Geomagic studio and SolidWorks were used to establish 3D dental models of mandibles with teeth and the models fibre periodontal splint restoration; the models of mandibular anterior loosen teeth was constructed under 30 degree oblique 25N loading on the labial and lingual sides respectively. Then, under different angles force with or without the splint, the analysis on dental mechanical state are given. Results It was determined that the sum of the maximal displacement of the loosen tooth model at the lingual and labial sides was 1 mm, which represented the degree I loosen model. After splint repair on the model, the maximal displacement of loosen tooth decreased 47.7%, 85.1% and 85.8% at 0 degree, 15 degree and 30 degree forces respectively, and the maximum stress of periodontal membrane decreased by 22.3%, 61.2% and 74.9%. Conclusion Fixation of loosen teeth through fibre periodontal splints can reduce the maximum stress of periodontal membrane and the maximal displacement of the teeth, thus ensuring the stability of loosen tooth.

Studies have shown that the morphology and function of living cells are greatly affected by the state of different high acceleration. Based on the centrifuge, we designed a centrifugal cell loading machine for the mechanical biology of cells under high acceleration loading. For the machine, the feasibility of the experiment was studied by means of constant acceleration or variable acceleration loading in the Petri dish fixture and/or culture flask. Here we analyzed the distribution of the acceleration of the cells with the change of position and size of the culturing device quantitatively. It is obtained that Petri dish fixture and/or culture flask can be used for constant acceleration loading by experiments; the centripetal acceleration of the adherent cells increases with the increase of the distance between the rotor center of the centrifuge and the fixture of the Petri dish and the size of the fixture. It achieves the idea that the general biology laboratory can conduct the study of mechanical biology at high acceleration. It also provides a basis for more accurate study of the law of high acceleration on mechanobiology of cells.