Advances of 3D Cell Co-Culture Technology Based on Microfluidic Chips.

Cell co-culture technology aims to study the communication mechanism between cells and to better reveal the interactions and regulatory mechanisms involved in processes such as cell growth, differentiation, apoptosis, and other cellular activities. This is achieved by simulating the complex organismic environment. Such studies are of great significance for understanding the physiological and pathological processes of multicellular organisms. As an emerging cell cultivation technology, 3D cell co-culture technology, based on microfluidic chips, can efficiently, rapidly, and accurately achieve cell co-culture. This is accomplished by leveraging the unique microchannel structures and flow characteristics of microfluidic chips. The technology can simulate the native microenvironment of cell growth, providing a new technical platform for studying intercellular communication. It has been widely used in the research of oncology, immunology, neuroscience, and other fields. In this review, we summarize and provide insights into the design of cell co-culture systems on microfluidic chips, the detection methods employed in co-culture systems, and the applications of these models.

Magnetic nanomaterials mediate precise magnetic therapy.

Magnetic nanoparticle (MNP)-mediated precision magnet therapy plays a crucial role in treating various diseases. This therapeutic strategy compensates for the limitations of low spatial resolution and low focusing of magnetic stimulation, and realizes the goal of wireless teletherapy with precise targeting of focal areas. This paper summarizes the preparation methods of magnetic nanomaterials, the properties of magnetic nanoparticles, the biological effects, and the measurement methods for detecting magnetism; discusses the research progress of precision magnetotherapy in the treatment of psychiatric disorders, neurological injuries, metabolic disorders, and bone-related disorders, and looks forward to the future development trend of precision magnet therapy.

Carbon monoxide-releasing molecule-3 exerts neuroprotection effects after cardiac arrest in mice: A randomized controlled study.

Background: Post-cardiac arrest brain injury (PCABI) is the leading cause of death in survivors of cardiac arrest (CA). Carbon monoxide-releasing molecule (CORM-3) is a water-soluble exogenous carbon monoxide that has been shown to have neuroprotection benefits in several neurological disease models. However, the effects of CORM-3 on PCABI is still unclear. Methods: A mice model combined asystole with hemorrhage was used. Mice were anesthetized and randomized into 4 groups (n = 12/group) and underwent either 9.5 min CA followed by cardiopulmonary resuscitation (CPR) or sham surgery. CORM-3 (30 mg/kg) or vehicle (normal saline) were administered at 1 h after return of spontaneous circulation or sham surgery. Survival, neurologic deficits, alterations in the permeability of the brain-blood barrier and cerebral blood flow, changes of oxidative stress level, level of neuroinflammation and neuronal degeneration, and the activation of Nrf2/HO-1 signaling pathway were measured. Results: In CORM-3 treated mice that underwent CA/CPR, significantly improved survival (75.00% vs. 58.33%, P = 0.0146 (24 h) and 66.67% vs. 16.67%, P < 0.0001 (72 h)) and neurological function were observed at 24 h and 72 h after ROSC (P < 0.05 for each). Additionally, increased cerebral blood flow, expression of tight junctions, and reduced reactive oxygen species generation at 24 h after ROSC were observed (P < 0.05 for each). CORM-3 treated mice had less neuron death and alleviated neuroinflammation at 72 h after ROSC (P < 0.05 for each). Notably, the Nrf2/HO-1 signaling pathway was significantly activated in mice subjected to CA/CPR with CORM-3 treatment. Conclusions: CORM-3 could improve survival and exert neuroprotection after CA/CPR in mice. CORM-3 may be a novel and promising pharmacological therapy for PCABI.

Optimizing energy efficiency in induction skull melting process: investigating the crucial impact of melting system structure.

Induction skull melting (ISM) technology could melt metals with avoiding contamination from crucible. A long-standing problem of ISM is that the low charge energy utilization and inhomogeneous fields have obstructed its application in many critical metal materials and manufacturing processes. The present work investigated the problem through the structure optimization strategy and established a numerical electromagnetic-field model to evaluate components' eddy current loss. Based on the model, the effect of crucible and inductor structure on charge energy utilization, etc. was studied. Furtherly, the charge energy utilization was increased from 27.1 to 45.89% by adjusting the system structure. Moreover, structure modifications are proposed for enhancing electromagnetic intensity and uniformity, charge soft contact and uniform heating. The work constructed a basis for framing new solutions to the problem through ISM device structure optimization.

Elucidating the Bioinspired Synthesis Process of Magnetosomes-Like Fe3O4 Nanoparticles.

Iron oxide nanoparticles are a kind of important biomedical nanomaterials. Although their industrial-scale production can be realized by the conventional coprecipitation method, the controllability of their size and morphology remains a huge challenge. In this study, a kind of synthetic polypeptide Mms6-28 which mimics the magnetosome protein Mms6 is used for the bioinspired synthesis of Fe3O4 nanoparticles (NPs). Magnetosomes-like Fe3O4 NPs with uniform size, cubooctahedral shape, and smooth crystal surfaces are synthesized via a partial oxidation process. The Mms6-28 polypeptides play an important role by binding with iron ions and forming nucleation templates and are also preferably attached to the [100] and [111] crystal planes to induce the formation of uniform cubooctahedral Fe3O4 NPs. The continuous release and oxidation of Fe2+ from pre-formed Fe2+-rich precursors within the Mms6-28-based template make the reaction much controllable. The study affords new insights into the bioinspired- and bio-synthesis mechanism of magnetosomes.

Magnetic vagus nerve stimulation alleviates myocardial ischemia-reperfusion injury by the inhibition of pyroptosis through the M2AChR/OGDHL/ROS axis in rats.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury is accompanied by an imbalance in the cardiac autonomic nervous system, characterized by over-activated sympathetic tone and reduced vagal nerve activity. In our preceding study, we pioneered the development of the magnetic vagus nerve stimulation (mVNS) system. This system showcased precise vagus nerve stimulation, demonstrating remarkable effectiveness and safety in treating myocardial infarction. However, it remains uncertain whether mVNS can mitigate myocardial I/R injury and its specific underlying mechanisms. In this study, we utilized a rat model of myocardial I/R injury to delve into the therapeutic potential of mVNS against this type of injury. RESULTS: Our findings revealed that mVNS treatment led to a reduction in myocardial infarct size, a decrease in ventricular fibrillation (VF) incidence and a curbing of inflammatory cytokine release. Mechanistically, mVNS demonstrated beneficial effects on myocardial I/R injury by inhibiting NLRP3-mediated pyroptosis through the M2AChR/OGDHL/ROS axis. CONCLUSIONS: Collectively, these outcomes highlight the promising potential of mVNS as a treatment strategy for myocardial I/R injury.

Endowing improved osteogenic activities with collagen membrane by incorporating biocompatible iron oxide nanoparticles.

Introduction: Collagen-based scaffolds, renowned for their exceptional biocompatibility, have garnered attention as promising scaffolds for advancing bone tissue regeneration. Nevertheless, these scaffolds possess inherent limitations, such as notably compromised osteo-conductivity and osteo-inductivity. Methods: Our study focused on enhancing the mechanical properties and osteogenic bioactivities of bovine-derived collagen membranes (CMs) from the Achilles tendon by incorporating FDA-approved iron oxide nanoparticles (IONPs), termed as IONP-CM. Three types of IONP-CMs (IONP-CM-0.5, IONP-CM-1, and IONPCM-1.5) were constructed by altering the amounts of feeding IONPs. Results: Surface topography analysis demonstrated comparable characteristics between the IONP-CM and neat CM, with the former exhibiting augmented mechanical properties. In vitro evaluations revealed the remarkable biocompatibility of IONP-CMs toward mouse calvarial pre-osteoblast MC3T3-E1 cells, concurrently stimulating osteogenic differentiation. Mechanistic investigations unveiled that the osteogenic differentiation induced by IONP-CMs stemmed from the activation of the Wnt/ß-catenin signaling pathway. Furthermore, in vivo bone regeneration assessment was performed by implanting IONP-CMs into the radial defect in rabbits. Results derived from micro-computed tomography and histological analyses unequivocally substantiated the capacity of IONP-CMs to expedite bone repair processes. Discussion: IONP-CMs emerged as scaffolds boasting exceptional biocompatibility and enhanced osteogenic properties, positioning them as promising candidates for facilitating bone tissue regeneration.

Expression of clMagR/clCry4 protein in mBMSCs provides T2-contrast enhancement of MRI.

Here, we propose for the first time the evaluation of magnetosensitive clMagR/clCry4 as a magnetic resonance imaging (MRI) reporter gene that imparts sensitivity to endogenous contrast in eukaryotic organisms. Using a lentiviral vector, we introduced clMagR/clCry4 into C57BL/6 mice-derived bone marrow mesenchymal stem cells (mBMSCs), which could specifically bind with iron, significantly affected MRI transverse relaxation, and generated readily detectable contrast without adverse effects in vivo. Specifically, clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which cells recruit exogenous iron and convert these stores into an MRI-detectable contrast; this is not achievable with control cells. Additionally, Prussian blue staining was performed together with ultrathin cell slices to provide direct evidence of natural iron-bearing granules being detectable on MRI. Hence, it was inferred that the sensitivity of MRI detection should be correlated with clMagR/clCry4 and exogenous iron. Taken together, the clMagR/clCry4 has great potential as an MRI reporter gene. STATEMENT OF SIGNIFICANCE: In this study, we propose the evaluation of magnetosensitive clMagR/clCry4 as an MRI reporter gene, imparting detection sensitivity to eukaryotic mBMSCs for endogenous contrast. At this point, the clMagR and clCry4 were located within the cytoplasm and possibly influence each other. The clMagR/clCry4 makes mBMSCs beneficial for enhancing the sensitivity of MRI-R2 for iron-bearing granules, in which protein could specifically bind with iron and convert these stores into MRI-detectable contrast; this is not achieved by control cells. The viewpoint was speculated that the clMagR/clCry4 and exogenous iron were complementary to each other. Additionally, Prussian blue staining was performed together with TEM observations to provide direct evidence that the iron-bearing granules were sensitive to MRI.

Preparation of Iron-Based Sulfides and Their Applications in Biomedical Fields.

Recently, iron-based sulfides, including iron sulfide minerals and biological iron sulfide clusters, have attracted widespread interest, owing to their excellent biocompatibility and multi-functionality in biomedical applications. As such, controlled synthesized iron sulfide nanomaterials with elaborate designs, enhanced functionality and unique electronic structures show numerous advantages. Furthermore, iron sulfide clusters produced through biological metabolism are thought to possess magnetic properties and play a crucial role in balancing the concentration of iron in cells, thereby affecting ferroptosis processes. The electrons in the Fenton reaction constantly transfer between Fe2+ and Fe3+, participating in the production and reaction process of reactive oxygen species (ROS). This mechanism is considered to confer advantages in various biomedical fields such as the antibacterial field, tumor treatment, biosensing and the treatment of neurodegenerative diseases. Thus, we aim to systematically introduce recent advances in common iron-based sulfides.

Transfection of clMagR/clCry4 imparts MR-T2 imaging contrast properties to living organisms (E. coli) in the presence of Fe3+ by endogenous formation of iron oxide nanoparticles.

Rapid development of medical imaging, such as cellular tracking, has increased the demand for "live" contrast agents. This study provides the first experimental evidence demonstrating that transfection of the clMagR/clCry4 gene can impart magnetic resonance imaging (MRI) T2-contrast properties to living prokaryotic Escherichia coli (E. coli) in the presence of Fe3+ through the endogenous formation of iron oxide nanoparticles. The transfected clMagR/clCry4 gene markedly promoted uptake of exogenous iron by E. coli, achieving an intracellular co-precipitation condition and formation of iron oxide nanoparticles. This study will stimulate further exploration of the biological applications of clMagR/clCry4 in imaging studies.

Fluorescence and antioxidant activity of heterologous expression of phycocyanin and allophycocyanin from Arthrospira platensis.

Phycocyanin and allophycocyanin are important active substances in Arthrospira platensis, because of their fluorescent characteristic and antioxidant capacity. In order to solve the problem of insufficient production and inconvenient modification of natural protein, recombinant expression was performed and the fluorescence activity and antioxidant activity was analyzed to meet the demand for phycocyanin and allophycocyanin. A total of seven recombinant strains were constructed in this study, including individual phycocyanin or allophycocyanin, co-expression of phycocyanin-allophycocyanin, and their co-expression with chromophore, and the expression strain for individual chromophore. Different molecular weights of phycocyanin and allophycocyanin were detected in the recombinant strains, which indicated the different polymers expressed. Through mass spectrometry identification, phycocyanin and allophycocyanin may form a dimer of 66 kDa and a polymer of 300 kDa. The results of fluorescence detection showed that phycocyanin and allophycocyanin combined with phycocyanobilin to show fluorescence activity. The fluorescence peak of recombinant phycocyanin was mainly concentrated at 640 nm, which was similar to natural phycocyanin, the fluorescence peak of purified recombinant allophycocyanin was at about 642 nm. The fluorescence peak of the co-expressed recombinant phycocyanin-allophycocyanin is located at 640 nm, and the fluorescence intensity is between the recombinant phycocyanin and the recombinant allophycocyanin. After purification, the fluorescence peak of the recombinant phycocyanin is more concentrated and the fluorescence intensity is higher, which is about 1.3 times of recombinant phycocyanin-allophycocyanin, 2.8 times of recombinant allophycocyanin, indicating that phycocyanin may be more suitable to be used as fluorescence probe in medicine. The antioxidant capacity was measured by using total antioxidant capacity (T-AOC) and DPPH (2,2'-diphenyl-1-triphenylhydrazino) free radical scavenging method, and the recombinant phycobiliprotein showed antioxidant activity. Phycocyanobilin also has certain antioxidant activity and could enhance the antioxidant activity of phycobiliprotein to a certain extent. Recombinant phycocyanin-allophycocyanin polymer has stronger T-AOC, which is about 1.17-2.25 times that of the other five recombinant proteins. And recombinant phycocyanin has stronger DPPH antioxidant activity, which is about 1.2-2.5 times that of the other five recombinant proteins. This study laid the foundation for the application of recombinant phycocyanin and allophycocyanin in medical detection and drug development.

Biological Scaffolds Assembled with Magnetic Nanoparticles for Bone Tissue Engineering: A Review.

Superparamagnetic iron oxide nanoparticles (SPION) are widely used in bone tissue engineering because of their unique physical and chemical properties and their excellent biocompatibility. Under the action of a magnetic field, SPIONs loaded in a biological scaffold can effectively promote osteoblast proliferation, differentiation, angiogenesis, and so on. SPIONs have very broad application prospects in bone repair, bone reconstruction, bone regeneration, and other fields. In this paper, several methods for forming biological scaffolds via the biological assembly of SPIONs are reviewed, and the specific applications of these biological scaffolds in bone tissue engineering are discussed.

Bionic Magnetic Sensor Based on the MagR/Cry4 Complex-Configured Graphene Transistor with an Integrated On-Chip Gate.

Magnetic-sensitive proteins are regarded as key factors in animals' precise perception of the geomagnetic field. Accurate feedback on the response of these tiny proteins to magnetic fields remains a challenge. Here, we first propose a real-time accurate magnetic sensor based on the MagR/Cry4 complex-configured graphene transistor with an integrated on-chip gate. A nanometer-thick denatured bovine serum albumin film was used as the bio-interface of graphene electrolyte-gated transistors (EGTs) to immobilize the MagR/Cry4 complex. With the optimization and characterization of this bionic graphene EGT, it could detect magnetic fields in real time with a sensitivity of 1 mT, which is far lower than in earlier research. It was concluded that our MagR/Cry4 complex-configured graphene EGTs with a side-gate held great promise in terms of geomagnetic field detection. Furthermore, the constructed approach in this paper could also be utilized as a general solution for recording the response of magnetically sensitive biomolecules to magnetic fields in real time.

Magnetic Nanomaterials Mediate Electromagnetic Stimulations of Nerves for Applications in Stem Cell and Cancer Treatments.

Although some progress has been made in the treatment of cancer, challenges remain. In recent years, advancements in nanotechnology and stem cell therapy have provided new approaches for use in regenerative medicine and cancer treatment. Among them, magnetic nanomaterials have attracted widespread attention in the field of regenerative medicine and cancer; this is because they have high levels of safety and low levels of invasibility, promote stem cell differentiation, and affect biological nerve signals. In contrast to pure magnetic stimulation, magnetic nanomaterials can act as amplifiers of an applied electromagnetic field in vivo, and by generating different effects (thermal, electrical, magnetic, mechanical, etc.), the corresponding ion channels are activated, thus enabling the modulation of neuronal activity with higher levels of precision and local modulation. In this review, first, we focused on the relationship between biological nerve signals and stem cell differentiation, and tumor development. In addition, the effects of magnetic nanomaterials on biological neural signals and the tumor environment were discussed. Finally, we introduced the application of magnetic-nanomaterial-mediated electromagnetic stimulation in regenerative medicine and its potential in the field of cancer therapy.

Rapid improvement of heart repair in rats after myocardial infarction by precise magnetic stimulation on the vagus nerve with an injectable magnetic hydrogel.

The imbalance between the sympathetic and the parasympathetic nervous system is one of the main pathogeneses of myocardial infarction (MI). Vagus nerve stimulation (VNS), which restores autonomic nervous balance by enhancing the parasympathetic drive, is shown to have benefits for patients with MI. As a clinically safe and effective remote neuromodulation method, magnetic stimulation is expected to overcome the problems of infection and nerve injury caused by electrode implantation. However, it is difficult to achieve precise stimulation on a single vagus nerve due to the poor focus of the magnetic field. Here, we described a novel magnetic vagus nerve stimulation (mVNS) system, which consisted of an injectable chitosan/ß-glycerophosphate (CS/GP) hydrogel loaded with superparamagnetic iron oxide (SPIO) nanoparticles and a mild magnetic pulse sequence. The injectable hydrogel prepared from clinically safe materials ensured minimally invasive implantation, and the SPIO nanoparticles in the hydrogel mediated the precise magnetic stimulation of a single vagus nerve. Under a mild magnetic field (∼100 mT), a decrease in heart rate and a change in vagus nerve potential were found in rats under in situ injection of a magnetic CS/GP hydrogel. Magnetic stimulation on the vagus nerve for 4 weeks (20 Hz, three times daily, 5 minutes each time) significantly improved the cardiac function and reduced the infarct size of the rats subjected to myocardial infarction, accompanied by suppression of inflammatory cell infiltration and inflammation factor expression. Taken together, these results demonstrated that the mVNS exhibited promising potential for treating myocardial infarction in the clinic.

Magnetic hydrogels with ordered structure for biomedical applications.

Magnetic hydrogels composed of hydrogel matrices and magnetic nanomaterials have attracted widespread interests. Thereinto, magnetic hydrogels with ordered structure possessing enhanced functionalities and unique architectures, show tremendous advantages in biomedical fields. The ordered structure brought unique anisotropic properties and excellent physical properties. Furthermore, the anisotropic properties of magnetic ordered hydrogels are more analogous to biological tissues in morphology and mechanical property, showing better biocompatibility and bioinducibility. Thus, we aim to systematically describe the latest advances of magnetic hydrogels with ordered structure. Firstly, this review introduced the synthetic methods of magnetic hydrogels focus on constructing ordered structure. Then, their functionalities and biomedical applications are also summarized. Finally, the current challenges and a compelling perspective outlook of magnetic ordered hydrogel are present.

DNA-mediated assembly of a gold-nanoparticle film with controllable sonic behavior detected by novel electric-induced ultrasound.

Two-dimensional gold-assembled nanomaterials have garnered considerable interest in biomedical applications such as wearable sensors and flexible devices. The assembly can be accomplished via attractive interactions between gold nanoparticles (GNPs) and a standard polymer. It is highly desirable and a great challenge to develop a new assembly method that can provide formed materials with novel properties. In this work, we explored complementary DNA-functionalized gold nanoparticles (DNA-GNPs) as building blocks to establish multifunctional two-dimensional gold nanomaterials via layer-by-layer (LBL) assembly. We found that the DNA-mediated assembly endows GNP films with a superlattice and their sonic behavior could be regulated in a controllable manner through altering the sequence of SH-DNA and linker DNA, which was detected by the electric-induced ultrasound method. Our observation suggested that this DNA-mediated assembly of GNP films with controllable sonic behaviors could greatly promote the biomedical application of two-dimensional assembled-gold nanomaterials.

A novel porous granular scaffold for the promotion of trabecular bone repair by time-dependent alteration of morphology.

Granular scaffolds have been extensively used in the clinic to repair irregular maxillofacial defects. There remain some challenges for the repair of trabecular structures in cancellous bone due to the reticular lamella-like morphology. In this study, we fabricated a novel granular scaffold by rational design of components with different degradation rates so that the morphology of the novel scaffold can evolve to match the growth period of bone cells. Here, polycaprolactone (PCL) was used to fabricate porous microspheres as a skeleton with slow degradation. The macropores were filled with quick degraded gelatin to form complete microspheres. Asynchronous degradation of the two components altered the morphology of the evolutive scaffold from compact to porous, gradually exposing the ridge-like skeletons. This scaffold reversed the decline of cellular adhesion to simple porous skeletons during the initial adhesion. Furthermore, the cells were able to grow into the pores and adhere onto the skeletons with an elongated cellular morphology, facilitating osteogenic differentiation. This novel scaffold was experimentally proven to promote the regeneration of alveolar bone along with a good percentage of bone volume and the formation of trabecular structures. We believe this morphology-evolved scaffold is highly promising for regenerative applications in the clinic.

Some Preliminary Results to Eradicate Leukemic Cells in Extracorporeal Circulation by Actuating Doxorubicin-Loaded Nanochains of Fe3O4 Nanoparticles.

Leukemia is a non-solid cancer which features the malignant proliferation of leukocytes. Excessive leukocytes of lesions in peripheral blood will infiltrate organs, resulting in intumescence and weakening treatment efficiency. In this study, we proposed a novel approach for targeted clearance of the leukocytes in the peripheral blood ex vivo, which employed magnetic nanochains to selectively destroy the leukocytes of the lesions. The nanochains were doxorubicin-loaded nanochains of Fe3O4 nanoparticles which were fabricated by the solvent exchange method combined with magnetic field-directed self-assembly. Firstly, the nanochains were added into the peripheral blood during extracorporeal circulation and subjected to a rotational magnetic field for actuation. The leukocytes of the lesion were then conjugated by the nanochains via folic acid (FA) targeting. Finally, the rotational magnetic field actuated the nanochains to release the drugs and effectively damage the cytomembrane of the leukocytes. This strategy was conceptually shown in vitro (K562 cell line) and the method's safety was evaluated in a rat model. The preliminary results demonstrate that the nanochains are biocompatible and suitable as drug carriers, showing direct lethal action to the leukemic cells combined with a rotational magnetic field. More importantly to note is that the nanochains can be effectively kept from entry into the body. We believe this extracorporeal circulation-based strategy by activating nanochains magnetically could serve as a potential method for leukemia treatment in the future.

Analysis of morphological change mechanism of linear Arthrospira platensis based on transcriptome results.

Arthrospira platensis is a kind of filament cyanobacteria, which is mainly helical with a few linear. The shape of the filaments, such as the length and the pitch, may change with the changes in the environment. Natural Arthrospira platensis FACHB793 is linear, although it has become helical due to a mutation introduced in the process of cultivation. To study the molecular mechanism responsible for the morphological changes of the filaments, two samples were isolated from a natural mutant of Arthrospira platensis FACHB793, which were helical shaped (named A793_H) and linear shaped (named A793_L). Transcriptome sequencing, GO and KEGG enrichment analysis showed that the expression of genes related to or involved in peptidoglycan biosynthesis, beta lactam resistance, photosynthetic antenna protein expression, bacterial secretion, and ABC transporter activity changed between the two samples. The expression of murE and murG in the peptidoglycan biosynthesis pathway and that of oppD in beta lactam resistance were all down-regulated in the helical filaments, which may be related to the longer cell wall and higher peptidoglycan synthesis in linear filaments than helical filaments. In helical filaments, the up-regulation of tatC gene expression in bacterial secretion may be related to the secretion of peptidoglycan degrading enzymes, which may help to change the shape from linear to helical. Moreover, apcA and cpcA in photosynthetic antenna protein expression and nrt and nirA in nitrogen metabolism were all down regulated in the helical filaments, which may be due to the deformed shape of A. platensis FACHB793, resulting in decreased photosynthetic activity in helical filaments. This research provides a foundation for elucidating the possible morphogenetic mechanism of Arthrospira platensis.