A long-acting C-natriuretic peptide for achondroplasia.

The C-natriuretic peptide (CNP) analog vosoritide has recently been approved for treatment of achondroplasia in children. However, the regimen requires daily subcutaneous injections in pediatric patients over multiple years. The present work sought to develop a long-acting CNP that would provide efficacy equal to or greater than that of vosoritide but require less frequent injections. We used a technology for half-life extension, whereby a drug is attached to tetra-polyethylene glycol hydrogels (tetra-PEG) by ß-eliminative linkers that cleave at predetermined rates. These hydrogels-fabricated as uniform ∼60-µm microspheres-are injected subcutaneously, where they serve as a stationary depot to slowly release the drug into the systemic circulation. We prepared a highly active, stable CNP analog-[Gln6,14]CNP-38-composed of the 38 C-terminal amino acids of human CNP-53 containing Asn to Gln substitutions to preclude degradative deamidation. Two microsphere [Gln6,14]CNP-38 conjugates were prepared, with release rates designed to allow once-weekly and once-monthly administration. After subcutaneous injection of the conjugates in mice, [Gln6,14]CNP-38 was slowly released into the systemic circulation and showed biphasic elimination pharmacokinetics with terminal half-lives of ∼200 and ∼600 h. Both preparations increased growth of mice comparable to or exceeding that produced by daily vosoritide. Simulations of the pharmacokinetics in humans indicated that plasma [Gln6,14]CNP-38 levels should be maintained within a therapeutic window over weekly, biweekly, and likely, monthly dosing intervals. Compared with vosoritide, which requires ∼30 injections per month, microsphere [Gln6,14]CNP-38 conjugates-especially the biweekly and monthly dosing-could provide an alternative that would be well accepted by physicians, patients, and patient caregivers.

Serologic Immunity to Tetanus in the United States, National Health and Nutrition Examination Survey, 2015-2016.

BACKGROUND: Tetanus, a life-threatening infection, has become rare in the United States since introduction of tetanus toxoid-containing vaccines (TTCVs), recommended as a childhood series followed by decennial boosters beginning at age 11-12 years; vaccination uptake is high in children but suboptimal in adults. The objective of this study was to estimate the prevalence of sero-immunity to tetanus among persons aged ≥6 years in the United States and to identify factors associated with tetanus sero-immunity. Understanding population protection against tetanus informs current and future vaccine recommendations. METHODS: Anti-tetanus toxoid antibody concentrations were measured for participants of the 2015-2016 National Health and Nutrition Examination Survey (NHANES) aged ≥6 years for whom surplus serum samples were available using a microsphere-based multiplex antibody capture assay. Prevalence of sero-immunity, defined as ≥0.10 IU/mL, was estimated overall and by demographic characteristics. Factors associated with tetanus sero-immunity were examined using multivariable regression. RESULTS: Overall, 93.8% of the US population aged ≥6 years had sero-protection against tetanus. Prevalence of sero-immunity was above 90% across racial/ethnic categories, sex, and poverty levels. By age, ≥ 90% had protective sero-immunity through age 69 years, but prevalence of sero-immunity declined thereafter, with 75.8% of those aged ≥80 years having protective sero-immunity. Older age (adjusted prevalence ratio [aPR]: 0.89, 95% confidence interval [CI]: .85-.92) and being born outside the United States (aPR: 0.96, 95% CI: .93-.98) were significantly associated with lower prevalence of sero-immunity. CONCLUSIONS: The majority of the US population has vaccine-induced sero-immunity to tetanus, demonstrating the success of the vaccination program.

Preparation and preliminary application of fluorescent microsphere test strips for feline parvovirus antibodies.

This study introduces a novel diagnostic modality for the detection of feline panleukopenia virus (FPV) antibodies in feline serum by using fluorescent microsphere immunochromatographic test strips (FM-ICTS). Leveraging the inherent specificity of antigen-antibody interactions, the FM-ICTS approach demonstrates considerable potential for efficient and accurate FPV antibody detection within a short timeframe. The FM-ICTS method demonstrates strong diagnostic performance, with consistent accuracy and stability over time. PBS buffer dilution enables detection across the range of FPV antibody haemagglutination inhibition (HI) titres in both healthy and immunized or infected cats. A high correlation (R² = 0.9733) between the T/C ratio and FPV antibody titres confirms the method's effectiveness in quantifying these titres. Clinical validation with 84 samples supports its reliability by matching results with HI assays. Additionally, stability tests show that the test strips maintain performance during storage, with a coefficient of variation (CV) below 12% over three months at 25℃. This innovative FM-ICTS framework emerges as a promising avenue for expedient and dependable disease diagnosis within the realm of veterinary science, offering implications for timely disease management and surveillance.

Solvothermal Synthesis and Pyrolysis Toward Heteroatom-Doped Carbon Microspheres for Zinc-Ion Hybrid Capacitors.

Heteroatom-doped porous carbon materials have investigated to promote the energy density of zinc-ion hybrid capacitors (ZICs). Yet, the quest for high-performance carbon materials or cathodes brings to light the question of which dopants facilitate fast energy storage kinetics and various types of pseudocapacitive reactions. Investigation of carbon materials with precise quantitative dopants as the key variable represents an effective appropriate approach to comprehending the intricate role of dopants in energy storage areas. Here, a straightforward solvothermal strategy is demonstrated for a variety of pristine and iron-incorporated polymer microspheres, used as precursors for durable spherical carbons intended for cathode applications in ZICs. The strategy effectively governs the incorporation of dopants within the carbon materials, whilewhile maintaining consistent morphology, microtexture, and pore structure across different carbon variations. The synergistic effect of various dopants enhance the pseudocapacitance and facilitate the ion storage process. In consequence, the optimal cathode delivers considerable capacity (178.8 mAh g-1 at 0.5 A g-1), good energy density (120.2 Wh kg-1 at 336 W kg-1), and excellent cycling stability (101.5% capacity retention at 35 000 cycles). The demonstration showcases a viable method for crafting carbon materials with precise dopants to accommodate the zinc anode, thus enabling high-capacity and high-energy ZICs.

Magnetic Micromotors with Spiky Gold Nanoshells as SERS Sensors for Thiram and Bacteria Detection.

Surface-enhanced Raman scattering (SERS) is widely used in all kinds of detection due to its ultrahigh sensitivity and selectivity. Micromotors, when used as SERS sensors, or the so-called "hotspots on the fly", can combine both controlled mobility and SERS sensing capacity, and are ideal for versatile in situ detection. In this work, mobile SERS sensors are successfully fabricated by growing gold nanospikes onto magnetic microsphere surfaces. These mobile micromotors can act as normal SERS sensors, characterized by the trace detection of thiram, a highly toxic fungicide. The detection limit can reach 0.1 nM, as good as most other noble metal deposited substrates. With significant magnetic gradient forces, separation of pathogenic bacteria from bulk solution is achieved once these magnetic micromotors bind with bacterial cells. Manipulated propulsion of micromotors, on the other hand, enables them to approach and contact pathogenic bacterial cells on command and further acquire Raman spectra under a controlled degree of contact, a capability never seen with passive sensors. The robotic SERS sensors have demonstrated unique sensing characteristics with controlled manipulations along with discriminative detection between bacterial species.

Intervention-Free Graphitization of Carbon Microspheres from a Non-Graphitizing Polymer at Low Temperature: Nanopores as Dynamic Nanoreactors.

Graphitizability of organic precursors is the topic of numerous investigations due to the wide applications of graphitic materials in the industry and emerging technologies of supercapacitors, batteries, etc. Most polymers, such as polydivinyl benzene (PDVB) are classified as non-graphitizings that do not convert to Graphite even after heating to 3000℃. Here, for the first time, the development of graphitic structure in the hierarchal porous sulfonated-PDVB microspheres without employing specific equipment or additives like metal catalysts, organic ingredients, or graphite particles, at 1100°C is reported. The abnormal additive-free graphitic structure formation is confirmed by Raman spectroscopy (ID/IG = 0.87), high-resolution transmission electron microscopy (HRTEM), and selected area diffraction patterns (SAED), as well as x-ray diffraction patterns (XRD), while preservation of aromatic compounds from the carbonization is detected by Fourier transform infrared (FTIR) analysis. Polymer evolution from room temperature to 1100°C is also studied by FTIR, Raman spectroscopy, and XRD techniques. Based on the obtained results, it is suggested that the hierarchal and complicated ink-bottle pore network with a high surface area besides super micropores in the sulfonated-PDVB microspheres has served as nano-sized reaction media. These pores, hereafter referred as "dynamic nanoreactors", are expected to have confined the in-situ produced thermal decomposition products containing broken bond benzene rings, while changing dimensionally and structurally during the designed carbonization regime. This confinement has led to the benzene rings fusion at 250°C, a remarkable extension of them at 450°C, their growth to graphene sheets at 900°C and finally, the stacking of curved graphene layers at 1100°C. The results of this research put stress on the capability of nanopores as nanoreactors to facilitate reactions of decomposition products at low temperatures and ambient pressures to form stacked layers of graphene; A transformation that normally requires catalysts and very high pressures for only specific polyaromatic hydrocarbons.

A Janus Microsphere Delivery System Orchestrates Immunomodulation and Osteoinduction by Fine-tuning Release Profiles.

Bone regeneration is a well-orchestrated process synergistically involving inflammation, angiogenesis, and osteogenesis. Therefore, an effective bone graft should be designed to target multiple molecular events and biological demands during the bone healing process. In this study, a biodegradable gelatin methacryloyl (GelMA)-based Janus microsphere delivery system containing calcium phosphate oligomer (CPO) and bone morphogenetic protein-2 (BMP-2) is developed based on natural biological events. The exceptional adjustability of GelMA facilitates the controlled release and on-demand application of biomolecules, and optimized delivery profiles of CPO and BMP-2 are explored. The sustained release of CPO during the initial healing stages contributes to early immunomodulation and promotes mineralization in the late stage. Meanwhile, the administration of BMP-2 at a relatively high concentration within the therapeutic range enhances the osteoinductive property. This delivery system, with fine-tuned release patterns, induces M2 macrophage polarization and creates a conducive immuno-microenvironment, which in turn facilitates effective bone regeneration in vivo. Collectively, this study proposes a bottom-up concept, aiming to develop a user-friendly and easily controlled delivery system targeting individual biological events, which may offer a new perspective on developing function-optimized biomaterials for clinical use.

Crack-Resistant Si-C Hybrid Microspheres for High-Performance Lithium-Ion Battery Anodes.

To effectively solve the challenges of rapid capacity decay and electrode crushing of silicon-carbon (Si-C) anodes, it is crucial to carefully optimize the structure of Si-C active materials and enhance their electron/ion transport dynamic in the electrode. Herein, a unique hybrid structure microsphere of Si/C/CNTs/Cu with surface wrinkles is prepared through a simple ultrasonic atomization pyrolysis and calcination method. Low-cost nanoscale Si waste is embedded into the pyrolysis carbon matrix, cleverly combined with the flexible electrical conductivity carbon nanotubes (CNTs) and copper (Cu) particles, enhancing both the crack resistance and transport kinetics of the entire electrode material. Remarkably, as a lithium-ion battery anode, the fabricated Si/C/CNTs/Cu electrode exhibits stable cycling for up to 2300 cycles even at a current of 2.0 A g-1, retaining a capacity of ≈700 mAh g-1, with a retention rate of 100% compared to the cycling started at a current of 2.0 A g-1. Additionally, when paired with an NCM523 cathode, the full cell exhibits a capacity of 135 mAh g-1 after 100 cycles at 1.0 C. Therefore, this synthesis strategy provides insights into the design of long-life, practical anode electrode materials with micro/nano-spherical hybrid structures.

Innovative Wearable Electronics: Next-Generation Nitrogen-Doped Lutetium-Carbon Microspheres Composites for Robust Energy Harvesting.

In the quest to advance wearable electronics, this study presents a novel method using nitrogen-doped lutetium-carbon microspheres (N, Lu-CMS) for high-performance piezoelectric energy harvesting. The synthesis of N, Lu-CMS begins with the polymerization of sucrose, followed by the preparation of N, Lu-CMS metal complexes through the incorporation of lutetium (III) nitrate hydrate and thiourea, yielding a black powder product. The wearable electronic device is designed with a silicon rubber (SR) matrix, reinforced with 0D fillers such as N, Lu-CMS, or molybdenum disulfide (MoS2). Mechanical testing revealed a significant improvement in compressive modulus, reaching 3.7 MPa (N, Lu-CMS) at a concentration of 3 parts per hundred rubber (phr). Electromechanical assessments demonstrated efficient energy conversion, while biomechanical analysis, including thumb pressing tests, showed a notable increase in output voltage, peaking at ≈285 mV (N, Lu-CMS) at 3 phr. This research provides a foundation for future engineering applications, particularly in electronic packaging for wearable electronics and smart devices, underscoring the significant impact of N, Lu-CMS in this emerging field. The surface power density achieved is 0.026 nW cm- 2 (N, Lu-CMS) and 0.0056 nW cm- 2 (Hybrid). Lastly, the conversion efficiency is 6.26% for N, Lu-CMS, and 1.05% for the hybrid system.

The characterization of cell traction force on nonflat surfaces with different curvature by elastic hydrogel microspheres.

It is of great importance to study the detachment/attachment behaviors of cells (cancer cell, immune cell, and epithelial cell), as they are closely related with tumor metastasis, immunoreaction, and tissue development at variety scales. To characterize the detachment/attachment during the interaction between cells and substrate, some researchers proposed using cell traction force (CTF) as the indicator. To date, various strategies have been developed to measure the CTF. However, these methods only realize the measurements of cell passive forces on flat cases. To quantify the active CTF on nonflat surfaces, which can better mimic the in vivo case, we employed elastic hydrogel microspheres as a force sensor. The microspheres were fabricated by microfluidic chips with controllable size and mechanical properties to mimic substrate. Cells were cultured on microsphere and the CTF led to the deformation of microsphere. By detecting the morphology information, the CTF exerted by attached cells can be calculated by the in-house numerical code. Using these microspheres, the CTF of various cells (including tumor cell, immunological cell, and epithelium cell) were successfully obtained on nonflat surfaces with different curvature radii. The proposed method provides a versatile platform to measure the CTF with high precision and to understand the detachment/attachment behaviors during physiology processes.

Quantitative characterization of tumor cell traction force on extracellular matrix by hydrogel microsphere stress sensor.

Cell traction force (CTF) is a kind of active force that is a cell senses external environment and actively applies to the contact matrix which is currently a representative stress in cell-extracellular matrix (ECM) interaction. Studying the distribution and variation of CTF during cell-ECM interaction help to explain the impact of physical factors on cell behaviors from the perspective of mechanobiology. However, most of the strategies of characterizing CTF are still limited by the measurement needs in three-dimensional (3D), quantitative characteristics and in vivo condition. Microsphere stress sensor (MSS) as a new type of technology is capable of realizing the quantitative characterization of CTF in 3D and in vivo. Herein, we employed microfluidic platform to design and fabricate MSS which possesses adjustable fluorescent performances, physical properties, and size ranges for better applicable to different cells (3T3, A549). Focusing on the common tumor cells behaviors (adhesion, spreading, and migration) in the process of metastasis, we chose SH-SY5Y as the representative research object in this work. We calculated CTF with the profile and distribution to demonstrate that the normal and shear stress can determined different cell behaviors. Additionally, CTF can also regulate cell adhesion, spreading, and migration in different cell states. Based on this method, the quantitative characterization of CFT of health and disease cells can be achieved, which further help to study and explore the potential mechanism of cell-ECM interaction.

Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

PURPOSE: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres. METHODS: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release. RESULTS: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%. IN CONCLUSION: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

Lactobacillus casei displaying MCP2α and FlaC delivered by PLA microspheres effectively enhances the immune protection of largemouth bass (Micropterus salmoides) against LMBV infection.

Largemouth bass ranavirus (LMBV) seriously affects the development of largemouth bass (Micropterus salmoides) industry and causes huge economic losses. Oral vaccine can be a promising method for viral disease precaution. In this study, MCP2α was identified as a valuable epitope region superior to MCP and MCP2 of LMBV by neutralizing antibody experiments. Then, recombinant Lactobacillus casei expressing the fusion protein MCP2αC (MCP2α as antigen, C represents flagellin C from Aeromonas hydrophila as adjuvant) on surface was constructed and verified. Further, PLA microsphere vaccine loading recombinant MCP2αC L. casei was prepared. The PLA microspheres vaccine were observed by scanning electron microscopy and showed a smooth, regular spherical surface with a particle size distribution between 100 and 200 µm. Furthermore, we evaluated the tolerance of PLA-MCP2αC vaccine in simulated gastric fluid and simulated intestinal fluid, and the results showed that PLA-MCP2αC can effectively resist the gastrointestinal environment. Moreover, the protective effect of PLA-MCP2αC against LMBV was evaluated after oral immunization and LMBV challenge. The results showed that PLA-MCP2αC effectively up-regulated the activity of serum biochemical enzymes (T-SOD, T-AOC, LZM, complement C3) and induced the mRNA expression of representative immune genes (IL-1ß, TNF-α, IFN-γ, MHC-IIα, Mx, IgM) in spleen and head kidney tissues. The survival rate of largemouth bass vaccinated with PLA-MCP2αC increased from 24 % to 68 %. Meanwhile, PLA-MCP2αC inhibited the LMBV burden in spleen, head kidney and liver tissues and attenuated tissue damage in spleen. These results suggested that PLA-MCP2αC can be used as a candidate oral vaccine against LMBV infection in aquaculture.

Nano-Micron Combined Hydrogel Microspheres: Novel Answer for Minimal Invasive Biomedical Applications.

Hydrogels, key in biomedical research for their hydrophilicity and versatility, have evolved with hydrogel microspheres (HMs) of micron-scale dimensions, enhancing their role in minimally invasive therapeutic delivery, tissue repair, and regeneration. The recent emergence of nanomaterials has ushered in a revolutionary transformation in the biomedical field, which demonstrates tremendous potential in targeted therapies, biological imaging, and disease diagnostics. Consequently, the integration of advanced nanotechnology promises to trigger a new revolution in the realm of hydrogels. HMs loaded with nanomaterials combine the advantages of both hydrogels and nanomaterials, which enables multifaceted functionalities such as efficient drug delivery, sustained release, targeted therapy, biological lubrication, biochemical detection, medical imaging, biosensing monitoring, and micro-robotics. Here, this review comprehensively expounds upon commonly used nanomaterials and their classifications. Then, it provides comprehensive insights into the raw materials and preparation methods of HMs. Besides, the common strategies employed to achieve nano-micron combinations are summarized, and the latest applications of these advanced nano-micron combined HMs in the biomedical field are elucidated. Finally, valuable insights into the future design and development of nano-micron combined HMs are provided.

Quantum dot fluorescent microsphere-based immunochromatographic strip for detecting PRRSV antibodies.

Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). Current vaccine prevention and treatment approaches for PRRS are not adequate, and commercial vaccines do not provide sufficient cross-immune protection. Therefore, establishing a precise, sensitive, simple, and rapid serological diagnostic approach for detecting PRRSV antibodies is crucial. The present study used quantum dot fluorescent microspheres (QDFM) as tracers, covalently linked to the PRRSV N protein, to develop an immunochromatography strip (ICS) for detecting PRRSV antibodies. Monoclonal antibodies against PRRSV nucleocapsid (N) and membrane (M) proteins were both coated on nitrocellulose membranes as control (C) and test (T) lines, respectively. QDFM ICS identified PRRSV antibodies under 10 min with high sensitivity and specificity. The specificity assay revealed no cross-reactivity with the other tested viruses. The sensitivity assay revealed that the minimum detection limit was 1.2 ng/mL when the maximum dilution was 1:2,048, comparable to the sensitivity of enzyme-linked immunosorbent assay (ELISA) kits. Moreover, compared to PRRSV ELISA antibody detection kits, the sensitivity, specificity, and accuracy of QDFM ICS after analyzing 189 clinical samples were 96.7%, 97.9%, and 97.4%, respectively. Notably, the test strips can be stored for up to 6 months at 4 °C and up to 4 months at room temperature (18-25 °C). In conclusion, QDFM ICS offers the advantages of rapid detection time, high specificity and sensitivity, and affordability, indicating its potential for on-site PRRS screening. KEY POINTS: • QDFM ICS is a novel method for on-site and in-lab detection of PRRSV antibodies • Its sensitivity, specificity, and accuracy are on par with commercial ELISA kits • QDFM ICS rapidly identifies PRRSV, aiding the swine industry address the evolving virus.

Microneedle delivery system with rapid dissolution and sustained release of bleomycin for the treatment of hemangiomas.

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.

GAPDH-Silence Microsphere via Reprogramming Macrophage Metabolism and eradicating Bacteria for Diabetic infection bone regeneration.

Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

In vivo study of the utility of selective intra-arterial injection of thiopental for neuroprotection in reversible cerebral ischemia.

BACKGROUND: Neuroprotective agents are needed to reduce cerebral damage during surgical or neurointerventional procedures including stroke patients. PURPOSE: To evaluate if thiopental can be used as a neuroprotective agent when injected intra-arterially in a transient ischemia model. MATERIAL AND METHODS: In total, 24 rabbits were studied as four groups of six animals. Group 1 served as the control group. In group 2, transient ischemia was obtained by intracarotid administration of degradable starch microspheres (DSM). Group 3 was administered thiopental intra-arterially via the carotid artery. Group 4 (experimental group) received both thiopental and DSM intra-arterially. DSM and thiopental were administered through a microcatheter placed into the common carotid artery via the central ear artery access. After sacrifice, apoptotic cells in the cerebral tissues of the animals were evaluated in H&E and TUNEL stained slides. RESULTS: There was a significant increase in the number of apoptotic glial or neuronal cells in group 2 compared to the control group and group 3. The mean number of both the apoptotic neuronal cells (6.8 ± 2.1 vs. 2.5 ± 1.3, P < 0.001) and the apoptotic glial cells (9.4 ± 3.1 vs. 4.6 ± 1.6, P < 0.001) were higher in group 2 compared to group 4. In addition, a higher level of neurological improvement was observed in group 4 compared to group 2 based on neurological assessment score. CONCLUSION: The intra-arterial administration of thiopental has a protective effect on both glial and neuronal cells during temporary cerebral ischemia in low doses.

Fabrication of quantum dot-immobilized Y2O3 microspheres with effective photoluminescence for cancer radioembolization therapy.

Microspheres composed of Y-containing materials are effective agents for cancer radioembolization therapy using ß-rays. The distribution and dynamics of these microspheres in tissues can be easily determined by providing the microspheres with an imaging function. In addition, the use of quantum dots will enable the detection of microspheres at the individual particle level with high sensitivity. In this study, core - shell quantum dots were bound to chemically modified yttria microspheres under various conditions, and the effect of reaction conditions on the photoluminescence properties of the microspheres was investigated. The quantum dots were immobilized on the surfaces of the microspheres through dehydration - condensation reactions between the carboxy groups of quantum dots and the amino groups of silane-treated microspheres. As the reaction time increased, the photoluminescence peak blue shifted, and the photoluminescence intensity and lifetime decreased. Therefore, a moderate period of the immobilization process was optimal for imparting effective photoluminescence properties. This study is expected to facilitate particle-level tracking of microsphere dynamics in biological tissues for the development of minimally invasive cancer radiotherapy of deep-seated tumors.

We have established a method to immobilize quantum dots on yttria microspheres for cancer radiotherapy and revealed that photoluminescence intensity can be optimized by controlling the immobilization treatment time.

A Review of Microsphere Super-Resolution Imaging Techniques.

Conventional optical microscopes are only able to resolve objects down to a size of approximately 200 nm due to optical diffraction limits. The rapid development of nanotechnology has increased the demand for greater imaging resolution, with a need to break through those diffraction limits. Among super-resolution techniques, microsphere imaging has emerged as a strong contender, offering low cost, simple operation, and high resolution, especially in the fields of nanodevices, biomedicine, and semiconductors. However, this technology is still in its infancy, with an inadequate understanding of the underlying principles and the technology's limited field of view. This paper comprehensively summarizes the status of current research, the advantages and disadvantages of the basic principles and methods of microsphere imaging, the materials and preparation processes, microsphere manipulation methods, and applications. The paper also summarizes future development trends.