Multifunctional co-loaded magnetic nanocapsules for enhancing targeted MR imaging and in vivo photodynamic therapy.

Drug delivery nanocarriers based on magnetic nanoparticles have attracted increasing attention due to their potential applications in magnetic resonance imaging, photodynamic therapy and targeted drug delivery. Herein, we have fabricated the multifunctional co-loaded magnetic nanocapsules (MNCPs) using a microemulsion process for enhancing targeted magnetic resonance imaging and in vivo photodynamic therapy. MNCPs were synthesized by co-loading Co@Mn magnetic nanoparticles and chlorin e6 into the matrix of an amphiphilic polymer, and further surface covalently coupled with target molecules. This work demonstrates that MNCPs have uniform sizes (dc: ~150 nm), favorable biocompatibility, long-term stability, excellent T2 relaxation values, and high drug loading efficiency. These advantages offer MNCPs successfully applied in targeted magnetic resonance imaging, real-time fluorescent labeling, and photodynamic therapy. The research results will contribute to rationally design novel nano-platform and provide a promising approach for further clinical integration of diagnosis and treatment in the near future.

Dialdehyde modified and cationic aerogel for efficient microplastics adsorption from environmental waters.

Recent reports had shown that microplastics could be transferred to organisms through various channels, severely and adversely affecting organisms' health and their physiological functions. Therefore, there remained an urgency to adopt an effective and environmentally friendly method to extract microplastics from water. In this paper, a cationic-modified d-DCPG aerogel with a three-dimensional network structure was successfully prepared by a directional freeze-drying technology in which double-aldehyde-modified cellulose nanofiber (CNF) was used as the matrix, betaine chloride hydrazide (GT) provided modification, and polyvinyl alcohol (PVA) provided cross-linking function. Aerogels had an excellent adsorption capacity (145.05 mg/g) for microplastics in aqueous environment, and when the pH was from 10 to 4, it exhibited an excellent adsorption efficiency from 90.01 % to 97.61 %; an excellent adsorption efficiency after 8 cycles (>89 %); pseudo-second-order kinetics and Freundlich adsorption isotherm had a high fitting effects on the adsorption process and adsorption results, respectively. And ultraviolet analysis also verified the occurrence of adsorption behavior. These results showed that d-DCPG aerogels had an excellent application prospects in microplastics removal in river, lake, reservoir, and marine environments.

3D Printed Pedicle Screws with Microarc Oxidation Ceramic Interfaces Enhance Osteointegration and Orthopedic Fixation Feasibility.

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.

Rapid adsorption of directional cellulose nanofibers/3-glycidoxypropyltrimethoxysilane/polyethyleneimine aerogels on microplastics in water.

Currently, cellulose-based aerogel materials are a hot topic owing to their high specific surface area and high porosity, as well as the green, degradable and biocompatible characteristics of cellulosic materials. Modification of cellulose to enhance the adsorption properties of cellulose-based aerogels has important research significance in solving the problem of water body pollution. In this paper, cellulose nanofibers (CNFs) were modified with polyethyleneimine (PEI), and modified aerogels with directional structures were prepared by a simple reaction and freeze-drying method. The adsorption behavior of the aerogel followed the adsorption kinetic models and isotherm models. More significantly, the aerogel could rapidly adsorb microplastics, reaching equilibrium within 20 min. Furthermore, the fluorescence displayed directly expresses the occurrence of the adsorption behavior of the aerogels. Therefore, the modified cellulose nanofiber aerogels were of reference significance for microplastic removal from water bodies.

Percutaneous Curved Vertebroplasty Versus Unipedicular Approach Vertebroplasty for Acute Osteoporotic Vertebral Compression Fractures : A Randomized Controlled Trial.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To clarify whether percutaneous curved vertebroplasty (PCVP) is superior to conventional unipedicular approach vertebroplasty (UVP) in patients with acute osteoporotic vertebral compression fractures (OVCFs). SUMMARY OF BACKGROUND DATA: Unilateral curved vertebroplasty devices were designed and applied to provide better control of cement placement, which may be superior to traditional UVP for the treatment of acute OVCFs. MATERIALS AND METHODS: Patients with single-level OVCFs of <6 weeks duration and visual analog scale (VAS) of back pain 5 or more were randomly allocated to undergo PCVP or UVP and were followed up for 1 year. The primary outcome was overall VAS scores for back pain during 12 months of follow-up. The secondary outcomes were scores on the Oswestry disability index at each postprocedure clinic visit. Radiographic (cement distribution) and surgical data (operation time, fluoroscopy frequency, and cement volume) were assessed. Complications and adverse events were recorded. RESULTS: No statistical difference was found between the PCVP and UVP groups with respect to VAS and Oswestry disability index scores at any follow-up time point. Operative time, fluoroscopy frequency, and cement leakage were similar in both groups, while the PCVP techniques had a larger injection of polymethylmethacrylate (5.5 ± 1.4 vs . 4.2 ± 1.0 mL) and a greater dispersion pattern of cement ( P < 0.001). Post hoc observations found that the analgesic effect was positively correlated with the symmetry of bone cement distribution, but not with the surgical method. Two serious adverse events occurred in the vertebroplasty group: one stress ulcer and one allergic reaction. CONCLUSIONS: Although PCVP achieved more symmetrical cement distribution, which seemed to be associated with a greater analgesic effect, PCVP did not result in significantly greater pain relief than a UVP in the 12 months after treatment.

Herbal Granules of Heat-Clearing and Detoxifying for Children with Mild Hand, Foot, and Mouth Disease: A Bayesian Network Meta-Analysis.

Background: Regarding ethical considerations of randomized controlled trials (RCTs) in children, limited evidence for mild hand, foot, and mouth disease (HFMD) is available. Recently, with the increasing but result-conflicting RCTs published around herbal granules of heat-clearing and detoxifying (HGs-HD), a head-to-head comparison is urgently needed to choose a suitable therapy for clinical practice. Materials and Methods: This study was conducted according to the preferred reporting items for systematic review and meta-analysis (PRISMA) extension statement for network meta-analysis (NMA). Eight databases (Medline, Embase, and so on) and two trial registry platforms (https://www.clinicaltrials.gov and https://www.chictr.org.cn) were searched from inception to May 26, 2021. The NMA was performed using a random-effect model. The treatment hierarchy was summarized and reported as the surface under the cumulative ranking curve (SUCRA) probability values. The rankings of each HGs-HD at primary outcomes were estimated by the inverse probability weighting (IPW) approach and averaged, which presents the comprehensive improvement effect. Results: Forty-five RCTs involving 18 interventions were included that studied 5,652 children with mild HFMD. The best performance probability for improving symptoms were respectively presented in terms of fever (Xiao'er Resuqing granules, XRGs, 94.9%), rash (Xiao'er Jinqiao granules, 83.9%), hospitalization (Xiao'er Chiqiao Qingre granules, XCQGs, 92.7%), vesicles (Jinlianhua granules, 91.0%), appetite (Xiao'er Chiqiao Qingre granules, XCQGs, 86.7%), and ulcers (Kouyanqing granules, KouGs, 88.8%). Furthermore, the top 5 rankings for comprehensive improvement effect were Yanning granules (YNGs, 2.256), XCQGs (2.858), XRGs (3.270), KouGs (7.223), and Houerhuan Xiaoyan granules (HXGs, 7.597). Conclusions: This is the first NMA of HGs-HD head-to-head comparisons for children with mild HFMD. Of those, YNGs, XCQGs, XRGs, KouGs, and HXGs could be recommended as potential choices for clinical practice. Of course, the results should be interpreted with caution due to the limited high-quality RCTs.

Approaching "stainless magnesium" by Ca micro-alloying.

Severe corrosion of Mg and Mg alloys is a major issue hindering their wider application in transportation industry, medical implants and aqueous batteries. Previously, no Mg-based material has been found with a significantly lower corrosion rate than that of ultra-high-purity Mg, i.e. 0.25 mm y-1 in concentrated NaCl solution. In this work for the first time, highly corrosion-resistant Mg is found to be accomplishable by Ca micro-alloying, bringing "stainless Mg" closer. The designed Mg-Ca lean alloys possess incredibly low corrosion rates, less than 0.1 mm y-1 in 3.5 wt% NaCl solution, which are significantly lower than that of ultra-high-purity Mg and all Mg alloys reported thus far. The outstanding corrosion resistance is attributed to inhibition of cathodic water reduction kinetics, impurities stabilizing and a protective surface film induced by Ca micro-alloying. Combined with the environmental benignity and economic viability, Ca micro-alloying renders huge feasibility on developing advanced Mg-based materials for diverse applications.

Injectable and In Situ-Formable Thiolated Chitosan-Coated Liposomal Hydrogels as Curcumin Carriers for Prevention of In Vivo Breast Cancer Recurrence.

To improve water solubility and bioavailability, curcumin (Cur) was encapsulated by liposomes (Cur-Lip), which was further coated with thiolated chitosan (CSSH) to form liposomal hydrogels (CSSH/Cur-Lip gel). The hydrogels were thermosensitive with in situ injectable performance, which were fluidic at room temperature and gelled quickly at 37 °C. The cumulative release ratio of the 200 µM CSSH/Cur-Lip gel was 31.57 ± 1.34% at 12 h, which could effectively delay the release of curcumin. Worthily, the resilient hydrogels were compressive even after five cycles of compression. The cytotoxicity test indicated that the liposomal hydrogels had good cytocompatibility, but after encapsulation of curcumin, MCF-7 cells were suppressed and killed dramatically after 72 h. The in vivo breast cancer recurrence experiment showed that the CSSH/Cur-Lip gel inhibited breast cancer recurrence after tumors were resected, and the tissue of defect in the CSSH/Cur-Lip gel group was repaired. The results showed that the drug-loaded liposomal hydrogels can deliver curcumin continuously and exerted an excellent tumoricidal effect in vitro and in vivo. The injectable, in situ-formable, and thermosensitive CSSH/Cur-Lip gel can be designed as a promising novel drug delivery vehicle to be used as carriers for local accurate and sustained drug delivery to minimize burst release and as tissue engineering scaffolds for tissue regeneration after tumor resection.

Bioinspired EVAL membrane modified with cilia-like structures showing simultaneously enhanced permeability and antifouling properties.

A simple and effective strategy to simultaneously enhance the permeability and antifouling properties of ethylene vinyl alcohol (EVAL) membrane was developed based on the bioinspired natural cleaner, cilia. Taking clue from the self-cleaning effect of cilia, supramolecular polyrotaxanes (PRs) with sliding and rotating cyclic molecules along linear chains were synthesized using azide-alkyne click chemistry. Cilia-like PRs were incorporated into EVAL matrix in the fabrication of modified EVAL membranes. Cilia-like structures protruding from the membrane surface have been observed by SEM, TEM and AFM. By imitating natural ciliary movements, these structures provided a proactive self-cleaning system to remove the foulants. The introduction of cilia-like PRs enhanced the surface roughness and hydrophilicity, and significantly enhanced permeability by 55.3% compared to raw EVAL membrane. Moreover, the membrane modified with cilia-like PRs showed an excellent antifouling property with a lower water flux decline (12.6%) and higher water flux recovery (94%) in dynamic fouling tests. Furthermore, this modified membrane develops the scope of bioinspired membranes, inspiring more attractive potential applications in self-cleaning materials, dynamic membranes and supramolecular machines.

Fluorescent supramolecular polypseudorotaxane architectures with Ru(II)/tri(bipyridine) centers as multifunctional DNA reagents.

A water-soluble supramolecular polypseudorotaxane was prepared via the host-guest interaction of cucurbit[8]uril and the Ru(bpy)3 complex with bis-naphthalene groups. By employing the intrinsic properties of the Ru(bpy)3 complex, the linear polypseudorotaxane can induce DNA condensation, be used as an inhibitor for DNA cleavage enzymes, and trace the translocation of DNA into 293T cells efficiently.

Synthesis of molecularly imprinted polymer with 7-chloroethyl-theophylline-immobilized silica gel as template and its molecular recognition function.

By reaction of 7-chloroethyl-theophylline with aminopropylsilanized silica gel we synthesized a 7-chloroethyl-theophylline-immobilized silica gel as template molecule and prepared a molecularly imprinted polymer (MIP-Si), which had special recognition sites to 7-chloroethyl-theophylline. A conventional molecularly imprinted polymer (MIP) using 7-chloroethyl-theophylline as template was also prepared for comparison. Binding abilities to 7-chloroethyl-theophylline and its structural analogs revealed that the MIP-Si shows much higher binding speed and much more binding capacity than the MIP does.

Recycling gene carrier with high efficiency and low toxicity mediated by L-cystine-bridged bis(ß-cyclodextrin)s.

Constructing safe and effective gene delivery carriers is becoming highly desirable for gene therapy. Herein, a series of supramolecular crosslinking system were prepared through host-guest binding of adamantyl-modified low molecular weight of polyethyleneimine with L-cystine-bridged bis(ß-cyclodextrin)s and characterized by (1)H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, flow cytometry and confocal fluorescence microscopy. The results showed that these nanometersized supramolecular crosslinking systems exhibited higher DNA transfection efficiencies and lower cytotoxicity than the commercial DNA carrier gold standard (25 kDa bPEI) for both normal cells and cancer cells, giving a very high DNA transfection efficiency up to 54% for 293T cells. Significantly, this type of supramolecular crosslinking system possesses a number of enzyme-responsive disulfide bonds, which can be cleaved by reductive enzyme to promote the DNA release but recovered by oxidative enzyme to make the carrier renewable. These results demonstrate that these supramolecular crosslinking systems can be used as promising gene carriers.

Development of a plastic embedding method for large-volume and fluorescent-protein-expressing tissues.

Fluorescent proteins serve as important biomarkers for visualizing both subcellular organelles in living cells and structural and functional details in large-volume tissues or organs. However, current techniques for plastic embedding are limited in their ability to preserve fluorescence while remaining suitable for micro-optical sectioning tomography of large-volume samples. In this study, we quantitatively evaluated the fluorescence preservation and penetration time of several commonly used resins in a Thy1-eYFP-H transgenic whole mouse brain, including glycol methacrylate (GMA), LR White, hydroxypropyl methacrylate (HPMA) and Unicryl. We found that HMPA embedding doubled the eYFP fluorescence intensity but required long durations of incubation for whole brain penetration. GMA, Unicryl and LR White each penetrated the brain rapidly but also led to variable quenching of eYFP fluorescence. Among the fast-penetrating resins, GMA preserved fluorescence better than LR White and Unicryl. We found that we could optimize the GMA formulation by reducing the polymerization temperature, removing 4-methoxyphenol and adjusting the pH of the resin solution to be alkaline. By optimizing the GMA formulation, we increased percentage of eYFP fluorescence preservation in GMA-embedded brains nearly two-fold. These results suggest that modified GMA is suitable for embedding large-volume tissues such as whole mouse brain and provide a novel approach for visualizing brain-wide networks.

A novel splicing mutation in COL1A1 gene caused type I osteogenesis imperfecta in a Chinese family.

Osteogenesis imperfect (OI) is a heritable connective tissue disorder with bone fragility as a cardinal manifestation, accompanied by short stature, dentinogenesis imperfecta, hyperlaxity of ligaments and skin, blue sclerae and hearing loss. Dominant form of OI is caused by mutations in the type I procollagen genes, COL1A1/A2. Here we identified a novel splicing mutation c.3207+1G>A (GenBank ID: JQ236861) in the COL1A1 gene that caused type I OI in a Chinese family. RNA splicing analysis proved that this mutation created a new splicing site at c.3200, and then led to frameshift. This result further enriched the mutation spectrum of type I procollagen genes.

Temozolomide/PLGA microparticles: a new protocol for treatment of glioma in rats.

Implantable and poly (d,l-lactide-co-glycolide) (PLGA) microparticles were developed to deliver temozolomide (TM) continuously in interstitial chemotherapy for glioma. The therapeutic effect of temozolomide/PLGA was evaluated in a rat C6 glioma model. C6 cells were implanted orthotopically into 100 rat brains in 5 groups (n=20 each): sham operation group, control group, local delivery of blank PLGA microspheres group, oral TM group, and local delivery of TM/PLGA group. Rats in oral TM group were orally administered temozolomide, and rats in TM/PLGA group were locally implanted with TM/PLGA microspheres. Ten rats were selected randomly from each group for observing the survival time, and the other 10 rats were killed on POD 14 to measure proliferation activity and apoptosis of the gliomas. Head MRI examination was performed before the rats were killed. The median survival time of sham operation group, control group, blank PLGA microspheres group, oral TM group, and TM/PLGA group was 19.5, 20, 19, 27, and 46.5 days, respectively. MRI demonstrated that the tumor volume was reduced in oral TM group and interstitial TM/PLGA group. PCNA-positive cell staining showed that proliferation activity of tumor cells treated with interstitial TM/PLGA therapy significantly decreased when compared with that of tumor cells treated with oral TM therapy. The apoptosis of C6 cells in interstitial TM/PLGA group significantly increased when compared with that in oral TM group. Interstitial TM/PLGA was effective in treating intracranial C6 rat gliomas and could prove to be a potential chemotherapy agent for human malignant gliomas.

Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and angiogenesis in an orthotopic glioma model.

Temozolomide (TM) has anti-tumor activity in patients with malignant glioma. Implantable poly (D,L-lactide-co-glycolide) (PLGA) microparticles of TM (TM-MS) have been developed, enhancing the cytotoxicity of TM to Glioma C6 cells. Vatalanib, as anti-angiogenic agent, has also shown anti-tumor activity with malignant gliomas. We examined the combined effects of TM-MS and vatalanib in a rat orthotopic glioma model and found TM-MS offered a greater tumor inhibition than TM, and combination treatment with both of them improved the survival time versus single agent therapy. The combination treatment also demonstrated an inhibition to rat glioma tumors, a significant decrease in cell proliferation, an increase in apoptosis, and a lower microvessel density within the glioma tumors. The results suggest that TM-MS can more effectively inhibit tumor than TM, and combination treatment with TM-MS and vatalanib inhibits tumor growth and angiogenesis and may prove to be a promising therapy for malignant gliomas.