Preparation and evaluation of decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair.

Following peripheral nerve anastomosis, the anastomotic site is prone to adhesions with surrounding tissues, consequently impacting the effectiveness of nerve repair. This study explores the development and efficacy of a decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair. Firstly, the entire epineurium was extracted from fresh porcine sciatic nerves, followed by a decellularization process. The decellularization efficiency was then thoroughly assessed. Subsequently, the decellularized epineurium underwent proteomic analysis to determine the remaining bioactive components. To ensure biosafety, the decellularized epineurium underwent cytotoxicity assays, hemolysis tests, cell affinity assays, and assessments of the immune response following subcutaneous implantation. Finally, the functionality of the biofilm was determined using a sciatic nerve transection and anastomosis model in rats. The result indicated that the decellularization process effectively removed cellular components from the epineurium while preserving a number of bioactive molecules, and this decellularized epineurium was effective in preventing adhesion while promoting nerve repairment and functional recovery. In conclusion, the decellularized epineurium represents a novel and promising anti-adhesion biofilm for enhancing surgical outcomes of peripheral nerve repair.

Exoskeleton rehabilitation robot training for balance and lower limb function in sub-acute stroke patients: a pilot, randomized controlled trial.

PURPOSE: This pilot study aimed to investigate the effects of REX exoskeleton rehabilitation robot training on the balance and lower limb function in patients with sub-acute stroke. METHODS: This was a pilot, single-blind, randomized controlled trial. Twenty-four patients with sub-acute stroke (with the course of disease ranging from 3 weeks to 3 months) were randomized into two groups, including a robot group and a control group. Patients in control group received upright bed rehabilitation (n = 12) and those in robot group received exoskeleton rehabilitation robot training (n = 12). The frequency of training in both groups was once a day (60 min each) for 5 days a week for a total of 4 weeks. Besides, the two groups were evaluated before, 2 weeks after and 4 weeks after the intervention, respectively. The primary assessment index was the Berg Balance Scale (BBS), whereas the secondary assessment indexes included the Fugl-Meyer Lower Extremity Motor Function Scale (FMA-LE), the Posture Assessment Scale for Stroke Patients (PASS), the Activities of Daily Living Scale (Modified Barthel Index, MBI), the Tecnobody Balance Tester, and lower extremity muscle surface electromyography (sEMG). RESULTS: The robot group showed significant improvements (P < 0.05) in the primary efficacy index BBS, as well as the secondary efficacy indexes PASS, FMA-LE, MBI, Tecnobody Balance Tester, and sEMG of the lower limb muscles. Besides, there were a significant differences in BBS, PASS, static eye-opening area or dynamic stability limit evaluation indexes between the robotic and control groups (P < 0.05). CONCLUSIONS: This is the first study to investigate the effectiveness of the REX exoskeleton rehabilitation robot in the rehabilitation of patients with stroke. According to our results, the REX exoskeleton rehabilitation robot demonstrated superior potential efficacy in promoting the early recovery of balance and motor functions in patients with sub-acute stroke. Future large-scale randomized controlled studies and follow-up assessments are needed to validate the current findings. CLINICAL TRIALS REGISTRATION: URL: https://www.chictr.org.cn/index.html.Unique identifier: ChiCTR2300068398.

Melt electrowritten poly-lactic acid /nanodiamond scaffolds towards wound-healing patches.

Multifunctional wound dressings, enriched with biologically active agents for preventing or treating infections and promoting wound healing, along with cell delivery capability, are highly needed. To address this issue, composite scaffolds with potential in wound dressing applications were fabricated in this study. The poly-lactic acid/nanodiamonds (PLA/ND) scaffolds were first printed using melt electrowriting (MEW) and then coated with quaternized ß-chitin (QßC). The NDs were well-dispersed in the printed filaments and worked as fillers and bioactive additions to PLA material. Additionally, they improved coating effectiveness due to the interaction between their negative charges (from NDs) and positive charges (from QßC). NDs not only increased the thermal stability of PLA but also benefitted cellular behavior and inhibited the growth of bacteria. Scaffolds coated with QßC increased the effect of bacteria growth inhibition and facilitated the proliferation of human dermal fibroblasts. Additionally, we have observed rapid extracellular matrix (ECM) remodeling on QßC-coated PLA/NDs scaffolds. The scaffolds provided support for cell adhesion and could serve as a valuable tool for delivering cells to chronic wound sites. The proposed PLA/ND scaffold coated with QßC holds great potential for achieving fast healing in various types of wounds.

Construction of emulsion gel based on the interaction of anionic polysaccharide and soy protein isolate: Focusing on structural, emulsification and functional properties.

In this study, the effects on the structures and emulsion gels of carrageenan (CA) and gum arabic (GA) with soybean protein isolate (SPI) were investigated. The results showed that CA and GA exposed hydrophobic groups to SPI, and formed complexes through non-covalent interactions to improve the stability of the complexes. Furthermore, the emulsion gels based on the emulsions exhibited that CA formed emulsion-filled gels with higher elasticity, stronger gel strength, and thermal reversibility, whereas GA formed emulsion-aggregated gels with higher viscosity, and a weak-gel network. The results of digestion showed that, CA was more helpful to slow down the release of free fatty acids and protect vitamin E during digestion. Compared with SPI-GA emulsion gel, SPI-CA emulsion gel had better physicochemical properties and stronger network structure. The results of this study may be useful in the development of anionic polysaccharides that interact with SPI, and they may provide new insights on the preparation of emulsion gels that slowly release fat-soluble nutrients.

Effects of ultrasonic and chemical dual modification treatments on the structural, and properties of cornstarch.

This study aimed to explore the changes in the structural and functional properties of cornstarch modified by oxidation, esterification, and cross-linking under ultrasonic pretreatment. FT-IR and XRD characteristic peaks revealed successful access to chemical functional groups. Both ultrasonic and the three chemical treatments eroded the surface of starch granules, reducing their particle size and increasing their RC. Meanwhile, the destruction of the granules was further enhanced by the dual modification treatments. The ultrasonic pretreatment synergized and improved the swelling power, solubility, and translucency of all three chemical treatments. Further, it improved the poorer freeze-thaw stability of cross-linked starch, resulting in a lower water precipitation rate. In addition, both ultrasonic and chemical treatments significantly decreased RDS and SDS, and increased RS content. The ultrasonic-chemical dual modification had a synergistic effect on in vitro digestibility, resulting in a further increase in RS. In conclusion, this study provided ideas for developing new starch modification technology and deep processing of cornstarch, expanding its application areas and thus meeting the different needs of starch-based products.

3D-printed PCL framework assembling ECM-inspired multi-layer mineralized GO-Col-HAp microscaffold for in situ mandibular bone regeneration.

BACKGROUND: In recent years, natural bone extracellular matrix (ECM)-inspired materials have found widespread application as scaffolds for bone tissue engineering. However, the challenge of creating scaffolds that mimic natural bone ECM's mechanical strength and hierarchical nano-micro-macro structures remains. The purposes of this study were to introduce an innovative bone ECM-inspired scaffold that integrates a 3D-printed framework with hydroxyapatite (HAp) mineralized graphene oxide-collagen (GO-Col) microscaffolds and find its application in the repair of mandibular bone defects. METHODS: Initially, a 3D-printed polycaprolactone (PCL) scaffold was designed with cubic disks and square pores to mimic the macrostructure of bone ECM. Subsequently, we developed multi-layer mineralized GO-Col-HAp microscaffolds (MLM GCH) to simulate natural bone ECM's nano- and microstructural features. Systematic in vitro and in vivo experiments were introduced to evaluate the ECM-inspired structure of the scaffold and to explore its effect on cell proliferation and its ability to repair rat bone defects. RESULTS: The resultant MLM GCH/PCL composite scaffolds exhibited robust mechanical strength and ample assembly space. Moreover, the ECM-inspired MLM GCH microscaffolds displayed favorable attributes such as water absorption and retention and demonstrated promising cell adsorption, proliferation, and osteogenic differentiation in vitro. The MLM GCH/PCL composite scaffolds exhibited successful bone regeneration within mandibular bone defects in vivo. CONCLUSIONS: This study presents a well-conceived strategy for fabricating ECM-inspired scaffolds by integrating 3D-printed PCL frameworks with multilayer mineralized porous microscaffolds, enhancing cell proliferation, osteogenic differentiation, and bone regeneration. This construction approach holds the potential for extension to various other biomaterial types.

Co-delivery of vitamin C and ß-carotene in W/O/W emulsions stabilized by modified aggregated insoluble soybean protein hydrolysate-xanthan gum complexes.

Environmentally friendly emulsifiers safe for human consumption are urgently needed to stabilize emulsions for applications in the food industry. In this study, we prepared complexes combining modified aggregated insoluble soybean protein hydrolysate (AISPH) mixed with xanthan gum (XG) (0.05-0.3 %, w/v), and further to construct water-in-oil-in-water (W/O/W) emulsions to deliver vitamin C and ß-carotene. We observed a decrease in the AISPH α-helix and ß-sheet content, surface hydrophobicity, and fluorescence intensity all decreased after binding. In contrast, the particle size and absolute ξ-potential significantly increased, indicating that molecular non-covalent interactions occurred in the solution. The emulsification property of AISPH was also improved by adding XG, and the AISPH-XG-stabilized emulsion showed improved stability, encapsulation efficiency, and rheological properties. Among them, AISPH-XG-0.25-stabilized emulsion exhibited a smaller particle size (8.41 ± 0.49 µm) and the highest encapsulation efficiency for vitamin C (90.03 ± 0.23 %) and ß-carotene (70.56 ± 0.06 %). Additionally, simulated gastric digestion indicated that vitamin C and ß-carotene bioavailability increased by 3.6 and 5.8 times, respectively. Finally, the emulsion exhibited good pH, ionic, and thermal stability. In general, AISPH-XG-stabilized W/O/W emulsions showed good stability and carrying capacity, providing a theoretical basis for improving their application.

Polycarboxylate functionalized magnetic nanoparticles Fe3O4@SiO2@CS-COOH: Preparation, characterization, and immobilization of bovine serum albumin.

Magnetic nanoparticles with increasing superparamagnetism and magnetic targeting have found widespread application in fields such as food and medicine. In this study, polycarboxylated magnetic nanoparticles (Fe3O4@SiO2@CS-COOH) were prepared by surface functionalizing iron tetraoxide (Fe3O4) nanoparticles with ethylenediaminetetraacetic acid (EDTA) as a modifier. The appropriate degree of functionalization modification was obtained by adjusting the EDTA concentration and the ratio of cross-linking agents. The prepared magnetic nanoparticles were analyzed with structural and property characterization. The results showed that the Fe3O4@SiO2@CS-COOH magnetic nanoparticles prepared with 4 % EDTA and cross-linking agents at a molar ratio of 3:4 were uniform in particle size, with an average size of roughly 7 nm, and possessed an abundant carboxylate content (310.8064 µmol/g) and a high magnetization intensity (35.05 emu/g). As a model protein, bovine serum albumin (BSA) was immobilized on the surface of magnetic particles. The largest amount of immobilized protein was 500.4376 mg BSA/g at pH 4.0 and no extra salt ions. According to molecular docking simulations, its immobilization was due to the interaction of amino and carboxyl groups at the Fe3O4@SiO2@CS-COOH/BSA interface. Fe3O4@SiO2@CS-COOH possesses a large number of carboxyl groups, strong protein immobilization, and magnetic responsiveness, which may have potential applications in biomedical and food fields.

A comprehensive evaluation of circ_0065214/ miR-188-3p/GPNMB axis in breast cancer.

CircRNAs are involved in multiple aspects during carcinogenesis, including tumorigenesis, vascularization, apoptosis and others. Exploring the role of circRNAs in breast cancer (BC) enables us to understand the development mechanism of BC more comprehensively. Here, we screened out and verified an up-regulated circRNA in BC from GEO data. Quantitative Real-time PCR (qRT-PCR) showed that circ_0065214 had a high expression level in BC patients. Besides, circ_0065214 had good diagnostic value in BC serum, and the area under the diagnostic curve, sensitivity and specificity were 0.78, 0.63 and 0.85, respectively. The combined application of circ_0065214 with CEA and CA-153 can further improve the diagnostic efficiency. The knockdown of circ_0065214 in vivo and in vitro inhibited the proliferation, migration and invasion of BC, but promoted autophagy. At last, dual-luciferase reporter assay and rescue assays revealed that circ_0065214 acted as a decoy to adsorb miR-188-3p, and then relieved the repressive effect of miR-188-3p on its target GPNMB. Our results demonstrated that circ_0065214 regulated the expression of GPNMB by competitively binding to miR-188-3p, thus promoting the proliferation, migration and invasion of breast cancer cells and inhibiting autophagy. These findings provided an original therapeutic strategy for BC.

Multifunctional electrospun nanofibrous scaffold enriched with alendronate and hydroxyapatite for balancing osteogenic and osteoclast activity to promote bone regeneration.

Electrospun composite nanofiber scaffolds are well known for their bone and tissue regeneration applications. This research is focused on the development of PVP and PVA nanofiber composite scaffolds enriched with hydroxyapatite (HA) nanoparticles and alendronate (ALN) using the electrospinning technique. The developed nanofiber scaffolds were investigated for their physicochemical as well as bone regeneration potential. The results obtained from particle size, zeta potential, SEM and EDX analysis of HA nanoparticles confirmed their successful fabrication. Further, SEM analysis verified nanofiber's diameters within 200-250 nm, while EDX analysis confirmed the successful incorporation of HA and ALN into the scaffolds. XRD and TGA analysis revealed the amorphous and thermally stable nature of the nanofiber composite scaffolds. Contact angle, FTIR analysis, Swelling and biodegradability studies revealed the hydrophilicity, chemical compatibility, suitable water uptake capacity and increased in-vitro degradation making it appropriate for tissue regeneration. The addition of HA into nanofiber scaffolds enhanced the physiochemical properties. Additionally, hemolysis cell viability, cell adhesion and proliferation by SEM as well as confocal microscopy and live/dead assay results demonstrated the non-toxic and biocompatibility behavior of nanofiber scaffolds. Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) assays demonstrated osteoblast promotion and osteoclast inhibition, respectively. These findings suggest that developed HA and ALN-loaded PVP/PVA-ALN-HA nanofiber composite scaffolds hold significant promise for bone regeneration applications.

A hyperthermia-enhanced nanocatalyst based on asymmetric Au@polypyrrole for synergistic cancer Fenton/photothermal therapy.

The specific tumor microenvironment is a conducive breeding ground for malignant tumors, favoring their survival, rapid proliferation, and metastasis, which is also an inevitable obstacle to tumor treatment, particularly for catalytic therapy. To address this issue, a hyperthermia-enhanced nanocatalyst (AuP@MnO2) consisting of an asymmetric Au@polypyrrole core and a MnO2 shell is constructed for synergistic cancer Fenton/photothermal therapy. In an ultra-short reaction time (15 min), the innovative introduction of a new oxidizer, tetrachloroauric acid trihydrate, not only successfully initiates the oxidative polymerization of pyrrole monomer while reducing itself to cubic Au, but also accelerates the polymerization process by supplying protic acid. After MnO2 coating, AuP@MnO2 catalyzes the conversion of antioxidant GSH and excess H2O2 into GSSG and ˙OH through Mn2+/Mn4+ ion couples, leading to oxidative damage of tumor cells. More importantly, after 1064 nm laser irradiation, more extreme oxidative imbalance and cell death are demonstrated in this work under the combined effect of photothermal and catalytic therapy, with insignificant toxicity to normal cells. This work develops an efficient one-step synthesis method of asymmetric Au@polypyrrole and provides constructive insight into its oxidative stress-based antitumor treatment.

Enantioselective Alkynylation of 2-Aryl-3H-indol-3-ones via Cooperative Catalysis of Copper/Chiral Phosphoric Acid.

A facile enantioselective alkynylation of cyclic ketimines attached to a neutral functional group utilizing the dual Cu(I)-CPA catalysis is described. The strategy of the alkynylation of 2-aryl-3H-indol-3-one directly to chiral propargylic amines containing indolin-3-one moiety in good yields and enantioselectivities. Moreover, gram-scale synthesis of chiral propargylamines based C2-quaternary indolin-3-ones was performed. The synthetic applications were confirmed by transformations of the products with no decrease in the yield and enantioselectivity.

Fluorescent Nanodiamonds for Tracking Single Polymer Particles in Cells and Tissues.

Polymer nanoparticles are widely used in drug delivery and are also a potential concern due to the increased burden of nano- or microplastics in the environment. In order to use polymer nanoparticles safely and understand their mechanism of action, it is useful to know where within cells and tissues they end up. To this end, we labeled polymer nanoparticles with nanodiamond particles. More specifically, we have embedded nanodiamond particles in the polymer particles and characterized the composites. Compared to conventional fluorescent dyes, these labels have the advantage that nanodiamonds do not bleach or blink, thus allowing long-term imaging and tracking of polymer particles. We have demonstrated this principle both in cells and entire liver tissues.

Prevalence and related factors of epilepsy in children and adolescents with cerebral palsy: a systematic review and meta-analysis.

Objective: To study the worldwide prevalence and associated factors of epilepsy in children and adolescents with Cerebral Palsy (CP) and to analyze the differences between various subgroups. Method: We identified all potential studies on the prevalence of epilepsy in children and adolescents with CP from PubMed, Web of Science, and Embase. The search time was from the establishment of the database to November 2022. Randomized effects meta-analysis models were used to calculate the prevalence of epilepsy in CP. Subgroup analysis and meta-regression were utilized to further explore heterogeneity between articles and prevalence disparities between subgroups. The funnel plot and Egger's test were used to investigate potential publication bias. Results: Seventy-two articles, comprising 53,969 children and adolescents with CP, were included in this study. The results indicated a total epilepsy prevalence of 38.0% (95% CI: 34.8%-41.2%) in CP. The prevalence of epilepsy was 46.4% (95% CI: 41.4%-51.5%) in clinical sample-based studies and 31.6% (95% CI: 28.7%-34.5%) in population-based studies. Meta-regression demonstrated that the sample source, neonatal seizure, family history of epilepsy, EEG or cranial imaging abnormalities, intellectual/cognitive impairment, and topographical types of CP were heterogeneous contributors to the epilepsy prevalence in CP. Conclusion: Approximately one-third of children and adolescents with CP have epilepsy, and the sample source can significantly impact the total prevalence of epilepsy. Neonatal seizures, family history of epilepsy, EEG abnormalities, cranial imaging abnormalities, severe intellectual disability, and quadriplegia may be contributing factors to epilepsy comorbid in CP. Further study is required to verify the strength of these associations with epilepsy. This study aids in identifying the clinical characteristics of young people with CP at risk of developing epilepsy, which may assist clinicians in the early prevention and diagnosis of epilepsy within this population.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367766, identifier CRD42022367766.

Investigation of soybean lipophilic proteins as carriers for vitamin B12: Focus on interaction mechanism, physicochemical functionality, and digestion characteristics.

This study aimed to explore the interaction mechanism between soybean lipophilic protein (LP) and vitamin B12 and the potential of LP as a vitamin B12 carrier. The results of spectroscopy indicated that the interaction between vitamin B12 and LP changed the conformation of LP and exposed hydrophobic groups largely. The results of molecular docking revealed that vitamin B12 interacted with LP through a hydrophobic pocket embedded on the surface of LP. With the enhancement of the interaction between LP and vitamin B12, the particle size of the LP-vitamin B12 complex gradually decreased to 588.31 nm and the absolute value of zeta potential gradually increased to 26.82 mV. Meanwhile, the LP-vitamin B12 complex showed excellent physicochemical properties and digestive characteristics. The present work enriched the means of vitamin B12 protection and provided a theoretical basis for applying the LP-vitamin B12 complex in food systems.

B(C6F5)3-catalyzed ß-C(sp3)-H alkylation of tertiary amines with 2-aryl-3H-indol-3-ones.

The ß-C-H functionalization of amines is one of the most powerful tools for the synthesis of saturated nitrogen-containing heterocycles in organic synthesis. However, the ß-C-H functionalization of amines via redox-neutral addition with cyclic-ketimines is still unprecedented. Herein, the ß-C-H functionalization of tertiary amines is described, providing the corresponding 1,3-diamines containing the indolin-3-one moiety in high yields via the B(C6F5)3-catalyzed borrowing hydrogen strategy. According to the experimental results, a possible catalytic cycle has been proposed to rationalize the process of this reaction. Notably, the ß-C-H alkylation of amines is external oxidant- and transition-metal-free, which makes a significant contribution to promoting economical chemical synthesis.

Organocatalyzed Enantioselective Aza-Morita-Baylis-Hillman Reaction of Cyclic Ketimine with α,ß-Unsaturated γ-Butyrolactam.

The enantioselective aza-MBH reaction is an efficient strategy for constructing novel carbon-carbon bonds, providing access to multitudinous chiral densely functionalized MBH products. However, the enantioselective aza-MBH reaction of cyclic-ketimines that would generate a versatile synthon is still missing and challenging. Herein, we developed a challenging direct organocatalytic asymmetric aza-MBH reaction involving cyclic ketimines attached to a neutral functional group. Moreover, the α,ß-unsaturated γ-butyrolactam was utilized as a rare nucleophile alkene in this work. The reactions provide enantiomerically enriched 2-alkenyl-2-phenyl-1,2-dihydro-3H-indol-3-ones, bearing with a tetra-substituted stereogenic center. Moreover, this reaction features high α-selectivities, high enantioselectivities (up to 99% ee), and good yields (up to 80%).

Characterization and utilization of soy protein isolate-(-)-epigallocatechin gallate-maltose ternary conjugate as an emulsifier for nanoemulsions: Enhanced physicochemical stability of the ß-carotene nanoemulsion.

In this study, a ternary conjugate was prepared by covalent bonding of protein, polysaccharide, and polyphenol via ultrasound and the Maillard reaction. Subsequently, the ß-carotene nanoemulsion was prepared with the soy protein isolate-(-)-epigallocatechin gallate-maltose (SPI-EGCG-maltose) conjugate as the emulsifiers via ultrasound. The SPI-EGCG-maltose conjugate showed superior solubility, emulsification and foaming properties at 4 h reaction time. Meanwhile, the retention rates of ß-carotene in the nanoemulsion after 30 d of storage, 8 h of light, and 55 °C of heat were >60%, >75%, and >60%, respectively. Furthermore, ultrasound treatment at 500 W for 10 min produced an inhibitory effect on the degradation of ß-carotene. This study indicates that the nanoemulsion based on the ternary conjugate can effectively inhibit the ß-carotene degradation by the external environment and prevent the oxidation and degradation of ß-carotene in the nanoemulsion.

Encapsulating vitamins C and E using food-grade soy protein isolate and pectin particles as carrier: Insights on the vitamin additive antioxidant effects.

Functional factors show additive effects in the same nutraceutical food. In this study, a core-shell structure based on soy protein isolate (SPI) and pectin was constructed as a delivery system for vitamins C and E under neutral (pH 7.0) and acidic environment (pH 4.0). The SPI-vitamin-pectin complex formed at pH 4.0 showed larger particle size, higher turbidity, lower fluorescence intensity, and higher vitamin E encapsulation efficiency than those formed at pH 7.0. Also, the addition of vitamin C significantly enhanced the vitamin E encapsulation efficiency in the particles. Furthermore, the antioxidant properties of DPPH, ABTS, and hydroxyl radicals were increased by the addition of vitamin C, maximum values of 77%, 82%, and 65%, suggesting that vitamins C and E have additive antioxidant effects. These findings proposed a simple, structured protein-polysaccharide-based food-grade delivery system, which could serve as the basis for the design of products having multiple functional factors.

Asymmetric aza-Friedel-Crafts Reaction of Cyclic Ketimines with 5-Aminopyrazole Derivatives: Expedient Access to Pyrazole-Based C2-quaternary Indolin-3-Ones.

A chiral phosphoric acid-catalyzed enantioselective aza-Friedel-Crafts reaction of 5-aminopyrazole derivatives with cyclic ketimines attached to a neutral functional group is reported. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 5-aminopyrazole-based C2-quaternary indolin-3-ones was performed, with no decrease in the yield and enantioselectivity.