NK-92 cells labeled with Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobes for the targeted treatment and noninvasive therapeutic evaluation of breast cancer.

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.

Developing and Validating an Intelligent Mouth-Opening Training Device: A New Solution for Restricted Mouth Opening.

Restricted mouth opening (trismus) is one of the most common complications following head and neck cancer treatment. Early initiation of mouth-opening exercises is crucial for preventing or minimizing trismus. Current methods for these exercises predominantly involve finger exercises and traditional mouth-opening training devices. Our research group successfully designed an intelligent mouth-opening training device (IMOTD) that addresses the limitations of traditional home training methods, including the inability to quantify mouth-opening exercises, a lack of guided training resulting in temporomandibular joint injuries, and poor training continuity leading to poor training effect. For this device, an interactive remote guidance mode is introduced to address these concerns. The device was designed with a focus on the safety and effectiveness of medical devices. The accuracy of the training data was verified through piezoelectric sensor calibration. Through mechanical analysis, the stress points of the structure were identified, and finite element analysis of the connecting rod and the occlusal plate connection structure was conducted to ensure the safety of the device. The findings support the effectiveness of the intelligent device in rehabilitation through preclinical experiments when compared with conventional mouth-opening training methods. This intelligent device facilitates the quantification and visualization of mouth-opening training indicators, ensuring both the comfort and safety of the training process. Additionally, it enables remote supervision and guidance for patient training, thereby enhancing patient compliance and ultimately ensuring the effectiveness of mouth-opening exercises.

Analysis of related factors of long-term complications after vascularized fibular transplantation.

OBJECTIVES: Free fibula flap is the first choice for jaw reconstruction in head and neck oncology, but postoperative complications in donor site are ignored always. The main purpose of this study was to investigate the long-term complications and potential risk factors of donor site after vascularized fibular transplantation, and to explore the precautions of preparing vascularized fibular flap and the measures of preventing donor site complications. MATERIALS AND METHODS: Data were retrospectively collected on 31 patients who had undergone immediate mandibular reconstruction with a fibular flap after segmental mandibulectomy from 2013 to 2018 in Shanghai Ninth People's Hospital. Thirty-one patients (24 male, 7 female) were available for the long-term complications in donor site analysis from 25 to 96 months after surgery. The data were collected and analyzed, including age at time of operation, early postoperative complications, incidence of dorsiflexion weakness of hallux, donor site missing fibula length, proximal and distal stump fibula length, and subjective evaluation of foot function (AOFAS-hallux, AOFAS-ankle hindfoot, Enneking lower limb function score). In the single-factor analysis in this study, the correlation between related factors and long-term complications was statistically analyzed. For inter-group comparisons of quantitative data, if the normal distribution was satisfied, two independent sample t-tests were used; p < 0.05 was statistical significant. If the normal distribution was not satisfied, Wilcoxon rank-sum test was used, and p < 0.05 was considered statistically significant. For qualitative data, the Fisher exact probability method was compared between group differences, and p < 0.05 was statistically significant. RESULTS: The most commonly encountered complication in our series was dorsiflexion disorder, flexion deformity, numbness of the lateral side of the lower leg, and dorsum of the foot. Ten patients (32.26%) developed hallux flexion deformity after operation, 17 patients (54.84%) had hallux dorsiflexion dysfunction after operation, and 10 patients (32.26%) had numbness of the lateral side of the lower leg and dorsum of the foot. The incidence of hallux dorsiflexion dysfunction, thumb flexion deformity, and sensory disturbance was higher than that of other long-term complications in the donor area. The residual length of fibular distal was related to the dorsiflexion dysfunction and flexion deformity of hallux (p < 0.05). The early complications of donor site were correlated with the hallux dorsiflexion dysfunction (p < 0.05). CONCLUSIONS: The incidence of dorsiflexion disorder and flexion deformity is higher in patients after fibula transplantation. The less the residual length of fibular distal, the more obvious the long-term complications in the donor site, and the higher the incidence of dorsiflexion dysfunction and flexion deformity of hallux. CLINICAL RELEVANCE: The long-term complications of donor site after fibular transplantation seriously affect the quality of life of patients and provide clinical reference for further reducing the occurrence of donor site complications.

Promoting Diabetic Wound Healing through a Hydrogel-Based Cascade Regulation Strategy of Fibroblast-Macrophage.

The management of diabetic wounds (DWs) continues to pose a significant challenge in the field of medicine. DWs are primarily prevented from healing due to damage to macrophage efferocytosis and fibroblast dysfunction. Consequently, a treatment strategy that involves both immunoregulation and the promotion of extracellular matrix (ECM) formation holds promise for healing DWs. Nevertheless, existing treatment methods necessitate complex interventions and are associated with increased costs, for example, the use of cytokines and cell therapy, both of which have limited effectiveness. In this study, a new type of ruthenium (IV) oxide nanoparticles (RNPs)-laden hybrid hydrogel dressing with a double network of Pluronic F127 and F68 has been developed. Notably, the hybrid hydrogel demonstrates remarkable thermosensitivity, injectability, immunoregulatory characteristics, and healing capability. RNPs in hydrogel effectively regulate both fibroblasts and macrophages in a cascade manner, stimulating fibroblast differentiation while synergistically enhancing the efferocytosis of macrophage. The immunoregulatory character of the hydrogel aids in restoring the intrinsic stability of the immune microenvironment in the wound and facilitates essential remodeling of the ECM. This hydrogel therefore offers a novel approach for treating DWs through intercellular communication.

Phthalate ester (PAEs) accumulation in wheat tissues and dynamic changes of rhizosphere microorganisms in the field with plastic-film residue.

Phthalates acid esters (PAEs) have accumulated in soil and crops like wheat as a result of the widespread usage of plastic films. It is yet unclear, nevertheless, how these dynamic variations in PAE accumulation in wheat tissues relate to rhizosphere bacteria in the field. In this work, a field root-bag experiment was conducted to examine the changes of PAEs accumulation in the rhizosphere soil and wheat tissues under film residue conditions at four different growth stages of wheat, and to clarify the roles played by the microbial community in the alterations. Results showed that the plastic film residues significantly increased the concentrations of PAEs in soils, wheat roots, straw and grains. The maximum ΣPAEs concentration in soils and different wheat tissues appeared at the maturity, with the ΣPAEs concentration of 1.57 mg kg-1, 4.77 mg kg-1, 5.21 mg kg-1, 1.81 mg kg-1 for rhizosphere soils, wheat roots, straw and grains, respectively. The plastic film residues significantly changed the functions and components of the bacterial community, increased the stochastic processes of the bacterial community assembly, and reduced the complexity and stability of the bacterial network. In addition, the present study identified some bacteria associated with plastic film residues and PAEs degradation in key-stone taxa, and their relative abundances were positive related to the ΣPAEs concentration in soils. The PAEs content and key-stone taxa in rhizosphere soil play a crucial role in the formation of rhizosphere soil bacterial communities. This field study provides valuable information for better understanding the role of microorganisms in the complex system consisting of film residue, soil and crops.

Preoperative OCT-Derived Nasal Perifoveal Retinal Nerve Fiber Layer Thickness Predictively Correlates Long-Term Visual Acuity Post Oil Removal Surgery.

Purpose: With the widespread application of silicone oil in vitreoretinal surgery, the purpose of this study was to determine the risk factors of long-term vision loss 12 months post oil removal in retina-detached eyes treated with vitrectomy and silicone oil tamponade. Methods: Of the 592 patients approached, eligible eyes completed the investigation up to 12 months post-oil-removal. Eligible eyes underwent pars-plana vitrectomy following oil tamponade. Oil removal was performed after 3 to 28 months in different individuals, under the condition that the retina has reattached as well as the hemorrhage and inflammation has dissolved. Postoperative best-corrected visual acuity (BCVA), age, sex, and interval between tamponade and removal were recorded, and retinal thickness was determined using optical coherence tomography (OCT). Results: Fifty eyes of 50 participants aged 31 to 83 years were enrolled. BCVA (LogMAR) 12 months post-oil-removal improved in 25 of 40 (62.5%) patients, varying from 0.05 (20/22) to 1.0 (20/200) (mean ± SD = 0.55 ± 0.32). Pre-oil-removal nasal perifoveal retinal nerve fiber layer thickness varied from 16 to 83 µm (38.40 ± 18.50), and was significantly linked with post-oil-removal BCVA (0.5%, 95% confidence interval 0.0%-1.0%; P = 0.046). Conclusions: This study demonstrates the risk factors and prognosis of visual function after long-term regeneration post vitrectomy, oil tamponade, and oil removal, thereby underscoring the need for a complete, dynamic examination of retinal structure via OCT measurement. Related studies should be conducted on a larger scale to facilitate the stratification of late-period vision damage in retina-detached eyes. Translational Relevance: This study developed OCT-based clinical markers for the postoperative visual prognosis of eyes affected by retinal detachment.

Glucose-sensitive poly(ether sulfone) composite membranes blended with phenylboronic acid-based amphiphilic block copolymer for self-regulated insulin release.

Glucose-sensitive membranes have promising applications in insulin release. Phenylboronic acid (PBA) is an important glucose reporter. Most of PBA-based glucose-sensitive materials are expansion-type, which cannot act as chemical valves in porous membranes for self-regulated insulin release. In this study, a glucose-sensitive membrane with PBA-based contraction-type amphiphilic block copolymer polystyrene-b-poly(N-isopropylacrylamide-co-2-(acrylamido) phenylboronic acid) (PSNB) as chemical valves was constructed through non-solvent induced phase separation (NIPS) method. Due to surface segregation, hydrophobic polystyrene (PS) component can anchor in the membrane matrix to improve the stability of the membrane, and glucose-sensitive hydrophilic poly(N-isopropylacrylamide-co-2-(acrylamido) phenylboronic acid) (PNB) component can expose on the surfaces of the membrane and the channels to provide glucose-sensitivity of the membrane. With increasing the polymer content or chain length of the hydrophilic component, the glucose sensitivity of the membrane was improved. The blend membrane showed glucose-sensitive insulin release behavior in simulated body fluids (SBF) and fetal bovine serum (FBS). The membrane also exhibited good antifouling properties and biocompatibility.

Ascorbic Acid-PEI Carbon Dots with Osteogenic Effects as miR-2861 Carriers to Effectively Enhance Bone Regeneration.

Nucleic acid transfer has shown significant potential in the treatment of bone damage because of its long lasting local effect and lower cost. Nonviral vectors, such as nanomaterials, with higher biocompatibility are increasedly applied in the study of bone defect repair. Carbon dots with various reactive groups on the surface not only provide a unique surface to carry therapeutic genes, but also some carbon dots have been reported to promote osteogenic differentiation. The bone regeneration effect of carbon dots in vivo, however, is rarely investigated. MiR-2861 has revealed osteogenic differentiation effects. In the current study, we created ascorbic acid-PEI carbon dots (CD), which were able to carry miR-2861, by the microwave-assisted pyrolysis method. Results demonstrated that CD had excellent fluorescence stability leading to good fluorescence imaging in vitro and in vivo. CD was efficiently internalized into bone marrow stromal cells (BMSCs) through the clathrin-mediated endocytosis pathway and distributed in the mitochondria, endoplasmic reticulum, lysosome, and nucleus. Results from alkaline phosphatase staining, alizarin red staining, and reverse transcription real-time PCR (RT-QPCR) showed that our CD indeed had osteogenic effects in vitro. Flow cytometry data indicated that CD could efficiently deliver miR-2861 into BMSCs in vitro, and CD carrying miR-2861 (CD@miR) had the strongest osteogenic effects. Analyses of hematology, serum biochemistry, and histology showed that CD and CD@miR did not have cytotoxicity and had higher biocompatibility in vivo. Most interestingly, CD and miR-2861 in the CD@miR could act synergistically to promote osteogenic differentiation in vitro and new bone regeneration in vivo remarkably. Our results clearly indicate that the osteogenic CD delivering osteogenic therapeutic gene, miR-2861, can obtain much stronger bone regeneration ability, suggesting that our CD has great potential in future clinical application.

Quantitative analysis of cake characteristics based on SEM imaging during coagulation-ultrafiltration process.

Cake formed by flocs is a crucial factor to affect membrane fouling during coagulation-ultrafiltration process. To investigate the role of floc properties on cake, cake characteristics under various coagulant dosage conditions were calculated by scanning electron microscope (SEM) imaging. Results found that one SEM image with × 5000 magnification could accurately estimate cake porosity with relative error lower than 5.00% for all conditions, whereas more SEM images with × 10,000 magnification or × 20,000 magnification should be applied to calculate cake porosity precisely. This could be explained by different pore information of SEM images with various magnifications. Compared to single SEM image with × 10,000 magnification and × 20,000 magnification, single SEM image with × 5000 magnification contained the most comprehensive pore information and slightly overestimated pore area for pore smaller than 0.4 µm2 due to lower resolution. To verify feasibility by SEM image evaluating cake characteristics, cake porosity calculated by SEM image and Carman-Kozeny equation were analyzed. The results showed that cake porosity estimated by these two methods were nearly the same, proving the feasibility of this method. Moreover, with the increase of coagulant dosage, cake porosity presented similar variation with floc average size, indicating that floc average size was likely to dominate cake porosity in this study. For pore characteristics, pore average characteristic length and pore average area were in accordance with floc fractal dimension, whereas pore fractal dimension and pore amount were consistent with floc average size. This gives specific information about the relation between floc properties and cake characteristics.

Composite poly(l-lactic-acid)/silk fibroin scaffold prepared by electrospinning promotes chondrogenesis for cartilage tissue engineering.

Nanofibrous materials produced by electrospinning have attracted considerable attention from researchers in regenerative medicine. A combination of nanofibrous scaffold and chondrocytes is considered promising for repair of cartilage defect or damage. In the present study, we fabricated a poly(l-lactic-acid) (PLLA)/silk fibroin (SF) nanofibrous scaffold by electrospinning and evaluated its chondrogenic potential. The PLLA/SF nanofibers were characterized for diameter, surface wettability, swelling ratio, and tensile strength. Throughin vitroexperiments, PLLA/SF scaffold-chondrocyte interactions were investigated relative to the unmodified PLLA scaffold with regard to cellular adhesion, spreading, and proliferation by scanning electron microscopy and confocal laser scanning microscopy, and through analyses of DNA, sulfated glycosaminoglycan, and collagen. In addition, hematoxylin-eosin and Alcian blue-nuclear fast red staining were used to observe growth of chondrocytes, and secretion and distribution of cartilage-specific extracellular matrices in the scaffolds. Expressions of cartilage-related genes (collagen II, aggrecan, sox9, collagen I, and collagen X) were detected by real-time quantitative PCR. The PLLA/SF scaffold had better hydrophilicity, and could support chondrocytes adhesion and spreading more effectively than the unmodified PLLA scaffold. Chondrocytes secreted more cartilage-specific extracellular matrices and maintained their phenotype on the PLLA/SF scaffold. So it is concluded that the PLLA/SF scaffold is more conducive toin vitroformation of cartilage-like new tissues than the unmodified PLLA scaffold, and may be a promising material in cartilage tissue engineering.