Tumor Cell Membrane-Encapsulated MLA Solid Lipid Nanoparticles for Targeted Diagnosis and Radiosensitization Therapy of Cutaneous Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is a common nonmelanoma skin cancer. Radiotherapy plays an integral role in treating SCC due to its characteristics, such as diminished intercellular adhesion, heightened cell migration and invasion capabilities, and immune evasion. These problems lead to inaccurate tumor boundary positioning and radiotherapy tolerance in SCC treatment. Thus, accurate localization and enhanced radiotherapy sensitivity are imperative for effective SCC treatment. To address the existing limitations in SCC therapy, we developed monoglyceride solid lipid nanoparticles (MG SLNs) and enveloped them with the A431 cell membrane (A431 CM) to create A431@MG. The characterization results showed that A431@MG was spherical. Furthermore, A431@MG had specific targeting for A431 cells. In A431 tumor-bearing mice, A431@MG demonstrated prolonged accumulation within tumors, ensuring precise boundary localization of SCC. We further advanced the approach by preparing MG SLNs encapsulating 5-aminolevulinic acid methyl ester (MLA) and desferrioxamine (DFO) with an A431 CM coating to yield A431@MG-MLA/DFO. Several studies have revealed that DFO effectively reduced iron content, impeding protoporphyrin IX (PpIX) biotransformation and promoting PpIX accumulation. Simultaneously, MLA was metabolized into PpIX upon cellular entry. During radiotherapy, the heightened PpIX levels enhanced reactive oxygen species (ROS) generation, inducing DNA and mitochondrial damage and leading to cell apoptosis. In A431 tumor-bearing mice, the A431@MG-MLA/DFO group exhibited notable radiotherapy sensitization, displaying superior tumor growth inhibition. Combining A431@MG-MLA/DFO with radiotherapy significantly improved anticancer efficacy, highlighting its potential to serve as an integrated diagnostic and therapeutic strategy for SCC.

Carbon Fiber-Based Flow-Through Electrode System (FES) for Water Disinfection via Direct Oxidation Mechanism with a Sequential Reduction-Oxidation Process.

Flow-through configuration for electrochemical disinfection is considered as a promising approach to minimize the formation of toxic byproducts and energy consumption via the enhanced convective mass transport as compared with conventional flow-by one. Under this hydrodynamic condition, it is essential to ascertain the effect of sequential electro-redox processes with the cathode/anode then anode/cathode arrangements on disinfection performance. Here, carbon fiber felt (CFF) was utilized to construct two flow-through electrode systems (FESs) with sequential reduction-oxidation (cathode-anode) or oxidation-reduction (anode-cathode) processes to systematically compare their disinfection performance toward a model Escherichia coli ( E. coli) pathogen. In-situ sampling and live/dead backlight staining experiments revealed that E. coli inactivation mainly occurred on anode via an adsorption-inactivation-desorption process. In reduction-oxidation system, after the cathode-pretreatment, bulk solution pH increased significantly, leading to the negative charge of E. coli cells. Hence, E. coli cells were adsorbed and inactivated easily on the subsequent anode, finally resulting in its much better disinfection performance and energy efficiency than the oxidation-reduction system. Application of 3.0 V resulted in ∼6.5 log E. coli removal at 1500 L m-2 h-1 (50 mL min-1), suggesting that portable devices can be designed from CFF-based FES with potential application for point-of-use water disinfection.

[Metal artifact reduction for dental implants in kilovoltage computed tomography using megavoltage cone-beam computer tomography].

This paper proposes a novel metal artifact reduction (MAR) algorithm for dental implants in kilovoltage computed tomography (kVCT) using megavoltage cone-beam computer tomography (MVCBCT). Firstly, two CT images were derived by scanning patient with dental implants using kVCT and MVCBCT. Metal image was derived by thresholding segmentation in kVCT. MVCBCT and kVCT images were fused to generate prior image which was forward projected to get surrogate sinogram of metal trace. The corrected image was generated by filtered backprojection (FBP) reconstruction in corrected sinogram. The results of proposed algorithm were compared with other frequently-used metal artifact reduction algorithm, such as normalized MAR (NMAR), normalized MAR using MVCBCT prior images (NMAR-MV), and linear interpolation MAR (LIMAR). The normalized root mean square deviation (NRMSD) and mean absolute deviation (MAD) were computed. The experiment showed that the proposed method removed serious metal artifacts without introducing new artifacts. The values of NRMSD and MAD for proposed method were the minimum in all methods. The values of NRMSD for NMAR, NMAR-MV, LIMAR and the proposed method were 21.0%, 22.1%, 41.9% and 17.0% respectively. And MAD values of them were 232, 235, 553, 205 HU, respectively. In conclusion, the proposed metal artifact reduction algorithm can successfully suppress metal artifacts for dental implants, and greatly improve the quality of CT image.

GAN-based metal artifacts region inpainting in brain MRI imaging with reflective registration.

BACKGROUND AND OBJECTIVE: Metallic magnetic resonance imaging (MRI) implants can introduce magnetic field distortions, resulting in image distortion, such as bulk shifts and signal-loss artifacts. Metal Artifacts Region Inpainting Network (MARINet), using the symmetry of brain MRI images, has been developed to generate normal MRI images in the image domain and improve image quality. METHODS: T1-weighted MRI images containing or located near the teeth of 100 patients were collected. A total of 9000 slices were obtained after data augmentation. Then, MARINet based on U-Net with a dual-path encoder was employed to inpaint the artifacts in MRI images. The input of MARINet contains the original image and the flipped registered image, with partial convolution used concurrently. Subsequently, we compared PConv with partial convolution, and GConv with gated convolution, SDEdit using a diffusion model for inpainting the artifact region of MRI images. The mean absolute error (MAE) and peak signal-to-noise ratio (PSNR) for the mask were used to compare the results of these methods. In addition, the artifact masks of clinical MRI images were inpainted by physicians. RESULTS: MARINet could directly and effectively inpaint the incomplete MRI images generated by masks in the image domain. For the test results of PConv, GConv, SDEdit, and MARINet, the masked MAEs were 0.1938, 0.1904, 0.1876, and 0.1834, respectively, and the masked PSNRs were 17.39, 17.40, 17.49, and 17.60 dB, respectively. The visualization results also suggest that the network can recover the tissue texture, alveolar shape, and tooth contour. Additionally, for clinical artifact MRI images, MARINet completed the artifact region inpainting task more effectively when compared with other models. CONCLUSIONS: By leveraging the quasi-symmetry of brain MRI images, MARINet can directly and effectively inpaint the metal artifacts in MRI images in the image domain, restoring the tooth contour and detail, thereby enhancing the image quality.

Polyvinylpyrrolidone Assisted One-Pot Synthesis of Size-Tunable Cocktail Nanodrug for Multifunctional Combat of Cancer.

Background: The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported. Methods: In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method. Results: The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release. Conclusion: In summary, Cur-Dox ND might be a promising ND for better cancer therapy.

[Study on the preparation and application of individual artificial bone with carbon/carbon composites].

The present paper is aimed to study the preparation and application of individual artificial bone of carbon/carbon composites. Using computer tomography images (CT), we acquired a three-dimensional image. Firstly, we described bone contour line outlined with manual and automatic method by the binary volume data. Secondly, we created 3D object surface information by marching cubes. Finally, we converted this information to non-uniform rational B-spine (NURBS) by using geomagic software. Individual artificial bone with carbon/carbon composite was prepared through the CNC Machining Center. We replaced the humeral head of the tested rabbit, and then observed the effects of implantation in neuroimaging and pathological section. Using this method, we found that the bone shape processed and bone shape replaced was consistent. After implantation, the implant and the surrounding bone tissue bound closely, and bone tissue grew well on the surface of the implant. It has laid a sound foundation of the preparation using this method for individual artificial bone of carbon/carbon composite material.

Study on injectable silver-incorporated calcium phosphate composite with enhanced antibacterial and biomechanical properties for fighting bone cement-associated infections.

Although commonly used in orthopedic surgery, bone cements often face a high risk of post-operative infection. Developing bone cement with antibacterial capability is an effective path for eliminating implant-associated infections. Herein, the potential of silver ions (Ag+) and silver nanoparticles (AgNPs) in modifying CPC for long-term antibacterial property was investigated. Ag+ ions or AgNPs of various concentrations were incorporated in starch-modified calcium phosphate bone cement (CPB) to obtain Ag+-containing (Ag+@CPB) and AgNPs-containing (AgNP@CPB) bone cements. The results showed that all silver-containing CPBs had setting times of about 25-40 min, compressive strengths of greater than 22 MPa, high cytocompatibility but inhibitory effect on Staphylococcus aureus growth. After soaking for 1 week, the mechanical properties and the cytocompatibility of all cements revealed no significant changes, but only CPB with a relatively high content of Ag+ (H-Ag+@CPB) maintained good antibacterial capability over the tested time period. In addition, all the cements showed high injectability and interdigitating capability in cancellous bone and demonstrated augmentation effect on the cannulated pedicle screws fixation in the Sawbones model. In summary, the sustainable antibacterial capability and enhanced biomechanical properties demonstrated that Ag+ ions were more suitable for the fabrication of antibacterial CPC compared to AgNPs. Also, the H-Ag+@CPB, with good injectability, high cytocompatibility, good interdigitating and biomechanical property in cancellous bone, and sustainable antibacterial effects, bears great potential for the treatments of bone infections or implant-associated infections.

Inpainting the metal artifact region in MRI images by using generative adversarial networks with gated convolution.

PURPOSE: Magnetic resonance imaging (MRI) plays an important role in clinical diagnosis, but it is susceptible to metal artifacts. The generative adversarial network GatedConv with gated convolution (GC) and contextual attention (CA) was used to inpaint the metal artifact region in MRI images. METHODS: MRI images containing or near the teeth of 70 patients were collected, and the scanning sequence was a T1-weighted high-resolution isotropic volume examination sequence. A total of 10 000 slices were obtained after data enhancement, of which 8000 slices were used for training. MRI images were normalized to [-1,1]. Based on the randomly generated mask, U-Net, pix2pix, PConv with partial convolution, and GatedConv were used to inpaint the artifact region of MRI images. The mean absolute error (MAE) and peak signal-to-noise ratio (PSNR) for the mask were used to compare the results of these methods. The inpainting effect on the test dataset using dental masks was also evaluated. Besides, the artifact area of clinical MRI images was inpainted based on the mask sketched by physicians. Finally, the earring artifacts and artifacts caused by abnormal signal foci were inpainted to verify the generalization of the models. RESULTS: GatedConv could directly and effectively inpaint the incomplete MRI images generated by masks in the image domain. For the results of U-Net, pix2pix, PConv, and GatedConv, the masked MAEs were 0.1638, 0.1812, 0.1688, and 0.1596, respectively, and the masked PSNRs were 18.2136, 17.5692, 18.2258, and 18.3035 dB, respectively. Using dental masks, the results of U-Net, pix2pix, and PConv differed more from the real images in terms of alveolar shape and surrounding tissue compared with GatedConv. GatedConv could inpaint the metal artifact region in clinical MRI images more effectively than the other models, but the increase in the mask area could reduce the inpainting effect. Inpainted MRI images by GatedConv and CT images with metal artifact reduction coincided with alveolar and tissue structure, and GatedConv could successfully inpaint artifacts caused by abnormal signal foci, whereas the other models failed. The ablation study demonstrated that GC and CA increased the reliability of the inpainting performance of GatedConv. CONCLUSION: MRI images are affected by metal, and signal void areas appear near metal. GatedConv can inpaint the MRI metal artifact region in the image domain directly and effectively and improve image quality. Medical image inpainting by GatedConv has potential value for tasks, such as positron emission tomography (PET) attenuation correction in PET/MRI and adaptive radiotherapy of synthetic CT based on MRI.

Liposome Loaded Ion/Temperature Dual Responsive Gellan Gum Hydrogel as Potential Nasal-To-Brain Delivery System.

Intranasal administration, which can bypass the blood-brain barrier (BBB), is widely recognized as a promising strategy for high-efficiency drug delivery to the brain. Herein, for the purpose of effectively delivering drugs to the brain via intranasal administration, glutathione (GSH)-modified gellan gum (GSH-GG) with ion/temperature dual responsive properties was synthesized and encapsulated on galanthamine hydrobromide (GH)-loaded liposomes (GH-Lipo) for effective GH delivery to the brain (GH-Lipo@GSH-GG). Our results demonstrated that GSH-GG greatly decreased the gelation temperature of GG from 44.0 °C to 22.1 °C without compromising its ion responsiveness. Moreover, GSH-GG had a good protection ability for GH-loaded liposomes without affecting its drug release. Most importantly, the finally obtained GH-Lipo@GSHGG showed acceptable targeted delivery of GH to the brain upon in vivo administration. Therefore, this formulation can be employed as a potential delivery system in nasal-to-brain delivery.

Small Molecule Modifications Significantly Increase the Transfection Efficiency of Low-Molecular Polymer.

Gene vectors with high biocompatibility and transfection efficiency are critical for successful gene therapy. PEI 25K (Polyethyleneimine 25K) is a common polymeric gene vector that has been employed as a positive control material in gene transfection studies due to its good performance in endosome escape. PEI 25K's indegradability and abundance of positive charges, on the other hand, cause toxicity in cells, limiting its use. In this study, we developed the PEI-ER non-viral vector by adding an endoplasmic reticulum (ER) targeting ligand to low molecular weight PEI 1.8K. These small molecule modifications dramatically improved PEI transfection efficiency while barely interfering with compatibility. PEI-ER/DNA complexes were discovered to enter the cell via caveolin-mediated endocytosis, avoiding destruction in the endosome. We believe that this little chemical alteration is a simple solution to enhance the efficacy of cationic polymer vectors in gene transport, and it has a lot of medicinal applications.

Strontium-calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration.

Vascularized bone tissue engineering is regarded as one of the optimal treatment options for large bone defects. The lack of angiogenic properties and unsatisfactory physicochemical performance restricts calcium phosphate cement (CPC) from application in vascularized bone tissue engineering. Our previous studies have developed a starch and BaSO4 incorporated calcium phosphate hybrid cement (CPHC) with improved mechanical strength and handling properties. However, the bioactivity-especially the angiogenic ability-is still absent and requires further improvement. Herein, based on the reported CPHC and the osteogenic and angiogenic properties of strontium (Sr) ions, a strontium-enhanced calcium phosphate hybrid cement (Sr-CPHC) was developed to improve both biological and physicochemical properties of CPC. Compared to CPC, the initial setting time of Sr-CPHC was prolonged from 2.2 min to 20.7 min. The compressive strength of Sr-CPHC improved from 11.21 MPa to 45.52 MPa compared with CPC as well. Sr-CPHC was biocompatible and showed promotion of alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic relative gene expression, suggesting high osteogenic-inductivity. Sr-CPHC also facilitated the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and up-regulated the expression of the vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1). In vivo evaluation showed marked new bone formation in a rat calvarial defect model with Sr-CPHC implanted. Sr-CPHC also exhibited enhancement of neovascularization in subcutaneous connective tissue in a rat subcutaneous implantation model. Thus, the Sr-CPHC with the dual effects of osteogenesis and angiogenesis shows great potential for clinical applications such as the repair of ischemic osteonecrosis and critical-size bone defects.

Metagenomics analysis of the key functional genes related to biofouling aggravation of reverse osmosis membranes after chlorine disinfection.

Chlorine disinfection is a common technology to control biofouling in the pretreatment of the reverse osmosis (RO) system for wastewater reclamation. However, chlorine disinfection could even aggravate the RO membrane biofouling because of the changes of microbial community structure. In this study, the mechanism of biofilm formation and EPS secretion after chlorine disinfection was investigated by analyzing the genes coding quorum sensing, exopolysaccharide biosynthesis, and amino acid biosynthesis. After 1, 5, and 15 mg-Cl2/L chlorine disinfection, the relative abundances of the functional genes all increased significantly. Compared with the control group, chlorine-resistant bacteria (Acidovorax, Arenimonas, and Pseudomonas) also harbored higher relative abundances of these functional genes. The high relative abundances of these genes might provide the bacterial community after chlorine disinfection with high potential of biofilm formation and EPS secretion and then cause severe RO membrane biofouling. In the sample with 5 mg-Cl2/L chlorine disinfection, the correlation coefficients (r) between each two of the three kinds of functional genes were more than 0.9 and much stronger than that in the control group. These results indicated that the bacterial community selected by chlorine disinfection could build more stable biofilm to resist chlorine but also could cause more severe RO membrane biofouling.

Polyvinyl Alcohol/Graphene Oxide Interlayer for Enhancing Adhesive Performance of HA Coating on C/C Composites Prepared by Hydrothermal Electrodeposition/Hydrothermal Treatment.

Hydroxyapatite (HA) coatings directly deposited by hydrothermal electrochemical technology (HET) onto carbon/carbon (C/C) composites exhibited a catastrophic failure occurring at the interface of the HA and C/C. To overcome this problem, a polyvinyl alcohol (PVA)/graphene oxide (GO) interlayer (P/G interlayer) was applied on the (NH4)2S2O8-pretreated C/C substrate (named P/G-C/C) by using a dipping method. Subsequently, a calcium phosphate coating was deposited on P/G-C/C, shortened as M-P/G-C/C, by HET, and then converted into HA coating (abbreviated as HA-P/G-C/C) through posthydrothermal treatment. For comparison, HA coating was prepared onto C/C without a P/G interlayer through the same process, which was denoted as HA-C/C. The composition, microstructure, and morphology of the samples were characterized by X-ray diffractometry (XRD), energy-dispersive spectroscopy (EDS), scanning electron microscopy (SEM), Raman spectra, Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS). The adhesive performance of the coatings on C/C was measured by a scratch test. Finally, an in vitro bioactivity of the coatings was evaluated in a simulated body fluid solution at 37 °C. Results showed no apparent differences in the morphology and phase of the posttreated coatings, both of which are composed of a dense structure containing needle-like HA crystals. However, the HA-P/G-C/C sample possessed a higher Ca/P ratio and denser interface, thereby exhibiting higher adhesive performance and better bioactivity. The adhesive strength of the HA-P/G coating was observed at a critical load of 41.04 N, which increased by 29.3% relative to the HA coating. Moreover, the failure site was on the HA-P/G coating rather than at the interface. The enhanced adhesive performance was ascribed to the PVA/GO-repairing pits on C/C and PVA and GO toughening effects on the HA coating. In vitro and in vivo tests revealed no statistical significance for the two HA-coated C/C samples, although the HA-P/G coating exhibited better bioactivity, inducing the growth of bonelike apatite than the HA coating.

Comparison of carbonized and graphitized carbon fiber electrodes under flow-through electrode system (FES) for high-efficiency bacterial inactivation.

The disinfection performance of a flow-through electrode system (FES) was systematically evaluated using different carbonized (C1, C2, and C3) and corresponding graphitized (G1, G2, and G3) carbon fiber felt (CFF) electrodes. The physicochemical and electrochemical properties were characterized to identify the differences among CFFs. Graphitized CFFs (gCFFs) can achieve complete inactivation of Escherichia coli (>6 log) at the voltage of 3 V and flux of 120-3600 L/(m2 h) for high conductivity and chemical stability, while carbonized CFFs (cCFFs) only achieved around 1 log removal with obvious carbon corrosion. For the gCFFs, G1 (>6 log removal) with higher conductivity, better graphite structure, and larger surface area (related to fiber diameter and density) presented better disinfection performance at the flow rate of 30 mL/min than G2 (∼3 log) and G3(∼1 log). Furthermore, no regrowth and reactivation of bacteria occurred during the storage under visible light illumination after FES treatment. Three parallel FESs with G1 were operated continuously for one week (24 h per day, 7 days) treating the solution with an E. coli concentration ranging from 106 to 107 CFU/mL at the applied voltage of 3 V and the flow rate of 20 mL/min. No live bacteria were detected in the effluent of any of these three FESs. In-situ sampling experiments demonstrated that the inactivation of bacteria on anode was the dominant mechanism for FES treatment, which can be attributed to the sequential adsorption, direct-oxidation and desorption process on anode, instead of indirect oxidation by generating chemical oxidants. In addition, hydroxide ion generated from cathode reaction enhanced anode adsorption and inactivation of bacteria by providing alkaline environment. Combining the analysis results of material properties and disinfection performance, the gCFF-based FES was suggested to be a low-cost, high-efficiency, and safe alternative for future water disinfection.

A comparative study of identical VMAT about two adjacent targets with and without fixed-jaw technique.

BACKGROUND: The radiation transmission through the multileaf collimators is undesired in modern techniques such as volumetric modulated arc therapy (VMAT). According to identical plans, in this study, we aim to investigate the dosimetric impact of jaw tracking on the VMAT plans on two adjacent targets. METHODS: Two treatment plans were designed for eight pelvic (cervical) patients with two targets using the same optimization parameters. The original plan (O-plan) used automatically selected jaw positions. In the new plan (F-plan), the jaws were fixed to block two targets in two beams. The dosimetric parameters of the two plans were compared to evaluate the improvement of dose sparing for the body volume between two targets (named interOAR) in F-VMAT. RESULTS: The mean dose of interOAR reduced significantly from 654.96 ± 113.38 cGy for O-VMAT, to 490.84 ± 80.26 cGy for F-VMAT (p = 0.018). The monitor units (MUs) in the F-plans were 1.49-fold higher than that in the O-plan. The F and O-plan performed similarly in target dose homogeneity. The differences in Dmax of spinal cord, Dmax of spinal cord planning organ at risk volume, and V20, V30, and V40 of the intestine were insignificant. CONCLUSIONS: VMAT plans with the fixed-jaw method can reduce the volume between two targets effectively. However, despite the plan quality, the method can only be used when the regular methods cannot reach the clinical requirements for critical organs because of additional MUs.

Deposition of calcium phosphate coatings using condensed phosphates (P2O7(4-) and P3O10(5-)) as phosphate source through induction heating.

In present work condensed phosphates (P2O7(4-) and P3O10(5-)) were used as phosphate source in induction heating to deposit calcium phosphate coatings. The phase, morphology, and composition of different phosphate-related coatings were characterized and compared using XRD, FTIR, and SEM analyses. Results showed that P2O7(4-)formed calcium pyrophosphate hydrate coatings with interconnected cuboid-like particles. The as-deposited calcium tripolyphosphate hydrate coating with P3O10(5-) was mainly composed of flower-like particles assembled by plate-like crystals. The bioactivity and cytocompatibility of the coatings were also studied. Moreover, the feasibility of using hybrid phosphate sources for preparing and depositing coatings onto magnesium alloy was investigated.