Cascade strategy for glucose oxidase-based synergistic cancer therapy using nanomaterials.

Nanomaterial-based cancer therapy faces significant limitations due to the complex nature of the tumor microenvironment (TME). Starvation therapy is an emerging therapeutic approach that targets tumor cell metabolism using glucose oxidase (GOx). Importantly, it can provide a material or environmental foundation for other diverse therapeutic methods by manipulating the properties of the TME, such as acidity, hydrogen peroxide (H2O2) levels, and hypoxia degree. In recent years, this cascade strategy has been extensively applied in nanoplatforms for ongoing synergetic therapy and still holds undeniable potential. However, only a few review articles comprehensively elucidate the rational designs of nanoplatforms for synergetic therapeutic regimens revolving around the conception of the cascade strategy. Therefore, this review focuses on innovative cascade strategies for GOx-based synergetic therapy from representative paradigms to state-of-the-art reports to provide an instructive, comprehensive, and insightful reference for readers. Thereafter, we discuss the remaining challenges and offer a critical perspective on the further advancement of GOx-facilitated cancer treatment toward clinical translation.

Bovine serum albumin-based and dual-responsive targeted hollow mesoporous silica nanoparticles for breast cancer therapy.

Combination therapy is an effective way to alleviate the shortcoming of monotherapy and enhances therapeutic efficacy. Herein, a distinctive hollow mesoporous silica nanoparticle (HMSNs) encapsulated with folic acid-modified bovine serum albumin (BSA-FA), denoted as HBF, was engineered for tumor targeting and dual-responsive release of loaded-therapeutic agents MD (methylene blue (MB) and doxorubicin (DOX)). The BSA molecule as a ''gatekeeper'' prevents premature drug leakage and actively unloads the cargos through BSA detachment in response to intracellular glutathione (GSH). Folic acid (FA) promotes the specific intracellular delivery of the drug to folate receptor (FR)-expressing cancer cells to improve the efficacy of chemo-photodynamic therapy (PDT). In vitro drug release profiles showed that the drug carrier could achieve pH/redox-responsive drug release from MD@HBF owing to the cleavage of the imine bonds between HMSNs-CHO and BSA-FA and BSA intramolecular disulfide bond. Additionally, a series of biological evaluations, such as cell uptake experiments, toxicity experiments, and in vivo therapeutic assays indicated that MD@HBF possesses the features of accurately targeting FR-expressing 4T1 cells to induce cells apoptosis in vitro, exhibits outstanding tumor cell synergistic killing efficiency of chemo-photodynamic therapy (combination index CI = 0.325), and inhibits tumors growth. These results demonstrated that the strategy of combining HMSNs with stimuli-responsive biodegradable protein molecules could provide a new potential direction toward the ''on-demand'' drug release for precision chemo-photodynamic therapy in cancer treatment.

Iterative Joint Estimation Procedure of Channel and PDP for OFDM Systems.

The power-delay profile (PDP) estimation of wireless channels is an important step to generate a channel correlation matrix for channel linear minimum mean square error (LMMSE) estimation. Estimated channel frequency response can be used to obtain time dispersion characteristics that can be exploited by adaptive orthogonal frequency division multiplexing (OFDM) systems. In this paper, a joint estimator for PDP and LMMSE channel estimation is proposed. For LMMSE channel estimation, we apply a candidate set of frequency-domain channel correlation functions (CCF) and select the one that best matches the current channel to construct the channel correlation matrix. The initial candidate set is generated based on the traditional CCF calculation method for different scenarios. Then, the result of channel estimation is used as an input for the PDP estimation whereas the estimated PDP is further used to update the candidate channel correlation matrix. The enhancement of LMMSE channel estimation and PDP estimation can be achieved by the iterative joint estimation procedure. Analysis and simulation results show that in different communication scenarios, the PDP estimation error of the proposed method can approach the Cramér-Rao lower bound (CRLB) after a finite number of iterations. Moreover, the mean square error of channel estimation is close to the performance of accurate PDP-assisted LMMSE.

Anatomical characteristics and potential gene mutation sites of a familial recurrent patellar dislocation.

BACKGROUND: Recurrent patellar dislocation is the result of anatomical alignment and imbalance of restraint of bone and soft tissue. We investigate the anatomical characteristics of the knee joint in a family of patients with recurrent patella dislocation, and to screen the possible pathogenic genes in this family by whole exome sequencing in 4 patients and 4 healthy subjects, so as to provide theoretical basis for the pathogenesis of this disease. METHODS: The data related to patella dislocation were measured by imaging data. The peripheral blood DNA of related family members was extracted for the whole exome sequencing, and then the sequencing results were compared with the human database. By filtering out synonymous variants and high-frequency variants in population databases, and then integrating single nucleotide non-synonymous variants of family members, disease-causing genes were found. RESULTS: All patients in this family have different degrees of abnormal knee anatomy, which is closely related to patella dislocation. The sequencing results of patients and normal persons in this patella dislocation family were compared and analyzed, and the data were filtered through multiple biological databases. Find HOXB9 (NM_024017.4:c.404A>G:p.Glu135Gly),COL1A1(NM_000088.3:c.3766G>A:p.Ala1256Thr),GNPAT(NM_014236.3:c1556A>G:p.Asp519Gly),NANS(NM_018946.3:c.204G>C:p.Glu68Asp),SLC26A2(NM_000112.3:c.2065A>T:p.Thr689Ser) are nonsynonymous variants (MISSENSE). Through Sanger sequencing, the identified mutations in HOXB9 and SLC26A2 genes were only present in samples from patients with recurrent patellar dislocation. CONCLUSIONS: The patients with recurrent patellar dislocation had markedly abnormal knee anatomy in this family. HOXB9 gene and SLC26A2 gene were found to be the possible pathogenic genes or related genes for patella dislocation.

Multimodal Magnetic Resonance Imaging to Diagnose Knee Osteoarthritis under Artificial Intelligence.

This work aimed to investigate the application value of the multimodal magnetic resonance imaging (MRI) algorithm based on the low-rank decomposition denoising (LRDD) in the diagnosis of knee osteoarthritis (KOA), so as to offer a better examination method in the clinic. Seventy-eight patients with KOA were selected as the research objects, and they all underwent T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), fat suppression T2WI (SE-T2WI), and fat saturation T2WI (FS-T2WI). All obtained images were processed by using the I-LRDD algorithm. According to the degree of articular cartilage lesions under arthroscopy, the patients were divided into a group I, a group II, a group III, and a group IV. The sensitivity, specificity, accuracy, and consistency of KOA diagnosis of T1WI, T2WI, SE-T2WI, and FS-T2WI were analyzed by referring to the results of arthroscopy. The results showed that the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) of the I-LRDD algorithm used in this work were higher than those of image block priori denoising (IBPD) and LRDD, and the time consumption was lower than that of IBDP and LRDD (p < 0.05). The sensitivity, specificity, accuracy, and consistency (Kappa value) of multimodal MRI in the diagnosis of KOA were 88.61%, 85.3%, 87.37%, and 0.73%, respectively, which were higher than those of T1WI, T2WI, SE-T2WI, and FS-T2WI. The sensitivity, specificity, accuracy, and consistency of multimodal MRI in diagnosing lesions in group IV were 95%, 96.10%, 95.88%, and 0.70%, respectively, which were much higher than those in groups I, II, and III (p < 0.05). In conclusion, the LRDD algorithm shows a good image processing efficacy, and the multimodal MRI showed a good diagnosis effect on KOA, which was worthy of promotion clinically.

[Mechanical properties and effect on osteodifferentiation of induced pluripotent stem cells of chitosan/whisker/calcium phosphate cement composite biomaterial].

Objective: To investigate the mechanical properties of the novel compound calcium phosphate cement (CPC) biological material as well as the biological activity and osteogenesis effects of induced pluripotent stem cells (iPS) seeding on scaffold and compare their bone regeneration efficacy in cranial defects in rats. Methods: Ac- cording to the different scaffold materials, the experiment was divided into 4 groups: pure CPC scaffold group (group A), CPC∶10% wt chitosan as 2∶1 ratio mixed scaffold group (group B), CPC∶10% wt chitosan∶whisker as 2∶1∶1 ratio mixed scaffold group (group C), and CPC∶10% wt chitosan∶whisker as 2∶1∶2 ratio mixed scaffold group (group D). Mechanical properties (bending strength, work-of-fracture, hardness, and modulus of elasticity) of each scaffold were detected. The scaffolds were cultured with fifth generation iPS-mesenchymal stem cells (MSCs), and the absorbance ( A) values of each group were detected at 1, 3, 7, and 14 days by cell counting kit 8 (CCK-8) method; the alkaline phosphatase (ALP) activity, Live/Dead fluorescence staining and quantitative detection, ALP, Runx2, collagen typeⅠ, osteocalcin (OC), and bone morphogenetic protein 2 (BMP-2) gene expressions by RT-PCR were detected at 1, 7, and 14 days; and the alizarin red staining were detected at 1, 7, 14, and 21 days. Twenty-four 3-month-old male Sprague Dawley rats were used to establish the 8 mm-long skull bone defect model, and were randomly divided into 4 groups ( n=6); 4 kinds of scaffold materials were implanted respectively. After 8 weeks, HE staining was used to observe the repair of bone defects and to detect the percentage of new bone volume and the density of neovascularization. Results: The bending strength, work-of-fracture, hardness, and modulus of elasticity in groups B, C, and D were significantly higher than those in group A, and in groups C, D than in group B, and in group D than in group C ( P<0.05). CCK-8 assay showed that cell activity gradually increased with the increase of culture time, the A values in groups B, C, and D at 3, 7, 14 days were signifiantly higher than those in group A, and in groups C, D than in group B ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). Live/Dead fluorescence staining showed that the proportion of living cells in groups B, C, and D at 7 and 14 days was significantly higher than that in group A ( P<0.05), and in groups C, D at 7 days than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). RT-PCR showed that the relative expressions of genes in groups B, C, and D at 7 and 14 days were significantly higher than those in group A, and in groups C, D than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). Alizarin red staining showed that the red calcium deposition on the surface of scaffolds gradually deepened and thickened with the prolongation of culture time; the A values in groups B, C, and D at 14 and 21 days were significantly higher than those in group A ( P<0.05), and in groups C and D than in group B ( P<0.05), but no significant difference was found between groups C and D ( P>0.05). In vivo repair experiments in animals showed that the new bone in each group was mainly filled with the space of scaffold material. Osteoblasts and neovascularization were surrounded by new bone tissue in the matrix, and osteoblasts were arranged on the new bone boundary. The new bone in groups B, C, and D increased significantly when compared with group A, and the new bone in groups C and D was significantly higher than that in group B. The percentage of new bone volume and the density of neovascularization in groups B, C, and D were significantly higher than those in group A, and in groups C and D than in group B ( P<0.05); but no significant difference was found between groups C and D ( P>0.05). Conclusion: The mechanical properties of the new reinforced composite scaffold made from composite chitosan, whisker, and CPC are obviously better than that of pure CPC scaffold material, which can meet the mechanical properties of cortical bone and cancellous bone. iPS-MSCs is attaching and proliferating on the new reinforced composite scaffold material, and the repair effect of bone tissue is good. It can meet the biological and osteogenic activity requirements of the implant materials in the bone defect repair.

[Tricaicium phosphate complex pre-loaded with bone morphogenetic protein-2 or platelet derived growth factor-BB for repairing critical-size cranial defects in SD rats].

OBJECTIVE: To observe the effect of a new biomaterial in promoting the bone regeneration for repairing critical-size cranial defects in SD rats. METHODS: Critical-size cranial defects were induced in 3-month-old male Sprague-Dawley rats and repaired with the implants of calcium phosphate from growth factor enhanced matrix 21 (CaPfromGEM21, control), CaPfromGEM21 preloaded with 10 ng bone morphogenetic protein-2 (BMP-2), CaPfromGEM21 preloaded with 100 ng BMP-2, CaPfromGEM21 preloaded with 0.3 µg platelet-derived growth factor-BB (PDGF-BB), or CaPfromGEM21 preloaded with 3 µg PDGF-BB. The defects were examined 6 weeks after the surgery with X-ray, micro-CT, HE staining and quantitative assessments. RESULTS: X-ray showed defect repair in all the groups. The fracture line became obscure, and the defects were almost fully repaired by the regenerated bone tissues in PDGF-BB group. Micro-CT demonstarted new bone formation in the defects. The new bone volume was significantly greater in PDGF-BB groups than in BMP-2 groups (P<0.05). HE staining revealed the presence of new bones in the defects and new vessels in and around the new bones without inflammatory cells. The new bone area fraction was significantly greater in 10 ng BMP-2 group and 0.3 µg PDGF-BB group than in the control group (P<0.05), and the new vessel density was similar in the all the 4 cytokine-preloaded groups and all significantly greater than that in the blank and CaPfromGEM21 control group (P<0.05). CONCLUSION: CaPfromGem21 combined with BMP-2 or PDGF-BB has good biocompatibility and can better promote bone regeneration for repairing bone defects.

The effect of extended passaging on the phenotype and osteogenic potential of human umbilical cord mesenchymal stem cells.

Retaining biological characteristics in the extended passaging is crucial for human umbilical cord mesenchymal stem cells (hUCMSCs) in tissue engineering. We aimed to assess morphology, viability, MSC marker expression, and osteogenic activity of hUCSMCs after extended passaging. Passages 4 (P4) and 16 (P16) hUCMSCs displayed similar morphology and viability. The flow cytometry results showed that CD73, CD90, and CD105 were highly expressed at P1-P16. CD166 expression decreased progressively from 90 % at P2 to 61.5 % at P5 (p < 0.05), followed by stable expression through P16. Results from calcium deposition alkaline phosphatase activity and RT-PCR assay showed that both P4 and P16 hUCMSCs differentiated down an osteogenic lineage, with no significant difference in osteogenic capacity (p < 0.05). High-passage UMCSCs maintained stable expression of MSC CD markers as well as stable osteogenic activity. hUCMSCs may thus be suitable for tissue engineering and regenerative medicine applications.

Aligned carbon nanotube sheets for the electrodes of organic solar cells.

Aligned carbon nanotube sheets are developed as a new family of electrodes to fabricate dye-sensitized solar cells. The energy conversion efficiency of the resulting cell is higher than the randomly dispersed carbon nanotube film and comparable with the platinum. Novel and flexible solar cells can be easily made from such carbon nanotube sheets with high potentials.