CRM197-scaffolded vaccines designed by epitope grafting ameliorate cognitive decline in an Alzheimer's disease model.

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Amyloid-beta (Aß) plaque accumulation and tau neurofibrillary tangles (NFTs) formation in the brain are major neuropathological hallmarks of AD. Immunotherapies targeting Aß and/or tau are deemed the most promising approaches for AD. Administrations with monoclonal antibodies against Aß have yielded substantial breakthroughs clinically. Most vaccines tested clinically so far failed to prove efficacious in large part due to inappropriate design of vaccine antigens. In this study, a structure-guided approach was employed to design novel antigens targeting Aß and/or tau by grafting multiple copies of Aß and/or tau B-cell epitope peptide onto CRM197, which is the most widely used carrier protein in polysaccharide conjugate vaccines. The immunogenicity of the vaccines was evaluated in BALB/c mice and the efficacy was tested in a transgenic mouse model of human amyloidopathy. The antigens were highly immunogenic early vaccination substantially ameliorated cognitive decline in APP/PS1 mice and significantly reduced insoluble Aß42/40 in the brains. These results demonstrate that the engineered antigens have protective effects on AD mice, offering a promising translatable strategy for the prevention and/or treatment of AD.

ZNF692 promotes osteosarcoma cell proliferation, migration, and invasion through TNK2-mediated activation of the MEK/ERK pathway.

BACKGROUND: Osteosarcoma is a diverse and aggressive bone tumor. Driver genes regulating osteosarcoma initiation and progression remains incompletely defined. Zinc finger protein 692 (ZNF692), a kind of Krüppel C2H2 zinc finger transcription factor, exhibited abnormal expression in different types of malignancies and showed a correlation with the clinical prognosis of patients as well as the aggressive characteristics of cancer cells. Nevertheless, its specific role in osteosarcoma is still not well understood. METHODS: We investigated the dysregulation and clinical significance of ZNF692 in osteosarcoma through bioinformatic method and experimental validation. A range of in vitro assays, including CCK-8, colony formation, EdU incorporation, wound healing, and transwell invasion tests, were conducted to assess the impact of ZNF692 on cell proliferation, migration, and invasion in osteosarcoma. A xenograft mouse model was established to evaluate the effect of ZNF692 on tumor growth in vivo. Western blot assay was used to measure the protein levels of MEK1/2, P-MEK1/2, ERK1/2, and P-ERK1/2 in cells that had been genetically modified to either reduce or increase the expression of ZNF692. The relationship between ZNF692 and tyrosine kinase non-receptor 2 (TNK2) were validated by qRT-PCR, chromatin immunoprecipitation and luciferase reporter assays. RESULTS: Expression of ZNF692 was increased in both human osteosarcoma tissues and cell lines. Furthermore, the expression of ZNF692 served as an independent predictive biomarker in osteosarcoma. The results of the survival analysis indicated that increased expression of ZNF692 was associated with worse outcome. Downregulation of ZNF692 inhibits the proliferation, migration, and invasion of osteosarcoma cells, whereas upregulation of ZNF692 has the opposite impact. Western blot assay indicates that reducing ZNF692 decreases phosphorylation of MEK1/2 and ERK1/2, whereas increasing ZNF692 expression enhances their phosphorylation. U0126, a potent inhibitor specifically targeting the MEK/ERK signaling pathway, partially counteracts the impact of ZNF692 overexpression on the proliferation, migration, and invasion of osteosarcoma cells. In addition, ZNF692 specifically interacts with the promoter region of TNK2 and stimulates the transcription of TNK2 in osteosarcoma cells. Forcing the expression of TNK2 weakens the inhibitory impact of ZNF692 knockdown on P-MEK1/2 and P-ERK1/2. Similarly, partly inhibiting TNK2 counteracts the enhancing impact of ZNF692 overexpression on the phosphorylation of MEK1/2 and ERK1/2. Functional tests demonstrate that the suppressive effects of ZNF692 knockdown on cell proliferation, migration, and invasion are greatly reduced when TNK2 is overexpressed. In contrast, the reduction of TNK2 hinders the ability of ZNF692 overexpression to enhance cell proliferation, migration, and invasion. CONCLUSION: ZNF692 promotes the proliferation, migration, and invasion of osteosarcoma cells via the TNK2-dependent stimulation of the MEK/ERK signaling pathway. The ZNF692-TNK2 axis might potentially function as a possible predictive biomarker and a promising target for novel therapeutics in osteosarcoma.

Exploring the Osteogenic Potential of Zinc-Doped Magnesium Phosphate Cement (ZMPC): A Novel Material for Orthopedic Bone Defect Repair.

In orthopedics, the repair of bone defects remains challenging. In previous research reports, magnesium phosphate cements (MPCs) were widely used because of their excellent mechanical properties, which have been widely used in the field of orthopedic medicine. We built a new k-struvite (MPC) cement obtained from zinc oxide (ZnO) and assessed its osteogenic properties. Zinc-doped magnesium phosphate cement (ZMPC) is a novel material with good biocompatibility and degradability. This article summarizes the preparation method, physicochemical properties, and biological properties of ZMPC through research on this material. The results show that ZMPC has the same strength and toughness (25.3 ± 1.73 MPa to 20.18 ± 2.11 MPa), that meet the requirements of bone repair. Furthermore, the material can gradually degrade (12.27% ± 1.11% in 28 days) and promote osteogenic differentiation (relative protein expression level increased 2-3 times) of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. In addition, in vivo confirmation revealed increased bone regeneration in a rat calvarial defect model compared with MPC alone. Therefore, ZMPC has broad application prospects and is expected to be an important repair material in the field of orthopedic medicine.

A Bioactive Gelatin-Methacrylate Incorporating Magnesium Phosphate Cement for Bone Regeneration.

Maintaining proper mechanical strength and tissue volume is important for bone growth at the site of a bone defect. In this study, potassium magnesium phosphate hexahydrate (KMgPO4·6H2O, MPC) was applied to gelma-methacrylate hydrogel (GelMA) to prepare GelMA/MPC composites (GMPCs). Among these, 5 GMPC showed the best performance in vivo and in vitro. These combinations significantly enhanced the mechanical strength of GelMA and regulated the degradation and absorption rate of MPC. Considerably better mechanical properties were noted in 5 GMPC compared with other concentrations. Better bioactivity and osteogenic ability were also found in 5 GMPC. Magnesium ions (Mg2+) are bioactive and proven to promote bone tissue regeneration, in which the enhancement efficiency is closely related to Mg2+ concentrations. These findings indicated that GMPCs that can release Mg2+ are effective in the treatment of bone defects and hold promise for future in vivo applications.

Construction of a prognostic risk score model based on the ARHGAP family to predict the survival of osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignancy of bone tumors. More and more ARHGAP family genes have been confirmed are to the occurrence, development, and invasion of tumors. However, its significance in osteosarcoma remains unclear. In this study, we aimed to identify the relationship between ARHGAP family genes and prognosis in patients with OS. METHODS: OS samples were retrieved from the TCGA and GEO databases. We then performed LASSO regression analysis and multivariate COX regression analysis to select ARHGAP family genes to construct a risk prognosis model. We then validated this prognostic model. We utilized ESTIMATE and CIBERSORT algorithms to calculate the stroma and immune scores of samples, as well as the proportions of tumor infiltrating immune cells (TICs). Finally, we conducted in vivo and in vitro experiments to investigate the effect of ARHGAP28 on osteosarcoma. RESULTS: We selected five genes to construct a risk prognosis model. Patients were divided into high- and low-risk groups and the survival time of the high-risk group was lower than that of the low-risk group. The high-risk group in the prognosis model constructed had relatively poor immune function. GSEA and ssGSEA showed that the low-risk group had abundant immune pathway infiltration. The overexpression of ARHGAP28 can inhibit the proliferation, migration, and invasion of osteosarcoma cells and tumor growth in mice, and IHC showed that overexpression of ARHGAP28 could inhibit the proliferation of tumor cells. CONCLUSION: We constructed a risk prognostic model based on five ARHGAP family genes, which can predict the overall survival of patients with osteosarcoma, to better assist us in clinical decision-making and individualized treatment.

RILP inhibits tumor progression in osteosarcoma via Grb10-mediated inhibition of the PI3K/AKT/mTOR pathway.

BACKGROUND: Rab-interacting lysosomal protein (RILP) contains an alpha-helical coil with an unexplored biological function in osteosarcoma. This study investigated the expression of RILP in osteosarcoma cells and tissues to determine the effect of RILP on the biological behaviors of osteosarcoma cells and the underlying mechanism. METHODS: Tumor Immune Estimation Resource (TIMER) database, The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were used for bioinformatic analysis. Co-immunoprecipitation experiment was used to determine whether the two proteins were interacting. In functional tests, cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell invasion assay, Immunofluorescence (IF) assay and immunohistochemical (IHC) assay were performed. RESULTS: Overexpression of RILP significantly inhibited proliferation and impaired metastasis ability of osteosarcoma cells, while silencing of RILP showed the opposite trend. RNA-seq data analysis was applied in 143B cells and pathway enrichment analysis revealed that differentially expressed genes were mainly enriched in the PI3K/AKT pathway. We further verified that overexpression of RILP restrained the PI3K/AKT/mTOR signaling pathway and induced autophagy in osteosarcoma cells, while the opposite trend was observed when PI3K pathway activator 740Y-P was used. 3-Methyladenine (3-MA), a selective autophagy inhibitor, partially attenuated the inhibitory effect of RILP on the migration and invasion ability of osteosarcoma cells, suggesting the involvement of autophagy in epithelial-mesenchymal transition regulation in osteosarcoma cells. Growth factor receptor binding protein-10 (Grb10), an adaptor protein, was confirmed as a potential target of RILP to restrain the PI3K/AKT signaling pathway. We subcutaneously injected stably overexpressing 143B osteosarcoma cells into nude mice and observed that overexpression of RILP inhibited tumor growth by inhibiting the PI3K/AKT/mTOR pathway. CONCLUSION: Our study revealed that the expression of RILP was associated with favorable prognosis of osteosarcoma and RILP inhibits proliferation, migration, and invasion and promotes autophagy in osteosarcoma cells via Grb10-mediated inhibition of the PI3K/AKT/mTOR signaling pathway. In the future, targeting RILP may be a potential strategy for osteosarcoma treatment.

Non-line-of-sight reconstruction via structure sparsity regularization.

Non-line-of-sight (NLOS) imaging allows for the imaging of objects around a corner, which enables potential applications in various fields, such as autonomous driving, robotic vision, medical imaging, security monitoring, etc. However, the quality of reconstruction is challenged by low signal-to-noise ratio (SNR) measurements. In this study, we present a regularization method, referred to as structure sparsity (SS) regularization, for denoising in NLOS reconstruction. By exploiting the prior knowledge of structure sparseness, we incorporate nuclear norm penalization into the cost function of the directional light-cone transform (DLCT) model for the NLOS imaging system. This incorporation effectively integrates the neighborhood information associated with the directional albedo, thereby facilitating the denoising process. Subsequently, the reconstruction is achieved by optimizing a directional albedo model with SS regularization using the fast iterative shrinkage-thresholding algorithm (FISTA). Notably, the robust reconstruction of occluded objects is observed. Through comprehensive evaluations conducted on both synthetic and experimental datasets, we demonstrate that the proposed approach yields high-quality reconstructions, surpassing the state-of-the-art reconstruction algorithms, especially in scenarios involving short exposure and low-SNR measurements.

TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling.

Osteosarcoma is a highly aggressive malignant tumor that is common in the pediatric population and has a high rate of disability and mortality. Recent studies have suggested that the tripartite motif-containing family genes (TRIMs) play critical roles in oncogenesis in several cancers. TRIM26, one of the TRIMs family genes, was more frequently reported to exert a tumor-suppressive role, while its detailed functional roles in the osteosarcoma progression were still unknown and require further investigation. Herein, we found that TRIM26 was markedly downregulated in osteosarcoma tissues and cells. Survival analysis revealed that higher expression of TRIM26 was associated with better prognosis and its expression was an independent protective factor in osteosarcoma. Functional analysis demonstrated that overexpression of TRIM26 inhibited osteosarcoma cell proliferation and invasion via inhibiting the EMT process and MEK/ERK signaling. In contrast, the silence of TRIM26 caused the opposite effect. RACK1, a member of the Trp-Asp repeat protein family, was identified as a novel target of TRIM26. TRIM26 could interact with RACK1 and accelerate the degradation of RACK1, thus inactivation of MEK/ERK signaling. Overexpression of RACK1 could attenuate the inhibitory effect of TRIM26 overexpression on p-MEK1/2 and p-ERK1/2, and silence of RACK1 could partly impair the effect of TRIM26 knockdown-induced upregulation of p-MEK1/2 and p-ERK1/2. Further, a series of gain- and loss-of-function experiments showed that decreased malignant behaviors including cell proliferation and invasion in TRIM26-upregulated cells were reversed when RACK1 was overexpressed, whereas RACK1 knockdown diminished the increased malignant phenotypes in TRIM26-silenced osteosarcoma cells. In conclusion, our study indicated that TRIM26 inhibited osteosarcoma progression via promoting proteasomal degradation of RACK1, thereby resulting in inactivation of MEK/ERK signaling, and impeding the EMT process.

Zyxin Inhibits the Proliferation, Migration, and Invasion of Osteosarcoma via Rap1-Mediated Inhibition of the MEK/ERK Signaling Pathway.

Zyxin (ZYX) is an actin-interacting protein with unknown biological functions in patients with osteosarcoma. This research sought to understand how ZYX affects the biological behavior of osteosarcoma cells and to identify the associated mechanism. Firstly, ZYX expression was decreased in osteosarcoma, and its higher expression indicated better outcomes in patients with osteosarcoma. ZYX overexpression significantly inhibited the proliferation, migration, and invasion of osteosarcoma cells, whereas ZYX silencing resulted in the opposite trend. Subsequently, we found that the Rap1 signaling pathway was significantly correlated with ZYX expression as reported in The Cancer Genome Atlas's database using bioinformatic analysis. Moreover, we found that ZYX overexpression regulated the Rap1/MEK/ERK axis, and osteosarcoma cell growth, migration, and invasion were consequently restrained. Additionally, by administering tumor cells subcutaneously to nude mice, a mouse model of transplanted tumors was created. Compared to the control group, the ZYX overexpression group's tumors were lighter and smaller, and the ZYX/Rap1 axis was activated in the ZYX overexpression group. Taken together, our results suggest that ZYX inhibits osteosarcoma cell proliferation, migration, and invasion by regulating the Rap1/MEK/ERK signaling pathway. ZYX might be crucial in the clinical management of osteosarcoma and is a promising novel therapeutic target in patients with this disease.

De-scattering Deep Neural Network Enables Fast Imaging of Spines through Scattering Media by Temporal Focusing Microscopy.

Today the gold standard for in vivo imaging through scattering tissue is point-scanning two-photon microscopy (PSTPM). Especially in neuroscience, PSTPM is widely used for deep-tissue imaging in the brain. However, due to sequential scanning, PSTPM is slow. Temporal focusing microscopy (TFM), on the other hand, focuses femtosecond pulsed laser light temporally while keeping wide-field illumination, and is consequently much faster. However, due to the use of a camera detector, TFM suffers from the scattering of emission photons. As a result, TFM produces images of poor quality, obscuring fluorescent signals from small structures such as dendritic spines. In this work, we present a de-scattering deep neural network (DeScatterNet) to improve the quality of TFM images. Using a 3D convolutional neural network (CNN) we build a map from TFM to PSTPM modalities, to enable fast TFM imaging while maintaining high image quality through scattering media. We demonstrate this approach for in vivo imaging of dendritic spines on pyramidal neurons in the mouse visual cortex. We quantitatively show that our trained network rapidly outputs images that recover biologically relevant features previously buried in the scattered fluorescence in the TFM images. In vivo imaging that combines TFM and the proposed neural network is one to two orders of magnitude faster than PSTPM but retains the high quality necessary to analyze small fluorescent structures. The proposed approach could also be beneficial for improving the performance of many speed-demanding deep-tissue imaging applications, such as in vivo voltage imaging.

Retraction: Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold.

Retraction of 'Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold' by Donghai Li et al., Biomater. Sci., 2018, 6, 519-537, https://doi.org/10.1039/C7BM00975E.

Isoquercitrin restrains the proliferation and promotes apoptosis of human osteosarcoma cells by inhibiting the Wnt/ß-catenin pathway.

Currently, chemotherapeutic drugs are widely used for the treatment of osteosarcoma. However, many of these drugs exhibit shortcomings such as poor efficacy, high toxicity, and tolerance. Isoquercitrin (ISO) is a traditional Chinese medicine that has been proved to exert good therapeutic effects on various tumors; however, its role in osteosarcoma has not been reported. Here, we observed that ISO exerted a marked inhibitory effect on the occurrence and development of osteosarcoma in a time- and dose-dependent manner. First, we determined that ISO significantly inhibited proliferation, induced EMT-related migration and invasion and induced apoptosis of osteosarcoma cells in vitro. Concurrently, we also observed that both ß-catenin and its downstream genes (c-Myc, CyclinD1, and Survivin) were significantly down-regulated. To verify if the anti-tumor effect of ISO was related to the Wnt/ß-catenin signaling pathway, we altered the protein expression level of ß-catenin using recombinant lentivirus, then we observed that the effects of ISO on the proliferation, metastasis, and apoptosis of osteosarcoma cells were significantly reversed. Additionally, we used a nude mouse xenograft model and observed that ISO significantly inhibited the growth of osteosarcoma and improved the survival rate of the animal models. In conclusion, this study demonstrates that ISO can exert anti-tumor effects in part by inhibiting the Wnt/ß-catenin signaling pathway, thus providing a new potential therapeutic strategy for the treatment of osteosarcoma.

Functionalized Magnesium Phosphate Cement Induces In Situ Vascularized Bone Regeneration via Surface Lyophilization of Chondroitin Sulfate.

Bone defect repair poses significant challenges in orthopedics, thereby increasing the demand for bone substitutes. Magnesium phosphate cements (MPCs) are widely used for bone defect repair because of their excellent mechanical properties and biodegradability. However, high crystallinity and uncontrolled magnesium ion (Mg2+) release limit the surface bioactivity of MPCs in bone regeneration. Here, we fabricate chondroitin sulfate (CS) as a surface coating via the lyophilization method, namely CMPC. We find that the CS coating is uniformly distributed and improves the mechanical properties of MPC through anionic electrostatic adsorption, while mediating degradation-related controlled ion release of Mg2+. Using a combination of in vitro and in vivo analyses, we show that the CS coating maintained cytocompatibility while increasing the cell adhesion area of MC3T3-E1s. Furthermore, we display accelerated osteogenesis and angiogenesis of CMPC, which are related to appropriate ion concentration of Mg2+. Our findings reveal that the preparation of a lyophilized CS coating is an effective method to promote surface bioactivity and mediate Mg2+ concentration dependent osteogenesis and angiogenesis, which have great potential in bone regeneration.

Identification of a novel gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment in osteosarcoma.

Ferroptosis is a novel form of non-apoptotic cell death that mainly results from the iron-dependent lethal accumulation of lipid peroxidation products. Here, we defined differentially expressed genes between control and RSL3-treated osteosarcoma cells as ferroptosis-associated genes (FAGs). These FAGs were then subjected to weighted gene correlation network analysis (WGCNA), and we found that the turquoise module, containing 71 FAGs, was markedly related to the patient's vital status. After that, FAGs in the turquoise module were utilized to construct a prognostic multigene (COL5A2, HOXB4, and UNC5B) signature for risk stratification in osteosarcoma. Validation in internal and external cohorts indicated the accuracy and clinical applicability of this signature in predicting the prognosis of patients with osteosarcoma. Univariate and multivariate Cox regression analyses suggested that the signature-derived risk score is an independent indicator of patient prognosis. Immunological analysis indicated that significant variations in stromal and ESTIMATE scores, as well as tumor purity, were found when the high- and low-risk groups were compared. Regarding immune cell infiltration, the proportion of activated CD4 memory T cells was significantly lower in the high-risk group than that in the low-risk group. The ssGSEA results suggested that CD8+ T, Tfh, and Th1 cell scores were consistently lower in the high-risk group than those in the low-risk group. In terms of immune-related activities, the high-risk group had considerably lower scores for promoting inflammation, T-cell co-inhibition, and T-cell co-stimulation than the low-risk group, indicating the differential immunological state of the high- and low-risk groups. Of the three FAGs included in the signature, the expression of COL5A2, HOXB4, and UNC5B was higher in the high-risk groups, and the expression of COL5A2 and UNC5B was negatively associated with patient prognosis. Additionally, the mRNA levels of COL5A2 and HOXB4 were lower and those of UNC5B were higher in RSL3-treated cells than in control cells. In all, we systematically analyzed the transcriptional changes of osteosarcoma cells induced by RSL3 and constructed a novel three-gene signature with regard to ferroptosis, prognosis prediction, and immune microenvironment. We also identified COL5A2, HOXB4, and UNC5B as potential therapeutic targets and important regulators of ferroptosis in osteosarcoma.

A Series of New Pyrrole Alkaloids with ALR2 Inhibitory Activities from the Sponge Stylissa massa.

Twelve new and four known alkaloids including five different structural scaffolds were isolated from the sponge Stylissa massa collected in the South China Sea. Compound 1 is the first identified precursor metabolite of the classic 5/7/5 tricyclic skeleton with unesterified guanidine and carboxyl groups, compounds 2-5 and 13-15 belong to the spongiacidin-type pyrrole imidazole alkaloids (PIAs). Z- and E-configurations of the spongiacidin-type PIAs often appeared concomitantly and were distinguished by the chemical shift analysis of 13C NMR spectra. The structures of all twelve new compounds were determined by NMR, MS, and ECD analysis combined with single-crystal data of compounds 1, 5, and 10. In the aldose reductase (ALR2) inhibitory assay, six 5/7/5 tricyclic compounds (2-5, 13-15) displayed significant activities. Compounds 13 and 14, as the representative members of spongiacidin-PIAs, demonstrated their ALR2-targeted activities in SPR experiments with KD values of 12.5 and 6.9 µM, respectively.

Copper-Lithium-Doped Nanohydroxyapatite Modulates Mesenchymal Stem Cells Homing to Treat Glucocorticoids-Related Osteonecrosis of the Femoral Head.

In situ tissue regeneration has been demonstrated to promote bone repair. To identify a better approach for treating osteonecrosis of the femoral head (ONFH), we prepared scaffolds using copper-lithium-doped nanohydroxyapatite (Cu-Li-nHA), which has the potential to modulate mesenchymal stem cells (MSCs) homing. The scaffold was fabricated using the gas foaming method and the migration, angiogenesis, and osteogenesis activities of MSCs were detected using Transwell assays, tube formation assays, alkaline phosphatase and alizarin red S staining, respectively. We then implanted the Cu-Li-nHA scaffold into the femoral heads of ONFH rabbits, and CFSE labeled exogenous MSCs were injected intravenously to verify cell homing. The repair effect was subsequently examined using micro-CT and histological analysis in vivo. The results showed that Cu-Li-nHA significantly promoted MSCs migration and homing by upregulating the HIF-1α/SDF-1 pathway. The Cu-Li-nHA group showed optimal osteogenesis and angiogenesis and greater improvements in new bone formation in ONFH rabbits. To summarize, Cu-Li-nHA promoted homing and induced the osteogenic differentiation of MSCs, thereby enhancing bone regeneration during ONFH repair. Thus, Cu-Li-nHA implantation may serve as a potential therapeutic strategy for ONFH in the future.

Identification of a Solute Carrier Family-Based Signature for Predicting Overall Survival in Osteosarcoma.

Given the important role of SLC family in essential physiological processes including nutrient uptake, ion transport, and waste removal, and that their dysregulation was found in distinct forms of cancer, here we identified a novel gene signature of SLC family for patient risk stratification in osteosarcoma. Gene expression data and relevant clinical materials of osteosarcoma samples were retrieved from The Cancer Genome Atlas (TCGA) database. Prognosis-related SLC genes were identified by performing univariate Cox regression analysis and were utilized to construct a four-SLC gene signature in osteosarcoma. It allowed patients to be classified into high- and low-risk groups, and Kaplan-Meier survival analysis in the training, testing, entire, and external GSE21257 cohorts suggested that the overall survival of patients in high-risk group was consistently worse than that in low-risk group, suggesting the promising accuracy and generalizability of the SLC-based signature in predicting the prognosis of patients with osteosarcoma. Moreover, univariate and multivariate Cox regression analyses indicated that the derived risk score was the only independent prognostic factor for osteosarcoma patients in TCGA and GSE21257 cohorts. Besides, a prognostic nomogram comprising the derived risk score and clinical features including gender and age was developed for clinical decision-making. Functional enrichment analyses of the differentially expressed genes between high- and low-risk group revealed that immune-related biological processes and pathways were significantly enriched. Estimation of tumor immune microenvironment using ESTIMATE algorithm revealed that patients with lower risk score had higher stromal, immune, and ESTIMATE score, and lower tumor purity. ssGSEA analyses indicated that the scores of various immune subpopulations including CD8+ T cells, DCs, and TIL were lower in high-risk group than these in low-risk group in both cohorts. As for the related immune functions, the scores of APC co-inhibition, CCR, check-point, T cell co-stimulation, and Type II IFN response were lower in high-risk group than these in low-risk group in both cohorts. In all, we identified a novel prognostic signature based on four SLC family genes that accurately predicted overall survival in osteosarcoma patients. Furthermore, the signature is linked to differences in immunological status and immune cell infiltrations in the tumor microenvironment.

Enhanced Fenton removal of phenol catalyzed by a modified red mud derived from the reduction of oxalic acid and L-ascorbic acid.

Red mud, a bauxite residue generated during alumina production through the Bayer process, contains oxides of Fe, Ti, Al, Mn, and rare earths, and has a latent performance for catalytic removal of phenol. We proposed a novel and facile approach for red mud modification by the reduction of oxalic acid and L-ascorbic acid in the acidic solution. By surveying characteristics of modified red mud and influencing factors of phenol removal, the optimum experiment conditions and the possible mechanism were explored, respectively. The results demonstrated that RO2V2 (treated red mud using 2 g of oxalic acid dehydrate and 2 g of L-ascorbic acid) and RO3V3 (treated red mud using 3 g of oxalic acid dehydrate and 3 g of L-ascorbic acid) showed the most efficient catalytic capacity for the phenol removal and removal efficiency of over 99.1% for the 200 mg/L of phenol solution within 5 min among investigated catalysts with the pH decreasing from 6.7 to 3. The excellent catalytic performance of modified red mud profited from the production of Fe3O4, Fe2O3, Mn2O3, Fe2SiO4, and FeTiO3 in the catalysts. It was motivating for removal of phenol to increase the dosage of catalyst and H2O2. The rate constants of the pseudo-first-order kinetics model of RO2V2 and RO3V3 were 1.0 and 1.073, respectively. The results of continuous experiments provided a positive reference for a future pilot scale test.

Adaptively Regularized Bases-Expansion Subspace Optimization Methods for Electrical Impedance Tomography.

OBJECTIVE: In this work, to deal with the difficulties in choosing regularization weighting parameters and low spatial resolution problems in difference electrical impedance tomography (EIT), we propose two adaptively regularized bases-expansion subspace optimization methods (AR-BE-SOMs). METHODS: Firstly, an adaptive L1-norm based total variation (TV) regularization is introduced under the framework of BE-SOM. Secondly, besides the additive regularization method, an adaptive weighted L2-norm multiplicative regularization is further proposed. The regularized objective functions are optimized by conjugate gradient method, where the unknowns in both methods are updated alternatively between induced contrast current (ICC) and conductivity domain. CONCLUSION: Both numerical and experimental tests are conducted to validate the proposed methods, where AR-BE-SOMs show better edge-preserving, anti-noise performance, lower relative errors, and higher structure similarity indexes than BE-SOM. SIGNIFICANCE: Unlike the common regularization techniques in EIT, the proposed regularization factors can be obtained adaptively during the optimization process. More importantly, AR-BE-SOMs perform well in reconstructions of some challenging geometry with sharp corners such as the "heart and lung" phantoms, deformation phantoms, triangles and even rectangles. It is expected that the proposed AR-BE-SOMs will find their applications for high-quality lung health monitoring and other clinical applications.

Emergency use of COVID-19 vaccines recommended by the World Health Organization (WHO) as of June 2021.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the outbreak of coronavirus disease 2019 (COVID-19), and the resulting pandemic has caused widespread health problems and social and economic disruption. Thus far in 2021, more than 4 million people worldwide have died from COVID-19, so safe and efficacious vaccines are urgently needed to restore normal economic and social activities. According to the official guidance documents of the World Health Organization (WHO), vaccines based on four major strategies including mRNA, adenoviral vectors, inactivated viruses, and recombinant proteins have entered the stage of emergency use authorization and pre-certification evaluation. The current review summarizes these vaccines and it looks ahead to the development of additional COVID-19 vaccines in the future.