3D bioprinting bioglass to construct vascularized full-thickness skin substitutes for wound healing.

Constructing three-dimensional (3D) bioprinted skin tissues that accurately replicate the mechanical properties of native skin and provide adequate oxygen and nutrient support remains a formidable challenge. In this study, we incorporated phosphosilicate calcium bioglasses (PSCs), a type of bioactive glass (BG), into the bioinks used for 3D bioprinting. The resulting bioink exhibited mechanical properties and biocompatibility that closely resembled those of natural skin. Utilizing 3D bioprinting technology, we successfully fabricated full-thickness skin substitutes, which underwent comprehensive evaluation to assess their regenerative potential in treating full-thickness skin injuries in rats. Remarkably, the skin substitutes loaded with PSCs exhibited exceptional angiogenic activity, as evidenced by the upregulation of angiogenesis-related genes in vitro and the observation of enhanced vascularization in wound tissue sections in vivo. These findings conclusively demonstrated the outstanding efficacy of PSCs in promoting angiogenesis and facilitating the repair of full-thickness skin wounds. The insights garnered from this study provide a valuable reference strategy for the development of skin tissue grafts with potent angiogenesis-inducing capabilities.

Sirt6 regulates the proliferation of neural precursor cells and cortical neurogenesis in mice.

Sirt6, a member of the class III histone deacetylases (HDACs), functions in the regulation of genomic stability, DNA repair, cancer, metabolism and aging. Sirt6 deficiency is lethal, and newborn SIRT6-null cynomolgus monkeys show unfinished brain development. After the generation of a cortex-specific Sirt6 conditional knockout mouse model, we investigated the specific deletion of Sirt6 in NPCs at E10.5. This study found that Sirt6 deficiency causes excessive proliferation of neural precursor cells (NPCs) and retards differentiation. The results suggest that endogenous Sirt6 in NPCs regulates histone acetylation and limits stemness-related genes, including Notch1, in order to participate in NPC fate determination. These findings help elucidate Sirt6's role in brain development and in NPC fate determination while providing data on species generality and differentiation.

Robust shape-based template matching algorithm for target localization under SEM.

A novel acceleration algorithm for geometric template matching is proposed based on the Cauchy-Schwartz inequality (C-S inequality) in this paper. The proposed approach is validated under a scanning electron microscope (SEM), and its effectiveness is demonstrated. In this approach, the object shape features are represented as column vectors with complex elements. Then, a threshold is determined to exclude the sliding windows without any matched objects. Finally, surface fitting is employed to obtain the subpixel positions of the targets, and least squares adjustment is utilized to fine-tune the obtained results. The experimental results demonstrate that the proposed method can significantly reduce the matching time by 59% - 96% compared with the traditional shape-based method. Furthermore, the strong robustness and high accuracy are verified under different disturbances. Additionally, the approach is shown to be robust and accurate under different types of disturbances, thus confirming its suitability for real-time targets tracking on SEM with high accuracy.

3D bioprinting microgels to construct implantable vascular tissue.

Engineered implantable functional thick tissues require hierarchical vasculatures within cell-laden hydrogel that can mechanically withstand the shear stress from perfusion and facilitate angiogenesis for nutrient transfer. Yet current extrusion-based 3D printing strategies are unable to recapitulate hierarchical networks, highlighting the need for bioinks with tunable properties. Here, we introduce an approach whereby crosslinkable microgels enhance mechanical stability and induce spontaneous microvascular networks comprised of human umbilical cord vein endothelial cells (HUVECs) in a soft gelatin methacryoyl (GelMA)-based bioink. Furthermore, we successfully implanted the 3D printed multi-branched tissue, being connected from the rat carotid artery to the jugular vein direct surgical anastomosis. The work represents a significant step toward in the field of large vascularized tissue fabrication and may have implications for the treatment of organ failure in the future.

RNA-sequencing analysis reveals the potential molecular mechanism of RAD54B in the proliferation of inflamed human dental pulp cells.

AIM: To investigate the role of RAD54B in the proliferation of inflamed human dental pulp cells (hDPCs) induced by lipopolysaccharide (LPS). METHODOLOGY: Normal, carious and pulpitic human dental pulp tissues were collected. Total RNA was subjected to RNA-sequencing (seq) and gene expression profiles were studied by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differentially expressed genes (DEGs) in homologous recombination repair (HRR) were validated with qRT-PCR. The expression of RAD54B and TNF-α in human dental pulp tissues was detected using immunohistochemistry. HDPCs were cultured and RAD54B level in hDPCs was detected after LPS stimulation using western blot. CCK-8 was used to investigate the proliferation of hDPCs transfected with negative control (Nc) small interfering RNA (siRNA), RAD54B siRNA, P53 siRNA or both siRNAs with or without LPS stimulation. Flow cytometry was used to detect the cell cycle distribution, and western blot and immunofluorescence were used to analyse the expression of RAD54B, P53 and P21 under the above treatments. One-way and two-way anova followed by least significant difference posttest were used for statistical analysis. RESULTS: RNA-seq results identified DEGs amongst the three groups. KEGG pathway analysis revealed enrichment of DEGs in the replication and repair pathway. HRR and non-homologous end joining (NHEJ) components were further verified and qRT-PCR results were basically consistent with the sequencing data. RAD54B, an HRR accessory factor highly expressed in carious and pulpitic tissues as compared to that in normal pulps, was chosen as our gene of interest. High RAD54B expression was confirmed in inflamed human dental pulp tissues and LPS-stimulated hDPCs. Upon RAD54B knockdown, P53 and P21 expressions in hDPCs were upregulated whereas the proliferation was significantly downregulated, accompanied by increased G2/M phase arrest. After inhibiting P53 expression in RAD54B-knockdown hDPCs, P21 expression and cell proliferation were reversed. CONCLUSIONS: Gene expression profiles of normal, carious and pulpitic human dental pulp tissues were revealed. HRR components were elucidated to function in dental pulp inflammation. Amongst the DEGs in HRR, RAD54B regulated the proliferation of inflamed hDPCs via P53/P21 signalling. This research deepens our understanding of dental pulp inflammation and provides new insight to clarify the underlying mechanisms.

Polyurethane-gelatin methacryloyl hybrid ink for 3D printing of biocompatible and tough vascular networks.

A polyurethane-gelatin methacryloyl (PU-GelMA) hybrid ink was developed as a photo-crosslinkable elastic hydrogel. With the additional acrylic monomer, the ink can be tuned to accommodate elasticity and printability. Attributed to the shear-thinning properties of GelMA, PU-GelMA was preferable for extrusion printing. 3D-constructs were printed by direct extrusion or by using a sacrificial scaffold to resemble the vascular networks. The proliferation of endothelial cells on the PU-GelMA hydrogel indicated decent biocompatibility and potential utilization in artificial vessels.

Identification of maternal serum biomarkers for prenatal diagnosis of nonsyndromic orofacial clefts.

Nonsyndromic orofacial clefts (NSOFCs) are the most common congenital defects in the oral and maxillofacial regions. It is mainly diagnosed prenatally through fetal ultrasonography. However, the accuracy of ultrasonography for NSOFC is unreliable. Maternal serological screening is a noninvasive method for the diagnosis of fetal malformations. In our study, we sought to identify specific biomarkers in maternal serum for predicting NSOFC prenatally. We quantified the alterations in maternal serum protein profiles between 20 pregnant women with NSOFC fetuses and 20 pregnant women with healthy fetuses by using isobaric tags for relative and absolute quantitation-based mass spectrometry (MS). The serum levels of 75 elevated and 50 decreased proteins in the NSOFC group were detected. Twenty-eight candidate biomarkers were selected for further confirmation by multiple reaction monitoring-MS; of these, 16 proteins were found to be significantly different. More importantly, the levels of three proteins (APOA, HPT, and CRP) were verified by ELISAs to be obviously altered in serum from pregnancies carrying fetuses with NSOFC. Our results indicate that analysis of the maternal serum proteome is a feasible strategy for biomarker discovery of NSOFC, and APOA, HPT, and CRP proteins are potential serum biomarkers for prenatal diagnosis of NSOFC.

Identification of Hub Gene GRIN1 Correlated with Histological Grade and Prognosis of Glioma by Weighted Gene Coexpression Network Analysis.

The function of glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) in neurodegenerative diseases has been widely reported; however, its role in the occurrence of glioma remains less explored. We obtained clinical data and transcriptome data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Hub gene's expression differential analysis and survival analysis were conducted by browsing the Gene Expression Profiling Interactive Analysis (GEPIA) database, Human Protein Atlas database, and LOGpc database. We conducted a variation analysis of datasets obtained from GEO and TCGA and performed a weighted gene coexpression network analysis (WGCNA) using the R programming language (3.6.3). Kaplan-Meier (KM) analysis was used to calculate the prognostic value of GRIN1. Finally, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Using STRING, we constructed a protein-protein interaction (PPI) network. Cytoscape software, a prerequisite of visualizing core genes, was installed, and CytoHubba detected the 10 most tumor-related core genes. We identified 185 differentially expressed genes (DEGs). GO and KEGG enrichment analyses illustrated that the identified DEGs are imperative in different biological functions and ascertained the potential pathways in which the DEGs may be enriched. The overall survival calculated by KM analysis showed that patients with lower expression of GRIN1 had worse prognoses than patients with higher expression of GRIN1 (p = 0.004). The GEPIA and LOGpc databases were used to verify the expression difference of GRIN1 among GBM, LGG, and normal brain tissues. Ultimately, immunohistochemical assay results showed that GRIN1 was detected in normal tissue and not in the tumor specimens. Our results highlight a potential target for glioma treatment and will further our understanding of the molecular mechanisms underlying the treatment of glioma.

3D Liver Tissue Model with Branched Vascular Networks by Multimaterial Bioprinting.

Complicated vessels pervade almost all body tissues and influence the pathophysiology of the human body significantly. However, current fabrication strategies have limited success at multiscale vascular biofabrication. This study reports a methodology to fabricate soft vascularized tissue at centimeter scale using multimaterial bioprinting by a customized multistage-temperature-control printer. The printed constructs can be perfused via the branched endothelialized vasculatures to support the well-formed 3D capillary networks, which ensure cellular activities with sufficient nutrient supply and then mimic a mature and functional liver tissue in terms of synthesis of liver-specific proteins. Moreover, an inner and external pressure-bearing layer is printed to support the direct surgical anastomosis of the carotid artery to the jugular vein. In summary, a versatile platform to recapitulate the vasculature network is presented, in which case sustaining the optimal cellularization in engineered tissues is achievable.

Upregulated bone morphogenetic protein 5 enhances proliferation and epithelial-mesenchymal transition process in benign prostatic hyperplasia via BMP/Smad signaling pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is one of the most common illnesses in aging men. Recent studies found that bone morphogenetic protein 5 (BMP5) is upregulated in BPH tissues, however, the role of BMP5 in the development of BPH has not been examined. The current study aims to elucidate the potential roles of BMP5 and related signaling pathways in BPH. METHODS: Human prostate cell lines (BPH-1, WPMY-1) and human/rat hyperplastic prostate tissues were utilized. Western blot, quantitative real-time polymerase chain reaction, immunofluorescent staining, and immunohistochemical staining were performed. BMP5-silenced and -overexpressed cell models were generated and then cell cycle progression, apoptosis, and proliferation were determined. The epithelial-mesenchymal transition (EMT) was also quantitated. And rescue experiments by BMP/Smad signaling pathway agonist or antagonist were accomplished. Moreover, BPH-related tissue microarray analysis was performed and associations between clinical parameters and expression of BMP5 were analyzed. RESULTS: Our study demonstrated that BMP5 was upregulated in human and rat hyperplastic tissues and localized both in the epithelial and stromal compartments of the prostate tissues. E-cadherin was downregulated in hyperplastic tissues, while N-cadherin and vimentin were upregulated. Overexpression of BMP5 enhanced cell proliferation and the EMT process via phosphorylation of Smad1/5/8, while knockdown of BMP5 induced cell cycle arrest at G0/G1 phase and blocked the EMT process. Moreover, a BMP/Smad signaling pathway agonist and antagonist reversed the effects of BMP5 silencing and overexpression, respectively. In addition, BMP5 expression positively correlated with prostate volume and total prostate-specific antigen. CONCLUSION: Our novel data suggest that BMP5 modulated cell proliferation and the EMT process through the BMP/Smad signaling pathway which could contribute to the development of BPH. However, further studies are required to determine the exact mechanism. Our study also indicated that BMP/Smad signaling may be rediscovered as a promising new therapeutic target for the treatment of BPH.

Susceptibility to DNA damage caused by abrogation of Rad54 homolog B: A putative mechanism for chemically induced cleft palate.

Exposure to environmental toxicants such as all-trans retinoic acid (atRA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may cause cleft palate (CP), which process is related to DNA damage. Rad54B, an important DNA damage repaired protein, has been proved to be associated with non-syndromic cleft lip with palate (NSCLP). In the present study, we sought to clarify the role of Rad54B in palatal development and environment-induced CP. atRA (100 mg/kg) and TCDD (40 µg/kg) were used to induce CP in mice (C57BL/6 J mice). In this study, mouse embryonic heads were collected on embryonic day (E) 13.5∼16.5. The expression level of DNA repair protein Rad54 homolog B (Rad54B) was significantly decreased while those of the DNA double-strand breaks (DSBs) marker γ-H2A.X, apoptosis marker caspase-3 and p53 were significantly increased in the palatal shelves upon exposure to atRA and TCDD relative to the control. Primary mouse embryonic palatal mesenchymal cells (MEPMs) were cultured and transfected with siRNA or adenovirus in vitro to knock down or increase the level of Rad54B. Rad54B knockdown resulted in increased cellular S-phase arrest and apoptosis as well as decreased cell proliferation. Rad54B overexpression also increased apoptosis and reduced cell proliferation. Western blotting was used to detect the level of γ-H2A.X in transfected cells stimulated with etoposide (ETO, a DSBs inducer), and after 5 µM ETO stimulation of transfected MEPMs, the expression of γ-H2A.X was increased in Rad54B-knockdown cells. The expression of Mdm2, Mdmx and p53 with changes in Rad54B was also detected and coimmunoprecipitation was performed to analyze the combination of Mdm2 and p53 when Rad54B was changed in MEPMs. Knockdown of Rad54B inhibited the expression of Mdm2 and Mdmx, while the level of p53 increased. The coimmunoprecipitation results showed a decreased combination of Mdm2 and p53 when Rad54B was knocked down. Therefore, Rad54B can regulate the cell cycle, proliferation, and apoptosis of MEPMs. The loss of Rad54B increased the sensitivity of MEPMs to DSBs inducers, promoted apoptosis, and suppressed the proliferation of MEPMs by inhibiting the degradation of p53. Taken together, these findings suggest that Rad54B may play a key regulatory role in environment-induced CP.

Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis.

Tongue cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, cell morphological observation, scratch wound-healing assay, transwell migration assay, transmission electron microscope, flow cytometry and cellular reactive oxygen species were assessed in vitro. The results showed that quisinostat can significantly inhibit the viability, growth and migration of TSCC cells. And quisinostat could significantly induce TSCC cells apoptosis, pyroptosis, and ferroptosis. Quisinostat significantly inhibited tumor tissue growth in animal experiments. Up-regulation of the expression of Bax, cleaved-caspase3, caspase-1, p53, phospho-p53 and down-regulated of the expression of caspase-3, Bcl-2, GPX4 in cell lines and tumor tissues of nude mice were observed by Western blotting analysis. Up-regulation of the expression of caspase-1, Bax, cleaved-caspase3, p53 and down-regulated of the expression of ki67, caspase-3, Bcl-2, GPX4 in tumor tissues of nude mice were observed by immunohistochemistry. TUNEL analysis showed that quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Based on these findings, quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.

RNA-seq analysis of palatal transcriptome changes in all-trans retinoic acid-induced cleft palate of mice.

Cleft palate is a common congenital maxillofacial malformation in newborns. All-trans retinoic acid (atRA) is an ideal exogenous stimulus to construct a mouse cleft palate model. However, the precise pathogenic mechanism remains to be elucidated. In our study, to explore the toxicity of atRA on palatal shelves during different stages of palate development, a total of 100 mg/kg atRA was administered to C57BL/6 mice at embryonic day 10.5 (E10.5). Mouse embryonic palatal shelves at E13.5, E14.5, E15.5, and E16.5 were collected for RNA extraction and histological treatment. Changes in gene expression were tested through RNA-seq. Selected differentially expressed genes (DEGs) related to metabolic pathways, such as Ptgds, Ttr, Cyp2g1, Ugt2a1 and Mgst3, were validated and analyzed by Quantitative real-time PCR (qRT-PCR). In addition, Gene Oncology analysis showed that transcriptional changes of genes from extracellular matrix (ECM) components, such as Spp1, and crystallin family might play important role in palatal shelves elevation (E13.5-E14.5). Therefore, the protein expression level of Ttr and Spp1 from E13.5 to E16.5 were tested by immunohistochemistry (IHC). Besides, the mRNA level of Spp1, were down-regulated at E16.5 and the protein were down-regulated at E15.5 and E16.5 in all-trans retinoic acid group, suggesting that atRA may involve in palatal bone formation by regulating Spp1. Overall, gene transcriptional profiles were obviously different at each time point of palate development. Thus, this study summarized some pathways and genes that may be related to palatogenesis and cleft palate through RNA-seq, to provide a direction for subsequent studies on the mechanism and targeted therapy of cleft palate.

Ginkgolic Acid, a SUMO-1 Inhibitor, Inhibits the Progression of Oral Squamous Cell Carcinoma by Alleviating SUMOylation of SMAD4.

Small ubiquitin-related modifiers (SUMO) represent a class of ubiquitin-like proteins that are conjugated, like ubiquitin, by a set of enzymes to form cellular regulatory proteins, and play key roles in the control of cell proliferation, differentiation, and apoptosis. We found that ginkgolic acid (GA) can significantly reduce cell vitality in a dose- and time-dependent manner and can also accelerate cyto-apoptosis in both Tca8113 and Cal-27 cells. Migration and wound-healing assays were executed to determine the anti-migration effect of GA in oral squamous cell carcinoma (OSCC) cell lines. GA represses transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) markers in OSCC cell lines. This investigation is the first evidence that GA suppresses TGF-ß1-induced SUMOylation of SMAD4. We show that GA affects the phosphorylation of SMAD2/3 protein and the release of SMAD4. In the xenograft mouse model, the OSCC progression was reduced by GA, effectively suppressing the growth of tumors. In addition, siSMAD4 improved cell migration and viability, which was inhibited by GA in Tca8113 cells. GA suppresses tumorigenicity and tumor progression of OSCC through inhibition of TGF-ß1-induced enhancement of SUMOylation of SMAD4. Thus, GA could be a promising therapeutic for OSCC.

Colorimetric determination of ascorbic acid using a polyallylamine-stabilized IrO2/graphene oxide nanozyme as a peroxidase mimic.

The authors describe a peroxidase-mimicking nanozyme composed of IrO2 and graphene oxide (GO). It was synthesized from monodisperse IrO2 nanoparticles with an average diameter of 1.7 ± 0.3 nm that were prepared by pulsed laser ablation in ethanol. The nanoparticles were then placed on polyallylamine-modified GO nanosheets through electrostatic interaction. The peroxidase-like activity of the resulting nanocomposites was evaluated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. Kinetic results demonstrated that the catalytic behavior of the nanocomposites follows Michaelis-Menten kinetics. Experiments performed with terephthalic acid and cytochrome C confirmed that the peroxidase-like activity originated from the electron transfer mechanism rather than from generation of hydroxy radicals. The peroxidase-like activity is inhibited in the presence of ascorbic acid (AA). Based on this property, a colorimetric assay was developed for the determination of AA by exploiting the peroxidase-like activity of IrO2/GO nanocomposites. The linear relationship between absorbance at 652 nm and the concentration of AA was acquired. The limit of detection for AA is 324 nM. Further applications of the method for AA detection in real samples were also successfully demonstrated. Graphical abstractSchematic of the preparation of polyallylamine (PAH)-stabilized IrO2/GO nanocomposites and the colorimetric detection of AA based on the peroxidase-like activity of IrO2/GO nanocomposites.

Facile synthesis of IrO2/rGO nanocomposites with high peroxidase-like activity for sensitive colorimetric detection of low weight biothiols.

In this work, we reported a novel nanozyme synthesized by decorating highly dispersed ultrafine IrO2 nanoparticles on reduced graphene oxide (rGO) nanosheets via a simple hydrothermal method. The as-prepared IrO2/rGO nanocomposites exhibited intrinsic peroxidase-like activity and could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue product in the presence of H2O2. Catalytic kinetic of IrO2/rGO nanocomposites followed Michaelis-Menten behavior, exhibiting a higher affinity to TMB than horseradish peroxidase (HRP) enzyme. Catalytic mechanism studies suggested that the peroxidase-like activity of IrO2/rGO nanocomposites originated from their ability of electron transfer between substrate and H2O2. On the basis of high peroxidase-like activity of IrO2/rGO nanocomposites, a colorimetric strategy for rapid and sensitive detection of low weight biothiols was developed. The colorimetric detection assays for low weight biothiols showed high selectivity against other amino acids. Therefore, the IrO2/rGO nanozyme is expected for promising potential applications in the biosensor, diagnostics and environment.

Multifunctional inhibitors of ß-amyloid aggregation based on MoS2/AuNR nanocomposites with high near-infrared absorption.

Recent advances in nanotechnology have developed a lot of opportunities for biological applications. In this work, multifunctional MoS2/AuNR nanocomposites with unique high NIR absorption were designed via combining MoS2 nanosheets and gold nanorods (AuNRs). The nanocomposites were synthesized through electrostatic self-assembly and showed high stability and good biocompatibility. Then they were used to modulate the aggregation of amyloid-ß peptides, destabilize mature fibrils under NIR irradiation, and eliminate Aß-induced ROS against neurotoxicity. The inhibition and destabilization effects were confirmed by Thioflavin T (ThT) fluorescence assay and transmission electron microscopy (TEM). Cell viability assay and ROS assay revealed that MoS2/AuNR nanocomposites could alleviate Aß-induced oxidative stress and cell toxicity. More importantly, both MoS2 nanosheets and AuNRs can be used as NIR photothermal agents, MoS2/AuNR nanocomposites have enhanced ability of disrupting Aß fibrils and improved cell viability by generating local heat under low power NIR irradiation. Our results provide new insights into the design of new multifunctional systems for the treatment of amyloid-related diseases.

MoO3-x nanodots with dual enzyme mimic activities as multifunctional modulators for amyloid assembly and neurotoxicity.

Development of effective inhibitors toward Aß aggregation and reactive oxygen species (ROS) scavengers are of crucial therapeutic implications for Alzheimer's disease (AD). Herein, a novel agent with dual enzyme mimic activities has been fabricated as a multifunctional Aß fibrillation modulator. MoO3-x nanodots were synthesized by pulsed laser ablation (PLA) method in MoS2 nanosheets solutions, which may act directly as numerous fine targets. MoO3-x nanodots showed a uniform and monodispersed morphology, and the tiny dots were around 3-5 nm with a narrow size distribution. Due to the efficient charge transition between Mo5+/Mo6+ on the dots surface, MoO3-x nanodots exhibited excellent catalase and SOD mimic activities, which were adopted to alleviate Aß-mediated oxidative stress. Moreover, MoO3-x nanodots can efficiently inhibit Aß aggregation and destabilize the preformed fibrils, and eventually protect neuronal cells from apoptosis induced by Aß. Taken together, MoO3-x nanodots with multifunctional roles can act as a potential therapeutic strategy for treatment of amyloid induced neurotoxicity.

Controllable fabrication of magnetic core-shell nanocomposites with high peroxide mimetic properties for bacterial detection and antibacterial applications.

Pathogenic bacterial infection has become a growing threat to public health; therefore, exploration of a sensitive and specific method for the identification of bacteria is very important. In this report, we fabricated a new magnetic core-shell nanocomposite with a homogenous morphology. The Fe3O4 nanoparticle core with a diameter of 15 nm was coated with a thin silica layer, and the thickness of the layer was finely adjusted to about 10 nm. Pt nanoclusters with a diameter of 2-3 nm were anchored uniformly on the surface to form Fe3O4@SiO2-Pt nanocomposites. These nanocomposites exhibited excellent peroxide enzyme activity and acted as a signal-output probe for the identification of pathogenic bacteria. This strategy was also based on using vancomycin (Van) as the capture agent in an ELISA procedure. The detection limit for S. aureus was around 1 × 101 cfu mL-1. Furthermore, Fe3O4@Si-Pt nanocomposites also show ideal bacteria separation and inhibition effects, and can act as a multifunctional platform for bacterial detection and antibacterial applications.

Role of Ku70 in the apoptosis of inflamed dental pulp stem cells.

AIM: The study aimed to investigate the effects of DNA repair proteins on cell apoptosis in human DPSCs during inflammation. METHODS: Lipopolysaccharide (LPS) was used to stimulate inflammation in dental pulp in vivo and in vitro. We identified the activation of DSB response and DNA repair proteins in inflamed pulp tissue and in LPS-treated human DPSCs. Then we transfected the cells with Ku70 (a key protein involved in NHEJ) siRNA and detected the expression changes of γ-H2A.X, DNA repair proteins and cell apoptosis. RESULTS: Immunohistochemical staining showed that at 4 and 6 days of pulpitis the expression of Ku70 and γ-H2A.X significantly increased. The levels of γ-H2A.X, Ku70, Xrcc4, and Rad51 increased considerably in the LPS-treated DPSCs. Furthermore, decreased expression of Ku70 could increase the number of γ-H2A.X foci, apoptotic cells and reduce cell viability in DPSCs. CONCLUSIONS: The results indicate that NHEJ pathway was the main mechanism involved in DNA damage response induced by repeated LPS stimulation in DPSCs. Meanwhile, the findings suggested that Ku70 serves importantly in the apoptosis of DPSCs in the inflammatory environment.