Enhancing the Biological Performance of Titanium Alloy through In Situ Modulation of the Surface Nanostructure: Near-Infrared-Responsive Antibacterial Function and Osteoinductivity.

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.

Association between falls and nonmotor symptoms in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a chronic neurodegenerative disorder. Falls are common in patients with PD and can lead to disability, bedridden status, and death. The mechanisms of falls induced by symptoms of PD have not been fully clarified. We investigated the association between falls and nonmotor symptoms in PD patients. METHODS: A total of 361 patients with Parkinson's disease were included. Whether the patients had fallen in the past half a year was recorded. Nonmotor symptoms were assessed by 30 items from the nonmotor symptom questionnaire (NMS Quest), Parkinson's Disease Sleep Scale (PDSS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Montreal Cognitive Assessment Scale (MOCA). RESULTS: A total of 63 patients experienced falls in the past six months, with an incidence of 17.5%. The patients with falls were elderly, had severe motor symptoms and disease severity, and the proportion of diabetic patients who experienced falls was higher. Adjusted for the above factors, the results showed that patients with falls had higher PD-NMS, HAMD and HAMA scores, but there was no significant difference in the total score and subscores of the MoCA scale between the two groups. The risk factors related to falling included age, history of diabetes, depression (HAMD), HAMD cognitive impairment, NMS urinary tract and NMS postural hypotension. CONCLUSIONS: Falls were a common symptom in patients with PD and were not only related to motor symptoms but also closely related to nonmotor symptoms. urinary tract symptoms, postural hypotension, depression and HAMD cognitive impairment were risk factors related to falling in patients with PD.

Constructing ROS-Responsive Supramolecular Gel with Innate Antibacterial Properties.

Bacterial infections, especially antibiotic-resistant bacterial infections, pose a significant threat to human health. Supramolecular gel with innate antibacterial properties is an advanced material for the treatment of bacterial infections, which have attracted great attention. Herein, a reactive oxygen species (ROS)-responsive innate antibacterial supramolecular gel is developed by a bottom-up approach based on phenylalanine and hydrazide with innate antibacterial properties. The structure of gelators and intermediate products was characterized by proton nuclear magnetic resonance (1H NMR) and a high-resolution mass spectrum (HRMS). The results of 1H NMR and the Fourier transform infrared spectrum (FT-IR) experiment disclosed that hydrogen bonding and the π-π stacking force are the important self-assembly driving forces of gelators. The microstructure and mechanical properties of gel were studied by Scanning electron microscope (SEM) and Rheometer, respectively. An in vitro degradation experiment proved that the gelator has ROS-responsive degradation properties. The in vitro drug release experiment further manifested that antibiotic-loaded gel has ROS-responsive drug-release performances. An in vitro cytotoxicity experiment showed that the supramolecular gel has good biocompatibility and could promote cell proliferation. The in vitro antibacterial experiment proved that the supramolecular gel has excellent inherent antibacterial properties, and the antibacterial rate against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was 98.6% and 99.1%, respectively. The ROS-responsive supramolecular gel as a novel antibacterial agent has great application prospects in treating antibiotic-resistant bacterial-infected wounds and preventing the development of bacterial resistance.

Dynamic interplay between IL-1 and WNT pathways in regulating dermal adipocyte lineage cells during skin development and wound regeneration.

Dermal adipocyte lineage cells are highly plastic and can undergo reversible differentiation and dedifferentiation in response to various stimuli. Using single-cell RNA sequencing of developing or wounded mouse skin, we classify dermal fibroblasts (dFBs) into distinct non-adipogenic and adipogenic cell states. Cell differentiation trajectory analyses identify IL-1-NF-κB and WNT-ß-catenin as top signaling pathways that positively and negatively associate with adipogenesis, respectively. Upon wounding, activation of adipocyte progenitors and wound-induced adipogenesis are mediated in part by neutrophils through the IL-1R-NF-κB-CREB signaling axis. In contrast, WNT activation, by WNT ligand and/or ablation of Gsk3, inhibits the adipogenic potential of dFBs but promotes lipolysis and dedifferentiation of mature adipocytes, contributing to myofibroblast formation. Finally, sustained WNT activation and inhibition of adipogenesis is seen in human keloids. These data reveal molecular mechanisms underlying the plasticity of dermal adipocyte lineage cells, defining potential therapeutic targets for defective wound healing and scar formation.

Edge Computing Deployment Algorithm and Sports Training Data Mining Based on Software Defined Network.

The wireless sensor network collects data from various areas through specific network nodes and uploads it to the decision-making layer for analysis and processing. Therefore, it has become a perception network of the Internet of Things and has made great achievements in monitoring and prevention at this stage. At this stage, the main problem is the motive power of sensor nodes, so the energy storage and transmission of wireless sensor network is imminent. Mobile edge computing technology provides a new type of technology for today's edge networks, enabling it to process resource-intensive data blocks and feedback to managers in time. It is a new starting point for cloud computing services, compared to traditional cloud computing services. The transmission speed is more efficient and will be widely used in various industries and serve them in the future. Among them, education and related industries urgently need in-depth information, which in turn promotes the rapid development of data mining by sensor networks. This article focuses on data mining technology, mainly expounds the meaning and main mining methods of data mining technology, and conducts data mining on sports training requirements from the aspects of demand collection and analysis, algorithm design and optimization, demand results and realization, etc. Monitor the training status and give the trainer reasonable suggestions. Through the processing of the training data mining results and proofreading the database standardized training data, we can formulate a personalized program suitable for sportsmen, reduce sports injuries caused by no trainer's guidance, and open new doors for training modes. Therefore, this paper studies the sensor network technology, edge computing deployment algorithm, and sports training data mining.

NIR-Responsive TiO2 Biometasurfaces: Toward In Situ Photodynamic Antibacterial Therapy for Biomedical Implants.

Implant-related microbial infection is a challenging clinical problem, and its treatment requires efficient eradication of the biofilm from the implant surface. Near-infrared (NIR)-responsive strategies are proposed as an emerging efficient antibacterial therapy. However, the utilization of photosensitizers or photocatalytic/photothermal nanomaterials in the available approach likely induces high potential risks of interfacial deterioration and biosafety compromise. Herein, a TiO2 /TiO2- x metasurface with potent NIR-responsive antibacterial activity is produced on a Ti alloy implant by a newly invented topochemical conversion-based alkaline-acid bidirectional hydrothermal method (aaBH). Electromagnetic simulations prove that NIR absorption and near-field distribution of the metasurface can be tuned by the dimension and arrangement of the nanostructural unit. Promising antibacterial efficacy is proved by both in vitro and in vivo tests, with low-power NIR irradiation for 10 min. Besides, the designed nanostructure in the metasurface itself also shows excellence in enhancing the adhesion-related gene expression of human gingival fibroblasts that are exposed to 10 min of NIR irradiation, proving the potent nanostructure-induced biological effects. This work provides a biosafe and upscalable metasurfacing approach with extraordinary capacity of manipulating light adsorption, photocatalysis, and biological properties.

User performance effects with graphical icons and training for elderly novice users: A case study on automatic teller machines.

This study investigated the effects with training and graphical icons on task performance for elderly novice users on automatic teller machines (ATMs). 124 elderly novice users who had no prior ATM experience participated in the training and test of ATM usage. Participants in the control group (n = 62) were training to use the traditional text-based ATM interface meanwhile those in the experimental group (n = 62) were training to use the alternative ATM interface with graphical icons. They were asked to learn how to perform three major tasks of ATMs. A test immediately following the training and a test one month after training was carried out. Task completion score was used for measuring user performance. The results showed although training could help elderly novice users succeed in learning to use ATMs, they still had a significant decline in user performance in the test one month later compared with the immediate test. Participants of the experimental group outperformed those of the control group in both the immediate test and one month test after training, especially in the latter. The finding suggested graphical icons could help to improve the learning and retention of ATM usage for elderly novice users, especially the latter, which would compensate for the drawback of training and reduce forgetting rate to some extent. Well-designed graphical icons could benefit elderly novice users much from learning phase to retention phase. The findings of this study can be applied to guide the design and development of ATMs or other public technology devices considering elderly novice users.

Multi-affinity sites of magnetic guanidyl-functionalized metal-organic framework nanospheres for efficient enrichment of global phosphopeptides.

Magnetic guanidyl-functionalized metal-organic framework (MOF) nanospheres with multi-affinity sites composed of an inherent Zn-O cluster based on MOAC and specific recognized groups (amino group and guanidyl group) were for the first time synthesized by a combination strategy of epitaxial growth and post-synthetic modification of magnetic amino-derived MOFs, and they exhibit great potential for efficient enrichment of global phosphopeptides.

Polyethylene Glycol-Functionalized Magnetic Fe3O4/P(MMA-AA) Composite Nanoparticles Enhancing Efficient Capture of Circulating Tumor Cells.

Circulating tumor cells (CTCs) played a significant role in early diagnosis and prognosis of carcinomas, and efficient capture of CTCs was highly desired to provide important and reliable evidence for clinical diagnosis. In present work, we successfully synthesized functional magnetic Fe3O4/P(MMA-AA) composite nanoparticles (FCNPs) inspired by a counterbalance concept for recognition and capture of CTCs. This counterbalance, composed of polyethylene glycol (PEG) suppressing cell adhesion and anti-epithelial-cell-adhesion-molecule (anti-EpCAM) antibody targeting tumor cells, could both enhance the specific capture of tumor cells and reduce unspecific adhesion of normal cells. The study showed that the PEG density on the surface of the FCNPs affected the specificity of the materials, and a density of ca. 15% was efficient for reducing the unspecific adhesion. After incubation with the mixture of HepG2 cells and Jurkat T cells, the FCNPs reached a capture efficiency as high as about 86.5% of the cancer cells, suggesting great potential on detection of CTCs in the diagnoses and prognoses of cancer metastasis.

Dopamine self-polymerized along with hydroxyapatite onto the preactivated titanium percutaneous implants surface to promote human gingival fibroblast behavior and antimicrobial activity for biological sealing.

The clinical success of dental implants requires not only the optimum osseointegration but also the integration of implant surface with soft tissues to form biological sealing. In this study, alkali-heat treatment was applied to modify the pure titanium surface constructing a unique micro-and nano-structure. Then, poly(dopamine), along and with the additional incorporation of hydroxyapatite and carboxymethyl chitosan have been successfully infiltrated into the preactivated Ti surface during dopamine self-polymerization proceeding. Here, the effects of poly(dopamine)-modified surface coating on the biological behaviors of human gingival fibroblasts (HGFs) and oral pathogens have been systematically studied, which was critical for the early peri-implant soft tissue integration. The results showed that the poly(dopamine)-modified alkali-heat-titanium surface was a superior substrate for human gingival fibroblast adhesion, spread and proliferation. Moreover, further enhancements on cytoskeleton organization, collagen secretion and fibronectin adsorption were generally observed through the additional incorporation of hydroxyapatite. The addition of carboxymethyl chitosan exerted a positive modulation effect on antibacterial activity. Overall, our study demonstrated that combined superior soft tissue integration and antibacterial activity can be achieved by using poly(dopamine)-modified titanium implant, which has great potential in the optimal design of dental implant.

Anti-Bacteria and Microecosystem-Regulating Effects of Dental Implant Coated with Dimethylaminododecyl Methacrylate.

The effects of dimethylaminododecyl methacrylate (DMADDM) modified titanium implants on bacterial activity and microbial ecosystem of saliva-derived biofilm were investigated for the first time. Titanium discs were coated with DMADDM solutions at mass fractions of 0 mg/mL (control), 1, 5 and 10 mg/mL, respectively. Biomass accumulation and metabolic activity of biofilms were tested using crystal violet assay and MTT (3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. 16S rRNA gene sequencing was performed to measure the microbial community. Live/dead staining and scanning electron microscopy (SEM) were used to value the structure of biofilm. The results showed that the higher mass fraction of DMADDM the coating solution had, the significantly lower the values of metabolic activity and accumulated biofilms got, as well as fewer live cells and less extracellular matrix. Moreover, 5 mg/mL of DMADDM was the most effective concentration, as well as 10 mg/mL. In microecosystem-regulation, the DMADDM modified titanium implant decreased the relative abundance of Neisseria and Actinomyces and increased the relative abundance of Lactobacillus, a probiotic for peri-implant diseases. In conclusion, via inhibiting growth and regulating microecosystem of biofilm, this novel titanium implant coating with DMADDM was promising in preventing peri-implant disease in an 'ecological manner'.

Protein Corona of Magnetic Hydroxyapatite Scaffold Improves Cell Proliferation via Activation of Mitogen-Activated Protein Kinase Signaling Pathway.

The beneficial effect of magnetic scaffolds on the improvement of cell proliferation has been well documented. Nevertheless, the underlying mechanisms about the magnetic scaffolds stimulating cell proliferation remain largely unknown. Once the scaffold enters into the biological fluids, a protein corona forms and directly influences the biological function of scaffold. This study aimed at investigating the formation of protein coronas on hydroxyapatite (HA) and magnetic hydroxyapatite (MHA) scaffolds in vitro and in vivo, and consequently its effect on regulating cell proliferation. The results demonstrated that magnetic nanoparticles (MNP)-infiltrated HA scaffolds altered the composition of protein coronas and ultimately contributed to increased concentration of proteins related to calcium ions, G-protein coupled receptors (GPCRs), and MAPK/ERK cascades as compared with pristine HA scaffolds. Noticeably, the enriched functional proteins on MHA samples could efficiently activate of the MAPK/ERK signaling pathway, resulting in promoting MC3T3-E1 cell proliferation, as evidenced by the higher expression levels of the key proteins in the MAPK/ERK signaling pathway, including mitogen-activated protein kinase kinases1/2 (MEK1/2) and extracellular signal regulated kinase 1/2 (ERK1/2). Artificial down-regulation of MEK expression can significantly down-regulate the MAPK/ERK signaling and consequently suppress the cell proliferation on MHA samples. These findings not only provide a critical insight into the molecular mechanism underlying cellular proliferation on magnetic scaffolds, but also have important implications in the design of magnetic scaffolds for bone tissue engineering.

Prognostic significance of fibroblast growth factor receptor 4 polymorphisms on biochemical recurrence after radical prostatectomy in a Chinese population.

Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane receptor with ligand-induced tyrosine kinase activity and is involved in various biological and pathological processes. Several polymorphisms of FGFR4 are associated with the incidence and mortality of numerous cancers, including prostate cancer. In this study, we investigated whether the polymorphisms of FGFR4 influence the biochemical recurrence of prostate cancer in Chinese men after radical prostatectomy. Three common polymorphisms (rs1966265, rs2011077, and rs351855) of FGFR4 were genotyped from 346 patients with prostate cancer by using the Sequenom MassARRAY system. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. Results showed biochemical recurrence (BCR) free survival was significantly affected by the genotypes of rs351855 but not influenced by rs1966265 and rs2011077. After adjusting for other variables in multivariable analysis, patients with rs351855 AA/AG genotypes showed significantly worse BCR-free survival than those with the GG genotype (HR = 1.873; 95% CI, 1.209-2.901; P = 0.005). Hence, FGFR4 rs351855 could be a novel independent prognostic factor of BCR after radical prostatectomy in the Chinese population. This functional polymorphism may also provide a basis for surveillance programs. Additional large-scale studies must be performed to validate the significance of this polymorphism in prostate cancer.

A magnetic-dependent protein corona of tailor-made superparamagnetic iron oxides alters their biological behaviors.

In recent years, it is becoming increasingly evident that once nanoparticles come into contact with biological fluids, a protein corona surely forms and critically affects the biological behaviors of nanoparticles. Herein, we investigate whether the formation of protein corona on the surface of superparamagnetic iron oxides (SPIOs) is influenced by static magnetic field. Under static magnetic field, there is no obvious variation in the total amount of protein adsorption, but the proportion of adsorbed proteins significantly changes. Noticeably, certain proteins including apolipoproteins, complement system proteins and acute phase proteins, increase in the protein corona of SPIOs in the magnetic field. More importantly, the magnetic-dependent protein corona of SPIOs enhances the cellular uptake of SPIOs into the normal cell line (3T3 cells) and tumor cell line (HepG2 cells), due to increased adsorption of apolipoprotein. In addition, SPIOs with the magnetic-dependent protein corona cause high cytotoxicity to 3T3 cells and HepG2 cells. This work discloses that superparamagnetism as a key feature of SPIOs affects the composition of protein corona to a large extent, which further alters the biological behaviors of SPIOs.

Ligand-Free Fe3 O4 /CMCS Nanoclusters with Negative Charges for Efficient Structure-Selective Protein Adsorption.

The easy and effective capture of a single protein from a complex mixture is of great significance in proteomics and diagnostics. However, adsorbing nanomaterials are commonly decorated with specific ligands through a complicated and arduous process. Fe3 O4 /carboxymethylated chitosan (Fe3 O4 /CMCS) nanoclusters are developed as a new nonligand modified strategy to selectively capture bovine hemoglogin (BHB) and other structurally similar proteins (i.e., lysozyme (LYZ) and chymotrypsin (CTP)). The ligand-free Fe3 O4 /CMCS nanoclusters, in addition to their simple and economical two-step preparation process, possess many merits, including uniform morphology, high negative charges (-27 mV), high saturation magnetization (60 emu g(-1) ), and high magnetic content (85%). Additionally, the ligand-free Fe3 O4 /CMCS nanoclusters are found to selectively capture BHB in a model protein mixture even within biological samples. The reason for selective protein capture is further investigated from nanomaterials and protein structure. In terms of nanomaterials, it is found that high negative charges are conducive to selectively adsorb BHB. In consideration of protein structure, interestingly, the ligand-free magnetic nanoclusters display a structure-selective protein adsorption capacity to efficiently capture other proteins structurally similar to BHB, such as LYZ and CTP, showing great potential of the ligand-free strategy in biomedical field.

SPAG4L, a novel nuclear envelope protein involved in the meiotic stage of spermatogenesis.

SUN domain-containing proteins belong to a novel protein family. To date, several members--SUN1, SUN2, SUN3, and SPAG4--have been identified as nuclear envelope (NE) proteins. In this study, we sought to characterize and define the potential function of SPAG4L, a newly identified SUN protein. Using bioinformatic analysis, we found that SPAG4L contained a conserved SUN domain in the C-terminal. Subcellular localization analysis indicated that the expression of green fluorescent protein-labeled full-length SPAG4L was localized to the NE and the endoplasmic reticulum (ER). Deletion analysis revealed that the transmembrane region and the coiled-coil domain, but not the SUN domain, were required for localization of SPAG4L to the NE and ER. Subsequently, we confirmed that the human testes expressed endogenous SPAG4L as a 43-kDa protein. Further studies revealed that mouse Spag4L colocalized with the NE marker Lamin B1 and the ER marker PDI in isolated mouse spermatocytes. In addition, the expression of Spag4L was observed in meiosis I and II stages, suggesting that Spag4L may be involved in NE reconstitution and nuclear migration occurring during the process of spermatocyte division. Together, the findings indicate that SPAG4L, a new NE protein, may play an important role in the meiotic stage of spermatogenesis.

[Prokaryotic expression and purification of SPAG4L, a novel human testis gene].

OBJECTIVE: To express SPAG4L, a novel human testis gene in E. coli and purify it's fusion protein. METHODS: The fragment encoding SPAG4L126-379 was amplified by RT-PCR and the PCR products were cloned into PUCm-T vectors. After digestion by EcoR I and Hind III, the fragment was subcloned into PQE-30, a prokaryotic expression vector with 6×His tag. The recombinant plasmid PQE-30-SPAG4L was sequenced and transformed into E.coli M15. The expression of his-tagged fusion protein was induced by IPTG. The fusion protein was identified by Western blotting and purified using Ni-NTA magnetic agarose beads. RESULTS: The recombinant plasmid PQE-30-SPAG4L was constructed successfully and expressed in E.coli M15. The fusion protein SPAG4Lwith 6×his-tag was confirmed by Western blotting. The micro-scale purification system of 6×His-tagged SPAG4Lprotein was established and purified fusion protein was obtained. CONCLUSION: The recombinant plasmid PQE-30-SPAG4L can be expressed in vitro and used for studying the biological function of SPAG4L in spermatogenesis.