Enhanced osteogenic and antibacterial properties of titanium implant surface modified with Zn-incorporated nanowires: Preclinical in vitro and in vivo investigations.

OBJECTIVE: This study aimed to synthesize zinc-incorporated nanowires structure modified titanium implant surface (Zn-NW-Ti) and explore its superior osteogenic and antibacterial properties in vitro and in vivo. MATERIALS AND METHODS: Zn-NW-Ti was synthesized via displacement reactions between zinc sulfate solutions and the titanium (Ti) surface, which was pretreated by hydrofluoric acid etching and hyperthermal alkalinization. The physicochemical properties of the Zn-NW-Ti surface were examined. Moreover, the biological effects of Zn-NW-Ti on MC3T3-E1 cells and its antibacterial property against oral pathogenic bacteria (Staphylococcus aureus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) compared with sandblasted and acid-etched Ti (SLA-Ti) and nanowires modified Ti (NW-Ti) surface were assessed. Zn-NW-Ti and SLA-Ti modified implants were inserted into the anterior extraction socket of the rabbit mandible with or without exposure to the mixed bacterial solution (S. aureus, P. gingivalis, and A. actinomycetemcomitans) to investigate the osteointegration and antibacterial performance via radiographic and histomorphometric analysis. RESULTS: The Zn-NW-Ti surface was successfully prepared. The resultant titanium surface appeared as a nanowires structure with hydrophilicity, from which zinc ions were released in an effective concentration range. The Zn-NW-Ti surface performed better in facilitating the adhesion, proliferation, and differentiation of MC3T3-E1 cells while inhibiting the colonization of bacteria compared with SLA-Ti and NW-Ti surface. The Zn-NW-Ti implant exhibited enhanced osseointegration in vivo, which was attributed to increased osteogenic activity and reduced bacterial-induced inflammation compared with the SLA-Ti implant. CONCLUSIONS: The Zn-incorporated nanowires structure modified titanium implant surface exhibited improvements in osteogenic and antibacterial properties, which optimized osteointegration in comparison with SLA titanium implant surface.

Surface characteristics and in vitro biocompatibility of titanium preserved in a vitamin C-containing saline storage solution.

The purpose of this study is to explore a storage solution for titanium implants and investigate its osteogenic properties. The commercial pure titanium (cp-Ti) surface and double-etched (SLA) titanium surface specimens were preserved in air, saline, 10 mM Vitamin C (VitC)-containing saline and 100 mM VitC-containing saline storage solutions for 2 weeks. The surface microtopography of titanium was observed by scanning electron microscopy (SEM), the surface elemental compositions of the specimens were analyzed by Raman and X-ray photoelectron spectroscopy (XPS), and water contact angle and surface roughness of the specimens were tested. The protein adsorption capacity of two titanium surfaces after storage in different media was examined by BCA kit. The MC3T3-E1 osteoblasts were cultured on two titanium surfaces after storage in different media, and the proliferation, adhesion and osteogenic differentiation activity of osteoblasts were detected by CCK-8, laser confocal microscope (CLSM) and Western blot. The SEM results indicated that the titanium surfaces of the air group were relatively clean while scattered sodium chloride or VitC crystals were seen on the titanium surfaces of the other three groups. There were no significant differences in the micromorphology of the titanium surfaces among the four groups. Raman spectroscopy detected VitC crystals on the titanium surfaces of two experimental groups. The XPS, water contact angle and surface roughness results suggested that cp-Ti and SLA-Ti stored in 0.9% NaCl and two VitC-containing saline storage solutions possessed less carbon contamination and higher surface hydrophilicity. Moreover, the protein adsorption potentials of cp-Ti and SLA-Ti surfaces were significantly improved under preservation in two VitC-containing saline storage solutions. The results of in vitro study showed that the preservation of two titanium surfaces in 100 mM VitC-containing saline storage solution upregulated the cell adhesion, proliferation, osteogenic related protein expressions of MC3T3-E1 osteoblasts. In conclusion, preservation of cp-Ti and SLA-Ti in 100 mM VitC-containing saline storage solution could effectively reduce carbon contamination and enhance surface hydrophilicity, which was conducive to osteogenic differentiation of osteoblasts.

[Investigation and analysis of the current situation of dental technical professionals in Shanghai medical institutions].

PURPOSE: To investigate the current situation of dental technical personnel team in medical institutions in Shanghai, and to provide reference for the construction of dental technical discipline and development of dental personnel team in the National Center for Stomatology (Shanghai). METHODS: Random sample questionnaire and expert interviews were used to find out the awareness, satisfaction and improvement suggestions of dental technicians among physicians, nursing and medical technicians in medical institutions in Shanghai. RESULTS: Among the positions engaged in by dental technicians, dental prosthetic technician, dental radiology technician and laboratory technician were the three most important positions at present, 62.3% of doctors and nurses were satisfied with the work of dental technicians, while 56.2% of dental medical technicians were generally or relatively unsatisfied with their current work. CONCLUSIONS: It is necessary to increase training and education opportunities for dental technicians, improve the talent echelon, introduce high-level talents, improve the working environment and treatment, broaden promotion channels, strengthen communication and exchange with medical care, and build a first-class medical technical personnel team that is compatible with the clinical level of stomatology.

Osteogenic and anti-inflammatory effects of SLA titanium substrates doped with chitosan-stabilized selenium nanoparticles via a covalent coupling strategy.

Osseointegration is a prerequisite for the function of dental implants, and macrophage-dominated immune responses triggered by implantation determine the outcome of ultimate bone healing mediated by osteogenic cells. The present study aimed to develop a modified titanium (Ti) surface by covalently immobilizing chitosan-stabilized selenium nanoparticles (CS-SeNPs) to sandblasted, large grit, and acid-etched (SLA) Ti substrates and further explore its surface characteristics as well as osteogenic and anti-inflammatory activities in vitro. CS-SeNPs were successfully prepared by chemical synthesis and characterized their morphology, elemental composition, particle size, and Zeta potential. Subsequently, three different concentrations of CS-SeNPs were loaded to SLA Ti substrates (Ti-Se1, Ti-Se5, and Ti-Se10) using a covalent coupling strategy, and the SLA Ti surface (Ti-SLA) was used as a control. Scanning electron microscopy images revealed different amounts of CS-SeNPs, and the roughness and wettability of Ti surfaces were less susceptible to Ti substrate pretreatment and CS-SeNP immobilization. Besides, X-ray photoelectron spectroscopy analysis showed that CS-SeNPs were successfully anchored to Ti surfaces. The results of in vitro study showed that the four as-prepared Ti surfaces exhibited good biocompatibility, with Ti-Se1 and Ti-Se5 groups showing enhanced adhesion and differentiation of MC3T3-E1 cells compared with the Ti-SLA group. In addition, Ti-Se1, Ti-Se5, and Ti-Se10 surfaces modulated the secretion of pro-/anti-inflammatory cytokines by inhibiting the nuclear factor kappa B pathway in Raw 264.7 cells. In conclusion, doping SLA Ti substrates with a modest amount of CS-SeNPs (1-5 mM) may be a promising strategy to improve the osteogenic and anti-inflammatory activities of Ti implants.

The Association of Midday Napping With Hypertension Among Chinese Adults Older Than 45 Years: Cross-sectional Study.

BACKGROUND: Hypertension is one of the main public health issues around worldwide, and midday napping is a popular habit. The association between the two remains to be explored. OBJECTIVE: The goal of the research was to explore the association of midday napping with hypertension. METHODS: This study separately selected 11,439, 12,689, and 9464 Chinese respondents aged over 45 years from the China Health and Retirement Longitudinal Study 2011, 2015, and 2018 data sets. Binary logistic regression was used to explore the association of midday napping with hypertension, and the 3-step method was used to test the mediation effect of BMI. RESULTS: Among all respondents, the prevalence rates of hypertension were 24.6% (2818/11439) in 2011, 21.1% (2683/12689) in 2015, and 22.1% (2092/9464) in 2018. Midday napping was positively correlated with hypertension. In 2011 and 2015, napping 60 to 90 minutes had the greatest odds ratios [OR] (OR2011 1.705, OR2015 1.494). In 2018, the biggest OR came from the group napping 30 to 60 minutes (OR 1.223), and ORs of different napping durations decreased from 2011 to 2018. In addition, BMI had a partial mediation effect in 2015 and 2018. CONCLUSIONS: Midday napping is a potential risk factor for hypertension with BMI acting as a mediator. To prevent hypertension, avoiding prolonged duration of midday napping and taking action to maintain a normal BMI level are recommended.

miR-497 promotes the migration and invasion of human medulloblast Daoy cell line through targeted regulation of ARHGDIA in vitro.

OBJECTIVES: To further investigate the effects of miR-497 on the biological behavior of human medulloblastoma cell line in vitro. METHODS: Human medulloblastoma cell lines, Daoy and D341, were used in this study, and the miR-497 expression in the cells was measured by Quantitative PCR with fluorescence. The Daoy cells were divided into the mimics group (Daoy cells treated with mimics), inhibitor group (Daoy cells treated with inhibitor), normal Daoy cells, ARHGDIA siRNA group (Daoy cells transfected with ARHGDIA siRNA), ARHGDIA control group (Daoy cells did not receive any treatment), and negative control group (normal cells transfected with ARHGDIA siRNA). The expression of miR-497 and ARHGDIA mRNA was measured by Quantitative PCR with fluorescence, while the level of ARHGDIA protein was measured by Western blot. The binding capability of ARHGDIA and miR-497 was assessed by luciferase assay, the migration of cells was assessed by wound healing assay, and the invasion of cells was assessed by Transwell assay. RESULTS: Compared to D341 cells, the miR-497 level was significantly higher in the Daoy cells (P < 0.01). The dual-luciferase reporter assay showed that miR-497 targets ARHGDIA. Transfecting the normal Daoy cells with miR-497 mimics significantly reduced the expression of ARHGDIA protein (P < 0.05), while transfecting normal Daoy cells with miR-497 inhibitor significantly increased the expression of ARHGDIA protein (P < 0.05). Consequently, the migration and invasion capability of cells increased significantly after transfection with miR-497 mimic (P < 0.05), and decreased significantly after transfection with miR-497 inhibitor (P < 0.05). In addition, the migration and invasion capabilities of the cells also increased significantly after transfection with ARHGDIA siRNA (P < 0.05). CONCLUSIONS: miR-497/ARHGDIA axis participates in the in vitro migration and invasion of human medulloblastoma cell lines.

Pt Decorated Ti3C2Tx MXene with NIR-II Light Amplified Nanozyme Catalytic Activity for Efficient Phototheranostics.

The clinical application of photothermal therapy (PTT) is severely limited by the tissue penetration depth of excitation light, and enzyme therapy is hampered by its low therapeutic efficiency. As a two-dimensional ultrathin nanosheet with high absorbance in the near-infrared-II (NIR-II) region, the titanium carbide (Ti3C2) nanosheet can be used as a substrate to anchor functional components, like nanozymes and nanodrugs. Here, we decorate Pt artificial nanozymes on the Ti3C2 nanosheets to synthesize Ti-based MXene nanocomposites (Ti3C2Tx-Pt-PEG). In the tumor microenvironment, the Pt nanoparticles exhibit peroxidase-like (POD-like) activity, which can in situ catalyze hydrogen peroxide to generate hydroxyl radicals (•OH) to induce cell apoptosis and necrosis. Meanwhile, the composite shows a desirable photothermal effect upon NIR-II light irradiation with a low power density (0.75 W cm-2). Especially, the POD-like activity is significantly enhanced by the elevated temperature arising from the photothermal effect of Ti3C2Tx. Therefore, satisfactory synergistic PTT/enzyme therapy has been accomplished, accompanied by an applicable photoacoustic imaging capability to monitor and guide the therapeutic process. This work may provide an approach for hyperthermia-amplified nanozyme catalytic therapy, especially based on metal catalysts and MXene nanocomposites.

Emergence and molecular characterization of multidrug-resistant Klebsiella pneumoniae isolates harboring bla CTX-M-15 extended-spectrum ß-lactamases causing ventilator-associated pneumonia in China.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common nosocomial infection associated with high morbidity due to multidrug-resistant (MDR) pathogens. The purpose of this study was to determine the occurrence of extended-spectrum ß-lactamase (ESBL) genes, especially bla CTX-M-15, in Klebsiella pneumoniae (K. pneumoniae)-associated VAP and to investigate the antimicrobial resistance patterns and molecular epidemiological characteristics of K. pneumoniae strains. MATERIALS AND METHODS: From January 2013 to December 2015, we retrospectively collected 89 VAP-causing K. pneumoniae isolates from tertiary-care hospitals in China, among which ESBL-producing strains were assessed for antimicrobial susceptibility. Several antibiotic resistance genes of clinical relevance in K. pneumonia isolates producing ESBL were investigated. Polymerase chain reaction (PCR) and DNA sequencing were employed to characterize the genetic contexts of bla CTX-M-15. Conjugative plasmids carrying bla CTX-M-15 were obtained by mating and further subjected to replicon typing. The genetic relatedness of isolates was assessed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. RESULTS: All of the 30 ESBL-producing isolates identified displayed MDR phenotype, with bla SHV, bla CTX-M, bla OXA, and bla TEM detected in 21, 21, 1, and 20 isolates, respectively. bla CTX-M-15 was the most prevalent ESBL gene (19/30, 63.33%), and ISEcp1 was detected 48 bp upstream of 15 bla CTX-M-15 genes. Based on S1-PFGE analyses, 25 isolates exhibited different plasmid profiles, ranging from ~70 to 320 kb. The bla CTX-M-15 with bla TEM and qnr genes and the ISEcp1 element from eight isolates were co-transferrable to recipients via conjugation, with IncFIB, IncFIC, and IncFII being the most prevalent replicons. Twenty different PFGE patterns and 11 sequence types were identified, with ST304 being dominant. CONCLUSION: This work reports the emergence of bla CTX-M-15 in K. pneumoniae-induced VAP in China. We showed that IncFIB, IncFIC, and/or IncFII plasmids carrying bla CTX-M-15 with bla TEM, qnr resistance genes, and the ISEcp1 element mediate the local prevalence in K. pneumoniae-associated VAP.

Author Correction: Cascaded Kerr photon-blockade sources and applications in quantum key distribution.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Measurement-device-independent quantum key distribution via quantum blockade.

Efficiency in measurement-device-independent quantum key distribution(MDI-QKD) can be improved not only by the protocol, but also single-photon sources. We study the behavior of MDI-QKD with statistical fluctuation using quantum blockade source. Numerical simulation for a type of 4-intensity protocol shows that, after parameter optimization, this source can improve the final key rate by 100 times compared with traditional weak coherent state sources.

Cascaded Kerr photon-blockade soruces and applications in quantum key distribution.

To raise the repetition rate, a single-photon source based on Kerr quantum blockade in a cascaded quantum system is studied. Using the quantum trajectory method, we calculate and simulate the photon number distributions out of a two-cavity system. A high quality single-photon source can be achieved through optimizing parameters. The designed photon source is further applied to the decoy state quantum key distribution (QKD). With and without statistical fluctuation, the key rate can be both raised drastically.

Tigecycline Susceptibility and Molecular Resistance Mechanisms Among Clinical Klebsiella pneumoniae Strains Isolated During Non-Tigecycline Treatment.

Tigecycline is one of the few therapeutic options that are available for treating serious clinical infections. However, tigecycline nonsusceptible Enterobacteriaceae has emerged recently in China. In this study, a total of 28 clinical Klebsiella pneumoniae isolates that were not previously exposed to tigecycline were collected and confirmed for tigecycline minimum inhibitory concentrations (MICs) using standard broth microdilution tests. To elucidate the mechanisms underlying molecular resistance to tigecycline, the expression levels of efflux pumps AcrAB and OqxAB and their regulators RamA, MarA, RarA, and SoxS were determined by quantitative polymerase chain reaction. The expression levels of the genes acrB, ramA, marA, and soxS were statistically different in different MIC groups (p < 0.05). Sequence analysis of the acrR and ramR genes revealed several nonsynonymous mutations in the nine resistance isolates. The values of MIC in these isolated strains with ramR mutations were significantly higher than those without ramR mutation (p = 0.029). Moreover, mutations in the ramR gene led to the overexpression of RamA. These results indicated that the mutation of the ramR gene through the upregulated expression of RamA contributed to tigecycline resistance and that several of the newly identified types of mutations in ramR and acrR were not previously reported in K. pneumoniae clinical isolates.

Measurement-Device-Independent Quantum Key Distribution Over a 404 km Optical Fiber.

Measurement-device-independent quantum key distribution (MDIQKD) with the decoy-state method negates security threats of both the imperfect single-photon source and detection losses. Lengthening the distance and improving the key rate of quantum key distribution (QKD) are vital issues in practical applications of QKD. Herein, we report the results of MDIQKD over 404 km of ultralow-loss optical fiber and 311 km of a standard optical fiber while employing an optimized four-intensity decoy-state method. This record-breaking implementation of the MDIQKD method not only provides a new distance record for both MDIQKD and all types of QKD systems but also, more significantly, achieves a distance that the traditional Bennett-Brassard 1984 QKD would not be able to achieve with the same detection devices even with ideal single-photon sources. This work represents a significant step toward proving and developing feasible long-distance QKD.

Emergence and characterization of tigecycline resistance in multidrug-resistant Klebsiella pneumoniae isolates from blood samples of patients in intensive care units in northern China.

Serious infections in intensive care unit patients caused by multidrug-resistant (MDR) Klebsiella pneumoniae represent a major threat worldwide owing to increased mortality and limited treatment options. With the application of tigecycline for MDR pathogens, tigecycline-non-susceptible K. pneumoniae isolates have recently emerged in China. To identify the susceptibility profile of MDR K. pneumoniae to tigecycline and evaluate the molecular characterization of tigecycline resistance, 214 MDR K. pneumoniae isolates were collected from blood samples of patients in intensive care units. MICs and clonal relatedness were determined by standard broth microdilution and multilocus sequence typing, respectively. Expression levels of efflux pumps and their global regulators were examined using real-time PCR. Mutations of local repressor were identified by PCR and sequencing. Our results show that the tigecycline resistance rate of 214 MDR K. pneumoniae isolates was 6.07 %. ST11 was the predominant clone type of tigecycline-non-susceptible K. pneumoniae isolates. Expression of efflux pump AcrB and global regulator RamA correlated with tigecycline MICs (AcrB: x2=8.91, P=0.03; RamA: x2=13.91, P<0.01), and mean expression levels of AcrB for the MICs ≥4 mg l-1 were significantly higher than MICs ≤2 mg l-1 (t=2.48, P=0.029). In addition, one tigecycline-resistant isolate harboured a deletion mutation in the ramR gene. These data indicated a linear correlative trend for overexpression of the AcrB and the tigecycline MICs resulting from the upregulation of RamA. The emergence of molecular type ST11 of MDR K. pneumoniae isolates should be monitored to identify factors that contribute to tigecycline resistance in intensive care units.

On-demand single-photon sources via quantum blockade and applications in decoy-state quantum key distribution.

Quantum blockades as a nonlinear quantum optical process have been well studied in recent years. Using the quantum trajectory method, we calculate and discuss the output photon number distributions of a single-photon blockade process in a Kerr nonlinear dissipative resonator, revealing that the probability of the single-photon state can be optimized. Then we show through numerical simulations that such a quasi-single-photon source can drastically raise the key rate in the decoy-state quantum key distribution.

MGMT promoter methylation and glioblastoma prognosis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: We undertook this study to comprehensively summarize the associations between MGMT promoter methylation and prognosis of glioblastoma (GBM). METHODS: We searched PubMed, EMBASE and Cochrane databases (from January 2003 to November 1, 2011) and the references of the relevant articles in English with hazard ratios (HRs) and 95% confidence intervals (95% CIs). Two reviewers independently extracted data using a standardized form. Discrepancies were adjudicated by discussion. RESULTS: Twenty four studies met the inclusion criteria. There were 22 studies reporting on the relationship between MGMT methylation and overall survival (OS) of GBM and 12 studies on the association between MGMT methylation and progression-free survival (PFS) of GBM. Patients with a methylated status of MGMT had significant OS and PFS advantage (HR = 0.48, 95% CI: 0.35-0.65; I² = 79.78 for OS; HR = 0.43, 95% CI: 0.32-0.56; I² = 50.38 for PFS). Pooled HRs remained significant in further subgroup analysis based on the year of publication and continents of studies. CONCLUSIONS: Patients with MGMT promoter methylation had significant OS and PFS advantage than those without methylated status.