Versatile Switchable Targeted Polysiloxanes for High-Resolution Visualization of Mitochondrial and Lysosomal Interactions during Ferroptosis.

Ferroptosis is an iron-dependent process that regulates cell death and is essential for maintaining normal cell and tissue survival. The explosion of reactive oxygen species characterizes ferroptosis in a significant way. Peroxynitrite (ONOO-) is one of the endogenous reactive oxygen species. Abnormal ONOO- concentrations cause damage to subcellular organelles and further interfere with organelle interactions. However, the proper conduct of organelle interactions is critical for cellular signaling and the maintenance of cellular homeostasis. Therefore, investigating the effect of ONOO- on organelle interactions during ferroptosis is a highly attractive topic. To date, it has been challenging to visualize the full range of ONOO- fluctuations in mitochondria and lysosomes during ferroptosis. In this paper, we constructed a switchable targeting polysiloxane platform. During the selective modification of NH2 groups located in the side chain, the polysiloxane platform successfully constructed fluorescent probes targeting lysosomes and mitochondria (Si-Lyso-ONOO, Si-Mito-ONOO), respectively. Real-time detection of ONOO- in lysosomes and mitochondria during ferroptosis was successfully achieved. Remarkably, the occurrence of autophagy during late ferroptosis and the interaction between mitochondria and lysosomes was observed via the differentiated responsive strategy. We expect that this switchable targeting polysiloxane functional platform will broaden the application of polymeric materials in bioimaging and provide a powerful tool for further deeper understanding of the ferroptosis process.

Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy.

Since being discovered in 2008, the STING (stimulator of interferon genes) pathway has gradually been recognized as a central and promising target for immunotherapy. The STING pathway can be stimulated by cyclic dinucleotides (CDNs), leading to the type I interferons (IFN) production for immunotherapy for cancer or other diseases. However, the negative charges, hydrophilicity, and instability of CDNs have hindered their further applications. In addition, chronic activation of the STING pathway has been found to be involved in autoimmune diseases as IFN overproduction. Thus, research and development of STING agonists and inhibitors has been a hot field for the treatment of several diseases. The past several years, especially 2018, has seen increasingly rapid advances in this field. Here, this review summarizes the synthesis and modification of CDNs, the identification of nonnucleotide agonists, the recent progress in delivery systems and the medical applications, such as personalized vaccine adjuvants, in detail. In addition, in this review, we summarize the STING inhibitors' advances from two aspects, covalent, and noncovalent inhibitors.

[Effect of vasoactive agents on the prognosis of children in the third stage of hand-foot-mouth disease].

OBJECTIVE: To study the effect of the application timing of vasoactive agents on the prognosis of children in the third stage of hand-foot-mouth disease (HFMD). METHODS: A retrospective analysis was performed on the medical data of children in the third stage of HFMD between April 2012 and September 2016. According to the application time of vasoactive agents (milrinone combined with phentolamine) after admission, the children were divided into an early stage (within 2 hours after admission) group with 32 children, a middle stage (within 2-6 hours after admission) group with 28 children, and a late stage (more than 6 hours after admission) group with 26 children. Venous blood samples were collected before vasoactive agent treatment and after 24 hours of vasoactive agent treatment to measure the levels of creatine kinase-MB (CK-MB), troponin (TnI), and brain natriuretic peptide (BNP). The recovery time of left ventricular ejection fraction (LVEF), respiratory rate, blood pressure, and heart rate were recorded. The response rate to the treatment within 72 hours of treatment was evaluated. RESULTS: The early stage group had a significantly higher overall response rate to the treatment than the middle stage and late stage groups (P<0.0167). After 24 hours of treatment, there were significant differences in heart rate, blood pressure, respiratory rate, and LVEF among the three groups (P<0.05). The early stage group showed the most significant improvement in these parameters (P<0.0167). Compared with the middle stage and late stage groups, the early stage group had significantly shorter recovery time of LVEF, respiratory rate, heart rate, and blood pressure (P<0.0167). After 24 hours of treatment, the early stage group had a significantly lower level of BNP than the middle stage and late stage groups (P<0.05). CONCLUSIONS: Vasoactive agents should be given to children with critical HFMD as early as possible to improve cardiovascular function, reduce the risk of disease progression, and improve prognosis.

[Asymmetric crying facies and vocal cord paralysis accompanied by congenital heart disease in an infant].

A female infant was admitted to the hospital due to perioral cyanosis two hours after birth. The infant was born at the gestational age of 35 weeks by cesarean section with a birth weight of 2 400 g. Physical examination revealed wry mouth to the left side while crying, small auricles, and high palatal arch; fibrolaryngoscopy suggested bilateral vocal cord paralysis; echocardiography suggested ventricular septal defect; single nucleotide polymorphism testing showed 22q11.21 microdeletion. Therefore, the infant was given a definite diagnosis of asymmetric crying facies syndrome accompanied by 22q11.21 microdeletion. After 8-month follow-up, the infant still had asymmetric crying facies with presence of growth retardation.

A site-specific branching poly-glutamate tag mediates intracellular protein delivery by cationic lipids.

Intracellular protein delivery is of significance for cellular protein analysis and therapeutic development, but remains challenging technically. Herein, we report a general and highly potent strategy for intracellular protein delivery based on commercially available cationic lipids. In this strategy, a designed double branching poly-glutamate tag is site-specifically attached onto the C-terminal of protein cargos via expressed protein ligation (EPL), which mediates the entrapment of proteins into cationic liposomes driven by electrostatic interaction. The resultant protein-lipid complexes can enter into cytosol with a high efficiency even at the low protein concentration while maintaining protein's biological activity.

Paper-Based Device for Colorimetric and Photoelectrochemical Quantification of the Flux of H2O2 Releasing from MCF-7 Cancer Cells.

In this work, a novel dual photoelectrochemical/colorimetric cyto-analysis format was first introduced into a microfluidic paper-based analytical device (µ-PAD) for synchronous sensitive and visual detection of H2O2 released from tumor cells based on an in situ hydroxyl radicals ((•)OH) cleaving DNA approach. The resulted µ-PAD offered an excellent platform for high-performance biosensing applications, which was constructed by a layer-by-layer modification of concanavalin A, graphene quantum dots (GQDs) labeled flower-like Au@Pd alloy nanoparticles (NPs) probe, and tumor cells on the surface of the vertically aligned bamboo like ZnO, which grows on a pyknotic Pt NPs modified paper working electrode (ZnO/Pt-PWE). It was the effective matching of energy levels between GQDs and ZnO levels that lead to the enhancement of the photocurrent response compared with the bare ZnO/Pt-PWE. After releasing H2O2, the DNA strand was cleaved by (•)OH generated under the synergistic catalysis of GQDs and Au@Pd alloy NPs and thus, reduced the photocurrent, resulting in a high sensitivity to H2O2 in aqueous solutions with a detection limit of 0.05 nmol observed, much lower than that in the previously reported method. The disengaged probe can result in catalytic chromogenic reaction of substrates, resulting in real-time imaging of H2O2 biological processes. Therefore, this work provided a truly low-cost, simple, and disposable µ-PAD for precise and visual detection of cellular H2O2, which had potential utility to cellular biology and pathophysiology.

Phospholipid-modified upconversion nanoprobe for ratiometric fluorescence detection and imaging of phospholipase D in cell lysate and in living cells.

Phospholipase D (PLD) is a critical component of intracellular signal transduction and has been implicated in many important biological processes. It has been observed that there are abnormalities in PLD expression in many human cancers, and PLD is thus recognized as a potential diagnostic biomarker as well as a target for drug discovery. We report for the first time a phospholipid-modified nanoprobe for ratiometric upconversion fluorescence (UCF) sensing and bioimaging of PLD activity. The nanoprobe can be synthesized by a facile one-step self-assembly of a phospholipid monolayer composed of poly(ethylene glycol) (PEG)ylated phospholipid and rhodamine B-labeled phospholipid on the surface of upconversion nanoparticles (UCNPs) NaYF4: 20%Yb, 2%Er. The fluorescence resonance energy transfer (FRET) process from the UCF emission at 540 nm of the UCNPs to the absorbance of the rhodamine B occurs in the nanoprobe. The PLD-mediated hydrolysis of the phosphodiester bond makes rhodamine B apart from the UCNP surface, leading to the inhibition of FRET. Using the unaffected UCF emission at 655 nm as an internal standard, the nanoprobe can be used for ratiometric UCF detection of PLD activity with high sensitivity and selectivity. The PLD activity in cell lysates is also determined by the nanoprobe, confirming that PLD activity in a breast cancer cell is at least 7-fold higher than in normal cell. Moreover, the nanoprobe has been successfully applied to monitoring PLD activity in living cells by UCF bioimaging. The results reveal that the nanoprobe provides a simple, sensitive, and robust platform for point-of-care diagnostics and drug screening in biomedical applications.

A dual amplification strategy for ultrasensitive electrochemiluminescence immunoassay based on a Pt nanoparticles dotted graphene-carbon nanotubes composite and carbon dots functionalized mesoporous Pt/Fe.

A facile and sensitive electrochemiluminescence (ECL) immunosensor for the detection of human carcinoembryonic antigen (CEA) was designed. The immunosensor used Pt nanoparticles dotted graphene-carbon nanotubes composites (Pt/Gr-CNTs) as a platform and carbon dots functionalized Pt/Fe nanoparticles (Pt/Fe@CDs) as bionanolabels. The Pt/Gr-CNTs was first synthesized using a facile ultrasonic method to modify the working electrode, which increases the surface area to capture a large amount of primary anti-CEA antibodies as well as improving the electronic transmission rate. The bionanolabels Pt/Fe@CDs prepared through ethanediamine linking, showed good ECL signal amplification performance. The reason is that the Pt/Fe@CDs nanocomposites as signal tags can increase CDs loading per immunoreaction in comparison with single CDs. The approach provided a good linear response range from 0.003 to 600 ng mL(-1) with a low detection limit of 0.8 pg mL(-1). The immunosensor showed good specificity, acceptable stability and reproducibility. Satisfactory results were obtained in the determination of CEA in human serum albumin samples. Hence, the proposed ECL immunosensor could become a promising method for tumor marker detection.

Polarity responsive polysiloxanes with twisting intramolecular charge transfer effect for monitoring lipophagy process and the detection of volatile organic compounds.

Polarity plays a critical role in biology and materials science, serving as a complex parameter. Imbalances in polarity within subcellular organelles are closely associated with various diseases. Moreover, volatile organic compounds (VOC) with low polarity pose significant health and safety risks, therefore, researchers have shown great interest in accurately detecting polarity. However, precise observation of polarity changes within organisms and identification of low-polarity volatile organic solvents are formidable challenges. To overcome these difficulties, we developed a versatile polymeric twisting intramolecular charge transfer (TICT) effect Polysiloxane-n (PDMS-n), utilizing polysiloxane molecular chains as "smart guides" to connect TICT molecules, inspired by the concept of "threading a needle." With the aid of PDMS-n, the process of polarity changes during cellular lipophagy was monitored in situ with high accuracy. Remarkably, the polarity changes of the local microstructure of the PDMS films were successfully visualized. PDMS-Films were also constructed, which enabled the recognition of Dichloromethane (DCM) gas during swelling. This work will contribute to the understanding of changes in cellular physiological processes, and facilitate the sensitive detection of VOCs.

[Short-term follow up of treatment effect using one-time one-abutment placement in implant restoration in 35 patients with single posterior teeth loss].

PURPOSE: To evaluate the effet of one-time one-abutment placement on peri-implant tissues. METHODS: Thirty-five patients with single posterior loss were collected, who received definitive abutment at the moment of implant placement. One day and after 1 year of implant loading, radiographic assessment of marginal bone level changes and clinical status of peri-implant soft tissues were conducted. Plaque index, pocket depth as well as sulcus bleeding index were assessed. RESULTS: During 1 year follow-up period after loading, no implant failure was observed. The mean marginal bone loss of implants were (0.225±0.113) mm mesially and (0.439±0.123) mm distally. Standard periodontal probes were used to measure plaque index, probing depth, and gingival crevicular bleeding index immediately after repair and 1 year later. CONCLUSIONS: In the posterior region, one-time one-abutment placement may better protect peri-implant tissues as an ideal treatment protocol.

In vitro evaluation of the impact of a bioceramic root canal sealer on the mechanical properties of tooth roots.

Bacground/purpose: Endodontically treated teeth are more prone to vertical root fracture with the mechanical property changes to some extent during root canal treatment. This study aimed to investigate the effects of a bioceramic sealer on the mechanical properties of tooth roots. Materials and methods: Dentin discs were dried by two different methods (ethanol drying and paper points drying) and then filled with a BC sealer named iRoot SP. SEM and EDS were used to analyze the newly formed minerals in dentin tubules. Elastic modulus and hardness of the secondary dentin in areas proximal to the primary dentin (PD-SD) and areas proximal to canal or iRoot SP (SD-C/SD-iRoot SP) were measured using nanoindentation technique. The compressive strength of roots filled with iRoot SP were tested by compressive loading test. Results: (1) Penetration and mineralization: Paper points drying was more conducive to iRoot SP adhesion, spreading and penetration into the dentin tubules than 95% ethanol drying. (2) Micromechanical properties: After filling root canal with iRoot SP, the elastic modulus and hardness of SD-iRoot SP were higher than those of PD-SD (P = 0.001 and P = 0.000). (3) Fracture resistance: The compressive strength of the roots filled with iRoot SP was not significantly different from that of the roots unprepared and unfilled (P = 0.957), but was higher than that of the roots prepared and unfilled (P = 0.009). Conclusion: Excessive drying (95% ethanol drying method) is not conducive to the penetration and mineralization of the BC sealer iRoot SP into dentin tubules. The good bioactivity of iRoot SP was responsible for increasing the elastic modulus and hardness of dentin, which strengthened the prepared roots.

Photoelectrochemical lab-on-paper device based on molecularly imprinted polymer and porous Au-paper electrode.

In this work, microfluidic paper-based analytical device (µ-PAD) was applied in a photoelectrochemical (PEC) method and thus a truly low-cost, simple, portable, and disposable microfluidic PEC origami device (µ-PECOD) was demonstrated. The molecular imprinting technique was introduced into microfluidic paper-based analytical devices (µ-PADs) through electropolymerization of molecular imprinted polyaniline (MPANI) in a novel Au nanoparticle (AuNP)-modified paper working electrode (Au-PWE). This is fabricated through the growth of an AuNP layer on the surfaces of cellulose fibers in the PWE. Under visible light irradiation, MPANI can generate the photoelectric transition from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO), delivering the excited electrons to the AuNPs, and then to the carbon working electrode. Simultaneously, it is believed that a positively charged hole of MPANI that took part in the oxidation process was consumed by ascorbic acid (AA) to promote the amplifying photocurrent response. On the basis of this novel MPANI-Au-PWE and the principle of origami, a microfluidic molecular imprinted polymer (MIP)-based photoelectrochemical analytical origami device (µ-MPECOD), comprised of an auxiliary tab and a sample tab, is developed for the detection of heptachlor in the linear range from 0.03 nmol L(-1) to 10.0 nmol L(-1) with a low detection limit of 8.0 pmol L(-1). The selectivity, reproducibility, and stability of this µ-MPECOD are investigated. This µ-MPECOD would provide a new platform for high-throughput, sensitive, specific, and multiplex assay in public health, environmental monitoring, and the developing world.

Ultrasensitive electrochemiluminescent immunosensor based on dual signal amplification strategy of gold nanoparticles-dotted graphene composites and CdTe quantum dots coated silica nanoparticles.

A facile and ultrasensitive electrochemiluminescent (ECL) immunosensor for detection of prostate-specific antigen (PSA) was designed by using CdTe quantum dots coated silica nanoparticles (SiO2@QDs) as bionanolabels. To construct such an electrochemiluminescence immunosensor, gold nanoparticles-dotted graphene composites were immobilized on the working electrode, which can increase the surface area to capture a large amount of primary antibodies as well as improve the electronic transmission rate. The as-prepared SiO2@QDs used as bionanolabels, showed good ECL performance and good ability of immobilization for secondary antibodies. The approach provided a good linear response ranging from 0.005 to 10 ng mL(-1) with a low detection limit of 0.0032 ng mL(-1). Such immunosensor showed good precision, acceptable stability, and reproducibility. Satisfactory results were obtained for determination of PSA in human serum samples. Therefore, the proposed method provides a new promising platform of clinical immunoassay for other biomolecules.

[Growth ability of human dental pulp cells on three bioactive scaffolds].

OBJECTIVE: To investigate the proliferation and differentiation of the human dental pulp cells (hDPCs) on the bioactive scaffolds. METHODS: Primary HDPCs were harvested from impacted third molars of healthy adult individuals (18-25 years of age) by enzyme digestion, expanded and cultured. The cells used for this investigation were the 4 th passage. Immunohistochemical methods were used to verify that the cells were dental pulp cells. The expression of stromal precursor antigen-1 (STRO-1) was determined by flow cytometry. Three different types of scaffolds were used: collagen (COL), collagen / bioglass (COL-BG) and collagen / bioglass / polycaprolactone (COL-BG-PCL). Cell proliferation on the scaffolds was determined using a MTT assay at hour 6, on days 1, 3, 5, 7, 14 and 21. On day 14, the scaffolds were stained with the alkaline phosphatase (ALP) staining kit. RESULTS: The tested cells had STRO-1 positive cells. The proliferation of HDPCs was significantly higher on the COL-BG scaffold and COL-BG-PCL scaffold as compared with COL scaffold (P<0.05). Especially on days 14 and 21, the optical density value of bioglass composite scaffold were 5 times that of the COL scaffold. The ALP positive staining area was observed more extensively on the COL-BG scaffold and COL-BG-PCL scaffold than on the COL scaffold. CONCLUSION: As comparison with the COL scaffold, HDPCs' proliferation and differentiation present more activity on the COL-BG and COL-BG-PCL scaffolds.

Polysiloxane-based hyperbranched fluorescent probe for dynamic visualization of HClO in lysosomes and vivo.

As a type of reactive oxygen species, hypochlorous acid (HClO) is associated with inducing oxidative stress in lysosomes. Once its concentration is abnormal, it may lead to lysosomal rupture and subsequent apoptosis. Meanwhile, this may provide new inspiration for cancer treatment. Therefore, it is crucial to visualize HClO in lysosomes at the biological level. So far, numerous fluorescent probes have emerged to identify HClO. However, fluorescent probes that combine low biotoxicity with lysosome-targetable properties are scarce. In this paper, hyperbranched polysiloxanes were modified by embedding perylenetetracarboxylic anhydride red fluorescent cores with naphthalimide derivative green fluorophores to synthesize novel fluorescent probe (PMEA-1). PMEA-1 was a lysosome-targetable fluorescent probe with unique dual emission, high biosafety, and good response speed. PMEA-1 exhibited excellent sensitivity and responsiveness to HClO in PBS solution and could dynamically visualize HClO fluctuations in cells and zebrafish. Simultaneously, PMEA-1 also had monitoring ability for HClO produced in the process of cellular ferroptosis. In addition, the bioimaging results indicated that PMEA-1 was capable of accumulating within the lysosomes. We anticipate that PMEA-1 will broaden the application of silicon-based fluorescent probes in the field of fluorescence imaging.

Hyperbranched polysiloxane-based probe with enhanced lipophilicity for visualizing ONOO- fluctuations in endoplasmic reticulum.

The endoplasmic reticulum, a cellular signaling regulator, participates in the synthesis and secretion of many proteins, glycogen, lipids and cholesterol substances. Peroxynitrite (ONOO-) is a highly oxidative and nucleophilic agent. Abnormal fluctuations of ONOO- induce oxidative stress in the endoplasmic reticulum, further disrupting the normal function of protein folding and transport and glycosylation modification, ultimately leading to neurodegenerative diseases, cancer and Alzheimer's disease. Up to now, most probes have tended to achieve targeting functions by introducing specific targeting groups. However, this approach increased the difficulty of the construction process. Therefore, a simple and efficient construction strategy for fluorescent probes with excellent specificity targeting the endoplasmic reticulum is lacking. To overcome this difficulty and put forward an efficient design strategy for the endoplasmic reticulum targeted probes, in this paper, we constructed alternating rigid and flexible polysiloxane-based hyperbranched polymeric probes (Si-Er-ONOO) by bonding perylenetetracarboxylic anhydride and silicon-based dendrimers for the first time. Efficient and specific targeting of the endoplasmic reticulum was successfully achieved by the excellent lipid solubility of Si-Er-ONOO. Furthermore, we observed different effects of metformin and rotenone on the changes of ONOO- volatility in the cellular and zebrafish internal environment by Si-Er-ONOO. We believe that Si-Er-ONOO will expand the application of organosilicon hyperbranched polymeric materials in bioimaging and provide an excellent indicator of reactive oxygen species fluctuations in biological systems.

Effect of a bioactive glass-based root canal sealer on root fracture resistance ability.

Background/purpose: The root fracture resistance of endodontically treated teeth is decreased significantly, and it is more likely to fracture. This study aimed to evaluate the effect of a novel root canal sealer based on bioactive glass (BG) on root fracture resistance and explore its mechanism. Materials and methods: The BG-based root canal sealer (BG Sealer) was prepared by mixing a kind of bioactive glass (10.8% P2O5, 54.2% SiO2, 35% CaO, mol.%, named PSC), zirconia (ZrO2) powder, sodium alginate (SA) and phosphate solution (PS). A pH meter was used to measure the pH of simulated body fluid (SBF) after immersion with BG Sealer at different time. After preparing the samples of BG sealer with a diameter of 4 mm and a height of 6 mm, the compressive strength was tested by a universal testing machine. The scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) were used to detect and analyze the mineral status of root canal systems filled with BG Sealer. The push out test was used to measure the push out bond strength of BG Sealer. The fracture resistance of root canals filled with BG Sealer was detected by the compressive loading test. Bioceramic root canal sealer iRoot SP was set as the control group. Results: (1) Physicochemical properties: The pH value of SBF immersed with BG Sealer increased slightly up to 7.68, while the pH of SBF immersed with iRoot SP increased to 12.08. The compressive strength of the novel BG Sealer was 4.62 ± 1.70 MPa, which was lower than that of iRoot SP (P < 0.05). (2) Mineralization: The hydroxyapatite layers were observed on the surface of BG Sealer and iRoot SP after being immersed in SBF for 4 weeks. BG Sealer and iRoot SP were both able to penetrate into the dentin tubules, duplicate the morphology of root canals well, and form a layer of hydroxyapatite. (3) Adhesion to dentin: There was no significant difference between the push out bond strength of the novel BG Sealer and iRoot SP (P > 0.05). (4) Fracture resistance: After immersion in SBF for 4 weeks, the fracture resistance of roots filled with BG Sealer and iRoot SP was 454.16 ± 155.39 N and 445.50 ± 164.73 N, respectively, both of which were not statistically different from that of the roots unprepared and unfilled (394.07 ± 62.12 N) (P > 0.05), whereas higher than that of the roots prepared and unfilled (235.36 ± 83.80 N) (P < 0.05). Conclusion: The novel BG Sealer has good adhesion to the root dentin, can penetrate into the dentin tubules to generate minerals, and meanwhile can improve the fracture resistance of the roots after root canal treatment. It is expected to be a bioactive root canal sealer with good clinical application prospects.

Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals.

IMPORTANCE: The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.

Association between Periodontitis and Aortic Calcification: A Cohort Study.

The present study investigated the association between the presence of periodontitis and aortic calcification (AC) risk among Chinese adults. A total of 6059 individuals who underwent regular health check-ups and received a diagnosis of periodontitis between 2009 and 2016 were included. The outcome was AC, assessed by a chest low-dose spiral CT scan. Cox proportional hazards regression analysis was used to assess the association between periodontitis and AC risk after adjusting for several confounders. After a median follow-up period of 2.3 years (interquartile range: 1.03-4.97 years), 843 cases of AC were identified, with 532 (12.13%) and 311 (18.59%) patients in the non-periodontitis group and periodontitis group, respectively. Multivariate analyses demonstrated that, compared with those without periodontitis, the hazard ratio and 95% confidence interval for AC risk in participants with periodontitis was 1.18 (1.02-1.36) (P = .025) in the fully adjusted model. Stratified analyses showed that the positive relationship between periodontitis and AC was more evident in males and participants <65 years of age (pinteraction = .005 and .004, respectively). Our results show that the presence of periodontitis was positively associated with AC among Chinese adults, especially among males and younger participants.

Ultrasensitive electrochemiluminescence detection of DNA based on nanoporous gold electrode and PdCu@carbon nanocrystal composites as labels.

A sensitive electrochemiluminescence (ECL) DNA biosensor based on nanoporous gold (NPG) electrode and PdCu@carbon nanocrystals (CNCs) composites is developed. The CNCs were obtained simply by electrooxidation with abundant carboxyl groups at their surfaces. The NPG can be easily prepared by a selective dissolution of silver from silver-gold alloy in nitric acid, which has free-standing noble metal membranes with controllable three-dimensional (3D) porosity. The PdCu bimetallic nanocomposites with hierarchically hollow structures were fabricated through a simple replacement reaction using dealloyed nanoporous copper (NPC) as both a template and reducing agent. Structure characterization was obtained by means of transmission electron microscope (TEM) and scanning electron microscope (SEM) images. The PdCu@CNCs composites exhibit 6 times higher ECL intensity than the pure CNC-labeled reporter DNA. Taking advantage of dual-amplification effects of the developed probe, a limit of detection as low as 18 aM can be achieved and the assay exhibits excellent selectivity for single-mismatched DNA detection even in human serum. The proposed ECL based method should have wide applications in diagnosis of genetic diseases due to its simplicity, low cost, and high sensitivity at extremely low concentrations.