Biodegradable Zn-5Dy Alloy with Enhanced Osteo/Angio-Genic Activity and Osteointegration Effect via Regulation of SIRT4-Dependent Mitochondrial Function.

Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.

Modulation recognition method of mixed signals based on cyclic spectrum projection.

The signal in the receiver is mainly a combination of different modulation types due to the complex electromagnetic environment, which makes the modulation recognition of the mixed signal a hot topic in recent years. In response to the poor adaptability of existing mixed signals recognition methods, this paper proposes a new recognition method for mixed signals based on cyclic spectrum projection and deep neural network. Firstly, through theoretical derivation, we prove the feasibility of using cyclic spectrum for mixed communication signal identification. Then, we adopt grayscale projections on the two-dimensional cyclic spectrum as identifying representation. And a new nonlinear piecewise mapping and directed pseudo-clustering method are used to enhance the above-mentioned grayscale images, which reduces the impact of energy ratios and symbol rates on signal identification. Finally, we use deep neural networks to extract deep abstract modulation information to achieve effective recognition of mixed signals. Simulation results show that the proposed method is robust against noise. When signal-to-noise ratio is not less than 0 dB, the average recognition rate is greater than 95%. Furthermore, this method exhibits good robustness towards the changes in signal symbol rates and energy ratios between mixed signals.

Mitochondrial impairment and downregulation of Drp1 phosphorylation underlie the antiproliferative and proapoptotic effects of alantolactone on oral squamous cell carcinoma cells.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent and fatal oral cancers. Mitochondria-targeting therapies represent promising strategies against various cancers, but their applications in treating OSCC are limited. Alantolactone (ALT) possesses anticancer properties and also regulates mitochondrial events. In this study, we explored the effects of ALT on OSCC and the related mechanisms. METHODS: The OSCC cells were treated with varying concentrations and duration of ALT and N-Acetyl-L-cysteine (NAC). The cell viability and colony formation were assessed. The apoptotic rate was evaluated by flow cytometry with Annexin V-FITC/PI double staining. We used DCFH-DA and flow cytometry to detect reactive oxygen species (ROS) production and DAF-FM DA to investigate reactive nitrogen species (RNS) level. Mitochondrial function was reflected by mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP levels. KEGG enrichment analyses determined the mitochondrial-related hub genes involved in OSCC progression. Dynamin-related protein 1 (Drp1) overexpression plasmids were further transfected into the cells to analyze the role of Drp1 in OSCC progression. Immunohistochemistry staining and western blot verified the expression of the protein. RESULTS: ALT exerted anti-proliferative and pro-apoptosis effects on OSCC cells. Mechanistically, ALT elicited cell injury by promoting ROS production, mitochondrial membrane depolarization, and ATP depletion, which were reversed by NAC. Bioinformatics analysis showed that Drp1 played a crucial role in OSCC progression. OSCC patients with low Drp1 expression had a higher survival rate. The OSCC cancer tissues presented higher phosphorylated-Drp1 and Drp1 levels than the normal tissues. The results further showed that ALT suppressed Drp1 phosphorylation in OSCC cells. Moreover, Drp1 overexpression abolished the reduced Drp1 phosphorylation by ALT and promoted the cell viability of ALT-treated cells. Drp1 overexpression also reversed the mitochondrial dysfunction induced by ALT, with decreased ROS production, and increased mitochondrial membrane potential and ATP level. CONCLUSIONS: ALT inhibited proliferation and promoted apoptosis of oral squamous cell carcinoma cells via impairment of mitochondrial homeostasis and regulation of Drp1. The results provide a solid basis for ALT as a therapeutic candidate for treating OSCC, with Drp1 being a novel therapeutic target in treating OSCC.

Activation of PGC-1α-dependent mitochondrial biogenesis supports therapeutic effects of silibinin against type I diabetic periodontitis.

AIM: To investigate whether silibinin impacts diabetic periodontitis (DP) via mitochondrial regulation. MATERIALS AND METHODS: In vivo, rats were divided into control, diabetes, DP and DP combined with silibinin groups. Diabetes and periodontitis were induced by streptozocin and silk ligation, respectively. Bone turnover was evaluated by microcomputed tomography, histology and immunohistochemistry. In vitro, human periodontal ligament cells (hPDLCs) were exposed to hydrogen peroxide (H2 O2 ) with or without silibinin. Osteogenic function was analysed by Alizarin Red and alkaline phosphatase staining. Mitochondrial function and biogenesis were investigated by mitochondrial imaging assays and quantitative polymerase chain reaction. Activator and lentivirus-mediated knockdown of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha (PGC-1α), a critical regulator of mitochondria biogenesis, was used to explore the mitochondrial mechanisms. RESULTS: Silibinin attenuated periodontal destruction and mitochondrial dysfunction and enhanced mitochondrial biogenesis and PGC-1α expression in rats with DP. Meanwhile, silibinin promoted cell proliferation, osteogenesis and mitochondrial biogenesis and increased the PGC-1α level in hPDLCs exposed to H2 O2 . Silibinin also protected PGC-1α from proteolysis in hPDLCs. Furthermore, both silibinin and activator of PGC-1α ameliorated cellular injury and mitochondrial abnormalities in hPDLCs, while knockdown of PGC-1α abolished the beneficial effect of silibinin. CONCLUSIONS: Silibinin attenuated DP through the promotion of PGC-1α-dependent mitochondrial biogenesis.

Ligand-Controlled Site- and Enantioselective Carbene Insertion into Carbon-Silicon Bonds of Benzosilacyclobutanes.

We report herein a highly efficient palladium-catalyzed carbene insertion into strained Si-C bonds of benzosilacyclobutanes, which provides an efficient method to access α-chiral silanes. With a sterically hindered ligand, carbene insertion into the C(sp3 )-Si bond of benzosilacyclobutanes occurred in excellent site- and enantioselectivity, while C(sp2 )-Si bond insertion occurred selectively with less sterically hindered ligands. Reaction mechanism, in particular the roles of the chiral ligands in controlling the site-selectivity of the insertion reactions, are elucidated by using hybrid density functional theory.

Effective external reminders impair the practice effect of time-based prospective memory.

The practice effect of time-based prospective memory (TBPM) refers to the phenomenon that TBPM task performance can be significantly improved by repetitive behavioural training. However, reminders are a common strategy for people to perform TBPM tasks in daily life. A large amount of evidence shows that reminders can improve TBPM performance when individuals pay less attention to time information. However, the present study was the first to explore whether external reminders might simultaneously impede the practice effect of TBPM. In this study, 81 undergraduate students were randomly assigned to control group (N = 27, Mage  = 20.00, SDage  = 1.04), reminder group (N = 26, Mage  = 20.35, SDage  = 1.70) and non-reminder group (N = 28, Mage  = 20.25, SDage  = 1.17). In the training stage, the reminder group could receive effective external reminders, while the non-reminder group could not. The results of the training stage revealed that compared with the non-reminder group, the reminder group had fewer time monitoring times and better TBPM performance. In the testing stage, when reminders were removed from the reminder group, we found that compared with the control group without TBPM training, the TBPM performance of the reminder group failed to improve, while that of the non-reminder group improved significantly. Meanwhile, the time estimation ability of the reminder group was not as improved as that of the non-reminder group.

Shaping ability of four single-file systems in the instrumentation of second mesiobuccal canals of three-dimensional printed maxillary first molars.

BACKGROUND: This study evaluated and compared the shaping ability of four advanced single-file nickel-titanium (NiTi) systems during the preparation of curved second mesiobuccal (MB2) canals in maxillary first molar replicas fabricated by three-dimensional (3D) printing via micro-computed tomography (Micro-CT) imaging. METHODS: A total of 60 3D-printed maxillary first molar replicas were constructed from one extracted tooth, with an angle of curvature ranging from 15° to 25°. The MB2 canals from these 60 replicas were divided into 4 groups of 15 replicas according to the canal instrumentation system used, namely, Waveone gold (WOG), Reciproc blue (RCB), XP-endo shaper (XPS) and M3-L. The specimens were scanned before and after preparation using Micro-CT. The pre- and post-instrumentation images of each specimen were superimposed, and the amount of resin removed, the change in surface area, the canal transportation, and centering ability were assessed using the Mimics software. Instrumentation time was also recorded. One-way analysis of variance and least significant difference (LSD) tests were used to statistically compare the groups. The significance level was set at 5%. RESULTS: Instrumentation time with M3-L was significantly longer than the other systems (P<0.05). The amount of resin removed and the change in surface area generated by the 4 systems were different at the apical, middle, and coronal thirds, and the total canal (P<0.05). Overall, WOG and XPS resulted in the less change than RCB and M3-L. There was no significant difference among the groups at the middle third regarding canal transportation and centering ability (P>0.05). However, a significant difference was found at the apical level (P<0.05), where RCB showed the poorest centering ability and the highest canal transportation (P<0.05). In addition, XPS resulted in the least canal transportation (P<0.05) at the coronal level, while there was no significant difference between the four groups in terms of centering ability. CONCLUSIONS: The M3-L instrument required more time to prepare the curved MB2 canals compared with the other systems. Overall, WOG and XPS showed the least resin removal and surface area change. M3-L, XPS, and WOG instruments respected the original canal curvature better than RCB files.

Palladium-Catalyzed Enantioselective Carbene Insertion into Carbon-Silicon Bonds of Silacyclobutanes.

We report herein a highly efficient palladium-catalyzed carbene insertion into strained Si-C bonds with excellent enantioselectivity, which provides a rapid and distinct method to access silacyclopentanes with a three- or four-substituted stereocenter asymmetrically. Mechanistic studies using hybrid density functional theory suggest a catalytic cycle involving oxidative addition, carbene migratory insertion, and reductive elimination. In addition, roles of the chiral ligands in controlling the reaction enantioselectivity are also elucidated.

Synthesis of Alkenylboronates from N-Tosylhydrazones through Palladium-Catalyzed Carbene Migratory Insertion.

The palladium-catalyzed oxidative borylation reaction of N-tosylhydrazones has been developed. The reaction features mild conditions, broad substrate scope, and good functional group tolerance. It thus represents a highly efficient and practical method for the synthesis of di-, tri-, and tetrasubstituted alkenylboronates from readily available N-tosylhydrazones. One-pot Suzuki coupling and other transformations highlight the synthetic utility of the approach. DFT calculations have revealed that palladium-carbene formation and subsequent boryl migratory insertion are the key steps in the catalytic cycle. The high stereoselectivity observed in the formation of trisubstituted alkenylboronates has been explained by distortion-interaction analysis and NBO analysis.

Experimental and Computational Studies on Rh(I)-Catalyzed Reaction of Siloxyvinylcyclopropanes and Diazoesters.

The Rh(I)-catalyzed reaction of siloxyvinylcyclopropanes and diazoesters leads to the formation of siloxyvinylcyclobutane and 1,4-diene derivatives. With [Rh(cod)Cl]2 as the catalyst, the formation of 1,4-diene was favored over the formation of siloxyvinylcyclobutane. By changing the catalyst to [Rh(cod)2OTf], siloxyvinylcyclobutane derivatives are formed with excellent chemoselectivities and in moderate to good yields. The alkene products are also obtained as single E configured isomers. A detailed mechanism for this transformation is proposed on the basis of mechanistic experiments and DFT calculations. The effect of catalysts on the chemoselectivity of these reactions is also examined computationally.

Genotype, biofilm formation ability and specific gene transcripts characteristics of endodontic Enterococcus faecalis under glucose deprivation condition.

OBJECTIVE: To study the relationship between the specific gene and biofilm formation ability of seven wild type Enterococcus faecalis (E. faecalis) under glucose deprivation conditions. DESIGN: Wild type E. faecalis (3RC, 5RC, 25RC, 31RC, 33RC, 37RC, 58RC) extracted from the teeth with persistent apical periodontitis were cultured under glucose deprivation conditions and then resequenced. The biofilm formation ability was compared using primary adherence assay, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The transcriptional level of biofilm formation-related genes (ace, gelE, efa, esp and fsrB) were detected. RESULTS: Genomic resequencing showed that 3RC and 58RC (Class B) were similar, while 5RC, 25RC, 31RC, 33RC and 37RC (Class A) were similar. Based on primary adherence assay, CLSM and SEM results, biofilm formation ability of Class B strains was lower, while Class A strains were higher when compared with control group (0.25 % glucose). Furthermore, compared with control group (0.25 % glucose), the transcriptional levels of ace, efa and fsrB genes were upregulated in all strains; the transcriptional levels of gelE were downregulated in Class B strains, upregulated in Class A strains; the transcriptional levels of esp of Class B strains were downregulated, while upregulated in 25RC, 31RC and 37RC (Class A), and not observed in 5RC and 33RC. CONCLUSION: The genotypes of wild type E. faecalis of different persistent periapical periodontitis teeth are different. The genotype differences and the transcription levels of related virulence genes (ace, gelE, efa, esp and fsrB) are related to the biological phenotype.

Palladium-Catalyzed Oxidative Cross-Coupling of Conjugated Enynones with Allylarenes: Synthesis of Furyl-Substituted 1,3-Dienes.

A new method for the synthesis of furyl-substituted 1,3-dienes via palladium-catalyzed oxidative cross-coupling of conjugated enynones with allylarenes is developed. This reaction shows broad substrate scope and good functional group tolerance. Palladium carbene migratory insertion is proposed as the key step for this transformation with conjugated enynones serving as the carbene precursors.

Palladium-catalyzed oxidative borylation of conjugated enynones through carbene migratory insertion: synthesis of furyl-substituted alkenylboronates.

A palladium-catalyzed oxidative borylation reaction of conjugated enynones is developed. This reaction represents a new method for the synthesis of furyl-substituted alkenylboronates. The reaction works well with a series of conjugated enynones. Boryl migratory insertion of the palladium carbene intermediate is proposed as the key step in these transformations.

High throughput sequencing-based analysis of microbial diversity in dental unit waterlines supports the importance of providing safe water for clinical use.

This study aims to explore the water quality of dental unit waterlines (DUWLs) and the diversity of microbial communities in DUWLs. Water samples from 33 dental chair units (DCUs) were collected, diluted and then spread on sterilized R2A plate for incubation. Subsequently, the microbial colony-forming units per milliliter (CFU/ml) were recorded by an automatic colony analyzer. Total DNA extracted from the rest of the samples was tested on the Illumina MiSeq PE300 platform. T-test and Kruskal-Wallis rank test were adopted for statistical analysis. Significance was assumed at a P<0.05. After incubation, the average total microbial count was 21,413.13±17,861.00CFU/ml. High-throughput sequencing revealed 10 bacterial phyla, including 9 identified and 1 unclassified phyla. Totally 63 sequences were identified at the genus level, including 42 genera, 3 tentative species and 18 unclassified genera. In addition, 7 potential human pathogenic bacteria were detected. In summary, department, brand and service life of DCUs do not influence the water quality of DUWLs significantly. The diversity of microbial communities in DUWLs is abundant and includes both pathogenic and some unknown bacteria.

Palladium-Catalyzed [3+3] Annulation of Vinyl Chromium(0) Carbene Complexes through Carbene Migratory Insertion/Tsuji-Trost Reaction.

Vinyl chromium(0) Fischer carbene complexes were employed as the source of π-allylic palladium species for catalytic [3+3] annulation under palladium catalysis. Mechanistically, this transformation is proposed to involve carbene migratory insertion and intramolecular Tsuji-Trost reaction as the key steps. Substituted six-membered heterocyclic flavonones and quinolines are obtained, depending on the nucleophilic functional group on the coupling partners.

Synthesis of α,ß-Unsaturated N-Sulfonyl Imides through Zinc-Catalyzed Intermolecular Oxidation of N-Sulfonyl Ynamides.

A novel zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides has been developed. A variety of functionalized α,ß-unsaturated N-sulfonyl imides are readily accessed by utilizing this approach, thus providing a viable alternative to synthetically useful α,ß-unsaturated imides. Importantly, the reaction is proposed to proceed by a vinyligous E2-type elimination pathway, but not metal carbene pathway.

Generation of α-Imino Gold Carbenes through Gold-Catalyzed Intermolecular Reaction of Azides with Ynamides.

The generation of α-imino gold carbenes via gold-catalyzed intermolecular reaction of azides and ynamides is disclosed. This new methodology allows for highly regioselective access to valuable 2-aminoindoles and 3-amino-ß-carbolines in generally good to excellent yields. A mechanistic rationale for this tandem reaction, especially for the observed high regioselectivity, is supported by DFT calculations.

Flexible and practical synthesis of 3-oxyindoles through gold-catalyzed intermolecular oxidation of o-ethynylanilines.

A novel gold-catalyzed intermolecular oxidation of o-ethynylanilines has been developed. A range of functionalized 3-oxyindoles are readily accessed by utilizing this strategy. Importantly, this gold-catalyzed oxidative process outcompetes the typical indole formation.