Lithium-Ion Dynamic and Storage of Atomically Precise Halogenated Nanographene Assemblies via Bottom-Up Chemical Synthesis.

Graphene has received much scientific attention as an electrode material for lithium-ion batteries because of its extraordinary physical and electrical properties. However, the lack of structural control and restacking issues have hindered its application as carbon-based anode materials for next generation lithium-ion batteries. To improve its performance, several modification approaches such as edge-functionalization and electron-donating/withdrawing substitution have been considered as promising strategies. In addition, group 7A elements have been recognized as critical elements due to their electronegativity and electron-withdrawing character, which are able to further improve the electronic and structural properties of materials. Herein, we elucidated the chemistry of nanographenes with edge-substituted group 7A elements as lithium-ion battery anodes. The halogenated nanographenes were synthesized via bottom-up organic synthesis to ensure the structural control. Our study reveals that the presence of halogens on the edge of nanographenes not only tunes the structural and electronic properties but also impacts the material stability, reactivity, and Li+ storage capability. Further systematic spectroscopic studies indicate that the charge polarization caused by halogen atoms could regulate the Li+ transport, charge transfer energy, and charge storage behavior in nanographenes. Overall, this study provides a new molecular design for nanographene anodes aiming for next-generation lithium-ion batteries.

Comparative Study of the Orientation and Order Effects on the Thermoelectric Performance of 2D and 3D Perovskites.

Calcium titanium oxide has emerged as a highly promising material for optoelectronic devices, with recent studies suggesting its potential for favorable thermoelectric properties. However, current experimental observations indicate a low thermoelectric performance, with a significant gap between these observations and theoretical predictions. Therefore, this study employs a combined approach of experiments and simulations to thoroughly investigate the impact of structural and directional differences on the thermoelectric properties of two-dimensional (2D) and three-dimensional (3D) metal halide perovskites. Two-dimensional (2D) and three-dimensional (3D) metal halide perovskites constitute the focus of examination in this study, where an in-depth exploration of their thermoelectric properties is conducted via a comprehensive methodology incorporating simulations and experimental analyses. The non-equilibrium molecular dynamics simulation (NEMD) was utilized to calculate the thermal conductivity of the perovskite material. Thermal conductivities along both in-plane and out-plane directions of 2D perovskite were computed. The NEMD simulation results show that the thermal conductivity of the 3D perovskite is approximately 0.443 W/mK, while the thermal conductivities of the parallel and vertical oriented 2D perovskites increase with n and range from 0.158 W/mK to 0.215 W/mK and 0.289 W/mK to 0.309 W/mK, respectively. Hence, the thermal conductivity of the 2D perovskites is noticeably lower than the 3D ones. Furthermore, the parallel oriented 2D perovskites exhibit more effective blocking of heat transfer behavior than the perpendicular oriented ones. The experimental results reveal that the Seebeck coefficient of the 2D perovskites reaches 3.79 × 102 µV/K. However, the electrical conductivity of the 2D perovskites is only 4.55 × 10-5 S/cm, which is one order of magnitude lower than that of the 3D perovskites. Consequently, the calculated thermoelectric figure of merit for the 2D perovskites is approximately 1.41 × 10-7, slightly lower than that of the 3D perovskites.

Targeting histone deacetylase 9 represses fibrogenic phenotypes in buccal mucosal fibroblasts with arecoline stimulation.

Background/purpose: Oral submucosal fibrosis (OSF) is a premalignant disorder positively associated with betel nut chewing. Recent studies supported the promising benefits of histone deacetylase (HDAC) inhibitors for fibrosis treatment. Here we aim to clarify the pro-fibrogenic role of HDAC9 in regulating OSF. Materials and methods: Healthy and OSF specimens were collected to investigate the clinical significance of HDAC9. Chronic arecoline treatment process was used to induce arecoline-mediated myofibroblasts-related activation of primary buccal mucosa fibroblasts (BMFs). Functional analysis of collagen gel contraction, transwell migration, and wound-healing assays were performed to assess the change in pro-fibrogenic properties of BMFs and fibrotic BMFs (fBMFs). Lentiviral-mediated HDAC9 knockdown was used to verify the role of HDAC9 in the pro-fibrogenic process. Results: We found that arecoline significantly increased the mRNA and protein expression of HDAC9 of BMFs in a dose-dependent manner. Knockdown of HDAC9 in BMFs reversed the strengthened effects of arecoline on collagen gel contraction, cell migration, and wound-healing ability. We further demonstrated that knockdown of HDAC9 in fBMFs significantly attenuated its inherent pro-fibrogenic properties. Furthermore, we confirmed a significantly increased expression of HDAC9 mRNA in OSF compared to normal tissues, which suggested a positive correlation between the up-regulation of HDAC9 and OSF. Conclusion: We demonstrated that silencing of HDAC9 inhibited arecoline-induced activation and inherent pro-fibrogenic properties, suggesting potential therapeutics by targeting HDAC9 in the OSF treatment.

NS5806 reduces carrageenan-evoked inflammation by suppressing extracellular signal-regulated kinase activation in primary sensory neurons and immune cells.

BACKGROUND: The compound NS5806 attenuates neuropathic pain via inhibiting extracellular signal-regulated kinase (ERK) activation in neuronal somata located at the dorsal root ganglion (DRG) and superficial spinal dorsal horn. NS5806 also reduces the expansion of DRG macrophages and spinal microglia several days after peripheral nerve injury, implying an anti-inflammatory effect. METHODS: To test whether NS5806 inhibits inflammation, as a model we intraplantarly injected carrageenan into a hind paw of the rat. To examine whether NS5806 reduces carrageenan-evoked mechanical allodynia, thermal hyperalgesia, and edema, as well as ERK activation in the nerve fibres, mast cells, and macrophages in the hind paw skin, we used behavioural, immunohistochemical, and cytological methods. RESULTS: NS5806 did not impair motor function, affect basal nociception, or cause edema in naive rats. Six hours after carrageenan injection, mechanical allodynia, thermal hyperalgesia, and edema appeared in the rat's ipsilateral hind paw, and all were reduced by intraplantar co-injection of NS5806. NS5806 suppressed carrageenan-evoked ERK activation in the peripheral axons and somata of L4 DRG neurons, as well as mast cells and macrophages in the paw skin. NS5806 also reduced carrageenan-evoked mast cell degranulation and macrophage proliferation. NS5806 and the ERK pathway inhibitor PD98059 had a similar effect in inhibiting the proliferation of cultured RAW264.7 macrophages. Furthermore, all the in vivo anti-inflammatory effects of NS5806 were similar to those of PD98059. CONCLUSIONS: Acting like an ERK pathway inhibitor, NS5806 reduces inflammation-evoked mechanical allodynia, thermal hyperalgesia, and edema by suppressing ERK activation in primary sensory neurons, mast cells, and macrophages. SIGNIFICANCE: Previous studies show that NS5806 only acts on neurons. This report unveils that NS5806 also acts on immune cells in the skin to exert its anti-inflammatory effects. Since NS5806 is lipid soluble for skin penetration, it suggests that NS5806 could also be developed into an anti-inflammatory drug for external use.

Hybrid Machine Learning-Enabled Potential Energy Model for Atomistic Simulation of Lithium Intercalation into Graphite from Plating to Overlithiation.

Graphite is one of the most widely used negative electrode materials for lithium ion batteries (LIBs). However, because of the rapid growth of demands pursuing higher energy density and charging rates, comprehensive insights into the lithium intercalation and plating processes are critical for further boosting the potential of graphite electrodes. Herein, by utilizing the dihedral-angle-corrected registry-dependent potential (DRIP) (Wen et al., Phys. Rev. B 2018, 98, 235404), the Ziegler-Biersack-Littmark (ZBL) potential (Ziegler and Biersack, Astrophysics, Chemistry, and Condensed Matter; 1985, pp 93-129), and the machine learning-based spectral neighbor analysis (SNAP) potential (Thompson et al., J. Comput, Phys. 2015, 285, 316-330), we have successfully trained a hybrid machine learning-enabled potential energy model capable of simulating a wide spectrum of lithium intercalation scenario from plating to overlithiation. Our extensive atomistic simulations reveal the trapping of intercalated lithium atoms close to the graphite edges due to high hopping barriers, resulting in lithium plating. Furthermore, we report a stable dense graphite intercalation compound (GIC) LiC4 with a theoretical capacity of 558 mAh/g, wherein lithium atoms occupy alternating upper/lower graphene hollow sites with a nearest Li-Li distance of 2.8 Å. Surprisingly, following the same lithium insertion manner would allow the nearest Li-Li distance to be retained until the capacity reaches 845.2 mAh/g, corresponding to a GIC of LiC2.6. Hence, the present study demonstrates that the hybrid machine learning approach could further extend the scope of machine learning energy models, allowing us to investigate the lithium intercalation into graphite over a wide range of intercalation capacity to unveil the underlying mechanisms of lithium plating, diffusion, and discovery of new dense GICs for advanced LIBs with high charging rates and high energy densities.

Decreased trends of using dental amalgam filling for decayed teeth in Taiwan from 1997 to 2013.

Background/purpose: Mercury within dental amalgam has been criticized for the potential toxicity and environmental hazard. Phasing down the use of dental amalgam is the transition for amalgam free dentistry. However, little is known about dental amalgam filling (AMF) in Taiwan. In this study, time trends of AMF were measured by using National Health Insurance Research Database (NHIRD). Materials and methods: A retrospective study was conducted to analyze the AMF data in registered database compiled by Taiwanese NHIRD from 1997 to 2013. The AMF data were further analyzed according to sex, age, and geographic location, respectively. Time trends of dental visits for AMF and medical expenses for AMF were also evaluated. Results: The average annual AMF ratio was 8.965% of nationwide population in Taiwan. The prevalence of AMF was significantly decreased both in male and female from 1997 to 2013 (P for trend <0.0001). The decreased pattern of AMF was found by the age stratification (P for trend <0.0001). The significant fall of AMF was also displayed in six districts (P for trend <0.0001). The number of dental visits were ranged from 821,749 in 1997 to 1,313,734 in 2013. However, time trends of dental visits for AMF were significantly decreased (P for trend <0.0001). The medical expenses for AMF were simultaneous significantly decreased from 1997 to 2013 (P for trend <0.0001). Conclusion: Form the results of this nationwide population-based database, a significant decrease of AMF in Taiwan was observed during past 17 years.

Down-regulation of miR-29c promotes the progression of oral submucous fibrosis through targeting tropomyosin-1.

BACKGROUND/PURPOSE: Various microRNAs (miRs) have been found to be associated with the development of the precancerous condition of the oral cavity, oral submucous fibrosis (OSF). The expression of miR-29c is dysregulated in oral cancer, but its role in OSF has not been investigated. The purpose of the study is to investigate the functional role of miR-29c and its target in OSF. METHODS: The expression levels of miR-29c in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were assessed using next-generation sequencing and real-time Polymerase Chain Reaction (PCR) analysis. MiR-29c mimic and inhibitors were employed to examine its functional role of myofibroblast transdifferentiation. In addition, several myofibroblast phenotypes, such as collagen gel contraction and migration were tested, and a luciferase reporter assay was conducted to confirm the relationship between miR-29c and its predicted target, tropomyosin-1 (TPM1). RESULTS: We observed that miR-29c expression was downregulated in fBMFs. fBMFs transfected with miR-29c mimics exhibited reduced migration ability and collagen gel contractility, whereas inhibition of miR-29c in normal BMFs induced the myofibroblast phenotypes. Results from the luciferase reporter assay showed that TPM1 was a direct target of miR-29c and the expression of TPM1 was suppressed in the fBMFs transfected with miR-29c mimics. Besides, we confirmed that the expression of miR-29c was indeed downregulated in OSF specimens. CONCLUSION: MiR-29c seems to exert an inhibitory effect on myofibroblast activation, such as collagen gel contractility and migration ability, via suppressing TPM1. These results suggested that approaches to upregulate miR-29c may be able to ameliorate the progression of OSF.

Molecular Simulations of the Microstructure Evolution of Solid Electrolyte Interphase during Cyclic Charging/Discharging.

Lithium (Li) metal is regarded as one of the most promising anode materials for use in next-generation high-energy-density rechargeable batteries because of its high volumetric and gravimetric specific capacity, as well as low reduction potential. Unfortunately, uncontrolled dendritic Li growth during cyclic charging/discharging leads to low columbic efficiency and critical safety issues. Hence, comprehensive understanding of the formation mechanism for Li-dendrite growth, particularly at the onset of dendrite formation, is essential for developing Li-metal anode batteries. In this study, reactive molecular dynamics (MD) simulations in combination with the electrochemical dynamics with implicit degrees of freedom (EChemDID) method were performed to investigate the formation and evolution of solid electrolyte interphase (SEI) films for a Li-metal anode under cyclic charging/discharging processes in two distinct dimensions, namely, electrolyte compositions and initial surface morphologies. Our simulations indicated that regardless of the electrolyte compositions and initial anode morphologies, inhomogeneous Li reduction, namely, the formation of Li-reduction "hotspots" during cyclic charging cycles, took place and could serve as the seed for subsequent dendrite growth. The fluorine-containing electrolyte additives could notably mitigate the Li-anode roughening processes by forming dense-SEI-layer products or suppressing electrolyte decomposition. A series of Li-ion-drifting simulations suggest that Li ions navigate through the SEI layer via pathways composed of low-density atoms and become reduced at these reduction hotspots, promoting inhomogeneous deposition and subsequent dendrite growth. The present study reveals atomistic details of the early stage of dendrite growth during cyclic loadings under different electrolyte compositions and anode morphologies, thereby providing insights for designing artificial SEI layers or electrolytes for long-life, high-capacity Li-ion batteries.

miR-1246 as a therapeutic target in oral submucosa fibrosis pathogenesis.

BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) is a precancerous condition of oral cancer with a complex etiology. Our previous work has demonstrated that non-coding RNA miR-1246 contributes to the cancer stemness of oral cancer. In the current study, we sought to investigate the effect of the inhibition of miR-1246 on the oral fibrogenesis. METHODS: The expression levels of miR-1246 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were examined by qRT-PCR. Collagen gel contraction and migration assays were conducted to evaluate the myofibroblast activities. The relationship between miR-1246 and type I collagen was assessed and the protein expression of type I collagen was determined by Western blot. RESULTS: MiR-1246 expression was upregulated in both OSF specimen and fBMFs compared to the normal counterparts. Inhibition of miR-1246 successfully suppressed the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, the expression of miR-1246 was positively correlated with type I collagen and the expression of type I collagen was abrogated by repression of miR-1246. CONCLUSION: MiR-1246 is not only critical to the maintenance of oral stemness but also important to the activation of myofibroblasts. Our results showed that miR-1246 is positively associated with the type I collagen, which may be a downstream effector of miR-1246 and responsible for the fibrosis effect on fBMFs.

Catalytic polymerization of naphthalene by HF/BF3 super acid: an ab initio density functional theory study.

Mesophase pitch fabricated through polymerization of polycyclic aromatic hydrocarbons (PAHs) is highly aromatic and of high quality, and it can be used as a raw material to produce other carbon-based materials. Hydrofluoride/boron trifluoride (HF/BF3) is currently an efficient reagent to catalyze the PAH polymerization to produce mesophase pitch. In this study, density functional theory (DFT) calculations are performed to propose a mechanism for naphthalene catalytic polymerization using HF/BF3. The overall reaction mechanism can be conceptualized as having two stages: activation, followed by polymerization. During activation, HF/BF3 acts a proton donor to activate naphthalene, whose then-protonated form can promote the formation of a C-C bond with another naphthalene molecule via electrophilic addition. We also propose a catalyst recovery pathway, which can stabilize the intermediate products. In the polymerization stage, two types of pathways are proposed, those of chain elongation and intramolecular cyclization. According to the proposed catalytic mechanism in this study, the predicted mesophase product shows highly aliphatic hydrogens, which is consistent with the experimental results. We propose the full catalytic mechanism using DFT calculations. Our results provide a better understanding of how to develop novel and green catalysts, which can replace the HF/BF3 reagent in future applications.

Malignant transformation of oral submucous fibrosis in Taiwan: A nationwide population-based retrospective cohort study.

BACKGROUND: Oral submucous fibrosis (OSF) is one of the well-recognized oral potentially malignant disorders. In this study, we investigated the malignant transformation of OSF in a Taiwanese population. METHODS: A retrospective cohort study was analyzed from Taiwan's National Health Insurance Research Database. A comparison cohort was randomly frequency-matched with the OSF cohort according to age, sex, and index year. Oral leukoplakia (OL) was further stratified to evaluate for the possible synergistic effects of OSF-associated malignant transformation. RESULTS: In this cohort, 71 (9.13%) of 778 cases of OSF were observed to transform into oral cancer. The malignant transformation rate was 29.26-fold in the OSF cohort than in the comparison cohort after adjustment (95% confidence intervals 20.55-41.67). To further stratify with OL, OSF with OL (52.46%; 95% confidence intervals 34.88-78.91) had higher risk of malignant transformation rate than OSF alone (29.84%; 95% confidence intervals 20.99-42.42). The Kaplan-Meier plot revealed the rate free of malignant transformation was significant over the 13-year follow-up period (log-rank test, P<.001). The mean duration of malignant transformation was 5.1, 2.7, and 2.2 years for non-OSF, OSF alone, and OSF with OL, respectively. CONCLUSION: Oral submucous fibrosis patients exhibited a significantly higher risk of malignant transformation than those without OSF. OL could enhance malignant transformation in patients with OSF.

Trends in the prevalence of diagnosed temporomandibular disorder from 2004 to 2013 using a Nationwide health insurance database in Taiwan.

BACKGROUND/PURPOSE: Temporomandibular disorder (TMD) is defined as various clinical signs and symptoms involving the masticatory muscles, the temporomandibular joint and associated structures. The aim of this study was to investigate the prevalence of diagnosed TMD in Taiwan using a National Health Insurance Research Database from 2004 to 2013. MATERIALS AND METHODS: A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance from 2004 to 2013. The diagnosis of TMDs was identified in accordance with the International Classification of Disease, Ninth revision (ICD-9-CM 524.6). The relative risk of TMD from 2004 to 2013 after adjusting for year, age, and gender was evaluated by logistic regression analysis. RESULTS: The prevalence of TMD increased significantly from 14 (per 104) to 26 (per 104) over the past 10 year period [odds ratio (OR), 1.07; 95% confidence interval (CI), 1.04-1.09]. The mean age with TMD from 2004 to 2013 was 52.31 ± 17.15 years and 45.12 ± 17.32 years, respectively. The female group had a higher risk of TMD than the male group (OR, 1.70; 95% CI, 1.49-1.94). CONCLUSION: Taken together, the estimated prevalence of TMD significantly increased from 2004 to 2013 in Taiwan. In addition, the risk for TMD was higher among women than among men.

Andrographolide impedes cancer stemness and enhances radio-sensitivity in oral carcinomas via miR-218 activation.

Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1+CD44+ OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1-CD44- non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it. Furthermore, we found tumor growth was reduced in mice bearing xenograft tumors after andrographolide treatment via activation of miR-218/Bmi1 axis. Together, these data demonstrated that the inhibition of tumor aggressiveness in OCSCs by andrographolide was mediated through the upregulation of miR-218, thereby reducing Bmi1 expression. These findings suggest that andrographolide may be a valuable natural compound for anti-CSCs treatment of OSCC.

Impact of Maspin Polymorphism rs2289520 G/C and Its Interaction with Gene to Gene, Alcohol Consumption Increase Susceptibility to Oral Cancer Occurrence.

BACKGROUND: The purpose of this study was to identify gene polymorphisms of mammary serine protease inhibitor (Maspin) specific to patients with oral cancer susceptibility and clinicopathological status. METHODOLOGY/PRINCIPAL FINDINGS: Three single-nucleotide polymorphisms (SNPs) of the Maspin gene from 741 patients with oral cancer and 601 non-cancer controls were analyzed by real-time PCR. The participants with G/G homozygotes or with G/C heterozygotes of Maspin rs2289520 polymorphism had a 2.07-fold (p = 0.01) and a 2.01-fold (p = 0.02) risk of developing oral cancer compared to those with C/C homozygotes. Moreover, gene-gene interaction increased the risk of oral cancer susceptibility among subjects expose to oral cancer related risk factors, including areca, alcohol, and tobacco consumption. CONCLUSION: G allele of Maspin rs2289520 polymorphism may be a factor that increases the susceptibility to oral cancer. The interactions of gene to oral cancer-related environmental risk factors have a synergetic effect that can further enhance oral cancer development.

Understanding the carbon-monoxide oxidation mechanism on ultrathin palladium nanowires: a density functional theory study.

The CO oxidation mechanism catalyzed by ultrathin helical palladium nanowires (PdNW) was investigated by density functional theory (DFT) calculation. The helical PdNW structure was constructed on the basis of the simulated annealing basin-hopping (SABH) method with the tight-binding potential and the penalty method in our previous studies (J. Mater. Chem., 2012, 22, 20319). The low-lying adsorption configurations as well as the adsorption energies for O2 and CO molecules on different PdNW adsorption sites were obtained by DFT calculation. The most stable adsorption configurations for the Langmuir-Hinshelwood (LH) mechanism processes were considered for investigating the CO oxidation mechanism. The nudged elastic band (NEB) method was adopted to obtain the transition state configuration and the minimum energy pathways (MEPs).

Conductivity enhancement of multiwalled carbon nanotube thin film via thermal compression method.

For the first time, the thermal compression method is applied to effectively enhance the electrical conductivity of carbon nanotube thin films (CNTFs). With the assistance of heat and pressure on the CNTFs, the neighbor multiwalled carbon nanotubes (CNTs) start to link with each other, and then these separated CNTs are twined into a continuous film while the compression force, duration, and temperature are quite enough for the reaction. Under the compression temperature of 400°C and the compression force of 100 N for 50 min, the sheet resistance can be reduced from 17 to 0.9 k Ω/sq for the CNTFs with a thickness of 230 nm. Moreover, the effects of compression temperature and the duration of thermal compression on the conductivity of CNTF are also discussed in this work.