Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice.

There has been increasing interest in adjunctive use of anti-inflammatory drugs to control periodontitis. This study was performed to examine the effects of pirfenidone (PFD) on alveolar bone loss in ligature-induced periodontitis in mice and identify the relevant mechanisms. Experimental periodontitis was established by ligating the unilateral maxillary second molar for 7 days in mice (n = 8 per group), and PFD was administered daily via intraperitoneal injection. The micro-computed tomography and histology analyses were performed to determine changes in the alveolar bone following the PFD administration. For in vitro analysis, bone marrow macrophages (BMMs) were isolated from mice and cultured with PFD in the presence of RANKL or LPS. The effectiveness of PFD on osteoclastogenesis, inflammatory cytokine expression, and NF-κB activation was determined with RT-PCR, Western blot, and immunofluorescence analyses. PFD treatment significantly inhibited the ligature-induced alveolar bone loss, with decreases in TRAP-positive osteoclasts and expression of inflammatory cytokines in mice. In cultured BMM cells, PFD also inhibited RANKL-induced osteoclast differentiation and LPS-induced proinflammatory cytokine (IL-1ß, IL-6, TNF-a) expression via suppressing the NF-κB signal pathway. These results suggest that PFD can suppress periodontitis progression by inhibiting osteoclastogenesis and inflammatory cytokine production via inhibiting the NF-κB signal pathway, and it may be a promising candidate for controlling periodontitis.

A hierarchical chain-based Archimedes optimization algorithm.

The Archimedes optimization algorithm (AOA) has attracted much attention for its few parameters and competitive optimization effects. However, all agents in the canonical AOA are treated in the same way, resulting in slow convergence and local optima. To solve these problems, an improved hierarchical chain-based AOA (HCAOA) is proposed in this paper. The idea of HCAOA is to deal with individuals at different levels in different ways. The optimal individual is processed by an orthogonal learning mechanism based on refraction opposition to fully learn the information on all dimensions, effectively avoiding local optima. Superior individuals are handled by an Archimedes spiral mechanism based on Levy flight, avoiding clueless random mining and improving optimization speed. For general individuals, the conventional AOA is applied to maximize its inherent exploration and exploitation abilities. Moreover, a multi-strategy boundary processing mechanism is introduced to improve population diversity. Experimental outcomes on CEC 2017 test suite show that HCAOA outperforms AOA and other advanced competitors. The competitive optimization results achieved by HCAOA on four engineering design problems also demonstrate its ability to solve practical problems.

Neurotoxicity of Diesel Exhaust Particles.

BACKGROUND: Air pollution particulate matter (PM) is strongly associated with risks of accelerated cognitive decline, dementia and Alzheimer's disease. Ambient PM batches have variable neurotoxicity by collection site and season, which limits replicability of findings within and between research groups for analysis of mechanisms and interventions. Diesel exhaust particles (DEP) offer a replicable model that we define in further detail. OBJECTIVE: Define dose- and time course neurotoxic responses of mice to DEP from the National Institute of Science and Technology (NIST) for neurotoxic responses shared by DEP and ambient PM. METHODS: For dose-response, adult C57BL/6 male mice were exposed to 0, 25, 50, and 100µg/m3 of re-aerosolized DEP (NIST SRM 2975) for 5 h. Then, mice were exposed to 100µg/m3 DEP for 5, 100, and 200 h and assayed for amyloid-ß peptides, inflammation, oxidative damage, and microglial activity and morphology. RESULTS: DEP exposure at 100µg/m3 for 5 h, but not lower doses, caused oxidative damage, complement and microglia activation in cerebral cortex and corpus callosum. Longer DEP exposure for 8 weeks/200 h caused further oxidative damage, increased soluble Aß, white matter injury, and microglial soma enlargement that differed by cortical layer. CONCLUSION: Exposure to 100µg/m3 DEP NIST SRM 2975 caused robust neurotoxic responses that are shared with prior studies using DEP or ambient PM0.2. DEP provides a replicable model to study neurotoxic mechanisms of ambient PM and interventions relevant to cognitive decline and dementia.

Emotional Responses to the Visual Patterns of Urban Streets: Evidence from Physiological and Subjective Indicators.

Despite recent progress in the research of people's emotional response to the environment, the built-rather than natural-environment's emotional effects have not yet been thoroughly examined. In response to this knowledge gap, we recruited 26 participants and scrutinized their emotional response to various urban street scenes through an immersive exposure experiment using virtual reality. We utilized new physiological monitoring technologies that enable synchronized observation of the participants' electroencephalography, electrodermal activity, and heart rate, as well as their subjective indicators. With the newly introduced measurement for the global visual patterns of the built environment, we built statistical models to examine people's emotional response to the physical element configuration and color composition of street scenes. We found that more diverse and less fragmented scenes inspired positive emotional feelings. We also found (in)consistency among the physiological and subjective indicators, indicating a potentially interesting neural-physiological interpretation for the classic form-function dichotomy in architecture. Besides the practical implications on promoting physical environment design, this study combined objective physiology-monitoring technology and questionnaire-based research techniques to demonstrate a better approach to quantify environment-emotion relationships.

Evaluation of cellular response and drug delivery efficacy of nanoporous stainless steel material.

OBJECTIVE: Various surface modification techniques that can further improve the function and usability of stainless steel as a medical device have been reported. In the present study, the physical and biological properties of nanoporous stainless steel as well as its usefulness for drug delivery were assessed. METHODS: The specimen was prepared with a circular disk shape (15 mm in diameter and 1 mm in thickness). The disk was subjected to electropolishing at a constant voltage of 20 V and 10 A for 10 min in an acidic environment (50% H2SO4). Everolimus (EVL) was used as a testing drug for drug-loading capacity of the material surface and release kinetics. The physiobiological properties of the material were assessed using platelet adhesion, and smooth muscle cell (SMC) adhesion, migration, and proliferation assays. RESULTS: The surface roughness of the postpolishing group was greater than that of the nonpolishing group. Platelet adhesion and SMC adhesion and migration were inhibited in the postpolishing group compared to those in the prepolishing group. In the postpolishing group, the total amount of EVL on the surface (i.e., drug storage rate) was higher and the drug release rate was lower, with half the amount of the EVL released within 4 days compared with only 1 day for that of the prepolishing group. CONCLUSION: Taken together, this stainless steel with a nanoporous surface could be used as a medical device for controlling cellular responses and carrying drugs.

DUSP6 Inhibitor (E/Z)-BCI Hydrochloride Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophage Cells via Activating the Nrf2 Signaling Axis and Inhibiting the NF-κB Pathway.

Macrophages play a fundamental role in human chronic diseases such as rheumatoid arthritis, atherosclerosis, and cancer. In the present study, we demonstrated that dual-specificity phosphatase 6 (DUSP6) was upregulated by lipopolysaccharide (LPS) treatment of macrophages. (E/Z)-BCI hydrochloride (BCI) functions as a small molecule inhibitor of DUSP6, and BCI treatment inhibited DUSP6 expression in LPS-activated macrophages. BCI treatment inhibited LPS-triggered inflammatory cytokine production, including IL-1ß and IL-6, but not TNF-α, and also affected macrophage polarization to an M1 phenotype. In addition, BCI treatment decreased reactive oxygen species (ROS) production and significantly elevated the levels of Nrf2. Interestingly, pharmacological inhibition of DUSP6 attenuated LPS-induced inflammatory responses was independent of extracellular signal-regulated kinase (ERK) signaling. Furthermore, BCI treatment inhibited phosphorylation of P65 and nuclear P65 expression in LPS-activated macrophages. These results demonstrated that pharmacological inhibition of DUSP6 attenuated LPS-induced inflammatory mediators and ROS production in macrophage cells via activating the Nrf2 signaling axis and inhibiting the NF-κB pathway. These anti-inflammatory effects indicated that BCI may be considered as a therapeutic agent for blocking inflammatory disorders.

Fabrication of stable zein nanoparticles by chondroitin sulfate deposition based on antisolvent precipitation method.

The purpose of this work is to stabilize zein nanoparticles with anionic polysaccharides-chondroitin sulfate (CS) to overcome the poor colloidal stability of zein nanoparticles. The average molecular weight of CS was 20.51 kDa and the disaccharide composition of CS was 70.71% monosulfated disaccharide Di2S and 29.29% disulfated disaccharide Di2,6 diS. Zein/CS composite nanoparticles were fabricated by antisolvent precipitation method at pH 4.0. The optimal mass ratio of zein to CS was 1:1 (w/w). Zein/CS composite nanoparticles showed mean size of 148 nm and PDI < 0.2, maintaining great stability at pH 3.0 to 8.0. Meanwhile, these prepared nanoparticles were also stable to heat treatment and was stable to a range of ionic strength of 0-15 mM at pH 4.0 and 0-10 mM at pH 7.0. The composite nanoparticles exhibited regular spherical structures, and CS was deposited on the surface of zein mainly by electrostatic interactions. In the process, the addition of urea and sodium dodecyl sulfate indicated that it also involved both hydrogen bonding and hydrophobic interactions. In addition, cytotoxicity assay on human renal epithelial cells-293 cells indicated that zein/CS composite nanoparticles were essentially nontoxic.

Investigation of Interfacial Layer for Ultrasonic Spot Welded Aluminum to Copper Joints.

The bonding formation for ultrasonic welding of dissimilar metals has been shrouded in mystery because of the complex thermomechanical behavior at the bonding interface. We investigated the microstructure and phases at the bonding interface of ultrasonically welded aluminum to copper joints using transmission electron microscopy, and found a ~10 nm thick transition layer composed of amorphous phase and nanocrystallines, which was believed to form the bonding between these two metals in addition to mechanical interlocking observed at a larger scale. Interdiffusion of parent elements (i.e. Al and Cu) was noticed in the amorphous phase, which was mainly driven by plastic deformation in solid state introduced by ultrasonic vibration. High densities of dislocations and stacking faults were also observed in the parent metals close to the transition layer, confirming the effects of severe plastic deformation.

Dislocation mechanisms and 3D twin architectures generate exceptional strength-ductility-toughness combination in CrCoNi medium-entropy alloy.

Combinations of high strength and ductility are hard to attain in metals. Exceptions include materials exhibiting twinning-induced plasticity. To understand how the strength-ductility trade-off can be defeated, we apply in situ, and aberration-corrected scanning, transmission electron microscopy to examine deformation mechanisms in the medium-entropy alloy CrCoNi that exhibits one of the highest combinations of strength, ductility and toughness on record. Ab initio modelling suggests that it has negative stacking-fault energy at 0K and high propensity for twinning. With deformation we find that a three-dimensional (3D) hierarchical twin network forms from the activation of three twinning systems. This serves a dual function: conventional twin-boundary (TB) strengthening from blockage of dislocations impinging on TBs, coupled with the 3D twin network which offers pathways for dislocation glide along, and cross-slip between, intersecting TB-matrix interfaces. The stable twin architecture is not disrupted by interfacial dislocation glide, serving as a continuous source of strength, ductility and toughness.

Scalable Production of the Silicon-Tin Yin-Yang Hybrid Structure with Graphene Coating for High Performance Lithium-Ion Battery Anodes.

Alloy anodes possessed of high theoretical capacity show great potential for next-generation advanced lithium-ion battery. Even though huge volume change during lithium insertion and extraction leads to severe problems, such as pulverization and an unstable solid-electrolyte interphase (SEI), various nanostructures including nanoparticles, nanowires, and porous networks can address related challenges to improve electrochemical performance. However, the complex and expensive fabrication process hinders the widespread application of nanostructured alloy anodes, which generate an urgent demand of low-cost and scalable processes to fabricate building blocks with fine controls of size, morphology, and porosity. Here, we demonstrate a scalable and low-cost process to produce a porous yin-yang hybrid composite anode with graphene coating through high energy ball-milling and selective chemical etching. With void space to buffer the expansion, the produced functional electrodes demonstrate stable cycling performance of 910 mAh g-1 over 600 cycles at a rate of 0.5C for Si-graphene "yin" particles and 750 mAh g-1 over 300 cycles at 0.2C for Sn-graphene "yang" particles. Therefore, we open up a new approach to fabricate alloy anode materials at low-cost, low-energy consumption, and large scale. This type of porous silicon or tin composite with graphene coating can also potentially play a significant role in thermoelectrics and optoelectronics applications.

Rational Design of Graphene-Reinforced MnO Nanowires with Enhanced Electrochemical Performance for Li-Ion Batteries.

Recently, transition metal oxides (TMOs) mixed with carbon materials have attracted attention as lithium-ion battery (LIB) anode materials. However, the aggregation issue in TMOs hinders the development of an ideal encapsulation structure with carbon materials. In this paper, we report graphene reinforced MnO nanowires with enhanced electrochemical performance as an anode in LIB. The graphene nanosheets (GNs)/MnO feature was confirmed by transmission electron microscopy, X-ray diffraction, Raman scattering, and X-ray photoelectron spectroscopy. The GNs/MnO nanowires delivered a highly stable discharge capacity of ∼815 mAh g(-1) at a current density of 100 mA g(-1) after 200 cycles, which is 1.5 times higher than that of pure MnO nanowires. This GNs/MnO structure with a specific capacity of ∼995 mAh g(-1) at a current density of 50 mA g(-1) also exhibited excellent Li storage properties. The superior cycling and high rate capability were attributed to the intimate incorporation between the MnO and GNs. The structure of the GNs/MnO nanowires effectively accommodated the volume change of the MnO nanowires and prevented structure collapse during cycling.

Dye-Sensitized Core/Active Shell Upconversion Nanoparticles for Optogenetics and Bioimaging Applications.

Near-infrared (NIR) dye-sensitized upconversion nanoparticles (UCNPs) can broaden the absorption range and boost upconversion efficiency of UCNPs. Here, we achieved significantly enhanced upconversion luminescence in dye-sensitized core/active shell UCNPs via the doping of ytterbium ions (Yb(3+)) in the UCNP shell, which bridged the energy transfer from the dye to the UCNP core. As a result, we synergized the two most practical upconversion booster effectors (dye-sensitizing and core/shell enhancement) to amplify upconversion efficiency. We demonstrated two biomedical applications using these UCNPs. By using dye-sensitized core/active shell UCNP embedded poly(methyl methacrylate) polymer implantable systems, we successfully shifted the optogenetic neuron excitation window to a biocompatible and deep tissue penetrable 800 nm wavelength. Furthermore, UCNPs were water-solubilized with Pluronic F127 with high upconversion efficiency and can be imaged in a mouse model.

Nanoscale origins of the damage tolerance of the high-entropy alloy CrMnFeCoNi.

Damage tolerance can be an elusive characteristic of structural materials requiring both high strength and ductility, properties that are often mutually exclusive. High-entropy alloys are of interest in this regard. Specifically, the single-phase CrMnFeCoNi alloy displays tensile strength levels of ∼ 1 GPa, excellent ductility (∼ 60-70%) and exceptional fracture toughness (KJIc>200 MPa√m). Here through the use of in situ straining in an aberration-corrected transmission electron microscope, we report on the salient atomistic to micro-scale mechanisms underlying the origin of these properties. We identify a synergy of multiple deformation mechanisms, rarely achieved in metallic alloys, which generates high strength, work hardening and ductility, including the easy motion of Shockley partials, their interactions to form stacking-fault parallelepipeds, and arrest at planar slip bands of undissociated dislocations. We further show that crack propagation is impeded by twinned, nanoscale bridges that form between the near-tip crack faces and delay fracture by shielding the crack tip.