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Protein-level regulations have gained importance in building synthetic circuits, as they offer a potential advantage in the speed of operation compared to gene regulation circuits. In nature, localized protein degradation is prevalent in polarizing cellular signaling. We, therefore, set out to systematically investigate whether localized proteolysis can be employed to construct intracellular asymmetry in Escherichia coli. We demonstrate that, by inserting a cognate cleavage site between the reporter and C-terminal degron, the unstable reporter can be stabilized in the presence of the tobacco etch virus protease. Furthermore, the split protease can be functionally reconstituted by the PopZ-based polarity system to exert localized proteolysis. Selective stabilization of the unstable reporter at the PopZ pole can lead to intracellular asymmetry in E. coli. Our study provides complementary evidence to support that localized proteolysis may be a strategy for polarization in developmental cell biology. Circuits designed in this study may also help to expand the synthetic biology repository for the engineering of synthetic morphogenesis, particularly for processes that require rapid control of local protein abundance.

The abnormal lattice expansion of commercial polypropylene (PP)/polyethylene (PE)/polypropylene (PP) separator in lithium-ion battery under different charging current densities was observed by in-situ X-ray diffraction. Significant lattice changes of both PP and PE were found during the low current density charging. The capacity fading and the resistance value of the cell measured at 0.025 C (5th retention, 92%) is unexpectedly larger than that at 1.0 C (5th retention, 97.3%) from the electrochemical impedance spectroscopic data. High-resolution scanning electron microscopy is employed to witness the pore changes of the trilayered membrane. Density functional theory calculations were used to investigate the mechanism responsible for the irregular results. The calculations revealed that the insertion of Li-ion and EC molecule into PP or PE are thermodynamically favourable process which might explain the anomalous significant lattice expansion during the low current density charging. Therefore, designing a new separator material with a more compact crystalline structure or surface modification to reduce the Li insertion during the battery operation is desirable.

This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.

In this research, the main purpose was to study the applicability of a machining method on microscale medical-equipment manufacturing. The characteristics of wire electrochemical micromachining (WECMM) against NiTi 50-50 wire was investigated. The study utilized a tungsten wire 0.03 mm in diameter as an electrode to cut a fine slot into the nickel–titanium wire. In order to reach a high-precision WECMM finish, an ultrashort pulse power generator was used as a power source to minimize the stray current effect, thus improving the machining accuracy. During the process, various machining parameters were tested for their effects on machining characteristics. In addition, ultrasonic-vibration-aided WECMM was investigated to determine whether it benefited the machining characteristics. The experiment’s results showed that under such an experiment setting, microslots can be successfully manufactured. Furthermore, with the advance adjustment of experimental parameters, the machining accuracy was improved. Finally, a fine slot was manufactured under the optimum experiment parameters and aided by ultrasonic vibration.

A cobalt oxide (Co3O4)-decorated silicon carbide (SiC) nano-tree array (denoted as Co3O4/SiC NTA) electrode is synthesized, and it is investigated for use in micro-supercapacitor applications. Firstly, the well-standing SiC nanowires (NWs) are prepared by nickel (Ni)-catalyzed chemical vapor deposition (CVD) method, and then the thin layer of Co3O4 and the hierarchical Co3O4 nano-flower-clusters are, respectively, fabricated on the side-walls and the top side of the SiC NWs via electrodeposition. The deposition of Co3O4 on the SiC NWs benefits the charge transfer at the electrode/aqueous electrolyte interface due to its extremely hydrophilic surface characteristic after Co3O4 decoration. Furthermore, the Co3O4/SiC NTA electrode provides a directional charge transport route along the length of SiC nanowires owing to their well-standing architecture. By using the Co3O4/SiC NTA electrode for micro-supercapacitor application, the areal capacitance obtained from cyclic voltammetry measurement reaches 845 mF cm−2 at a 10 mV s−1 scan rate. Finally, the capacitance durability is also evaluated by the cycling test of cyclic voltammetry at a high scan rate of 150 mV s−1 for 2000 cycles, exhibiting excellent stability.

It has been previously reported that a supercapacitor with activated carbon (AC)-based electrodes has a high degree of nanoporosity and a large specific surface area, leading to a larger capacitance than one using conventional materials for its electrodes. This study investigates the diffusive behavior of organic electrolyte molecules in activated carbon electrodes with different pore sizes and densities using the coarse-grained molecular model and constant-potential molecular dynamics (MD) simulation. This organic electrolyte consists of the tetraethylammonium cation (NEt4+) and tetrafluoroborate anion (BF4−) dissolved in an acetonitrile (ACN) solvent. Combining the time-stamped force-bias Monte Carlo (tfMC) and simulated-annealing methods, AC electrodes with different densities and pore sizes were constructed. This study provides an atomistic scale understanding for the ion exchange mechanism between the nanoporous electrode and electrolyte region. The simulation results were also used for comparison to the graphite electrode supercapacitors of our previous study.

The diblock copolymer polystyrene-block-poly(N-methyl 4-vinylpyridine iodide) (PS-b-P4VPQ) with the molecular weight of PS 3.5 × 103 g/mol and P4VPQ 11.6 × 103 g/mol forms core-shell polymer micelles in aqueous solution. The cationic brush shell of the polymer micelle can be used to accommodate hydrophilic drugs and biomolecules, such as DNA, for biomedical applications. It is essential to understand how biomolecules are adsorbed within the brush layer. Here we investigated the interaction of the cationic brush of the polymer micelle with DNA by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). It is found when adding only relatively small amounts of on average 30 base pairs (bp) DNA, at 19.6 and 39.2 μM for 0.1 mM PS-b-P4VPQ, most of the polymer micelle/DNA complexes remain well dispersed. The brush layer of the polymer micelles are slightly swelled due to the adsorption of DNA within the brush layer. When the DNA concentration is increased to 58.8 μM or higher, the polymer micelle/DNA complexes form closely packed agglomerates. At high DNA concentrations, some adsorbed DNA will start to build up at the edge or surface of the brush layer which could induce aggregation of the polymer micelle/DNA complexes. This means that it is possible to prepare mostly dispersed polymer/DNA complexes by keeping the DNA concentration below the aggregation concentration. The well dispersed polymer micelle/DNA complexes are advantageous for many DNA related biomedical applications.

Clean water is essential in our daily life. However, nearly one billion people are forced to drink water contaminated with bacteria, leading to diarrhea, dehydration, and even death. Previously, various photocatalysts have been applied to replace high-cost and highly toxic methods for sewage treatment. Nevertheless, the requirement of external light sources limits their application. Herein, we develop a new type of nanocatalyst based on single- and few-layered molybdenum disulfide (MoS2) nanosheets (NSs) that can catalyze the generation of reactive oxygen species (ROS) to inactivate bacteria either through a piezoelectric effect (mechanical vibration) or photocatalytic effect (light irradiation). After 60 min of mechanical vibration or visible-light irradiation, the MoS2 NSs can reduce Escherichia coli (E. Coli) by 99.999%. In addition, the ROS generation efficiency and bacterial disinfection performance of the catalyst can be enhanced by depositing Au nanoparticles (NPs) on MoS2 NSs. The period of mechanical vibration or visible-light irradiation that achieves the same 99.999% reduction in E. coli is shortened to 45 min. Moreover, a hybridization of the piezoelectric and photocatalytic effects results in a performance superior to that obtained with the individual effects. A 99.999% reduction in E. coli is also accomplished within 15 min through a combination of mechanical vibration and near-infrared (NIR)-light irradiation. This MoS2 nanocatalyst is a promising candidate for nextgeneration water purification systems because of its ability to be triggered by diverse environmental stimuli.

Gastrointestinal stromal tumors (GISTs) are c-Kit (CD117)-expressing mesenchymal tumors of the gastrointestinal tract. Understanding the molecular characteristics of these uncommon tumors has led to the use of c-Kit-targeting tyrosine kinase inhibitors in the treatment of patients with advanced GISTs. Although imatinib, sunitinib, and regorafenib have drastically improved survival in patients with advanced GISTs, there remains a need for salvage treatment options for patients whose tumors progress despite tyrosine kinase inhibitor treatment. Historically considered to be chemoresistant and radioresistant, a substantial amount of research has focused on the use of targeted therapies for patients with advanced GISTs. Herein, we present a patient with an advanced GIST who had clinical and radiographic responses to radiotherapy after failure of imatinib and sunitinib. Keywords: Gastrointestinal stromal tumors, Radiotherapy

Background Rhodamine B (RhB) is generally used as a fluorescent dye and colorant in the textile and food industries. Tetracycline (TC) is another most frequently detected antibiotic in surface water, sludge, and effluents from hospitals, and may have a critical impact on the aquatic environment. In this study, self-assembly L-cysteine (L-Cys)-based 2D g-C3N4 nanoflakes (CN_Sx; x = 2, 5, and 10) with a porous structure were employed for the visible-light photocatalytic degradation of rhodamine B (RhB) and tetracycline (TC). Methods Upon introduction of L-Cys, the g-C3N4 nanoflakes underwent folding and contained more wrinkles and pinholes than the parent g-C3N4, thus forming porous structures that provided more active sites for the reaction. The COO‒ group of the L-Cys residue could react with either the ‒NH2 of melamine or g-C3N4 to undergo an addition reaction. An excess of L-Cys might induce unwanted defects and distort the structure to enhance the charge recombination, thus hindering the photocatalytic activity. Significant findings Self-assembly L-cysteine (L-Cys)-based 2D g-C3N4 nanoflakes exhibited a light-dependent photocatalytic activity; the CN_S5 showed up to 90 and 70% removal efficiency for RhB (5 ppm) and TC (20 ppm), respectively, within 180 min under irradiation. The enhanced photocatalytic activity could be attributed to its mesoporosity, abundant photoexcited electrons, and few structure defects. These results suggested that self-assembly L-Cys-assisted synthesis is an effective and facile method for the preparation of 2D g-C3N4 nanoflakes for environmental remediation.

In this work, we have developed a novel fabrication technique for preparing N-functionalized carbon nanodots (CNDs) through one-pot hydrothermal route using various isomers, exhibiting highly intense fluorescence under blue light illumination. Three types of isomers, o-, m-, and p-phenylenediamine (PD), serving as the carbon and nitrogen sources were employed where the N/C atomic ratio in the CNDs structure was precisely tuned within the range of 20.2–25.7 at.% via tailoring the isomer precursors. The application of the m-PD precursor resulted in implanting the “lattice N” functionalities while the o-PD precursor enabled the formation of N-oxide groups. The CND suspensions in highly-polarity solvents (e.g., water and ethanol) emit intense fluorescence with ultrahigh quantum yield (QY: 85‒99%), whereas the fluorescence from the CND suspensions in propylene glycol methyl ether acetate is significantly quenched. The ultrahigh QY is majorly due to an intense radiative emission mechanism induced by the substitutional N atoms (via high electron-withdrawing) and N- and O-rich edge groups as the major contributors for boosting the affinity to high-polar solvents. Given the widespread applications of quantum dots as high-performance nanomaterials, this study paves the way for engineering N-functionalized CNDs to be used in optical, sensing, energy storage/conversion, and biological devices.

The design principle of establishing an intracellular protein gradient for asymmetric cell division is a long-standing fundamental question. While the major molecular players and their interactions have been elucidated via genetic approaches, the diversity and redundancy of natural systems complicate the extraction of critical underlying features. Here, we take a synthetic cell biology approach to construct intracellular asymmetry and asymmetric division in Escherichia coli, in which division is normally symmetric. We demonstrate that the oligomeric PopZ from Caulobacter crescentus can serve as a robust polarized scaffold to functionalize RNA polymerase. Furthermore, by using another oligomeric pole-targeting DivIVA from Bacillus subtilis, the newly synthesized protein can be constrained to further establish intracellular asymmetry, leading to asymmetric division and differentiation. Our findings suggest that the coupled oligomerization and restriction in diffusion may be a strategy for generating a spatial gradient for asymmetric cell division., Establishing protein gradients for asymmetric cell division is fundamental across all kingdoms of life. Here the authors construct asymmetric cell division in E. coli by localizing the expression of RNA polymerase using an orthogonal unipolar scaffold, and restricting diffusion of its products.

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.

Obesity is a health problem associated with many metabolic disorders. Weight reduction can effectively alleviate obesity-associated complications. Sleeve gastrectomy is a commonly used bariatric surgery and is considered safe and effective for improving outcomes. Glutamine (GLN) is an amino acid with anti-oxidative and anti-inflammatory properties. This study used a mouse model of sleeve gastrectomy to investigate the impacts of intravenous GLN administration on glucose tolerance and adipocyte inflammation short-term after surgery. C57BL6 male mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat for 10 weeks to induce obesity. Mice fed the high-fat diet were then assigned to a sham (SH) or sleeve gastrectomy with saline (S) or GLN (G) groups. The S group was intravenously injected with saline, while the G group was administered GLN (0.75 g/kg body weight) via a tail vein postoperatively. Mice in the experimental groups were sacrificed on day 1 or 3 after the surgery. Results showed that obesity resulted in fat accumulation, elevated glucose levels, and adipokines production. Sleeve gastrectomy aggravated expressions of inflammatory cytokine and macrophage infiltration markers, cluster of differentiation 68 (CD68), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR-1), and macrophage chemoattractant protein-1, in adipose tissues. Treatment of obese mice with GLN downregulated hepatic proteomic profiles associated with the gluconeogenesis pathway and improved glucose tolerance. Moreover, macrophage infiltration and adipose tissue inflammation were attenuated after the sleeve gastrectomy. These findings imply that postoperative intravenous GLN administration may improve glucose tolerance and attenuate inflammation shortly after the bariatric surgery in subjects with obesity.

Depression is a common mental disorder affecting more than 300 million people worldwide and is one of the leading causes of disability among all medical illnesses. The accumulation of preclinical data has fueled the revival of interest in targeting glutamatergic neurotransmission for the treatment of major depressive disorder. GLYX-13, a glutamatergic compound that acts as an N-methyl-d-aspartate (NMDA) modulator with glycine-site partial agonist properties, produces rapid and long-lasting antidepressant effects in both animal models and patients. However, the mechanisms underlying the antidepressant actions of GLYX-13 have not been fully characterized, especially in the midbrain ventrolateral periaqueductal gray (vlPAG), a brain stem area that controls stress-associated depression-like behavior. Here, we use a combination of electrophysiological recordings, behavioral tests, and pharmacological manipulations to study the antidepressant actions of GLYX-13 in the vlPAG. A single intravenous injection of a GLYX-13 rapidly mitigated footshock stress (FS)-induced depression-like behavior in rats. The FS-induced diminished glutamatergic transmission in the vlPAG was also reversed by a single GLYX-13 intravenous injection. Moreover, intra-vlPAG GLYX-13 microinjection produced a long-lasting antidepressant effect; however, this effect was prevented by the intra-vlPAG microinjection of tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, a selective mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, and CNQX, an AMPA receptor antagonist. Additionally, a bath application of GLYX-13 enhanced glutamatergic transmission in vlPAG neurons; however, this enhancement effect was blocked by the co-application of ANA-12 and rapamycin. These results demonstrate that BDNF-TrkB-mTORC1 signaling in the vlPAG is required for the sustained antidepressant effects of GLYX-13.

Recent reports have shown that sleeve gastrectomy (SG) accelerates gastric emptying (GE), but the etiology remains unclear. This study aimed to investigate the factors affecting GE before and after SG. We enrolled 35 normal weight healthy subjects and 23 obese patients receiving SG. The normal individuals and obese patients before and 3 months after SG received oatmeal-based scintigraphy to measure GE. Gastrointestinal symptoms and circulating levels of peptide YY (PYY) were also measured. There were no differences in the GE parameters, including simple half-time at 3 h and percentage of gastric retention at 0.5, 1, 2, and 3 h between healthy controls and pre-SG obese subjects. SG led to accelerated GE, more gastrointestinal symptoms, and increased fasting PYY levels postoperatively. Based on our previously established normal GE values, 18 (78.3%) obese patients with rapid postoperative GE had higher levels of preoperative fasting glucose and glycated hemoglobin, and homeostasis model assessment of the insulin resistance index than those with normal postoperative GE. Twelve (52.2%) obese patients had preoperative diabetes mellitus (DM), and only four (17.4%) remained diabetic after SG. The post-SG gastric retention at 0.5 and 1 h was lower in patients with preoperative DM than in those without preoperative DM. Neither severity of gastrointestinal symptoms nor fasting PYY levels were associated with postoperative GE alterations. Most of the obese patients had accelerated GE after SG. A higher preoperative glycemic profile was associated with rapid post-SG GE.

The donor–acceptor conjugated polymers (CPs) of terthiophene–thieno[3,4-c]pyrrole-4,6-dione (3T-TPD) are widely used to fabricate low-cost flexible electronics. We present a comprehensive study of the side chain effect on the optical properties, electrochemical properties, thermal properties, and self-assembly behavior of 3T-TPD CPs, including side chain location (outward vs inward), type (tetraethylene glycol (TEG) vs dodecyl), and length (octyl vs hexyl vs butyl). For the side chain location effect, the polymers with outward side chains show better coplanarity of backbone than the polymers with inward side chains, leading to form lamellae structure. However, interestingly, the inward series polymers exhibit novel hexagonal structure. Through replacing dodecyl chains with TEG chains and changing the side chain length, ultrahigh ordered lamellae and hexagonal structure can be obtained. Furthermore, two models are purposed to explain the formation mechanism of lamellae and hexagonal structure. This study c...

Combining the time-stamped force-bias Monte Carlo (tfMC) and simulated-annealing methods, different densities of activated carbon (AC) in different quench rates were constructed. Six AC models were constructed, corresponding to densities of 0.5, 0.7, and 1.3 g/cm3 and quench rates of 5 K per 30 tfMC steps and 5 K per 6000 tfMC steps, respectively. The structural properties of these models were examined, including porosity, specific surface area (SSA) and pore distribution. In uniaxial tensile simulation, the Young's modulus and the fracture of microstructures were also investigated. The specific surface area and Young's modulus are proportional to the density of AC, but the porosity and the main distribution of pore size are inversely related. The probability distribution of the ring size shows that six-atom rings translate to four- and five- atom ring during tensile simulation. The local shear strain analysis indicates that the fractures appear adjacent to the non-hexagonal ring defects and at the edge of the carbon wall frame in AC and will expand vertically along the tensile axis. This study not only constructs a structural prediction procedure of AC but also provides several detailed information of AC fracture.

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.

Colorectal cancer (CRC) is one of the most common cancers worldwide and its incidence is increasing; therefore, an understanding of its oncogenic mechanisms is critical for improving its treatment and management. Methylglyoxal (MGO) has a highly reactive aldehyde group and has been suggested to play a role in oncogenesis. However, no standardized data are currently available on MGO levels in colorectal precancerous and cancerous lesions. We collected 40 matched colorectal tumor and peritumor tissues from patients with low-grade dysplasia (LGD), high-grade dysplasia (HGD), and invasive cancer (IC). MGO levels increased between LGD, HGD, and IC tumor tissues (215.25 ± 39.69, 267.45 ± 100.61, and 587.36 ± 123.19 μg/g protein, respectively; p = 0.014). The MGO levels in peritumor tissue increased and were significantly higher than MGO levels in tumor tissue (197.99 ± 49.40, 738.09 ± 247.87, 933.41 ± 164.83 μg/g protein, respectively; p = 0.002). Tumor tissue MGO levels did not correlate with age, sex, underlying disease, or smoking status. These results suggest that MGO levels fluctuate in progression of CRC and warrants further research into its underlying mechanisms and function in tumor biology.

Cellular senescence is the progressive impairment of function and proliferation in response to various regulators. Dihydrolipoic acid-coated gold nanoclusters (DHLA-Au NCs), which are molecular clusters with covalently linked dihydroxyl lipoic acid, preserve cellular activities for long-term incubation. DHLA-Au NC delivery was characterized, and we determined the role of growth supplements on internalization, allowing the optimization of DHLA-Au NC bioactivity. In the optimized medium, DHLA-Au NCs attenuated the levels of the senescence-associated phenotype. Molecular mechanism analysis further indicated that during DHLA-Au NC treatment, the activation of the stress signal JNK and its downstream c-Jun were impaired under LPS induction, which led to a decline in AP-1-mediated TNF-α transactivation. Confocal microscopy and subcellular fractionation analysis suggested that DHLA-Au NCs interacted with mitochondria through their lipid moiety and attenuated mitochondria-derived reactive oxygen species. With adequate treatment, DHLA-Au NCs show protection against cellular senescence and inflammation in vitro and in vivo.

The present study elucidated mechanisms through which sulforaphane (SFN) protects retinal pigment epithelial (RPE) cells from blue light-induced impairment. SFN could activate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increase the expression of the heme oxygenease-1 (HO-1) gene and production of glutathione. SFN reduced blue light-induced oxidative stress, and effectively activated cytoprotective components including Nrf-2, HO-1, thioredoxin-1, and glutathione. The protective effect of SFN on blue light-induced injury was blocked by the Nrf2 inhibitor ML385, suggesting that the SFN-induced Nrf2 pathway is involved in the cytoprotective effect of SFN. SFN inhibited intercellular adhesion molecule-1 expression induced by TNF-α or blue light, suggesting the anti-inflammatory activity of SFN. The inhibitory effect of SFN was associated with the blocking of NF-κB p65 nuclear translocation in blue light-exposed RPE cells. SFN protected RPE cells from blue light-induced interruption of the mitochondrial membrane potential and reduction of the Bcl-2/Bax ratio and cleaved caspase-3 and PARP-1 expression, suggesting the antiapoptotic activity of SFN. SFN alone or together with blue light exposure increased the expression of the autophagy-related proteins LC3BII and p62. An autophagy inhibitor, 3-MA, inhibited the protective effect of SFN on blue light-induced cell damage. SFN increased sirtuin-1 (SIRT1) expression; however, treatment with blue light induced peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) expression. Our study results demonstrated that SFN exerts its protective effect under blue light exposure by maintaining the Nrf2-related redox state and upregulating SIRT1 and PGC-1α expression and autophagy.

Langmuir-Blodgett monolayers of thiolated gold nanoparticles mixed with dipalmitoylphosphatidylcholine/sodium dodecyl sulfate (DPPC/SDS) were investigated by combining the X-ray reflectivity, grazing-incident scattering, and TEM analyses to reveal the in-depth and in-plane organization and the 2D morphology of such mixed monolayers. It was found that the addition of a charged single-tail surfactant to the thiolated Au nanoparticle monolayer helps to stabilize the Au nanoparticle monolayer and to strengthen the mechanical property of the mixed monolayer film. For mixing with lipids, it was found that the thiolated gold nanoparticles could be pushed on top of the lipid monolayer when the mixed monolayer is compressed. At a typical comparable total surface area ratio of gold nanoparticle to lipid, the thiolated gold nanoparticles could form a uniform domain on top of the DPPC monolayer. When there are more thiolated gold nanoparticles than that could be supported by the lipid monolayer, domain overlapping could occur to form bilayer gold nanoparticle domains at some regions. At low total surface area ratio of thiolated gold nanoparticle to lipid, the thiolated gold nanoparticles tend to form a connected threadlike aggregation structure. Evidently, the morphology of the thiolated gold nanoparticle monolayer is highly depending on the total surface area ratio of the thiolated gold nanoparticle to lipid. SDS is found to have a dispersion power capable of dispersing the originally uniform Au-8C nanoparticle domain of the mixed Au-8C/DPPC monolayer into a foamlike structure for the mixed Au-8C/SDS/DPPC monolayer. It is evident that not only the concentration ratio but also the size and shape of the template formed by the amphiphilic molecules and their interaction with the thiolated gold nanoparticles can all have great effects on the organizational structure as well as morphology of the thiolated gold nanoparticle monolayer.

Molecular dynamics (MD) simulations were carried out to investigate the conformations of fourth generation polyamidoamine (G4 PAMAM) dendrimer-encapsulated Au nanoparticles (AuNPs) of different sizes at different pH conditions. The consistent valence force field (CVFF) was used to model the interaction between the atoms of G4 PAMAM dendrimer and water molecules as well as their interactions with the Au atoms of AuNP. The many-body tight-binding potential was adopted to describe the interaction between Au atoms. The simulation results show a single G4 PAMAM dendrimer can only partially cover the AuNP when its diameter is larger than 2.3 nm. According to the variations of radius of gyration ( R g ) values, the conformations of PAMAM dendrimers become more compact after covering the AuNP at neutral pH. According to the Stokes–Einstein (SE) relation and the diffusion coefficients obtained by the Einstein equation, it was proposed that both the PAMAM dendrimer conformation and the interaction strength between the PAMAM/AuNP and water molecules have significant influences on the diffusion behaviors of PAMAM/AuNP systems.

A molecular dynamics (MD) simulation with the optimized potentials for liquid simulations-all atom (OPLS-AA) force field was carried out to investigate the dynamic behaviors of organic electrolyte molecules between a graphite cathode and anode. This study considered the tetraethylammonium cation (NEt4+) and tetrafluoroborate anion (BF4−) in acetonitrile (ACN) solvent. The predicted NEt4–BF4 solution density at 1 M from the MD isothermal–isobaric ensemble (NPT) is about 0.861 g cm−3, which is very close to the corresponding experimental value. This indicates that the OPLS-AA force field can accurately describe the interactions between these molecules. The detailed diffusion mechanism and the corresponding viscosity solution for different NEt4–BF4 mole fractions were explored. The charge density distribution of electrolyte molecules between the graphite cathode and anode from MD simulation was further used to obtain the potential drop by solving the Poisson equation and to obtain system capacitance. This study provides a method to determine the proper molar concentration of electrolyte NEt4–BF4 in ACN solution which can balance ionic conductivity and capacitance to enhance supercapacitor performance.

// Po-Yu Yang 1, 2, 4, * , Pei-Ling Hsieh 3, * , Tong Hong Wang 5, 6, 7, * , Cheng-Chia Yu 1, 2, 3, 4, * , Ming-Yi Lu 1, 2, 3, 4 , Yi-Wen Liao 1 , Tzu-Hsin Lee 1, 2 , Chih-Yu Peng 1, 2, 3, 4 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 Oral Medicine Center, Chung Shan Medical University, Taichung, Taiwan 5 Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan 6 Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan 7 Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan * These authors contributed equally to this work Correspondence to: Chih-Yu Peng, email: cyp@csmu.edu.tw Keywords: oral squamous cell carcinomas, andrographolide, miR-218, cancer stemness Received: October 31, 2016 Accepted: November 23, 2016 Published: December 01, 2016 ABSTRACT 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.

The production of nitric oxide (NO) by endothelial NO synthase (eNOS) plays a major role in maintaining vascular homeostasis. This study elucidated the potential role of carbon monoxide (CO)-releasing molecules (CORMs) in NO production and explored the underlying mechanisms in endothelial cells. We observed that 25μM CORM-2 could increase NO production and stimulate an increase in the intracellular Ca2+ level. Furthermore, ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetra acetic acid caused CORM-2-induced NO production, which was abolished by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetraacetoxy-methyl ester (BAPTA-AM), indicating that intracellular Ca2+ release plays a major role in eNOS activation. The inhibition of the IP3 receptor diminished the CORM-2-induced intracellular Ca2+ increase and NO production. Furthermore, CORM-2 induced eNOS Ser1179 phosphorylation and eNOS dimerization, but it did not alter eNOS expression. CORM-2 (25μM) also prolonged Akt phosphorylation, lasting for at least 12h. Pretreatment with phosphatidylinositol 3-kinase inhibitors (wortmannin or LY294002) inhibited the increases in NO production and phosphorylation but did not affect eNOS dimerization. CORM-2-induced eNOS Ser1179 phosphorylation was intracellularly calcium-dependent, because pretreatment with an intracellular Ca2+ chelator (BAPTA-AM) inhibited this process. Although CORM-2 increases intracellular reactive oxygen species (ROS), pretreatment with antioxidant enzyme catalase and N-acetyl-cysteine did not abolish the CORM-2-induced eNOS activity or phosphorylation, signifying that ROS is not involved in this activity. Hence, CORM-2 enhances eNOS activation through intracellular calcium release, Akt phosphorylation, and eNOS dimerization.

A series of conjugated polythiophenes (PTs) having low band gap energies (PDPP, PDPCz21, PDPCz11), with 2-ethylhexyl-functionalized 2,5-thienyl diketopyrrolopyrrole (TDPP) as the electron acceptor and terpyridine-substituted carbazole (TPCz) as the electron donor, have been synthesized and studied for their applicability in polymer-based photovoltaic cells (PVCs). The thermal stability and solvent solubility of PTs increased upon increasing the content of the TPCz derivative. PVCs were fabricated having the following architecture: indium tin oxide/poly(3,4-ethylenedioxythiophene):polystyrenesulfonate/PT:6,6-phenyl-C71-butyric acid methyl ester (PC71BM)/Ca/Ag. The compatibility between the PT and PC71BM improved upon increasing the TPCz content. The photovoltaic properties of the PDPCz21-based PVCs were superior to those of their PDPP- and PDPCz11-based counterparts.

The most common cause of vision loss among the elderly is age‑related macular degeneration (AMD). The aim of the present study was to investigate the potential cytoprotective and anti‑inflammatory effects of carbon monoxide‑releasing molecules (CORMs), and their ability to activate the expression of nuclear factor erythroid 2‑related factor 2 (Nrf2)‑related genes in human retinal pigment epithelium (RPE) cells, as well as the inhibition of endothelial cell migration. It was first determined that CORM2 and CORM3 suppressed blue light‑induced cell damage. In addition, a decrease in the level of cleaved poly(ADP‑ribose) polymerase 1 protein and dissipation of mitochondrial membrane potential were considered to reflect the anti‑apoptotic activity of CORMs. Furthermore, CORM2 induced Nrf‑2 activation and the expression of the Nrf2‑related genes heme oxygenase‑1 and glutamate‑cysteine ligase. Pretreatment with CORM2 abolished the blue light‑induced increase in oxidative stress, suggesting that CORM2‑induced antioxidant activity was involved in the cytoprotection against blue light. It was also demonstrated that CORMs markedly suppressed tumor necrosis factor (TNF)α‑induced intercellular adhesion molecule‑1 expression. Moreover, it was further observed that CORMs exert their inhibitory effects through blocking nuclear factor‑κB/p65 nuclear translocation and IκBα degradation in TNFα‑treated RPE cells. It was observed that CORM2, but not CORM3, protected against oxidative stress‑induced cell damage. CORMs abolished vascular endothelial growth factor‑induced migration of endothelial cells. The findings of the present study demonstrated the cytoprotective, antioxidant and anti‑inflammatory effects of CORMs on RPE cells and anti‑angiogenic effects on endothelial cells, suggesting the potential clinical application of CORMs as anti‑AMD agents.

Mixed lineage leukemia 1 (MLL1)-mediated histone H3 lysine 4 trimethylation (H3K4me3) of a subset of genes has been linked to the transcriptional activation critical for synaptic plasticity, but its potential contribution to neuropathic allodynia development remains poorly explored. Here, we show that MLL1, which is induced in dorsal horn neuron after spinal nerve ligation (SNL), is responsible for mechanical allodynia and increased H3K4me3 at metabotropic glutamate receptor subtype 5 (mGluR5) promoter. Moreover, SNL induced WD (Trp-Asp) repeat domain 5 subunit (WDR5) expression as well as the MLL1-WDR5 interaction accompany with H3K4me3 enrichment and transcription of mGluR5 gene in the dorsal horn in neuropathic allodynia progression. Conversely, WDR5-0103, a novel inhibitor of the MLL1-WDR5 interaction, reversed SNL-induced allodynia and inhibited SNL-enhanced mGluR5 transcription/expression as well as MLL1, WDR5, and H3K4me3 at the mGluR5 promoter in the dorsal horn. Furthermore, disrupting the expression of MLL1 or WDR5 using small interfering RNA attenuated mechanical allodynia and reversed protein transcription/expression and complex localizing at mGluR5 promoter in the dorsal horn induced by SNL. This finding revealed that MLL1-WDR5 complex integrity regulates MLL1 and WDR5 recruitment to H3K4me3 enrichment at mGluR5 promoter in the dorsal horn underlying neuropathic allodynia. Collectively, our findings indicated that SNL enhances the MLL1-WDR5 complex, which facilitates MLL1 and WDR5 recruitment to H3K4me3 enrichment at mGluR5 promoter in spinal plasticity contributing to neuropathic allodynia pathogenesis.

Helium ion beam induced deposition (HIBID) is an attractive technique capable of precise fabrication of nanostructures. However, the damage caused by helium ion irradiation is the major drawback of conventional HIBID. In this study, area-selective atomic layer deposition (ALD) accompanied with the HIBID technique is explored to solve this problem. A platinum (Pt) seed layer was prepared by HIBID with a helium dose much lower than that of the conventional HIBID to reduce the damage due to the bombardment of energetic ions. Afterwards, Pt was selectively deposited on the seed layer to achieve area-selective ALD. Accordingly, the Pt nanolines with a feature size of ~15 nm are accomplished by the area-selective ALD and the HIBID technique under the condition of the damage-free does.

The current guidelines recommend that potassium iodide be given in the immediate preoperative period for patients with Graves' disease who are undergoing thyroidectomy. Nonetheless, the evidence behind this recommendation is tenuous. The purpose of this study is to clarify the benefits of preoperative iodine administration from published comparative studies.We searched PubMed, Embase, Cochrane, and CINAHL from 1980 to June 2018.Studies were included that compared preoperative iodine administration and no premedication before thyroidectomy. For the meta-analysis, studies were pooled with the random-effects model.A total of 510 patients were divided into the iodine (n = 223) and control (n = 287) groups from 9 selected studies. Preoperative iodine administration was significantly associated with decreased thyroid vascularity and intraoperative blood loss. Significant heterogeneity was present among studies. We found no significant difference in thyroid volume or operative time. Furthermore, the meta-analysis showed no difference in the risk of postoperative complications, including vocal cord palsy, hypoparathyroidism/hypocalcemia, and hemorrhage or hematoma after thyroidectomy.Preoperative iodine administration decreases thyroid vascularity and intraoperative blood loss. Nonetheless, it does not translate to more clinically meaningful differences in terms of operative time and postoperative complications.

Observations of quasiparticle interference have been used in recent years to examine exotic carrier behavior at the surfaces of emergent materials, connecting carrier dispersion and scattering dynamics to real-space features with atomic resolution. We observe quasiparticle interference in the strongly Rashba split 2DEG-like surface band found at the tellurium termination of BiTeBr and examine two mechanisms governing quasiparticle scattering: We confirm the suppression of spin-flip scattering by comparing measured quasiparticle interference with a spin-dependent elastic scattering model applied to the calculated spectral function. We also use atomically resolved STM maps to identify point defect lattice sites and spectro-microscopy imaging to discern their varying scattering strengths, which we understand in terms of the calculated orbital characteristics of the surface band. Defects on the Bi sublattice cause the strongest scattering of the predominantly Bi 6p derived surface band, with other defects causing nearly no scattering near the conduction band minimum.

Glucose transporters (GLUTs) are required for glucose uptake in malignant cells, and they can be used as molecular targets for cancer therapy. An RT-PCR analysis was performed to investigate the mRNA levels of 14 subtypes of GLUTs in human colorectal cancer (COLO 205 and HT-29) and normal (FHC) cells. RT-PCR (n = 27) was used to assess the differences in paired tissue samples (tumor vs normal) isolated from colorectal cancer patients. GLUT2 was detected in all tested cells. The average GLUT2 mRNA level in 12 of 27 (44.4%) cases was 2.4-fold higher in tumor compared to normal tissues (*, p = 0.027). Higher GLUT2 mRNA expression was preferentially detected in advanced-stage tumors (stage 0 vs 3 = 16.38-fold, 95% CI = 9.22-26.54-fold; *, p = 0.029). The apple polyphenol phloretin (Ph) and siRNA methods were used to inhibit GLUT2 protein expression. Ph (0-100 μM, for 24 h) induced COLO 205 cell growth cycle arrest in a p53-dependent manner, which was confirmed by pretreatment of the cells with a p53-specific dominant negative expression vector. Hepatocyte nuclear factor 6 (HNF6), which was previously reported to be a transcription factor that activates GLUT2 and p53, was also induced by Ph (0-100 μM, for 24 h). The antitumor effect of Ph (25 mg/kg or DMSO twice a week for 6 weeks) was demonstrated in vivo using BALB/c nude mice bearing COLO 205 tumor xenografts. In conclusion, targeting GLUT2 could potentially suppress colorectal tumor cell invasiveness.

An unconventional route was adopted for fabricating Si/graphene composite anodes. Well crystallized silicon powders purified from the silicon waste mortar of solar cell fabrication were mixed with graphene suspended polyvinylidene fluoride (PVDF) solutions, and calcined directly on metal current collectors. It was found that PVDF was pyrolyzed to form a carbon scaffold which laminated the Si and graphene. The graphene sheets were able to hold the Si powers, preventing them from stress-cracking due to large volume change during charge and discharge processes. Silicon anodes using conventional coating method with PVDF binder and carbon black were also fabricated for comparison. The carbon laminated Si anodes (Si/C) exhibit an initial delithiation capacity of more than 2500 mAh/g at 0.1 C, which is greatly higher than the pristine Si anode (capacity of only 8 mAh/g at 0.1 C). By adding graphene in the composite, the carbon laminated Si/graphene anodes show improved cycling stability, with a 1 C delithiation capacity of 1420 mAh/g after 60 cycles, which is twice as high as Si/C anodes. The results indicate that high capacity and high cycling stability can be achieved by a pyrolysis based carbon lamination process in which graphene and Si powders are attached to each other.

Excess lipids are stored in the form of neutral lipids in lipid droplets. The inability to convert excess lipids into neutral lipids during anaphase creates a lipid imbalance that perturbs the normal dynamics of cytokinesis molecules, causing a delay in cell separation., The neutral lipids steryl ester and triacylglycerol (TAG) are stored in the membrane-bound organelle lipid droplet (LD) in essentially all eukaryotic cells. It is unclear what physiological conditions require the mobilization or storage of these lipids. Here, we study the budding yeast mutant are1Δ are2Δ dga1Δ lro1Δ, which cannot synthesize the neutral lipids and therefore lacks LDs. This quadruple mutant is delayed at cell separation upon release from mitotic arrest. The cells have abnormal septa, unstable septin assembly during cytokinesis, and prolonged exocytosis at the division site at the end of cytokinesis. Lipidomic analysis shows a marked increase of diacylglycerol (DAG) and phosphatidic acid, the precursors for TAG, in the mutant during mitotic exit. The cytokinesis and separation defects are rescued by adding phospholipid precursors or inhibiting fatty acid synthesis, which both reduce DAG levels. Our results suggest that converting excess lipids to neutral lipids for storage during mitotic exit is important for proper execution of cytokinesis and efficient cell separation.

This paper reports the multifunctional responsive fluorescence chemosensory phenomena of two terpyridine-functionalized conjugated polyfluorenes (PFs), poly[2,7-(9,9-dihexylfluorene)- alt -4′-((4-[N,N-(4-phenyl)amino]styryl)phenyl)-2,2′:6′,2″-terpyridine] ( P1 ) and poly[2,7-(9,9-dihexylfluorene)- alt -4′-phenyl-2,2′:6′,2″-terpyridine] ( P2 ), which were exposed to solvents, metal ions, and protons through Suzuki polymerization. Compared with P2 , P1 exhibited enhanced sensing ability that resulted from efficient interactions between the specific triphenylamine-linked terpyridine units with protons and metal ions. P1 and P2 both showed high sensitivity toward Cu 2+ , with the Stern-Volmer constants of 2.30 × 10 5 M −1 and 1.05 × 10 5 M −1 , respectively. Because of the very high stability constants of the CN − –Cu 2+ complexes, the fluorescence of P1 and P2 solutions that were quenched by Cu 2+ recovered upon addition of trace CN − , with a detection limit as low as 3.7 × 10 −6 M −1 and 5.2 × 10 −6 M −1 for P1 and P2 , respectively. P1 showed fluorescence quenching when pH decreased from 5.0 to 1.0; however, a pH of 13.0 had little effect on fluorescence intensity. Our results suggest that P1 is a promising material for chemosensory applications.

The surface of Ptshell–Rucore nanocatalysts was modified with an atomic-scaled Au cluster of different sizes by a polyol reduction technique using sequence and composition control. Our results, combining the structure, surface chemical analysis, and density functional theory calculation, elucidate that these clusters reduced the oxidation current of carbon monoxide to a maximum extent of ∼53%; consequently, the anti-CO poisoning factor of the NCs was doubled by increasing the Au/Pt ratios from 0 to 15 at%. Such substantial improvement is caused by steric shielding and the electron localization field that reject the sorption of electronegative ligands/molecules at the NC surface by Au clusters. Most importantly, this work clarifies the mechanistic insights of the charge relocation at core–shell nanoparticles by subnanoscaled cluster intercalation and the impacts of cluster size for the chemical durability of catalysts in fuel cell applications.

We demonstrate that the lamella-forming polystyrene-block-poly(N-methyl-4-vinylpyridinium iodine) (PS-b-P4VPQ), with similar sizes of the PS and P4VPQ blocks, can be dispersed in the aqueous solutions by forming lipid/PS-b-P4VPQ multilamellae. Using small-angle neutron scattering (SANS) and 1,2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (d62-DPPC) in D2O, a broad correlation peak is found in the scattering profile that signifies the formation of the loosely ordered d62-DPPC/PS-b-P4VPQ multilamellae. The thicknesses of the hydrophobic and hydrophilic layers of the d62-DPPC/PS-b-P4VPQ multilamellae are close to the PS layer and the condensed brush layer thicknesses as determined from previous neutron reflectometry studies on the PS-b-P4VPQ monolayer at the air-water interface. Such well-dispersed d62-DPPC/PS-b-P4VPQ multilamellae are capable of forming multilamellae with DNA in aqueous solution. It is found that the encapsulation of DNA in the hydrophilic layer of the d62-DPPC/PS-b-P4VPQ multilamellae slightly increases the thickness of the hydrophilic layer. Adding CaCl2 can enhance the DNA adsorption in the hydrophilic brush layer, and it is similar to that observed in the neutron reflectometry study of the DNA adsorption by the PS-b-P4VPQ monolayer.