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An acid-base bifunctional zeolitic imidazolate framework catalyst (ZIF8-A61-SO3H) with amine and sulfonic acid groups was successfully prepared through simple two step post-synthetic modification: preparation of amine-functionalized ZIF-8 with amine contents of 61% (ZIF8-A61) by the ligand exchange of 2-mIM with 3-amino-1,2,4-triazole (Atz), followed by the sulfonic acid functionalization by the ring-opening reaction of 1,3-propanesultone with –NH2 groups in ZIF8-A61. Amine-functionalized ZIF8-A materials with difference amine contents (15%, 34%, and 61%, respectively) were also prepared by controlling the synthesis time. All obtained ZIF catalysts evaluated as a heterogeneous catalyst for one-pot deacetalization-Knoevenagel condensation tandem reaction. Compared with ZIF-8 and amine-functionalized ZIF-8 catalysts, ZIF8-A61-SO3H catalyst showed good catalytic performance with 100% conversion of the reactant and 98% selectivity of the final Knoevenagel product. An enhanced catalytic activity can be attributed to the co-existence of site-isolated acid-base groups on the ZIF8-A61-SO3H catalyst in close proximity. The heterogeneous nature of the catalytic system was confirmed by a hot-filtering test and the catalyst also exhibited reusable in the five repeated cycles. A plausible catalytic mechanism of deacetalization-Knoevenagel condensation reaction over ZIF8-A61-SO3H was also proposed.

In this study, polyphenylene sulfide (PPS) was introduced in polyphenylene ether (PPE) blend to improve the processability of PPE and to secure the flame retardancy of the blend without deteriorating physical properties. Through the study of the binary blend of PPE/PPS, it was found that the shear thinning behavior and the external lubrication effect of PPS can improve the processability of PPE. Thermal analysis of the blend showed that the glass transition temperature of the PPS component decreases by the plasticization while that of the PPE component increases by the anti-plasticization effect. The modulus of the binary blend increased with the PPS content, and the tensile strength decreased but followed the additive rule. The change in tensile properties can be explained by the synergy effect of partial miscibility between PPE and PPS due to structural similarity, and non-isotropic morphology formation. Impact strength increased sharply in PPE60 due to the mechanical grafting effect by co-continuous phase formation. In the ternary blend with SEBS-MAH applied to PPE60, the impact strength steep increased at a content of 10 wt% or more due to the dramatic morphology change based on the compatibilization effect. Flame retardancy of V0 was also observed in all compositions where SEBS-MAH was applied within 20 phr.

ER stress and activation of the unfolded protein response in the periphery as well as the central nervous system have been linked to various metabolic abnormalities. Chemically lowering protein kinase R–like ER kinase (PERK) activity within the hypothalamus leads to decreased food intake and body weight. However, the cell populations required in this response remain undefined. In the current study, we investigated the effects of proopiomelanocortin-specific (POMC-specific) PERK deficiency on energy balance and glucose metabolism. Male mice deficient for PERK in POMC neurons exhibited improvements in energy balance on a high-fat diet, showing decreased food intake and body weight, independent of changes in glucose and insulin tolerances. The plant-based inhibitor of PERK, celastrol, increases leptin sensitivity, resulting in decreased food intake and body weight in a murine model of diet-induced obesity (DIO). Our data extend these observations by demonstrating that celastrol-induced improvements in leptin sensitivity and energy balance were attenuated in mice with PERK deficiency in POMC neurons. Altogether, these data suggest that POMC-specific PERK deficiency in male mice confers protection against DIO, possibly providing a new therapeutic target for the treatment of diabetes and metabolic syndrome.

A catalytic hydrolysis rate of nerve agents can be a significant issue because of their severe toxicity which can lead to severe damage to human life. Regarding the issue, much effort has been given rise to the development of the various design of Zr(IV)-based MOF catalysts so that high catalytic performance. However, we still have feasibility issues. To this end, we turned our attention to develop the method for facile, scalable, and efficient synthesis of Zr(IV)-based MOFs (UiO-66) with high-performance hydrolysis by imparting enriched active sites to the catalysts, as well as to examine its feasibility using the combination of UiO-66 with the organic bases including 4-ethylmorpholine (4-EM) and linear-/ branch-type polyethyleneimine (PEI). The modulated UiO-66 catalysts were synthesized by varying the total reaction concentration. The synthesized three different UiO-66 catalysts were characterized and then applied for hydrolysis rates of the methylparaoxon (MPO) nerve agent simulant. From these investigations, we found that the highest concentration led to the smallest particle size (ca. 100 nm) and highest defect density (1.8 per cluster), resulting in 3-times higher catalytic activity (0.548 s−1) in turnover frequency (TOF) relative to that of the uncontrolled UiO-66 (ca. 580 nm and 1.6 per cluster) (0.188 s−1) which is prepared by the reported procedure. In addition, the reaction process significantly influenced on the catalytic activity of UiO-66, in which the simple change of the reagent mixing method led to a ca. 182-times difference in the catalytic activity for MPO hydrolysis despite using the same reagents including catalysts and bases. Importantly, we found that the reaction process-dependent catalytic activity of UiO-66 can be significantly associated with the chelation of Zr(IV) Lewis acidic active sites by base materials of 4-EM and PEI (Lewis base). Furthermore, the solid-state catalytic system based on the polymer composite of UiO-66S/LPEI10k on the cotton fabric was also examined for MPO hydrolysis at various relative humidity and temperature conditions to create actual atmosphere conditions, which gave the possibility for actual military applications such as protective suits and equipment. In addition, we schematically demonstrated the loss of active sites on UiO-66 by chelation effects based on experimental and density functional theory (DFT)-derived computational simulation because it is highly correlated to the feasibility of Zr(IV)-based MOF catalysts for detoxification of nerve agents. In addition, we carefully propose a plausible reaction mechanism step on the nucleophilic attack by hydroxide group on the basis of the computational simulation.

Development of new hole-transport layer (HTL) materials for organic photovoltaic (OPV) applications is one crucial issue to mitigate such limitations of low power efficiency, processibility, and stability derived from poly(3,4-ethylene dioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) as a common HTL material. To this end, poly(3-hexylthiophene) (P3HT)-based diblock copolymers including the different ratios between polystyrene (PSty) or/and poly(neopentyl styrene sulfonate) (PNSS) as a second block segment were designed and then used for incorporating with single wall carbon nanotubes (SWCNTs) to form potentially self-dopable nanocomposites. The structure of fabricated P3HT-based diblock copolymer/SWCNT nanocomposites was examined by microscopic and spectroscopic characterizations, exhibiting a charge transfer behavior between P3HT and SWCNT, and growth of the P3HT crystalline phase along the SWCNT surface with a form of the conducting path. The acquired SWCNT nanocomposites exhibited good solubility and dispersion in various organic solvents including toluene, chlorobenzene, THF, chloroform, and DMF, which are good solvents for the PSty or/and PNSS neutral second block. The concept for the neutralized second block by protecting groups can prevent the poisoning ITO substrate by water contamination as shown in the conventional aqueous PEDOT-PSS solution. Notably, the PNSS constituent in the nanocomposite was merely acidified to give in-situ sulfonic acid groups in PSty by simple thermolysis process at 160 °C for 30 min after a solution process for fabrication of a thin film. The thermolysis step provided efficient doping of P3HT by PSS, in which the thiophene groups worked as Bronsted base are protonated by taking protons from sulfonic acid groups and then lead to a form of ionic bonds between cationic thiophene and anionic sulfonate groups. In addition, the formed ionic bonds in the nanocomposites led to an insoluble thin film, which has a good advantage for the further solvent process without substantial damages. The beneficial features of the conducting path along SWCNT and the efficient doping of P3HT by PSS in the acquired nanocomposites led to ca. 5-fold higher electrical conductivity (3.16 S cm−1) and similar work function (5.1 eV) in comparison to water contained commercial PEDOT:PSS (0.6 S cm−1 and 5.0 eV, respectively). As such, the rationally designed potentially self-dopable SWCNT nanocomposites can be one of the promising alternatives beyond the commercial PEDOT: PSS HTL material.

All organisms begin protein synthesis with methionine (Met). The resulting initiator Met of nascent proteins is irreversibly processed by Met aminopeptidases (MetAPs). N-terminal (Nt) Met excision (NME) is an evolutionarily conserved and essential process operating on up to two-thirds of proteins. However, the universal function of NME remains largely unknown. MetAPs have a well-known processing preference for Nt-Met with Ala, Ser, Gly, Thr, Cys, Pro, or Val at position 2, but using CHX-chase assays to assess protein degradation in yeast cells, as well as protein-binding and RT-qPCR assays, we demonstrate here that NME also occurs on nascent proteins bearing Met–Asn or Met–Gln at their N termini. We found that the NME at these termini exposes the tertiary destabilizing Nt residues (Asn or Gln) of the Arg/N-end rule pathway, which degrades proteins according to the composition of their Nt residues. We also identified a yeast DNA repair protein, MQ-Rad16, bearing a Met–Gln N terminus, as well as a human tropomyosin–receptor kinase–fused gene (TFG) protein, MN-TFG, bearing a Met–Asn N terminus as physiological, MetAP-processed Arg/N-end rule substrates. Furthermore, we show that the loss of the components of the Arg/N-end rule pathway substantially suppresses the growth defects of naa20Δ yeast cells lacking the catalytic subunit of NatB Nt acetylase at 37 °C. Collectively, the results of our study reveal that NME is a key upstream step for the creation of the Arg/N-end rule substrates bearing tertiary destabilizing residues in vivo.

Mitochondria behave as functional and structural hubs for innate defense against intracellular infection. While the mitochondrial membrane serves as a platform for the assembly of signaling complexes activated by intracellular infection, various danger molecules derived from impaired mitochondria activate innate signaling pathways. Using methionyl-tRNA formyl transferase (MTFMT)-deficient cells, which exhibit impaired mitochondrial activity, we examined the role of mitochondrial integrity in regulating innate defense against infection. Since MTFMT functions at the early steps of mitochondrial translation, its loss was expected to cause defects in mitochondrial activity. Under transient MTFMT gene silencing conditions, we observed shortened mitochondria along with reduced activity. MTFMT-silenced cells were more susceptible to intracellular infection, as examined by infection with RNA viruses and the intracellular bacterium Shigella flexneri. In support of this observation, MTFMT-silenced cells possessed lowered basal NF-κB activity, which remained low after S. flexneri infection. In addition, the mitochondrial accumulation of evolutionarily conserved signaling intermediate in Toll pathway (ECSIT), an adaptor protein for NF-κB activation, was significantly decreased in MTFMT-silenced cells, explaining the reduced NF-κB activity observed in these cells. Since impaired mitochondria likely release mitochondrial molecules, we evaluated the contribution of mitochondrial N-formyl peptides to the regulation of bacterial infection. Transient transfection of mitochondrial-derived N-formyl peptides favored S. flexneri infection, which was accompanied by enhanced bacterial survival, but did not affect host cell viability. However, transient transfection of mitochondrial-derived N-formyl peptides did not affect basal NF-κB activity. Altogether, these data suggest that the integrity of mitochondria is essential to their proper function in protecting against infection, as intact mitochondria not only block the release of danger molecules but also serve as signaling hubs for the downstream NF-κB pathway.

Abstract Background Lanreotide is a long-acting somatostatin analogue with proven antitumour effects against well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumours (GEP-NETs). However, there are no globally established prognostic factors associated with the efficacy of lanreotide as a treatment for GEP-NETs. We investigated the prognostic value of [68Ga]Ga-DOTA-TOC positron emission tomography (PET)/computed tomography (CT) somatostatin receptor imaging for patients with WD GEP-NETs treated with lanreotide. Methods In this retrospective study, we included 31 patients with unresectable or metastatic WD GEP-NETs who received lanreotide and underwent [68Ga]Ga-DOTA-TOC PET/CT before receiving lanreotide. We captured the following clinicopathological variables: Eastern Cooperative Oncology Group (ECOG) performance status, primary tumour site, NET World Health Organization grade, existence of carcinoid symptoms, previous surgery, previous chemotherapy, and hepatic tumour volume assessed by CT or magnetic resonance imaging (MRI). We also assessed the following [68Ga]Ga-DOTA-TOC PET/CT variables: Krenning score, tumour-to-liver ratio (TLR), maximum standardized uptake value (SUVmax), whole tumour volume (WTV), and total receptor expression (TRE, WTV multiplied by SUVmean). The associations between these markers and progression-free survival (PFS) with lanreotide were analysed. Results The mean age was 55.1 ± 15.5 years (range 16.0–81.0). The most common primary tumour site was the pancreas, followed by the stomach, and rectum. The median PFS interval with lanreotide was 14.4 months (range 1.3–34.9), with identified disease progression in 20 patients (64.5%). Among the [68Ga]Ga-DOTA-TOC PET/CT variables, TLR (< 8.1 vs. ≥ 8.1; p = 0.013), SUVmax (< 42.9 vs. ≥ 42.9; p = 0.037), and WTV (≥ 58.9 cm3 vs. < 58.9 cm3; p = 0.030) were significantly associated with PFS in the univariate analyses, but only TLR (hazard ratio 3.182 [95% CI 1.189–8.514], p = 0.021) remained an independent factor for PFS in the multivariate analysis. Conclusions Low TLR, determined via [68Ga]Ga-DOTA-TOC PET/CT, can be a factor of worse prognosis in patients with advanced WD GEP-NETs treated with lanreotide.

A series of UV-curable hybrid composite blends containing a carboxylic acid functionalized polyimidewith varying amounts of high molecular weight (~1 K) PEG-grafted ladder-structured polysilsesquioxanes copolymerized with methacryl groups were fabricated and their structural, thermal, mechanical, and surface properties characterized. At a composite weight ratio of polyimide above 50 wt.%, a stark shift from amorphous to crystalline polyethylene glycol (PEG) phases were observed, accompanied by a drastic increase in both surface moduli and brittleness index. Moreover, fabricated composites were shown to have a wide range water contact angle, 9.8&deg, &ndash, 73.8&deg, attesting to the tunable surface properties of these amphiphilic hybrid polymer composites. The enhanced mechanical properties, combined with the utility of tunable surface hydrophilicity allows for the possible use of these hybrid polymer composites to be utilized as photosensitive polyimide negative photoresists for a myriad of semiconductor patterning processes.

Perilipin 2 (PLIN2) is a major lipid droplet (LD)-associated protein that regulates intracellular lipid homeostasis and LD formation. Under lipid-deprived conditions, the LD-unbound (free) form of PLIN2 is eliminated in the cytosol by an as yet unknown ubiquitin (Ub)-proteasome pathway that is associated with the N-terminal or near N-terminal residues of the protein. Here, using HeLa, HEK293T, and HepG2 human cell lines, cycloheximide chase, in vivo ubiquitylation, split-Ub yeast two-hybrid, and chemical cross-linking–based reciprocal co-immunoprecipitation assays, we found that TEB4 (MARCH6), an E3 Ub ligase and recognition component of the Ac/N-end rule pathway, directly targets the N-terminal acetyl moiety of Nα-terminally acetylated PLIN2 for its polyubiquitylation and degradation by the 26S proteasome. We also show that the TEB4-mediated Ac/N-end rule pathway reduces intracellular LD accumulation by degrading PLIN2. Collectively, these findings identify PLIN2 as a substrate of the Ac/N-end rule pathway and indicate a previously unappreciated role of the Ac/N-end rule pathway in LD metabolism.

Carbon molecular sieve (CMS) membranes are a promising candidate for natural gas processing due to their peculiar pore structure-induced excellent separation performance. Formulating ultrathin, defect-free CMS hollow fiber membranes is, however, still challenging due to damage on porous sub-structures induced by thermal relaxation of polymer chains during pyrolysis. Herein, we report a new methodology enabling high separation performance and good plasticization resistance in CMS fiber membranes by uniform integration of double-stranded polysilsesquioxanes into the polyimide matrix. Our polyimide/ladder-structured polysilsesquioxane CMS fibers substantially enhanced CO2 permeance by as much as 546% compared to the precursor fiber analogues due to the thin molecular sieve selective layer. Also, poly(dimethylsiloxane) coating delayed physical aging, still showing a high CO2 permeance of 354 GPU with CO2/CH4 selectivity of 56 after 72 days of aging. Furthermore, they exhibited excellent plasticization resistance up to a CO2 partial pressure of 13.2 bar with CO2/CH4 separation factor of 74 for an equimolar CO2/CH4 feed mixture.

The field of terminal proteomics is limited in that it is optimized for large-scale analysis via multistep processes involving liquid chromatography. Here, we present an integrated N-terminal peptide enrichment method (iNrich) that can handle as little as 25 μg of cell lysate via a single-stage encapsulated solid-phase extraction column. iNrich enables simple, rapid, and reproducible sample processing, treatment of a wide range of protein amounts (25 μg ∼ 1 mg), multiplexed parallel sample preparation, and in-stage sample prefractionation using a mixed-anion-exchange filter. We identified ∼5000 N-terminal peptides (Nt-peptides) from only 100 μg of human cell lysate including Nt-formyl peptides. Multiplexed sample preparation facilitated quantitative and robust enrichment of N-terminome with dozens of samples simultaneously. We further developed the method to incorporate isobaric tags such as a tandem mass tag (TMT) and used it to discover novel peptides during ER stress analysis. The iNrich facilitated high-throughput N-terminomics and degradomics at a low cost using commercially available reagents and apparatus, without requiring arduous procedures.

Lanreotide autogel is a long-acting somatostatin analogue with proven efficacy and safety in patients with well-differentiated (WD) gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) in a prior randomized phase III trial (CLARINET). However, the CLARINET study only enrolled patients with Ki-67 index10%, and few patients of Asian ethnicity were included. We retrospectively analyzed the efficacy and safety of lanreotide in Korean patients with GEP-NETs in the daily practice setting. Between January 2015 and May 2018, 64 patients with metastatic WD GEP-NETs received lanreotide at Asan Medical Center, Seoul, Korea. Of them, 45 (70.3%) patients who received lanreotide as monotherapy were included in the current analysis. The most common primary tumor site was the pancreas (n = 22, 48.9%), followed by the rectum (10, 22.2%) and the small bowel (7, 15.6%). According to RECIST v1.1, a partial response was achieved in one patient (2.2%) and stable disease was achieved in 40 patients (88.9%). The median progression-free survival (PFS) was 16.4 months (95% confidence interval, 9.5-23.3 months). There were no differences in PFS according to the primary tumor site (p = 0.77). Hepatic tumor volume 25% and prior systemic therapy were significantly associated with poorer PFS in the multivariate analysis. Lanreotide is well-tolerated and effective for Korean patients with GEP-NETs in the daily practice setting.

A vertical cell is the best structure for optimizing dynamic random access memory size. However, this structure has a fatal weakness called the floating-body effect (FBE). In this letter, we propose a new vertical structure to suppress FBE and short-channel effects, and successfully demonstrate the structure through simulation. In the new structure, the band-to-band tunnel diode body contact is built in the source region, which effectively releases the accumulated body carriers. In the buried contact, a heavily doped $\text{p}^{+}$ layer is introduced next to the $\text{n}^{+}$ source region, effectively connecting the body and source through tunneling. Furthermore, the proposed structure shows an extremely high ON-state to OFF-state current ( $\text{I}_{ON}/\text{I}_{OFF})$ ratio of ~107 for a channel length of 100 nm.

Well-defined methacrylate based amphiphilic block copolymers (BCs) consisting of poly(methyl methacrylate) (PMMA) and poly(ethylene glycol) methacrylate (PPEGMA) were synthesized by atom transfer radical polymerization (ATRP) and used as additives in DMAc casting solution to fabricate poly(vinylidene fluoride) (PVDF) ultra-filtration (UF) membranes in non-solvent induced phase separation (NIPS) process, where the amphiphilic BC additives hydrophilically altered PVDF with PPEGMA block segment by strong interaction with the other PMMA block segment, which reduced water resistance to the PVDF polymer solution during phase separation. FT-IR and XPS studies showed carbonyl groups of BCs in the PVDF membranes, which were not changed even after IPA treatment, indicating that BCs in the membrane were very stable. Obtained PVDF membranes with BCs showed porous surface layer and finger-like pore structures with macrovoids on the sublayers, of which sizes were increased with the increase of BC contents, which were then compared to the pristine PVDF membranes and the PVDF membrane with corresponding other additives such as hydrophobic PMMA, hydrophilic PPEGMA, LiCl and BC/LiCl. Obtained PVDF membranes showed MWCO with 100 K PEO and the best water flux (140 LMH) was achieved in the PVDF membrane with BC/LiCl additive, which was almost 4 times higher than the pristine PVDF membrane. In addition, the PVDF membranes with BC and BC/LiCl additives improved the anti-fouling property for BSA protein, of which reversible fouling resistance ratio was ca. 7 times higher than that of the pristine PVDF membrane.

Depression causes mental and physical changes which affect quality of life. It is estimated to become the second most prevalent disease, but despite its commonness, the pathophysiology of depression remains unclear and medicine is not sufficiently protective. p-Coumaric acid (p-CA) is a dietary phenolic acid which has been proven to have antifungal, anti-HIV, anti-melanogenic, antioxidant and anti-inflammatory effects. Considering these effects, we investigated whether p-CA can prevent depressive symptoms by reducing inflammatory cytokines in animals injected with lipopolysaccharide (LPS). Changes in despair-related behaviors, inflammatory cytokines, neurotrophic factors and synaptic activity were measured. In these animals, p-CA improved despair-related behavioral symptoms induced by LPS in the forced swim test (FST), tail suspension test (TST) and sucrose splash test (SST). p-CA also prevented the increase of inflammatory cytokines in the hippocampus such as cycloxigenase-2 and tumor necrosis factor-α due to LPS. Similarly, it prevented the reduction of brain-derived neurotrophic factor (BDNF) by LPS. Electrophysiologically, p-CA blocked the reduction of long-term depression in LPS-treated organotypic tissue slices. In conclusion, p-CA prevented LPS-induced depressive symptoms in animals, as determined by behavioral, biochemical and electrophysiological measures. These findings suggest the potential use of p-CA as a preventive and therapeutic medicine for depression., Graphical Abstract

Two series of water-soluble metalloporphyrin-cored amphiphilic star block copolymers were synthesized by controlled radical polymerizations such as atom transfer radical polymerization (ATRP) and reversible addition fragmentation chain transfer (RAFT), which gave eight amphiphilic block copolymer arm chains consisting of poly(n-butyl acrylate-b-poly(ethylene glycol) methyl ether methacylate) (PnBA-b-PEGMEMA, Mn,GPC = 78,000, Mw/Mn = 1.2, 70 wt% of PPEGMEMA) and poly(styrene-b-2-dimethylamino ethyl acrylate) (PS-b-PDMAEA, Mn,GPC = 83,000, Mw/Mn = 1.2, 67 wt% of PDMAEA), yielding porphyrin(Pd)-(PnBA-b-PPEGMEMA)8 and porphyrin(Pd)-(PS-b-PDMAEA)8, respectively. Obtained metalloporphyrin polymer photocatalysts were homogeneously solubilized in water to apply to the removal of chlorophenols in water, and was distinguished from conventional water-insoluble small molecular metalloporphyrin photocatalysts. Notably, we found that the water-soluble star block copolymers with hydrophobic–hydrophilic core–shell structures more effectively decomposed the chlorophenol, 2,4,6-trichlorophenol (2,4,6-TCP), in water under visible light irradiation (k = 1.39 h−1, t1/2 = 0.5 h) in comparison to the corresponding water-soluble star homopolymer, because the hydrophobic core near the metalloporphyrin effectively captured and decomposed the hydrophobic chlorophenols in water.

Objective Long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs), like liraglutide and semaglutide, are viable treatments for diabetes and obesity. Liraglutide directly activates hypothalamic proopiomelanocortin (POMC) neurons while indirectly inhibiting Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons ex vivo. While temporal control of GLP-1R agonist concentration as well as accessibility to tissues/cells can be achieved with relative ease ex vivo, in vivo this is dependent upon the pharmacokinetics of these agonists and relative penetration into structures of interest. Thus, whether liraglutide or semaglutide modifies the activity of POMC and NPY/AgRP neurons in vivo as well as mechanisms required for any changes in cellular activity remains undefined. Methods In order to resolve this issue, we utilized neuron-specific transgenic mouse models to examine changes in the activity of POMC and NPY/AgRP neurons after injection of either liraglutide or semaglutide (intraperitoneal - I.P. and subcutaneous - S·C.). POMC and NPY/AgRP neurons were targeted for patch-clamp electrophysiology as well as in vivo fiber photometry. Results We found that liraglutide and semaglutide directly activate and increase excitatory tone to POMC neurons in a time-dependent manner. This increased activity of POMC neurons required GLP-1Rs in POMC neurons as well as a downstream mixed cation channel comprised of TRPC5 subunits. We also observed an indirect upregulation of excitatory input to POMC neurons originating from glutamatergic cells that also required TRPC5 subunits. Conversely, GLP-1Ra's decreased excitatory input to and indirectly inhibited NPY/AgRP neurons through activation of K-ATP and TRPC5 channels in GABAergic neurons. Notably, the temporal activation of POMC and inhibition of NPY/AgRP neuronal activity after liraglutide or semaglutide was injected [either intraperitoneal (I.P.) or subcutaneous (S·C.)] was dependent upon the nutritional state of the animals (fed vs food-deprived). Conclusions Our results support a mechanism of liraglutide and semaglutide in vivo to activate POMC while inhibiting NPY/AgRP neurons, which depends upon metabolic state and mirrors the pharmacokinetic profile of these compounds in vivo., Graphical abstract Image 1, Highlights • Liraglutide and semaglutide directly activates POMC neurons and indirectly inhibits NPY neurons in vivo. • GLP-1R agonists recruit additional synaptic activity to arcuate POMC and NPY/AgRP neurons in vivo and ex vivo. • Changes in the temporal activity are dependent upon the nutritional state. • Exercise potentiates the effects of long-acting GLP-1R agonists to activate POMC and inhibit NPY neurons.

Blends of poly(2,6-dimethyl-1,4-phenylene ether) (PPE) and poly(phenylene sulfide) (PPS) have shown potential as a new class of high-performance engineering plastics by reciprocally complementing the drawbacks of each component. However, improving their inherently poor toughness remains a challenge. Here, we report the design of PPE/PPS-based quaternary blends with increased impact strength without a significant loss of mechanical and flame-retardant properties. Introducing reactive polystyrene (RPS) with an oxazoline functional group as a compatibilizer improved the miscibility between the discrete PPE domain and continuous PPS matrix phases. The impact modifier styrene-ethylene-butadiene-styrene (SEBS) was compatibilized within the PPS matrix phase in the presence of RPS, enabling extraordinary impact strength. The tensile strength of the quaternary blends decreased slightly with increasing SEBS content, but the values exceeded the criteria for engineering plastic. All quaternary blends passed the V-0 grade in the UL-94 test because of the inherently excellent flame retardancy of the majority components.

A new method for enhancing condensable gas-induced plasticization resistance of aromatic polyimides (PIs) as well as increasing the flux of gas penetrants with negligible selectivity loss was demonstrated via a so-called bromination/debromination-induced thermal crosslinking. Our newly developed crosslinking approach essentially loosened the polymeric chain packing of 6FDA-Durene PIs by forming ethylene crosslinking bonds, while retaining its rigid PI backbone. As the degree of crosslinking increased, the permeability increased with trivial selectivity loss. Notably, the 75% bromination/debromination-induced crosslinked PI membranes drastically improved CO2 and C3H6 permeabilities by as much as 157% and 172%, respectively, compared to those of the pristine-PI analogs due to the debromination-induced free volume enhancement, while maintaining good selectivity due to the crosslinked ethylene bridges. As a result, outstanding separation performances for CO2/N2, CO2/CH4 and C3H6/C3H8 gas pairs have been obtained, and most importantly, a high tolerance to CO2- or C3H6-induced plasticization was observed up to CO2 or C3H6 pressure of 24 and 10 atm, respectively. Our current crosslinking approach can be extended to industrially attractive hollow fiber forms of various aromatic PIs for high plasticization resistance as well as high flux.

Pourable and room temperature flowable ladder-structured polysilsesquioxanes were synthesized and applied as functional optical hard coatings. Organic functional group type (propyl, hexyl, octyl, dodecyl) and their copolymer composition with UV-curable methylacryloxypropyl group were selected as to control both pre-cured viscosity and final mechanical properties independent of molecular weight. Ladder-structured polysilsesquioxanes with longer alkyl side chains exhibited higher fluidity and flexibility while maintaining its optical property and mechanical strength. The solvent-free processability of our synthesized materials along with their superior optical and mechanical properties over commercial solvent-based hard coatings suggest the high value of our hybrid materials for the coatings industry.

Increases in human life expectancy have led to increases in the prevalence of senile dementia and neurodegenerative diseases. This is a major problem because there are no curative treatments for these diseases, and patients with unmanaged cognitive and neurodegenerative symptoms experience many social problems. Sulforaphane is a type of organosulfur compound known as an isothiocyanate. It is derived from glucoraphanin, a compound found in cruciferous vegetables such as broccoli, brussels sprouts, and cabbages, via an enzymatic reaction that is triggered by plant damage (e.g., chewing). Sulforaphane exhibits activity against cancer, inflammation, depression, and severe cardiac diseases. It can also alleviate oxidative stress and neural dysfunction in the brain. However, there is insufficient knowledge about the electrophysiological and behavioral basis of the effects of sulforaphane on learning and memory. Therefore, we evaluated whether acute sulforaphane administration affected long-term potentiation (LTP) in organotypic cultured rat hippocampal tissues. We also measured the effect of sulforaphane on the performance of three behavioral tests, the Y-maze test, the passive avoidance test, and the Morris water maze, which assess short-term memory, avoidance memory, and short and long-term spatial memory, respectively. We found that sulforaphane increased the total field excitatory postsynaptic potential (fEPSP) in a dose-dependent manner after high frequency stimulation and attenuated scopolamine-induced interference of the fEPSP in the hippocampal CA1 area. Sulforaphane also restored cognitive function and inhibited memory impairment as indicated by the alleviation of the negative neurological effects of scopolamine, i.e, a lowered ratio of spontaneous alternation in the Y-maze, a reduced step-through latency in the passive avoidance test, and an increased navigation time in the Morris water maze. These results indicate that sulforaphane can effectively prevent the attenuation of LTP and cognitive abilities induced by cholinergic and muscarinic receptor blockade. Further research is warranted to explore the potential therapeutic and prophylactic utility of sulforaphane for improving learning and memory, especially in those suffering from neurodegenerative disorders.

Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders. In this study, we investigated whether RUR modulates inflammatory processes in lipopolysaccharide (LPS)-stimulated BV2 microglia cells and the mouse brain. RUR exerted anti-neuroinflammatory effects by inhibiting the production of nitric oxide and reactive oxygen species induced by LPS via the downregulation of transcription factors such as inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) without causing cytotoxicity. RUR also regulated mitogen-activated protein kinase pathway by inhibiting phosphorylation of p38 and c-Jun N-terminal kinases and translocation of nuclear factor kappa B. Moreover, RUR attenuated LPS-induced glial activation and COX-2 expression in the substantia nigra and hippocampus of the mouse brain. These results indicate that RUR is a potential candidate to treat neurodegenerative diseases by regulating neuroinflammation.

In this paper, the effects of hydrogen (H 2 ) plasma treatment on the molybdenum (Mo)-doped indium oxide (InO) thin film that was formed on glass using the polymer-assisted deposition (PAD) process were investigated. The sheet resistance for the sample treated at the ICP power of 15 W was quenched to 167 Ω/sq. from the 680 Ω/sq. for the as-deposited sample. Compared with the as-deposited sample, both the mobility and the concentration of the sample treated at the 15 W ICP power were also increased simultaneously, resulting in an increased conductivity. From these results, it was concluded that the H 2 plasma treatment is an efficient method for the enhancement of the electrical property, as well as to remove nano-sized cracks on the surface of the PAD-Mo-doped InO without a deterioration the optical transmittance.

Most inorganic nucleating agents for poly(ethylene terephthalate) (PET) have limited nucleating ability due to poor compatibility with PET. Polyhedral oligomeric silsesquioxanes (POSS) is a type of cage-shaped organic/inorganic hybrid nanoparticles with three different particle sizes: octameric (T8), decameric (T10), and dodecameric (T12). POSS is considered as a promising nucleating agent for PET because the inorganic moieties contribute to high thermal stability and nucleation and the organic moieties can be tethered to PET chains. In contrast to T8 POSS, the nucleation ability of T12 POSS for PET has been poorly reported. In this study, our newly synthesized aminopropyl functionalized T12 POSS (A-POSS) is proposed as a potential nucleating agent for PET. The amine group of A-POSS is able to be chemically conjugated to PET chains, thereby giving a more homogeneous dispersion of T12 POSS in PET than non-functional T12 Phenyl POSS (N-POSS). Its PET composites gave a ∼1.2 fold higher crystallization temperature and ∼2.7 fold higher shear-induced crystallization rate over pristine PET. Such nucleating effects for PET is more effective than those of non-functional T12 POSS and the more widely studied T8 POSS. This strategy is potentially beneficial for the high-shear melt processes of PET such as spinning and film extrusion.

Heteroleptic ruthenium-complexed ladder-like structured polysilsesquioxane (LPSQ-Ru) was synthesized by post coordination reaction of bidentate ligand side chains in LPSQ with reactive Ru(II) complexes, which was well characterized by 1H and 29Si NMR, FT-IR, and spectroscopic techniques. The photophysical properties of LPSQ-Ru were examined by UV and PL analyses in both solution and solid states, comparing to analogous polymers of ruthenium-complexed polystyrene (PS-Ru). Obtained absorptions of LPSQ-Ru and PS-Ru were broadened ranging from 390-490 nm regardless of the states. However, LPSQ-Ru exhibited higher and shaper PL emission spectrum in comparison to that of PS-Ru, particularly in the solid state, because Ru-complexes in LPSQ were much effectively isolated, preventing their aggregations due to the rigid double strained siloxane backbone. This extinguished photophysical property in LPSQ-Ru kept after intensive thermal treatment at 250 °C for 90 min, which was not achieved in PS-Ru (~5-fold decrease). These differences originated from the backbone structures were also appeared in electrochemical properties in the solid states.

A TiO 2 :CaO mixed overlayer was formed on TiO 2 photoelectrodes, and the resulting photoelectrodes were applied to dye-sensitized solar cells (DSSCs). DSSC with the mixed overlayer showed an increase in short-circuit current ( J sc ), open-circuit voltage ( V oc ), and fill factor ( FF ), resulting in a 17% enhancement in photovoltaic performance, compared to that of reference cell. It was found that, by incorporating the mixed overlayer, light harvesting and electron collection efficiency were enhanced, thereby increasing J sc . The enhancement in V oc resulted from a reduced back electron transfer, and the increased FF was attributed to a decreased series resistance and an increased shunt resistance.

A multifunctional crosslinkable and ionic-group functionalized ladder-like polysilsesquioxane was synthesized and utilized for the fabrication of hybrid ionogels for lithium ion batteries. The ionic-group functionalized ladder-like polysilsesquioxane combined the synergistic effects of hybrid materials in improving the thermal stability of conventional battery electrolytes, whilst maintain facile solution processability and chemically crosslinkable function in ionic conducting ionic liquid electrolyte media. Fabricated iongel electrolytes exhibiting exceptional thermal stability, mechanical properties, high ionic conductivity, and electrochemical stability. Lithium ion batteries fabricated with the hybrid ionic ladder-like polysilsesquioxane ionogels exhibited initial discharge capacities on par with neat liquid electrolytes, good rate performance, as well as stable cyclability and excellent Coulombic efficiency.

Increasing the rating of the HVDC cable causes an inevitable increase in the heat generated inside cable. Thus, it is necessary to improve the thermal conductivity of the Cross-linked polyethylene (XLPE) insulation material used in the extruded cable for effective thermal management. Also, several methods have been pro-posed so far to increase the thermal conductivity of XLPE. However, the influence of the filler addition on the thermal conductivity has been mainly studied experimentally so far. Therefore, numerical analysis was performed to investigate the effect of filler size and its content on thermal conductivity of XLPE. In the modelling of XLPE composite for numerical analysis spherical Al2O3 particles with a radius of 25, 50, 100 and 200 nm were considered. Additionally, filler contents were considered with up to 20 wt%. Numerical analysis of XLPE composite model showed that the effective thermal conductivity increased with the smaller filler size. Also, as the content of filler increased, the effective thermal conductivity increased. A coupled electro-thermal model considering the previously derived thermal conductivities was used to investigate the influence of the thermal conductivity of XLPE on temperature and electric field distribution. From the simulation results it can be concluded that, higher thermal conductivity of XLPE can reduce the thermal and electrical stress of the cable. Therefore, it is considered that the smaller the size of the filler added to the insulation or the larger the content of the filler, the thermal and electrical stress in the cable can be reduced.

Spontaneous abortion represents a common form of embryonic loss caused by early pregnancy failure. In the present study, we investigated the prophylactic effects of bee venom phospholipase A2 (bvPLA2), a regulatory T cell (Treg) inducer, on a lipopolysaccharide (LPS)-induced abortion mouse model. Fetal loss, including viable implants, the fetal resorption rate, and the fetal weight, were measured after LPS and bvPLA2 treatment. The levels of serum and tissue inflammatory cytokines were determined. To investigate the involvement of the Treg population in bvPLA2-mediated protection against fetal loss, the effect of Treg depletion was evaluated following bvPLA2 and LPS treatment. The results clearly revealed that bvPLA2 can prevent fetal loss accompanied by growth restriction in the remaining viable fetus. When the LPS-induced abortion mice were treated with bvPLA2, Treg cells were significantly increased compared with those in the non-pregnant, PBS, and LPS groups. After LPS injection, the levels of proinflammatory cytokines were markedly increased compared with those in the PBS mouse group, while bvPLA2 treatment showed significantly decreased TNF-&alpha, and IFN-&gamma, expression compared with that in the LPS group. The protective effects of bvPLA2 treatment were not detected in Treg-depleted abortion-prone mice. These findings suggest that bvPLA2 has protective effects in the LPS-induced abortion mouse model by regulating Treg populations.

Membrane-based separation technology is attractive for upgrading small-scale natural gas due to the benefits of the pressure-driven process with a small footprint. Very few carbon molecular sieve (CMS) membranes with high N2/CH4 separation efficiency have been reported since the relationship between CMS structure and separation performance has not been fully elucidated. Here, we report the significance of controlling the effective pore size in our newly developed hybrid CMS matrix for enhanced N2/CH4 selectivity based on experimental characterizations and density functional theory (DFT) calculations. A new class of CMS membranes with an excellent N2/CH4 selectivity is demonstrated by pyrolysis of a homogeneous, hydrogen-bonded blend of BTDA-Durene:DABA (3:2) polyimide and ladder-structured poly(phenyl-co-3-(2-aminoethylamino)propyl)silsesquioxane (LPDA64). DFT calculations suggest that electron accumulation at SiOx phases of hybrid CMS membranes strongly hinders the diffusion of CH4 compared to N2 due to a larger electron overlap, resulting in a smaller effective pore size. Moreover, elevating the pyrolysis temperatures enhanced the N2/CH4 solubility selectivity due to the strong repulsive interaction between the newly formed ultramicropores with CH4. As a result, the hybrid CMS membranes showed an excellent single gas and N2/CH4/C2H6 (20/76/4) mixed gas N2/CH4 selectivity (28 and 16, respectively).

A new methodology for fabrication of inorganic–organic hybrid ionogels and scaffolds is developed through facile cross-linking and solution extraction of a newly developed ionic polyhedral oligomeric silsesquioxane with inorganic core. Through design of various cationic tertiary amines, as well as cross-linkable functional groups on each arm of the inorganic core, high-performance ionogels are fabricated with excellent electrochemical stability and unique ion conduction behavior, giving superior lithium ion battery performance. Moreover, through solvent extraction of the liquid components, hybrid scaffolds with well-defined, interconnected mesopores are utilized as heterogeneous catalysts for the CO2-catalyzed cycloaddition of epoxides. Excellent catalytic performance, as well as highly efficient recyclability are observed when compared to other previous literature materials.

An in-depth examination of the self-healing properties of both dienophile and diene functionalized ladder-like structured polysilsesquioxane copolymers and terpolymers was investigated. Through functionalization of both diene and dienophile on the double-stranded siloxane backbone with ternary n-alkyl functional groups acting as chain mobility control, the effect of chain mobility and chemical structure on self-healing and mechanical properties were elucidated. All of the single component self-healing hybrid materials exhibited fast healing times (∼5 min), and their de-crosslinked adducts exhibited exceptional retention of solubility in common organic solvents for good reusability, all while having inherent high thermal stability and optical transparency.

A series of trimethylsilyl-capped hybrid ladder-like polysilsesquioxane (LPSQ-TMS) derivatives were synthesized comprising an inorganic backbone functionalized with various organic side moieties and compositional ratios with application towards gate dielectrics or surface modifying materials. The surface energy (γ) and roughness (Rq) values of the LPSQ-TMS coated SiO2 dielectrics were considerably affected by the side moieties of the polymer series; methyl, n-propyl, phenyl (P), naphthyl (N), methacryloxypropyl (MA), and fluorooctyl moieties. The γ values varied from 17.0 to 42.0 mJ m−2, while the Rq values also ranged from 0.34 to 1.10 nm. On polymer-treated SiO2 dielectrics possessing smooth and semiconductor-compatible surface properties, pentacene developed terrace-like crystallites formed through layer-by-island growth modes, a stark contrast to the three-dimensionally grown crystal islands formed on rough or extremely hydrophobic surfaces, which led to unfavorable conduction pathways. Depending on the order of conjugation and interconnections between the pentacene domains, the average mobility (μFET) values of the resulting 50 nm thick pentacene organic field-effect transistors were varied by two orders of magnitude and reached 0.8 cm2 V−1 s−1, specifically, for both the P- and MA-substituted LPSQ-TMS treated SiO2 dielectrics (γ = 37.0 mJ m−2 and Rq = 0.40 nm). Moreover, we were able to demonstrate that a thermally cured 500 nm thick LPSQ-TMS layer on an Au gate-patterned flexible polyimide substrate could yield pentacene OFETs with μFET values as high as 0.60 cm2 V−1 s−1, comparable to that of the LPSQ-TMS treated SiO2 system. Also, the proper introduction of organic substituents to LPSQ improved the gate-bias stress stability for high performance OFETs.

An investigation into the hydrolysis kinetics of an aqueous base-catalyzed sol-gel reaction yielding ladder-like polysilsesquioxanes was studied using NMR. Under various variables of monomer concentration, water concentration, solvent type, and monomer type, the various effects on molecular weight and degree of condensation were elucidated. Moreover, the various rate orders and rate constants were calculated and compared with previous reports of the hydrolysis of organosilane precursors. Through this study we were able to ascertain the optimal conditions of hydrolysis-polycondensation for obtaining highly condensed, high molecular weight ladder-like polysilsesquioxanes.

Boron containing ionogels were fabricated through chemical crosslinking of boron allyloxide with polyethylene glycol dimethacrylate in an ionic liquid electrolyte solution to obtain mechanically robust gels. Because of the relatively small concentration of crosslinking agent required to fully solidify the ionic liquid electrolyte, good characters of high ionic conductivity, high thermal stability, and good electrochemical stability were observed. A spectroscopic investigation of the boronic ionogels revealed that the lithium mobility was noticeably enhanced compared with ionogels fabricated without the boronic crosslinker, leading to promising Li-ion battery performance at elevated temperatures.

A comprehensive and fundamental gas transport study of ladder-structured polysilsesquioxanes (LPSQs) was systematically performed by investigating the effects of various alkyl substituents, different copolymer ratios, and UV-irradiation induced photo-crosslinking on gas separations. Overall, LPSQ membranes are more suitable for CO 2 /N 2 and CO 2 /H 2 separations due to a relatively high affinity towards CO 2 as well as rubbery polymer properties. The gas transport in LPSQ membranes was well interpreted by two important parameters, the inter-chain distance and the side chain mobility. A combination of larger inter-chain distance and higher side chain rigidity tends to increase the fractional free volume, resulting in higher gas permeability. Also, it was successfully demonstrated that the separation performance of LPSQ membranes can be predicted by using a logarithmic permeability relationship based on the transport characterization for a series of ladder-structured poly(phenyl- co -methacryloxypropyl)silsesquioxanes. Lastly, the UV-curing process reduced the permeability of LPSQ membranes, increasing the selectivity due to the restricted chain mobility.

In this study, the effect of novel BMP-2-loaded photo-cured hydrogels on in vitro and in vivo osteogenesis were explored. The well-defined HA-heparin hydrogel was prepared by a photopolymerization of aminoethyl methacrylate (AEMA) grafted hyaluronic acid (HA) and AEMA-grafted heparin. Subsequently, the resulting hydrogels contained BMP-2 at different concentrations. First, a series of BMP-2-loaded hydrogels were characterized to determine their mechanical properties and release profiles. The results from rheology, swelling ratio, and release kinetics suggest that BMP-2 contained HA-g-Hhep gel (B/HA-g-Hhep gel) had sustained release during 4 weeks with minimal initial burst. Furthermore, the released BMP-2 maintained its biological activity. MTT and live/dead assays showed that the B/HA-g-Hhep gel had good biocompatibility to be used as a scaffold for bone regeneration. In vivo studies of B/HA-g-Hhep gel exhibited significantly enhanced osteogenesis, compared with other types of HA-heparin hydrogels. These excellent results indicated that B/HA-g-Hhep gel has a great potential for a controlled release of growth factor, leading to a good bone regeneration. Open image in new window

For the first time, an inorganic-organic hybrid polymer binder was used for the coating of hybrid composites on separators to enhance thermal stability and to prevent formation of lithium dendrite in lithium metal batteries. The fabricated hybrid-composite-coated separators exhibited minimal thermal shrinkage compared with the previous composite separators (5% change in dimension), maintenance of porosity (Gurley number ∼400 s/100 cm(3)), and high ionic conductivity (0.82 mS/cm). Lithium metal battery cell examinations with our hybrid-composite-coated separators revealed excellent C-rate and cyclability performance due to the prevention of lithium dendrite growth on the lithium anode even after 200 cycles under 0.2-5C (charge-discharge) conditions. The mechanism for lithium dendrite prevention was attributed to exceptional nanoscale surface mechanical properties of the hybrid composite coating layer compared with the lithium metal anode, as the elastic modulus of the hybrid-composite-coated separator far exceeded those of both the lithium metal anode and the required threshold for lithium metal dendrite prevention.

A photosensitive ladder-structured polysilsesquioxane was synthesized for the development of flexible copper clad laminates through electroless plating of Cu. The developed ladder-structured polysilsesquioxane with controlled structure enabled easy introduction of protected thiol and allyl functional group, which under acidic conditions, the thiol group becomes deprotected. This deprotected thiol group enables UV-initiated thiol-ene curing of the exposed regions, while the unexposed regions containing free thiol groups act as seed initiators for Cu electroless plating, and the corresponding negative pattern fabrication process also possible. Through this facile method, we were able to develop flexible copper clad laminates of tunable Cu interconnect width size of high electrical conductivity according to photomask pattern and the insulating dielectric surrounding layer exhibiting low dielectric constant and low loss behavior without any corrosive Cu etching steps.

A novel inorganic–organic hybrid crosslinker was prepared through synthesis of a fully condensed, high molecular weight ladder-like poly(methacryloxypropyl)silsesquioxane (LPMASQ) in one pot with a facile, base-catalysed system. The fully condensed LPMASQ revealed good thermal (∼380 °C) and electrochemical stability (∼5.0 V) due to the absence of uncondensed silanol groups. LPMASQ also revealed good solubility in various organic solvents and fully gelated 1 M LiPF6 in ethyl carbonate–diethyl carbonate (EC–DEC, 3/7, v/v) electrolyte solution through fast thermal and photocuring even at a very low concentration of 2 wt%. These observations were attributed to the polymeric nature of LPMASQ containing over one hundred methacryl moieties on the rigid double-stranded siloxane backbone. To the best of our knowledge, formation of a gel polymer electrolyte with 2 wt% gelator is the smallest gelation concentration that has ever been reported. This leads to high ionic conductivity (∼6.0 mS cm−1), excellent Coulombic efficiency and battery cell performance, comparable with those of the neat liquid electrolyte. The small crosslinker content, thermal and electrochemical stability, fast thermal and photocuring and facile processing of the LPMASQ based GPEs, as well as excellent Li battery cell performances strongly hold great promise for future industrial battery applications.

Korean red pine (Pinus densiflora Sieb. et Zucc.) bark is a by-product of the wood industry and contains a high level of antioxidative phenolics including flavonoids, which have a variety of beneficial health effects. This study aimed to investigate the antihypertensive effects of P. densiflora bark extract (Korean red pine bark extract, KRPBE) in spontaneously hypertensive rats (SHRs). A group of Wistar-Kyoto rats (WKRs) as a normotensive group was orally fed tap water. Four groups of SHRs were orally fed tap water, captopril (a positive control), 50 mg/kg/day of KRPBE, and 150 mg/kg/day of KRPBE, respectively. Blood pressure of rats was measured once every week for seven weeks of oral administration. After seven weeks, the lungs, kidneys, and serum were collected from rats, then angiotensin-converting enzyme (ACE) activity, angiotensin II content, and malondialdehyde (MDA) content were determined. Blood pressure of the captopril- and KRPBE-treated groups was significantly lower than that of the SHR control group. The ACE activity, angiotensin II content, and MDA content significantly decreased in the captopril- and KRPBE-treated groups than those in the SHR control group. High-performance liquid chromatography analysis revealed six phenolics in KRPBE: protocatechuic acid, procyanidin B1, catechin, caffeic acid, vanillin, and taxifolin. KRPBE, which contains plenty of antioxidative phenolics, has antihypertensive effects partly due to reduction of ACE activity and angiotensin II content, and its antioxidative effect.

Nanoporous composite membranes coated on the microporous support with a ladder-like ionic polymer were prepared and the structural selectivity effect of the membrane on a non-aqueous vanadium redox flow battery (RFB) was investigated. Crosslinkable ladder-like ionic polysilsesquioxane (L-PSQ) was synthesized and a Celgard 2400 membrane was used for the support. An L-PSQ/Celgard composite membrane was prepared by the thermal crosslinking reaction of crosslinkable L-PSQ after the dip-coating process. The permeability of ionic L-PSQ/Celgard composite membranes decreased by two orders of magnitude upon thin coating while maintaining its high ion conductivity of the porous support, which provides higher charge/discharge capacity and cell efficiencies of RFB at all current densities compared to those of the RFB with the porous Celgard 2400 membrane. Due to the reduction of the crossover, the coulombic and energy efficiencies of non-aqueous vanadium RFB increase and reached 62.7% and 43.7%, respectively, for the RFB with the membrane containing 5.4 wt% of L-PSQ. These values are higher than those obtained for the Celgard membrane and the commercial Neosepta AHA membrane. This result implies that structure control of the membrane is a practical solution for the adaptation of the non-aqueous RFB for the future energy storage systems.