Prevention of neointimal hyperplasia after coronary artery bypass graft via local delivery of sirolimus and rosuvastatin: network pharmacology and in vivo validation.

BACKGROUND: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown. METHODS: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery. RESULTS: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis. CONCLUSIONS: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG.

Amidoxime-Containing Zr and Hf Atomic Layer Deposition Precursors for Metal Oxide Thin Films.

In this article, we discuss the synthesis of eight novel zirconium and hafnium complexes containing amidoxime ligands as potential precursors for atomic layer deposition (ALD). Two amidoximes, viz., (E)-N'-hydroxy-N,N-dimethylacetimidamide (mdaoH) and (Z)-N'-hydroxy-N,N-dimethylpivalimidamide (tdaoH), along with their Zr and Hf homoleptic complexes, Zr(mdao)4 (1), Hf(mdao)4 (2), Zr(tdao)4 (3), and Hf(tdao)4 (4) were prepared. We further synthesized heteroleptic compounds with different physical properties by introducing cyclopentadienyl (Cp) ligand, namely, CpZr(mdao)3 (5), CpHf(mdao)3 (6), CpZr(tdao)3 (7), and CpHf(tdao)3 (8). Thermogravimetric analysis was used for the assessment of the evaporation characteristics of complexes 1, 2, 5, and 6, and it revealed multistep weight losses with high residues. On the other hand, the thermogravimetric analysis curves of complexes 3, 4, 7, and 8 comprising tdao ligands revealed single-step weight losses with moderate residues. Single-crystal X-ray diffraction studies of complexes 1, 3, and 7 showed that all of the complexes have monomeric molecular structures. Complex 7 exhibited a low melting point (75 °C), good volatility, and high thermal stability compared with other complexes. Therefore, an atomic layer deposition process for the growth of ZrO2 was developed by using ZrCp(tdao)3 (7) as a novel precursor.

New Heteroleptic Germanium Precursors for GeO2 Thin Films by Atomic Layer Deposition.

This study describes the synthesis of 12 new germanium complexes containing ß-diketonate and/or N-alkoxy carboxamidate-type ligands as precursors for GeO2 through atomic layer deposition (ALD). A series of Ge(ß-diketonate)Cl complexes such as Ge(acac)Cl (1) and Ge(tmhd)Cl (2) were synthesized by using acetylacetone (acacH) and 2,2,6,6-tetramethyl-3,5-heptanedione (tmhdH). N-Alkoxy carboxamidate-type ligands such as N-methoxypropanamide (mpaH), N-methoxy-2,2-dimethylpropanamide (mdpaH), N-ethoxy-2-methylpropanamide (empaH), N-ethoxy-2,2-dimethylpropanamide (edpaH), and N-methoxybenzamide (mbaH) were used to afford further substituted complexes Ge(acac)(mpa) (3), Ge(acac)(mdpa) (4), Ge(acac)(empa) (5), Ge(acac)(edpa) (6), Ge(acac)(mba) (7), Ge(tmhd)(mpa) (8), Ge(tmhd)(mdpa) (9), Ge(tmhd)(empa) (10), Ge(tmhd)(edpa) (11), and Ge(tmhd)(mba) (12), respectively. Thermogravimetric analysis curves, which mostly exhibited single-step weight losses, were used to determine the evaporation properties of complexes 1-12. Interestingly, liquid complex 2 has no residue at 198 °C and therefore exhibits excellent vaporization properties and high volatility. Single-crystal X-ray diffraction studies of 1 and 7 demonstrated that the complexes had monomeric molecular structures with germanium chelated by the oxygen atoms of one or two bidentate ligands, respectively. An ALD process was developed for the growth of GeO2 using Ge(tmhd)Cl (2) as a new precursor and H2O2 as an oxidant. This study demonstrates the achievement of self-limiting growth of GeO2 films by varying the duration of injection/purge, with an observed ALD window at deposition temperatures ranging from 300 to 350 °C. The saturated growth per cycle of the GeO2 film was determined as 0.27 Å/cycle at a deposition temperature of 300 °C. The deposited films were observed to be amorphous consisting of GeO2.

Effect of sequential release of sirolimus and rosuvastatin using silk fibroin microneedle to prevent intimal hyperplasia.

Intimal hyperplasia (IH) is a major cause of vascular restenosis after bypass surgery, which progresses as a series of processes from the acute to chronic stage in response to endothelial damage during bypass grafting. A strategic localized drug delivery system that reflects the pathophysiology of IH and minimizes systemic side effects is necessary. In this study, the sequential release of sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, and statin, an HMG-COA inhibitor, was realized as a silk fibroin-based microneedle device in vivo. The released sirolimus in the acute stage reduced neointima (NI) and vascular fibrosis through mTOR inhibition. Furthermore, rosuvastatin, which was continuously released from the acute to chronic stage, reduced vascular stiffness and apoptosis through the inactivation of Yes-associated protein (YAP). The sequential release of sirolimus and rosuvastatin confirmed the synergistic treatment effects on vascular inflammation, VSMC proliferation, and ECM degradation remodeling through the inhibition of transforming growth factor (TGF)-beta/NF-κB pathway. These results demonstrate the therapeutic effect on preventing restenosis with sufficient vascular elasticity and significantly reduced IH in response to endothelial damage. Therefore, this study suggests a promising strategy for treating coronary artery disease through localized drug delivery of customized drug combinations.

Evaluation of tin nitride (Sn3N4) via atomic layer deposition using novel volatile Sn precursors.

Novel Sn precursors, Sn(tbip)2, Sn(tbtp)2, and Sn(tbta)2, were synthesized and characterized using various analytical techniques and density functional theory calculations. These precursors contained cyclic amine ligands derived from iminopyrrolidine. X-ray crystallography revealed the formation of monomeric SnL2 with distorted seesaw geometry. Thermogravimetric analysis demonstrated the exceptional volatility of all complexes. Sn(tbtp)2 showed the lowest residual weight of 2.7% at 265 °C. Sn3N4 thin films were successfully synthesized using Sn(tbtp)2 as the Sn precursor and NH3 plasma. The precursor exhibited ideal characteristics for atomic layer deposition, with a saturated growth per cycle value of 1.9 Å cy-1 and no need for incubation when the film was deposited at 150-225 °C. The indirect optical bandgap of the Sn3N4 film was approximately 1-1.2 eV, as determined through ultraviolet-visible spectroscopy. Therefore, this study suggests that the Sn3N4 thin films prepared using the newly synthesized Sn precursor are suitable for application in thin-film photovoltaic devices.

Synthesis of Mononuclear Strontium Complexes with Polyether and ß-Diketonato Ligands.

Strontium ß-diketonate complexes were synthesized by the substitution reaction of the bis(trimethylsilyl) amide of Sr(btsa)2·2DME with an ethereal group and ß-diketonate ligands. The compounds [Sr(tmge)(btsa)]2 (1), [Sr(tod)(btsa)]2 (2), Sr(tmgeH)(tfac)2 (3), Sr(tmgeH)(acac)2 (4), Sr(tmgeH)(tmhd)2 (5), Sr(todH)(tfac)2 (6), Sr(todH)(acac)2 (7), Sr(todH)(tmhd)2 (8), Sr(todH)(hfac)2 (9), Sr(dmts)(hfac)2 (10), [Sr(mee)(tmhd)2]2 (11), and Sr(dts)(hfac)2·DME (12) were obtained and analyzed by various techniques, including FT-IR, NMR, TGA (thermogravimetric analyses), and elemental analysis. Complexes 1, 3, 8, 9, 10, 11, and 12 were further structurally confirmed by single-crystal X-ray crystallography, where complexes 1 and 11 showed dimeric structures with µ2-O bonds of ethereal groups or tmhd ligands, and complexes 3, 8, 9, 10, and 12 displayed monomeric structures. Interestingly, compounds 10 and 12, which preceded trimethylsilylation of the coordinating ethereal alcohols such as tmhgeH and meeH in the presence of HMDS as by-products due to highly increasing acidity of them, originated from electron-withdrawing two hfac ligands.

Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model.

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B-embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.

Chair stand test as a proxy for physical performance and muscle strength in sarcopenia diagnosis: the Korean frailty and aging cohort study.

BACKGROUND: The 5-times chair stand test (5CST) is a proxy tool for measuring physical performance and muscle strength in diagnosing sarcopenia. The Asian Working Group for Sarcopenia 2019 guidelines recommends the 5CST for evaluating gait speed, whereas the European Working Group on Sarcopenia in Older People guidelines recommend the chair stand test as a proxy for muscle strength. AIMS: This study sought to determine whether the chair stand test correlates with handgrip strength and gait speed, and investigate sex differences in these relationships. METHODS: We used data collected from 1416 participants (678 men and 738 women) in the 2017 Korean Frailty and Aging Cohort Study (KFACS). RESULTS: The 5CST time had a higher correlation with gait speed (r = - 0.470) than handgrip strength (r = - 0.309). In addition, 5CST time predicted low gait speed (area under the curve [AUC] 0.727) better than low handgrip strength (AUC 0.641). The optimal cutoff values of the 5CST to estimate low gait speed were 10 s for men (sensitivity 62%, specificity 64%) and 11 s for women (sensitivity 68%, specificity 67%). The optimal cutoff values of the 5CST for low handgrip strength were the same as those for low gait speed (10 s for men and 11 s for women). CONCLUSIONS: The 5-times chair stand test fits with gait speed and handgrip strength but seems to be a better proxy of gait speed than handgrip strength. The optimal cutoff values of the 5CST to estimate low gait speed and low handgrip strength were lower in men than women. Although none of the AWGS 2019 or EWGSOP guidelines present sex-specific cutoffs for the 5CST, it needs to be considered in the next guidelines.

Time-dependent pathobiological and physiological changes of implanted vein grafts in a canine model.

Although autologous vein grafting is essential, the high vein failure rate and specific clinical interventions are not clear, so a potential treatment is critically needed; thus, complex analyses of the relationship between pathobiological and physiological processes in preclinical are essential. The interposition of the femoral vein was performed in a canine model. Maximized expansion and velocity were measured at 8 weeks post-implantation, and a relative decrease was observed at 12 weeks. However, NI formation and NI/Media ratio significantly increased time dependently, and differences between the mechanical properties were observed. Additionally, RhoA-mediated TNF-α induced by rapid structural changes and high shear stress was confirmed. After adaptation to the arterial environment, vascular remodeling occurred by SMC proliferation and differentiation, apoptosis and autophagy were induced through YAP activity without vasodilation and RhoA activity. Our results show that understanding pathobiological processes in which time-dependent physiological changes contribute to vein failure can lead to a potential strategy. The implanted vein graft within the arterial environment undergoes pathobiological processes through RhoA and YAP activity, leading to pathophysiological changes.

Novel Heteroleptic Tin(II) Complexes Capable of Forming SnO and SnO2 Thin Films Depending on Conditions Using Chemical Solution Deposition.

A new heteroleptic complex series of tin was synthesized by the salt metathesis reaction of SnX2 (X = Cl, Br, and I) with aminoalkoxide and various N-alkoxy-functionalized carboxamide ligands. The complexes, [ClSn(dmamp)]2 (1), [BrSn(dmamp)]2 (2), and [ISn(dmamp)]2 (3), were prepared from the salt metathesis reaction of SnX2 with one equivalent of dmamp; [Sn(dmamp)(empa)]2 (4), [Sn(dmamp)(mdpa)]2 (5), and [Sn(dmamp)(edpa)]2 (6) were prepared via the salt metathesis reaction using complex 2 with one equivalent of N-alkoxy-functionalized carboxamide ligand. Complexes 1-5 displayed dimeric molecular structures with tin metal centers interconnected by µ2-O bonding via the alkoxy oxygen atom. The molecular structures of complexes 1-5 showed distorted trigonal bipyramidal geometries with lone pair electrons in the equatorial position. Using complex 6 as a tin precursor, SnO x films were deposited by chemical solution deposition (CSD) and subsequent post-deposition annealing (PDA) at high temperatures. SnO and SnO2 films were selectively obtained under controlled PDA atmospheres of argon and oxygen, respectively. The SnO films featured a tetragonal romarchite structure with high crystallinity and a preferred growth orientation along the (101) plane. They also exhibited a lower transmittance of >52% at 400 nm due to an optical band gap of 2.9 eV. In contrast, the SnO2 films exhibited a tetragonal cassiterite crystal structure and an extremely high transmittance of >97% at 400 nm was observed with an optical band gap of 3.6 eV.

Selective Formation of Mononuclear Palladium and Acetonitrile-Bridged Dinuclear Palladium Complexes Containing a Chiral Tridentate Ligand.

From the chiral Schiff base tridentate ligand LPh, unusual acetonitrile-bridged dinuclear palladium complex 1 and organopalladium complex 1' were synthesized selectively by using acetonitrile and ethanol, respectively. The chiral tridentate Schiff base ligand was bound to the palladium metal center with different chelation modes ([ONO] for 1 and [CNO] for 1'). Complex 1 constitutes the first example of dinuclear metal complexes connected only by a bridging acetonitrile, in which an exceptionally short C≡N bond distance [0.945(12) Å] of bridged acetonitrile was observed. To study the influence of a phenyl group attached to an imine, the phenyl-free ligand LH was prepared and used. In that case, an acetonitrile bridge was not observed. Theoretical calculation studies supporting the formation of 1 and 1' are favored.

New Volatile Tantalum Imido Precursors with Carboxamide Ligands.

A series of Ta(V) t Bu-imido/N-alkoxy carboxamide complexes, TaCl2(N t Bu)(pyridine)(edpa) (1), TaCl(N t Bu)(edpa)2 (2), Ta(N t Bu)(edpa)3 (3), TaCl2(N t Bu)(pyridine)(mdpa) (4), and Ta(N t Bu)(mdpa)3 (5), were successfully synthesized by metathesis reactions between Ta(N t Bu)Cl3(py)2 and several equivalents of Na(edpa) (edpaH = N-ethoxy-2,2-dimethylpropanamide) and Na(mdpa) (mdpaH = N-methoxy-2,2-dimethylpropanamide). Furthermore, complexes 3 and 5 were simply transformed to new dimeric structures [Ta(µ2-O)(edpa)3]2 (6) and [Ta(µ2-O)(mdpa)3]2 (7) with the elimination of the N t Bu imido group by air exposure. Compounds 1-7 were characterized by 1H and 13C nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, elemental analysis, thermogravimetric analysis (TGA), and single-crystal X-ray diffraction. Single-crystal X-ray diffraction analysis revealed that complexes 3 and 5 have a distorted pentagonal bipyramidal geometry around the central Ta atom, with three monoanionic bidentate N-alkoxy carboxamide ligands and one t Bu imido ligand saturating the coordination of tantalum ions. TGA revealed that complexes 3 and 5 had superior thermal characteristics and stability. These complexes could potentially be applied as precursors for tantalum oxide thin films.

Synthesis and Crystal Structures of New Strontium Complexes with Aminoalkoxy and ß-Diketonato Ligands.

New heteroleptic strontium complexes were synthesized using substitution reaction of bis(trimethylsilyl)amide of Sr(btsa)2·2DME with aminoalkoxide and ß-diketonate ligands. The complexes [Sr(bdmp)(btsa)]2·2THF (1), [Sr(bdeamp)(btsa)]2 (2), [Sr(dadamb)(btsa)]2 (3), [Sr(bdmp)(hfac)]3 (4), [Sr(bdeamp)(hfac)]3 (5), [Sr(dadamb)(hfac)]3 (6), and [Sr3(dadamb)4(tmhd)2] (7) were prepared and characterized by means of various analysis techniques such as Fourier transform infrared, NMR, thermogravimetric analysis, and elemental analysis. Complexes 1-3 were further structurally confirmed by single-crystal X-ray crystallography, and they displayed dimeric structures in which strontium atoms were connected by alkoxide oxygen atoms of the µ2 type. Compound 1 has a trigonal prismatic structure, whereas 2 and 3 have a distorted square pyramidal structure. In complexes 5-7, trimeric structures were obtained with strontium atoms connected by µ3-O bonds of alkoxide oxygen atoms and µ2-O bonds of alkoxide and ß-diketonate oxygen atoms. The crystal structures of 5, 6, and 7 showed distorted capped octahedral geometry, while 7 (middle Sr atom) displayed a distorted trigonal prism geometry. Complexes 5-7 displayed ∼70% mass loss in the temperature range from 25 to 315 °C.

Catechol enhances chemo­ and radio­sensitivity by targeting AMPK/Hippo signaling in pancreatic cancer cells.

Overcoming chemo­ and radio­resistance is a major challenge in pancreatic cancer treatment. Therefore, there is an urgent need to discover novel therapeutic approaches to avoid chemo­ and radio­resistance in pancreatic cancer. Catechol is a phytochemical found in some fruits and vegetables. A few studies have reported on the potential anticancer effects of pure catechol. The present study aimed to explore the chemo­ and radio­sensitizing effects of catechol in Panc­1 human pancreatic cancer cells. The effects of catechol on Panc­1 cell proliferation, clonogenic survival, invasion, and migration were assessed using MTT, cell migration, and Transwell invasion assays. The chemo­ and radio­sensitizing effects of catechol on Panc­1 cells were evaluated via MTT assay and flow cytometry. Western blotting was conducted to analyze the expression of proteins involved in several mechanisms induced by catechol in Panc­1 cells, including growth inhibition, apoptosis, suppression of epithelial­mesenchymal transition (EMT), and chemo­ and radio­sensitizing activities. The results indicated that catechol inhibited proliferation, promoted apoptosis, and suppressed cell migration, invasion, and EMT in Panc­1 cells in a dose­dependent manner. Catechol treatment also induced the phosphorylation of AMP­activated protein kinase (AMPK) with a concomitant reduction in the expression of Hippo signaling pathway components, including Yes­associated protein, cysteine­rich angiogenic inducer 61, and connective tissue growth factor. In addition, catechol enhanced the chemosensitivity of Panc­1 cells to gemcitabine, a commonly used chemotherapy in pancreatic cancer treatment. A combination of catechol and radiation enhanced apoptosis and increased the expression of two radiation­induced DNA damage markers, p­ATM and p­Chk2. Collectively, the present results demonstrated that catechol, a naturally occurring compound, could suppress the proliferation of pancreatic cancer cells, reduce the expression of EMT­related proteins, and enhance the chemo­ and radio­sensitivity of Panc­1 cells by targeting AMPK/Hippo signaling.

Identification of Single-Atom Ni Site Active toward Electrochemical CO2 Conversion to CO.

Electrocatalytic conversion of CO2 into value-added products offers a new paradigm for a sustainable carbon economy. For active CO2 electrolysis, the single-atom Ni catalyst has been proposed as promising from experiments, but an idealized Ni-N4 site shows an unfavorable energetics from theory, leading to many debates on the chemical nature responsible for high activity. To resolve this conundrum, here we investigated CO2 electrolysis of Ni sites with well-defined coordination, tetraphenylporphyrin (N4-TPP) and 21-oxatetraphenylporphyrin (N3O-TPP). Advanced spectroscopic and computational studies revealed that the broken ligand-field symmetry is the key for active CO2 electrolysis, which subordinates an increase in the Ni redox potential yielding NiI. Along with their importance in activity, ligand-field symmetry and strength are directly related to the stability of the Ni center. This suggests the next quest for an activity-stability map in the domain of ligand-field strength, toward a rational ligand-field engineering of single-atom Ni catalysts for efficient CO2 electrolysis.

Current status and future perspective of external herbal dispensaries preparing traditional herbal medicine in South Korea: the first National-Wide Survey results.

BACKGROUND: An external herbal dispensary (EHD) is a type of pharmacy that provides various types of personalized herbal medicines (PHMs) to other traditional Korean medicine (TKM) institutions. Such dispensaries were legalized by the Ministry of Health and Welfare (MoHW) in 2008 in South Korea. The purpose of this study is to understand the current status of the EHD facilities and their quality controls and compare them with the good manufacture practice (GMP) guidelines to contribute to the establishment of the safety and quality control criteria for PHMs. METHODS: We contacted 107 EHD representatives or people in charge of the preparation of PHMs (TKM pharmacists) and invited them to complete a survey questionnaire; of the total, 81 responded. The survey questionnaire was developed in 3 stages: drafting, revision by external experts, and final editing. It consisted of 20 questions covering 3 sections: basic characteristics of EHDs, facility, and quality control. The survey was hosted online from December 2017 to January 2018 as guided by the MoHW. RESULTS: The completion rate was 75.7% (n = 81). In terms of facilities, the five facilities (water supply, manufacture, pest control, hygiene management and warehousing) that corresponded to the legal requirements of EHD were mostly equipped, but the types of facilities and equipment differed. Two facilities (sterilization and cross-contamination that were not legally required for EHD were found to have mostly pharmacopuncture-EHD (P-EHD), but hardly any herbal medicine-EHD (H-EHD). In our findings regarding quality control of non-medicinal herbs, sensory evaluation that included checks for foreign bodies and deterioration were conducted. In terms of the quality control of herbal medicines, residual pesticides and heavy metals tests were performed and for pharmacopuncture, pH, salinity, sterility, and endotoxin tests along with gross examination were performed. In the end, we found that 6 of the 38 standard items as required by the Korea GMP were suitable. CONCLUSIONS: In this study, detailed information for each existing EHD law was determined through a nationwide questionnaire. Moreover, the basis for its reflection in additional legal standards should be introduced so that safe herbal medicine can be prepared in EHDs.

Catalytic enantioselective synthesis of tetrasubstituted chromanones via palladium-catalyzed asymmetric conjugate arylation using chiral pyridine-dihydroisoquinoline ligands.

Highly enantioselective conjugate addition reactions of arylboronic acids to 2-substituted chromones catalyzed by palladium complexes with new chiral Pyridine-Dihydroisoquinoline (PyDHIQ) ligands have been developed. These reactions provide highly enantioselective access to chromanones containing tetrasubstituted stereocenters. Various arylboronic acids and 2-substituted chromones can be used in the catalytic reaction to afford the chiral tetrasubstituted chromanones in good yields and excellent enantioselectivities (25 examples, up to 98% yields, up to 99% ee).

Effect of Roasting and Brewing on the Antioxidant and Antiproliferative Activities of Tartary Buckwheat.

We evaluated the effect of the roasting and brewing conditions of Tartary buckwheat (TB), which is widely used in infusion teas, on its antioxidant and antiproliferative activities in vitro. TB was roasted at 210 °C for 10 min and brewed at a high temperature for a short time (HTST; 85-90 °C, 3 min) or at room temperature for a long time (RTLT; 25-30 °C, 24 h). Roasted TB (RTB) tea brewed at RTLT had the highest total polyphenol content (TPC) and total flavonoid content (TFC) among the four TB teas for different roasting and brewing conditions. Moreover, RTB brewed at RTLT showed the greatest 2,2-diphenyl-1-picrylhydrazyl-, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)-, and alkyl-scavenging activities. The TB tea brewed at RTLT had higher Fe2+-chelating activity than that brewed at HTST, irrespective of roasting. Moreover, RTB tea brewed at RTLT inhibited the proliferation of human pancreatic and breast cancer cells. Overall, RTB-RTLT displayed the largest effect on antioxidant and antiproliferative effects. Finally, rutin was found to possess the most pronounced effect on the antioxidant and antiproliferative activities of the TB teas. These results indicate that the antioxidant and antiproliferative activities of RTB are enhanced by RTLT brewing.

Dysregulated Autophagy Mediates Sarcopenic Obesity and Its Complications via AMPK and PGC1α Signaling Pathways: Potential Involvement of Gut Dysbiosis as a Pathological Link.

Sarcopenic obesity (SOB), which is closely related to being elderly as a feature of aging, is recently gaining attention because it is associated with many other age-related diseases that present as altered intercellular communication, dysregulated nutrient sensing, and mitochondrial dysfunction. Along with insulin resistance and inflammation as the core pathogenesis of SOB, autophagy has recently gained attention as a significant mechanism of muscle aging in SOB. Known as important cellular metabolic regulators, the AMP-activated protein kinase (AMPK) and the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) signaling pathways play an important role in autophagy, inflammation, and insulin resistance, as well as mutual communication between skeletal muscle, adipose tissue, and the liver. Furthermore, AMPK and PGC-1α signaling pathways are implicated in the gut microbiome-muscle axis. In this review, we describe the pathological link between SOB and its associated complications such as metabolic, cardiovascular, and liver disease, falls and fractures, osteoarthritis, pulmonary disease, and mental health via dysregulated autophagy controlled by AMPK and/or PGC-1α signaling pathways. Here, we propose potential treatments for SOB by modulating autophagy activity and gut dysbiosis based on plausible pathological links.

Crystal structure of 1,4-bis-[5-(2-meth-oxy-phen-yl)-2H-tetra-zol-2-yl]butane.

The title compound, C20H22N8O2, was synthesized by the coupling reaction of a sodium tetra-zolate salt and di-bromo-butane in a molar ratio of 2:1. The reaction can produce several possible regioisomers and the title compound was separated as the major product. The X-ray crystallographic study confirmed that the title compound crystallizes in the monoclinic P21/c space group and possesses a bridging butyl-ene group that connects two identical phenyl tetra-zole moieties. The butyl-ene group is attached not to the first but the second nitro-gen atoms of both tetra-zole rings. The dihedral angles between the phenyl groups and the adjacent tetra-zolyl rings are 5.32 (6) and 15.37 (7)°. In the crystal, the mol-ecules form centrosymmetric dimers through C-H⋯O hydrogen bonds between a C-H group of the butyl-ene linker and the O atom of a meth-oxy group.