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Parkinson's disease (PD) is characterized by the formation of α-synuclein (α-syn) aggregates, which lead to dopaminergic neuronal degeneration. The incidence of PD increases with age, and senescence is considered to be a major risk factor for PD. In this study, we evaluated the effect of senescence on PD pathology using α-synuclein preformed fibrils (PFF) injection model in senescence-accelerated mice. We injected PFF into the substantia nigra (SN) of senescence-accelerated prone 8 (SAMP8) mice and senescence-accelerated resistant 1 (SAMR1) mice. At 24 weeks after injection of saline or PFF, we found that SAMP8 mice injected with PFF exhibited robust Lewy pathology and exacerbated degeneration of dopaminergic neurons in the SN compared to PFF-injected SAMR1 mice. We further observed an increase in the number of Iba1-positive cells in the brains of PFF-injected SAMP8 mice. RNA sequencing revealed that several genes related to neuroinflammation were upregulated in the brains of PFF-injected SAMP8 mice compared to SAMR1 mice. Inflammatory chemokine CC-chemokine ligand 21 (CCL21) was upregulated in PFF-injected SAMP8 mice and expressed in the glial cells of these mice. Our research indicates that accelerated senescence leads to persistent neuroinflammation, which plays an important role in the exacerbation of α-synucleinopathy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The symmetry of one of the simplest hexamonodentate complexes, [M(H 2 O) 6 ] 2+ (M = Fe, Co, Ni, and Zn), was controlled by tuning interactions in the second coordination sphere. Highly symmetric Ti-Mo or Zr-Mo cluster cations acted as symmetry templates, imposing a crystallographic trigonal coordination geometry in the hexamonodentate complexes through intermolecular hydrogen-bonding interactions. Magnetic measurements revealed that the ideal trigonal symmetry results in weak spin-orbit coupling for high-spin Fe II complexes, despite the T-term ground state in the octahedral geometry. In contrast, high-spin Co II analogues with the T-term ground state exhibited strong spin-orbit coupling. DFT studies supported that a d 6 Fe II ion in the D 3 symmetry has a 5 A 1 ground state while a d 7 Co II in the same symmetry has a 4 E ground state. Single-ion magnet behavior was observed in the Co II complexes. These results demonstrate that incorporating a diamagnetic, highly symmetric cluster enables precise symmetry control in single-ion magnets containing only monodentate ligands.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an unknown pathogenesis. It has been reported that mutations in the gene for Cu/Zn superoxide dismutase (SOD1) cause familial ALS. Mutant SOD1 undergoes aggregation and forms amyloid more easily, and SOD1-immunopositive inclusions have been observed in the spinal cords of ALS patients. Because of this, SOD1 aggregation is thought to be related to the pathogenesis of ALS. Some core regions of amyloid have been identified, but the issue of whether these regions form aggregates in living cells remains unclear, and the mechanism responsible for intracellular SOD1 aggregation also remains unclear. The findings reported in this study indicate that the aggregation of the ALS-linked mutant SOD1-EGFP was significantly enhanced when the BioID2 gene was fused to the N-terminus of the mutant SOD1-EGFP plasmid for cellular expression. Expression of a series of BioID2-(C-terminal deletion peptides of SOD1)-EGFP permitted us to identify 1-35 as a minimal N-terminal sequence and Ile35 as an essential amino acid residue that contributes to the intracellular aggregation of SOD1. The findings also showed that an additional substitution of Ile35 with Ser into the ALS mutant SOD1 resulted in the significant suppression of aggregate formation. The fact that no Ile35 mutations have been reported to date in ALS patients indicates that all ALS mutant SOD1s contain Ile35. Taken together, we propose that Ile35 plays a pivotal role in the aggregation of the ALS-linked SOD1 and that this study will contribute to our understanding of the mechanism responsible for SOD1 aggregation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triokinase/FMN cyclase (Tkfc) is involved in fructose metabolism and is responsible for the phosphorylation of glyceraldehyde to glyceraldehyde-3-phosphate. In this study, we showed that refeeding induced hepatic expression of Tkfc in mice. Luciferase reporter gene assays using the Tkfc promoter revealed the existence of 2 hepatocyte nuclear factor 4α (HNF4α)-responsive elements (HNF4RE1 and HNF4RE2) and 1 carbohydrate-responsive element-binding protein (ChREBP)-responsive element (ChoRE1). Deletion and mutation of HNF4RE1 and HNF4RE2 or ChoRE1 abolished HNF4α and ChREBP responsiveness, respectively. HNF4α and ChREBP synergistically stimulated Tkfc promoter activity. ChoRE1 mutation attenuated but maintained HNF4α responsiveness, whereas HNF4RE1 and HNF4RE2 mutations abolished ChREBP responsiveness. Moreover, Tkfc promoter activity stimulation by ChREBP was attenuated upon HNF4α knockdown. Furthermore, Tkfc expression was decreased in the livers of ChREBP-/- and liver-specific HNF4-/- (Hnf4αΔHep) mice. Altogether, our data indicate that Tkfc is a target gene of ChREBP and HNF4α, and Tkfc promoter activity stimulation by ChREBP requires HNF4α., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Metacrimenes fenestra, a new palaemonid genus and species is described on the basis of an ovigerous female and one juvenile specimen from Suruga Bay, central Japan. The specimens were associated with the stalked crinoid Metacrinus rotundus Carpenter, 1885, collected at a depth of 131200 m. Photographs taken in situ indicate that the shrimp lives ectosymbiotically on its crinoid host. The greatly reduced bud-like exopod on the third maxilliped links the new genus to Mesopontonia Bruce, 1967 (Indo-West Pacific) and Waldola Holthuis, 1951 (East Pacific), in which the exopod is absent, but the presence of antennal spine on the carapace and the non-elongate, symmetrical second pereopods immediately distinguish Metacrimenes n. gen. from these genera. Molecular phylogenetic analysis using a dataset concatenating two mitochondrial markers (16S rRNA and COI genes) clusters the new genus with Paraclimenes gorgonicola (Bruce, 1967), two species of Mesopontonia and Brucecaris tenuis (Bruce, 1969). However, in Paraclimenes Bruce, 1995 and Brucecaris Marin & Chan, 2006, the third maxilliped exopod is normally developed, flagellum-like. Other differentiating characters between the new taxon and the presumably allied taxa are discussed.

Breast cancer has become one of the top five commonest causes of cancer death. The use of ferroptosis to induce the generation of reactive oxygen species (ROS) in cancer cells presents a promising and potential strategy for cancer treatment. Herein, a series of facile bimetallic nanoparticles ( x % Fe-doped ZIF-8) were synthesized and tested, and doxorubicin (DOX), a classic drug for breast cancer therapy, was encapsulated. After comparing the ratios of Fe 2+ /(Fe 2+ + Zn 2+ ), 7% Fe-doped ZIF-8 (7FZ) was found to be the most suitable particle for medical application. The drug loading efficiency of DOX@7FZ was 58.01 ± 0.02%. The pH-sensitive DOX@7FZ was degraded and DOX was released in lysosomes once internalized. Both the intracellular content of iron and ROS increased significantly. Meanwhile, the cell viability declined to 13.98% in 24 h at a concentration of 60 μg mL -1 and the IC 50 was 42.68 μg mL -1 . Moreover, the expression of Bcl-2 and GPX-4 proteins decreased in a time-dependent manner, indicating that DOX@7FZ was able to enhance the ROS level in cancer cells via a synergistic effect between apoptosis and ferroptosis. The mechanism of action of DOX@7FZ was further verified using hematoxylin and eosin staining and immunohistochemical staining of Bcl-2 and GPX-4. These remarkable characteristics of DOX@7FZ may inspire further advancements in the treatment of breast cancer.

The efficient removal of organic contaminants from wastewater is, nowadays, a prominent area of study due to its biological as well as environmental significance. Antibiotics are now found in wastewater because of their high use, which has become a source of aquatic pollution. These antibiotics have dangerous implications for people's health. Hence, effective pharmaceutical removal from wastewater and contaminated water bodies, especially the removal of antibiotics, is of major interest to global research organizations. This is why it is necessary to investigate this class of toxic material in wastewater discharge. We synthesized three different coordination polymers (CPs) in the presence of various assistant carboxylate linkers, namely, [Zn(Hbtc)(dip)] n ( 1 ), [Zn 4 (1,2-bdc) 4 (dip) 4 ] n ( 2 ), and [Zn(1,4-bdc)(dip)] n ( 3 ) (3,5-di(1H-imidazol-1-yl)pyridine = dip, 1,3,5-benzenetricarboxylic acid = H 3 btc, 1,2-benzenedicarboxylic acid = 1,2-H 2 bdc, and 1,4-benzendicarboxylic acid = 1,4-bdc). These CPs were characterized by using different techniques, including single-crystal X-ray diffraction. The structural studies demonstrated that in 2 , there are four Zn(II) centers and both centers are in different coordination environments (Zn2 has distorted tetrahedral geometry, whereas Zn1, Zn3, and Zn4 have square pyramidal geometry). Hirshfeld surfaces analysis revealed that different types of intermolecular interactions (C⋯C, H⋯C, H⋯H, O⋯C, N⋯H, and O⋯H) are present in the synthesized CPs. We examined the different antibiotics, such as metronidazole (MDZ), nitrofurazone (NFZ), dimetridazole (DTZ), sulfasalazine(SLA), and oxytetracycline (OXY), degradation behaviors of the synthesized CPs, which showed remarkable degradation efficiency. 1 showed photocatalytic behavior toward the NFZ antibiotic in an aqueous media. This study also showed that these catalysts are stable and reusable under mild conditions.

Obesity appears to be a major contributing factor for many health problems. Effective treatments for reducing weight gain, other than caloric restriction and exercise, are limited. The consumption of sugars is a major factor in the development of obesity in part by stimulating the transcription factor, carbohydrate response element binding protein (ChREBP), a process that is driven by de novo lipogenesis. Therefore, we hypothesized that inhibiting the action of ChREBP would be a promising strategy for alleviating these diseases. Using ChREBP deficient mice, the effect of a high intake of sucrose on body weight and blood glucose levels were investigated. Unlike wild type mice, ChREBP deficient mice did not gain much weight and their blood glucose and cholesterol levels remained relatively constant. In tracing it's cause, we found that the levels of expression of sucrase, an enzyme that digests sucrose, and both Glut2 and Glut5, a transporter of glucose and fructose, were not induced by feeding a high sucrose diet in the small intestine of ChREBP deficient mice. Our findings suggest that the inhibition of ChREBP could suppress weight gain even on a high sucrose diet., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Chemodynamic therapy when combined with chemotherapy opens up a new avenue for treatment of cancer. However, its development is still restricted by low targeting, high dose and toxic side effects. Herein, rational designing and construction of a new multifunctional platform with the core-shell structure 5-ALA@UiO-66-NH-FAM@CP1 (ALA = 5-aminolevulinic acid, CP1 = zirconium-pemetrexed (Zr-MTA)) has been performed. In this platform, CP1 acting as a shell is encapsulated with the UiO-66-NH 2 to engender a core-shell structure that promotes and achieves a high MTA loading rate through high affinity between MTA and unsaturated Zr site of UiO-66-NH 2 . The 5-ALA and 5-carboxyl fluorescein (5-FAM) was successfully loaded and covalently combined with UiO-66-NH 2 due to its high porosity and presence of amino groups. The characterization results indicated that the loading rate of MTA (41.03 wt%) of platform is higher than the reported values. More importantly, the in vitro and in vivo results also demonstrated that it has a good folate targeting ability and realizes high efficient antitumor activity by chemotherapy combied with photodynamic therapy (PDT). This newly developed multifunctional platform could provide a new idea for designing and constructing the carrier with chemotherapy and PDT therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Iron, an essential element for most of living organisms, participates in many biological functions. Since iron is redox-active transition metal, it is known that excessive levels stimulate the formation of reactive oxygen species (ROS) and exacerbate cytotoxicity. An iron deficiency is the most common nutritional deficiency disorder in the world (about 30% of the population) and is more common than cases of iron overload. However, the effects of iron deficiency on ROS-induced cytotoxicity and the maintenance of intracellular redox homeostasis are not fully understood. The present study reports on an evaluation of the effects of iron deficiency on cytotoxicity induced by several ROS generators. In contrast to hydrogen peroxide and erastin, the cytotoxicity of 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a redox cycling agent that induces intracellular superoxide anion formation, was exacerbated by iron deficiency. Cytochrome b 5 reductase was identified as a candidate enzyme responsible for the redox cycling of DMNQ under conditions of iron depletion. Moreover, the DMNQ-induced intracellular accumulation of ROS and a decrease in NADH/NAD + ratios were enhanced by an iron deficiency. These negative changes were found to be ameliorated by overexpressing NAD(P)H:quinone oxidoreductase 1 (NQO1) in kidney-derived cells that originally showed a very low expression of NQO1. These results indicate that NQO1 plays a protective role against redox cycling quinone-mediated cytotoxicity under iron-depleted conditions. This is because NQO1 generates less-toxic hydroquinones via the two-electron reduction of quinones. The collective findings reported herein demonstrate that not only an iron overload but also an iron deficiency exacerbates ROS-mediated cytotoxicity.

A mixed-valent trinuclear complex with 1,3-bis(5-chlorosalicylideneamino)-2-propanol (H 3 clsalpr) was synthesized, and the crystal structure was determined by the single-crystal X-ray diffraction method at 90 K. The molecule is a trinuclear Co III -Co II -Co III complex with octahedral geometries, having a tetradentate chelate of the Schiff-base ligand, bridging acetate, monodentate acetate coordination to each terminal Co 3+ ion and four bridging phenoxido-oxygen of two Schiff-base ligands, and two bridging acetate-oxygen atoms for the central Co 2+ ion. The electronic spectral feature is consistent with the mixed valent Co III -Co II -Co III . Variable-temperature magnetic susceptibility data could be analyzed by consideration of the axial distortion of the central Co 2+ ion with the parameters Δ = -254 cm -1 , λ = -58 cm -1 , κ = 0.93, tip = 0.00436 cm 3 mol -1 , θ = -0.469 K, g z = 6.90, and g x = 2.64, in accordance with a large anisotropy. The cyclic voltammogram showed an irreversible reduction wave at approximately -1.2 V·vs. Fc/Fc + , assignable to the reduction of the terminal Co 3+ ions.

Only a limited number of multinucleating ligands can stably maintain multinuclear metal structures in aqueous solutions. In this study, a water-soluble dinucleating ligand, 2,6-bis{[ N -(carboxylatomethyl)- N -methyl-amino]methyl}-4-methylphenolate (( sym -cmp) 3- ), was prepared and its copper(II) complexes were structurally characterized. Using the single-crystal X-ray diffraction method, their dimer-of-dimers type defect cubane tetranuclear copper(II) structures were characterized for [Cu 4 ( sym -cmp) 2 Cl 2 (H 2 O) 2 ] and [Cu 4 ( sym -cmp) 2 (CH 3 O) 2 (CH 3 OH) 2 ]. In the complexes, each copper(II) ion has a five-coordinate square-pyramidal coordination geometry. The coordination bond character was confirmed by the density functional theory (DFT) calculation on the basis of the crystal structure, whereby we found the bonding and anti-bonding molecular orbitals. From the cryomagnetic measurement and the magnetic analysis, overall antiferromagnetic interaction was observed, and this magnetic behavior is also explained by the DFT result. Judging from the molar conductance and the electronic spectra, the bridging chlorido ligand dissociates in water, but the dinuclear copper(II) structure was found to be maintained in an aqueous solution. In conclusion, the tetranuclear copper(II) structures were crystallographically characterized, and the dinuclear copper(II) structures were found to be stabilized even in an aqueous solution.

Many effluents contain various antibiotics commonly, where the simultaneous removal of them is a big challenge. In this study, the magnetic biocomposite (eggshell-zeolitic imidazolate framework) was designed and synthesized by green and facile method. Zeolitic imidazolate framework-8 (ZIF-8) particles were stabilized on the surface of magnetic eggshell (Fe 3 O 4 -ES), generating a new Fe 3 O 4 -ES/ZIF-8 adsorbent, which was also fully characterized using FTIR, XRD, SEM and BET techniques. Thereafter, norfloxacin (NOR) adsorption processes were investigated through different influencing factors (dosage, concentration, pH and temperature). The Langmuir adsorption isotherm could confirm a maximum removal efficiency of 80.13% for NOR. Kinetic studies illustrated that the pseudo-first-order model was in line with the experimental data of the simultaneous removal of NOR. Moreover, the magnetic nature of the adsorbent caused an easy separation from the aqueous solution.

The blood-brain barrier (BBB) controls the entry of chemicals from the blood to the brain. Since brain drugs need to penetrate the BBB, rapid and reliable prediction of BBB penetration (BBBP) is helpful for drug development. In this study, free-form and in-blood-form datasets were prepared by modifying the original BBBP dataset, and the effects of the data modification were investigated. For each dataset, molecular descriptors were generated and used for BBBP prediction by machine learning (ML). For ML, the dataset was split into training, validation, and test data by the scaffold split algorithm MoleculeNet used. This creates an unbalanced split and makes the prediction difficult; however, we decided to use that algorithm to evaluate the predictive performance for unknown compounds dissimilar to existing ones. The highest prediction score was obtained by the random forest model using 212 descriptors from the free-form dataset, and this score was higher than the existing best score using the same split algorithm without using any external database. Furthermore, using a deep neural network, a comparable result was obtained with only 11 descriptors from the free-form dataset, and the resulting descriptors suggested the importance of recognizing the glucose-like characteristics in BBBP prediction.

The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that increases the transcription of multiple genes. ChREBP is highly localized in the liver, where it upregulates the expression of genes that code for glycolytic and lipogenic enzymes, resulting in the conversion of excess carbohydrate into storage fat. ChREBP knockout (KO) mice display an anti-obese phenotype. However, at this time, role of ChREBP in adipose tissue remains unclear. Therefore, the energy metabolism and morphology of mitochondrial brown adipose tissue (BAT) in ChREBP KO mice was examined. We found increased expression levels of electron transport system proteins including the mitochondrial uncoupling protein (UCP1), and mitochondrial structural alterations such as dysplasia of the cristae and the presence of small mitochondria in BAT of ChREBP KO mice. Mass spectrometry analyses revealed that fatty acid synthase was absent in the BAT of ChREBP KO mice, which probably led to a reduction in fatty acids and cardiolipin, a regulator of various mitochondrial events. Our study clarified the new role of ChREBP in adipose tissue and its involvement in mitochondrial function. A clearer understanding of ChREBP in mitochondria could pave the way for improvements in obesity management., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The carbohydrate response element-binding protein (ChREBP), a glucose-responsive transcription factor that plays a critical role in the glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis, exists as two isoforms: ChREBPα and ChREBPβ. However, the mechanism responsible for regulating the expression of both ChREBPα and β, as well as the mechanism that determines which specific isoform is more responsive to different stimuli, remains unclear. To address this issue, we compared the effects of several stimuli, including oxidative stress, on the mRNA and protein expression levels of ChREBPα and β in the hepatocyte cell line, HepG2. We found that H 2 O 2 stimulation suppressed the expression of both mRNA and protein in HepG2 cells, but the mRNA expression level of ChREBPβ was < 1% of that for ChREBPα levels. In addition, the reduction in both ChREBPα and β mRNA levels was reversed by PD98059, a selective and cell permeable inhibitor of the MEK/ERK pathway. Additionally, the administration of 12-O-tetradecanoylphorbol 13-acetate (TPA) and staurosporine (STS), activators of extracellular-signal-regulated kinase (ERK) signaling, also resulted in a decrease in the levels of both ChREBPα and β mRNA in HepG2 cells through ERK signaling. These collective data suggest that oxidative stress, including STS treatment, suppresses the expression of ChREBPα and β via the activation of ERK signaling in HepG2 cells. Such a decrease in the levels of expression of ChREBPα and β could result in the suppression of hepatic glycolysis and lipogenesis, and this would be expected to prevent further oxidative stress., (© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected daily life. COVID-19 often causes asymptomatic or mild disease in children; however, delayed routine childhood immunization is a concern, as it could increase the risk of vaccine-preventable disease. No study has evaluated the status of childhood vaccinations in Japan during the COVID-19 pandemic., Methods: This retrospective observational study evaluated the number of vaccine doses administered to children in 4 Japanese cities (2 cities in the Tokyo metropolitan area and 2 cities far from Tokyo) during the period from 2016 to 2020. Vaccine doses administered between January and September 2020 during the COVID-19 pandemic were compared, by month, with those given during 2016-2019. Age-stratified demographic data were collected to determine whether factors other than change in the child population over time affected vaccination trends., Results: In all cities the decrease in vaccine doses administered was most apparent in March and April 2020, i.e., just before or coincident with the declaration of a nationwide COVID-19 emergency on April 7, 2020. The decrease started as early as February in the Tokyo metropolitan area. As child age increased, the decrease became more apparent. Before the lift of national emergency on May 25, catch-up of the vaccination was observed in all age groups in all cities. Vaccine doses persistently increased in older age groups but not in infants. The overall vaccination trends did not differ significantly among the 4 cities., Conclusions: The COVID-19 pandemic significantly affected routine childhood immunization in Japan. Thus, a nationwide electronic surveillance system and announcements for guardians to encourage timely routine immunization are warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Team-based learning (TBL) is an active learning method used in many educational institutions. However, there are few examples of its use in basic medicine, such as biochemistry in medical schools. This study used TBL to teach glucose metabolism to first-year medical students. The process was in four phases: preclass preparation, readiness assurance tests, advanced questions, and a TBL test, with peer evaluation and a questionnaire. There were positive correlations between the TBL test, peer evaluation, and individual readiness test performance. Tests were taken immediately after learning and 2 weeks later, and scores decreased significantly less with TBL than traditional lectures (-2.3% vs. -17.5%). This suggests that TBL was more effective than traditional lectures in supporting knowledge retention. We used a Moodle system to facilitate communication between students and teachers, and this was evaluated positively by both groups. It was particularly useful for managing TBL. These findings suggest that TBL could be used to improve student performance in biochemistry., (© 2020 International Union of Biochemistry and Molecular Biology.)

Oxido bridges commonly form between iron(III) ions, but their bond angles and symmetry vary with the circumstances. A large number of oxido-bridged dinuclear iron(III) complexes have been structurally characterized. Some of them belong to the C 2 point group, possessing bent Fe-O-Fe bonds, while some others belong to the C i symmetry, possessing the linear Fe-O-Fe bonds. The question in this study is what determines the structures and symmetry of oxido-bridged dinuclear iron(III) complexes. In order to gain further insights, three oxido-bridged dinuclear iron(III) complexes were newly prepared with 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) ligands: [Fe 2 OCl 2 (bpy) 4 ][PF 6 ] 2 ( 1 ), [Fe 2 O(NO 3 ) 2 (bpy) 4 ][PF 6 ] 2 ·0.6MeCN·0.2(2-PrOH) ( 2 ), and [Fe 2 OCl 2 (phen) 4 ][PF 6 ] 2 ·MeCN·0.5H 2 O ( 3 ). The crystal structures of 1 , 2 , and 3 were determined by the single-crystal X-ray diffraction method, and all of them were found to have the bent Fe-O-Fe bonds. Judging from the crystal structure, some intramolecular interligand hydrogen bonds were found to play an important role in fixing the structures. Additional density functional theory (DFT) calculations were conducted, also for a related oxido-bridged dinuclear iron(III) complex with a linear Fe-O-Fe bond. We conclude that the Fe-O-Fe bridge tends to bend like a water molecule, but is often stretched by interligand steric repulsion, and that the structures are mainly controlled by the intramolecular interligand interactions.

Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (p38 MAPK) in the peripheral nervous system. To investigate whether GJG can suppress inflammation in the central nervous system (CNS) in the context of neurological disorders, we examined the effect of GJG on the activation of resident glial cells and on p38-TNF signaling in two mouse models of neurological disorders: the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. GJG administration relieved the severity of clinical EAE symptoms and MPTP-induced inflammation by decreasing the number of microglia and the production of TNF-α in the spinal cord of EAE mice and the substantia nigra of MPTP-treated mice. Accordingly, GJG suppressed the phosphorylation of p38 in glial cells of these two mouse models. We conclude that GJG attenuates inflammation of the CNS by suppressing glial cell activation, followed by a decrease in the production of TNF-α via p38-TNF signaling.

The correlation between magnetic relaxation dynamics and the alignment of single-ion magnets (SIMs) in a crystal was investigated using four analogous cobalt(ii) complexes with unique hydrogen-bond networks. The hydrogen-bonding interactions in the crystals resulted in a relatively short intermolecular Co⋯Co distance, which led to non-zero intermolecular magnetic coupling. All the complexes with a Co⋯Co distance shorter than 6.5 Å exhibited zero-field slow magnetic relaxation as weak magnetic interactions split the ground ±M s levels and suppressed quantum tunneling of magnetization (QTM). In particular, antiferromagnetically coupled one-dimensional chain SIM networks effectively suppressed QTM when the two intrachain Co⋯Co distances were non-equivalent. However, when the two distances in a chain were equivalent and each molecular symmetry axis aligned parallell within the chain, QTM suppression was insufficient because magnetic coupling from the adjacent molecules was virtually cancelled. Partial substitution of the Co II ion with the diamagnetic Zn II ion up to 33% for this complex resulted in complete QTM suppression in the absence of an external field. These results show that the manipulation of intermolecular distances and alignments is effective for suppressing undesired QTM events in SIMs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The carbohydrate response element binding protein (ChREBP) is a glucose-responsive transcription factor that plays a critical role in glucose-mediated induction of genes involved in hepatic glycolysis and lipogenesis. In response to fluctuating blood glucose levels ChREBP activity is regulated mainly by nucleocytoplasmic shuttling of ChREBP. Under high glucose ChREBP binds to importin α and importin β and translocates into the nucleus to initiate transcription. We have previously shown that the nuclear localization signal site (NLS) for ChREBP is bipartite with the NLS extending from Arg158 to Lys190. Here, we report the 2.5 Å crystal structure of the ChREBP-NLS peptide bound to importin α. The structure revealed that the NLS binding is monopartite, with the amino acid residues K171RRI174 from the ChREBP-NLS interacting with ARM2-ARM5 on importin α. We discovered that importin α also binds to the primary binding site of the 14-3-3 proteins with high affinity, which suggests that both importin α and 14-3-3 are each competing with the other for this broad-binding region (residues 117-196) on ChREBP. We screened a small compound library and identified two novel compounds that inhibit the ChREBP-NLS/importin α interaction, nuclear localization, and transcription activities of ChREBP. These candidate molecules support developing inhibitors of ChREBP that may be useful in treatment of obesity and the associated diseases., (© 2020 The Author(s).)

Objective: To elucidate the prevalence of Japanese ADSSL1 myopathy and determine the clinicopathologic features of the disease., Methods: We searched for ADSSL1 variants in myopathic patients from January 1978 to March 2019 in our repository and assessed the clinicopathologic features of patients with variants., Results: We identified 63 patients from 59 families with biallelic variants of ADSSL1 . Among the 7 distinct variants identified, c.781G>A and c.919delA accounted for 53.2% and 40.5% of alleles, respectively, suggesting the presence of common founders, while the other 5 were novel. Most of the identified patients displayed more variable muscle symptoms, including symptoms in the proximal and/or distal leg muscles, tongue, masseter, diaphragm, and paraspinal muscles, in adolescence than previously reported patients. Dysphagia with masticatory dysfunction developed in 26 out of 63 patients; hypertrophic cardiomyopathy developed in 12 out of 48 patients; and restrictive ventilatory insufficiency developed in 26 out of 34 patients in later stages. Radiologically, fat infiltration into the periphery of vastus lateralis, gastrocnemius, and soleus muscles was observed in all patients. Pathologically, nemaline bodies in addition to increased lipid droplets and myofibrillar disorganization were commonly observed in all patients, suggesting that the disease may be classified as nemaline myopathy. This finding revealed that ADSSL1 myopathy is the most frequent among all genetically diagnosable nemaline myopathies in our center., Conclusions: ADSSL1 myopathy is characterized by more variable manifestations than previously reported. It is the most common among all genetically diagnosable nemaline myopathies in our center, although mildly increased lipid droplets are also constantly observed features., (© 2020 American Academy of Neurology.)

Pentakis(dimethylsulfoxide-κ O )oxidovanadium(iv) bis(tetraphenylborate), [VO(dmso) 5 ][BPh 4 ] 2 (dmso: dimethylsulfoxide), was synthesized, and its pseudo- C 4 VO 6 coordination geometry was revealed by a single-crystal X-ray method. A novel equation set was obtained for magnetic susceptibility and magnetization of the d 1 complexes, considering the axial distortion and the spin-orbit coupling for the 2 D free-ion term. The equation set enabled magnetic simulation for significantly symmetry-lowered d 1 complexes to obtain the anisotropic g -values and also the excitation energies. In addition, conformational prediction was conducted, using the enumeration results on the basis of the group theory. The dominant conformers were predicted on the basis of the density functional theory (DFT) method, and especially, the conformer in the crystal was successfully predicted by a deep neural network method., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The reactions of [Ru 2 (O 2 CCH 3 ) 4 Cl] with 2-aminopyridine (Hamp) and 2-amino-4-methylpyridine (Hammp) afforded two novel Ru 2 complexes, [Ru 2 (amp) 4 Cl 2 ] (1) and [Ru 2 (ammp) 4 Cl 2 ] (2), respectively. Single crystal X-ray diffraction analyses revealed that 1 and 2 adopted typical paddlewheel-type structures, where the Ru 2 units are coordinated with four aminopyridinate ligands with a cis-2:2 arrangement at the equatorial positions and two chloride ligands at the axial positions. The stabilities of 1 and 2 were supported by unrestricted density functional theory (uDFT) calculations. The zero-point energies of the three structural isomers (trans-2:2, 3:1, and 4:0 arrangements) of 1 and 2 were less stable than those of the respective cis-2:2 arrangements. Temperature-dependences of the magnetic susceptibility measurements and uDFT calculations showed that the oxidation and spin states of the Ru 2 units in 1 and 2 were commonly Ru 2 6+ and triplet states, respectively. Cyclic voltammetry showed that 1 and 2 underwent one-electron reduction processes, i.e., 1/1 - and 2/2 - , at redox potentials (E 1/2 ) of -0.08 and -0.18 V vs. SCE, respectively. These results agreed well with the DFT-calculated E 1/2 values of 1 (-0.08 V vs. SCE) and 2 (-0.18 V vs. SCE) and were theoretically attributed to Ru 2 -centred (δ*(Ru 2 )) redoxes. Moreover, 1 and 2 showed unique near-infrared absorption bands at approximately 1200-1500 nm, which were theoretically attributed to the ligand-to-metal charge transfer (LMCT) with π(amp or ammp) →δ*(Ru 2 ) transition characteristics.

Strains of Rotarix, a live attenuated monovalent oral rotavirus vaccine, replicate in the intestine and are shed for about one month in immunocompetent recipients. The current study aimed to identify genetic changes of shed strains to reveal any significant mutations and their clinical impact on recipients. Stool samples of recipients of the first dose of Rotarix were sequentially collected for one month from the day of administration. Sequence analyses of the VP7 gene in eight recipients revealed five amino acid substitutions. Among them, two were observed in aa123, which is located in antigenic region 7-1a. Since there were no associated clinical symptoms, the genetic changes were unlikely to have caused reversion of pathogenicity of vaccine strain. Of interest, the virus in one case became closer to wild-type rotavirus via an amino acid change at aa123 occurring 14 days after administration, which might have resulted from multiple replications and long-term shedding of the vaccine strain., Competing Interests: The authors declare that there are no conflicts of interest., (© 2019 The Authors.)

The crystal structure of a new magnesium(ii) complex, [Mg(dmso) 6 ][BPh 4 ] 2 (1) (dmso: dimethylsulfoxide), was determined, and the reason for the observed structure was clarified by conformational analysis. For a dmso-ligand arm, three conformations, α, β, and γ, are possible. The α-arm is the most energetically favourable and is suitable for reducing the steric repulsion between the arms; the β-arm is less energetically favourable, but can be stabilized by interaction with surroundings (e.g. CHπ interaction); the γ-arm is not energetically favourable, but is effective in reducing the size of the complex cation. From the conformational analysis, the most stable conformer of the [Mg(dmso) 6 ] 2+ complex cation was found to be the α 6 conformer, and the complex cation in dmso solution was predicted to exist as a mixture of α 6 , α 5 β, and trans-α 4 β 2 species. On the contrary, in the crystal structure, the trans-β 2 γ 4 species, considered to be unstable, was observed. From the conformational analysis in the tetraphenylborate surroundings, the trans-β 2 γ 4 structure was found to become more stable, due to its small size suitable for crystal packing with bulky tetraphenylborate anions.

University lectures are mainly passive in nature, and there are few subjects in which students need to learn and function independently. Tutorial education and related activities at universities that specialize in medical and pharmaceutical training have been actively carried out, and lectures in conjunction with practical skills are gradually being developed, although progress has been slow in this area. In past years, our biochemistry practice classes have been evaluated in reports dealing with experiments and written examinations, as is done in other universities. However, using this methodology, we are not able to evaluate the extent to which students master biochemical experimental skills. To address this, we introduced a basic skill test to our biochemical curriculum for the first time. Our exams contributed to a deeper understanding of student skills and could be good tools for evaluating the degree of understanding of the students. The students understood the contents of the training well and felt interested in research in the field of basic medicine. Thus, we conclude that introducing practical testing to biochemical practice was effective for medical students in the field of biochemistry. © 2019 International Union of Biochemistry and Molecular Biology, 47(3):279-287, 2019., (© 2019 International Union of Biochemistry and Molecular Biology.)

We report a biomimetic polyelectrolyte based on amphiphilic polymer nanosheet multilayer films. Copolymers of poly( N-dodecylacrylamide- co-vinylphosphonic acid) [p(DDA/VPA)] form a uniform monolayer at the air-water interface. By depositing such monolayers onto solid substrates using the Langmuir-Blodgett (LB) method, multilayer lamellae films with a structure similar to a bilayer membrane were fabricated. The proton conductivity at the hydrophilic interlayer of the lamellar multilayer films was studied by impedance spectroscopy under temperature- and humidity-controlled conditions. At 60 °C and 98% relative humidity (RH), the conductivity increased with increasing mole fraction of VPA ( n) up to 3.2 × 10 -2 S cm -1 for n = 0.41. For a film with n = 0.45, the conductivity decreased to 2.2 × 10 -2 S cm -1 despite the increase of proton sources. The reason for this decrease was evaluated by studying the effect of the distance between the VPAs ( l VPA ) on the proton conductivity as well as their activation energy. We propose that for n = 0.41, l VPA is the optimal distance not only to form an efficient two-dimensional (2D) hydrogen bonding network but also to reorient water and VPA. For n = 0.45, on the other hand, the l VPA was too close for a reorientation. Therefore, we concluded that there should be an optimal distance to obtain high proton conductivity at the hydrophilic interlayer of such multilayer films.

Caffeine intake is associated with a reduced risk developing non-alcoholic fatty liver disease (NAFLD), but the underlying molecular mechanisms remain to be fully elucidated. We report here that caffeine markedly improved high fat diet-induced NAFLD in mice resulting in a 10-fold increase in circulating IL-6 levels, leading to STAT3 activation in the liver. Interestingly, the expression of IL-6 mRNA was not increased in the liver, but increased substantially in the muscles of caffeine-treated mice. Caffeine was found to stimulate IL-6 production in cultured myotubes but not in hepatocytes, adipocytes, or macrophages. The inhibition of p38/MAPK abrogated caffeine-induced IL-6 production in muscle cells. Caffeine failed to improve NAFLD in IL-6 and hepatocyte-specific STAT3 knockout mice, indicating that the IL-6/STAT3 pathway is vital for the hepatoprotective effects of caffeine in NAFLD. The possibility that IL-6/STAT3-mediated hepatic autophagosome induction and hepatocytic oxygen consumption are involved in the anti-NAFLD effects of caffeine cannot be excluded, based on the findings presented here. Our results reveal that caffeine ameliorates NAFLD via crosstalk between muscle IL-6 production and liver STAT3 activation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Three tetracoordinated cobalt(ii) complexes with a series of unsymmetrical bidentate ligands were synthesized and crystallographically characterized. Although their static magnetic properties are similar, their dynamic magnetic properties differ drastically depending indirectly on intermolecular hydrogen-bonding interactions.

Under certain conditions, amyloid-like fibrils can develop into three-dimensional networks and form hydrogels by a self-assembly process. When Cu/Zn superoxide dismutase (SOD1), an anti-oxidative enzyme, undergoes misfolding, fibrillar aggregates are formed, which are a hallmark of a certain form of familial amyotrophic lateral sclerosis (ALS). However, the issue of whether SOD1 fibrils can be assembled into hydrogels remains to be tested. Here, we show that the SOD1 polypeptides undergo hydrogelation accompanied by the formation of thioflavin T-positive fibrils at pH 3.0 and 4.0, but not at pH 5.0 where precipitates are formed. The results of viscoelastic analyses indicate that the properties of SOD1 hydrogels (2%) were similar to and slightly more fragile than a 0.25% agarose gel. In addition, monitoring by a quartz crystal microbalance with admittance analysis showed that the denaturing of immobilized SOD1 on a sensor under the hydrogelation conditions at pH 3.0 and 4.0 resulted in an increase in the effective acoustic thickness from ~3.3 nm (a folded rigid form) to ~50 and ~100 nm (an extended water-rich state), respectively. In contrast, when SOD1 was denatured under the same conditions at pH 5.0, a compact water-poor state with an effective acoustic thickness of ~10 nm was formed. The addition of physiological concentrations of NaCl to the pH 4.0 sample induced a further extension of the SOD1 with larger amounts of water molecules (with an effective acoustic thickness of ~200 nm) but suppressed hydrogel formation. These results suggest that different denatured intermediate states of the protein before self-assembly play a major role in determining the characteristics of the resulting aggregates and that a conformational change to a suitable level of extended water-rich intermediate state before and/or during intermolecular assembling is required for fibrillation and hydrogelation in the case of globular proteins., Competing Interests: The authors have declared that no competing interests exist.

The magnetostructural correlation of the hexakis-dmso cobalt(ii) complex, [Co(dmso) 6 ](BPh 4 ) 2 (dmso: dimethylsulfoxide), was investigated by single-crystal X-ray diffraction study and magnetic measurements. The magnetic analysis concluded the negative Δ value (H = Δ(L - 2/3) + E(L - L) - (3/2)κλL·S + β[-(3/2)κL u + g e S u ]·H u (u = x, y, z)), and this was explained by the tetragonal elongation of the octahedral geometry. The magnetostructural correlation was ascertained by both the angular overlap model calculation and the density functional theory calculation.

An unusual Cu(ii) coordination polymer [Cu(Him) 2 (L)] (1) having a 4,4'-{[1,2-phenylene bis-(methylene)]bis(oxy)}dibenzoic acid ligand and an imidazole ligand possessing a 1D zig-zag chain was constructed and its magnetic behaviour was investigated, which indicated a magnetic phase transition below 25 K as well as long-range magnetic ordering.

To make a porous material with high magnetic ordering temperature is challenging because the low density of the material is adverse to the dense magnetic moment, a prerequisite to high-performance magnets. Herein, we report a hollow magnetic metal-organic framework (MMOF) [Co 3 (bpdc) 3 (tpt) 0.66 ] 1 (H 2 bpdc = 4,4'-biphenyldicarboxylic acid) with a Langmuir surface area of 1118 m 2 /g and spin-canted long-range magnetic ordering up to 22 K. Such a high performance is owing to the unique antiferromagnetic Kagomé lattice made of ferromagnetic Co 3 clusters and conjugated 2,4,6-tri(4-pyridinyl)-1,3,5-triazine (tpt) ligands, which is closely coupled with each other via double-interpenetration of the porous networks. Moreover, a parameter defined as the product of magnetic ordering/blocking temperature and the surface area for measuring the performance of porous molecular magnets is proposed.

An 80-year-old woman had an aortic valve replacement 1 month before admission and took warfarin for transient atrial fibrillation. She developed a disturbance of consciousness and left hemiplegia. On admission, the right radial artery was slightly palpable. Head MRI images showed a hyper-intense area in the right middle cerebral artery territory. MRA images showed an occlusion of the right M1 distal site and decreased signal at the right internal carotid artery. Contrast CT images of the ascending aorta showed an embolus in the innominate artery. She was diagnosed with an innominate artery saddle embolus and occlusion of the right cerebral artery due to cardiac embolism. She was treated with a heparin infusion and warfarin. She recovered consciousness and from hemiplegia gradually. Recanalization of the innominate artery and right cerebral artery was confirmed. In cases where the radial artery is slightly palpable, it is necessary to consider an innominate artery saddle embolus in addition to aortic dissection.

Magnetic properties of dinuclear nickel(II) complex [Ni 2 (sym-hmp) 2 ](BPh 4 ) 2 ·3.5DMF·0.5(2-PrOH) (1), where (sym-hmp) - is 2,6-bis[(2-hydroxyethyl)methylaminomethyl]-4-methylphenolate anion and DMF indicates dimethylformamide, were investigated using high-frequency and -field electron paramagnetic resonance (HFEPR). To magnetically characterize the mononuclear nickel(II) species forming the dimer, its two dinuclear zinc(II) analogues, [Zn 2 (sym-hmp) 2 ](BPh 4 ) 2 ·3.5DMF·0.5(2-PrOH) (2) and [Zn 2 (sym-hmp) 2 ](BPh 4 ) 2 ·2acetone·2H 2 O (2'), were prepared. One of them (2') was structurally characterized by X-ray diffractometry and doped with 5% mol nickel(II) ions to prepare a mixed crystal 3. From the HFEPR results on complex 1 obtained at 40 K, the spin Hamiltonian parameters of the first excited spin state (S = 1) of the dimer were accurately determined as |D 1 | = 9.99(2) cm -1 , |E 1 | = 1.62(1) cm -1 , and g 1 = [2.25(1), 2.19(2), 2.27(2)], and for the second excited spin state (S = 2) at 150 K estimated as |D 2 | ≈ 3.5 cm -1 . From these numbers, the single-ion zero-field splitting (ZFS) parameter of the Ni(II) ions forming the dimer was estimated as |D Ni | ≈ 10-10.5 cm -1 . The HFEPR spectra of 3 yielded directly the single-ion parameters for D Ni = +10.1 cm -1 , |E Ni | = 3.1 cm -1 , and g iso = 2.2. On the basis of the HFEPR results, the previously obtained magnetic data (Sakiyama, H.; Tone, K.; Yamasaki, M.; Mikuriya, M. Inorg. Chim. Acta 2011, 365, 183) were reanalyzed, and the isotropic interaction parameter between the Ni(II) ions was determined as J = -70 cm -1 (H ex = -J S A ·S B ). Finally, density functional theory calculations yielded the J value of -90 cm -1 in a qualitative agreement with the experiment.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic diseases, and results in the development of fibrosis. Oxidative stress is thought to be one of the underlying causes of NAFLD. Copper/zinc superoxide dismutase (SOD1) is a primary antioxidative enzyme that scavenges superoxide anion radicals. Although SOD1 knockout (KO) mice have been reported to develop fatty livers, it is not known whether this lack of SOD1 leads to the development of fibrosis. Since the accumulation of collagen typically precedes liver fibrosis, we assessed the balance between the synthesis and degradation of collagen in liver tissue from SOD1 KO mice. We found a higher accumulation of collagen in the livers of SOD1 KO mice compared to wild type mice. The level of expression of HSP47, a chaperone of collagen, and a tissue inhibitor (TIMP1) of matrix metalloproteinases (a collagen degradating enzyme) was also increased in SOD1 KO mice livers. These results indicate that collagen synthesis is increased but that its degradation is inhibited in SOD1 KO mice livers. Moreover, SOD1 KO mice liver sections were extensively modified by advanced glycation end products (AGEs), which suggest that collagen in SOD1 KO mice liver might be also modified with AGEs and then would be more resistant to the action of collagen degrading enzymes. These findings clearly show that oxidative stress plays an important role in the progression of liver fibrosis.

The carbohydrate-response element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays an essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose levels, ChREBP is regulated by nuclear/cytosol trafficking via interaction with 14-3-3 proteins, CRM-1 (exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain α-ketoacids, saturated and unsaturated fatty acids, or 5-aminoimidazole-4-carboxamide ribonucleotide. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N terminus of ChREBP-α2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Aims: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort., Methods and Results: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively., Conclusion: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Polarized neutron diffraction (PND) experiments were carried out at low temperature to characterize with high precision the local magnetic anisotropy in two paramagnetic high-spin cobalt(II) complexes, namely [Co(II) (dmf)6 ](BPh4 )2 (1) and [Co(II) 2 (sym-hmp)2 ](BPh4 )2 (2), in which dmf=N,N-dimethylformamide; sym-hmp=2,6-bis[(2-hydroxyethyl)methylaminomethyl]-4-methylphenolate, and BPh4 (-) =tetraphenylborate. This allowed a unique and direct determination of the local magnetic susceptibility tensor on each individual Co(II) site. In compound 1, this approach reveals the correlation between the single-ion easy magnetization direction and a trigonal elongation axis of the Co(II) coordination octahedron. In exchange-coupled dimer 2, the determination of the individual Co(II) magnetic susceptibility tensors provides a clear outlook of how the local magnetic properties on both Co(II) sites deviate from the single-ion behavior because of antiferromagnetic exchange coupling., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Copper/zinc superoxide dismutase (SOD1), a primary anti-oxidative enzyme, protects cells against oxidative stress. We report herein on a comparison of behavioral and neurobiological changes between SOD1 knockout (KO) and wild-type mice, in an attempt to assess the role of SOD1 in brain functions. SOD1 KO mice exhibited impaired motivational behavior in both shuttle-box learning and three-chamber social interaction tests. High levels of dopamine transporter protein and an acceleration of serotonin turnover were also detected in the cerebrums of the SOD1 KO mice. These findings suggest that SOD1 deficiency disturbs monoaminergic neurotransmission leading to a decrease in motivational behavior.

A large up-field shift (-763 ppm) has been observed for the carboxyl carbons of the dichlorido complex TBA[Ru(2)(O(2)CCH(3))(4)Cl(2)] (TBA(+) = tetra(n-butyl)ammonium cation) in the (13)C NMR spectrum (CD(2)Cl(2) at 25 °C). The DFT calculations showed spin delocalization from the paramagnetic Ru(2)(5+) core to the ligands, in agreement with the large up-field shift.

Two isoreticular metal-organic frameworks with chemical formulae [Cu(L)(4,4'-bipy)(H2O)]n 1.5nCH3CN (1) and [Cu(L)(4,4'-bipy)(H2O)]n·4nH2O (2) (H2L = diphenylmethane-4,4'-dicarboxylic acid) were synthesized and structurally characterized. They show the CdSO4 (6(5) 8) net and have an obvious 1D channel that is spread along the crystallographic c axis. More importantly, 1 shows high selectivity for H2 over N2 and CO2 at low pressure, which could be confirmed via computational calculations using the Connolly algorithm to reveal the size and shape of accessible voids. The incorporation of the drug 5-fluorouracil (5-FU) into the desolvated 1 was around 27.5 wt% per gram of the dehydrated 1. 5-FU is released in a highly controlled and progressive fashion with 61% of the drug released after 95 hours. In addition, we have applied molecular docking calculations to investigate the preferred conformation of 5-FU molecules upon binding to MOF 1. These calculations provide a structural basis to explain the 5-FU release from MOF 1.

Here we report a versatile magnetic susceptibility equation for tetranuclear octahedral high-spin cobalt(ii) complexes and a magnetic analysis for a tetranuclear defect cubane cobalt(ii) complex based on this equation. We concluded that the interaction is essentially ferromagnetic despite the decrease in the χT product on cooling from 300 K, and the decrease is due to the spin-orbit coupling.