Ninjin'yoeito reduces fatigue-like conditions by alleviating inflammation of the brain and skeletal muscles in aging mice.

Fatigue can lead to several health issues and is particularly prevalent among elderly individuals with chronic inflammatory conditions. Ninjin'yoeito, a traditional Japanese herbal medicine, is used to address fatigue and malaise, anorexia, and anemia. This study aimed to examine whether relieving inflammation in the brain and skeletal muscle of senescence-accelerated mice prone 8 (SAMP8) could reduce fatigue-like conditions associated with aging. First, SAMP8 mice were divided into two groups, with and without ninjin'yoeito treatment. The ninjin'yoeito-treated group received a diet containing 3% ninjin'yoeito for a period of 4 months starting at 3 months of age. At 7 months of age, all mice underwent motor function, treadmill fatigue, and behavioral tests. They were then euthanized and the skeletal muscle weight, muscle cross-sectional area, and concentration of interleukin (IL)-1ß and IL-1 receptor antagonist (IL-1RA) in both the brain and skeletal muscle were measured. The results showed that the ninjin'yoeito-treated group had higher motor function and spontaneous locomotor activity than the untreated group did and ran for significantly longer in the treadmill fatigue test. Moreover, larger muscle cross-sectional area, lower IL-1ß concentrations, and higher IL-1RA concentrations were observed in both the brain and skeletal muscle tissues of the ninjin'yoeito-treated group than in the untreated group. The results suggest that ninjin'yoeito improves age-related inflammatory conditions in both the central and peripheral tissues and reduces fatigue.

Unusual flexibility of transparent poly(methylsilsesquioxane) aerogels by surfactant-induced mesoscopic fiber-like assembly.

High-performance thermal insulators represented by aerogels are regarded as one of the most promising materials for energy savings. However, significantly low mechanical strength has been a barrier for aerogels to be utilized in various social domains such as houses, buildings, and industrial plants. Here, we report a synthetic strategy to realize highly transparent aerogels with unusually high bending flexibility based on poly(methylsilsesquioxane) (PMSQ) network. We have constructed mesoscopic fine fiber-like structures of various sizes in PMSQ gels by the combination of phase separation suppression by tetramethylammonium hydroxide (TMAOH) and mesoscopic fiber-like assembly by nonionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO) type surfactant. The optimized mesoscale structures of PMSQ gels have realized highly transparent and resilient monolithic aerogels with much high bendability compared to those reported in previous works. This work will provide a way to highly insulating materials with glasslike transparency and high mechanical flexibility.

1,5-anhydro-D-fructose induces anti-aging effects on aging-associated brain diseases by increasing 5'-adenosine monophosphate-activated protein kinase activity via the peroxisome proliferator-activated receptor-γ co-activator-1α/brain-derived neurotrophic factor pathway.

5'-Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor that serves as a cellular housekeeper; it also controls energy homeostasis and stress resistance. Thus, correct regulation of this factor can enhance health and survival. AMPK signaling may have a critical role in aging-associated brain diseases. Some in vitro studies have shown that 1,5-anhydro-D-fructose (1,5-AF) induces AMPK activation. In the present study, we experimentally evaluated the effects of 1,5-AF on aging-associated brain diseases in vivo using an animal model of acute ischemic stroke (AIS), stroke-prone spontaneously hypertensive rats (SHRSPs), and the spontaneous senescence-accelerated mouse-prone 8 (SAMP8) model. In the AIS model, intraperitoneal injection of 1,5-AF reduced cerebral infarct volume, neurological deficits, and mortality. In SHRSPs, oral administration of 1,5-AF reduced blood pressure and prolonged survival. In the SAMP8 model, oral administration of 1,5-AF alleviated aging-related decline in motor cognitive function. Although aging reduced the expression levels of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and brain-derived neurotrophic factor (BDNF), we found that 1,5-AF activated AMPK, which led to upregulation of the PGC-1α/BDNF pathway. Our results suggest that 1,5-AF can induce endogenous neurovascular protection, potentially preventing aging-associated brain diseases. Clinical studies are needed to determine whether 1,5-AF can prevent aging-associated brain diseases.

Powdered Hierarchically Porous Silica Monoliths for the Selective Extraction of Scandium.

Scandium (Sc) is a high value Critical Material that is most commonly used in advanced alloys. Due to current and potential supply limitations, there has been an international effort to find new and improved ways to extract Sc from existing and novel resources. Solid-phase extraction (SPE) is one promising approach for Sc recovery, particularly for use with low-grade feedstocks. Here, unfunctionalized, powdered hierarchically porous silica monoliths from DPS Inc. (DPS) are used for Sc extraction in batch and semicontinuous flow systems at model conditions. The sorbent exhibits excellent mass transfer properties, much like the whole monoliths, which should permit Sc to be rapidly recovered from large volumes of feedstock. The Sc adsorption capacity of the material is ∼142.7 mg/g at pH 6, dropping to ∼12.0 mg/g at pH 3, and adsorption is furthermore highly selective for Sc compared with the other rare earth elements (REEs). Under semicontinuous flow conditions, recovery efficiency is limited by a kinetic process. The primary mechanism responsible for the system's slow approach to equilibrium is the Sc adsorption reaction kinetics rather than inter- or intraparticle diffusion. Overall, this unmodified hierarchically porous silica powder from DPS shows great promise for the selective extraction of Sc from various feedstocks.

Effects of low-intensity exercise on spontaneously developed knee osteoarthritis in male senescence-accelerated mouse prone 8.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease associated with aging, which often leads to joint stiffness and disability. Exercise is one of the most important non-pharmacological treatments and is prescribed as an indispensable treatment for OA. However, whether physical exercise is beneficial for preventing the progression of OA symptoms with age is poorly understood. We investigated the effects of exercise on spontaneously developed knee OA using male senescence-accelerated mouse prone 8 (SAMP8). METHODS: To examine age-related changes in the knee joints of SAMP8, knee articular cartilage changes, synovitis, knee joint flexion and extension angles, swelling, walking ability, and quadriceps muscle atrophy were analyzed at 3, 5, 7, and 9 months. SAMP8 were required to run at a speed of 10 m/min for 15 min/day from 7 to 9 months of age. The knee joint pathologies and symptoms of exercising and non-exercising mice were compared by histological, immunohistochemical, and morphometrical analyses. RESULTS: The mice presented with various histological changes, including cartilage destruction, osteocyte formation, synovitis, declined joint angles, and swelling. Notably, medial and posterior cartilage destruction was more severe than that of the lateral and anterior cartilage. Knee joint angles were significantly correlated with the histological scores (modified Mankin and OARSI, osteophyte formation and synovial lining cell layer). Exercise did not attenuate cartilage degeneration in the medial and posterior tibial plateau, although the articular cartilage of the anterior and lateral tibial plateau and its histological scores was remained and significantly improved, respectively, by exercise. Exercise suppressed the age-related decline of collagen type II-positive areas in the remaining articular cartilage and improved the OA symptoms. Exercise reduced the expression of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α positive macrophages in the synovium. CONCLUSION: This study revealed that SAMP8 developed spontaneous knee OA with age, which resembled the disease symptoms in humans. Low-intensity exercise temporarily alleviated degeneration of the remaining cartilage, synovitis, and age-related decreases in knee flexion angle, stride length, and muscle atrophy in SAMP8. However, exercise during OA progression with age may cause mechanical stress that could be both beneficial and detrimental to joint health.

Redox Activity of IrIII Complexes with Multidentate Ligands Based on Dipyrido-Annulated N-Heterocyclic Carbenes: Access to High Valent and High Spin State with Carbon Donors.

Synthetic strategies to access high-valent iridium complexes usually require use of π donating ligands bearing electronegative atoms (e. g. amide or oxide) or σ donating electropositive atoms (e. g. boryl or hydride). Besides the η5 -(methyl)cyclopentadienyl derivatives, high-valent η1 carbon-ligated iridium complexes are challenging to synthesize. To meet this challenge, this work reports the oxidation behavior of an all-carbon-ligated anionic bis(CCC-pincer) IrIII complex. Being both σ and π donating, the diaryl dipyrido-annulated N-heterocyclic carbene (dpa-NHC) IrIII complex allowed a stepwise 4e- oxidation sequence. The first 2e- oxidation led to an oxidative coupling of two adjacent aryl groups, resulting in formation of a cationic chiral IrIII complex bearing a CCCC-tetradentate ligand. A further 2e- oxidation allowed isolation of a high-valent tricationic complex with a triplet ground state. These results close a synthetic gap for carbon-ligated iridium complexes and demonstrate the electronic tuning potential of organic π ligands for unusual electronic properties.

Effects of early exercise intervention and exercise cessation on neuronal loss and neuroinflammation in a senescence-accelerated mouse prone 8.

Physical exercise is beneficial for preventing Alzheimer's disease (AD) and cognitive decline through several mechanisms, including suppression of neuroinflammation and neuronal loss in the hippocampus. Despite these exercise-induced benefits in AD pathology, less attention has been paid to the importance of maintaining exercise and the consequences of detraining. This study aimed to investigate the effects of early exercise intervention and detraining on age-related cognitive decline and its protective mechanisms using senescence-accelerated mouse prone 8 (SAMP8). These mice were divided to four groups: no-exercise (No-Ex, n = 9), 4 months (4 M)-detraining (n = 11), 2 months (2 M)-detraining (n = 11), and long-term exercise (LT-Ex, n = 13). Age-related cognitive decline was prevented in the LT-Ex group compared with the No-Ex group through the suppression of neuronal loss, enhanced brain-derived neurotrophic factor (BDNF), and inhibition of neuroinflammation corresponding to reduced M1 and increased M2 microglia in the hippocampus. No significant differences were observed in cognitive function between the detraining and No-Ex groups. However, the 2 M-detraining group showed increased BDNF positive area in the CA1 region and the enhancement of anti-inflammatory M2 phenotype microglia. In contrast, no statistically beneficial exercise-induced changes in the hippocampus were observed in the 4 M-detrainig group. These results showed that early exercise intervention prevented age-related cognitive deficits in AD progression by suppressing neuronal loss and neuroinflammation in the hippocampus. Exercise-induced benefits, including the anti-inflammation in the hippocampus, may be retained after exercise cessation, even if exercise-induced beneficial effects decline in a time-dependent manner.

Efficient one-pot synthesis of dan-substituted organo- and silyl-boron compounds.

Direct, transition metal-free B(dan)-installation into organic frameworks has been developed. Heteroaryl-H bonds were transformable into the respective heteroaryl-B(dan) bonds through deprotonation. The resulting heteroaryl-B(dan) compounds, which are otherwise difficult to access, can undergo the direct Suzuki-Miyaura coupling. The method was demonstrated to apply to a silicon nucleophile, giving Lewis acidity-diminished stable silyl-B(dan) and -B(aam) in one pot.

Effects of different remote ischemia perconditioning methods on cerebral infarct volume and neurological impairment in rats.

Remote ischemic perconditioning (RIPerC) is a novel neuroprotective method against cerebral infarction that has shown efficacy in animal studies but has not been consistently neuroprotective in clinical trials. We focused on the temporal regulation of ischemia-reperfusion by RIPerC to establish an optimal method for RIPerC. Rats were assigned to four groups: 10 min ischemia, 5 min reperfusion; 10 min ischemia, 10 min reperfusion; 5 min ischemia, 10 min reperfusion; and no RIPerC. RIPerC interventions were performed during ischemic stroke, which was induced by a 60-min left middle cerebral artery occlusion. Infarct volume, sensorimotor function, neurological deficits, and cellular expressions of brain-derived neurotrophic factor (BDNF), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase 3 were evaluated 48 h after the induction of ischemia. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) was also performed. RIPerC of 10 min ischemia/10 min reperfusion, and 5 min ischemia/10 min reperfusion decreased infarct volume, improved sensorimotor function, decreased Bax, caspase 3, and TUNEL-positive cells, and increased BDNF and Bcl-2 expressions. Our findings suggest RIPerC with a reperfusion time of approximately 10 min exerts its neuroprotective effects via an anti-apoptotic mechanism. This study provides important preliminary data to establish more effective RIPerC interventions.

Fabrication process development and basic evaluation of eggshell-based column packing material for reversed-phase preparative separation.

Purification of basic drugs in reversed-phase mode is often difficult, mainly due to adsorption of positively charged compounds to the silica gel-based stationary phase. Since this adsorption can be suppressed under alkaline condition, columns with alkali-resistance are required. In addition, compounds with acid-sensitive structures are sometimes degraded during separation on silica gel-based columns which exhibit acidity due to their surface structure. We prepared an alkali-resistant reversed-phase packing material, Eggshell-PMAcO based on eggshells modified with an amphiphilic copolymer, poly(maleic acid-alt-1-octadecene) (PMAcO). The height equivalent to a theoretical plate (HETP) of the Eggshell-PMAcO column was improved by surface treatment with ammonium acetate buffer (900 mM, pH = 3.7), which is an inexpensive reagent, and the retention behavior for hydrophobic compounds was compared to a typical ODS column based on silica gel, resulting in sufficient selectivity of the eggshell-based column for hydrophobic compounds, as indicated by the ratio of retention factors of pentylbenzene and butylbenzene (Eggshell-PMAcO column: 1.55, ODS column: 1.65). Column temperature-dependent retention behavior of naphthalene was investigated in the temperature range from 25 °C to 45 °C, followed by the calculation of thermodynamic parameters. There was little difference in the standard molar enthalpy (Eggshell-PMAcO: -19.6 kJ/mol, ODS: -21.7 kJ/mol). The absolute value of the standard free Gibbs energy for the Eggshell-PMAcO column was much smaller than that of the ODS column (Eggshell-PMAcO: -0.284 kJ/mol, ODS: -13.0 kJ/mol), indicating that the Eggshell-PMAcO column had a weaker retention strength for naphthalene than the ODS column mainly due to the large difference in the standard molar entropy (Eggshell-PMAcO: -64.9 J/mol K, ODS column: -29.2 J/mol K). The retention capacities for imipramine under neutral (water/methanol) and alkaline (0.1% triethylamine water/methanol) conditions were 0.2 mg and 5 mg, respectively, based on injection mass-dependent HETP, retention factor and symmetry factor. Finally, the prepared column was applied to the purification of a building block for nucleic acid drugs. This study demonstrated that reversed-phase columns, which can be fabricated from eggshells and an amphiphilic copolymer in an inexpensive and eco-friendly way, have the ability to purify basic compounds and acid-sensitive compounds.

Stimulation of functional recovery via neurorepair mechanisms by the traditional Japanese Kampo medicine, Ninjin'yoeito, and physical exercise in a rat ischemic stroke model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ninjin'yoeito (NYT), a traditional Japanese Kampo medicine consisting of 12 herbs, has been reported to improve cognitive dysfunction, depression, and neurological recovery in patients with neurovascular diseases such as Alzheimer's disease and stroke. Several studies have reported that the NYT components exert neurotrophic, neurogenic, and neuroprotective effects. In addition, exercise enhances neuroprotection and functional recovery after stroke. Rehabilitative exercises and pharmacological agents induce neurophysiological plasticity, leading to functional recovery in stroke patients. These reports indicate that NYT treatment and exercise may promote functional recovery following stroke through their beneficial effects. However, no study has determined the effects of NYT and the possible mechanisms of neurorepair and functional recovery after stroke. AIM OF THE STUDY: This study aimed to investigate the combined effects of NYT and exercise on neuroprotection and functional recovery and the underlying mechanisms in a rat ischemic stroke model. MATERIALS AND METHODS: Stroke was induced with 60-min middle cerebral artery occlusion (MCAO) followed by reperfusion in adult male Sprague-Dawley rats. After stroke, the rats were assigned to four groups: ischemia reperfusion (IR), NYT, exercise (Ex), and NYT + Ex. NYT-treated rats were fed a diet containing 1% NYT one day after stroke. Exercise was performed using a motorized treadmill for 5 days a week (8-15 m/min, 20 min/day), starting 3 days after stroke. The NYT treatment and exercise were continued for 4 weeks after the stroke. Infarct volume, neurological deficits, sensorimotor functions, expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase A (TrkA) and B (TrkB), caspase-3 activity, and the p-Akt/Akt ratio were examined by immunohistochemistry and western blotting. RESULTS: Compared to the IR group, all treated groups indicated reduced infarct volumes. The NYT + Ex group showed significantly improved waking time and beam walking score compared with the IR group. The expression of NGF/TrkA/p-TrkA and BDNF/TrkB was significantly increased in the NYT + Ex group compared with those in the IR group, whereas the number of caspase-3 positive cells around the lesion was significantly lower in the NYT + Ex group than in the IR group. In addition, the ratio of p-Akt/Akt was significantly higher in the NYT + Ex group than in the IR group. CONCLUSIONS: This study suggests that NYT in combination with exercise provides neuroprotective effects and improves sensorimotor function by stimulating NGF/TrkA and BDNF/TrkB, and by activating the Akt pathway in ischemic stroke of rats. NYT may be an effective adjunctive agent in post-stroke rehabilitation.

Oxide-on-Oxide Porous Electrodes Revealing Superior Reversible Li+-Coupled Electron-Transfer Properties by Unconventional Heterojunction Effects.

Internal spacing of electrodes is a key point for controlling electron-transfer (ET)-related phenomena. However, their disordered porous structures often prevent the observation of microscopic effects. It hampers the development of modern electrochemical theories. The development of model porous electrodes therefore provides an ideal platform to discover intriguing fundamental principles of electrode processes. We developed a new synthetic strategy for all-oxide monolithic ruthenium dioxide (RuO2)/antimony-doped tin oxide (ATO) electrodes with a controlled hierarchically porous structure and oxide-oxide heterojunction. The use of the obtained RuO2/ATO electrodes as model electrodes suppressed influences related to different mass diffusion efficiencies between electrodes with heterojunctions of different types. Then, we showed unconventional oxide-oxide heterojunction effects, improving reversible Li+-coupled electron-transfer properties using model electrodes constituted of various nanostructured (nano-) RuO2 on porous ATO. In addition to the superior electrochemical properties of the nano-RuO2/ATO heterojunction, the quasi-two-dimensional (2D) RuO2/ATO heterojunction led to improved specific capacity at a high rate and longer cycle life. We anticipate that this oxide-oxide heterojunction effect and developed all-oxide model porous electrodes can provide a path to develop advanced reversible energy storage devices.

Mechanisms of Neuropathic Pain and Pain-Relieving Effects of Exercise Therapy in a Rat Neuropathic Pain Model.

Purpose: Pain disrupts the daily and social lives of patients with neuropathic pain. Effective treatment of neuropathic pain is difficult. Pharmacological treatments for neuropathic pain are limited, and 40-60% of patients do not achieve even partial relief of their pain. This study created a chronic constriction injury (CCI) model in rats to examine the effects of regular exercise on neuropathic pain relief, elucidate the mechanism, and determine the effects of neuropathic pain in the hippocampus. Methods: CCI model rats were randomly divided into exercise (Ex) and no exercise (No-Ex) groups. Normal rats (Normal group) were used as controls. The Ex group exercised on a treadmill at 20 m/min for 30 min, 5 days per week for 5 weeks post-CCI. The 50% pain response threshold was assessed by mechanical stimulation. Using immunohistochemistry, we examined activation of glial cells (microglia and astrocytes) by CCR2 and TRAF6 expression in the spinal cord dorsal horn and DCX and PROX1 expression in the hippocampal dentate gyrus. Results: The 50% pain response threshold was significantly lower in the Ex than in the No-Ex group at 5 weeks post-CCI, indicating pain relief. In the spinal cord dorsal horn, IBA1, CCR2, and TRAF6 expression was markedly lower in the Ex group than in the No-Ex group at 3 weeks post-CCI. IBA1, GFAP, CCR2, and TRAF6 expression was markedly lower in the Ex group than in the No-Ex group at 5 weeks post-CCI. In the hippocampus, DCX, but not PROX1, expression was significantly higher in the Ex group than in the No-Ex group at 3 weeks post-CCI. At 5 weeks post-CCI, both DCX and PROX1 expression was markedly increased in the Ex group compared to the No-Ex group. Conclusion: Our findings suggest that regular exercise can improve the neuropathic pain-induced neurogenic dysfunction in the hippocampal dentate gyrus.

A stable silylborane with diminished boron Lewis acidity.

A new dimethyl(phenyl)silylborane having a naphthalene-1,8-diaminato (dan) substituent on the boron center, PhMe2Si-B(dan), was synthesized. Owing to the diminished boron Lewis acidity, it is highly stable toward air. Synthetic application of the silylborane to catalytic silylboration and silylation of alkynes is also described.

E8002 Reduces Adhesion Formation and Improves Joint Mobility in a Rat Model of Knee Arthrofibrosis.

Knee arthrofibrosis is a common complication of knee surgery, caused by excessive scar tissue, which results in functional disability. However, no curative treatment has been established. E8002 is an anti-adhesion material that contains L-ascorbic acid, an antioxidant. We aimed to evaluate the efficacy of E8002 for the prevention of knee arthrofibrosis in a rat model, comprising injury to the surface of the femur and quadriceps muscle 1 cm proximal to the patella. Sixteen male, 8-week-old Sprague Dawley rats were studied: in the Adhesion group, haemorrhagic injury was induced to the quadriceps and bone, and in the E8002 group, an adhesion-preventing film was implanted between the quadriceps and femur after injury. Six weeks following injury, the restriction of knee flexion owing to fibrotic scarring had not worsened in the E8002 group but had worsened in the Adhesion group. The area of fibrotic scarring was smaller in the E8002 group than in the Adhesion group (p < 0.05). In addition, the numbers of fibroblasts (p < 0.05) and myofibroblasts (p < 0.01) in the fibrotic scar were lower in the E8002 group. Thus, E8002 reduces myofibroblast proliferation and fibrotic scar formation and improves the range of motion of the joint in a model of knee injury.

Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis.

Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1ß), 14-3-3γ, p-ß-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14-3-3γ were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-α, IL-6, IL-1ß, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14-3-3γ/p-ß-catenin Ser37/Bax/caspase-3 pathway.

Synthesis and Isolation of an Anionic Bis(dipyrido-annulated) N-Heterocyclic Carbene CCC-Pincer Iridium(III) Complex by Facile C-H Bond Activation.

Meridional tridentate N-heterocyclic carbene (NHC)-based pincer ligands contribute to a substantial growth in modern organometallic chemistry in both homogeneous catalysis and luminescence materials. Among all NHC-based pincer ligands, the dianionic LX2-type CCC-pincer ones constitute the smallest subcategory owing to their limited ligand frameworks suitable for complexation. This work reports a one-pot, high-yield synthesis of a homoleptic anionic all-carbon bis-pincer iridium(III) complex (4) directly from a bis(aryl)-substituted dipyrido-annulated (dpaAr2) imidazolium salt and [Ir(COD)Cl]2 via a cascade of deprotonation/C-H activation processes. Both experimental complexation chemistry and computational mechanistic investigation suggest that the large bite angle and π-rich character of the dpaAr2 NHC are responsible for its facile complexation as a dianionic LX2-type CCC-pincer ligand precursor. The all-carbon ligated iridium(III) complex (4) bearing a π-conjugated ligand scaffold showed remarkably low oxidation potentials, which allows future investigations in its redox chemistry and photophysical properties.

Effects of detraining on preconditioning exercise-induced neuroprotective potential after ischemic stroke in rats.

Preconditioning exercise prior to stroke exerts neuroprotection, which is an endogenous strategy that leads the brain cells to express several intrinsic factors and inhibits their apoptosis. However, it is unclear how long these benefits last after exercise cessation. The aim of this study was to investigate the effects of detraining on preconditioning exercise-induced neuroprotective potential after stroke. Rats were trained using a treadmill for aerobic exercise 5 days each week for 3 weeks, and their neuroprotective effects were examined until 3 weeks after exercise cessation. Stroke was induced by 60 min of left middle cerebral artery occlusion at 3 days, 1, 2, and 3 weeks after exercise cessation. Infarct volume, neurological deficits, sensorimotor function, expression levels of brain-derived neurotrophic factor (BDNF), hypoxia-induced factor-1α (HIF-1α), glial fibrillary acidic protein (GFAP), and P2X7 receptors, and apoptosis activity were examined using immunohistochemical and western blot analyses. Preconditioning exercise significantly reduced infarct volume and ameliorated sensorimotor function after stroke, and its beneficial effects were observed until 2 weeks after exercise cessation. The expression level of BDNF in the ischemic brain was significantly upregulated at 3 days after exercise cessation; however, the expression levels of HIF-1α, GFAP, and P2X7 receptor were significantly increased until 2 weeks after exercise cessation; thereby, significant anti-apoptotic effects were lost at 3 weeks of detraining. Our findings suggest that preconditioning exercise-induced neuroprotective potential may be lost shortly after exercise cessation. Neuroprotection through intrinsic protective factors, such as BDNF and HIF-1α, may provide different neuroprotective mechanisms in a time-dependent manner during detraining.

Effect of low-intensity motor balance and coordination exercise on cognitive functions, hippocampal Aß deposition, neuronal loss, neuroinflammation, and oxidative stress in a mouse model of Alzheimer's disease.

It is well known that physical exercise reduces the risk of Alzheimer's disease (AD) and age-related cognitive decline. However, its mechanisms are still not fully understood. This study aimed to investigate the effect of aging and rotarod exercise (Ex) on cognitive function and AD pathogenesis in the hippocampus using senescence-accelerated mice prone 8 (SAMP8). Cognitive functions clearly declined at 9-months of age. Amyloid-beta (Aß) deposition, neuronal loss, and glia activation-induced neuroinflammation increased with aging. The rotarod Ex prevented the decline of cognitive functions corresponding to the suppression of Aß deposition, neuroinflammation, neuronal loss, inducible nitric oxide synthase (NOS) activities, and neuronal NOS activities. In addition, the rotarod Ex suppressed proinflammatory M1 phenotype microglia and A1 phenotype astrocytes. Our findings suggest that low-intensity motor balance and coordination exercise prevented age-related cognitive decline in the early stage of AD progression, possibly through the suppression of hippocampal Aß deposition, neuronal loss, oxidative stress, and neuroinflammation, including reduced M1 and A1 phenotypes microglia and astrocytes.

Diurnal Profiles of Locomotive and Household Activities Using an Accelerometer in Community-Dwelling Older Adults with Musculoskeletal Disorders: A Cross-Sectional Survey.

The present study investigates the diurnal profiles of locomotive and household activities in older adults with musculoskeletal disorders (MSDs) using an accelerometer. Furthermore, we examined the effect of chronic pain on their diurnal profiles in both activities. Seventy-one older adults with MSDs (73-89 years) were included in this cross-sectional survey, and 25 age-matched older adults (75-86 years) were selected as healthy older adults. The daily physical activities, including steps walked and locomotive and household activity intensities, were recorded using a triaxial accelerometer in terms of metabolic equivalent task-hours per week (MET-h/week). The diurnal profiles of steps and locomotive activities in older adults with MSDs were considerably lower than those of healthy older adults. In contrast, there was no significant decline in household activity. However, the locomotive and household activities were reduced by severe chronic pain. This survey demonstrated that the diurnal profiles of household activity in older people with MSDs as well as those in age-matched healthy older adults were maintained. Furthermore, severe chronic pain influenced both activities. Therefore, the maintenance of household activity throughout the day, as well as the management of chronic pain, may be important strategies for the promotion of physical activity in older people with MSDs.