Effects of different exercise modes and intensities on cognitive performance, adult hippocampal neurogenesis, and synaptic plasticity in mice.

Exercise can induce beneficial improvements in cognition. However, the effects of different modes and intensities of exercise have yet to be explored in detail. This study aimed to identify the effects of different exercise modes (aerobic and resistance) and intensities (low and high) on cognitive performance, adult hippocampal neurogenesis and synaptic plasticity in mice. A total of 40 C57BL/6J mice were randomised into 5 groups (n = 8 mice per group): control, low-intensity aerobic exercise, high-intensity aerobic exercise, low-intensity resistance exercise, and high-intensity resistance exercise. The aerobic exercise groups underwent treadmill training, while the resistance exercise groups underwent ladder climbing training. At the end of the exercise period, cognitive performance was assessed by the Y-maze and Barnes maze. In addition, adult hippocampal neurogenesis was evaluated immunohistochemically by 5-bromo-2'-deoxyuridine (BrdU)/ neuronal nuclei (NeuN) co-labeling. The levels of synaptic plasticity-related proteins in the hippocampus, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95), were analyzed by western blotting. Our results showed no significant differences in cognitive performance among the groups. However, high-intensity aerobic exercise significantly increased hippocampal adult neurogenesis relative to the control. A trend towards increased adult neurogenesis was observed in the low-intensity aerobic group compared to the control group. No significant changes in synaptic plasticity were observed among all groups. Our results indicate that high-intensity aerobic exercise may be the most potent stimulator of adult hippocampal neurogenesis.

Effects of acute- and long-term aerobic exercises at different intensities on bone in mice.

INTRODUCTION: Exercise intensity determines the benefits of aerobic exercise. Our objectives were, in aerobic exercise at different intensities, to determine (1) changes in bone metabolism-related genes after acute exercise and (2) changes in bone mass, strength, remodeling, and bone formation-related proteins after long-term exercise. MATERIALS AND METHODS: Total 36 male C57BL/6J mice were divided into a control group and exercise groups at 3 different intensities: low, moderate, or high group. Each exercise group was assigned to acute- or long-term exercise groups. Tibias after acute exercise were evaluated by real-time PCR analysis. Furthermore, hindlimbs of long-term exercise were assessed by micro-CT, biomechanical, histological, and immunohistochemical analyses. RESULTS: Acute moderate-intensity exercise decreased RANKL level as bone resorption marker, whereas low- and high-intensity exercise did not alter it. Additionally, only long-term exercise at moderate intensity increased bone mass and strength. Moderate-intensity exercise promoted osteoblast activity and suppressed osteoclast activity. After low- and high-intensity exercise, osteoblast and osteoclast activity were unchanged. An increase in the number of ß-catenin-positive cells and a decrease in sclerostin-positive cells were observed in the only moderate group. CONCLUSION: These results showed that moderate-intensity exercise can inhibit bone resorption earlier, and long-term exercise can increase bone mass and strength through promoted bone formation via the Wnt/ß-catenin activation. High-intensity exercise, traditionally considered better for bone, may fail to stimulate bone remodeling, leading to no change in bone mass and strength. Our findings suggest that moderate-intensity exercise, neither too low nor high, can maintain bone health.

Interaction effect between low birthweight and resistin gene rs1862513 variant on insulin resistance and type 2 diabetes mellitus in adulthood: Toon Genome Study.

AIMS/INTRODUCTION: Gene-environment interactions are considered to critically influence type 2 diabetes mellitus development; however, the underlying mechanisms and specific interactions remain unclear. Given the increasing prevalence of low birthweight (LBW) influenced by the intrauterine environment, we sought to investigate genetic factors related to type 2 diabetes development in individuals with LBW. MATERIALS AND METHODS: The interaction between 20 reported type 2 diabetes susceptibility genes and the development of type 2 diabetes in LBW (<2,500 g) individuals in a population-based Japanese cohort (n = 1,021) was examined by logistic regression and stratified analyses. RESULTS: Logistic regression analyses showed that only the G/G genotype at the rs1862513 locus of the resistin gene (RETN), an established initiator of insulin resistance, was closely related to the prevalence of type 2 diabetes in individuals with LBW. Age, sex and current body mass index-adjusted stratified analyses showed a significant interaction effect of LBW and the RETN G/G genotype on fasting insulin, homeostatic model assessment 2-insulin resistance, Matsuda index and the prevalence of type 2 diabetes (all P-values for interaction <0.05). The adjusted odds ratio for type 2 diabetes in the LBW + G/G genotype group was 7.33 (95% confidence interval 2.43-22.11; P = 0.002) compared with the non-LBW + non-G/G genotype group. Similar results were obtained after excluding the influence of malnutrition due to World War II. CONCLUSIONS: Simultaneous assessment of LBW and the RETN G/G genotype can more accurately predict the risk of future type 2 diabetes than assessing each of these factors alone, and provide management strategies, including early lifestyle intervention in LBW population.

Higher-intensity ultrasound accelerates fracture healing via mechanosensitive ion channel Piezo1.

Osteoporosis-related fractures are a major public health problem. Mechanobiological stimulation utilizing low-intensity pulsed ultrasound (LIPUS) is the most widely accepted modality for accelerating fracture healing. However, recent evidence has demonstrated the ineffectiveness of LIPUS, and the biophysical mechanisms of ultrasound-induced bone formation also remain elusive. Here, we demonstrate that ultrasound at a higher intensity than LIPUS effectively accelerates fracture healing in a mouse osteoporotic fracture model. Higher-intensity ultrasound promoted chondrogenesis and hypertrophic differentiation of chondrocytes in the fracture callus. Higher-intensity ultrasound also increased osteoblasts and newly formed bone in the callus, resulting in accelerated endochondral ossification during fracture healing. In addition, we found that accelerated fracture healing by ultrasound exposure was attenuated when the mechanosensitive ion channel Piezo1 was inhibited by GsMTx4. Ultrasound-induced new bone formation in the callus was attenuated in fractured mice treated with GsMTx4. Similar results were also confirmed in a 3D osteocyte-osteoblast co-culture system, where osteocytic Piezo1 knockdown attenuated the expression of osteoblastic genes after ultrasound exposure. Together these results demonstrate that higher-intensity ultrasound than clinically used LIPUS can accelerate endochondral ossification after fractures. Furthermore, our results suggest that mechanotransduction via Piezo1 mediates ultrasound-stimulated fracture healing and bone formation.

Effects of different modes and intensities of exercise on longevity proteins in middle-aged mouse skeletal muscle.

Physical exercise represents one of the most effective approaches to anti-aging. The goal of this study was to verify the effects of different modes and intensities of exercise on longevity proteins in the skeletal muscle in midlife. Middle-aged mice were trained in aerobic or resistance exercise for 8 weeks, and the changes in sirtuin 1 (SIRT1), adenosine monophosphate-activated kinase (AMPK), and mammalian target of rapamycin (mTOR) pathways in the skeletal muscle were evaluated by western blotting. Long-term exercise had no effects on skeletal muscle SIRT1 abundance, whereas high-intensity aerobic exercise increased AMPK phosphorylation and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Low-intensity resistance exercise facilitated Akt/mTOR/p70 ribosomal protein kinase S6 (p70S6K) signaling but did not induce muscle hypertrophy. Conversely, high-intensity resistance exercise stimulated muscle hypertrophy without phosphorylation of mTOR signaling-related proteins. These results suggest the importance of setting exercise modes and intensities for anti-aging in midlife.

Effects of uphill and downhill walking on post-traumatic osteoarthritis development in mice.

Using destabilization of the medial meniscus (DMM) to induce models of osteoarthritis (OA), we sought to clarify how flat, uphill and downhill walking affects OA-related inflammation and articular cartilage degeneration. Thirty-two male C57BL/6J mice 7 weeks old underwent DMM surgery in their right knee and sham surgery in their left knee, and were then assigned to either the no walking after DMM group or the flat, uphill or downhill walking after DMM group (n = 8/group). After creating the knee OA model, the mice in the walking groups were subjected to treadmill walking 1 day after surgery, which included walking at 12 m/min for 30 min/day, 7 days/week, at inclines of 0, 20, or -20 degrees. Knee joints were harvested at the end of the intervention period. Non-demineralized frozen sections were prepared and samples were examined histologically. Osteoarthritis Research Society International scores were significantly decreased in both the uphill and flat-walking groups, compared with the no-walking group. Immunohistochemical staining showed increased levels of aggrecan and Sry-related high-mobility group box9; conversely, decreased levels of matrix metalloproteinase-13 and A disintegrin and metalloproteinase with thrombospondin motifs-5 in both the uphill and flat-walking groups. Micro-CT results showed a higher bone-volume fraction in the uphill and flat-walking groups than that in the no-walking group. Our findings indicate that flat and uphill walking may prevent the progression of OA. KEY POINTS: Flat and uphill treadmill walking can prevent the development of post-traumatic osteoarthritis in mice. Flat and uphill walking increases anabolic proteins and decreases catabolic proteins and inflammatory cytokines in articular cartilage, resulting in protection against cartilage degeneration. Downhill walking increases catabolic proteins and inflammatory cytokines in cartilage, which has negative effects on articular cartilage.

Investigation of biomarkers in a rare case of fulminant necrotizing enterocolitis in a preterm infant.

We encountered a very rare case of fulminant necrotizing enterocolitis (F-NEC) in a preterm male baby. The course of NEC and sepsis in this case was clearly different from the usual course. After onset at 14 days of life, catheter-related bloodstream infection was first assumed, and antibiotics and γ-globulin administration were started. However, 12 hours after onset, the baby's abdominal distension increased remarkably, and his entire abdominal wall turned red to purple. Escherichia coli were isolated from the blood culture, but the catheter tip culture was negative. Exchange transfusion was performed 32 hours after onset, but no significant changes were observed in the baby's general condition, and he died 46 hours after onset. The acute phase reactants of CRP and α1-acid glycoprotein increased, but haptoglobin did not. Although IL-1ß and TNFα increased as expected with sepsis, IL-6, IL-8, IL-10, and G-CSF however increased to a greater extent than expected. From the above, we diagnosed the development of intestinal necrosis as a result of widespread intestinal ischemia, and that sepsis was associated with this poor condition.

New species and record of Tyrodes Raffray (Coleoptera: Staphylinidae: Pselaphinae) from Japan.

The tyrine species Tyrodes segrex Kurbatov, 1990, known from Far East Russia, is newly discovered from Japan, and Tyrodes amamianus sp. nov. is described from Amami-shima Is., Japan. Also, we suggest that some characteristics may be useful for the diagnosis of the genus and provide an updated diagnosis of Tyrodes segrex.

Comparative distribution of Arcadlin/Protocadherin-8 mRNA in the intact and ischemic brains of adult mice.

The structural plasticity of dendritic spines serves as the adaptive capabilities of the central nervous system to various stimuli. Among these stimuli, cerebral ischemia induces dynamic alterations in neuronal network activity. Arcadlin/Paraxial protocadherin/Protocadherin-8 (Acad), a regulator of dendritic spine density, is strongly induced by activating stimuli to the neurons. However, the detailed distribution of Acad in normal and ischemic adult brains remains unclear. We comprehensively described Acad expression patterns in normal and ischemic adult brains by in situ hybridization histochemistry. We found that intact adult brains expressed Acad in the piriform cortex, dentate gyrus, hippocampal CA3, entorhinal cortex, amygdala, and hypothalamus. Acad expression was dramatically upregulated in the piriform cortex, olfactory area, dentate gyrus, entorhinal cortex, prefrontal cortex, insular cortex, amygdala, and septohippocampal nucleus 4 h after cerebral ischemia. Cerebral ischemia induced widespread neuronal activation, which was required for Acad upregulation. Our data suggested the involvement of Acad in the adaptive plasticity and remodeling of the neuronal network in the limbic and paralimbic systems.

HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning with very low-dose antithymocyte globulin for relapsed/refractory acute leukemia in pediatric patients: a single-institution retrospective analysis.

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.

Suppression of axillary odor and control of axillary bacterial flora by erythritol.

BACKGROUND: Erythritol is a sugar alcohol with 4 carbon atoms that has approximately 75% of the sweetness of sucrose. It is a safe and widely used food component. AIMS: We herein investigated the growth inhibitory effects on axillary odor-causing bacteria and axillary odor-reducing effects of erythritol. METHODS: Growth tests in vitro were performed on Corynebacterium minutissimum, C. striatum, and Staphylococcus epidermidis. An axillary odor sensory test and axillary bacterial flora analysis were then conducted. A test product containing erythritol was applied to the axillae of 18 subjects. RESULTS: Erythritol significantly inhibited the growth of tested bacteria. The results of the axillary odor sensory test showed that the median values for each odor intensity of Total axillary odor intensity, Animal, Milk-fat, Damp-dried dust cloth, and Sourness were significantly lower in the test product application group than in the placebo group (p = 0, 0.008, 0.025, 0.004, 0, 0.001, respectively). The axillary flora analysis revealed that the relative abundance of the most dominant bacteria was lower in the test product application group than in the placebo group. Furthermore, the diversity of the total bacterial flora was significantly higher in the test product application group (p = 0.048). CONCLUSION: The present results suggest that erythritol inhibits the growth of the predominant bacteria in the axilla, increases the diversity of the bacterial flora, controls the bacterial flora of the skin to a healthy abundance ratio, and reduces axillary odor.

Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children.

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m2, melphalan (MEL) 210 mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.

Stieltjes constants of L-functions in the extended Selberg class.

Let f be an arithmetic function and let S # denote the extended Selberg class. We denote by L ( s ) = ∑ n = 1 ∞ f ( n ) n s the Dirichlet series attached to f. The Laurent-Stieltjes constants of L ( s ) , which belongs to S # , are the coefficients of the Laurent expansion of L at its pole s = 1 . In this paper, we give an upper bound of these constants, which is a generalization of many known results.

Two new species of Pseudophanias Raffray from Myanmar (Coleoptera: Staphylinidae: Pselaphinae).

Two new species of the genus Pseudophanias Raffray, P. spinicornis sp. nov. and P. tanintharyiensis sp. nov., are described as the first named species of the genus from Myanmar.

Effects of cyclic tensile strain and microgravity on the distribution of actin fiber and Fat1 cadherin in murine articular chondrocytes.

Chondrocytes as mechano-sensitive cells can sense and respond to mechanical stress throughout life. In chondrocytes, changes of structure and morphology in the cytoskeleton have been potentially involved in various mechano-transductions such as stretch-activated ion channels, integrins, and intracellular organelles. However, the mechanism of cytoskeleton rearrangement in response to mechanical loading and unloading remains unclear. In this study, we exposed chondrocytes to a physiological range of cyclic tensile strain as mechanical loading or to simulated microgravity by 3D-clinostat that produces an unloading environment. Based on microarray profiling, we focused on Fat1 that implicated in the formation and rearrangement of actin fibers. Next, we examined the relationship between the distribution of Fat1 proteins and actin fibers after cyclic tensile strain and microgravity. As a result, Fat1 proteins did not colocalize with actin stress fibers after cyclic tensile strain, but accumulated near the cell membrane and colocalized with cortical actin fibers after microgravity. Our findings indicate that Fat1 may mediate the rearrangement of cortical actin fibers induced by mechanical unloading.

Starburst-Shaped D-π-A Chromophores Possessing a Hexaethynylbenzene Core for Dye-Sensitized Solar Cells.

Two starburst-shaped organic chromophores, incorporating a hexaethynylbenzene core modified by five donor branches (D-branches) of (p-dioctylaminostyryl)benzene and one acceptor/anchoring branch (A-branch) of either carboxylic acid-terminated phenylethynylbenzene (SB-07) or cyanoacrylic acid-terminated diketopyrrolopyrrole (DPP)-thiophene (SB-08), were synthesized and applied to dye-sensitized solar cells (DSSCs). In these chromophores, the common donor moiety, five (p-dioctylaminostyryl)phenyl groups, exhibits excellent optical absorption in the visible region (molar absorption coefficient ε > 105 M-1 cm-1 below 500 nm). The A-branch of SB-07 does not possess strong electron-accepting properties; however, the A-branch of SB-08, the DPP-thiophene moiety, serves as a strong electron acceptor site. Furthermore, the intramolecular charge-transfer (ICT) transition between the thiophene and DPP moieties extends the optical absorption range to the near-infrared region (∼800 nm). Optimized DSSC devices using SB-08 with coadsorption of chenodeoxycholic acid, in conjunction with iodide/triiodide-based electrolytes, exhibited incident photon-to-current conversion efficiency (IPCE) exceeding 70% in the 370-700 nm range and over 20% even at 800 nm, with a short-circuit photocurrent density (Jsc) of 19.3 mA cm-2 and a power conversion efficiency (PCE) of 6.4% under AM 1.5G illumination (100 mW cm-2). These results are considerably better than those of SB-07 (Jsc = 7.0 mA cm-2, PCE = 3.3%). The starburst-shaped architecture presented here can be used as a novel structural motif for metal-free organic sensitizers because it enables flexible modification of the multiple D-branches that enhance light-harvesting ability and the A-branch that serves as an excited electron transport pathway.

Voluntary running exercise after focal cerebral ischemia ameliorates dendritic spine loss and promotes functional recovery.

Cerebral infarction causes motor, sensory, and cognitive impairments. Although rehabilitation enhances recovery of activities of daily living after cerebral infarction, its mechanism remains elusive due to the lack of reproducibility and low survival rate of brain ischemic model animals. Here, to investigate the relationship between rehabilitative intervention, motor function, and pathophysiological remodeling of the tissue in the ipsilateral hemisphere after cerebral infarction, we took advantage of a highly reproducible model of cerebral infarction using C.B-17/Icr-+/+Jcl mice. In this model, we confirmed that voluntary running exercise improved functional recovery after ischemia. Exercise did not alter the volume of infarction or survived cortex, or the number of NeuN-labeled cells in the peri-infarct cortex. In mice who did not exercise, the number of basal dendritic spines of layer 5 pyramidal cells decreased in the peri-infarct motor cortex, whereas in mice who exercised it remained at the normal level. The voluntary exercise intervention maintained basal dendritic spine density within the peri-infarct area, which may reflect an adaptive remodeling of the surviving neural circuitry that might contribute to promoting the recovery of activities of daily living.

Utilization of Mechanical Stress to Treat Osteoporosis: The Effects of Electrical Stimulation, Radial Extracorporeal Shock Wave, and Ultrasound on Experimental Osteoporosis in Ovariectomized Rats.

Current treatment options for osteoporosis primarily involve pharmacotherapies, but they are often accompanied by undesirable side effects. Utilization of mechanical stress which can noninvasively induce bone formation has been suggested as an alternative to conventional treatments. Here, we examined the efficacy of mechanical stress induced by electrical stimulation, radial extracorporeal shock waves, and ultrasound for estrogen-deficient osteoporosis. Female Wistar rats were divided into following five groups: sham-operated group, untreated after ovariectomy, and treated with electrical stimulation, radial extracorporeal shock wave, or ultrasound starting at 8 weeks after ovariectomy for 4 weeks. Trabecular bone architecture of the femur was assessed by micro-CT and its biomechanical properties were obtained by mechanical testing. The femurs were further evaluated by histochemical, immunohistochemical, and real-time PCR analyses. Radial extracorporeal shock wave and ultrasound treatment improved trabecular bone microarchitecture and bone strength in osteoporotic rats, but not electrical stimulation. The shock wave decreased osteoclast activity and RANKL expression. The exposure of ultrasound increased osteoblast activity and ß-catenin-positive cells, and they decreased sclerostin-positive osteocytes. These findings suggest that mechanical stress induced by radial extracorporeal shock wave and ultrasound can improve estrogen-deficient bone loss and bone fragility through promoted bone formation or attenuated bone resorption.