Novel powder processing technologies for production of rare-earth permanent magnets.

Post-neodymium magnets that possess high heat resistance, coercivity, and (BH)max are desired for future-generation motors. However, the candidate materials for post-neodymium magnets such as Sm2Fe17N3 and metastable magnetic alloys have certain process-related problems: low sinterability due to thermal decomposition at elevated temperatures, deterioration of coercivity during sintering, and the poor coercivity of the raw powder. Various developments in powder processing are underway with the aim of overcoming these problems. So far, the development of advanced powder metallurgy techniques has achieved Sm2Fe17N3 anisotropic sintered magnets without coercivity deterioration, and advances in chemical powder synthesis techniques have been successful in producing Sm2Fe17N3 fine powders with huge coercivity. The challenge of a new powder process is expected to open the way to realizing post-neodymium magnets.

Upregulation of IFN-ß induced by Sema4D-dependent partial Erk1/2 inhibition promotes NO production in microglia.

Interactions between Sema4D and its receptors, PlexinB1 and CD72, induce various functions, including axon guidance, angiogenesis, and immune activation. Our previous study revealed that Sema4D is involved in the upregulation of nitric oxide production in microglia after cerebral ischemia. In this study, we investigated the underlying mechanisms of the enhancement of microglial nitric oxide production by Sema4D. Primary microglia expressed PlexinB1 and CD72, and cortical microglia expressed CD72. Sema4D promoted nitric oxide production and slightly inhibited Erk1/2 phosphorylation in microglia. Partial Erk1/2 inhibition enhanced microglial nitric oxide production. Inhibition of Erk1/2 phosphorylation induced the expression of Ifn-ß mRNA, and IFN-ß promoted nitric oxide production in microglia. In the ischemic cortex, the expression of Ifn-ß mRNA was downregulated by Sema4D deficiency. These findings indicated that the enhancement of nitric oxide production by Sema4D is involved in partial Erk1/2 inhibition and upregulation of IFN-ß.

Endothelial specific deletion of FOXO1 alters pericyte coverage in the developing retina.

Pericytes are mural cells that cover small blood vessels. While defects in pericyte coverage are known to be involved in various vessel related pathologies, including diabetic retinopathy, the molecular mechanisms underlying pericyte coverage are not fully understood. In this study, we investigated the contribution of the forkhead transcription factor FOXO1 in endothelial cells to pericyte coverage in the developing retina. We observed retinal pericytes in tamoxifen-inducible endothelium-specific Foxo1 deletion mice. Tamoxifen was injected at postnatal day 1-3 and the retinas were harvested at P21. Our results demonstrated that Foxo1 deletion in the endothelium affected arteriole pericyte morphology without altering pericyte number, proliferation, and apoptosis. We hypothesized that abnormal pericyte morphogenesis in the knockout retina was caused by impaired pericyte differentiation. FOXO1 silencing by siRNA in the primary artery endothelium further revealed that THBS1 (thrombospondin 1), which promotes pericyte differentiation via TGFß activation, was reduced in the FOXO1-deficient endothelium. Immunohistochemistry of FOXO1 knockout mice showed reduced numbers of phospho-Smad3+ arteriole pericytes compared with wild-type mice. In addition, endothelium-pericyte co-culture analysis revealed that pericytes cultured with FOXO1-deficient endothelial cells failed to differentiate sufficiently; this failure was partially rescued by the addition of recombinant THBS1 to the supernatant. The findings suggest that endothelial FOXO1 contributes to pericyte differentiation via regulation of THBS1 expression. This study provides new insights into the molecular mechanism of pericyte coverage in the context of endothelium-derived regulation and highlights a new therapeutic target for pericyte-related pathology.

Green Tea Polyphenol Epigallocatechin-3-gallate Suppresses Toll-like Receptor 4 Expression via Up-regulation of E3 Ubiquitin-protein Ligase RNF216.

Toll-like receptor 4 (TLR4) plays an essential role in innate immunity through inflammatory cytokine induction. Recent studies demonstrated that the abnormal activation of TLR4 has a pivotal role in obesity-induced inflammation, which is associated with several diseases, including hyperinsulinemia, hypertriglyceridemia, and cardiovascular disease. Here we demonstrate that (-)-epigallocatechin-3-O-gallate, a natural agonist of the 67-kDa laminin receptor (67LR), suppressed TLR4 expression through E3 ubiquitin-protein ring finger protein 216 (RNF216) up-regulation. Our data indicate cyclic GMP mediates 67LR agonist-dependent RNF216 up-regulation. Moreover, we show that the highly absorbent 67LR agonist (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3″Me) significantly attenuated TLR4 expression in the adipose tissue. EGCG3″Me completely inhibited the high-fat/high-sucrose (HF/HS)-induced up-regulation of tumor necrosis factor α in adipose tissue and serum monocyte chemoattractant protein-1 increase. Furthermore, this agonist intake prevented HF/HS-induced hyperinsulinemia and hypertriglyceridemia. Taken together, 67LR presents an attractive target for the relief of obesity-induced inflammation.

Study of entropic characteristics of strongly correlated systems using VO2 as a model case.

To explain the huge caloric effects often observed in the first-order electronic phase transition in the strongly correlated oxides, the entropic characteristics are investigated in VO2. By evaluating the spin and charge fluctuations based on the local moment model and the Sommerfeld coefficient in the high-temperature rutile phase, it is found that these fluctuations of the high-temperature phase are the main source of the entropic change during the transition. This mode of entropic change is realized by the quenching of these fluctuations owing to the formation of a singlet bonding state in the low-temperature monoclinic phase. By introducing oxygen deficiency, a vagueness in the gap at the Fermi level is confirmed by the transport data, the X-ray photoelectron spectra and also the electronic structure calculated by the first-principles calculations. In this case, the entropic feature at the transition is weakened. Consequently, the large caloric phenomena of the strongly correlated oxides are a result of the conversion of the internal energy gain owing to the orbital selection at the ground state into the free energy gain owing to the spin and charge fluctuations at finite temperature.

A Case of a Nasopharyngeal Chondroma Originating from the Eustacian Tube.

Chondroma of the head and neck are commonly found in the nasal cavity, paranasal sinus, or larynx but rarely at other sites. Here we report a rare case of nasopharyngeal chondroma arising from the Eustacian tube. The patient was a 55-year-old male with chief complaints of nasal obstruction and left ear fullness. Nasal observation showed a white mass lesion filling the area extending from the left Eustachian tube to the nasopharynx. Computed tomography and magnetic resonance imaging of the pharynx showed a mass lesion occupying the nasopharyngeal cavity. We performed surgical excision of the nasopharyngeal tumor via the endoscopic endonasal approach. Histopathological examination performed at our hospital led to the diagnosis of chondroma. As of this report, 4 months have passed since surgery and the patient has not experienced a relapse. Although chondroma is a benign tumor, local recurrence or malignant transformation is possible. Therefore, these patients should continue to be followed up regularly.

Effects of self-monitoring using an accelerometer on physical activity of older people with long-term care insurance in Japan: a randomized controlled trial.

PURPOSE: This study aimed to investigate the effects of a self-monitoring intervention to promote an increase in physical activity, as measured by step count, and reduce sedentary behavior in older people covered by the long-term care insurance system (LTCI) in Japan. METHODS: This was a randomized controlled trial conducted at a daycare center from October 2022 to January 2023. Fifty-two older adults with LTCI who were able to walk with or without aids were assigned to an intervention (n = 26) group and control (n = 26) group. During the 5-week follow-up period, the intervention group received education on physical activity and self-monitoring such as goal setting, self-management and feedback. The primary outcome was step count, and the secondary outcome was sedentary behavior. RESULTS: Participants who completed the study to the end of the 5-week follow-up and drop-out participants for whom outcome data were available were included in the final analysis of 57 participants, n = 24 (79.8 ± 8.8 years, male 25.5%) in the intervention group and n = 23 (82.5 ± 8.5 years, male 39.1%) in the control group. Comparisons between the two groups at baseline showed no significant differences. In the results of a two-way mixed analysis of variance (ANOVA) including 2 (group: control, intervention) × 2 (term: baseline, 5-week follow-up) factors, an interaction was observed in the number of steps, sedentary behavior, and light physical activity (p < 0.05). CONCLUSION: Self-monitoring of physical activity using an accelerometer may be effective in increasing the number of steps and light physical activity and in reducing sedentary behavior in older people with LTCI. CLINICAL TRIAL REGISTRATION: UMIN000052044, registered on 2023/08/29.

Sema4D as an inhibitory regulator in oligodendrocyte development.

The specific functions of intrinsic regulators of OL differentiation are poorly understood. Sema4D, originally found as a negative regulator of axon guidance, is mainly expressed by oligodendrocytes in the postnatal brain, and our previous study revealed that the lack of Sema4D induced an increase in the number of oligodendrocytes in the cerebral cortex, suggesting that Sema4D may function as an intrinsic regulator of oligodendrocyte development. In this study, we assessed the effects of Sema4D deficiency and of the exogenous addition of Sema4D on oligodendrocyte differentiation. Sema4D deficiency induced an increase in the number of oligodendrocytes in the cerebral cortex at postnatal day 14 and later, without increase in the number of oligodendrocyte progenitor cells. This increase was also observed in cultured oligodendrocytes obtained from Sema4D-deficient mice. Then we investigated whether Sema4D deficiency can increase the proliferation of the progenitor cells or influence the apoptosis. Apoptotic oligodendrocytes were markedly reduced in number in the developing cerebral cortex and in cultured oligodendrocytes obtained from Sema4D-deficient mice, although no significant change was found in proliferation of oligodendrocyte progenitor cells. Exogenous addition of Sema4D prevented the oligodendrocytes from this reduction of apoptosis, and further enhanced apoptosis in oligodendrocytes. Thus, Sema4D may act as an intrinsic inhibitory regulator of oligodendrocyte differentiation by promoting apoptosis.

Identification of a negative regulatory region for the exchange activity and characterization of T332I mutant of Rho guanine nucleotide exchange factor 10 (ARHGEF10).

The T332I mutation in Rho guanine nucleotide exchange factor 10 (ARHGEF10) was previously found in persons with slowed nerve conduction velocities and thin myelination of peripheral nerves. However, the molecular and cellular basis of the T332I mutant is not understood. Here, we show that ARHGEF10 has a negative regulatory region in the N terminus, in which residue 332 is located, and the T332I mutant is constitutively active. An N-terminal truncated ARHGEF10 mutant, ARHGEF10 ΔN (lacking amino acids 1-332), induced cell contraction that was inhibited by a Rho kinase inhibitor Y27632 and had higher GEF activity for RhoA than the wild type. The T332I mutant also showed the phenotype similar to the N-terminal truncated mutant. These data suggest that the ARHGEF10 T332I mutation-associated phenotype observed in the peripheral nerves is due to activated GEF activity of the ARHGEF10 T332I mutant.

Massive transformation in FeNi nanopowders with nanotwin-assisted nitridation.

L10-ordered FeNi alloy (tetrataenite), a promising candidate for rare-earth-free and low-cost permanent magnet applications, is attracting increasing attention from academic and industrial communities. Highly ordered single-phase L10-FeNi is difficult to synthesis efficiently because of its low chemical order-disorder transition temperature (200-320 °C). A non-equilibrium synthetic route utilizing a nitrogen topotactic reaction has been considered a valid approach, although the phase transformation mechanism is currently unknown. Herein, we investigated the basis of this reaction, namely the formation mechanism of the tetragonal FeNiN precursor phase during the nitridation of FeNi nanopowders. Detailed microstructure analysis revealed that the FeNiN precursor phase could preferentially nucleate at the nanotwinned region during nitridation and subsequently grow following a massive transformation, with high-index irrational orientation relationships and ledgewise growth motion detected at the migrating phase interface. This is the first report of a massive phase transformation detected in an Fe-Ni-N system and provides new insights into the phase transformation during the nitriding process. This work is expected to promote the synthetic optimization of fully ordered FeNi alloys for various magnetic applications.

Incomplete pseudo-Meigs' syndrome caused by endometrial ovarian cyst: A case report.

A 63-year-old female was admitted to our hospital with history of persistent dyspnea. Right pleural effusion and ovarian tumor were discovered, but here were no significant findings on thoracoscopy under local anesthesia. The pleural effusion was suspected to be secondary to Meigs' syndrome, and a diagnosis of endometriotic ovarian cyst was made. Since the pleural effusion resolved after surgery, the patient was diagnosed with incomplete pseudo-Meigs' syndrome. We consider this to be a valuable case, as there are no previously reported cases of pseudo-Meigs' syndrome derived from an endometriotic ovarian cyst, to the best of our knowledge.

Sema4D deficiency results in an increase in the number of oligodendrocytes in healthy and injured mouse brains.

Semaphorins, a family of secreted and membrane-bound proteins, are known to function as repulsive axon guidance molecules. Sema4D, a class 4 transmembrane-type semaphorin, is expressed by oligodendrocytes in the central nervous system, but its role is unknown. In this study, the effects of Sema4D deficiency on oligodendrocytes were studied in intact and ischemic brains of adult mice. As observed in previous studies, Sema4D marked by beta-galactosidase in Sema4D mutant mice was localized exclusively on myelin-associated glycoprotein (MAG)-positive oligodendrocytes but not on NG2-positive oligodendrocyte progenitor cells (OPCs). Although there was no difference in the number of the latter cells between Sema4D-deficient and wild-type mice, the number of MAG-positive cells was significantly increased in the cerebral cortex of both nonischemic and postischemic brains of Sema4D-deficient mice. Cell proliferation, observed by using bromodeoxyuridine incorporation, was evident in the MAG-positive cells that developed after cerebral ischemia. These data indicate that Sema4D is involved in oligodendrogenesis during development and during recovery from ischemic injury.

Changes in L-arginine metabolism by Sema4D deficiency induce promotion of microglial proliferation in ischemic cortex.

Cerebral ischemia induces neuroinflammation and microglial activation, in which activated microglia upregulate their proliferative activity and change their metabolic states. In activated microglia, l-arginine is metabolized competitively by inducible nitric oxide synthase (iNOS) and arginase (Arg), which then synthesize NO or polyamines, respectively. Our previous study demonstrated that Sema4D deficiency inhibits iNOS expression and promotes proliferation of ionized calcium-binding adaptor molecule 1 (Iba1)-positive (Iba1+) microglia in the ischemic cortex, although the underlying mechanisms were unclear. Using middle cerebral artery occlusion, we tested the hypothesis that Sema4D deficiency alters the balance of l-arginine metabolism between iNOS and Arg, leading to an increase in the production of polyamines, which are an essential factor for cell proliferation. In the peri-ischemic cortex, almost all iNOS+ and/or Arg1+ cells were Iba1+ microglia. In the peri-ischemic cortex of Sema4D-deficient (Sema4D-/-) mice, the number of iNOS+ Arg1- Iba1+ microglia was smaller and that of iNOS- Arg1+ Iba1+ microglia was greater than those of wild-type (WT) mice. In addition, urea and polyamine levels in the ischemic cortex of Sema4D-/- mice were higher than those of WT mice; furthermore, the presence of Sema4D inhibited polyamine production in primary microglia obtained from Sema4D-/- mice. Finally, microglia cultured under polyamine putrescine-supplemented conditions demonstrated increased proliferation rates over non-supplemented controls. These findings indicate that Sema4D regulates microglial proliferation at least in part by regulating the competitive balance of l-arginine metabolism.

[Case of pulmonary coccidioidomycosis presented with multiple infiltrative opacities].

A 54-year-old man was admitted to our hospital to be operated on for inguinal hernia, but complained of dry cough and cervical lymph nodes swelling after traveling to California in the United States. The chest X-ray films taken on admission showed consolidations in both lungs. The laboratory data revealed an increase in white blood cell counts with eosinophilia, and elevated ESR, IgE and beta-D-glucan. The biopsied lung specimen by VATS showed epithelioid granulomas consisting of giant cells and eosinophils. In addition, spherulitic forms filled with endopores were detected in the specimen. A diagnosis of primary pulmonary coccidioidomycosis was made. Eosinophilia and elevated in IgE and beta-D-glucan were closely related to the severity of the disease gravity after the treatment with fluconazole.

Sema4D-plexin-B1 implicated in regulation of dendritic spine density through RhoA/ROCK pathway.

Plexin-B1, Sema4D receptor, mediates retraction and extension signals in axon guidance by associating with PDZ-containing Rho guanine nucleotide exchange factors (PDZ-RhoGEFs) which can activate a small Rho GTPase RhoA. RhoA is implicated in spine formation by rearranging actin cytoskeleton. Exogenous application of Sema4D to cultured neurons caused activation of RhoA, increase of spine density and changes in spine shape. Sema4D-induced changes in spine density were blocked by either Rho-kinase (a downstream of RhoA, ROCK) inhibitor Y-27632 or by overexpression of plexin-B1 mutant lacking the C-terminus which no longer associates with PDZ-RhoGEFs. This study suggests that Sema4D-plexin-B1 play a crucial role in spine formation by regulating RhoA/ROCK pathway.

Absence of Sema4D improves oligodendrocyte recovery after cerebral ischemia/reperfusion injury in mice.

Sema4D, originally identified as a negative regulator of axon guidance during development, is involved in various physiological and pathological responses. In this study, we evaluated the effect of Sema4D-deficiency on oligodendrocyte restoration after the cerebral ischemia/reperfusion using direct ligation of the middle cerebral artery followed by reperfusion. In both Sema4D(+/+) wild-type and Sema4D(-/-) null mutant mice, the peri-infarct area showed a decrease in the number of oligodendrocytes at 3 days post-reperfusion. Subsequently, the number of oligodendrocytes was observed to gradually recover in both groups. Sema4D-deficient mice, however, showed an enhanced recovery of oligodendrocytes and an upregulation of oligodendrocyte progenitor cells at days 14 and 28 of reperfusion. Cell proliferation identified by incorporation of bromodeoxyuridine was enhanced in Sema4D(-/-) mice from days 3 to 14 post-reperfusion compared to the Sema4D(+/+) mice. Furthermore, apoptotic cell death of oligodendrocytes was reduced at days 7 post-reperfusion in Sema4D(-/-) mice compared to Sema4D(+/+) mice. These findings indicate that enhanced proliferation of progenitor cells and survival of oligodendrocytes resulted in improved oligodendrocyte recovery in Sema4D(-/-) mice. This may provide a new approach for neurorestorative treatment in patients with stroke, which aims to manipulate endogenous oligodendrogenesis and thereby to promote brain repair after stroke.

Green tea extract containing a highly absorbent catechin prevents diet-induced lipid metabolism disorder.

We investigated the effects of extracts of Benifuuki (a tea cultivar that contains methylated catechins such as epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me)) in mice fed a high-fat/high-sucrose (HF/HS) diet. This tea cultivar was then compared with an extract of Yabukita (a popular tea cultivar that lacks methylated catechins). For 6 weeks, C57BL/6J mice were fed either HF/HS diet with or without tea extracts from tea cultivars, which contained almost identical ingredients except for methylated catechins (i.e., Yabukita (0.2% and 1%) or Benifuuki (0.2% and 1%) extract powders). Supplementation with Benifuuki 0.2% markedly lowered plasma levels of TG and NEFAs compared with mice supplemented with Yabukita 0.2%. The diet containing Benifuuki 1% decreased adipose tissue weights, liver TG, and expression of lipogenic genes in the liver. These results suggested that Benifuuki had much greater lipid-lowering effects than Yabukita. Taken together, these data suggest that methylated catechins direct the strong lipid-lowering activity of Benifuuki.

Reduction of N2 by supported tungsten clusters gives a model of the process by nitrogenase.

Metalloenzymes catalyze difficult chemical reactions under mild conditions. Mimicking their functions is a challenging task and it has been investigated using homogeneous systems containing metal complexes. The nitrogenase that converts N(2) to NH(3) under mild conditions is one of such enzymes. Efforts to realize the biological function have continued for more than four decades, which has resulted in several reports of reduction of N(2), ligated to metal complexes in solutions, to NH(3) by protonation under mild conditions. Here, we show that seemingly distinct supported small tungsten clusters in a dry environment reduce N(2) under mild conditions like the nitrogenase. N(2) is reduced to NH(3) via N(2)H(4) by addition of neutral H atoms, which agrees with the mechanism recently proposed for the N(2) reduction on the active site of nitrogenase. The process on the supported clusters gives a model of the biological N(2) reduction.

Change in PGC-1α expression in rat skeletal muscle after low-intensity prolonged swimming exercise.

After 6-h low-intensity swimming exercise (LIE), peroxisome proliferator-activated receptor γ coactivator -1α (PGC-1α) in whole and nuclear fractions in rat skeletal muscle was higher than the control rats' muscles up to 18 h after LIE. However, no study has reported change in PGC-1α content after that. Therefore, we measured PGC-1α in whole and nuclear fractions in rat skeletal muscle up to 24 h after LIE. Furthermore, we evaluated change in the mRNA of δ-aminolevulinate synthase (ALAS), a mitochondrial protein, to clarify in which fraction of PGC-1α has a physiological role as a transcriptional coactivator for enhancing the mitochondrial oxidative enzymes after exercise. We measured PGC-1α protein content in whole and nuclear fractions in the epitrochlearis (EPI) muscle of male Sprague-Dawley rats (age: 6 w; body weight: 180-200 g) after LIE by Western-blot analysis. The ALAS mRNA content was quantified by RT-PCR. The PGC-1α contents in whole fractions in the rat EPI muscle were 73% and 75% higher than that of the control rats' muscle, 18 h and 24 h after LIE, respectively. The PGC-1α content in nuclear fractions in the muscle and ALAS mRNA was higher than that of the control rats' muscle by 58% and 25%, respectively, while they returned to the control level 24 h after LIE. The present investigation demonstrated that the time-course of PGC-1α content in nuclear fractions in the EPI muscle was the same as the ALAS mRNA, suggesting that PGC-1α in the nucleus may have a physiological function as a transcriptional coactivator for enhancing mitochondrial protein expression after exercise.

A DIGE proteomic analysis for high-intensity exercise-trained rat skeletal muscle.

Exercise training induces various adaptations in skeletal muscles. However, the mechanisms remain unclear. In this study, we conducted 2D-DIGE proteomic analysis, which has not yet been used for elucidating adaptations of skeletal muscle after high-intensity exercise training (HIT). For 5 days, rats performed HIT, which consisted of 14 20-s swimming exercise bouts carrying a weight (14% of the body weight), and 10-s pause between bouts. The 2D-DIGE analysis was conducted on epitrochlearis muscles excised 18 h after the final training exercise. Proteomic profiling revealed that out of 800 detected and matched spots, 13 proteins exhibited changed expression by HIT compared with sedentary rats. All proteins were identified by MALDI-TOF/MS. Furthermore, using western immunoblot analyses, significantly changed expressions of NDUFS1 and parvalbumin (PV) were validated in relation to HIT. In conclusion, the proteomic 2D-DIGE analysis following HIT-identified expressions of NDUFS1 and PV, previously unknown to have functions related to exercise-training adaptations.