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The energy transfer from wave to particle occurs in collisionless plasma through the interaction between particle and wave, associated with the deformation of ion velocity space from Maxwell-Boltzmann distribution. Here we show the direct observation of mass-dependent collisionless energy transfer via Landau and transit-time damping in a laboratory plasma. The Landau and transit-time damping are confirmed by the bipolar velocity-space signature of the ion velocity distribution function, measured by fast charge exchange spectroscopy with a time resolution less than ion-ion collision time. The excellent agreement between the resonant phase velocity evaluated from the bipolar velocity-space signature and the wave's phase velocity, estimated from the frequency of the magnetohydrodynamics oscillation measured with the plasma displacement is clear evidence for the Landau damping. The energy transfer from solitary wave to fully ionized carbon impurity ions is larger than that of bulk ions 2-3 times due to heavier mass. Landau damping and transit-time damping are known resonant wave-particle interactions in which energy is transferred from the wave to ions or electrons in the plasma. The authors study collisionless energy transfer in a plasma of deuterium and carbon atoms, observing that more energy is transferred to the heavier carbon ions, suggestive of a mass-dependence in the process. [ABSTRACT FROM AUTHOR]

Bexarotene selectively activates retinoid X receptor, which is a commonly used anticancer agent for cutaneous T-cell lymphoma. In this study, we aimed to investigate the anticancer effect of bexarotene and its underlying mechanism in ovarian cancer in vitro. The ES2 and NIH:OVACAR3 ovarian cancer cell lines were treated with 0, 5, 10, or 20 µM of bexarotene. After 24 h, cell number measurement and lactate dehydrogenase (LDH) cytotoxicity assay were performed. The effect of bexarotene on CDKN1A expression, cell cycle-related protein, cell cycle, pyroptosis, and apoptosis was evaluated. Bexarotene reduced cell proliferation in all concentrations in both the cells. At concentrations of > 10 µM, extracellular LDH activity increased with cell rupture. Treatment using 10 µM of bexarotene increased CDKN1A mRNA levels, decreased cell cycle-related protein expression, and increased the sub-G1 cell population in both cells. In ES2 cells, caspase-4 and GSDME were activated, whereas caspase-3 was not, indicating that bexarotene-induced cell death might be pyroptosis. A clinical setting concentration of bexarotene induced cell death through caspase-4–mediated pyroptosis in ovarian cancer cell lines. Thus, bexarotene may serve as a novel therapeutic agent for ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether granulocyte–macrophage colony-stimulating factor (GM-CSF)-containing medium could improve embryo-transfer outcomes in frozen-thawed blastocyst transfer. Methods: Patients who underwent frozen-thawed blastocyst transfer (430 women, aged 30–39 years, 566 cycles) were analyzed. Frozen-thawed blastocysts were cultured in GM-CSF-containing medium or control medium for 3–5 h, followed by transfer to the uterus. The embryo-transfer outcomes in the two groups were measured and compared, and a propensity score matching (1:1) method was used to balance the differences in baseline characteristics. We analyzed 213 matched samples. Results: In patients who underwent frozen-thawed blastocyst transfer with GM-CSF, the percentage of human chorionic gonadotropin-positive cases, biochemical pregnancies, clinical pregnancies, ongoing pregnancies, and live birth rates was 60.6%, 7.98%, 52.6%, 42.9%, and 40.9%, respectively, as compared with 45.1%, 3.29%, 41.8%, 31.1%, and 30.5%, respectively, for the control groups. The rates of human chorionic gonadotropin positivity (odds ratio [OR]: 1.87, 95% confidence interval: [CI]: 1.27–2.75), biochemical pregnancy (2.55, 1.04–6.29), clinical pregnancy (1.54, 1.05–2.27), ongoing pregnancy (1.64, 1.13–2.41), and live birth (1.67, 1.14–2.45) were significantly higher in the GM-CSF group than the control group. The incidence of pregnancy loss (22.3% vs. 27.0%) did not significantly differ between the groups. Conclusion: The use of a GM-CSF-containing medium for blastocyst-recovery culture improved the live birth rate as a result of increased implantation rate in the frozen-thawed blastocyst-transfer cycle. The use of GM-CSF-containing medium following blastocyst thawing could be an effective choice for improving the blastocyst-transfer outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To analyze whether the morphokinetics algorithm based on data from day 5 blastocyst transfer (KIDScoreD5 version 3) can predict the pregnancy rate of both day 5 and day 6 blastocyst transfers. Methods: The relationship between KIDScoreD5 and clinical pregnancy rate was evaluated using the Cochran–Armitage test and receiver‐operating characteristic (ROC) curve analysis. Results: A positive correlation was observed between the KIDScoreD5 value and clinical pregnancy rate for both day 5 (p = 0.0003) and day 6 blastocysts (p = 0.0019) using the Cochrane–Armitage test. ROC curve analysis showed that the area under the curve (AUC) of KIDScoreD5 for clinical pregnancy was 0.627 (0.575–0.677, p < 0.0001) for day 5 blastocysts and 0.685 (0.571–0.780, p = 0.0009) for day 6 blastocysts. The combined analysis of both day 5 and day 6 blastocysts also showed an AUC of 0.680 (0.636–0.720, p < 0.0001), suggesting that it is possible to select embryos that are more likely to result in pregnancy. Conclusions: KIDScoreD5 could predict pregnancy not only in day 5 blastocysts but also in day 6 blastocysts. When both day 5 and day 6 blastocysts are vitrified, embryo selection by KIDScoreD5 is possible with a high prediction ability of pregnancy.The morphokinetics algorithm (KIDScoreD5) was able to predict pregnancy not only in day 5 blastocyst transfer but also in day 6 blastocysts. ROC curve analysis showed that the area under the curve (AUC) of KIDScoreD5 for clinical pregnancy was 0.627 (0.575‐0.677, p < 0.0001) for day 5 blastocysts and 0.685 (0.571‐0.780, p = 0.0009) for day 6 blastocysts. The combined analysis of both day 5 and day 6 blastocysts also showed an AUC of 0.680 (0.636‐0.720, p < 0.0001), suggesting that it is possible to select embryos that are more likely to lead to pregnancy. [ABSTRACT FROM AUTHOR]

We aimed to investigate why the incidence of embryos derived from oocytes with no pronuclei (0PN) decreases using time-lapse monitoring (TLM) versus fixed-point assessment in conventional IVF cycles. We analyzed 514 embryos monitored with TLM 6–9 h after insemination and 144 embryos monitored using microscopic assessment 18–21 h after insemination. The primary endpoint of this study was the incidence of 0PN-derived embryos in short insemination followed by TLM. The secondary endpoint was the duration of insemination. As exploratory endpoints, we analyzed the blastulation rate and cryo-warmed blastocyst transfer outcome of embryos with early PN fading, whereby PN disappeared within < 20 h following the initiation of insemination. The incidence of 0PN-derived embryo reduced more significantly through TLM than through fixed-point observation. The microscopic assessment time was more significantly delayed in the 0PN-derived embryo than that in the 2PN-derived embryo. The embryo with early PN fading formed good-quality blastocysts, and their pregnancy outcomes were similar to those of other embryos. Most 0PN-derived embryos in the fixed-point assessment might have resulted from missed observation of PN appearance in the early-cleaved embryos. TLM or strict laboratory schedule management may reduce 0PN-derived embryos by reducing missed PN observations. [ABSTRACT FROM AUTHOR]

Background: Although Escherichia coli is the most frequently isolated microorganism in acute biliary tract infections with bacteremia, data regarding its virulence are limited. Results: Information on cases of bacteremia in acute biliary tract infection in a retrospective study was collected from 2013 to 2015 at a tertiary care hospital in Japan. Factors related to the severity of infection were investigated, including patient background, phylogenetic typing, and virulence factors of E. coli, such as adhesion, invasion, toxins, and iron acquisition. In total, 72 E. coli strains were identified in 71 cases, most of which primarily belonged to the B2 phylogroup (68.1%). The presence of the iutA gene (77.3% in the non-severe group, 46.4% in the severe group, P = 0.011) and the ibeA gene (9.1% in the non-severe group, and 35.7% in the severe group, P = 0.012) was significantly associated with the severity of infection. Among the patient characteristics, diabetes mellitus with organ involvement and alkaline phosphatase were different in the severe and non-severe groups. Conclusions: We showed that bacteremic E. coli strains from acute biliary tract infections belonged to the virulent (B2) phylogroup. The prevalence of the iutA and ibeA genes between the two groups of bacteremia severity was significantly different. [ABSTRACT FROM AUTHOR]

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156–0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427–2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793–1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272–1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the fertilization, developmental, and pregnancy potentials in oocytes with narrow perivitelline space. Methods: Perivitelline space (PVS) of oocytes was evaluated at the time of ICSI, and those without sufficient PVS were judged as oocytes with narrow PVS (NPVS oocytes), and those with sufficient PVS formation were judged as oocytes with non-narrow PVS (non-NPVS oocytes). The analysis included 634 NPVS oocytes from 278 cycles and 12,121 non-NPVS oocytes from 1698 cycles. The fertilization and developmental potentials of NPVS and non-NPVS oocytes were compared by calculating odds ratios using a mixed-effects logistic regression model. We also compared the embryo transfer outcomes of those used for single vitrified-warmed blastocyst transfer after developing into the blastocyst stage. Results: NPVS oocytes had higher odds ratios for degeneration (adjusted odds ratio [aOR], 1.555; 95% confidence interval [CI], 1.096–2.206; p = 0.0133) and 0PN (aOR, 1.387; 95% CI, 1.083–1.775; p = 0.0095), resulting in a lower 2PN rate (aOR, 0.761; 95% CI, 0.623–0.929; p = 0.0072). Even embryos with confirmed 2PN had lower odds ratios for cleavage (aOR, 0.501; 95% CI, 0.294–0.853; p = 0.0109) and blastocyst development (Gardner criteria; CC–AA) rates (aOR, 0.612; 95% CI, 0.476–0.788; p = 0.0001). Blastocysts developed from NPVS oocytes had significantly lower odds ratios for clinical pregnancy (aOR, 0.435; 95% CI, 0.222–0.854; p = 0.0156) than those developed from non-NPVS oocytes. Conclusions: Oocytes with NPVS have low fertilization and developmental potential, as well as low likelihood of pregnancy. [ABSTRACT FROM AUTHOR]

Trapa spp. dominate many shallow eutrophic lakes in Japan, which must affect the nutrient dynamics in lakes. Trapa spp. are utilized by several animals, in particular the leaf beetle, Galerucella. To quantify the trophic links and material transfers between Trapa spp. and G. nipponensis, their seasonal dynamics, the amount of leaves being consumed, and carbon and nitrogen stable isotope ratios (δ13C and δ15N) in Lake Inba were tracked. Trapa spp. began to increase in May, reached their highest biomass in September, and disappeared in October. G. nipponensis exhibited continuous reproduction from May until October. Grazing by G. nipponensis did not seem to affect the abundance of Trapa, as the average percentage of Trapa leaf consumed was 3%. Rather, G. nipponensis was influenced by Trapa, as δ13C and δ15N of Trapa spp. and G. nipponensis showed very similar seasonal fluctuations. The difference in δ15N was 3-4‰, which indicates that Trapa leaves were a main food source for G. nipponensis and a trophic linkage exists between them. The estimated nitrogen and phosphorus amounts in Trapa corresponded to 1% of nitrogen and 18% of phosphorus in the entire lake. If G. nipponensis migrate and die in a terrestrial environment, G. nipponensis can transport certain nutrients from lake to terrestrial environments. The nutrients from Trapa spp. are mostly regenerated, except for that biomass transported to terrestrial ecosystems by humans. [ABSTRACT FROM AUTHOR]

Tensile and low cycle fatigue properties of Sn-5Sb (mass%) and Sn-10Sb (mass%) were investigated using miniature size specimens, and fracture behaviors of the specimens were observed. Tensile strength and 0.1% proof stress of both alloys decrease with increasing the temperature. The tensile strength and 0.1% proof stress of Sn-10Sb are higher than those of Sn-5Sb at 25°C. Elongation of Sn-5Sb decreases with increasing the temperature except for a strain rate of 2 × 10−1 s−1, while Sn-10Sb increases with increasing temperature. Although elongation of Sn-10Sb is lower than that of Sn-5Sb at 25°C, the difference between them is small at 150°C. Chisel-point fracture was observed in both alloys regardless of conditions of the tensile test. The low cycle fatigue lives of Sn-5Sb and Sn-10Sb alloys obey the Manson–Coffin equation, and the fatigue ductility exponent, α, was 0.54 for Sn-5Sb and 0.46 for Sn-10Sb in the temperature range from 25°C to 150°C. On the basis of the observation of fractured specimens and the investigation of α, it was clarified that the crack progress can be delayed by the formation of coarse SbSn compounds in the Sn-Sb alloy, and thus the fatigue properties can be improved. [ABSTRACT FROM AUTHOR]

Power cycle reliability of solder joints with Sn-5Sb (mass%) and Sn-10Sb (mass%) alloys was investigated. The effects of power cycling and heat aging on the growth of intermetallic compound (IMC) layers at the interfaces between Sn-Sb alloys and Cu plates were also investigated. In the power cycling test, the solder joint with Sn-10Sb has high reliability compared with that of Sn-5Sb. IMC layers grew in both joints with increasing number of power cycles. Compared with Sn-5Sb and Sn-10Sb, difference in growth kinetics of IMC layers was negligible. A similar tendency was observed in the heat aging test. Compared with the power cycling and the heat aging, growth of IMC layers at the aging temperature of 200°C is faster than that in the power cycling test at the temperature range of 100°C to 200°C, while that at the aging temperature of 100°C, the growth is slower. On the basis of the comparison between the power cycling and the heat aging, it was clarified that growth kinetics of IMC layers in the power cycling can be predicted by investigating growth kinetics of the IMC layer at the temperatures in the vicinity of the peak temperature in power cycling. [ABSTRACT FROM AUTHOR]

In this study, the fabrication of nickel (Ni)-cellulose nanofiber (CNF) composite electroplating films was attempted using sodium carboxymethyl cellulose (CMC) and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-oxidized CNF as CNF introduced with carboxy groups. As a result, co-deposition was confirmed for both CNFs, and the former showed 82% improvement in surface Vickers hardness compared to the plated film deposited from a conventional Watts bath without CNF. Although the latter showed slightly inferior 71% improvement, the surface roughness measurement showed a smoother surface than that of the plated copper material C1100. On the other hand, the film with CMC had a rough surface. The image analysis showed that the distance between co-deposited CNF on the surface of the plated film was 40% shorter on the specimen with TEMPO CNF than CMC, indicating that a fine dispersion was obtained. In addition, a co-deposition model was proposed in which Ni is deposited from the chelate complex formed between the carboxylate of CNF and Ni ions. CNF is fixed to the plated film surface by Ni deposition and the simultaneous bond of hydrogen ions to the carboxylate, resulting in a return to the carboxy group. [ABSTRACT FROM AUTHOR]

Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively (p = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively (p = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology. [ABSTRACT FROM AUTHOR]

Abstract: We previously demonstrated that an alarm pheromone released by male Wistar rats evokes several physiological and behavioral responses in other rats. In addition to these responses, the alarm pheromone increased the number of mounts needed for an ejaculation and decreased the hit rate (number of intromissions/sum of the mounts and intromissions). These effects were blocked by pretreatment by a corticotropin releasing hormone (CRH) receptor antagonist. However, the neural mechanisms underlying the modulation of sexual behavior by this pheromone remain unknown. In this study, we measured c-Fos expression in 22 brain sites in pheromone-exposed male rats 60min after their first ejaculation. The paraventricular nucleus was double-stained for c-Fos and CRH to determine which neurons were activated by the pheromone. The alarm pheromone increased the number of mounts, decreased the hit rate, and increased the number of cells double-labeled for c-Fos and CRH in the paraventricular nucleus. These results indicate that the alarm pheromone is a stressor. Pheromone-exposed rats also showed significantly increased c-Fos expression in the anterior division medial group, anterior division lateral group, and posterior division of the bed nucleus of the stria terminalis, the anterior part of the medial and the basolateral region of the amygdala, and the nucleus paragigantocellularis. Based on these results and previous findings, we propose that the alarm pheromone modifies sexual behavior by inducing CRH release that indirectly activates the nucleus paragigantocellularis. [Copyright &y& Elsevier]

N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) is the sulfotransferase responsible for biosynthesis of highly sulfated chondroitin sulfate CS-E. Although involvements of CS-E in neuronal cell functions have been extensively analyzed, the role of GalNAc4S-6ST in astrocytic tumor progression remains unknown. Here, we reveal that GalNAc4S-6ST transcripts were detected in astrocytic tumors derived from all 30 patients examined using quantitative reverse transcription-PCR analysis. Patients with high GalNAc4S-6ST mRNA expression had significantly worse outcome compared with patients with low expression, and multivariate survival analysis disclosed that GalNAc4S-6ST is an independent poor prognostic factor for astrocytic tumors. We then tested whether CS-E enhanced haptotaxic migration of glioblastoma U251- MG cells that endogenously express both the CS-E's scaffold tyrosine phosphatase ζ (PTPζ) and GalNAc4S-6ST, in the presence of CS-E's preferred ligands, pleiotrophin (PTN) or midkine (MK), using a modified Boyden chamber method. Haptotaxic stimulation of cell migration by PTN was most robust on control siRNA-transfected U251-MG cells, while that enhancing effect was cancelled following transduction of GalNAc4S-6ST siRNA. Similar results were obtained using MK, suggesting that both PTN and MK enhance migration of U251-MG cells by binding to CS-E. We also found that PTPζ as well as PTN and MK were frequently expressed in astrocytic tumor cells. Thus, our findings indicate that GalNAc4S-6ST mRNA expressed by astrocytic tumor cells is associated with poor patient prognosis likely by enhancing CS-E-mediated tumor cell motility in the presence of PTN and/or MK. [ABSTRACT FROM AUTHOR]

Information about the topics of the studies featured at the 33rd Annual Meeting of the American Society for Bone and Mineral Research held in San Diego, California on September 16-20, 2011 is presented. The topics of the studies include chondrocytes, cartilage biology and signaling systems. Other topics include gene regulation, transcription factors and epigenetics.

A winter outbreak of ascites in cultured Japanese amberjack Seriola quinqueradiata was examined. Affected fish displayed bloody ascitic fluid in the peritoneal cavity, their hearts were covered with a white membrane, their livers were congested and their kidneys were swollen. Renal tubular epithelia displayed extensive necrosis and often contained hyaline droplets, while some glomeruli showed atrophy and necrosis. Hematopoietic tissue in the kidney contained some swollen reticular cells. In the heart, an inflammatory reaction accompanied by edema, hemorrhage and fibrin deposition occurred in the epicardium of the atrium and ventricle and in the pericardial cavity. The epicardium and pericardium were partially adhered to each other. Hepatic lesions included dilatation of sinusoids accompanied by severe edema and congestion. Edema and fibrin deposition were often observed in the hepatic serosa and perivascular tissue. Splenic tissues with atrophied pulp showed definite increases in trabecula thickness. These findings suggest that the examined fish might have a systemic circulatory disturbance due to cardiac lesions associated with renal failure. [ABSTRACT FROM AUTHOR]

Summary: During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-chase studies showed that osterix-expressing osteoblast precursors, labeled in the perichondrium prior to vascular invasion of the cartilage, give rise to trabecular osteoblasts, osteocytes, and stromal cells inside the developing bone. Throughout the translocation, some precursors were found to intimately associate with invading blood vessels, in pericyte-like fashion. A similar coinvasion occurs during endochondral healing of bone fractures. In contrast, perichondrial mature osteoblasts did not exhibit perivascular localization and remained in the outer cortex of developing bones. These findings reveal the specific involvement of immature osteoblast precursors in the coupled vascular and osteogenic transformation essential to endochondral bone development and repair. [ABSTRACT FROM AUTHOR]

A guinea pig (9-week-old) that had been placed in a control group for a pharmacological test was found to have a single nodule on the surface of the right ventricular wall. In a transverse section of the heart after fixation, a whitish mass was found that extended from the subendocardium to the subepicardium of the right ventricular wall. Histopathological examination revealed a spongy network consisting of vacuolated spaces in the myocardium of the right ventricle extending to the myocardium and subepicardium of the right atrium. The vacuolated space was PAS-positive. Immunohistochemical examinations revealed that the lesions contained striated fibers that were positive for anti-desmin and anti-myoglobin. Electron micrographs revealed the lesions resulting in affected striated muscle fibers and accumulations of many glycogen granules. Based on the findings, the lesions were diagnosed as a cardiac rhabdomyoma. This is the first report of application of immunohistochemical examinations to diagnosis of cardiac rhabdomyoma in the guinea pig. [ABSTRACT FROM AUTHOR]

Information on several papers discussed at the 31st Annual Meeting of the American Society for Bone and Mineral Research (ASBMR) on chondrocytes and cartilage biology is presented. Among the research topics highlighted in the annual meeting include the signaling and transcription factors in chondrocytes, thienoindazole-derivative compound, and on epigenetics. Moreover, it also discussed the role of endoplasmic reticulum (ER) stress on the functions of chondrocytes.

Small noncoding RNAs, microRNAs (miRNAs), bind to messenger RNAs through base pairing to suppress gene expression. Despite accumulating evidence that miRNAs play critical roles in various biological processes across diverse organisms, their roles in mammalian skeletal development have not been demonstrated. Here, we show that Dicer, an essential component for biogenesis of miRNAs, is essential for normal skeletal development. Dicer-null growth plates show a progressive reduction in the proliferating pool of chondrocytes, leading to severe skeletal growth defects and premature death of mice. The reduction of proliferating chondrocytes in Dicer-null growth plates is caused by two distinct mechanisms: decreased chondrocyte proliferation and accelerated differentiation into postmitotic hypertrophic chondrocytes. These defects appear to be caused by mechanisms downstream or independent of the Ihh-PTHrP signaling pathway, a pivotal signaling system that regulates chondrocyte proliferation and differentiation. Microarray analysis of Dicer-null chondrocytes showed limited expression changes in miRNA-target genes, suggesting that, in the majority of cases, chondrocytic miRNAs do not directly regulate target RNA abundance. Our results demonstrate the critical role of the Dicer-dependent pathway in the regulation of chondrocyte proliferation and differentiation during skeletal development. [ABSTRACT FROM AUTHOR]

Over the past few decades, osteoblast differentiation has been studied extensively in a variety of culture systems and findings from these experiments have shaped our understanding of the bone-forming cell lineage. However, in vitro assays are bound by intrinsic limitations and are unable to effectively mirror many aspects related to osteoblasts in vivo, including their origin, destiny, and life span. Therefore, these fundamental questions strongly advocate the need for novel models to characterize the osteoblast lineage in vivo. Here, we developed a transgenic mouse system to study stage-specific subsets of osteoblast lineage cells. We believe that this system will prove to be a helpful tool in deciphering multiple aspects of osteoblast biology in vivo. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) play important roles at multiple stages of endochondral bone formation. However, the roles of BMP signaling in chondrocytes in vivo are still contentious. In the present study, we overexpressed a constitutively active BMP receptor 1A (caBmpr1a) in chondrocytes by using two systems: caBmpr1a was directly driven by a rat type II collagen promoter in a conventional transgenic system and indirectly driven in a UAS- Gal4 binary system. CaBmpr1a expression caused shortening of the columnar layer of proliferating chondrocytes and up-regulation of maturation markers, suggesting acceleration of differentiation of proliferating chondrocytes toward hypertrophic chondrocytes. In addition to the acceleration of chondrocyte differentiation, conventional transgenic mice showed widening of cartilage elements and morphological alteration of perichondrial cells, possibly due to stimulation of differentiation of prechondrogenic cells. Moreover, bigenic expression of caBmpr1a rescued the differentiation defect of prechondrogenic cells in Bmpr1b-null phalanges. This finding indicates that BMP signaling is necessary for phalangeal prechondrogenic cells to differentiate into chondrocytes and that signaling of BMP receptor 1B in this context is replaceable by that of a constitutively active BMP receptor 1A. These results suggest that BMP signaling in prechondrogenic cells and in growth plate chondrocytes stimulates their chondrocytic differentiation and maturation toward hypertrophy, respectively. [ABSTRACT FROM AUTHOR]

In the developing growth plate, periarticular chondrocytes proliferate, differentiate into columnar chondrocytes, and then further differentiate into postmitotic hypertrophic chondrocytes. Parathyroid hormone-related (PTH-related) protein (PTHrP), regulated by Indian hedgehog (Ihh), prevents premature hypertrophic differentiation, thereby maintaining the length of columns. Ihh regulates cartilage development through PTHrP-independent pathways as well. Here we show that Ihh stimulates differentiation of periarticular to columnar chondrocytes (periarticular chondrocyte differentiation) and thereby regulates the length of columns independently of PTHrP. Mosaic ablation of the PTH/PTHrP receptor in the growth plate caused upregulation of Ihh action, PTHrP upregulation, acceleration of periarticular chondrocyte differentiation, and elongation of the columnar region. Decreasing Ihh action in these mice reduced elongation of columns, whereas decreasing PTHrP showed only a modest effect on column length. Overexpression of Ihh caused PTHrP upregulation, elongation of columns, and acceleration of periarticular chondrocyte differentiation. PTHrP heterozygosity in this model had a minimal effect on the elongation of columns. Moreover, the elongation of columns and stimulation of periarticular chondrocyte differentiation in these models were still observed when PTHrP signaling was maintained so that it remained constant. These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate their differentiation, thereby regulating the columnar cell mass independently of PTHrP. [ABSTRACT FROM AUTHOR]

Background. It was reported that connective tissue growth factor (CTGF) was expressed in the tubular epithelial cells of the diabetic kidney. CTGF has, among other factors, been implicated in mediating the downstream, profibrotic effects of transforming growth factor-β (TGF-β), though is precise role in interstitial fibrogenesis in the diabetic kidney has not yet been clarified. Methods. We employed a coculture system involving cultured murine proximal tubular epithelial cells (mProx24) and renal fibroblasts (TFB), as a model of the subepithelial mesenchyme in the kidney in order to examine the profibrotic effects of CTGF derived from mProx24 cells in response to high glucose (30mM). Results. We showed that glucose stimulated CTGF expression in cultured mProx24 in both a dose- and a time-dependent manner, and that this effect was mediated by increased levels of TGF-β. We also found that high glucose significantly stimulated TFB cells to produce profibrotic molecules, such as type I collagen, the EIIIA isoform of fibronectin, and plasminogen activator inhibitor-1. The induction of these molecules was both direct and indirect, the latter induction being mediated by mProx24 cell-derived CTGF, which, in turn, was induced by TGF-β that was produced by the mProx24 cells. Conclusions. CTGF plays an important role in mediating renal interstitial fibrogenesis in response to high glucose and, as such, is a reasonable target for anti-fibrotic therapy. [ABSTRACT FROM AUTHOR]

The von Hippel Lindau tumor suppressor protein (pVHL) is a component of a ubiquitin ligase that promotes proteolysis of the transcription factor hypoxia-inducible. factor 1α (HIF1α), the key molecule in the hypoxic response. We have used conditional inactivation of murine VHL (Vhlh) in all cartilaginous elements to investigate its role in endochondral bone development. Mice lacking Vhlh in cartilage are viable, but grow slower than control littermates and develop a severe dwarfism. Morphologically, Vhlh null growth plates display a significantly reduced chondrocyte proliferation rate, increased extracellular matrix, and presence of atypical large cells within the resting zone. Furthermore, stabilization of the transcription factor HIF1α leads to increased expression levels of HIF1α target genes in Vhlh null growth plates. Lastly, newborns lacking both Vhlh and Hif1a genes in growth plate chondrocytes display essentially the same phenotype as Hif1a null single mutant mice suggesting that the Vhlh null phenotype could result, at least in part, from increased activity of accumulated HIF&1alpha;. This is the first study reporting the novel and intriguing findings that pVHL has a crucial role in endochondral bone development and is necessary for normal chondrocyte proliferation in vivo. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of low-dose dexamethasone (DXM) therapy in patients with hormone-refractory prostate cancer (HRPC) was evaluated. Patients and Methods: Prostate-specific antigen (PSA) response and survival following DXM therapy were analyzed in 27 Japanese patients exhibiting HRPC. Concurrent therapies and antiandrogen withdrawal syndrome, which may affect PSA levels and palliative effects, were excluded from the study. A dose of 1.5 mg of DXM was administered, and androgen deprivation therapy was maintained during DXM therapy. A decline in PSA levels of at least 50% from baseline was considered a significant PSA response. Prognostic factors for PSA response and survival were examined by univariate and multivariate analyses. Results: A significant PSA response was observed in 16 of the 27 cases (59.3%). Median survival period of patients exhibiting significant PSA response was 15.9 months and was significantly longer than that of patients demonstrating a decline in PSA of less than 50% (median 7.7 months, p < 0.0001). Effect on pain control also correlated with the significant PSA response. No meaningful prognostic factors for PSA response were detected; however, a PSA decline of greater than 50% was the prognostic factor for survival. Conclusion: DXM therapy remains one of the most beneficial treatment modalities in patients with HRPC.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Simple Summary: The molecular machineries regulating resistance against photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) in glioblastomas (GBM)s and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced both caspase-dependent and -independent GBM cell death in a NPe6 dose-dependent manner. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was revealed resistance to re-NPe6-PDT, migration, and invasion of GBM cells that survived following NPe6-PDT (NPe6-PDT-R cells) were enhanced. Immunoblotting of NPe6-PDT-R revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT. To manage refractory and invasive glioblastomas (GBM)s, photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) was recently approved in clinical practice. However, the molecular machineries regulating resistance against NPe6-PDT in GBMs and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced GBM cell death in a NPe6 dose-dependent manner. However, this NPe6-PDT-induced GBM cell death was not completely blocked by the pan-caspase inhibitor, suggesting NPe6-PDT induces both caspase-dependent and -independent cell death. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was also revealed resistance to re-NPe6-PDT of GBM cells and GBM stem cells survived following NPe6-PDT (NPe6-PDT-R cells), as well as migration and invasion of NPe6-PDT-R cells were enhanced. Immunoblotting of NPe6-PDT-R cells to assess the behavior of the proteins that are known to be stress-induced revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT and is therefore considered as a potential therapeutic target against GBM. [ABSTRACT FROM AUTHOR]

Small regulatory microRNAs (miRNAs) post-transcriptionally suppress gene expression. MiRNAs expressed in skeletal progenitor cells and chondrocytes regulate diverse aspects of cellular function and thus skeletal development. In this review, we discuss the role of miRNAs in skeletal development, particularly focusing on those whose physiological roles were revealed in vivo. Deregulation of miRNAs is found in multiple acquired diseases such as cancer; however congenital diseases caused by mutations in miRNA genes are very rare. Among those are mutations in miR-140 and miR-17~92 miRNAs which cause skeletal dysplasias. We also discuss pathological mechanisms underlining these skeletal dysplasias. • MiRNAs regulate diverse aspects of chondrocyte function and chondrogenesis. • MiR-140 and let-7 miRNAs regulate differentiation and proliferation of chondrocytes. • Mutations in miR-140 and miR-17~92 miRNAs cause skeletal dysplasias in humans. [ABSTRACT FROM AUTHOR]

Background: Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin.Methods: In total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009-2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting.Results: MPA administration significantly increased serum PRL levels at 3 and 6 months and upregulated IGFBP-1 and PRL mRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-induced IGFBP-1 and PRL mRNA expression during fertility-sparing treatment and significantly inhibited the upregulation of IGFBP-1 and PRL mRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases.Conclusions: MPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment. [ABSTRACT FROM AUTHOR]

Background: Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin. Methods: In total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009–2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting. Results: MPA administration significantly increased serum PRL levels at 3 and 6 months and upregulated IGFBP-1 and PRL mRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-induced IGFBP-1 and PRL mRNA expression during fertility-sparing treatment and significantly inhibited the upregulation of IGFBP-1 and PRL mRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases. Conclusions: MPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment. [ABSTRACT FROM AUTHOR]

• The outcomes of very severe nerve injury by long nerve resection were investigated. • A 9-mm section of XII nerve was resected in adult rats. • The number of XII neurons was counted after the nerve resection. • Extensive nerve resection led to slow cell death of the injured neurons. Crush injury to peripheral nerves in adult animals is considered not to trigger retrograde neuronal cell death; however, several studies reported neuronal cell death following severe injuries including nerve transection, resection, or avulsion. However, the rate of neuronal cell death varied among studies. In this study, we evaluated the outcomes of very severe nerve injury by long nerve resection in adult rats. Right hypoglossal (XII) nerve was exposed, and a 9-mm section was resected. At 4, 8, and 12 weeks after the resection, the number of XII neurons were counted in from the rostral to caudal sections. The number of XII neurons in the injured right side was reduced after the XII nerve resection compared with the uninjured left side. The mean rates of surviving neurons at 4, 8, and 12 weeks after the nerve resection were 83.5 %, 73.9 %, and 61.1 %, respectively, which were significantly lower than those of the control. The number of XII neurons after extensive XII nerve resection declined gradually over a relatively long time period, revealing that extensive nerve resection led to slow cell death of the injured neurons. [ABSTRACT FROM AUTHOR]

The tricyclic ring system of tricycloclavulone was synthesized from 2-methoxycarbonyl-2-cyclopenten-1-one (2). Key reactions include Lewis acid-catalyzed [2+2]-cycloaddition of α,β-unsaturated ester 2 with thioacetylene derivatives and construction of the A-ring by using the Grubbs catalyst. [Copyright &y& Elsevier]

Glioblastoma (GBM) is the most common malignant tumor arising from brain parenchyma. Although many efforts have been made to develop therapies for GBM, the prognosis still remains poor, mainly because of the difficulty in total resection of the tumor mass from brain tissue and the resistance of the residual tumor against standard chemoradiotherapy. Therefore, novel adjuvant therapies are urgently needed. Recent genome-wide analyses of GBM cases have clarified molecular signaling mechanisms underlying GBM biology. However, results of clinical trials targeting phosphorylation-mediated signaling have been unsatisfactory to date. Protein phosphatases are enzymes that antagonize phosphorylation signaling by dephosphorylating phosphorylated signaling molecules. Recently, the critical roles of phosphatases in the regulation of oncogenic signaling in malignant tumor cells have been reported, and tumorigenic roles of deregulated phosphatases have been demonstrated in GBM. However, a detailed mechanism underlying phosphatase-mediated signaling transduction in the regulation of GBM has not been elucidated, and such information is necessary to apply phosphatases as a therapeutic target for GBM. This review highlights and summarizes the phosphatases that have crucial roles in the regulation of oncogenic signaling in GBM cells. [ABSTRACT FROM AUTHOR]

In this study, the wear resistance of nickel (Ni)–cellulose nanofiber (CNF) composite electroplated films on steel plates (JIS SPCC, cold-rolled steel) was evaluated, including their surface and microstructural properties. In the CNF sample, 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-oxidized CNF was used. As a result of the ball-on-disk abrasion test, in which steel (SUJ2) balls were used as the counterpart material, the plated film obtained with the addition of 1 g/L of CNF to the plating solution showed the highest wear resistance in this study. Compared to the conventional Ni-plated film without CNF, the abrasion loss volume on the plated side was reduced by approximately 79%, and that on the ball side was reduced remarkably by 94%. A microstructural analysis of the abrasion scars showed areas where co-deposited CNFs were stretched in the direction of abrasion, suggesting that the wear reduction effect was caused by sliding between the individual CNFs within the aggregates. Moreover, the hardness of the plated film increased when the Ni crystallite size became finer. It was confirmed that the co-deposition of fine CNFs is effective in improving hardness, whereas the co-deposition of a certain degree of aggregated CNFs is effective in exhibiting the wear reduction effect. [ABSTRACT FROM AUTHOR]

Methanogens are used as catalysts for cathodes in microbial fuel cells, to reduce CO2 to CH4. However, the attachment of microbes to the electrodes via culturing is time‐consuming, and inadequate biofilm formation can lead to lesser surface area coverage, resulting in reduced methane formation. This study aims to improve the production efficiency and performance of methanogen cathodes developed using 3D printing of bioink containing live methanogens. A progressive cavity pump is used for the 3D gel‐printing of methanogens and micro‐sized white charcoal particles into the desired structure. Despite the absence of anaerobic conditions during printing, the 3D‐printed cathodes with higher concentrations of microbial inoculum in the bioink produce more methane gas. Even with an unconcentrated inoculum, the methanogens multiply 800‐fold during incubation, resulting in increased methane gas production. The predominant methanogens in the electrodes included the hydrogenotrophic Methanobacterium spp. Therefore, the technique used in this study can be used to successfully develop 3D‐printed biocathodes catalyzed by methanogenic microbes with verifiable practical applicability. This study is the first to report the growth of methanogens and their methanogenic activity in 3D‐printed cathodes. [ABSTRACT FROM AUTHOR]

Vertebral compression fractures are common in elderly people and most are due to osteoporosis. Osteoporosis treatment is effective for secondary prophylaxis, so initiation is recommended. Despite the clear benefits, the rate of initiation of osteoporosis treatment is very low. It is reported to be due to several factors including insufficient systems-based approaches for hospitals and post-acute care. Hospitalists, who are physicians dedicated to the treatment of patients in hospital and whose activity is generalist rather than specialized, are reported to be associated with higher-quality inpatient care because of, among other things, closer adherence to guidelines. Co-management by hospitalists for patients with vertebral compression fractures has potential benefits towards improving the outcomes. We compared the rate of initiation of osteoporosis treatment for patients with vertebral compression fractures between conventional orthopedic surgeon-led care (conventional group) and hospitalist co-management care (co-management group). This is a single-center retrospective cohort study to evaluate the rate of initiation of osteoporosis treatment and reasons for non-initiation of osteoporosis treatment. Other clinical indicators were also evaluated, including length of hospital stay, preventable complications during hospitalization, and rate of 30-day readmission. We identified 55 patients in the conventional group and 93 patients in the co-management group. The rate of initiation of osteoporosis treatment was higher in the co-management group (45.2% vs. 3.6%, OR 21.5; 95%CI 5.12–192.0; P < 0.01). Most of the patients with non-initiation in the co-management group had reasons for it described in the medical records, but in the conventional group the reasons were unknown. There was no significant difference in length of hospital stay, preventable complications during hospitalization, or 30-day readmission between the groups. Hospitalist co-management of patients with vertebral compression fractures showed significantly higher rate of initiation of osteoporosis treatment than conventional orthopedic surgeon-led care. [ABSTRACT FROM AUTHOR]

The mutual interaction of drift wave-type modes and zonal flows causes the formation of higher-order nonlinear structures. This study focuses on the spatio-temporal behavior of these higher-order structures in a linear magnetized plasma. The structures include a solitary vortex, a long-lived circumnavigating motion localized both radially and azimuthally, and a short-lived packet of finer-scale fluctuations excited at the position of the solitary vortex. Observing the time evolution of the two-dimensional cross-sectional structures revealed that the packet of finer-scale fluctuations is trapped in the solitary vortex. The trapping times found are consistent with the theoretical evaluation. [ABSTRACT FROM AUTHOR]

Recently, there have been moves to replace Si power devices with SiC ones, which will require new materials with higher thermal conductivity for power module assemblies owing to their higher operating temperatures. Al wire bond interconnections suffer from a mismatch in the coefficient of thermal expansion (CTE) between the SiC chip and the wire material, leading to a degradation of the power module reliability owing to the higher junction temperature (T j) operation caused by the current density increase. Various studies have been conducted to improve the reliability of such interconnections. In this study, Al wires were bonded on a thick Cu over-pad metallization (OPM) layer that was formed on an Al pad of a SiC Schottky barrier diode, and active power cycling tests were performed while changing T jmax to investigate the contribution of such a thick Cu-OPM layer on the reliability of Al wire bonds. Compared with the case of Al wire bonds on an Al pad, in active power cycling tests, the lifetime of Al wire bonds on a 25 μm-thick Cu-OPM layer was 1.3-times longer at ΔT j = 75 °C, and 1.5-times longer at ΔT j = 100 °C. The results of Joule heating analysis and elastic thermal-stress analysis showed that the lifetime prolongation effect of Al wire bonds on Cu-OPM was not derived from the heat dissipation effect of the thick Cu-OPM layer, but from a stress-reduction effect obtained by keeping the Al wire bonds away from the SiC diode chip, with which the CTE mismatch is large. [ABSTRACT FROM AUTHOR]

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms. [ABSTRACT FROM AUTHOR]

How phosphate levels are detected in mammals is unknown. The bone-derived hormone fibroblast growth factor 23 (FGF23) lowers blood phosphate levels by reducing kidney phosphate reabsorption and 1,25(OH)2D production, but phosphate does not directly stimulate bone FGF23 expression. Using PET scanning and LC-MS, we found that phosphate increases kidney-specific glycolysis and synthesis of glycerol-3-phosphate (G-3-P), which then circulates to bone to trigger FGF23 production. Further, we found that G-3-P dehydrogenase 1 (Gpd1), a cytosolic enzyme that synthesizes G-3-P and oxidizes NADH to NAD+, is required for phosphate-stimulated G-3-P and FGF23 production and prevention of hyperphosphatemia. In proximal tubule cells, we found that phosphate availability is substrate-limiting for glycolysis and G-3-P production and that increased glycolysis and Gpd1 activity are coupled through cytosolic NAD+ recycling. Finally, we show that the type II sodiumdependent phosphate cotransporter Npt2a, which is primarily expressed in the proximal tubule, conferred kidney specificity to phosphate-stimulated G-3-P production. Importantly, exogenous G-3-P stimulated FGF23 production when Npt2a or Gpd1 were absent, confirming that it was the key circulating factor downstream of glycolytic phosphate sensing in the kidney. Together, these findings place glycolysis at the nexus of mineral and energy metabolism and identify a kidney-bone feedback loop that controls phosphate homeostasis. [ABSTRACT FROM AUTHOR]

Lumped element kinetic inductance detector (LEKID) is a promising superconducting energy detector that will advance the search for rare physics events, for instance, double-beta decay. We focus on the application of LEKIDs in the search for double-beta decay with particular attention to 94\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$^{94}$$\end{document}Zr. This proceeding reports the implementation of LEKID on unique material substrate, ZrO2\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$_2$$\end{document} substrate. It was confirmed that it actually worked. This achievement marks a significant milestone toward realizing the search of rare physics events utilizing LEKIDs. [ABSTRACT FROM AUTHOR]

Uterine fibroids (UFs), the most common tumors in women of reproductive age, are characterized by sex steroid-dependent growth and excessive deposition of extracellular matrix (ECM) surrounding UF smooth muscle cells. Women with symptomatic UFs experience heavy menstrual bleeding and consequent iron-deficiency anemia. They also have a risk of recurrent pregnancy loss, preterm birth, and cesarean delivery, indicating that UFs can negatively affect reproductive outcomes. Various types of immune cells, including innate and adaptive cells, are observed in UFs; however, the impact of these cells on the pathophysiology of UFs remains unclear. Inflammation may play important roles in the growth of UFs, and expression levels of proinflammatory and inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-β, are upregulated in UFs. These cytokines play important roles in the interaction between growth factors and ECM that is regulated by the sex steroids estrogen and progesterone. Furthermore, proinflammatory mediators are upregulated in females with UFs, with higher expression levels in the endometrium with submucosal and intramural UFs than in the endometrium without UFs, indicating that these proinflammatory cytokines may impair endometrial receptivity, leading to implantation failure in in vitro fertilization programs. Hormonal treatments using gonadotropin releasing hormone analogs and the selective progesterone receptor modulator ulipristal acetate significantly shrink UFs and improve UF-related symptoms. These compounds can regulate local inflammation in UFs and adjacent myometrium. Controlling and improving local inflammation caused by UFs may represent a novel therapeutic strategy for UFs and potentially improve reproductive outcomes in women with symptomatic UFs. [Display omitted] • Uterine fibroids (UFs) have sex steroid-dependent growth and excess extra cellular matrix (ECM). • UFs negatively impact the reproductive outcomes even after myomectomy. • Expression levels of many inflammatory cytokines are upregulated in UFs. • Cytokines impact cell proliferation, fibrotic changes, and ECM remodeling of UFs. • Impact of immune response on the pathogenesis of UFs remain unclear. [ABSTRACT FROM AUTHOR]

During skeletal development, mesenchymal progenitor cells undergo a multistage differentiation process in which they proliferate and become bone- and cartilage-forming cells. This process is tightly regulated by multiple levels of regulatory systems. The small non-coding RNAs, microRNAs (miRNAs), post-transcriptionally regulate gene expression. Recent studies have demonstrated that miRNAs play significant roles in all stages of bone formation, suggesting the possibility that miRNAs can be novel therapeutic targets for skeletal diseases. Here, we review the role and mechanism of action of miRNAs in bone formation. We discuss roles of specific miRNAs in major types of bone cells, osteoblasts, chondrocytes, osteoclasts, and their progenitors. Except a few, the current knowledge about miRNAs in bone formation has been obtained mainly by in vitro studies; further validation of these findings in vivo is awaited. We also discuss about several miRNAs of particular interest in the light of future therapies of bone diseases. [ABSTRACT FROM AUTHOR]