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In this paper, we summarize current progress on using the observed magnetic fields for magnetohydrodynamics (MHD) modeling of the coronal magnetic field and of solar eruptions, including solar flares and coronal mass ejections (CMEs). Unfortunately, even with the existing state-of-the-art solar physics satellites, only the photospheric magnetic field can be measured. We first review the 3D extrapolation of the coronal magnetic fields from measurements of the photospheric field. Specifically, we focus on the nonlinear force-free field (NLFFF) approximation extrapolated from the three components of the photospheric magnetic field. On the other hand, because in the force-free approximation the NLFFF is reconstructed for equilibrium states, the onset and dynamics of solar flares and CMEs cannot be obtained from these calculations. Recently, MHD simulations using the NLFFF as an initial condition have been proposed for understanding these dynamics in a more realistic scenario. These results have begun to reveal complex dynamics, some of which have not been inferred from previous simulations of hypothetical situations, and they have also successfully reproduced some observed phenomena. Although MHD simulations play a vital role in explaining a number of observed phenomena, there still remains much to be understood. Herein, we review the results obtained by state-of-the-art MHD modeling combined with the NLFFF.

Estrogen is an essential sex steroid hormone that functions primarily in female reproductive system, as well as in a variety of tissues and organs with pleiotropic effects, such as in cardiovascular, nervous, immune, and musculoskeletal systems. Women with low estrogen, as exemplified by those in postmenopause, are therefore prone to suffer from various disorders, i.e., cardiovascular disease, dementia, metabolic syndrome, osteoporosis, sarcopenia, frailty, and so on. Estrogen regulates the expression of its target genes by binding to its cognate receptors, estrogen receptors (ERs) α and β. Notably, the estrogen-related receptors (ERRs) α, β, and γ are originally identified as orphan receptors that share substantial structural homology and common transcriptional targets with ERs. Accumulating evidence suggests that ERs and ERRs play crucial roles in skeletal muscles, such as muscle mass maintenance, muscle exercise physiology, and muscle regeneration. In this article, we review potential regulatory roles of ERs and ERRs in muscle physiology, particularly with regard to mitochondrial function and metabolism.

Long non‐coding RNAs (lncRNAs) are RNA transcripts larger than 200 nucleotides that do not code for proteins the aberrant expression of which has been documented in various types of cancer, including prostate cancer. Lack of appropriate sensitive and specific biomarkers for prostate cancer has led to overdiagnosis and overtreatment, making lncRNAs promising novel biomarkers as well as therapeutic targets for the disease. The present review attempts to summarize the current knowledge of lncRNA expression patterns and mechanisms in prostate cancer, which contribute to carcinogenesis. In particular, we focused on lncRNAs regulated by androgen receptor and expressed in castration‐resistant prostate cancer. Long non‐coding (Lnc) RNAs modulate key cellular processes in normal physiology and diseases such as cancer. In this review, expression patterns of lncRNAs in prostate cancer and mechanisms which contribute to prostate carcinogenesis have been summarized.

Vitamin K is a fat-soluble vitamin that was originally found as an essential factor for blood coagulation. With the discovery of its role as a co-factor for γ-glutamyl carboxylase (GGCX), its function for blood coagulation was understood as the activation of several blood coagulation factors by their γ-carboxylation. Over the last two decades, other modes of vitamin K actions have been discovered, such as the regulation of transcription by activating the steroid and xenobiotic receptor (SXR), physical association to 17β-Hydroxysteroid dehydrogenase type 4 (17β-HSD4), covalent modification of Bcl-2 antagonist killer 1 (Bak), and the modulation of protein kinase A (PKA) activity. In addition, several epidemiological studies have revealed that vitamin K status is associated with some aging-related diseases including osteoporosis, osteoarthritis, and sarcopenia. Clinical studies on single nucleotide polymorphisms of GGCX suggested an association between higher GGCX activity and bone protective effect, while recent findings using conditional knockout mice implied that a contribution in protective effect for bone loss by GGCX in osteoblastic lineage was unclear. GGCX in other cell lineages or in other tissues might play a protective role for osteoporosis. Meanwhile, animal experiments by our groups among others revealed that SXR, a putative receptor for vitamin K, could be important in the bone metabolism. In terms of the cartilage protective effect of vitamin K, both GGCX- and SXR-dependent mechanisms have been suggested. In clinical studies on osteoarthritis, the γ-carboxylation of matrix Gla protein (MGP) and gla-rich protein (GRP) may have a protective role for the disease. It is also suggested that SXR signaling has protective role for cartilage by inducing family with sequence similarity 20a (Fam20a) expression in chondrocytes. In the case of sarcopenia, a high vitamin K status in plasma was associated with muscle strength, large muscle mass, and high physical performance in some observational studies. However, the basic studies explaining the effects of vitamin K on muscular tissue are limited. Further research on vitamin K will clarify new biological mechanisms which contribute to human longevity and health through the prevention and treatment of aging-related musculoskeletal disorders.

The majority of breast cancers are primarily hormone‐sensitive and can be managed by endocrine therapy, although therapy‐resistant or hormone‐refractory cancers need alternative treatments. Recently, increasing attention is being paid to RNA‐binding proteins (RBP) in cancer pathophysiology. The precise role of RBP in breast cancer, however, remains to be clarified. We herein show that an RBP non‐POU domain‐containing octamer binding (NONO) plays a critical role in the pathophysiology of breast cancers regardless of their hormone dependency. Clinicopathological and immunohistochemical study of 127 breast cancer cases showed that NONO is a significant independent prognostic factor for breast cancer patients. Notably, siRNA‐mediated NONO knockdown substantially repressed the proliferation of both hormone‐sensitive MCF‐7 and hormone‐refractory MB‐MDA‐231 breast cancer cells. Integrative analysis combined with expression microarray and RIP‐sequencing (RNA immunoprecipitation‐sequencing) showed that NONO post‐transcriptionally regulates the expression of cell proliferation‐related genes by binding to their mRNAs, as exemplified by S‐phase‐associated kinase 2 and E2F transcription factor 8. Overall, these results suggest that NONO is a key regulator for breast cancer proliferation through the pre‐mRNA splicing of cell proliferation‐related genes and could be a potential new diagnostic and therapeutic target for advanced disease. The present study shows that Drosophila behavior human splicing family RNA‐binding protein NONO plays a critical role in breast cancer tumorigenesis. Clinicopathological study defines that NONO immunoreactivity significantly correlates with poor overall and distant disease‐free survival of breast cancer patients. Cell‐based experiments show that NONO contributes to breast cancer proliferation by regulating SKP2 and E2F8 expression at the post‐transcriptional level. Our findings provide a new cancer strategy by applying NONO as a potential diagnostic and therapeutic target for breast cancer.

Estrogens are important endocrine hormones that control physiological functions in reproductive organs, and play a pivotal role in the generation and progression of breast cancer. Therapeutic drugs including anti-estrogen and aromatase inhibitors are used to treat patients with breast cancer. The estrogen receptors, ERa and ERβ, function as hormone-dependent transcription factors that directly regulate the expression of their target genes. Therefore, a better understanding of the function and regulation of estrogen-responsive genes provides insight into the gene regulation network associated with breast cancer. Recent technological developments in high- throughput sequencing have enabled the genome-wide identification of estrogen-responsive genes. Further elucidating the estrogen gene cascade is critical for advancements in the diagnosis and treatment of breast cancer.

Solar eruptions are well-known drivers of extreme space weather, which can greatly disturb the Earth’s magnetosphere and ionosphere. The triggering process and initial dynamics of these eruptions are still an area of intense study. Here we perform a magnetohydrodynamic simulation taking into account the observed photospheric magnetic field to reveal the dynamics of a solar eruption in a real magnetic environment. In our simulation, we confirmed that tether-cutting reconnection occurring locally above the polarity inversion line creates a twisted flux tube, which is lifted into a toroidal unstable area where it loses equilibrium, destroying the force-free state, and driving the eruption. Consequently, a more highly twisted flux tube is built up during this initial phase, which can be further accelerated even when it returns to a stable area. We suggest that a nonlinear positive feedback process between the flux tube evolution and reconnection is the key to ensure this extra acceleration. Solar eruptions are large explosions occurring in the solar atmosphere. Here, the authors perform magnetohydrodynamic simulations to unveil the dynamics of a solar eruption, and find that these are dominated by nonlinear processes involving flux tube evolution and reconnection.

Osteoclasts form a specialized cell–matrix adhesion structure, known as the “sealing zone”, during bone resorption. The sealing zone is a dynamic actin-rich structure that defines the resorption area of the bone. The detailed dynamics and fine structure of the sealing zone have been elusive. Osteoclasts plated on glass do not form a sealing zone, but generate a separate supra-molecular structure called the “podosome belt”. Podosomes are integrin-based adhesion complexes involved in matrix adhesion, cell migration, matrix degradation, and mechanosensing. Invadopodia, podosome-like protrusions in cancer cells, are involved in cell invasion into other tissues by promoting matrix degradation. Both podosomes and invadopodia exhibit actin pattern transitions during maturation. We previously found that Arp2/3-dependent actin flow occurs in all observed assembly patterns of podosomes in osteoclasts on glass. It is known that the actin wave in Dictyostelium cells exhibits a similar pattern transition in its evolution. Because of significant advances in our understanding regarding the mechanism of podosomes/invadopodia formation over the last decade, we revisited the structure and function of the sealing zone in this review, highlighting the possible involvement of self-organized actin waves in the organogenesis of the sealing zone.

Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.

The mitochondrial electron transport chain (ETC) plays an essential role in energy production by inducing oxidative phosphorylation (OXPHOS) to drive numerous biochemical processes in eukaryotic cells. Disorders of ETC and OXPHOS systems are associated with mitochondria- and metabolism-related diseases, including cancers; thus, a comprehensive understanding of the regulatory mechanisms of ETC and OXPHOS systems is required. Recent studies have indicated that noncoding RNAs (ncRNAs) play key roles in mitochondrial functions; in particular, some ncRNAs have been shown to modulate ETC and OXPHOS systems. In this review, we introduce the emerging roles of ncRNAs, including microRNAs (miRNAs), transfer-RNA-derived fragments (tRFs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), in the mitochondrial ETC and OXPHOS regulation.