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The self-similarity has been discussed repeatedly for the singular dynamics such as breakup of a fluid drop and its resemblance to critical phenomena in thermodynamic transitions has also been pointed out. Although critical phenomena have been well understood by the renormalization group (RG) theory, the counterpart has not been developed for the breakup problem. Here, we apply an RG analysis developed in mathematics for partial differential equations (PDEs) without noise terms to the bubble breakup, or the formation of a fluid drop surrounded by a more viscous fluid. As a result, we show a wide class of nonlinear and complex PDEs shares the same self-similar solution with a simple PDE that describes the interfacial phenomena, forming the bubble-breakup universality class. We reveal that the experimentally observed self-similar dynamics appear as a stable fixed point of the RG. The framework clarifies that the physical origin of the emergence of the self-similar solution is the invariance of the governing equation under a scale transformation, where the invariance, if not initially exists, could be aquired after the repetition of RG. The present study elucidates that the self-similarity and universality in the hydrodynamic analog emerges as a result of the physics at small scales becoming so important, just as the universality in critical phenomena appears as a result of the physics at large scales becoming so important.

Certain biocomposites exploit the combination of soft and hard elements to achieve high strength and toughness. In nacre, found inside certain seashells or on the surface of pearls, hard layers of micron-scale thickness are glued together by thin layers of soft proteins to realize remarkable strength and toughness. In spider webs, stiffer radial threads are connected by softer spiral threads to produce a light and resistant structure. In the exoskeleton of lobsters, organic fibers form a chiral structure in an inorganic matrix. This article reviews progress in the understanding of the mechanical superiority of such soft-hard biocomposites. In particular, simple physical views are presented that allow an intuitive understanding of how their remarkable structures contribute to enhancing their fracture resistance in the presence of cracks, and how such structures are physically optimized in terms of mechanical properties. Such fundamental insights could be useful as guiding principles for developing artificial, reinforced materials.

Needs to impart appropriate elasticity and high toughness to viscoelastic polymer materials are ubiquitous in industries such as concerning automobiles and medical devices. One of the major problems to overcome for toughening is catastrophic failure linked to a velocity jump, i.e., a sharp transition in the velocity of crack propagation occurred in a narrow range of the applied load. However, its physical origin has remained an enigma despite previous studies over 60 years. Here, we propose an exactly solvable model that exhibits the velocity jump incorporating linear viscoelasticity with a cutoff length for a continuum description. With the exact solution, we elucidate the physical origin of the velocity jump: it emerges from a dynamic glass transition in the vicinity of the propagating crack tip. We further quantify the velocity jump together with slow- and fast-velocity regimes of crack propagation, which would stimulate the development of tough polymer materials.

Fibrinolytic factors like plasminogen, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA) dissolve clots. Though mere extracellular-matrix-degrading enzymes, fibrinolytic factors interfere with many processes during primary cancer growth and metastasis. Their many receptors give them access to cellular functions that tumor cells have widely exploited to promote tumor cell survival, growth, and metastatic abilities. They give cancer cells tools to ensure their own survival by interfering with the signaling pathways involved in senescence, anoikis, and autophagy. They can also directly promote primary tumor growth and metastasis, and endow tumor cells with mechanisms to evade myelosuppression, thus acquiring drug resistance. In this review, recent studies on the role fibrinolytic factors play in metastasis and controlling cell-death-associated processes are presented, along with studies that describe how cancer cells have exploited plasminogen receptors to escape myelosuppression.

IL-33, a member of the IL-1-related cytokines, is considered to be a proallergic cytokine that is especially involved in Th2-type immune responses. Moreover, like IL-1α, IL-33 has been suggested to act as an “alarmin” that amplifies immune responses during tissue injury. In contrast to IL-1, however, the precise roles of IL-33 in those settings are poorly understood. Using IL-1- and IL-33-deficient mice, we found that IL-1, but not IL-33, played a substantial role in induction of T cell-mediated type IV hypersensitivity such as contact and delayed-type hypersensitivity and autoimmune diseases such as experimental autoimmune encephalomyelitis. Most notably, however, IL-33 was important for innate-type mucosal immunity in the lungs and gut. That is, IL-33 was essential for manifestation of T cell-independent protease allergen-induced airway inflammation as well as OVA-induced allergic topical airway inflammation, without affecting acquisition of antigen-specific memory T cells. IL-33 was significantly involved in the development of dextran-induced colitis accompanied by T cell-independent epithelial cell damage, but not in streptozocin-induced diabetes or Con A-induced hepatitis characterized by T cell-mediated apoptotic tissue destruction. In addition, IL-33-deficient mice showed a substantially diminished LPS-induced systemic inflammatory response. These observations indicate that IL-33 is a crucial amplifier of mucosal and systemic innate, rather than acquired, immune responses.

Novel methods for detecting transplant rejection are craved, since conventional methods can detect ongoing rejection that may sometimes have already caused irreversible damage in transplanted organs. Here, we applied a transcriptomics database of recipients’ peripheral blood mononuclear cells (PBMCs) before liver or kidney transplantation on the weighted gene co-expression network and machine learning models to evaluate the risk of rejection. Gene clusters positively correlated with rejection were enriched for genes related to antiviral response and regulation/production of interleukin-1(IL-1) in liver transplantation, and genes related to innate immune responses (IL-8 and toll-like receptor signaling pathways) and T cell responses were positively correlated with rejection in kidney transplantation. Our study presents a novel approach for feature engineering based on RNA-seq data of PBMCs collected before transplantation. The features derived from this method demonstrated potential in predicting the risk of rejection and may serve as candidate predictors in future clinically applicable models.

Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process. We observe that, in several mouse tumour models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma cells and CMS5 MCA-induced fibrosarcoma cells naturally expressing mutated extracellular signal-regulated kinase (ERK) antigen, the action of antigen-specific cytotoxic T cell (CTL) in vivo results in the emergence of resistant cancer cell clones only in the presence of IFN-γ within the tumour microenvironment. Moreover, we show that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression. These results suggest that enhanced genetic instability might be one of the mechanisms by which CTLs and IFN-γ immunoedits tumours, altering their immune resistance as a result of genetic evolution. T cell mediated anti-tumour immune responses result in the emergence of an immune-resistant population in a process called immunoediting. Here, the authors show that immunoediting is associated with an increase in genomic rearrangements of tumour cells that requires both cytotoxic T cells and IFNγ exposure.

Human β-defensin-3 (hBD-3) exhibits antimicrobial and immunomodulatory activities; however, its contribution to autophagy regulation remains unclear, and the role of autophagy in the regulation of the epidermal barrier in atopic dermatitis (AD) is poorly understood. Here, keratinocyte autophagy was restrained in the skin lesions of patients with AD and murine models of AD. Interestingly, hBD-3 alleviated the IL-4- and IL-13-mediated impairment of the tight junction (TJ) barrier through keratinocyte autophagy activation, which involved aryl hydrocarbon receptor (AhR) signaling. While autophagy deficiency impaired the epidermal barrier and exacerbated inflammation, hBD-3 attenuated skin inflammation and enhanced the TJ barrier in AD. Importantly, hBD-3-mediated improvement of the TJ barrier was abolished in autophagy-deficient AD mice and in AhR-suppressed AD mice, suggesting a role for hBD-3-mediated autophagy in the regulation of the epidermal barrier and inflammation in AD. Thus, autophagy contributes to the pathogenesis of AD, and hBD-3 could be used for therapeutic purposes.Human β-defensin-3 (hBD-3) exhibits antimicrobial and immunomodulatory activities; however, its contribution to autophagy regulation remains unclear, and the role of autophagy in the regulation of the epidermal barrier in atopic dermatitis (AD) is poorly understood. Here, keratinocyte autophagy was restrained in the skin lesions of patients with AD and murine models of AD. Interestingly, hBD-3 alleviated the IL-4- and IL-13-mediated impairment of the tight junction (TJ) barrier through keratinocyte autophagy activation, which involved aryl hydrocarbon receptor (AhR) signaling. While autophagy deficiency impaired the epidermal barrier and exacerbated inflammation, hBD-3 attenuated skin inflammation and enhanced the TJ barrier in AD. Importantly, hBD-3-mediated improvement of the TJ barrier was abolished in autophagy-deficient AD mice and in AhR-suppressed AD mice, suggesting a role for hBD-3-mediated autophagy in the regulation of the epidermal barrier and inflammation in AD. Thus, autophagy contributes to the pathogenesis of AD, and hBD-3 could be used for therapeutic purposes.

There are several reports suggesting that the pathophysiology of psoriasis may be associated with aberrant circadian rhythms. However, the mechanistic link between psoriasis and the circadian time-keeping system, “the circadian clock,” remains unclear. This study determined whether the core circadian gene, Clock, had a regulatory role in the development of psoriasis. For this purpose, we compared the development of psoriasis-like skin inflammation induced by the Toll-like receptor 7 ligand imiquimod (IMQ) between wild-type mice and mice with a loss-of-function mutation of Clock. We also compared the development of IMQ-induced dermatitis between wild-type mice and mice with a loss-of-function mutation of Period2 (Per2), another key circadian gene that inhibits CLOCK activity. We found that Clock mutation ameliorated IMQ-induced dermatitis, whereas the Per2 mutation exaggerated IMQ-induced dermatitis, when compared with wild-type mice associated with decreased or increased IL-23 receptor (IL-23R) expression in γ/δ+ T cells, respectively. In addition, CLOCK directly bound to the promoter of IL-23R in γ/δ+ T cells, and IL-23R expression in the mouse skin was under circadian control. These findings suggest that Clock is a novel regulator of psoriasis-like skin inflammation in mice via direct modulation of IL-23R expression in γ/δ+ T cells, establishing a mechanistic link between psoriasis and the circadian clock.

We study the dependence of the fracture surface energy on the pulling velocity for nanoporous polypropylene (PP) sheets to identify two components: static and dynamic components. We show that these terms can be interpreted, respectively, as plastoelastic and viscoelastic components, as has been shown for soft polyethylene (PE) foams in previous work. Considering significant differences in the pore size, volume fraction, and Young’s modulus of the present PP and previous PE sheets, the present results suggest a universal physical mechanism for the fracture of porous polymer sheets. The simple physical interpretation emerging from the mechanism could be useful for developing tough polymers. Equivalence of Griffith's energy balance in fracture mechanics to a stress criterion is also discussed and demonstrated using the present experimental data.The dependence of the fracture surface energy on the stretching velocity for nanoporous polypropylene (PP) sheets was found to consists of static and dynamic components. These terms can be interpreted respectively as plastoelastic and viscoelastic components, as has been shown for soft polyethylene (PE) foams in a previous work. This simple physical interpretation suggests a universal mechanism for the fracture of porous polymer sheets, and could be useful for designing new tough polymers.