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Abstract Rapid advancements in electronic devices yield an urgent demand for high‐performance electronic packaging materials with high thermal conductivity, low thermal expansion, and great mechanical properties. However, it is a great challenge for current design philosophies to fulfill all the requirements simultaneously. Here, an effective strategy is proposed for significantly promoting the thermal conductivity and machinability of negative thermal expansion alloy (Zr,Nb)Fe2 through eutectic precipitation of copper networks. The eutectic dual‐phase alloy exhibits an isotropic chips‐matched thermal expansion coefficient and a thermal conductivity enhancement exceeding 200% compared with (Zr,Nb)Fe2, along with an ultimate compressive strength of 550 MPa. The addition of copper reorganizes the composition of (Zr,Nb)Fe2, which smooths the magnetic transition and shifts it toward higher temperature, resulting in linear low thermal expansion in a wide temperature range. The highly fine eutectic copper lamellae construct high thermal conductivity networks within (Zr,Nb)Fe2, serving as highways for heat transfer electrons and phonons. The in situ forming of eutectic copper lamellae also facilitates the mechanical properties by enhancing interfacial bonding and bearing additional stress after yielding of (Zr,Nb)Fe2. This work provides a novel strategy for promoting thermal conductivity and mechanical properties of negative thermal expansion alloys via eutectic precipitation of copper networks.

For isotropic dissimilar materials, it is well known that the stress state can be expressed by two independent material composite parameters named Dundurs parameters αiso, βiso. Similar composite parameters were also derived for orthotropic dissimilar materials as α , β , ΓA , ΓB , ρA , ρB . Compared to two parameters in isotropic dissimilar materials, anisotropic dissimilar materials have such six independent material parameters, making it much more difficult to use previous analysis results and requiring the new analysis each time. In this study, first, the interface crack in orthotropic dissimilar materials is analyzed by applying the proportional method. Second, the singular stress field in orthotropic materials is compared with that in the isotropic dissimilar material under the condition α = αiso，β = βiso. The results show that the singular stress field in orthotropic dissimilar material can be evaluated within a few percent error in most cases from that in isotropic dissimilar material when α = αiso，β = βiso. In this isotropic replacement by applying α = αiso，β = βiso, the singular interface stress distributions in orthotropic dissimilar plates can be estimated within the 10% error even when the material anisotropy is widely changed.

The fidelity of vertical transmission is a critical factor in maintaining mutualistic associations with microorganisms. The obligate mutualism between termites and intestinal protist communities has been maintained for over 130 million years, suggesting the faithful transmission of diverse protist species across host generations. Although a severe bottleneck can occur when alates disperse with gut protists, how protist communities are maintained during this process remains largely unknown. In this study, we examined the dynamics of intestinal protist communities during adult eclosion and alate dispersal in the termite Reticulitermes speratus. We found that the protist community structure in last-instar nymphs differed significantly from that in workers and persisted intact during adult eclosion, whereas all protists disappeared from the gut during moults between worker stages. The number of protists in nymphs and alates was substantially lower than in workers, whereas the proportion of protist species exhibiting low abundance in workers was higher in nymphs and alates. Using a simulation-based approach, we demonstrate that such changes in the protist community composition of nymphs and alates improve the transmission efficiency of whole protist species communities. This study thus provides novel insights into how termites have maintained mutualistic relationships with diverse gut microbiota for generations.

Abstract Background During metastasis, cancer cells undergo epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β), which is abundant in the tumor microenvironment, and acquire invasive and metastatic potentials. Metastasis to distant organs requires intravascular invasion and extravasation of cancer cells, which is accompanied by the disruption of the adhesion between vascular endothelial cells. Cancer cell-derived extracellular vesicles (EVs) have been suggested to induce the destabilization of normal blood vessels at the metastatic sites. However, the roles of EVs secreted from cancer cells that have undergone EMT in the destabilization of blood vessels remain to be elucidated. In the present study, we characterized EVs secreted by oral cancer cells undergoing TGF-β-induced EMT and elucidated their effects on the characteristics of vascular endothelial cells. Methods Induction of EMT by TGF-β in human oral cancer cells was assessed using quantitative RT-PCR (qRT-PCR) and immunocytochemistry. Oral cancer cell-derived EVs were isolated from the conditioned media of oral cancer cells that were treated with or without TGF-β using ultracentrifugation, and characterized using nanoparticle tracking analysis and immunoblotting. The effects of EVs on human umbilical artery endothelial cells were examined by qRT-PCR, cellular staining, and permeability assay. The significant differences between means were determined using a t-test or one-way analysis of variance with Tukey’s multiple comparisons test. Results Oral cancer cells underwent EMT in response to TGF-β as revealed by changes in the expression of epithelial and mesenchymal cell markers at both the RNA and protein levels. Oral cancer cells treated with TGF-β showed increased EV production and altered EV composition when compared with untreated cells. The EVs that originated from cells that underwent EMT by TGF-β induced endothelial-mesenchymal transition, which was characterized by the decreased and increased expression of endothelial and mesenchymal cell markers, respectively. EVs derived from oral cancer cells also induced intercellular gap formation which led to the loss of endothelial cell barrier stability. Conclusions EVs released from oral cancer cells that underwent TGF-β-induced EMT target endothelial cells to induce vascular destabilization. Detailed characterization of oral cancer-derived EVs and factors responsible for EV-mediated vascular instability will lead to the development of agents targeting metastasis.

Abstract Takotsubo syndrome (TTS) is a transient cardiomyopathy that is often associated with cerebrovascular diseases. Earlier studies have supported the concept that the cardiovascular system is regulated by a central autonomic network (CAN) consisting of the insular cortex (IC), anterior cingulate gyrus and amygdala. We report the case of a 79‐year‐old female diagnosed with a mid‐ventricular variant of TTS concomitant with right IC ischaemic stroke. After 12 h of hospitalization, she experienced a sudden collapse. Rapid cardiopulmonary resuscitation resulted in a return of spontaneous circulation. Subsequent left ventriculography revealed akinesis in the mid‐portion of the left ventricle with vigorous contraction of the basal and apex segment. Two weeks after admission, cardiac ultrasound showed improved left ventricular contraction. Right IC ischaemia in this patient might have been associated with a dysregulation of the CAN and subsequent increased sympathetic nervous system activity that triggered TTS.

Hepatitis B is an infectious hepatocellular disease of global concern caused by hepatitis B virus (HBV), which belongs to Hepadnaviridae. Recently, a novel HBV-like virus, domestic cat hepadnavirus (DCH), was detected from an immunocompromised cat with a hepatic disease in Australia. Subsequent molecular investigation by independent research groups revealed that its prevalence rates were 6.5% in Australia, 10.8% in Italy, 12.4% in Thailand, 12.3% in Malaysia, 3.08% in the United Kingdom, and 0.78% in Japan. Although the correlation between DCH infection and hepatic diseases remains to be elucidated, understanding the diversity of circulating DCH will contribute to its prevention and control in domestic cats. Herein, we summarize the current epidemiological data of DCH in these countries.

We have fabricated nanocarbon-based palm-sized cubic paper balloons that can be levitated by light irradiation. These paper balloons are composed of carbon nanotube (CNT) freestanding films and cellulose nanofiber (CNF) freestanding films. The number of CNT freestanding films (NCNT) and the number of CNF freestanding films (6-NCNT) among the six walls of the cube were varied. We investigated the effect of NCNT on the levitation behaviors under light irradiation. We found that the balloons were levitated when NCNT was greater than or equal to two. The levitation height was found to be increased by increasing NCNT.

TEA domain family transcription factor 4 (Tead4) is known to be important for the trophectoderm (TE) segregation in murine embryos. However, the role of TEAD4 in early development of porcine embryos is still unknown. We examined TEAD4 expression patterns and attempted to determine the functions of TEAD4 during porcine preimplantation development using RNA interference. TEAD4 mRNA was upregulated from the 2–4-cell to 8–16-cell stages and then decreased to the blastocyst stage. Nuclear localization of TEAD4 protein was detected at the 16-cell stage, as well as at subsequent developmental stages. In porcine embryos injected with TEAD4 siRNA, transformation from morula to blastocyst was inhibited. Although TEAD4 downregulation did not affect the expression levels of POU class 5 homeobox 1 (OCT-4), transcription of SRY-related HMG-box gene 2 (SOX2) was detected at high level in TEAD4-downregulated embryos. It is possible that TEAD4 contributes to blastocyst formation in porcine embryos through downregulation of SOX2 expression. Collectively, our results indicate that TEAD4 is an important factor for the preimplantation development of porcine embryos.

Zinc finger and SCAN domain containing 4 (Zscan4) is a gene that is specifically expressed during zygotic genome activation (ZGA) in mouse preimplantation embryos, and a reduction of Zscan4 transcripts leads to developmental failure. In mouse embryonic stem cells (ESCs), Zscan4 is expressed transiently in as little as 1–5% of the cell population. Zscan4 has also been shown to enhance the efficiency of mouse induced pluripotent stem cells (iPSCs) generation and their quality. Although ZSCAN4 plays important roles in murine embryos and stem cells, its expression and role in bovine embryos is unknown. This study examines ZSCAN4 transcripts in bovine embryos at various developmental stages and attempts to elucidate the functions of ZSCAN4 during bovine preimplantation development. ZSCAN4 transcripts were found to be upregulated at the 8- and 16-cell stages. We next attempted ZSCAN4 downregulation in bovine early embryos by RNA interference and evaluated developmental competency and transcripts levels of genes involved in ZGA and iPSCs generation. Although the bovine embryos injected with ZSCAN4-siRNA could develop to the 8-cell stage, very few were developing beyond the 16-cell stage. PIWIL2 expression was reduced in ZSCAN4 downregulated embryos. It is possible that ZSCAN4 downregulated embryos fail to regulate gene expression during ZGA. Our results indicate that ZSCAN4 is an important factor for the preimplantation development of bovine embryos.

A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.

When a mobile robot moves in an environment where there are moving obstacles such as pedestrians and other robots, the robot is required to avoid collisions with these obstacles. However, trying to avoid all the predicted positions on the trajectory of the moving obstacle would overly restrict the robot’s movement. In order to solve this problem, we should be able to generate trajectories in which the robot and moving obstacles do not approach at the same time in the future. However, an approach such as optimizing the robot’s trajectory for the predicted trajectory of a moving obstacle would result in a very large number of states to be considered. This paper proposes a method to generate a set of candidate trajectories based on the robot’s motion model and determine the trajectories considering the collision probability with the predicted trajectories of moving obstacles at each time. In the proposed method, the action of the robot is determined by the following process. First, candidate trajectories of the robot based on its motion model are generated. Next, at each time step of each candidate trajectory, the collision probability with each obstacle is calculated. The same calculation is made for all obstacles and the collision probability with one or more obstacles is calculated. If the maximum probability of a candidate trajectory is greater than the threshold, the trajectory is considered dangerous and is removed from the candidate list. Depending on the distance from the target, the robot selects a trajectory from among the remaining candidate trajectories and determines the next action. In a simulation environment with 30 moving obstacles, the performance is compared with other methods and shown to be comparable or better. In addition, experiments using a real robot were conducted to show the usefulness of the proposed method.

The substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is a repressive mark that undergoes global dynamic changes during preimplantation development of several species. To ascertain the role of H3K27me3 in bovine preimplantation development we perturbed the activity of KDM6B, which demethylates H3K27me3. Knockdown of maternal KDM6B mRNA inhibited the reduction in global levels of H3K27me3 from 2-cell to 8-cell embryo stages and compromised development to the blastocyst stage; embryos that developed to the blastocyst stage had fewer inner cell mass (ICM) and trophectoderm (TE) cells. In addition, the transcriptome of KDM6B knockdown embryos was altered at the 8-cell stage and characterized by downregulation of transcripts related to transcriptional regulation, chromatin remodeling, and protein catabolism. Inhibiting the catalytic activity of KDM6B with a specific small molecule inhibitor also prevented the global decrease in H3K27me3 and compromised development to the blastocyst stage. These results indicate that histone demethylation activity, mediated by KDM6B, is required for the global decrease in H3K27me3, correct activation of the embryonic genome, and development to the blastocyst stage in bovine embryos.

In Japan, traffic congestions often occur on the expressways connecting tourism areas with the Tokyo metropolitan area. This congestion can be mitigated if tourists delayed their departure of homeward trips to avoid peak traffic hours. A potential method to promote staggered departure times is providing the estimates of near-future traffic congestion. This study hypothesized and experimentally confirmed that some tourists would delay their departure to avoid traffic based on near-future traffic estimates. The experiment was conducted in the Yatsugatake area using a mobile application that provided this information to tourists. The results suggest that approximately 40% of self-driving tourists will perform an additional stopover if the returning route is congested and near-future traffic congestion estimate is provided.

Soft Computing Optimizer (SCO) as a new software tool for design of robust intelligent control systems is described. It is based on the hybrid methodology of soft computing and stochastic simulation. It uses as an input the measured or simulated data about the modeled system. SCO is used to design an optimal fuzzy inference system, which approximates a random behavior of control object with the certain accuracy. The task of the fuzzy inference system construction is reduced to the subtasks such as forming of the linguistic variables for each input and output variable, creation of rule data base, optimization of rule data base and refinement of the parameters of the membership functions. Each task by the corresponding genetic algorithm (with an appropriate fitness function) is solved. The result of SCO application is the design of Knowledge Base of a Fuzzy Controller, which contains the value information about developed fuzzy inference system. Such value information can be downloaded into the actual fuzzy controller to perform online fuzzy control. Simulations results of robust fuzzy control of nonlinear dynamic systems and experimental results of application on automotive semi-active suspension control are demonstrated.

This article presents a case report of a 17-year-old boy with Kikuchi-Fujimoto disease (KFD), a condition characterized by fever and swollen lymph nodes in the neck. The boy experienced low body temperature, slow heart rate, and low blood pressure while being treated with glucocorticoids or cyclosporine A. These side effects resolved after stopping the medications and providing fluids. The article suggests that using a low dose of cyclosporine A may be a viable alternative for KFD patients who experience these adverse effects. It also mentions that caution should be exercised when using nonsteroidal anti-inflammatory drugs (NSAIDs) alongside this treatment. [Extracted from the article]

Background. Insulin resistance is a risk factor for sarcopenia. The triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is an indirect indicator of insulin resistance. We aimed to assess the association between sarcopenia and the TG/HDL-C ratio in Japanese older adults. Methods: Older adults in Wakasa town, Fukui, Japan, were examined between June 2019 and November 2021. We collected data regarding age, sex, height, weight, body mass index, muscle mass, fat mass, muscle mass to fat mass ratio, appendicular lean muscle mass, skeletal muscle mass index, glycated haemoglobin, TG, HDL-C, low-density lipoprotein cholesterol, TG/HDL-C ratio, 5-m gait speed, and grip strength (both sides). Sarcopenia was defined in accordance with the 2019 criteria of the Asian Working Group for Sarcopenia via grip strength, gait speed, and skeletal muscle indices. Results: In total, 65 men and 93 women (mean age, 78 years) were classified as normal (n=114), pre-sarcopenic (n=35), or sarcopenic (n=9). Compared with the normal and pre-sarcopenia groups, the sarcopenia group had the lowest HDL-C level (p=0.013) and highest TG/HDL-C ratio (p=0.008). Risk factors associated with sarcopenia were age (odds ratio=1.35, p=0.002) and the TG/HDL-C ratio (odds ratio=1.62, p=0.008). Conclusions: Older age and an elevated TG/HDL-C ratio are risk factors for sarcopenia. An elevated TG/HDL-C ratio may indicate progression from pre-sarcopenia to sarcopenia. [ABSTRACT FROM AUTHOR]