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We present observations and analysis of the starburst PACS-819 at z = 1.45 ( M _* = 10 ^10.7 M _⊙ ), using high-resolution (0.″1; 0.8 kpc) Atacama Large Millimeter/submillimeter Array (ALMA) and multiwavelength JWST images from the COSMOS-Web program. Dissimilar to Hubble Space Telescope (HST) ACS images in the rest-frame UV, the redder NIRCam and MIRI images reveal a smooth central mass concentration and spiral-like features, atypical for such an intense starburst. Through dynamical modeling of the CO ( J = 5–4) emission with ALMA, PACS-819 is rotation dominated and thus consistent with having a disk-like nature. However, kinematic anomalies in CO and asymmetric features in the bluer JWST bands (e.g., F150W) support a more disturbed nature likely due to interactions. The JWST imaging further enables us to map the distribution of stellar mass and dust attenuation, thus clarifying the relationships between different structural components not discernible in the previous HST images. The CO ( J = 5–4) and far-infrared dust continuum emission are cospatial with a heavily obscured starbursting core (

With an X-ray stacking analysis of |$\simeq 12\, 000$| Lyman-break galaxies (LBGs) using the Chandra Legacy Survey image, we investigate average supermassive black hole (SMBH) accretion properties of star-forming galaxies (SFGs) at 4 ≲ z ≲ 7. Although no X-ray signal is detected in any stacked image, we obtain strong 3σ upper limits for the average black hole accretion rate (BHAR) as a function of star formation rate (SFR). At z ∼ 4 (5) where the stacked image is deeper, the 3σ BHAR upper limits per SFR are ∼1.5 (1.0) dex lower than the local black hole-to-stellar mass ratio, indicating that the SMBHs of SFGs in the inactive (BHAR |$\lesssim 1 \, \mathrm{M}_\odot$| yr−1) phase are growing much more slowly than expected from simultaneous evolution. We obtain a similar result for BHAR per dark halo accretion rate. QSOs from the literature are found to have ∼1 dex higher SFRs and ≳ 2 dex higher BHARs than LBGs with the same dark halo mass. We also make a similar comparison for dusty starburst galaxies and quiescent galaxies from the literature. A duty-cycle corrected analysis shows that for a given dark halo, the SMBH mass increase in the QSO phase dominates over that in the much longer inactive phase. Finally, a comparison with the TNG300, TNG100, SIMBA100, and EAGLE100 simulations finds that they overshoot our BHAR upper limits by ≲ 1.5 dex, possibly implying that simulated SMBHs are too massive. [ABSTRACT FROM AUTHOR]

We present the HINOTORI (Star Formation History Investigation To Find Rejuvenation) project to reveal the nature of rejuvenation galaxies (RGs), which are galaxies that restarted their star formation after being quiescent. As the first step of HINOTORI, we construct the largest RG sample with 1071 sources. We select these RGs from 8857 MaNGA (Mapping Nearby Galaxies at APO) survey galaxies by reconstructing their star formation histories with the Prospector spectral energy distribution fitting code. Both optical spectral data and UV to IR photometric data are used for the fitting. Using mock data, we confirm that our method can detect weak rejuvenation events that form only about |$0.1$| % of the total stellar mass with high completeness. The RGs account for |${\sim}10$| % of the whole sample, and rejuvenation events contribute on average only about |$0.1$| % of the total stellar mass in those galaxies but |$17$| % of the cosmic star formation rate density today. Our RGs have a similar mass distribution to quiescent galaxies (QGs). However, the morphology of the RGs is more disk-like than QGs, suggesting that rejuvenation may occur selectively in disk-like QGs. Our results also suggest the possibility of multiple-time rejuvenation events in a single galaxy. Further spatially resolved analyses of integral field unit data and radio observations and comparisons to simulations are needed to identify the mechanism and the role of rejuvenation in galaxy evolution. [ABSTRACT FROM AUTHOR]

Abstract Objective In 2004, after consuming angel-wing mushrooms, Pleurocybella porrigens, 59 incidents of food poisoning were reported in Japan. Consequently, 17 individuals died of acute encephalopathy. In 2023, we proved that a lectin, pleurocybelline, and pleurocybellaziridine from this mushroom caused damage to the brains of mice. Although we reported genomic and transcriptomic data of P. porrigens in 2013, the assembly quality of the transcriptomic data was inadequate for accurate functional annotation. Thus, we obtained detailed transcriptomic data on the fruiting bodies and mycelia of this mushroom using Illumina NovaSeq 6000. Results De novo assembly data indicated that the N50 lengths for the fruiting bodies and mycelia were improved compared with those previously reported. The differential expression analysis between the fruiting bodies and the mycelia revealed that 1,937 and 1,555 genes were significantly up-regulated in the fruiting bodies and the mycelia, respectively. The biological functions of P. porrigens transcripts, including PA biosynthetic pathways, were investigated using BLAST search, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The obtained results revealed L-valine, a predicted precursor of PA, is biosynthesized in the fruiting bodies and mycelia. Furthermore, real-time RT-PCR was performed to evaluate the accuracy of the results of differential expression analysis.

Objective(s): A simple noninvasive microsphere (SIMS) method using 123I-IMP and an improved brain uptake ratio (IBUR) method using 99mTc-ECD for the quantitative measurement of regional cerebral blood flow have been recently reported. The input functions of these methods were determined using the administered dose, which was obtained by analyzing the time activity curve of the pulmonary artery (PA) for SIMS and the ascending aorta (AAo) for the IBUR methods for dynamic chest images. If the PA and AAo regions of interest (ROIs) can be determined using deep convolutional neural networks (DCNN) for segmentation, the accuracy of these ROI-setting methods can be improved through simple analytical operations to ensure repeatability and reproducibility. The purpose of this study was to develop new PA and AAo-ROI setting methods using a DCNN (DCNN-ROI method).Methods: A U-Net architecture based on convolutional neural networks was used to determine the PA and AAo candidate regions. Images of 290 patients who underwent 123I-IMP RI-angiography and 108 patients who underwent 99mTc-ECD RI-angiography were used. The PA and AAo-ROI results for the DCNN-ROI method were compared to those obtained using manual methods. The counts for the input function on the PA and AAo-ROI were determined by integrating the area under the curve (AUC) counts of the time-activity curve of PA and AAo-ROI, respectively. The effectiveness of the DCNN-ROI method was elucidated through a comparison with the integrated AUC counts of the DCNN-ROI and the manual ROI.Results: The coincidence ratio for the locations of the PA and AAo-ROI obtained using the DCNN method and that for the manual method was 100%. Strong correlations were observed between the AUC counts using the DCNN and manual methods.Conclusion: New ROI- setting programs were developed using a deep convolution neural network DCNN to determine the input functions for the SIMS and IBUR methods. The accuracy of these methods is comparable to that of the manual method.

Type I interferons (IFN-Is) play a significant role in systemic lupus erythematosus (SLE) pathogenesis. Double-filtration plasmapheresis (DFPP) is a treatment option for SLE; however, its effect on IFN-Is remains unclear. Therefore, we investigated the effects of DFPP on IFN-Is. Plasma from patients with SLE (n = 11) who regularly underwent DFPP was analysed using a cell-based reporter system to detect the bioavailability and inducing activity of IFN-I. The concentration of plasma dsDNA was measured, and western blotting analysis was used to assess the phosphorylation of the STING pathway. A higher IFN-I bioavailability and inducing activity were observed in patients compared to healthy controls, and both parameters decreased after DFPP. The reduction in IFN-I-inducing activity was particularly prominent in patients with high disease activity. Notably, this reduction was not observed in STING-knockout reporter cells. Additionally, plasma dsDNA levels decreased after DFPP treatment, suggesting that inhibition of the STING pathway was responsible for the observed decrease in activity. Western blotting analysis revealed suppression of STING pathway phosphorylation after DFPP. DFPP reduced IFN-I bioavailability and the inducing activity of plasma. This reduction is likely attributable to the inhibition of the STING pathway through the elimination of dsDNA.

This paper presents a novel control strategy for drone networks to improve the quality of 3D structures reconstructed from aerial images by drones. Unlike the existing coverage control strategies for this purpose, our proposed approach simultaneously controls both the camera orientation and drone translational motion, enabling more comprehensive perspectives and enhancing the map's overall quality. Subsequently, we present a novel problem formulation, including a new performance function to evaluate the drone positions and camera orientations. We then design a QP-based controller with a control barrier-like function for a constraint on the decay rate of the objective function. The present problem formulation poses a new challenge, requiring significantly greater computational efforts than the case involving only translational motion control. We approach this issue technologically, namely by introducing JAX, utilizing just-in-time (JIT) compilation and Graphical Processing Unit (GPU) acceleration. We finally conduct extensive verifications through simulation in ROS (Robot Operating System) and show the real-time feasibility of the controller and the superiority of the present controller to the conventional method.

This paper presents a novel angle-aware coverage control method to enhance monitoring efficiency for large-scale 3D map reconstruction using drone networks. The proposed method integrates a Voronoi-based coverage control as the nominal input into the quadratic programming problem required to solve in the original angle-aware coverage control. This approach provides a practical solution, ensuring diverse viewing angles to improve the quality of 3D map reconstruction and offers effective coverage of distant unobserved areas, particularly for large-scale area missions. We then implement the present method and validate its effectiveness through simulation on Robot Operating System as well as experiments conducted on a robotic testbed. The comparative analysis demonstrates the advantages of our proposed approach, resulting in increased monitoring efficiency for large-scale 3D map reconstruction.

Abstract Background Photodynamic therapy (PDT) is an antitumor therapy and has traditionally been regarded as a localized therapy in itself. However, recent reports have shown that it not only exerts a direct cytotoxic effect on cancer cells but also enhances body's tumor immunity. We hypothesized that the immunological response induced by PDT could potentially enhance the efficacy of programmed death‐1 (PD‐1) / programmed death‐ligand 1 (PD‐L1) blockade. Methods The cytotoxic effects of PDT on colon 26 cells were investigated in vitro using the WST assay. We investigated whether the antitumor effect of anti‐PD‐1 antibodies could be amplified by the addition of PDT. We performed combination therapy by randomly allocating tumor‐bearing mice to four treatment groups: control, anti‐PD‐1 antibodies, PDT, and a combination of anti‐PD‐1 antibodies and PDT. To analyze the tumor microenvironment after treatment, the tumors were resected and pathologically evaluated. Results The viability rate of colon 26 cells decreased proportionally with the laser dose. In vivo experiments for combined PDT and anti‐PD‐1 antibody treatment, combination therapy showed an enhanced antitumor effect compared with the control. Immunohistochemical findings of the tumor microenvironment 10 days after PDT indicated that the number of CD8+ cells, the area of Iba‐1+ cells and the area expressing PD‐L1 were significantly higher in tumors treated with combination therapy than in tumors treated with anti‐PD‐1 antibody alone, PDT alone, or the control. Conclusions PDT increased immune cell infiltration into the tumor microenvironment. The immunological response induced by PDT may enhance the efficacy of PD‐1/PD‐L1 blockade.

Abstract Dissipative structures often appear as an unstable counterpart of ordered structures owing to fluctuations that do not form a homogeneous phase. Even a multiphase mixture may simultaneously undergo one chemical reaction near equilibrium and another one that is far from equilibrium. Here, we observed in real time crystal seed formation and simultaneous nanocrystal aggregation proceeding from CeIV complexes to CeO2 nanoparticles in an acidic aqueous solution, and investigated the resultant hierarchical nanoarchitecture. The formed particles exhibited two very different size ranges, resulting in further pattern formation with opalescence. The hierarchically assembled structures in solutions were CeO2 colloids, viz. primary core clusters (1–3 nm) of crystalline ceria and secondary clusters (20–30 nm) assembled through surface ions. Such self-assembly is widespread in multi-component complex fluids, paradoxically moderating hierarchical reactions. Stability and instability are not only critical but also complementary for co-optimisation around the nearby free energy landscape prior to bifurcation.

Abstract Human-assistive robots need to perform trajectory making for and control of a robotic hand along the many rotating mechanisms in our living spaces. If such trajectory control can be performed without high-cost sensors, certainly a significant cost reduction in building the robot will be achieved. This paper describes a method of retrieving a file binder by generating a pseudo-curved trajectory for tilting it using a simple system. A simple claw mechanism with a switch sensor to grasp an object was designed and 3D-printed, and it was attached to a 6-DOF foldable robotic hand developed by the authors. A method for generating a pseudo-curved trajectory using the switch sensor was developed, and the robotic hand was successfully moved along this trajectory to tilt and grasp a file binder to retrieve it from a bookshelf. Experiments to clarify the success rate were also conducted, and it was found that the results depend on the rotational speed of manipulator links and the vibration of the claw mechanism link. A rubber sponge was added to give flexibility to the claw mechanism, which significantly improved the success rate. Furthermore, a control system to recover from tilting failure was constructed, and its effectiveness was validated by experiments.

Abstract STAT3 is constitutively activated in many cancer types, including lung cancer, and can induce cancer cell proliferation and cancer stem cell (CSC) maintenance. STAT3 is activated by tyrosine kinases, such as JAK and SRC, but the mechanism by which STAT3 maintains its activated state in cancer cells remains unclear. Here, we show that PRMT5 directly methylates STAT3 and enhances its activated tyrosine phosphorylation in non-small cell lung cancer (NSCLC) cells. PRMT5 expression is also induced by STAT3, suggesting the presence of a positive feedback loop in cancer cells. Furthermore, methylation of STAT3 at arginine 609 by PRMT5 is important for its transcriptional activity and support of tumour growth and CSC maintenance. Indeed, NSCLC cells expressing the STAT3 mutant which R609 was replaced to alanine (R609K) show significantly impaired tumour growth in nude mice. Overall, our study reveals a mechanism by which STAT3 remains activated in NSCLC and provides a new target for cancer therapeutic approaches.

Abstract Background Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) using mesh are popular approaches for treating pelvic organ prolapse (POP). However, it is not uncommon that native tissue repair (NTR) should be presented as an option to patients who are expected to have extensive intraperitoneal adhesion or patients for whom LSC or RSC is difficult owing to various risk factors. Laparoscopic vaginal stump–uterosacral ligament fixation (Shull method) has been introduced as a method for NTR in case of POP. However, effective repair using this surgical procedure may not be possible in severe POPs. To solve the problems of the Shull method, we devised the laparoscopic vaginal stump–round ligament fixation (Kakinuma method) in which the vaginal stump is fixed to the uterine round ligament, a histologically strong tissue positioned anatomically higher than the uterosacral ligament. This study aimed to retrospectively and clinically compare the two methods. Methods Of the 78 patients who underwent surgery for POP between January 2017 and June 2022 and postoperative follow-up for at least a year, 40 patients who underwent the Shull method (Shull group) and 38 who underwent the Kakinuma method (Kakinuma group) were retrospectively analyzed. Results No significant differences were observed between the two groups in patient background variables such as mean age, parity, body mass index, and POP-Q stage. The mean operative duration and mean blood loss in the Shull group were 140.5 ± 31.7 min and 91.3 ± 96.3 ml, respectively, whereas the respective values in the Kakinuma group were 112.2 ± 25.3 min and 31.4 ± 47.7 ml, respectively. Thus, compared with the Shull group, the operative duration was significantly shorter (P

Abstract We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2–177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

In the current media environment, John Durham Peters emphasizes the importance of non-verbal communication and notes that underpinned by digital technology, “media” is returning to its original meaning as the milieu that surrounds living beings. To concretize and critically discuss this idea, this paper examines the artworks created by the authors, which incorporate microorganisms into digital technology. These works applied luminous bacteria as ink to digitally screen print text and images. The first work, A Medium for Images or Luminous Bacteria (2022), prints Japanese text with luminous bacteria ink. The second work, ‘イ(I)’ (1926) by BioLuminescent Bacteria (2024), recreates the first image in the history of Japanese television, ‘イ(I)’, with luminous bacteria. This paper compares and analyzes these practices in light of classical media theory, including the work of William Ivins Jr. and Marshall McLuhan. The paper introduces another work, Grow.|Glow. (2023), to further expand the discussion to contemporary digital media. Finally, drawing on the recent arguments of Anna Tsing and Antonio Damasio, we elucidate the critical implications that the works of luminous bacteria bring to the current media environment.

Ruminal methane production functions as the main sink for metabolic hydrogen generated through rumen fermentation and is recognized as a considerable source of greenhouse gas emissions. Methane production is a complex trait affected by dry matter intake, feed composition, rumen microbiota and their fermentation, lactation stage, host genetics, and environmental factors. Various mitigation approaches have been proposed. Because individual ruminants exhibit different methane conversion efficiencies, the microbial characteristics of low-methane-emitting animals can be essential for successful rumen manipulation and environment-friendly methane mitigation. Several bacterial species, including Sharpea, uncharacterized Succinivibrionaceae, and certain Prevotella phylotypes have been listed as key players in low-methane-emitting sheep and cows. The functional characteristics of the unclassified bacteria remain unclear, as they are yet to be cultured. Here, we review ruminal methane production and mitigation strategies, focusing on rumen fermentation and the functional role of rumen microbiota, and describe the phylogenetic and physiological characteristics of a novel Prevotella species recently isolated from low methane-emitting and high propionate-producing cows. This review may help to provide a better understanding of the ruminal digestion process and rumen function to identify holistic and environmentally friendly methane mitigation approaches for sustainable ruminant production.

Abstract The objective of this study is to compare the efficacy of apalutamide and bicalutamide in combination with androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively collected the data of about 330 patients with metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and August 2023. Sixty-one patients were administered apalutamide (240 mg/day) with androgen deprivation therapy (group A), and 269 patients were administered bicalutamide (80 mg/day) with androgen deprivation therapy (group B). Propensity score matching was used to adjust for clinical background factors between the two groups. PSA progression-free survival and overall survival were significantly longer in group A than in group B among the matched patients. Apalutamide therapy was a significant independent factor for OS in matched patients. The second progression-free survival of group A was significantly longer than that of group B in matched patients. Patients treated with apalutamide achieved ≥ 90% PSA decline from baseline faster and in larger numbers than those with bicalutamide. Apalutamide combined with ADT may be superior to bicalutamide alone in terms of OS and PSA-PFS in patients with mHSPC.

Abstract The neuromuscular junction (NMJ)—formed between a motor nerve terminal and skeletal muscle fiber—plays an important role in muscle contraction and other muscle functions. Aging and neurodegeneration worsen NMJ formation and impair muscle function. Downstream of tyrosine kinase-7 (Dok-7), expressed in skeletal muscle fibers, is essential for the formation of NMJ. Exercise increases the expression of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) in skeletal muscles and restores NMJ formation. In this study, we used skeletal muscle-specific PGC1α knockout or overexpression mice to examine the role of PGC1α in regulating Dok-7 expression and NMJ formation. Our findings revealed that Dok-7 expression is regulated by PGC1α, and luciferase activity of the Dok-7 promoter is greatly increased by coexpressing PGC1α and estrogen receptor-related receptor α. Thus, we suggest PGC1α is involved in exercise-mediated restoration of NMJ formation.

In this article, we study a one-human-multiple-robot interaction for human-enabled multi-robot navigation in three dimensions. We employ two fully distributed control architectures designed based on human passivity and human passivity shortage. The first half of this article focuses on human modeling and analysis for the passivity-based control architecture through human operation data on a 3-D human-in-the-loop simulator. Specifically, we compare virtual reality (VR) interfaces with a traditional interface, and examine the impacts that VR technology has on human properties in terms of model accuracy, performance, passivity and workload, demonstrating that VR interfaces have a positive effect on all aspects. In contrast to 1-D operation, we confirm that operators hardly attain passivity regardless of the network structure, even with the VR interfaces. We thus take the passivity-shortage-based control architecture and analyze the degree of passivity shortage. We then observe through user studies that operators tend to meet the degree of shortage needed to prove closed-loop stability.

In this study, the expansion behavior of cement materials after high-temperature heating and water immersion was observed experimentally. Two experiments were conducted using mortar specimens with different sand-to-cement ratios subjected to different high-temperature histories up to 1000 °C. In Case 1, the specimens were immersed in water after high-temperature heating and then cooled naturally; in Case 2, the specimens were immersed in water at high temperatures without the cooling process. Based on the results, it was confirmed that lime expansion due to the rehydration of CaO by heating occurred in Case 1. In contrast, dynamic continuous explosive spalling occurred in Case 2 because of water penetration into the specimen at a high temperature. The explosive spalling in water observed in Case 2 is a phenomenon that has not been reported to date. Possible failure mechanisms for lime expansion and continuous expansive spalling in water are suggested.

Electrohydraulic soft actuators are a promising soft actuation technology for constructing bio-inspired underwater robots owing to the features of this technology such as large deformations and forces, fast responses, and high electromechanical efficiencies. However, this actuation technology requires high voltages, thereby limiting the use of these actuators in water and hindering the development of underwater robots. This paper describes a method for creating bio-inspired underwater robots using silicone-layered electrohydraulic soft actuators. The silicone layer functions as an insulator, enabling the application of high voltages underwater. Moreover, bending and linear actuation can be achieved by applying the silicone layers on one or both sides of the actuator. As a proof of concept, bending and linear actuators with planar dimensions of 20 mm × 40 mm (length × width) are fabricated and characterized. Underwater actuation is observed in both types of actuators. The bending actuators exhibit a bending angle and blocked force of 39.0° and 9.6 mN, respectively, at an applied voltage of 10 kV. Further, the linear actuators show a contraction strain and blocked force of 6.6% and 956.1 mN, respectively, at an applied voltage of 10 kV. These actuators are tested at a depth near the surface of water. This ensured that they can operate at least at that depth. The actuators are subsequently used to implement various soft robotic devices such as a ray robot, a fish robot, a water-surface sliding robot, and a gripper. All of the robots exhibit movements as expected; up to 31.2 mm/s (0.91 body length/s) of locomotion speed is achieved by the swimming robots and a retrieve and place task is performed by the gripper. The results obtained in this study indicate the successful implementation of the actuator concept and its high potential for constructing bio-inspired underwater robots and soft robotics applications.

IntroductionMaternal obstructive sleep apnea (OSA) during pregnancy is the risk factor for impaired fetal growth with low birth weight in the offspring. However, it is unclear whether gestational intermittent hypoxia (IH, a hallmark of maternal OSA) has long-term detrimental consequences on the skeletal development of offspring. This study aimed to investigate postnatal maxillofacial bone growth and cartilage metabolism in male and female offspring that were exposed to gestational IH.MethodsMother rats underwent IH at 20 cycles/h (nadir, 4% O2; peak, 21% O2; 0% CO2) for 8 h per day during gestational days (GD) 7–20, and their male and female offspring were analyzed postnatally at 5 and 10 weeks of age. All male and female offspring were born and raised under normoxic conditions.ResultsThere was no significant difference in whole-body weight and tibial length between the IH male/female offspring and their control counterparts. In contrast, the mandibular condylar length was significantly shorter in the IH male offspring than in the control male offspring at 5 and 10 weeks of age, while there was no significant difference in the female offspring. Real-time polymerase chain reaction (PCR) showed that gestational IH significantly downregulated the mRNA level of SOX9 (a chondrogenesis marker) and upregulated the mRNA level of HIF-1α (a hypoxia-inducible factor marker) in the mandibular condylar cartilage of male offspring, but not in female offspring.ConclusionGestational IH induced underdeveloped mandibular ramus/condyles and reduced mRNA expression of SOX9, while enhancing mRNA expression of HIF-1α in a sex-dependent manner.

Ruminal methane production is the main sink for metabolic hydrogen generated during rumen fermentation, and is a major contributor to greenhouse gas (GHG) emission. Individual ruminants exhibit varying methane production efficiency; therefore, understanding the microbial characteristics of low-methane-emitting animals could offer opportunities for mitigating enteric methane. Here, we investigated the association between rumen fermentation and rumen microbiota, focusing on methane production, and elucidated the physiological characteristics of bacteria found in low methane-producing cows. Thirteen Holstein cows in the late lactation stage were fed a corn silage-based total mixed ration (TMR), and feed digestion, milk production, rumen fermentation products, methane production, and rumen microbial composition were examined. Cows were classified into two ruminal fermentation groups using Principal component analysis: low and high methane-producing cows (36.9 vs. 43.2 L/DMI digested) with different ruminal short chain fatty acid ratio [(C2+C4)/C3] (3.54 vs. 5.03) and dry matter (DM) digestibility (67.7% vs. 65.3%). However, there were no significant differences in dry matter intake (DMI) and milk production between both groups. Additionally, there were differences in the abundance of OTUs assigned to uncultured Prevotella sp., Succinivibrio, and other 12 bacterial phylotypes between both groups. Specifically, a previously uncultured novel Prevotella sp. with lactate-producing phenotype was detected, with higher abundance in low methane-producing cows. These findings provide evidence that Prevotella may be associated with low methane and high propionate production. However, further research is required to improve the understanding of microbial relationships and metabolic processes involved in the mitigation of enteric methane.

Abstract Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing that can negatively impact patient quality of life. The lack of animal models has limited research on pathogenesis or developing effective treatments, and the etiology of keloids remains unknown. Here, we found that the characteristics of stem-like cells from keloid lesions and the surrounding dermis differ from those of normal skin. Furthermore, the HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient–derived stem-like cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, the HH signal inhibitor vismodegib reduced keloid reconstituted tumor size and keloid-related gene expression in nude mice and the collagen bundle and expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic targets of keloids.

Abstract Increasing the number of degrees of freedom for multi-finger robotic hands is necessary to achieve high performance. However, this increases structural complexity and the obtained improvement may be small. Humans change the shape of their hands by extending or bending the fingers to apply force to an object through contact with a wide surface or two or more fingers. In some cases, continuous finger movements are not necessary or some fingers do not make contact with the object. A robotic hand with a small number of degrees of freedom could effectively use its fingers to perform many tasks by properly arranging the fingers, increasing the movable range of joints, and utilizing the back and sides of the fingers. This paper proposes a hand system and conducts a theoretical analysis of the transformation of the hand shape into a scissor-like motion to handle a cylindrical object. It is found that the scissor-like motion is unsuitable for cylindrical objects that exceed a certain size. Experiments show the effectiveness of the proposed hand system. The correlation between the contact position of a finger with an object and the success ratio of pinching is demonstrated. Furthermore, a control system that can switch from pinching to grasping when the robot judges that pinching is difficult is developed and experimentally validated.

Abstract Background There is a lack of large, nationwide, birth cohort studies in Japan that examine the relationships of initial feeding habits and breastfeeding period duration with offspring functional constipation at 3 years of age. This study assessed the impact of breastfeeding during infancy on early childhood functional constipation. Methods The fixed data of 70,078 singleton births from the ongoing Japan Environment and Children’s Study cohort study that commenced in 2011 were used to identify functional constipation as estimated by Rome III at 3 years of age. The exposure variables were breastfeeding period duration until 12 months of age (never, up to 6 months, or ≥ 7 months) as well as breastfeeding status at 1 month and 6 months of age (breastfeeding exclusively, partial breastfeeding, or infant formula feeding only). Multiple logistic regression analysis was employed to search for correlations for functional constipation development with breastfeeding period duration until 12 months of age and breastfeeding status during infancy. Results We identified 8,118 toddlers (11.6%) who met the Rome III criteria at 3 years of age. After controlling for potential covariates, a breastfeeding period duration of 7 months or more was inversely related to functional constipation development (≥ 7 months: adjusted odds ratio [OR] [95% confidence interval (CI)] 0.76 [0.65, 0.88] versus never breastfed, P for trend

Abstract Purpose This investigation assessed the impact of dog and/or cat ownership during infancy on the presence of functional constipation (FC) at 3 years of age. Methods The fixed data of 73,936 singleton births from a large national birth cohort study commencing in 2011 were used to identify FC as estimated by Rome III at 3 years of age. Multiple logistic regression analysis was employed to search for correlations between FC development and dog and/or cat ownership in early childhood. Results A total of 8,459 toddlers (11.6%) met the Rome III criteria for FC at 3 years of age. Overall, 57,264 (77.5%) participants had never owned a dog or cat. We identified 7,715 (10.4%) infant-period owners, 1,295 (1.8%) current owners, and 7,762 (10.5%) long-term owners. Multivariate analysis showed that infant-period ownership remained significantly associated with the risk of developing FC at 3 years of age after adjusting for covariates (adjusted OR [95% CI] 1.09 [1.01–1.19] based on non-ownership). Conclusions This Japanese large nationwide survey uncovered a possible adverse effect of infant-period dog and/or cat ownership prior to 6 months of age on FC status at 3 years of age.

Abstract “Preprocessing” is the first step required in brain image analysis that improves the overall quality and reliability of the results. However, it is computationally demanding and time-consuming, particularly to handle and parcellate complicatedly folded cortical ribbons of the human brain. In this study, we aimed to shorten the analysis time for data preprocessing of 1410 brain images simultaneously on one of the world's highest-performing supercomputers, “Fugaku.” The FreeSurfer was used as a benchmark preprocessing software for cortical surface reconstruction. All the brain images were processed simultaneously and successfully analyzed in a calculation time of 17.33 h. This result indicates that using a supercomputer for brain image preprocessing allows big data analysis to be completed shortly and flexibly, thus suggesting the possibility of supercomputers being used for expanding large data analysis and parameter optimization of preprocessing in the future.

Abstract Cisplatin treatment is effective against several types of carcinomas. However, it frequently leads to kidney injury, which warrants effective prevention methods. Sodium valproic acid is a prophylactic drug candidate with a high potential for clinical application against cisplatin‐induced kidney injury. Therefore, in this study, we aimed to elucidate the mechanism underlying the prophylactic effect of valproic acid on cisplatin‐induced kidney injury in a mouse model and HK2 and PODO cells with cisplatin‐induced toxicity. In the mouse model of cisplatin‐induced kidney injury, various renal function parameters and tubular damage scores were worsened by cisplatin, but they were significantly improved upon combination with valproic acid. No difference was observed in cisplatin accumulation between the cisplatin‐treated and valproic acid‐treated groups in whole blood and the kidneys. The mRNA expression levels of proximal tubular damage markers, apoptosis markers, and inflammatory cytokines significantly increased in the cisplatin group 72 h after cisplatin administration but significantly decreased upon combination with valproic acid. In HK2 cells, a human proximal tubular cell line, the cisplatin‐induced decrease in cell viability was significantly suppressed by co‐treatment with valproic acid. Valproic acid may inhibit cisplatin‐induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidneys by suppressing proximal tubular cell damage. However, prospective controlled trials need to evaluate these findings before their practical application.

Abstract SpaceOAR, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. Previously, our group reported the modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex. This study aimed to investigate the impact of separated distance at prostate-apex and our modifier technique, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level