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Abstract For the first time under laboratory conditions, the virulence of a unique cypovirus strain, DsCPV-1, which has broad host specificity, was tested on nontarget aquatic organisms (natural species: Gammarus lacustris, Anopheles messeae, Coenagrion lunulatum, Cloeon robusta, Chironomus sp., Ilyocoris cimicoides, and Plea minutissima; laboratory species: Aedes aegypti and Daphnia magna), a terrestrial pollinator species (Apis mellifera), and an entomophage (Podisus maculiventris). The probability of this virus’s accumulation in the bodies of invertebrates and of its transmission along a trophic chain was evaluated by two approaches: bioassays and a molecular diagnostic analysis. In the bioassays, there was no significant increase in mortality among all the tested aquatic and terrestrial nontarget species exposed to DsCPV-1 as compared with control groups (no virus). When we fed Podisus maculiventris with caterpillars having active DsCPV-1 infection (i.e., with the virus replicating in the host) no viral replication was observed in bug. No replication was also observed in mosquitos as well as in bee after viral treatment. Thus, the results show that the DsCPV-1 virus has excellent environmental safety toward many invertebrate species and can be recommended for the control of lepidopteran pests in forestry and agriculture as insecticide with light effect on environment.

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

The hazardous plasma environment surrounding Earth poses risks to satellites due to internal charging and surface charging effects. Accurate predictions of these risks are crucial for minimizing damage and preparing for system failures of satellites. To forecast the plasma environment, it is essential to know the current state of the system, as the accuracy of the forecast depends on the accuracy of the initial condition of the forecast. In this study, we use data assimilation techniques to combine observational data and model predictions, and present the first global validation of a data-assimilative electron ring current nowcast during a geomagnetic storm. By assimilating measurements from one satellite and validating the results against another satellite in a different magnetic local time sector, we assess the global response and effectiveness of the data assimilation technique for space weather applications. Using this method, we found that the simulation accuracy can be drastically improved at times when observations are available while eliminating almost all of the bias previously present in the model. These findings contribute to the construction of improved operational models in estimating surface charging risks and providing realistic source populations for radiation belt simulations.

Abstract Adult myogenic cell lines are useful to study muscle development, repair and regeneration. In newts, which are known for their high regenerative capacity, myogenic cell lines have not been established in species other than the Eastern newt Notophthalmus viridescens. In this study, we established another myogenic cell line, named CpM01, from the skeletal muscle of the forearm of the adult Japanese fire-bellied newt Cynops pyrrhogaster. CpM01 maintained high proliferative ability even after numerous passages, and could be induced to differentiate into myotubes by changing the culture medium. CpM01 expressed myogenic regulatory factors (MRFs) such as Myf5, MRF4 and myogenin. Changes in the immunorectivities of MRFs during differentiation of CpM01 into myotubes were consistent with those during new muscle generation in limb regeneration. In newts, myogenic cells have two origins, muscle fibers or satellite cells. CpM01 expressed Pax7, suggesting the origin might be satellite cells. scRNA-seq analysis deeply characterized CpM01 and demonstrated that the expression patterns of myogenic genes (Pax3, Pax7, myocyte-specific enhancer factor 2 A, and genes encoding MRFs) in CpM01 are related to progress of the cell cycle. CpM01 can be a useful tool for future studies of limb muscle regeneration in adult newts.

Abstract Serum leucine-rich alpha-2 glycoprotein (LRG) can monitor disease activities during biologics treatment in patients with inflammatory bowel disease (IBD). It is unclear whether the pretreatment serum LRG level can predict clinical effectiveness including serum trough levels of ustekinumab in patients with IBD. This multicenter prospective cohort study included 184 patients (Crohn’s disease, 104; ulcerative colitis, 80) who received ustekinumab (n = 119) or anti-tumor necrosis factor (n = 65) between January 2019 and March 2023. Multivariate logistic regression analysis revealed serum LRG level at week 0 (0w-LRG, odds ratio 0.12, 95% confidence interval 0.02–0.68) as one of significant factors for clinical remission at week 8. We divided patients into the low- and the high-LRG groups by the median 0w-LRG (18.2 µg/mL) and compared the effectiveness. In patients who received ustekinumab, the proportion of clinical remission at week 8 was significantly different between in the low- (76.9%) and in the high-LRG group (59.3%, P = 0.038), and median serum trough level at week 8 was significantly different between in the low- (10.9 µg/mL, interquartile range 6.7–13.4) and the high-LRG group (5.3 µg/mL, interquartile range 2.4–8.3, P

Abstract Chondroitin extends lifespan and healthspan in C. elegans, but the relationship between extracellular chondroitin and intracellular anti-aging mechanisms is unknown. The basement membrane (BM) that contains chondroitin proteoglycans is anchored to cells via hemidesmosomes (HDs), and it accumulates damage with aging. In this study, we found that chondroitin regulates aging through the formation of HDs and inhibition of tubular lysosomes (TLs). Reduction of chondroitin due to a mutation in sqv-5/Chondroitin synthase (ChSy) causes the earlier and excessive formation of TLs and leakage of the lysosomal nuclease in a manner dependent on VHA-7, the a-subunit of V-type ATPase. VHA-7, whose mutation suppresses the short lifespan of the sqv-5 mutant, is initially localized to the basal side of the hypodermal cells and transported to lysosomes with aging. These results demonstrate that endogenous chondroitin suppresses aging by inhibiting the earlier excessive formation of TLs. This is a novel anti-aging mechanism that is controlled by the BM.

Abstract Long-duration spaceflight creates a variety of stresses due to the unique environment, which can lead to compromised functioning of the skeletal and immune systems. However, the mechanisms by which organisms respond to this stress remain unclear. The present study aimed to investigate the impact of three different gravitational loadings (microgravity, 1/6 g [lunar gravity], and 1 g) on the behavior, bone, thymus, and spleen of mice housed for 25–35 days in the International Space Station. The bone density reduction under microgravity was mostly recovered by 1 g but only partially recovered by 1/6 g. Both 1 g and 1/6 g suppressed microgravity-induced changes in some osteoblast and osteoclast marker gene expression. Thymus atrophy induced by microgravity was half recovered by both 1 g and 1/6 g, but gene expression changes were not fully recovered by 1/6 g. While no histological changes were observed due to low gravity, alterations in gene expression were noted in the spleen. We found that in bone and thymus, lunar gravity reduced microgravity-induced histological alterations and partially reversed gene expression changes. This study highlighted organ-specific variations in responsiveness to gravity, serving as an animal test for establishing a molecular-level gravity threshold for maintaining a healthy state during future spaceflight.

The Earth's magnetic field traps charged particles which are transported longitudinally around Earth, generating a near-circular current, known as the ring current. While the ring current has been measured on the ground and space for many decades, the enhancement of the ring current during geomagnetic storms is still not well understood, due to many processes contributing to its dynamics on different time scales. Here, we show that existing ring current models systematically overestimate electron flux observations of 10-50 keV on the nightside during storm onset. By analyzing electron drift trajectories, we show that this systematic overestimation of flux can be explained through a missing loss process which operates in the pre-midnight sector. Quantifying this loss reveals that the theoretical upper limit of loss has to be reached over a broad region of space in order to reproduce the observations. This missing loss may be attributed to inaccuracies in the parameterization of the loss due to chorus wave interactions, combined with the scattering by electrostatic electron cyclotron harmonic waves which is currently not included in ring current models.

The Earth's ionosphere affects the propagation of signals from the Global Navigation Satellite Systems (GNSS). Due to the non-uniform coverage of available observations and complicated dynamics of the region, developing accurate models of the ionosphere has been a long-standing challenge. Here, we present a Neural network-based model of Electron density in the Topside ionosphere (NET), which is constructed using 19 years of GNSS radio occultation data. The NET model is tested against in situ measurements from several missions and shows excellent agreement with the observations, outperforming the state-of-the-art International Reference Ionosphere (IRI) model by up to an order of magnitude, especially at 100-200 km above the F2-layer peak. This study provides a paradigm shift in ionospheric research, by demonstrating that ionospheric densities can be reconstructed with very high fidelity. The NET model depicts the effects of numerous physical processes governing the topside dynamics and can have wide applications in ionospheric research.

In the last years, electron density profile functions characterized by a linear dependence on the scale height showed good results when approximating the topside ionosphere. The performance above 800 km, however, is not yet well investigated. This study investigates the capability of the semi-Epstein functions to represent electron density profiles from the peak height up to 20,000 km. Electron density observations recorded by the Van Allen Probes were used to resolve the scale height dependence in the plasmasphere. It was found that the linear dependence of the scale height in the topside ionosphere cannot be directly used to extrapolate profiles above 800 km. We find that the dependence of scale heights on altitude is quadratic in the plasmasphere. A statistical model of the scale heights is therefore proposed. After combining the topside ionosphere and plasmasphere by a unified model, we have obtained good estimations not only in the profile shapes, but also in the Total Electron Content magnitude and distributions when compared to actual measurements from 2013, 2014, 2016 and 2017. Our investigation shows that Van Allen Probes can be merged to radio-occultation data to properly represent the upper ionosphere and plasmasphere by means of a semi-Epstein function.