Experience-Learning Inspired Two-Step Reward Method for Efficient Legged Locomotion Learning Towards Natural and Robust Gaits

Multi-legged robots offer enhanced stability in complex terrains, yet autonomously learning natural and robust motions in such environments remains challenging. Drawing inspiration from animals' progressive learning patterns, from simple to complex tasks, we introduce a universal two-stage learning framework with two-step reward setting based on self-acquired experience, which efficiently enables legged robots to incrementally learn natural and robust movements. In the first stage, robots learn through gait-related rewards to track velocity on flat terrain, acquiring natural, robust movements and generating effective motion experience data. In the second stage, mirroring animal learning from existing experiences, robots learn to navigate challenging terrains with natural and robust movements using adversarial imitation learning. To demonstrate our method's efficacy, we trained both quadruped robots and a hexapod robot, and the policy were successfully transferred to a physical quadruped robot GO1, which exhibited natural gait patterns and remarkable robustness in various terrains

Pharmacokinetic study of isoquercitrin in rat plasma after intravenous administration at three different doses

O objetivo deste estudo é desenvolver um método simples e específico de HPLC usando vitexina como padrão interno para investigar a farmacocinética do isoquercitrina (ISOQ) após três doses diferentes administradas por via intravenosa a ratos. Os parâmetros farmacocinéticos foram calculados pelas abordagens compartimental e não compartimental. Os resultados mostraram que ISOQ se encaixa no modelo de três compartimentos. Os valores de AUC aumentaram proporcionalmente na faixa de 5-10 mg·kg-1. Além disso, a meia-vida, b meia-vida, ªCL, MRT0-t and MRT0→∞ de ISOQ em ratos mostraram diferenças significativas entre 20 mg·kg-1 e outras doses, o que significa que ISOQ apresenta farmacocinética dose-dependente no intervalo de 5-10 mg·kg-1 e farmacocinética não linear em doses mais elevadas.The aim of this study is to develop a simple and specific HPLC method using vitexin as the internal standard to investigate the pharmacokinetics of isoquercitrin (ISOQ) after three different doses administrated intravenously to rats. The pharmacokinetic parameters were calculated by both compartmental and non-compartmental approaches. The results showed that ISOQ fitted a three-compartment open model. The values of AUC increased proportionally within the range of 5-10 mg·kg-1. Moreover, a half-life, b half-life, ªCL, MRT0-t and MRT0→∞ of ISOQ in rats showed significant differences between 20 mg·kg-1 and other doses, indicating that ISOQ presented dose-dependent pharmacokinetics in the range of 5-10 mg·kg-1 and non-linear pharmacokinetics at higher doses

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Genetic variants in the genes encoding rho GTPases and related regulators predict cutaneous melanoma-specific survival

Rho GTPases control cell division, motility, adhesion, vesicular trafficking and phagocytosis, which may affect progression and/or prognosis of cancers. Here, we investigated associations between genetic variants of Rho GTPases-related genes and cutaneous melanoma-specific survival (CMSS) by re-analyzing a published melanoma genome-wide association study (GWAS) and validating the results in another melanoma GWAS. In the single-locus analysis of 36,018 SNPs in 129 Rho-related genes, 427 SNPs were significantly associated with CMSS (p  C, ARHGAP22 rs3851552 T > C, ARHGAP44 rs72635537 C > T and ARHGEF10 rs7826362 A > T) were independently predictive of CMSS (a meta-analysis derived p = 9.04 × 10-4 , 9.58 × 10-4 , 1.21 × 10-4 and 8.47 × 10-4 , respectively). Additionally, patients with an increasing number of unfavorable genotypes (NUGs) of these loci had markedly reduced CMSS in both discovery dataset and validation dataset (ptrend =1.47 × 10-7 and 3.12 × 10-5 ). The model including the NUGs and clinical variables demonstrated a significant improvement in predicting the five-year CMSS. Moreover, rs10916352C and rs3851552C alleles were significantly associated with an increased mRNA expression levels of RHOU (p = 1.8 × 10-6 ) and ARHGAP22 (p = 5.0 × 10-6 ), respectively. These results may provide promising prognostic biomarkers for CM personalized management and treatment

Mushroom-derived bioactive components with definite structures in alleviating the pathogenesis of Alzheimer’s disease

Alzheimer’s disease (AD) is a complicated neurodegenerative condition with two forms: familial and sporadic. The familial presentation is marked by autosomal dominance, typically occurring early in individuals under 65 years of age, while the sporadic presentation is late-onset, occurring in individuals over the age of 65. The majority of AD cases are characterized by late-onset and sporadic. Despite extensive research conducted over several decades, there is a scarcity of effective therapies and strategies. Considering the lack of a cure for AD, it is essential to explore alternative natural substances with higher efficacy and fewer side effects for AD treatment. Bioactive compounds derived from mushrooms have demonstrated significant potential in AD prevention and treatment by different mechanisms such as targeting amyloid formation, tau, cholinesterase dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, neurotrophic factors, ER stress, excitotoxicity, and mitochondrial dysfunction. These compounds have garnered considerable interest from the academic community owing to their advantages of multi-channel, multi-target, high safety and low toxicity. This review focuses on the various mechanisms involved in the development and progression of AD, presents the regulatory effects of bioactive components with definite structure from mushroom on AD in recent years, highlights the possible intervention pathways of mushroom bioactive components targeting different mechanisms, and discusses the clinical studies, limitations, and future perspectives of mushroom bioactive components in AD prevention and treatment

Identification of differentially expressed genes of blood leukocytes for Schizophrenia

BackgroundSchizophrenia (SCZ) is a severe neurodevelopmental disorder with brain dysfunction. This study aimed to use bioinformatic analysis to identify candidate blood biomarkers for SCZ.MethodsThe study collected peripheral blood leukocyte samples of 9 SCZ patients and 20 healthy controls for RNA sequencing analysis. Bioinformatic analyses included differentially expressed genes (DEGs) analysis, pathway enrichment analysis, and weighted gene co-expression network analysis (WGCNA).ResultsThis study identified 1,205 statistically significant DEGs, of which 623 genes were upregulated and 582 genes were downregulated. Functional enrichment analysis showed that DEGs were mainly enriched in cell chemotaxis, cell surface, and serine peptidase activity, as well as involved in Natural killer cell-mediated cytotoxicity. WGCNA identified 16 gene co-expression modules, and five modules were significantly correlated with SCZ (p < 0.05). There were 106 upregulated genes and 90 downregulated genes in the five modules. The top ten genes sorted by the Degree algorithm were RPS28, BRD4, FUS, PABPC1, PCBP1, PCBP2, RPL27A, RPS21, RAG1, and RPL27. RAG1 and the other nine genes belonged to the turquoise and pink module respectively. Pathway enrichment analysis indicated that these 10 genes were mainly involved in processes such as Ribosome, cytoplasmic translation, RNA binding, and protein binding.ConclusionThis study finds that the gene functions in key modules and related enrichment pathways may help to elucidate the molecular pathogenesis of SCZ, and the potential of key genes to become blood biomarkers for SCZ warrants further validation

Gene Expression in the Hippocampus in a Rat Model of Premenstrual Dysphoric Disorder After Treatment With Baixiangdan Capsules

Objective: To explore the targets, signal regulatory networks and mechanisms involved in Baixiangdan (BXD) capsule regulation of premenstrual dysphoric disorder (PMDD) at the gene transcription level, since the etiology and pathogenesis of PMDD are not well understood.Methods: The PMDD rat model was prepared using the resident-intruder paradigm. The rats were tested for aggressive behavior, and those with scores in the lowest 30% were used as controls, while rats with scores in the highest 30% were divided into a PMDD model group, BXD administration group and fluoxetine administration group, which were evaluated with open-field tests and aggressive behavior tests. We also analyzed gene expression profiles in the hippocampus for each group, and verified differential expression of genes by real-time PCR.Results: Before and after BXD or fluoxetine administration, scores in the open-field test exhibited no significant differences. The aggressive behavior of the PMDD model rats was improved to a degree after administration of both substances. Gene chip data indicated that 715 genes were differentially expressed in the control and BXD groups. Other group-to-group comparisons exhibited smaller numbers of differentially expressed genes. The effective targets of both drugs included the Htr2c, Cdh3, Serpinb1a, Ace, Trpv4, Cacna1a, Mapk13, Mapk8, Cyp2c13, and Htr1a genes. The results of real-time PCR tests were in accordance with the gene chip data. Based on the target genes and signaling pathway network analysis, we have elaborated the impact and likely mechanism of BXD in treating PMDD and premenstrual irritability.Conclusion: Our work contributes to the understanding of PMDD pathogenesis and the mechanisms of BXD treatment. We speculate that the differentially expressed genes could participate in neuroactive ligand-receptor interactions, mitogen-activated protein kinase, calcium, and gamma-aminobutyric acid signal transduction

EGFR deficiency leads to impaired self-renewal and pluripotency of mouse embryonic stem cells

Background Self-renewal and pluripotency are considered as unwavering features of embryonic stem cells (ESCs). How ESCs regulate the self-renewal and differentiation is a central question in development and regenerative medicine research. Epidermal growth factor receptor (EGFR) was identified as a critical regulator in embryonic development, but its role in the maintenance of ESCs is poorly understood. Methods Here, EGFR was disrupted by its specific inhibitor AG1478 in mouse ESCs (mESCs), and its self-renewal and pluripotency were characterized according to their proliferation, expression of pluripotency markers, embryoid body (EB) formation, and mRNA expression patterns. We also used another EGFR inhibitor (gefitinib) and RNA interference assay to rule out the possibility of non-specific effects of AG1478. Results EGFR inhibition by AG1478 treatment in mESCs markedly reduced cell proliferation, caused cell cycle arrest at G0/G1 phase, and altered protein expressions of the cell cycle regulatory genes (CDK2 (decreased 11.3%) and proliferating cell nuclear antigen (decreased 25.2%)). The immunoreactivities and protein expression of pluripotency factors (OCT4 (decreased 26.9%)) also dramatically decreased, while the differentiation related genes (GATA4 (increased 1.6-fold)) were up-regulated in mESCs after EGFR inhibition. Meanwhile, EGFR inhibition in mESCs disrupted EB formation, indicating its impaired pluripotency. Additionally, the effects observed by EGFR inhibition with another inhibitor gefitinib and siRNA were consistent with those observed by AG1478 treatment in mESCs. These effects were manifested in the decreased expression of proliferative and pluripotency-related genes and the increased expression of genes involved in differentiation. Moreover, RNA-seq analysis displayed that transcript profiling was changed significantly after EGFR inhibition by AG1478. A large number of differentially expressed genes were involved in cell cycle, apoptotic process, epigenetic modification, and metabolic process, which were related to self-renewal and pluripotency, confirming that EGFR deficiency impaired self-renewal and pluripotency in mESCs. Conclusions Taken together, our results demonstrated the importance of EGFR in guarding the stemness of mESCs

Pharmacokinetic study of isoquercitrin in rat plasma after intravenous administration at three different doses

The aim of this study is to develop a simple and specific HPLC method using vitexin as the internal standard to investigate the pharmacokinetics of isoquercitrin (ISOQ) after three different doses administrated intravenously to rats. The pharmacokinetic parameters were calculated by both compartmental and non-compartmental approaches. The results showed that ISOQ fitted a three-compartment open model. The values of AUC increased proportionally within the range of 5-10 mg·kg-1. Moreover, a half-life, b half-life, ªCL, MRT0-t and MRT0→∞ of ISOQ in rats showed significant differences between 20 mg·kg-1 and other doses, indicating that ISOQ presented dose-dependent pharmacokinetics in the range of 5-10 mg·kg-1 and non-linear pharmacokinetics at higher doses

CRAFTS for HI cosmology:I. data analysis and preliminary results

We present the results from calibrating the data of the Commensal Radio Astronomy FAST Survey (CRAFTS) for \HI intensity mapping by the Five-hundred-meter Aperture Spherical Radio Telescope (FAST). Using 70 hours of drift-scan observation with the L-band (1.05-1.45GHz) 19-beam receiver, we obtain the data covering $270\,\rm deg^2$ sky area. We employ both the pulsar backend and the spectrum backend to calibrate the spectral time-ordered-data (TOD) before projecting them onto HEALPix maps. We produce calibrated TOD with frequency resolution of 30 kHz and time resolution of 1 s and the map data-cube with frequency resolution of 30kHz and spatial resolution of $2.95\,\rm arcmin^2$. We carefully examine the pointing errors, noise overflow, RFI contamination and their effect on the data quality. The resulting noise level is $\sim$ 5.7 mJy for the calibrated TOD and 1.6 mJy for the map, which is consistent with the theoretical predictions within 5\% at RFI-free channels. We also validate the data by Principal Components Analysis (PCA) and find most foreground components are concentrated in the first 30 modes. We identify 447 isolated bright continuum sources in our data matching the NRAO-VLA Sky Survey (NVSS) catalog, with relative flux error of 8.3\% for TOD and 11.9\% for the map-level. We also measure the \HI emission of 90 galaxies with redshift $