From Knowing to Doing: Learning Diverse Motor Skills through Instruction Learning

Recent years have witnessed many successful trials in the robot learning field. For contact-rich robotic tasks, it is challenging to learn coordinated motor skills by reinforcement learning. Imitation learning solves this problem by using a mimic reward to encourage the robot to track a given reference trajectory. However, imitation learning is not so efficient and may constrain the learned motion. In this paper, we propose instruction learning, which is inspired by the human learning process and is highly efficient, flexible, and versatile for robot motion learning. Instead of using a reference signal in the reward, instruction learning applies a reference signal directly as a feedforward action, and it is combined with a feedback action learned by reinforcement learning to control the robot. Besides, we propose the action bounding technique and remove the mimic reward, which is shown to be crucial for efficient and flexible learning. We compare the performance of instruction learning with imitation learning, indicating that instruction learning can greatly speed up the training process and guarantee learning the desired motion correctly. The effectiveness of instruction learning is validated through a bunch of motion learning examples for a biped robot and a quadruped robot, where skills can be learned typically within several million steps. Besides, we also conduct sim-to-real transfer and online learning experiments on a real quadruped robot. Instruction learning has shown great merits and potential, making it a promising alternative for imitation learning

Quadruped robot traversing 3D complex environments with limited perception

Traversing 3-D complex environments has always been a significant challenge for legged locomotion. Existing methods typically rely on external sensors such as vision and lidar to preemptively react to obstacles by acquiring environmental information. However, in scenarios like nighttime or dense forests, external sensors often fail to function properly, necessitating robots to rely on proprioceptive sensors to perceive diverse obstacles in the environment and respond promptly. This task is undeniably challenging. Our research finds that methods based on collision detection can enhance a robot's perception of environmental obstacles. In this work, we propose an end-to-end learning-based quadruped robot motion controller that relies solely on proprioceptive sensing. This controller can accurately detect, localize, and agilely respond to collisions in unknown and complex 3D environments, thereby improving the robot's traversability in complex environments. We demonstrate in both simulation and real-world experiments that our method enables quadruped robots to successfully traverse challenging obstacles in various complex environments.Comment: 10 pages, 8 figures,submitted to iros202

Integrated multi-omics analysis reveals complement component 3 as a central driver of immune dysregulation in polycystic ovary syndrome

BackgroundPolycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder with a complex pathophysiology, affecting various aspects of women’s health. Despite its widespread impact, the molecular basis and immunological aspects of PCOS remain insufficiently understood, limiting effective diagnosis and treatment strategies.ObjectiveThis study aims to elucidate the molecular and immunological landscape of PCOS by integrating gene expression profiles from healthy and PCOS-affected ovaries using both bulk and single-cell omics data, with the goal of constructing a comprehensive bioinformatics network that identifies potential biomarkers and therapeutic targets.MethodsLeveraging publicly available omics datasets, we compared gene expression between healthy ovaries and those affected by PCOS through both bulk and single-cell analyses. Our approach focused on differential gene expression analysis, identification of distinct cell types and gene signatures in PCOS, construction of disease-specific gene expression modules, and mapping of cellular differentiation trajectories. Additionally, we examined the alterations in the immune microenvironment within PCOS to identify immune-related changes.ResultsOur analyses uncovered unique molecular signatures and immune modules in PCOS, characterized by differential gene expression, the presence of unique cell types, and altered pathways compared to healthy controls. Notably, we identified a significant role for Complement Component 3 (C3) in mediating these changes. Through gene intervention targeting C3 in granulosa cells and functional studies examining the effects of secreted C3 protein on H295R cells, Low level C3 mitigated inflammatory responses, while excess C3 proved detrimental to cell growth.ConclusionOur integrative omics analysis provides new insights into the molecular and immunological underpinnings of PCOS, highlighting the role of C3 in the disease’s pathogenesis. The identification of key molecular signatures and immune modules, including the involvement of C3, opens promising avenues for the development of novel diagnostic and therapeutic strategies for PCOS. These observations suggest that modulating C3 levels could have therapeutic implications for managing PCOS

The Antidepressant Sertraline Provides a Promising Therapeutic Option for Neurotropic Cryptococcal Infections

Therapeutic treatment for systemic mycoses is severely hampered by the extremely limited number of antifungals. The difficulty of treatment of fungal infections in the central nervous system is further compounded by the poor central nervous system (CNS) penetration of most antifungals due to the blood-brain barrier. Only a few fungistatic azole drugs, such as fluconazole, show reasonable CNS penetration. Here we demonstrate that sertraline (Zoloft), the most frequently prescribed antidepressant, displays potent antifungal activity against Cryptococcus neoformans, the major causative agent of fungal meningitis. In in vitro assays, this neurotropic drug is fungicidal to all natural Cryptococcus isolates tested at clinically relevant concentrations. Furthermore, sertraline interacts synergistically or additively with fluconazole against Cryptococcus. Importantly, consistent with our in vitro observations, sertraline used alone reduces the brain fungal burden at an efficacy comparable to that of fluconazole in a murine model of systemic cryptococcosis. It works synergistically with fluconazole in reducing the fungal burden in brain, kidney, and spleen. In contrast to its potency against Cryptococcus, sertraline is less effective against strains of Candida species and its interactions with fluconazole against Candida strains are often antagonistic. Therefore, our data suggest the unique application of sertraline against cryptococcosis. To understand the antifungal mechanisms of sertraline, we screened a whole-genome deletion collection of Saccharomyces cerevisiae for altered sertraline susceptibility. Gene ontology analyses of selected mutations suggest that sertraline perturbs translation. In vitro translation assays using fungal cell extracts show that sertraline inhibits protein synthesis. Taken together, our findings indicate the potential of adopting this antidepressant in treating cryptococcal meningitis

Key sugar transporters drive development and pathogenicity in Aspergillus flavus

Aspergillus flavus is a ubiquitous filamentous fungus that poses significant threats as both a causative agent of invasive aspergillosis and a major source of crop contamination due to production of aflatoxin B1 (AFB1). Sugars are essential for fungal metabolism, cell wall biosynthesis, and virulence, yet sugar transporters (STPs) in A. flavus remain largely uncharacterized. In this study, we systematically investigated three putative STP genes (G4B84_001982, G4B84_005374, and G4B84_009351) by comprehensive functional characterization of gene deletion mutants. Growth assays revealed that G4B84_001982 and G4B84_005374 mediate uptake of diverse sugar substrates, while G4B84_009351 appeared to be non-essential under tested conditions. Heterologous expressions in the hexose transport-deficient Saccharomyces cerevisiae strain confirmed their sugar transporter activity. Phenotypic analysis revealed that the Δ1982 and Δ5374 mutants showed pleiotropic defects, including impaired growth, reduced sporulation, delayed germination, increased sensitivity to cell wall stressors, and completely abolished sclerotium formation. Pathogenicity assays demonstrated that the two mutants exhibited attenuated virulence in both plants (crop seeds) and animal (Galleria mellonella) infection model. Our findings highlight the essential of two STPs in A. flavus development, stress tolerance, and pathogenicity, offering insights into sugar-mediated pathogenicity in this economically and medically important fungus

Palmitic Acid Analogs Exhibit Nanomolar Binding Affinity for the HIV-1 CD4 Receptor and Nanomolar Inhibition of gp120-to-CD4 Fusion

Background: We recently reported that palmitic acid (PA) is a novel and efficient CD4 fusion inhibitor to HIV-1 entry and infection. In the present report, based on in silico modeling of the novel CD4 pocket that binds PA, we describe discovery of highly potent PA analogs with increased CD4 receptor binding affinities (Kd) and gp120-to-CD4 inhibition constants (Ki). The PA analogs were selected to satisfy Lipinski’s rule of drug-likeness, increased solubility, and to avoid potential cytotoxicity. Principal Findings: PA analog 2-bromopalmitate (2-BP) was most efficacious with Kd,74 nM and Ki,122 nM, ascorbyl palmitate (6-AP) exhibited slightly higher Kd,140 nM and Ki,354 nM, and sucrose palmitate (SP) was least efficacious binding to CD4 with Kd,364 nM and inhibiting gp120-to-CD4 binding with Ki,1486 nM. Importantly, PA and its analogs specifically bound to the CD4 receptor with the one to one stoichiometry. Significance: Considering observed differences between K i and K d values indicates clear and rational direction for improving inhibition efficacy to HIV-1 entry and infection. Taken together this report introduces a novel class of natural small molecules fusion inhibitors with nanomolar efficacy of CD4 receptor binding and inhibition of HIV-1 entry

Functional profile of perilesional gray matter in focal cortical dysplasia: an fMRI study

ObjectivesWe aim to investigate the functional profiles of perilesional gray matter (GM) in epileptic patients with focal cortical dysplasia (FCD) and to correlate these profiles with FCD II subtypes, surgical outcomes, and different antiseizure medications (ASMs) treatment response patterns.MethodsNine patients with drug-responsive epilepsy and 30 patients with drug-resistant epilepsy (11 were histologically confirmed FCD type IIa, 19 were FCD type IIb) were included. Individual-specific perilesional GM and contralateral homotopic GM layer masks were generated. These masks underwent a two-voxel (2 mm) dilation from the FCD lesion and contralateral homotopic region, resulting in 10 GM layers (20 mm). Layer 1, the innermost, progressed to Layer 10, the outermost. Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analyses were conducted to assess the functional characteristics of ipsilateral perilesional GM and contralateral homotopic GM.ResultsCompared to the contralateral homotopic GM, a significant reduction of ALFF was detected at ipsilateral perilesional GM layer 1 to 6 in FCD type IIa (after Bonferroni correction p < 0.005, paired t-test), whereas a significant decrease was observed at ipsilateral perilesional GM layer 1 to 2 in FCD type IIb (after Bonferroni correction p < 0.005, paired t-test). Additionally, a significant decrease of the ReHo was detected at ipsilateral perilesional GM layer 1 compared to the CHRs in FCD type IIb. Notably, complete resection of functional perilesional GM alterations did not correlate with surgical outcomes. Compared to the contralateral homotopic GM, a decreased ALFF in the ipsilateral perilesional GM layer was detected in drug-responsive patients, whereas decreased ALFF in the ipsilateral perilesional GM layer 1–6 and decreased ReHo at ipsilateral perilesional GM layer 1 were observed in drug-resistant patients (after Bonferroni correction p < 0.005, paired t-test).ConclusionOur findings indicate distinct functional profiles of perilesional GM based on FCD histological subtypes and ASMs’ response patterns. Importantly, our study illustrates that the identified functional alterations in perilesional GM may not provide sufficient evidence to determine the epileptogenic boundary required for surgical resection

Dominance of HIV-1 Subtype CRF01_AE in Sexually Acquired Cases Leads to a New Epidemic in Yunnan Province of China

BACKGROUND: Dating back to the first epidemic among injection drug users in 1989, the Yunnan province has had the highest number of human immunodeficiency virus type 1 (HIV-1) infections in China. However, the molecular epidemiology of HIV-1 in Yunnan has not been fully characterized. METHODS AND FINDINGS: Using immunoassays, we identified 103,015 accumulated cases of HIV-1 infections in Yunnan between 1989 and 2004. We studied 321 patients representing Yunnan's 16 prefectures from four risk groups, 11 ethnic populations, and ten occupations. We identified three major circulating subtypes: C/CRF07_BC/CRF08_BC (53%), CRF01_AE (40.5%), and B (6.5%) by analyzing the sequence of p17, which is part of the gag gene. For patients with known risk factors, 90.9% of injection drug users had C/CRF07_BC/CRF08_BC viruses, whereas 85.4% of CRF01_AE infections were acquired through sexual transmission. No distinct segregation of CRF01_AE viruses was found among the Dai ethnic group. Geographically, C/CRF07_BC/CRF08_BC was found throughout the province, while CRF01_AE was largely confined to the prefectures bordering Myanmar. Furthermore, C/CRF07_BC/CRF08_BC viruses were found to consist of a group of viruses, including C, CRF08_BC, CRF07_BC, and new BC recombinants, based on the characterization of their reverse transcriptase genes. CONCLUSIONS: This is the first report of a province-wide HIV-1 molecular epidemiological study in Yunnan. While C/CRF07_BC/CRF08_BC and CRF01_AE are codominant, the discovery of many sexually transmitted CRF01_AE cases is new and suggests that this subtype may lead to a new epidemic in the general Chinese population. We discuss implications of our results for understanding the evolution of the HIV-1 pandemic and for vaccine development

H5N1 Vaccine-Specific B Cell Responses in Ferrets Primed with Live Attenuated Seasonal Influenza Vaccines

Live attenuated influenza H5N1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza A virus infection (Suguitan et al., Plos Medicine, e360:1541, 2006). However, the preexisting influenza heterosubtypic immunity on live attenuated H5N1 vaccine induced immune response has not been evaluated.Primary and recall B cell responses to live attenuated H5N1 vaccine viruses were examined using a sensitive antigen-specific B cell ELISpot assay to investigate the effect of preexisting heterosubtypic influenza immunity on the development of H5N1-specific B cell immune responses in ferrets. Live attenuated H5N1 A/Hong Kong/213/03 and A/Vietnam/1203/04 vaccine viruses induced measurable H5-specific IgM and IgG secreting B cells after intranasal vaccination. However, H5-specific IgG secreting cells were detected significantly earlier and at a greater frequency after H5N1 inoculation in ferrets previously primed with trivalent live attenuated influenza (H1N1, H3N2 and B) vaccine. Priming studies further revealed that the more rapid B cell responses to H5 resulted from cross-reactive B cell immunity to the hemagglutinin H1 protein. Moreover, vaccination with the H1N1 vaccine virus was able to induce protective responses capable of limiting replication of the H5N1 vaccine virus to a level comparable with prior vaccination with the H5N1 vaccine virus without affecting H5N1 vaccine virus induced antibody response. vaccine and the heterosubtypic immunity may be beneficial for pandemic preparedness