Towards Generalist Robots: A Promising Paradigm via Generative Simulation

This document serves as a position paper that outlines the authors' vision for a potential pathway towards generalist robots. The purpose of this document is to share the excitement of the authors with the community and highlight a promising research direction in robotics and AI. The authors believe the proposed paradigm is a feasible path towards accomplishing the long-standing goal of robotics research: deploying robots, or embodied AI agents more broadly, in various non-factory real-world settings to perform diverse tasks. This document presents a specific idea for mining knowledge in the latest large-scale foundation models for robotics research. Instead of directly using or adapting these models to produce low-level policies and actions, it advocates for a fully automated generative pipeline (termed as generative simulation), which uses these models to generate diversified tasks, scenes and training supervisions at scale, thereby scaling up low-level skill learning and ultimately leading to a foundation model for robotics that empowers generalist robots. The authors are actively pursuing this direction, but in the meantime, they recognize that the ambitious goal of building generalist robots with large-scale policy training demands significant resources such as computing power and hardware, and research groups in academia alone may face severe resource constraints in implementing the entire vision. Therefore, the authors believe sharing their thoughts at this early stage could foster discussions, attract interest towards the proposed pathway and related topics from industry groups, and potentially spur significant technical advancements in the field

Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.

Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.Funding information: National Heart, Lung, and Blood Institute, Grant/Award Numbers: HL 122596, HL124021, HL124074, HL128297, HL141080, HL155346-01, R35HL150807, R56HL141206 Prithu Sundd was supported by NIH-NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027. SuamyaDaswas supported by NIH grants R35HL150807, UH3 TR002878 andAHASFRN35120123. ZhenjiaWangwas supported by NIH grant (R01EB027078). Pilar Martín was supported by MCIN-ISCIII-Fondo de Investigación Sanitaria grant PI22/01759. KennethW.Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 andUH3CA241694. Tianji Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH, NIH-NHLBI grant R56HL141206 and Chicago Biomedical ConsortiumCatalyst Award. EduardoMarbán was supported byNIH R01 HL124074 and HL155346-01.S

Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

Previous studies indicated that (+)-13a-(S)-Deoxytylophorinine (1) showed profound anti-cancer activities both in vitro and in vivo and could penetrate the blood brain barrier to distribute well in brain tissues. CNS toxicity, one of the main factors to hinder the development of phenanthroindolizidines, was not obviously found in 1. Based on its fascinating activities, thirty-four derivatives were designed, synthesized; their cytotoxic activities in vitro were tested to discover more excellent anticancer agents. Considering the distinctive mechanism of 1 and interesting SAR of deoxytylophorinine and its derivatives, the specific impacts of these compounds on cellular progress as cell signaling transduction pathways and cell cycle were proceeded with seven representative compounds. 1 as well as three most potent compounds, 9, 32, 33, and three less active compounds, 12, 16, 35, were selected to proform this study to have a relatively deep view of cancer cell growth-inhibitory characteristics. It was found that the expressions of phospho-Akt, Akt, phospho-ERK, and ERK in A549 cells were greater down-regulated by the potent compounds than by the less active compounds in the Western blot analysis. To the best of our knowledge, this is the first report describing phenanthroindolizidines alkaloids display influence on the crucial cell signaling proteins, ERK. Moreover, the expressions of cyclin A, cyclin D1 and CDK2 proteins depressed more dramatically when the cells were treated with 1, 9, 32, and 33. Then, these four excellent compounds were subjected to flow cytometric analysis, and an increase in S-phase was observed in A549 cells. Since the molecular level assay results of Western blot for phospho-Akt, Akt, phospho-ERK, ERK, and cyclins were relevant to the potency of compounds in cellular level, we speculated that this series of compounds exhibit anticancer activities through blocking PI3K and MAPK signaling transduction pathways and interfering with the cell cycle progression

Fabrication of TiO2-modified polytetrafluoroethylene ultrafiltration membranes via plasma-enhanced surface graft pretreatment

Surface hydrophilic modification of polymer ultrafiltration membrane using metal oxide represents an effective yet highly challenging solution to improve water flux and antifouling performance. Via plasma-enhanced graft of poly acryl acid (PAA) prior to coating TiO2, we successfully fixed TiO2 functional thin layer on super hydrophobic polytetrafluoroethylene (PTFE) ultrafiltration (UF) membranes. The characterization results evidenced TiO2 attached on the PTFE-based UF membranes through the chelating bidentate coordination between surface-grafted carboxyl group and Ti4+. The TiO2 surface modification may greatly reduce the water contact angle from 115.8° of the PTFE membrane to 35.0° without degradation in 30-day continuous filtration operations. The novel TiO2/PAA/PTFE membranes also exhibited excellent antifouling and self-cleaning performance due to the intrinsic hydrophilicity and photocatalysis properties of TiO2, which was further confirmed by the photo-degradation of MB under Xe lamp irradiation

Effect of Point Cloud Data Simplification and Encryption on Micro-Topography Data Analysis

Simplification and encryption are performed on the point cloud data concerning high-relief (20 cm tillage) and low-relief (raking bare slope) terrain on a different scale of observation. We select three indicators (surface curvature, slope aspect and surface roughness) to evaluate the effect of simplification and encryption on micro-topography data analysis. The results show that simplification and encryption have a significant impact on the curvature of high-relief terrain, but have no significant impact on low-relief terrain. The slope aspect change is not significant after 5, 10 mm data simplification and encryption; 1 mm simplification has a regular impact on surface roughness; 5 mm encryption and simplification have a complex impact on high-relief terrain; 10 mm encryption has a complex impact on high-relief terrain roughness change but a regular impact on bare slope change

Application value of ST2 combined with CEA and CYFRA211 in diagnosis of early non-small cell lung cancer

Objective: To explore soluble growth stimulation expressed gene 2 protein (ST2), carcinoembryonic antigen（CEA） and cytokeratin fragment 21-1 (CYFRA211) in diagnosing early non-small cell lung cancer (NSCLC). Methods: From January to August 2023, 91 patients with early NSCLC (TNM stage Ⅰ) and 21 patients with middle and advanced NSCLC [TNM stage Ⅱ (16 cases) and Ⅲ (5 cases)] admitted to Ruijin Hospital were collected, and 50 patients with benign lung lesions(BL) and 50 healthy people(HC) were served as controls. Plasma ST2 levels were detected by fluorescence immunochromatography, and serum CEA and CYFRA211 levels were detected by chemiluminescence. The differences between groups were compared, and the diagnostic value of index alone or in combination for NSCLC was analyzed. Results: ST2 level in the early NSCLC group was higher than that in the BL and HC group （P<0.001), and ST2 level in BL group was higher than HC group (P<0.001). The CEA level in the early NSCLC group were higher than that in the HC group (P<0.05), BL group was higher than HC group (P<0.05). The CYFRA211 level in the early NSCLC group was higher than that in the HC group (P<0.05). When the cutoff values of ST2, CEA and CYFRA211 were set as 25.0 ng/L, 1.8 ng/mL and 2.0 ng/mL, areas under receiver operator characteristic (ROC) curve for diagnosing early NSCLC were 0.957, 0.660 and 0.570, respectively. The sensitivity of ST2,CEA and CYFRA211 for diagnosing early NSCLC were 89.0%, 46.2% and, 17.6%,and specificity were 98.0%, 80.0%, 96.0%, respectively. The area under the curve of the combined detection were 0.973, with a sensitivity of 92.3% and the specificity of 98.0%,which were higher than that of any index. In terms of clinicopathological features, plasma ST2 level was higher in NSCLC patients with larger tumors than with smaller tumors（P<0.05）. There were statistical differences in CEA levels among groups with different degrees of tumor differentiation, between groups with and without regional lymph node metastasis, groups with and without airway spread, groups with and without pleural invasion, and groups with TMN stage Ⅰ and TMN Ⅱ/Ⅲ/Ⅳ（P<0.05）. CYFRA211 levels were significantly different between diffe-rent sex groups, age groups and lung cancer types (P<0.05). Conclusions: Compared with CEA and CYFRA211, ST2 alone is more advantageous in distinguishing early NSCLC patients from patients with benign lung lesions and healthy controls. However, combined detection of the three tests has higher diagnostic value and is recommended to assist the diagnosis of early NSCLC