Recent publications
Transfection of proteins, mRNA, and chimeric antigen receptor (CAR) transgenes into immune cells remains a critical bottleneck in cell manufacturing. Current methods, such as viruses and bulk electroporation, are hampered by low transfection efficiency, unintended transgene integration, and significant cell perturbation. The Nanostraw Electro-actuated Transfection (NExT) technology offers a solution by using high aspect-ratio nanostraws and localized electric fields to precisely deliver biomolecules into cells with minimal disruption. We demonstrate that NExT can deliver proteins, polysaccharides, and mRNA into primary human CD8+ and CD4+ T cells, and achieve CRISPR/Cas9 gene knockout of CXCR4 and TRAC in CD8+ T cells. We showcase NExT’s versatility across a range of primary human immune cells, including CD4+ T cells, γδ-T cells, dendritic cells, NK cells, Treg cells, macrophages, and neutrophils. Finally, we developed a scalable, high-throughput multiwell NExT system capable of transfecting over 14 million cells and delivering diverse cargoes into multiple cell types from various donors simultaneously. This technology holds promise for streamlining high-throughput screening of allogeneic donors and reducing optimization costs for large-scale CAR-immune cell transfection.
While technological advancements in treating electroplating wastewater continue, removing high concentrations of Ni2+ and Co2+ remains a challenge. Surface functionalization of clay has emerged as a pivotal approach for effectively removing heavy metals, rivaling intercalation modification in its effectiveness. This study investigated the adsorption performance and mechanisms of a phosphonate-modified layered double hydroxide material, employing batch experiments and simulation calculations to elucidate the impact of surface modification on adsorption behavior. Briefly, various characterization techniques confirmed that the layered double hydroxide synthesized through co-precipitation exhibited a sheet-like morphology, with phosphonate groups anchoring onto the clay surface following functionalization. Under optimal conditions (pH=6.0, t=60 min, and C0=300 mg/L), the material demonstrated high uptake capacities for Ni2+ (198.01 mg/g) and Co2+ (180.18 mg/g), surpassing most previously reported adsorbents. The adsorption kinetics for Ni2+ and Co2+ on the modified material followed a pseudo-second-order model, and the isotherms conformed to the Langmuir equation, indicating a monolayer chemical adsorption process. Moreover, after five adsorption-desorption cycles, the adsorbent demonstrated exceptional reusability and stability, and its potential for practical application preliminarily assessed using electroplating wastewater containing Ni2+. To further clarify the adsorption mechanism, a molecular dynamics simulation employing the CLAYFF-CVFF force field was conducted to examine the electrostatic interaction of modifiers at the clay surface. Wavefunction analyses derived from quantum chemical calculations provided insights into interactions, identified molecular reactive sites, and elucidated orbital interactions within chelation complexes. This research presents a feasible approach for developing high-performance materials for wastewater remediation in practical applications.
In the field of motion planning for autonomous driving systems, ensuring the safety of multi-vehicle navigation is one of the crucial topics. An unavoidable problem in practice is that the noise-induced uncertainties in real-world applications highly degrade the safety of multi-vehicle navigation. It is also challenging to guarantee the required computation efficiency of motion planning algorithms in such uncertain environments. In this work, we present a novel motion planning framework to enhance the safety and computation efficiency of multi-vehicle navigation. This framework utilizes the iterative linear quadratic Gaussian (iLQG) algorithm to deal with the nonlinearity of the vehicle dynamics and overcomes the difficulties in handling inequality constraints (e.g., collision avoidance constraints). Furthermore, we propose an innovative Alternating direction method of multipliers based Linearized Chance Constraint (ALCC) method to address collision constraints in noisy uncertain environments. Simulation experimental results demonstrate that our method achieves higher safety with high computational efficiency compared to other methods in various multi-vehicle motion planning and navigation scenarios.
Many multi-robot applications require allocating a team of heterogeneous agents (robots) with different abilities to cooperatively complete a given set of spatially distributed tasks as quickly as possible. We focus on tasks that can only be initiated when all required agents are present otherwise arrived agents would be waiting idly. Agents need to not only execute a sequence of tasks by dynamically forming and disbanding teams to satisfy/match diverse ability requirements of each task but also account for the schedules of other agents to minimize unnecessary idle time. Conventional methods such as mix-integer programming generally require centralized scheduling and a long optimization time, which limits their potential for real-world applications. In this work, we propose a reinforcement learning framework to train a decentralized policy applicable to heterogeneous agents. To address the challenge of complex cooperation learning, we further introduce a constrained flashforward mechanism to guide/constrain the agents' exploration and help them make better predictions. Through an attention mechanism that reasons about both short-term cooperation and long-term scheduling dependency, agents learn to reactively choose their next tasks (and subsequent coalitions) to avoid wasting abilities and to shorten the overall task completion time (makespan). We compare our method with state-of-the-art heuristic and mixed-integer programming methods, demonstrating its generalization ability and showing it closely matches or outperforms these baselines while remaining at least two orders of magnitude faster.
We report herein an unprecedented desymmetrization of 1,4‐diynes via a Rh‐catalyzed asymmetric redox cycloisomerization. This method adopts allylic alcohol‐containing diynes and provides efficient access to multi‐functional pyrrolidines and tetrahydrofurans in high to excellent stereoselectivities. Mechanistic studies highlighted an innovative catalytic pathway that differs from the classical enyne cycloisomerization and involves initiation at the allylic alcohol moiety. Diverse derivatizations of the heterocyclic products including intriguing skeletal rearrangements have also been demonstrated.
Background:
Universal health coverage (UHC) and global health security (GHS) should be pursued synergistically to strengthen health systems. However, existing studies found that the efforts toward the two agendas were divergent worldwide. We reviewed the synergy status between UHC and GHS in the Western Pacific Region (WPR) to provide evidence for decision-makers to promote synergy.
Methods:
We collected the UHC service coverage index (UHC SCI) and the GHS index (GHSI) scores. We created a four-quadrant diagram to discover the gap in UHC and GHS capacities within WPR and divide WPR countries into four groups based on the global mean scores. Further, we adopted global spatial autocorrelation analysis to discover spatial aggregations of high and low scores by calculating Moran's I. In addition, we conducted a correlation analysis to assess the synergy level in WPR and reveal the gap between Pacific Island countries or territories (PICTs) and non-PICTs. We conducted key informant interviews to uncover actual scenarios and address gaps in the quantitative evidence.
Results:
Compared to the global mean UHC SCI and GHSI scores, nine out of 13 non-PICTs had higher scores, while all 14 of the PICTs had lower scores for both indexes. The Moran's I for WPR countries' UHC SCI and GHSI scores in 2021 were 0.20 and 0.23, respectively (Z-score >2.58; P < 0.01). The correlation coefficients between the two index scores were 0.722 (P < 0.001) at the global level and 0.869 (P < 0.001) at WPR. Within the WPR, the correlation coefficients were 0.859 (P < 0.001) in the non-PICTs and -0.026 (P > 0.05) in the PICTs.
Conclusions:
The synergy level between UHC and GHS was high in the WPR, but this mainly came from the synergy in the non-PICTs. The two agendas have barely synergised the PICTs. To build a safer and healthier WPR, it is important to pay more attention to the countries that have weaker health capacities in the region and narrow the gap.
Shotgun metagenomics has become a pivotal technology in microbiome research, enabling in‐depth analysis of microbial communities at both the high‐resolution taxonomic and functional levels. This approach provides valuable insights of microbial diversity, interactions, and their roles in health and disease. However, the complexity of data processing and the need for reproducibility pose significant challenges to researchers. To address these challenges, we developed EasyMetagenome, a user‐friendly pipeline that supports multiple analysis methods, including quality control and host removal, read‐based, assembly‐based, and binning, along with advanced genome analysis. The pipeline also features customizable settings, comprehensive data visualizations, and detailed parameter explanations, ensuring its adaptability across a wide range of data scenarios. Looking forward, we aim to refine the pipeline by addressing host contamination issues, optimizing workflows for third‐generation sequencing data, and integrating emerging technologies like deep learning and network analysis, to further enhance microbiome insights and data accuracy. EasyMetageonome is freely available at https://github.com/YongxinLiu/EasyMetagenome.
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