Synthetic Cells and Molecules in Cellular Immunotherapy.

Cellular immunotherapy has emerged as an exciting strategy for cancer treatment, as it aims to enhance the body's immune response to tumor cells by engineering immune cells and designing synthetic molecules from scratch. Because of the cytotoxic nature, abundance in peripheral blood, and maturation of genetic engineering techniques, T cells have become the most commonly engineered immune cells to date. Represented by chimeric antigen receptor (CAR)-T therapy, T cell-based immunotherapy has revolutionized the clinical treatment of hematological malignancies. However, serious side effects and limited efficacy in solid tumors have hindered the clinical application of cellular immunotherapy. To address these limitations, various innovative strategies regarding synthetic cells and molecules have been developed. On one hand, some cytotoxic immune cells other than T cells have been engineered to explore the potential of targeted elimination of tumor cells, while some adjuvant cells have also been engineered to enhance the therapeutic effect. On the other hand, diverse synthetic cellular components and molecules are added to engineered immune cells to regulate their functions, promoting cytotoxic activity and restricting side effects. Moreover, novel bioactive materials such as hydrogels facilitating the delivery of therapeutic immune cells have also been applied to improve the efficacy of cellular immunotherapy. This review summarizes the innovative strategies of synthetic cells and molecules currently available in cellular immunotherapies, discusses the limitations, and provides insights into the next generation of cellular immunotherapies.

The impact study of variable diameter stabilizer on drilling fluid and cuttings transport.

Through numerical simulation, this study investigates the flow field characteristics of the variable diameter stabilizer in drilling tools under various conditions. It analyzes the influence of different flow rates and speeds on axial velocity and pressure distribution. The results indicate that more significant flow rates correspond to higher average axial velocities across sections, facilitating the transport of drilling fluid and cuttings. Increasing rotational speed leads to greater pressure differences between adjacent sections, consequently elevating the overall pressure drop of the tool, which, to some extent, aids in transporting drilling fluid with cuttings. During rotation, the vortex zone on the backside of the stabilizer creates a hovering and accumulation of cuttings, causing mud agglomeration, thereby affecting tool performance. During structural optimization of the tool, priority should be given to a transitional design of the outlet area in the functional core zone, aiming to alleviate the impact of abrupt structural expansions on cuttings transport.

LA-ViT: A Network With Transformers Constrained by Learned-Parameter-Free Attention for Interpretable Grading in a New Laryngeal Histopathology Image Dataset.

Grading laryngeal squamous cell carcinoma (LSCC) based on histopathological images is a clinically significant yet challenging task. However, more low-effect background semantic information appeared in the feature maps, feature channels, and class activation maps, which caused a serious impact on the accuracy and interpretability of LSCC grading. While the traditional transformer block makes extensive use of parameter attention, the model overlearns the low-effect background semantic information, resulting in ineffectively reducing the proportion of background semantics. Therefore, we propose an end-to-end network with transformers constrained by learned-parameter-free attention (LA-ViT), which improve the ability to learn high-effect target semantic information and reduce the proportion of background semantics. Firstly, according to generalized linear model and probabilistic, we demonstrate that learned-parameter-free attention (LA) has a stronger ability to learn highly effective target semantic information than parameter attention. Secondly, the first-type LA transformer block of LA-ViT utilizes the feature map position subspace to realize the query. Then, it uses the feature channel subspace to realize the key, and adopts the average convergence to obtain a value. And those construct the LA mechanism. Thus, it reduces the proportion of background semantics in the feature maps and feature channels. Thirdly, the second-type LA transformer block of LA-ViT uses the model probability matrix information and decision level weight information to realize key and query, respectively. And those realize the LA mechanism. So, it reduces the proportion of background semantics in class activation maps. Finally, we build a new complex semantic LSCC pathology image dataset to address the problem, which is less research on LSCC grading models because of lacking clinically meaningful datasets. After extensive experiments, the whole metrics of LA-ViT outperform those of other state-of-the-art methods, and the visualization maps match better with the regions of interest in the pathologists' decision-making. Moreover, the experimental results conducted on a public LSCC pathology image dataset show that LA-ViT has superior generalization performance to that of other state-of-the-art methods.

Monocytes in allo-HSCT with aged donors secrete IL-1/IL-6/TNF to increase the risk of GVHD and damage the aged HSCs.

Aging is considered a critical factor of poor prognosis in allogenic hemopoietic stem cell transplantation (allo-HSCT). To elucidate the underlying mechanisms, we comprehensively reintegrated our clinical data from patients after allo-HSCT and public single-cell transcriptomic profile from post-allo-HSCT and healthy individuals, demonstrating that old donors were more prone to acute GVHD (aGVHD) with pronounced inflammation accumulation and worse overall survival (OS). We also found the presence of inflammation-related CXCL2+ HSC subpopulation during aging with significantly enriched pro-inflammatory pathways. Shifting attention to the HSC microenvironment, we deciphered that IL-1/IL-6 and TRAIL (i.e., TNFSF10) ligand‒receptor pair serves as the crucial bridge between CD14/CD16 monocytes and hematopoietic stem/progenitor cells (HSPCs). The profound upregulation of these signaling pathways during aging finally causes HSC dysfunction and lineage-biased differentiation. Our findings provide the theoretical basis for achieving tailored GVHD management and enhancing allo-HSCT regimens efficacy for aged donors.

Dynamics of self-hybridized exciton-polaritons in 2D halide perovskites.

Excitons, bound electron-hole pairs, in two-dimensional hybrid organic inorganic perovskites (2D HOIPs) are capable of forming hybrid light-matter states known as exciton-polaritons (E-Ps) when the excitonic medium is confined in an optical cavity. In the case of 2D HOIPs, they can self-hybridize into E-Ps at specific thicknesses of the HOIP crystals that form a resonant optical cavity with the excitons. However, the fundamental properties of these self-hybridized E-Ps in 2D HOIPs, including their role in ultrafast energy and/or charge transfer at interfaces, remain unclear. Here, we demonstrate that >0.5 µm thick 2D HOIP crystals on Au substrates are capable of supporting multiple-orders of self-hybridized E-P modes. These E-Ps have high Q factors (>100) and modulate the optical dispersion for the crystal to enhance sub-gap absorption and emission. Through varying excitation energy and ultrafast measurements, we also confirm energy transfer from higher energy E-Ps to lower energy E-Ps. Finally, we also demonstrate that E-Ps are capable of charge transport and transfer at interfaces. Our findings provide new insights into charge and energy transfer in E-Ps opening new opportunities towards their manipulation for polaritonic devices.

Optical Nonlinearity in Silicon Nanowires Enabled by Bound States in the Continuum.

Intense electromagnetic fields localized within resonant photonic nanostructures provide versatile opportunities for engineering nonlinear optical effects on a subwavelength scale. For dielectric structures, optical bound states in the continuum (BICs, resonant nonradiative modes that exist within the radiation continuum) are an emerging strategy to localize and intensify fields. Here, we report efficient second and third harmonic generation from Si nanowires (NWs) encoded with BIC and quasi-BIC resonances. In situ dopant modulation during vapor-liquid-solid NW growth was followed by wet-chemical etching to periodically modulate the diameter of the Si NWs and create cylindrically symmetric geometric superlattices (GSLs) with precisely defined axial and radial dimensions. By variation of the GSL structure, BIC and quasi-BIC resonant conditions were created to span visible and near-infrared optical frequencies. To probe the optical nonlinearity of these structures, we collected linear extinction spectra and nonlinear spectra from single-NW GSLs, demonstrating that quasi-BIC spectral positions at the fundamental frequency are directly correlated with enhanced harmonic generation at second and third harmonic frequencies. Interestingly, we find that deliberate geometric detuning from the BIC condition leads to a quasi-BIC resonance with maximal harmonic generation efficiency by providing a balance between the capacity to trap light and the capacity to couple to the external radiation continuum. Moreover, under focused illumination, as few as 30 geometric unit cells are required to achieve more than 90% of the approximate maximum theoretical efficiency of an infinite structure, indicating that nanostructures with projected areas smaller than ∼10 µm2 can support quasi-BICs for efficient harmonic generation. The results represent an important step toward the design of efficient harmonic generation at the nanoscale and further highlight the photonic utility of BICs at optical frequencies in ultracompact one-dimensional nanostructures.

Inflammation and aging: signaling pathways and intervention therapies.

Aging is characterized by systemic chronic inflammation, which is accompanied by cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there is an urgent need for a systematic organization of inflammaging through dimensionality reduction. Factors secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP), promote chronic inflammation and can induce senescence in normal cells. At the same time, chronic inflammation accelerates the senescence of immune cells, resulting in weakened immune function and an inability to clear senescent cells and inflammatory factors, which creates a vicious cycle of inflammation and senescence. Persistently elevated inflammation levels in organs such as the bone marrow, liver, and lungs cannot be eliminated in time, leading to organ damage and aging-related diseases. Therefore, inflammation has been recognized as an endogenous factor in aging, and the elimination of inflammation could be a potential strategy for anti-aging. Here we discuss inflammaging at the molecular, cellular, organ, and disease levels, and review current aging models, the implications of cutting-edge single cell technologies, as well as anti-aging strategies. Since preventing and alleviating aging-related diseases and improving the overall quality of life are the ultimate goals of aging research, our review highlights the critical features and potential mechanisms of inflammation and aging, along with the latest developments and future directions in aging research, providing a theoretical foundation for novel and practical anti-aging strategies.

Brain organoids are new tool for drug screening of neurological diseases.

At the level of in vitro drug screening, the development of a phenotypic analysis system with high-content screening at the core provides a strong platform to support high-throughput drug screening. There are few systematic reports on brain organoids, as a new three-dimensional in vitro model, in terms of model stability, key phenotypic fingerprint, and drug screening schemes, and particularly regarding the development of screening strategies for massive numbers of traditional Chinese medicine monomers. This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases. The paper also highlights the prospects from model stability, induction criteria of brain organoids, and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system.

Second Harmonic Generation from a Single Plasmonic Nanorod Strongly Coupled to a WSe2 Monolayer.

Monolayer transition metal dichalcogenides, coupled to metal plasmonic nanocavities, have recently emerged as new platforms for strong light-matter interactions. These systems are expected to have nonlinear-optical properties that will enable them to be used as entangled photon sources, compact wave-mixing devices, and other elements for classical and quantum photonic technologies. Here, we report the first experimental investigation of the nonlinear properties of these strongly coupled systems, by observing second harmonic generation from a WSe2 monolayer strongly coupled to a single gold nanorod. The pump-frequency dependence of the second-harmonic signal displays a pronounced splitting that can be explained by a coupled-oscillator model with second-order nonlinearities. Rigorous numerical simulations utilizing a nonperturbative nonlinear hydrodynamic model of conduction electrons support this interpretation and reproduce experimental results. Our study thus lays the groundwork for understanding the nonlinear properties of strongly coupled nanoscale systems.