Sustained Antitumor Immunity Based on Persistent Luminescence Nanoparticles for Cancer Immunotherapy

Immunotherapy holds great promise for cancer treatment. The key to improving the therapeutic effect is to drive the patient's own immune system to produce a strong, effective, and enduring tumor-specific immune response. Engineered nanoplatforms show promising potential in strengthening antitumor immune responses. However, current nanotherapeutic platforms based on exogenous responses stimulate the immune system only in a transitory and limited manner, which translates into insufficient immune activation and a low therapeutic efficacy. A novel targeted nano-immunostimulant (ZGS-Si-Pc@HA) is fabricated by coupling persistent luminescence nanoparticles with a photosensitizer and hyaluronic acid for sustained immune stimulation upon irradiation with biological window (659 nm) light. ZGS-Si-Pc@HA persistently drives reactive oxygen species production to induce immunogenic cell death, causing a durable tumor-specific immune response. Upon intratumoral injection, ZGS-Si-Pc@HA effectively alleviates immune tolerance and promotes T lymphocyte tumor infiltration. Further, ZGS-Si-Pc@HA enhances the therapeutic effect of checkpoint blockade immunotherapy, effectively inhibiting bilateral tumor growth and triggering an immunological memory effect. Nano-immunostimulants not only provide a new way to boost cancer immunotherapy, but also offer a reliable strategy for fighting cancer metastasis and recurrence clinically.     

基于免疫算法的Hopfield神经网络多用户检测器

提出的基于免疫算法的Hopfield神经网络多用户检测器，将扰乱的Hopfield神经网络多用户检测器的输出作为免疫算法的初始种群，利用了免疫算法的全局收敛的特点，从而克服了Hopfield易收敛到局部能量最小点的缺点。理论分析和仿真结果表明：该检测器具有良好的抗多址干扰和抗远近效应的能力。     

Effect of indomethacin on the immunological indices of patients with inoperable stomach cancer

Immunoregulatory T-lymphocytes (T mu- and T gamma-lymphocytes) and circulating immune complexes were studied in inoperable patients with the stomach carcinoma of stages III-IV. It is established that the absolute number of T-lymphocytes, mainly of T-helpers/inductors increases after the administration of indomethacin and 5-fluorouracil with indomethacin. The T mu/T gamma-lymphocyte ratio increases and approaches the control values. The level of the circulating immune complexes tends to be normalized. The main effect of indomethacin is determined by the effect of T-lymphocytes on immunoregulatory subpopulations.     

Interrelation of erythropoiesis and lymphopoiesis in experimental infectious processes and in viral leukemogenesis

Interrelation of erythropoiesis and immune response was studied in mice of various lines infected with mycoplasma species, Shigella flexneri 2a and Rauscher leukemia virus (R-MLV). Intensity of erythropoiesis was estimated by the endocolonization data of sublethally irradiated mice and 59Fe incorporation, while immune reactivity--by generation of splenic antibody-forming cells in response to immunization with sheep erythrocytes. The inverse correlation between the ability of infectious agents to enhance erythropoiesis and to depress immune reactivity was found. Enhanced state of erythropoiesis was observed with concomitant diminished immune response when R-MLV and M. arthritidis or S. flexneri 2a (strain 516) were used. There was a positive correlation between the ability of mycoplasmae and shigellae to activate erythropoiesis and their stimulatory effect on R-MLV reproduction tested by the spleen focus-forming units (SFFU) enumeration technique. Possible role of mononuclear phagocytes in the phenomena mentioned is discussed.     

Engineered Oxygen Factories Synergize with STING Agonist to Remodel Tumor Microenvironment for Cancer Immunotherapy

Immunotherapy is a revolutionary achievement in cancer treatment. However, inadequate immune cells infiltration in tumor microenvironment (TME) always leads to treatment failure. Moreover, hypoxic TME hampers normal functions of immune cells. Here, it is found that hypoxia suppresses the STING signaling and immune cells activation in the work. Remodeling tumor immune microenvironment and relieving hypoxia are thus essential for enhancing immunotherapy efficiency. Herein, a spirulina platensis (SP)-based magnetic biohybrid system is constructed as an oxygen factory and loaded with stimulator of interferon genes (STING) agonist ADU-S100 (ADU@Fe-SP) for tumor immunotherapy. Magnet-guided biohybrid SP can actively target tumor tissues and produce oxygen in situ through photosynthesis, which reverses the hypoxic TME and facilitates the function of immune cells. Besides, the targeted delivery of ADU-S100 can activate the STING/TBK1/IRF3 signaling and boost cytokines production in tumor and innate immune cells. The ADU@Fe-SP system thus induces efficient immune cells infiltration in TME, which efficiently inhibits tumor progression and significantly enhances anti-PD-1 therapy efficiency in SCC VII-bearing tumor xenograft. ADU@Fe-SP exerts antitumor effect in a STING-dependent manner by in vivo STING-knockout mice model. The efficiency of this immunotherapy strategy is also demonstrated in patient-derived xenograft model originating from oral cancer, showing great clinical potential.     

Possible zymosan stimulation of the immune response of BALB/c mice to sheep erythrocytes and tumor target cells

Zymosan and its combinations with cyclophosphamide were tested for their effect on various immune responses. Zymosan alone had only minor effect on the cytotoxicity of lymphocytes to allogeneic and syngeneic tumour cells but significantly stimulated delayed-type hypersensitivity response, rosette formation and plaque forming cell response to sheep red blood cells in normal mice. Zymosan diminished immunosuppressive action of cyclophosphamide on the plaque and rosette formations and nonspecific allogeneic lysis of target cells by lymph node lymphocytes. Delayed-type hypersensitivity skin reaction and syngeneic T-killer cell activity increased significantly after the procedure of combination therapy. Lymphocyte stimulation action by the polysaccharide depended on the injection schedule used. Preliminary injection of zymosan was an optimal condition for enhancement of the cellular immune response.     

The effect of biocarbazine on the indices of humoral and cellular immunity in mice

Biocarbazin (5-3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide) when administered in different doses and schedules depressed the primary immune response of mice to erythrocytes (SE). A dose-dependent effect on the immunosuppression degree is revealed. Both the inductive and productive stages of antibody formation are sensitive to the immunosuppressive action of the agent. Under certain conditions biocarbazin induced a sharp suppression of humoral immune response. At the same time, it enhanced significantly the delayed-type hypersensitivity (DTH) response to SE.     

Persistent Luminescence Immune Hydrogel for Photodynamic-Immunotherapy of Tumors In Vivo

Persistent luminescence material (PLM)-based photodynamic therapy (PDT) has shown tremendous promise in tumor elimination via avoiding continuous external light illumination. In addition, the tumor-associated antigens produced by PDT can trigger systemic antitumor immune responses, but only exhibit a limited immunotherapy effect. Herein, a persistent luminescence immune hydrogel is developed via a “turning solid into gel” strategy by introducing a PLM and an immunoadjuvant (R837) into an alginate-Ca²⁺ hydrogel for rechargeable photodynamic-immunotherapy of tumors, for the first time. The designed PLM-R837-ALG hydrogel exhibits the intact persistent luminescence of the PLM, 100% of utilization efficiency of the hydrophobic precursors, good biocompatibility and syringeability, and can be easily injected into tumors to serve as an internal light source for efficiently activating photosensitizers to induce a sustained PDT effect. Moreover, the loaded R837 can significantly amplify the immunogenicity of tumor-associated antigens originating from PL sensitized PDT, thereby leading to a powerful immune response to suppress tumors in vivo. The proposed PL-based photodynamic-immunotherapy provides a novel combined tumor treatment paradigm.     

Size/Charge Changeable Acidity‐Responsive Micelleplex for Photodynamic‐Improved PD‐L1 Immunotherapy with Enhanced Tumor Penetration

The checkpoint blockade‐based immunotherapy has recently emerged as a promising approach for tumor treatment, but its clinical implementation has been impeded by poor tumor penetration of the nanocarriers and activation of antitumor immune response. To overcome the obstacles, a tumor acidity‐responsive micellar nanocomplex co‐loaded with programmed death‐ligand 1 (PD‐L1)‐blockade siRNA and mitochondrion‐targeting photosensitizer for the synergistic integration of photodynamic therapy and immunotherapy is reported in the present study. The nanosystem is coated with long‐circulating polyethylene glycol (PEG) shells, which can be shed in response to the weakly acidic tumor microenvironment and lead to significant size reduction and increasing positive charge. These transitions facilitate penetration and uptake of nanocarriers against tumors. Subsequently, under the mild acidic endo/lysosome condition, the micellar nanocomplexes are rapidly protonated and disintegrated to release the PD‐L1‐blockade siRNA and photosensitizer through sponge effect. Results from in vitro and in vivo experiments collectively reveal that the nanosystem efficiently activates a photodynamic therapy‐induced immune response and silences immune resistance mediated by the checkpoint gene PD‐L1. In consequence, melanoma growth is inhibited and the recurrence rate is reduced via triggering systemic antitumor immune responses. This study offers an alternative strategy for the development of efficient antitumor immune therapy.     

Injectable Adhesive Hydrogel as Photothermal-Derived Antigen Reservoir for Enhanced Anti-Tumor Immunity

Low vaccine immunogenicity and tumor heterogenicity greatly limit the therapeutic effect of tumor vaccine. In this study, a novel injectable adhesive hydrogel, based on thermosensitive nanogels containing catechol groups and loaded with in situ-forming MnO₂ nanoparticles, is constructed to overcome these issues. The concentrated nanogel dispersion transforms into an adhesive hydrogel in situ after intratumoral injection. The photothermal effect of the loaded MnO₂ nanoparticles induces immunogenic cell death to release mass autologous tumor-derived protein antigens under near-infrared irradiation, which act as ideal immune stimulating substances avoiding the problem of tumor heterogenicity and are captured by the in situ-forming adhesive hydrogel. The antigens-captured adhesive hydrogel acts as an “antigen reservoir” and releases these captured antigens to recruit more dendritic cells to stimulate an intensive and lasting anti-tumor immune response mediated by CD8⁺ T cells. The primary tumors can be almost completely disappeared within 4 days without relapse, and the growth of the distal tumors and rechallenged tumors are also effectively inhibited by the treatment with the injectable adhesive hydrogel-based photothermal therapy. Therefore, the proposed “antigen reservoir” strategy shows the great potential application as an in situ-forming personalized vaccine to enhancing the cancer immune therapy.     

基于免疫克隆选择的图像压缩算法研究

针对在图像压缩过程中压缩质量与压缩时间相互间存在矛盾,文中提出了一种基于免疫克隆选择的图像压缩算法。该算法结合免疫克隆算法的抗体的多样性、全局寻优和小波变换多分辨率分析的特点。在压缩过程中不仅采用了小波分解后的低频分量,还加入了一定的高频部分,使压缩后的图像信噪比更低,从而保证了图像的质量。实验结果表明,所提出的图像压缩方法具有相对较高的压缩比和良好的压缩效果。     

Bacterial Outer Membrane-Based Biomimetic Immune Adaptors: Mild Immunomodulatory and Bacterial Targeted Delivery Strategy Against Implant-Related Infections

Implant-related infections (IRIs) are difficult to manage and are a major cause of surgical failure. The formation of biofilms with a solid barrier on the surface of implants and concomitant suppression of the local immune response constitute major challenges for treating IRIs. This study develops a multifunctional biomimetic immune adaptor (Hybrid Membrane@Levo@SiO₂; HMLS) generated by loading the antibiotic levofloxacin (Levo) into silica nanoparticles and coating the particles with a hybrid membrane formed from outer membrane vesicles (OMVs) of Escherichia coli and red blood cell membranes (RBCMs). The HMLS nanoplatform is designed to address the challenges associated with IRIs through a dual-approach strategy. First, the unique immunogenicity of OMVs regulates the antibacterial immune responses of innate immune cells and reverses the immunosuppressive microenvironment around IRIs. Second, the homotypic targeting effect of OMVs in the hybrid membrane provides HMLS with bacterial targeting functions and efficient bactericidal effects. Additionally, the RBCMs endow the hybrid membrane with mild immunogenicity, which prevents excessive inflammatory stimulation. The synergistic strategy of HMLS exhibits superior antibiofilm effects both in vivo and in vitro, providing a new option for the clinical treatment of refractory IRIs.     

A Biodegradable Antigen Nanocapsule Promotes Anti-Tumor Immunity via the cGAS-STING Pathway

Materials-based antigen delivery systems can augment the immune response by improving antigen uptake in antigen-presenting cells, targeting lymph nodes, prolonging antigen exposure, enhancing cross-presentation, etc. Recent research revealed that some antigen carriers activate the innate immune pathways without additional adjuvant. Here, a vaccine delivery platform (antigen nanocapsules) constructed by a one-step in situ polymerization is reported, weaving a biodegradable polymer network around the antigen surface. This simple technology allowed us to study the immunomodulatory effect of various antigen carriers. An antigen nanocapsule (NC7) capable of inducing dendritic cell activation and cross-presentation is identified. Further mechanistic studies revealed that NC7 activated the cGAS-STING pathway in a cGAS-dependent manner. Moreover, the subcutaneously injected NC7 accumulated in the lymph nodes and elicited strong cytotoxic T cell immunity and T cell memory against established cancer. Collectively, the often-neglected immunomodulatory effect of various cationic antigen carriers, enabling potential application in cancer vaccines, is uncovered.     

氦氖激光针对甲状腺手术病人免疫功能的影响

应用氦氖激光针穴位组织内照射行甲状腺手术镇痛，以确定其对手术应激状态下人体免疫功能的影响。结果显示氦氖激光针作用于深部感受器产生与电针相似的作用．     

光控伺服系统建立、建模与仿真

介绍了一种具有抗电磁干扰,信息传输快的光控伺服系统的组成,并详细阐述了此系统关键组成部分——光伺服阀中光驱动器所应用的光致伸缩陶瓷材料(PLZT)的应用原理以及其在阀中具体的实用结构。对光控伺服系统的各个环节进行系统级的建模与仿真分析,讨论其抗电磁干扰能力,比较不同控制方式PLZT光执行机构精度的影响。探讨了光控伺服系统,尤其是光伺服阀光驱动器的实用性以及其有待解决的问题。     

Enhancing Triple Negative Breast Cancer Immunotherapy by ICG‐Templated Self‐Assembly of Paclitaxel Nanoparticles

Combination cancer immunotherapy has shown promising potential for simultaneously eliciting antitumor immunity and modulating the immunosuppressive tumor microenvironment (ITM). However, combination immunotherapy with multiple regimens suffers from the varied chemo‐physical properties and inconsistent pharmacokinetic profiles of the different therapeutics. To achieve tumor‐specific codelivery of the immune modulators, an indocyanine green (ICG)‐templated self‐assembly strategy for preparing dual drug‐loaded two‐in‐one nanomedicine is reported. ICG‐templated self‐assembly of paclitaxel (PTX) nanoparticles (ISPN), and the application of ISPN for combination immunotherapy of the triple negative breast cancer (TNBC) are demonstrated. The ISPN show satisfied colloidal stability and high efficacy for tumor‐specific codelivery of ICG and PTX through the enhanced tumor permeability and retention effect. Upon laser irradiation, the ICG component of ISPN highly efficiently induces immunogenic cell death of the tumor cells via activating antitumor immune response through photodynamic therapy. Meanwhile, PTX delivered by ISPN suppresses the regulatory T lymphocytes (T_regs) to combat ITM. The combination treatment of TNBC with ISPN and αPD‐L1‐medaited immune checkpoint blockade therapy displays a synergistic effect on tumor regression, metastasis inhibition, and recurrence prevention. Overall, the ICG‐templated nanomedicine may represent a robust nanoplatform for combination immunotherapy.     

Modification of 3-methylcholanthrene-induced blastomogenesis in BALB/c mice by using the subcellular components of Bac. megaterium H

It is shown that the cytoplasm of Bac. megaterium H possessing the antigenic affinity with the malignant tumour cells, being injected 7 days before the 3-methylcholanthrene injection promotes intensification of its blastomogenic effect, reduces both the period of tumour appearance and longevity of the tumour-bearing animals. On the contrary the cell wall preparation under the similar conditions, produces a therapeutic effect. An assumption is advanced that the effect of these preparations is associated with their different influence on the immune system.     

Vibration immunity for optical-fiber current measurement

Optical-fiber measurement of electric current can be rendered immune from the effects of environmental vibration by utilizing the nonreciprocity of the Faraday effect in an arrangement which propagates light simultaneously in the two directions around a fiber loop enclosing an electric current. The system is compared with a back-reflection arrangement. Temperature variations are also suppressed     

一种基于周期平稳的上行OFDMA系统同步参数盲估计方法

该文给出了一种应用于上行正交频分多址(OFDMA)系统的同步参数盲估计方法。该方法利用信号的二阶周期平稳特性,针对不同的子载波分配策略,对信道的频偏和时延进行了估计。性能仿真证明,这种盲估计方法具有较高的精度和很好的抗噪特性。     

人工免疫系统的研究进展与展望

人工免疫是受生物免疫系统的启发而发展起来的,并逐步成为人工智能研究的热点。首先介绍人工免疫系统的生物原型,并对免疫系统群体计算中的免疫学习、免疫记忆、免疫遗传等算法进行描述;对近几年典型的人工免疫算法与系统进行了深入探讨,通过人工免疫算法在不同领域的应用,展示人工免疫系统在解决复杂问题时具有自组织、自适应、鲁棒性的特点。最后提出免疫算法在未来一段时间内的发展趋势与应用领域,尤其是在免疫协同防御、人工免疫系统与模糊系统集成、量子技术与免疫算法的融合以及人工免疫在无人驾驶技术中的应用,是未来人工免疫系统的发展趋势和研究方向。