N-desmethyldauricine from Menispermum dauricum DC suppresses triple-negative breast cancer growth in 2D and 3D models by downregulating the NF-κB signaling pathway.

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, for which targeted therapy regimens are lacking. The traditional Chinese medicine Menispermum dauricum DC (M. dauricum) and its compounds have been reported to have antitumor activity against various cancers; however, their anti-TNBC activity is unknown. In this work, dauricine and N-desmethyldauricine from M. dauricum were separated and identified to have anti-TNBC via a multi-component bioactivity and structure-guided method. The cell counting kit 8 assay showed that dauricine and N-desmethyldauricine inhibited the proliferation of four tested TNBC cell lines, with half maximal inhibitory concentration values ranging from 5.01 µM to 13.16 µM. Further research suggested that N-desmethyldauricine induced cell apoptosis, arrested cell cycle progression in the G0/G1 phase, and inhibited cell migration. Western blot analysis revealed that the proapoptotic protein cleaved-poly-ADP-ribose polymerase 1 was upregulated, and the G0/G1 phase-related proteins cyclin-dependent kinase 2 and cyclin D1 and the migration-related protein matrix metallopeptidase 9 were downregulated. Furthermore, N-desmethyldauricine decreased the protein expression of p65, an important subunit of nuclear factor kappa-beta (NF-κB). Moreover, an antiproliferation assay of three-dimensional (3D) tumor spheroids showed that N-desmethyldauricine diminished cell‒cell adhesion and suppressed the growth of TNBC 3D spheroids. Taken together, these findings indicate that N-desmethyldauricine inhibited the proliferation of TNBC cells and decreased the expression of p65 in the NF-κB pathway.

Concentration-dependent dual roles of proanthocyanidins on oxidative stress and docosahexaenoic acid production in Schizochytrium sp. ATCC 20888.

Antioxidant addition is an effective strategy to achieve docosahexaenoic acid (DHA) overproduction in oleaginous microorganisms. Nevertheless, antioxidants like phenolic compounds sometimes exert pro-oxidant activity. In this work, effects of proanthocyanidins (PAs) on fermentation performance and oxidative stress in Schizochytrium sp. were investigated. Low PAs addition (5 mg/L) reduced reactive oxygen species and enhanced lipogenic enzymes activities and NADPH, resulting in significant increase in lipid (20.3 g/L) by 33.6 % and DHA yield (9.8 g/L) by 53.4 %. In contrast, high PAs addition (500 mg/L) exerted pro-oxidant effects, aggravated oxidative damage and lipid peroxidation, leading to sharp decrease in biomass (21.3 g/L) by 35.1 %, lipid (8.2 g/L) by 46.0 %, and DHA (2.9 g/L) by 54.8 %. Therefore, the antioxidant concentration is especially crucial in DHA production. This study is the first to report concentration-dependant dual roles of PAs in oxidative stress and DHA production in Schizochytrium sp., providing new insights into microbial DHA production.

Contrastive Masked Autoencoders are Stronger Vision Learners.

Masked image modeling (MIM) has achieved promising results on various vision tasks. However, the limited discriminability of learned representation manifests there is still plenty to go for making a stronger vision learner. Towards this goal, we propose Contrastive Masked Autoencoders (CMAE), a new self-supervised pre-training method for learning more comprehensive and capable vision representations. By elaboratively unifying contrastive learning (CL) and masked image model (MIM) through novel designs, CMAE leverages their respective advantages and learns representations with both strong instance discriminability and local perceptibility. Specifically, CMAE consists of two branches where the online branch is an asymmetric encoder-decoder and the momentum branch is a momentum updated encoder. During training, the online encoder reconstructs original images from latent representations of masked images to learn holistic features. The momentum encoder, fed with the full images, enhances the feature discriminability via contrastive learning with its online counterpart. To make CL compatible with MIM, CMAE introduces two new components, i.e., pixel shifting for generating plausible positive views and feature decoder for complementing features of contrastive pairs. Thanks to these novel designs, CMAE effectively improves the representation quality and transfer performance over its MIM counterpart. CMAE achieves the state-of-the-art performance on highly competitive benchmarks of image classification, semantic segmentation and object detection. Notably, CMAE-Base achieves 85.3% top-1 accuracy on ImageNet and 52.5% mIoU on ADE20k, surpassing previous best results by 0.7% and 1.8% respectively.

Learning Degradation-Robust Spatiotemporal Frequency-Transformer for Video Super-Resolution.

Video Super-Resolution (VSR) aims to restore high-resolution (HR) videos from low-resolution (LR) videos. Existing VSR techniques usually recover HR frames by extracting pertinent textures from nearby frames with known degradation processes. Despite significant progress, grand challenges remain to effectively extract and transmit high-quality textures from high-degraded low-quality sequences, such as blur, additive noises, and compression artifacts. This work proposes a novel degradation-robust Frequency-Transformer (FTVSR++) for handling low-quality videos that carry out self-attention in a combined space-time-frequency domain. First, video frames are split into patches and each patch is transformed into spectral maps in which each channel represents a frequency band. It permits a fine-grained self-attention on each frequency band so that real visual texture can be distinguished from artifacts. Second, a novel dual frequency attention (DFA) mechanism is proposed to capture the global and local frequency relations, which can handle different complicated degradation processes in real-world scenarios. Third, we explore different self-attention schemes for video processing in the frequency domain and discover that a "divided attention" which conducts joint space-frequency attention before applying temporal-frequency attention, leads to the best video enhancement quality. Extensive experiments on three widely-used VSR datasets show that FTVSR++ outperforms state-of-the-art methods on different low-quality videos with clear visual margins.

Mobile mechanical signal generator for macrophage polarization.

The importance of mechanical signals in regulating the fate of macrophages is gaining increased attention recently. However, the recently used mechanical signals normally rely on the physical characteristics of matrix with non-specificity and instability or mechanical loading devices with uncontrollability and complexity. Herein, we demonstrate the successful fabrication of self-assembled microrobots (SMRs) based on magnetic nanoparticles as local mechanical signal generators for precise macrophage polarization. Under a rotating magnetic field (RMF), the propulsion of SMRs occurs due to the elastic deformation via magnetic force and hydrodynamics. SMRs perform wireless navigation toward the targeted macrophage in a controllable manner and subsequently rotate around the cell for mechanical signal generation. Macrophages are eventually polarized from M0 to anti-inflammatory related M2 phenotypes by blocking the Piezo1-activating protein-1 (AP-1）-CCL2 signaling pathway. The as-developed microrobot system provides a new platform of mechanical signal loading for macrophage polarization, which holds great potential for precise regulation of cell fate.

Reliability and validity evaluation of the chinese revision of the attitude towards adult vaccination scale.

BACKGROUND: Although vaccination is one of the critical interventions to address global health issues, inadequate vaccination rates has become an international challenge. Vaccine hesitancy is the key to affecting inadequate vaccination rates. According to the WHO SAGE working group's definition, vaccine hesitancy refers to delaying or refusing vaccination and has been ranked as one of the top 10 health threats. There has yet to be a scale that evaluates vaccination attitudes among Chinese adults. However, an attitude quantity, the adult vaccination attitude scale, has been developed to assess adult vaccination attitudes and reasons for vaccine hesitancy. OBJECTIVE: The Adult Attitudes to Vaccination Scale (ATAVAC) was initially developed by Professor Zoi Tsimtsiou et al. This study aimed to analyze the structure of the Chinese version of the ATAVAC and explore the relationship between adult vaccination attitudes, e-health literacy, and medical distrust. METHODS: After obtaining author permission for the initial scales, the study was translated using the Brislin back-translation method. 693 adults were enrolled to the study. To validate this hypothesis, participants finished the socio-demographic questionnaire, the Chinese version of the ATAVAC, the electronic Health Literacy Scale (e-HEALS) and the Medical Mistrust Index (MMI). The exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the underlying structure of the factors of the Chinese version of the Adult Vaccination Attitude Scale and to measure its reliability and validity. RESULTS: The Cronbach's alpha coefficient for the Chinese version of the ATAVAC was 0.885, with Cronbach's alpha coefficients ranging from 0.850 to 0.958 for each dimension. The content validity index was 0.90, and the retest reliability was 0.943. The exploratory factor analysis (EFA) supported the 3-factor structure of the translation instrument, and the scale had good discriminant validity. The confirmatory factor analysis (CFA) revealed a degree of freedom of 1.219, a model fit index (GFI) of 0.979, a normative fit index (NFI) of 0.991, a Tucker-Lewis index (TLI) of 0.998, a comparability index (CFI) of 0.998 and a root mean square error of approximation (RMSEA) of 0.026. CONCLUSION: The results show that the Chinese version of the ATAVAC has demonstrated good reliability and validity. Hence, it can be used as an effective tool to assess vaccination attitudes among Chinese adults.

Real-Time Micromotor Probe for Immune Neutrophil Activation State.

Neutrophil activation is a hallmark of the immune response. Approaches to identify neutrophil activation in real time are necessary but are still lacking. In this study, magnetic Spirulina micromotors are used as label-free probes that exhibit differences in motility under different neutrophil activation states. This is correlated with different secretions into the extracellular environment by activated/non-activated cells and local environmental viscoelasticity. The micromotor platform can bypass non-activated immune cells while being stopped by activated cells. Thus, the micromotors can serve as label-free biomechanical probes of the immune cell state. They can detect the activation state of target immune cells in real time and with single-cell precision, which provides new ideas for the diagnosis and treatment of diseases while deepening understanding of the biomechanics of activated immune cells.

Offline two-dimensional normal-phase × reversed-phase liquid chromatography coupled with high-resolution mass spectrometry for comprehensive analysis of chemical constituents in Euphorbia kansui.

Euphorbia kansui is the dried root of Euphorbia kansui T. N. Liou ex T.P. Wang. Its main chemical components are diterpenoids, triterpenes, and volatile oil. In this study, an offline two-dimensional (2D) normal-phase × reversed-phase liquid chromatography method coupled with quadrupole time-of-flight mass spectrometry was established to comprehensively analyze the chemical constituents in E. kansui. A total of 240 compounds were identified from the E. kansui extract, including 218 diterpenoids (77 known, 141 new), 16 known volatile oils, and six known triterpenes. The relationship between the structural characteristics and tandem mass spectroscopy fragments of diterpenoids was further analyzed. Based on the characteristic fragment ions, 141 new diterpenoids were determined as 118 ingenane diterpenoids and 23 jatrophane diterpenoids. The newly identified diterpenoids may provide lead compounds for drug discovery, improving the medicinal value of E. kansui.

Adaptive particle patterning in the presence of active synthetic nanomotors.

For the maintenance of a biological system, spatial organization of material condensates within the cell through the dissipation of energy is crucial. Besides directed transport via microtubules, material arrangement can be achieved via motor protein facilitated adaptive active diffusiophoresis. For example, the distribution of membrane proteins during the cell division of Escherichia coli is affected by the MinD system. Synthetic active motors exhibit the ability to simulate natural motors. Here we propose an active Au-Zn nanomotor driven by water and discovered an interesting adaptive interaction mode of the diffusiophoretic Au-Zn nanomotors with passive condensate particles in different environments. It is found that the attraction/repulsion between the nanomotor and passive particles is adaptive, while an interesting hollow pattern is formed with a negatively charged substrate and a cluster pattern is favored with a positively charged substrate.

Clinical study of the combined use of dexmedetomidine and remifentanil in patients with coronary heart disease undergoing 3D laparoscopic surgery with EEG bispectral index monitoring.

OBJECTIVE: This study sought to investigate the safety and clinical outcomes associated with the combined administration of dexmedetomidine (Dex) and remifentanil (Rem) in patients with coronary heart disease undergoing three-dimensional (3D) laparoscopic surgery, with concurrent monitoring of the electroencephalography (EEG) bispectral index. METHODS: This study is of a retrospective nature and involved a total of 60 patients with coronary heart disease who underwent 3D laparoscopic surgery at our hospital between June 2020 and September 2021. In a double-blind manner, these patients were randomly assigned to two groups: the control group (Group I), which consisted of 30 patients, and the treatment group (Group II) receiving a combination of Dex and Rem, also comprising 30 patients. The study's primary objective was to compare and assess the treatment outcomes in these two patient groups. RESULTS: Patients in Group II who developed postoperative coronary heart disease experienced a significant reduction in blood pressure, heart rate, and electrocardiogram values (P<0.05). Additionally, Group II exhibited lower bispectral index (BIS) and visual analog scale (VAS) values (P<0.05). CONCLUSION: In patients with coronary heart disease undergoing 3D laparoscopic surgery, the intraoperative use of Dex combined with Rem anesthesia offers several advantages. It helps stabilize hemodynamics, reducing the risk of myocardial ischemia, and significantly alleviates postoperative pain, all without increasing the likelihood of adverse postoperative reactions. Furthermore, this approach effectively dampens the intraoperative and postoperative stress response, facilitating enhanced recovery after surgery (ERAS). Overall, the clinical impact is positive, safe, and reliable.

Hemp Seed Fermented by Aspergillus oryzae Attenuates Lipopolysaccharide-Stimulated Inflammatory Responses in N9 Microglial Cells.

The objective of our present work was to explore the possible enhanced anti-neuroinflammatory ability of Aspergillus oryzae fermented hemp seed in lipopolysaccharide (LPS)-stimulated N9 microglial cells and elucidate its underlying mechanism. The water extract of hemp seed was fermented by Aspergillus oryzae. LPS-stimulated N9 microglial cells were employed for the inflammatory cell model. The release of nitric oxide (NO) was determined by Griess assay. The cytokines and inflammatory mediator expression were measured by qPCR and ELISA. The phosphorylated key signaling proteins, including nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), and phosphatidylinositol 3-kinase (PI3K/Akt), were quantified by western blot analysis. The production of intracellular reactive oxygen species (ROS) was measured by DCFH oxidation. Fermented hemp seed (FHS) reduced NO production by downregulating inducible nitric oxide synthase (iNOS) expression in LPS-stimulated N9 microglial cells. FHS treatment decreased LPS-stimulated expression of inflammatory cytokines either on mRNA or protein levels. Moreover, FHS inhibited LPS-stimulated phosphorylation of NF-κB, MAPKs, and PI3K/Akt signaling pathways. Furthermore, FHS significantly reduced the ROS production in the cells. It was concluded that FHS exerted its anti-neuroinflammatory activities by suppressing ROS production, thus inhibiting NF-κB, MAPKs, and PI3K/Akt activation, consequently decreasing the expression levels of inflammatory mediators and cytokines.

Mechanically Optimize T Cells Activation by Spiky Nanomotors.

T cell activation is vital for immune response initiation and modulation. Except for the strength of the interaction between T cell receptors (TCR) and peptides on major histocompatibility complex molecules (MHC), mechanical force, mediated by professional mechanosensitive ion channels, contributes to activating T cells. The intrinsic characteristic of synthetic micro/nanomotors that convert diverse energy sources into physical movement and force, opening up new possibilities for T cell regulation. In this work, Pd/Au nanomotors with spiky morphology were fabricated, and in the presence of low concentrations of hydrogen peroxide fuel, the motors exhibited continuous locomotion in the cellular biological environment. Physical cues (force and pressure) generated by the dynamic performance are sensed by mechanosensitive ion channels of T cells and trigger Ca2+ influx and subsequent activation. The successful demonstration that mechanical signals generated in the bio microenvironment can potentiate T cells activation, represents a potential approach for cell-based cancer immunotherapy.

Mechanical Activation of Immune T Cells via a Water Driven Nanomotor.

As a key step during immune response, antigen recognition requires direct mechanical interaction between T cells and antigen presenting cells. Upon subjection to mechanical forces, mechanotransduction is triggered. In this study, the mechanical forces generated by water driven synthetic Au-Zn nanomotors are used to activate mechanosensitive Jurkat T cells. The triggering and activation of the cellular Ca2+ channel is observed. It is revealed that the mechanosensitive cells experience different degrees of activation upon receiving different mechanical input signals and demonstrate that external mechanical forces can optimize T cell activation. Compared with T cell activation with cytokines which can lead to the risky widespread activation of T cells and systemic immune storm, nanomotors can present mechanical force and achieve localized immune cell stimulation. It is expected that mechano nanomotors will contribute to the emerging T cell immunology field and facilitate more comprehensive understanding of the T cell mechanical response and function.

Classification of ASD based on fMRI data with deep learning.

Autism spectrum disorder (ASD) is a neuro-developmental disorder that affects the social abilities of patients. Studies have shown that a small number of abnormal functional connections (FCs) exist in the cerebral hemisphere of ASD patients. The identification of these abnormal FCs provides a biological ground for the diagnosis of ASD. In this paper, we propose a combined deep feature selection (DFS) and graph convolutional network method to classify ASD. Firstly, in the DFS process, a sparse one-to-one layer is added between the input and the first hidden layer of a multilayer perceptron, thus each functional connection (FC) feature can be weighted and a subset of FC features can be selected accordingly. Then based on the selected FCs and the phenotypic information of subjects, a graph convolutional network is constructed to classify ASD and typically developed controls. Finally, we test our proposed method on the ABIDE database and compare it with some other methods in the literature. Experimental results indicate that the DFS can effectively select critical FC features for classification according to the weights of input FC features. With DFS, the performance of GCN classifier can be improved dramatically. The proposed method achieves state-of-the-art performance with an accuracy of 79.5% and an area under the receiver operating characteristic curve (AUC) of 0.85 on the preprocessed ABIDE dataset; it is superior to the other methods. Further studies on the top-ranked thirty FCs obtained by DFS show that these FCs are widespread over the cerebral hemisphere, and the ASD group appears a significantly higher number of weak connections compared to the typically developed group.

Deciphering the O-Glycosylation of HKU1 Spike Protein With the Dual-Functional Hydrophilic Interaction Chromatography Materials.

HKU1 is a human beta coronavirus and infects host cells via highly glycosylated spike protein (S). The N-glycosylation of HKU1 S has been reported. However, little is known about its O-glycosylation, which hinders the in-depth understanding of its biological functions. Herein, a comprehensive study of O-glycosylation of HKU1 S was carried out based on dual-functional histidine-bonded silica (HBS) materials. The enrichment method for O-glycopeptides with HBS was developed and validated using standard proteins. The application of the developed method to the HKU1 S1 subunit resulted in 46 novel O-glycosylation sites, among which 55.6% were predicted to be exposed on the outer protein surface. Moreover, the O-linked glycans and their abundance on each HKU1 S1 site were analyzed. The obtained O-glycosylation dataset will provide valuable insights into the structure of HKU1 S.

Enzyme-assisted Solvent Extraction of High-yield Paeonia suffruticosa Andr. Seed Oil and Fatty Acid Composition and Anti-Alzheimer's Disease Activity.

Enzyme-assisted solvent extraction (EASE) of Paeonia suffruticosa Andr. seed oil (PSO) was optimized by response surface methodology (RSM). The fatty acid composition and anti-Alzheimer's disease (AD) activity of PSO were analyzed. An enzyme mixture composed of cellulase and hemicellulase (1:1, w/w) was most effective in determining the extraction yield of PSO. The ideal extraction conditions were a pH value of 5.1, an enzymolysis time of 68 min, and a temperature of 50℃. The average extraction yield of PSO was 38.2 mL/100 g, 37.4% higher than that of untreated peony seed (27.8 mL/100 g). The fatty acid composition of PSO under optimal conditions for EASE was analyzed by gas chromatography-mass spectrometry (GC-MS). The predominant unsaturated fatty acids of PSO were determined to be more than 90.00%, including n-3 α-linolenic acid (43.33%), n-6 linoleic acid (23.40%) and oleic acid (23.59%). In this experiment, the anti-AD effect of PSO was also analyzed by performing learning and memory ability tests with Drosophila. PSO retarded the decrease in climbing ability in AD Drosophila. The 1% and 5% PSO groups were significantly different from the model group (b p < 0.05). The smell short-term memory ability test revealed the number of Drosophila in barrier and barrier-free centrifuge tubes in each group. PSO feeding improved learning and memory in AD Drosophila, with the highest number entering the barrierfree centrifuge tube. The performance index (PI) measured by the Pavlov olfactory avoidance conditioning test also demonstrated the effect of PSO on the learning and memory abilities of Drosophila. The PI of the PSO group was significantly increased compared to that of the model group. HE-stained brain tissue sections of AD Drosophila showed higher neurodegenerative changes, while PSO significantly reduced neurodegenerative damage. These results indicated that PSO can significantly improve the cognitive function of AD Drosophila and may help to prevent AD.

Circular RNA_0001495 increases Robo1 expression by sponging microRNA-527 to promote the proliferation, migration and invasion of bladder cancer cells.

Bladder cancer (BCa) is a heterogeneous disease that poses great threats on public health. Increasing studies have identified the vital functions of circular RNAs (circRNAs) in BCa treatment. Hence, this current study set out to explore the modulatory role of circ_0001495 in BCa development. First, the expression of circ_0001495 was determined by reverse transcription quantitative polymerase chain reaction. Cell biological processes were then analyzed after altering the circ_0001495 expression in T24 cells. Next, interactions among circ_0001495, microRNA-527 (miR-527) and roundabout guidance receptor 1 (Robo1) were investigated by dual luciferase reporter gene assay, RNA pull down assay and FISH assay. Lastly, xenograft tumors in nude mice were established to explore the effect of circ_0001495 in vivo. It was found that circ_0001495 was highly expressed in BCa tissues and cells, and was further correlated with poor prognosis in BCa patients. In addition, circ_0001495 inhibited the activity of miR-527 by acting as a sponge to sponge miR-527, which further elevated the Robo1 expression. Lastly, circ_0001495 was found to promote the proliferation, migration and invasion of BCa cells in vitro through the miR-527/Robo1 axis and promote the growth and metastasis of BCa tumors in vivo. Altogether, findings in our study highlight the promoting role of circ_0001495 in the progression of BCa by increasing Robo1 via sponging miR-527, representing a promising target for BCa management.

Simple and efficient preparation of high-purity trehalulose from the waste syrup of isomaltulose production using solid-phase extraction followed by hydrophilic interaction chromatography.

A simple and efficient method was developed for the preparation of high-purity trehalulose from the waste syrup of isomaltulose production. The waste syrup was pre-treated with C18 solid-phase extraction, where 98% decolorization and 97% reducing sugar recovery were obtained, followed by hydrophilic interaction liquid chromatography separation on a cysteine-bonded zwitterionic column. Under optimized conditions, trehalulose was separated from isomaltulose isomer and prepared on a semi-preparative scale with >99% purity. The structure of the prepared trehalulose was subsequently confirmed by nuclear magnetic resonance, and three tautomers of trehalulose (α-D-glucosylpyranosyl-1,1-ß-D-fructopyranose, α-D-glucosylpyranosyl-1,1-ß-D-fructofuranose, and α-D-glucosylpyranosyl-1,1-α-D-fructofuranose) were detected and completely characterized by 13 C NMR spectroscopy for the first time in this study. The tautomerization of α-D and ß-D type transition was observed by hydrophilic interaction liquid chromatography on an AdvanceBio Glycan Mapping column, with smaller particle size (2.7 µm). Furthermore, the prepared trehalulose was applied as a standard for trehalulose quantification during the sucrose conversion by Klebsiella sp. LX3. The combination of solid-phase extraction and hydrophilic interaction liquid chromatography offers a new avenue for the preparation of sugar isomers from complex natural or fermentation products.

Learning Region-Based Attention Network for Traffic Sign Recognition.

Traffic sign recognition in poor environments has always been a challenge in self-driving. Although a few works have achieved good results in the field of traffic sign recognition, there is currently a lack of traffic sign benchmarks containing many complex factors and a robust network. In this paper, we propose an ice environment traffic sign recognition benchmark (ITSRB) and detection benchmark (ITSDB), marked in the COCO2017 format. The benchmarks include 5806 images with 43,290 traffic sign instances with different climate, light, time, and occlusion conditions. Second, we tested the robustness of the Libra-RCNN and HRNetv2p on the ITSDB compared with Faster-RCNN. The Libra-RCNN performed well and proved that our ITSDB dataset did increase the challenge in this task. Third, we propose an attention network based on high-resolution traffic sign classification (PFANet), and conduct ablation research on the design parallel fusion attention module. Experiments show that our representation reached 93.57% accuracy in ITSRB, and performed as well as the newest and most effective networks in the German traffic sign recognition dataset (GTSRB).

Interactions between Biomedical Micro-/Nano-Motors and the Immune Molecules, Immune Cells, and the Immune System: Challenges and Opportunities.

Mobile micro- and nano-motors (MNMs) emerge as revolutionary platforms for biomedical applications, including drug delivery, biosensing, non-invasive surgery, and cancer therapy. While for applications in biomedical fields and practical clinical translation, the interactions of these untethered tiny machines with the immune system is an essential issue to be considered. This review highlights the recent approaches of surpassing immune barriers to prevent foreign motors from triggering immune responses. In addition to trials focusing on the function preservation of MNMs, examples of versatile MNMs working with the immune components (immune molecules, immune cells and the whole system) to achieve cancer immunotherapy, immunoassay, and detoxification are outlined. The immune interference part provides researchers an idea about what is the limit presented by the immune components. The coworking part suggests ways to bypass or even utilize the limit. With interdisciplinary cooperation of nanoengineering, materials science, and immunology field, the rationally designed functional MNMs are expected to provide novel opportunities for the biomedical field.