Optimal design of integrated visible light communication and positioning system with energy harvesting.

In this paper, an optimization scheme that can simultaneously transmit communication information, positioning the information and energy in a visible light communication and positioning (VLCP) system with energy harvesting is proposed. The time switching-power splitting (TS-PS) method is applied, where the power and time allocation factors are defined as optimization variables, so that the system can maximize the harvested energy under the constraints of the information rate and positioning error. The multi-verse optimization (MVO) algorithm is introduced to obtain the optimal power and time allocation. In addition, the performance of the integrated system using the TS-PS method is investigated and compared with that using other conventional methods. The results show that a maximized harvested energy solution using the TS-PS method can harvest the most energy. Moreover, the effects of main external environment conditions, namely, the room height and field of view (FoV) of a photo diode (PD) on the system performance are also analyzed. The increase of the room height and FoV of the PD reduces the harvested energy, but does not change the information rate and positioning accuracy in the optimized system adopted in this paper.

The ubiquitin-editing enzyme TNFAIP3 exerts neuroprotective roles in epilepsy rats through repressing inflammation.

The ubiquitin-editing enzyme TNF alpha-induced protein 3 (TNFAIP3) emerges protective roles in neurological disorder, such as cerebral trauma. However, the molecular mechanisms of TNFAIP3 in epilepsy are not very clear. Hereon, the epileptic mouse models and BV2 microglial cellular models were established by kainic acid (KA) and lipopolysaccharide (LPS) respectively. We found that TNFAIP3 was highly expressed in the hippocampus of epileptic mice. Besides, TNFAIP3 overexpression relieved the spatial learning and memory, reduced the hot plate latency, as well as inhibited neuronal apoptosis in KA-treated mice. In vivo and in vitro experiments indicated that inflammation, a key characteristic of epilepsy, was inhibited by TNFAIP3 upregulation, as evidenced by the downregulated expression of pro-inflammatory cytokine interleukin (IL)-1ß and inducible NO synthase (iNOS), along with the decreased levels of NLRP3 inflammasome, which could activate inflammation. Collectively, we infer that TNFAIP3 relieves neuronal injury in epilepsy by suppressing inflammation.

[Clinical and genetic analysis of a child with mental retardation autosomal dominant 7].

OBJECTIVE: To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face. METHODS: The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants. RESULTS: The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin. CONCLUSION: The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.

General Route to Colloidal Nanocrystal Clusters with Precise Hierarchical Control via Star-like Nanoreactors.

A colloidal nanocrystal cluster (CNC) is a hierarchical nanostructure formed by clustering several nanocrystals into one nano-ensemble, which may exhibit unique optical or catalytic properties different from individual nanocrystals owing to the mutual interactions among neighboring component nanocrystals. However, there is still no universal synthetic route that could be applicable to diverse material compositions with precisely controlled hierarchical structures (i.e., nanocrystal number density, component nanocrystal size, and overall diameter of the CNC) up to now. Herein, a general and novel synthetic strategy was reported for crafting a wide range of inorganic CNCs (i.e., noble metal, semiconductor, and metal oxide) via utilizing amphiphilic star-like poly(4-vinylpyridine)-block-polystyrene diblock copolymers as nanoreactors prepared by sequential atom transfer radical polymerization. The hierarchical structure of rationally designed CNCs could be readily tailored by varying the P4VP molecular weight of star-like nanoreactors and the parameter optimization during the CNC preparation process, which was inaccessible by conventional synthetic methods.

Inhibition of miR-181a-5p reduces astrocyte and microglia activation and oxidative stress by activating SIRT1 in immature rats with epilepsy.

MicroRNAs regulate gene expression at the posttranscriptional level, and this process has been shown to be implicated in the pathological processes of temporal lobe epilepsy. At present, studies about the impact of microRNA-181a (miR-181a) on epilepsy have focused on hippocampal neurons, and the effect of miR-181a on other cells in the hippocampus remains poorly understood. Herein, we explored the role of miR-181a-5p in a lithium-pilocarpine model of epilepticus in immature rats. We found that the hippocampal expression level of miR-181a-5p was increased. Inhibition of miR-181a-5p protected the hippocampus against epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, oxidative stress, mitochondrial function, and cognitive dysfunction. Moreover, miR-181a-5p inhibition exerted a seizure-suppressing effect via SIRT1 upregulation. Overall, our findings reveal the potential role of the miR-181a-5p/SIRT1 pathway in the development of temporal lobe epilepsy, and this pathway may represent a novel target for ameliorating epilepsy and its sequelae.

A Versatile Strategy for Unimolecular Micelle-Derived Hollow Polymer Nanoparticles as General Nanoreactors.

We reported the synthesis of a well-defined hollow polymer nanoparticle derived from star-shaped unimolecular micelles. ß-Cyclodextrin was first applied as an efficient macroinitiator to prepare a star-shaped PCL via ring-opening polymerization (ROP). Then, the star-shaped PCL was modified to be a macro-RAFT agent for photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization of S-Cl monomers. The prepared unimolecular micelles can be photocross-linked under UV irradiation after a simple nucleophilic substitution reaction, which made -Cl groups to be -N3 groups. After the selective removal of the PCL core, hollow polymer nanoparticles were achieved and exhibited to be a general nanoreactor strategy for the fabrication of nanocrystals with well-controlled architectures. Compared with unimolecular micelle templates, the nanocrystals prepared by hollow templates are absolutely pure as no polymer chains are embedded in the inorganic nanocrystals. In addition, by changing the concentration of the precursor, the structure of the nanocrystal can be changed from a normal spherical structure to a hollow structure.

Germacrone attenuates cerebral ischemia/reperfusion injury in rats via antioxidative and antiapoptotic mechanisms.

Germacrone (GM) is an anti-inflammatory compound extracted from Rhizoma curcuma. Here, we strived to investigate the neuroprotective effects of GM in rat models of transient middle cerebral artery occlusion/reperfusion injury. Rats immediately after cerebral ischemia were intraperitoneally injected with GM at doses of 5, 10, and 20 mg/kg. After 1 day of reperfusion, the water content in the brain, infarct volume, and neurological deficits were assessed. Hippocampus neurons were histopathologically examined by hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Activities of glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) in brain tissue were detected. Real-time PCR and Western blotting were utilized to quantify the expression of apoptosis markers, such as caspase-3, Bax, and Bcl-2. The content of phospho-Akt (p-Akt) was also measured using Western blotting. GM treatment markedly decreased the brain water content, infarct volume and the neurological deficits, which was corroborated by attenuated histopathologic change. MDA levels were reduced and activities of GSH, SOD, and GSH-PX were elevated after GM treatment. Caspase-3 and Bax were decreased, and Bcl-2 was increased at both messenger RNA and protein levels by GM treatment. The p-Akt expression was increased by GM. Our data indicated that the neuroprotective effects of GM may attenuate the injuries from cerebral ischemia/reperfusion in rats through antioxidative and antiapoptotic mechanisms.

[Identification of pathogenic mutation in a Chinese pedigree affected with split hand/split foot malformation].

OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with split hand/split foot malformation (SHFM). METHODS: The patients were screened for genome-wide copy number variations with single nucleotide polymorphism (SNP) microarray. Copy number variations were verified by real-time fluorescence quantitative PCR. RESULTS: There were 3 SHFM patients from three generations, which conformed to an autosomal dominant inheritance. SNP microarray assay revealed that all patients have carried a 0.34 Mb duplication in 10q24.31-q24.32 (102 993 649-103 333 271) encompassing the BTRC and DPCD genes. The result was verified by real-time fluorescence quantitative PCR, confirming that the duplication has co-segregated with the SHFM phenotype in the pedigree. CONCLUSION: The 10q24.31-q24.32 duplication probably underlies the pathogenesis of SHFM in this pedigree. Tiny copy number variations can result in diseases featuring autosomal dominant inheritance.

[Effect of a microRNA-132 antagonist on pilocarpine-induced status epilepticus in young rats].

OBJECTIVE: To study the effect of a microRNA-132 antagonist on lithium-pilocarpine-induced status epilepticus (SE) in young Sprague-Dawley (SD) rats. METHODS: Forty-five 3-week-old SD rats were randomly and equally divided into epilepticus model group, microRNA-132 antagonist group, and microRNA-132 antagonist negative control group. The young SD rat model of SE was established using lithium-pilocarpine. For the microRNA-132 antagonist group and the negative control group, pretreatment was performed 24 hours before the model establishment. Behavioral observation was performed to assess the latency of SE and success rate of induction of SE. The scale of Lado was used to evaluate the seizure severity. Electroencephalography (EEG) was used to assess the frequency and amplitude of epileptiform discharges. The mortality rate was calculated in each group. RESULTS: There was no significant difference in the success rate of induction of SE between the three groups (P>0.05). Compared with the microRNA-132 negative control group and the epilepticus model group, the microRNA-132 antagonist group had significantly prolonged SE latency after model establishment (P<0.05), a significantly lower Lado score of seizure (P<0.05), significantly lower frequency and amplitude of epileptiform discharges on EEG (P<0.05), and a slightly reduced mortality rate. CONCLUSIONS: The treatment with the microRNA-132 antagonist shows an inhibitory effect on the development and progression of lithium-pilocarpine-induced SE in young SD rats. The inhibition of microRNA-132 is likely to be a potential target or direction for drug treatment of SE.

[Roles of PKCα on the biological functions of T cells].

OBJECTIVE: To study the roles of PKCα on the proliferation, apoptosis, differentiation, cytokine production and inducible regulatory T cell (iTreg) induction of T cells. METHODS: T cells from WT (PKCα⁺/⁺) or PKCα knockout (PKCα⁻/⁻) mice were isolated and cultured in vitro. T cell proliferation and apoptosis were determined using ³H thymidine incorporation and CSFE/Annexin V staining. Cytokines production (IL-2, IL-4, IFN-γ and IL-17) was detected using ELISA. CD4⁺T cells were isolated and cultured in vitro via Th17 or iTreg biased condition. Flow cytometry was used to detect the cell differentiation. RESULTS: The production of IL-2 upon TCR stimulation increased, while the contents of IL-4 and IL-17 decreased in the PKCα⁻/⁻ group compared with the PKCα⁺/⁺ group. The differentiation rate of Th17 cells decreased, while the iTreg production increased in the PKCα⁻/⁻ group compared with the PKCα⁺/⁺ group. CONCLUSIONS: PKC-α is proinflammatory.

Changes in microglial inflammation-related and brain-enriched MicroRNAs expressions in response to in vitro oxygen-glucose deprivation.

Microglia plays important role in central nervous system immune surveillance and has emerged as an essential cellular component for understanding brain diseases. MicroRNAs (miRs) are small, noncoding RNAs that regulate the post-transcriptional expression of protein-coding mRNAs, which may have key roles in microglial activation in response to brain ischemia and other stressors. Primary cultured rat microglial cells were prepared, and then microglial activation model was established by oxygen-glucose deprivation (OGD) method. Morphological observation, CD11b/c immunofluorence, MTT assay and Propidium iodide staining were done to test microglia viability at different OGD time points (0, 5, 10, 15, 30, 60 min). qPCR were performed to detect the dynamic changes in expressions of inflammation-related miRs (146a, 21, 181a, 221, and 222) and brain-enriched miRs (124, 134, 9, 132, and 138) in resting microglia and after challenge with OGD for the same time points. The activation and viability of the microglia was time dependent. Similarly, expressions of different miRs in microglia were significantly upregulated and reached the peak at different time points before reaching the baseline level with extension of OGD. Our data demonstrates for the first time that OGD as a model of an ischemic insult modulates the expressions of some inflammation-related and brain-enriched miRs. These changes may help to explore the molecular basis of microglia activation on the post-transcriptional level in response to different time points of OGD.

An antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo.

The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membrane-fusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editing-mediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design.

Engineered Nanomaterials to Potentiate CRISPR/Cas9 Gene Editing for Cancer Therapy.

Clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) gene-editing technology shows promise for manipulating single or multiple tumor-associated genes and engineering immune cells to treat cancers. Currently, most gene-editing strategies rely on viral delivery; yet, while being efficient, many limitations, mainly from safety and packaging capacity considerations, hinder the use of viral CRISPR vectors in cancer therapy. In contrast, recent advances in non-viral CRISPR/Cas9 nanoformulations have paved the way for better cancer gene editing, as these nanoformulations can be engineered to improve safety, efficiency, and specificity through optimizing the packaging capacity, pharmacokinetics, and targetability. In this review, the advance in non-viral CRISPR delivery is highlighted, and there is a discussion on how these approaches can be potentially used to treat cancers in addressing the aforementioned limitations, followed by the perspectives in designing a proper CRISPR/Cas9-based cancer nanomedicine system with translational potential.

CRISPR/Cas detection with nanodevices: moving deeper into liquid biopsy.

The emerging field of liquid biopsy has garnered significant interest in precision diagnostics, offering a non-invasive and repetitive method for analyzing bodily fluids to procure real-time diagnostic data. The precision and accuracy offered by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas) technology have advanced and broadened the applications of liquid biopsy. Significantly, when combined with swiftly advancing nanotechnology, CRISPR/Cas-mediated nanodevices show vast potential in precise liquid biopsy applications. However, persistent challenges are still associated with off-target effects, and the current platforms also constrain the performance of the assays. In this review, we highlight the merits of CRISPR/Cas systems in liquid biopsy, tracing the development of CRISPR/Cas systems and their current applications in disease diagnosis particularly in liquid biopsies. We also outline ongoing efforts to design nanoscale devices with improved sensing and readout capabilities, aiming to enhance the performance of CRISPR/Cas detectors in liquid biopsy. Finally, we identify the critical obstacles hindering the widespread adoption of CRISPR/Cas liquid biopsy and explore potential solutions. This feature article presents a comprehensive overview of CRISPR/Cas-mediated liquid biopsies, emphasizing the progress in integrating nanodevices to improve specificity and sensitivity. It also sheds light on future research directions in employing nanodevices for CRISPR/Cas-based liquid biopsies in the realm of precision medicine.

Functionalized extracellular nanovesicles as advanced CRISPR delivery systems.

The clustered regularly interspaced short palindromic repeat (CRISPR) system, an emerging tool for genome editing, has garnered significant public interest for its potential in treating genetic diseases. Despite the rapid advancements in CRISPR technology, the progress in developing effective delivery strategies lags, impeding its clinical application. Extracellular nanovesicles (EVs), either in their endogenous forms or with engineered modifications, have emerged as a promising solution for CRISPR delivery. These EVs offer several advantages, including high biocompatibility, biological permeability, negligible immunogenicity, and straightforward production. Herein, we first summarize various types of functional EVs for CRISPR delivery, such as unmodified, modified, engineered virus-like particles (VLPs), and exosome-liposome hybrid vesicles, and examine their distinct intracellular pathways. Then, we outline the cutting-edge techniques for functionalizing extracellular vesicles, involving producer cell engineering, vesicle engineering, and virus-like particle engineering, emphasizing the diverse CRISPR delivery capabilities of these nanovesicles. Lastly, we address the current challenges and propose rational design strategies for their clinical translation, offering future perspectives on the development of functionalized EVs.

Effects of MRP8, LPS, and lenalidomide on the expressions of TNF-α , brain-enriched, and inflammation-related microRNAs in the primary astrocyte culture.

Astrocytes are now recognized as a heterogeneous class of cells with many important and diverse functions in healthy and diseased central nervous system (CNS). MicroRNAs (miRNAs) are small, noncoding RNAs which may have key roles in astrocytes activation in response to various stimuli. We performed quantitative real-time PCR (qPCR) to detect changes in the expressions of brain-enriched miRNAs (124, 134, 9, 132, and 138), inflammation-related miRNAs (146a, 21, 181a, 221, and 222), and tumor necrosis factor alpha (TNF- α ) in the rat primary astrocyte cultures after stimulation with myeloid-related protein 8 (MRP8) and lipopolysaccharides (LPS). Further, we inhibited the expression of TNF- α in the astrocytes by using TNF- α inhibitor (lenalidomide) and tested for the first time the effect of this inhibition on the expressions of the same tested miRNAs. Stimulation of the astrocytes with MRP8 or LPS leads to significant upregulation of miRNAs (124, 134, 9, 132, 146a, 21, 181a, 221, and 222), while miRNA-138 was downregulated. TNF- α inhibition with lenalidomide leads to opposite expressions of the tested miRNAs. These miRNAs may play an important role in activation of the astrocytes and may be a novel target for cell-specific therapeutic interventions in multiple CNS diseases.

GKLF, a transcriptional activator of Txnip, drives microglia activation in kainic acid-induced murine models of epileptic seizures.

Neuroinflammation is a major component of epilepsy. Gut-enriched Kruppel-like factor (GKLF), a transcription factor of Kruppel-like factor family, has been reported to promote microglia activation and mediate neuroinflammation. However, the role of GKLF in epilepsy remains poorly characterized. This study focused on the function of GKLF in neuron loss and neuroinflammation in epilepsy and the molecular mechanism underlying microglia activation induced by GKLF upon lipopolysaccharides (LPS) treatment. An experimental epileptic model was induced by an intraperitoneal injection of 25 mg/kg kainic acid (KA). Lentivirus vectors (Lv) carrying Gklf CDS or short hairpin RNA targeting Gklf (shGKLF) was injected into the hippocampus, resulting in Gklf overexpression or knockdown in the hippocampus. BV-2 cells were co-infected with Lv-shGKLF or/and Lv carrying thioredoxin interacting protein (Txnip) CDS for 48 h and treated with 1 µg/mL LPS for 24 h. Results showed that GKLF enhanced KA-induced neuronal loss, pro-inflammatory cytokine secretion, activation of NOD-like receptor protein-3 (NLRP3) inflammasomes and microglia, and TXNIP expression in the hippocampus. GKLF inhibition showed negative effects on LPS-induced microglia activation, as evidenced by reduced pro-inflammatory cytokine secretion and activation of NLRP3 inflammasomes. GKLF bound to Txnip promoter and increased TXNIP expression in LPS-activated microglia. Interestingly, Txnip overexpression reversed the inhibitory effect of Gklf knockdown on microglia activation. These findings indicated that GKLF was involved in microglia activation via TXNIP. This study demonstrates the underlying mechanism of GKLF in the pathogenesis of epilepsy and uncovers that GKLF inhibition may be a therapeutic strategy for epilepsy treatment.

A Retrospective Study on Clinical Features of Childhood Moyamoya Disease.

BACKGROUND: Childhood moyamoya disease (MMD) can lead to progressive and irreversible neurological impairment. Early age at onset is likely associated with a worst prognosis of the disease. The study aims to summarize the clinical characteristics of childhood MMD for supporting the diagnosis and treatment of early MMD. METHODS: A retrospective study was conducted on children aged zero to 16 years who were diagnosed with MMD in the Department of Neurology and neurosurgery of our hospital from October 2016 to April 2020. The clinical characteristics of children with MMD were summarized for analysis, and the distribution of sex and initial attack type among different age groups was determined by data comparison. RESULTS: The study surveyed 114 children (male to female sex ratio of 1:1.07) with MMD, and 6.1% of them had family history. The mean age of onset was 7.15 ± 3.30 years, and the peak age of onset was five to eight years. The most common initial attack type was transient ischemic attack (TIA) (62 cases, 54.4%) with limb weakness. The incidence of the initial attack type in the three age groups was varied (P < 0.05). The result of overall prognosis was good in 86 cases (89.6%). CONCLUSIONS: In this study, MMD cases were mainly ischemic type and TIA was the most common initial attack type. Infant group was more prone to have cerebral infarction, whereas preschool and school-age groups tended to have TIA. The treatments and prognosis of the studied MMD cases were achieved with good outcomes.

Metabolic and cardiovascular responses to continuous and intermittent plank exercises.

BACKGROUND: Plank exercise (PE) is a whole-body isometric muscle training which is beneficial for physical health. However, none of the previous studies investigated the responses within a typical isometric muscle training or PE protocol consisting of multiple sets. The application of PE was restricted for the understudied metabolic and cardiovascular responses, especially for the patients with cardiovascular diseases. This study is to alleviate the safety concerns of PE by investigating the PE-induced metabolic and cardiovascular responses. METHODS: Eleven male recreational-level college students completed a baseline cardiopulmonary exercise test, continuous PE (CPE) and intermittent PE (IPE). Ratio of maximal oxygen uptake per kilogram of body mass (%VO2max/kg), ratio of maximal heart rate (%HRmax), and respiratory exchange ratio (RER) were continuously measured during PEs and divided into seven equal timepoints. Blood pressure (BP) was measured every minute during, before, and after PEs. A mixed-model repeated measures ANOVA was used to examine the interaction effect of exercise × phase. RESULTS: The %VO2max/kg (F6,69=11.25, P < 0.001), %HRmax (F6,65=7.74, P < 0.001), RER (F6,69=11.56, P < 0.001), and BP (systolic BP, F2,26=8.42, P = 0.002; diastolic BP, F2,24=22.63, P < 0.001) increased by safe magnitudes. Compared with the corresponding period in the IPE group, the %VO2max/kg (33.5 [2.2] vs. 27.7 [1.9], P = 0.043) and %HRmax (63.2 [3.9] vs. 53.3 [2.1], P = 0.019) increased more significantly from the 40% duration of CPE. Systolic BP increased by larger magnitudes during CPE than IPE (154.2 [3.8] vs. 142.3 [4.8] mmHg, P = 0.002). RERs were over 1 during PEs without cardiovascular and metabolic variables over the anaerobic threshold. CONCLUSION: Energy was mainly supplied by anaerobic metabolism during PEs. CPE may be preferable for trainees aiming at anaerobic capacity enhancement. IPEs may be preferable to CPEs for youth patients with mild and borderline cardiovascular diseases due to their lower metabolic and cardiovascular responses.

Membrane-Fusion-Mediated Multiplex Engineering of Tumor Cell Surface Glycans for Enhanced NK Cell Therapy.

Natural killer (NK) cell therapies show potential for tumor treatment but are immunologically resisted by the overexpressed immunosuppressing tumor cell surface glycans. To reverse this glycan-mediated immunosuppression, the surface NK-inhibitory glycan expressions need to be downregulated and NK-activating glycan levels should be elevated synchronously with optimal efficiency. Here, a core-shell membrane-fusogenic liposome (MFL) is designed to simultaneously achieve the physical modification of NK-activating glycans and biological inhibition of immunosuppressing glycans on the tumor cell surface via a membrane-fusion manner. Loaded into a tumor-microenvironment-triggered-degradable thermosensitive hydrogel, MFLs could be conveniently injected and controllably released into local tumor. Through fusion with tumor cell membrane, the released MFLs could simultaneously deliver sialyltransferase-inhibitor-loaded core into cytoplasm, and anchor NK-activating-glycan-modified shell onto tumor surface. This spatially-differential distribution of core and shell in one cell ensures the effective inhibition of intracellular sialyltransferase to downregulate immunosuppressing sialic acid, and direct presentation of NK-activating Lewis X trisaccharide (LeX) on tumor surface simultaneously. Consequentially, the sialic acid-caused immunosuppression of tumor surface is reprogrammed to be LeX-induced NK activation, resulting in sensitive susceptibility to NK-cell-mediated recognition and lysis for improved tumor elimination. This MFL provides a novel platform for multiplex cell engineering and personalized regulation of intercellular interactions for enhanced cancer immunotherapy.