Universal Murray's law for optimised fluid transport in synthetic structures.

Materials following Murray's law are of significant interest due to their unique porous structure and optimal mass transfer ability. However, it is challenging to construct such biomimetic hierarchical channels with perfectly cylindrical pores in synthetic systems following the existing theory. Achieving superior mass transport capacity revealed by Murray's law in nanostructured materials has thus far remained out of reach. We propose a Universal Murray's law applicable to a wide range of hierarchical structures, shapes and generalised transfer processes. We experimentally demonstrate optimal flow of various fluids in hierarchically planar and tubular graphene aerogel structures to validate the proposed law. By adjusting the macroscopic pores in such aerogel-based gas sensors, we also show a significantly improved sensor response dynamics. In this work, we provide a solid framework for designing synthetic Murray materials with arbitrarily shaped channels for superior mass transfer capabilities, with future implications in catalysis, sensing and energy applications.

Seasonal human coronavirus NL63 epidemics in children in Guilin, China, reveal the emergence of a new subgenotype of HCoV-NL63.

Introduction: Seasonal human coronavirus NL63 (HCoV-NL63) is a frequently encountered virus linked to mild upper respiratory infections. However, its potential to cause more severe or widespread disease remains an area of concern. This study aimed to investigate a rare localized epidemic of HCoV-NL63-induced respiratory infections among pediatric patients in Guilin, China, and to understand the viral subtype distribution and genetic characteristics. Methods: In this study, 83 pediatric patients hospitalized with acute respiratory infections and positive for HCoV-NL63 were enrolled. Molecular analysis was conducted to identify the viral subgenotypes and to assess genetic variations in the receptor-binding domain of the spiking protein. Results: Among the 83 HCoV-NL63-positive children, three subgenotypes were identified: C4, C3, and B. Notably, 21 cases exhibited a previously unreported subtype, C4. Analysis of the C4 subtype revealed a unique amino acid mutation (I507L) in the receptor-binding domain of the spiking protein, which was also observed in the previously reported C3 genotype. This mutation may suggest potential increases in viral transmissibility and pathogenicity. Discussion: The findings of this study highlight the rapid mutation dynamics of HCoV-NL63 and its potential for increased virulence and epidemic transmission. The presence of a unique mutation in the C4 subtype, shared with the C3 genotype, raises concerns about the virus's evolving nature and its potential public health implications. This research contributes valuable insights into the understanding of HCoV-NL63's epidemiology and pathogenesis, which is crucial for effective disease prevention and control strategies. Future studies are needed to further investigate the biological significance of the observed mutation and its potential impact on the virus's transmissibility and pathogenicity.

Efficacy and safety of bismuth quadruple regimens containing minocycline and vonoprazan for eradication of Helicobacter pylori: Real-world evidence.

Background and Aim: To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods: From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. Results: For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). Conclusions: The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.

Kinetic Evaluation on Lithium Polysulfide in Weakly Solvating Electrolyte toward Practical Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are highly considered as next-generation energy storage techniques. Weakly solvating electrolyte with low lithium polysulfide (LiPS) solvating power promises Li anode protection and improved cycling stability. However, the cathodic LiPS kinetics is inevitably deteriorated, resulting in severe cathodic polarization and limited energy density. Herein, the LiPS kinetic degradation mechanism in weakly solvating electrolytes is disclosed to construct high-energy-density Li-S batteries. Activation polarization instead of concentration or ohmic polarization is identified as the dominant kinetic limitation, which originates from higher charge-transfer activation energy and a changed rate-determining step. To solve the kinetic issue, a titanium nitride (TiN) electrocatalyst is introduced and corresponding Li-S batteries exhibit reduced polarization, prolonged cycling lifespan, and high actual energy density of 381 Wh kg-1 in 2.5 Ah-level pouch cells. This work clarifies the LiPS reaction mechanism in protective weakly solvating electrolytes and highlights the electrocatalytic regulation strategy toward high-energy-density and long-cycling Li-S batteries.

Understanding the drying mechanism of straw substrate culture block: Physicochemical properties, pore structure, and drying optimization.

As a new type of agricultural waste block substrate utilization, the initial wet base state of the substrate culture block needs to be dried. Therefore, studying the drying mechanism of substrate culture block is critical. In this study, the substrate culture block in a dry state was taken as the research object. Based on physical and chemical properties, the internal section of the substrate culture block was characterized by scanning electron microscopy and the pore condition of the particles was quantified. The results showed that the internal pore structure was uniform and favorable for plant root growth. Based on the pore structure, pore channel modeling was constructed to investigate the distribution of the internal multiphase medium and to distinguish between channels and pore-blind channels. The applicability of the modeling was verified and discussed. By measuring the drying rate of the substrate culture block and classifying its drying stages as fast speed, constant speed, and slow speed, it is clarified that the forms of moisture existence are bound-state water and free-state water, and the moisture migration is prioritized as surface adsorption water, interparticle water, particle attached water, and capillary water. Innovate a method to quantify the change of pore space in the drying process by pore coefficient ratio to evaluate the drying quality. The results show that when the pore coefficient ratio is about 40 %, its moisture content is 20 %∼30 %, and the drying effect is best at this time. The physical drying test further confirmed the correctness of the conclusion of the drying stage division and water loss law. This study can provide a theoretical reference for the modeling study of the pore structure of the block matrix and the exploration of its drying mechanism.

Retrospective study of the deep circumflex iliac artery flap and the vascularized fibula free flap for maxillary defect repair.

OBJECTIVES: The deep circumflex iliac artery flap (DCIA) and vascularized fibular free flap (FFF) are mainstay flaps for maxillary defect reconstruction. This study compared the functional outcomes and success rates of these flaps to provide midface reconstruction strategies. MATERIALS AND METHODS: Maxillary defects reconstructed with DCIA or FFF at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology between May 2016 and May 2023 were retrospectively analyzed. The length, width, and height of the grafted bone segments; intermaxillary distance; buttress reconstruction rate (BRR); dental arch reconstruction rate (DAR); success rate; and dental implantation rate were compared. RESULTS: The DCIA and FFF groups had 33 and 27 patients, respectively. Success rate in the DCIA group was 93.94 % and 100 % in the FFF group. The DCIA length was less than that of FFF; however, the width and height were significantly larger. 87.10 % of cases in the DCIA group were classified as Brown class b and c, 51.85 % of cases in the FFF group were classified as Brown class d. The average BRR in the DCIA group was 69.89 % ± 16.05 %, which was significantly higher than that in the FFF group. A total of 38.7 % and 11.1 % patients in the DCIA and FFF groups, respectively, had completed implantation. CONCLUSION: DCIA has a greater width and height, and is more suitable for repairing Brown class b and c defects, providing sufficient bone for implantation, while the FFF is longer and more suitable for Brown class d defect reconstruction.

Single Crystal Seed Induced Epitaxial Growth Stabilizes α-FAPbI3 in Perovskite Solar Cells.

FAPbI3 stands out as an ideal candidate for the photoabsorbing layer of perovskite solar cells (PSCs), showcasing outstanding photovoltaic properties. Nonetheless, stabilizing photoactive α-FAPbI3 remains a challenge due to the lower formation energy of the competitive photoinactive δ-phase. In this study, we employ tetraethylphosphonium lead tribromide (TEPPbBr3) single crystals as templates for the epitaxial growth of PbI2. The strategic use of TEPPbBr3 optimizes the evolution of intermediates and the crystallization kinetics of perovskites, leading to high-quality and phase-stable α-FAPbI3 films. The TEPPbBr3-modified perovskite exhibits optimized carrier dynamics, yielding a champion efficiency of 25.13% with a small voltage loss of 0.34 V. Furthermore, the target device maintains 90% of its initial PCE under maximum power point (MPP) tracking over 1000 h. This work establishes a promising pathway through single crystal seed based epitaxial growth for achieving satisfactory crystallization regulation and phase stabilization of α-FAPbI3 perovskites toward high-efficiency and stable PSCs.

Defective state regulation of Ru-doped Nb2O5 boosts fast lithium storage.

Breaking through the limitations of lithium-ion transmission is imperative for high-power rechargeable batteries. As a promising anode material for fast-charging lithium-ion batteries (LIBs), niobium pentoxide (Nb2O5) has garnered considerable research attention due to its exceptional rate performance, stable lithium storage performance and high safety attributes. Nevertheless, the limited intrinsic conductivity of Nb2O5, coupled with its structural degradation during the cycling process, imposes constraints on its viability as a commercially viable electrode material. Herein, a ruthenium (Ru) doping method is employed to regulate the oxygen defects and the interlayer spacing of the tetragonal Nb2O5 (M-Nb2O5), offering superior reaction kinetics, higher stability for lithium storage sites and more unobstructed lithium-ion transport channels. Ru-doped Nb2O5 (RNO) manifests excellent electrochemical properties, including remarkable rate capacity (166 mAh/g at 80C), reversible capacity (246.98 mAh/g at 0.5C), improved initial Coulombic efficiency (95.77 % compared to 81.44 % of the pure sample) and cycling stability (maintaining a capacity of 113.5 mAh/g at 10C for 2,000 cycles). The enhancement mechanism of Ru doping on the structural stability and ion transport kinetics in tetragonal Nb2O5 is comprehensively elucidated through diverse electrochemical analyses and in-situ techniques.

A novel molecularly imprinted electrochemical sensor from poly (3, 4-ethylenedioxythiophene)/chitosan for selective and sensitive detection of levofloxacin.

The improper usage of levofloxacin (LEV) endangers both environmental safety and human public health. Therefore, trace analysis and detection of LEV have extraordinary significance. In this paper, a novel molecularly imprinted polymer (MIP) electrochemical sensor was developed for the specific determination of LEV by electrochemical polymerization of o-phenylenediamine (o-PD) using poly(3,4-ethylenedioxythiophene)/chitosan (PEDOT/CS) with a porous structure and rich functional groups as a carrier and LEV as a template molecule. The morphology, structure and properties of the modified materials were analyzed and studied. The result showed that the electron transfer rate and the electroactive strength of the electrode surface are greatly improved by the interconnection of PEDOT and CS. Meanwhile, PEDOT/CS was assembled by imprinting with o-PD through non-covalent bonding, which offered more specific recognition sites and a larger surface area for the detection of LEV and effectively attracted LEV through intermolecular association. Under the optimized conditions, MIP/PEDOT/CS/GCE showed good detection performance for LEV in a wide linear range of 0.0019- 1000 µM, with a limit of detection (LOD, S/N = 3) of 0.4 nM. Furthermore, the sensor has good stability and selectivity, and exhibits excellent capabilities in the microanalysis of various real samples.

An ionic liquid-modified PEDOT/Ti3C2TX based molecularly imprinted electrochemical sensor for pico-molar sensitive detection of L-Tryptophan in milk.

L-Tryptophan (L-Trp) is essential for the human body and can only be obtained externally. It is important to develop a method to efficiently detect L-Trp in food. In this work, ionic liquid (IL) modified poly(3,4-ethylendioxythiophene)/ Titanium carbide (PEDOT/Ti3C2TX) was used as a substrate material to improve detection sensitivity. Molecular imprinted polymers (MIP) film for specific recognition of L-Trp was fabricated on the surface of modified electrodes using electrochemical polymerization. The monitoring results showed that the molecularly imprinted electrochemical sensors (MIECS) exhibited good linearity ranges (10-6 - 0.1 µM and 0.1-100 µM) with a low detection limit (LOD) of 2.09 × 10-7 µM. In addition, the MIECS exhibited remarkable stability, reproducibility, and immunity to interference. A good recovery (93.54-99.59%) was demonstrated in the detection of milk. The sensor was expected to be developed as a highly selective and sensitive portable assay, and applied to the detection of L-Trp in food.

Post-marketing safety concerns with palbociclib: a disproportionality analysis of the FDA adverse event reporting system.

OBJECTIVES: To explore the association between palbociclib and related adverse events (AEs) in the real world through U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: The signal strength of palbociclib-related AEs was done by disproportionality analysis. Clinical priority of palbociclib-related AEs was scored and ranked by assessing five different features. Outcome analysis, time to onset analysis, dose-report /AEs number analysis, and stratification analysis were all performed. RESULTS: There were 61,821 'primary suspected (PS)' reports of palbociclib and 195,616 AEs associated with palbociclib. The four algorithms simultaneously detected 18 positive signals at the SOC level, and 65 positive signals at the PT level. Bone marrow failure, neuropathy, peripheral, pleural effusion, myelosuppression, pulmonary edema, and pulmonary thrombosis were also found to have positive signals. Gender (female vs male, χ2 = 5.287, p = 0.022) and age showed significant differences in serious and non-serious reports. Palbociclib-related AEs had a median onset time of 79 days (interquartile range [IQR] 20-264 days). CONCLUSIONS: The study identified potential Palbociclib-related AEs and offered warnings for special AEs, providing further data for palbociclib safety studies in breast cancer patients. Nonetheless, prospective clinical trials are needed to validate these results and explain their relationship.

Carbon Fiber Reinforced Recycled Polypropylene/Polyolefin Elastomer Composites with High Mechanical Properties.

The treatment of waste plastics has gradually become a hot topic in the current scientific community. In response to the needs for high-impact performance R-PP-based composites, carbon fiber (CF)-reinforced polyolefin elastomer (POE)/recycled polypropylene (R-PP) composite (CF/POE/R-PP) was prepared by the mechanical blending method, and its mechanical and thermal properties were systematically studied. It was found that the CF could effectively improve the bending and notch impact strength as well as enhance the thermal stability of POE/R-PP. Furthermore, a stable and dispersed composite interface formed by the combination of maleic anhydride-grafted polypropylene (PP-g-MAH) with the surface of CF and the fusion alkyl chains in R-PP and POE further enhanced the CF's reinforcing effect. As a result, the addition of 9 wt.% CF successfully improved the heat resistance of the composite material, and the residual carbon content increased by 97.84% after sintering. The composite toughening of POE and CF effectively improved the impact strength of the composite material, with a maximum increase of over 1000%. This study ultimately resulted in a high-impact-resistant composite material.

[Yeast extract improves the inflammatory response of HepG2 cells induced by ethyl alcohol and lipopolysaccharide].

OBJECTIVE: To explore the ameliorative effect of yeast extract(YE) on the inflammatory response of human hepatoma cells(HepG2) induced by ethyl alcohol(EtOH) and lipopolysaccharide(LPS), and further explore the potential molecular mechanism based on Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB) signaling pathway. METHODS: HepG2 cells were induced by 50 mmol/L EtOH and 1 µg/mL LPS combined with YE intervention. The expression level of inflammatory cytokines was detected by ELISA. The expression level of TLR4 and the nuclear translocation of NF-κB were detected by immunofluorescence staining. The expression levels of TLR4, NF-κB, phospho-NF-κB-P65(P-NF-κB-p65), nucleus-phospho-NF-κB-p65(N-P-NF-κB-p65), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) were detected by Western blot. RESULTS: Compared with the control group, the cells in EtOH+LPS group produced a large number of inflammatory factors and had a significant inflammatory response. YE intervention significantly alleviated EtOH+LPS induced hepatocyte inflammatory response. Further molecular mechanism studies showed that YE significantly reduced TLR4 expression level and inhibited NF-κB nuclear translocation in hepatocytes. CONCLUSION: YE can effectively inhibit the inflammatory response of HepG2 cells induced by EtOH and LPS, and its molecular mechanism may be related to the down-regulation of TLR4/NF-κB pathway.

L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons.

As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons. By whole-cell patch clamp recording, we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents (sEPSCs) and also increases the amplitude of sEPSCs in hippocampal neurons. This phenomenon lasts for > 10 min after LIPUS exposure. Together with Ca2+ imaging, we clarified that LIPUS increases the [Ca2+]cyto level by facilitating L-type Ca2+ channels (LTCCs). In addition, due to the [Ca2+]cyto elevation by LIPUS exposure, the Ca2+-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression. Our work suggests that LIPUS regulates neuronal activity in a Ca2+-dependent manner via LTCCs. This may also explain the multi-activation effects of LIPUS beyond neurons. LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca2+ influx.

ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition.

The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how arginine levels fluctuate in the TME to shape T cell fates. Here, we find that the 20-µM low arginine condition, representing the levels found in the plasma of patients with cancers, confers Treg-like immunosuppressive capacities upon activated T cells. In vivo mouse tumor models and human single-cell RNA-sequencing datasets reveal positive correlations between low arginine condition and intratumoral Treg accumulation. Mechanistically, low arginine-activated T cells engage in metabolic and transcriptional reprogramming, using the ATF4-SLC7A11-GSH axis, to preserve their suppressive function. These findings improve our understanding of the role of arginine in human T cell biology with potential applications for immunotherapy strategies.

Epidemiology and risk factors of bloodstream infections among adolescents and young adults with acute lymphoblastic leukaemia: An 11-year retrospective cohort study.

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (<15 years old) and older adults (>39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram-negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended-spectrum beta-lactamase (ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine ≥ 177 µmol/L) were influencing factors for 30-day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children.

Neutrophil Targeting Platform Reduces Neutrophil Extracellular Traps for Improved Traumatic Brain Injury and Stroke Theranostics.

Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia-reperfusion injury (CIRI), in addition to the blood-brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)-responsive neutrophil-targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Theoretical and experimental study of attenuation in cancellous bone.

Significance: Photoacoustic (PA) technology shows great potential for bone assessment. However, the PA signals in cancellous bone are complex due to its complex composition and porous structure, making such signals challenging to apply directly in bone analysis. Aim: We introduce a photoacoustic differential attenuation spectrum (PA-DAS) method to separate the contribution of the acoustic propagation path to the PA signal from that of the source, and theoretically and experimentally investigate the propagation attenuation characteristics of cancellous bone. Approach: We modified Biot's theory by accounting for the high frequency and viscosity. In parallel with the rabbit osteoporosis model, we build an experimental PA-DAS system featuring an eccentric excitation differential detection mechanism. Moreover, we extract a PA-DAS quantization parameter-slope-to quantify the attenuation of high- and low-frequency components. Results: The results show that the porosity of cancellous bone can be evaluated by fast longitude wave attenuation at different frequencies and the PA-DAS slope of the osteoporotic group is significantly lower compared with the normal group (**p<0.01). Conclusions: Findings demonstrate that PA-DAS effectively differentiates osteoporotic bone from healthy bone, facilitating quantitative assessment of bone mineral density, and osteoporosis diagnosis.

Tumor Microenvironment-Activatable Nanosystem Capable of Overcoming Multiple Therapeutic Obstacles for Augmenting Immuno/Metal-Ion Therapy.

Abnormal tumor microenvironment (TME) imposes barriers to nanomedicine penetration into tumors and evolves tumor-supportive nature to provide tumor cell protection, seriously weakening the action of antitumor nanomedicines and posing significant challenges to their development. Here, we engineer a TME-activatable size-switchable core-satellite nanosystem (Mn-TI-Ag@HA) capable of increasing the effective dose of therapeutic agents in deep-seated tumors while reversing tumor-supportive microenvironment for augmenting immuno/metal-ion therapy. When activated by TME, the nanosystem disintegrates, allowing ultrasmall-sized Ag nanoparticles to become unbound and penetrate deep into solid tumors. Simultaneously, the nanosystem produces O2 and releases TGF-ß inhibitors in situ to drive macrophage M2-to-M1 polarization, increasing intratumoral H2O2 concentration, and ultimately augmenting metal-ion therapy by accelerating hypertoxic Ag+ production. The nanosystem can overcome multiple obstacles that aid in tumor resistance to nanomedicine, demonstrating effective tumor penetration, TME regulation, and tumor inhibition effects. It can provoke long-term immunological memory effects against tumor rechallenge when combined with immune checkpoint inhibitor anti-PD-1. This work provides a paradigm for designing efficient antitumor nanomedicines.