Robust Spectral π Pairing in the Random-Field Floquet Quantum Ising Model.

Motivated by an experiment on a superconducting quantum processor [X. Mi et al., Science 378, 785 (2022).SCIEAS0036-807510.1126/science.abq5769], we study level pairings in the many-body spectrum of the random-field Floquet quantum Ising model. The pairings derive from Majorana zero and π modes when writing the spin model in Jordan-Wigner fermions. Both splittings have log-normal distributions with random transverse fields. In contrast, random longitudinal fields affect the zero and π splittings in drastically different ways. While zero pairings are rapidly lifted, the π pairings are remarkably robust, or even strengthened, up to vastly larger disorder strengths. We explain our results within a self-consistent Floquet perturbation theory and study implications for boundary spin correlations. The robustness of π pairings against longitudinal disorder may be useful for quantum information processing.

A novel homozygous CLN6 Tyr142Cys variant in a nonconsanguineous family with Kufs disease.

BACKGROUND: Neuronal ceroid lipofuscinoses are a genetically heterogeneous group of inherited lysosomal storage disorders. Kufs disease is the predominant form of neuronal ceroid lipofuscinosis in adults, but it's rare and challenging to diagnose. CASE DESCRIPTION: The proband initially presented with cognitive deterioration and parkinsonian traits. At 35, he was admitted to hospital following a tonic-clonic seizure. Brain magnetic resonance imaging showed atrophy of the cerebral cortex and cerebellum, enlarged ventricles, and thinned corpus callosum. The proband's younger brother and sister were also affected, and the clinical phenotype within the family was consistent. Whole-exome Sequencing of the proband revealed a novel homozygous mutation in CLN6 (NM_017882: c.425A > G, p. Tyr142Cys). Co-segregation analysis revealed that two other affected individuals carried a homozygous mutation at the same locus, with both parents exhibiting heterozygous mutations of c.425A > G. CONCLUSION: Our study not only provides insights into the clinical presentation and development of the disease within the affected family but also expanded the mutational and phenotypical spectrum of the CLN6 gene.

A ferroptosis-related signature predicts the clinical diagnosis and prognosis, and associates with the immune microenvironment of lung cancer.

Targeting ferroptosis-related pathway is a potential strategy for treatment of lung cancer (LC). Consequently, exploration of ferroptosis-related markers is important for treating LC. We collected LC clinical data and mRNA expression profiles from TCGA and GEO database. Ferroptosis-related genes (FRGs) were obtained through FerrDB database. Expression analysis was performed to obtain differentially expressed FRGs. Diagnostic and prognostic models were constructed based on FRGs by LASSO regression, univariate, and multivariate Cox regression analysis, respectively. External verification cohorts GSE72094 and GSE157011 were used for validation. The interrelationship between prognostic risk scores based on FRGs and the tumor immune microenvironment was analyzed. Immunocytochemistry, Western blotting, and RT-qPCR detected the FRGs level. Eighteen FRGs were used for diagnostic models, 8 FRGs were used for prognostic models. The diagnostic model distinguished well between LC and normal samples in training and validation cohorts of TCGA. The prognostic models for TCGA, GSE72094, and GSE157011 cohorts significantly confirmed lower overall survival (OS) in high-risk group, which demonstrated excellent predictive properties of the survival model. Multivariate Cox regression analysis further confirmed risk score was an independent risk factor related with OS. Immunoassays revealed that in high-risk group, a significantly higher proportion of Macrophages_M0, Neutrophils, resting Natural killer cells and activated Mast cells and the level of B7H3, CD112, CD155, B7H5, and ICOSL were increased. In conclusion, diagnostic and prognostic models provided superior diagnostic and predictive power for LC and revealed a potential link between ferroptosis and TIME.

Engineering Properties and Microstructure of Soils Stabilized by Red-Mud-Based Cementitious Material.

Red mud (RM) is an industrial waste generated in the process of aluminum refinement. The recycling and reusing of RM have become urgent problems to be solved. To explore the feasibility of using RM in geotechnical engineering, this study combined magnesium oxide (MgO) (or calcium oxide (CaO)) with RM as an RM-based binder, which was then used to stabilize the soil. The physical, mechanical, and micro-structural properties of the stabilized soil were investigated. As the content of MgO or CaO in the mixture increased, the unconfined compressive strength (UCS) of the RM-based cementitious materials first increased and then decreased. For the soils stabilized with RM-MgO or RM-CaO, the UCS increased and then decreased, reaching a maximum at RM:MgO = 5:5 or RM:CaO = 8:2. The addition of sodium hydroxide (NaOH) promoted the hydration reaction. The UCS enhancement ranged from 8.09% to 66.67% for the RM-MgO stabilized soils and 204.6% to 346.6% for the RM-CaO stabilized soils. The optimum ratio of the RM-MgO stabilized soil (with NaOH) was 2:8, while that of the RM-CaO stabilized soil (with NaOH) was 4:6. Freeze-thaw cycles reduced the UCS of the stabilized soil, but the resistance of the stabilized soil to freeze-thaw erosion was significantly improved by the addition of RM-MgO or RM-CaO, and the soil stabilized with RM-MgO had better freeze-thaw resistance than that with RM-CaO. The hydrated magnesium silicate generated by the RM-MgO stabilized soil and the hydrated calcium silicate generated by the RM-CaO stabilized soil helped to improve the UCS of the stabilized soil. The freeze-thaw cycles did not weaken the formation of hydration products in the stabilized soil but could result in physical damage to the stabilized soils. The decrease in the UCS of the stabilized soil was mainly due to physical damage.

Advancing treatment strategies for posterior malleolar malunion: The ankle dislocation method.

BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.

Combined use of Panax notoginseng and leech provides new insights into renal fibrosis: Restoration of mitochondrial kinetic imbalance.

In this study, we aimed to investigate the protective effects of Panax notoginseng and leech (PL) on renal fibrosis and explore the mechanisms underlying their actions. For this study, we created an adenine-induced renal fibrosis model in SD rats to investigate the protective effect of PL on renal fibrosis and explore its underlying mechanism. Initially, we assessed the renal function in RF rats and found that Scr, BUN, and urine protein content decreased after PL treatment, indicating the protective effect of PL on renal function. Histological analysis using HE and Masson staining revealed that PL reduced inflammatory cell infiltration and decreased collagen fiber deposition in renal tissue. Subsequently, we analyzed the levels of α-SMA, Col-IV, and FN, which are the main components of the extracellular matrix (ECM), using IHC, RT-qPCR, and WB. The results demonstrated that PL was effective in reducing the accumulation of ECM, with PL1-2 showing the highest effectiveness. To further understand the underlying mechanisms, we conducted UPLC-MS/MS analysis on the incoming components of the PL1-2 group. The results revealed several associations between the differential components and antioxidant and mitochondrial functions. This was further confirmed by enzyme-linked immunosorbent assay and biochemical indexes, which showed that PL1-2 ameliorated oxidative stress by reducing ROS and MDA production and increasing GSH and SOD levels. Additionally, transmission electron microscopy results indicated that PL1-2 promoted partial recovery of mitochondrial morphology and cristae. Finally, using RT-qPCR and WB, an increase in the expression of mitochondrial fusion proteins Mfn1, Mfn2, and Opa1 after PL1-2 treatment was observed, coupled with a decline in the expression and phosphorylation of mitochondrial cleavage proteins Fis and Drp1. These findings collectively demonstrate that PL1-2 ameliorates renal fibrosis by reducing oxidative stress and restoring mitochondrial balance.

Vegetation restoration in an alpine meadow: Insights from soil microbial communities and resource limitation across soil depth.

Aboveground vegetation restoration shapes the soil microbial community structure and affects microbial resource acquisition. However, the changes in soil microbial resource limitation in subsoil during vegetation restoration are still unclear. In this study, the microbial community structure and resource limitation in an alpine meadow soil profile that had undergone natural restoration for short-term (4-year) and long-term (10-year) restoration in response to vegetation restoration were explored through high-throughput sequencing analysis and extracellular enzyme stoichiometry (EES). There was no significant difference in microbial composition and α diversity between short- and long-term restoration soils. Soil microorganisms in this alpine meadow were mainly limited by phosphorus. Carbon limitation of soil microorganisms was significantly decreased in each layer (0-15, 15-30, 30-45, 45-60, and 60-80 cm corresponding to L1, L2, L3, L4, and L5, respectively) of long-term restoration soils when compared to that of the short-term restoration soil layers, while phosphorus limitation of microorganisms in subsoil (60-80 cm) was significantly increased by 17.38%. Soil nutrients, pH, moisture content, and microbial composition are the main drivers of microbial resource limitation in restoration, and their effects on microbial resource limitation were different in short- and long-term restoration. Meanwhile, key microbial taxa have a significant impact on microbial resource limitation, especially in short-term restoration soils. This study suggested that vegetation restoration significantly affected soil microbial resource limitation, and could alleviate microbial resource limitations by adding nutrients, thus accelerating the process of vegetation restoration in alpine ecosystems.

Chemical profiling of principle active and toxic constituents in herbs containing aristolochic acids.

Objective: To clear the amounts of the principal active/toxic components in herbs containing aristolochic acids (HCAAs), which are still used as medicine and/or seasoning in many ethnic minority areas of China. Methods: In this study, six major active and toxic components in HCAAs were extracted with ultrasonic extraction. With 6-O-methyl guanosine as internal standard, the target compounds were analyzed qualitatively and quantitatively by using ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) with multiple reaction monitoring-information dependent acquisition-enhanced production ion scanning mode (MRM-IDA-EPI) combined with dynamic background subtraction (DBS) function. Results: The method showed good linearity in the linear range of the six analytes. The limit range of detection was from 0.01 ng/mL to 0.27 ng/mL. All of the detection repeatability, extraction repeatability and accuracy of the method were good. After extraction, the samples remained stable at 15 °C within 24 h. Six analytes were all found in samples except aristolactam (AL) in sample 2, and the contents varied greatly. The contents of these compounds decreased in fruits, leaves and stems of Aristolochia delavayi successively. Conclusion: This method has the advantages of less sample dosage, simple operation, short analysis cycle, high sensitivity, specificity and accuracy. It laid a good foundation for guiding the safety of HCAAs, the in-depth study of pharmacological and toxicological effects and the scientific and standardized processing and compatibility of HCAAs.

Tumor targeted porphyrin-based metal-organic framework for photodynamic and checkpoint blockade immunotherapy.

Photodynamic therapy (PDT) has become a promising approach and non-invasive modality for cancer treatment, however the therapeutic effect of PDT is limited in tumor metastasis and local recurrence. Herein, a tumor targeted nanomedicine (designated as PCN@HA) is constructed for enhanced PDT against tumors. By modified with hyaluronic acid (HA), which could target the CD44 receptor that expressed on the cancer cells, the targeting ability of PCN@HA has been enhanced. Under light irradiation, PCN@HA can produce cytotoxic singlet oxygen (1O2) and kill cancer cells, then eliminate tumors. Furthermore, PCN@HA exhibits fluorescence (FL)/ photoacoustic (PA) effects for multimodal imaging-guided cancer treatment. And PCN@HA-mediated PDT also can induce immunogenic cell death (ICD) and stimulate adaptive immune responses by releasing of tumor antigens. By combining with anti-PD-L1 checkpoint blockade therapy, it can not only effectively suppress the growth of primary tumor, but also inhibit the metastatic tumor growth.

Design and Synthesis of Novel Macrocyclic Derivatives as Potent and Selective Cyclin-Dependent Kinase 7 Inhibitors.

The duality of function (cell cycle regulation and gene transcription) of cyclin-dependent kinase 7 (CDK7) makes it an attractive oncology target and the discovery of CDK7 inhibitors has been a long-term pursuit by academia and pharmaceutical companies. However, achieving selective leading compounds is still difficult owing to the similarities among the ATP binding pocket. Herein, we detail the design and synthesis of a series of macrocyclic derivatives with pyrazolo[1,5-a]-1,3,5-triazine core structure as potent and selective CDK7 inhibitors. The diverse manners of macrocyclization led to distinguished selectivity profiles of the CDK family. Molecular dynamics (MD) simulation explained the binding difference between 15- and 16-membered macrocyclic compounds. Further optimization generated compound 37 exhibiting good CDK7 inhibitory activity and high selectivity over other CDKs. This work clearly demonstrated macrocyclization is a versatile method to finely tune the selectivity profile of small molecules and MD simulation can be a valuable tool in prioritizing designs of the macrocycle.

Microstructure and Mechanical Properties of Refill Friction Stir Spot-Welded Joints of 2A12Al and 7B04Al: Effects of Tool Size and Welding Parameters.

To solve problems in dissimilarly light metal joints, refilled friction stir spot welding (RFSSW) is proposed instead of resistance spot welding. However, rotation speed, dwell time, plunge depth, and the diameter of welding tools all have a great influence on joints, which brings great challenges in optimizing welding parameters to ensure their mechanical properties. In this study, the 1.5 mm thick 2A12Al and 2 mm thick 7B04Al lap joints were prepared by Taguchi orthogonal experiment design and RFSSW. The welding tool (shoulder) diameters were 5 mm and 7 mm, respectively. The macro/microstructures of the cross-section, the geometrical characteristics of the effective welding depth (EWD), the stir zone area (SZA), and the stir zone volume (SZV) were characterized. The shear strength and failure mode of the lap joint were analyzed using an optical microscope. It was found that EWD, SZA, and SZV had a good correlation with tensile-shear force. The optimal welding parameters of 5 mm diameter joints are 1500 rpm of rotation speed, 2.5 mm of plunge depth, and 0 s of dwell time, which for 7 mm joints are 1200 rpm, 1.5 mm, and 2 s. The tensile-shear force of 5 mm and 7 mm joints welded with these optical parameters was 4965 N and 5920 N, respectively. At the same time, the 5 mm diameter joints had better strength and strength stability.

Preparation of Peptoid Antifreeze Agents and Their Structure-Property Relationship.

The development of nontoxic and efficient antifreeze agents for organ cryopreservation is crucial. However, the research remains highly challenging. In this study, we designed and synthesized a series of peptoid oligomers using the solid-phase submonomer synthesis method by mimicking the amphiphilic structures of antifreeze proteins (AFPs). The obtained peptoid oligomers showed excellent antifreeze properties, reducing the ice crystal growth rate and inhibiting ice recrystallization. The effects of the hydrophobicity and sequence of the peptoid side chains were also studied to reveal the structure-property relationship. The prepared peptoid oligomers were detected as non-cytotoxic and considered to be useful in the biological field. We hope that the peptoid oligomers presented in this study can provide effective strategies for the design of biological cryoprotectants for organ preservation in the future.

Self-Assembly Study of Block Copolypeptoids in Response to pH and Temperature Stimulation.

Polypeptoids with well-designed structures have the ability to self-assemble into nanomaterials, which have wide potential applications. In this study, a series of diblock copolypeptoids were synthesized via ring-opening polymerization followed by click chemistry and exhibited both temperature and pH stimulation responsiveness. Under specific temperature and pH conditions, the responsive blocks in the copolypeptoids became hydrophobic and aggregated to form micelles. The self-assembly process was monitored using the UV-Vis and DLS methods, which suggested the reversible transition of free molecules to micelles and bigger aggregates upon instituting temperature and pH changes. By altering the length and proportion of each block, the copolypeptoids displayed varying self-assembly characteristics, and the transition temperature could be tuned. With good biocompatibility, stability, and no cytotoxicity, the polypeptoids reported in this study are expected to be applied as bionanomaterials in fields including drug delivery, tissue engineering, and intelligent biosensing.

Bioinspired construction of petal-like regenerated PVDF/cellulose fibers for efficient fog harvesting.

Water collection from atmospheric fog was deemed to be an efficient and sustainable strategy to defuse the freshwater scarcity crisis. Fog harvesting and trapping fibers, therefore, has aroused extensive interest due to their ease of preparation, weave, and use. However, the traditional fibers used in fog collector usually have a low fog collection capacity and efficiency because of their unreasonable morphology and structure design. Herein, we proposed a simple process to construct advanced fibers using a one-step wet spinning of hydrophobic polyvinylidene fluoride (PVDF) and hydrophilic cellulose mixture fiber for fog harvesting. The as-prepared fibers featured a petaloid structure and surface hydrophobic gradient, thus facilitating fog deposition, water droplet formation, and drainage. The unique longitudinal groove structure above enabled the hybrid fiber to achieve an excellent fog collection efficiency of 2750.26 mg/cm2/h per monofilament, which outstripped most of other fiber materials. When woven these fibers were in a longitudinal array network with an interval of 1 mm, and the fog collection efficiency can maintain at 10.30 L/m2/h. Therefore, this work provided a new strategy for further exploration of effective fog collection by cellulose-based fiber materials.

Would Combination Be Better: Swimming Exercise and Intermittent Fasting Improve High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Obese Rats via the miR-122-5p/SREBP-1c/CPT1A Pathway.

Background: Swimming and intermittent fasting can both improve obesity-induced NAFLD, but which of the two is more effective and whether the combination of the two has a superimposed effect is inconclusive. Methods: The model of NAFLD in obese rats was established by a high-fat diet and performed swimming, intermittent fasting, and a combination of both interventions for 8 weeks. Serum lipids and enzyme activity were measured by an automatic biochemical analyzer. Liver morphostructural analysis was observed by transmission electron microscopy, and morphology was observed by HE staining. RT‒PCR was used to detect the mRNA level. Results: Morphology and microstructure of the liver of model rats were impaired, with the upregulation of miR-122-5p, SREBP-1c, FASN and ACC1. Eight weeks of swimming exercise, intermittent fasting and the combination of both attenuate these effects, manifested by the downregulation of miR-122-5p and upregulation of CPT1A mRNA levels. There was no significant stacking effect of the combination of the swimming and intermittent fasting interventions. Conclusion: NAFLD leads to pathology in model rats. Eight weeks of swimming exercise, intermittent fasting and the combination of both can inhibit miR-122-5p and improve hepatic lipid metabolism, while no significant additive effects of combining the interventions were found.

Heterogeneous nucleation induced A. pernyi/B. mori silk fibroin coatings on AZ31 biometals with enhanced corrosion resistance, adhesion and biocompatibility.

Silk fibroin coatings on biomedical magnesium alloys have garnered significant attention due to their enhanced corrosion resistance and biocompatibility. However, the utilization of wild A. pernyi silk fibroin, known for its RGD sequence that facilitates tissue regeneration, presents a challenge for corrosion-resistant coatings on magnesium alloys due to its weak adhesion and high dissolution rate. In this study, we employed hexafluoroisopropanol as a solvent to blend A. pernyi silk fibroin with B. mori silk fibroin. The resulting blended fibroin coating at a 3:7 mass ratio exhibited a heterogeneous nucleation effect, enhancing ß-sheet content (32.3 %) and crystallinity (28.6 %). This improved ß-sheet promoted the "labyrinth effect" with an Icorr of 2.15 × 10-6 A cm-2, resulting in significantly improved corrosion resistance, which is two orders of magnitude lower than that of pure magnesium alloy. Meanwhile, the increased content of exposed serine in zigzag ß-sheet contributes to a higher adhesion strength. Cell cytotoxicity evaluation confirmed the enhanced cell adhesion and bioactivity. This work provides a facile approach for wild A. pernyi silk fibroin coatings on magnesium alloys with enhanced corrosion resistance, adhesion and biocompatibility.

H9N2 Avian Influenza Virus Downregulates FcRY Expression in Chicken Macrophage Cell Line HD11 by Activating the JNK MAPK Pathway.

The H9N2 avian influenza virus causes reduced production performance and immunosuppression in chickens. The chicken yolk sac immunoglobulins (IgY) receptor (FcRY) transports from the yolk into the embryo, providing offspring with passive immunity to infection against common poultry pathogens. FcRY is expressed in many tissues/organs of the chicken; however, there are no reports investigating FcRY expression in chicken macrophage cells, and how H9N2-infected HD11 cells (a chicken macrophage-like cell line) regulate FcRY expression remains uninvestigated. This study used the H9N2 virus as a model pathogen to explore the regulation of FcRY expression in avian macrophages. FcRY was highly expressed in HD11 cells, as shown by reverse transcription polymerase chain reactions, and indirect immunofluorescence indicated that FcRY was widely expressed in HD11 cells. HD11 cells infected with live H9N2 virus exhibited downregulated FcRY expression. Transfection of eukaryotic expression plasmids encoding each viral protein of H9N2 into HD11 cells revealed that nonstructural protein (NS1) and matrix protein (M1) downregulated FcRY expression. In addition, the use of a c-jun N-terminal kinase (JNK) activator inhibited the expression of FcRY, while a JNK inhibitor antagonized the downregulation of FcRY expression by live H9N2 virus, NS1 and M1 proteins. Finally, a dual luciferase reporter system showed that both the M1 protein and the transcription factor c-jun inhibited FcRY expression at the transcriptional level. Taken together, the transcription factor c-jun was a negative regulator of FcRY, while the live H9N2 virus, NS1, and M1 proteins downregulated the FcRY expression through activating the JNK signaling pathway. This provides an experimental basis for a novel mechanism of immunosuppression in the H9N2 avian influenza virus.

DNA damage-regulated autophagy modulator 1 prevents glioblastoma cells proliferation by regulating lysosomal function and autophagic flux stability.

Glioblastoma (GBM) is the most aggressive and life-threatening brain tumor, characterized by its highly malignant and recurrent nature. DNA damage-regulated autophagy modulator 1 (DRAM-1) is a p53 target gene encoding a lysosomal protein that induces macro-autophagy and damage-induced programmed cell death in tumor growth. However, the precise mechanisms underlying how DRAM-1 affects tumor cell proliferation through regulation of lysosomal function and autophagic flux stability remain incompletely understood. We found that DRAM-1 expressions were evidently down-regulated in high-grade glioma and recurrent GBM tissues. The upregulation of DRAM-1 could increase mortality of primary cultured GBM cells. TEM analysis revealed an augmented accumulation of aberrant lysosomes in DRAM-1-overexpressing GBM cells. The assay for lysosomal pH and stability also demonstrated decreasing lysosomal membrane permeabilization (LMP) and impaired lysosomal acidity. Further research revealed the detrimental impact of lysosomal dysfunction, which impaired the autophagic flux stability and ultimately led to GBM cell death. Moreover, downregulation of mTOR phosphorylation was observed in GBM cells following upregulation of DRAM-1. In vivo and in vitro experiments additionally illustrated that the mTOR inhibitor rapamycin increased GBM cell mortality and exhibited an enhanced antitumor effect.

Hypoxia-triggered degradable porphyrinic covalent organic framework for synergetic photodynamic and photothermal therapy of cancer.

Nanomedicines receive great attention in cancer treatment. Nevertheless, nonbiodegradable and long-term retention still limit their clinical translation. Herein, we successfully synthesize a hypoxia-triggered degradable porphyrinic covalent organic framework (HPCOF) for antitumor therapy in vivo. HPCOF possesses wide absorption in near infrared region (NIR) which endows HPCOF excellent photothermal conversion efficiency and photoacoustic (PA) imaging ability. Moreover, HPCOF exhibits excellent photodynamic and photothermal effect under special-wavelength laser irradiation. For the first time, the in vitro and in vivo tests demonstrate that HPCOF shows effective therapeutic effect for the combination of PDT and PTT under the monitoring of PA imaging. Importantly, in tumor region, HPCOF could be triggered by hypoxia microenvironment and collapsed gradually, then cleared from the body after treatment. This work fabricates a novel COF for cancer treatment and testifies great potential of HPCOF in clinical application with reducing long-term toxicity.