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149 result(s) for "Fu, Zhendong"
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Histidine modulates amyloid-like assembly of peptide nanomaterials and confers enzyme-like activity
Amyloid-like assembly is not only associated with pathological events, but also leads to the development of novel nanomaterials with unique properties. Herein, using Fmoc diphenylalanine peptide (Fmoc–F–F) as a minimalistic model, we found that histidine can modulate the assembly behavior of Fmoc–F–F and induce enzyme-like catalysis. Specifically, the presence of histidine rearranges the β structure of Fmoc–F–F to assemble nanofilaments, resulting in the formation of active site to mimic peroxidase-like activity that catalyzes ROS generation. A similar catalytic property is also observed in Aβ assembled filaments, which is correlated with the spatial proximity between intermolecular histidine and F-F. Notably, the assembled Aβ filaments are able to induce cellular ROS elevation and damage neuron cells, providing an insight into the pathological relationship between Aβ aggregation and Alzheimer’s disease. These findings highlight the potential of histidine as a modulator in amyloid-like assembly of peptide nanomaterials exerting enzyme-like catalysis. In this work, the authors report that Histidine residues play a critical role in modulating amyloid-like assembly and building active sites for Fmoc–F–F and Aβ aggregates. Aβ1-42 filaments were found to perform peroxidase-like activity to enhance oxidative stress, which might also be ascribed to the interaction mode of His and F-F.
Stable peptide-assembled nanozyme mimicking dual antifungal actions
Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical β-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions. Natural antimicrobial peptides and enzymes are good candidates for application but suffer from low stability. Here, the authors report on biomimetic self-assembling peptides which mimic both antimicrobial peptide and enzyme functionality, demonstrating application against fungal infection.
Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection
Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor ( IRF4 ) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro . In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis.
Optimizing Photoelectrochemical UV Imaging Photodetection: Construction of Anatase/Rutile Heterophase Homojunctions and Oxygen Vacancies Engineering in MOF-Derived TiO2
Self-powered photoelectrochemical (PEC) ultraviolet photodetectors (UVPDs) are promising for next-generation energy-saving and highly integrated optoelectronic systems. Constructing a heterojunction is an effective strategy to increase the photodetection performance of PEC UVPDs because it can promote the separation and transfer of photogenerated carriers. However, both crystal defects and lattice mismatch lead to deteriorated device performance. Here, we introduce a structural regulation strategy to prepare TiO2 anatase-rutile heterophase homojunctions (A-R HHs) with oxygen vacancies (OVs) photoanodes through an in situ topological transformation of titanium metal–organic framework (Ti-MOF) by pyrolysis treatment. The cooperative interaction between A-R HHs and OVs suppresses carrier recombination and accelerates carrier transport, thereby significantly enhancing the photodetection performance of PEC UVPDs. The obtained device realizes a high on/off ratio of 10,752, a remarkable responsivity of 24.15 mA W−1, an impressive detectivity of 3.28 × 1011 Jones, and excellent cycling stability. More importantly, under 365 nm light illumination, a high-resolution image of “HUST” (the abbreviation of Harbin University of Science and Technology) was obtained perfectly, confirming the excellent optical imaging capability of the device. This research not only presents an advanced methodology for constructing TiO2-based PEC UVPDs, but also provides strategic guidance for enhancing their performance and practical applications.
Senescence-driven molecular subtyping in pancreatic cancer: a multi-omics framework for precision medicine
Background Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with a five-year survival rate below 15%, largely due to tumor heterogeneity and limited therapeutic options. While senescence-related genes (SRGs) are implicated in cancer progression, their pancreas-specific roles in PDAC subtyping and treatment remain unexplored. Methods We integrated multi-omics data (RNA-seq, ATAC-seq, and whole-genome sequencing) from 402 pancreas-specific SRGs to classify PDAC subtypes through unsupervised clustering. Independent validation cohorts (TCGA-PAAD, n  = 183; patient-derived organoids, n  = 40) and drug sensitivity screens were used to define subtype-specific therapeutic vulnerabilities. A machine learning-based random forest model identified key SRG biomarkers for clinical stratification. Results Three distinct PDAC subtypes were identified: Cluster 1, characterized by extensive immune infiltration; Cluster 2, mixed features with moderate prognosis; and Cluster 3, defined by significant metabolic reprogramming. Drug screens revealed Cluster 3 as uniquely sensitive to Metformin and Trametinib, suggesting combinatory therapy potential. A 20-gene random forest classifier achieved high accuracy in subtype prediction (AUC = 0.96). Conclusion This study establishes the first pancreas-specific SRG-driven classification of PDAC, resolving prior inconsistencies in Metformin trial outcomes. Our framework enables risk stratification and subtype-guided therapy, with immediate clinical implications: Metabolic-targeting agents (Metformin) may benefit the high-risk Cluster 3, while immunotherapy could be prioritized for Cluster 1.
Analytical Study on Gas-Oil Separation of a Heat Pump System under Lunar Gravity
A heat pump in the aerospace industry can significantly reduce the area of radiator by elevating the rejection temperature. Especially for a Lunar base, the heat pump can improve the heat rejection capability of the thermal control system to adapt the high-temperature environment. However, gravity on the Lunar (about 1/6 g) may have an adverse impact on a gas-oil separator of the heat pump, and solving this problem is the key for a heat pump used on Lunar base. At present, the gas-oil separator all based on gravity separation theories, the researches under low or micro gravity were blank. In this work, a gravity separation model based on a single-particle principle was built, and the effects of the vapor velocity, the oil droplet initial velocity, and the oil droplet diameter were investigated under normal gravity. Then the variations of the separation efficiency under Lunar gravity were discussed and the numerical calculation results showed that the separation efficiency was reduced when the vapor velocity or droplet initial velocity increased in a certain height of the separator whenever under normal or Lunar gravity. Particularly, the separation efficiency under Lunar gravity was reduced from 99% to 55% than it under normal gravity.
Engineering zinc oxide hybrid selenium nanoparticles for synergetic anti-tuberculosis treatment by combining Mycobacterium tuberculosis killings and host cell immunological inhibition
As a deadly disease induced by Mycobacterium tuberculosis (Mtb), tuberculosis remains one of the top killers among infectious diseases. The low intracellular Mtb killing efficiency of current antibiotics introduced the long duration anti-TB therapy in clinic with strong side effects and increased drug-resistant mutants. Therefore, the exploration of novel anti-TB agents with potent anti-TB efficiency becomes one of the most urgent issues for TB therapies. Here, we firstly introduced a novel method for the preparation of zinc oxide-selenium nanoparticles (ZnO-Se NPs) by the hybridization of zinc oxide and selenium to combine the anti-TB activities of zinc oxide nanoparticles and selenium nanoparticles. We characterized the ZnO-Se NPs by dynamic laser light scattering and transmission electron microscopy, and then tested the inhibition effects of ZnO-Se NPs on extracellular Mtb by colony-forming units (CFU) counting, bacterial ATP analysis, bacterial membrane potential analysis and scanning electron microscopy imaging. We also analyzed the effects of ZnO-Se NPs on the ROS production, mitochondrial membrane potential, apoptosis, autophagy, polarization and PI3K/Akt/mTOR signaling pathway of Mtb infected THP-1 macrophages. At last, we also tested the effects of ZnO-Se NPs on intracellular Mtb in THP-1 cells by colony-forming units (CFU) counting. The obtained spherical core-shell ZnO-Se NPs with average diameters of 90 nm showed strong killing effects against extracellular Mtb, including BCG and the virulent H37Rv, by disrupting the ATP production, increasing the intracellular ROS level and destroying the membrane structures. More importantly, ZnO-Se NPs could also inhibit intracellular Mtb growth by promoting M1 polarization to increase the production of antiseptic nitric oxide and also promote apoptosis and autophagy of Mtb infected macrophages by increasing the intracellular ROS, disrupting mitochondria membrane potential and inhibiting PI3K/Akt/mTOR signaling pathway. These ZnO-Se NPs with synergetic anti-TB efficiency by combining the Mtb killing effects and host cell immunological inhibition effects were expected to serve as novel anti-TB agents for the development of more effective anti-TB strategy.
Photoelectrochemical-Type Photodetectors Based on Ball Milling InSe for Underwater Optoelectronic Devices
In this paper, InSe nanosheets were synthesized by a ball milling method, and photoelectrochemical-type photodetectors (PEC PDs) based on the ball milling InSe (M-InSe) were fabricated using simulated seawater as the electrolyte. M-InSe nanosheets show good absorption in the visible region of 450–600 nm. The M-InSe PEC PDs display a good self-powered photoresponse under 525 nm irradiation, including a high responsivity of 0.8 mA/W, fast response time of 28/300 ms, and good stability. Furthermore, the InSe PEC PDs successfully demonstrated prototype application in wireless underwater optical communication and optical imaging. These results demonstrate that M-InSe holds good application prospects in underwater optoelectronic devices.
A Novel “Three‐in‐One” Copper‐Based Metal‐Organic Framework Nanozyme Eradicates Colorectal Cancer and Overcomes Chemoresistance for Tumor Therapy
Despite considerable advancements in the treatment of colorectal cancer (CRC), the overall survival rate for patients with advanced CRC remains below 50%, primarily due to challenges posed by drug resistance and metastasis. Here, a novel “Three‐in‐One” Cu‐based metal‐organic framework nanozyme with peroxidase‐like (POD‐like) activity has been successfully developed, aiming to promote CRC cell death by dual targeting of oxidative stress and copper ion homeostasis, which could promote CRC cell death via apoptosis and cuproptosis, and facilitate hypoxia‐inducible factor 1α (HIF‐1α) degradation, leading to the reversal of chemoresistance in tumor therapy. These nanozymes, composed of copper and 2‐propylimidazole (Cu‐PrIm), feature a distorted Cu‐N4 catalytic active center that mimics natural enzyme structures consisting of copper and histidine residues, endowing them with enzyme‐like activities. The antitumor efficacy of Cu‐PrIm nanozymes is validated in various in vivo models of CRC. Especially Cu‐PrIm nanozymes exhibit excellent biocompatibility, biodegradability, and a tolerable toxicity profile in mouse models, making them a strong candidate for clinical translation. Taken together, the study introduces a novel therapeutic paradigm in CRC treatment by targeting these vulnerabilities and leveraging the potential using “Three‐in‐One” Cu‐PrIm nanozymes to address multiple pathways simultaneously. In this study, a novel “Three‐in‐One” Cu‐PrIm nanozymes with peroxidase (POD)‐like activity has been developed, which could promote colorectal cancer (CRC) cell death via apoptosis and cuproptosis, and facilitate hypoxia‐inducible factor 1α (HIF‐1α) degradation leading to reversal of chemoresistance. This represents a promising treatment paradigm that leverages the potential of “Three‐in‐One” Cu‐PrIm nanozymes to simultaneously address multiple tumor‐specific vulnerabilities.
High-Performance Vis–NIR Photodetectors Based on Two-Dimensional Bi2Te3 Thin Film and Applications
Two-dimensional materials have excellent optoelectronic properties and have great significance in the field of photodetectors. We have prepared a thin film photodetector based on bismuth telluride (Bi2Te3) topological insulator using dual-temperature-zone vapor deposition technology. Due to the high-quality lattice structure of Bi2Te3 and the uniform and dense surface morphology of the Bi2Te3 thin film, the device exhibits excellent photoelectric response and Vis–NIR spectral range. Under 405 nm illumination, the responsivity is 5.6 mA/W, the specific detectivity is 1.22 × 107 Jones, and the response time is 262/328 ms. We designed a photodetector single-point scanning imaging system and successfully achieved high-resolution imaging at a wavelength of 532 nm. This work provides guidance for the application of two-dimensional materials, especially Bi2Te3, in the fields of photodetectors and imaging.