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Cell Death & Disease · 2025 ·Vol. 16 ·期 1 ·1-11 · IF 9.6

Ubiquitination of gasdermin D N-terminal domain directs its membrane translocation and pore formation during pyroptosis

Chu Xiufeng,Zhang Ting,Bukhari Ihtisham,Hu Mei,Xu Jixuan,Xing Yamin,Liang Xinfeng,Zhang Zisen,Zheng Pengyuan

Gasdermin D (GSDMD) is a critical pyroptosis mediator, consisting of one N-terminal pore-forming domain and one C-terminal auto-inhibitory domain. The free N-terminal domain (GD-NT), which is released through caspase-1/11 cleavage, exhibits distinct features from the full-length GSDMD (GD-FL), including oligomerization, membrane translocation, and pore-formation. However, the underlying mechanisms are not well elucidated. Here, we found that GD-NT, but not GD-FL, was massively ubiquitinated in cells. The K63-linked polyubiquitination of GD-NT at Lys236/237 (human/mouse), catalyzed by TRAF1, directly prompted its membrane translocation and pore-formation during pyroptosis. Inhibition of GD-NT ubiquitination via site-directed mutations or the UBA1 inhibitor PYR-41 suppressed cell death in several pyroptosis cell models. Additionally, applying PYR-41 in septic mice efficiently suppressed the release of IL-18 and TNFα. Thus, GD-NT ubiquitination is a key regulatory mechanism controlling its membrane localization and activation, which may provide a novel target for modulating immune activity in pyroptosis-related diseases.

研究领域: 免疫学 · 细胞生物学
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DESALINATION · 2024 · IF 8.3

Synthesizing high performance robust PSf loose nanofiltration membranes through nanobubble-assisted pore-forming

Zongrui Song,Yujie Wu,Junjie Lv,Yanhong Ji,Mohammad Younas,Benqiao He

Loose nanofiltration (LNF) membranes have extensive applications in precision separation processes, however, synthesizing highly permselective LNF membranes is still a considerable obstacle. Nanobubble-assisted pore-forming method was adapted to prepare a highly perm-selective LNF membrane for the first time in this work, using polysulfone (PSf) as the membrane-forming material, azodicarbonamide (AC) as the reactive pore-forming agents, and NaOH solution as the coagulation and immersion baths. By leveraging nano-bubbles produced through the reaction between AC and NaOH without adding other pore-forming agents, the membrane-forming process of PSf was regulated. It was found that the PSf LNF membranes prepared in NaOH-solution coagulation and immersion baths exhibited significantly enhanced permeation performance without compromising the rejection. These results suggested that the coagulation and immersion post-treatment processes under NaOH solution had a great effect upon the structure and the property of the membranes. The LNF membrane prepared from 20 wt% PSf casting solution with 8 wt% AC achieved a permeation flux of 188.7 L m −2  h −1 , and a Congo red (CR, Mw =696 Da) rejection of over 99 %, while a rejection of NaCl below 7 %, showing a good separation for the CR/NaCl mixed solution. Additionally, the membrane exhibited favorable mechanical properties, with a tensile strength as high as 6.5 MPa and a fracture elongation reaching as much as 32.3 %. This work provided a novel approach for producing high-performance LNF membranes in treating dye wastewater.

CAS / MDL: 123-77-3
研究领域: 材料科学 · 环境工程
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Journal of Environmental Chemical Engineering · 2023 · IF 7.7

Porous ceramic membranes from coal fly ash with addition of various pore-forming agents for oil-in-water emulsion separation

Jiguang Huang,Haiping Chen,Run Qi,Jihao Yang,Zhaohao Li,Heng Zhang

Coal fly ash (CFA) is a substitute material for ceramic membrane which can effectively reduce the preparation cost. However, CFA based ceramic membranes usually show insufficient mechanical strength for application. Revealing pore-forming mechanisms of different pore-forming agents in membranes preparation is of great significance to improve mechanical strength without harming permeability. In this work, three different pore-forming agents, carbon powder, dolomite and dextrin, were adopted to prepare CFA membranes. Characters including porosity, pore size distribution and permeability of membranes were comparatively analyzed. Effects of pore-forming agents on membranes were discussed. The membrane with dextrin at 1200 °C sintering showed the best comprehensive properties. Its porosity, flexural strength and Darcian permeability coefficient were 39.46 %, 35.56 MPa and 3.84 × 10 −14 m 2 , respectively. Application in oil-in-water emulsion separation indicated higher than 94 % oil rejection. This research provides experimental bases for improving performances of low-cost CFA membranes, thereby conducive to engineering applications.

研究领域: 材料科学 · 环境工程
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MOLECULAR BIOLOGY · 2022 ·Vol. 56 ·期 6 ·1012-1019 · IF 1.54

Mechanism of Leakage in Phosphatidylserine-Containing Membranes by Melittin

Wang R.,Shi M.-Y.,Ma B.-B.,Sheng J.

Abstract Phosphatidylserine (PS) is an important apoptotic-cell surface signal that exists in bacterial and cancer cells. The mechanism by which melittin interacts with the PS membrane remains unclear. Here, we revealed this mechanism by using a dual-channel fluorescence microscope to observe the concentration-dependent process of pore formation in giant unilamellar vesicles (GUVs) that were exposed to melittin solution. We found that unsaturated PS membranes differed significantly from saturated PS membranes in different phases. This study provides a reference for research and development of anticancer drugs.

研究领域: 生物化学 · 细胞生物学 · 药理学
✓ 已验证 DOI 高影响因子
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2017 · IF 3.756

Engineering hot-melt extruded solid dispersion for controlled release of hydrophilic drugs

Shuli Zhang,Xuan Meng,Zheng Wang,Aiping Fan,Guocheng Wang,Yanjun Zhao,Yu Tang

It is often challenging to precisely manipulate the release behavior of hydrophilic drugs that is believed to be crucial for a satisfactory therapeutic outcome. The aim of this work was to regulate the dissolution of hydrophilic drug from hot-melt extruded solid dispersion via rational screening of the pore-forming agents. Venlafaxine hydrochloride and Compritol® 888 ATO was selected as the model drug and carrier excipient, respectively. Hydrophilic polyethylene glycol (PEG 6000) and polyvinylpyrolidone (PVP K30) were chosen as the transient pore-forming agents. The X-ray diffraction and thermal analysis showed that both drug and carrier existed in the crystalline form. Both types of polymers could generate pores upon dissolution test and the drug release rate was proportionally correlated to the pore-forming agent content. The mathematical modelling showed that the Ritger-Peppas model gave the best fit to the release curves, which demonstrates a diffusion-dominant release mechanism. The scanning electron microscopy and mercury intrusion porosimetry analysis proved that PVP K30 could generate large pores with low porosity, but PEG 6000 produced smaller pores with relatively high porosity. The in vivo pharmacokinetics study in rat revealed that solid dispersions containing either PEG 6000 or PVP K30 (both at 2.5%, w/w) exhibited an elevated bioavailability compared to the commercial product, Effexor® XR. The current work implied that rational screening of transient pore-forming polymer in solid dispersion could be a robust approach for controlling hydrophilic drug release.

研究领域: 药剂学 · 药物释放系统
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Nano Materials · 2024 · IF 5.3

Nitrogen-Doped Porous Carbon with Staged Nanopore Formation for Capacitors

Wenwu Fu,Jun Zheng,Zhiguang Lin,Kai Zhang,Ming Zhang,Xiaokang Cai,Chao Liu,Zhongrong Shen

The design of nanopore structures in porous carbon materials plays a crucial role in achieving high capacitance and rate performance in capacitors. This study introduced a method for the synthesis of high specific surface area nitrogen-doped porous carbon (HNPC) materials by staged nanopore formation. The method involved designing a composite reaction precursor using oxalic acid (H2C2O4), p-phenylenediamine (PDA), and potassium hydroxide (KOH), as well as creating micropores during the pyrolysis process and constructing micropores and mesopores during potassium carbonate (K2CO3) activation stage. HNPC materials synthesized in this study demonstrated a high specific capacitance and exceptional rate performance in aqueous electrolytes across a broad pH spectrum (acidic, neutral, and alkaline) as well as in organic electrolytes. Specific capacitances of 263.3 F g–1, 366.1 F g–1, and 304.4 F g–1 (at a scanning rate of 2 mV s–1) were attained in 1 M lithium sulfate (Li2SO4), 6 M KOH, and 1 M sulfuric acid (H2SO4) electrolytes, respectively, indicating high capacitance values. By configuring them as symmetric supercapacitors, they performed high energy densities of 8.2 Wh kg–1 and 22.9 Wh kg–1 in aqueous and organic electrolytes, respectively, while maintaining capacity retention rates of 81.2% and 83.9% after 10 000 and 5000 cycles.

研究领域: 材料科学 · 电化学
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BIOMEDICINE & PHARMACOTHERAPY · 2024 · IF 6.9

The interaction of plant flavones with amphotericin B: Consequences for its pore-forming ability

Anna I. Malykhina,Svetlana S. Efimova,Vladimir S. Andriianov,Olga S. Ostroumova

The growth of antibiotic resistance to antifungal drugs contributes to the search for new ways to enhance their effectiveness and reduce toxicity. The undeniable advantage of polyene macrolide antibiotic amphotericin B (AmB) which ensures low pathogen resistance is its mechanism of action related to the formation of transmembrane pores in target lipid membranes. Here, we investigated the effects of plant flavones, chrysin, wogonin, baicalein, apigenin, scutellarein, luteolin, morin and fisetin on the pore-forming activity of AmB in the sterol-enriched membranes by electrophysiological assays. Сhrysin, wogonin, baicalein, apigenin, scutellarein, and luteolin were shown to decrease the AmB pore-forming activity in the bilayers composed of palmitoyloleylphosphocholine independently of their sterol composition. Morin and fisetin led to the increase and decrease in the AmB pore-forming activity in the ergosterol- and cholesterol-containing bilayers respectively. Differential scanning microcalorimetry of the gel-to-liquid crystalline phase transition of membrane forming lipids, molecular dynamics simulations, and absorbance spectroscopy revealed the possibility of direct interactions between AmB and some flavones in the water and/or in the lipid bilayer. The influence of these interactions on the antibiotic partitioning between aqueous solution and membrane and/or its transition between different states in the bilayer was discussed.

研究领域: 药理学 · 生物物理学 · 微生物学
✓ 已验证 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2022 · IF 10.723

Construction of porous chitosan macrospheres via dual pore-forming strategy as host for alkaline protease immobilization with high activity and stability

Ying Tang,Penghui Wang,Hui Zeng,Zebao Rui

Fabrication of highly-efficient enzymatic supports having excellent affinity to enzymes and superior mass transfer properties is highly desirable for enzymatic bio-catalysis. Herein, newly engineered chitosan macrospheres having interconnected and interlaced network pores are prepared via dual pore-forming strategy and applied as novel host for the effective immobilization of alkaline protease. The synergetic effect of SiO 2 templates and gas-induced pore-forming agents play an important role in inhibiting the over-crosslinking of chitosan chains and promoting the elevation of interior porosity. Benefited from the highly exposed surface and abundant available binding sites, the as-developed porous support P 2 CSM achieves a maximum loading capacity of 43.8 ± 0.8 mg/g and ultra-high activity recovery of 92.4 % for alkaline protease. P 2 CSM is competent to effectively stabilize the structural conformation of alkaline protease from inactivation through the flexible covalent interaction. Considering these attributes, Protease@P 2 CSM demonstrates remarkably better structural stability, reusability and SDS-resistance than free alkaline protease, as well as excellent proteolytic ability, and the residual activity of Protease@P 2 CSM is evaluated as high as 70.3 % after 7 consecutive reuses. This work provides a promising avenue to construct highly-active enzyme-composites for widespread utilization in various practical applications.

CAS / MDL: 64-19-7 151-21-3
研究领域: 生物化学 · 酶工程 · 材料科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2021 · IF 7.46

One-step assay of pore-forming biotoxins based on biomimetic perovskite nanocrystals

Menglu Li,Tian Tian,Yujing Zeng,Sha Zhu,Chao Li,Yongmei Yin,Genxi Li

As one of the emerging inorganic materials, perovskite nanocrystals (NCs) have inspired the development of various optoelectronic applications in recent years; however the effective utilization in biomedical fields is still limited. Herein, we report a quantitative measurement of broad-spectrum pore-forming toxins in complex media based on biomimetic CsPbBr 3 NCs. Specifically, by coating CsPbBr 3 NCs with phospholipid (CsPbBr 3 NCs@PL), the outer micelle membrane can not only serve as a shell to protect the stability of CsPbBr 3 NCs, but also interact with broad-spectrum biotoxins. Meanwhile, toxin-triggered transmembrane pore formation can cause water permeation, which breaks down the structure of CsPbBr 3 NCs@PL, generating striking fluorescent and electrochemical dual responses. Therefore, direct quantitative measurements of biotoxins are realized via dual-readout signals with inverse change trend, resulting in a detection limit of 50 nM. Our report represents the first example of CsPbBr 3 NCs for the develpment of biosensors. Meanwhile, such a label-free, cost-effective and widely applicable biomimetic CsPbBr 3 NCs@PL may present a valuable tool for the detection of biotoxin infections, and overcomes the limitations of perovskite materials in biosensing.

研究领域: 生物医学工程 · 材料科学 · 毒理学
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MACROMOLECULES · 2024 · IF 5.1

Design of Precursor Polymers Assists the Processing of Poly(ether ether ketone) Membranes in Solvents

Chi Zhang,Jiang-An You,Xue Wang,Rui Hou,Xiaofeng Li,Yuxuan Sun,Guorui Qin,Shenghai Li,Suobo Zhang

By examining the structural patterns of the imine monomers engaged in polycondensation, a series of poly(ether ether ketone) precursor polymers (PEEKi-N-acyl) modified with N-acyl Imine groups were designed in this work. Contrary to poly(ether ether ketone) (PEEK), these precursor polymers have superior solubility, enabling their production in solution and processing of membrane components. The membrane components’ substance could undergo an imine hydrolysis reaction in an acidic environment, turning them back into PEEK and giving them solvent resistance. In addition, the homogeneous polymer membranes of this series exhibit spontaneous pore formation under the action of ethanol, which was caused by solvent-induced internal stress relaxation. By utilizing the properties of this type of polymer, precursor polymers can be processed into PEEK sponge-like porous membranes, expanding the processing morphology and application range of PEEK.

研究领域: 材料科学 · 高分子化学
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Polymers · 2020 ·Vol. 12 ·期 9 ·2066 · IF 3.426

Construction and Transition Metal Oxide Loading of Hierarchically Porous Carbon Aerogels

Jintian Wang,Xinyang Ruan,Jiahao Qiu,Hao Liang,Xingzhong Guo,Hui Yang

Hierarchically porous carbon aerogels (CAs) were prepared by organic condensation gelation method combined with atmospheric drying and pore-formation technology, followed by a carbonization process. With as-prepared CAs as substrate, the transition metal oxide nanoparticles loaded CAs composites (MnO2/Mn2O3@CA and Ni/NiO@CA) were achieved by means of liquid etching method combined with heat treatment, respectively. The catalyst, pore-forming agent and etching have important roles on the apparent density and pore structure of CAs. The hydrochloric acid (catalyst) significantly accelerates the gelation process and influences the size and distribution of macropores, whereas the addition of PEG2000 (pore-forming agent) and the etching of liquid solution leads to the formation of mesopore structure in CAs. Appropriate amounts of hydrochloric acid and PEG2000 allow the formation of hierarchically porous CAs with a BET surface area of 482.9 m2·g−1and a macropore size of 11.3 μm. After etching and loading, the framework of CAs is etched to become a mesoporous structure, and the transition metal oxide nanoparticles can be uniformly loaded in CAs. These resultant composites have promising application in super capacitor, electrocatalysis, batteries and other fields.Keywords:carbon aerogel;hierarchically porous material;atmospheric drying;pore formation;transition metal oxide

研究领域: 材料科学 · 化学工程
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Small · 2022 ·Vol. 18 ·期 25 ·2106357 · IF 15.153

Micropore-Forming Gelatin Methacryloyl (GelMA) Bioink Toolbox 2.0: Designable Tunability and Adaptability for 3D Bioprinting Applications

Sili Yi,Qiong Liu,Zeyu Luo,Jacqueline Jialu He,Hui-Lin Ma,Wanlu Li,Di Wang,Cuiping Zhou,Carlos Ezio Garciamendez,Linxi Hou,Jin Zhang,Yu Shrike Zhang

It is well-known that tissue engineering scaffolds that feature highly interconnected and size-adjustable micropores are oftentimes desired to promote cellular viability, motility, and functions. Unfortunately, the ability of precise control over the microporous structures within bioinks in a cytocompatible manner for applications in 3D bioprinting is generally lacking, until a method of micropore-forming bioink based on gelatin methacryloyl (GelMA) was reported recently. This bioink took advantage of the unique aqueous two-phase emulsion (ATPE) system, where poly(ethylene oxide) (PEO) droplets are utilized as the porogen. Considering the limitations associated with this very initial demonstration, this article has furthered the understanding of the micropore-forming GelMA bioinks by conducting a systematic investigation into the additional GelMA types (porcine and fish, different methacryloyl-modification degrees) and porogen types (PEO, poly(vinyl alcohol), and dextran), as well as the effects of the porogen concentrations and molecular weights on the properties of the GelMA-based ATPE bioink system. This article exemplifies not only the significantly wider range of micropore sizes achievable and better emulsion stability, but also the improved suitability for both extrusion and digital light processing bioprinting with favorable cellular responses.

CAS / MDL: 9048-71-9 9004-54-0
研究领域: 生物材料 · 组织工程 · 生物打印 · 材料科学
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