Advanced Science
·
2025
·Vol. 12
·期 30
·e01908
·
IF 14.1
Ningqiang Shi,Xiaofei Xiao,Mingyu Zhang,Zhijun Li,Chuncheng Ban,Jinchang Meng,Nannan Shi,Mingyang Wu,Zebo Zheng,Ling Li
Boron nitride nanotubes (BNNTs) are an emerging mid-infrared optical material that exhibits significant potential in nanoscale resonators, lasers, detectors, and sensors due to the strong light-matter interactions induced by phonon polaritons (PhPs). However, the large-scale controllable synthesis and device applications of BNNTs still face huge challenges. In this study, a substrate-pretreated and boron source dual-catalyst infiltrated growth method, and a damage-free purification method toward the high-density and aligned BNNT (ABNNT) thin films is developed. The polarization sensitivity and linear dichroism characteristics of BNNTs with a maximum anisotropy ratio of 4.53 in the mid-infrared and near-infrared regions are comprehensively verified. The nanotube-alignment induced permittivity anisotropy outside RB and the near-isotropic PhP absorption within RB enable a wavelength-selective polarizer and absorber throughout a broad infrared range. Uniquely, the BNNT polarizer exhibits excellent stability of polarization dichroism under severe bending conditions, demonstrating great potential in flexible and wearable optical devices. This work can initiate the utilization of high-density BNNT thin films in quantum information processing and high-resolution infrared imaging applications.
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ACS Applied Bio Materials
·
2026
·
IF 4.7
Jingjie Zhang,Yanmin Chen,Zhenyi Lin,Changhua Xu,Lijuan Zhu,Chuan Zhang
Androgenetic alopecia (AGA), a prevalent form of hair loss primarily affecting younger individuals, remains a significant therapeutic challenge due to the lack of effective treatments. The pathogenesis of AGA is driven by the interaction between androgen receptors (AR) and androgens, as well as by dysregulation of the follicular ecological niche resulting from excessive reactive oxygen species (ROS) and insufficient vascularization in the perifollicular microenvironment. Given the multifactorial nature of AGA, a multi-target therapeutic strategy, rather than a single-target approach, has emerged as a promising method to enhance treatment efficacy. In this study, we developed nanoliposomes (NLPs) formulation by self-assembling AR-PROTAC (ARV110) and NFKBIZ siRNA (siNFKBIZ) into nanoparticles, followed by surface modification with liposomes. This design simultaneously targets AR degradation and alleviates oxidative stress, thereby improving the follicular microenvironment and promoting hair regrowth. The NLPs formulation effectively addresses the challenge of delivering payloads to keratinocytes (HaCaT), facilitates efficient skin penetration, scavenges excess ROS, and inhibits the inflammatory response in hair follicles. Additionally, NLPs downregulate AR protein expression to modulate hair growth-associated signaling pathways, achieving a multimodal synergistic therapeutic effect for AGA. Our design offers an effective multi-target strategy for AGA, resulting in enhanced therapeutic effects for hair loss treatment.
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Autophagy
·
2026
·
IF 18.6
Zhengran Li,Huiqing Zhao,Danjie Zhang,Jing Wei,Xiyue Tao Liu,Ruiyan Kong,Xuejing Ren,Hang Zhao,Xiaomin Fang,Jingyan Fu,Zhouhua Li
The self-renewal and differentiation of stem cells are tightly controlled to maintain tissue homeostasis. Failure in stem cell maintenance results in stem cell depletion and precocious aging. However, how stem cells are maintained still remains not fully understood. Here, through a large-scale RNAi screen for maintenance and proliferation of adult Drosophila intestinal stem cells (ISCs), we identify several subunits of V-ATPase including Vha68-2/ATP6V1A, required for ISC proliferation, differentiation and tissue regeneration. Inactivation of Vha68-2 results in accumulation of plasma membrane (PM)-derived structures in autophagosomes and lysosomes through Atg16 and Rab5. Furthermore, Vha68-2-defective ISCs undergo direct differentiation due to ectopic Notch activation. Mechanistically, Vha68-2 facilitates Notch receptor internalization and subsequent degradation in autolysosomes to quench ectopic Notch activation, thereby maintaining ISC fate. Truncated Notch product devoid of its extracellular domain is accumulated in autolysosomes upon Vha68-2 deficiency. The Notch products accumulated in autolysosomes still require further cleavage to drive ISC differentiation. The functions of Vha68-2 in macroautophagy/autophagy and ISC maintenance are evolutionarily conserved. Our results provide new insights into the underlying mechanism of how autophagy is involved in stem cell maintenance under physiological conditions.Abbreviations: aph-1: anterior pharynx defective 1; ATP6V1A: ATPase H+ transporting V1 subunit A; CASM: conjugation of ATG8s to single membranes; EB: enteroblast; EC: absorptive enterocyte; ER: endoplasmic reticulum; ISC: intestinal stem cell; kuz: kuzbanian; LTDR: LysoTracker Deep Red; LTR: LysoTracker Red; MARCM: mosaic analysis with a repressible cell marker; NECD: Notch extracellular domain; NICD: Notch intracellular domain; PM: plasma membrane; PAS: phagophore assembly site; SNARE: soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TEM: transmission electron microscopy; TM: tunicamycin.
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ENZYME AND MICROBIAL TECHNOLOGY
·
2026
·
IF 3.9
Zhicen Liu,Caiyun Wang,Junjian Wu,Ming Chen,Yue Zhang
This study developed a highly efficient immobilized phospholipase D (PLD) system using a magnetic chitosan-based carrier with the natural crosslinking agent genipin (Fe 3 O 4 @CS-Gnp-PLD). Systematic characterization confirmed successful PLD immobilization, with chitosan's abundant amino and hydroxyl groups providing stable binding sites that enhanced both enzyme loading and stability. In the sodium deoxycholate-based mixed micelle system, the Fe 3 O 4 @CS-Gnp-PLD achieved an 8.05-fold higher phosphatidylserine (PS) conversion rate than free PLD, owing to enhanced substrate solubility and improved enzyme accessibility. The immobilized enzyme demonstrated exceptional operational stability, retaining 80% activity after 6 reuse cycles and 72% activity after 12 days of storage at 4 °C. This integrated platform, combining chitosan-based enzyme immobilization with a mixed micelle system, offers an efficient, stable, and recyclable approach for sustainable PS biomanufacturing.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yan Gong,Qiurong Sun,Gao He,Jiarui Wang,Dequan Xiao,Lile Dong
Insufficient intracellular Fe 2+ ions availability and hypoxic tumor microenvironment significantly hamper the efficiency of ferroptosis. There is an urgent need for breakthrough research in the development and delivery of ferroptosis inducers and the reprogramming of the immune microenvironment. Herein, Ti 3 FeBi 5 O 15 (TFBO) piezoelectric nanosheets were engineered to amplify ferroptosis and trigger immunogenic cell death via ultrasound (US) activation. TFBO nanosheets feature a narrow bandgap (2.03 eV) and high piezoelectric coefficient (d 33 = 22.1 pm V −1 ), enabling efficient electron-hole separation under US irradiation. Notably, TFBO nanosheets generate an internal piezoelectric field that promotes Fe 3+ to Fe 2+ conversion and ·OH generation from H 2 O under US irradiation, while simultaneously depleting intracellular GSH under US irradiation, leading to lipid peroxidation and GPX4 suppression. Importantly, TFBO nanosheets activate immunogenic cell death (ICD), stimulating antitumor immune responses. Therefore, combined with its high biocompatibility, effective tumor inhibiting performance, and minimal systemic toxicity, TFBO represents a mechanistically distinct and translationally promising ferroptosis amplifier for tumor therapy.
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Acta Biomaterialia
·
2025
·
IF 9.6
Kaijun Li,Qinsheng Hu,Ling Wang,Chengcheng Wu,Li Yang,Gongyan Liu,Yunbing Wang
Bioprosthetic heart valves (BHVs) are frequently utilized in surgeries for heart valve replacement to address valvular heart disease (VHD). Despite their widespread use, BHVs still face challenges in clinical applications, such as thrombosis, calcification, immune responses, poor re-endothelialization, infection, component degradation, and mechanical failure, which are largely due to the heterogeneous cross-linking effects. To address these issues, we propose a synergistic engineering strategy based on sequential zwitterionic surface modification and zirconium cross-linking to improve the biocompatibility and durability of BHVs. After surface modification via ring-opening reactions of zwitterionic epoxy copolymers (PGSB) on collagen fibers of decellularized porcine pericardium (D-PP), the zwitterionic PGSB significantly promoted the uniform transfer of zirconium ions (Zr 4+ ) and further coordinated with Zr 4+ to achieve homogeneous cross-linking between collagen fibers. Compared to conventional glutaraldehyde (GA)-cross-linked PP, PGSB/Zr-PP showed enhanced anti-thrombotic performance, attenuated immune rejection, accelerated endothelialization, and over 95% reduction in calcification after 90 days of subcutaneous implantation, collectively indicating improved biocompatibility. Furthermore, this homogeneously cross-linked PGSB/Zr-PP exhibited undetectable component degradation and simultaneous improvements in both strength and toughness, all of which are essential for improving the durability of BHVs. Intriguingly, the zwitterionic sulfobetaine groups could be converted into bactericidal quaternary ammonium groups upon coordination with Zr 4+ , resulting in strong antibacterial and anti-biofilm activities beneficial for preventing life-threatening prosthetic valve endocarditis. More importantly, PGSB/Zr-PP met the ISO 5840-3 standards required for BHV applications in terms of hydrodynamic performance and 200-million-cycle durability. These results demonstrate that PGSB/Zr-PP would be a promising alternative to GA-cross-linked BHVs. Statement of Significance Mainstream glutaraldehyde-cross-linked BHV face persistent clinical challenges, including thrombosis, calcification, immune response, poor re-endothelialization, infection, component degradation, and mechanical failure. Although various non-glutaraldehyde cross-linkers have been investigated, few strategies effectively address these challenges due to the heterogeneous nature of cross-linking. Herein, we present a synergistic engineering strategy based on sequential zwitterionic surface modification and zirconium cross-linking. This strategy produces homogeneously cross-linked BHVs with comprehensive improvements in anti-thrombogenicity, immune compatibility, endothelialization, resistance to calcification and infection, enzymatic stability, and mechanical strength. Notably, the aortic BHV fabricated via this method met the ISO 5840-3 standards for hydrodynamic performance and durability, demonstrating its long-term clinical potential.
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International Journal of Nanomedicine
·
2026
·
IF 8.7
Jieying Zhou,Wei Luo,Lingxin Zeng,Shihao Xu,Ruohan Wu,Jiaqi Lu,Ying Li,Wei Xiong
Purpose While bubble-carrier systems hold great promise for enhancing the oral bioavailability of poorly water-soluble drugs, a deeper understanding of their underlying absorption mechanisms is still required. This study aimed to address this gap by developing a bubble-driven delivery system (BDDS) using the poorly water-soluble andrographolide (AG) as a model drug, and systematically evaluating its solubilization capacity and intestinal permeability.Methods The BDDS was optimized through the screening of effervescent formulations (citric acid: Na2CO3 = 6:5) and bile salts (sodium deoxycholate, SDC). Its performance was comprehensively assessed via in vitro dissolution tests, an everted intestinal sac assay, Caco-2 cell monolayer experiments, pharmacokinetic studies, and yeast-induced fever rat models.Results The BDDS achieved 75.0%–88.7% dissolution in gastrointestinal pH media, which was markedly superior to that of commercial dripping pills (DP; 30.5–50.2%). Its apparent permeability coefficient was 7.7-fold and 3.6-fold higher than that of free AG and DP, respectively. Transport studies indicated that SDC enhanced AG permeability primarily via the apical sodium-dependent bile acid transporter (ASBT)-mediated pathway, a mechanism further confirmed by inhibition with linerixibat. The relative oral bioavailability of BDDS versus DP reached 257.1%. BDDS demonstrated enhanced efficacy by significantly inhibiting key pro-inflammatory cytokines and thermoregulatory mediators in yeast-induced fever rats.Discussion The BDDS effectively overcomes AG’s low solubility (by SDC solubilization and CO2 bubbles) and permeability (via ASBT transport), outperforming conventional formulations in terms of preparation simplicity and storage stability.Conclusion BDDS is a promising strategy to improve oral absorption and therapeutic efficacy of BCS Class IV drugs like AG, with ASBT-mediated transport as a key mechanism.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Chuntian Shao,Jingwei Zhong,Junwen Liu,Yiyan Yang,Meilin Li,Yang Yu,Yaqin Xu,Libo Wang
Native polysaccharide was obtained from Lonicera caerulea L. fruits (PLP). Two selenized polysaccharides (PSLP-1 and PSLP-2) were synthesized by the microwave-assisted HNO 3 -Na 2 SeO 3 method, where the selenium (Se) contents were 228 ± 24 and 353 ± 36 μg/g, respectively. The molecular weights of PLP, PSLP-1, and PSLP-2 were 5.9 × 10 4 , 5.6 × 10 4 , and 5.1 × 10 4 kDa, respectively. PSLP-1 and PSLP-2 contained the same type of monosaccharides as PLP but with different molar ratios. The main chain structure of the native polysaccharide was not changed after selenization. PLP, PSLP-1, and PSLP-2 contained the same six types of glycosidic bonds. Bioactivity assays revealed that the two selenized polysaccharides possessed better antioxidant activities than PLP, but their bile acid-binding abilities and inhibitory activities on acetylcholinesterase (AChE) had weakened. In summary, PLP, PSLP-1, and PSLP-2 may be promising Se supplements in functional foods and inhibitors for the treatment of AChE.
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Drug Design Development and Therapy
·
2023
·
IF 4.8
Qin Guo,Jie Cai,Pengyu Li,Dongling Xu,Xiaomin Ni,Hui Wen,Dan Liu,Suizhen Lin,Haiyan Hu
Androst-3β,5α,6β-triol (Triol) is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC) after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of drug-loaded mixed micelles.
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Journal of Ocean University of China
·
2022
·Vol. 21
·期 3
·782-788
·
IF 1.179
Zhang Pengpeng,Zhang Miaomiao,Dong Kaiyu,Zhang Yicong,Yang Shuang,Wang Yuanhong,Jiang Tingfu,Yu Mingming,Lv Zhihua
Chito-oligosaccharide (COS) had shown a variety of biological activities and potential biomedical implications. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of COS with degrees of polymerization (DPs) 2–7 and explored the influence of DPs on them. From Caco-2 cell permeation studies, COS were low permeability compounds with no directional effects, suggesting a low in vivo absorption mediated by facilitation diffusion and paracellular absorption. After an intragastrical administration to rats, COS2 showed the highest systemic exposure in six oligosaccharides. The bioavailability of COS2–7 was 7.33%, 6.11%, 4.67%, 4.13%, 4.02%, 0.99%, respectively. Differences in bioavailability for each COS correlated to structural variations, with high DPs contributing to a decrease in bioavailability. In conclusion, COS could be absorbed by the intestinal tract both in vitro and in vivo . The very low oral bioavailability of COS could be due to low permeability. DPs can affect absorption and bioavailability of COS2–7. This study provided evidence for the absorption characteristics of COS2–7 to help us better understanding the pharmacological actions.
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
·
2022
·
IF 5.589
Chu-tong Tian,Jing-jing Guo,Yi-fan Miao,He-lin Wang,Qing Ye,Chun-lin Guo,Ming-yang Zhang,Zhong-gui He,Jin Sun
Oral administration of chemotherapy agents , such as docetaxel (DTX), is expected to reduce side effects significantly and increase dosing frequency. However, they often suffer from poor oral bioavailability, impeding their oral application. Dietary lipids such as triglycerides favor lymphatic transport nor vein system, bypassing the first-pass metabolism. Inspired by this concept, we developed a triglyceride-like prodrug of DTX (named as OATG) and explored the effect of lipid types on the OATG oral delivery. The plasma profile in rats revealed that long chain triglyceride (LCT)-based lipid formulations (LBLF) were more promising for OATG delivery than medium chain triglyceride (MCT) ones. The OATG LBLF elicited a markedly enhanced absorption compared with oral Taxotere or DTX LBLF, resulting in relative bioavailability 6.11 or 2.47-fold higher, respectively. The coincident intestinal behaviors of lipid excipients and TG-like prodrug facilitate the oral absorption of the prodrug. The effectiveness of the prodrug formulation was also examined in beagles with absolute bioavailability up to 41.08%, in sharp contrast to that of control DTX group (8%). Besides, the OATG oral formulation could be schedule-intensively administrated with no hypersensitivity, gastrointestinal and hematological toxicity. The current strategy provides an effective lipid formulation and a promising chance for chemotherapy at home.
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CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 40
·期 10
·1154-1164
·
IF 3.815
Wang Cong-Yu,Sun Min,Fan Zhen,Du Jian-Zhong
Imatinib has been widely used as a selective kinase inhibitor for treating a variety of cancers, and this molecule is very hydrophobic so it is usually modified with mesylate salt in clinic to increase bioavailability. However, pH-dependent aqueous solubility and relatively high dosage of imatinib mesylate greatly reduce the clinical outcomes. To solve this problem, we developed an intestine enzyme-responsive hydrogel to efficiently encapsulate hydrophobic imatinib with long-term controlled release and enhanced intestinal permeability through oral administration. Methacrylic anhydride-modified carboxymethyl chitosan (MA-CMCS) was synthesized via amidation reaction and then MA-CMCS was crosslinked with photoinitator under UV-irradation to form a three-dimensional hydrophilic polymer network. The intestine enzyme responsiveness was endowed with imatinib-loaded hydrogel through hydrolyzation of glucosidic bond, which could achieve enzyme-triggered long-term drug release of up to 2 days. Furthermore, sodium deoxycholate was embedded into the hydrogel to synchronously open epithelial tight junctions with improved intestinal permeability. In vitro studies revealed similar lethality against colon cancer cell for both imatinib mesylate and imatinib-loaded hydrogels. Moreover, significantly enhanced in vivo tumor inhibition (6-fold higher compared to imatinib mesylate) was achieved after oral administration with imatinib-loaded hydrogels. Overall, this enzyme-responsive hydrogel could achieve long-term synchronous release of kinase inhibitor (imatinib) and tight junction permeation enhancer (sodium deoxycholate) at intestine with enhanced therapeutic efficiency, which could provide an effective approach to improve the bioavailability of hydrophobic anticancer chemodrugs with oral administration.
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危险品化学品经营许可证（带存储）