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NEURON · 2026 · IF 15

Gut-brain cholinergic signaling mediates the antiseizure effects of Bacteroides fragilis

Yicong Jia,Hong Chen,Qianhui Zou,Sijing Chen,Jiahao Li,Yiming Chen,Liming Lu,Feng Hong,Shuhui Jia,Xiaoyuan Jing,Jiayan Ren,Fahim Muhammad,JiaYu Mi,Jing Duan,Jianxiang Liao,Qing Liu,Fuqiang Xu,Paul J. Kenny,Ming-Hu Han,Liping Wang,Zuxin Chen,Dezhi Cao,Xin-an Liu

Gut dysbiosis has been implicated in epilepsy, yet probiotic efficacy and mechanisms remain unclear. Here, we identify that Bacteroides fragilis ( B. fragilis ) is markedly reduced in children with epilepsy and show that oral B. fragilis administration suppresses seizures in both pentylenetetrazole- and kainic-acid-induced mouse models. Mechanistically, B. fragilis activates colonic choline acetyltransferase-positive (ChAT + ) cells and enhances gut-vagus-brain cholinergic signaling, as demonstrated by vagal recordings, pharmacological blockade, and chemogenetic manipulation, identifying a colonic ChAT + -nodose ganglion circuit mediating seizure suppression. Its antiseizure effects associate with enriched intestinal Lactobacillus colonization. A randomized clinical trial (CHiCTR2100042203) further confirms the therapeutic efficacy of B. fragilis in pediatric refractory epilepsy. These findings define a gut-brain cholinergic pathway through which B. fragilis exerts antiseizure effects and establish a mechanistic basis for microbiota-targeted therapies in epilepsy.

CAS / MDL: 137-58-6
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Acta Biomaterialia · 2026 · IF 10.4

Preparation of nanofibrous membrane-covered saccule gastric tubes and their treatment of radiation esophagitis

Shutao Ma,Li Weng,Xiang Yin,Mohamed EL-Newehy,Meera Moydeen Abdulhameed,Jiahui Song,Lu Han,Linpeng Fan,Mingyi Shang,Xiumei Mo

Radiation esophagitis (RE) is a frequent acute complication in patients receiving radiotherapy, yet effective local treatment remain unavailable due to the anatomical constraints of the esophagus. Severe cases often require gastric tube placement for symptomatic relief only. In this study, we engineered a therapeutic gastric tube by integrating a compliant medical saccule into the esophageal segment of the tube. The saccule exhibits excellent softness and predictable radial expansion upon gas inflation, returning to its original shape after deflation. A drug-loaded core-shell nanofibrous membrane—comprising a Poly(L-lactide-co-caprolactone) (PLCL) core and a PLCL/collagen (3:1, w/w) shell and encapsulating dexamethasone and lidocaine—was deposited onto the saccule surface via coaxial electrospinning under a 16 kV positive voltage. This design enables intimate contact with the injured esophageal mucosa and sustained local drug release for both prevention and treatment of RE. This membrane demonstrated controlled drug-release behavior, good biocompatibility, and significant anti-inflammatory effects in vitro. In vivo, implantation of the membrane-covered gastric tube markedly alleviated symptoms and improved mucosal healing in a rat RE model. These findings indicate that this therapeutic gastric tube not only mitigates RE-related discomfort but also delivers targeted, localized treatment to the affected site. This work presents a promising interventional strategy for managing radiation esophagitis using a nanofibrous membrane-covered saccule gastric tube. Statement of significance Radiation esophagitis is a common clinical acute adverse reaction that usually occurs in cancer patients undergoing radiotherapy. There is currently no direct treatment for radiation esophagitis, Severe patients can only relieve their symptoms by gastric tubes. In this study, a compliant saccule was added to the esophageal section of the gastric tube. The drug-loaded core-shell nanofibrous membrane was covered on the surface of the saccule through coaxial electrospinning, so that the nanofibrous membrane could be combined to the affected esophageal area to release the drug, thereby treating and preventing radiation esophagitis. The results of this study indicate that drug-loaded membrane-covered gastric tubes can not only improve the symptoms of radiation esophagits but also provide direct treatment.

CAS / MDL: 137-58-6
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JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Supramolecular nanoarchitectonics of phenolic-based nanofiller for controlled diffusion of versatile drugs in hydrogels

Jiezhou Pan,Haotian Liao,Guidong Gong,Yunxiang He,Qin Wang,Lang Qin,Yaoyao Zhang,Hirotaka Ejima,Blaise L. Tardy,Joseph J. Richardson,Jiaojiao Shang,Orlando J. Rojas,Yong Zeng,Junling Guo

Drug-dependent design of hydrogels is currently required for engineering the controlled release of therapeutics, which is a major contributor to the technical challenges relating to the clinical translation of hydrogel-drug systems. Herein, by integrating supramolecular phenolic-based nanofillers (SPFs) into hydrogel microstructures we developed a facile strategy to endow a range of clinically relevant hydrogels with controlled release properties for diverse therapeutic agents. The assembly of multiscale SPF aggregates leads to tunable mesh size and multiple dynamic interactions between SPF aggregates and drugs, which relaxes the available choices of drugs and hydrogels. This simple approach allowed for the controlled release of 12 representative drugs evaluated with 8 commonly used hydrogels. Moreover, the anesthetic drug lidocaine was loaded into SPF-integrated alginate hydrogel and demonstrated sustained release for 14 days in vivo, validating the potential for long-term anesthesia in patients.

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Drug Design Development and Therapy · 2022 · IF 4.319

Lidocaine Inhibits Myoblast Cell Migration and Myogenic Differentiation Through Activation of the Notch Pathway

Xiangtian Ling,Xinqi Ma,Xielan Kuang,Yuxiu Zou,Han Zhang,Han Tang,Han Du,Binbin Zhu,Hao Huang,Qing Xia,Minghao Chen,Danyi Mao,Dongli Chen,Huangxuan Shen,Jianhua Yan

Purpose To assess the cellular and molecular effects of lidocaine on muscles/myoblasts.Methods Cultured myogenic precursor (C2C12) cells were treated with varying concentrations of lidocaine.Results Cell viability of C2C12 cells was inhibited by lidocaine in a concentration-dependent manner, with concentrations ≥0.08%, producing a dramatic reduction in cell viability. These ≥0.08% concentrations of lidocaine arrested cell cycles of C2C12 cells in the G0/G1 phase. Moreover, lidocaine inhibited cell migration and myogenic processes in C2C12 cells at low concentrations. Results from QRT-PCR assays revealed that following treatment with lidocaine, Notch1, Notch2, Hes1, Csl and Dll4 all showed higher levels of expression, while no changes were observed in Mmal1, Hey1, Dll1 and Jag1.Conclusion This work provides the first description of the effects of lidocaine upon the regeneration of muscles and maintenance of satellite cells at the cellular and molecular levels. In specific, we found that the Dll4-Notch-Csl-Hes1 axis was up-regulated suggesting that the Notch signaling pathway was involved in producing these effects of lidocaine. These findings provide a new and important foundation for future investigations into the effects of drug therapies in muscle diseases.

CAS / MDL: 137-58-6
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MICROCHEMICAL JOURNAL · 2022 · IF 5.304

Vortex-assisted liquid–liquid microextraction based on hydrophobic deep eutectic solvent for the urinary excretion study of Taraxacum mongolicum extract in rats

Meichao Liao,Lin Yang,Xiaoyue Yang,Erxu Wang,Bin Lu,Jiye Wang,Li Duan

A novel green vortex-assisted liquid–liquid microextraction based on hydrophobic deep eutectic solvents (VALLME-HDES) technique was developed and applied to the urinary excretion study of Taraxacum mongolicum (TM) extract in rats. Deep eutectic solvent (DES), a less toxic extraction phase, was formed by camphor and 1-hexanol at a molar ratio of 1:2. The key factors affecting the extraction efficiency of the VALLME-HDES method, such as DES volume, vortex time, molar rations of camphor and 1-hexanol, and amount of salts, were systematically examined through one-factor-at-a-time strategy. Under optimum conditions, the developed method exhibited a good linearity (r ≥ 0.9994). The acceptable precision and repeatability were less than 1.10 % and 4.78 %, respectively. Recoveries from urine samples spiked at different concentration levels were 80.0–89.5 % (RSD ≤ 4.78 %). To further investigate the applicability and effectiveness of hydrophobic DES, the validated method was applied to the urinary excretion study of two flavone aglycones in rats after oral administration of the TM extract. The average 48 h cumulative urinary excretion of luteolin and diosmetin accounted for 0.12 % and 1.71 % of the respective administered dose. In addition, the greenness of the proposed method was assessed using the Analytical GREEnness (AGREE) tool. All these results indicated that the proposed method was feasible and efficient, which had great development potential for pharmacokinetic studies and clinical sample analysis.

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JOURNAL OF MOLECULAR LIQUIDS · 2022 · IF 6.633

A separation strategy of Au(III), Pd(II) and Pt(IV) based on hydrophobic deep eutectic solvent from hydrochloric acid media

Ronghao Liu,Jinjie Hao,Yangyang Wang,Yuanyuan Meng,Yanzhao Yang

A hydrophobic deep eutectic solvent (HDES) based on lidocaine and thymol was examined for selective extraction and separation of Au(III), Pd(II) and Pt(IV) in the acidic leaching solution of secondary resources. At first, the properties of HDES were characterized by 1 H NMR, DSC, TGA, RDF and ESP to prove its suitability for extraction process. In addition, extraction behaviors, maximum extraction capacities and competitive extraction experiment were investigated to explore the extraction ability of HDES. The results show that the maximum extraction capacity of Au(III), Pd(II) and Pt(IV) reached 761.2 g/L, 98.3 g/L and 299.3 g/L, respectively. Meanwhile, their extraction efficiency was affected by the changing acidity of aqueous. And then, ion-association mechanism in the extraction process was proposed through the analysis of FT-IR. Finally, a separation process was proposed for the recovery of Au(III), Pd(II) and Pt(IV) based on acidity control and KSCN, which achieved recovery efficiency of 97.8 % Au(III), 99.9 % Pd(II) and 89.5 % Pt(IV). After collecting and regenerating the used HDES, their extraction performance of Au(III), Pd(II) and Pt(IV) were still maintained.

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MICROCHEMICAL JOURNAL · 2022 · IF 5.304

A greener and sustainable route for medicinal plant analysis: Recycle utilization of hydrophobic deep eutectic solvent

Meichao Liao,Yang Zhao,Xiaoyue Yang,Lin Yang,E-Hu Liu,Bin Lu,Jiye Wang,Xiaopeng Liu,Yanzhong Chang,Li Duan

The green and efficient extraction of bioactive compounds from plant biomass is an extraordinary area of interest in the pharmaceutical industries. In a perspective of sustainable development, we investigate an eco-friendly route using recycle hydrophobic deep eutectic solvent-assisted water extraction (RHD-WE) to effectively and simultaneously extract five main phenolic acids (caftaric acid, chlorogenic acid, caffeic acid, cichoric acid, 3,5-di-O-caffeoylquinic acid) from medicinal plant. In the procedure, 20 mg Taraxacum mongolicum powder was mixed with 800 µL water and 200 µL camphor/p-chlorophenol-based hydrophobic deep eutectic solvent (DES) at a molar ratio of 1:3. After 10 min vortex and centrifugation, the mixture was separated into aqueous phase and DES phase. Compared with other published procedures, phenolic acids were enriched in the aqueous phase. Aqueous solution of phenolic acid could be directly used as raw materials without further purification in pharmaceutical industries. Besides, hydrophobic DES phase could easily be recovered and reused in recycling studies. This is the first study of the recyclability of hydrophobic DES. Generally speaking, the model for the extraction of phenolic acids was well established and verified. The extraction efficiency was higher than other traditional extraction methods, approximately 14 mg/g of phenolic acids were obtained in the aqueous phase. In addition, the extraction mechanism was preliminarily discussed in this research. Such novel RHD-WE method might improve the existing schemes for extraction of bioactive compounds from plant materials. This study suggested that hydrophobic DESs could be used as green and safe auxiliary extractant for pharmaceutical applications.

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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2022 · IF 5.518

The development of an artificial skin membrane mimicking the lipid bilayer structure for in vitro permeation study

Yuemei Cen,Haihang Wang,Ping Wen,Genying Xu,Feng Tian,Fenggang Bian,Xiangqiong Zeng

In vitro permeation test is an important method to predict permeability of transdermal formulation. We developed a liquid crystal artificial skin membrane (LC ASM) with the combination of hydrophobic polydimethylsiloxane , hydrophilic chitosan network and liquid crystal to mimic the lipid structure, for preliminary in vitro permeation test. The characterization results suggested that polydimethylsiloxane formed the main framework of the artificial skin membrane and it contained crystalline compartment . It has good thermal stability and mechanical strength , with elastic modulus about 0.2–6.2 MPa. The permeation study of model drugs with different polarity, aminopyrine and lidocaine, ketoprofen , flurbiprofen , through the synthetic LC ASMs were carried out. Results indicated that a good correlation of the permeability coefficients between the liquid crystal artificial skin and the human skin permeation tests was obtained. Therefore, it was suggesting that a synthetic artificial skin membrane could be an alternative option for preliminary in vitro permeation test to evaluate of the permeability of drug compounds.

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Journal of Materials Chemistry B · 2022 ·Vol. 10 ·期 25 ·4810-4822 · IF 7.571

A novel decellularized trachea preparation method for the rapid construction of a functional tissue engineered trachea to repair tracheal defects

Boyou Zhang,Fei Sun,Yi Lu,Zhihao Wang,Zhiming Shen,Lei Yuan,Qiang Wu,Cong Wu,Hongcan Shi

Long segment trachea defects are repaired by tracheal substitution, while decellularized technology has been effectively employed to prepare tissue engineering trachea (TET). However, its clinical application is restricted by the long preparation cycle, while poor vascularization is associated with the transplantation failure. In the present study, we used sodium lauryl ether sulfate (SLES) to develop a novel rapid decellularized tracheal preparation method, then constructed a TET with revascularization functions. Summarily, we decellularized rabbit trachea using various SLES concentrations. Results from histological analysis, immunohistochemical and DAPI staining, as well as DNA quantitative assay, revealed that 1–0.1% (v/v) SLES treatment not only entirely removed cellular components to reduce its immunogenicity, but also retained the tracheal matrix's gross structure. SEM images, safranine O-fast green staining, total collagen content assay and collagen II immunofluorescence revealed that low SLES concentrations preserved the bioactive components of the decellularized tracheal matrix. Next, we performed cytobiocompatible and cytotoxin assays to verify biocompatibility of the decellularized tracheal matrix, and is confirmed by the omentum transplantation of rats. Results from omentum transplantation revealed that the decellularized tracheal matrix had low immunogenicity and excellent biocompatibility. Its revascularization capacity was confirmed by histologic appearance and CD31 immunofluorescence. Based on these findings, we selected 0.1% (v/v) as the optimal SLES concentration for preparing a decellularized tracheal matrix. Next, we seeded allogeneic bone marrow stem cells (BMSC) onto the matrix to construct TET patches. In vivo tracheal defect reconstruction confirmed the biocompatibility and revascularization capacity of this novel TET, and the formation of a vascular network around the patch promoted submucosa and mucosa regeneration without significant stenosis, 4 weeks post-surgery. In conclusion, we used SLES to successfully develop a novel decellularized approach for the preparation of TET, which has low immunogenic and inflammatory responses, as well as excellent biocompatibility, and revascularization ability in vivo without additional exogenous cytokines.

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Annals of Translational Medicine · 2021 · IF 3.932

Lidocaine-eluting endotracheal tube effectively attenuates intubation related airway response

Jing Lu,Wenjie Tian,Linxian Cui,Bing Cai,Tingting Zhang,Nan Huang,Lei Lu,Tao Zhu

Background Lidocaine (LDC) is a local anesthetic widely used to relieve intubation-related airway responses. However, low drug concentration and short effective duration of LDC is inadequate to provide a satisfactory anesthetic effect on the surface of the airway. The present study sought to develop a LDC-delivery endotracheal tube (ETT) to achieve high local drug concentration and sustained drug release with the aim of attenuating an intubation-related airway response. Methods ETTs and polyvinyl chloride (PVC) discs were coated with different molecular weight (MW) poly lactic-co-glycolic acid (PLGA: 50/50; MW: 3,000, 6,000, and 10,000) loaded with LDC by airbrush spray. The morphology of LDC-eluting coatings was analyzed using scanning electron microscopy. In vitro drug release was determined by ultraviolet spectrophotometer. An in vivo study was performed to investigate the differences in plasma LDC concentration, intubation tolerance, and tracheal tissue injury in rabbits undergoing intubation of blank, LDC-spray, or LDC-coated ETTs. Results Approximate 5 mg/cm 2 coatings (containing 2.5 mg/cm 2 LDC) were deposited onto the PVC discs and ETTs. While even distribution and smooth surfaces were generated in PLGA3000 + LDC and PLGA6000 + LDC coatings, PLGA10000 + LDC formed uneven and gullied coatings. Burst release within the first 4 h and sustained release for at least 5 days was achieved in vitro in PLGA + LDC coatings and the in vivo study demonstrated higher plasma LDC concentration and longer drug release duration in LDC-coated ETTs compared with LDC-spray. LDC-coated ETTs significantly improved intubation tolerance in rabbits, as measured by less general anesthetic consumption and longer tube tolerance duration in contrast to blank ETTs with or without LDC spray. Histology assessment showed less mucosal edema area in the PLGA3000 + LDC and PLGA6000 + LDC groups compared to the control, LDC-spray, and PLGA10000 + LDC groups. Among the different MW PLGAs, PLGA6000 presented optimal morphological characteristics, drug release, and anesthetic effect. Conclusions ETTs coated with PLGA + LDC effectively attenuate an intubation-related airway response via increasing local drug concentration and extending drug action duration, which demonstrates a potential therapeutic benefit for patients undergoing intubation.

CAS / MDL: 137-58-6
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2020 · IF 4.389

Enhancement of transdermal delivery of artemisinin using microemulsion vehicle based on ionic liquid and lidocaine ibuprofen

Yongqiang Zhang,Yingying Cao,Xiangzhan Meng,Chunshan Li,Hui Wang,Suojiang Zhang

A microemulsion system based on ionic liquid (IL) and deep eutectic compound was proposed to improve the transdermal delivery of artemisinin. Deep eutectic lidocaine ibuprofen (Lid·Ibu) was selected as the oil phase, and the imidazolium ionic liquid, 1-hydroxyethyl-3-methylimidazolium chloride ([HOEmim]Cl), was incorporated into the aqueous phase as a transdermal enhancer. The ingredients for the microemulsion in this study were selected, and their ratios were optimized. The optimal microemulsion carrier was composed of 45 wt% of water phase, 45 wt% surfactant phase (containing Tween-80, Span-20, and ethanol (co-surfactant) with the weight ratio of 1:1:1), and 10 wt% Lid·Ibu as the oil phase with artemisinin loading of 1.0 wt% (all the ratios were based on the total weight of microemulsion). Physical properties of this microemulsion, including particle size (41.95 ± 0.85 nm), viscosity (26.65 ± 0.13 mPa·s) and density (1.02 g/cm 3 ), were measured. In-vitro transdermal assay showed a remarkable enhancement of artemisinin transport through the skin, with the permeation flux being 3-fold of the value for iso propyl myristate system in 6 h. The impact of IL-based microemulsion (ILME) on stratum corneum (SC) was investigated by DSC, ATR-FTIR and AFM, which unveiled that the ILME possesses the ability of reducing the SC barrier by disrupting the regular arrangement of keratin, resulting in enhancement of transdermal delivery of artemisinin. This current work suggested that the microemulsion proposed here had an excellent capability to promote the transdermal delivery of artemisinin, which might also be a promising vehicle for the skin delivery of other hydrophobic natural drugs.

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CANADIAN JOURNAL OF CHEMICAL ENGINEERING · 2021 ·Vol. 100 ·期 8 ·1747-1754 · IF 2.007

Treatment of oil-based drill cuttings by hydrophobic deep eutectic solvents

Jing Li,Yanjun Jiao,Qin Luo,Weixin Hu,Shenwen Fang,Chunling Tang,Qiang Liu

During the exploitation of shale gas, there are many oil-based drill cuttings (OBDC) produced, which are hazardous waste. In this paper, the characteristics of OBDC were analyzed and 25 hydrophobic deep eutectic solvents (DESs) were prepared as extractants for treating OBDC. The results showed that the DES formed by lauric acid and thymol had the highest extraction efficiency. The significant parameters of the extraction process were studied by using total petroleum hydrocarbon (TPH) as an index and the rational extraction conditions were recommended as follows: 0.8:1 mole ratio of lauric acid to thymol, 10:1 mass ratio of DES to OBDC, and 1 h extraction time at 60°C. The TPH of OBDC can be decreased from 14.75 to 0.87 wt.% at this recommended condition. The high extraction efficiency was also confirmed by energy dispersive spectrum results of treated OBDC. In addition, the lauric acid/thymol DES can be recycled and the TPH was still smaller than 1% after three cycles. This research suggests that hydrophobic DES extraction is an effective technology for TPH removal from OBDC.

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