"Light-On" Fluorescent Nanoprobes for Monitoring Dynamic Distribution of Cellular Nucleolin During Pyroptosis.

Nucleolin (NCL) is a multifunctional nuclear protein that plays significant roles in regulating physiological activities of the cells. However, it remains a challenge to monitor the dynamic distribution and expression of nucleolin within living cells during cell stress processes directly. Here, we designed "turn-on" fluorescent nanoprobes composed of specific AS1411 aptamer and nucleus-targeting peptide on gold nanoparticles (AuNPs) to effectively capture and track the NCL distribution and expression during pyroptosis triggered by electrical stimulation (ES). The distribution of nucleolin in the cell membrane and nucleus can be easily observed by simply changing the particle size of the nanoprobes. The present strategy exhibits obvious advantages such as simple operation, low cost, time saving, and suitability for living cell imaging. The ES can induce cancer cell pyroptosis controllably and selectively, with less harm to the viability of normal cells. The palpable cell nuclear stress responses of cancerous cells, including nucleus wrinkling and nucleolus fusion after ES at 1.0 V were obviously observed. Compared with normal cells (MCF-10A), NCL is overexpressed within cancerous cells (MCF-7 cells) using the as-designed nanoprobes, and the ES can effectively inhibit NCL expression within cancerous cells. The developed NCL sensing platform and ES-based methods hold great potential for cellular studies of cancer-related diseases.

Electrostimulation Evokes Caspase-3-Activated Fast Cancer Cell Pyroptosis and Its Nuclear Stress Response Pathways.

Pyroptosis of programmed cell death has been recognized as a more effective way to inhibit the occurrence and development of tumors than the better-studied apoptosis. However, it is still challenging to quickly and effectively trigger pyroptosis of cancer cells for high-efficacy cancer treatment. Here, we report on the first use of mild constant-potential electrostimulation (cp-ES) to quickly trigger cancer cell pyroptosis with a probability up to ∼91.4% and significantly shortened time (within 1 h), ∼3-6 times faster than typical drug stimulation to induce pyroptosis. We find that the ES-induced cancer cell pyroptosis is through the activated caspase-3 (pathway) cleavage of gasdermin E (GSDME) to form an N-terminal fragment (GSDME-N) and observe nuclear shrinkage and reduction of the number of nucleoli as well as down-/up-regulated expression of two important nucleoproteins of nucleolin and nucleophosmin (NPM1). The study enriches the basic understanding of pyroptosis and provides a new avenue for potential effective treatment of cancer.

Label-Free Single-Cell SERS Detection and Fluorescence Imaging of Molecular Responses to Endoplasmic Reticulum Stress under Electrical Stimulation.

The endoplasmic reticulum (ER) is one of the most important organelles in eukaryotic cells, in which most proteins and lipids are synthesized to regulate complex cellular processes. Generally, the excessive accumulation of unfolded or misfolded proteins can disturb ER homeostasis and induce endoplasmic reticulum stress (ERS). Howbeit, the molecular stress responses within ERS and metastatic behaviors of tumor cells during electrical stimulation (ES) are still poorly investigated and remain a challenge. In this study, by the combined use of fluorescence imaging, ER-targeting plasmonic nanoprobes were developed to trace molecular stress response profiling within the ER during a constant-voltage ES process at ∼1 V based on label-free surface-enhanced Raman spectroscopy (SERS). The excess accumulation of ß-misfolded proteins was found after the ES, leading to breaking of the ER homeostasis and further inducing mitochondrial dysfunction. Notably, the excessive stress of ER under ES can destroy the calcium ion balance and induce significant upregulation of calreticulin expression. Importantly, the content ratio of two kinds of cadherin between E-cadherin and N-cadherin was gradually improved with the voltages boosted. Meanwhile, the epithelial adhesion factor expression was ascended with voltages amplified, leading to inhibiting tumor cell migration at low voltages or death under higher voltages (∼1 V). This study provides cellular insights into the ES approach for tumor therapy and also provides a simple and effective method for detecting molecular stress responses in endoplasmic reticulum stress.

Synthesis Strategies and Applications for Pitch-Based Anode: From Industrial By-Products to Power Sources.

It is significant for saving energy to manufacture superb-property batteries. Carbon is one of the most competitive anode materials in batteries, but it is hard for commercial graphite anodes to meet the increasingly higher energy-storage requirements. Moreover, the price of other better-performing carbon materials (such as graphene) is much higher than graphite, which is not conducive to massive production. Pitch, the cheap by-product in the petroleum and coal industries, has high carbon content and yield, making it possible for commercialization. Developing pitch-based anodes can not only lower raw material costs but also realize the pitch's high value-added utilization. We comprehensively reviewed the latest synthesis strategies of pitch-derived materials and then introduced their application and research progress in lithium, sodium, and potassium ion batteries (LIBs, SIBs, and PIBs). Finally, we summarize and suggest the pitch's development trend for anodes and in other fields.

Nephrotoxicity assessment of podophyllotoxin-induced rats by regulating PI3K/Akt/mTOR-Nrf2/HO1 pathway in view of toxicological evidence chain (TEC) concept.

Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.

Label-Free SERS Detection of Protein Damage in Organelles under Electrostimulation with 2D AuNPs-based Nanomembranes as Substrates.

Proteins as the material basis of life are the main undertakers of life activities. However, it is difficult to identify the related proteins in organelles during stimuli-induced stress responses in cells and remains a great challenge in early diagnosis and treatment of disease. Here, proteins in the cell nucleus and mitochondria of cells under the electrical stimulation (ES) process were collected and sensitively detected based on label-free surface-enhanced Raman spectroscopy (SERS) by using AuNP-based nanomembranes as high-performance SERS substrates. Due to the existence of rich "hot spots" on the 2D plasmonic sensing platform, high-quality SERS spectra of proteins were obtained with superior sensitivity and repeatability. From the SERS analyses in vitro, it was found that the conformation of some proteins in the two kinds of organelles from cancerous HCT-116 cells (compared with normal NCM-460 cells) changed significantly and the expression levels of tyrosine, phenylalanine, and tryptophan were significantly promoted during the stimulation process. Although currently the exact proteins are still unknown, the damage of proteins in the organelles of cells at the amino acid level under ES can be revealed by the method. The developed plasmonic SERS sensing platform would be promising for bioassay and cell studies.

Multi modular toxicity assessment of nephrotoxicity in podophyllotoxin exposure rats on account of toxicological evidence chain (TEC) concept.

Early diagnosis of kidney injuries caused by herbs is necessary to enable effective treatments, prevent kidney failure and promote the internationalization and modernization of herbal medicine. Whereas the toxic assessment evidence has not integrated yet, and the evaluation method has not been unanimously agreed. For example, the gold standard assessing toxicity in animals remains to be histopathology, but serum biochemical indexes are the primary measures for monitoring organs dysfunction in humans. In this study, using Sprague Dawley rats, we investigated whether integrated analyses of transcriptomic and metabolomic data with toxicological evidence chain (TEC) concept could identify indicators of injury and provide new insights into the mechanisms of nephrotoxicity. Firstly, the objective phenotype of the animals was observed in detail and the toxicity performance was collected after administration. Subsequently, histopathological examination and serum biochemical toxicity evidence were collected. Next, we obtained concurrent measurements of transcriptomic changes in kidneys, and changes along with metabolic profiles in serum, after exposure to PT(Podophyllotoxin) to acquire evidence at the molecular level. Last but not least, the GTEA (Grades of Toxicological Evidence Assessment) based on GRADE(Grading of Recommendations Assessment, Development, and Evaluation) system was used to evaluate toxic evidence which can be assigned to a toxic level. The orally gavaged rats with PT have been confirmed with dose-dependent kidney damage from 5 to 15 mg/kg after 4 d. Our findings suggest that the main pathological changes occurred in Glycerophosphatidylcholine metabolism, Arachidonic acid metabolism, Energy metabolism, Tyrosine metabolism, Tryptophan metabolism and so on.Moreover, the alteration of the potential metabolites lipid (i.e. LPC, palmitic acid) and sulfate could serve as plausible markers of PT-induced kidney injury. Our approach provides a mechanistic framework for the refinement of the grading standard of toxicity evidence, which is applicable to other toxicants originated from herbal medicine based on multi-omics data.

Safety and efficacy of botulinum toxin type A in preventing and treating scars in animal models: A systematic review and meta-analysis.

Previous studies have used botulinum toxin type A (BTXA) to improve postoperative and hypertrophic scars; however, there is lack of detailed verification on the safety and effectiveness of this approach. This study aimed to evaluate the therapeutic effect of BTXA on postoperative hypertrophic scars and its influence on cytokine expression in animal models. A computerised search of different databases was performed, including PubMed, Web of Science, Scopus, Cochrane, Embase, CNKI, and Wanfang, up to 10 March 2021. A meta-analysis was performed using R 4.0.0 based on hypertrophic index, epithelialisation time, wound area, and vascular endothelial growth factor (VEGF) expression. Eleven studies were included. The meta-analysis showed a significant difference in hypertrophic index (standardised mean difference [SMD] = -2.63, 95% confidence interval [CI]: -3.50 to -1.76, P < .01), wound area (SMD = -0.54, 95% CI: -1.24 to 0.16, P < .01), and VEGF expression (SMD = -2.56, 95% CI: -3.50 to -1.62, P < .01). This study shows that BTXA is safe and effective in preventing and treating scar hypertrophy in animal models, but excessive doses of BTXA and BTXA to treat large areas should be avoided.

[Mechanism of hepatotoxicity induced by ethanol extract of Dysosma versipellis based on "quantity-weight-evidence" network toxicology].

In this study, the toxicological/pharmacological research method of "quantity-weight-evidence" network was first proposed and practiced to supplement the existing methodology of network toxicology. We transformed the traditional qualitative network into a quantitative network in this study by attributing weights to toxic component content and target frequency, which improved the reliability of data and provided a research idea for the systematic safety evaluation and toxicological research of Chinese medicinal herbs. Firstly, 50% ethanol extract of Dysosma versipellis(DV) was administrated to rats via gavage and the potential hepatotoxic components were identified by serum pharmacochemistry. Then, the component targets were obtained from SwissTargetPrediction, PharmMapper and other online databases, and the target weights were given according to the relative content of components and target fishing frequency. Meanwhile, the targets of hepatotoxicity were predicted from online databases such as Comparative Toxicology Database(CTD) and GeneCards. Subsequently, protein-protein interaction analysis and KEGG pathway enrichment were performed with the STRING database. Finally, the quantitative network of "toxic components-weighted targets-pathways" was constructed. Eleven potential toxic compounds were predicted, including podophyllotoxin, podophyllotoxone, deoxypodophyllotoxin, and 6-methoxypodophyllotoxin. A total of 106 hepatotoxic targets and 65 weighted targets(e.g., Cdk2, Egfr, and Cyp2 c9) were identified. The results of Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment showed that these targets could act on PI3 K-AKT, MAPK, and Ras signaling pathways to play a role in inflammatory response and oxidative stress. However, traditional network toxicology showed that 51 targets such as AKT1, Alb, and Stat3 may lead to hepatotoxicity by mediating inflammation and cell proliferation. In conclusion, we proposed "quantity-weight-evidence" network toxicology in this study and used it to study the mechanism of DV-induced hepatotoxicity in rats. This study confirms the feasibility of this new methodology in toxicological evaluation and further improves the systematic evaluation of the safety of Chinese medicinal herbs.

Methylation Status of the miR-141-3p Promoter Regulates miR-141-3p Expression, Inflammasome Formation, and the Invasiveness of HTR-8/SVneo Cells.

MicroRNA-141 (miR-141-3p) is upregulated in preeclampsia. This study investigated the effect of methylation of the miR-141-3p promoter on cell viability, invasion capability, and inflammasomes in vitro. The expression of miR-141-3p and methylation status of the miR-141-3p promoter were examined by RT-qPCR and pyrosequencing in villus tissues of women with spontaneous delivery (VTsd), villus tissues of women with preeclampsia (VTpe), and also in HTR-8/SVneo cells treated with a miR-141-3p inhibitor and 20 µmol/L 5-aza-2'-deoxycytidine (5-Aza), a DNA methyltransferase inhibitor. Cell viability and invasion were evaluated by CCK-8 and transwell assays. In addition, the levels of CXCL12, CXCR4, CXCR2, MMPs, NLRP3, and ASC expression were assessed by western blotting, and IL-1ß and IL-18 concentrations were assayed by ELISA. miR-141-3p expression was upregulated, and the levels of miR-141-3p promoter methylation and CXCL12, CXCR4, and CXCR2 expression were decreased in VTpe relative to VTsd. In HTR-8/SVneo cells, hypomethylation caused by 5-Aza treatment increased miR-141-3p expression, while DNA methyltransferase 3 (DNMT3) transfection decreased miR-141-3p expression. miRNA-141-3p induced NLRP3, IL-1ß, and IL-18 production, decreased CXCR4, MMP, and MMP2 production, and suppressed cell growth and invasion. Furthermore, we observed that NLRP3 plays an important mediatory role in the effects of miR-141-3p described above. Decreased methylation of the miR-141-3p promoter increases miR-141-3p expression, which in turn increases NLRP3 expression, resulting in higher IL-1ß and IL-18 levels and lower levels of MMP2/9 and CXCR4. We conclude that modification of the miR-141-3p promoter might be a curial mediator in preeclampsia.

One-pot synthesis of AuAgPd trimetallic nanoparticles with peroxidase-like activity for colorimetric assays.

In this work, AuAgPd trimetallic nanoparticles (AuAgPd TNPs) with intrinsic and broad-spectrum peroxidase-like activity were synthesized through a one-pot method by co-reduction of HAuCl4, AgNO3, and Na2PdCl4 with NaBH4. The morphology and composition of AuAgPd TNPs were characterized. The peroxidase-like activity of AuAgPd TNPs were highly dependent on the composition and nanostructure of AuAgPd TNPs. Rationally designed AuAgPd TNPs could catalyze the oxidation of various chromogenic substrates including 3,3'5,5'-tetramethylbenzidine (TMB), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and o-phenylenediamine (OPD) by H2O2 to generate blue, green, and yellow products, respectively. Kinetic assays indicated that AuAgPd TNPs exhibited high affinity to H2O2. Then, sensitive colorimetric assays were developed for H2O2 detection by using ABTS, OPD, and TMB as chromogenic substrates, respectively. Lowest limit of detection (LOD) of 3.1 µM with wide linear range of 6-250 µM was obtained by using ABTS as substrate. Hydrogen sulfide ion (HS-) could effectively inhibit the peroxidase-like activity of AuAgPd TNPs. Thus, a selective colorimetric assay was further fabricated for HS- detection with LOD of 2.3 µM. This work provides an effective way for the synthesis of trimetallic nanozyme with peroxidase-like activity and also for tailoring their catalytic activity for desired use. Graphical abstract.

Study on potential toxic material base and mechanisms of hepatotoxicity induced by Dysosma versipellis based on toxicological evidence chain (TEC) concept.

Dysosma Versipellis (DV), a traditional Chinese medicine, has the functions of eliminating phlegm, detoxification, dispersing knots . However, its serious toxicity limits its further use. Therefore, it is necessary to conduct a comprehensive toxicity study of DV, screen the basis of potential toxic substances and understand its toxic mechanism. Based on the concept of toxicological evidence chain (TEC), this study utilizes the technologies and means of chemomics, metabolomics, molecular docking and network toxicology flexibly, step by step to find the evidence of potential toxic components in the development of hepatotoxicity induced by DV, evidence of critical toxicity events, evidence of adverse outcomes, thus, a chain of toxicity evidence with reference and directivity can be organized. It further confirmed the toxic damage and potential molecular mechanism of DV. 5 potential toxic components were identified, namely, Podophyllotoxin-4-O-D-glucoside, Podorhizol, Podophyllotoxin, Podophyllotoxone and 3',4'-O,O-Didemethylpophyllotoxin. These chemical constituents affect phenylalanine metabolism, glycerophospholipid metabolism, energy metabolism and other related pathways by regulating PAH, SOD1, SOD2 and other related targets, then it induces oxidative stress, cell apoptosis, inflammatory reaction and energy consumption, which ultimately induces the occurrence of liver injury. The results of this study provide some reference for the follow-up analysis of toxicity mechanism of DV.

A 3D Homochiral MOF [Cd2(d-cam)3]•2Hdma•4dma for HPLC Chromatographic Enantioseparation.

Up to now, some chiral metal-organic frameworks (MOFs) have been reported for enantioseparation in liquid chromatography. Here we report a homochiral MOF, [Cd2(d-cam)3]·2Hdma·4dma, used as a new chiral stationary phase for high-performance liquid chromatographic enantioseparation. Nine racemates of alcohol, naphthol, ketone, and base compounds were used as analytes for evaluating the separation properties of the chiral MOF packed column. Moreover, some effects such as mobile phase composition, column temperature, and analytes mass for separations on this chiral column also were investigated. The relative standard deviations for the resolution values of run-to-run and column-to-column were less than 2.1% and 3.2%, respectively. The experimental results indicate that the homochiral MOF offered good recognition ability, which promotes the application of chiral MOFs use as stationary phase for enantioseparation.

Homochiral metal-organic framework used as a stationary phase for high-performance liquid chromatography.

Metal-organic frameworks are promising porous materials. Chiral metal-organic frameworks have attracted considerable attention in controlling enantioselectivity. In this study, a homochiral metal-organic framework [Co(2) (D-cam)(2) (TMDPy)] (D-cam = D-camphorates, TMDPy = 4,4'-trimethylenedipyridine) with a non-interpenetrating primitive cubic net has been used as a chiral stationary phase in high-performance liquid chromatography. It has allowed the successful separation of six positional isomers and six chiral compounds. The good selectivity and baseline separation, or at least 60% valley separation, confirmed its excellent molecular recognition characteristics. The relative standard deviations for the retention time of run-to-run and column-to-column were less than 1.8 and 3.1%, respectively. These results demonstrate that [Co(2) (D-cam)(2) (TMDPy)] may represent a promising chiral stationary phase for use in high-performance liquid chromatography.

Protection of Qingfei Xieding prescription from idiopathic pulmonary fibrosis by regulating renin-angiotensin and ferroptosis in MLE-12 cells.

Idiopathic pulmonary fibrosis (IPF) is a lifelong lung disease, but there is no specific drug for treatment. Qingfei Xieding prescription (QF) is active in the treatment of lung diseases. More comprehensive mechanisms over how QF exhibits anti-pulmonary fibrosis need to be elucidated. TGF-ß was used to construct a pulmonary fibrosis cell model in vitro. Bleomycin was applied to induce a lung tissue fibrosis model in mice in vivo. Flow cytometry was used to detect cellular ROS and lipid oxidation levels. Cell substructure was observed by Transmission Electron Microscopy. ELISA was used to determine the levels of inflammatory factors. HE staining, Masson staining and immunohistochemistry were performed to evaluate the degree of fibrosis. Western Blot assay was used to determine the protein expressions of different molecules. In TGF-ß-exposed lung epithelial MLE-12 cell model, α-SMA and Collagen I were significantly elevated and cell viability was reduced. QF treatment restored the cell viability decreased by exogenous TGF-ß. Ferroptosis inducer Erastin administration could reverse the beneficial effects such as lipid oxidation and ROS reduction caused by QF treatment. QF was proven to inhibit ferroptosis and alleviated the process of IPF by activating ACE2 signal axis. In bleomycin induced IPF mice model, QF altered lung coefficient, body weight and the expression of inflammatory factors, which were prevented by ferroptosis activator Erastin. QF was demonstrated to affect the ACE2-ERK signaling axis in vivo. QF alleviated idiopathic pulmonary fibrosis by regulating renin-angiotensin through blocking ferroptosis. This research offers evidence for the potentiality of QF in clinical application for IPF therapy.

Menstrual blood-derived stem cells exosomal miR-let-7 to ameliorate pulmonary fibrosis through inhibiting ferroptosis by Sp3/HDAC2/Nrf2 signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a serious, lifelong lung disease with high morbidity and high mortality. Menstrual blood-derived stem cells (MenSCs) derived exosomes (MenSCs-Exo) emerge as an attractive tool for the treatment of acute lung injury and fibrosis-related diseases. However, more comprehensive mechanism over how MenSCs derived exosomes exhibits anti-pulmonary fibrosis needs to be elucidated. In this study, TGF-ß was used to construct cell fibrosis model, and bleomycin (BLM) was applied to induce lung tissue fibrosis mice model. BLM- and TGF-ß1-induced cellular reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, and lung epithelial cell apoptosis were alleviated by MenSCs-Exo treatment in vivo and in vitro. Besides, it was found that MenSCs-Exo delivered miR-let-7 into MLE-12 cells/lung epithelial cell and the reduction of miR-let-7 blocked the improvement produced by MenSCs-Exo. Mechanistically, miR-let-7 directly bound to Sp3 and negatively regulated its expression. Sp3 elevation promoted the expression of ferroptosis-related protein and mitochondrial DNA (mtDNA) damage markers via recruiting HDAC2, thereby inactivating keap1/Nrf2 signal cascade, which were confirmed in BLM-induced pulmonary fibrosis mice model under the combination therapy of the MenSCs-Exo and let-7 inhibitor. Collectively, MenSCs derived exosomes could transmit miR-let-7 into MLE-12 cells to inhibit the expression of Sp3, thereby weakening the recruitment effect of Sp3 on HDAC2, lifting the deacetylation restriction of HDAC2 on Nrf2, and enhancing the Nrf2 pathway. These changes further declined ferroptosis and delayed the pathological process of oxidative damage and lung epithelial cell apoptosis in PF.

Functional characterization of Fagopyrum tataricum ZIP gene family as a metal ion transporter.

The zinc/iron-regulated transporter-like proteins (ZIP) family acts as an important transporter for divalent metal cations such as Zn, Fe, Mn, Cu, and even Cd. However, their condition is unclear in Tartary buckwheat (Fagopyrum tataricum). Here, 13 ZIP proteins were identified and were predicted to be mostly plasma membrane-localized. The transient expressions of FtZIP2 and FtZIP6 in tobacco confirmed the prediction. Multiple sequence alignment analysis of FtZIP proteins revealed that most of them had 8 putative transmembrane (TM) domains and a variable region rich in histidine residues between TM3 and TM4, indicating the reliable affinity to metal ions. Gene expression analysis by qRT-PCR showed that FtZIP genes were markedly different in different organs, such as roots, stems, leaves, flowers, fruits and seeds. However, in seedlings, the relative expression of FtZIP10 was notably induced under the CdCl2 treatment, while excessive Zn2+, Fe2+, Mn2+ and Cd2+ increased the transcript of FtZIP5 or FtZIP13, in comparison to normal conditions. Complementation of yeast mutants with the FtZIP family genes demonstrate that FtZIP7/10/12 transport Zn, FtZIP5/6/7/9/10/11 transport Fe, FtZIP12 transports Mn and FtZIP2/3/4/7 transport Cd. Our data suggest that FtZIP proteins have conserved functions of transportation of metal ions but with distinct spatial expression levels.

A wearable electrostimulation-augmented ionic-gel photothermal patch doped with MXene for skin tumor treatment.

A wearable biological patch capable of producing multiple responses to light and electricity without interfering with daily activities is highly desired for skin cancer treatment, but remains a key challenge. Herein, the skin-mountable electrostimulation-augmented photothermal patch (eT-patch) comprising transparent ionic gel with MXene (Ti3C2Tx) doping is developed and applied for the treatment of melanoma under photostimulation at 0.5 W/cm2. The eT-patch designed has superior photothermal and electrical characteristics owing to ionic gels doped with MXene which provides high photothermal conversion efficiency and electrical conductivity as a medium. Simultaneously, the ionic gel-based eT-patch having excellent optical transparency actualizes real-time observation of skin response and melanoma treatment process under photothermal and electrical stimulation (PES) co-therapy. Systematical cellular study on anti-tumor mechanism of the eT-patch under PES treatment revealed that eT-patch under PES treatment can synergically trigger cancer cell apoptosis and pyroptosis, which together lead to the death of melanoma cells. Due to the obvious advantages of relatively safe and less side effects in healthy organs, the developed eT-patch provides a promising cost-effective therapeutic strategy for skin tumors and will open a new avenue for biomedical applications of ionic gels.

Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking.

OBJECTIVE: To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG). METHODS: The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies. RESULTS: FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking. CONCLUSION: FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.