F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

SnSe2 Quantum Dots and Chlorhexidine Acetate Suppress Synergistically Non-radiative Recombination Loss for High Efficiency and Stability Perovskite Solar Cells.

Non-radiative recombination losses limit the property of perovskite solar cells (PSCs). Here, a synergistic strategy of SnSe2QDs doping into SnO2 and chlorhexidine acetate (CA) coating on the surface of perovskite is proposed. The introduction of 2D SnSe2QDs reduces the oxygen vacancy defects and increases the carrier mobility of SnO2. The optimized SnO2 as a buried interface obviously improves the crystallization quality of perovskite. The CA containing abundant active sites of ─NH2/─NH─, ─C═N, CO, ─Cl groups passivate the defects on the surface and grain boundary of perovskite. The alkyl chain of CA also improves the hydrophobicity of perovskite. Moreover, the synergism of SnSe2QDs and CA releases the residual stress and regulates the energy level arrangement at the top and bottom interface of perovskite. Benefiting from these advantages, the bulk and interface non-radiative recombination loss is greatly suppressed and thereby increases the carrier transport and extraction in devices. As a result, the best power conversion efficiency (PCE) of 23.41% for rigid PSCs and the best PCE of 21.84% for flexible PSCs are reached. The rigid PSC maintains 89% of initial efficiency after storing nitrogen for 3100 h. The flexible PSCs retain 87% of the initial PCE after 5000 bending cycles at a bending radius of 5 mm.

Overexpression of Wnt5a promoted the protective effect of mesenchymal stem cells on Lipopolysaccharide-induced endothelial cell injury via activating PI3K/AKT signaling pathway.

BACKGROUND: Lung endothelial barrier injury plays an important role in the pathophysiology of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Mesenchymal stem cells (MSCs) therapy has shown promise in ARDS treatment and restoration of the impaired barrier function. It has been reported that Wnt5a shows protective effects on endothelial cells. Therefore, the study aimed to investigate whether overexpression of Wnt5a could promote the protective effects of MSCs on Lipopolysaccharide (LPS)-induced endothelial cell injury. METHODS: To evaluate the protective effects of MSCs overexpressing Wnt5a, we assessed the migration, proliferation, apoptosis, and angiogenic ability of endothelial cells. We assessed the transcription of protective cellular factors using qPCR and determined the molecular mechanism using Western blot analysis. RESULTS: Overexpression of Wnt5a upregulated the transcription of protective cellular factors in MSCs. Co-culture of MSCWnt5a promoted endothelial migration, proliferation and angiogenesis, and inhibited endothelial cell apoptosis through the PI3K/AKT pathway. CONCLUSIONS: Overexpression of Wnt5a promoted the therapeutic effect of MSCs on endothelial cell injury through the PI3K/AKT signaling. Our study provides a novel approach for utilizing genetically modified MSCs in the transplantation therapy for ARDS.

Spin Hall effect modulated by an electric field in asymmetric two-dimensional MoSiAs2Se.

Spin current generation from charge current in nonmagnetic materials promises an energy-efficient scheme for manipulating magnetization in spintronic devices. In some asymmetric two-dimensional (2D) materials, the Rashba and valley effects coexist owing to strong spin-orbit coupling (SOC), which induces the spin Hall effect due to spin-momentum locking of both effects. Herein, we propose a new Janus structure MoSiAs2Se with both valley physics and the Rashba effect and reveal an effective way to modulate the properties of this structure. The results demonstrated that applying an external electric field is an effective means to modulating the electronic properties of MoSiAs2Se, leading to both type I-II phase transitions and semiconductor-metal phase transitions. Furthermore, the coexistence of the Rashba and valley effects in monolayer MoSiAs2Se contributes to the spin Hall effect (SHE). The magnitude and direction of spin Hall conductivity can also be manipulated with an out-of-plane electric field. Our results enrich the physics and materials of the Rashba and valley systems, opening new opportunities for the applications of 2D Janus materials in spintronic devices.

Development of a polyphenol-enriched whole kiwifruit dietary supplement and its potential in ameliorating hyperlipidemia.

BACKGROUND: Kiwifruit pomace, which contains abundant phenolic compounds, is typically discarded during the juicing process, leading to wastage of valuable resources. To address this issue, various indicators (including total acidity, sugar/acid ratio, vitamin C, total polyphenols, polyphenol monomers, and soluble solids content) of 15 kiwifruit cultivars were evaluated and juiced. Then, a polyphenol-concentrated solution from kiwifruit pomace was backfilled into kiwi juice to prepare whole nutritious compound kiwi juice, and its anti-hyperlipidemic activity on obese model mice was then investigated. RESULTS: Through grey relational analysis and the technique for order preference by similarity to an ideal solution (TOPSIS), Kuimi and Huayou were identified as the predominant varieties for juicing, with weighted relevance scores of 0.695 and 0.871 respectively and TOPSIS scores of 0.6509 and 0.8220 respectively. The polyphenol content of Cuixiang pomace was 43.97 mg g-1 , making it the most suitable choice for polyphenol extraction. By backfilling a polyphenol-concentrated solution derived from Cuixiang pomace into compound kiwi juice of Huayou and Kuimi, the whole nutritious compound kiwi juice with polyphenols was produced and exhibited superior bioactivities, including enhanced hepatic oxidative stress defense, and alleviated serum lipid abnormalities. Furthermore, whole nutritious compound kiwi juice with polyphenols ameliorated host intestinal microbiota dysbiosis by increasing the relative abundance of the phyla Bacteroidota and Verrucomicrobiota. CONCLUSION: A hypolipidemic dietary supplement based on kiwifruit pomace polyphenols has been successfully developed, providing an effective solution for hyperlipidemia intervention. © 2023 Society of Chemical Industry.

Homogeneous Polyporus polysaccharide exerts anti-bladder cancer effects via autophagy induction.

CONTEXT: Polyporus polysaccharide (PPS), the leading bioactive ingredient extracted from Polyporus umbellatus (Pers.) Fr. (Polyporaceae), has been demonstrated to exert anti-bladder cancer and immunomodulatory functions in macrophages. OBJECTIVE: To explore the effects of homogeneous Polyporus polysaccharide (HPP) on the proliferation and autophagy of bladder cancer cells co-cultured with macrophages. MATERIALS AND METHODS: MB49 bladder cancer cells and RAW264.7 macrophages were co-cultured with or without HPP intervention (50, 100, or 200 µg/mL) for 24 h. The cell counting kit-8 (CCK-8) assay and 5-ethynyl-2″-deoxyuridine (EdU) staining evaluated MB49 cell proliferation. Monodansylcadaverine (MDC) staining and transmission electron microscopy (TEM) observed autophagosomes. Western blotting detected the expression levels of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins. RESULTS: HPP inhibited the proliferation of MB49 cells co-cultured with RAW264.7 cells but not MB49 cells alone. HPP altered the expression of autophagy-related proteins and promoted the formation of autophagosomes in MB49 cells in the co-culture system. Autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) not only antagonized HPP-induced autophagy but also attenuated the inhibitory effects of HPP on MB49 cell proliferation in the co-culture system. HPP or RAW264.7 alone was not sufficient to induce autophagy in MB49 cells. In addition, HPP suppressed the protein expression of the PI3K/Akt/mTOR pathway in MB49 cells in the co-culture system. DISCUSSION AND CONCLUSIONS: HPP induced bladder cancer cell autophagy by regulating macrophages in the co-culture system, resulting in the inhibition of cancer cell proliferation. The PI3K/Akt/mTOR pathway was involved in HPP-induced autophagy in the co-culture system.

Amplification-Free Ratiometric Electrochemical Aptasensor for Point-of-Care Detection of Therapeutic Monoclonal Antibodies.

The rapid quantification of therapeutic monoclonal antibodies (mAbs) is of great significance to their pharmacokinetics/pharmacodynamics (PK/PD) research and the personalized medication for disease treatment. Taking advantage of the direct decoration of tens of redox tags to the target of interest, we illustrate herein an amplification-free ratiometric electrochemical aptasensor for the point-of-care (POC) detection of trace amounts of therapeutic mAbs. The POC detection of therapeutic mAbs involved the use of the methylene blue (MB)-conjugated aptamer as the affinity element and the decoration of therapeutic mAbs with ferrocene (Fc) tags via the boronate crosslinking, in which the MB-derived peak current was used as the reference signal, and the peak current of the Fc tag was used as the output signal. As each therapeutic mAb carries tens of diol sites for the site-specific decoration of the Fc output tags, the boronate crosslinking enabled the amplification-free detection, which is cost-effective and quite simple in operation. In the presence of bevacizumab (BevMab) as the target, the resulting ratiometric signal (i.e., the IFc/IMB value) exhibited a good linear response over the range of 0.025-2.5 µg/mL, and the limit of detection (LOD) of the electrochemical aptasensor was 6.5 ng/mL. Results indicated that the aptamer-based affinity recognition endowed the detection of therapeutic mAbs with high selectivity, while the ratiometric readout exhibited satisfactory reproducibility and robustness. Moreover, the ratiometric electrochemical aptasensor is applicable to the detection of therapeutic mAbs in serum samples. Taking together, the amplification-free ratiometric electrochemical aptasensor holds great promise in the POC detection of therapeutic mAbs.

Dually Amplified Electrochemical Aptasensor for Endotoxin Detection via Target-Assisted Electrochemically Mediated ATRP.

As the entering of bacterial endotoxin into blood can cause various life-threatening pathological conditions, the screening and detection of low-abundance endotoxin are of great importance to human health. Taking advantage of signal amplification by target-assisted electrochemically mediated atom transfer radical polymerization (teATRP), we illustrate herein a simple and cost-effective electrochemical aptasensor capable of detecting endotoxin with high sensitivity and selectivity. Specifically, the aptamer receptor was employed for the selective capture of endotoxin, of which the glycan chain was then decorated with ATRP initiators via covalent coupling between the diol sites and phenylboronic acid (PBA) group, followed by the recruitment of ferrocene signal reporters via the grafting of polymer chains through potentiostatic eATRP under ambient temperature. As the glycan chain of endotoxin can be decorated with hundreds of ATRP initiators while the further grafting of polymer chains through eATRP can recruit hundreds to thousands of signal reporters to each initiator-decorated site, the teATRP-based strategy allows for the dual amplification of the detection signal. This dually amplified electrochemical aptasensor has the ability to sensitively and selectively detect endotoxin at a concentration as low as 1.2 fg/mL, and its practical applicability has been further demonstrated using human serum samples. Owing to the simplicity, high efficiency, biocompatibility, and inexpensiveness of the teATRP-based amplification strategy, this electrochemical aptasensor holds great application potential in the sensitive and selective detection of low-abundance endotoxin and many other glycan chain-containing bio-targets.

Buried Interface Optimization for Flexible Perovskite Solar Cells with High Efficiency and Mechanical Stability.

The power conversion efficiency (PCE) and stability of perovskite solar cells (PSCs) are significantly reduced by defect-induced charge non-radiative recombination. Also, unexpected residual strain in perovskite films leads to an unfavorable impact on the stability and efficiency of PSCs, notably flexible PSCs (f-PSCs). Considering these problems, a thorough and effective strategy is proposed by incorporating phytic acid (PA) into SnO2 as an electron transport layer (ETL). With the addition of PA, the Sn inherent dangling bonds are passivated effectively and thus enhance the conductivity and electron mobility of SnO2 ETL. Meanwhile, the crystallization quality of perovskite is increased largely. Therefore, the interface/bulk defects are reduced. Besides, the residual strain of perovskite film is significantly reduced and the energy level alignment at the SnO2 /perovskite interface becomes more matched. As a result, the champion f-PSC obtains a PCE of 21.08% and rigid PSC obtains a PCE of 21.82%, obviously surpassing the PCE of 18.82% and 19.66% of the corresponding control devices. Notably, the optimized f-PSCs exhibit outstanding mechanical durability, after 5000 cycles of bending with a 5 mm bending radius, the SnO2 -PA-based device preserves 80% of the initial PCE, while the SnO2 -based device only remains 49% of the initial value.

Innovative beverage creation through symbiotic microbial communities inspired by traditional fermented beverages: current status, challenges and future directions.

Fermented beverages (FBs) are facing challenges in functional performance and flavor complexity, necessitating the development of new multi-functional options. Traditional fermented beverages (TFBs), both alcoholic and nonalcoholic, have gained increased attention for their health-promoting effects during the COVID-19 pandemic. This review summarized the primary commercially available probiotics of FBs, along with the limitations of single and mixed probiotic FBs. It also examined the recent research progress on TFBs, emphasizing the typical microbial communities (MC) of TFBs, and TFBs made from crops (grains, vegetables, fruits, etc.) worldwide and their associated functions and health benefits. Furthermore, the construction, technical bottlenecks of the synthetic MC involved in developing innovative FBs were presented, and the promising perspective of FBs was described. Drawing inspiration from the MC of TFBs, developing of stable and multifunctional FBs using synthetic MC holds great promise for beverage industry. However, synthetic MC suffers from structural instability and poorly acknowledged interaction mechanisms, resulting in disappointing results in FBs. Future researches should prioritize creating synthetic MC fermentation that closely resemble natural fermentation, tailored to meet the needs of different consumers. Creating personalized FBs with high-tech intelligence is vital in attracting potential consumers and developing novel beverages for the future.

Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

Should additional value elements be included in cost-effectiveness analysis in pharmacoeconomic evaluation: a novel commentary.

In recent years, international academics recognized that quality-adjusted life-years (QALYs) may not always fully capture the benefits produced by an intervention, and considered incorporating additional elements of value into cost-effectiveness analysis (CEA). Examples of these elements are adherence-improving factors, insurance value, value of hope, and real option value, which form the "value flower". In order to explore whether it is scientific and reasonable to incorporate additional elements into CEA, this paper focuses on what pharmacoeconomic evaluation should do and what it can do. By elaborating the connotation of value, the connotation of decision, and tracing the origin of pharmacoeconomic evaluation, we believe that it is unscientific and unreasonable to incorporate additional elements of value into CEA, which has exceeded the essential connotation and capability of pharmacoeconomic evaluation. The analysis results belong to the theoretical level, empirical test is needed to verify the correctness and scientificity of this conclusion in the future.

Cost-effectiveness thresholds or decision-making threshold: a novel perspective.

The use of multiple cost-effectiveness thresholds in pharmacoeconomic evaluation is a hotly debated topic in the international academic community. This study analyzed and discussed thresholds in the context of pharmacoeconomic evaluation and reimbursement decision-making. We suggest that the thresholds inferred from reimbursement decisions should be distinguished from cost-effectiveness threshold in pharmacoeconomic evaluation. Pharmacoeconomic evaluations should adopt a fixed threshold, which should not vary with the subjects evaluated. This would help avoid the invitation of numerous cost-effectiveness thresholds for a specific drug, an exceptional disease, a type of innovation, or a certain level of malignancy, which misleads economic evaluation adopting restless changing standards and making pharmacoeconomic evaluation and decision-making more complex and contradictory.

Quantum manifestations in electronic properties of bilayer phosphorene nanoribbons.

Recently, a new edge structure named ZZ(U) has been evidenced as the lowest-energy structure for bilayer phosphorene nanoribbons (PNRs). Owing to strong quantum confinement effects and edge states, width and edge are the two most important factors that influence the properties of PNRs in nanosized microelectronics. In this study, we systematically investigated the evolution of the electronic properties of bilayer PNRs with different edge configurations as the widths vary. The four types of edges explored include ZZ(Pristine), ZZ(Klein), ZZ(Tube), and newly found ZZ(U). As the widths change from 14 to 40 Å, the ZZ(Pristine) are always metallic with edge states penetrating the Fermi level, while the others are semiconductors. The edge states in ZZ(Klein) are located in the two lowest conduction bands. However, in ZZ(U), the edge states are nearly hidden in the bulk band structure, and its carrier transportation exhibits almost perfect 2D layers, nearly eliminating the U-edge influence. Our results pave the way for phosphorene's utilization in electronics and optoelectronics.

Cloning, expression, and characterization of two pectate lyases isolated from the sheep rumen microbiome.

Pectate lyases (Pels) have a vital function in degradation of the primary plant cell wall and the middle lamella and have been widely used in the industry. In this study, two pectate lyase genes, IDSPel16 and IDSPel17, were cloned from a sheep rumen microbiome. The recombinant enzymes were expressed in Escherichia coli and functionally characterized. Both IDSPel16 and IDSPel17 proteins had an optimal temperature of 60 ℃, and an optimal pH of 10.0. IDSPel16 was relatively stable below 60 °C, maintaining 77.51% residual activity after preincubation at 60 °C for 1 h, whereas IDSPel17 denatured rapidly at 60 °C. IDSPel16 was relatively stable between pH 6.0 and 12.0, after pretreatment for 1 h, retaining over 60% residual activity. IDSPel16 had high activity towards polygalacturonic acid, with a Vmax of 942.90 ± 68.11, whereas IDSPel17 had a Vmax of only 28.19 ± 2.23 µmol/min/mg. Reaction product analyses revealed that IDSPel17 liberated unsaturated digalacturonate (uG2) and unsaturated trigalacturonate (uG3) from the substrate, indicating a typical endo-acting pectate lyase (EC 4.2.2.2). In contrast, IDSPel16 initially generated unsaturated oligogalacturonic acids, then converted these intermediates into uG2 and unsaturated galacturonic acid (uG1) as end products, a unique depolymerization profile among Pels. To the best of our knowledge, the IDSPel16 discovered with both endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities. These two pectate lyases, particularly the relatively thermo- and pH-stable IDSPel16, will be of interest for potential application in the textile, food, and feed industries. KEY POINTS: • Two novel pectate lyase genes, IDSPel16 and IDSPel17, were isolated and characterized from the sheep rumen microbiome. • Both IDSPel16 and IDSPel17 are alkaline pectate lyases, releasing unsaturated digalacturonate and unsaturated trigalacturonate from polygalacturonic acid. • IDSPel16, a bifunctional pectate lyase with endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities, could be a potential candidate for industrial application.

Molecular dynamics simulations of electrochemical interfaces.

Molecular dynamics (MD) simulations have become a powerful tool for investigating electrical double layers (EDLs), which play a crucial role in various electrochemical devices. In this Review, we provide a comprehensive overview of the techniques used in MD simulations for EDL studies, with a particular focus on methods for describing electrode polarization, and examine the principle behind these methods and their varying applicability. The applications of these approaches in supercapacitors, capacitive deionization, batteries, and electric double-layer transistors are explored, highlighting recent advancements and insights in each field. Finally, we emphasize the challenges and potential directions for future developments in MD simulations of EDLs, such as considering movable electrodes, improving electrode property representation, incorporating chemical reactions, and enhancing computational efficiency to deepen our understanding of complex electrochemical processes and contribute to the progress in the field involving EDLs.

Maternal BPAF exposure impaired synaptic development and caused behavior abnormality in offspring.

Bisphenol A (BPA) has been widely restricted, leading to a significant increase in the production of bisphenol AF (BPAF), one of the most common bisphenol analogs use as a substitute for BPA. However, there is limit evidence on the neurotoxicity of BPAF, especially the potential effects of maternal exposed to BPAF on offspring. A maternal BPAF exposure model was used to evaluate its effects on long-term neurobehaviors in offspring. We found that maternal BPAF exposure resulted in immune disorders, characterized by abnormal CD4+T cell subsets, and their offspring exhibited anxiety- and depression-like behaviors, as well as impairments in learning-memory, sociability and social novelty. Further, brain bulk RNA-sequencing (RNA-seq) and hippocampus single-nucleus RNA-sequencing (snRNA-seq) of offspring showed that differentially expressed genes (DEGs) were enriched in pathways related to synaptic and neurodevelopment. Synaptic ultra-structure of offspring was damaged after maternal BPAF exposure. In conclusion, maternal BPAF exposure induced behavior abnormality in adult offspring, together with synaptic and neurodevelopment defects, which might be related to maternal immune dysfunction. Our results provide a comprehensive insight into the neurotoxicity mechanism of maternal BPAF exposure during gestation. Given the increasing and ubiquitous exposure to BPAF, especially during sensitive periods of growth and development, the safety of BPAF requires urgent attention.

Gender differences in the authorship of Global Major Gastroenterology Society Guidelines.

BACKGROUND: Gender differences remain a serious issue in the gastroenterology field, which negatively affect the career success and academic advancement of female gastroenterologists. In this study, we aim to identify gender differences in the authors of global major Gastroenterology Society guidelines. METHODS: We included six associations and collected guidelines published between 2003 and 2022. The genders of authors were determined and recorded for each guideline. Linear by linear association test was used to assess trends every 5 years. RESULTS: We included 210 guidelines and 461 authors. The proportion of female first and senior authors was 11.3% and 9.8%, respectively. The number of female first and senior authors in most societies has improved over the past 20 years, with the largest increase in the AGA. CONCLUSIONS: Women are still underrepresented among the authors of guidelines. Although gender differences have gained more attention in recent years, there are many obstacles to achieving gender equality.

Ternary Deep Eutectic Solvents System of Colchicine, 4-Hydroxyacetophenone, and Protocatechuic Acid and Characterization of Transdermal Enhancement Mechanism.

This study aimed to prepare colchicine (CO), 4-hydroxyacetophenone (HA), and protocatechuic acid (CA) contained in transdermal rubber plasters into a more releasable and acrylate pressure-sensitive adhesive (PSA) to optimize traditional Touguling rubber plasters (TOU) with enhanced transdermal permeability by using deep eutectic solvents (DES) technology. We compared the difference in the release behavior of CO between rubber plaster and PSA, determined the composition of the patch through pharmacodynamic experiments, explored the transdermal behavior of the three components, optimized the patch formula factors, and improved the penetration of CO through the skin. We also focused on elucidating the interactions among the three components of DES and the intricate relationship between DES and the skin. The melting point of DES was determined using DSC, while FTIR, 13C NMR, and ATR-FTIR were used to explore the intricate molecular mechanisms underlying the formation of DES, as well as its enhancement of skin permeability. The results of this investigation confirmed the successful formation of DES, marked by a discernible melting point at 27.33°C. The optimized patch, formulated with a molar ratio of 1:1:1 for CO, HA, and CA, significantly enhanced skin permeability, with the measured skin permeation quantities being 32.26 ± 2.98 µg/cm2, 117.67 ± 7.73 µg/cm2, and 56.79 ± 1.30 µg/cm2 respectively. Remarkably, the optimized patch also demonstrated similar analgesic and anti-inflammatory effects compared to commercial diclofenac diethylamide patches in different pharmacodynamics studies. The formation of DES altered drug compatibility with skin lipids and increased retention, driven by the interaction among the three component molecules through hydrogen bonding, effectively shielding the skin-binding sites and enhancing component permeation. In summary, the study demonstrated that optimized DES patches can concurrently enhance the penetration of CO, HA, and CA, thereby providing a promising approach for the development of DES in transdermal drug delivery systems. The findings also shed light on the molecular mechanisms underlying the transdermal behavior of DES and offer insights for developing more effective traditional Chinese medicine transdermal drug delivery systems.

Electrochemically Controlled Atom Transfer Radical Polymerization for Electrochemical Aptasensing of Tumor Biomarkers.

Tumor biomarkers are of great value in the liquid biopsy of malignant tumors. In this work, a simple and cost-friendly electrochemical aptasensor was presented for the highly sensitive and selective detection of glycoprotein tumor biomarkers. The DNA aptamer-modified electrode was used as the sensing interface to specifically capture the target glycoprotein tumor biomarkers, to which the alkyl halide initiators for atom transfer radical polymerization (ATRP) were then attached via the esterification crosslinking between the boronic acid group and the cis-dihydroxyl sites of the conjugated oligosaccharide chains on glycoprotein tumor biomarkers followed by the growth of long-chain polymers through electrochemically controlled ATRP (eATRP) to efficiently recruit the ferrocene detection tags. As there are tens to hundreds of cis-dihydroxyl sites on a glycoprotein tumor biomarker for attaching ATRP initiators while each long-chain polymer can recruit hundreds to thousands of ferrocene detection tags, a significantly high current signal can be generated even in the presence of ultralow-abundance targets. Hence, the eATRP-based electrochemical aptasensor is capable of sensitively and selectively detecting glycoprotein tumor biomarkers. Using alpha-fetoprotein as the model target, the limit of detection was demonstrated to be 0.32 pg/mL. Moreover, the aptasensor has been successfully applied to detect glycoprotein tumor biomarkers in human serum samples. In view of its high sensitivity and selectivity, simple operation, and cost-friendliness, the eATRP-based electrochemical aptasensor shows great promise in the glycoprotein-based liquid biopsy of malignant tumors, even at the early stage of development.