Flexible and wearable sensor for in situ monitoring of gallic acid in plant leaves.

Gallic acid (GA) is one of the main phenolic components naturally occurring in many plants and foods and has been a subject of increasing interest owing to its antioxidant and anti-mutagenic properties. This study introduces a novel flexible sensor designed for in situ detecting GA in plant leaves. The sensor employs a laser-induced graphene (LIG) flexible electrode, enhanced with MXene and molybdenum disulfide (MoS2) nanosheets. The MXene/MoS2/LIG flexible sensor not only demonstrates exceptional mechanical properties, covering a wide detection range of 1-1000 µM for GA, but also exhibits remarkable selectivity and stability. The as-prepared sensor was successfully applied to in situ determination of GA content in strawberry leaves under salt stress. This innovative sensor opens an attractive avenue for in situ measurement of metabolites in plant bodies with flexible electronics.

In Vivo Detection of Abscisic Acid in Tomato Leaves Based on a Disposable Stainless Steel Electrochemical Immunosensor.

Abscisic acid (ABA) plays an important regulatory role in plants. It is very critical to obtain the dynamic changes of ABA in situ for botanical research. Herein, coupled with paper-based analysis devices, electrochemical immunoelectrodes based on disposable stainless steels sheet were developed for ABA detection in plants in situ. The stainless steel sheets were modified with carbon cement, ferrocene-graphene oxide-multi walled carbon nanotubes nanocomposites, and ABA antibodies. The system can detect the ABA in the range of 1 nM to 100 µM, with a limit of detection of 100 pM. The ABA content in tomato leaves under high salinity was detected in situ. The trend of ABA changes was similar to the expression of SlNCED1 and SlNCED2. Overall, this study offers an approach for in situ detection of ABA in plants, which will help to study the regulation mechanism of ABA in plants and to promote the development of precision agriculture.

Genome-wide analysis of MYB transcription factor family and AsMYB1R subfamily contribution to ROS homeostasis regulation in Avena sativa under PEG-induced drought stress.

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

Immunocyte membrane-derived biomimetic nano-drug delivery system: a pioneering platform for tumour immunotherapy.

Tumor immunotherapy characterized by its high specificity and minimal side effects has achieved revolutionary progress in the field of cancer treatment. However, the complex mechanisms of tumor immune microenvironment (TIME) and the individual variability of patients' immune system still present significant challenges to its clinical application. Immunocyte membrane-coated nanocarrier systems, as an innovative biomimetic drug delivery platform, exhibit remarkable advantages in tumor immunotherapy due to their high targeting capability, good biocompatibility and low immunogenicity. In this review we summarize the latest research advances in biomimetic delivery systems based on immune cells for tumor immunotherapy. We outline the existing methods of tumor immunotherapy including immune checkpoint therapy, adoptive cell transfer therapy and cancer vaccines etc. with a focus on the application of various immunocyte membranes in tumor immunotherapy and their prospects and challenges in drug delivery and immune modulation. We look forward to further exploring the application of biomimetic delivery systems based on immunocyte membrane-coated nanoparticles, aiming to provide a new framework for the clinical treatment of tumor immunity.

Development of surface molecular-imprinted electrochemical sensor for palmitic acid with machine learning assistance.

Palmitic acid (PA) is a kind of saturated high fatty acid, which is involved in physiological safety and food quality. A surface molecularly imprinted polymer (MIP) electrochemical sensor was prepared on MXene surface using dopamine (DA) as functional monomer. The electrode was modified with gold nanoparticles (AuNPs), ferrocene-graphene oxide-multiwalled carbon nanotubes (Fc-GO-MWCNT) composite to enhance the electroactive area and conductivity. The sensor was characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), electrochemical impedance spectroscopy (EIS) and Differential pulse voltammetry (DPV), respectively. The parameters concerning this assay and various regeneration conditions have been carefully studied. The sensor can detect PA in the range of 1 nM-1 mM (R2 = 0.995), the limit of detection (LOD) is 0.48 nM (S/N = 3), and the limit of quantification (LOQ) is 1.61 nM. The artificial neural network (ANN) model in machine learning is further used to analyze the data collected by the sensor. The results show that the back propagation (BP) neural network in ANN is more suitable for the intelligent analysis of PA. The practicality of the sensor was confirmed by detecting PA in pork samples. This is the first MIP-based electrochemical sensor for PA, and it has great potential in practical applications.

Plant-derived nanovesicles: Further exploration of biomedical function and application potential.

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Metabolism, pharmacokinetics, and bioavailability of yuanhuacine in rat using LC-MS.

Yuanhuacine is a Daphne-type diterpene ortho-ester and is one of the main active ingredients of genkwa flos. Anticancer activity of yuanhuacine has been well investigated in various tumor cells and animal models, but information on metabolism and pharmacokinetics is limited. The aims of the present study were to investigate the metabolic and pharmacokinetic profiles of yuanhuacine in rat. The metabolic profile of yuanhuacine was obtained from rat plasma, urine, and feces using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. A total of seven metabolites were detected, and the proposed metabolic pathways involved oxidation and glucuronidation. A simple and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the determination of yuanhuacine in rat plasma. The linear range of yuanhuacine was 1-1000 ng/ml (R2  = 0.998). The intra- and inter-precision (coefficient of variation %) of the assay was 3.86-6.18% and 2.65-5.75%, respectively, and the intra- and inter-accuracy (relative error %) was -3.83-4.77% and -3.03-5.11%, respectively. The extraction recovery, matrix effect, stability, and incurred sample reanalysis of yuanhuacine were within acceptable levels. The established method was validated and successfully applied to the preclinical pharmacokinetic study of yuanhuacine. The absolute oral bioavailability of yuanhuacine was calculated as 1.14%, and it reached the maximum plasma concentration of 28.21 ± 2.79 ng/ml in rat plasma at 2 h in the oral dosing group. The apparent volume of distribution of intravenous and intragastric administrations was 26.07 ± 6.45 and 21.83 ± 3.54 L/kg, respectively. The half-life of elimination of yuanhuacine was 9.64 ± 1.53 h in the intravenous dosing group.

An ultrasensitive probe-free electrochemical immunosensor for gibberellins employing polydopamine-antibody nanoparticles modified electrode.

Gibberellins (GA3) is an ubiquitous plant hormone, which plays a regulatory role in different growth stages of plants, so it is of great significance to develop a sensitive quantitative analysis method for GA3. In this study, carboxylated graphene oxide- carboxylated multi-walled carbon nanotubes-Fc (GO-MWNT-Fc) composite material and PDANPs-antibody (PDANPs-Ab) were sequentially modified to screen-printed electrodes (SPEs), and an ultrasensitive probe-free immunosensor for GA3 was developed. Fc was applied to generate electrochemical signals. GO-COOH and MWNT-COOH can increase the catalytic ability of the sensor and bind the PDANPs-Ab nanoparticles. PDANPs nanomaterial were synthetized by a facile self-polymerization and used to bind with antibody, so as to increase the antibody loading of the sensor. The as-prepared immunosensor has the widest detection range (100 aM-1 mM) and lowest detection limit (17.4 aM) for GA3 up to date. To our knowledge, it is the first electrochemical immunosensor for GA3. By changing the GA3 antibody to ABA antibody, a sensitive and selective immunosensor for ABA was also fabricated. This immunosensor platform is simple, sensitive, and low cost. It opens broad prospect in on-site applications for biosensors in detecting of various biomolecules in precision agriculture.

A novel COOH-GO-COOH-MWNT/pDA/AuNPs based electrochemical aptasensor for detection of AFB1.

Aflatoxin B1 (AFB1), one of the most common mycotoxins in food matrixes, has been identified as the most toxic contaminant with mutagenic, teratogenic, immunosuppressive, and carcinogenic effects. In this study, an electrochemical aptamer sensor was developed for the on-site detection of AFB1. Carboxylated graphene oxide (COOH-GO) and carboxylated multi-walled carbon nanotubes (COOH-MWNT) nanocomposites, dopamine polymers (pDA) and gold nanoparticles (AuNPs) were used to enhance the electrochemical activity and the biocompatibility of the screen-printed electrodes (SPE). Once AFB1 was captured by the aptamer immobilized on the electrode surface, the redox current of [Fe(CN)6]3-/4- decreased. Therefore, the binding of aptamer (Apt) and AFB1 can be reflected by the change of the peak current. The as-prepared sensor showed a wide detection range of 0.1 fg ml-1-100 pg ml-1 and a low detection limit of 15.16 ag ml-1. It is also simple and low-cost, which shows great potential in practical application.

Natural cell based biomimetic cellular transformers for targeted therapy of digestive system cancer.

Digestive system cancer is the most common cause of cancer death in the world. Although cancer treatment options are increasingly diversified, the mortality rate of malignant cancer of the digestive system remains high. Therefore, it is necessary to explore effective cancer treatment methods. Recently, biomimetic nanoparticle delivery systems based on natural cells that organically integrate the low immunogenicity, high biocompatibility, cancer targeting, and controllable, versatile functionality of smart nanocarrier design with natural cells have been expected to break through the bottleneck of tumor targeted therapy. In this review, we focus on the dynamic changes and complex cellular communications that occur in vivo in natural cells based vehicles. Recent studies on the development of advanced targeted drug delivery systems using the dynamic behaviors such as specific surface protein affinity, morphological changes, and phenotypic polarization of natural cells are summarized. In addition to drug delivery mediated by dynamic behavior, functional "delivery" based on the natural cell themselves is also involved. Aiming to make the best use of the functions of cells, providing clues for the development of advanced drug delivery platforms.

In Vivo Detection of Glutamate in Tomatoes by an Enzyme-Based Electrochemical Biosensor.

The in vivo and on-site detection of key physiology parameters in plants will be of great relevance for precision agriculture and food technology. In this work, a sensitive enzymatic glutamate sensor was successfully developed. To enhance the conductivity and catalytic ability and to fix the glutamate oxidase, Au-Pt nanoparticles were first deposited on screen-printed electrodes, and then carboxylated graphene oxide and carboxylated multiwalled carbon nanotubes were fabricated for the synthesis of the electrode. The detection range of the glutamate sensor is widest (2 µM to 16 mM) up to date, and its detection limit is relatively low (0.14 µM). A number of standard curves were built in the pH range of 3.5-7.5, which can be applied in various plants and fruits. Using this sensor, the glutamate level in tomatoes was determined in vivo. This glutamate sensor has important practical value in precision agriculture. Our strategy also provides a way to establish the detection modes for other biomolecules in plants.

αvß3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma.

BACKGROUND: Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy. RESULTS: We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice. CONCLUSION: The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma.

Unlocking All-Solid Ion Selective Electrodes: Prospects in Crop Detection.

This paper reviews the development of all-solid-state ion-selective electrodes (ASSISEs) for agricultural crop detection. Both nutrient ions and heavy metal ions inside and outside the plant have a significant influence on crop growth. This review begins with the detection principle of ASSISEs. The second section introduces the key characteristics of ASSISE and demonstrates its feasibility in crop detection based on previous research. The third section considers the development of ASSISEs in the detection of corps internally and externally (e.g., crop nutrition, heavy metal pollution, soil salinization, N enrichment, and sensor miniaturization, etc.) and discusses the interference of the test environment. The suggestions and conclusions discussed in this paper may provide the foundation for additional research into ion detection for crops.

A probe-free electrochemical immunosensor for methyl jasmonate based on a Cu-MOF-carboxylated graphene oxide platform.

Methyl jasmonate (MeJA) is an important phytohormone which can regulate plant growth and stress tolerance. It is very necessary to develop sensitive and accurate detection methods for MeJA. In this work, a probe-free electrochemical immunosensor for MeJA detection was developed based on a Cu-MOF-carboxylated graphene oxide (COOH-GO) platform. The Cu2+ in the Cu-MOFs was used to provide redox signals, which avoids the application of an external redox probe in the electrolyte solutions as conventional immunosensors. COOH-GO was used to improve the structural stability and provide more sites for binding MeJA antibodies. The linear range of the MeJA immunosensor is from 10 pM to 100 µM, which can cover the whole concentration range of MeJA in most plants. And its detection limit is very low (0.35 pM), and it can detect very low concentrations of MeJA. This immunosensor is simple, low cost, and does not need redox probe solutions for measurements. It shows remarkable potential for on-site application in precision agriculture.

Enzyme-Free Electrochemical Sensors for in situ Quantification of Reducing Sugars Based on Carboxylated Graphene-Carboxylated Multiwalled Carbon Nanotubes-Gold Nanoparticle-Modified Electrode.

The reducing sugars of plants, including glucose, fructose, arabinose, galactose, xylose, and mannose, are not only the energy source of plants, but also have the messenger function of hormones in signal transduction. Moreover, they also determine the quality and flavor of agricultural products. Therefore, the in situ quantification of reducing sugars in plants or agriculture products is very important in precision agriculture. However, the upper detection limit of the currently developed sugar sensor is not high enough for in situ detection. In this study, an enzyme-free electrochemical sensor for in situ detection of reducing sugars was developed. Three-dimensional composite materials based on carboxylated graphene-carboxylated multi-walled carbon nanotubes attaching with gold nanoparticles (COOH-GR-COOH-MWNT-AuNPs) were formed and applied for the non-enzymatic determination of glucose, fructose, arabinose, mannose, xylose, and galactose. It was demonstrated that the COOH-GR-COOH-MWNT-AuNP-modified electrode exhibited a good catalysis behavior to these reducing sugars due to the synergistic effect of the COOH-GR, COOH-MWNT, and AuNPs. The detection range of the sensor for glucose, fructose, arabinose, mannose, xylose, and galactose is 5-80, 2-20, 2-50, 5-60, 2-40, and 5-40 mM, respectively. To our knowledge, the upper detection limit of our enzyme-free sugar sensor is the highest compared to previous studies, which is more suitable for in situ detection of sugars in agricultural products and plants. In addition, this sensor is simple and portable, with good reproducibility and accuracy; it will have broad practical application value in precision agriculture.

Disposable Stainless-Steel Wire-Based Electrochemical Microsensor for In Vivo Continuous Monitoring of Hydrogen Peroxide in Vein of Tomato Leaf.

As one of the pivotal signal molecules, hydrogen peroxide (H2O2) has been demonstrated to play important roles in many physiological processes of plants. Continuous monitoring of H2O2 in vivo could help understand its regulation mechanism more clearly. In this study, a disposable electrochemical microsensor for H2O2 was developed. This microsensor consists of three parts: low-cost stainless-steel wire with a diameter of 0.1 mm modified by gold nanoparticles (disposable working electrode), an untreated platinum wire with a diameter of 0.1 mm (counter electrode), and an Ag/AgCl wire with a diameter of 0.1 mm (reference electrode), respectively. The microsensor could detect H2O2 in levels from 10 to 1000 µM and exhibited excellent selectivity. On this basis, the dynamic change in H2O2 in the vein of tomato leaf under high salinity was continuously monitored in vivo. The results showed that the production of H2O2 could be induced by high salinity within two hours. This study suggests that the disposable electrochemical microsensor not only suits continuously detecting H2O2 in microscopic plant tissue in vivo but also reduces the damage to plants. Overall, our strategy will help to pave the foundation for further investigation of the generation, transportation, and elimination mechanism of H2O2 in plants.

Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis.

As well as their ion transportation function, the voltage-dependent potassium channels could act as the cell signal inducer in a variety of pathogenic processes. However, their roles in neurogenesis after stroke insults have not been clearly illustrated. In our preliminary study, the expressions of voltage-dependent potassium channels Kv4.2 was significantly decreased after stroke in cortex, striatum and hippocampus by real-time quantitative PCR assay. To underlie the neuroprotection of Kv4.2 in stroke rehabilitation, recombinant plasmids encoding the cDNAs of mouse Kv4.2 was constructed. Behavioral tests showed that the increased Kv4.2 could be beneficial to the recovery of the sensory, the motor functions and the cognitive deficits after stroke. Temozolomide (TMZ), an inhibitor of neurogenesis, could partially abolish the mentioned protections of Kv4.2. The immunocytochemical staining showed that Kv4.2 could promote the proliferations of neural stem cells and induce the neural stem cells to differentiate into neurons in vitro and in vivo. And Kv4.2 could up-regulate the expressions of ERK1/2, p-ERK1/2, p-STAT3, NGF, p-TrkA, and BDNF, CAMKII and the concentration of intracellular Ca2+. Namely, we concluded that Kv4.2 promoted neurogenesis through ERK1/2/STAT3, NGF/TrkA, Ca2+/CAMKII signal pathways and rescued the ischemic impairments. Kv4.2 might be a potential drug target for ischemic stroke intervention.

Hybrid Membrane-Coated Biomimetic Nanoparticles (HM@BNPs): A Multifunctional Nanomaterial for Biomedical Applications.

The application of nanoparticles in the diagnosis and treatment of diseases has undergone different developmental stages, but phagocytosis and nonspecific distribution have been the main factors restricting the transformation of nanobased drugs into clinical practice. In the past decade, the design of membrane-coated nanoparticles has gained increasing attention. It is hoped that the combination of the cell membrane's natural biological properties and the functional integration of synthetic nanoparticle systems can compensate for the shortage of traditional nanoparticles. The membrane coating gives the nanoparticles unique biological functions such as immune evasion and targeting capability. However, when the encapsulation of monotypic membranes does not meet the diverse demands of biomedicine, the combination of different cell membranes may offer more possibilities. In this review, the composition, preparation, and advantages of biomimetic nanoparticles coated with hybrid cell membranes are summarized, and the applications of hybrid membrane-coated biomimetic nanoparticles (HM@BNPs) in drug delivery, phototherapy, liquid biopsy, tumor vaccines, immune therapy, and detoxification are reviewed. Finally, the current challenges and opportunities with regard to HM@BNPs are discussed.

Cell-derived biomimetic nanocarriers for targeted cancer therapy: cell membranes and extracellular vesicles.

Nanotechnology provides synthetic carriers for cancer drug delivery that protect cargos from degradation, control drug release and increase local accumulation at tumors. However, these non-natural vehicles display poor tumor targeting and potential toxicity and are eliminated by the immune system. Recently, biomimetic nanocarriers have been widely developed based on the concept of 'mimicking nature.' Among them, cell-derived biomimetic vehicles have become the focus of bionics research because of their multiple natural functions, such as low immunogenicity, long circulation time and targeting ability. Cell membrane-coated carriers and extracellular vesicles are two widely used cell-based biomimetic materials. Here, this review summarizes the latest progress in the application of these two biomimetic carriers in targeted cancer therapy. Their properties and performance are compared, and their future challenges and development prospects are discussed.

A probe-free electrochemical immunosensor for methyl jasmonate based on ferrocene functionalized-carboxylated graphene-multi-walled carbon nanotube nanocomposites.

Methyl jasmonate (MeJA) is an endogenous plant hormone, which plays an important role in agriculture production. A novel probe-free electrochemical immunosensor was fabricated for detecting of MeJA. Fc, carboxylated graphene (COOH-GR) and carboxylated multi-walled carbon nanotubes (COOH-MWNT) composite was formed and used to fabricate screen-printed electrode (SPE). Fc was used as the electronic medium. COOH-GR and COOH-MWNT were used to improve the conductivity and catalytic activity of the sensor and to immobilize the MeJA antibody. Thus, the immunosensor can be used to detect MeJA without external redox probe solution. The designed sensor can detect MeJA in a wide range of 100 fM-100 µM, and its detection limit is as low as 31.26 fM (S/N = 3). The as-prepared probe-free immunosensor is simple, low cost, and does not need redox probe solutions for measurements, which shows great promise for future application in precision agriculture.