With a substantial demand for new anti-obesity drugs for the treatment of obesity, screening lipase inhibitors from natural products has become a popular approach toward drug discovery. Due to the ...significant advantages of excellent reusability, stability and endurance in extreme pH and temperature conditions, lipase immobilization has been employed as a promising strategy to screen lipase inhibitors. Support is a key factor in the process of enzyme immobilization used to provide excellent biocompatibility, stable physical and chemical properties and abundant binding sites for enzymes. Thus, various supports, including nanofibers, polymeric monoliths, mesoporous materials, nanomaterials, membrane and cellulose paper, are systematically introduced and discussed in this review. Considering these supports, the application of the immobilization of lipase in screening compounds from natural products is also comprehensively reviewed, and the outlook for future research directions is described.
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•Immobilized enzyme strategy has been currently recognized as a powerful tool in the field of inhibitors screening.•A variety of materials have been systematically introduced and employed as the supports for lipase immobilization.•Lipase inhibitors screening based on the immobilized enzyme technology has been detailed presented.•Future perspectives of novel supports for immobilizing lipase and screening techniques for inhibitors are stated as well.
Conductive polymers are recognized as ideal candidates for the development of noninvasive and wearable sensors for real‐time monitoring of potassium ions (K+) in sweat to ensure the health of life. ...However, the low ion‐to‐electron transduction efficiency and limited active surface area hamper the development of high‐performance sensors for low‐concentration K+ detection in the sweat. Herein, a wearable K+ sensor is developed by tailoring the nanostructure of polypyrrole (PPy), serving as an ion‐to‐electron transduction layer, for accurately and stably tracing the K+ fluctuation in human sweat. The PPy nanostructures can be tailored from nanospheres to nanofibers by controlling the supramolecular assembly process during PPy polymerization. Resultantly, the ion‐to‐electron transduction efficiency (17‐fold increase in conductivity) and active surface area (1.3‐fold enhancement) are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofibers‐based K+ sensor achieved a high sensitivity of 62 mV decade−1, good selectivity, and solid stability. After being integrated with a temperature sensor, the manufactured wearable sensor realized accurate monitoring of K+ fluctuation in the human sweat.
The polypyrrole (PPy) nanostructures are tailored from nanospheres to nanofibers via controlling the supramolecular assembly process, which is utilized as the ion‐to‐electron conductive layer. Resultantly, the ion‐to‐electron transduction efficiency and active surface area are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofiber‐based potassium ion (K+) sensor achieved a high sensitivity of 62 mV decade−1, good selectivity, and solid stability.
A new magnetic molecularly imprinted polymers (MMIPs) for quercetagetin was prepared by surface molecular imprinting method using super paramagnetic core-shell nanoparticle as the supporter. ...Acrylamide as the functional monomer, ethyleneglycol dimethacrylate as the crosslinker and acetonitrile as the porogen were applied in the preparation process. Fourier transform infrared spectrometer (FT-IR), X-ray diffraction (XRD) and Vibrating sample magnetometer (VSM) were applied to characterize the MMIPs, and High performance liquid chromatography (HPLC) was utilized to analyze the target analytes. The selectivity of quercetagetin MMIPs was evaluated according to their recognition to template and its analogues. Excellent binding for quercetagetin was observed in MMIPs adsorption experiment, and the adsorption isotherm models analysis showed that the homogeneous binding sites were distributed on the surface of the MMIPs. The MMIPs were employed as adsorbents in solid phase extraction for the determination of quercetagetin in Calendula officinalis extracts. Furthermore, this method is fast, simple and could fulfill the determination and extraction of quercetagetin from herbal extract.
Quercetagetin imprinted polymer shell layer were coated on the surface of the super-paramagnetic Fe3O4 nanoparticles through surface imprinting method, so novel magnetic molecularly imprinted polymers (MMIPs) for quercetagetin were prepared. The MMIPs were applied in the determination and extraction of quercetagein in Calendula officinalis extracts followed by high-performance liquid chromatography. Display omitted
•Quercetagetin imprinted polymer shell layer were prepared by surface imprinting.•The obtained MMIPs served as sorbents were used to recognize quercetagetin in TCM.•The prepared MMIPs were investigated by FT-IR, XRD and VSM.•The MMIPs were proved to be highly selective, easy to collect and low cost.
With the increasing demands for novel flexible organic electronic devices, conductive polymers are now becoming the rising star for reaching such targets, which has witnessed significant ...breakthroughs in the fields of thermoelectric devices, solar cells, sensors, and hydrogels during the past decade due to their outstanding conductivity, solution‐processing ability, as well as tailorability. However, the commercialization of those devices still lags markedly behind the corresponding research advances, arising from the not high enough performance and limited manufacturing techniques. The conductivity and micro/nano‐structure of conductive polymer films are two critical factors for achieving high‐performance microdevices. In this review, the state‐of‐the‐art technologies for developing organic devices by using conductive polymers are comprehensively summarized, which will begin with a description of the commonly used synthesis methods and mechanisms for conductive polymers. Next, the current techniques for the fabrication of conductive polymer films will be proffered and discussed. Subsequently, approaches for tailoring the nanostructures and microstructures of conductive polymer films are summarized and discussed. Then, the applications of micro/nano‐fabricated conductive films‐based devices in various fields are given and the role of the micro/nano‐structures on the device performances is highlighted. Finally, the perspectives on future directions in this exciting field are presented.
Micro/nano‐structured conductive polymer films are critical for achieving high‐performance organic electronic devices. This review covers various micro/nano‐fabrication techniques and applications of micro/nano‐fabricated conductive films‐based devices in various fields such as sensors, energy devices, photonic devices, and actuators. The micro/nano‐structures play an important role in improving their performances.
Effective and safe hemodialysis is essential for patients with acute kidney injury and chronic renal failures. However, the development of effective anticoagulant agents with safe antidotes for use ...during hemodialysis has proven challenging. Here, we describe DNA origami-based assemblies that enable the inhibition of thrombin activity and thrombus formation. Two different thrombin-binding aptamers decorated DNA origami initiates protein recognition and inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model. In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the origami-based aptamer nanoarray effectively prevented thrombosis formation. Oligonucleotides containing sequences complementary to the thrombin-binding aptamers can efficiently neutralize the anticoagulant effects. The nanoarray is safe and immunologically inert in healthy mice, eliciting no detectable changes in liver and kidney functions or serum cytokine concentration. This DNA origami-based nanoagent represents a promising anticoagulant platform for the hemodialysis treatment of renal diseases.
A colorimetric method based on TMB/H2O2/HRP and AA-2 G/α-Glu systems was developed for AGIs screening.
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•A colorimetric method is developed for AGIs screening.•The colorimetric method ...is based on the AA-2 G/α-Glu and TMB/H2O2/HRP systems.•AA released from the AA-2 G/α-Glu system suppresses the oxidation of TMB to oxTMB.•The existence of AGIs can be easily observed by color variation of blue oxTMB.•AGIs are screened from 7 flavonoids based on this colorimetric method.
A facile and novel colorimetric method for screening of α-glucosidase inhibitors (AGIs) from flavonoids using 3,3’,5,5’-tetramethylbenzidine (TMB) as a chromogenic probe is proposed. This method is based on the colorimetric detection of ascorbic acid (AA) through the TMB oxidation reaction catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). In the TMB/H2O2/HRP system, HRP catalyzes the oxidation of H2O2 to ‧OH radical which oxidizes TMB to blue-colored oxidized TMB (oxTMB). In the presence of AA, the production of ‧OH radical is suppressed and causes the decrease of oxTMB, resulting in the fading of the blue color and the decrease of absorbance at 652 nm. Based on this, the existence of AA can be facilely identified. In the 2-O-α-d-glucopyranosyl-l-ascorbic acid (AA-2 G)/α-glucosidase (α-Glu) system, the produced AA inhibits the oxidation of TMB to blue-colored oxTMB. In the presence of AGIs, the production of AA is inhibited, which inhibits the reduction of oxTMB, resulting in a blue color recovery and an increase of the absorbance at 652 nm. Based on this, the colorimetric method is developed for screening of AGIs from 7 flavonoids.
Porcine circovirus 4 (PCV4), a new circovirus with a distinct relationship to other circoviruses, was identified in 2019 in several pigs with severe clinical disease in Hunan Province, China. To ...investigate the epidemic profile and genetic diversity of the virus, 63 clinical samples were collected from 24 different pig farms in 14 cities in Henan and Shanxi Provinces, China, between February 2018 and December 2019, and the partial Cap gene of PCV4 was amplified by PCR. Among the 63 samples, 16 (25.40%) were positive for PCV4, and 50% (12/24) of the pig farms were positive for PCV4. PCV4 was detected in samples from pigs with different clinical presentations. One PCV4 strain (Henan‐LY1‐2019) was sequenced in this study, and shared 98.4% genomic nucleotide identity with PCV4 strain HNU‐AHG1‐2019 (accession no. MK986820) detected on a pig farm in Hunan Province in 2019. A phylogenetic analysis based on the genomes of Henan‐LY1‐2019 and 31 reference strains showed that the Henan‐LY1‐2019 strain together with PCV4 strain HNU‐AHG1‐2019 was grouped in a relatively independent sub‐branch, and separated from other viruses in the genus Circovirus. The results of this study extend our understanding of the molecular epidemiology of PCV4.
Pyroptosis is a lytic and inflammatory form of programmed cell death and could be induced by chemotherapy drugs via caspase-3 mediation. However, the key protein gasdermin E (GSDME, translated by the ...DFNA5 gene) during the caspase-3-mediated pyroptosis process is absent in most tumor cells because of the hypermethylation of DFNA5 (deafness autosomal dominant 5) gene. Here, we develop a strategy of combining decitabine (DAC) with chemotherapy nanodrugs to trigger pyroptosis of tumor cells by epigenetics, further enhancing the immunological effect of chemotherapy. DAC is pre-performed with specific tumor-bearing mice for demethylation of the DFNA5 gene in tumor cells. Subsequently, a commonly used tumor-targeting nanoliposome loaded with cisplatin (LipoDDP) is used to administrate drugs for activating the caspase-3 pathway in tumor cells and trigger pyroptosis. Experiments demonstrate that the reversal of GSDME silencing in tumor cells is achieved and facilitates the occurrence of pyroptosis. According to the anti-tumor activities, anti-metastasis results, and inhibition of recurrence, this pyroptosis-based chemotherapy strategy enhances immunological effects of chemotherapy and also provides an important insight into tumor immunotherapy.
Using the DNA origami technique, we constructed a DNA nanodevice functionalized with small interfering RNA (siRNA) within its inner cavity and the chemotherapeutic drug doxorubicin (DOX), ...intercalated in the DNA duplexes. The incorporation of disulfide bonds allows the triggered mechanical opening and release of siRNA in response to intracellular glutathione (GSH) in tumors to knockdown genes key to cancer progression. Combining RNA interference and chemotherapy, the nanodevice induced potent cytotoxicity and tumor growth inhibition, without observable systematic toxicity. Given its autonomous behavior, exceptional designability, potent antitumor activity and marked biocompatibility, this DNA nanodevice represents a promising strategy for precise drug design for cancer therapy.
An autonomous tubular DNA nanodevice is constructed to deliver a chemotherapeutic drug and siRNAs. This nanodevice can realize on‐demand targeting, respond to stimuli in the intracellular environment and release multiple molecular payloads for combined antitumor activity.
•This is a novel study investigating the effect of PRLR gene on mouse model of depression.•PRLR gene was expressed at a higher level in the mouse model of depression.•The JAK2-STAT5 signaling pathway ...was activated in the mouse model of depression.•PRLR gene silencing promotes BDNF and inhibits hippocampal neurons apoptosis.•This study provides a new insight for the treatment of depression.
Patients suffering from depression most commonly present with symptoms associated with the autonomic nervous system. Despite the satisfactory results achieved following treatment with vagus nerve stimulation and drug treatment, recurrence is a common occurrence in many patients. As described in numerous studies, prolactin receptor (PRLR) has been identified as an anxiolytic and anti-depressant factor in depression. However, the effect of PRLR on chronic mild stress (CMS)-induced depression remains to be thoroughly demonstrated. Therefore, the present study was conducted on the effect of PRLR gene on brain derived neurotrophic factor (BDNF) expression and hippocampal neuron apoptosis through the establishment of CMS-induced depression mouse models, with aims of providing a new and effective therapeutic option for depression. Microarray-based analysis was initially used to retrieve depression-related expression dataset and PRLR-related signaling pathway. Lentiviral vectors overexpressing PRLR or expressing PRLR-specific shRNA were used to up- or down-regulated the expression of PRLR in mice. Subsequently, the effects of PRLR on hippocampal neurons and pyramidal cells in CA1 and CA3 regions, and ultrastructure in hippocampal region were evaluated. Serum BDNF level and the positive rate of cleaved-Caspase-3 in hippocampal CA3 region were determined. Next, the regulatory mechanism by which PRLR gene silencing influences hippocampal neuron apoptosis via the JAK2-STAT5 signaling pathway was detected. PRLR gene was assumed to participate in the development of depression by regulating the JAK-STAT signaling pathway. Our results found that the mice with CMS-induced depression exhibited locomotion activity and anhedonia. In addition, a decrease in the number of pyramidal cells was observed in the hippocampus while that of apoptotic cells was increased. In addition, serum BDNF level was increased, and the expression of Caspase-3 and Bax in hippocampal neurons and the JAK2-STAT5 signaling pathway was decreased in response to PRLR silencing, along with increased expression of BDNF and Bcl-2. From the aforementioned findings, we concluded that PRLR gene silencing results in the inhibition of hippocampal neuron apoptosis and alleviation of CMS-induced depression by inactivating the JAK2-STAT5 signaling pathway and elevating BDNF expression, providing a new insight for the treatment of depression.
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