Portable dual-mode paper chips for highly sensitive and rapid determination of aflatoxin B1 via an aptamer-gated MOFs.

Paper chip as a representative microfluidic device has been mushroomed for rapid identification of contaminants in agro-food. However, the sensitivity and accuracy have still been challenged by inevitable background noise or interference in food matrix. Herein, we designed and fabricated a dual-mode paper chip (DPC) by assembling a patterned paper electrode with a platinum nanoparticles-treated colorimetric region through a flow channel. Dual-mode outputs were guided by an aptamer-gated UiO-66-NH2 metal-organic frameworks (MOFs). UiO-66-NH2 loaded with 3, 3', 5, 5'-tetramethylbenzidine (TMB) was controlled by a switch comprised of CdS quantum dots-aptamer. Aflatoxin B1 (AFB1, a kind of carcinogenic mycotoxin) target came and induced TMB release, triggering colorimetric and ECL signals on DPC, ultra-high sensitivity with a detection limit of 7.8 fg/mL was realized. The practicability of the DPC was also confirmed by spiking AFB1 in real corn samples. This portable paper-based device provides an ideal rapid detection platform tailored for diverse food contaminants analysis.

Development of a chitosan and whey protein-based, biodegradable, colorimetric/fluorescent dual-channel monitoring label for real-time sensing of shrimp freshness.

To address the growing and urgent need for quick and accurate food spoilage detection systems as well as to reduce food resource wastage, recent research has focused on intelligent bio-labels using pH indicators. Accordingly, we developed a dual-channel intelligent label with colorimetric and fluorescent capabilities using black lycium anthocyanin (BLA) and 9,10-bis(2,2-dipyridylvinyl) anthracene (DSA4P) as colorimetric and fluorescent indicators within a composite film consisting of chitosan (Cs), whey protein (Wp), and sodium tripolyphosphate (STPP). The addition of STPP as a cross-linking agent significantly improved the hydrophobicity, mechanical properties, and thermal stability of the Cs/Wp composite films under low pH conditions. After the incorporation of BLA and DSA4P, the resulting dual-channel intelligent label (Cs/Wp/STPP/BLA/DSA4P) exhibited superior hydrophobicity, as indicated by a water contact angle of 78.03°. Additionally, it displayed enhanced mechanical properties, with a tensile strength (TS) of 3.04 MPa and an elongation at break (EAB) of 81.07 %, while maintaining a low transmittance of 28.48 % at 600 nm. After 25 days of burial in soil, the label was significantly degraded, which showcases its eco-friendly nature. Moreover, the label could visually detect color changes indicating volatile ammonia concentrations (25-25,000 ppm). The color of the label in daylight gradually shifted from brick-red to light-red, brownish-yellow, and finally light-green as the ammonia concentration increased. Correspondingly, its fluorescence transitioned from no fluorescence to green fluorescence with increasing ammonia concentration, gradually intensifying under 365-nm UV light. Furthermore, the label effectively monitored the freshness of shrimp stored at temperatures of 4 °C, 25 °C, and - 18 °C. Thus, the label developed in this study exhibits significant potential for enhancing food safety monitoring.

Research progress on ginger polysaccharides: extraction, purification and structure-bioactivity relationship.

Ginger is a widespread source of herbal medicine and traditional spices. Among its various bioactive components, ginger polysaccharides (GPs) have attracted the attention of researchers worldwide because of their significant bioactivity. Recent studies have demonstrated the antioxidant, antitumour, anti-inflammatory, immunomodulatory, hypoglycaemic, cough suppressant and thrombotic anticoagulant effects of GPs. However, the structure-bioactivity relationship of GPs has yet to be comprehensively investigated. This review aims to explore all the current published studies on GPs. It further examines various aspects, including the extraction and purification methods, structure, bioactivity, application and structure-bioactivity relationship of GPs. Thus, this review intends to provide a reference for future GP-related research and development.

Intelligent biogenic pH-sensitive and amine-responsive color-changing label for real-time monitoring of shrimp freshness.

BACKGROUND: This study developed an intelligent, pH-sensitive and amine-responsive colorimetric label based on chitosan, whey protein and thymol blue by controlling the pH value of the film-forming solution. The obtained label was used to monitor shrimp freshness in real time. The results of this study offer a new approach for developing highly intelligent biogenic labels for freshness monitoring during seafood preservation and processing. RESULTS: The pH 2.0 chitosan-whey protein-thymol blue (CWT-pH 2.0) label exhibited remarkable properties, including the highest tensile strength (5.90 MPa), excellent thermal stability, low water solubility (27.80%) and highly sensitive color responsiveness. The characterization techniques of scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy confirmed the effective immobilization of thymol blue within the film-forming matrix through hydrogen bonding. Furthermore, the CWT-pH 2.0 label demonstrated visible color changes in the presence of volatile ammonia concentrations ranging from 25 to 25 000 ppm. Consequently, the label successfully facilitated real-time monitoring of shrimp freshness during storage at 4 °C. Importantly, the release rate of thymol blue from the label in food simulants was minimal, measuring only 2.53%. CONCLUSION: The CWT-pH 2.0 label exhibits significant potential as a highly intelligent biogenic label for freshness monitoring in seafood preservation and processing. © 2023 Society of Chemical Industry.

Structure modulation of two-dimensional transition metal chalcogenides: recent advances in methodology, mechanism and applications.

Together with the development of two-dimensional (2D) materials, transition metal dichalcogenides (TMDs) have become one of the most popular series of model materials for fundamental sciences and practical applications. Due to the ever-growing requirements of customization and multi-function, dozens of modulated structures have been introduced in TMDs. In this review, we present a systematic and comprehensive overview of the structure modulation of TMDs, including point, linear and out-of-plane structures, following and updating the conventional classification for silicon and related bulk semiconductors. In particular, we focus on the structural characteristics of modulated TMD structures and analyse the corresponding root causes. We also summarize the recent progress in modulating methods, mechanisms, properties and applications based on modulated TMD structures. Finally, we demonstrate challenges and prospects in the structure modulation of TMDs and forecast potential directions about what and how breakthroughs can be achieved.

High-performance electrochemiluminescence sensors based on ultra-stable perovskite quantum dots@ZIF-8 composites for aflatoxin B1 monitoring in corn samples.

Aflatoxin B1 (AFB1) that is prone to contaminate corns brings a serious threat to human health. Therefore, it is of great significance to construct novel detection methods for AFB1 tracing. Here, methylamine perovskite quantum dots (MP QDs) encapsulated by ZIF-8 metal-organic frameworks (MP QDs@ZIF-8) were prepared and then ultra-stable electrochemiluminescence (ECL) sensors were developed. By the confinement of cavities structure, multiple MP QDs were crystallized and embedded inside ZIF-8 to form MP QDs@ZIF-8, achieving stable and robust ECL responds in aqueous environment. Further combined with AFB1-imprinted polymer, the constructed ECL sensor showed good selectivity and ultra-sensitivity (the detection limit was 3.5 fg/mL, S/N = 3) with a wide linear range from 11.55 fg/mL to 20 ng/mL for AFB1 quantification. Satisfactory recoveries in corn samples indicated the reliable practicability of the proposed sensor for AFB1 assay. This work provided a novel pathway in designing high-performance ECL sensing platform for food safety.

Shen-Qi-Jiang-Tang granule ameliorates diabetic nephropathy via modulating tumor necrosis factor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored. AIM OF THE STUDY: The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments. METHODS AND MATERIALS: The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by H&E, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines. RESULTS: Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment. CONCLUSIONS: SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN.

Development and characterization of pectin and chitosan films incorporated with a new cross-linking agent.

BACKGROUND: In this study, a new crosslinking agent (CA) containing whey protein, papin, glycerin, and epigallocatechin gallate (EGCG), was prepared. The effects of CA content (0, 10, 20, 30, and 40%, v/v) on food packaging properties, crystallinity, microstructure, and antioxidant properties of pectin-CA and chitosan-CA composite films were analyzed. The results of this research offer a theoretical basis for engineering improved films for food packing. RESULTS: Pectin-CA (30%) and chitosan-CA (40%) composite films showed the best light transmission, water retention, breathability, plasticity, and antioxidant activity. Scanning electron microscopy revealed that these composite films exhibited a uniform and homogeneous structure without obvious pores. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) indicated that the amino acids and EGCG in CA were bonded to the film substrate (pectin/chitosan) via electrostatic interactions, hydrogen bonding, and covalent bonding, which led to an improvement in the film's properties. CONCLUSION: The CA has broad application prospects in food packaging as a cross-linking agent and antioxidant. © 2022 Society of Chemical Industry.

AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations.

Transcription factors (TFs) are proteins that interact with specific DNA sequences to regulate gene expression and play crucial roles in all kinds of biological processes. To keep up with new data and provide a more comprehensive resource for TF research, we updated the Animal Transcription Factor Database (AnimalTFDB) to version 4.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB4/) with up-to-date data and functions. We refined the TF family rules and prediction pipeline to predict TFs in genome-wide protein sequences from Ensembl. As a result, we predicted 274 633 TF genes and 150 726 transcription cofactor genes in AnimalTFDB 4.0 in 183 animal genomes, which are 86 more species than AnimalTFDB 3.0. Besides double data volume, we also added the following new annotations and functions to the database: (i) variations (including mutations) on TF genes in various human cancers and other diseases; (ii) predicted post-translational modification sites (including phosphorylation, acetylation, methylation and ubiquitination sites) on TFs in 8 species; (iii) TF regulation in autophagy; (iv) comprehensive TF expression annotation for 38 species; (v) exact and batch search functions allow users to search AnimalTFDB flexibly. AnimalTFDB 4.0 is a useful resource for studying TF and transcription regulation, which contains comprehensive annotation and classification of TFs and transcription cofactors.

Real-Time Sniffing Mass Spectrometry Aided by Venturi Self-Pumping Applicable to Gaseous and Solid Surface Analysis.

Based on the Venturi self-pumping effect, real-time sniffing with mass spectrometry (R-sniffing MS) is developed as a tool for direct and real-time mass spectrometric analysis of both gaseous and solid samples. It is capable of dual-mode operation in either gaseous or solid phase, with the corresponding techniques termed as Rg-sniffing MS and Rs-sniffing MS, respectively. In its gaseous mode, Rg-sniffing MS is capable of analyzing a gaseous mixture with response time (0.8-2.1 s rise time and 7.3-9.6 s fall time), spatial resolution (<80 µm), three-dimensional diffusion imaging, and aroma distribution imaging of red pepper. In its solid mode, an appropriate solvent droplet desorbs the sample from a solid surface, followed by the aspiration of the mixture using the Venturi self-pumping effect into the mass spectrometer, wherein it is ionized by a standard ion source. Compared with the desorption electrospray ionization (DESI) technique, Rs-sniffing MS demonstrated considerably improved limit of detection (LOD) values for arginine (0.07 µg/cm2 Rs-sniffing vs 1.47 µg/cm2 DESI), thymopentin (0.10 µg/cm2 vs 2.67 µg/cm2), and bacitracin (0.16 µg/cm2 vs 2.28 µg/cm2). Rs-sniffing is applicable for the detection of C60(OCH3)6Cl-, an intermediate in the methoxylation reaction involving C60Cl6 (solid) and methanol (liquid). The convenient and highly sensitive R-sniffing MS has a characteristic separation of desorption from the ionization process, in which the matrix atmosphere of desorption can be interfaced by a pipe channel and self-pumped by the Venturi effect with consequent integration using a standard ion source. The R-sniffing MS operates in a voltage-, heat-, and vibration-free environment, wherein the analyte is ionized by a standard ion source. Consequently, a wide range of samples can be analyzed simultaneously by the R-sniffing MS technique, regardless of their physical state.

Ruthenium(II) complex encapsulated multifunctional metal organic frameworks based electrochemiluminescence sensor for sensitive detection of hydrogen sulfide.

Metal organic frameworks (MOFs) based sensors exhibited a good deal of merits on sensitive detection like low reagent consumption, good chemical stability and high detection efficacy. Here, we reported a novel electrochemiluminescence (ECL) sensor which was based on tris(2,2'-bipyridyl) ruthenium(II) (Ru(bpy)32+) encapsulated multifunctional metal organic frameworks (Ru-MOFs) as nanocarrier and nanoreactor for sensitive detection of H2S. Moreover, novel co-reactants NBD-amine was introduced into the ECL sensor as recognition probe. The introducing of Ru-MOFs successfully increased the amount of luminescent probe in the sensing system. At the same time, the Ru-MOFs as nanoreactors improved the molecule reaction efficiency inside the MOFs, including Ru(bpy)32+/co-reactants, and NBD-amine/H2S. Furthermore, the Ru-MOFs has superior adsorption capacity for H2S, which will facilitate the enrichment of H2S at the sensing interface. These were all contributed to enhance the ECL signal and improve the sensitivity of proposed ECL sensor. As a result, the proposed ECL sensor had excellent detection performance for H2S with the dynamic range from 1.0 × 10-11 mol L-1 to 1.0 × 10-4 mol L-1 and the detection limit was 2.5 × 10-12 mol L-1.

An ultrasensitive CH3NH3PbBr3 quantum dots@SiO2-based electrochemiluminescence sensing platform using an organic electrolyte for aflatoxin B1 detection in corn oil.

Mycotoxins contamination, especially aflatoxin B1 (AFB1) in edible oils, is a health hazard. Therefore, AFB1 trace analysis methods are urgently needed. Electrochemiluminescence (ECL) is a popular sensing method because of its low background interference and high sensitivity. However, existing ECL assays for AFB1 detection are based on aqueous rather than oil systems. Herein, we report a CH3NH3PbBr3 quantum dots (MAPB QDs)@SiO2-based ECL sensor for AFB1 quantification in corn oil using an organic electrolyte. The luminophore loading and stability of the MAPB QDs@SiO2 particles were significantly improved compared to those of bulky MAPB materials, resulting in an enhanced ECL response. Further, exploiting molecular imprinting technology, an ECL sensor for AFB1 detection with an ultra-low detection limit of 8.5 fg/mL was prepared. The reliability of the sensor was confirmed by comparable recoveries of corn oil samples with those obtained by high-performance liquid chromatography, indicating its potential for food safety evaluation.

Tetraphenylethylene-Functionalized Metal-Organic Frameworks with Strong Aggregation-Induced Electrochemiluminescence for Ultrasensitive Analysis through a Multiple Convertible Resonance Energy Transfer System.

Since aggregation-induced electrochemiluminescence (AIECL) combined the merits of aggregation-induced emission (AIE) and electrochemiluminescence (ECL), it has become a research hotspot recently. Herein, novel kinds of functional metal-organic frameworks (MOFs) with strong AIECL were reported through doping tetraphenylethylene (TPE) into UiO-66. Due to the porosity and highly ordered topological structure that caused the confinement effect of MOFs, the molecular motion of TPE was effectively limited within UiO-66, resulting in strong AIE. Meanwhile, the large specific surface area and porous structure of UiO-66 allowed TPE to react with coreactants more effectively, which was beneficial to ECL. Thus, the TPE-functionalized UiO-66 (TPE-UiO-66) showed excellent AIECL performance surprisingly. Inspired by this, a multiple convertible ECL resonance energy transfer (ECL-RET) system was constructed through a DNA Y structure that regulated the distance between the energy donor (TPE-UiO-66) and different energy acceptors (gold nanoparticles and Adriamycin). Furthermore, an ultrasensitive ECL biosensor for the detection of Mucin 1 (MUC1) was developed through the introduction of the novel ECL-RET system. In the presence of MUC1, the DNA Y structure was constructed, keeping the gold nanoparticles (AuNPs) away from TPE-UiO-66. Then, Adriamycin (Dox) could be embedded in the DNA Y structure and act as an energy acceptor to receive the energy of TPE-UiO-66, which made the biosensor produce a strong ECL response. As expected, the developed ECL biosensor exhibited superior detection performance for MUC1. This work provided a novel way to realize AIECL and board the application of AIECL in analytical chemistry.

Effects of Ultrasound-Assisted Immersion Freezing on the Protein Structure, Physicochemical Properties and Muscle Quality of the Bay Scallop (Argopecten irradians) during Frozen Storage.

In this study, the comparison effects of ultrasound-assisted immersion freezing (UIF) at different ultrasonic power, immersion freezing (IF), and air freezing (AF) on the protein thermal stability, protein structure, and physicochemical properties of adductor muscle of scallop (Argopecten irradians) (AMS) during frozen storage were investigated. Principal component analysis and the Taylor diagram were used to comprehensively analyze all the indicators tested. The results showed that the UIF at 150 W (UIF-150) treatment was the most effective way to delay the quality deterioration of AMS during 90-day frozen storage. This was mainly because, compared to AF and IF treatments, UIF-150 treatment more effectively minimized the changes in the primary, secondary and tertiary structures of myofibrillar proteins, and it preserved the protein thermal stability of AMS by producing small and regular ice crystals in the AMS tissue during the freezing process. Moreover, the results of physicochemical properties indicated that UIF-150 treatment significantly inhibited the fat oxidation and microbiological activities of frozen AMS, and it finally maintained the microstructure and texture of AMS during frozen storage. Overall, UIF-150 has potential industrial application prospects in the rapid freezing and quality preservation of scallops.

Bioimaging of Pb by LA-ICP-MS and Pb isotopic compositions reveal distributions and origins of Pb in wheat grain.

Atmospheric heavy metal deposition in agroecosystems has increased recently, especially in northern China, which poses serious risks to crop safety and human health via food chain. Wheat grains can accumulate high levels of Pb even when wheat is planted in soils with low levels of Pb. However, the influence of atmospheric deposition on the accumulation and distribution of Pb in wheat grain is still unclear. A field survey was conducted in three districts (A: a district with industrial and traffic pollution; B: a district with traffic pollution; and C: an unpolluted district) in Hebei Province, North China. The grain of wheat cultivated in district A accumulated more Pb from soil and atmospheric deposition than those in other districts, and the bran from district A contained 3.50 and 2.04 times more Pb than those from districts B and C, respectively. The Pb distribution pattern in wheat grain detected by laser ablation inductively coupled mass spectrometry (LA-ICP-MS) was characterized by accumulation mostly in the pericarp and seed coat rather than in the crease, embryo and endosperm. Furthermore, Pb isotopic data showed that airborne Pb was the major source (>50%) of Pb in wheat grain. Interestingly, average contributions of Pb from atmospheric deposition to white flour (78.22%) were higher than its contributions to bran (56.27%). In addition, wheat flag leaves were exposed to PbSO4 at the booting stage, and much greater Pb accumulation (0.33-0.48 mg/kg) was observed in exposed wheat grain than in the control (P < 0.05), PbSO4 constituted most (82.80-100%) of the Pb in the wheat grain. In summary, the results confirmed the efficient foliar Pb uptake and transfer from atmospheric deposition into wheat grain. It would be a new sight for understanding the contribution of airborne Pb to Pb accumulation in wheat grains.

A specific and bioactive polysaccharide marker for Cordyceps.

Cordyceps is one of the most expensive and widely used functional foods. But the authenticity is still a concern due to the lack of appropriate markers. By targeting polysaccharides, this study aimed to develop a specific, and bioactive marker for Cordyceps. Firstly, the results of screening tests of 250 samples by examining both genetic markers and polysaccharide profile showed that a unique polysaccharide fraction (named CCP) was particular to the caterpillar parts. Its potential as a marker was further demonstrated by its ability to induce NO and cytokine production in RAW 264.7 cells. CCP was characterized to be an α-1,4-glucan with a branch at C-6 by the conventional structure analyzing and de novo oligosaccharides sequencing. The content of CCP was closely correlated to the traditional classification criteria. Generally, CCP was a marker that simultaneously enables qualitative and quantitative analysis of Cordyceps.

Retraction notice to "MicroRNA-19a and -19b regulate cervical carcinoma cell proliferation and invasion by targeting CUL5" [Canc. Lett. 322 (2012) 148-158].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Upon investigation, it was discovered that 4 out of 8 images contain fabrication. Fig. 6D, E, 8E and 7F have used the same microscopic image for different experimental settings. The Figure represented in 8E is the correct image placement. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Simple MoS2-Nanofiber Paper-Based Fluorescence Immunosensor for Point-of-Care Detection of Programmed Cell Death Protein 1.

Programmed cell death protein 1 (PD-1) is one of the coinhibitory checkpoints upon T cell activation, the abnormal expression of which severely threatens host immune modulatation for chronic infection. Thus, fast and sensitive monitoring of PD-1 is of vital importance for early diagnosis and cancer treatment. The current detection methods largely based on enzyme-linked immunosorbent assay (ELISA) require time-consuming incubation and complicated washing steps. Herein, we designed a simple and portable nanofiber paper (NFP)-based fluorescence "off-on" immunosensor for PD-1 rapid determination. Molybdenum disulfide (MoS2) nanosheets modified NFP (MoS2-NFP) was employed for adsorbing and immobilizing CdSe/ZnS quantum dots-antibody (QDs-Ab) complex to construct a ready-to-use fluorescent immunosensor. The fluorescent signal of QDs-Ab was initially quenched by MoS2 under the Förster resonance energy transfer (FRET) effect. When the PD-1 target was specifically captured onto NFP by immunization, the QDs-Ab-PD-1 complex was promptly desorbed from the MoS2-NFP surface, resulting in FRET impediment and fluorescence recovery. As an alternative quenching agent, graphene oxide (GO) served as a contrast to investigate NFP-based sensing performance. Owing to superior quenching and desorption efficiency, the MoS2-NFP-based fluorescence immunosensor exhibited nearly 2-fold lower detection limit (85.5 pg/mL) than GO-NFP-based sensor (151 pg/mL) for PD-1 monitoring. Excellent selectivity and satisfactory recovery in PD-1 mouse cell culture supernatant samples were confirmed as well. In addition, the comparable detectability of the MoS2-NFP-based immunosensor was accurately evaluated by a standard PD-1 mouse ELISA kit. This study displayed a simple, rapid, low-cost, and portable point-of-care PD-1 assay, indicating its broad application prospect toward clinical diagnoses.

Astrocytic Kir6.1 deletion aggravates neurodegeneration in the lipopolysaccharide-induced mouse model of Parkinson's disease via astrocyte-neuron cross talk through complement C3-C3R signaling.

Complement pathway over-activation has been implicated in a variety of neurological diseases. However, the signaling pathways governing astrocytic complement activation in Parkinson's disease (PD) are poorly understood. Kir6.1, a pore-forming subunit of ATP-sensitive potassium (K-ATP) channel, is prominently expressed in astrocytes and exhibits anti-inflammatory effects. Therefore, we hypothesize that Kir6.1/K-ATP channel may regulate astrocytic complement activation in the pathogenesis of PD. In this study, astrocytic Kir6.1 knockout (KO) mice were used to examine the effect of astrocytic Kir6.1/K-ATP channel on astrocytic complement activation triggered by the lipopolysaccharide (LPS). Here, we found that astrocytic Kir6.1 KO mice showed more dopaminergic neuron loss and more astrocyte reactivity in substantia nigra compacta than controls. We also found that astrocytic Kir6.1 KO increased the expression of complement C3 in astrocytes in LPS-induced mouse model of PD. Mechanistically, astrocytic Kir6.1 KO promoted astroglial NF-κB activation to elicit extracellular release of C3, which in turn interacted with neuronal C3aR to induce neuron death. Blocking complement function by NF-κB inhibitor or C3aR antagonist rescued the aggravated neuron death induced by Kir6.1 KO. Collectively, our findings reveal that astrocytic Kir6.1/K-ATP channel prevents neurodegeneration in PD via astrocyte-neuron cross talk through NF-κB/C3/C3aR signaling and suggest that targeting astroglial Kir6.1/K-ATP channel-NF-κB-C3-neuronal C3aR signaling represents a novel therapeutic strategy for PD.

A Three-Dimensional Conductive Scaffold Microchip for Effective Capture and Recovery of Circulating Tumor Cells with High Purity.

Effective acquirement of highly pure circulating tumor cells (CTCs) is very important for CTC-related research. However, it is a great challenge since abundant white blood cells (WBCs) are always co-collected with CTCs because of nonspecific bonding or low depletion rate of WBCs in various CTC isolation platforms. Herein, we designed a three-dimensional (3D) conductive scaffold microchip for highly effective capture and electrochemical release of CTCs with high purity. The conductive 3D scaffold was prepared by dense immobilization of gold nanotubes (Au NTs) on porous polydimethylsiloxane and was functionalized with a CTC-specific biomolecule facilitated by a Au-S bond before embedding into a microfluidic device. The spatially distributed 3D macroporous structure compelled cells to change migration from linear to chaotic and the densely covered Au NTs enhanced the topographic interaction between cells and the substrate, thus synergistically improving the CTC capture efficiency. The Au NT-coated 3D scaffold had good electrical conductivity and the Au-S bond was breakable by voltage exposure so that captured CTCs could be specifically released by electrochemical stimulation while nonspecifically bonded WBCs were not responsive to this process, facilitating recovery of CTCs with high purity. The 3D conductive scaffold microchip was successfully applied to obtain highly pure CTCs from cancer patients' blood, benefiting the downstream analysis of CTCs.