Irisin suppresses pancreatic ß cell pyroptosis in T2DM by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.

BACKGROUND: Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet ß-cells, remains unknown. METHODS: In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1ß, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and ß cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results. RESULTS: We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1ß and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets. CONCLUSION: We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet ß-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.

Early-Life Factors and Multimorbidity Risk Later in Older Age: Evidence Based on CHARLS.

INTRODUCTION: Early-life factors were reported to exert influence on the health condition of individuals in the long-term. However, limited research explored the connection between early-life factors and multimorbidity in later years. METHODS: We utilized the data from the China Health and Retirement Longitudinal Study to assess this possible association in the present cross-sectional study. Multimorbidity was determined based on 14 common chronic diseases included in the study. Logistic regression was employed to examine the link between early-life factors and subsequent multimorbidity. RESULTS: Out of 7,578 participants who met the inclusion criteria for analysis, 3,765 (49.68%) were females. The mean age was 68.25 ± 6.70 years. Participants who rated their health during childhood as average (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63-0.96) or better [OR 0.72, 95% CI 0.57-0.91] were significantly less likely to experience multimorbidity in older life. By contrast, experiencing violence from two of the family members was significantly associated with future multimorbidity (OR [95% CI], 1.29 [1.04-1.60]). A superior family financial situation was also negatively associated with multimorbidity, with average (OR [95% CI], 0.72 [0.63-0.83]) and better off than average (OR [95% CI], 0.76 [0.62-0.93]). DISCUSSION: Individuals with poor health status, inferior family socioeconomic status, or experienced violence from family members in childhood were more likely to suffer from multimorbidity in later life. Enhanced social monitoring of potentially adverse conditions in youngsters and targeted interventions could help mitigate the progression of multimorbidity in later life.

Irisin attenuates pyroptosis in high glucose-induced pancreatic beta cells via the miR-133a-3p/FOXO1 axis.

INTRODUCTION: Irisin is closely related to type 2 diabetes mellitus (T2DM) and other metabolic diseases. It can improve the homeostasis of T2DM. MiR-133a-3p is decreased in the peripheral blood of patients with T2DM. Forkhead box protein O1 (FOXO1) is widely expressed in beta-cells and affects the occurrence of diabetes through transcriptional regulation and signalling pathway regulation. MATERIAL AND METHODS: The miR-133a-3p inhibitor was constructed to verify the effect of irisin on pyroptosis through miR-133a-3p. Next, we predicted the presence of targeted binding sequences between FOXO1 and miR-133a-3p by bioinformatics software, which was then confirmed with a double fluorescence assay. Finally, the FOXO1 overexpression vector was used to further verify the effect of irisin through the miR-133a-3p/FOXO1 axis. RESULTS: We first observed that irisin inhibited the protein levels of N-terminal gasdermin D (GSDMD-N) and cleaved caspase-1 and the secretion of interleukins (IL): IL-1beta and IL-18 in Min6 cells treated with high glucoes (HG). Irisin inhibited pyroptosis of Min6 cells treated with HG by reinforcing miR-133a-3p. Then, FOXO1 was validated to be the target gene of miR-133a. Both miR-133a-3p inhibitor and overexpression of FOXO1 restrained the force of irisin on pyroptosis in HG-induced Min6 cells. CONCLUSION: We explored the protective effect of irisin on HG-induced pyroptosis of islet b-cells in vitro and explained its mechanism of inhibiting pyroptosis through the miR-133a-3p/FOXO1 axis, to provide a theoretical basis for finding new molecular targets to delay beta-cell failure and the treatment of T2DM.

Methylammonium Cation-Regulated Controllable Preparation of CsPbBr3 Perovskite Quantum Dots in Polystyrene Fiber with Enhanced Water and UV Light Stabilities.

In situ fabrication of lead halide perovskite quantum dots (PQDs) is important for narrow-band emitters for LED displays due to the simple work procedure and convenient usability; however, the growth of PQDs is not readily controllable in the preparation, resulting in low quantum efficiency and environmental instability of PQDs. Here, we demonstrate an effective strategy to controllably prepare CsPbBr3 PQDs in polystyrene (PS) under the regulation of methylammonium bromide (MABr) via electrostatic spinning and thermal annealing techniques. MA+ slowed down the growth of CsPbBr3 PQDs and acted as a surface defect passivation reagent, which was proved by Gibbs free energy simulation, static fluorescence spectra, transmission electron microscopy, and time-resolved photoluminescence (PL) decay spectra. Among a series of prepared Cs1-xMAxPbBr3@PS (0 ≤ x ≤ 0.2) nanofibers, Cs0.88MA0.12PbBr3@PS shows the regular particle morphology of CsPbBr3 PQDs and the highest photoluminescence quantum yield of up to 39.54%. The PL intensity of Cs0.88MA0.12PbBr3@PS is 90% of the initial intensity after immersing in water for 45 days and 49% of the initial value after persistent ultraviolet (UV) irradiation for 27 days. A high color gamut containing 127% of the National Television Systems Committee standard with long-time working stability was also obtained on light-emitting diode package measurements. These results demonstrate that MA+ can effectively control the morphology, humidity, and optical stability of CsPbBr3 PQDs in the PS matrix.

Insight into the Role of Copper in the Transformation of a [Ag25(2,5-DMBT)16(DPPF)3]+ Nanocluster: Doping or Oxidation.

Structural transformation in nanoclusters is important not only in obtaining functional nanoclusters controllably but also in understanding their structural evolution. This study investigated the role of Cu2+ ions in structural transformation. It was revealed that Cu2+ exhibits two different functions, doping and oxidation, in determining the final products. Starting with a new silver nanocluster, [Ag25(2,5-DMBT)16(DPPF)3]+ (Ag25), a doping process would occur when no more than 0.5 equiv of Cu2+ was added, resulting in the formation of [Ag25-xCux(2,5-DMBT)16(DPPF)3]+ (Ag25-xCux). When 1 equiv of Cu2+ was introduced to Ag25, a structural transformation process would occur instead, forming [Ag22-xCux(2,5-DMBT)12(DPPF)4Cl4]2+ (Ag22-xCux). Considering the similar Cu doping amounts in Ag25-xCux and Ag22-xCux, an oxidation process induced by Cu2+ in the solution can account for this transformation process, which was further demonstrated by the addition of other oxidant substitutions. On the other hand, the role of other valence states of copper in the transformation of the Ag25 cluster was explored. It was found that copper powder can hardly change Ag25 and Cu+ can only proceed the doping process, both of which are different from the role of Cu2+. Overall, this work explores the role of copper in the transformation of the Ag25 cluster in detail, including its concentrations and valence states.

Insight into the Effects of Chiral Diphosphine Ligands on the Structure and Optical Properties of the Au24Cd2 Nanocluster.

Introduction of chiral ligands has been regarded as an effective strategy to obtain nanoclusters with optical purity. However, how the chiral ligands work is still unclear due to the lack of structural comparison between racemic nanoclusters and the corresponding optically active ones. In this work, three structurally related Au24Cd2 nanoclusters, including one racemic and two homochiral nanoclusters, were synthesized, and their crystal structures were characterized using single-crystal X-ray crystallography (SC-XRD). Based on their crystal structures, the origin of the chirality in Au24Cd2 was found to be the twist of the kernel and the chiral arrangement of the metal-ligand surface. Au24Cd2 protected with chiral ligands exhibits a more twisted kernel than the racemic one. Therefore, the chirality of chiral diphosphine was found to transfer from the ligands to the metal-ligand interface and then to the metal core, inducing its distortion to produce enhanced chirality. In addition, the optical properties including optical absorption and circular dichroism of these structurally related Au24Cd2 nanoclusters were compared.

A benzocoumarin-based fluorescent probe for ultra-sensitive and fast detection of endogenous/exogenous hypochlorous acid and its applications.

Hypochlorous acid (HOCl) is widely used in daily production and life because of its green and strongly oxidizing properties. Additionally, as a vital reactive oxygen species (ROS), it is an innate immune system weapon and performs a critical function in many pathophysiology processes. In this paper, a novel water-soluble fluorescent probe, BMH, with excellent performance is designed and synthesized by simple condensation of benzocoumarin and 2-mercaptoethanol. BMH has specific selectivity, excellent sensitivity, ultra-fast response (<3 s), and a wide pH detection range. The fluorescence intensity of BMH has an excellent linear correlation with the concentration of HOCl in the scope of 0-10 µM, and the calculated detection limit (DL) is 2.45 nM. The intramolecular charge transfer (ICT) sensing mechanism of BL has been verified by fluorescence, UV, and MS studies as well as density functional theory (DFT) calculations. Furthermore, BMH can be incorporated into a solid-state visual sensor to detect HOCl conveniently. BMH was applied to detect HOCl-spiked actual water samples and achieved satisfying recovery rates. Also, the low-toxicity BMH can be successfully used to track changes in endogenous/exogenous HOCl in living cells. In short, BL provides a robust and reliable monitoring tool to reveal the biological functions of HOCl and ensure its safe use.

Red-light-responsive coordination polymers nanorods: New strategy for ultrasensitive photothermal detection of targeted cancer cells.

The development of highly sensitive and simple detection methods for cancer cells is an important challenge to achieve early cancer diagnosis and effective treatment. In this paper, folic acid (FA)-conjugated platinum (IV) methylene blue (MB) coordination polymers nanorods (denoted as FA-PtCPs NRs) were developed by the photochemical method. The structure of the PtCPs NRs was investigated using the meta-dynamics and genetic algorithms (MTD-GC) method, and it was found that the coordination bond was formed between platinum (IV) and N atoms of MB. The field emission scanning electron microscope (FE-SEM) and transmission electron microscope (TEM) indicated that the morphology of PtCPs NRs was rod-like. The resulting FA-PtCPs NRs was used for the specific and ultra-sensitive temperature detection of cancer cells based on PtCPs NRs as a signal trigger unit and FA as a target recognition tool. After three-step reaction, oxidized 3,3',5,5'-tetramethylbenzidine (ox-TMB) with photothermal effect was obtained. Under 660 nm laser irradiation, such detection platform can convert the molecular recognition signal between FA and folate receptor (FR) of cancer cells into readable temperature value, which can be directly read by an ordinary thermometer, with a detection limit as low as 2 cells/mL. In addition, FA-PtCPs NRs could be used as fluorescent probes for in-situ bioimaging. Therefore, this photothermal sensing platform has a broad prospect in the field of point-of-care detection of cancer cells.

Surface engineering of linearly fused Au13 units using diphosphine and Cd doping.

Herein, surface engineering was delicately performed to assemble two new Au-Cd alloy nanoclusters, including [Cd2Au17(S-c-C6H11)12(DPPP)2](BPh4) and Cd2Au29(TBBT)17(DPPF)2. Both the Au13 (in Cd2Au17) and Au25 (in Cd2Au29) cores were covered by two identical Au2Cd(SR)6 motifs and two diphosphine ligands. In addition, their optical properties were explored to give clues on the kernel- and surface-dependent electronic structures.

Knockdown of Malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p/VEGF-A axis.

Diabetic retinopathy (DR), characterized by intraretinal vessel formation, is a major complication in diabetes. Neovascularization is an important characteristic of DR, but its formation mechanism remains unclear. In this research, Malat1, miR-205-5p, and VEGF-A levels in high glucose (HG) treat-human retinal microvascular endothelial cells (hRMECs) was detected with qRT-PCR. CCK-8 assay, transwell assay, and tube formation assay was applied to access hRMEC viability, migration, and angiogenesis. Expression level of endothelial-mesenchymal transition (EndMT) markers (VE-cadherin, FSP1, and α-SMA) was detected by western blotting assay. Interaction among Malat1, miR-205-5p, and VEGF-A was confirmed by dual-luciferase reporter assay. Furthermore, in vivo DR mouse model was induced, and the effect of Malat1 on DR and EndMT markers was confirmed through hematoxylin-eosin (HE) staining and western blotting. As a result, Malat1 and VEGF-A was upregulated while miR-205-5p was suppressed under HG conditions. Malat1 could sponge miR-205-5p to regulate VEGF-A expression. Malat1 knockdown inhibited hRMEC proliferation, migration, and tube formation by targeting miR-205-5p under HG conditions. Furthermore, inhibition of Malat1 prevented the HG-induced EndMT process. In summary, Malat1 knockdown diminished hRMEC dysfunctions by regulating miR-205-5p/VEGF-A, providing a useful insight for exploring new therapeutic target for DR.

Spatiotemporally controlled O2 and singlet oxygen self-sufficient nanophotosensitizers enable the in vivo high-yield synthesis of drugs and efficient hypoxic tumor therapy.

Carrying out the in vivo syntheses of drugs toxic to tumors based on the specific features of the tumor microenvironment is critical for ensuring specific antitumor efficacy. However, achieving in situ high-yield synthetic toxic drugs from non-toxic agents and reducing their drug resistance in hypoxic tumors remain challenges. Herein we created a tumor-microenvironment-responsive porous Pt/Pt(iv) methylene blue coordination polymer nanoshuttle (Pt/PtMBCPNS) photosensitizer with spatiotemporally controlled O2 and singlet oxygen (1O2) self-sufficient for the in vivo high-yield synthesis of drugs and efficient hypoxic tumor therapy. After being endocytosed, the nanophotosensitizer as a cascade catalyst was observed to effectively catalyze the conversion of endogenous H2O2 to O2, and was hence found to play a dual role in the enhanced tumor therapy. PtMBCPNSs, upon being irradiated with red light, efficiently converted O2 into 1O2. Subsequently, 1O2 oxidized non-toxic 1,5-dihydroxynaphthalene to form the anticancer agent juglone with a high yield. In addition, O2 was found to be able to improve the hypoxic microenvironment without light irradiation, thus enhancing the antitumor efficacy of the produced drugs and reducing drug resistance. As a result, by enhancing the synergistic effect of the treatment, this nanophotosensitizer significantly inhibited the growth of tumors and avoided damage to normal tissues/organs. Collectively, this work highlights a robust nanoplatform with the spatiotemporally controlled in vivo high-yield synthesis of drugs and generation of O2 to help overcome the current limitations of chemical-based therapies against hypoxic tumors.

Smart Responsive Luminescent Aptamer-Functionalized Covalent Organic Framework Hydrogel for High-Resolution Visualization and Security Protection of Latent Fingerprints.

Covalent organic frameworks (COFs) have been proposed as alternative candidates for "smart" materials due to their ordered π-columnar structures. However, it remains a challenge to develop external-stimuli-responsive luminescent COFs for confidential information protection. Here, we have designed and synthesized a water-dispersible and smart responsive luminescent carboxymethyl cellulose-COF hydrogel encapsulated 5-(dimethylamino)-N,N-bis (pyridin-2-ylmethyl) napthalene-1-sulfonamide, named CMC-COF-LZU1⊃DPYNS, for latent fingerprint imaging and encryption. We show that the fluorescence of CMC-COF-LZU1⊃DPYNS is reversibly switchable upon addition of Cu2+/H2O. This effect endows potential applications of tunable luminescent COFs based hydrogel as an invisible security probe for imaging, recording, storage, and security of latent fingerprint information. It is shown that the latent fingerprint information incubated by the aptamer-functionalized CMC-COF-LZU1⊃DPYNS hydrogel is invisible in the presence of Cu2+, but three levels of fingerprint features with high-resolution patterns could be readable upon addition of H2O under UV light. The design strategy provides a promising platform for the development of smart responsive luminescent COFs and their detection and protection of valuable latent fingerprint information.

Facile preparation of a Ca(ii) carboxymethyl cellulose complex with enhanced calcium bioavailability for treatment of osteoporosis.

At present, though calcium (Ca) reagents with high calcium contents are widely synthesized, their wide application is limited due to their low absorption rates and poor bioavailability. Here we use a carboxymethyl cellulose (CMC) derivative with high water solubility and biocompatibility as a ligand to bind Ca2+. The resulting CaCMC complex exhibits remarkable solubility and absorbability under both basic and acidic conditions as well as in stomach mimicking and the gastrointestinal tract. Importantly, this Ca reagent shows high in vivo calcium bioavailability. Data from osteoporosis mouse models show that the CaCMC complex is superior to calcium carbonate in the treatment of osteoporosis. Therefore, the resulting CaCMC complex is used as a new, highly effective and desirable Ca supplement for daily life and clinical applications.

Photochemical strategies for the green synthesis of ultrathin Au nanosheets using photoinduced free radical generation and their catalytic properties.

Two-dimensional gold nanosheets represent a class of materials with excellent chemical and structural properties, which are often prepared using a template or toxic CO in organic solvents. Here, we report methylene blue (MB) radicals as a reducing agent to grow freestanding hexagonal ultrathin Au nanosheets with well-tuned thicknesses in water. This is the first time that carbon organic radicals have been used as a reducing agent in metal nanosheet synthesis. Notably, no template is used throughout the synthesis process, and the yield of Au nanosheets is very high. It is found that MB is decisive in the growth of Au nanosheets because no Au nanosheets are obtained in the absence of MB with the same reaction parameters. The resulting nanosheets exhibit excellent catalytic activity during H2O2 decomposition to generate nontoxic O2. Thus, folic acid-conjugated oxygen generating nanosheets could detect cancer cells in serum samples with high sensitivity through pressure signals. Furthermore, the nanosheets exhibit highly efficient activity and selectivity toward the hydrogenation of α,ß-unsaturated aldehydes. We anticipate that using MB radicals for the high-yield synthesis of 2D materials in this unique system has demonstrated their effectiveness and provides a green alternative route for producing other 2D nanomaterials.

Formation of porous Cu hydroxy double salt nanoflowers derived from metal-organic frameworks with efficient peroxidase-like activity for label-free detection of glucose.

Currently, nanomaterials with peroxidase activity have become an important colorimetric tool for biomolecular detection. However, compared with natural enzymes, the efficiency of most nanozymes is still lower. Here, with a leaf-like metal-organic-framework-5 as both a precursor and a template and copper acetate as a second precursor, hierarchical Cu hydroxy double salt (HDS) nanoflowers have been prepared and used as a label-free glucose colorimetric detection platform. We have demonstrated a scalable and facile synthesis of hierarchical Cu HDS nanoflowers, and density functional theory (DFT) calculations confirmed that there exists a hydrogen bond between the terephthalate anions and the layer OH group. The composition of Cu hydroxyl double salt is [Cu4(OH)6][BDC]·2H2O. Importantly, for the first time, the as-prepared Cu HDSs were demonstrated as peroxidase mimics to catalyze the oxidation of the enzyme substrate, 3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, which accompanies a color change from colorless to blue and followed classic Michaelis-Menten models. Based on these findings, a colorimetric method based on Cu HDSs that is highly sensitive and selective for the detection of glucose was developed, with a low detection limit of 0.5 µM. The clinical applicability of the sensor is also proven to be suitable for sensing glucose in blood, suggesting that Cu HDSs could be used in the construction of portable sensors for point-of-care diagnosis and on-site tests.

Reversible Response of Luminescent Terbium(III)-Nanocellulose Hydrogels to Anions for Latent Fingerprint Detection and Encryption.

Fingerprint fluorescence imaging has become one of the most prominent technologies in the field of forensic medicine, but it seldom considers the security protection of detection information, which is of great importance in modern society. Herein we demonstrate that luminescent TbIII -carboxymethyl cellulose (CMC) complex binding aptamer hydrogels that are reversibly responsive to ClO- /SCN- can be used for the selective detection, protection, and storage of fingerprint information. The imaging information of the fingerprint can be quenched and recovered by ClO- /SCN- regulation, respectively, resulting in reversible on/off conversion of the luminescence signals for the encryption and decryption of multiple levels of information. The present study opens new avenues for multilevel imaging, data recording, and security protection of fingerprint information with tunable fluorescent hydrogels.

Facile synthesis of ultrathin two-dimensional nanosheets-constructed MCo2O4 (M = Ni, Cu, Zn) nanotubes for efficient photocatalytic oxygen evolution.

Hierarchical nanosheets-assembled nanotubes are of great interest for their unique physicochemical properties as well as their potential applications in a variety of fields. However, the synthesis of hierarchical mixed transition-metal oxides-based nanosheets-assembled nanotubes for highly efficient photocatalytic oxygen evolution is rarely reported. Herein, a simple and versatile approach was developed to synthesize hierarchical nanosheets-constructed MCo2O4 (M = Ni, Cu, Zn) nanotubes. Core-shell polyacrylonitrile (PAN)/M-cobalt hydroxide ultrathin nanosheet composite nanofibers were first synthesized by hydroxylation reaction between PAN/M-cobalt acetate hydroxide precursors and NaBH4. After calcination, these nanofibers as precursors were easily transformed into the corresponding hierarchical nanosheets-constructed MCo2O4 nanotubes. By applying a photocatalyst, the resultant MCo2O4 nanotubes, particularly the CuCo2O4 nanotubes, exhibited high photocatalytic activity and cycle stability toward water oxidation reaction with O2 generation rates of 51.1 mmol g-1 h-1 under visible light irradiation, which is higher than most reported catalysts. This approach is very versatile and can be applied to synthesize other hierarchical multi-element oxides-based nanosheets-constructed nanotubes for advanced applications.

Efficient Hydrogen-Generation CuO/Co3O4 Heterojunction Nanofibers for Sensitive Detection of Cancer Cells by Portable Pressure Meter.

Portable, low-cost, and quantitative detection of cancer cells at home and in the field has the potential to revolutionize medical diagnostics. We first report the design and synthesis of highly efficient folic-acid-conjugated hydrogen-generation tube-in-tube CuO/Co3O4 heterojunction nanofibers for highly sensitive and rapid recognition of cancer cells through a pressure signal under visible-light irradiation. The resultant nanofibers can dramatically enhance the hydrogen-generation activity of ammonia borane under visible-light irradiation. Such hydrogen-generation reaction can translate a molecular recognition event between folic acid and folate receptor to measurable pressure signal readout through a low-cost and portable pressure meter for target cancer cell detection. Limits of detection (LODs) down to 50 cells mL-1 in only 15 min can be achieved. This result is superior to those of the other reported methods, indicating the superiority of the new pressure-based sensor in terms of sensitivity. The present study establishes the pressure meter as a useful tool for early clinical point-of-care cancer diagnosis.

Monte Carlo cross-validation analysis screens pathway cross-talk associated with Parkinson's disease.

We purposed to identify underlying functional pathway cross-talk in Parkinson's disease (PD) through Monte Carlo cross-validation analysis. Microarray data set of E-GEOD-6613 was downloaded from ArrayExpress database. First, the identification of differentially expressed genes (DEGs) was implemented, following by extracting the potential disrupted pathway enriched by DEGs. In addition, a discriminating score (DS) was computed based on the distribution of gene expression levels by quantifying their pathway cross-talk for each pair of pathways. Furthermore, random forest (RF) classification model was utilized to identify the top ten paired pathways with high AUC between PD and healthy control samples using the tenfold cross-validation method. Finally, Monte Carlo cross-validation was repeated 50 times to explore the best pairs of pathways. After quantile normalization, a total of 9331 genes with higher than 0.25-fold quantile average across all samples were obtained. Totally, 42 DEGs and 19 differential pathways enriched from DEGs were identified. We then ranked each pathway according to their AUC values, the pair of pathways, phosphatidylcholine biosynthesis I, and PPAR signaling obtained the best AUC value of 0.942. Moreover, the paired pathways of mTOR signaling and CD28 signaling in T helper cells had higher AUC value of 0.837 in five bootstraps. Two paired pathways, including phosphatidylcholine biosynthesis I and PPAR signaling, as well as mTOR signaling and CD28 signaling in T helper cells were able to accurately classify PD and healthy control samples. Significantly, these paired pathways might be underlying biomarkers for early diagnosis and therapy of PD.

Two Schiff-base fluorescent sensors for selective sensing of aluminum (III): Experimental and computational studies.

Two Schiff-base fluorescent sensors have been synthesized, which both can act as fluorescent probes for Al(3+), upon addition of Al(3+), they exhibit a large fluorescence enhancement which might be attributed to the formation of 1:1 ligand-Al complexes which inhibit photoinduced electron transfer (PET) progress, and that the proposed binding modes of the sensors and Al(3+) are identified by theoretical calculations.