THBru attenuates diabetic cardiomyopathy by inhibiting RAGE-dependent inflammation.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

A Practical and Modular Method for Direct C-H Functionalization of the BODIPY Core via Thianthrenium Salts.

Direct structural modification of small-molecule fluorophores represents a straightforward and appealing strategy for accessing new fluorescent dyes with desired functionalities. We report herein a general and efficient visible-light-mediated method for the direct C-H functionalization of BODIPY, an important fluorescent chromophore, using readily accessible and bench-stable aryl and alkenylthianthrenium salts. This practical approach operates at room temperature with extraordinary site-selectivity, providing a step-economical means to construct various valuable aryl- and alkenyl-substituted BODIPY dyes. Remarkably, this protocol encompasses a broad substrate scope and excellent functional-group tolerance, and allows for the modular synthesis of sophisticated symmetrical and asymmetrical disubstituted BODIPYs by simply employing different combinations of thianthrenium salts. Moreover, the late-stage BODIPY modification of complex drug molecules further highlights the potential of this novel methodology in the synthesis of fluorophore-drug conjugates.

A novel ratiometric sensor for fluorimetric and visual dual-mode detection of Al3+ in environmental water based on the target-regulated formation of Eu MOFs.

Herein, a novel ratiometric sensor for fluorimetric and smartphone-assisted visual detection of Al3+ in environmental water was developed based on the target-regulated formation of Eu metal-organic frameworks (Eu MOFs). By employing 2-[4-(2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid (Hepes), Eu3+ and tetracycline (TC) as raw materials, Eu MOFs with red emission were facilely synthesized through the coordination of Eu3+ with Hepes and TC. However, upon the introduction of Al3+, a higher affinity of TC towards Al3+ resulted in the formation of a TC-Al3+ complex with green fluorescence and inhibited the generation of Eu MOFs. This led to an increase in green fluorescence and a decrease in red fluorescence accompanied by the fluorescence color of the solution changing from red to green under the illumination of the UV lamp. Thus, a ratiometric sensor for fluorimetric and the smartphone-assisted visual detection of Al3+ was established. The ratiometric sensor exhibited high sensitivity for Al3+ detection with a detection limit of 0.14 µM for fluorescence detection and 1.21 µM for visual detection. Additionally, the proposed strategy was successfully applied to detect Al3+ in the environmental water samples with satisfactory results, indicating great application prospects for environmental monitoring.

Cerebral endothelial cells mediated enhancement of brain pericyte number and migration in oxygen-glucose deprivation involves the HIF-1α/PDGF-ß signaling.

The present study focused on whether hypoxia-inducible factor-1alpha (HIF-1α) and platelet-derived factor-beta (PDGF-ß) are involved in the crosstalk between brain microvascular endothelial cells (BMECs) and brain vascular pericytes (BVPs) under ischaemic-hypoxic conditions. Mono-cultures or co-cultures of BVPs and BMECs were made for the construction of the blood-brain barrier (BBB) model in vitro and then exposed to control and oxygen-glucose deprivation (OGD) conditions. BBB injury was determined by assessing the ability, apoptosis, and migration of BVPs and the transendothelial electrical resistance and horseradish peroxidase permeation of BMECs. Relative mRNA and protein levels of HIF-1α and PDGF-ß, as well as tight junction proteins ZO-1 and claudin-5 were analyzed by western blotting, reverse transcription quantitative PCR, and/or immunofluorescence staining. Dual-luciferase reporter assays assessed the relationship between PDGF-ß and HIF-1α. Co-culturing with BMECs alleviated OGD-induced reduction in BVP viability, elevation in BVP apoptosis, and repression in BVP migration. Co-culturing with BVPs protected against OGD-induced impairment on BMEC permeability. OGD-induced HIF-1α upregulation enhanced PDGF-ß expression in mono-cultured BMECs and co-cultured BMECs with BVPs. Knockdown of HIF-1α impaired the effect of BMECs on BVPs under OGD conditions, and PDGFR-ß silencing in BVPs blocked the crosstalk between BMECs and BVPs under OGD conditions. The crosstalk between BMECs and BVPs was implicated in OGD-induced BBB injury through the HIF-1α/PDGF-ß signaling.

Hydrophilic 1T-WS2 Nanosheet Arrays toward Conductive Textiles for High-Efficient and Continuous Hydroelectric Generation and Storage.

Flexible hydroelectric generators (HEGs) are promising self-powered devices that spontaneously derive electrical power from moisture. However, achieving the desired compatibility between a continuous operating voltage and superior current density remains a significant challenge. Herein, a textile-based van der Waals heterostructure is rationally designed between conductive 1T phase tungsten disulfide@carbonized silk (1T-WS2 @CSilk) and carbon black@cotton (CB@Cotton) fabrics with an asymmetric distribution of oxygen-containing functional groups, which enhances the proton concentration gradients toward high-performance wearable HEGs. The vertically staggered 1T-WS2 nanosheet arrays on the CSilk fabric provide abundant hydrophilic nanochannels for rapid carrier transport. Furthermore, the moisture-induced primary battery formed between the active aluminum (Al) electrode and the conductive textiles introduces the desired electric field to facilitate charge separation and compensate for the decreased streaming potential. These devices exhibit a power density of 21.6 µW cm-2 , an open-circuit voltage (Voc ) of 0.65 V sustained for over 10 000 s, and a current density of 0.17 mA cm-2 . This performance makes them capable of supplying power to commercial electronics and human respiratory monitoring. This study presents a promising strategy for the refined design of wearable electronics.

A facile fluorescence Eu MOF sensor for ascorbic acid and ascorbate oxidase detection.

In this work, a facile fluorescence Eu3+-based metal-organic framework (Eu MOF) sensor for ascorbic acid (AA) and ascorbate oxidase (AAO) detection was developed. The fluorescence of the Eu MOF could be effectively quenched by Ce3+ but not by Ce4+ at an appropriate concentration, and thus, when the reductant AA was added into the solution containing Ce4+, Ce4+ was chemically reduced to Ce3+, which induced the decreased fluorescence signal of the Eu MOF. However, when AAO was introduced, AA was effectively oxidized to dehydroascorbic acid (DHAA) under the catalysis of AAO, and thus, Ce4+ could not be reduced, resulting in the fluorescence restoration of the Eu MOF. Hence, the concentration of AA and AAO could be determined by the fluorescence decrease and restoration of the Eu MOF. The fluorescent platform showed high sensitivity with a limit of detection of 0.32 µM for AA and 1.18 U L-1 for AAO, respectively. Moreover, the proposed method was successfully applied for AA and AAO determination in real samples, indicating great potential for biomedical application in complex matrices.

MXene-Decorated Smart Textiles with the Desired Mid-Infrared Emissivity for Passive Personal Thermal Management.

Multifunctional and long-term stable wearable heating systems have attracted extensive attention from experts, yet smart textiles that only rely on harvesting the body's heat without additional energy still face huge challenges in practical applications. Herein, we rationally prepared the monolayer MXene Ti3C2Tx nanosheets via an in situ hydrofluoric acid generation method, which was further employed to construct a wearable heating system of MXene @ polyester polyurethane blend fabrics (MP textile) for the passive personal thermal management through a simple spraying process. Owing to the unique two-dimensional (2D) structure, the MP textile presents the desired mid-infrared emissivity, which could efficiently suppress the thermal radiation loss from the human body. Notably, the MP textile with an MXene concentration of 28 mg/mL exhibits a low mid-infrared emissivity of 19.53% at 7-14 µm. Significantly, these prepared MP textiles demonstrate an enhanced temperature of more than 6.83 °C compared with those of favorably traditional fabrics, involving the black polyester fabric, pristine polyester polyurethane blend fabric (PU/PET), and cotton, suggesting a charming indoor passive radiative heating performance. The temperature of real human skin covered by MP textile is 2.68 °C higher than that covered by cotton fabric. Impressively, these prepared MP textiles simultaneously possess attractive breathability, moisture permeability, mechanical strength, and washability, which provide new insight into human body temperature regulation and physical health.

Isolation and identification of the components in Cybister chinensis Motschulsky against inflammation and their mechanisms of action based on network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Cybister chinensis Motschulsky belongs to the family Dytiscidae. As a traditional Chinese medicine, the insect is called Longshi in the folk and is commonly used to treat enuresis in children and frequent urination in the elderly. AIM OF THE STUDY: Inflammation is involved in chronic kidney disease. The previous study proved ethanol extract of C. chinensis exhibited anti-inflammation effects in the Doxorubicin-induced kidney disease. However, the material basis and their possible mechanism of the insect were still unclear. Thus, we aimed to separate the active compounds of the ethanol extract from C. chinensis and to investigate their possible mechanism of anti-inflammation by network pharmacology and molecular docking. MATERIALS AND METHODS: The insect was extracted with 75% ethanol to produce ethanol extracts and then were extracted by petroleum ether, ethyl acetate and n-butanol respectively. Silica gel column chromatography and preparative HPLC were applied to separate the compounds of the extract. The compounds were characterized and identified by NMR and mass. The compound associated genes were collected by BATMAN-TCM database and the inflammation associated genes were obtained through DigSee database. The protein-protein interaction (PPI) network was carried out via Search Tool for the Retrieval of Interacting Genes/Protein (STRING) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) target pathway analysis was performed in Database for Annotation, Visualization and Integrated Discovery (DAVID). The possible mechanism of compounds against inflammation was investigated by molecular docking. Finally, the anti-inflammatory effect of the representative compound was verified by the LPS-induced Raw 264.7 cell inflammatory model. TNF-α, IL-1ß and IL-6 of the cell supernatants were analyzed via using ELISA kits and the key proteins in JAK2/STAT3 signaling pathway were verified via the Western blot assays. RESULTS: Among crude extracts from C. chinensis, ethyl acetate extract showed the obvious anti-inflammatory effects. Nine compounds were isolated from ethyl acetate extract of Cybister chinensis for the first time, including benzoic acid (1), hydroxytyrosol (2), protocatechualdehyde (3), N-[2-(4-hydroxyphenyl)ethyl]acetamide (4), (2E)-3-phenylprop-2-enoic acid (5), 3-phenylpropionic acid (6), methyl 3,4-dihydroxybenzoate (7), 1,4-diphenyl butane-2,3-diol (8) and p-N,N-dimethylaminobenzaldehyde (9). After searching in the database, 1079 compound associated genes and 467 inflammation associated genes were found. The 137 common targets covered 77 signaling pathways, in which HIF-1 signaling pathway, TNF signaling pathway, influenza A, PI3K/Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and Jak-STAT signaling pathway were important for inflammation. Molecular docking studies showed compound 1, 4, 5, 6, 7 and 8 were the potential inhibitors of JAK2 protein. In addition, the in vitro test showed compound 5 reduced the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner. Furthermore, it was found that compound 5 inhibited the expression of p-JAK2 and p-STAT3 in LPS-induced RAW264.7 cells in a dose-dependent manner. CONCLUSIONS: Based on the network pharmacology and molecular docking, the study suggested that C. chinensis could relieve the inflammation based on the multi-compounds and multi-pathways, which provided the foundation for the medicinal application of C. chinensis.

[Effects of puerarin on rats with type 2 diabetes mellitus].

OBJECTIVE: To investigate the therapeutic effects of puerarin on rats with type 2 diabetes mellitus (T2DM). METHODS: T2DM models were established by high fat and high glucose feeding combined with a one-time intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Then the rats were randomly divided into normal group, model group, metformin group (MET, 40 mg/kg), puerarin low-dose group, medium-dose group and high-dose group (40, 80, 160 mg/kg), n=10. After the model was successfully established, rats were treated with corresponding drug intervention by intragastrical administration for 4 weeks. The body weight and fasting blood glucose (FBG) were measured per week, and blood samples were collected 24 h after the last administration, and serum levels of blood glucose, serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholestrol (HDL-C), serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine (SCr), and blood uric acid (UA) were measured. RESULTS: As compared with normal group, the body weight was decreased after 4 weeks-intervention in the model group, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were all increased,while HDL-C level was decreased (P＜0.05). As compared with model group,the body weight was increased after 4 weeks-intervention in metformin group and puerarin groups, and the levels of FBG, TC, TG, LDL-C, ALT, AST, BUN, SCr and UA were decreased (P＜0.01); meanwhile, HDL-C level was increased significantly (P＜0.05). CONCLUSION: Puerarin can reduce the weight loss of T2DM rats, decrease the blood lipid and blood glucose levels of T2DM rats, which can be used to control T2DM.

[The study of selecting sample detecting position and lead plate inner material in thin film method X-ray fluorescence measurement].

(1) In this paper type 316 stainless steel metal plate as the research object, the selection of sample detecting position was studied when thin film method X-ray fluorescence measurement was conducted. The study showed that the optimal location for the sample detection was sample distance X-ray tube and detector baseline 1cm with the baseline into a 16°angle. (2) Heavy metal pollutants of Pb, Cd and Cr in industrial ambient air as the main analysis object, when thin film method X-ray fluorescence conducted with lead plate protection, X-rays will penetrate the membrane and continuely stimulate the protective lead plate. Therefore there is lead spectral line interference in the filter membrane background spectrum, which will affect the detection of lead element in real samples. Studies show that when a layer of isolating material was applied between the thin sample and the protective lead plate, the interference of lead line can effectively be avoided. (3) Several rigid insulating material of type 316 stainless steel, brass, aluminum, red copper and PTEE as lead inner material were selected and studied. The study results showed that compared with X-ray fluorescence spectra of other lead inner materials, the X-ray fluorescence spectrum of red copper contained the least element spectral lines. There were not Cr, Cd and Pb spectrum peaks in the X-ray fluorescence spectrum of red copper. And the target timber scattering spectrum intensity in the high energy part was weaker compared to other X-ray fluorescence spectrum. The above analysis shows that red copper has the minimal disturbance to the actual measurement of heavy metals Cr, Cd and Pb. At the same time, red copper as lead inner materials can effectively avoid the interference of lead spectrum line in lead plate. So red copper is the best lead plate inner materials in thin film method X-ray fluorescence spectroscopy measurement. This study provides an important theoretical basis for the assembling and setting'up air and water weight metal X-ray fluorescence spectrometer.

[Inhibitory effect of DMPP on soil nitrification as affected by soil moisture content, pH and organic matter].

A laboratory incubation test with meadow brown soil was conducted to study the inhibitory effect of 3,4-dimethylpyrazole phosphate (DMPP) on soil nitrification as affected by soil moisture content (40%, 60% and 80% of the maximum field capacity), pH (4, 7 and 10), and organic matter (retained and removal). With the decrease of soil moisture content, the degradation of DMPP in soil tended to slow down, and the oxidation of soil NH4+ was more inhibited. At pH 10, more DMPP was remained in soil, and had the greatest inhibitory effect; at pH 7 and pH 4, the DMPP was lesser remained, with a smaller inhibitory effect. The removal of organic matter prolonged the remaining time of DMPP in soil, and decreased the apparent soil nitrification rate significantly.