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This study described the quality detection and rapid identification of frying oil waste points based on gas chromatography–ion mobility spectrometry (GC-IMS). A total of 48 volatile substances were identified, among which the levels of 11 components, including 2-pentylfuran, 2-butylfuran, and 2-hexanone, increased with prolonged frying time after 40 h in cottonseed oil. Conversely, the levels of hexanal, heptanal, and E,E-2,4-heptadienal decreased as frying time extended. Correlation analysis revealed a significant association between volatile substances of the oil and acid value (p < 0.05) and polar components with volatile substances (p < 0.05). Furthermore, significant differences in the types and contents of flavor substances were observed in cottonseed oil at different frying times (including before and after reaching the discard point) (p < 0.05). Subsequently, principal component analysis (PCA) results clearly showed that the cottonseed oil samples at different frying times were well distinguished by the volatile compounds; moreover, discriminant model analysis indicated a model accuracy rate of 100%. These results showed the potential of GC-IMS-based approaches in discriminating the waste points of frying oil.

Five different lignocellulosic raw materials (coconut shells, Moso bamboo, sawtooth oak, Chinese fir, and Masson pine) were used to prepare activated carbons by steam activation at 850 °C to evaluate the effects of their structures on physical activation. The chemical compositions, botanic forms, and pore structures of the lignocellulose-based charcoal samples were systematically characterized by proximate and ultimate analyses, scanning electron microscopy, and mercury injection porosimetry. It was found that the rate of the activation reaction between charcoal and steam is determined by the porosity of the precursor. Pore structure results show that the steam activation of coconut shell and bamboo charcoals primarily produced micropores, thus yielding microporous activated carbon materials with just a few mesopores, even following a high burn-off of >66%. The steam activation of sawtooth oak charcoals produced mainly micropores at a low burn-off of 50%. The steam activation of Chinese fir and Masson pine charcoals produced mainly mesopores at a burn-off of 0–80%. These mesopores were remarkably broadened to >20 nm on extending the activation time, resulting in a high vitamin B12 (VB12) adsorption capacity of ~530 mg/g. In conclusion, the raw lignocellulosic materials used as precursors have a decisive effect on the development of pore structures in activated carbon materials obtained through physical activation.

Microbial contamination has profoundly impacted human health, and the effective eradication of widespread microbial issues is essential for addressing serious hygiene concerns. Taking polystyrene (PS) membrane as an example, we herein developed report a robust strategy for the in situ preparation of chlorine-regenerable antimicrobial polymer molecular sieve membranes through combining post-crosslinking and nucleophilic substitution reaction. The cross-linking PS membranes underwent a reaction with 5,5-dimethylhydantoin (DMH), leading to the formation of polymeric N-halamine precursors (PS-DMH). These hydantoinyl groups within PS-DMH were then efficiently converted into biocidal N-halamine structures (PS-DMH-Cl) via a simple chlorination process. ATR-FTIR and XPS spectra were recorded to confirm the chemical composition of the as-prepared PS-DMH-Cl membranes. SEM analyses revealed that the chlorinated PS-DMH-Cl membranes displayed a rough surface with a multitude of humps. The effect of chlorination temperature and time on the oxidative chlorine content in the PS-DMH-Cl membranes was systematically studied. The antimicrobial assays demonstrated that the PS-DMH-Cl membranes could achieve a 6-log inactivation of E. coli and S. aureus within just 4 min of contact time. Additionally, the resulting PS-DMH-Cl membranes exhibited excellent stability and regenerability of the oxidative chlorine content.

Ligustrazine (TMP) is the main active ingredient extracted from Rhizoma Chuanxiong, which is used in the treatment of cardiovascular and cerebrovascular diseases, with the drawback of being unstable and readily sublimated. Cocrystal technology is an effective method to improve the stability of TMP. Three benzoic acid compounds including P-aminobenzoic acid (PABA), 3-Aminobenzoic acid (MABA), and 3,5-Dinitrobenzoic acid (DNBA) were chosen for co-crystallization with TMP. Three novel cocrystals were obtained, including TMP-PABA (1:2), TMP-MABA (1.5:1), and TMP-DNBA (0.5:1). Hygroscopicity was characterized by the dynamic vapor sorption (DVS) method. Three cocrystals significantly improved the hygroscopicity stability, and the mass change in TMP decreased from 25% to 1.64% (TMP-PABA), 0.12% (TMP-MABA), and 0.03% (TMP-DNBA) at 90% relative humidity. The melting points of the three cocrystals were all higher than TMP, among which the TMP-DNBA cocrystal had the highest melting point and showed the best stability in reducing hygroscopicity. Crystal structure analysis shows that the mesh-like structure formed by the O-H⋯N hydrogen bond in the TMP-DNBA cocrystal was the reason for improving the stability of TMP.

Using the aldehyde amine condensation procedure and the triphenylamine group as the skeleton structure, the new triphenylamine-aromatic aldehyde-succinylhydrazone probe molecule DHBYMH was created. A newly created acylhydrazone probe was structurally characterized by mass spectrometry (MS), NMR, and infrared spectroscopy (FTIR). Fluorescence and UV spectroscopy were used to examine DHBYMH’s sensing capabilities for metal ions. Notably, DHBYMH achieved a detection limit of 1.62 × 10−7 M by demonstrating exceptional selectivity and sensitivity towards Cu2+ ions in an optimum sample solvent system (DMSO/H2O, (v/v = 7/3); pH = 7.0; cysteine (Cys) concentration: 1 × 10−4 M). NMR titration, high-resolution mass spectrometry analysis, and DFT computation were used to clarify the response mechanism. Ultimately, predicated on DHBYMH’s reversible identification of Cu2+ ions in the presence of EDTA, a molecular logic gate was successfully designed.

It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, cholesterol lowering, neuroprotective, cardioprotective and so on. To our disappointment, poor solubility, low permeability and inferior bioavailability seriously limit its clinical application and market development. To optimize the solubility, permeability and bioavailability of daidzein, the cocrystal of daidzein and piperazine was prepared through a scientific and reasonable design, which was thoroughly characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Combining single-crystal X-ray diffraction analysis with theoretical calculation, detailed structural information on the cocrystal was clarified and validated. In addition, a series of evaluations on the pharmacogenetic properties of the cocrystal were investigated. The results indicated that the cocrystal of daidzein and piperazine possessed the favorable stability, increased solubility, improved permeability and optimized bioavailability of daidzein. Compared with the parent drug, the formation of cocrystal, respectively, resulted in 3.9-, 3.1-, 4.9- and 60.8-fold enhancement in the solubility in four different media, 4.8-fold elevation in the permeability and 3.2-fold in the bioavailability of daidzein. Targeting the pharmaceutical defects of daidzein, the surprising elevation in the solubility, permeability and bioavailability of daidzein was realized by a clever cocrystal strategy, which not only devoted assistance to the market development and clinical application of daidzein but also paved a new path to address the drug-forming defects of insoluble drugs.

Regulator of ribosome synthesis 1 (RRS1), a crucial regulatory factor in ribosome biogenesis, exerts a remarkable impact on the progression of breast cancer (BC). However, the exact mechanisms and pathways have not yet been fully elucidated. To investigate the impact of RRS1 on BC growth and metastasis, along with its underlying mechanisms. We discovered that RRS1 is overexpressed in BC tissues and cell lines. This study aims to regulate the level of RRS1 through lentiviral transfection technology to explore its potential function in BC cells. Knockdown of RRS1 resulted in the inhibition of cell proliferation, invasion, and migration, whereas overexpression had the opposite effects. We firstly identified the interaction between RRS1 and Glucose-Regulated Protein 78 (GRP78) using Co-immunoprecipitation (Co-IP) combined with mass spectrometry analysis, providing evidences of co-localization and positive regulation between RRS1 and GRP78. We observed that RRS1 inhibited the degradation of GRP78 through the ubiquitin–proteasome pathway, resulting in the stabilization of GRP78. In addition, our findings suggested that RRS1 promoted BC progression by activating the GRP78-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. In conclusion, this newly discovered RRS1/GRP78 signaling axis provides a molecular and theoretical basis for further exploring the mechanisms of breast cancer invasion and metastasis.

As emerging pollutants, organophosphate esters (OPEs) have been reported in coastal environments worldwide. Nevertheless, information on the occurrence and ecological risks of OPEs, especially the related transformation products, in mangrove wetlands is scarce. For the first time, the coexistence and distribution of OP triesters and their transformation products in three mangrove wetlands in the Beibu Gulf were investigated using ultrasonication and solid-phase extraction, followed by UHPLC-MS/MS detection. The studied OPEs widely existed in all the sampling sites, with the total concentrations ranging from 6.43 ng/g dry weight (dw) to 39.96 ng/g dw and from 3.33 ng/g dw to 22.50 ng/g dw for the OP triesters and transformation products, respectively. Mangrove wetlands tend to retain more OPEs than the surrounding coastal environment. Pearson correlation analysis revealed that the TOC was not the sole factor in determining the OPEs’ distribution, and degradation was not the main source of the transformation products in mangrove sediments in the Beibu Gulf. The ecological risks of selected OPEs for different organisms were also assessed, revealing a medium to high risk posed by OP diesters to organisms. The levels or coexistence of OPEs and their metabolites in mangroves need constant monitoring, and more toxicity data should be further studied to assess the effect on normal aquatic organisms.

Photocatalytic degradation of Malachite Green oxalate (MG) in a water body is of significant importance to our health protection, as it could cause various serious diseases. However the photocatalytic activity of most catalysts is still unsatisfactory, due to the poor reactive oxygen species production as a result of sluggish charge separation. Here, innovative nanoflower-shaped Bi2S3/BiFeO3 heterojunctions are prepared via a facile sol–gel method, exhibiting an enhanced reactive oxygen species generation, which leads to the excellent photocatalytic performance toward MG degradation. We verify that interfacing BiFeO3 with Bi2S3 could form a fine junction and offers a built-in field to speed up charge separation at the junction area; as a result, this shows much higher charge separation efficiency. By virtue of the aforementioned advantages, the as-prepared Bi2S3/BiFeO3 heterojunctions exhibit excellent photocatalytic performance toward MG degradation, where more than 99% of MG is removed within 2 h of photocatalysis. The innovative design of nanoflower-like Bi2S3/BiFeO3 heterojunctions may offer new viewpoints in designing highly efficient photocatalysts for environmentally related applications.

Plant flavonoids have attracted increasing attention as new antimicrobial agents or adjuvants. In our previous work, it was confirmed that the cell membrane is the major site of plant flavonoids acting on the Gram-positive bacteria, which likely involves the inhibition of the respiratory chain. Inspired by the similar structural and antioxidant characters of plant flavonoids to hydro-menaquinone (MKH2), we deduced that the quinone pool is probably a key target of plant flavonoids inhibiting Gram-positive bacteria. To verify this, twelve plant flavonoids with six structural subtypes were preliminarily selected, and their minimum inhibitory concentrations (MICs) against Gram-positive bacteria were predicted from the antimicrobial quantitative relationship of plant flavonoids to Gram-positive bacteria. The results showed they have different antimicrobial activities. After their MICs against Staphylococcus aureus were determined using the broth microdilution method, nine compounds with MICs ranging from 2 to 4096 μg/mL or more than 1024 μg/mL were eventually selected, and then their MICs against S. aureus were determined interfered with different concentrations of menaquinone−4 (MK−4) and the MKs extracted from S. aureus. The results showed that the greater the antibacterial activities of plant flavonoids were, the more greatly their antibacterial activities decreased along with the increase in the interfering concentrations of MK−4 (from 2 to 256 μg/mL) and the MK extract (from 4 to 512 μg/mL), while those with the MICs equal to or more than 512 μg/mL decreased a little or remained unchanged. In particular, under the interference of MK−4 (256 μg/mL) and the MK extract (512 μg/mL), the MICs of α-mangostin, a compound with the greatest inhibitory activity to S. aureus out of these twelve plant flavonoids, increased by 16 times and 8 to 16 times, respectively. Based on the above, it was proposed that the quinone pool is a key target of plant flavonoids inhibiting Gram-positive bacteria, and which likely involves multiple mechanisms including some enzyme and non-enzyme inhibitions.

Rutin, as a biological flavonoid glycoside, has very important medicinal value. The accurate and rapid detection of rutin is of great significance. Herein, an ultrasensitive electrochemical rutin sensor based on β-cyclodextrin metal–organic framework/reduced graphene oxide (β-CD-Ni-MOF-74/rGO) was constructed. The obtained β-CD-Ni-MOF-74 was characterized by X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and nitrogen adsorption and desorption. The β-CD-Ni-MOF-74/rGO presented good electrochemical properties benefiting from the large specific surface area and good adsorption enrichment effect of β-CD-Ni-MOF-74 and the good conductivity of rGO. Under optimal conditions for the detection of rutin, the β-CD-Ni-MOF-74/rGO/GCE showed a wider linear range (0.06–1.0 μM) and lower detection limit (LOD, 0.68 nM, (S/N = 3)). Furthermore, the sensor shows good accuracy and stability for the detection of rutin in actual samples.

Sepsis-associated acute kidney injury (SA-AKI) results in significant morbidity and mortality, and ferroptosis may play a role in its pathogenesis. Our aim was to examine the effect of exogenous H2S (GYY4137) on ferroptosis and AKI in in vivo and in vitro models of sepsis and explore the possible mechanism involved. Sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice, which were randomly divided into the sham, CLP, and CLP + GYY4137 group. The indicators of SA-AKI were most prominent at 24 h after CLP, and analysis of the protein expression of ferroptosis indicators showed that ferroptosis was also exacerbated at 24 h after CLP. Moreover, the level of the endogenous H2S synthase CSE (Cystathionine-γ-lyase) and endogenous H2S significantly decreased after CLP. Treatment with GYY4137 reversed or attenuated all these changes. In the in vitro experiments, LPS was used to simulate SA-AKI in mouse renal glomerular endothelial cells (MRGECs). Measurement of ferroptosis-related markers and products of mitochondrial oxidative stress showed that GYY4137 could attenuate ferroptosis and regulate mitochondrial oxidative stress. These findings imply that GYY4137 alleviates SA-AKI by inhibiting ferroptosis triggered by excessive mitochondrial oxidative stress. Thus, GYY4137 may be an effective drug for the clinical treatment of SA-AKI.

Ecdysone receptor (EcR) and chitinase play a critical role in the molting stage of insect pests. Each of them is considered a promising target for the development of novel insect growth regulators (IGRs). In the present paper, a total of 24 (23 novel) hexacyclic pyrazolamide derivatives were designed and synthesized by reducing the heptacycle and inserting small flexible linkers on the basis of the previously discovered dual-target compound D-27 acting simultaneously on EcR and Ostrinia furnacalis chitinase (OfChtI). Their insecticidal activities against Plutella xylostella, Spodoptera frugiperda, and Ostrinia furnacalis larvae were evaluated. The results revealed that the insecticidal activity was not significantly enhanced when the heptacycle on the pyrazole ring was reduced to a hexacycle. However, the insertion of an additional methylene spacer between the substituted phenyl ring and the amide bond can improve the insecticidal activity. Among the derivatives, the most potent compound, 6j, exhibited promising insecticidal activities against P. xylostella and S. frugiperda. Further protein binding assays and molecular docking indicated that 6j could target both EcR and OfChtI, and is a potential lead compound for IGRs. The present work provides valuable clues for the development of new dual-target IGRs.

With the rapid development of nanotechnology, electrospun nanofiber membranes (ENM) application and preparation methods have attracted attention. With many advantages such as high specific surface area, obvious interconnected structure, and high porosity, ENM has been widely used in many fields, especially in water treatment, with more advantages. ENM solves the shortcomings of traditional means, such as low efficiency, high energy consumption, and difficulty in recycling, and it is suitable for recycling and treatment of industrial wastewater. This review begins with a description of electrospinning technology, describing the structure, preparation methods, and factors of common ENMs. At the same time, the removal of heavy metal ions and dyes by ENMs is introduced. The mechanism of ENM adsorption on heavy metal ions and dyes is chelation or electrostatic attraction, which has excellent adsorption and filtration ability for heavy metal ions and dyes, and the adsorption capacity of ENMs for heavy metal ions and dyes can be improved by increasing the metal chelation sites. Therefore, this technology and mechanism can be exploited to develop new, better, and more effective separation methods for the removal of harmful pollutants to cope with the gradually increasing water scarcity and pollution. Finally, it is hoped that this review will provide some guidance and direction for research on wastewater treatment and industrial production.

Many ribosomal proteins are highly expressed in tumors and are closely related to their diagnosis, prognosis and pathological characteristics. However, few studies are available on the correlation between ribosomal proteins and chemoresistance. RRS1 (human regulator of ribosome synthesis 1), a critical nuclear protein involved in ribosome biogenesis, also plays a key role in the genesis and development of breast cancer by protecting cancer cells from apoptosis. Given that apoptosis resistance is one of the causes of the cisplatin resistance of tumor cells, our aim was to determine the relationship between RRS1 and cisplatin resistance in breast cancer cells. Here, we report that RRS1 is associated with cisplatin resistance in breast cancer cells. RRS1 silencing increased the sensitivity of MCF-7/DDP cells to cisplatin and inhibited cancer cell proliferation by blocking cell cycle distribution and enhancing apoptosis. AEG-1 (astrocyte elevated gene-1) promotes drug resistance by interfering with the ubiquitination and proteasomal degradation of MDR1 (multidrug resistance gene 1), thereby enhancing drug efflux. We found that RRS1 binds to and stabilizes AEG-1 by inhibiting ubiquitination and subsequent proteasomal degradation, which then promotes drug efflux by upregulating MDR1. Furthermore, RRS1 also induces apoptosis resistance in breast cancer cells through the ERK/Bcl-2/BAX signaling pathway. Our study is the first to show that RRS1 sensitizes breast cancer cells to cisplatin by binding to AEG-1, and it provides a theoretical basis to improve the efficacy of cisplatin-based chemotherapy.

Herein, we prepared Pt2CeO2 heterojunction nanocluster (HJNS) on multiwalled carbon nanotubes (MWCNTs) in deep eutectic solvents (DESs) which is a special class of ionic liquids. The catalyst was then heat-treated at 400 °C in N2 (refer to Pt2CeO2/CNTs-400). The Pt2CeO2/CNTs-400 catalyst showed remarkably improved electrocatalytic performance towards methanol oxidation reaction (MOR) (839.1 mA mgPt−1) compared to Pt2CeO2/CNTs-500 (620.3 mA mgPt−1), Pt2CeO2/CNTs-300 (459.2 mA mgPt−1), Pt2CeO2/CNTs (641.6 mAmg−1) (the catalyst which has not been heat-treated) and commercial Pt/C (229.9 mAmg−1). Additionally, the Pt2CeO2/CNTs-400 catalyst also showed better CO poisoning resistance (onset potential: 0.47 V) compared to Pt2CeO2/CNTs (0.56 V) and commercial Pt/C (0.58 V). The improved performance of Pt2CeO2/CNTs-400 catalyst is attributed to the addition of appropriate CeO2, which changed the electronic state around the Pt atoms, lowered the d-band of Pt atoms, formed more Ce-O-Pt bonds acting as new active sites, affected the adsorption of toxic intermediates and weakened the dissolution of Pt; on the other hand, with the assistance of thermal treatment at 400 °C, the obtained Pt2CeO2 HJNS expose more new active sites at the interface between Pt and CeO2 to enhance the electrochemical active surface area (ECSA) and the dehydrogenation process of MOR. Thirdly, DES is beneficial to the increase of the effective component Pt(0) in the carbonization process. The study shows a new way to construct high-performance Pt-CeO2 catalyst for the direct methanol fuel cell (DMFC).

Allylation of N-unsubstituted isatin N,N′-cyclic azomethine imines with Morita-Baylis-Hillman carbonates in the presence of 1–10 mol% DABCO in DCM at room temperature, rapidly gave N-allylated and N, β-diallylated isatin N,N′-cyclic azomethine imine 1,3-dipoles in moderate to high yields. The reaction features mild reaction conditions, easily practical operation, and short reaction times in most cases. Furthermore, the alkylated products were transformed into novel bicyclic spiropyrrolidine oxoindole derivatives through the [3+2] or [3+3]-cycloaddition with maleimides or Knoevenagel adducts.

Both insect ecdysone receptors and ultraspiracle belong to the nuclear receptor family. They form a nanoscale self-assembling complex with ecdysteroids in cells, transit into the nucleus, bind with genes to initiate transcription, and perform specific biological functions to regulate the molting, metamorphosis, and growth processes of insects. Therefore, this complex is an important target for the development of eco-friendly insecticides. The diamondback moth (Plutella xylostella) is a devastating pest of cruciferous vegetable crops, wreaking havoc worldwide and causing severe economic losses, and this pest has developed resistance to most chemical insecticides. In this study, highly pure EcR and USP functional domains were obtained by constructing a prokaryotic expression system for the diamondback moth EcR and USP functional domain genes, and the differences between EcR and USP binding domain monomers and dimers were analyzed using transmission electron microscopy and zeta potential. Radioisotope experiments further confirmed that the binding affinity of PonA to the EcR/USP dimer was enhanced approximately 20-fold compared with the binding affinity to the PxGST−EcR monomer. The differences between PonA and tebufenozide in binding with EcR/USP were examined. Molecular simulations showed that the hydrogen bonding network formed by Glu307 and Arg382 on the EcR/USP dimer was a key factor in the affinity enhancement. This study provides a rapid and sensitive method for screening ecdysone agonists for ecdysone receptor studies in vitro.

Picolinic acid and picolinate compounds are a remarkable class of synthetic auxin herbicides. In recent years, two new picolinate compounds, halauxifen-methyl (ArylexTM active) and florpyrauxifen-benzyl (RinskorTM active), have been launched as novel herbicides. Using their structural skeleton as a template, 33 4-amino-3,5-dicholor-6-(5-aryl-substituted-1-pytazolyl)-2-picolinic acid compounds were designed and synthesized for the discovery of compounds with potent herbicidal activity. The compounds were tested for inhibitory activity against the growth of Arabidopsis thaliana roots, and the results demonstrated that the IC50 value of compound V-7 was 45 times lower than that of the halauxifen-methyl commercial herbicide. Molecular docking analyses revealed that compound V-7 docked with the receptor auxin-signaling F-box protein 5 (AFB5) more intensively than picloram. An adaptive three-dimensional quantitative structure–activity relationship model was constructed from these IC50 values to guide the next step of the synthetic strategy. Herbicidal tests of the new compounds indicated that compound V-8 exhibited better post-emergence herbicidal activity than picloram at a dosage of 300 gha−1, and it was also safe for corn, wheat, and sorghum at this dosage. These results demonstrated that 6-(5-aryl-substituted-1-pyrazolyl)-2-picolinic acid compounds could be used as potential lead structures in the discovery of novel synthetic auxin herbicides.

The synthesis of dicyclic spiropyridazine oxoindole derivatives by using [3+3]-cycloaddition of N-unsubstituted isatin N,N′-cyclic azomethine imine 1,3-dipoles was reported. The products bearing two consecutive stereocenters, including spiroquaternary stereocenters in one ring structure, can be effectively obtained in moderate to excellent yields (20–93%) and low to moderate diastereoselectivities (1:9–10:1 dr). The synthesized compounds (>35 examples) were characterized by single-crystal XRD, FTIR, NMR, and mass spectral analysis.

Polysaccharides are important bioactive components of Nitraria retusa fruit (NRF). In this study, the ultrasonic-assisted extraction (UAE) conditions of polysaccharides from Nitraria retusa fruit (NRFPs) were optimized by response surface methodology (RSM). The structural characteristics and antioxidant activity were investigated. The maximum NRFPs yield of 3.35% was obtained under the following optimal conditions: temperature of 59.5 °C, time of 30.5 min, liquid-to-solid ratio of 19.5 mL/g. Three polysaccharide fractions, NRFP-1 (20.01 kDa), NRFP-2 (28.96 kDa), and NRFP-3 (67.45 kDa), were isolated. Glucose, galactose, and arabinose in different percentages were identified as the primary monosaccharide units. The Fourier transform infrared spectrometer (FT-IR) and nuclear magnetic resonance (NMR) analysis indicated the presence of α- and β-glycosidic bonds in NRFPs. The NRFP-3 exhibited the highest scavenging activities against DPPH, ABTS, -OH free radicals, and Fe+3-reducing activity.

Tetrahydrocurcumin (THC), one of the major metabolites of CUR, possesses several CUR-like pharmacological effects; however, its mechanisms of action are largely unknown. This manuscript aims to summarize the literature on the preventive role of THC on vascular dysfunction and the development of hypertension by exploring the effects of THC on hemodynamic status, aortic elasticity, and oxidative stress in vasculature in different animal models. We review the protective effects of THC against hypertension induced by heavy metals (cadmium and iron), as well as its impact on arterial stiffness and vascular remodeling. The effects of THC on angiogenesis in CaSki xenografted mice and the expression of vascular endothelial growth factor (VEGF) are well documented. On the other hand, as an anti-inflammatory and antioxidant compound, THC is involved in enhancing homocysteine-induced mitochondrial remodeling in brain endothelial cells. The experimental evidence regarding the mechanism of mitochondrial dysfunction during cerebral ischemic/reperfusion injury and the therapeutic potential of THC to alleviate mitochondrial cerebral dysmorphic dysfunction patterns is also scrutinized and explored. Overall, the studies on different animal models of disease suggest that THC can be used as a dietary supplement to protect against cardiovascular changes caused by various factors (such as heavy metal overload, oxidative stress, and carcinogenesis). Additionally, the reviewed literature data seem to confirm THC’s potential to improve mitochondrial dysfunction in cerebral vasculature during ischemic stroke through epigenetic mechanisms. We suggest that further preclinical studies should be implemented to demonstrate THC’s vascular-protective, antiangiogenic, and anti-tumorigenic effects in humans. Applying the methods used in the presently reviewed studies would be useful and will help define the doses and methods of THC administration in various disease settings.

Background: Targeting the CD47/SIRPα signaling pathway represents a novel approach to enhance anti-tumor immunity. However, the crystal structure of the CD47/SIRPα has not been fully studied. This study aims to analyze the structure interface of the complex of CD47 and IMM01, a novel recombinant SIRPα-Fc fusion protein. Methods: IMM01-Fab/CD47 complex was crystalized, and diffraction images were collected. The complex structure was determined by molecular replacement using the program PHASER with the CD47-SIRPαv2 structure (PDB code 2JJT) as a search model. The model was manually built using the COOT program and refined using TLS parameters in REFMAC from the CCP4 program suite. Results: Crystallization and structure determination analysis of the interface of IMM01/CD47 structure demonstrated CD47 surface buried by IMM01. Comparison with the literature structure (PDB ID 2JJT) showed that the interactions of IMM01/CD47 structure are the same. All the hydrogen bonds that appear in the literature structure are also present in the IMM01/CD47 structure. These common hydrogen bonds are stable under different crystal packing styles, suggesting that these hydrogen bonds are important for protein binding. In the structure of human CD47 in complex with human SIRPα, except SER66, the amino acids that form hydrogen bonds are all conserved. Furthermore, comparing with the structure of PDB ID 2JJT, the salt bridge interaction from IMM01/CD47 structure are very similar, except the salt bridge bond between LYS53 in IMM01 and GLU106 in CD47, which only occurs between the B and D chains. However, as the side chain conformation of LYS53 in chain A is slightly different, the salt bridge bond is absent between the A and C chains. At this site between chain A and chain C, there are a salt bridge bond between LYS53 (A) and GLU104 (C) and a salt bridge bond between HIS56 (A) and GLU106 (C) instead. According to the sequence alignment results of SIRPα, SIRPβ and SIRPγ in the literature of PDB ID 2JJT, except ASP100, the amino acids that form common salt bridge bonds are all conserved. Conclusion: Our data demonstrated crystal structure of the IMM01/CD47 complex and provides a structural basis for the structural binding interface and future clinical applications.

Flexible supercapacitors (FSCs) are limited in flexible electronics applications due to their low energy density. Therefore, developing electrode materials with high energy density, high electrochemical activity, and remarkable flexibility is challenging. Herein, we designed nitrogen-doped porous MXene (N-MXene), using melamine-formaldehyde (MF) microspheres as a template and nitrogen source. We combined it with an electrospinning process to produce a highly flexible nitrogen-doped porous MXene nanofiber (N-MXene-F) as a self-supporting electrode material and assembled it into a symmetrical supercapacitor (SSC). On the one hand, the interconnected mesh structure allows the electrolyte to penetrate the porous network to fully infiltrate the material surface, shortening the ion transport channels; on the other hand, the uniform nitrogen doping enhances the pseudocapacitive performance. As a result, the as-assembled SSC exhibited excellent electrochemical performance and excellent long-term durability, achieving an energy density of 12.78 Wh kg−1 at a power density of 1080 W kg−1, with long-term cycling stability up to 5000 cycles. This work demonstrates the impact of structural design and atomic doping on the electrochemical performance of MXene and opens up an exciting possibility for the fabrication of highly FSCs.

Moxidectin (MXD) is an antiparasitic drug used extensively in veterinary clinics. In this study, to develop a new formulation of MXD, a thermosensitive gel of MXD (MXD-TG) was prepared based on poloxamer 407/188. Furthermore, the gelation temperature, the stability, in vitro release kinetics and in vivo pharmacokinetics of MXD-TG were evaluated. The results showed that the gelation temperature was approximately 27 °C. MXD-TG was physically stable and can be released continuously for more than 96 h in vitro. The Korsmeyer–Peppas model provided the best fit to the release kinetics, and the release mechanism followed a diffusive erosion style. MXD-TG was released persistently for over 70 days in sheep. Part of pharmacokinetic parameters had a difference in female and male sheep (p < 0.05). It was concluded that MXD-TG had a good stability, and its release followed the characteristics of a diffusive erosion style in vitro and a sustained release pattern in vivo.

Polyphenolic acids are the widely occurring natural products in almost each herbal plant, among which rosmarinic acid (RA, C18H16O8) is well-known, and is present in over 160 species belonging to many families, especially the Lamiaceae. Aside from this herbal ingredient, dozens of its natural derivatives have also been isolated and characterized from many natural plants. In recent years, with the increasing focus on the natural products as alternative treatments, a large number of pharmacological studies have been carried out to demonstrate the various biological activities of RA such as anti-inflammation, anti-oxidation, anti-diabetes, anti-virus, anti-tumor, neuroprotection, hepatoprotection, etc. In addition, investigations concerning its biosynthesis, extraction, analysis, clinical applications, and pharmacokinetics have also been performed. Although many achievements have been made in various research aspects, there still exist some problems or issues to be answered, especially its toxicity and bioavailability. Thus, we hope that in the case of natural products, the present review can not only provide a comprehensive understanding on RA covering its miscellaneous research fields, but also highlight some of the present issues and future perspectives worth investigating later, in order to help us utilize this polyphenolic acid more efficiently, widely, and safely.

Removal of steroid hormones from aqueous environment is of prevailing concern because of their adverse impact on organisms. Using biochar derived from biomass as adsorbent to remove pollutants has become more popular due to its low cost, effectiveness, and sustainability. This study evaluated the feasibility of applying corn straw biochar (CSB) and dewatered sludge biochar (DSB) to reduce 17β-estradiol (E2) from aquatic solutions by adsorption. The experimental results showed that the adsorption kinetics and isotherm behavior of E2 on the two biochars were well described by the pseudo-second-order (R2 > 0.93) and Langmuir models (R2 > 0.97). CSB has higher E2 adsorption capacity than DSB, and the maximum adsorption capacity was 99.8 mg/g obtained from Langmuir model at 298 K, which can be attributed to the higher surface area, porosity, and hydrophobicity of this adsorbent. Higher pH levels (>10.2) decreased the adsorption capacities of biochar for E2, while the ionic strength did not significantly affect the adsorption process. The regeneration ability of CSB was slightly better than that of DSB. The possible adsorption mechanism for E2 on biochar is suggested as π–π interactions, H–bonding, and micropores filling. These results indicated that CSB has more potential and application value than DSB on reducing E2 from aqueous solutions when considering economy and removal performance.

Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using the SAG method have the structural characteristics of carboxylic acid dimer, and two cocrystals prepared using the SSE method formed cocrystal solvates with the structural characteristics of carboxylic acid monomer. For phenolic acids containing only one phenolic hydroxyl group (ferulic acid), when preparing cocrystals with PRA by using SAG and SSE, the same product was obtained. In addition, the weak molecular interactions that were observed in the cocrystal are explained at the molecular level by using theoretical calculation methods. Finally, the in vitro solubility of cocrystals without crystal solvents and in vivo bioavailability of PRA-FA were evaluated to further understand the influence on the physicochemical properties of API for the introduction of CCF.

The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures.

Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx–Que (1:1) and Apx–Que–2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx–Que–2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx–Que was increased compared with the physical mixture and Apx, and Apx–Que remained stable in high temperature and illumination conditions. Therefore, a drug–drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.

Shanxi-aged vinegar, a traditional Chinese grain-fermented food that is rich in polyphenols, has been shown to have therapeutic effects on a variety of diseases. However, there has been no comprehensive evaluation of the anti-inflammatory activity of polyphenols extracted from Shanxi-aged vinegar (SAVEP) to date. The anti-inflammatory activities of SAVEP, both in RAW 264.7 macrophages and mice, were extensively investigated for the potential application of SAVEP as a novel anti-inflammatory agent. In order to confirm the notion that polyphenols could improve inflammatory symptoms, SAVEP was firstly detected by gas chromatography mass spectrometry (GC-MS). In total, 19 polyphenols were detected, including 12 phenolic acids. The study further investigated the protective effect of SAVEP on lipopolysaccharide-induced inflammation in RAW264.7 macrophages and ICR mice. The results showed that compared with those of the model group, SAVEP could remarkably recover the inflammation of macrophage RAW264.7 and ICR mice. SAVEP can normalise the expression of related proteins via the suppression of MAPK/NF-κB pathway activation, inhibiting the expression of iNOS and COX-2 proteins, and consequently the production of inflammatory factors, thus alleviating inflammatory stress. These results suggest that SAVEP may have a potential function against inflammation.

Nujiangexanthone A (NJXA), a bioactive component isolated from the leaves of Garcinia nujiangensis, has been reported to exhibit anti-inflammatory, antioxidant, and antitumor effects. Our previous work has shown that NJXA induced G0/1 arrest and apoptosis, thus suppressing cervical cancer cell growth. The present study provides new evidence that NJXA can induce cell death in HeLa cells by promoting mitophagy. We first identified that NJXA triggered GFP-LC3 and YFP-Parkin puncta accumulation, which are biomarkers of mitophagy. Moreover, NJXA degraded the mitochondrial membrane proteins Tom20 and Tim23 and mitochondrial fusion proteins MFN1 and MFN2, downregulated Parkin, and stabilized PINK1. Additionally, we revealed that NJXA induced lysosome degradation and colocalization of mitochondria and autophagosomes, which was attenuated by knocking down ATG7, the key regulator of mitophagy. Furthermore, since mitophagy is induced under starvation conditions, we detected the cytotoxic effect of NJXA in nutrient-deprived HeLa cells and observed better cytotoxicity. Taken together, our work contributes to the further clarification of the mechanism by which NJXA inhibits cervical cancer cell proliferation and provides evidence that NJXA has the potential to develop anticancer drugs.

A co-crystal of rosiglitazone (Rsg) with berberine (Bbr), Rsg-Bbr, was prepared by the solvent evaporation method and characterized. The results showed that the electrostatic attraction existed between the nitrogen anion of rosiglitazone and the quaternary ammonium cation of berberine, and C-H···O hydrogen bonds were formed between Rsg and Bbr. In the crystal structure, rosiglitazone molecules stack into a supramolecular layer through π-π interactions while π-π interactions between berberine cations also result in a similar layer. The co-crystal presented a low moisture adsorption curve in the range of 0−95% relative humidity values at 25 °C. The improved dissolution rate of rosiglitazone in pH = 6.8 buffer solution could be achieved after forming co-crystal.

Recent advances in polymerase engineering have made it possible to isolate aptamers from libraries of synthetic genetic polymers (XNAs) with backbone structures that are distinct from those found in nature. However, nearly all of the XNA aptamers produced thus far have been generated against protein targets, raising significant questions about the ability of XNA aptamers to recognize small molecule targets. Here, we report the evolution of an ATP-binding aptamer composed entirely of α-L-threose nucleic acid (TNA). A chemically synthesized version of the best aptamer sequence shows high affinity to ATP and strong specificity against other naturally occurring ribonucleotide triphosphates. Unlike its DNA and RNA counterparts that are susceptible to nuclease digestion, the ATP-binding TNA aptamer exhibits high biological stability against hydrolytic enzymes that rapidly degrade DNA and RNA. Based on these findings, we suggest that TNA aptamers could find widespread use as molecular recognition elements in diagnostic and therapeutic applications that require high biological stability.

The volatile components of milks fermented using traditional starter cultures (Streptococcus thermophilus and Lactobacillus bulgaricus) and probiotics (Lactobacillus lactis, Lactobacillus bifidus, Lactobacillus casei, and Lactobacillus plantarum) were investigated by means of gas chromatography-mass spectrometry (GC-MS) combined with simultaneous distillation extraction (SDE). A total of 53 volatile compounds were detected, being 10 aldehydes, 11 ketones, 10 acids, 11 hydrocarbons, 7 benzene derivatives, and 4 other compounds. The starter culture was found to significantly affect the composition of volatile components in the fermented milks. Ketones and hydrocarbons were the dominant compounds in milk before fermentation, while acids were dominant compounds in the fermented samples. Compared with probiotics, there was greater abundance of volatile components in fermented milks with traditional strains. The importance of each volatile compound was assessed on the basis of odor, thresholds, and odor activity values (OAVs). Of the volatile compounds, 31 of them were found to be odor-active compounds (OAV > 1). The component with the highest OAVs in most samples was (E,E)-2,4-decadienal. Heatmap analysis and principal component analysis were employed to characterize the volatile profiles of milks fermented by different starter cultures. The results could help to better understand the influence of starter cultures on the odor quality of milks.

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics.

A multidrug crystal based on drug combinations was synthesized by the solvent evaporation method. This multicomponent crystal consisted of antidiabetic drugs Glimepiride (Gli) and Metformin (Met), which was performed by single crystal X-ray structure analysis. The results showed an enhancement of the pharmaceutical properties such as lower hygroscopicity and greater accelerated stability than the parent drug Met, and a higher solubility and dissolution rate than Gli.

Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S,12S,13R)-huperzine D-16-O-β-d-glucopyranoside (4), along with ten known analogues 5−14, were isolated from the whole plant of Lycopodiastrum casuarinoides. The structures of the new compounds were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. Compounds 1 and 2 possessed four connected six-membered rings, while compounds 3 and 4 were piperidine ring cleavage products. In particular, compound 4 was a lycopodium alkaloidal glycoside which is reported for the first time. Among the isolated compounds N-demethylhuperzinine (7), huperzine C (8), huperzine B (9) and lycoparin C (13) possessed significant inhibitory activity against acetylcholinesterase, and the new compound 1 showed moderate inhibitory activity. The structure activity relationships were discussed.

Euphorbia kansui is a Traditional Chinese Medicine widely used for the treatment of oedema, ascites and asthma. However, its serious hepatotoxicity hinders its safe clinical application. The process of stir-baking with vinegar is regularly used to reduce the toxicity of kansui. Up till now, the exact mechanism of the reduction in hepatotoxicity of kansui stir-baked with vinegar has been poorly defined. In this study, decreased contents of five diterpene and one triterpene in kansui (GS-1) after stir-baking with vinegar (GS-2) was investigated by UPLC-QTOF/MS. Flow cytometry and Hoechst staining were used to show that the stir-baking with vinegar process reduces kansui-induced cell apoptosis. Furthermore, the result also indicated that kansui stir-baked with vinegar protects LO2 cells from apoptosis by increasing the cell mitochondrial membrane potential (ΔΨm), decreasing the release of cytochrome c and inhibiting the activities of caspase-9 and caspase-3 as evidenced by means of high content screening (HCS), ELISA and western blotting. These results suggested that the stir-baking vinegar could reduce the hepatotoxicity of kansui by effectively decreasing the contents of toxic terpenoids and inhibiting the intrinsic pathway of hepatocyte cell apoptosis. In conclusion, the study provided significant data for promoting safer and better clinical use of this herb.

Background: Solasodine is a major bioactive ingredient in Solanum nigrum L. that has strong pharmacological characteristics. Therefore, the development of a simple and effective extraction method for obtaining solasodine is highly important. This study aims to provide a rapid and effective method for extracting solasodine from Solanum nigrum L. by microwave-assisted aqueous two-phase extraction (MAATPE). Methods: First, the high-performance liquid chromatography (HPLC) conditions were established for the detection of solasodine. Then, the aqueous two-phase system (ATPS) compositions were examined. On the basis of the results of single-factor experiments, for a better yield, response surface methodology (RSM) was used to optimize influential factors including the extraction temperature, extraction time and liquid-to-solid ratio. Results: The maximum extraction yield of 7.11 ± 0.08 mg/g was obtained at 44 °C, an extraction time of 15 min, and a liquid-to-solid ratio of 42:1 mL/g in the ATPS consisting of EtOH solvent, (NH4)2SO4, and water (28:16:56, w/w/w). The extraction yield of the alkaloid obtained using this method was markedly higher than those of microwave-assisted extraction (MAE) and ultrasonic-assisted extraction (UAE). Conclusions: In this work, solasodine was extracted by MAATPE for the first time and a high yield was obtained. MAATPE is a simple, rapid, and green technique for extraction from medical plants. Thus, the present study will enable the development of a feasible extraction method of active alkaloids from Solanum nigrum L.

The present work is devoted to the study of the electric properties: electric dipole moment, electric quadrupole moment, electric field gradients and electric dipole polarizability of molecule Zr2Fe on base of the full relativistic theory with basis set 3–21G. The electric dipole moment of Zr2Fe is symmetrical to the axis of C 2 V —the vector sum of two projections for two chemical bond FeZr (3.2883 Å), based on when there is charge distribution. The force constant k 2 is directly connected with electric field gradients.

Gastrodia elata tuber (GET) is a popular traditional Chinese medicines (TCMs). In this study, response surface methodology (RSM) with a Box⁻Behnken design (BBD) was performed to optimize the extraction parameters of gastrodin-type components (gastrodin, gastrodigenin, parishin A, parishin B, parishin C and parishin E). Different from the conventional studies that merely focused on the contents of phytochemical, we gave consideration to both quantitative analysis of the above six components by HPLC and representative bioactivities of GET, including antioxidation and protection of human umbilical vein endothelial cells (HUVEC). Four independent variables (ethanol concentration, liquid-material ratio, soaking time and extraction time) were investigated with the integrated evaluation index of phytochemical contents. With the validation experiments, the optimal extraction parameters were as follows: ethanol concentration of 41%, liquid⁻solid ratio of 28.58 mL/g, soaking time of 23.91 h and extraction time of 46.60 min. Under the optimum conditions, the actual standardized comprehensive score was 1.8134 ± 0.0110, which was in accordance with the predicted score of 1.8100. This firstly established method was proved to be feasible and reliable to optimize the extraction parameters of the bioactive components from GET. Furthermore, it provides some reference for the quality control and extraction optimization of TCMs.

The nuclear receptor, estrogen-related receptor alpha (ERRα; NR3B1), plays a pivotal role in energy homeostasis. Its expression fluctuates with the demands of energy production in various tissues. When paired with the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), the PGC/ERR pathway regulates a host of genes that participate in metabolic signaling networks and in mitochondrial oxidative respiration. Unregulated overexpression of ERRα is found in many cancer cells, implicating a role in cancer progression and other metabolism-related diseases. Using high throughput screening assays, we screened the Tox21 10K compound library in stably transfected HEK293 cells containing either the ERRα-reporter or the reporter plus PGC-1α expression plasmid. We identified two groups of antagonists that were potent inhibitors of ERRα activity and/or the PGC/ERR pathway: nine antineoplastic agents and thirteen pesticides. Results were confirmed using gene expression studies. These findings suggest a novel mechanism of action on bioenergetics for five of the nine antineoplastic drugs. Nine of the thirteen pesticides, which have not been investigated previously for ERRα disrupting activity, were classified as such. In conclusion, we demonstrated that high-throughput screening assays can be used to reveal new biological properties of therapeutic and environmental chemicals, broadening our understanding of their modes of action.

Suppressor of cytokine signaling 3 (SOCS3) is a cytokine-induced negative feedback-loop regulator of cytokine signaling. More and more evidence has proved it to be an inhibitor of signal transducers and activators of transcription 5 (STAT5). Here, we used dairy cow mammary epithelial cells (DCMECs) to analyze the function of SOCS3 and the interaction between SOCS3 and STAT5a. The expression of SOCS3 was found in cytoplasm and nucleus of DCMECs by fluorescent immunostaining. Overexpression and inhibition of SOCS3 brought a remarkable milk protein synthesis change through the regulation of JAK2/STAT5a pathway activity, and SOCS3 expression also decreased SREBP-1c expression and fatty acid synthesis. Inhibited STAT5a activation correlated with reduced SOCS3 expression, which indicated that SOCS3 gene might be one of the targets of STAT5a activation, DCMECs treated with L-methionine (Met) resulted in a decrease of SOCS3 expression. SOCS3 could also decrease cell proliferation and viability by CASY-TT detection. Together, our findings indicate that SOCS3 acts as an inhibitor of JAK2/STAT5a pathway and disturbs fatty acid synthesis by decreasing SREBP-1c expression, which validates its involvement in both milk protein synthesis and fat synthesis. In aggregate, these results reveal that low SOCS3 expression is required for milk synthesis and proliferation of DCMECs in vitro.

Carbonized pollen grains of Typha (CPT) were widely used in clinical for antithrombosis, wound and bleeding in China. In order to ensure the role of drugs, it is very important to control the quality of drugs. However, there is a lack of monitoring methods in the process of charcoal preparation. To characterize the process of CPT, we used thermal analysis, scanning electron microscope (SEM), color measurement, Fourier transform infrared spectrometry (FTIR) and HPLC. In this study, 7 min was the optimal processing time and the heating process condition should be controlled under 272.35 ± 7.23 °C. This comprehensive strategy to depict the whole carbonizing process would provide new ideas for researches on quality control of Traditional Chinese Medicine (TCM) and processing theory of charcoal medicine.

In this study, the ultra-high pressure extraction (UHPE) conditions for obtaining the maximum flavonoid yield from Xinjiang jujube (Ziziphus jujuba Mill.) leaves (XJL) were optimized by response surface methodology (RSM). Box–Behnken design (BBD) was applied to evaluate the effects of four variables (extraction temperature, pressure, time and liquid-to-solid ratio) on flavonoid yield. The results showed that the optimal flavonoid yield (25.45 ± 0.21 mg/g) was derived at 50.0 °C, 342.39 MPa, 11.56 min, and a liquid-to-solid ratio of 43.95 mL/g. Eight compounds were tentatively identified and quantified as kaempferol and quercetin glycosides with UPLC-ESI-MS. Compared to ultrasound-assisted extraction (UAE), UHPE can obtain higher concentrations of total flavonoids and stronger DPPH and ABTS radical-scavenging activities in a much shorter time. Therefore, UHPE is an alternative to UAE for obtaining flavonoids from XJL, which may be an optional method for large-scale industrial flavonoid extraction from XJL.

Euphorbia kansui stir-fried with vinegar (V-kansui) has promising biological activities toward treating malignant ascites with reduced toxicity compared to crude kansui. But the mechanism concerning promoting the excretion of ascites has not been systematically studied. The purpose of this paper was to investigate the possible mechanism of V-kansui in treating malignant ascites, including metabolic pathways and molecular mechanism using an integrated serum and urine metabolomics coupled with network pharmacology. Serum and urine samples of rats were collected and analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A comparison with crude kansui was also made to demonstrate the feasibility of processing. Principle component analysis (PCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were conducted to discriminate the groups, search important variables and reveal the possible pathways. A compound-target-metabolite network was finally constructed to identify the crucial targets to further understand the molecular mechanism. Sixteen significant metabolites contributing to the discrimination of model and control groups were tentatively screened out. They were mainly involved in the arachidonic acid metabolism, steroid hormone biosynthesis and primary bile acid to possibly reduce inflammatory and modulate the renin-angiotensin-aldosterone system to achieve treating malignant ascites. A bio-network starting from the compounds and ending in the metabolites was constructed to elucidate the molecular mechanism. HSP90AA1, ANXA2, PRDX6, PCNA, SOD2 and ALB were identified as the potential key targets that were responsible for the treatment of malignant ascites by the parameter combining the average shortest path length and betweenness centrality. The correlated 17 compounds were considered as the potential active ingredients in V-kansui. In addition, the metabolomics showed that the effect of V-kansui was almost in accordance with crude kansui. These results systematically revealed the mechanism of V-kansui against malignant ascites for the first time using metabolomics coupled with network pharmacology. V-kansui could be a promising safe and therapeutic medicine for the excretion of ascites.

Microwave-promoted efficient synthesis of a (Z)-3-methyleneisoindolin-1-one library from 2-bromobenzamides and terminal alkynes using Cu(OAc)2•H2O/DBU is described. Various benzamide substituents, ring substitutions, including heteroaryl, aryl acetylenes and aliphatic alkynes, could be applied to afford the desired products in good to moderate yield with high stereoselectivity. It is noteworthy that DBU maybe play a dual role as not only the base, but also as a ligand for copper. The reaction is catalyzed by the complex of Cu(OAc)2•H2O and DBU without other additives.

Salvianolic acid A (SalA) is one of the main efficacious, water-soluble constituents of Salvia miltiorrhiza Bunge. This study investigated the protective effects of SalA on peripheral nerve in diabetic rats. Administration of SalA (0.3, 1 and 3 mg/kg, ig) was started from the 5th week after strepotozotocin (STZ60 mg/kg) intraperitoneal injection and continued for 8 weeks. Paw withdrawal mechanical threshold (PWMT) and motor nerve conduction velocity (MNCV) were used to assess peripheral nerve function. The western blot methods were employed to test the expression levels of serine-threonine liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), silent information regulator protein3 (sirtuin 3/Sirt3) and neuronal nitric oxide synthase (nNOS) in sciatic nerve. Results showed that SalA administration could increase PWMT and MNCV in diabetic rats; reduce the deterioration of sciatic nerve pathology; increase AMPK phosphorylation level, up-regulate PGC-1α, Sirt3 and nNOS expression, but had no influence on LKB1. These results suggest that SalA has protective effects against diabetic neuropathy. The beneficial effects of SalA on peripheral nerve function in diabetic rats might be attributed to improvements in glucose metabolism through regulation of the AMPK-PGC1α-Sirt3 axis.

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, compared with scutellarin, it is very difficult to obtain scutellarein from Nature. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score and cerebral infarction volume with the administration of scutellarein were then used to compare its neuroprotective effects on focal cerebral ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO) with those of scutellarin. The results showed that scutellarein had better protective effect on focal cerebral ischemia/reperfusion than scutellarin, which laid the foundation for further research and development of scutellarein as a promising candidate for ischemic cerebro-vascular disease.