Preparation of ionic porous polymers for extraction of four phenolic endocrine disrupting chemicals from fish and water samples.

In this paper, series of ionic polymers were synthesized by crosslinking alkyl quaternary ammonium salts with 1,4-bis(chloromethyl)benzene. Among them, hyper-crosslinked polymer fabricated with dodecyl dimethyl benzyl ammonium chloride (HCP-DD) as monomer delivered superior adsorption performance for endocrine disrupting chemicals (EDCs). The adsorption mechanism mainly includes π-π stacking, hydrophobic and electrostatic interaction. With HCP-DD as solid phase extraction sorbent, a high performance liquid chromatography-diode array detection method was developed for the detection of four phenolic EDCs in water and fish samples. The detection limits of the method were 0.005-0.02 ng mL-1 for water samples and 3-30 ng g-1 for fish samples. The recoveries of EDCs in water samples and fish samples were 80-119% and 81.3-117% (relative standard deviations <4.4%), respectively. The study not only provides a route for preparation ionic porous polymers, but also highlights the applications of ionic polymers as efficient adsorbent to enrich organic pollutants.

NiFeB-assisted adsorption and activation of nitrogen to improve the photooxidation activity of zinc porphyrin.

This study effectively addresses the challenge of nitrogen adsorption and activation in photocatalytic nitrogen fixation by introducing an oxidizing co-catalyst, NiFeB hydroxides. The NiFeB hydroxides could provide reactive active sites and significantly enhance the nitrogen oxidation activity, offering a novel pathway for co-catalysts in nitrogen fixation reactions.

Fabrication of imidazoline-linked cationic covalent triazine framework for enrichment of environmental estrogens.

Imidazoline-linked cationic covalent triazine framework (IM-iCTF) was facilely prepared through the Debus-Radziszewski reaction, involving 4,4',4''-(1,3,5-triazine-2,4,6-triyl)trianiline, formaldehyde and methylglyoxal. The IM-iCTF was applied as a sorbent for cartridge solid-phase extraction (SPE). It provided good adsorption performance for estrogen and estrogen mimics including bisphenol F, bisphenol A, 7ß-estradiol, bisphenol B and estrone. The adsorption isotherm, adsorption kinetic model, thermodynamic calculations and adsorption mechanism were investigated to reveal the adsorption behavior. The IM-iCTF was employed for the extraction of the estrogens and estrogen mimics from water, fish and shrimp (fish and shrimp samples were extracted with acetonitrile before the SPE). The analytes were then determined by high-performance liquid chromatography with diode array detection. The limits of detection were 0.008-0.05 ng mL-1 for water, 0.015-0.11 µg g-1 for fish, and 0.012-0.10 µg g-1 for shrimp samples. This research not only offers a new approach to construct cationic covalent triazine framework, but also provides a reliable strategy for the adsorption/enrichment trace level of organic pollutants.

Mucin Binding Protein of Lactobacillus casei Inhibits HT-29 Colorectal Cancer Cell Proliferation.

Many Lactobacillus casei strains are reported to exhibit anti-proliferative effects on colorectal cancer cells; however, the mechanism remains largely unknown. While there has been considerable interest in bacterial small metabolites such as short chain fatty acids, prior reports suggested that larger-sized molecules mediate the anti-proliferative effect of L. casei. Here, other possible ways of communication between gut bacteria and its host are investigated. LevH1 is a protein displayed on the surface of L. casei, and its mucin binding domain is highly conserved. Based on previous reports that the cell-free supernatant fractions decreased colorectal cell proliferation, we cloned the mucin binding domain of the LevH1 protein, expressed and purified this mucin binding protein (MucBP). It has a molecular weight of 10 kDa, is encoded by a 250 bp gene, and is composed primarily of a ß-strand, ß-turns, and random coils. The amino acid sequence is conserved while the 36th amino acid residue is arginine in L. casei CAUH35 and serine in L. casei IAM1045, LOCK919, 12A, and Zhang. MucBP36R exhibited dose-dependent anti-proliferative effects against HT-29 cells while a mutation of 36S abolished this activity. Predicted structures suggest that this mutation slightly altered the protein structure, thus possibly affecting subsequent communication with HT-29 cells. Our study identified a novel mode of communication between gut bacteria and their host.

ERK1/2-dependent BDNF synthesis and signaling is required for the antidepressant effect of microglia stimulation.

Depressed mice have lower numbers of microglia in the dentate gyrus (DG). Reversal of this decline by a single low dose of lipopolysaccharide (LPS) may have antidepressant effects, but there is little information on the molecular mechanisms underlying this effect. It is known that impairment of brain-derived neurotrophic factor (BDNF) signaling is involved in the development of depression. Here, we used a combination of neutralizing antibodies, mutant mice, and pharmacological approaches to test the role of BDNF-tyrosine kinase receptor B (TrkB) signaling in the DG in the effect of microglial stimulation. Our results suggest that inhibition of BDNF signaling by infusion of an anti-BDNF antibody, the BDNF receptor antagonist K252a, or knock-in of the mutant BDNF Val68Met allele abolished the antidepressant effect of LPS in chronically stressed mice. Increased BDNF synthesis in DG, mediated by extracellular signal-regulated kinase1/2 (ERK1/2) signaling but not protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling, was essential for the antidepressant effect of microglial stimulation. These results suggest that increased BDNF synthesis through activation of ERK1/2 caused by a single LPS injection and subsequent TrkB signaling are required for the antidepressant effect of hippocampal microglial stimulation.

Acceptability of Vegetable Fortified Ugali in Sub-Saharan Africa.

Corn flour-based porridge like dough, ugali, is the staple food of low-income population in sub-Saharan Africa. Lack of vitamin A, carotenoids, and dietary fibers brings about serious health issues to this population. In this study, vegetables including bok choy, broccoli, cabbage, carrot, Chinese onion stalk (C_onion), mushroom, are added during the cooking of ugali, as nutritional supplements. The freeze-dried powder of each vegetable was used for its long storage, stable nutrients, and similar particle size. Sub-Saharan African assessors were trained and sensory evaluated the six different vegetable fortified ugali with the plain, unfortified as the control on five attributes. The plain ugali was indistinguishable with the C_onion stalk fortified in color, with the carrot and C_onion stalk fortified in odor, with all vegetables (except broccoli and mushroom) fortified ugali in taste, with carrot and C_onion stalk fortified in granularity, and with cabbage, carrot, C_onion stalk fortified in viscosity. Preference ranking analysis showed that the C_onion stalk fortified ugali is even more favorably preferred than the plain, unfortified ugali, probably due to the umami components in C_onion that serve as the taste enhancer. This study indicates that Chinese onion stalk is a potential vegetable supplement to population in the sub-Saharan Africa.

Statistics on the bioactive anthocyanin/proanthocyanin products in China online sales.

Due to their potential beneficial effects, anthocyanins and proanthocyanins have attracted great concern worldwide. Recently, anthocyanin/proanthocyanin-related health products have occupied a certain proportion of the market. However, there has not been a systematical assessment on collecting and analyzing the relevant information. In this study, information of anthocyanin/proanthocyanin-related health products on sale on the four major online shopping platforms in China has been collected from November 2020 to February 2021. A total of 144 valid samples from 91 brands were collected, among which blueberries and grape seeds are the main sources of anthocyanins and proanthocyanins, respectively. Besides, the average anthocyanins/proanthocyanins content in these products is 22.71%. Improving eyesight, anti-asthenopia and anti-oxidation are widely mentioned among the anthocyanin-related products, while more proanthocyanin-related products declare for anti-oxidation, whitening & spot lighting, and delay of skin aging & repairing skin damage effects. Among the products, 77.78% are capsules and tablets, and the average unit price of anthocyanins/proanthocyanins is $ 5.26/g. Data analysis shows that searching for high-quality raw materials, researching on the varieties and content of anthocyanins/proanthocyanins, focusing on the intake of specific population, and exploring better storage forms of anthocyanins/proanthocyanins may be important field in the future to promote the development of the anthocyanin/proanthocyanin-related health products.

Purification, Characterization, and Self-Assembly of the Polysaccharide from Allium schoenoprasum.

The major polysaccharide component from the stalk of Allium schoenoprasum (AssP) was extracted and purified. Gel filtration chromatography purified AssP exhibited a molecular weight of around 1.7 kDa, which was verified by MALDI-ToF-MS. The monosaccharide analysis revealed its composition as rhamnose: arabinose: galactose: glucose: mannose: fructose with a molar ratio of 0.03:2.46:3.71:3.35:1.00:9.93, respectively. The Congo-red assay indicated that there was no tertiary structure of this polysaccharide, however, it self-assembled into a homogenous nanoparticle with a diameter of ~600 nm as revealed by the dynamic light scattering measurement. The solution behavior of this polysaccharide was simulated. The association of this polysaccharide was both time dependent and concentration dependent. AssP forms spherical particles spontaneously as time passes by, and when the AssP concentration increased, the spherical particles increased their sizes and eventually merged into cylindrical micelles. The diversity of AssP hydrodynamic behavior endowed potential versatility in its future applications.

Antidepressive properties of macrophage-colony stimulating factor in a mouse model of depression induced by chronic unpredictable stress.

Previous studies have reported that macrophage-colony stimulating factor (M-CSF), a drug that is used to treat hematological system disease, can ameliorate chronic stress-induced depressive-like behaviors in mice. This indicates that M-CSF could be developed into a novel antidepressant. Here, we investigated the antidepressive properties of M-CSF, aiming to explore its potential values in depression treatment. Our results showed that a single M-CSF injection at the dose of 75 and 100 µg/kg, but not at 25 or 50 µg/kg, ameliorated chronic unpredictable stress (CUS)-induced depressive-like behaviors in mice at 5 h after the drug treatment. In a time-dependent experiment, a single M-CSF injection (100 µg/kg) was found to ameliorate the CUS-induced depressive-like behaviors in mice at 5 and 8 h, but not at 3 h, after the drug treatment. The antidepressant effect of the single M-CSF injection (100 µg/kg) in chronically-stressed mice persisted at least 10 days and disappeared at 14 days after the drug treatment. Moreover, 14 days after the first injection, a second M-CSF injection (100 µg/kg) still produced antidepressant effects at 5 h after the drug treatment in chronically-stressed mice who re-displayed depressive-like phenotypes. The antidepressant effect of M-CSF appeared to be mediated by the activation of the hippocampal microglia, as pre-inhibition of microglia by minocycline (40 mg/kg) or PLX3397 (290 mg/kg) pretreatment prevented the antidepressant effect of M-CSF in CUS mice. These results demonstrate that M-CSF produces rapid and sustained antidepressant effects via the activation of the microglia in the hippocampus in a dose- and time-dependent manner.

Apoptosis-triggered decline in hippocampal microglia mediates adolescent intermittent alcohol exposure-induced depression-like behaviors in mice.

Depression-alcohol addiction comorbidity is a common clinical phenomenon. Alcohol exposure in adolescence has been shown to induce depression-like behaviors in rodents. However, the mechanism of action for this type of depression remains unclear. Previous studies have reported that several different types of stress, such as chronic unpredictable stress and early social isolation, trigger depression-like symptoms in mice by inducing hippocampal microglial decline, which is mediated by the initial activation of the microglial cells. Since alcohol also activates microglia, we evaluated the dynamic changes in hippocampal microglia in mice receiving adolescent intermittent alcohol exposure (AIE). Our results showed that 14 days of AIE, followed by 21 days period of no treatment, induced behavioral abnormalities as well as a significant loss and dystrophy of hippocampal microglia in mice. We found that this AIE-induced decline in hippocampal microglia was mediated by both microglial activation and apoptosis, as (i) 1 day of alcohol exposure induced a distinct activation of hippocampal microglia followed by their apoptosis, and (ii) blocking the initial activation of hippocampal microglia by pretreatment with minocycline suppressed the AIE-induced apoptosis and loss of hippocampal microglia as well as the AIE-induced depression-like symptoms. Lipopolysaccharide (LPS), a classical activator of microglia, ameliorated the AIE-induced depression-like symptoms by reversing the decline in the hippocampal microglia. These results reveal a possible mechanism for AIE-induced depression and demonstrate that the restoration of hippocampal microglial homeostasis may be a therapeutic strategy for depression induced by alcohol intake and withdrawal.

Inhibition of tanshinone IIA on renin activity protected against osteoporosis in diabetic mice.

Context: Salvia miltiorrhiza Bge. (Labiatae) (SMB) is applied clinically for management of diabetic osteoporosis in China, and research results has suggested its potential action on renin-angiotensin system (RAS).Objective: This study screens and explores naturally occurring bioactive constituents from the root of SMB acting on renin activity and evaluates its osteoprotective efficacy in diabetic mice.Materials and methods: Human embryonic kidney (HEK) 293 cells, engineered to express human renin, were used as an in vitro model to identify bioactive compound, tanshinone IIA, inhibiting renin activity. The C57BL/6 mice (n = 10 in each group) with diabetes induced by streptozotocin (STZ) were intraperitoneally injected with tanshinone IIA (10 and 30 mg/kg). The mice without STZ treatment and the diabetic mice treated with aliskiren were used as non-diabetic control and positive control, respectively.Results: Tanshinone IIA was found to display inhibitory effects on renin activity of HEK-293 cells; moreover, it down-regulated protein expression of ANG II in human renin-expressed HEK-293 cells. Treatment of diabetic mice with tanshinone IIA with both doses could significantly decrease ANG II level in serum (from 16.56 ± 1.70 to 10.86 ± 0.68 and 9.14 ± 1.31 pg/mL) and reduce ANG II expression in bone, consequently improving trabecular bone mineral density and micro-structure of proximal tibial end and increasing trabecular bone area of distal femoral end in diabetic mice.Conclusions: This study revealed beneficial effects of tanshinone IIA on bone of diabetic mice, and potentially suggested the application of Salvia miltiorrhiza in the treatment of osteoporosis and drug development of tanshinone IIA as a renin inhibitor.

Antidepressive properties of microglial stimulation in a mouse model of depression induced by chronic unpredictable stress.

The decrease of microglia in the hippocampus is a novel mechanism for depression onset. Reversal of this decrease can ameliorate stress-induced depression-like behaviors in rodents. However, the property of this therapeutic strategy remains unclear. We addressed this issue by designing a series of behavioral experiments. Results showed that a single lipopolysaccharide (LPS) injection at the dose of 75 and 100 µg/kg, but not at 30 or 50 µg/kg, produced obvious antidepressant effects in chronic unpredictable stress (CUS) mice at 5 h after the drug administration. In the time-dependent experiment, a single LPS injection (100 µg/kg) ameliorated the CUS-induced depression-like behaviors in mice at 5 and 8 h, but not at 3 h, after the drug administration. The antidepressant effect of a single LPS injection persisted at least 10 days and disappeared at 14 days after the drug administration. 14 days after the first injection, a second LPS injection (100 µg/kg) still produced antidepressant effects in chronically-stressed mice who re-displayed depression-like behaviors at 5 h after the drug administration. The antidepressant effect of LPS appears to be dependent on microglia, as at 5 h after LPS administration (100 µg/kg), the CUS-induced decrease in microglial numbers and Iba-1 mRNA levels in the hippocampus was reversed markedly, and inhibition of microglia by minocycline (40 mg/kg) or PLX33297 (290 mg/kg) prevented the antidepressant effect of LPS in CUS mice. These results indicate that a single LPS injection displays rapid and sustained antidepressant effects in chronically stressed mice likely through stimulating hippocampal microglia.

Evaluation of the antidepressive property of ß-hydroxybutyrate in mice.

ß-hydroxybutyrate, a ketone body metabolite, has been shown to suppress depression-like behavior in rodents. In this study, we examined its antidepressive property in acute and chronic administration modes in mice by using forced swim test and tail suspension test. Results showed that the decrease effect of ß-hydroxybutyrate (300 mg/kg) on immobility time in the tail suspension test and forced swim test in stress-naive mice began to be significant at day 11. In a dose-dependent experiment, ß-hydroxybutyrate treatment (11 days) showed significant antidepressant activities at the dose of 200 and 300 mg/kg. Unlike fluoxetine, ß-hydroxybutyrate treatment (300 mg/kg) showed no antidepressant activities in the acute (1 hour before the test) and three times administration mode within 24 hours (1, 5, and 24 hours before the test). But in a co-administration mode, ß-hydroxybutyrate (100 mg/kg) -fluoxetine (2.5 mg/kg) co-administration exhibited an obvious antidepressant activity in the tail suspension test and forced swim test. Further analysis showed that the antidepressant effects of ß-hydroxybutyrate and fluoxetine were not associated with the change in mouse locomotor activity. Furthermore, both chronic ß-hydroxybutyrate treatment and ß-hydroxybutyrate-fluoxetine co-treatment suppressed chronic unpredictable stress-induced increase in immobility time in the tail suspension test and forced swim test as well as chronic unpredictable stress-induced decrease in mouse body weight. Taken together, these results indicate that ß-hydroxybutyrate (1) needs a relatively long time to show comparable behavioral activity to that of fluoxetine in assays that are sensitive to the behavioral effects of established antidepressant compounds and (2) can augment the antidepressant action of a sub-therapeutic dose of fluoxetine.

Identification of a microglial activation-dependent antidepressant effect of amphotericin B liposome.

Chronic stress-induced decline in microglia in the hippocampus is a newly hypothesized mechanism of depression, and reversal of this decline by microglial activators has been shown to suppress depression-like behaviors in mice. This suggests that activation of immune cells in the hippocampus may be a potential strategy for depression therapy. Since amphotericin B, an anti-fungal medication, is known to activate macrophages and microglia, we investigated whether conventional amphotericin B or its liposomal form displays antidepressant activity. Our results showed that both amphotericin B and its liposomal form at various doses induced obvious depression-like behaviors in naïve mice, likely owing to increased serum interleukin-6 (IL-6) and IL-1ß levels. However, under stressed conditions, amphotericin B liposome, but not amphotericin B itself, reversed chronic unpredictable stress (CUS)-induced increase in immobility time in the tail suspension test and forced swim test as well as CUS-induced decrease in sucrose intake in the sucrose preference test and the time spent in the center region of the open field test in a dose-dependent manner. Immunofluorescence analysis showed that amphotericin B liposome reversed the CUS-induced decline in dentate gyrus (DG) microglia, and inhibition or ablation of microglia in the hippocampus by minocycline (40 mg/kg) or PLX3397 pre-treatment (290 mg/kg) abrogated the antidepressant effect of the amphotericin B liposome in CUS-treated mice. These results not only identify a novel pharmacological effect of amphotericin B liposome, but further support the notion that microglial activation in the hippocampus is a potential strategy for depression therapy.