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Objective: Two experiments were conducted to provide a new approach for evaluating feed nutritional value by metabolizable glucose (MG) in piglet diets with different levels of starch and crude fiber. In Exp 1, a regression equation for MG was generated. In Exp 2, the equation was verified, and the optimal growth performance of piglets under appropriate MG levels was tested.Methods: In Exp 1, 20 weaned piglets (7.74±0.81 kg body weight [BW]) were randomly assigned to 1 of 4 treatments, including the basal diet containing different levels of MG (starch, 25.80%, 31.67%, 45.71%, 49.36%; crude fiber, 1.23%, 1.35%, 1.80%, 1.51%). The piglets were implanted with an ileal fistula, cannulation of the carotid artery, portal vein, and mesenteric artery. The chyme from the ileum fistula and blood samples were collected. In Exp 2, 30 weaned piglets (8.96±0.50 kg BW) were randomly assigned to 1 of 5 treatments, including the experimental diets with different levels of MG (37.6, 132.5, 300.0, 354.3, and 412.5 g/kg). The piglets’ BW, and feed consumption were recorded to calculate growth performance during the 28-d experiment.Results: In Exp 1, the MG levels in 4 diets were 239.62, 280.68, 400.79, and 454.35 g/kg. The regression equation for the MG levels and dietary nutrients was: Y (MG) = 12.13×X1 (starch)+23.18×X2 (crude fiber)−196.44 (R2 = 0.9989, p = 0.033). In Exp 2, treatments with 132.5 and 300.0 g/kg MG significantly (p

The hydroxyl radical, •OH, is one of the most reactive free radicals and plays significant roles in the oxidative degradation of organic pollutants and the electron transfer of inorganic ions in natural and engineered environmental processes. To quantitatively determine the contribution of •OH to oxidative reactions, a specific scavenger, such as tert-butyl alcohol (TBA), is usually added to eliminate •OH effects. Although TBA is commonly assumed to transform •OH into oxidatively inert products, this study demonstrates that utilizing TBA as an •OH scavenger generates the secondary peroxyl radical (ROO•), influencing the oxidation of transition metals, such as Mn. Although ROO• is less reactive than •OH, it has an extended half-life and a longer diffusion distance that enables more redox reactions, such as the oxidation of Mn2+(aq) to MnIV oxide solids. In addition to promoting Mn2+(aq) oxidation kinetics, TBA can also affect the crystalline phases, oxidation states, and morphologies of Mn oxide solids. Thus, the oxidative roles of •OH in aqueous redox reactions cannot be examined simply by adding TBA: the effects of secondary ROO• must also be considered. This study urges a closer look at the potential formation of secondary radicals during scavenged oxidative reactions in environmental systems.

How to efficiently and economically remove heavy metals from sewage has been a huge challenge in the world. This article reports on an adsorbing material with comb-shaped chitosan–grafted polyethyleneimine dithiocarbamate (CC-GP-D), which is prepared by grafting polyethyleneimine on chitosan as main chain via glutaraldehyde, then reduce the generated C=N double bond using NaBH4, and finally functionalizing primary and secondary amino groups with CS2. This comb-shaped structure adsorbent material can better contact with heavy metal ions, so that it can absorb more heavy metal ions at a faster rate. This material is more green, environmentally friendly and economical with chitosan as the main chain. The material can effectively adsorb heavy metals in sewage, such as cadmium (II), copper (II), lead (II), nickel (II), and cobalt (II). After 80 min of adsorption, its adsorption capacity for cadmium (II), copper (II), lead (II), nickel (II), and cobalt (II) reached 178.7 mg/g, 138.9 mg/g, 337.7 mg/g, 109.2 mg/g, 157.6 mg/g respectively.

This paper rationally designs the morphology and phase structure of carbon nanotube/polyaniline@MoS2 (CNT/PANI@MoS2) composites, with MoS2 conductive wrapping growing vertically on the outer layer of the composites via hydrothermal method. The crystalline nature and chemical properties are characterized by X-ray diffraction (XRD), Flourier transformation infrared spectroscopy (FT-IR), Raman spectroscopy (Raman), X-ray photoelectron spectroscopy (XPS). Morphology and microstructures are determined by Scanning electric microscopy (SEM), Transmission electron microscope (TEM) and Brunauer–Emmett–Teller (BET). The developed composites possess excellent electrochemical properties (the specific capacitance is substantially increased by ~119%, reaching 700.0 F g−1 after wrapping by MoS2) and good cycling stability (after over 5000 cycles retains 80.8% capacitance) in three-electrode systems, which indicating that the unique morphology of MoS2 shells endow the channels to composites for rapid charge transport and ionic diffusion. Furthermore, symmetric supercapacitors devices assembled with the CNT/PANI@MoS2 composites achieve specific capacitance of 459.7 F g−1 at 1 A g−1, capacitance retention is 97.4% after 10,000 cycles and reach superior energy density of 40.9 Wh kg−1 at the power density of 400 W kg−1. This strategy of three-dimensional wrapping method may open up a new potential to relieve the dilemma of degraded performance of supercapacitor, while improving the capacitance and stability for supercapacitors.

Neuroinflammation plays an important role in the onset and progression of neurodegenerative diseases. Microglia-mediated neuroinflammation have been proved to be the main reason for causing the neurodegenerative diseases. Ganoderic acid A (GAA), isolated from Ganoderma lucidum, showed anti-inflammatory effect in metabolism diseases. However, little research has been focused on the effect of GAA in neuroinflammation and the related mechanism. In the present study, lipopolysaccharide(LPS)-stimulated BV2 microglial cells were used to evaluate the anti-inflammatory capacity of GAA. Our data showed that GAA significantly suppressed LPS-induced BV2 microglial cells proliferation and activation in vitro. More strikingly, GAA promoted the conversion of BV2 microglial cells from M1 status induced by LPS to M2 status. Furthermore, GAA inhibited the pro-inflammatory cytokines release and promoted neurotrophic factor BDNF expression in LPS-induced BV2 microglial cells. Finally, we found that the expression of farnesoid-X-receptor (FXR) was prominently downregulated in LPS-stimulated BV2 microglial cells, antagonism of FXR with z-gugglesterone and FXR siRNA can reverse the effect of GAA in LPS-induced BV2 microglial cells. Taking together, our findings demonstrate that GAA can significantly inhibit LPS-induced neuroinflammation in BV2 microglial cells via activating FXR receptor.

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/d-phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers., Graphical abstract L/d-phenylalanine-based enantiomers are employed as building blocks to fabricate chiral nanofibers. Right-handed helical nanofibers significantly promote RPC neuronal differentiation, migration and synapse formation, which are mainly ascribed to activation of the RA metabolic pathway. This provides a feasible strategy to address retinal degeneration if chiral structure of extracellular microenvironment is considered.Image 1, Highlights • This is the first attempt to utilize chiral structure to induce retinal progenitor cell neuronal differentiation. • Right-handed nanofibers promote cell neuronal differentiation, whereas left-handed fibers decrease this effect. • The different cell differentiations are attributed to the stereoselective interaction between chiral fibers and proteins. • It provides new strategies for treatment of neurodegenerative diseases via optimizing chiral structures of biomaterials.

The concept of “umpolung” reactivity of π-allylmetal complexes has been developed as a powerful method for the allylation of aldehydes. This paper describes the photocatalytic umpolung strategy for...

Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents. Herein, icebreaker-inspired Janus nanomotors (JMs) are developed to address these transportation barriers. Janus nanorods (JRs) are constructed via seed-defined growth of mesoporous silica nanoparticles on doxorubicin (DOX)-loaded hydroxyapatite (HAp) nanorods. One side of JRs is grafted with urease as the motion power via catalysis of physiologically existed urea, and hyaluronidase (HAase) is on the other side to digest the viscous extracellular matrices (ECM) of tumor tissues. The rod-like feature of JMs prolongs the blood circulation, and the self-propelling force and instantaneous digestion of hyaluronic acid along the moving paths promote extravasation across blood vessels and penetration in tumor mass, leading to 2-fold higher drug levels in tumors after JM administration than those with JRs. The digestion of ECM in the diffusion paths is more effective to enhance drug retention and diffusion in tumors compared with enzyme-mediated motion. The ECM digestion and motion capabilities of JMs show no influence on the endocytosis mechanism, but lead to over 3-fold higher cellular uptake than those of pristine JRs. The JM treatment promotes therapeutic efficacy in terms of survival prolongation, tumor growth inhibition and cell apoptosis induction and causes no tumor metastasis to lungs with normal alveolar spaces. Thus, the self-driven motion and instantaneous clearance of diffusion routes demonstrate a feasible strategy to combat a series of biological barriers in the delivery of chemotherapeutic agents in favor of antitumor efficacy.

The development of long-wavelength emission carbon dots as a label-free sensing platform for the direct detection of glutathione (GSH) is still of great challenge. Herein, novel rose-red fluorescence carbon dots (wCDs) with a long-wavelength emission of 654 nm were successfully synthesized by a one-step microwave-solvothermal treatment of biomass Wedelia trilobata. The biomass-based wCDs could sensitively respond to copper ions (Cu2+) with a limit of detection (LOD) of 0.22 μM, which could be utilized as the fluorescence turn off–on sensor for the detection of GSH through recovering their fluorescence quenched by Cu2+. Moreover, the label-free wCDs with abundant active functional groups could be used to construct a direct quenching platform for the sensitive and selective detection of GSH by the dynamic quenching effect within 20 s without further modification, displaying a good linear range of 0–3.0 mM with a LOD of 35 μM that fits well with the GSH content in living cells (0.5–10 mM). Additionally, confocal imaging of living cells indicates that as-prepared wCDs with high photobleaching resistance and favorable biocompatibility possess the capacity for real-time monitoring of the variations of intracellular Cu2+ and GSH levels, and distinguishing cancerous cells from normal cells owing to the overexpression of GSH in cancerous cells. This study opens a new vision for developing an efficient and sensitive fluorescent sensor for the detection of GSH, and demonstrates the great prospects for wCDs in ion/molecule tracking, bioimaging and cancer diagnosis.

The on-surface synthesis of highly ordered, large-area covalent organic framework (COF) monolayers remains a major challenge in polymer chemistry. Herein, we investigate the polymerization of asymm...

The uneven dispersion of graphene in the resin matrix hinders its application in anticorrosion coatings. This study reports a new method where graphene oxide (GO) is coated on the surface of the poly(glycidyl methacrylate) (PGMA) microspheres to promote the dispersion of GO in epoxy resin (EP) to improve the anticorrosion performance of EP. GO-coated PGMA microspheres (PGMA@GO) were successfully fabricated by electrostatic interaction, which was confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, Raman spectroscopy, transmission electron microscopy, and zeta potential analysis. The scanning electron microscopy results showed that the PGMA microspheres were uniformly coated with GO, when the weight ratio of PGMA@GO was 1:2 (PGMA: GO). Electrochemical impedance spectroscopy and salt immersion experiments were performed to evaluate the corrosion resistance of the EP composite coatings. Comparing with pure EP and GO/EP coatings, the mechanical properties and anticorrosion properties of coatings were improved after adding PGMA@GO. When the addition amount of PGMA@GO (of 50 g EP) was 1.0 wt% and about 0.67 wt% GO was only needed, the PGMA@GO/EP composite coating possessed a high impedance of 5.68 × 108 Ω cm2 and a low breakpoint frequency of 0.39 Hz for 21-day immersion in 3.5 wt% NaCl solution. The anticorrosion mechanism of PGMA@GO/EP composite coating was also discussed.

Cardiovascular disease (CVD) has been considered as a major risk factor of death in recent decades. In CVDs, the NLRP3 inflammasome is important for inflammatory response and vascular damage. Therefore, safe and effective treatments to decrease NLRP3 inflammasome activation are required. Increased levels of free fatty acid (FFA) have been associated with the progression of CVD. Humanin, a kind of mitochondrial-derived peptide, has shown its beneficial effects in different types of cells. However, the roles of humanin in the NLRP3 inflammasome induced by FFA are still unknown. Here, we investigated the molecular mechanisms whereby humanin was found to exert protective effects in human aortic endothelial cells (HAECs) against FFA-caused endothelial injury. Here, treatment with humanin inhibited FFA-induced lactate dehydrogenase release, thereby demonstrating a protective capacity against cell death. Humanin also suppressed oxidative stress by downregulating the expression of reactive oxygen species and NOX2. Notably, humanin reduced NLRP3 and p10 and rescued FFA-induced dysfunction of adenosine monophosphate-activated protein kinase. Consequently, humanin inhibited the expression of IL-1β and IL-18. These results conclude that humanin might be a promising therapeutic agent for CVD.

Hexagonal boron nitride (hBN), as one of the two-dimensional (2D) materials, possesses many excellent properties like others. Herein, we report a novel self-healing epoxy filled with hBN. High compatibility between hBN and the epoxy matrix was obtained by the modification of hBN with silane coupling agent (Mi-Si). At the meantime, excellent self-healing behavior was achieved by retro Diels–Alder (r-DA) reaction between the maleimide functional group in the modified hBN (m-hBN-OH) and the added furfurylamine. Besides, the inadequate curing of epoxy led to the glass transition temperature (Tg), which is also seemed as the transition temperature for the shape memory of the epoxy, below the r-DA reaction temperature, and endowed the system with the shape memory-assisted self-healing properties. The m-hBN-OH was characterized by Fourier transform infrared spectra, nuclear magnetic resonance (1H-NMR) spectra, X-ray diffraction experiments, X-ray photoelectron spectroscopy measurements and so on. The new m-hBN-OH modifier was prepared with the optimized Mi-Si/hBN-OH weight ratio of 3.0, which could both improve the thermal property and achieve better thermal conductivity. This designed m-hBN-OH/epoxy could actually show ideal self-healing properties due to the shape memory-assisted self-healing effect. The thermal conductivity of the neat epoxy resin and the m-hBN-OH/epoxy was 0.2156 W m−1 K−1 and 0.4358 W m−1 K−1, respectively. As a novel material with efficient thermal conductivity, hBN made great contribution to the thermally induced shape memory and self-healing property. Systematic researches reveal that the composites are promising as long durable thermal interface materials, anti-scratch materials and so on.

Fucoxanthin (Fx), an allenic carotenoid from brown seaweeds or diatoms, has been demonstrated to prevent obesity. Gut dysbiosis and inflammation are two counted important incidence reasons of obesity and related diseases. In this paper, a mouse model induced by high-fat diet (HFD) was used to reveal the role of Fx in modulating intestinal homeostasis and treating obesity. In addition, 16S rRNA sequencing results inferred that Fx alleviated HFD-induced gut microbiota dysbiosis by significantly inhibiting the growth of obesity-/inflammation-related Lachnospiraceae and Erysipelotrichaceae while promoting the growth of Lactobacillus/Lactococcus, Bifidobacterium, and some butyrate-producing bacteria. The correlation analysis showed that some gut microbiota taxa were strongly correlated with obesity phenotypes and the inflammation level. In conclusion, dietary Fx has the potential to alleviate the development of obesity and related symptoms through mediating the composition of gut microbiota as demonstrated in mice. This study provides scientific evidence for the potential effects of Fx on obesity treatment.

Background Cervical cancer during pregnancy is rare. The management for stage IB3 during pregnancy remains unclear and challenging. We report a successful preserved pregnancy in a stage IB3 patient who was treated with neoadjuvant chemotherapy (NACT) plus radical surgery. Case presentation A 36-year-old pregnant woman was diagnosed with a 5-cm-diameter stage IB3 squamous cell carcinoma of the uterine cervix at 13 gestational weeks. The patient received 5 courses of systemic chemotherapy with carboplatin and paclitaxel every 3 weeks, followed by caesarean section and radical hysterectomy. Both the mother and infant are in good general condition. Conclusion This case suggests that NACT plus radical surgery could be one method to maintain pregnancy in stage IB3 cervical cancer diagnosed as early as 13 gestational weeks.

Developing highly efficient non-precious metal bifunctional catalysts towards both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is vital for pushing the development of Zn–air batteries. Here, we propose a nitrogen source-mediated strategy to synthesize active-N-rich defective carbon nanotube encapsulated Fe/Fe3C nanoparticles (denoted as Fe-N-OCNT) via one-step pyrolysis of OCNTs, Fe-Phen and an additional small molecule nitrogen source. N-source-regulated N configuration and steric hindrance effect of Fe-Phen coordination structures is proved to be a key factor affecting the electrocatalytic activity towards ORR and OER. The resulting Fe-N-OCNT exhibits a high half-wave potential of 0.86 V (vs. RHE) for ORR, and a low overpotential of 0.353 V for OER as well as a reversible oxygen electrode index of 0.723 V, superior to those of most recently reported advanced bifunctional catalysts. Multiple active component Fe/Fe3C cores strongly synergized with active N-rich carbon layers are responsible for the superior bifunctional electrocatalytic activity by forming a favorable interfacial electron interaction. Impressively, the assembled Zn–air batteries with the Fe-N-OCNT catalyst as the bifunctional air electrode deliver excellent charging–discharging performance, high power density (128.8 mW cm−2), energy density (779.3 W h kg−1) and long lifespan, demonstrating great potential for practical implementation.

To optimize the dispersion and interfacial interaction of ZnO nanoparticles in UV-curing poly(urethane acrylate) (PUA) nanocomposites, a series of amphiphilic polyurethane (APU)-functionalized ZnO ...

The changes of neurochemicals in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients has been observed via magnetic resonance spectroscopy in several studies. However, whether it exists the consistent pattern of changes of neurochemicals in the encephalic region during the progression of MCI to AD were still not clear. The study performed meta-analysis to investigate the patterns of neurochemical changes in the encephalic region in the progress of AD. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases, and finally included 63 studies comprising 1,086 MCI patients, 1,256 AD patients, and 1,907 healthy controls. It showed that during the progression from MCI to AD, N-acetyl aspartate (NAA) decreased continuously in the posterior cingulate (PC) (SMD: −0.42 [95% CI: −0.62 to −0.21], z = −3.89, P < 0.05), NAA/Cr (creatine) was consistently reduced in PC (SMD: −0.58 [95% CI: −0.86 to −0.30], z = −4.06, P < 0.05) and hippocampus (SMD: −0.65 [95% CI: −1.11 to −0.12], z = −2.44, P < 0.05), while myo-inositol (mI) (SMD: 0.44 [95% CI: 0.26–0.61], z = 4.97, P < 0.05) and mI/Cr (SMD: 0.43 [95% CI: 0.17–0.68], z = 3.30, P < 0.05) were raised in PC. Furthermore, these results were further verified by a sustained decrease in the NAA/mI of PC (SMD: −0.94 [95% CI: −1.24 to −0.65], z = −6.26, P < 0.05). Therefore, the levels of NAA and mI were associated with the cognitive decline and might be used as potentially biomarkers to predict the possible progression from MCI to AD.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020200308.

Lung cancer is the leading cause of death worldwide, and its incidence continues to increase. The treatment of lung cancer is related to the subtypes and stages of cancer, but the therapeutic effect is still unsatisfactory. We found that 10 of the 13 genes were differentially expressed in lung cancer, YTHDF1, RBM15, HNRNPC, KIAA1429, METTL3 and YTHDF2 are high expression while METTL14, ZC3H13, FTO and WTAP are low expression. HNRNPC and METTL3 genes were associated with the risk and prognosis of LUAD and could regard as biomarkers for early diagnosis and treatment, which provides a theoretical basis for LUAD.

Homocysteine (Hcy) is a non-essential amino acid produced from methionine. It has been reported that high concentrations of Hcy are related to the pathogenesis of neurodegenerative diseases and induce the disruption of the blood-brain barrier (BBB) by triggering oxidative stress and inflammation. LCZ696 is a novel antihypertensive agent that has been recently reported to possess promising anti-inflammatory properties. However, whether it has a protective effect on the BBB disruption is still unknown. For the first time, in this study, we aim to investigate whether LCZ696 exerts anti-inflammatory effects on Hcy-induced injury in brain endothelial cells and explore its neuroprotective properties. In in vivo experiments, we found that treatment with LCZ696 ameliorated oxidative stress by reducing malondialdehyde (MDA) and increasing glutathione (GSH). Furthermore, LCZ696 downregulated the excessive release of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at mRNA and protein levels. Importantly, it reversed the disruption of the BBB induced by Hcy stimulation. In the in vitro human brain microvascular endothelial cell (HBMVEC) experiments, compared to the control, the permeability of the endothelial monolayer was significantly enlarged, the expression level of occludin declined, and Egr-1 upregulated by the introduction of Hcy, and these were all reversed by the treatment with LCZ696. Lastly, we found that the protective effects of LCZ696 against Hcy-induced reduction of occludin and hyper-permeability of the endothelial monolayer were greatly abolished by the overexpression of Egr-1. Taken together, we found that LCZ696 protected against Hcy-induced impairment of BBB integrity by increasing the expression of occludin, all mediated by the inhibition of Egr-1.

Mammary epithelial cells are the only cells in the mammary glands that are capable of lactation and they are ideal for studying cellular and molecular biology mechanisms during growth, development and lactation of the mammary glands. The limiting factors in most of the currently available mammary epithelial cells are low cell viability, transgenerational efficiency and lactation function that renders them unsuitable for subsequent studies on mammary gland's cellular and lactation mechanisms and utilizing them as bioreactors. Hence, new methods are required to obtain mammary epithelial cells with high transgenerational efficiency and lactation function. In this study, transdifferentiation of goat ear fibroblasts (GEFs) into goat mammary epithelial cells (CiMECs) was induced in only eight days by five small molecule compounds, including 500 μg/mL VPA, 10 μM Tranylcypromine, 10 μM Forskolin, 1 μM TTNPB, 10 μM RepSox. Morphological observation, marker genes comparison, specific antigen expression and comparison of gene expression levels by transcriptome sequencing between the two types of cells that led to the primary deduction that CiMECs have similar biological properties to goat mammary epithelial cells (GMECs) and comparatively more lactation capacity. Therefore, we establish a novel reprogramming route to convert fibroblasts into CiMECs under fully chemically conditions. This study is expected to provide an in vitro platform for understanding cellular mechanisms such as mammary epithelial cells' fate determination and developmental differentiation, and also to find a new way to obtain a large number of functional mammary epithelial cells in vitro.

Associated with reduced hydrogen sulfide (H2 S) production in Hcy metabolic disorders, Plasma Hcy accumulation can bring about vascular dysfunction. Nevertheless, recently proposed therapies for vascular damage by estrogen could contribute to promoting endogenous hydrogen sulfide production. This study explores whether estrogen can come into play in protection in hyperhomocysteinemia and hypertensive patients at a population level, and then analyses the specific mechanism of estrogen protection in homocysteine (Hcy)-treated human umbilical vein endothelial cells (HUVECs) at the foundational level. A case-control study, conducted on 1277 female hypertension and non-hypertensive patients from Hunan Provincial People's Hospital, showed that the Hcy concentration of hypertensive patients emerged higher than that of healthy controls (P < .001), and that of estrogen was the reverse (P < .001). Estrogen had a negative correlation with systolic blood pressure and plasma Hcy concentration. HUVECs were treated with estrogen and Hcy in the basic experimental part, and 17β-estradiol (E2β) stimulated proliferation and inhibited damage in Hcy-treated umbilical vein endothelial cells. Treatment with Hcy dampens the expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) then cuts down H2 S production in cultured HUVECs, however, E2β reverses this process. To sum up, we have demonstrated a significant correlation between estrogen, Hcy concentration and systolic blood pressure reduction, which is bound up with Hcy metabolism and endogenous hydrogen sulfide production. The role of E2β was further strengthened by CBS and the CSE inhibitor through overthrowing the change in hydrogen sulfide of Hcy-treated HUVECs.

Epithelial cell adhesion molecule (EpCAM), which is a transmembrane glycoprotein, is related to tumor progression. We demonstrated that EpCAM plays important roles in proliferation, apoptosis, and metastasis during breast cancer (BC) progression. But the role of N-glycosylation in EpCAM in tumor aggressiveness is not clear. Here, we evaluated the role of N-glycosylation of EpCAM in stemness and epithelial-mesenchymal transition (EMT) characteristics. EpCAM overexpression increases the expression of stemness markers (NANOG，SOX2, and OCT4) and EMT markers (N-cadherin and vimentin) under the condition of hypoxia in BC. Knockdown of EpCAM and mutation of N-glycosylation of EpCAM maintained in severe hypoxia lead to a significant reduction of stemness/EMT markers. In addition, we found that N-glycosylation of EpCAM is a crucial factor during this process. This demonstrates that EpCAM has a novel regulatory role in stemness/EMT dependence of hypoxia-inducible factor 1-alpha via regulating nuclear factor kappa B in BC cells. Hence, our study reveals EpCAM glycosylation modification as a new regulator of stemness/EMT under hypoxic in BC and points out EpCAM as a potential therapeutic target.

This study focuses on developing a new colloidal gold immunochromatographic strip for the rapid and specific detection of subgroup A of avian leukosis virus (ALV-A) in clinical practice based on immunochemistry responses using colloidal gold nanoparticles, monoclonal antibody (MAb) and polyclonal antibody (PAb). The solution containing colloidal gold particles (Ф20 nm) is prepared by the reduction of chloroauric acid and sodium citrate. The MAb and PAb are used to target ALV-A as colloidal gold-MAb conjugates and capture antibodies, and their optimum concentrations are 10 μg/mL and 2.0 mg/mL, respectively. The optimum pH in the reaction system for the colloidal gold-MAb complex is pH 8.3. The specificity results show that the developed strip can detect ALV-A but not ALV-B/J/K. The sensitivity of the strip is 32˜64 TCID50/mL for ALV-A detection and 8˜80 ng/mL for ALV-A gp85 protein. The strip remains stable in storage at 4 °C for 180 d and can detect ALV-A in many tissue samples, including blood, cloacal swab, and egg albumin samples as well as cell samples in vitro. Additionally, it does not require any equipment, and its assay time and cost are much less than those of ELISA. Therefore, this strip is convenient, rapid and effective for detecting ALV-A in avian clinical applications.

Production of polyhydroxyalkanoates (PHA) from wastes has gained increasing attention for the related low costs and high environmental benefits. Phosphorus limitation is a potential strategy used to facilitate PHA production, yet excessive limitation was previously reported to cause negative effects. This study was the first to investigate the optimum phosphorus limitation for PHA accumulation from thermal-hydrolyzed sludge. The results showed that the maximum PHA content increased from 23 wt% to 51 wt% when phosphorus concentration was limited from 127.60 to 1.35 mg/L, indicating that a lower phosphorus concentration would promote maximum PHA accumulation. Batch tests performed with synthetic substrates (containing one specific VFA for each batch) confirmed that the effect of phosphorus content on PHA production was mainly devoted by the efficiency of the conversion of acetate to PHA. The PHA yields on acetate (YPHA/ac) were 0.68 and 0.05 Cmol/Cmol under phosphorus-limited (1 mg/L) and -excess (100 mg/L) conditions, respectively. A mathematical model was developed to describe the correlation between phosphorus concentration and YPHA/ac, which can fit the experimental data and predict the results properly. Finally, further (ammonium-) nitrogen restriction did not efficiently cause the additional improvement of PHA production under the conditions of phosphorus limitation.

With the use of contact material simulating test device, experiments are conducted for the contact materials AgW60, CuW60 and Cu and their different pairing under the conditions of DC voltage and current 270VDC/200A and surrounding atmosphere of carbon dioxide and nitrogen. The welding resistance, average welding force and the relationship between welding force and the number of operations during welding were measured and analyzed. Experiments show that the anti-welding ability of the three materials in the symmetric pairing of carbon dioxide and nitrogen is ranked as AgW60>Cu>CuW60. The "intermediate effect" occurs in the anti-welding properties of the asymmetric pairing. The relationship between the number of operations required for each welding and the average average welding force is approximately an inverse proportional function.

Objective This study aimed to identify and evaluate the mechanism by which apoptosis and cell cycle arrest were induced by dinaciclib in lymphoma Raji cells. Methods The colony formation assay was used to detect cell proliferation of Raji cells. Cell cycle arrest and cell apoptosis were determined by flow cytometry and TUNEL assays, respectively. Protein expression related to the Raji cell state was evaluated by Western blot. The Raji/Dinaciclib drug‐resistant cell line was established, where the regulating functions of CDK1‐involved pathway were verified. In addition, the effect of dinaciclib in vivo was examined in orthotopically implanted tumors in nude mice. Results Cell apoptosis was induced, and DNA synthesis ability was decreased in a time‐dependent manner in dinaciclib‐treated lymphoma Raji cells. Furthermore, the cell cycle was found to be blocked in the G2/M Phase. Further study indicated that CDK1‐involved pathway played a key regulatory role in this process. It was revealed by cell transfection that the expression of cell cycle proteins was downregulated after treatment with dinaciclib through a CDK1‐involved pathway, which eventually led to apoptosis. Knockdown of CDK1 restored the sensitivity of the Raji/Dinaciclib cells to dinaciclib. Xenograft model of nude mice showed that dinaciclib treatment in vivo could effectively inhibit tumor growth, consistent with the experiment results mentioned before. Conclusion In this study, we clarified the mechanisms through which dinaciclib induces Raji cell apoptosis and blocks the cell cycle through a CDK1‐involved pathway, which supported that dinaciclib had potential values in the treatment of lymphoma.

Wound healing requires an anti-inflammatory microenvironment and a healing cascade reaction, while transition from the inflammatory to the proliferative phase is necessary for the regeneration process. However, the use of biomimetic materials may induce local chronic inflammation, which could lead to serious infection and adhesion, when their ability to modulate inflammatory conditions has not been evaluated. To accelerate the wound-healing process, we envisioned a scaffold that can better regulate the immune response while reducing the inflammatory response. In the present study, in addition to the unique mechanical properties and higher rates of selective protein adsorption, electrospun fibers provided an anti-inflammatory microenvironment and closely resembled features of natural extracellular matrix, which could regulate immune-cell migration by its molecular component, providing greater regeneration potential in wound healing. Moreover, we grafted basic fibroblast growth factor (bFGF) on the surface of poly- l -lactic acid (PLLA) to improve the hydrophilicity, ensuring the strength and biocompatibility of the material, which could affect the immune cytokines and inhibit the inflammatory reaction through a constant bFGF release. Furthermore, the pattern of cell–material interaction exhibited by PLLA-bFGF promoted human vaginal fibroblast proliferation, improved the expression of collagen genes and secretion of the proteins, including COL-1/3, and regulated the expression of immune-related cytokines, including transforming growth factor β1 and tumor necrosis factor-α. The rabbit abdominal wall hernia in vivo model revealed the same effects. Overall, the PLLA-bFGF scaffold may promote pelvic organ prolapsed (POP) regeneration through its properties of providing an anti-inflammatory microenvironment and regulating the activities of immune-regulative factors, and may thus be highly practical as a template for transvaginal repair in POP treatment.

Glycosylation inhibition can improve the efficacy of antitumor drugs and enhance the apoptosis of cancer cells, thus holding great potential for cancer treatment. Inhibition of N-glycosylation induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), and eventually triggers ER stress-related apoptosis. Unfortunately, the detailed timeline of these cell responses and protein expression alterations related to N-glycosylation inhibition is not explicit yet, and the pathways involved in different stages of N-glycosylation inhibition still need to be characterized. In this study, the dynamic proteome alterations related to N-glycosylation inhibition were investigated by further analyzing our previously published quantitative proteomics data from tunicamycin (TM)-treated ovarian carcinoma (OVCAR-3) cells. The results revealed that N-glycosylation inhibition not only directly affects the expression of glycosylated proteins but also alters an extended scale of proteins. Functional annotation of these altered proteins demonstrated that proteins related to ER stress start changing within 6 h, followed by UPR within 24 h, and eventually ER stress-related apoptosis is triggered after 48 h, indicating the conversion of cellular response from positive to negative. The dynamic proteome data presented here provide important information for better understanding of the significance of N-glycosylation to cell survival and TM-related cancer treatment.

Carbon-based nano-composite materials obtained via simple thermolysis of metal-organic framework (MOF) have competitive virtues in accordance of layered porosity, controllable morphologies, and easily functionalizing with other metal/metallic oxides or hetero atoms. These make them directly as high activity catalysts or supports for various electrochemical sensor. Herein, we developed a novel ZnO/porous carbon matrix (ZnO/MPC)-based electrochemical immunosensing through thermolysis of a mixed-ligand MOF (Zn-BDC-TED) for real sample analysis of C-reactive protein. The ZnO/MPC and ionic liquid (IL) composite membrane modified electrode displayed prominent conductivity and biocompatibility for ultrasensitive detection of C-reactive protein (CRP). Subsequently, the step-by-step assembly process of the CRP immunosensor was monitored by electrochemical measurements including cyclic voltammogram (CV) and electrochemical impedance spectra (EIS). After the parameter optimization, the differential pulse voltammetry (DPV) response decreased linearly with the logarithm of CRP levels in an extensive range of 0.01–1000 ng·mL−1, and the detection limit was as low as 5.0 pg·mL−1. Meanwhile, the lable-free immunosensor also showed excellent selectivity, reproducibility and stability. We believe that ZnO/MPC composite and many carbon-based nano-composite materials obtained via simple thermolysis of MOF will be a prospective platform for sensitive detecting other biomarkers.

Metal-free photocatalysts have attracted growing concern in recent years. In this work, a new class of carbon quantum dots (CQDs) modified porous graphitic carbon nitride (g-C3N4) is synthesized via a facile polymerization method. With the optimal CQDs loading, the CQDs modified g-C3N4 exhibits ∼15 times higher degradation kinetic towards diclofenac (DCF) than that of pure g-C3N4. The enhanced photocatalytic activity can be ascribed to the improved separation of charge carriers as well as the tuned band structure. Moreover, a photosensitation-like mechanism is proposed to elucidate the photo-generated electrons transfer and reactive radicals formation. CQDs are anchored to g-C3N4 surface via C-O bond, which provide channels for the preferential transfer of photo-excited electrons on DCF molecule to the conduction band of g-C3N4. Superoxide radical (·O2-) dominates the degradation of DCF, while holes (h+) show a negligible contribution. Density functional theory (DFT) calculation successfully predicts that the sites on DCF molecule with high Fukui index (f0) are preferable to be attacked by radicals. DCF degradation pathway mainly includes ring hydroxylation, ring closure and C-N bond cleavage processes. Acute toxicity estimation indicates the formation of less toxic intermediates/products compared to DCF after photocatalysis. Moreover, the hybrid photocatalysts exhibit good reusability in five consecutive cycles. This work not only proposes a deep insight into photosensitation-like mechanism in the photocatalysis system by using C3N4-based materials, but also develops new photocatalysts for potential application on removal of emerging organic pollutants from waters and wastewaters.

Combined water pollution with the coexistence of heavy metals and organic contaminants is of great concern for practical wastewater treatment. In this study, a jaboticaba-like nanocomposite, titanate nanotubes supported TiO2 (TiO2/TiNTs), was synthesized by a two-step hydrothermal treatment. TiO2/TiNTs had large surface area, abundant of –ONa/H groups and fine crystal anatase phase, thus exhibited both good adsorptive performance for Cu(II) and high photocatalytic activity for phenanthrene degradation. The maximum Cu(II) adsorption capacity on TiO2/TiNTs was 115.0 mg/g at pH 5 according to Langmuir isotherm model, and >95% of phenanthrene was degraded within 4 h under UV light. TiO2/TiNTs showed about 10 times higher observed rate constant (kobs) for phenanthrene degradation compared to the unmodified TiNTs. More importantly, the coexistence of Cu(II) promoted photocatalytic degradation of phenanthrene, because the incorporated Cu(II) in the lattice of TiNTs could trap photo-excited electron and thus inhibited the electron-hole recombination. Density functional theory (DFT) calculation indicated that the sites of phenanthrene with high Fukui index (f0) preferred to be attacked by OH radicals. The quantitative structure–activity relationship (QSAR) analysis revealed that the degradation intermediates had lower acute toxicity and mutagenicity than phenanthrene. TiO2/TiNTs also owned high stability, as only slight loss of Cu(II) and phenanthrene removal efficiency was observed even after four reuse cycles. The developed material in this study is of great application potential for water or wastewater treatment with multi-contaminants, and this work can help us to better understand the mechanisms on reaction between Ti-based nanomaterials and different kinds of contaminants.

This study investigated the subcellular distribution and chemical forms of cadmium (Cd) in Hydrilla verticillata and the physiological mechanism underlying H. verticillata responses to Cd stress. Hydrilla verticillata was grown in a hydroponic system and was treated with various Cd concentrations (0, 10, 50, 100, 125, and 150 µM) for 7 days. Cadmium analysis of the leaves at the subcellular level showed that Cd was mainly stored in the soluble fraction (77.98-83.62%) and in smaller quantities in the cell wall fraction (11.99-17.30%) and the cell organelles (4.30-4.88%). The Cd taken up by H. verticillata was in different chemical forms. In the leaves and stems, the Cd was mostly extracted using 1 M NaCl and smaller amounts of Cd were extracted using 2% acetic acid. The malondialdehyde content significantly increased at all Cd concentrations, which indicated oxidative stress. The superoxide dismutase, guaiacol peroxidase, and catalase activities were enhanced. The proline, ascorbate, and glutathione contents increased at lower Cd concentrations, but decreased consistently as the Cd concentration rose. These results suggest that H. verticillata can be successfully used in the phytoremediation of Cd-contaminated water.

Background: The multiple sequence alignment (MSA) algorithms are the traditional ways to compare and analyze DNA sequences. However, for large DNA sequences, these algorithms require a long time computationally. Objective: Here we will propose a new numerical method to characterize and compare DNA sequences quickly. Method: Based on a new 2-dimensional (2D) graphical representation of DNA sequences, we can obtain an 8-dimensional vector using two basic concepts of probability, the mean and the variance. Results: We perform similarity/dissimilarity analyses among two real DNA data sets, the coding sequences of the first exon of beta-globin gene of 11 species and 31 mammalian mitochondrial genomes, respectively. Conclusion: Our results are in agreement with the existing analyses in our literatures. We also compare our approach with other methods and find that ours is more effective.

Three novel copper(ii) complexes, Cu(L1)2 (1), Cu(L2)2·2DMF (2), and Cu(L3)2·2DMF (3), were synthesized using three aroylhydrazone ligands, (E)-2-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL1), (E)-3-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL2) and (E)-4-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL3). The complexes were characterized by elemental analysis, infrared (IR), and Ultraviolet-visible light (UV-vis) spectroscopy. The X-ray crystal structures of the complexes all possess a distorted octahedral coordination geometry. Both an absorption spectral titration and a competitive binding assay (ethidium bromide, 4',6-diamidino-2-phenylindole (DAPI), and methyl green) revealed that complexes 2 and 3 bind readily to calf thymus DNA (ctDNA) through intercalative and minor groove binding modes. Complexes 2 and 3 also exhibited oxidative cleavage of supercoiled plasmid DNA (pUC19) in the presence of ascorbic acid as an activator. Cytotoxicity studies showed that complexes 2 and 3 possessed high cytotoxicities toward the HeLa human cervical cancer cell line, but weak toxicities toward the L929 normal mouse fibroblast cell line. We therefore have reason to believe that complexes 2 and 3 both show potential as promising anticancer candidate drugs.

Background SIRT1 plays a protective role against diabetic retinopathy as it regulates inflammation, apoptosis and autophagy of cells. Objectives This study was designed to investigate the effects of arbutin and to identify a potential mechanism of action. Adult human retinal pigment epithelial (ARPE-19) cells were exposed to high glucose (HG) or treated with different concentrations of arbutin. Material and methods The protein levels of pro-inflammatory cytokines, like tumor necrosis factor-α (TNF-α), interleukin (IL)-1β), IL-6, and p65 were assessed using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB p65 and cyclooxygenase-2 (COX-2) was detected with western blot assay. Cell apoptosis was analyzed with TUNEL assay, and expression levels of Bcl2, BAX, cleaved caspase-3, cleaved PARP, LC3II, LC3I, and beclin1 were detected with western blot assay. Autophagy levels were detected using LC3II immunofluorescence staining. Results Arbutin treatment markedly enhanced viability and autophagy mediators, decreased pro-inflammatory proteins and reduced apoptosis in ARPE cells under HG exposure, while increasing SIRT1 protein level. This could be blocked by Sirtinol treatment. Additionally, 3MA treatment significantly reduced the efficacy of arbutin against inflammatory markers and apoptosis in ARPE cells exposed to HG. Conclusions Arbutin suppressed inflammation and apoptosis of ARPE cells induced by HG by promoting autophagy via SIRT1. A potential target, SIRT1, was identified for the treatment of DR, and new effects of and action mechanisms for arbutin were found and confirmed.

Naphthenes are key intermediates in the formation of aromatic compounds during the methanol to aromatics (MTA) reaction, and the dehydrogenation process is more important than the hydrogen transfer process. Theoretical studies were performed to investigate the methylcyclopentane, which represents a naphthene, to benzene MTA process catalyzed by ZSM-5 before and after introducing Ga, showing that Ga-ZSM-5 was more favorable for carrying out the reaction than two H-type ZSM-5 (H-Z1 and H-Z2) models. H-Z1 and H-Z2 are favorable for the transfer of H during ring expansion reactions and the reformation of Bronsted acids, but the dehydrogenation reactions involving H-Z1 and H-Z2 require high free-energy barriers to be overcome. Although introducing Ga to ZSM-5 is not conducive to the transfer of H after dehydrogenation, it can reduce the extremely high dehydrogenation free-energy barrier compared with H-Z1 and H-Z2; this is mainly because Ga at dehydrogenation active centers, [GaH]2+, can accept electrons and donate them to the H atoms of [GaH]2+, giving H negative charge and making it easy to combine with positive B-acid H atoms that come from methylcyclopentane, cyclohexene, and cyclohexadiene to produce H2. Also, analysis of the transition state structures of all DH processes shows that Ga-ZSM-5 is more favorable for promoting the combination of H to produce H2 than H-Z1 and H-Z2.

Graves’ disease (GD) is the most common cause of hyperthyroidism, yet a relatively rare disease in the pediatric population. GD is a complex disorder influenced by both genetic and environmental factors. In this study, we aimed to find new environmental factors influencing the pathogenesis of GD. We investigated serum substances in 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We measured total iodine by inductively coupled plasma-mass spectrometry (ICP-MS), analyzed perfluorinated compounds via ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS), and explored other environmental substances using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) analysis. Twenty-nine single-nucleotide polymorphisms (SNPs) in eight genes related to GD were analyzed by SNaPshot. The serum total iodine was significantly higher in GD group, but its association with GD onset was weak, only with Exp(B) value near 1. The perfluorinated compound levels were not different between the two groups. More importantly, we found 16 environmental substances significantly different between GD and control groups, among which ponasterone A is a risk factor (p = 0.007 and Exp(B) = 14.14), while confertifoline is a protective factor against GD onset (p = 0.002 and Exp(B) = 0.001). We also identified 10 substances correlated significantly with thyroid indices in GD patients, among which seven associated with levels of the thyroid autoantibody TPOAb. No known SNPs were found predisposing GD. In this study, we explored a broad variety of environmental substances and identified novel factors that are potentially involved in the pediatric GD pathogenesis.

Aβ1-42-conjugated magnetic nanoparticles, Aβ1-42@MNP, were prepared by covalently coupling Aβ1-42 to hyperbranched polyethyleneimine (PEI)-modified magnetic nanoparticles via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC). Aβ1-42's high binding capacity to glycosyl groups facilitates Aβ1-42@MNP composite to be a promising selective adsorbent for glycoproteins in egg whites. In our study, under conditions of pH 4.0, the adsorption efficiency of Aβ1-42@MNP composite for ovalbumin (100 μg mL-1) was 98.4% and its maximum adsorption capacity was 344.8 mg g -1; under the condition of pH 4.0 and 200 mmol L-1 NaCl, its adsorption efficiencies for ovalbumin and ovotransferrin were 96.9% and 60.0%, respectively. According to these primary data, in practice, ovalbumin was removed from egg white by Aβ1-42@MNP composite at pH 4.0 (step I), and then after adding NaCl until the final salt concentration reached 200 mmol L-1 (pretreated egg white), we utilized the same adsorbent to further isolate/purify glycoproteins (step II). SDS-PAGE results showed that Aβ1-42@MNP composite could largely remove ovalbumin in step I and could isolate/purify the remaining ovalbumin and ovotransferrin in step II. LC-MS/MS analysis results showed that the removal of ovalbumin reduced its percentage in egg white samples from 32.93% to 11.05% in step I and the remaining ovalbumin and ovotransferrin were enriched in step II, where the final percentage reached 11.6% and 12.6%, respectively. In summary, 81 protein species were identified after two-step extraction with Aβ1-42@MNP on egg white, while only 46 protein species were identified directly from raw egg white without any pretreatment. This work well illustrates the excellent adsorption performance of Aβ1-42@MNP composite to glycoproteins and its potential in the application of proteomic studies on low-abundance proteins in egg white.

This study focuses on the recycling of a spent fluid catalytic cracking (FCC) catalyst to produce catalyst-based non-sintered bricks (CN-bricks) for the recovery of its aluminosilicate components and the solidification of heavy metals. The effects of the content of cement (10–20%), the proportion of FCC (10–40%), and the type of an activator (NaOH/Na2SiO3/Na2SO4) on the performance of a CN-brick were investigated in terms of the mechanical strength and leaching behavior. The results show that an optimal binder system of 20% cement + Na2SO4 could promote the compressive strength up to 42.3 MPa; the proportion of an optimal spent FCC catalyst of 20% could achieve the lowest porosity and water absorption. The microscopic mechanism of a cementitious process was analyzed by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), proving that C-S-H and ettringite (AFt) are the two main hydration products of a CN-brick. Na2SO4 is superior to NaOH or Na2SiO3 as an activator since Na2SO4 takes advantage of the aluminum-rich property of a spent FCC catalyst and specifically promote the formation of a needle-like AFt. Quantitative environmental risk assessment for the utilization of a CN-brick on roads was carried out based on the leaching test of a toxicity characteristic leaching procedure (TCLP), NEN 7371 maximum availability test, and the hazard Index (HI) identification, and a final HI 0.0045 (

Major depressive disorder (MDD) is a common, chronic, recurrent disease. The existing drugs are ineffective for approximately half of patients, so the development of antidepressant drugs with novel mechanisms is urgent. Cumulative evidence has shown neuro-inflammation plays a key role in the etiology of major depressive disorder. Clinical studies implicated that bile acids, an important component of gut-brain axis, inhibit neuro-inflammation and mediate the pathophysiology of the MDD. Here, we found that ganoderic acid A (GAA) modulated bile acid receptor FXR (farnesoid X receptor), inhibited brain inflammatory activity, and showed antidepressant effects in the chronic social defeat stress depression model, tail suspension, forced swimming, and sucrose preference tests. GAA directly inhibited the activity of the NLRP3 inflammasome, and activated the phosphorylation and expression of the AMPA receptor by modulating FXR in the prefrontal cortex of mice. If we knocked out FXR or injected the FXR-specific inhibitor z-gugglesterone (GS), the antidepressant effects induced by GAA were completely abolished. These results suggest that GAA modulates the bile acid receptor FXR and subsequently regulates neuroimmune and antidepressant behaviors. GAA and its receptor FXR have potential as targets for the treatment of MDD.

Lysins are a class of hydrolytic enzymes used by bacteriophages to target and cleave the peptidoglycan of bacterial cell walls during their lytic cycle. The lysins from bacteriophages that infect Gram-positive bacteria are typically monomeric and consist of one or two catalytic domains (CD) and a cell binding domain (CBD). However, multimeric lysins encoded by a single gene have also been reported, among which Lys170 from enterococcal phage F170/08 was one of the first identified. Here, we determined the crystal structure of Lys170 CBD at 1.40 Å resolution. The structure reveals that Lys170 CBDs assemble into a tetrameric functional unit and that each monomer folds into a three-stranded β-sheet core capped on each side by an α-helix. In addition, we identified key residues of Lys170 CBD involved in host cell binding. Our work provides a basis for designing highly efficient lysins targeting Enterococcus faecalis.

Fascial adipocytes are recently identified as a unique population of adipose cells, which have different developmental origins, anatomical locations, cytological and functional characteristics compared with subcutaneous or visceral adipocytes. Superficial fascia in rats (also in pigs but not obviously in mice) contains numbers of lineage committed preadipocytes which possess adipogenic potential in vivo. The present study aimed to investigate the physiological factors that contribute to fascial adipogenesis in rats. We detected that mast cells, adipose progenitor cells, and mature adipocytes distributed in certain fascia areas were closely associated with each other, and numerous heparin-loaded granules released from mast cells were distributed around fascial preadipocytes. The culture supernatants of rat peritoneal mast cells and RBL-2H3 mast cells contained 20–30 μg/ml of heparin, effectively activated PPAR-responsive luciferase activity, promoted mRNA and protein expressions of key adipogenic genes, and hence increased adipogenic differentiation of fascia- or epididymal adipose-derived stromal cells. Adipogenic effects of mast cell supernatants were mimicked by heparin but not by histamine or 5-hydroxytryptamine, and were antagonized by protamine sulfate. In rats, local administration of heparin-loaded microspheres for 30 days induced adipogenesis in local areas of superficial fascia. This adipogenic effects of heparin might be related by chain length of glucosamine units, because heparin stimulated stronger adipogenesis than dalteparin and enoxaparin with relatively short chains. Our findings suggested that mast cell and its granule heparin could serve as the endogenous physiological factors to initiate and accelerate local adipogenesis in superficial fascia, or in adipose tissue with the fascia naturally embedded inside.

Previously, we reported the myelin regulatory factor (MYRF) as a candidate gene for nanophthalmos. We have also produced Myrf knockdown (Myrf+/−) mouse strain to investigate the cellular and molecular phenotypes of reduced MYRF expression in the retina. Myrf+/− mouse strain was generated using the CRISPR/Cas9 system. Optomotor response system, electroretinogram (ERG), spectral-domain optical coherence tomography (SD-OCT), histology, and immunohistochemistry were performed to evaluate retinal spatial vision, electrophysiological function, retinal thickness, and pathological changes in cone or rod photoreceptors, respectively. RNA sequencing (RNA-seq) was performed to investigate the underlying molecular mechanism linking Myrf deficiency with photoreceptor defects. The genotype and phenotype of CRISPR/Cas9-induced Myrf+/− mice and their offspring were comprehensively investigated. Photoreceptor defects were detected in the retinas of Myrf+/− mice. Visual acuity and ERG responses were decreased in Myrf+/− mice compared with the control mice (Myrf+/+). The loss of cone and rod neurons was proportional to the decreased outer nuclear layer (ONL) thickness. Moreover, RNA-seq revealed that phototransduction and estrogen signaling pathways played important roles in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Myrf+/− mouse strain provides a good model to investigate the function of the MYRF gene. Photoreceptor defects with impaired functions of spatial vision and retinal electrophysiology indicate an important role played by MYRF in retinal development. Alterations in phototransduction and estrogen signaling pathways play important roles in linking Myrf deficiency with retinal photoreceptor defects.

Retinal photodamage is a high-risk factor for age-related macular degeneration (AMD), the leading cause of irreversible blindness worldwide. However, both the pathogenesis and effective therapies for retinal photodamage are still unclear and debated.The anti-inflammatory effects of thrombospondin-1 on blue light-induced inflammation in ARPE-19 cells and in retinal inflammation were evaluated. Furthermore, the anti-angiogenic effects of thrombospondin-1 on human microvascular endothelial cells (hMEC-1 cells) and a laser-induced choroidal neovascularisation (CNV) mouse model were evaluated. in vitro experiments, including western blotting, immunocytochemistry, migration assays and tube formation assays, as well as in vivo experiments, including immunofluorescence, visual electrophysiology, spectral-domain optical coherence tomography, and fluorescein angiography, were employed to evaluate the anti-inflammatory and anti-angiogenic effects of thrombospondin-1.Specific effects of blue light-induced retinal inflammation and pathological angiogenesis were reflected by up-regulation of pro-inflammatory factors and activation of angiogenic responses, predominantly regulated by the NF-κB and VEGFR2 pathways respectively. During the blue light-induced pathological progress, THBS-1 derived from retinal pigment epithelium down-regulated proteomics and biological assays. Thrombospondin-1 treatment also suppressed inflammatory infiltration and neovascular leakage. The protective effect of Thrombospondin-1 was additionally demonstrated by a substantial rescue of visual function. Mechanistically, thrombospondin-1 reversed blue light-induced retinal inflammation and angiogenesis by blocking the activated NF-κB and VEGFR2 pathways, respectively.Thrombospondin-1, with dual anti-inflammatory and anti-neovascularisation properties, is a promising agent for protection against blue light-induced retinal damage and retinal degenerative disorders which are pathologically associated with inflammatory and angiogenic progress.This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.

Ionic liquids (ILs), also known as green solvents, are widely acknowledged in several fields, such as chemical separation, synthesis, and electrochemistry, owing to their excellent physiochemical properties. However, their poor biodegradability may lead to environmental and health risks, posing a severe threat to humans, thus requiring further research. In this study, the biotoxicities of the imidazolium-based ILs were evaluated in Tetrahymena pyriformis. Moreover, IL detoxification was investigated by addition of glutathione (GSH), cysteine, and nicotinamide adenine dinucleotide (NADH). Reactive oxygen species (ROS) initiated by different IL types caused damage to Tetrahymena, while glutathione, cysteine, and NADH eliminated ROS, achieving the detoxification purposes. Detoxification results showed that NADH exhibited the best detoxification ability, followed by glutathione and cysteine. Finally, RT-PCR results suggested that metallothionein might have participated in IL detoxification.

The nicotinamide adenine dinucleotide (NAD+) is an important small biomolecule that participates in a variety of physiological functions, and it has been regarded as a potential biomarker for disease diagnosis and a promising target for disease treatment. The conventional methods for NAD+ assay often suffer from complicated procedures, expensive labeling, poor selectivity, and unsatisfactory sensitivity. Herein, we develop a label-free and sensitive method for NAD+ assay based on the integration of a trifunctional split dumbbell probe with ligation-triggered isothermal rolling circle amplification (RCA). We design a trifunctional split dumbbell probe that can act as a probe for NAD+ recognition, a template for RCA reaction, and a substrate for SYBR Green I binding. In the presence of target NAD+, it can serve as a cofactor to active E. coli DNA ligase which subsequently catalyzes the ligation of split dumbbell probe to form a circular template for RCA reaction, generating numerous dumbbell probe amplicons which can be easily and label-free monitored by using SYBR Green I as the fluorescent indicator. Due to the high fidelity of NAD+-dependent ligation and high amplification efficiency of RCA amplification, this method exhibits high sensitivity with a detection limit of 85.6 fM and good selectivity with the capability of discriminating target NAD+ from its analogs. Moreover, this method can be applied for accurate and sensitive detection of NAD+ in complex biological samples and cancer cells, holding great potential in NAD+-related biological researches and clinical diagnosis.

Small white apricot is well known as a famous fresh fruit and even a folk medicine in Xinjiang. To investigate nutritive value, antioxidant activity, and flavor of small white apricot, sugars, organic acids, total flavonoids, phenolic compounds, antioxidant activities, and volatile compounds in five apricot cultivars were examined by high-performance liquid chromatography (HPLC) and headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results showed that sucrose (32.94% to 42.49%), malic acid (69.21% to 76.75%), and quercetin-3-rutinoside (72.84% to 74.05%) were the dominant sugar, organic acid, and phenolic compounds in small white apricot, respectively. The antioxidant activity reached up to 61.72 to 135.52 mg TEs 100 g-1 . Furthermore, the aroma fingerprint of the small white apricot consisted of 1-octen-3-ol, 1-dodecanol, pentanal, hexanal, (E)-2-hexenal, (E)-2-heptenal, 6-methyl-5-hepten-2-one, (E)-2-nonenal, 1-octen-3-one, β-myrcene, and linalool, providing clear green, grassy, and fatty notes. Apricots from different cultivars possessed a similar flavor, while linalool and (E)-2-hexenal had been identified as the characteristic aroma compounds in small white apricot. The results provide a complete chemical characterization of the taste, functional ingredients and aroma of the small white apricot. PRACTICAL APPLICATION: The nutritive value, antioxidant activity and flavor of small white apricot were investigated in this study. The results will provide a theoretical basis for developing characteristic variety aroma, nutritive value, and medicinal value of small white apricot.