Dietary methionine restriction (MetR) offers an integrated set of beneficial health effects, including delaying aging, extending health span, preventing fat accumulation, and reducing oxidative ...stress. This study aimed to investigate whether MetR exerts entero-protective effects by modulating intestinal flora, and the effect of MetR on plasma metabolites in rats. Rats were fed diets containing 0.86% methionine (CON group) and 0.17% methionine (MetR group) for 6 weeks. Several indicators of inflammation, gut microbiota, plasma metabolites, and intestinal barrier function were measured. 16S rRNA gene sequencing was used to analyze the cecal microbiota. The MetR diet reduced the plasma and colonic inflammatory factor levels. The MetR diet significantly improved intestinal barrier function by increasing the mRNA expression of tight junction proteins, such as zonula occludens (
)-1, claudin-3, and claudin-5. In addition, MetR significantly increased the levels of short-chain fatty acids (SCFAs) by increasing the abundance of SCFAs-producing
and
and decreasing the abundance of pro-inflammatory bacteria
and
. Furthermore, MetR reduced the plasma levels of taurochenodeoxycholate-7-sulfate, taurocholic acid, and tauro-ursodeoxycholic acid. Correlation analysis identified that colonic acetate, total colonic SCFAs, 8-acetylegelolide, collettiside I, 6-methyladenine, and cholic acid glucuronide showed a significant positive correlation with
abundance but a significant negative correlation with
and
abundance. MetR improved gut health and altered the plasma metabolic profile by regulating the gut microbiota in rats.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Our previous studies showed that macrophages (MФs), especially myeloma-associated MФs (MAMs), induce chemoresistance in human myeloma. Here we explored the potential of targeting MФs, by using ...colony-stimulating factor 1 receptor (CSF1R)-blocking mAbs, to treat myeloma. Our results showed that CSF1R blockade specifically inhibited the differentiation, proliferation and survival of murine M2 MФs and MAMs, and repolarized MAMs towards M1-like MФs in vitro. CSF1R blockade alone inhibited myeloma growth in vivo, by partially depleting MAMs, polarizing MAMs to the M1 phenotype, and inducing a tumor-specific cytotoxic CD4
T-cell response. Similarly, genetically depleting MФs in myeloma-bearing MM
mice retarded myeloma growth in vivo. Furthermore, the combination of CSF1R blockade and chemotherapy such as bortezomib or melphalan displayed an additive therapeutic efficacy against established myeloma. Finally, a fully human CSF1R blocking mAb, similar to its murine counterpart, was able to inhibit the differentiation, proliferation and survival of human MФs. Thus, this study provides the first direct in vivo evidence that MΦs and MAMs are indeed important for myeloma development and progression. Our results also suggest that targeting MAMs by CSF1R blocking mAbs may be promising methods to (re)sensitize myeloma cells to chemotherapy and promote anti-myeloma immune responses in patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•The IC50 of Cu(II) on Anammox mixed culture was 12.9mgL−1 in short-term test.•The mathematical models used to quantify the performance fit the trial data well.•Cu(II) changed the properties of ...granular sludge after long-term operation.•Anammox performance can be recovered from Cu2+ stress after long-term operation.•Controlling CLR ⩽0.12kgm−3d−1 was necessary for long-term stable operation.
The short-term effects of Cu(II) on the Anaerobic Ammonium Oxidation (Anammox) process were evaluated using batch tests. The IC50 of Cu(II) on Anammox mixed culture was 12.9mgL−1. The long-term effects of Cu(II) on the Anammox process were examined in two upflow anaerobic sludge blanket reactors, a test reactor (R1) and a control reactor (R0). The performance of R1 was strongly inhibited by Cu(II) at a concentration of 5mgL−1 with a specific Anammox activity of 0.9mg TN g−1 volatile suspended solids h−1, which corresponded to a 94% loss in activity. Without Cu(II) addition, the recovery phase of R1 was consistent with the typical characteristics seen in an Anammox process startup, with a good fit to both the modified Boltzmann model (R2=0.9860) and the modified Stover–Kincannon model (R2=0.9701). Maintaining the influent Cu(II) at a low level of no more than 4mgL−1 was necessary for preventing the copper inhibition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A series of BN-incorporated borafluorenate heterocycles, bis(borafluorene-phosphinimine)s (11–15), have been formed via intramolecular Staudinger-type reactions. The reactions were promoted by ...light or heat using monodentate phosphine-stabilized 9-azido-9-borafluorenes (R3P-BF-N3; 6–10) and involve the release of dinitrogen (N2), migration of phosphine from boron to nitrogen, and oxidation of the phosphorus center (PIII to PV). Density functional theory (DFT) calculations provide mechanistic insight into the formation of these compounds. Compounds 11–15 are blue emissive in the solution and solid states with absolute quantum yields (ΦF) ranging from 12 to 68%.
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IJS, KILJ, NUK, PNG, UL, UM
•The ANAMMOX performance under transient OTC stress was investigated.•The factors influencing the stability were evaluated.•The changes in sludge characteristics were provided.•The indicators for ...robustness and recovery performance were addressed.
The effect of transient oxytetracycline (OTC) shock on the stability of anaerobic ammonium oxidation (ANAMMOX) process was evaluated in the present study. The shock test was implemented with 155–1731mgL−1 OTC, lasting for 1 to 3-fold hydraulic retention times, under the nitrogen loading rate (NLR) of 6.72 and 13.4kgm−3d−1. The response of the process was divided into shock and recovery stage and the performance under the stress was indicated by stability index and granule characteristic. In the shock period, nitrogen removal rate (NRR) was ranged from 12.1 to 12.1–4.04kgm−3d−1. The specific ANAMMOX activity (SAA) and heme c content, were respectively reduced by 1.4% and 17.6–29.4%. Foremost, the OTC shock was restorable and the recovery lasted for 4–353h. The robustness of ANAMMOX process was dependent on OTC level, duration of shock and NLR applied.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Ultraviolet (UV) radiation and reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelium (RPE) cells by inducing cell apoptosis, which is the main cause of ...age-related macular degeneration (AMD). The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER) stress-AMP activated protein kinase (AMPK) signaling axis in UV and hydrogen peroxide (H2O2)-treated RPE cells. UV and H2O2 induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal), ceramide production (fumonisin B1) and AMPK activation (compound C) suppressed UV- and H2O2-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide) mimicked UV and H2O2's effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H2O2 activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study aimed to assess the effect of various source of high-fiber ingredients on growth performance, apparent digestibility of nutrients, and blood para- meters of piglets by investigating their ...in vitro fermentation characteristics. A total of 300 healthy crossbred piglets were randomly allocated to one of five diets including corn-soybean meal basal diet (CON), sugar beet pulp (SBP), soybean hull (SBH), fermented distillers’ grains (FDG), and kelp powder (KP). In vitro fermentation analysis revealed that the predominant short-chain fatty acids produced were acetate and valerate. Sugar beet pulp and kelp powder exhibited rapid fermentation rates, in contrast to SBH, oat bran, and FDG. The apparent total tract digestibility of dry matter (P < 0.05), gross energy (P < 0.05), and crude protein were decreased (P < 0.001) in different fiber diets than the CON diet. The serum concentration of threonine was increased by feeding fibers diets (P < 0.05). In conclusion, a diet containing 3% SBP (with a soluble-to-insoluble dietary fiber ratio of 17.04%) showed the best effects on increasing nutrients digestibility and serum amino acid concentrations. These findings may inform future applications of SBP in piglet nutrition.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Uveal melanoma (UVM), an uncommon yet potentially life-threatening ocular cancer, arises from melanocytes in the uveal tract of the eye. The exploration of novel oncotargets for UVM is of paramount ...importance. In this study, we show that PCK1 (phosphoenolpyruvate carboxykinase 1) expression is upregulated in various UVM tissues as well as in primary UVM cells and immortalized lines. Furthermore, bioinformatics studies reveal that PCK1 overexpression in UVM correlates with advanced disease stages and poor patient survival. Genetic silencing (utilizing viral shRNA) or knockout (via CRISPR/Cas9) of PCK1 significantly curtailed cell viability, proliferation, cell cycle progression, and motility, while provoking apoptosis in primary and immortalized UVM cells. Conversely, ectopic overexpression of PCK1, achieved through a viral construct, bolstered UVM cell proliferation and migration. Gαi3 expression and Akt phosphorylation were reduced following PCK1 silencing or knockout, but increased after PCK1 overexpression in UVM cells. Restoring Akt phosphorylation through a constitutively active mutant Akt1 (S473D) ameliorated the growth inhibition, migration suppression, and apoptosis induced by PCK1 silencing in UVM cells. Additionally, ectopic expression of Gαi3 restored Akt activation and counteracted the anti-UVM cell effects by PCK1 silencing. In vivo, the growth of subcutaneous xenografts of primary human UVM cells was significantly inhibited following intratumoral injection of adeno-associated virus (aav) expressing PCK1 shRNA. PCK1 depletion, Gαi3 downregulation, Akt inhibition, proliferation arrest, and apoptosis were detected in PCK1-silenced UVM xenografts. Collectively, our findings demonstrate that PCK1 promotes UVM cell growth possibly by modulating the Gαi3-Akt signaling pathway.
Background
It is well known that lipids are vital for axonal myelin repair. Diffuse axonal injury (DAI) is characterized by widespread axonal injury. The association between serum lipids and DAI is ...not well known. The purpose of this study was to investigate the associations of serum lipid profile variables (triglycerides, high- and low-density lipoproteins, and total cholesterol) with DAI detected by magnetic resonance imaging (MRI) and with clinical outcome for patients suffering from traumatic brain injury (TBI).
Methods
This study included 176 patients with a history of TBI who had undergone initial serum lipid measurements within 1 week and brain MRIs within 30 days. Based on MRI findings, patients were divided into negative and positive DAI groups.
Results
Of the 176 patients, 70 (39.8%) were assigned to DAI group and 106 (60.2%) patients to non-DAI group. Compared with the non-DAI group, patients with DAI had significantly lower levels of high-density lipoprotein cholesterol (HDL-C) in serum during the first week following TBI. Multivariate analysis identified HDL-C as an independent predictor of DAI. Patients with lower serum HDL-C levels were less likely to regain consciousness within 6 months in TBI patients with DAI lesions identified by MRI.
Conclusions
Plasma levels of HDL-C may be a viable addition to biomarker panels for predicting the presence and prognosis of DAI on subsequent MRI following TBI.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Cytokinesis is essential for development and survival of all organisms by increasing cell number and diversity. It is a highly regulated process that requires spatiotemporal coordination of hundreds ...of proteins functioning in the assembly, constriction, and disassembly of a contractile actomyosin ring, targeted vesicle fusion, and localized extracellular matrix remodeling. Cytokinesis has been studied in multiple systems with a wide range of technologies to learn the common principles. In this chapter, we describe the analysis of protein dynamics during cytokinesis in the budding yeast Saccharomyces cerevisiae by several live-cell imaging methods. This, in combination with the power of yeast genetics, has yielded novel insights into the mechanism of cytokinesis. Similar approaches are increasingly used to study this fundamental process in more complex systems.
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