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Background Bone formation plays an important role in early tendon–bone healing after anterior cruciate ligament reconstruction (ACLR). Dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) have enhanced osteogenic potential. This study aimed to investigate the effect of De-BMSCs transplantation on the promotion of bone formation at the tendon–bone interface after ACLR and to further explore the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Methods BMSCs from the femurs and tibias of New Zealand white rabbits were subjected to osteogenic induction and then cultured in medium without osteogenic factors; the obtained cell population was termed De-BMSCs. De-BMSCs were induced to undergo osteo-, chondro- and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. An ACLR model with a semitendinosus tendon was established in rabbits, and the animals were divided into a control group, BMSCs group, and De-BMSCs group. At 12 weeks after surgery, the rabbits in each group were sacrificed to evaluate tendon–bone healing by histologic staining, micro-computed tomography (micro-CT) examination, and biomechanical testing. During osteogenic differentiation of De-BMSCs, an siRNA targeting nuclear factor of activated T-cells 1 (NFATc1) was used to verify the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Results De-BMSCs exhibited some properties similar to BMSCs, including multiple differentiation potential and cell surface markers. Bone formation at the tendon–bone interface in the De-BMSCs group was significantly increased, and biomechanical strength was significantly improved. During the osteogenic differentiation of De-BMSCs, the expression of Nanog and NFATc1 was synergistically increased, which promoted the interaction of NFATc1 and Osterix, resulting in increased expression of osteoblast marker genes such as COL1A, OCN, and OPN. Conclusions De-BMSCs transplantation could promote bone formation at the tendon–bone interface after ACLR and improve the biomechanical strength of the reconstruction. The Nanog/NFATc1/Osterix signaling pathway mediated the enhanced osteogenic differentiation efficiency of De-BMSCs.

BACKGROUND The beneficial function of phytase and 25-hydroxyvitamin D3 (HyD) on the feed utilization rate has been widely investigated. However, studies concerning its influence on weaned piglets largely lag behind. The aim of this study was to investigate the effects of phytase and HyD supplementation on the growth performance and bone development in weaned piglets under dietary Ca and P deficiency. RESULTS The results showed that dietary Ca and P deficiency decreased (P

Two new supramolecular polyoxmetalates were synthesized from 1, 4-bis[4-nitrile-pyridine)-N-methylene]phenyldibromide (L1) and 1, 2-bis[4-nitrile-pyridine)-N-methylene]phenyldibromide (L2) and (NH4)6Mo7–O24·4H2O under hydrothermal conditions. They are named p-[C20H18N2O4][Mo8O26] 0.5·H2O (1) and o-[C20H18N2O4][Mo8O26] ċ 0.5·H2O (2) respectively. The structures have been confirmed through single-crystal X-ray diffraction analyses and further characterized by elemental analyses, IR spectra. The adsorption test of compound 1 and compound 2 in organic dyes were carried out. It was found that compound 1 had a good adsorption effect on methylene blue (MB) and rhodamine B (RhB). The adsorption effect of compound 2 on MB is stronger than that of compound 1.

Aims Reproduction can induce maternal oxidative stress, and resveratrol is able to alleviate oxidative stress. This study aimed to investigate the protective effects of resveratrol supplementation in mice during pregnancy and lactation. Methods and results Pregnant mice were randomly divided into three groups: (i) Pure water (Con); (ii) Cellulose sodium dissolves with 20 mg kg-1 resveratrol (R1) and (iii) Cellulose sodium dissolves with 40 mg kg-1 resveratrol (R2). The experiment starts at pregnancy and ends at weaning. The results showed that resveratrol increased mammary cell proliferation and the mRNA expressions of UDP glucuronosyltransferase family 1 member A1 (UGT1A1) and cytochrome P450 proteins (CYP1A1), while decreased superoxide dismutase, extracellular (SOD3) in the mammary gland. Further study showed that resveratrol promoted the mRNA expressions of genes involved in mitophagy, such as transcription factor Eβ (Tfeβ), Bcl1lc3β, homosapiens microtubule-associated protein 1 light-chain 3 beta (Map1lc3β), Parkin, sequestosome1 (p62), autophagy-related protein (Atg5) and Beclin-1 (Becn1) in the mammary gland. Moreover, resveratrol increased the abundances of some intestinal microbial species. 40 mg kg-1 resveratrol significantly increased the contents of Acidobacteri, unidentified acidbacteria, Bacilales, Staphylococcaceae and Staphylococcus at phylum, class, order, family and genus level respectively. Conclusion Our results indicate that resveratrol supplementation may promote mammary cell proliferation and antioxidant ability through mitophagy and regulating gut microbiota in pregnant mice. Significance and impact of the study Current study proved that resveratrol could affect mammary cell proliferation and antioxidation capacity during pregnancy and lactation in mice for the first time. The underlying mechanisms may be related to mitophagy and gut microbiota.

Long-term high temperature in conventional vanadium extraction process would cause particles to be sintered and wrapped, thus reducing extraction efficiency of vanadium. Based on the purpose of directional conversion and process intensification, this work proposed a combination of low temperature sodium roasting and high efficiency selective oxidation leaching in vanadium extraction. The investigation of the reaction mechanism suggested that the structure of vanadium slag was changed by roasting, which also caused the fracture of spinel. The addition of MnO2 promoted the directional oxidation of low-valent vanadium into high valence. It also found that Na2S2O8 could oxidize low-valent vanadium effectively in leaching. The leaching efficiency of vanadium reached 87.74% under the optimum conditions, including a roasting temperature of 650 °C, a roasting time of 2.0 h, a molar ratio of sodium-to-vanadium of 0.6, a MnO2 (roasting additive) dosage of 5 wt% and a Na2S2O8 (leaching oxidant) dosage of 5 wt%. This percentage is 7.18% higher than that of direct roasting-and-leaching under the same conditions.

Magnesium and its alloys, as the metal materials with the lowest density among structural materials, have attracted much attention due to their excellent properties such as high specific stiffness,...

As major fuels for the small intestinal mucosa, dietary amino acids (AA) are catabolized in the mitochondria and serve as sources of energy production. The present study was conducted to investigate AA metabolism that supply cell energy and the underlying signaling pathways in porcine enterocytes. Intestinal porcine epithelial cells (IPEC-J2) were treated with different concentrations of AA, inhibitor, or agonist of mammalian target of rapamycin complex 1 (mTORC1) and adenosine monophosphate activated protein kinase (AMPK), and mitochondrial respiration was monitored. The results showed that AA treatments resulted in enhanced mitochondrial respiration, increased intracellular content of pyruvic acid and lactic acid, and increased hormone-sensitive lipase mRNA expression. Meanwhile, decreased citrate synthase, isocitrate dehydrogenase alpha, and carnitine palmitoyltransferase 1 mRNA expression were also observed. We found that AA treatments increased the protein levels of phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated-p70 ribosomal protein S6 kinase, and phosphorylated-4E-binding protein 1. What is more, the protein levels of phosphorylated AMPK α (p-AMPKα) and nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-1 (SIRT1) were decreased by AA treatments in a time depending manner. Mitochondrial bioenergetics and the production of tricarboxylic acid cycle intermediates were decreased upon inhibition of mTORC1 or AMPK. Moreover, AMPK activation could up-regulate the mRNA expressions of inhibitor of nuclear factor kappa-B kinase subunit beta (Ikbkβ), integrin-linked protein kinase (ILK), unconventional myosin-Ic (Myo1c), ribosomal protein S6 kinase beta-2 (RPS6Kβ2), and vascular endothelial growth factor (VEGF)-β, which are downstream effectors of mammalian target of rapamycin (mTOR). The mRNA expressions of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD) and 5′-AMP-activated protein kinase subunit gamma-1 (PRKAG1), which are upstream regulators of mTOR, were also up-regulated by AMPK activation. On the other hand, AMPK activation also down-regulated FK506-binding protein 1A (FKBP1A), serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform, phosphatase and tensin homolog (PTEN), and unc-51 like autophagy activating kinase 1 (Ulk1), which are up-stream regulators of mTORC1. Taken together, these data indicated that AA regulated cellular energy metabolism through mTOR and AMPK pathway in porcine enterocytes. These results demonstrated interactions of AMPK and mTORC1 pathways in AA catabolism and energy metabolism in intestinal mucosa cells of piglets, and also provided reference for using AA to remedy human intestinal diseases. Keywords: Amino acids, Mammalian target of rapamycin, Adenosine monophosphate activated protein kinase, Mitochondrial respiration, Energy utilization

Even though lithium-sulfur batteries have appealing advantages including a high theoretical capacity and energy density, their commercial implementation has been seriously hindered by some notorious reasons, particularly the severe shuttling effect, the insulating nature of sulfur, the large volumetric variation during cycling and the sluggish redox reaction kinetics. To tackle these issues, a biomass (ginkgo-nut) derived N,S-codoped porous carbon (GC) with an interconnected honeycomb-like hierarchical structure is synthesized by a templated carbonization method, followed by hydrothermal growth of transition metal sulfide MS2 (M = Co, Ni) nanocrystals, giving rise to a hybrid 3D electrocatalyst. The unique structure constructed by N,S-codoping can expose more active sites and polar surfaces to physically confine and chemically adsorb polysulfides. Meanwhile, the embedded MS2 polyhedral-like nanoparticles further enhance the interaction with polysulfides and improve conversion and redox kinetics of polysulfides. Remarkably, with 80 wt% sulfur loading (∼2.5 mg cm-2), GC-CoS2 exhibits a reversible capacity of 988.8 mA h g-1 after 500 cycles at 0.1 C and an excellent capacity of 610.3 mA h g-1 after 1000 cycles at 2 C, outperforming bare GC and GC-NiS2. Compared with the electrochemical performances of the representative reported biomass-derived sulfur host for Li-S batteries, evidently, both the discharge capacity and cycling stability of our GC-CoS2 sample are superior. Density functional theory (DFT) calculation results suggest that CoS2 exhibits a higher binding energy towards lithium polysulfides and a lower energy barrier for Li+ diffusion on the surface compared to the NiS2 counterpart, suggesting that CoS2 is a better choice for lithium-sulfur batteries than NiS2. This work provides a new avenue to rationally design a carbonaceous catalyst host for high-performance lithium-sulfur batteries.

Many tailed bacteriophages assemble ejection proteins and a portal-tail complex at a unique vertex of the capsid. The ejection proteins form a transenvelope channel extending the portal-tail channel for the delivery of genomic DNA in cell infection. Here, we report the structure of the mature bacteriophage T7, including the ejection proteins, as well as the structures of the full and empty T7 particles in complex with their cell receptor lipopolysaccharide. Our near-atomic-resolution reconstruction shows that the ejection proteins in the mature T7 assemble into a core, which comprises a fourfold gene product 16 (gp16) ring, an eightfold gp15 ring, and a putative eightfold gp14 ring. The gp15 and gp16 are mainly composed of helix bundles, and gp16 harbors a lytic transglycosylase domain for degrading the bacterial peptidoglycan layer. When interacting with the lipopolysaccharide, the T7 tail nozzle opens. Six copies of gp14 anchor to the tail nozzle, extending the nozzle across the lipopolysaccharide lipid bilayer. The structures of gp15 and gp16 in the mature T7 suggest that they should undergo remarkable conformational changes to form the transenvelope channel. Hydrophobic α-helices were observed in gp16 but not in gp15, suggesting that gp15 forms the channel in the hydrophilic periplasm and gp16 forms the channel in the cytoplasmic membrane.

Epidemiological investigations have shown that individuals treated with dexamethasone during pregnancy have an increased risk of osteoporosis after birth. Our studies reported that peak bone mass was decreased in the prenatal dexamethasone exposure (PDE) offspring before chronic stress, while further decrease was observed after chronic stress. Simultaneously, increase of bone local active corticosterone was observed in the PDE offspring, while further increase was also observed after chronic stress. Moreover, the histone H3 lysine 9 acetylation (H3K9ac) level of 11-beta hydroxysteroid dehydrogenase 2 (11β-HSD2) and its expression in bone tissue of PDE offspring rats remained lower than the control before and after birth. Injection of 11β-HSD2 overexpression lentivirus into the bone marrow cavity could partially alleviate the accumulation of bone local active corticosterone and bone loss induced by PDE. In vitro, dexamethasone inhibited the expression of 11β-HSD2 and aggravated the inhibitory effect of corticosterone on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Overexpression of 11β-HSD2 partially alleviated the inhibitory effect of corticosterone. Moreover, dexamethasone promoted the nuclear translocation of glucocorticoid receptor (GR), which resulted in the stimulation of 11β-HSD2 expression due to the binding of GR to the 11β-HSD2 promoter region directly, as well as increasing H3K9ac level in the 11β-HSD2 promoter region by recruiting histone deacetylase 11 (HDAC11). Our results indicated that low expression of 11β-HSD2 in bone tissue is an important mediator for the high susceptibility to osteoporosis in PDE adult offspring.

Milk fat is a major source of energy that determines the growth of neonates. Recently, studies have shown that valine is closely related to lipid metabolism. Therefore, this study was designed to investigate the effects of dietary valine supplementation on milk fat synthesis using a pig model. Thirty gilts were allotted to low (LV, total valine:lysine = 0.63:1), medium (MV, total valine:lysine = 0.73:1), and high (HV, total valine:lysine = 0.93:1) valine feeding levels from Day 75 of gestation till farrowing. The results demonstrated that the concentration of milk fat at Days 1, 3, and 7 of lactation in the HV group was higher than that in the MV and LV groups. The HV group had an increased (p, Dietary valine supplementation increases the content of milk fat in the colostrum Dietary valine supplementation increases the proportion of fatty acids in colostrum. Valine can activate the signaling pathway related to fatty acids synthesis. Valine promote fatty acids synthesis may via the upregulation of proteins ACACA and FASN

[Image: see text] [(18)F]AV-45 (florbetapir f18, Amyvid) is an FDA-approved PET imaging agent targeting Aβ plaques in the brain for diagnosis of Alzheimer’s disease (AD). Its metabolites led to a high background in the brain and large bone uptake of [(18)F]F(–), produced from dealkylation of the PEG chain. To slow down the in vivo metabolism, we report the design, synthesis, and evaluation of a highly deuterated derivative, [(18)F]D15FSP, and compared it with N-methyl-deuterated [(18)F]D3FSP and nondeuterated [(18)F]AV-45. D15FSP displayed excellent binding affinity (K(i) = 7.52 nM) to Aβ aggregates. In vitro autoradiography of [(18)F]D15FSP, [(18)F]D3FSP, and [(18)F]AV-45 showed excellent binding to Aβ plaques in human AD brain sections. Biodistribution studies displayed lower bone uptake at 120 min for [(18)F]D15FSP compared to that for [(18)F]D3FSP and [(18)F]AV-45 (1.44 vs 4.23 and 4.03%ID/g, respectively). As the highly deuterated [(18)F]D15FSP displayed excellent Aβ binding affinity, high initial brain penetration, and lower bone retention, it might be suitable for PET imaging in detecting Aβ plaques.

Background: Antibiotic exposure in early life has shown to be a significant risk factor for later fat accumulation in human. However, whether early sub-therapeutic antibiotic (STA) exposure affects body composition and its mechanisms remains unclear. The present study used a combination of comparative slaughter method, microbiota, and metabolomics measurement to investigate the effects of early STA administration and its subsequent withdrawal on body composition, colonic microbiota and metabolite profiles in a pig model. The piglets were fed the same basal starter diet added with STA (STA) or without STA (CON) for two weeks during the administration period, and then all piglets were switched to the same nursery diet without STA during the withdrawal period until they reached approximately 25 kg body weight. Results: Results showed that STA did not significantly improve piglet growth performance during the administration period and the withdrawal period. Piglets treated with the STA had a lower body water deposition (g/d) during the withdrawal period, and tended to have increased body lipid deposition (g/d) during the withdrawal period and the whole period than CON group. It was found that STA was initially effective in decreasing the abundance of pathogenic bacteria during the administration period, such as Alloprevotella, Bacteroides, Solobacterium, and Sutterella. However, they could not continue the effect during the withdrawal period, leading to the rebound of pathogenic bacteria such as Alloprevotella and the increase of the abundance of other pathogenic bacteria like Oscillibacter. Remarkably, STA treatment decreased the abundance of Blautia that play a potential protective role against obesity either during the administration period or the withdrawal period. Metabolomic analysis indicated that STA mainly altered amino acid metabolism, lipid metabolism, and carbohydrate metabolism during the two periods. Furthermore, Spearman's correlation analysis showed that the gut microbiota was highly correlated with microbial metabolites changes. Conclusion: These results suggest that STA administration may alter tissue deposition through reshaping the gut microbiota and their metabolite profiles.

Obesity is an issue of great concern to people all over the world. It is accompanied by serious complications, leading to reduced quality of life and higher morbidity and mortality. Over the past few years, there has been an explosion in knowledge about the roles of potential therapeutic agents in obesity management. Among them, amino acid (AA) derivatives, such as taurine, glutathione (GSH), betaine, α-ketoglutarate (AKG), β-aminoisobutyric acid (BAIBA), and β-hydroxy-β-methylbutyrate (HMB), have recently gained popularity due to their beneficial effects on the promotion of weight loss and improvement in the lipid profile. The mechanisms of action of these derivatives mainly include inhibiting adipogenesis, increasing lipolysis, promoting brown/beige adipose tissue (BAT) development, and improving glucose metabolism. Therefore, this review summarizes these AA derivatives and the possible mechanisms responsible for their anti-obesity effects. Based on the current findings, these AA derivatives could be potential therapeutic agents for obesity and its related metabolic diseases.

In this work, three dimensional self-supported Co3O4@Ni3S2 nanowire arrays on nickel foam substrates are prepared by a multi-step method. The as-synthesized product harvests the advantages of the high electrical conductivity of the Co3O4 nanowire arrays, large surface area provided by the Ni3S2 nanosheets, and the efficient ion diffusion pathway offered by the self-supported structure. The sample is subsequently used as the electrode material for supercapacitors, at a current density of 2 mA cm−2 a charge storage capability of 2.41C cm−2 (5.5 F cm−2) was achieved. When the sample is charged and discharged at 50 mA cm−2 for 10000 cycles, a stable capacity of 0.86C cm−2 (1.5 F cm−2) can still be maintained at the end of the test. Such a performance is better than those values reported in the literature obtained with similar systems even at a lower current density. We also assemble an asymmetric supercapacitor by pairing the Co3O4@Ni3S2 nanoarrays with activated carbon, and it shows good cyclability over 10000 cycles. The device yields energy densities of 65 and 32.3 Wh kg−1 at power densities of 361 and 9090 W kg−1, respectively. Furthermore, it is able to light up 12 red light-emitting diodes, showing promising potential for practical applications.

High-performance CH3NH3PbBr3 (MAPbBr3) room-temperature NO2 sensors have been developed for the first time based on MAPbBr3 films prepared directly from perovskite precursor solutions (PSFs) and from surface-capped MAPbBr3 nanoparticles (NPFs). AFM images of these films revealed that the grain size of MAPbBr3 crystal in PSFs decreases with the increasing on the concentration of precursor solution, and XRD patterns demonstrate MAPbBr3 in PSFs packed along with (00l) crystal orientation. However, MAPbBr3 NPFs have no preferential crystal orientation despite the good crystallinity of MAPbBr3 NPs. I-V curves revealed different hysteresis loops for these two kinds of films. Sensors with PSF or NPF as semiconducting layer exhibited remarkable and reversible change when they are exposed to NO2 gas. Interestingly, NPF sensors show better sensing performance with a lower detection limit (0.1 ppm) and a larger sensitivity. Experiments also revealed that the selectivity of NPF is better than that of PSF sensors. More importantly, NPF sensors are much more stable than PSF sensors due to the protected surface of perovskite NPs. This study opens a new promising application for organometallic halide perovskite materials, especially for the protected perovskite NPs.

We report the preparation of a novel glutamine derivative, (2S,4S)-2,5-diamino-4-(4-(2-fluoroethoxy)benzyl)-5-oxopentanoic acid, (2S, 4S)4-[18F]FEBGln ([18F]4), through efficient organic and radiosyntheses. In vitro assays of [18F]4 using MCF-7 cells showed that it entered cells via multiple amino acid transporter systems including system L and ASC2 transporters but not through the system A transporter. [18F]4 showed promising properties for tumor imaging and may serve as a lead compound for further optimizing and targeting the system L transporter associated with enhanced glutamine metabolism in cancer cells.

To locate the site of a liver lesion by positron emission tomography (PET) imaging and then remove the lesion site under the guidance of fluorescence imaging, we designed an aggregate-induced emission (AIE)-based PET probe [nat/68Ga] 5 based on the effects of the reticuloendothelial system. By modifying derivatives of tetraphenylethene, we obtained a bifunctional chelating agent with AIE characteristics, which can complex with natGa3+ or 68Ga3+ at room temperature to form [natGa] 5 or [68Ga] 5. [natGa] 5 has typical AIE characteristics and can form nanomicelles when its concentration is greater than the critical micelle concentration (CMC). Cellular fluorescence confocal imaging experiments and radioactive uptake experiments showed that Kupffer cells had a high uptake of [nat/68Ga] 5 while HepG2 cells had lower uptake of [nat/68Ga] 5, indicating that liver function imaging was achieved by the phagocytosis of [nat/68Ga] 5 by Kupffer cells into the liver. A biodistribution study showed that [68Ga] 5 shows high accumulation in the liver after intravenous injection into rats. The in vivo PET imaging profile demonstrated an excellent liver to muscle ratio. Thus, [nat/68Ga] 5 could potentially be used as a liver function PET imaging agent for clinical diagnosis and intraoperative navigation.

This study aims to investigate the effects of dietary gamma-aminobutyric acid (GABA) supplementation on the growth performance, intestinal immunity, intestinal GABAergic system, amino acid profiles and gut microflora of the weaned piglets. Totally sixteen healthy piglets were randomly assigned into two groups to be fed with the basal diet (Con group) or the basal diet with GABA (20 mg kg-1) supplementation. Body weights and feed intakes were monitored weekly. Piglets were sacrificed after 3 weeks of GABA supplementation to collect the blood, ileum, ileal mucosa and luminal content. Immune-associated factors, GABAergic system, amino acid profiles, and microbiota in the ileum and serum amino acid profiles were explored. The results showed that GABA supplementation improved the growth performance and modulated the intestinal immunity with inhibiting the gene expressions of IL-22, proinflammatory cytokines (IL-1 and IL-18), and Muc1, but promoted the expressions of anti-inflammatory cytokines (IFN-γ, IL-4, and IL-10), TLR6 and MyD88. GABA regulated a few components of the intestinal GABAergic system, increased the levels of most amino acids in the ileal mucosa but reduced the serum amino acid profiles. GABA regulated the population and diversity of intestinal microbiota, such as the abundances of the dominant microbial populations, the community richness, and diversity of the ileal microbiota. In conclusion, GABA supplementation modulated the intestinal functions, including intestinal immunity, intestinal amino acid profiles and gut microbiota, and the results can be helpful for understanding the functions of GABA in the intestine.

The objective of this study was to evaluate the effects of protein restriction and subsequent protein realimentation on the body composition, gut microbiota and metabolite profiles of piglets. Fifty weaned piglets were randomly assigned to two treatments: a normal protein (NP) group (20% crude protein (CP)) or a low protein (LP) group (16% CP) with five animals per pen and five pens per group. Treatment diets were fed for 14 d during the protein restriction phase, and then all pigs were fed the same nursery diets with a normal CP level (19% CP) during the protein realimentation phase until they reached an average target body weight (BW) of 25 ± 0.15 kg. At day 14 and the end of the experiment, one piglet close to the average BW of each pen was slaughtered to determine body composition, microbial composition and microbial metabolites. Results showed that there was no difference (p &gt, 0.05) in the experimental days to reach target BW between the LP and NP groups. The average daily gain (ADG) and gain:feed ratio (G:F) during the protein restriction phase as well as BW at day 14, were significantly decreased (p &lt, 0.05) in the LP group compared with the NP group. However, there were no significant differences (p &gt, 0.05) during the protein realimentation phase and the overall experiment. Similarly, piglets in the LP group showed a significantly decreased body protein content (p &lt, 0.05) at day 14, but not (p &gt, 0.05) at the end of the experiment. The relative abundance of Parabacteroides, Butyricicoccus, Olsenella, Succinivibrio and Pseudoramibacter were significantly increased (p &lt, 0.05), while the relative abundance of Alloprevotella and Faecalicoccus were significantly decreased (p &lt, 0.05) in the LP group at day 14. At the end of the experiment, the piglets in the LP group showed a higher (p &lt, 0.05) colonic relative abundances of Parabacteroides, unidentified Christensenellaceae and Caproiciproducens, and a lower (p &lt, 0.05) relative abundance of unidentified Prevotellaceae, Haemophilus, Marvinbryantia, Faecalibaculum, Neisseria and Dubosiella than those in the NP group. Metabolomics analyses indicated that tryptophan metabolism and vitamin metabolism were enriched in the LP group at day 14, and glycerophospholipid metabolism and fatty acid esters of hydroxy fatty acid metabolism were enriched at the end of the experiment. Moreover, Spearman’s correlation analysis demonstrated that the microbial composition was highly correlated with changes in colonic metabolites. Collectively, these results indicated that protein restriction and subsequent realimentation lead to compensatory growth and compensatory protein deposition in piglets and contribute to animal intestinal health by altering the gut microbiota and its metabolites.

Background and purpose Prenatal caffeine exposure (PCE) can cause developmental toxicity of long bones in offspring, but the long-term effects and the underlying mechanism have not been fully clarified. Here, we investigated the effects of PCE peak bone mass accumulation and osteoporosis susceptibility in offspring and its intrauterine programming mechanism. Experimental approach Pregnant Wistar rats were administrated intragastrically with saline or caffeine (120 mg·kg-1 ·day-1 ) on gestational days 9-20. The serum and bone samples were collected from the fetal and postnatal offspring for bone mass, genes expression and corticosterone analysis. Then, rat bone marrow mesenchymal stem cells (BMSCs) were treated with corticosterone in vitro to confirm the molecular mechanism. Key results PCE caused fetal bone dysplasia in male and female offspring. In adulthood, PCE reduced peak bone mass and increased osteoporosis susceptibility in male offspring but not in females. Meanwhile, PCE only decreased the H3K9ac and expression levels of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) before and after birth in the male offspring but not in the females. Moreover, the high level of corticosterone induced by PCE down-regulated the H3K9ac and expression levels of 11β-HSD2 through promoting glucocorticoid receptor (GR; NR3C1) into the nucleus of bone marrow mesenchymal stem cells (BMSCs) and recruiting histone deacetylase 11 (HDAC11) binding to 11β-HSD2 promoter region, which further enhanced the effect of corticosterone on suppressing osteogenic function of BMSCs. Conclusion and implications PCE caused osteoporosis susceptibility in male adult offspring, which attributed to the low-functional programming of 11β-HSD2 induced by corticosterone via GR/HDAC11 signalling.

Background: The objective of the present study was to determine the optimal standardized ileal digestible arginine to lysine (SID Arg: Lys) ratio on the reproductive performance, plasma free amino acids and biochemical parameters of sows during gestation , as well as colostrum compositions and performance of their offspring litter . Methods: A total of 174 multiparous sows (3+ parity,Landrace × Large white ) were randomly allocated to five treatment groups with different dietary SID Arg: Lys ratios (0.91, 1.02, 1.14, 1.25 and 1.38) by modifying the supplementation of Arg or alanine (Ala) for isonitrogenous equilibrium. All diets were formulated with the same composition levels including DE at 3.14 Mcal/kg and SID Lys at 0.64%. The reproductive performance of sows during gestation and lactation and the performance of offspring litters during lactation were evaluated. Blood samples were obtained on days 90 and 110 of gestation for analyses of plasma biochemical indexes and free amino acids, and colostrum samples were collected for determination of the composition. Results: The results showed that increasing the dietary SID Arg: Lys ratio increased litter size alive linearly ( P =0.001) and quadratically ( P =0.001), and decreased the number of stillborns linearly ( P

Sulfate, nitrate and ammonium (SNA) are the dominant components of water-soluble ions (WSIs) in PM2.5, which are of great significance for understanding the sources and transformation mechanisms of PM2.5. In this study, daily PM2.5 samples were collected from September 2017 to August 2018 within the Guiyang urban area and the concentrations of the major WSIs in the PM2.5 samples were characterized. The results showed that the average concentration of SNA (SO42&minus, NO3&minus, NH4+) was 15.01 &plusmn, 9.35 &mu, g m&minus, 3, accounting for 81.05% (48.71&ndash, 93.76%) of the total WSIs and 45.33% (14.25&ndash, 82.43%) of the PM2.5 and their possible chemical composition in PM2.5 was (NH4)2SO4 and NH4NO3. The highest SOR (sulfur oxidation ratio) was found in summer, which was mainly due to the higher temperature and O3 concentrations, while the lowest NOR (nitrogen oxidation ratio) found in summer may ascribe to the volatilization of nitrates being accelerated at higher temperature. Furthermore, the nitrate formation was more obvious in NH4+-rich environments so reducing NH3 emissions could effectively control the formation of nitrate. The results of the trajectory cluster analysis suggested that air pollutants can be easily enriched over short air mass trajectories from local emission sources, affecting the chemical composition of PM2.5.

The rise and gradually developing of global value chains (GVC) have changed the essence of international trade, and further complicated the issue of carbon emission. It is of great significance to identify and study the practical carbon intensity in a country under the condition of GVC. Based on Inter-country Input-Output (ICIO) model, this paper establishes a framework for measuring the carbon intensities embodied in aggregated demand and distinguishing pure domestic demand, traditional trade, simple GVC route, complex GVC route at the global level and for 41 economies from 2010 to 2014 according to demand heterogeneity, and uses multiplicative structural decomposition analysis (SDA) method to decompose the driving factors affecting their changes. The results indicate that, in most developed countries, the carbon intensities embodied in international trade were significantly greater than pure domestic carbon intensity, whereas it was opposite in most developing countries. The carbon intensity embodied in traditional trade was generally lower than that in GVC routes, and in low carbon intensity (high carbon intensity) sub-group, the carbon intensity embodied in simple GVC route was lower (higher) than that in complex GVC route. Moreover, the emission coefficient effect was the main driver of the decline in almost all carbon intensities, especially embodied carbon intensity in GVC routes. On the contrary, the intermediate import effect was the main inhibitor, and this effect would cause more rise to embodied carbon intensity in simple GVC route, compared to embodied carbon intensity in complex GVC route.

Maternal dexamethasone decreases the body length of the newborn. However, whether dexamethasone inhibits the development of the growth plate of the fetal long bone is still unknown. Here, we found that lengths of fetal femur and growth plate were both shorter in the fetuses with maternal dexamethasone (0.2 mg/kg.d from gestation day 9 to 20), with a decreased proteoglycan content of the growth plate in the fetal rat. Notable decreases in both the gene expression and H3K9 acetylation of UDP-glucose dehydrogenase (Ugdh) gene, which codes a key enzyme in the proteoglycan biosynthesis in the chondrocyte, were also observed. Meanwhile, up-regulation of glucocorticoid receptor (GR), specific protein 3 (Sp3), and histone deacetylase 1 (Hdac1) gene expression were detected in the fetal growth plate. Similar changes were also observed in the chondrogenic rat bone marrow stromal cells (BMSCs) with excessive exogenous dexamethasone. However, antagonizing GR with RU486 and silencing Hdac1 or Sp3 with specific siRNAs could all stimulate the H3K9 acetylation and gene expression of Ugdh previously inhibited by dexamethasone. Meanwhile, dexamethasone also induced the nuclear translocation of GR, which further directly bound to the Ugdh promoter and interacted with HDAC1 and Sp3, respectively. Collectively, our study revealed that maternal dexamethasone induced the direct binding of GR to the Ugdh promoter of the chondrocyte in the rat fetal growth plate, which recruited HDAC1 and Sp3, induced deacetylation of the H3K9, and subsequently inhibited Ugdh gene expression. Such changes further led to attenuated proteoglycan synthesis in the developing chondrocyte and therefore disrupted the development of growth plate and fetal long bone.

In this study, the O3/Fenton system in a rotating packed bed (RPB) in tandem with coagulation process was applied to the advanced treatment of coal gasification wastewater (CGW). The removal of COD reached 35.4% in the O3/Fenton@RPB process, and the total removal of COD rose to 47.8% after the effluent of the O3/Fenton@RPB process was further treated with coagulation. The O3/Fenton@RPB + coagulation tandem process also demonstrates good effect on enhancing biodegradation and removing color of the CGW, with the BOD5/COD and decolorization in the tandem process reaching 0.49 and 87.5%, respectively. In addition, an artificial neural network model was established to predict the mass transfer performance of the O3/Fenton system in the RPB and exhibited a good predictability. The O3/Fenton@RPB + coagulation tandem process shows the application potential in the advanced treatment of CGW.

Objectives Serotonin transporters (SERT) play an important role in controlling serotonin concentration in the synaptic cleft and in managing postsynaptic signal transduction. Inhibitors of SERT binding are well known as selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, paroxetine, and escitalopram, that are commonly prescribed antidepressants. Positron emission tomography (PET) and single photon emission tomography (SPECT) imaging agents targeting SERT may be useful for studying its function and providing a tool for monitoring drug treatment. Methods A series of novel 18F-labeled diphenyl sulfide derivatives were prepared and tested for their binding affinity. Among them, 2-((2-((dimethylamino)-methyl)-4-(2-(2-fluoroethoxy)ethoxy)phenyl)thio)aniline, 1, which showed excellent binding toward serotonin transporter (SERT) in the brain (Ki = 0.09 nM), was selected for further evaluation. An active OTs intermediate, 7, was treated with [18F]F−/K222 to provide [18F]1 in one step and in high radiochemical yields. This new SERT targeting agent was evaluated in rats by biodistribution studies and animal PET imaging studies. Results The radiolabeling reaction led to the desired [18F]1. After HPLC purification no-carrier-added [18F]1 was obtained (radiochemical yield, 23–47% (n = 10,); radiochemical purity >99%; molar activity, 15–28 GBq/μmol). Biodistribution studies with [18F]1 showed good brain uptake (1.04% dose/g at 2 min post-injection), high uptake into the hypothalamus (1.55% dose/g at 30 min), and a high target-to-non-target (hypothalamus to cerebellum) ratio of 6.1 at 120 min post-injection. A PET imaging study in normal rats showed excellent uptake in the midbrain and thalamus regions known to be rich in SERT binding sites at 60 min after iv injection. Chasing experiment with escitalopram (iv, 2 mg/kg) in a rat at 60 min after iv injection caused a noticeable reduction in the regional radioactivity and the target-to-non-target ratio, suggesting binding by [18F]1 was highly specific and reversible for SERT binding sites in the brain. Conclusions A novel diphenyl sulfide derivative, [18F]1 for SERT imaging was successfully prepared and evaluated. Results suggest that this new chemical entity is targeting SERT binding sites in the brain, and it is a suitable candidate for future commercial development.

The use of avidin or streptavidin in the purification of biotinylated proteins has been highly restricted due to the harsh and denaturing elution conditions. Here, we use biotinylated bovine serum albumin as a working model to demonstrate a simple and rapid method for biotin-tagged protein purification under non-denaturing conditions. The biotinylated bovine serum albumin is specifically bound to the anti-biotin antibody agarose beads and competitively eluted with free biotin under near-neutral conditions. The optimized elution conditions include using 4 mg/ml biotin (pH 8.5) as the elution buffer and allowing the buffer to incubate with agarose beads for 30 min prior to elution. The elution recovery rate is over 85% without apparent protein denaturation. The method is applicable for both immunoprecipitation and column chromatography.

We report a case of a previously well 58-year-old man, who presented with delirium and low GCS, and was found to have extreme hypernatraemia (Na+ = 191 mmol/L) and hyperglycaemia (glucose = 31 mmol/L). This resulted in a corrected serum sodium of 202 mmol/L. He was treated with fluid and electrolyte replacement in the intensive care unit, and had returned to essentially normal function by hospital discharge. The aetiology was believed to be due to severe dehydration and a new diagnosis of diabetes mellitus. Extreme hypernatraemia (serum sodium level greater than 190 mmol/L) is rare and associated with a high mortality. The mainstay of treatment is careful fluid and electrolyte management. Most recommendations advise to reduce the serum sodium by 0.5 mmol/L/hour, due to concerns over cerebral oedema; however, there are reports that slower correction is associated with higher mortality. In this case, the initial corrected sodium of 202 mmol/L was steadily corrected to 160 mmol/L over 91 hours, at a rate of 0.46 mmol/L/hour. This demonstrates the safety of the recommended approach.

Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multiple organs in offspring. Here, we verified the intergenerational effect of low peak bone mass induced by PDE and investigated its intrauterine programming mechanism. Pregnant rats were injected subcutaneously with 0.2 mg/kg/d dexamethasone from gestation day (GD) 9 to 20. Some pregnant rats were killed for the fetuses on GD20, and the rest went on to spontaneous labor to produce the first-generation (F1) offspring. The adult F1 male offspring were mated with normal females to produce the F2 offspring. In vivo, PDE leads to low peak bone mass in F1 male offspring rats at postnatal week (PW) 28. Furthermore, PDE reduced the bone mass in F1 male offspring from GD20 to PW12. Meanwhile, the osteogenic differentiation was suppressed and the local renin–angiotensin system (RAS) was activated continuously by PDE. Moreover, the histone 3 lysine 27 acetylation (H3K27ac) level in angiotensin-converting enzyme (ACE) promoter region was increased by PDE from GD20 to PW12. Likewise, PDE induced the low peak bone mass and the activated local RAS in F2 male offspring. Meaningfully, the H3K27ac level of ACE was increased by PDE in the F2 offspring. In vitro, dexamethasone inhibited bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation and promoted RAS activation. Furthermore, dexamethasone recruited CCAAT/enhancer-binding protein α and p300 into the BMSCs nucleus by activating glucocorticoid receptor, which cooperatively increased the H3K27ac level in the ACE promoter region. In conclusion, PDE induced the low peak bone mass and its intergenerational effect, which was mediated by sustained activation of RAS via increasing H3K27ac level of ACE.

Cassette dosing is also known as N-in-One dosing: several compounds are simultaneously administrated to a single animal and then the samples are rapidly detected by LC-MS/MS. This approach is a successful strategy to enhance the efficiency of drug discovery and reduce animal usage. However, no report on the utility of the cassette approach in radiotracer discovery has appeared in the literature. This study designed a cassette microdose with LC-MS/MS method to enhance the throughput for screening radiopharmaceutical biodistribution in the rat brain directly. Three unradiolabeled compounds (FPBM FPBM2 and AV-133) were chosen as model drugs administrated intravenously to the rats as a cassette as opposed to discrete study. The rat brain biodistribution data, target localization, the differential uptake ratio (%ID/g) and the brain tissue-specific binding ratio were obtained by the LC-MS/MS analysis. These data matched very well with the values obtained by the standard radioactivity measurements. Moreover, no significant differences between discrete dosing and cassette dosing were observed. By circumventing the need for radiolabeled molecules, this method may be high-throughput and safe for the research and development of new PET imaging agents. The combination of cassette microdosing and LC-MS/MS would be a medium throughput screening tool at an early stage in the discovery/development process of PET imaging agents.

CuSbS2 is regarded as a promising photo-absorber for solar energy conversion due to its proper bandgap, high absorptivity and earth abundance. Herein, novel low-cost ZnO/CdS/CuSbS2 core-shell nanowire arrays were constructed as photoanode for hydrogen evolution through non-aqueous electrodeposition and cation exchange. The nanowire demonstrates even and compact multilayer structure. The optimal ZnO/CdS/CuSbS2 photoanode achieves a photocurrent of 6.48 mA/cm2 at 0 V versus Ag/AgCl and the remarkable IPCE value with approximately 52% at 480 nm in an electrolyte solution containing 0.35 mol/L Na2SO3 and 0.25 mol/L Na2S. It also exhibited a good stability, maintained 87.9% of the initial current after 1 h measurement. The high performance benefits from well-crystalline and compact multilayer structure, high absorptivity of CuSbS2 and CdS, p-n junction formed between CdS and CuSbS2 which promotes the electron-hole separation and ZnO nanowire array as three dimensional scaffolds for electron percolation pathway. This work suggests the potential applications of low-cost p-n junction core-shell nanowire arrays as a highly efficient photoanode for hydrogen evolution in oil-field waste water with reductive sulfide.

The source and fate of N-nitrosamines and their precursors in terms of formation potential (FP) was investigated quantitatively in the city level for the first time. Different sources of nitrosamines and their precursors were investigated in one city in the Yangtze River delta, China. The source water located downstream of the city contained 8.4 ng/L of N-nitrosodimethyamine (NDMA) and 153 ng/L of NDMA FP. The contribution of each discharge source was evaluated based on the concentration, the river water flux, and the amount of wastewater discharges. Textile printing and dyeing wastewater, and electroplating industrial wastewater contained high concentration of nitrosamines and were important discharge sources. Taking NDMA and NDMA FP attenuation by photolysis and biodegradation into consideration, the mass load calculation showed upstream surface water brought about 13 ± 4% of NDMA and 21 ± 3% of NDMA FP to downstream source water. Local wastewater discharges contributed 30 ± 8% of NDMA and 17 ± 2% of NDMA FP to downstream source water. Endogenous formation via amino acids metabolism could contribute 36% of NDMA FP (maximum) to downstream source water. Overall, this study provides a protocol for quantitative evaluation of the nitrosamine contribution to urban water supply from different contamination sources.

High anthropogenic N loads and abundant bacteria are characteristic of highly contaminated urban rivers. To better understand the dispersal and accumulation of bacteria, we determined contents and isotopic compositions of suspended particulate organic matter (SPOM) and bacteria in a highly contaminated urban river (the Nanming) and effluents in winter and summer of 2013. Relative to SPOM, bacterial biomass in the river was depleted in 13C and 15N and its C/N ratio was lower (δ13C: − 33.2‰ ± 3.1‰; δ15N: − 1.5‰ ± 1.2‰; C/N: 4.8 ± 0.6), while effluents showed higher 13C and 15N contents and C/N ratios (δ13C: − 25‰ ± 2.1‰; δ15N: + 8.5‰ ± 1.1‰; C/N: 8.1 ± 1.2). Source recognition of SPOM was based on carbon isotopes because they are conservative and distinct between end-members (effluent detritus and bacterial biomass). Using a mixing model, bacterial biomass in the river was calculated to account for

Facing the issues for ineffective visible light utilization, insufficient separation of photogenerated electron-hole pairs of WO 3 photoanode, herein, ultrasmall MoS 2 quantum dots (QDs) are exploited as surface sensitizers to boost the photoelectrochemical (PEC) properties of MoS 2 /WO 3 . The MoS 2 /WO 3 photoanode is prepared by decorating 2D WO 3 nanoplatelet arrays with ultra-small MoS 2 QDs via a facile and effective assembly method. The interspersing of MoS 2 QDs, not only broadens the photoabsorption region, but also provides more active sites for the surface reactions and enhances charge separation of the photogenerated electron-hole pairs, leading to a 2.13-fold enhancement in photocurrent density at 1.0 V vs. Ag/AgCl (1.23 V vs. RHE). MoS 2 /WO 3 photoanodes hold potentialities for the straightforward building of molecular level devices for PEC production.

In this paper, an efficient approach to modify graphitic carbon nitride (g-C3N4) by simple treatment using low-concentration acid under heating was developed. The obtained acidified g-C3N4 sample exhibits about fivefold improvement in the rate of H2 evolution compared to the pristine g-C3N4. The prepared catalysts retained the framework of g-C3N4 but with enhanced separation of photogenerated charge carriers and longer lifetime as well. In addition, according to solid 1H NMR and theoretical calculation, the formed hydrogen bond is enhanced, which can reduce the distance between g-C3N4 and water molecules effectively. The enhanced H-bonding and the formed H-bonding networks are deemed to be the main factors for the improvement of hydrogen evolution.

A two-step hydrothermal process for preparing Ni-doped WO3 nanoplate arrays (NPAs) is developed, and the obtained samples were used as a photoanode to produce a highly active and stable electrocatalyst for photoelectrochemical (PEC) water splitting under visible light. The NPAs are formed as a single-phase solid solution with high purity. X-ray photoelectron spectroscopy measurement verifies the binding energy of W element is negatively shifted due to the substitution of W6+ by Ni2+ in the monoclinic lattice and thereby the formation of Ni-O-W bonds. Notably, the two-step 3 at% Ni-doped WO3 NPAs exhibits the highest PEC performance, compared with pure and one-step Ni-doped WO3 NPAs. At 1.0 V (vs Ag/AgCl), the current density of two-step 3 at% Ni-doped WO3 is 0.80 mA/cm2, which is about 1.74- and 2.35-fold of that of WO3 (0.46 mA/cm2) and one-step 3 at% Ni-doped WO3 (0.34 mA/cm2), respectively. The PEC performance of WO3 NPAs can be modified by Ni doping in a two-step hydrothermal process; both the changes of band gap and electrochemically active surface area (ECSA) are playing important roles on improving the activity of the WO3 NPAs photoanode.

Biomarkers of serum fatty acids in hyperlipidemia need to be elucidated. 90 SPF KM male mice were randomly divided into 18 groups (n=5/group), control groups, and high fat diet (HFD) groups at 9 time points. On day 7, 10, 15, 18, 21, 24, 28, 31, and 35, the mice were sacrificed; blood was collected into tubes from the eyes, serum samples for clinical biochemistry assays and gas chromatography-mass spectroscopy were attained after centrifugation, and the contents of serum fatty acids were detected with GC-MS. Sections of livers were taken and stored in formalin solution for histological assessments. No species differences existed in all these groups. The contents of C16:1, C18:1, C22:6 were significantly different between HFD groups and the corresponding controls; meanwhile, the proportion of fatty acids, especially the monounsaturated degree, the polyunsaturated degree, changed significantly and regularly (P

The thermally expandable microspheres (TEMs) were prepared via suspension polymerization with acrylonitrile (AN), methyl methacrylate (MMA) and methyl acrylate (MA) as monomers and n -hexane as the blowing agent. Meanwhile, a novel type of functional and conductive thermal expandable microsphere was obtained through strongly covering the surface of microsphere by conductive polymers with the mass loading of 1.5%. The optimal conditions to prepare high foaming ratio and equally distributed microcapsules were investigated with AN-MMA-MA in the proportion of 70%/20%/10% (m/m/m), and 25 wt% of n -hexane in oil phase. The further investigation results showed that the unexpanded TEMs were about 30 μm in diameter and the maximum expansion ratio was nearly 125 times of original volume. The polypyrrole (PPy) was smoothly coated on the surface of the TEMs and the expansion property of PPy-coated TEMs was almost the same as the uncoated TEMs. Moreover, the structure and expanding performance of TEMs and PPy-coated TEMs were characterized by scanning electron microscopy (SEM), laser particle size analyzer and dilatometer (DIL).

Lactobacillus reuteri LR1 improved growth performance of weaned pigs in our previous study. The objective of this study was to reveal effects of L. reuteri LR1 on amino acid (AA) metabolism in weaned pigs and its underlying mechanism using metabolomic and proteomics methods. Weaned pigs were fed a basal diet (CON) or the basal diet supplemented with 5 × 1010 cfu kg-1L. reuteri LR1 (LR1) for a 14 d period. Untargeted metabolomic analysis of the liver showed that LR1 up-regulated 33 metabolites and most of them were related to AA metabolism. Quantitative proteomics found that differential proteins were mainly involved in a metabolic process in the ileal mucosa of LR1 vs. CON. Integrated metabolomic and proteomics analysis showed that the LR1's enhancement of AA metabolism in the gut-liver axis is mediated by the up-regulated intestinal AA transporters in the pathway of protein digestion and absorption. Moreover, qPCR results confirmed that LR1 increased (p < 0.05) mRNA abundances of AA transporters (PepT1, EAAT3, rBAT, B0AT1, and b0,+AT) in the ileal mucosa compared with CON. Furthermore, western blot analysis showed that LR1 activated the mammalian target of the rapamycin complex 1 (mTORC1) signaling pathway by increasing the phosphorylation of S6 and 70S6K1 in the gut-liver axis of weaned pigs. Together, these data indicated that dietary supplemented LR1 enhanced AA metabolism by up-regulating intestinal AA transporter expression and activating the mTORC1 signaling pathway in the gut-liver axis of weaned pigs.

Obesity increases the risk of developing insulin resistance and diabetes and is a major public health concern. Our previous study shows that dietary β-hydroxy-β-methylbutyrate (HMB) improves lipid metabolism in a pig model. However, it remains unclear whether HMB blocks obesity through gut microbiota. In this study, we found that HMB reduced body weight, alleviated the whitening of brown adipose tissue, and improved insulin resistance in mice fed a high-fat diet (HFD). High-throughput pyrosequencing of the 16S rRNA demonstrated that HMB administration significantly reversed the gut microbiota dysbiosis in HFD-fed mice, including the diversity of gut microbiota and relative abundances of Bacteroidetes and Firmicutes. Moreover, microbiota transplantation from HMB-treated mice attenuated HFD-induced lipid metabolic disorders. Furthermore, HFD-fed mice showed lower short-chain fatty acids, whereas administration of HMB increased the propionic acid production. Correlation analysis identified a significant correlation between propionic acid production and the relative Bacteroidetes abundance. Sodium propionate treatment also attenuated HFD-induced lipid metabolic disorders. Collectively, our results indicated that HMB might be used as a probiotic agent to reverse HFD-induced obesity, and the potential mechanism was associated with reprogramming gut microbiota and metabolism, especially Bacteroidetes-mediated propionic acid production. In future studies, more efforts should be made to confirm and expand the beneficial effects of HMB to human models.-Duan, Y., Zhong, Y., Xiao, H., Zheng, C., Song, B., Wang, W., Guo, Q., Li, Y., Han, H., Gao, J., Xu, K., Li, T., Yin, Y., Li, F., Yin, J., Kong, X. Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.

Unstable and low-abundance protein complexes represent a large family of transient protein complexes that are difficult to characterize, even by means of high-resolution NMR spectroscopy. A method to assign the NMR signals of these unstable complexes through a combination of selective isotope labeling of amino acids in a protein and site-specific labeling the protein with a paramagnetic tag is presented herein. By using this method, the resonances of unstable thioester intermediate complex (lifetime

Aromatase is an attractive target for the diagnosis and treatment of breast cancer. To combine the anti-photobleaching properties of Aggregation Induced Emission (AIE) with the high sensitivity and whole-body imaging characteristics of positron emission tomography (PET), we designed a bifunctional complexing agent with AIE characteristics by modifying the structure of tetraphenylethene, which is linked with triazole derivatives capable of complexing with natGa3+/68Ga3+ to obtain [natGa/68Ga] 2 for targeting the aromatase. [natGa] 2 has typical AIE characteristics, which can form uniform nanomicelles above the critical micelle concentration, and illuminate estrogen receptor (+) MCF-7 cells. [natGa] 2 itself is almost nonemissive in PBS buffer solution, but it turns on its fluorescence upon interaction with human aromatase, with a detection limit of 0.15 μg/mL [68Ga] 2 is easy to prepare and has high stability. Compared to the estrogen receptor that is negatively expressed by MDA-MB-231 cells, MCF-7 cells positively expressing estrogen have a higher uptake of [natGa] 2. The distribution of aromatase in a tumor can be co-localized by using [68Ga] 2. These results can be used to effectively assess estrogen receptor status and aromatase levels at the cellular level. We anticipate that this research could provide a new strategy for the fabrication of PET probes with AIE characteristics, providing useful probes for PET- FL (Fluorescence imaging) bimodal imaging.