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As ancient bacterial endosymbionts of eukaryotic cells, mitochondria have retained their own circular DNA as well as protein translation system including mitochondrial ribosomes (mitoribosomes). In recent years, methodological advancements in cryoelectron microscopy and mass spectrometry have revealed the extent of the evolutionary divergence of mitoribosomes from their bacterial ancestors and their adaptation to the synthesis of 13 mitochondrial DNA encoded oxidative phosphorylation complex subunits. In addition to the structural data, the first assembly pathway maps of mitoribosomes have started to emerge and concomitantly also the assembly factors involved in this process to achieve fully translational competent particles. These transiently associated factors assist in the intricate assembly process of mitoribosomes by enhancing protein incorporation, ribosomal RNA folding and modification, and by blocking premature or non-native protein binding, for example. This review focuses on summarizing the current understanding of the known mammalian mitoribosome assembly factors and discussing their possible roles in the assembly of small or large mitoribosomal subunits.

The purpose of this study is to examine the bidirectional relationship between children’s language development and challenging behaviors as well as the moderating roles of gender and race/ethnicity. We conducted a number of structural equation modeling analyses with a national representative sample ( N = 2,462) of Head Start children from the 2014 Head Start Family and Child Experiences Survey. Results suggest that there is no bidirectional relationship between vocabulary development and challenging behavior in the full sample. However, gender, race/ethnicity, and the interaction between the two moderate associations between language and behavior.

Family systems are dynamic and interconnected, yet very limited research has considered both fathers’ and mothers’ perceptions of family support, stress and Family Quality of Life (FQOL) in a dynamic manner, especially in the Chinese context. The current study examines the association between parenting stress, FQOL and family support using a dyadic approach. We employed the actor-partner interdependence mediation model (APIMeM) to analyze a sample (N = 219 dyads) of Chinese fathers’ and mothers’ of children with autism spectrum disorder. Results suggested a strong actor effect of family support on decreasing stress and improving FQOL for mother and father respectively. However, the partner effect was largely contrasted with mothers’ perceived family support and positively associated with fathers’ FQOL, and fathers’ perceived family support negatively associated with mothers’ FQOL. There were no mediating effects of stress on partners’ perceived support on FQOL. Despite being in a family system, the contrast pattern (opposite direction of the effects) between mothers and fathers suggest large discrepancies and perceptions, which may be due to different family roles and parenting involvement. Policy and practical implications are provided.

This study aimed to explore the association between vaginal microbiota and infertility. We searched a range of electronic databases for appropriate articles, including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang, from inception to 8th September 2019. Identified articles were then screened using strict inclusion and exclusion criteria. By referring to Tamarelle’s method, we divided vaginal microbiota into two categories: low-Lactobacillus vaginal microbiota (LL-VMB) and high-Lactobacillus vaginal microbiota (HL-VMB). Patients were defined as HL-VMB if they had a Nugent score of 0–3, a negative Amesel/Spiegel’s test, or if the vaginal community status was dominated by either L. crispatus, L. iners, L. gasseri and L. jensenii via 16S rRNA sequencing. Otherwise, cases were regarded as LL-VMB. Statistical analyses were performed with STATA 13.0 statistical software. Effect estimates are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Fifteen articles were included in our final analysis. The HL-VMB was negatively related to infertility; a fixed model showed that the pooled OR was 0.83 (95% CI 0.77–0.90). There was no significant publication bias, as determined by Begg’s test (P = 0.488) and Egger’s test (P = 0.652). Using a random effect model, the pooled OR for intermediate bacterial vaginitis (BV) and infertility was 1.39 (95% CI 1.10–1.76) and the pooled OR for positive BV was 1.72 (95% CI 1.10–2.69). Subgroup and sensitivity analyses further demonstrated that the associations identified were stable. However, the acquired evidence was not sufficient to make inferences with regards to the mechanisms underlying these relationships. This systematic review and meta-analysis identified a negative correlation between HL-VMB and female infertility. However, due to a variety of limitations, the evidence acquired does not allow us to identify the specific mechanisms underlying this association. Further high-quality studies are needed to verify the causal relationship and explore the molecular mechanisms involved.

This experiment was conducted to investigate the effects of dietary lipid-to-carbohydrate ratio on growth and carbohydrate metabolism in juvenile cobia (Rachycentron canadum). Six isonitrogenous diets were prepared to vary in lipid-to-carbohydrate ratio (g/g) as follows: D1, 2.26; D2, 1.31; D3, 0.78; D4, 0.47; D5, 0.34; and D6, 0.23. Cobias were fed to satiety for 8 weeks. The weight gain and protein efficiency ratio in D1 group were significantly lower than those in other groups (P

Grona styracifolia (Osbeck) Merr. (GS), a popular folk medicine, is clinically applied to treat nephrolithiasis. In this study, a urinary metabolic analysis was performed in a mouse model of renal calcium oxalate (CaOx) crystal deposition to identify the differentially altered metabolites in mice with oxalate-induced renal injury and explore the therapeutic mechanisms of GS against nephrolithiasis. Twenty-four mice were randomly divided into the control, oxalate and GS-treated groups. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to analyze the metabolic profiles of the urine samples. In addition, network pharmacology analysis was performed with different databases. As a result, the protective effects of GS were verified by measuring biochemical parameters and detecting crystal deposition. Fifteen metabolites were identified as the differentially altered metabolites in mice with crystal-induced renal injury. Most were involved in amino acid and fatty acid metabolism. Thirteen of these metabolites showed a reversal trend following GS treatment. A component-target-metabolite network was further constructed and nine overlapping target proteins of GS and the differentially altered metabolites were discovered. Among these proteins, the expression of estrogen receptor 2 (ESR2) in renal tissues was significantly down-regulated while androgen receptor (AR) expression was obviously increased in the oxalate group compared with the control group. These changes were reversed by the GS treatment. In conclusion, GS exerts its therapeutic effect by regulating multiple metabolic pathways and the expression of ESR and AR in mice with oxalate-induced renal injury.

Increasing evidence suggests that long noncoding RNAs can exert neuroprotective effects in cerebral ischemia-reperfusion injury. Levels of the long noncoding RNA ANRIL (ANRIL) are reportedly altered in ischemic stroke (IS) patients, but its role in IS requires further clarification. This study was designed to explore the mechanistic function of ANRIL in IS. In vitro, HT22 cells was treated with an oxygen-glucose deprivation/reperfusion (OGD/R). In vivo, brain ischemia/reperfusion was induced by 60-minute transient middle cerebral artery occlusion/ reperfusion (MCAO/R) IS model in C57/BL6 mice. Additionally, cells were transfected with si-ANRIL, pcDNA3.1-ANRIL, pcDNA3.1-NF-κB, or appropriate negative controls, and si-ANRIL and pcDNA3.1-NF-κB were administered into the lateral ventricles in MCAO/R model mice. Cell viability and apoptosis were detected via MTT and flow cytometry assays. mRNA and protein expression of NF-κB were detected via qRT-PCR and Western blotting. IL-1β, IL-6, TNF-a, and iNOS levels were detected via ELISA. In addition, infarcted area and neuronal injury were evaluated via TTC, Nissl, and immunofluorescent staining. We found that ANRIL knockdown increased cell viability and reduced apoptosis in vitro. Additionally, we found that ANRIL knockdown decreased p-P65, P65, IL-1β, IL-6, TNF-a, and iNOS levels, whereas these effects were reversed by NF-κB overexpression both in vitro and in vivo. Our results suggest that ANRIL knockdown attenuates neuroinflammation by suppressing the expression of NF-κB both in vitro and vivo model of IS, sugguesting that ANRIL might be a potentially viable therapeutictarget to diminish neuroinflammation in IS patients.

BACKGROUND Eupatilin, an active flavone separated from Artemisia species, has various biological activity such as anti-inflammatory activity. The aim of the present study was to find out the influence of eupatilin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. MATERIAL AND METHODS The administration of LPS was used to induce ALI; eupatilin was given 1 hour before the LPS administration. Lung structural damage of rats was analyzed by hematoxylin and eosin staining and the wet/dry lung ratio. The related inflammatory factors and lung injury markers were examined by enzyme-linked immunosorbent assay. The oxidative stress factors were analyzed by corresponding kits. The expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) was assayed by western blot and immunohistochemical staining. RESULTS The results showed that eupatilin alleviated LPS-induced structural damage and decreased the wet/dry lung ratio concentration-dependently. Eupatilin decreased the level of surfactant protein (SP)-A, SP-D, and inflammatory factors such as interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and monocyte chemo-attractant protein (MCP)-1. LPS trigged nitric oxide (NO) generation, improved the production of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and decreased the activity of superoxide dismutase (SOD), which were reversed when rats treated with eupatilin in a concentration-dependent way. Besides, the expression of PPAR-a was increased under the treatment of eupatilin. CONCLUSIONS Collectively, eupatilin alleviated LPS-induced ALI through inhibiting inflammation and oxidative stress in a concentration-dependent way, which was likely to be closely related with the activation of PPAR-alpha.

Two novel sugar-conjugated 5-fluorocytosine (5-FC) antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter (GLUT). The antitumor activity of these compounds was evaluated in four different human cancer cell lines: A549 (human lung cancer cell line), HT29 (human colorectal cancer cell line), H460 (human lung cancer cell line), and PC3 (human prostate cancer cell line). The sugar conjugates exhibited cytotoxicity similar to or higher than 5-FC and 1-hexylcarbamoyl-5-FC in A549, HT29, H460, and PC3. Furthermore, GLUT-mediated transport of the glycoconjugate was investigated with GLUT inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing HT29 cell line. The cell-killing potency of 5-FC glycoconjugate was found to depend significantly on the GLUT inhibitor, and the cellular uptake of molecules was regulated by GLUT-mediated transport. All the results demonstrate the potential advantages of glycoconjugation for Warburg effect-targeted drug design.

The effects of N‐carbamylglutamate (NCG) on growth, intestinal enzyme activities, immunological and antioxidant parameters were evaluated by a 56‐d feeding trial in Pelteobagrus fulvidraco fed diets containing NCG with 0, 250, 500, 1,000 or 2,000 mg/kg, respectively. The results showed that 250 mg/kg of NCG resulted in significantly higher weight gain, intestine fold height, intestine lipase, serum lysozyme, glutathione peroxidase and total antioxidant capacity than control (p

Phosphoinositides play important roles in the regulation of protein recruitment at specialized membrane domains, protein activity, and membrane dynamics. Phosphoinositide-protein interplay occurs via multiple mechanisms and proteins associate with membranes through different binding patterns. Determinations of membrane-binding mode and membrane penetration depth of proteins in lipid bilayer are thus important steps in characterizing the molecular mechanisms of membrane-protein interactions. Here, we show two standard in vitro assays using liposomes, diphenylhexatriene (DPH) anisotropy, and fluorescence quenching by brominated lipids to determine membrane penetration of proteins into lipid bilayer. These methods will provide useful tools to study membrane-protein association and uncover molecular details of protein-lipid interplay, which are important for understanding biological functions of membrane-associated proteins and membrane dynamics.

A large proportion of proteins are expected to interact with cellular membranes to carry out their physiological functions in processes such as membrane transport, morphogenesis, cytoskeletal organization, and signal transduction. The recruitment of proteins at the membrane-cytoplasm interface and their activities are precisely regulated by phosphoinositides, which are negatively charged phospholipids found on the cytoplasmic leaflet of cellular membranes and play critical roles in membrane homeostasis and cellular signaling. Thus, it is important to reveal which proteins interact with phosphoinositides and to elucidate the underlying mechanisms. Here, we present two standard in vitro methods, liposome co-sedimentation and co-flotation assays, to study lipid-protein interactions. Liposomes can mimic various biological membranes in these assays because their lipid compositions and concentrations can be varied. Thus, in addition to mechanisms of lipid-protein interactions, these methods provide information on the possible specificities of proteins toward certain lipids such as specific phosphoinositide species and can hence shed light on the roles of membrane interactions on the functions of membrane-associated proteins.

Seipin is an oligomeric integral endoplasmic reticulum (ER) protein involved in lipid droplet (LD) biogenesis. To study the role of seipin in LD formation, we relocalized it to the nuclear envelope and found that LDs formed at these new seipin-defined sites. The sites were characterized by uniform seipin-mediated ER-LD necks. At low seipin content, LDs only grew at seipin sites, and tiny, growth-incompetent LDs appeared in a Rab18-dependent manner. When seipin was removed from ER-LD contacts within 1 h, no lipid metabolic defects were observed, but LDs became heterogeneous in size. Studies in seipin-ablated cells and model membranes revealed that this heterogeneity arises via a biophysical ripening process, with triglycerides partitioning from smaller to larger LDs through droplet-bilayer contacts. These results suggest that seipin supports the formation of structurally uniform ER-LD contacts and facilitates the delivery of triglycerides from ER to LDs. This counteracts ripening-induced shrinkage of small LDs.

Condensed tannins (CT) have been observed to be beneficial to maintain glucose homeostasis and improve carbohydrate utilization for livestock, whereas little information is available about the effects of CT on glycometabolism of fish. Three diets were formulated to contain approximately 15 % carbohydrate (G1), 39 % carbohydrate (G2), and G2 supplemented with 0.1 % CT. A total of 225 juvenile Lateolabrax japonicus were randomly assigned to 3 groups (triplicate tanks per group) with 25 fish in each tank and fed to apparent satiation during 56-d feeding trial. Results indicated that fish fed G2 had lower (p < 0.05) final body weight, weight gain rate, feed intake, specific growth rate and serum insulin concentration, but higher (p < 0.05) feed efficiency ratio and serum glucose, total antioxidant capacity, superoxide dismutase, immunoglobulin M and lipopolysaccharide than those fish fed G1 or G3. The activity of pyruvate kinase (PK) was lower (p < 0.05) but glucokinase (GK) was higher (p < 0.05) in G2 than in G1 or G3. Gene expression of insulin like growth factor Ⅰ and PK were down-regulated (p < 0.05), whereas GK was up-regulated (p < 0.05) in G2 than in G1 or G3. No difference (p> 0.05) in these gene expressions were observed between G1 and G3. It was concluded that L. japonicus fed diet with 39 % carbohydrate exhibited depressed growth performance, increased antioxidant and immune capacity, and hyperglycemia. Supplementation of 0.1 % CT resulted in improved growth performance and decreased serum glucose concentration, mainly due to the positive effects of CT on the activity and gene expression of hepatic glycolysis and gluconeogenesis enzymes of L. japonicus.

Chinese sacbrood virus (CSBV) is a serious threat to eastern honeybees (Apis cerana), especially larvae. However, the pathological mechanism of this deadly disease remains unclear. Here, we employed mRNA and small RNA (sRNA) transcriptome approach to investigate the microRNAs (miRNAs) and small interfering RNAs (siRNAs) expression changes of A. cerana larvae infected with CSBV under natural condition. We found that serine proteases involved in immune response were down-regulated, while the expression of siRNAs targeted to serine proteases were up-regulated. In addition, CSBV infection also affected the expression of larvae cuticle proteins such as larval cuticle proteins A1A and A3A, resulting in increased susceptibility to CSBV infection. Together, our results provide insights into sRNAs that they are likely to be involved in regulating honeybee immune response.

Varroa destructor is by far the most serious threat to the western honey bee, Apis mellifera. A screen bottom board, a cultural method for mite control, is a modified bottom board with a screen that allows mites to fall onto a sticky board, or the grass or soil below the screen. Whether or not a screen bottom board can reduce varroa significantly has been controversial. Most studies show a trend of lower varroa populations in colonies with these boards, but the results are usually not statistically significant. To understand whether the negative results have been due to small sample sizes, or because the board is actually ineffective, we conducted a meta-analysis with seven published studies with a total of 145 colonies. Meta-analysis showed that the confidence intervals of the combined effect sizes were negative with a Hedges&rsquo, g of &minus, 1.09 (SE 0.39, 95% CI &minus, 2.0 to &minus, 0.19, p &lt, 0.01), which suggests that the varroa population in colonies with screen bottom boards is significantly lower compared to those with traditional wooden floors. We thus conclude that the screen bottom board does have a significantly negative impact on the varroa population and can be part of tool kits for mite control.

Background Nephrolithiasis is a systemic metabolic disease with a high prevalence worldwide and is closely related to lipid-mediated oxidative stress and inflammation. Orthosiphon stamineus Benth. (OS) is a traditional medicinal herb mainly containing flavonoids, caffeic acid derivatives, and terpenoids, which has the effect of treating urinary stones. However, the active ingredients of OS for the treatment of kidney stones and their regulatory mechanisms remain unknown. As a powerful antioxidant, flavonoids from herbs can mitigate calcium oxalate stone formation by scavenging radical. Thus, this work focused on EtOAc extract of OS (EEOS, mainly flavonoids) and aimed to reveal the potential intrinsic mechanism of EEOS in the treatment of kidney stones disease. Methods Firstly, 75% ethanol extract of OS was further extracted with EtOAc to obtain EtOAc extract containing 88.82% flavonoids. Secondly, the extract was subjected to component analysis and used in animal experiments. Then, an untargeted lipidomics based on ultrahigh performance liquid chromatography coupled with TripleTOF 5600 mass spectrometer (UPLC-QTOF-MS) was performed to test the lipid changes of kidneys in the control group, model group and EEOS treatment groups. Finally, multivariate statistical analysis was used to identify differences between the lipid profiles of mice in the model group and the EEOS group. Results Fifty-one lipid metabolites were significantly different between the mice in the model group and the EEOS intervention group, including glycerophosphocholines, glycerophosphoethanolamines, glycerophosphoinositols, and glycerophosphoglycerols. And the composition of glycerophospholipids-esterified ω-3 polyunsaturated fatty acids and glycerophospholipid subclasses in the kidneys of the EEOS group significantly changed compared to model group. Conclusions The EEOS can inhibit the stones formation by improving oxidative stress and inflammation mediated by glycerophospholipid metabolism. This study reveals the potential mechanism of EEOS for kidney stones treatment at the lipid molecule level, providing a new direction for further study of the efficacy of OS.

Coating and cross-linking have been widely used to improve the properties of materials in tissue engineering. A chitosan/hydroxyapatite (CS/HA) comby scaffold with high porosity was prepared via a 3D printed pore-forming mold. The scaffold was then treated with gelatin (Gel) coating and was cross-linked by glutaraldehyde (GA) in order to improve the mechanical strength. The materials were characterized by infrared spectroscopy (IR) and X-ray diffraction (XRD). The structure of the scaffolds was observed by Scanning Electron Microscopy (SEM). Compression tests were carried out to evaluate the strength of the scaffolds. The behaviors and responses of preosteoblast cells on the scaffolds were studied as well. The results showed that gelatin coating and cross-linking significantly enhanced the mechanical strength of the porous scaffolds. Cell culture experiment indicated that the scaffold had good cytocompatibility. The combined application of 3DP structure construction and biopolymer coating/cross-linking would offer some new ideas in fabrication of porous scaffolds with enhanced strength and good biocompatibility for tissue engineering.

Honey bee viruses are associated with honey bee colony decline. Israeli acute paralysis virus (IAPV) is considered to have a strong impact on honey bee survival. Phylogenetic analysis of the viral genomes from several regions of the world showed that various IAPV lineages had substantial differences in virulence. Chronic bee paralysis virus (CBPV), another important honey bee virus, can induce two significantly different symptoms. However, the infection characteristics and pathogenesis of IAPV and CBPV have not been completely elucidated. Here, we constructed infectious clones of IAPV and CBPV using a universal vector to provide a basis for studying their replication and pathogenesis. Infectious IAPV and CBPV were rescued from molecular clones of IAPV and CBPV genomes, respectively, that induced typical paralysis symptoms. The replication levels and expression proteins of IAPV and CBPV in progeny virus production were confirmed by qPCR and Western blot. Our results will allow further dissection of the role of each gene in the context of viral infection while helping to study viral pathogenesis and develop antiviral drugs using reverse genetics systems.

Background Accumulating evidence shows that circulating levels of trimethylamine N-oxide, which is generated from the metabolism of dietary choline, may predict cardiovascular disease among Caucasians. Acute coronary syndrome (ACS), one common presentation of cardiovascular disease, is a spectrum of signs and symptoms due to acute decreased blood flow in the coronary arteries. The relationship between the metabolites from choline pathway and ACS remains unclear. We aimed to assess the associations of circulating metabolites from the choline pathway with ACS among a Chinese population, who consume a different dietary pattern than their Western counterparts. Methods We recruited 501 participants who were admitted to the Department of Cardiology, Zhongshan Hospital,Shanghai China between March 2017 and June 2018, including 254 ACS cases and 247 controls. Liquid chromatography-tandem mass spectrometry was used to measure circulating concentrations of metabolites in the choline pathway, including betaine, choline, trimethylamine, and trimethylamine N-oxide. A composite metabolite score using a weighted sum of these four metabolites, and the betaine/choline ratio were calculated. Multivariable logistic regressions were applied to estimate the association of metabolites with ACS, with adjustment of age, sex, body mass index, smoking index, history of diseases, and kidney function. Results After adjusting for traditional risk factors, per 1-standard deviation (SD) increment in choline was positively associated with the odds of ACS [odds ratio (OR), 95% confidence interval (CI), 1.77(1.44–2.18)], and the other metabolites were not associated with ACS at a statistical significance level. Compared with participants in the lowest quartile of the metabolite score, those in the highest quartile had higher odds of ACS [OR (95% CI), 3.18(1.85–5.54), p Conclusions Among our Chinese participants, trimethylamine N-oxide was not associated with ACS, while a composite metabolite score of metabolites from the choline pathway was associated with increased odds of ACS. The choline pathway metabolites may be related to the pathophysiology of ACS among Chinese.

An orthogonal aminoacyl-tRNA synthetase/tRNA pair is a crucial prerequisite for site-specific incorporation of unnatural amino acids. Due to its high codon suppression efficiency and full orthogonality, the pyrrolysyl-tRNA synthetase/pyrrolysyl-tRNA pair is currently the ideal system for genetic code expansion in both eukaryotes and prokaryotes. There is a pressing need to discover or engineer other fully orthogonal translation systems. Here, through rational chimera design by transplanting the key orthogonal components from the pyrrolysine system, we create multiple chimeric tRNA synthetase/chimeric tRNA pairs, including chimera histidine, phenylalanine, and alanine systems. We further show that these engineered chimeric systems are orthogonal and highly efficient with comparable flexibility to the pyrrolysine system. Besides, the chimera phenylalanine system can incorporate a group of phenylalanine, tyrosine, and tryptophan analogues efficiently in both E. coli and mammalian cells. These aromatic amino acids analogous exhibit unique properties and characteristics, including fluorescence, post-translation modification., Orthogonal aminoacyl-tRNA synthetase/tRNA pairs are crucial for the incorporation of unnatural amino acids in a site-specific manner. Here the authors use rational chimera design to create multiple efficient pairs that function in bacterial and mammalian systems for genetic code expansion.

Since the discovery that honey bee viruses play a role in colony decline, researchers have made major breakthroughs in understanding viral pathology and infection processes in honey bees. Work on virus transmission patterns and virus vectors, such as the mite Varroa destructor, has prompted intense efforts to manage honey bee health. However, little is known about the occurrence of honey bee viruses in bee predators, such as vespids. In this study, we characterized the occurrence of 11 honey bee viruses in five vespid species and one wasp from four provinces in China and two vespid species from four locations in France. The results showed that all the species from China carried certain honey bee viruses, notably Apis mellifera filamentous virus (AmFV), Deformed wing virus (DWV), and Israeli acute paralysis virus (IAPV), furthermore, in some vespid colonies, more than three different viruses were identified. In France, DWV was the most common virus, Sacbrood virus (SBV) and Black queen cell virus (BQCV) were observed in one and two samples, respectively. Phylogenetic analyses of IAPV and BQCV sequences indicated that most of the IAPV sequences belonged to a single group, while the BQCV sequences belonged to several groups. Additionally, our study is the first to detect Lake Sinai virus (LSV) in a hornet from China. Our findings can guide further research into the origin and transmission of honey bee viruses in Vespidae, a taxon of ecological, and potentially epidemiological, relevance.

Limbal niche cells located in the limbal Palisades of Vogt are mesenchymal stem cells that reside next to limbal basal epithelial cells. Limbal niche cells are progenitors that express embryonic stem cell markers such as Nanog, Nestin, Oct4, Rex1, Sox2 and SSEA4, mesenchymal cell markers such as CD73, CD90 and CD105, and angiogenesis markers such as Flk‐1, CD31, CD34, VWF, PDGFRβ and α‐SMA, but negative for CD45. In addition, the stemness of limbal niche cells can be maintained during their cell culture in a three‐dimension environment. Furthermore, expanded limbal niche cells have the capability to undergo adipogenesis, chondrogenesis, osteogenesis and endogenesis in vitro, indicating that they are in fact a valuable resource of adult progenitors. Furthermore studies on how the limbal niche cells regulate the aforementioned stemness and corneal fate decision are warranted, as those investigations will shed new light on how mesenchymal progenitors reverse limbal stem cell deficiency and lead to new methods for limbal niche cell treatment.

Recently, increasing regulatory and public attention has been paid to the exposure risks of antibiotics due to their occurrence and antibiotic resistance worldwide. However, limited information on antibiotic levels in general populations is available. Forty antibiotics, including 9 sulfonamides, 5 fluoroquinolones, 4 macrolides, 4 tetracyclines, 3 chloramphenicols, 12 β-lactams and 3 others, were analyzed in 107 serum samples of normal adults collected from a hospital in Dalian, North China, between 2015 and 2016 using solid-phase extraction (SPE) coupled with HPLC-MS/MS. The results clearly showed that antibiotics were present in the serum of these adults. Specifically, 28 antibiotics were detected in the samples, with detection frequencies ranging from 0.9% to 17.8%. The total antibiotic concentrations in 26.2% of the serum samples were between the LOD and 20.0ng/mL. Importantly, the maximum concentrations of 5 antibiotics (trimethoprim, ciprofloxacin, cefaclor, lincomycin and erythromycin) were above 1000ng/mL in 3.7% of the samples. Furthermore, the detection frequencies of 5 veterinary antibiotics, 7 human antibiotics and 16 human/veterinary antibiotics in the serum samples were 23.4%, 17.8% and 29.0%, respectively. Significant differences of the veterinary antibiotics between female and male adults and of the sulfonamides between different BMI (body mass index) groups were observed (p

Aethina tumida is a parasite and predator of honeybee causing severe loss to the bee industry. No effective and environmentally friendly methods are available to control this pest at present. Chemosensory genes play key roles in insect behavior which can potentially be used as targets for developing environmentally friendly pest control agents. In this study, the putative chemosensory genes in antennae and forelegs of A. tumida involved in olfaction or contact chemical communication of adults were investigated using RNA transcriptome sequencing and PCR methods. Based on transcriptomic data, unigenes encoding 38 odorant receptors (ORs), 24 ionotropic receptors (IRs), 14 gustatory receptors (GRs), 3 sensory neuron membrane proteins (SNMPs), 29 odorant binding proteins (OBPs), and 22 chemosensory proteins (CSPs) were identified. The analyses of tissue expression profiles revealed that genes encoding 38 ORs, 13 antennal IRs, 11 GRs, 1 SNMP, 24 OBPs, and 12 CSPs were predominately expressed in antennae. No significant differences in expression levels of these genes were found between males and females. Genes encoding 5 non-NMDA iGluRs, 3 GRs, 2 SNMPs, 5 OBPs, and 12 CSPs were predominately expressed in forelegs. RT-PCR assays for SNMPs, OBPs and CSPs further revealed that 3 OBPs (AtumOBP3, 26 and 28) and 3 CSPs (AtumCSP7, 8 and 21) were highly expressed in antennae. Our results enrich the gene inventory of A. tumida and facilitate the discovery of potential novel targets for developing new pest control measures.

Populus cathayana was employed as a model species to study sexual differences in plant growth, physiological, biochemical, and ultrastructural responses to manganese (Mn) stress with two different nitrogen sources (NH4 + and NO3 −). Results showed that NH4 +-N (3.75 mM) and NO3 −-N (3.75 mM) significantly increased plant growth, gas exchange capacity, as well as superoxide dismutase (SOD) and peroxidase (POD) activities in the leaves of both male and female P. cathayana. In addition, NH4 +-N supply could improve tolerance to Mn stress in both male and female P. cathayana with higher photosynthetic capabilities, biomass accumulation, antioxidant enzyme activities, superoxide radicals (O2 −) and thiobarbituric acid-reactive substances (TBARS) in leaves. Under the same condition, female plants grown under NO3 − supply exhibited significantly lower biomass accumulation, photosynthetic capabilities, and antioxidant enzyme activities than male plants because of higher Mn accumulation in both above- and belowground organs and higher ROS releasing rate in leaves. Moreover, damage to cellular ultrastructure was also observed in leaves of males and females exposed to Mn stress, but more strongly in females, with more visible degradation of mitochondrion in plant leave cells. The difference in the preferences for different N sources between male and female P. cathayana under Mn stress provides important guidance in fertilizing strategy to minimise intraspecific competition between female and male plants.

Polybrominated diphenylethers (PBDE) have been demonstrated to be associated with significant alterations in hormone levels in humans. However, yet few epidemiological human evidence has associated thyroid function with hydroxylated polybrominated diphenylethers (OH-PBDEs), which may be more potent in disrupting thyroid hormone homeostasis. In the present study, the body burdens of 7 PBDEs and 11 OH-PBDEs as well as the serum thyroid status were examined in a cohort of 33 thyroid cancer patients. The levels of ∑PBDEs and ∑OH-PBDEs ranged from 1.07 to 39ng/g lipid, and 0.01-0.46ng/g lipid, respectively. BDE-47, 6-OH-BDE-47 and 3-OH-BDE-47 were the predominant congeners. The associations between these PBDE congeners and thyroid function were not significant after controlling for sociodemographic characteristics, as well as the associations between OH-PBDEs and free T3. There were an inverse association between lg3-OH-BDE-47 and lgFT4 (free T4) but a positive association between lg4'-OH-BDE-49 and TSH. Both lgΣ5OH-PBDEs (the sum of HO-tetra-BDEs) and lgΣOH-PBDEs were significantly and positively associated with lgTSH. Our results are consistent with most human studies, suggesting that OH-PBDEs can alter thyroid function by enhancing the elimination of serum FT4 with elevated TSH levels. To our knowledge, this is the first study to examine and report associations between OH-PBDEs and thyroid function in a cancer population.

The Hippo pathway regulates cell proliferation, apoptosis, and stem cell self-renewal, and its inactivation in animal models causes organ enlargement followed by tumorigenesis. Hippo pathway deregulation occurs in many human cancers, but the underlying mechanisms are not fully understood. Here, we report tyrosine phosphorylation of the Hippo pathway tumor suppressor LATS1 as a mechanism underlying its regulation by cell adhesion. A tyrosine kinase library screen identified Src as the kinase to directly phosphorylate LATS1 on multiple residues, causing attenuated Mob kinase activator binding and structural alteration of the substrate-binding pocket in the kinase domain. Cell matrix adhesion activated the Hippo pathway effector transcription coactivator YAP partially through Src-mediated phosphorylation and inhibition of LATS1. Aberrant Src activation abolished the tumor suppressor activity of LATS1 and induced tumorigenesis in a YAP-dependent manner. Protein levels of Src in human breast cancer tissues correlated with accumulation of active YAP dephosphorylated on the LATS1 target site. These findings reveal tyrosine phosphorylation of LATS1 by Src as a novel mechanism of Hippo pathway regulation by cell adhesion and suggest Src activation as an underlying reason for YAP deregulation in tumorigenesis. Cancer Res; 77(18); 4868–80. ©2017 AACR.

Ilexgenin A (IA) is a novel pentacyclic triterpenoid, which extracted from leaves of Ilex hainanensis Merr. In the present study, we aim to explore anti-inflammatory activity of IA on LPS-induced peritonitis and its underlying molecular mechanism. The results determined that IA was capable of suppressing peritonitis in mice induced by intraperitoneal (i.p.) injection of lipopolysaccaride (LPS). Furthermore, the results showed that IA dramatically inhibited levels of inflammatory cells infiltration in peritoneal cavity and serum in LPS-induced mice peritonitis model. Besides, IA could dramatically inhibit levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in peritoneal cavity in LPS-induced mice peritonitis model. In vitro study, the results showed that IA inhibited production of IL-1β, IL-6 and TNF-α at transcriptional and translational levels in RAW 264.7 cells induced by LPS. Furthermore, IA could suppress the LPS-induced activation of Akt and downstream degradation and phosphorylation of kappa B-α (IκB-α). Moreover, IA could significantly inhibit ERK 1/2 phosphorylation in RAW 264.7 cells induced by LPS. These results were concurrent with molecular docking which revealed ERK1/2 inhibition. These results demonstrated that IA might as an anti-inflammatory agent candidate for inflammatory disease therapy.

Chromosome segregation in mitosis requires the removal of catenation between sister chromatids. Timely decatenation of sister DNAs at mitotic centromeres by topoisomerase IIα (TOP2A) is crucial to maintain genomic stability. The chromatin factors that recruit TOP2A to centromeres during mitosis remain unknown. Here, we show that histone H2A Thr‐120 phosphorylation (H2ApT120), a modification generated by the mitotic kinase Bub1, is necessary and sufficient for the centromeric localization of TOP2A. Phosphorylation at residue‐120 enhances histone H2A binding to TOP2A in vitro. The C‐gate and the extreme C‐terminal region are important for H2ApT120‐dependent localization of TOP2A at centromeres. Preventing H2ApT120‐mediated accumulation of TOP2A at mitotic centromeres interferes with sister chromatid disjunction, as evidenced by increased frequency of anaphase ultra‐fine bridges (UFBs) that contain catenated DNA. Tethering TOP2A to centromeres bypasses the requirement for H2ApT120 in suppressing anaphase UFBs. These results demonstrate that H2ApT120 acts as a landmark that recruits TOP2A to mitotic centromeres to decatenate sister DNAs. Our study reveals a fundamental role for histone phosphorylation in resolving centromere DNA entanglements and safeguarding genomic stability during mitosis.

Snail is a master inducer of epithelial-mesenchymal transition (EMT) and metastasis, however, Snail protein is labile and is quickly degraded through the predominate ubiquitination-mediated proteasome pathway. Deubiquitinases (DUBs) can counteract the Snail degradation process to maintain high level of Snail protein in cancer cells. In this study, we screened a cDNA library containing 79 DUBs, and discovered that a panel of DUBs consisting of USP13, USP28, USP29, USP37, OTUD6A, and DUB3 can markedly stabilize Snail protein, with USP29 displaying the strongest activity to prevent Snail degradation. Mechanistically, USP29 enhances the interaction of Snail and SCP1, resulting in simultaneous dephosphorylation and deubiquitination of Snail and thereafter cooperative prevention of Snail degradation. Biologically, ectopic expression of USP29 promotes gastric cancer cell migration, and depletion of Snail abolishes USP29-mediated cell migration; and USP29 can be induced by major EMT and metastatic inducing factors such as TGFβ, TNFα, and hypoxia. More importantly, high expression levels of Snail, USP29, and SCP1 are associated with poor survival and prognosis. Collectively, these data indicate that Snail is a crucial substrate for USP29 to promote cell migration and USP29/SCP1 complex may be new therapeutic targets to treat metastatic cancer.

The greater wax moth, Galleria mellonella Linnaeus (Lepidoptera: Galleriinae), is a ubiquitous pest of the honeybee, and poses a serious threat to the global honeybee industry. G. mellonella pheromone system is unusual compared to other lepidopterans and provides a unique olfactory model for pheromone perception. To better understand the olfactory mechanisms in G. mellonella, we conducted a transcriptomic analysis on the antennae of both male and female adults of G. mellonella using high-throughput sequencing and annotated gene families potentially involved in chemoreception. We annotated 46 unigenes coding for odorant receptors, 25 for ionotropic receptors, two for sensory neuron membrane proteins, 22 for odorant binding proteins and 20 for chemosensory proteins. Expressed primarily in antennae were all the 46 odorant receptor unigenes, nine of the 14 ionotropic receptor unigenes, and two of the 22 unigenes coding for odorant binding proteins, suggesting their putative roles in olfaction. The expression of some of the identified unigenes were sex-specific, suggesting that they may have important functions in the reproductive behavior of the insect. Identification of the candidate unigenes and initial analyses on their expression profiles should facilitate functional studies in the future on chemoreception mechanisms in this species and related lepidopteran moths.

Background Research has shown that support for families with children with autism spectrum disorder (ASD) in the United States has led to reduce parental stress. To better understand the situation in China, it is crucial to evaluate the current status of family support and provide clear evidence of the impact of family support on positive family outcomes. Aims This study aims to provide initial evidence to examine these interrelations among family support, parental stress, and family quality of life in mainland China. Method A total of 226 parents of children with ASD completed two questionnaires (Beach Center Family Quality of Life (FQOL) Scale and the Family Support Scale for Chinese Children with ASD) and a demographic family information form. Structural equation modeling was used to examine the interrelation among parental stress, family support, and FQOL. Results Parents perceived a moderate to low level of family support and FQOL and high level of parental stress. Family support had a direct positive effect on FQOL (β = .54) and an indirect effect on FQOL through parental stress (β = .06). Conclusion Resources should be devoted to establishing a family support system that promotes FQOL and buffers parental stress for families of children with ASD.

A rapid quantitative analysis model for determining the hydroxy-2-decenoic acid (10-HDA) content of royal jelly based on near-infrared spectroscopy combining with PLS has been developed. Firstly, near-infrared spectra of 232 royal jelly samples with different 10-HDA concentrations (0.35% to 2.44%) were be collected. Second-order derivative processing of the spectra was carried out to construct a full-spectrum PLS model. Secondly, GA-PLS, CARS-PLS, and Si-PLS were used to select characteristic wavelengths from the second-order derivative spectrum to construct a PLS calibration model. Finally, 58 samples were used to select the best predictive model for 10-HDA content. The result show that the PLS model constructed after wavelength selection was significantly more accurate than the full spectrum model. The Si-PLS algorithm performed best and the corresponding characteristic wavelength range were: 980 to 1038, 1220 to 1278, 1340 to 1398, and 1688 to 1746 nm. The prediction results were RMSEP = 0.1496% and RP = 0.9380. Hence, it is feasible to employ near-infrared spectra to analyze 10-HDA in royal jelly.

A representative congener of polybrominated diphenyl ethers in the environment, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), is associated with male reproductive toxicity, yet the underlying mechanisms remain largely unclear. In this study, mice were administered environmentally relevant concentrations of BDE-47 for six weeks. Histopathological observations showed that BDE-47 induced inflammatory reactions and damaged the testes. By conducting an integrated proteomic and metabolomic analysis coupled with a bioinformatic analysis using ingenuity pathway analysis (IPA) methods, we found that BDE-47 mainly affected the molecules involved in free radical scavenging, cell death and survival, neurological disease, and inflammatory response. IPA canonical pathways showed inflammatory and apoptosis pathways, including hepatic fibrosis/hepatic stellate cell activation, the GP6 signaling pathway, tight junction signaling, acute phase response signaling, LXR/RXR activation, unfolded protein response, and FXR/RXR activation, which are related to male reproductive toxicity. Key transcriptional regulator networks were activated via a focus on upstream regulator analysis. The expression of MYC and Clu as the core transcriptional factor and targeted protein, respectively, was verified. It is further proposed that MYC may contribute to the etiology of male reproductive toxicity. These findings will improve our understanding of the mechanisms responsible for BDE-47-induced male reproductive toxicity, which may promote the discovery of useful biomarkers indicative of BDE-47 exposure.

This study aimed to determine whether MG-132 as a proteasome inhibitor can effectively hinder pterygium progression, and to screen out potential regulators involved in MG-132 mediated process. Human pterygium fibroblasts (HPFs) were derived from pterygium tissues from 5 patients. Cell proliferation was examined by MTT, cell cycle and apoptosis were detected by flow cytometry. The overgrowth pterygium tissues were characterized by H&E staining and IHC compared with normal tissues. Differential mRNA expression with MG-132 treatment was determined by RNA sequencing and analyzed by GO and KEGG pathways. The expression levels of Nrf2, MCPIP1, CDKN1B and XBP1, four genes closely associated with pterygium, were detected by RT-qPCR and western blotting. MG-132 dose-dependently inhibited the growth of HPFs, induced G2/M phase arrest of cell cycle at a certain dose, and also caused cell apoptosis, with the levels of cleaved caspase3, cleaved PARP, Bax and p21 increased. Ki-67 and Bcl-2 were highly expressed while Bax was decreased in pterygium tissues. Total 7199 differentially expressed genes (DEGs) were identified, including HSPA family most significantly increased, and AL590428.1, AL122125.1 and lincRNAs such as FGF14-AS2 decreased. The up-regulated DEGs were mainly enriched in RNA degradation pathway, while down-regulated DEGs were related to the regulation of cell cycle. The expressions of Nrf2 and MCPIP1 were significantly increased, while XBP1 and CDKN1B were decreased. In conclusion, MG-132 inhibited the proliferation and induced apoptosis of HPFs in vitro with 7199 DEGs participated in, which may provide a useful reference for the exploitation of MG-132 in treating pterygium.

The effects of dietary sodium butyrate (SB) on serum metabolic parameters, intestinal antioxidant status, immune response and resistance to ammonia stress in Pelteobagrus fulvidraco were investigated. The fish were fed with diets containing 0, 250, 500, 1000 or 2000 mg/kg SB for 56 days followed by a 72-h ammonia challenge (2.65 mg/L unionized ammonia-N). The results showed that 500 and 1000 mg/kg SB groups showed significantly higher weight gain rate than control. Dietary SB significantly decreased cumulative mortality after 72 h ammonia nitrogen stress (P

The actin cytoskeleton powers membrane deformation during many cellular processes, such as migration, morphogenesis, and endocytosis. Membrane phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2], regulate the activities of many actinbinding proteins (ABPs), including profilin, cofilin, Dia2, N-WASP, ezrin, and moesin, but the underlying molecular mechanisms have remained elusive. Moreover, because of a lack of available methodology, the dynamics of membrane interactions have not been experimentally determined for any ABP. Here, we applied a combination of biochemical assays, photobleaching/activation approaches, and atomistic molecular dynamics simulations to uncover the molecular principles by which ABPs interact with phosphoinositide-rich membranes. We show that, despite using different domains for lipid binding, these proteins associate with membranes through similar multivalent electrostatic interactions, without specific binding pockets or penetration into the lipid bilayer. Strikingly, our experiments reveal that these proteins display enormous differences in the dynamics of membrane interactions and in the ranges of phosphoinositide densities that they sense. Profilin and cofilin display transient, low-affinity interactions with phosphoinositide-rich membranes, whereas F-actin assembly factors Dia2 and N-WASP reside on phosphoinositide-richmembranes for longer periods to performtheir functions. Ezrin and moesin, which link the actin cytoskeleton to the plasma membrane, bindmembranes with very high affinity and slow dissociation dynamics. Unlike profilin, cofilin, Dia2, and N-WASP, they do not require high "stimulus-responsive" phosphoinositide density for membrane binding. Moreover, ezrin can limit the lateral diffusion of PI(4,5)P-2 along the lipid bilayer. Together, these findings demonstrate that membrane-interaction mechanisms of ABPs evolved to precisely fulfill their specific functions in cytoskeletal dynamics.

Two novel fluorescent bioprobes, namely, 6N-Gly-Cy3 and 6N-Gly-Cy5, were designed and synthesized for real-time glucose transport imaging as well as potentially useful tracer for galactokinase metabolism. The structure of the bioprobes was fully characterized by 1H NMR, 13C NMR, IR, and HRMS. The fluorescence properties, glucose transporter (GLUT) specificity, and the quenching and safety profiles were studied. The cellular uptake of both bioprobes was competitively diminished by d-glucose, 2-deoxy-d-glucose and GLUT specific inhibitor in a dose-dependent manner in human colon cancer cells (HT29). Comparison study results revealed that the 6N-derived bioprobes are more useful for real-time imaging of cell-based glucose uptake than the structurally similar fluorescent tracer 6-NBDG which was not applicable under physiological conditions. The up to 96 h long-lasting quenching property of 6N-Gly-Cy5 in HT29 suggested the potential applcability of the probe for cell labeling in xenograft transplantation as well as in vivo animal imaging studies.

This experiment was conducted to investigate the effects of dietary arginine levels on growth performance, body composition, serum biochemical indices and resistance ability against ammonia-nitrogen stress in juvenile yellow catfish (Pelteobagrus fulvidraco). Five isonitrogenous and isolipidic diets (42% protein and 9% lipid) were formulated to contain graded levels of arginine (2.44%, 2.64%, 2.81%, 3.01% and 3.23% of diet), by supplementing L-Arginine HCl. Seven hundred juvenile yellow catfish with an initial average body weight of 1.13 ± 0.02 g were randomly divided into 5 groups with 4 replicates of 35 fish each and each group was fed one of the diets. After 56 d feeding, fish were exposed to 100 mg/L of ammonia-nitrogen for 72 h. The results showed that weight gain (WG) and specific growth rate (SGR) in 2.64% and 2.81% groups were significantly higher than those in 3.23% group (P 0.05). After the fish were challenged to ammonia-nitrogen for 72 h, their cumulative mortality rate in 2.81% group was significantly lower than that in 2.44% group (P

The herbal pair Zhimu-Baihe (Zhimu: Anemarrhena asphodeloides; Baihe: Lilium brownii var. viridulum) is a traditional Chinese medicament used for the treatment of depression. However, the relevant mechanisms of action has not been clarified. This study investigated the anti-depressant activity of the total saponins from Zhimu and Baihe and the mechanisms underlying using a chronic unpredictable mild stress (CUMS)-induced rat model of depression. High performance liquid chromatography with electrochemical detection (HPLC-ECD) was applied to determine the levels of three monoamine neurotransmitters, 5-hydroxytryptamine (5-HT), noradrenaline (NE) and dopamine (DA), in the rat hippocampus. Optimized pretreatment of samples and mass spectrometry conditions were used to analyse the metabonomic profile of the hippocampus. The 5-HT and NE levels in the CUMS group were reduced compared with the control group, whereas all groups had similar DA levels. The metabonomic profile of the hippocampus revealed 32 differential metabolites between the CUMS and control group, among which 18 metabolites were significantly recovered in the Anemarrhena saponins and Lilium saponins (AL) combination intervention group. These results suggested an anti-depressant effect of AL. Moreover, 24 metabolites in AL group were better recovered compared with the Anemarrhena saponins (AS) or Lilium saponins (LS) intervention groups, suggesting a synergetic effect of AS and LS in the treatment of depression. The anti-depressant effect might be related to the regulation of several metabolic pathways, including monoamine neurotransmitter synthesis (especially 5-HT and NE), and amino acid, fatty acid, and phospholipid metabolism in rats.

A missed abortion (MA) is an in utero death of the embryo or fetus before the 20th week of gestation with retained products of conception, and this condition is currently common in China. In order to discover novel biomarkers for MA, ultrahigh performance liquid chromatography was applied to study plasma metabolite profiles for 33 patients with MA and 29 control subjects. Thirty-seven differential plasma metabolites were found to discriminate between the two groups in the initial cohort (15 subjects with MA and 15 healthy controls). The feasibility of using these potential biomarkers to predict MA was further evaluated in the validation cohort (18 subjects with MA and 14 healthy controls) and 15 had an area under the receiver operating characteristic curve of >0.80, making them satisfactory. Tryptophan metabolism and sphingolipid metabolism were identified as important potential target pathways for MA using metabolic pathway impact analysis. Furthermore, three of the 15 satisfactory metabolites (glyceric acid, indole and sphingosine) were combined to establish a predictive model with 100% sensitivity and 100% specificity in the validation cohort. Taken together, these results suggest that MA results in significant disturbance of metabolism and those various novel biomarkers have satisfactory diagnostic and predictive power for MA.

Primates of the Colobinae subfamily are highly folivorous. They possess a sacculated foregut and are believed to rely on a specialized gut microbiota to extract sufficient energy from their hard-to-digest diet. Although many colobines are endangered and would benefit from captive breeding programs, maintaining healthy captive populations of colobines can be difficult since they commonly suffer from morbidity and mortality due to gastrointestinal (GI) distress of unknown cause. While there is speculation that this GI distress may be associated with a dysbiosis of the gut microbiota, no study has directly examined the role of the gut microbiota in colobine GI health. In this study, we used high-throughput sequencing to examine the gut microbiota of three genera of colobines housed at the San Diego Zoo: doucs ( Pygathrix) ( N = 7 ), colobus monkeys ( Colobus) ( N = 4 ), and langurs ( Trachypithecus) ( N = 5 ). Our data indicated that GI-healthy doucs, langurs, and colobus monkeys possess a distinct gut microbiota. In addition, GI-unhealthy doucs exhibited a different gut microbiota compared to GI-healthy individuals, including reduced relative abundances of anti-inflammatory Akkermansia. Finally, by comparing samples from wild and captive Asian colobines, we found that captive colobines generally exhibited higher relative abundances of potential pathogens such as Desulfovibrio and Methanobrevibacter compared to wild colobines, implying an increased risk of gut microbial dysbiosis. Together, these results suggest an association between the gut microbiota and GI illness of unknown cause in doucs. Further studies are necessary to corroborate these findings and determine cause-and-effect relationships. Additionally, we found minimal variation in the diversity and composition of the gut microbiota along the colobine GI tract, suggesting that fecal samples may be sufficient for describing the colobine gut microbiota. If these findings can be validated in wild individuals, it will facilitate the rapid expansion of colobine gut microbiome research.

Two novel cyanine-based 1-amino-1-deoxy-β-glucose conjugates (Glu-1N-Cy3 and Glu-1N-Cy5) were designed, synthesized and their fluorescence characteristics were studied. Both Glu-1N-Cy3 and Glu-1N-Cy5 accumulate in living HT29 human colon cancer cells, which overexpress glucose transporters (GLUTs). The cellular uptake of the bioprobes was inhibited by natural GLUT substrate d-glucose and 2-deoxy-d-glucose. The GLUT specificity of the probes was validated with quercetin, which is both a permeant substrate via GLUTs and a high-affinity inhibitor of GLUT-mediated glucose transport. Competitive fluorometric assay for GLUT substrate cell uptake revealed that Glu-1N-Cy3 and Glu-1N-Cy5 are 5 and 10 times more sensitive than 2-NBDG, a leading fluorescent glucose bioprobe. This study provides fundamental data supporting the potential of these two conjugates as new powerful tools for GLUT-mediated theranostics, in vitro and in vivo molecular bioimaging and drug R&D.

Male and female poplars (Populus cathayana Rehd.) respond differently to nitrogen (N) and phosphorus (P) deficiencies. In this study, an iTRAQ-based quantitative proteomic analysis was performed. N and P deficiencies caused 189 and 144 proteins to change in abundance in males and 244 and 464 in females, respectively. Compared to N- and P-deficient males, both N- and P-deficient females showed a wider range of changes in proteins that are involved in amino acid, carbohydrate and protein metabolism, and the sexual differences were significant. When comparing the effects of N- and P-deficiencies, N-deficient females expressed more changes in proteins that are involved in stress responses and gene expression regulation, while P-deficient females showed more changes in proteins that are involved in energy and lipid metabolism, stress responses and gene expression regulation. The quantitative RT-PCR analysis of stress-related proteins showed that males have a better expression correlation between mRNA and protein levels than do females. This study shows that P. cathayana females are more sensitive and have more rapid metabolic mechanisms when responding to N and P deficiencies than do males, and P deficiency has a wider range of effects on females than does N deficiency.

Stroke is one of the most fatal diseases in the world, which is seriously threatening human life. Raf kinase inhibitory protein (RKIP) is involved in the regulation of several signaling pathways and is important for cell growth, proliferation, differentiation and apoptosis. In the present study, the protective effect of RKIP on stroke was investigated by the metabonomics method based on the UHPLC-Q-TOF-MS technique. TTC staining of brain tissues showed that RKIP overexpression by the lentivirus markedly reduced the necrotic area after ischemic stroke. Subsequent metabolomic profiling revealed that the protective effect of RKIP overexpression on ischemic stroke is mainly reflected in the metabolism of energy, amino acids and lipids. Several metabolites involved in purine, pyrimidine and fatty acid metabolism were identified. It was also shown that the protective effect of RKIP on ischemic stroke might be mediated by inhibiting the inflammatory response. The current study provided insight into the molecular mechanism of ischemic stroke and a reliable basis for the development of novel therapeutic targets for the treatment of ischemic stroke.

Osteoporosis, characterized by bone mass reduction and increased fractures, has become a global health problem that seriously affects the health of people, especially postmenopausal women; however, the current pathogenesis of postmenopausal osteoporosis (PMOP) has not been thoroughly elucidated to date. In this study, bilateral ovariectomy was performed to establish an OVX mouse model of osteoporosis. UPLC-Q-TOF-MS-based lipidomics in combination with metabolomics were used to analyze the femur tissue of osteoporosis mice. We found that 11 polar metabolites and 93 lipid metabolites were significantly changed and were involved in amino acid metabolism, nucleotide metabolism and lipid metabolism. Among the lipids, fatty acyls, glycerolipids, glycerophospholipids, sphingolipids and sterols showed robust changes. These results revealed that several metabolic disorders caused by changes in the hormone levels in OVX, especially disordered lipid metabolism, are closely related to the imbalance between bone resorption and formation and may underlie the development of PMOP. The data generated via lipidomics and metabolomics presented in this study shows good applicability and wide coverage in the construction of the metabolic profile of bone tissue. Therefore, this approach may provide the pathway focusing and data support at the metabolite level for the in-depth mechanism of PMOP.

Cationic liposomes (CLs) are vital nonviral vectors with a wide range of applications. Although the toxicity of CLs is far lower than that of viral vectors, increasing evidence suggests that there are limited clinical applications of CLs because of their potential toxicity. In the present study, the toxicity of CLs toward L02 cells was investigated and comprehensively analyzed based on proteomics and metabolomics data. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UHPLC-Q-TOF-MS based metabolomics, we determined that exposure to CLs generated 90 significantly altered proteins and 65 altered metabolites in cells. Metabolomic analysis also showed significant alterations in metabolic pathways, including small molecules involved in energy and lipid metabolism. Proteomics revealed that exposure to CLs significantly influenced multiple proteins, including those involved in the folding of proteins and metabolism. Furthermore, the proteins participated in oxidative stress, which also influenced lipid metabolism. Overall, our findings indicate that high-throughput metabolomics and proteomics can provide insight into the toxicological mechanisms of CLs using high-resolution mass spectrometry. To our knowledge, this is the first study combining proteomics and metabolomics to investigate the potential effects of CLs on any cells. Specifically, we integrated quantitative iTRAQ-based proteomics with UHPLC-Q-TOF-MS-based metabolomics datasets to comprehensively assess the potential mechanisms of CL toxicity towards L02 cells.

Most of the modern rose cultivars are susceptible to the highly destructive rose black spot disease caused by Marssonina rosae. In order to clarify the effect of hybridization with diploid Rosa rugosa on the morphological performance and black spot disease resistance of modern roses, we created the hybrid R. hybrida ‘Porcelina’ × R. rugosa ‘Dahong Zizhi’ and analyzed the morphological diversity and genetic constitution of 142 progeny. The progeny showed a wide range of variation, with a coefficient of variation of all traits of 40% and a maximum internode length of 118.9%. Cluster analysis of morphological traits and principal coordinate analysis of simple sequence repeats indicated that most of the progeny clustered with the female parent, while only a few individuals grouped with the male parent. Detached leaf assays were used to evaluate the black spot disease resistance of 75 lines and the two parents. The mean leaf area with symptoms (LAS) of the tested leaves of ‘Porcelina’ was 72.0 ± 12.9%, classifying it as highly susceptible, while R. rugosa showed high resistance to black spot disease. The coefficient of variation in LAS of the progeny was 68.1%, which indicates that the broad-spectrum resistance of rose black spot disease is controlled by multiple genes. A total of 11 progeny had an LAS