Polychlorinated biphenyls exposure and type 2 diabetes: Molecular mechanism that causes insulin resistance and islet damage.

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that have been associated with type 2 diabetes (T2DM) in cohort studies. This review aims to comprehensively assess the molecular mechanisms of PCBs-induced T2DM. Recent progress has been made in the research of PCBs in liver tissue, adipose tissue, and other tissues. By influencing the function of nuclear receptors, such as the aryl hydrocarbon receptor (AhR), pregnancy X receptor (PXR), and peroxisome proliferator activated receptor γ (PPARγ), as well as the inflammatory response, PCBs disrupt the balance of hepatic glucose and lipid metabolism. This is associated with insulin resistance (IR) in the target organ of insulin. Through androgen receptor (AR), estrogen receptor α/ß (ERα/ß), and pancreato-duodenal-homeobox gene-1 (PDX-1), PCBs affect the secretion of insulin and increase blood glucose. Thus, this review is a discussion on the relationship between PCBs exposure and the pathogenesis of T2DM. It is hoped to provide basic concepts for diabetes research and disease treatment.

Identification of LsPIN1 gene and its potential functions in rhizome turning of Leymus secalinus.

BACKGROUND: Continuous tilling and the lateral growth of rhizomes confer rhizomatous grasses with the unique ability to laterally expand, migrate and resist disturbances. They play key roles especially in degraded grasslands, deserts, sand dunes, and other fragile ecological system. The rhizomatous plant Leymus secalinus has both rhizome buds and tiller buds that grow horizontally and upward at the ends of rhizome differentiation and elongation, respectively. The mechanisms of rhizome formation and differentiation in L. secalinus have not yet been clarified. RESULTS: In this study, we found that the content of gibberellin A3 (GA3) and indole-3-acetic acid (IAA) were significantly higher in upward rhizome tips than in horizontal rhizome tips; by contrast, the content of methyl jasmonate and brassinolide were significantly higher in horizontal rhizome tips than in upward rhizome tips. GA3 and IAA could stimulate the formation and turning of rhizomes. An auxin efflux carrier gene, LsPIN1, was identified from L. secalinus based on previous transcriptome data. The conserved domains of LsPIN1 and the relationship of LsPIN1 with PIN1 genes from other plants were analyzed. Subcellular localization analysis revealed that LsPIN1 was localized to the plasma membrane. The length of the primary roots (PRs) and the number of lateral roots (LRs) were higher in Arabidopsis thaliana plants overexpressing LsPIN1 than in wild-type (Col-0) plants. Auxin transport was altered and the gravitropic response and phototropic response were stronger in 35S:LsPIN1 transgenic plants compared with Col-0 plants. It also promoted auxin accumulation in root tips. CONCLUSION: Our findings indicated that LsPIN1 plays key roles in auxin transport and root development. Generally, our results provide new insights into the regulatory mechanisms underlying rhizome development in L. secalinus.

Comprehensive analysis of cucumber C-repeat/dehydration-responsive element binding factor family genes and their potential roles in cold tolerance of cucumber.

BACKGROUND: Cold stress is one of the main abiotic stresses limiting cucumber (Cucumis sativus L.) growth and production. C-repeat binding factor/Dehydration responsive element-binding 1 protein (CBF/DREB1), containing conserved APETALA2 (AP2) DNA binding domains and two characteristic sequences, are key signaling genes that can be rapidly induced and play vital roles in plant response to low temperature. However, the CBF family has not been systematically elucidated in cucumber, and the expression pattern of this family genes under cold stress remains unclear. RESULTS: In this study, three CsCBF family genes were identified in cucumber genome and their protein conserved domain, protein physicochemical properties, gene structure and phylogenetic analysis were further comprehensively analyzed. Subcellular localization showed that all three CsCBFs were localized in the nucleus. Cis-element analysis of the promoters indicated that CsCBFs might be involved in plant hormone response and abiotic stress response. Expression analysis showed that the three CsCBFs could be significantly induced by cold stress, salt and ABA. The overexpression of CsCBFs in cucumber seedlings enhanced the tolerance to cold stress, and importantly, the transcript levels of CsCOR genes were significantly upregulated in 35S:CsCBFs transgenic plants after cold stress treatment. Biochemical analyses ascertained that CsCBFs directly activated CsCOR genes expression by binding to its promoter, thereby enhancing plant resistance to cold stress. CONCLUSION: This study provided a foundation for further research on the function of CsCBF genes in cold stress resistance and elucidating its mechanism.

Understanding the knowledge gaps between air pollution controls and health impacts including pathogen epidemic.

Sustainable development calls for a blue sky with quality air. Encouragingly, the current mass reduction-oriented pollution control is making substantial achievements, as the data from Chinese Environmental Monitoring Stations show a significant drop in the annual average concentrations of particulate matters (i.e., PM10 and PM2.5) and SO2. But many challenges and knowledge gaps are still confronted nowadays. On one hand, long-term health impacts of fine air particles have to be closely probed through both epidemiological and laboratory studies, and the toxic effects owing to the interactions between particles and associated chemical pollutants should be differentially teased out. On the other hand, due to sole mass control, there are significant changes of overall pollutant fingerprint, such as the increase of ground-level ozone concentration, which should be taken into account for altered health effects relative to the past. Moreover, the interplays with air pollutants and air-borne pathogens should be scrutinized in more details. In other words, it is worth investigating likely spread of pathogens (even for SARS-CoV-2) with aid of aerosols. Here, we recapitulate the current knowledge gaps between air pollution controls and health impacts including pathogen epidemic, and we also propose future research directions to support policy making in balance mass control and health impacts.

Carbon black-induced detrimental effect on osteoblasts at low concentrations: Remarkably compromised differentiation without significant cytotoxicity.

Due to similar aerodynamic and micro-nano sized properties between airborne particles and synthetic nanoparticles, a large number of studies have been conducted using carbon-based particles, such as carbon black (CB), carbon nanotubes and graphite, in order to achieve deeper understandings of their adverse effects on human health. It has been reported that particulate matters can aggravate morbidity of patients suffering from bone and joint diseases, e.g. arthritis. However, the molecular mechanism is still elusive thus far. Under this context, we employed two cell lines of osteoblasts, MC3T3-E1 and MG-63, upon exposure to 4 different CB samples with differential physicochemical properties in research of mechanistic insights. Our results indicated that the carbon/oxygen ratio differed in these 4 CB materials showing the order: SB4A < Printex U < C1864 < C824455. In stark contrast, their cytotoxicity and capacity to trigger reactive oxygen species (ROS) in MC3T3-E1 and MG-63 cells closely correlated to oxygen content, revealing the reverse order: SB4A < Printex U < C1864 < C824455. It would be reasonable to speculate that ROS production was a predominant cause of CB cytotoxicity, which strongly relied on the oxygen content of CB. Our study further manifested that all CB samples even at low concentrations significantly inhibited osteoblast differentiation, as reflected by remarkably reduced activity of alkaline phosphatase (ALP) and compromised expression of the differentiation-related genes. And the inhibition on osteoblast differentiation also closely correlated to oxygen content of CB samples. Taken together, our combined data recognized oxygen-associated toxicity towards osteoblasts for CBs. More importantly, we uncovered a new adverse effect of CB exposure: suppression on osteoblast differentiation, which has been overlooked in the past.

Characterization of S-adenosylhomocysteine/Methylthioadenosine nucleosidase on secretion of AI-2 and biofilm formation of Escherichia coli.

S-adenosylhomocysteine/Methylthioadenosine nucleosidase (SAHN E.C.3.2.2.9) does not exist in mammalian cells but is essential for methyl recycling in numerous bacterial and protozoan species. Inhibition of this enzyme could limit synthesis of autoinducers of bacterial quorum sensing (QS), and hence, causes reduction in biofilm formation and may attenuate virulence. In this study, sahn deletion mutant of E. coli MG1655, sahn-complemented strain, and SANH-overexpressing strain were established and used to identify the secretion of autoinducer-2 (AI-2) and biofilm formation. The results indicated that deletion of the sahn gene abolished the production of the QS signal AI-2 and biofilm formation in mutant strain MG1655-Δsahn. And the complementation strain MG1655-Δsahn (pET-28a-sahn) showed restored production of AI-2 and biofilm formation, which indicates that the sahn gene plays an important role in bacterial quorum sensing. The recombinant SAHN protein was overexpressed and purified. The enzymatic activity of SAHN was successfully determined by a coupling-enzyme analysis based on xanthine oxidase, with the Vmax and Km of SAHN enzymatic reaction confirmed. Given that sahn is essential for the quorum sensing of both Gram-negative and Gram-positive bacteria, SAHN could be a potential target for wide-spectrum antibiotics.

Characterization of human S-adenosyl-homocysteine hydrolase in vitro and identification of its potential inhibitors.

Human S-adenosyl-homocysteine hydrolase (SAHH, E.C.3.3.1.1) has been considered to be an attractive target for the design of medicines to treat human disease, because of its important role in regulating biological methylation reactions to catalyse the reversible hydrolysis of S-adenosylhomocysteine (SAH) to adenosine (Ado) and l-homocysteine (Hcy). In this study, SAHH protein was successfully cloned and purified with optimized, Pichia pastoris (P. pastoris) expression system. The biological activity results revealed that, among the tested compounds screened by ChemMapper and SciFinder Scholar, 4-(3-hydroxyprop-1-en-1-yl)-2-methoxyphenol (coniferyl alcohol, CAS: 458-35-5, ZINC: 12359045) exhibited the highest inhibition against rSAHH (IC50= 34 nM). Molecular docking studies showed that coniferyl alcohol was well docked into the active cavity of SAHH. And several H-bonds formed between them, which stabilized coniferyl alcohol in the active site of rSAHH with a proper conformation.

Effects of co-exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls on nonalcoholic fatty liver disease in mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants which coexist in environment, and human are co-exposed to these chemicals. Our present study was aimed to investigate the possible enhanced nonalcoholic fatty liver disease (NAFLD) in ApoE(-/-) mice co-exposed to TCDD and PCBs and to reveal the potential mechanisms involved in. Male ApoE(-/-) mice were exposed to TCDD (15 µg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over a 6-week period. Those mice co-exposed to PCBs and TCDD developed serious liver steatosis, necrosis, and inflammatory stimuli. Interestingly, all treatment induced hepatic cytochrome P450 1A1 (CYP1A1) expression, but the maximal level of CYP1A1 was not observed in the co-exposure group. Furthermore, microarray analysis by ingenuity pathway analysis software showed that the nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated oxidative stress response pathway was significantly activated following co-exposure to TCDD and PCBs. Our data demonstrated that co-exposure to TCDD and PCBs markedly worsen NAFLD in ApoE(-/-) mice.

Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants found as complex mixtures in the environment throughout the world. Therefore, humans are ubiquitously and simultaneously exposed to TCDD and PCBs. TCDD and PCBs alone have been linked to atherosclerosis. However, the effects of interactions or synergism between TCDD and PCBs on atherogenesis are unknown. We investigated the possible enhanced atherogenesis by co-exposure to TCDD and PCBs and the potential mechanism(s) involved in this enhancement. Male ApoE(-/-) mice were exposed to TCDD (15 µg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) alone or in combination by intraperitoneal injection four times over six weeks of duration. Our results showed that mice exposed to TCDD alone, but not Aroclor1254 alone, developed atherosclerotic lesions. Moreover, we found that atherosclerotic disease was exacerbated to the greatest extent in mice co-exposed to TCDD and Aroclor1254. The enhanced lesions correlated with several pro-atherogenic changes, including a marked increase in the accumulation of the platelet-derived chemokine PF4, and the expression of the proinflammatory cytokine MCP-1 and the critical immunity gene-RIG-I. Our data demonstrated that co-exposure to TCDD and Aroclor1254 markedly enhanced atherogenesis in ApoE(-/-) mice. Significantly, our observations suggest that combined exposure to TCDD and PCBs may be a greater cardiovascular health risk than previously anticipated from individual studies.

The first convergent total synthesis of penarolide sulfate A2, a novel α-glucosidase inhibitor.

Penarolide sulfate A2, a 31-membered macrolide encompassing a proline residue and three sulfate groups, was firstly synthesized in 16 linear steps with 4.8% overall yield. Three consecutive stereogenic centers in penarolide sulfate A2 were efficiently derived from natural chiral template l-arabinose. The crucial assembly reactions included Brown asymmetric allylation, olefin cross-metathesis, alkyne-epoxide coupling, and macrolactamization. The anti-yeast α-glucosidase activities of penarolide sulfate A2 and its fully desulfated derivative were examined showing IC50 values of 4.87 and 10.74 µg mL(-1), respectively.

Microbial Community, Co-Occurrence Network Relationship and Fermentation Lignocellulose Characteristics of Broussonetia papyrifera Ensiled with Wheat Bran.

Broussonetia papyrifera has a high lignocellulose content leading to poor palatability and low digestion rate of ruminants. Thus, dynamic profiles of fermentation lignocellulose characteristics, microbial community structure, potential function, and interspecific relationships of B. papyrifera mixing with wheat bran in different ratios: 100:0 (BP100), 90:10 (BP90), 80:20 (BP80), and 65:35 (BP65) were investigated on ensiling days 5, 15, 30, and 50. The results showed that adding bran increased the degradation rate of hemicellulose, neutral detergent fiber, and the activities of filter paper cellulase, endoglucanase, acid protease, and neutral protease, especially in the ratio of 65:35. Lactobacillus, Pediococcus, and Weissella genus bacteria were the dominant genera in silage fermentation, and Pediococcus and Weissella genus bacteria regulated the process of silage fermentation. Compared with monospecific B. papyrifera silage, adding bran significantly increased the abundance of Weissella sp., and improved bacterial fermentation potential in BP65 (p < 0.05). Distance-based redundancy analysis showed that lactic acid bacteria (LAB) were significantly positive correlated with most lignocellulose content and degrading enzymes activities, while Monascus sp. and Syncephalastrum sp. were opposite (p < 0.05). Co-occurrence network analysis indicated that there were significant differences in microbial networks among different mixing ratios of B. papyrifera silage prepared with bran. There was a more complex, highly diverse and less competitive co-occurrence network in BP65, which was helpful to silage fermentation. In conclusion, B. papyrifera ensiled with bran improved the microbial community structure and the interspecific relationship and reduced the content of lignocellulose.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Polychlorinated Biphenyl Coexposure Alters the Expression Profile of MicroRNAs in the Liver Associated with Atherosclerosis.

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that exist as complex mixtures in vivo. When humans are simultaneously exposed to these compounds, the development of atherosclerosis is known to be enhanced. However, the roles of miRNA in TCDD- and PCB-induced atherosclerosis are largely unknown. Therefore, the present study is aimed at elucidating the possible dysregulation of miRNAs in atherogenesis induced by coexposure to TCDD and PCBs. Eight-week-old male ApoE-/- mice were coexposed to TCDD (15 µg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) by intraperitoneal injection four times over a 6-week period. Microarray analysis of miRNAs and mRNAs in the liver of ApoE-/- mice with or without TCDD and Aroclor1254 coexposure was performed. We discovered that 68 miRNAs and 1312 mRNAs exhibited significant expression changes in response to TCDD and PCB coexposure and revealed that both changed miRNAs and mRNAs are involved in cardiovascular disease processes. An integrated miRNA-mRNA approach indicated that miRNA-26a-5p, miRNA-193a-3p, and miRNA-30c-5p participated in specific TCDD and Aroclor1254 coresponsive networks which are relevant to the cardiovascular system development and function network. Furthermore, our results also indicated that miRNA-130a-3p and miRNA-376a-3p were novel players in the regulation of TCDD- and Aroclor1254-induced atherosclerosis pathways. In summary, our finding provided new insights into the mechanism of atherosclerosis in response to TCDD and PCB coexposure.

Effect of LINC00657 on Apoptosis of Breast Cancer Cells by Regulating miR-590-3p.

OBJECTIVE: To investigate the effect of LINC00657 on breast carcinoma by regulating miR-590-3p. METHODS: Ninety-seven cases with breast carcinoma who were admitted to Qingdao Chengyang People's Hospital were collected. The breast carcinoma (n=97) and tumor-adjacent tissues (n=97) of patients were collected during the operation with the permission of the patients. The expressions of LINC00657 and miR-590-3p were detected in breast carcinoma cells and tissues. The breast carcinoma cells were transfected and their proliferation, migration, invasion and apoptosis were detected. RESULTS: LINC00657 was highly expressed in breast carcinoma tissues, while miR-590-3p was reduced (P<0.05). The proliferation, invasion and migration of cells transfected with si-LINC00657 or miR-590-3p-mimics were significantly inhibited, and the apoptosis rate increased, resulting in the up-regulation of the expressions of apoptosis-related proteins Bax and Caspase-3 and the reduction of Bcl-2 (P<0.05). After si-LINC00657 or miR-590-3p-mimics, the level of GOLPH3 decreased. Through double luciferase report and RIP experiment, it was confirmed that LINC00657 could act as a sponge of miR-590-3p to negatively regulate its expression. After correlation analysis, it was concluded that there was a negative correlation between LINC00657 and miR-590-3p. Rescue experiments concluded that co-transfection of si-LINC00657+miR-590-3P-inhibitor could reverse the inhibitory action of si-LINC00657 on breast carcinoma cells. CONCLUSION: LINC00657 can participate in the biological behavior process of breast carcinoma by regulating miR-590-3p/GOLPH3 signal.

Understanding the Multiple Effects of PCBs on Lipid Metabolism.

Polychlorinated biphenyls (PCBs) are a typical class of environmental contaminants recently shown to be metabolism-disrupting chemicals. Lipids are a highly complex group of biomolecules that not only form the structural basis of biofilms but also act as signaling molecules and energy sources. Lipid metabolic disorders contribute to multiple diseases, including obesity, diabetes, fatty liver, and metabolic syndromes. Although previous literature has reported that PCBs can affect lipid metabolism, including lipid synthesis, uptake, and elimination, few systematic summaries of the detailed process of lipid metabolism caused by PCB exposure have been published. Lipid metabolic processes involve many molecules; however, the key factors that are sensitive to PCB exposure have not been fully clarified. Here, we summarize the recent developments in PCB research with a focus on biomarkers of lipid metabolic disorders related to environmental exposures.

Exposure to 2,3,3',4,4',5-hexachlorobiphenyl promotes nonalcoholic fatty liver disease development in C57BL/6 mice.

Previous in vitro studies have indicated that 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156) may be a new contributor to metabolic disruption and may further cause the occurrence of nonalcoholic fatty liver disease (NAFLD). However, no study has clarified the specific contributions of PCB 156 to NAFLD progression by constructing an in vivo model. Herein, we evaluated the effects of PCB 156 treatment (55 mg/kg, i.p.) on the livers of C57BL/6 mice fed a control diet (CD) or a high-fat diet (HFD). The results showed that PCB 156 administration increased intra-abdominal fat mass, hepatic lipid levels and dyslipidemia in the CD-fed group and aggravated NAFLD in HFD-fed group. By using transcriptomics studies and biological methods, we found that the genes expression involved in lipid metabolism pathways, such as lipogenesis, lipid accumulation and lipid ß-oxidation, was greatly altered in liver tissues exposed to PCB 156. In addition, the cytochrome P450 pathway, peroxisome proliferator-activated receptors (PPARs) and the glutathione metabolism pathway were significantly activated following exposure to PCB 156. Furthermore, PCB 156 exposure increased serum transaminase levels and lipid peroxidation, and the redox-related genes were significantly dysregulated in liver tissue. In conclusion, our data suggested that PCB 156 could promote NAFLD development by altering the expression of genes related to lipid metabolism and inducing oxidative stress.

Overexpression of lncRNA MT1JP Mediates Apoptosis and Migration of Hepatocellular Carcinoma Cells by Regulating miR-24-3p.

OBJECTIVE: This study aimed to determine the effects of the long non-coding (lnc) RNA MT1JP on the apoptosis and migration of hepatocellular carcinoma cells. PATIENTS AND METHODS: Patients with liver cancer admitted to the Second People's Hospital of Liaocheng were included in this study. We transfected hepatocellular carcinoma cells with MT1JP and miR-24-3p and assessed their expression and effects on apoptosis and migration. Correlations were verified using a dual-luciferase reporter and RNA-binding protein coimmunoprecipitation. RESULTS: The expression of MT1JP was downregulated (P < 0.05), whereas that of miR-24-3p was upregulated in liver cancer. Serum MT1JP levels were correlated with tumor size, alpha-fetoprotein (AFP), TNM stage, differentiation, and lymph node metastasis. Both MT1JP overexpression and miR-24-3p inhibition inhibited cellular proliferation and migration and increased apoptosis rates. They significantly downregulated expression of the cell migration-associated proteins matrix metalloproteinase -2, -9 (MMP-2, MMP-9) (P < 0.05). They upregulated the expression of Bcl-2-related X protein (Bax) and cysteinyl aspartate-specific proteinases (Caspase-3 and -9) proteins that are involved in apoptosis. They decreased expression of B-cell lymphoma/leukemia-2 (Bcl-2; P < 0.05). A target relationship between MT1JP and miR-24-3p was identified using dual-luciferase gene reporter assays and RNA-binding protein coimmunoprecipitations. MT1JP overexpression significantly downregulated miR-24-3p expression (P < 0.05). MT1JP and miR-24-3p expression were negatively correlated in liver cancer tissues (r = -0.561, P < 0.001; Pearson χ2 tests). Rescue experiments showed that upregulating miR-24-3p expression could counteract MT1JP overexpression in hepatocellular carcinoma cells. CONCLUSION: MT1JP, even when expressed at low levels, participates in the proliferation, apoptosis, and migration of liver cancer cells by regulating miR-24-3p.

Transcriptome analysis in normal human liver cells exposed to 2, 3, 3', 4, 4', 5 - Hexachlorobiphenyl (PCB 156).

BACKGROUNDS: Polychlorinated biphenyls are persistent environmental pollutants associated with the onset of non-alcoholic fatty liver disease in humans, but there is limited information on the underlying mechanism. In the present study, we investigated the alterations in gene expression profiles in normal human liver cells L-02 following exposure to 2, 3, 3', 4, 4', 5 - hexachlorobiphenyl (PCB 156), a potent compound that may induce non-alcoholic fatty liver disease. METHODS: The L-02 cells were exposed to PCB 156 for 72 h and the contents of intracellular triacylglyceride and total cholesterol were subsequently measured. Microarray analysis of mRNAs and long non-coding RNAs (lncRNAs) in the cells was also performed after 3.4 µM PCB 156 treatment. RESULTS: Exposure to PCB 156 (3.4 µM, 72 h) resulted in significant increases of triacylglyceride and total cholesterol concentrations in L-02 cells. Microarray analysis identified 222 differentially expressed mRNAs and 628 differentially expressed lncRNAs. Gene Ontology and pathway analyses associated the differentially expressed mRNAs with metabolic and inflammatory processes. Moreover, lncRNA-mRNA co-expression network revealed 36 network pairs comprising 10 differentially expressed mRNAs and 34 dysregulated lncRNAs. The results of bioinformatics analysis further indicated that dysregulated lncRNA NONHSAT174696, lncRNA NONHSAT179219, and lncRNA NONHSAT161887, as the regulators of EDAR, CYP1B1, and ALDH3A1 respectively, played an important role in the PCB 156-induced lipid metabolism disorder. CONCLUSION: Our findings provide an overview of differentially expressed mRNAs and lncRNAs in L-02 cells exposed to PCB 156, and contribute to the field of polychlorinated biphenyl-induced non-alcoholic fatty liver disease.

Low-dose PCB126 compromises circadian rhythms associated with disordered glucose and lipid metabolism in mice.

It has been documented that 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) elicits diverse detrimental effects on human health including metabolic syndrome and non-alcoholic fatty-liver disease (NAFLD), through a wide array of non-carcinogenic mechanisms, which require further detailed investigations. The circadian clock system consists of central clock machinery (located in the suprachiasmatic nucleus in the hypothalamus) and the peripheral clocks (located in nearly all peripheral tissues). Peripheral clocks in the liver play fundamental roles in maintaining liver homeostasis, including the regulation of energy metabolism and the expression of enzymes that fine-tune the absorption and metabolism of xenobiotics. However, the molecular basis of whether PCB126 disrupts liver homeostasis (e.g., glucose and lipid metabolism) by dysregulating the circadian clock system is still unknown. Thus, we performed a set of comprehensive analyses of glucose and lipid metabolism in the liver tissues from low-dose PCB126-treated mice. Our results demonstrated that PCB126 diminished glucose and cholesterol levels in serum and elevated glucose and cholesterol levels in the liver. Moreover, PCB126 compromised PGC1α and PDHE1α, which are the driving force for mitochondrial biogenesis and entry of pyruvate into the tricarboxylic acid (TCA) cycle, respectively, and resulted in the accumulation of glucose, glycogen and pyruvate in the liver after PCB126 exposure. Additionally, PCB126 blocked hepatic cholesterol metabolism and export pathways, leading to an elevated localization of hepatic cholesterol. Mechanistic investigations illustrated that PCB126 greatly altered the expression profile of core clock genes and their target rhythm genes involved in orchestrating glucose and cholesterol metabolism. Together, our results demonstrated that a close correlation between PCB126-disturbed glucose and lipid metabolism and disordered physiological oscillation of circadian genes.

Synthesis and affinities of C3-symmetric thioglycoside-containing trimannosides.

Thioglycoside-containing trimannose analogs were designed and prepared to mimic the natural N-glycan core trisaccharide α-d-Man-(1→3)-[α-d-Man-(1→6)]-d-Man. (1→6)-S-Linked trimannoside 1 and its trivalent cluster 2 were synthesized in 11 and 15 steps, respectively, taking advantages of the armed mannopyranosyl trichloroacetimidate as glycosyl donor. Hemagglutination inhibition of the two new thiomannotriose analogs was preliminarily examined. Comparing to the parent trimannoside α-d-Man-(1→3)-[α-d-Man-(1→6)]-d-Man-OMe, the cluster mannotrioside 2 presented a comparable binding affinity to Con A, while the monomer 6-S-trimannoside 1 exhibited a slightly lower inhibition ability.

A "turn-on" fluorescent Hg2+ chemosensor based on Ferrier carbocyclization.

A "turn-on" fluorescent chemosensor with excellent selectivity and satisfactory sensitivity on Hg(2+) detection in 100% water media has been established employing a carbohydrate based Ferrier carbocyclization reaction. The probe has also presented satisfactory results for the imaging of Hg(2+) ions in cells and organisms.