The Resistance of Soybean Variety Heinong 84 to Apple Latent Spherical Virus Is Controlled by Two Genetic Loci.

Apple latent spherical virus (ALSV) is widely used as a virus-induced gene silencing (VIGS) vector for function genome study. However, the application of ALSV to soybeans is limited by the resistance of many varieties. In this study, the genetic locus linked to the resistance of a resistant soybean variety Heinong 84 was mapped by high-throughput sequencing-based bulk segregation analysis (HTS-BSA) using a hybrid population crossed from Heinong 84 and a susceptible variety, Zhonghuang 13. The results showed that the resistance of Heinong 84 to ALSV is controlled by two genetic loci located on chromosomes 2 and 11, respectively. Cleaved amplified polymorphic sequence (CAPS) markers were developed for identification and genotyping. Inheritance and biochemical analyses suggest that the resistance locus on chromosome 2 plays a dominant dose-dependent role, while the other locus contributes a secondary role in resisting ALSV. The resistance locus on chromosome 2 might encode a protein that can directly inhibit viral proliferation, while the secondary resistance locus on chromosome 11 may encode a host factor required for viral proliferation. Together, these data reveal novel insights on the resistance mechanism of Heinong 84 to ALSV, which will benefit the application of ALSV as a VIGS vector.

Gut Microbiota Control the Bioavailability and Metabolism of Organoarsenicals of Seaweeds in Mice after Oral Ingestion.

Edible seaweed consumption is an essential route of human exposure to complex organoarsenicals, including arsenosugars and arsenosugar phospholipids. However, the effects of gut microbiota on the metabolism and bioavailability of arsenosugars in vivo are unknown. Herein, two nori and two kelp samples with phosphate arsenosugar and sulfonate arsenosugar, respectively, as the predominant arsenic species, were administered to normal mice and gut microbiota-disrupted mice treated with the broad-spectrum antibiotic cefoperazone for 4 weeks. Following exposure, the community structures of the gut microbiota, total arsenic concentrations, and arsenic species in excreta and tissues were analyzed. Total arsenic excreted in feces and urine did not differ significantly between normal and antibiotic-treated mice fed with kelp samples. However, the total urinary arsenic of normal mice fed with nori samples was significantly higher (p < 0.05) (urinary arsenic excretion factor, 34-38 vs 5-7%), and the fecal total arsenic was significantly lower than in antibiotic-treated mice. Arsenic speciation analysis revealed that most phosphate arsenosugars in nori were converted to arsenobetaine (53.5-74.5%) when passing through the gastrointestinal tract, whereas a large portion of sulfonate arsenosugar in kelp was resistant to speciation changes and was excreted in feces intact (64.1-64.5%). Normal mice exhibited greater oral bioavailability of phosphate arsenosugar from nori than sulfonate arsenosugar from kelp (34-38 vs 6-9%). Our work provides insights into organoarsenical metabolism and their bioavailability in the mammalian gut.

Molecular insights of 2,6-dichlorobenzoquinone-induced cytotoxicity in zebrafish embryo: Activation of ROS-mediated cell cycle arrest and apoptosis.

2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), as an emerging disinfection by-product, has been frequently detected in waters, posing potential health risk on public health. Although some studies have pointed out that 2,6-DCBQ exposure can induce cytotoxicity, limited information is available for underlying mechanism for 2,6-DCBQ-induced cytotoxicity. To explore this mechanism, we assessed the levels of reactive oxygen species (ROS), acridine orange (AO) staining, and the mRNA transcriptions of genes (Chk2, Cdk2, Ccna, Ccnb and Ccne) involved in cell-cycle and genes (p53, bax, bcl-2 and caspase 3) involved in apoptosis in zebrafish embryo, after exposed to different concentrations (10, 30, 60, 90 and 120 µg/L) of 2,6-DCBQ for 72 h. Our results indicated that 2,6-DCBQ exposure induced ROS generation and cell apoptosis, and disturbed the mRNA transcription of genes related to cell cycle and apoptosis in zebrafish embryo. Moreover, we also found that 30 ~ 60 µg/L 2,6-DCBQ is the important transition from cell-cycle arrest to cell apoptosis. These results provided novel insight into 2,6-DCBQ-induced cytotoxicity.

Influence of spatial distribution pattern of buildings on the distribution of urban gaseous pollutants.

Buildings are the main component of urban, and their three-dimensional spatial patterns affect meteorological conditions and consequently, the spatial distribution of gaseous pollutants (CO, NO, NO2, and SO2). This study uses the Jinan Central District as the study area and constructs a building spatial distribution index system based on DEM, urban road network, and building big data. ANOVA and spatial regression models were used to study the effects of building spatial distribution indicators on the distribution of gaseous pollutants along with their spatial heterogeneity. The results showed that (1) the effects of most of spatial distribution indexes of building on the concentration distribution of the four gaseous pollutants were significant, with one-way ANOVA outcomes reaching a significance level of 0.01 or more. The DEM mean, building altitude, and their interaction with other building spatial distribution indicators are important factors affecting the distribution of gaseous pollutants; The interaction of other three-factor indicators did not have a significant effect on the distribution of gaseous pollutant concentrations. (2) The spatial distribution of CO and NO2 is mainly influenced by the indicators of the spatial distribution of buildings in this study unit, and the effects of CO and NO2 concentrations in adjacent study units are the result of the action of stochastic factors. The NO and SO2 concentrations are influenced by the spatial distribution index of buildings in this study unit, the neighborhood homogeneity index, and NO and SO2 concentrations. (3) Spatial heterogeneity was observed in the effects of building spatial distribution indicators on the concentrations of different pollutants. The GWR models constructed using CO and NO concentrations and building spatial distribution indicators were well fitted globally and locally. The CO and NO concentrations were negatively correlated with the mean topographic elevation and NO concentrations were correlated with building density.

Toxicokinetics, in vivo metabolic profiling, and in vitro metabolism of gelsenicine in rats.

Gelsenicine, mainly isolated from Gelsemium elegans Benth., is one of the most toxic alkaloids. The lack of information on gelsenicine leads to inaccurate risk and poisoning evaluation. In this study, the metabolic profiling and toxicokinetics of gelsenicine was studied by ultra-high performance liquid chromatography (UPLC) with quadrupole time-of-flight (Q-ToF) and tandem mass spectrometry in rats after intraperitoneal (i.p., 40 µg/kg) and intragastric (i.g., 60 µg/kg) administration. After i.p. administration, the area under the curve (AUC), the apparent volume of distribution (V), and the total body clearance (CL/F) of gelsenicine in plasma were 3.79 µg/L h, 38.47 L/kg, and 11.87 mL/h kg, respectively. After i.g. administration, the corresponding values were slightly increased (5.49 µg/L h; 53.10 mL/kg, and 12.66 mL/h kg). The toxicokinetic results indicated that the hepatic first-pass effect was predominant after i.p. administration. The UPLC-Q-ToF-MS data revealed nine metabolites in plasma, urine, and bile which were largely obtained by demethylation, hydroxylation, acetylation and glycine conjugation. Metabolites were mainly excreted through urine and bile, most of which in urine was basically eliminated in 24 h. Molecular docking and liver microsome experiments further showed that gelsenicine was metabolized by cytochrome P450 3A4 and 3A5. Summarizing, the present study provides metabolic and toxicokinetic information on gelsenicine which in turn may help in future risk assessment and forensic identification after poisonings.

Metabolic profiling of soyasaponin Bb in rat plasma, urine, bile, and feces after intragastric administration.

Soyasaponin Bb is one of the bioactive oleanolic acid-type triterpenoid saponins mainly isolated from soybean. It possesses significant antithrombosis, hypolipidemic, anticancer, and antioxidant activities. However, the metabolic profiles of soyasaponin Bb are still unknown. The present study investigated the metabolites of soyasaponin Bb in plasma, bile, urine, and feces samples after intragastric administration using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight-mass spectrometry, and its possible metabolic pathways were subsequently proposed. Using the metabolite profiling strategy, 11 metabolites were first identified from urine, plasma, bile, and feces of rats after intragastric administration of soyasaponin Bb. Hydroxylation and hydrolysis were the major metabolic pathways of soyasaponin Bb in rat. The results expand our knowledge of the metabolism of soyasaponin Bb, which could provide valuable information for better comprehension of future pharmacological research.

Chemical constituents of radix Actinidia chinensis planch by UPLC-QTOF-MS.

Radix Actinidia decoction and its prescriptions are used to treat tumors and other diseases. Although some chemical components have been isolated from Radix Actinidia, systematic analysis of its chemical components has not been reported, which hinders the basic research on its effective substances and its quality control. In this work, a UPLC-QTOF-MS method was employed to profile and characterize the chemical constituents of water extracts from Radix Actinidia Chinensis Planch (RACP). We unambiguously or tentatively identified 295 chemical components from RACP, including 46 pentacyclic triterpenes, 72 flavonoids, 53 phenolic acids, 24 coumarins, three anthraquinones and other compounds. Most of the chemical components have not been described so far in Actinidia. More than 180 phytochemicals are reported in Actinidia for the first time. 2α,3α,24-trihydroxyurs-12-en-28-oic acid, asiatic acid, syringic acid, fraxin, esculetin, 5,7-dihydroxychromone, esculin, (+)-catechin, (-)-epi-catechin, vanillic acid, ferulic acid, protocatechuic acid and rutin were unambiguously identified by comparison with the reference standards. Catechin derivatives, coumarin derivatives and phenolic acid derivatives were the main water-soluble components in RACP. This study broadened the chemical profiles of RACP, and laid the foundation for subsequent research on the effective components and their mechanism of action. This work also provides an important reference for the quality control and evaluation of RACP.

Environmentally relevant concentrations of arsenic induces apoptosis in the early life stage of zebrafish.

Arsenic (As) in the aquatic environment is a considerable environmental issue, previous studies have reported the toxic effects of low concentrations (≤ 150 µg/L) of As on fish. However, limited information is available regarding the impact of low levels of As on apoptosis. To evaluate this, zebrafish embryos were exposed to different concentrations (0, 25, 50, 75, and 150 µg/L) of As (arsenite [AsIII] and arsenate [AsV]) for 120 h. Our results indicated that low concentrations of AsIII exposure significantly inhibited the survival of zebrafish larvae, and significantly increased the transcription of Caspase-9 and Caspase-3, the ratio of Bax/Bcl-2 transcription, and protein levels of Caspase-3. In contrast, AsV decreased the ratios of Bax/Bcl-2 transcription and protein levels, as well as protein levels of Caspase-3. Our data demonstrated that AsIII and AsV exert different toxic effects, AsIII induced apoptosis via the mitochondrial pathway and the extrinsic pathway, while AsV induced apoptosis only via the mitochondrial pathway.

Synthesis of Fe2+ Substituted High-Performance LiMn1-xFexPO4/C (x = 0, 0.1, 0.2, 0.3, 0.4) Cathode Materials for Lithium-Ion Batteries via Sol-Gel Processes.

A series of carbon-coated LiMn1-xFexPO4 (x = 0, 0.1, 0.2, 0.3, 0.4) materials are successfully constructed using glucose as carbon sources via sol-gel processes. The morphology of the synthesized material particles are more regular and particle sizes are more homogeneous. The carbon-coated LiMn0.8Fe0.2PO4 material obtains the discharge specific capacity of 152.5 mAh·g-1 at 0.1 C rate and its discharge specific capacity reaches 95.7 mAh·g-1 at 5 C rate. Iron doping offers a viable way to improve the electronic conductivity and lattice defects of materials, as well as improving transmission kinetics, thereby improving the rate performance and cycle performance of materials, which is an effective method to promote the electrical properties.

[Determination of domoic acid in shellfish by liquid chromatography- tandem mass spectrometry coupled with dispersive solid phase extraction].

OBJECTIVE: A method utilizing liquid chromatography-tandem mass spectrometry(LC-MS/MS) coupled with dispersive solid phase extraction for quantitative analysis of domoic acid in four kinds of shellfish was established. METHODS: The sample of 0. 1 g was extracted with 25% methanol aqueous solution, the extract was purified by dispersive solid phase extraction with 50 mg HLB and 5 mg GCB, and then filtered through a PTFE membrane. The analytes were separated on a C_(18) column(100 mm×2. 1 mm, 1. 9 µm), and detected in selected reaction monitoring(SRM) mode via positive electrospray ionization. The matrix matching and external standard method was used for quantitation. RESULTS: Domoic acid showed good linearity in the concentration range between 1. 0 ng/mL and 50. 0 ng/mL with correlation coefficients higher than 0. 9994. The detection limits of domoic acid in shellfish was 5 µg/kg. The inter-and intra-day recoveries were 91. 6%-109. 2% and 90. 9%-109. 3%, respectively. The inter-and intra-day ralitive standard deviations(RSDs) were lower than 8. 2% at spiked concentrations of 20, 50 and 100 µg/kg. CONCLUSION: The method is accurate, fast, easy to operate, which can satisfy the requirements of public health emergency testing or routine testing.

Nioella ostreopsis sp. nov., isolated from toxic dinoflagellate, Ostreopsis lenticularis.

A novel short-rod-shaped bacterial strain with poly-ß-hydroxybutyric acid granules inside, designated as Z7-4T, was isolated from a culture of a marine dinoflagellate with palytoxin-producing capacity, Ostreopsis lenticularis OS06, collected from the East China Sea. Cells of Z7-4T were Gram-stain-negative, non-motile, strictly aerobic, 0.9-1.2 µm wide and 2.0-3.9 µm long. Growth occurred in 1-4 % (w/v) NaCl, at 15-37 °C and at pH 5.0-10.0, with optimum growth in 3.5 % (w/v) NaCl, at 30 °C and at pH 7.0. Analysis of 16S rRNA gene sequence revealed that Z7-4T shared the highest 16S rRNA gene sequence similarities with Nioella aestuarii JCM 30752T (98.8 %), followed by Nioella sediminis KCTC 42144T (98.6 %) and Nioella nitratireducens KCTC 32417T (96.9 %). Phylogenetic analysis based on nearly complete 16S rRNA gene sequences revealed that Z7-4T clearly represented a member of the genus Nioella within the family Rhodobacteraceae. The respiratory quinone of Z7-4T was identified as Q-10. Polar lipids of Z7-4T were phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, three unidentified aminophospholipids and one unidentified phospholipid. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The DNA G+C content of Z7-4T was 63.0 mol%. DNA-DNA hybridization values of the isolate against the closely related type strains were far below the 70 % limit for species delineation. The average nucleotide identity and in silico DNA-DNA genome hybridization relatedness between Z7-4T and the closely related members of the genus Nioella, N. sediminis KCTC 42144T and N. nitratireducens KCTC 32417T, were 91.1 and 46.3 %, and 79.3 and 19.4 %, respectively. On the basis of the results of polyphasic analysis, Z7-4T is proposed to represent a novel species of the genus Nioella, for which the name Nioella ostreopsis sp. nov. is proposed. The type strain of Nioella ostreopsis is Z7-4T (=KCTC 62459T=CCTCC AB 2017231T).

Limnobacter alexandrii sp. nov., a thiosulfate-oxidizing, heterotrophic and EPS-bearing Burkholderiaceae isolated from cultivable phycosphere microbiota of toxic Alexandrium catenella LZT09.

A novel Gram-negative, aerobic, motile and short rod-shaped bacterium with exopolysaccharides production, designated as LZ-4T, was isolated from cultivable phycosphere microbiota of harmful algal blooms-causing marine dinoflagellate Alexandrium catenella LZT09 which produces paralytic shellfish poisoning toxins. Strain LZ-4T was able to use thiosulfate (optimum concentration 10 mM) as energy source for bacterial growth. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain LZ-4T belonged to the genus Limnobacter, showing high 16S rRNA gene sequences similarities with L. thiooxidans DSM 13612T (99.4%), L. humi NBRC 11650T (98.2%) and L. litoralis NBRC 105857T (97.2%), respectively. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between LZ-4T and L. thiooxidans DSM 13612T were 78.9 and 21.9%, respectively. Both values were far lower than the thresholds (95-96% for ANI and 70% for dDDH) generally accepted for new species delineation. The respiratory quinone of strain LZ-4T was Q-8. The dominant cellular fatty acids were determined as summed feature 3 (C16:1 ω6c/ω7c), summed feature 8 (C18:1 ω6c/ω7c) and C16:0. Polar lipids profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminolipids and three unidentified polar lipids. The genomic DNA G+C content of strain LZ-4T was 52.5 mol%. Based on polyphasic characterization, strain LZ-4T represents a novel species of the genus Limnobacter, for which the name Limnobacter alexandrii sp. nov. is proposed. The type strain is LZ-4T (=CCTCC AB 2019004T =KCTC 72281T).

[Analysis of multi-minerals in seafoods in Zhejiang Province].

OBJECTIVE: To analyze the contents of Ca, K, Na, Mg, Fe, Zn, Cu and Mn in 33 kinds of marine products, such as fish, shrimp, crab, shellfish and mollusk. METHODS: The national standard GB 5009. 268-2016 Determination of multi elements in foods was used for determination. The correlation between multi elements was statistically analyzed. RESULTS: The highest level of Ca was found in clam(510. 2 mg/100 g edible), K in mackerel(444. 4 mg/100 g edible), Na in clam(487. 6 mg/100 g edible), Mg in conch(132. 7 mg/100 g edible). The highest level of Fe and Mn was in conch(37. 35 and 2. 6 mg/100 g edible). The highest level of Zn and Cu was in oyster(15. 92 and 8. 58 mg/100 g edible). The correlation analysis showed that Mn-Ca was highly correlated in fish and shrimp(r=0. 9438 and 0. 8585, P < 0. 05), while Cu-Mg, Cu-Zn, Zn-Na were highly correlated in shellfish(r=-0. 9102, 0. 8501 and 0. 8428, P < 0. 05). CONCLUSION: There are rich mineral elements in different seafood, which can provide reference for the reasonable diet of residents.

Anti-Inflammatory Activity of a Peptide from Skipjack (Katsuwonus pelamis).

In this paper, the effect of skipjack (Katsuwonus pelamis) enzymatic peptide (SEP), which was prepared and purified from a byproduct of skipjack, on inflammation, ulcerative colitis and the regulation of intestinal flora was studied in a mouse ulcerative colitis model and a transgenic zebrafish inflammation model. The aggregation of transgenic granulocyte neutrophils in zebrafish from a normal environment and from a sterile environment was calculated, and the anti-inflammatory activity of SEP was evaluated. To evaluate the anti-ulcerative colitis activity of SEP, DSS-induced colitis mice were given SEP, salicylazosulfapyridine (SASP), or SASP + SEP. Then, the concentrations of IL-6, IL-10 and TNF-α in the serum were detected, the HE-stained colon tissue was examined by microscopy the species composition and abundance distribution of the intestinal flora was analyzed. The results showed that 500 µg/mL SEP treatment significantly alleviated neutrophil granulocyte aggregation in the zebrafish inflammation model; Diarrhea, hematochezia and body weight loss were alleviated to a certain extent in mice gavaged with SEP and SASP, and the combination of SASP with SEP was the most effective in mice. The damage to villi in the intestine was completely repaired, and the levels of IL-6, IL-10 and TNF-α, which are associated with inflammation, were all reduced. In addition, the proportion of intestinal probiotics or harmless bacteria increased, while that of pathogenic bacteria decreased, and the effect of the combined treatment was the most pronounced. These results show that SEP could relieve inflammation, cure ulcerative colitis, regulate intestinal flora and enhance the therapeutic effect of the clinical drug SASP. This study provides a theoretical basis for the development of SEP as an anti-inflammatory adjuvant therapy and intestinal flora regulator.

Soil contamination with antibiotics in a typical peri-urban area in eastern China: Seasonal variation, risk assessment, and microbial responses.

The prevalence and persistence of antibiotics in soils has become an emerging environmental issue and an increasing threat to soil security and global public health. The problem is more severe in areas undergoing rapid urbanization; however, the ecological risks of antibiotics, seasonal variability, and associated soil microbial responses in peri-urban soils have not been well-explored. The seasonal soil sampling campaigns were conducted in a typical peri-urban watershed in eastern China to investigate distribution of antibiotics. The results demonstrated higher mean concentrations of most antibiotic compounds in winter than in summer in peri-urban soils. The seasonal variations of norfloxacin, enrofloxacin, and ciprofloxacin were more significant than those of other antibiotics, due to their higher migration ability and bioavailability. An ecological risk assessment demonstrated that chlortetracycline, ciprofloxacin, doxycycline, and ofloxacin can pose high risks to soil microorganisms. Furthermore, the coexistence of multiple antibiotics obviously poses higher risks than individual compounds. A redundancy analysis demonstrated that tetracyclines mainly showed negative correlations with Firmicutes and Chloroflexi, and quinolones showed obviously negative correlations with Acidobacteria, Gemmatimonadetes, and Nitrospirae, suggesting potential inhibition from antibiotics on biological activities or biodegradation processes. However, the persistence of antibiotics in soil results in a significant decrease in bacterial diversity and a change in dominant species. Our results provide an overview of the seasonal variability of antibiotics and the associated effects on bacterial communities in peri-urban soils. The results can provide scientific guidance on decreasing soil contamination with antibiotics to enhance soil security in similar areas.

Simultaneous Improvements of Pseudomonas Cell Growth and Polyhydroxyalkanoate Production from a Lignin Derivative for Lignin-Consolidated Bioprocessing.

Cell growth and polyhydroxyalkanoate (PHA) biosynthesis are two key traits in PHA production from lignin or its derivatives. However, the links between them remain poorly understood. Here, the transcription levels of key genes involved in PHA biosynthesis were tracked in Pseudomonas putida strain A514 grown on vanillic acid as the sole carbon source under different levels of nutrient availability. First, enoyl-coenzyme A (CoA) hydratase (encoded by phaJ4) is stress induced and likely to contribute to PHA synthesis under nitrogen starvation conditions. Second, much higher expression levels of 3-hydroxyacyl-acyl carrier protein (ACP) thioesterase (encoded by phaG) and long-chain fatty acid-CoA ligase (encoded by alkK) under both high and low nitrogen (N) led to the hypothesis that they likely not only have a role in PHA biosynthesis but are also essential to cell growth. Third, 40 mg/liter PHA was synthesized by strain AphaJ4C1 (overexpression of phaJ4 and phaC1 in strain A514) under low-N conditions, in contrast to 23 mg/liter PHA synthesized under high-N conditions. Under high-N conditions, strain AalkKphaGC1 (overexpression of phaG, alkK, and phaC1 in A514) produced 90 mg/liter PHA with a cell dry weight of 667 mg/liter, experimentally validating our hypothesis. Finally, further enhancement in cell growth (714 mg/liter) and PHA titer (246 mg/liter) was achieved in strain Axyl_alkKphaGC1 via transcription level optimization, which was regulated by an inducible strong promoter with its regulator, XylR-PxylA, from the xylose catabolic gene cluster of the A514 genome. This study reveals genetic features of genes involved in PHA synthesis from a lignin derivative and provides a novel strategy for rational engineering of these two traits, laying the foundation for lignin-consolidated bioprocessing.IMPORTANCE With the recent advances in processing carbohydrates in lignocellulosics for bioproducts, almost all biological conversion platforms result in the formation of a significant amount of lignin by-products, representing the second most abundant feedstock on earth. However, this resource is greatly underutilized due to its heterogeneity and recalcitrant chemical structure. Thus, exploiting lignin valorization routes would achieve the complete utilization of lignocellulosic biomass and improve cost-effectiveness. The culture conditions that encourage cell growth and polyhydroxyalkanoate (PHA) accumulation are different. Such an inconsistency represents a major hurdle in lignin-to-PHA bioconversion. In this study, we traced and compared transcription levels of key genes involved in PHA biosynthesis pathways in Pseudomonas putida A514 under different nitrogen concentrations to unveil the unusual features of PHA synthesis. Furthermore, an inducible strong promoter was identified. Thus, the molecular features and new genetic tools reveal a strategy to coenhance PHA production and cell growth from a lignin derivative.

The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10, APM1 and FUT6 genes.

Genome-wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region, China. In this case-control study, we genotyped 13 single-nucleotide polymorphisms (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). Allelic carriers of rs3792267-A, rs1501299-T, and rs3760776-T had a 2.24-fold [OR (95% CI): 1.35-3.71], 0.59-fold [OR (95% CI): 0.39-0.91], 0.57-fold [OR (95% CI): 0.34-0.95] increased risk for T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, particularly among non-obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2DM in a Uyghur population.

China suboptimal health cohort study: rationale, design and baseline characteristics.

BACKGROUND: Suboptimal health status (SHS) is a physical state between health and disease, characterized by the perception of health complaints, general weakness, chronic fatigue and low energy levels. SHS is proposed by the ancient concept of traditional Chinese medicine (TCM) from the perspective of preservative, predictive and personalized (precision) medicine. We previously created the suboptimal health status questionnaire 25 (SHSQ-25), a novel instrument to measure SHS, validated in various populations. SHSQ-25 thus affords a window of opportunity for early detection and intervention, contributing to the reduction of chronic disease burdens. METHODS/DESIGN: To investigate the causative effect of SHS in non-communicable chronic diseases (NCD), we initiated the China suboptimal health cohort study (COACS), a longitudinal study starting from 2013. Phase I of the study involved a cross-sectional survey aimed at identifying the risk/protective factors associated with SHS; and Phase II: a longitudinal yearly follow-up study investigating how SHS contributes to the incidence and pattern of NCD. RESULTS: (1) Cross-sectional survey: in total, 4313 participants (53.8 % women) aged from 18 to 65 years were included in the cohort. The prevalence of SHS was 9.0 % using SHS score of 35 as threshold. Women showed a significantly higher prevalence of SHS (10.6 % in the female vs. 7.2 % in the male, P < 0.001). Risk factors for chronic diseases such as socioeconomic status, marital status, highest education completed, physical activity, salt intake, blood pressure and triglycerides differed significantly between subjects of SHS (SHS score ≥35) and those of ideal health (SHS score <35). (2) Follow up: the primary and secondary outcomes will be monitored from 2015 to 2024. CONCLUSIONS: The sex-specific difference in prevalence of SHS might partly explain the gender difference of incidence of certain chronic diseases. The COACS will enable a thorough characterization of SHS and establish a cohort that will be used for longitudinal analyses of the interaction between the genetic, lifestyle and environmental factors that contribute to the onset and etiology of targeted chronic diseases. The study together with the designed prospective cohort provides a chance to characterize and evaluate the effect of SHS systemically, and it thus generates an unprecedented opportunity for the early detection and prevention of chronic disease.

Quantifying lipid contents in enveloped virus particles with plasmonic nanoparticles.

Phosphatidylserine (PS) and monosialotetrahexosylganglioside (GM1 ) are examples of two host-derived lipids in the membrane of enveloped virus particles that are known to contribute to virus attachment, uptake, and ultimately dissemination. A quantitative characterization of their contribution to the functionality of the virus requires information about their relative concentrations in the viral membrane. Here, a gold nanoparticle (NP) binding assay for probing relative PS and GM1 lipid concentrations in the outer leaflet of different HIV-1 and Ebola virus-like particles (VLPs) using sample sizes of less than 3 × 10(6) particles is introduced. The assay evaluates both scattering intensity and resonance wavelength, and determines relative NP densities through plasmon coupling as a measure for the target lipid concentrations in the NP-labeled VLP membrane. A correlation of the optical observables with absolute lipid contents is achieved by calibration of the plasmon coupling-based methodology with unilamellar liposomes of known PS or GM1 concentration. The performed studies reveal significant differences in the membrane of VLPs that assemble at different intracellular sites and pave the way to an optical quantification of lipid concentration in virus particles at physiological titers.

Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1/CD169.

Human immunodeficiency virus type 1 (HIV-1) interactions with myeloid dendritic cells (DCs) can result in virus dissemination to CD4⁺ T cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (GSL), GM3. The mechanism of DC-mediated trans infection is extremely efficacious and can result in infection of multiple CD4⁺ T cells as these cells make exploratory contacts on the DC surface. While it has long been appreciated that activation of DCs with ligands that induce type I IFN signaling pathway dramatically enhances DC-mediated T cell trans infection, the mechanism by which this occurs has remained unclear until now. Here, we demonstrate that the type I IFN-inducible Siglec-1, CD169, is the DC receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of GSLs from virions, abrogated DC-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. HIV-1 particles co-localized with CD169 on DC surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the DC--T cell infectious synapses upon initiation of T cell contact. Together, these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (GM3--CD169 interaction) for DC-dependent HIV dissemination.