Integrated analysis of miRNA-mRNA expression of newly emerging swine H3N2 influenza virus cross-species infection with tree shrews.

BACKGROUND: Cross-species transmission of zoonotic IAVs to humans is potentially widespread and lethal, posing a great threat to human health, and their cross-species transmission mechanism has attracted much attention. miRNAs have been shown to be involved in the regulation of IAVs infection and immunity, however, few studies have focused on the molecular mechanisms underlying miRNAs and mRNAs expression after IAVs cross-species infection. METHODS: We used tree shrews, a close relative of primates, as a model and used RNA-Seq and bioinformatics tools to analyze the expression profiles of DEMs and DEGs in the nasal turbinate tissue at different time points after the newly emerged swine influenza A virus SW2783 cross-species infection with tree shrews, and miRNA-mRNA interaction maps were constructed and verified by RT-qPCR, miRNA transfection and luciferase reporter assay. RESULTS: 14 DEMs were screened based on functional analysis and interaction map, miR-760-3p, miR-449b-2, miR-30e-3p, and miR-429 were involved in the signal transduction process of replication and proliferation after infection, miR-324-3p, miR-1301-1, miR-103-1, miR-134-5p, miR-29a, miR-31, miR-16b, miR-34a, and miR-125b participate in negative feedback regulation of genes related to the immune function of the body to activate the antiviral immune response, and miR-106b-3p may be related to the cross-species infection potential of SW2783, and the expression level of these miRNAs varies in different days after infection. CONCLUSIONS: The miRNA regulatory networks were constructed and 14 DEMs were identified, some of them can affect the replication and proliferation of viruses by regulating signal transduction, while others can play an antiviral role by regulating the immune response. It indicates that abnormal expression of miRNAs plays a crucial role in the regulation of cross-species IAVs infection, which lays a solid foundation for further exploration of the molecular regulatory mechanism of miRNAs in IAVs cross-species infection and anti-influenza virus targets.

First principles studies on the adsorption of rare base-pairs on the surface of B/N atom doped γ-graphyne.

Rare base-pairs consists of guanine (G) paired with rare bases, such as 5-methylcytosine (5-meCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-caCyt), and 5-formylcytosine (5-fCyt), have become the focus of epigenetic research because they can be used as markers to detect some chronic diseases and cancers. However, the correlation detection of these rare base-pairs is limited, which in turn limits the development of diagnostic tests and devices. Herein, the interaction of rare base-pairs adsorbed on pure and B/N-doped γ-graphyne (γ-GY) nanosheets was explored using the density functional theory. The calculated adsorption energy showed that the system of rare base-pairs on B-doped γ-GY is more stable than that on pure γ-GY or N-doped γ-GY. Translocation time values indicate that rare base-pairs can be successfully distinguished as the difference in their translocation times is very large for pure and B/N-doped γ-GY nanosheets. Meanwhile, sensing response values illustrated that pure and B-doped γ-GY are the best for G-5-hmCyt adsorption, while the N-doped γ-GY is the best for G-Cyt adsorption. The findings indicate that translocation times and sensing response can be used as detection indexes for pure and B/N doped γ-GY, which will provide a new way for experimental scientists to develop the biosensor components.

Insufficient compensatory pancreatic ß-cells function might be closely associated with hyperuricemia in U.S. adults: evidence from the National Health and Nutrition Examination Survey.

BACKGROUND: The prevalence of hyperuricemia (HUA) is gradually increasing worldwide. HUA is closely related to diabetes, but the relationship between HUA and pancreatic ß-cells function in the population is unclear. The purpose of this article is to investigate the association between pancreatic ß-cells and HUA. METHODS: This cross-sectional study examined the association between pancreatic ß-cells and HUA in 1999-2004 using data from the National Health and Nutrition Examination Survey (NHANES). Subjects were divided into two groups: HUA and non-HUA. Pancreatic ß-cells function levels were assessed using homeostasis model assessment version 2-%S (HOMA2-%S), homeostasis model assessment version 2-%B (HOMA2-%B) and disposition index (DI). Multivariate logistic regression models and restricted cubic spline models were fitted to assess the association of pancreatic ß-cells function with HUA. RESULTS: The final analysis included 5496 subjects with a mean age of 46.3 years (standard error (SE), 0.4). The weighted means of HOMA2-%B, HOMA2-%S and DI were 118.1 (SE, 1.0), 69.9(SE, 1.1) and 73.9 (SE, 0.7), respectively. After adjustment for major confounders, participants in the highest quartile of HOMA2-%B had a higher risk of HUA (OR = 2.55, 95% CI: 1.89-3.43) compared to participants in the lowest quartile. In contrast, participants in the lowest quartile of HOMA2-%S were significantly more likely to have HUA than that in the highest quartile (OR = 3.87, 95% CI: 2.74-5.45), and similar results were observed in DI (OR = 1.98, 95% CI: 1.32-2.97). Multivariate adjusted restricted cubic spline analysis found evidence of non-linear associations between HOMA2-%B, HOAM2-%S, DI and the prevalence of HUA. CONCLUSION: Our finding illustrated the indicators of inadequate ß-cells compensation might be a new predictor for the presence of HUA in U.S. adults, highlighting a critical role of pancreatic ß-cells function on HUA.

The association between psychological resilience and hair cortisol concentration in adults: A systematic review and meta-analysis.

BACKGROUND: Resilience measures are typically based on subjective self-assessment, which is prone to bias. Objective biological/physiological measures of resilience are therefore needed. Hair cortisol concentration is a particularly promising candidate as a biomarker for resilience. METHODS: We conducted a meta-analytic review from inception to April 2023 in PubMed, EMBASE, Cochrane Library, and Psych Info databases. All data were analyzed using a random-effects model. RESULTS: Eight studies were identified that included a total of 1,064 adults. The random effects model demonstrated that resilience and hair cortisol concentration were inversely correlated (r = -0.18, 95% confidence interval [CI] = -0.27 to -0.09) with substantial heterogeneity (I2 = 54.2%, p = 0.03). The inverse association was stronger in those who were age 40 years or younger compared to those who were over 40 years. The correlation coefficients between psychological resilience and hair cortisol concentration among adults assessed by different resilience measures were r = -0.29 (95% CI = -0.49 to -0.08) for the CD-RISC-10; r = -0.21 (95% CI = -0.31 to -0.11) for the CDRISC- 25, and r = -0.08 (95% CI = -0.22 to 0.06) for the BRS. Six of eight studies examined the connection between resilience and perceived stress, where the weighted mean correlation coefficient was r = -0.45 (95% CI = -0.56 to -0.33), with considerable heterogeneity (I2 = 76.2%, p = 0.001). CONCLUSIONS: There is a negative association between psychological resilience and hair cortisol concentration based on these eight studies. Additional research, particularly prospective studies, is needed to determine whether hair cortisol concentration can be used as a biomarker for psychological resilience.

Preparation of Pinoresinol and Dehydrodiconiferyl Alcohol from Eucommiae Cortex Extract by Fermentation with Traditional Mucor.

Eucommiae Cortex (EC) is frequently used alone or in combination with other active ingredients to treat a range of illnesses. An efficient technical instrument for changing cheap or plentiful organic chemicals into rare or costly counterparts is biotransformation. It combines EC with biotransformation techniques with the aim of producing some novel active ingredients, using different strains of bacteria that were introduced to biotransform EC in an aseptic environment. The high-quality strains were screened for identification after the fermentation broth was found using HPLC, and the primary unidentified chemicals were separated and purified in order to be structurally identified. Strain 1 was identified as Aspergillus niger and strain 2 as Actinomucor elegans; the main transformation product A was identified as pinoresinol (Pin) and B as dehydrodiconiferyl alcohol (DA). The biotransformation of EC utilizing Aspergillus niger and Actinomucor elegans is reported for the first time in this study's conclusion, resulting in the production of Pin and DA.

Chromosome-level wild Hevea brasiliensis genome provides new tools for genomic-assisted breeding and valuable loci to elevate rubber yield.

The rubber tree (Hevea brasiliensis) is grown in tropical regions and is the major source of natural rubber. Using traditional breeding approaches, the latex yield has increased by sixfold in the last century. However, the underlying genetic basis of rubber yield improvement is largely unknown. Here, we present a high-quality, chromosome-level genome sequence of the wild rubber tree, the first report on selection signatures and a genome-wide association study (GWAS) of its yield traits. Population genomic analysis revealed a moderate population divergence between the Wickham clones and wild accessions. Interestingly, it is suggestive that H. brasiliensis and six relatives of the Hevea genus might belong to the same species. The selective sweep analysis found 361 obvious signatures in the domesticated clones associated with 245 genes. In a 15-year field trial, GWAS identified 155 marker-trait associations with latex yield, in which 326 candidate genes were found. Notably, six genes related to sugar transport and metabolism, and four genes related to ethylene biosynthesis and signalling are associated with latex yield. The homozygote frequencies of the causal nonsynonymous SNPs have been greatly increased under selection, which may have contributed to the fast latex yield improvement during the short domestication history. Our study provides insights into the genetic basis of the latex yield trait and has implications for genomic-assisted breeding by offering valuable resources in this new domesticated crop.

Mechanistic Study on CpRh(III)-Catalyzed [3 + 2] Annulation of Aniline Derivatives with Vinylsilanes: A DFT Study.

The rhodium(III)-catalyzed reaction of aniline derivatives that contain a pyrimidine-directing group with vinylsilanes results in the formation of C3-substituted indoline derivatives. The reaction path and formation of the indoline product with density functional theory calculations were analyzed. This study reveals that the whole catalysis can be characterized in the following stages: (I) C-H activation via concerted metalation deprotonation, (II) 2,1-vinylsilane insertion, (III) deprotonation of the NH amide proton, (IV) the oxidation of Ag+, and (V) reductive elimination. These steps are kinetically and thermodynamically feasible for experimental realization under mild conditions, and the insertion step with a barrier of 22.0 kcal/mol should not only be the critical step of regioselectivity but also the rate-determining step during the whole catalysis. Computations reveal that the Ag+ oxidation can accelerate the reductive elimination step after the formation of natural intermediate, thus highlighting the role of Ag+ as a catalytic promoter for the oxidatively induced reactivity of the Rh catalyst in C3-substituted indoline synthesis.

Ab initio studies on graphyne (GY) for the detection of rare bases in DNA.

Graphyne (GY) and functionalized GY have become cutting-edge research materials for the scientific community. In the present work, the adsorption of rare bases -cytosine (Cyt), 5-methylcytosine (5-meCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-formoxylcytosine (5-fCyt), and 5-carboxylcytosine (5-caCyt) on pristine, B- and N-doped γ-GY was investigated by the first-principles density functional method; methods were designed to distinguish these rare bases by the translocation time and sensitivity. Initially, the stability of pristine, B- and N-doped γ-GY was ascertained by the cohesion energy, and the electronic properties were also analyzed by the energy gap and density of state (DOS). When adsorbing over pristine γ-GY, the translocation times of rare bases were 1.34 × 101, 4.71 × 101, 1.19 × 104, 3.77 × 10-1 and 1.93 × 101 s, respectively. The sensitivities were 2.19%, 0.88%, 0.22%, 2.41%, and 0.88%, respectively, which indicates that they were not clearly separated. By doping the impurity atom, the electronic properties can be fine-tuned to change their selectivity. When adsorbing on the B-doped γ-GY, these rare bases showed sensitivities of 24.69%, 27.20%, 43.32%, 29.97%, and 32.24%, respectively. The rare bases showed sensitivities of 10.15%, 9.02%, 17.29%, 0.38%, and 3.76%, respectively, when adsorbing over the N-doped γ-GY, which greatly increases selectivities for recognization. Thus, these results indicate that pristine and doped γ-GY, as the electrical sensing material, can be used to detect rare bases.

Bis(benzonitrile) dichloroplatinum (II) interrupts PD-1/PD-L1 interaction by binding to PD-1.

Checkpoint inhibitors such as PD-1/PD-L1 antibody therapeutics are a promising option for the treatment of multiple cancers. Due to the inherent limitations of antibodies, great efforts have been devoted to developing small-molecule PD-1/PD-L1 signaling pathway inhibitors. In this study we established a high-throughput AlphaLISA assay to discover small molecules with new skeletons that could block PD-1/PD-L1 interaction. We screened a small-molecule library of 4169 compounds including natural products, FDA approved drugs and other synthetic compounds. Among the 8 potential hits, we found that cisplatin, a first-line chemotherapeutic drug, reduced AlphaLISA signal with an EC50 of 8.3 ± 2.2 µM. Furthermore, we showed that cisplatin-DMSO adduct, but not semplice cisplatin, inhibited PD-1/PD-L1 interaction. Thus, we assessed several commercial platinum (II) compounds, and found that bis(benzonitrile) dichloroplatinum (II) disturbed PD-1/PD-L1 interaction (EC50 = 13.2 ± 3.5 µM). Its inhibitory activity on PD-1/PD-L1 interaction was confirmed in co-immunoprecipitation and PD-1/PD-L1 signaling pathway blockade bioassays. Surface plasmon resonance assay revealed that bis(benzonitrile) dichloroplatinum (II) bound to PD-1 (KD = 2.08 µM) but not PD-L1. In immune-competent wild-type mice but not in immunodeficient nude mice, bis(benzonitrile) dichloroplatinum (II) (7.5 mg/kg, i.p., every 3 days) significantly suppressed the growth of MC38 colorectal cancer xenografts with increasing tumor-infiltrating T cells. These data highlight that platinum compounds are potential immune checkpoint inhibitors for the treatment of cancers.

Ecological risk characteristics of sediment-bound heavy metals in large shallow lakes for aquatic organisms: The case of Taihu Lake, China.

Heavy metal contamination in the surface sediments of large shallow lakes in China is becoming increasingly serious. However, more attention has been paid to the human health risk of heavy metals in the past, while little consideration has been given to aquatic organisms. Taking Taihu Lake as an example, we explored the spatial and temporal heterogeneity of the potential ecological risks of seven heavy metals (Cd, As, Cu, Pb, Cr, Ni, and Zn) to species at different taxonomic scales using an improved species sensitivity distribution (SSD) method. The results showed that all six heavy metals, except Cr, were exceeded to some extent compared to background levels, with Cd being the most severe exceedance. Based on the hazardous concentration for 5% of the species (HC5), Cd had the lowest HC5 value, implying the highest ecological risk of toxicity. Ni and Pb had the highest HC5 values and the lowest risk. Cu, Cr, As and Zn were at a relatively moderate levels. For the different groups of aquatic organisms, the ecological risk of most heavy metals was generally lower for vertebrates than for the whole species. The risk for invertebrates and algae was higher than that for all species. Zn and Cu had the highest potentially affected fractions (PAFs) for all classification cases, with mean PAFs of 30.25% and 47.2%, respectively. Spatially, the high ecological risk of sediment heavy metals was significantly related to the spatial characteristics of the type and intensity of human activities in the catchment. Administratively, the environmental quality standards for freshwater sediments proposed by America and Canada are insufficient to protected against the ecological risks of heavy metals in Taihu Lake. In the absence of such standards, China urgently needs to establish an approptiate system of environmental quality standards for heavy metals in lake sediments.

Ecological risk of phenol on typical biota of the northern Chinese river from an integrated probability perspective: the Hun River as an example.

Phenol, known for its bioaccumulative nature and severe toxicity to riverine organisms, poses complex challenges for ecological risk assessment. To tackle this issue, we developed a three-stage incremental assessment method, providing an integrated perspective on phenol toxicity risk for aquatic organisms. The findings indicated that phenol concentrations were generally higher in the aquatic environments of northern rivers, such as the Hun River, Taizi River, and Liao River, compared to those in southern China. The evaluation results at individual points showed that the ecological risk of phenol to aquatic organisms ranked from high to low during rainy, dry, and normal seasons, showing seasonal variation characteristics. Regarding spatial variation along the river, the ecological risk of phenol gradually increased from upper reaches, peaked in the middle reaches, and then decreased in the lower reaches. Considering the different species types, fish face a higher risk of toxic effects of phenol than invertebrates when exposed to phenol over a long period of time, probably due to the bioaccumulative nature of phenol. To address ecological risk control at the watershed scale, there is an urgent need to revise China's current river water quality standards. It is essential to increase the emphasis on ecological risk control for aquatic organisms. Developing more targeted and refined ecological risk control strategies for river phenols is crucial to maintain a healthier and more vibrant river ecosystem.

Association between household incense burning and executive function in Chinese children.

Incense burning is common in Asia including China. Research investigating the association between household incense burning and children's neurodevelopment is scarce. We aimed to examine this association in Chinese children. In 2019, we randomly enrolled 8293 children aged 6-12 years from 5 elementary schools in Guangzhou, southern China. Information on duration and frequency of household incense burning was collected using a questionnaire. Children's executive function was evaluated using the parental report of the Behavioral Rating Inventory of Executive Function. A general linear model was used to assess the associations between incense burning and executive function. Children who occasionally and frequently exposed to incense burning exhibited worse performance on executive function. For example, frequent incense burning was associated with increases in behavioral regulation index (BRI) of 1.77 (95%CI: 0.97, 2.58) points and metacognition index (MI) of 1.40 (95%CI: 0.60, 2.20) points, compared to never incense burning group. Parental smoking and household income were significant modifiers of the associations, with the stronger associations were observed in children having smoking parent(s) and poorer household income. The findings suggest that household incense burning was associated with poorer executive function, especially in children whose parent(s) were smokers and in those with low household income.

Association between the 24-hour movement guidelines and executive function among Chinese children.

OBJECTIVE: Childhood is a critical period for brain development. However, it remains unknown whether the behaviors in a typical 24-h day are related to children's executive function (EF). This study aimed to investigate the relationship between the 24-h movement guidelines and children's EF. METHOD: Children aged 7-12 years (n = 376) were studied in 2017 in China. Physical activity (PA) was accelerometer-derived, while screen time (ST) and sleep duration were self-reported. Meeting the 24-h movement guidelines was defined as: 1) ≥ 60 min/day of moderate-to-vigorous PA; 2) ≤ 2 h/day of recreational ST; 3) 9-11 h/night of sleep. EF was assessed by the Wisconsin Card Sorting Test (WCST). Number of completed categories (CC), shifting efficiency (SE), non-perseverative errors (NPE), and failure to maintain set (FMS) were used to measure four processes of EF, respectively represented global performance, cognitive flexibility, efficiency in rule discovery, and sustained attention. Generalized linear mixed models (GLMM) were completed to explore the associations of meeting the PA, ST, and sleep duration recommendations with four processes of EF. RESULTS: Statistically significant positive associations were observed between the number of guidelines met, regarded as a continuous variable, with CC [ß = 0.343 (95% confidence interval [CI]: 0.125, 0.561)] and SE [ß = 4.028 (95% CI: 0.328, 7.727)], while number of guidelines met negatively related to NPE [ß = - 4.377 (95% CI:-7.952,-0.802)]. Participants not meeting the two recommendations for PA and sleep duration had lower scores in CC [ß = -0.636(95% CI:-1.125,-0.147)] and SE [ß = -10.610 (95% CI:-18.794,-2.425)] compared with those meeting the two, suggesting inferior global performance and worse efficiency in rule discovery. However, ST recommendation had no significant association with any processes of EF. CONCLUSION: Meeting more recommendations of the 24-h movement guidelines was associated with superior EF in children. Specifically, more PA and healthy sleep duration should be encouraged to promote children's EF.

Utility-Privacy Trade-Off in Distributed Machine Learning Systems.

In distributed machine learning (DML), though clients' data are not directly transmitted to the server for model training, attackers can obtain the sensitive information of clients by analyzing the local gradient parameters uploaded by clients. For this case, we use the differential privacy (DP) mechanism to protect the clients' local parameters. In this paper, from an information-theoretic point of view, we study the utility-privacy trade-off in DML with the help of the DP mechanism. Specifically, three cases including independent clients' local parameters with independent DP noise, dependent clients' local parameters with independent/dependent DP noise are considered. Mutual information and conditional mutual information are used to characterize utility and privacy, respectively. First, we show the relationship between utility and privacy for the three cases. Then, we show the optimal noise variance that achieves the maximal utility under a certain level of privacy. Finally, the results of this paper are further illustrated by numerical results.

Gossypol, a novel modulator of VCP, induces autophagic degradation of mutant huntingtin by promoting the formation of VCP/p97-LC3-mHTT complex.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein (mHTT) in the brain. Decreasing mHTT is a potential strategy for therapeutic purpose of HD. Valosin-containing protein (VCP/p97) is a crucial regulator of proteostasis, which regulates the degradation of damaged protein through proteasome and autophagy pathway. Since VCP has been implicated in pathogenesis of HD as well as other neurodegenerative diseases, small molecules that specifically regulate the activity of VCP may be of therapeutic benefits for HD patients. In this study we established a high-throughput screening biochemical assay for VCP ATPase activity measurement and identified gossypol, a clinical approved drug in China, as a novel modulator of VCP. Gossypol acetate dose-dependently inhibited the enzymatic activity of VCP in vitro with IC50 of 6.53±0.6 µM. We further demonstrated that gossypol directly bound to the interface between the N and D1 domains of VCP. Gossypol acetate treatment not only lowered mHTT levels and rescued HD-relevant phenotypes in HD patient iPS-derived Q47 striatal neurons and HD knock-in mouse striatal cells, but also improved motor function deficits in both Drosophila and mouse HD models. Taken together, gossypol acetate acted through a gain-of-function way to induce the formation of VCP-LC3-mHTT ternary complex, triggering autophagic degradation of mHTT. This study reveals a new strategy for treatment of HD and raises the possibility that an existing drug can be repurposed as a new treatment of neurodegenerative diseases.

Identification and characterization of isocitrate dehydrogenase 1 (IDH1) as a functional target of marine natural product grincamycin B.

Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.

Synthesis and anti-OXPHOS, antitumor activities of DLC modified spinosyn derivatives.

A series of DLC (delocalized lipophilic cation) modified spinosyn derivatives were synthesized and evaluated for antitumor efficacies both in vitro and in vivo. Cancer cell based antiproliferative assays indicated that the more lipophilic derivatives had stronger inhibitory effects on the tested cancer cell lines. Compound 7b and 8b exhibited strong anti-OXPHOS and apoptosis inducing ability. Notable antitumor efficacies of 7b (5 mg/kg) and 8b (2.5 mg/kg) were observed in the in vivo tumor xenograft experiments, however, lethal toxicities were observed on higher dosages. Our findings indicated that DLC modification is a viable strategy to enhance the anti-OXPHOS and antitumor efficacies of spinosyn derivatives.

Effects of ambient particulate matter on fasting blood glucose among primary school children in Guangzhou, China.

BACKGROUND: Exposure to ambient particulate matter (PM) has been linked with diabetes and elevated blood glucose in adults. However, there are few reports on the effects of PM on fasting blood glucose (FBG) among children. OBJECTIVES: The study aimed to assess the associations between medium-term exposure of ambient particles with diameters ≤2.5 µm (PM2.5), and ≤10 µm (PM10) and FBG in a general population of children, and also to explore the modifying effects of diet. METHODS: In this cross-sectional study, we enrolled 4234 children (aged 6-13 years) residing in Guangzhou, China, in 2017. Individual PM2.5 and PM10 exposures during the 186-day period before each physical examination were retrospectively estimated by an inverse distance weighting interpolation and time-weighted approach according to their home address, school address, and activity patterns. Linear mixed effect models were used to examine the relationships between PM2.5 and PM10 with FBG after adjusting for covariates. RESULTS: We found that per 10 µg/m3 increase in PM2.5 and PM10 levels during the 186-day period were associated with 2.3% (95% CI: 1.0%, 3.8%) higher FBG and 0.9% (95% CI: 0.5%, 1.4%) higher FBG, respectively. Stronger effect estimates were observed among subgroups of children with a family history of diabetes, and higher intake of sugar-sweetened beverages (SSBs). Also, we found significant interactions between PM2.5 concentration and family history of diabetes and SSBs intake on FBG. CONCLUSIONS: Medium-term exposure to ambient PM2.5 and PM10 were associated with higher FBG levels in children, and that higher SSBs intake might modify these associations.

Synthesis and antiproliferative activities of novel quartenary ammonium spinosyn derivatives.

In order to enhance the mitochondria-targeting ability of spinosad. A series of quartenary ammonium spinosyn derivatives was designed and synthesized. Some of the derivatives displayed greatly enhanced antiproliferative ability towards tested human cancer cell lines. The structure activity relationship study indicated that lipophilicity has a great influence on the antiproliferative effects of these derivatives. The most active compound 11d exhibited remarkably enhanced OXPHS inhibition and apoptosis inducing ability than spinosyn A.