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Enantioselective cyclopropanation of α-carbonyl sulfoxonium ylides (SY) has so far been limited to addition/ring closure reactions on electron-poor olefins. Herein, we report the iridium-catalyzed intramolecular cyclopropanation of SY in the presence of a chiral diene in up to 96% yield and 98% enantioselectivity. Moreover, density functional theory calculations suggest that the re face of the olefin preferably attacks an iridium carbene intermediate in an asynchronous concerted step that is independent of the geometry of the olefin.

Understanding mechanistic details of the nickel-catalyzed coupling reactions of Csp3 alcohol derivatives is key to developing selective reactions of this widely prevalent functional group. In this manuscript, we utilize a combination of experimental data and DFT studies to define the key intermediates, stereochemical outcome, and competing pathways of a nickel-catalyzed cross-electrophile coupling reaction of 1,3-dimesylates. Stereospecific formation of a 1,3-diiodide intermediate is achieved in situ by the Grignard reagent. The overall stereoablative stereochemical outcome is due to a nickel-catalyzed halogen atom abstraction with a radical rebound that is slower than epimerization of the alkyl radical. Finally, lifetimes of this alkyl radical intermediate are compared to radical clocks to enhance the understanding of the lifetime of the secondary alkyl radical.

Although the combination antiretroviral treatment (cART) has considerably lowered the risk of HIV associated dementia (HAD), the incidence of neurocognitive impairments(NCI) have not decreased likely due to the insidious and slow progressive nature of HIV infection. Recent studies show that the rest state functional magnetic resonance imaging (rs-fMRI) is a prominent technique in helping the non-invasive analysis of neucognitive impairment. Our study is to explore the neuroimaging characteristics among people living with HIV(PLW-HIV) with or without NCI in terms of cerebral regional and neural network by rs-fMRI, based on the hypothesis that HIV patients with and without NCI have independent brain imaging characteristics. 33 HIV subjects with NCI and 33 HIV subjects without NCI, classified into HIV-NCI group and HIV-control group respectively according to Mini-Mental State Examination(MMSE) results. The fraction amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) were calculated to characterize the cerebral regional and neural network alterations. Finally, the correlation among fALFF/FC values in certain cerebral regions and clinical characteristics were calculated. Compared to the HIV-control group, the fALFF values of bilateral calcarine gyrus, bilateral superior occipital gyrus, left middle occipital gyrus, left cuneus in the HIV-NCI group were increased. The FC values between right superior occipital gyrus and right olfactory cortex, bilateral gyrus rectus, right orbital part of middle frontal gyrus in the HIV-NCI group were increased. The FC values between left hippocampus and bilateral medial prefrontal gyrus, bilateral superior frontal gyrus were decreased. The fALFF values of left cuneus in both two groups was negatively correlated with international HIV dementia scale scores (IHDS) (R=-0.255, P=0.037) ; The fALFF values of left calcarine gyrus in both two groups was negatively correlated with MMSE scores (R=-0.316, P=0.009) ; The FC values between right superior occipital gyrus and right olfactory cortex (R=-0.396, P=0.001) in both two groups was negatively correlated with MMSE scores. Our study showed that the abnormal fMRI patterns in specific brain regions of the occipital cortex, while the defects in brain network mostly associated with prefrontal cortex, were associated with HIV-related cognitive impairment. The variation of fALFF and FC in given brain regions can be used to distinguish HIV subjects with and without cognitive impairment.

The effects of local factors on activation of immune cells infiltrating the central nervous system (CNS) in a rat model of traumatic brain injury (TBI) remain elusive. The cytokine, interleukin (IL)-15, is crucial for development and activation of CD8 T lymphocytes, a prominent lymphocytic population present in TBI lesions. We investigated whether IL-15 originates from astrocytes and whether IL-15 can evoke the CD8 T-lymphocyte response in TBI. We observed that astrocytes were activated in a rat model of TBI and that IL-15 was overexpressed on the surface of astrocytes. Further, CD8 T lymphocytes infiltrating TBI lesions colocalized with IL-15-expressing astrocytes. Activated CD8 T lymphocytes released granzyme B (Gra-b), which, in turn, activated caspase-3-induced poly(ADP-ribose) polymerase cleavage and, ultimately, neuronal apoptosis. Conversely, inhibition of astrocyte activation by pre-treatment with the specific inhibitor, fluorocitrate (FC), that reduces carbon flux through the Krebs cycle in astrocytes resulted in improved neurological function and memory. FC pre-treatment was also associated with downregulated IL-15 expression and CD8 T-cell activation as well as decreased levels of neuronal apoptosis, suggesting that IL-15 initiated a domino effect toward apoptosis. In contrast, rats pre-treated with recombinant rat IL-15 showed upregulated CD8 T-cell numbers and Gra-b levels, in addition to induction of neuronal apoptosis. Together, our results indicated that IL-15 could induce neuronal apoptosis by enhancing CD8 T-cell function in a rat model of TBI.

Parabens, as suspected endocrine disruptors, are widely used in personal care products and pharmaceuticals. However, variability, predictors, and risk assessments of human exposure to parabens are not well characterized.To evaluate within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men.We measured four parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) in repeated urine samples from 850 Chinese adult men. We examined the variability by intraclass correlation coefficients (ICCs) and identified the predictors by multivariable linear mixed models. We assessed risks of paraben exposures based on the estimated daily intake (EDI).The four parabens were detected in76% of urinary samples. We observed fair to good to high reproducibility (ICCs: 0.71 to 0.86) for urinary paraben concentrations within one day. Use of facial cleanser was associated with higher four urinary paraben concentrations. Increasing age, taking medicine, intravenous injection, and interior decoration in the workplace were related to higher urinary concentrations of specific parabens. Smoking and drinking were associated with lower urinary concentrations of specific parabens. The maximum EDIs for the four parabens ranged from 13.76 to 848.68 μg/kg bw/day, and 0.9% of participants had the hazard quotient values 1 driven by PrP exposure.Urinary paraben concentrations were less variable within one day. Several lifestyle characteristics including use of facial cleanser and pharmaceuticals may contribute to paraben exposures.

We examine the theoretical underpinnings of the seminal discoveries by Reiner Sustmann about the ambiphilic nature of Huisgen's phenyl azide cycloadditions. Density functional calculations with ωB97X-D and B2PLYP-D3 reproduce the experimental data and provide insights into ambiphilic control of reactivity. Distortion/interaction-activation strain and energy decomposition analyses show why Sustmann's use of dipolarophile ionization potential is such a powerful predictor of reactivity. We add to Sustmann's data set several modern distortion-accelerated dipolarophiles used in bioorthogonal chemistry to show how these fit into the orbital energy criteria that are often used to understand cycloaddition reactivity. We show why such a simple indicator of reactivity is a powerful predictor of reaction rates that are actually controlled by a combination of distortion energies, charge transfer, closed-shell repulsion, polarization, and electrostatic effects.

Background Epidemiological and experimental studies suggest that preeclampsia has a negative impact on maternity and offspring health. Previous studies report that dysregulation in utero-environment increases risk for elderly disease such as cardiovascular disease. However, the underlying mechanisms remain elusive. Specific microRNAs (miRNAs) are packaged in exosomes may regulate microvascular dysfunction in offspring of mothers with preeclampsia. The present study aimed to identify the differential expression profiles of microRNAs in the serum exosomes between patients with preeclampsia and normal pregnancies. Methods A comprehensive miRNA sequence-based approach was performed to compare exosomes carry miRNAs (Exo-miRNAs) expression levels in umbilical serum between normal and preeclampsia patients. Exosomes were isolated using the ExoQuick precipitation kit. Serum exosomes were then viewed under electron microscopy, and their characteristics determined by western blotting and nanoparticle-tracking analysis. Illumina platform was used to perform sequencing. Bioinformatics analysis was used to explore differentially expressed Exo-miRNAs in umbilical serum. Results Based on sequence similarity, 1733 known miRNAs were retrieved. Furthermore, 157 mature miRNAs in serum exosomes were significantly differential expressed between PE and those control groups (P2|FC| > 1). Out, of the 157 miRNAs, 96 were upregulated miRNAs whereas 61 miRNAs were downregulated. The 157 differentially expressed miRNAs targeted 51,424 differentially expressed genes. Functional analysis through KEGG pathway and Gene Ontology results uncovered that target genes of miRNAs with differential expression were significantly linked to several pathways and biological processes. Conclusion The findings of this study showed differential expression of umbilical serum Exo-miRNAs in normal compared with PE patients, implying that these Exo-miRNAs may associate with microvascular dysfunction in offspring of mothers with preeclampsia.

Posttraumatic stress disorder (PTSD) and other anxiety disorders stem from dysregulated fear memory in which the basolateral amygdala (BLA) plays an integral role. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (IAHP) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergic neurons. However, definitive evidence for the involvement of the SK2 channel in the BLA in fear extinction is lacking. Here, we discovered that fear conditioning decreased the levers of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levers of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane palmitoylated protein 2 (MPP2). Collectively, our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of fear memory. These findings expand our understanding of the neurobiological mechanism of PTSD and provide a new direction for PTSD treatment.

Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce.To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology.We included 725 women from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort conducted in Wuhan, China during December 2018 and January 2020. Urine samples collected at recruitment were quantified for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. At day 2-5 of menstruation, serum reproductive hormones including luteinizing hormone (LH), estradiol (EAfter adjusting for relevant confounders, we observed that higher urinary DCAA levels were associated with increased serum PRGE (9.2%; 95% CI: -0.55%, 19.8% for the highest vs. lowest tertile; P for trend = 0.06). Based on NCS models, we observed U-shaped associations of urinary DCAA with serum PRGE and PRL; each ln-unit increment in urinary DCAA concentrations above 3.61 μg/L and 6.30 μg/L was associated with 18.9% (95% CI: 4.8%, 34.7%) and 23.3% (95% CI: -0.92%, 53.5%) increase in serum PRGE and PRL, respectively. The U-shaped associations were further confirmed in RCS models (P for overall association ≤0.01 and P for non-linear associations ≤0.04). We did not observe evidence of associations between urinary TCAA and reproductive hormones.Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

Background Preeclampsia and gestational hypertension can cause vascular function impairment in offspring. In our previous work, we described the protein expression profiles of umbilical artery tissues from patients with preeclampsia. Methods To gain insights into the mechanisms of vascular dysfunction in adult rats born to preeclamptic dams, we analyzed thoracic aorta tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS. Results By using the iTRAQ method, we analyzed 1825 proteins, of which 106 showed significantly different expression in the thoracic aortic. Ingenuity pathway analysis (IPA) showed that the majority of differentially expressed proteins (DEPs) were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, had the strongest effect on cardiovascular function. The expression of G6PD was upregulated in thoracic aorta tissues, as confirmed by Western blotting. The expression of two other vascular function-related proteins, cysteine- and glycine-rich protein 2 (CSRP2) and tubulin alpha-4 A (TUBA4A), was upregulated, as demonstrated by mass spectrometry (MS). Conclusions Although the results require further functional validation, these data provide novel findings related to vascular function impairment in the adult offspring of preeclamptic mothers.

Background: Preeclampsia and gestational hypertension can cause impaired vascular function in offspring. In our previous work, we described the profiles of protein expression in umbilical artery tissues of patients with preeclampsia. Methods: In order to gain insights into the mechanisms of vascular dysfunction in adult rats born by preeclampsia dams, we present analysis of thoracic aortic tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS. Results: By using iTRAQ method, we analyzed 1825 proteins in which 106 proteins have shown significantly differential expression in thoracic aortic. Results from ingenuity pathway analysis (IPA) showed majority of proteins with differential expression (DEP)were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, was most affect the cardiovascular function. The expression level of G6PD was up-regulated in thoracic aortic tissues as confirmed by western blot results. Two other vascular function proteins Cysteine and glycine-rich protein 2 (CSRP2) and Tubulin alpha-4A (TUBA4A) were upregulated as demonstrated by mass spectrometry (MS). Conclusions: Although the results need further functional validation, these data provide novel findings relating to impaired vascular function in adult offsprings of preeclamptic mothers.

Ni-catalyzed C(sp(3))-O bond activation provides a useful approach to synthesize enantioenriched products from readily available enantioenriched benzylic alcohol derivatives. The control of stereospecificity is key to the success of these transformations. To elucidate the reversed stereospecificity and chemoselectivity of Ni-catalyzed Kumada and cross-electrophile coupling reactions with benzylic ethers, a combined computational and experimental study is performed to reach a unified mechanistic understanding. Kumada coupling proceeds via a classic cross-coupling mechanism. Initial rate-determining oxidative addition occurs with stereoinversion of the benzylic stereogenic center. Subsequent transmetallation with the Grignard reagent and syn reductive elimination produces the Kumada coupling product with overall stereoinversion at the benzylic position. The cross-electrophile coupling reaction initiates with the same benzylic C-O bond cleavage and transmetallation to form a common benzylnickel intermediate. However, the presence of the tethered alkyl chloride allows a facile intramolecular S(N)2 attack by the benzylnickel moiety. This step circumvents the competing Kumada coupling, leading to the excellent chemoselectivity of cross-electrophile coupling. These mechanisms account for the observed stereospecificity of the Kumada and cross-electrophile couplings, providing a rationale for double inversion of the benzylic stereogenic center in cross-electrophile coupling. The improved mechanistic understanding will enable design of stereoselective transformations involving Ni-catalyzed C(sp(3))-O bond activation.

Background: Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known. Objective: To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age. Methods: Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose–response associations between exposures and outcomes. Results: Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: −0.44, −0.15 and −0.21 cm, 95% CI: −0.36, −0.07 comparing the extreme exposure groups, respectively, both p for trends

Prenatal exposure to metals has been linked with adverse pregnancy outcomes. Oxidative stress and epigenetic changes are potential mechanisms of action.We aimed to examine the associations of individual and mixtures of metal exposures with oxidative stress and DNA methylation among pregnant women.We measured a panel of 16 metals and 3 oxidative stress biomarkers including 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-isoprostaglandin F2α (8-isoPGF2α) in urine from 113 pregnant women in a Chinese cohort. Biomarkers of global DNA methylation including Alu and long interspersed nucleotide element-1 (LINE-1) in cord blood were measured. Multivariable linear regression and Bayesian kernel machine regression (BKMR) models were separately applied to estimate the associations between individual and mixtures of metal exposures and biomarkers of oxidative stress and global DNA methylation.In single-metal analyses, we observed positive associations between 11 metals [arsenic (As), cadmium (Cd), thallium (Tl), barium (Ba), nickel (Ni), vanadium (V), cobalt (Co), zinc (Zn), copper (Cu), selenium (Se) and molybdenum (Mo)] and at least one of oxidative stress biomarkers (all FDR-adjusted P-values0.05). In mixture analyses, we found positive overall associations of metal mixtures with 8-OHdG and 8-isoPGF2α, and Se was the most important predictor. There was no evidence on associations of urinary metals as individual chemicals and mixtures with Alu and LINE-1 methylation.Urinary metals as individual chemicals and mixtures were associated with increased oxidative stress, especially Se.

Studies indicate that phthalates can disrupt spermatogenesis and lead to the reduction of semen quality. However, the underlying mechanisms remain unclear. This study aimed to examine the associations of phthalate exposures as individual chemicals and mixtures with spermatogenesis-related miRNA106a. We detected eight phthalate metabolites in repeated urine samples and a single seminal plasma specimen among 111 men from an infertility clinic in Wuhan, China. Spermatogenesis-related miRNA106a was measured in seminal plasma. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) models to separately evaluate the associations of phthalate metabolites as individual chemicals and mixtures with spermatogenesis-related miRNA106a. Elevated tertiles of urinary mono (2-ethylhexyl) phthalate (MEHP) was associated with decreased miRNA106a (−61.71%; 95%CI: 81.92, −18.93% for the highest vs. lowest tertile; P for trend = 0.01). Similarly, an inverse exposure-response relationship between seminal plasma MEHP concentrations and miRNA106a was also observed (−59.44%; 95%CI: 79.19, −20.95% for the highest vs. lowest tertile; P for trend = 0.01). The BKMR models showed that the mixtures of seminal plasma phthalate metabolites were associated with decreased miRNA106a when the chemical mixtures were ≥35th percentile compared to their medians. Nonlinear associations with miRNA106a were estimated for urinary and seminal plasma MEHP while fixing other phthalate metabolites at their medians. Our findings suggest that mixtures of phthalate metabolites in seminal plasma were negatively associated with spermatogenesis-related miRNA106a, and individual MEHP was the major contributor to the adverse effects.

Background: ABCB1, EPHX1 and SCN1A gene polymorphisms have been reported play important roles in individual variability carbamazepine (CBZ) metabolism and resistance, but the result of that association still remains controversial. Objective: To clarify the associations among ABCB1, EPHX1 and SCN1A gene polymorphisms and CBZ metabolism and resistance. Methods: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology medicine disc and Wan Fang Database were searched for appropriate studies up to April 2020. Results: A total of 18 studies involving 3293 related epilepsy patients were included. ABCB1 c.3435C>T polymorphism was significantly associated with adjusted concentrations of CBZ (CC vs. CT, P=0.004), and EPHX c.416A>G polymorphism was significantly associated with carbamazepine-10, 11-trans dihydrodiol (CBZD) (AA vs. GG, P=0.045; AG vs. GG, P=0.010). Furthermore, ABCB1 c.3435C>T polymorphism was also observed to be significantly influenced CBZ resistance (CT vs TT, P=0.01; CC+CT vs TT, P=0.006). Conclusion: ABCB1 c.3435C>T polymorphism may affect the CBZ metabolism and resistance, EPHX1 c.416A>G polymorphism may only affect CBZ metabolism. These findings provided further evidence for individualized therapy of epilepsy patients in clinics. Nevertheless further large studies are still warranted to provide conclusive evidences.

Cross-electrophile coupling reactions of two Csp(3)–X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.

Background Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. Methods Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 μm (PM2.5) and ≤10 μm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. Results Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. Conclusions Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.

The application of amine derivatives as coupling partners is rare due to the inherent strength of the C-N bond. Herein, we report the first cross-electrophile coupling reaction of unstrained benzylic sulfonamides. Nickel-catalyzed intramolecular cross-electrophile coupling reactions of acyclic and cyclic benzylic sulfonamides with pendant alkyl chlorides generate cyclopropane products. Mechanistic experiments and DFT calculations are consistent with initiation of the reaction by magnesium iodide accelerated oxidative addition of the benzylic sulfonamide. This work establishes neutral and unstrained amine derivatives as XEC partners, furnishes structural rearrangement of benzylic sulfonamides, and provides valuable information regarding catalyst design for the development of new cross-electrophile coupling reactions of carbon-heteroatom bonds.

Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F

Pulmonary fibrosis is the final outcome of a variety of diffuse pulmonary interstitial diseases, and it has an unclear pathogenesis. There is no effective drug treatment, so the clinical prognosis is poor. As an effective component of ginseng, total ginsenoside (TG) inhibits acute lung injury. This study determined whether TG has protective effects on pulmonary fibrosis and investigated its protective mechanisms. A pulmonary fibrosis model in BALB/c mice was established by injecting the bleomycin chemotherapeutic agent into the trachea. TG (40, 80, and 160 mg/kg/d) was given continuously for 28 days from the second day after development of the model. Pulmonary fibrosis was determined by measuring the lung coefficient, haematoxylin and eosin, and Masson’s trichrome staining of lung samples, and detection of alpha smooth muscle actin expression in lung tissues. To investigate the mechanisms of anti-pulmonary fibrosis by TG, we detected the genes and proteins of the transforming growth factor-β1 (TGF-β1)/Smad signalling pathway and matrix metalloproteinase (MMP) system. Treatment with TG (40, 80, and 160 mg/kg/d) ameliorated pulmonary fibrosis induced by bleomycin in mice, downregulated the expression of TGF-β1, Smad2, Smad3, MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1, and upregulated the protein expression of Smad7. These results suggest that the protective effects of TG on pulmonary fibrosis induced by bleomycin are related to regulation of the TGF-β1/Smad signalling pathway and MMP system.

Sodium ferulate (SF) is the sodium salt of ferulic acid which is an active ingredient of Radix Angelica Sinensis and Ligusticum chuanxiong hort. Here, we investigated SF inhibition in a rat model of myocardial hypertrophy induced by coarctation of the abdominal aorta. Following coarctation, rats were given SF (20, 40, and 80 mg/kg/day) for 25 consecutive days. We characterized myocardial hypertrophy using myocardial hypertrophic parameters, histopathology, and gene expression of atrial natriuretic factor (ANF) ―a gene related to myocardial hypertrophy. We detected the levels of angiotensin II (Ang II) and endothelin-1 (ET-1), protein kinase C beta (PKC-β), Raf-1, extracellular regulated protein kinase 1/2 (ERK1/2), and mitogen-activated protein kinase phosphatase-1 (MKP-1) in myocardium. Notably, coarctation of the abdominal aorta increases myocardial hypertrophic parameters, cardiac myocyte diameter, the concentration of Ang II and ET-1 in myocardium, and gene expression of ANF. SF significantly ameliorates myocardial hypertrophy caused by coarctation of the abdominal aorta; reduces concentrations of Ang II and ET-1; suppresses the overexpression of ANF, PKC-β, Raf-1, and ERK1/2; and increases the expression of MKP-1. These results indicate that SF alleviates myocardial hypertrophy induced by coarctation of the abdominal aorta, and these protective effects could be related to the inhibition of PKC and mitogen-activated protein kinase (MAPK) signaling pathways.

Objectives Familial hypercholesterolemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Three recognized genes (LDLR, APOB and PCSK9) present in only 20–30% of patients with possible FH cases. Additional FH-causing genes need to be explored. The present study found an isolated gene change, sEH R287Q, in a core family of FH. In this study, we aimed to investigate the roles of R287Q on sEH expression and on LDLR expression, LDL binding to LDLR and LDL internalization. Materials and methods 167 lipid-related genes of a core FH family were sequenced using a gene-capture chip. Through carrier dependent protein expression, the expression level (western blot), hydrolase activity (fluorescent chemistry) and intracellular localization (immunofluorescence and Confocal Laser Scanning Microscope) of recombinant sEH R287Q in cultured BEL-7402 cells were conducted. The effect of wild type and R287Q of sEH on LDLR expression, LDL binding to LDLR and LDL internalization were also conducted through Flow Cytometry. Results sEH R287Q was the only gene changes among 167 lipid-related genes in the FH core family. Both expression level and hydrolase activity of recombinant sEH R287Q in cultured cells were significantly declined compared with that of the wild type sEH. sEH R287Q also decreased the binding of LDL to LDLR and LDL internalization and had no effect on cell-surface LDLR protein level. Conclusion Our results suggest that sEH R287Q may have a role in the elevation of blood LDL in FH. The exactly role of sEH R287Q on FH deserves further study.

An MJ-class superconducting magnetic energy storage (SMES) system has a wide range of potential applications in electric power systems. The composite high-temperature superconducting HTS conductor, which has the advantages of carrying large critical currents and withstanding high magnetic fields, is suitable for winding an MJ-class magnet coil. However, the Lorentz force of an HTS wire is so large that its induced mechanical stresses should be examined to ensure that the magnet is in good condition. By means of the equivalent material properties method and the sequential coupling method, this paper studies the mechanical properties of a three MJ toroidal SMES magnet wound by a composite HTS conductor. Based on the electromagnetic-structural coupling analysis, the Von-Mises stress, the radial stress, and the hoop stress of a magnet coil are calculated and employed to validate the stability of the MJ-class toroidal SMES magnet.

In order to develop a new process for concentrating and separating sodium sulfate (Na 2 SO 4 ) and magnesium sulfate (MgSO 4 ) of the bloedite by gas hydrate, the equilibrium of the ternary system H 2 O–Na 2 SO 4 –C 3 H 8 , H 2 O–MgSO 4 –C 3 H 8 and the quaternary system H 2 O–Na 2 SO 4 –MgSO 4 –C 3 H 8 with tetrahydrofuran (THF) additive were studied at 0 °C. It showed that the mass percentage of Na 2 SO 4 (MgSO 4 ) in equilibrium liquid was higher than in feed. It proved that gas hydrate could be used to the concentration and separation of Na 2 SO 4 and MgSO 4 . The solubility of the propane was calculated based on the Krichevsky–Kasarnovsky equation. The extended Pitzer model of electrolyte–electrolyte–nonelectrolyte–water system was derived and applied into H 2 O–Na 2 SO 4 –MgSO 4 –C 3 H 8 system and its sub-systems. The necessary thermodynamic parameters had been derived from a least-squares optimization program. The model calculation value was in good agreement with experimental solubility for ternary and quaternary mixtures, which indicated that the Pitzer model could be successfully used to predict the phase equilibrium of the electrolyte–electrolyte–nonelectrolyte–water systems containing gas hydrate.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder. Although genetic testing is an important tool for detecting FH-causing mutations in patients, diagnostic methods for young patients with severe hypercholesterolemia are understudied. This study compares the target exome sequencing (TES) technique with the DNA resequencing array technique on young patients with severe hypercholesterolemia. A total of 20 unrelated patients (mean age 14.8 years) with total cholesterol > 10 mmol/L were included. 12 patient samples were processed by DNA resequencing array, 14 patient samples were processed by TES, and 6 patient samples were processed by both methods. Functional characterization of novel mutations was performed by flow cytometry. The mutation detection rate (MDR) of DNA resequencing array was 75%, while the MDR of TES was 100%. A total of 27 different mutations in the LDLR were identified, including 3 novel mutations and 8 mutations with previously unknown pathogenicity. Functional characterization of c.673delA, c.1363delC, p.Leu575Phe and p.Leu582Phe variants found that all of them are pathogenic. Additionally, 7 patients were diagnosed with Heterozygous FH (HeFH) in which lipid levels were significantly higher than common HeFH patients. This data indicates that TES is a very efficient tool for genetic diagnosis in young patients with severe hypercholesterolemia.

This paper solved the problem that lash bars were difficult to be quickly and accurately counted,and proposed a kind of lash bar count algorithm based on image recognition through observation and study of the morphology of lash bars, namely the algorithm that combines cross type algorithm and flexible T type algorithm. Firstly,the color image is processed by graying and threshold method binarization. Secondly,the cross type discriminance is used in the middle section of the binary image. Thirdly,the flexible T type discriminance is used to detect on the boundary. Experimental analysis indicates that the detection algorithm saves time, which can be identified and gives the number of bars in a time less than 3s. The accuracy of bar count is as high as 98%. After joining the artificial modification, it can reach 100%.

In recent years, the measurement and controlment of the tiny gas flow have been gained widely attention in some emerging areas, such as biological, medical, aerospace and so on. In order to study the characteristics of the tiny gas flow meter, the tiny gas flow calibrator based on the principle of the Symmetric plunger is designed, which the flow range of the calibrator is from 5mL/h to 1000mL/h. The structure and the working principle are introduced, the uncertainty's Sources and classification of the tiny gas flow calibrator are analyzed, the uncertainty components are analyzed and calculated, The expanded uncertainty of the device is less than 0.126%, which conforms to the design requirements of the device, and it have reached the advanced level at home and abroad. Finally, according to the experiment of the soap film flowmeter, The expanded uncertainty of calibration for the soap film flowmeter is less than 0.77%.

To investigate the differentiation potential of rat adipose tissue-derived cells (ADSCs) into neuron-like cells in vitro using a two-step induction protocol.ADSCs isolated from the epididymal fat pads in male SD rats by means of differential attachment were cultured in vitro and subjected to adipogenic induction. After flow cytometric identification of the cell surface antigens CD106, CD11b, CD45, CD49d, CD90 and CD29, the third-passage ADSCs were induced to transdifferentiate into neural stem cell (NSC)-like cells in DMEM/F12 medium containing 10 ng/ml basic fibroblast growth factor (bFGF), 20 ng/ml epidermal growth factor (EGF) and 2% B27. The resultant NSC-like cells were then induced to differentiate into neuron-like cells in the neurobasal medium containing 10 ng/ml brain-derived neurotrophic factor (BDNF), 10 ng/ml glial cell line-derived neurotrophic factor (GDNF) and 1 µmol/L retinoic acid (RA). Immunocytochemistry was employed to identify the expression of the cell surface markers nestin, MAP2 and NeuN.The isolated ADSCs were positive for CD90 and CD29, and oil red O staining of the induced adipose-like cells yielded positive results. The third-passage ADSCs induced for 7 days aggregated as floating cell spheres positive for NSC surface antigen nestin. Further induction in neurobasal medium for 4 h resulted in adhesion of the cell spheres and the formation of cell processes extending from some peripheral cells, suggesting a morphological resemblance to neurons. Most of the cells showed positivity for MAP2 and NeuN.ADSCs can be induced to differentiate into neuron-like cells in vitro under appropriate conditions.

Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, which characteristic by tendon xanthoma, severely elevated LDL cholesterol (LDL-C) and premature coronary heart disease. The main pathogenic gene is low density lipoprotein receptor (LDLR) gene, which can explain 75