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All-trans-retinoic acid (RA) inhibits adipogenesis in established preadipocyte cell lines. Dosing pharmacological amounts of RA reduces weight gain in mice fed a high-fat diet, i.e. counteracts diet-induced obesity (DIO). The aldehyde dehydrogenase Raldh1 (Aldh1a1) functions as one of three enzymes that converts the retinol metabolite retinal into RA, and one of many proteins that contribute to RA homeostasis. Female Raldh1-ablated mice resist DIO. This phenotype contrasts with ablations of other enzymes and binding-proteins that maintain RA homeostasis, which gain adiposity. The phenotype observed prompted the conclusion that loss of Raldh1 causes an increase in adipose tissue retinal, and therefore, retinal functions independently of RA to prevent DIO. A second deduction proposed that low nM concentrations of RA stimulate adipogenesis, in contrast to higher concentrations. Using peer-reviewed LC/MS/MS assays developed and validated for quantifying tissue RA and retinal, we show that endogenous retinal and RA concentrations in adipose tissues from Raldh1-null mice do not correlate with the phenotype. Moreover, male Raldh1-null mice resist weight gain regardless of dietary fat content. Resistance to weight gain occurs during adolescence in both sexes. We show that RA concentrations as low as 1 nM, i.e. in the sub-physiological range, impair adipogenesis of embryonic fibroblasts from wild-type mice. Embryonic fibroblasts from Raldh1-null mice resist differentiating into adipocytes, but retain ability to generate RA. These fibroblasts remain sensitive to an RA receptor pan-agonist, and are not affected by an RA receptor pan-antagonist. Thus, the data do not support the hypothesis that retinal itself represses weight gain and adipogenesis independently of RA. Instead, the data indicate that Raldh1 functions as a retinal and atRA-independent promoter of adiposity during adolescence, and enhances adiposity through pre-adipocyte cell autonomous actions.

Chronic intestinal inflammation accompanies familial adenomatous polyposis (FAP) and is a major risk factor for colorectal cancer in patients with this disease, but the cause of such inflammation is unknown. Because retinoic acid (RA) plays a critical role in maintaining immune homeostasis in the intestine, we hypothesized that altered RA metabolism contributes to inflammation and tumorigenesis in FAP. To assess this hypothesis, we analyzed RA metabolism in the intestines of patients with FAP as well as APCMin/+ mice, a model that recapitulates FAP in most respects. We also investigated the impact of intestinal RA repletion and depletion on tumorigenesis and inflammation in APCMin/+ mice. Tumors from both FAP patients and APCMin/+ mice displayed striking alterations in RA metabolism that resulted in reduced intestinal RA. APCMin/+ mice placed on a vitamin A-deficient diet exhibited further reductions in intestinal RA with concomitant increases in inflammation and tumor burden. Conversely, restoration of RA by pharmacologic blockade of the RA-catabolizing enzyme CYP26A1 attenuated inflammation and diminished tumor burden. To investigate the effect of RA deficiency on the gut immune system, we studied lamina propria dendritic cells (LPDC) because these cells play a central role in promoting tolerance. APCMin/+ LPDCs preferentially induced Th17 cells, but reverted to inducing Tregs following restoration of intestinal RA in vivo or direct treatment of LPDCs with RA in vitro These findings demonstrate the importance of intestinal RA deficiency in tumorigenesis and suggest that pharmacologic repletion of RA could reduce tumorigenesis in FAP patients. Cancer Immunol Res; 4(11); 917-26. ©2016 AACR.

Although all-trans-retinoic acid (atRA) is a key regulator of intestinal immunity, its role in colorectal cancer (CRC) is unknown. We found that mice with colitis-associated CRC had a marked deficiency in colonic atRA due to alterations in atRA metabolism mediated by microbiota-induced intestinal inflammation. Human ulcerative colitis (UC), UC-associated CRC, and sporadic CRC specimens have similar alterations in atRA metabolic enzymes, consistent with reduced colonic atRA. Inhibition of atRA signaling promoted tumorigenesis, whereas atRA supplementation reduced tumor burden. The benefit of atRA treatment was mediated by cytotoxic CD8(+) T cells, which were activated due to MHCI upregulation on tumor cells. Consistent with these findings, increased colonic expression of the atRA-catabolizing enzyme, CYP26A1, correlated with reduced frequencies of tumoral cytotoxic CD8(+) T cells and with worse disease prognosis in human CRC. These results reveal a mechanism by which microbiota drive colon carcinogenesis and highlight atRA metabolism as a therapeutic target for CRC.

MEMS sensor is a new type of sensor manufactured by micro electronics and micro machining technology. Compared with traditional sensors, it has the characteristics of small size, light weight, low cost, low power consumption, high reliability, suitable for batch production, easy integration and intelligent realization. This project adopts a multi in one sensor based on MEMS principle. The sensor is a wireless passive three-axis sensor that integrates acceleration, speed, displacement, temperature, inclination and other parameters. It is very convenient to install and disassemble, and can realize the cycle monitoring of the whole wind field.

Wind speed and wind direction indicator in wind turbine is a very important component in the whole power generation system. Inaccurate or incorrect sensor signals will not only make the wind turbine inefficient, but also affect the safe operation of the wind turbine and the life of other components. After the warranty period, after the wind power plant takes over the wind power operation and maintenance, the maintenance demand of the above sensors will be greatly increased. In this project, numerical simulation is used to evaluate the status of wind speed and direction indicator, so as to automatically capture data, compare data, and generate correction coefficients.

We report an ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to quantify all-trans-retinal in biological samples of limited size (15-35mg), which is especially advantageous for use with adipose. To facilitate recovery, retinal and the internal standard 3,4-didehydroretinal were derivatized in situ into their O-ethyloximes. UHPLC resolution combined with high sensitivity and specificity of MS/MS allowed quantification of retinal-O-ethyloximes with a 5-fmol lower limit of detection and a linear range from 5fmol to 1pmol. This assay revealed that extraocular concentrations of retinal range from approximately 2 to 40pmol/g in multiple tissues-the same range as all-trans-retinoic acid. All-trans-retinoic acid has high affinity (kd⩽0.4nM) for its nuclear receptors (RARα, -β, and -γ), whereas retinal has low (if any) affinity for these receptors, making it unlikely that these retinal concentrations would activate RAR. We also show that the copious amount of vitamin A used in chow diets increases retinal in adipose depots 2- to 5-fold relative to levels in adipose of mice fed a vitamin A-sufficient diet, as recommended for laboratory rodents. This assay also is proficient for quantifying conversion of retinol into retinal in vitro and, therefore, provides an efficient method to study metabolism of retinol in vivo and in vitro.

Brown adipose tissue (BAT) possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ). While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

Leaf mass per area (LMA) is a key structural parameter that reflects the functional traits of leaves and plays a vital role in simulating the material and energy cycles of plant ecosystems. In this study, vertical whorl-by-whorl sampling of LMA was conducted in a young Larix principis-rupprechtii plantation during the growing season at the Saihanba Forest Farm. The vertical and seasonal variations in LMA were analysed. Subsequently, a predictive model of LMA was constructed. The results revealed that the LMA varied significantly between different crown whorls and growing periods. In the vertical direction of the crown, the LMA decreased with increasing crown depth, but the range of LMA values from the tree top to the bottom was, on average, 30.4 g/m2, which was approximately 2.5 times greater in the fully expanded phase than in the early leaf-expanding phase. During different growing periods, the LMA exhibited an allometric growth trend that increased during the leaf-expanding phase and then tended to stabilize. However, the range of LMA values throughout the growing period was, on average, 40.4 g/m2. Among the univariate models, the leaf dry matter content (LDMC) performed well (adjusted determination coefficient (Ra2) = 0.45, root mean square error (RMSE) = 13.48 g/m2) in estimating the LMA. The correlation between LMA and LDMC significantly differed at different growth stages and at different vertical crown whorls. The dynamic predictive model of LMA constructed with the relative depth in the crown (RDINC) and date of the year (DOY) as independent variables was reliable in both the assessments (Ra2 = 0.68, RMSE = 10.25 g/m2) and the validation (absolute mean error (MAE) = 8.05 g/m2, fit index (FI) = 0.682). Dynamic simulations of crown LMA provide a basis for elucidating the mechanism of crown development and laying the foundation for the construction of an ecological process model. [ABSTRACT FROM AUTHOR]

In the photolithography process of integrated circuits （IC） manufacturing, it is desired that the photoresist resins have both smaller polydispersity index (PDI) and lower trace metal ion concentrations. The commercial environmentally stable chemical amplified photoresist (ESCAP) resins for 248 nm lithography are synthesized by free radical polymerization with PDI >1.5. Although using atom transfer radical polymerization (ATRP) can result in lower PDI, the potential of high metal ion contamination is a major concern, as the reaction initiators usually are copper‐containing compounds. In this study, copolymer of p‐acetoxy styrene and tert‐butyl acrylate [poly(AOST‐co‐TBA)] is synthesized via ATRP achieving PDI as low as 1.25. It is then purified by ion exchange with two different resins, IRC747 and A15, which are effective at removing Cu and other metal ions. This reduces the total metal ion concentration in the copolymer powder to <30 ppb with individual metal ion <6 ppb. This is the first reported ATRP synthesized ESCAP resin having both low PDI and metal ion concentrations suitable for 248 nm photoresist application. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)-derived splenic CD11b(+)CD8α(-)Esam(high) DCs and the developmentally related CD11b(+)CD103(+) subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC-derived CD11b(-)CD8α(+) and CD11b(-)CD103(+) nor monocyte-derived CD11b(+)CD8α(-)Esam(low) or CD11b(+)CD103(-) DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b(+)CD8α(-) subset, whereas transfer into vitamin A-deficient (VAD) hosts caused diversion to the CD11b(-)CD8α(+) lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II-restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC-derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation.