Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Associations of circulation levels of cytokines with birthweight, preterm birth, spontaneous miscarriages, and stillbirth: A Mendelian randomization analysis.

Background: The association between immune imbalances and adverse pregnancy outcomes has been extensive investigated by observational studies, but remain unclear. Thus, this study aimed to establish the causality of the circulation levels of cytokines on adverse pregnancy outcomes, such as offspring's birthweight (BW), preterm birth (PTB), spontaneous miscarriage (SM), and stillbirth (SB). Methods: Two-sample Mendelian randomization (MR) analysis was employed to investigate potential causal relations between 41 cytokines and pregnancy outcomes on the basis of previously published GWAS datasets. Multivariable MR (MVMR) analysis was implemented to investigate the effect of the composition of cytokine networks on the pregnancy outcomes. Potential risk factors were further estimated to explore the potential mediators. Results: Genetic correlation analysis based on large GWAS data sources revealed that genetically predicted MIP1b (ß = -0.027, S.E. = 0.010, p = 0.009) and MCSF (ß = -0.024, S.E. = 0.011, p = 0.029) were associated with reduced offspring's BW, MCP1 (OR: 0.90, 95% CI: 0.83-0.97, p = 0.007) was associated with reduced SM risk, SCF (ß = -0.014, S.E. = 0.005, p = 0.012) associated with decreased number of SB in MVMR. The univariable MR showed that GROa (OR: 0.92, 95% CI: 0.87-0.97, p = 0.004) was associated with decreased PTB risk. Except for the MCSF-BW association, all above associations surpassed the Bonferroni corrected threshold. The MVMR results revealed that MIF, SDF1a, MIP1b, MCSF and IP10 composed cytokine networks, associated with offspring's BW. Risk factors analysis indicated that the above causal associations might be mediated by smoking behaviors. Conclusion: These findings suggest the causal associations of several cytokines with adverse pregnancy outcomes, which were potentially mediated by smoking and obesity. Some of the results did not been corrected through multiple tests and larger samples verification is required in further studies.

Correction: Surface modification of intraocular lenses with hyaluronic acid and lysozyme for the prevention of endophthalmitis and posterior capsule opacification.

[This corrects the article DOI: 10.1039/C4RA13499K.].

Evaluation of Preparation and Detoxification of Hemicellulose Hydrolysate for Improved Xylitol Production from Quinoa Straw.

Quinoa straw is rich in hemicellulose, and it could be hydrolyzed into xylose. It is a promising energy resource alternative that acts as a potential low-cost material for producing xylitol. In this study, quinoa straw was used as a substrate subjected to the hydrolysis of dilute sulfuric acid solution. Based on the production of xylose and inhibitors during hydrolysis, the optimal conditions for the hydrolysis of hemicellulose in quinoa straw were determined. Detoxification was performed via activated carbon adsorption. The optimal detoxification conditions were determined on the basis of major inhibitor concentrations in the hydrolysate. When the addition of activated carbon was 3% at 30 °C for 40 min, the removal of formic acid, acetic acid, furfural, and 5-HMF could reach 66.52%, 64.54%, 88.31%, and 89.44%, respectively. In addition to activated carbon adsorption, vacuum evaporation was further conducted to perform two-step detoxification. Subsequently, the detoxified hydrolysate was used for xylitol fermentation. The yield of xylitol reached 0.50 g/g after 96 h of fermentation by Candida tropicalis (CICC 1779). It is 1.2-fold higher than that obtained through the sole vacuum evaporation method. This study validated the feasibility of xylitol production from quinoa straw via a biorefinery process.

Co-immobilization of multi-enzyme on reversibly soluble polymers in cascade catalysis for the one-pot conversion of gluconic acid from corn straw.

The difficulties in the process of cellulose cascade conversion based on immobilization technology lies in the recycling enzymes from rich solid-containing straw hydrolysate and the incompatibility of conventional immobilization with this process. In this study, three types of enzyme (cellulase, glucose oxidase and catalase) were successfully immobilized on a reversible soluble Eudragit L-100. Through the determination of the preparation conditions, enzymatic properties and catalytic conditions, the co-immobilized enzyme was applied to the catalytic reaction of one-pot conversion of corn straw to gluconic acid. The yield of gluconic acid achieved 0.28 mg/mg, conversion rate of cellulose in corn straw to gluconic acid reached 61.41%. The recovery of co-immobilized enzyme from solid substrate was achieved by using reversible and soluble characteristics of the carrier. After 6 times of recycling, the activity of co-immobilized enzyme was maintained at 52.38%, confirming the feasibility of multi-enzyme immobilization strategy using reversible soluble carrier in cascade reactions.

Direct Loading and Tunable Release of Antibiotics from Polyelectrolyte Multilayers To Reduce Bacterial Adhesion and Biofilm Formation.

Bacteria adhesion on the surface of biomaterials and following biofilm formation are important problems in biomedical applications. The charged antibiotics with small molar mass can hardly deposit alternately with polymers into multilayered films to load the drug. Herein, the (poly(acrylic acid)-gentamicin/poly(ethylenimine))n ((PAA-GS/PEI)n) multilayer film was designed and constructed via a layer-by-layer self-assembly method. Low molar mass GS cations were first combined with polyanion PAA and self-assembled with PEI to form multilayer films showing exponential growth behavior. The GS dosage could be adjusted by changing the layer number of films. Furthermore, the thermal cross-linking method was used to control the release rate of GS in PBS buffer. Owing to the diffusion of GS, a zone of inhibition of about 7.0 mm showed the efficient disinfection activity of the multilayer film. It could also be seen from the biofilm inhibition assay that the multilayer film effectively inhibited bacterial adhesion and biofilm formation. As the drug loading dosage was 160 µg/cm(2), the multilayer films showed very low cytotoxicity against human lens epithelial cells. The present work provides an easy way to load GS into multilayer films which can be applied to surface modification of implants and biomedical devices.