P144 Increases Adipose Tissue Volume by Inhibiting TGF-<i>β</i>1-Mediated Fibrous Capsule Formation in a Tissue Engineering Chamber

Tissue engineering chambers (TECs) represent a new and attractive in vivo tissue engineering model that can successfully generate mature adipose tissue. However, the newly formed adipose tissue is not able to fill the volume of the chamber as expected. To investigate whether the capsule surrounding the newly formed adipose tissue limits the adipose tissue volume in the chamber, we detected fibrotic parameters two months after these chambers were implanted into rats. The results showed that the newly formed adipose tissue was surrounded by a thick layer of capsule, and the protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad2 (p-Smad2), connective tissue growth factor (CTGF), collagen type I (COL-I) and α-smooth muscle actin (α-SMA) in the capsule were increased. The levels of these proteins decreased following systemic administration of P144 (a peptide inhibitor of TGF-β1). Furthermore, the capsule thickness was significantly reduced, and the adipose tissue volume was markedly greater when using P144. These findings indicate that capsule formation, which is mediated through a TGF-β1 signaling pathway, restricted the volume of the engineered adipose tissue that was formed. This study may provide a new approach to regenerate amounts of adipose tissue for the reconstruction of large soft tissue defects.

Multi-omics analyses of 398 foxtail millet accessions reveal genomic regions associated with domestication,metabolite traits,and antiinflammatory effects

Foxtail millet(Setaria italica),which was domesticatedfromthewild speciesgreenfoxtail(Setaria viridis),isa richsource of phytonutrientsfor humans.To evaluate how breeding changed themetabolome offoxtail millet grains,we generated and analyzed the datasets encompassing the genomes,transcriptomes,metabolomes,and anti-inflammatory indices from 398 foxtail millet accessions.We identified hundreds of common variants that influence numerous secondary metabolites.We observed tremendous differences in natural variations of the metabolites and their underlying genetic architectures between distinct sub-groups of foxtail millet.Furthermore,we found that the selection of the gene alleles associated with yellow grains led to altered profiles of metabolites such as carotenoids and endogenous phytohormones.Using CRiSPR-mediated genome editing wevalidated the function of PHYTOENE SYNTHASE1(PSY1)gene in affecting milletgrain colorand quality.Interestingly,our in vitro cell inflammation assays showed that 83 metabolites in millet grains have anti-inflammatory effects.Taken together,ourmulti-omics study illustrates how the breeding history of foxtail millet has shaped its metabolite profile.The datasets we generated in this study also provide important resources for further understanding how millet grain quality is affected by different metabolites,laying the foundations for future millet genetic research and metabolome-assisted improvement.

DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS-STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan(CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA(ds DNA) from the intestine, leading to cyclic-GMP-AMP synthase(c GAS)-stimulator of interferon genes(STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination(HR) repair and downregulate ds DNA-c GAS-STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

Analyzing and quantitatively evaluating the organic matter source at different ecologic zones of tidal salt marsh, North Jiangsu Province, China

In order to explore the effect of different eco-logical zones and their above plants in the organic matter cycling of the whole tidal salt marsh,indicators such as total organic carbon(TOC),total nitrogen(TN),C/N ratio,δ13C and d15N of surface,core sediments,and plants of tidal salt marshes in North Jiangsu Province are analyzed.Subse-quently,distribution regularities of these measurement indi-cators are discussed,and the biogeochemistry processes between sediments and plants are also analyzed.Lastly,the organic matter sources of different ecologic zones in tidal salt marsh are evaluated,and the organic matter accumu-lations in different ecologic zones induced by their plants are also compared.These results indicate that TOC,TN,C/N ratio and δ13C showed obvious zonal distribution.The organic matter sources are dominated by marine input in the silt flat,artemisia schrenkiana flat,and the transition zone between silt and spartina alterniflora flat,and are controlled by terrigenous input in spartina alterniflora flat.Spartina alterniflora plays an important role in the accumulation of organic matter in the whole tidal salt marshes ecosystem.In the study area,the annually increased TOC,organic matter and TN in the spartina alterniflora,artemisia schrenkiana and reed flats reach 6,451,12,043 and 536 t,respectively.The amount of TOC,organic matter and TN accumulated in the spartina alterniflora flat is more than that in other ecological zones,which shows that the spartina alterniflora flat exert a non-replaceable effect on the material cycle and exchange in the whole tidal salt marshes ecosystem.

Preparation and luminescent properties of CaF_2:Ln^(3+)(Ln:Er, Er/Yb)/Nafion composite films

In this work, CaF_2:Ln^(3+)(Ln:Er,Er/Yb)/Nafion composite films were prepared using Nafion as modifications and matrices by dripping method. The composite films were characterized by Fourier transform infrared spectroscopy(FT-IR), X-ray diffraction(XRD) and scanning electron microscopy(SEM). Composite films are transparent and CaF_2:Ln^(3+)(Ln:Er,Er/Yb) nanoparticles are well dispersed in Nafion films.The thicknesses of CaF_2:Er^(3+)/Nafion and CaF_2:Er^(3+),Yb^(3+)/Nafion composite film are about 77 and 73 μm,respectively. The nanoparticles in composite film possess cubic phase. CaF_2:Er^(3+),Yb^(3+)/Nafion composite film has stronger characteristic emission of Er^(3+) around 1530 nm with full width at half-maximum(FWHM) of 73 nm and longer luminescence lifetimes of 22.04 μs(25.03%) and 100.77 μs(74.97%).