Ancestral body plan and adaptive radiation of sauropterygian marine reptiles.

Sauropterygia is the most diversified and dominant clade among marine reptiles, but their early evolution is scarcely understood. Here we report the earliest known complete specimen related to sauropterygians from the Early Triassic. It is referred to Hanosaurus hupehensis by an exclusive combination of features and shows mosaic morphology integrating the characters of multiple sauropterygian sub-lineages. In phylogenetic results from both parsimony and Bayesian analyses employing our reconstructed dataset, Hanosaurus is stably resolved as the basal-most member of Sauropterygiformes, a clade comprising all sauropterygians and saurosphargids. This skeleton reveals an unexpected ancestral body plan for sauropterygiforms with an elongate trunk and four short limbs, differing from many of its immediate descendants but more similar to non-sauropterygiform marine reptiles at their early aquatic stage as axial swimmers. After this convergence on body plan, we quantitatively confirm the rapid divergence of sauropterygiform reptiles following the end-Permian mass extinction.

Bioinspired Screening of Anti-Adhesion Peptides against Blood Proteins for Intravenous Delivery of Nanomaterials.

Nanomaterials (NMs) inevitably adsorb proteins in blood and form "protein corona" upon intravenous administration as drug carriers, potentially changing the biological properties and intended functions. Inspired by anti-adhesion properties of natural proteins, herein, we employed the one-bead one-compound (OBOC) combinatorial peptide library method to screen anti-adhesion peptides (AAPs) against proteins. The library beads displaying random peptides were screened with three fluorescent-labeled plasma proteins. The nonfluorescence beads, presumed to have anti-adhesion property against the proteins, were isolated for sequence determination. These identified AAPs were coated on gold nanorods (GNRs), enabling significant extension of the blood circulating half-life of these GNRs in mice to 37.8 h, much longer than that (26.6 h) of PEG-coated GNRs. In addition, such AAP coating was found to alter the biodistribution profile of GNRs in mice. The bioinspired screening strategy and resulting peptides show great potential for enhancing the delivery efficiency and targeting ability of NMs.

Nanoantagonists with nanophase-segregated surfaces for improved cancer immunotherapy.

The blockade of PD-1/PD-L1 interaction by peptide antagonists can unleash and enhance pre-existing anti-cancer immune responses of T cells to eradicate cancer cells. However, low proteolytic stability is the "Achilles' Heel" of peptides. Here, we first report a nanoantagonist with a physiological temperature sensitive nanophase-segregated surface that exhibits significantly enhanced blood circulation, peptide stability and PD-L1 immune checkpoint blockade efficacy. Thermosensitive polymers with different phase transition temperatures (Tt) are used to form the nanophase-segregated surface on an Au nanorod core. Importantly, the nanophase-segregated surface aids the nanoantagonist to resist protein adsorption and enhance the systemic stability of the linked peptides. Finally, the as-designed nanoantagonist effectively blocks PD-1/PD-L1 interaction in vitro and in vivo, enhances the pre-existing CD8+ T cell tumor destruction capability and inhibits tumor growth. This study offers a new strategy for designing nano-formulations for cancer immunotherapy.

Photothermal Ring Integrated Intraocular Lens for High-Efficient Eye Disease Treatment.

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. So far, the only method for PCO treatment is the precisely focused laser surgery. However, it causes severe complications such as physical damages and neuron impairments. Here, a nanostructured photothermal ring integrated intraocular lens (Nano-IOLs) is reported, in which the rim of commercially available IOLs (C-IOLs) is decorated with silica coated Au nanorods (Au@SiO2 ), for high-efficient prevention of PCO after cataract surgery. The Nano-IOLs is capable of eliminating the residual lens epithelial cells (LECs) around Nano-IOLs under mild laser treatment and block the formation of disordered LECs fibrosis, which eventually leads to the loss of vision. The Nano-IOLs shows good biocompatibility as well as extraordinary region-confined photothermal effect. In vivo studies reveal that PCO occurrence in rabbit models is about 30%-40% by using Nano-IOLs, which is significantly lower than the control group that treated with C-IOLs (100% PCO occurrence) 30 d postsurgery. To the best of our knowledge, it is the first example to integrate nanotechnology with intraocular implants aiming to clinically relevant PCO. Our findings indicate that spatial controllability of photothermal effect from nanomaterials may provide a unique way to intervene the PCO-induced loss of vision.

Difference of adherence, proliferation and osteogenesis of mesenchymal stem cells cultured on different HA/ZrO2 composites.

OBJECTIVE: To study the adherence, proliferation and osteogenesis of mesenchymal stem cells (MSCs) cultured on different HA/ZrO2 composites. METHODS: The simplex and graded HA/ZrO2 compo-sites were prepared using dry-laid method. The surface topography of the composites was observed by scanning electron microscope (SEM). The MSCs were isolated from rabbits and cultured on experimental groups (simplex HA/ZrO2 composite, graded HA/ZrO2 composite, pure HA or pure ZrO2 coatings respectively) and control group (ordinary culture plate). Then, we observed the adherence, proliferation and osteogenesis of the MSCs, detected the cellular alkaline phosphatase (ALP) activities, extracted total RNA and detected the mRNA expression of collagen I, osteocalcin and osteopontin using the reverse transcription and polymerase chain reaction (RT-PCR) method. RESULTS: The SEM images confirmed that the surface of the simplex HA/ZrO2 composite was coverd by discon-tiguous HA layer with clear visualization of the partial ZrO2 matrix, while the surface of the graded HA/ZrO2 composite was fairly rough with porosity. X-ray diffraction showed that after high temperature sintering, the ZrO2 phase still remained, while the HA phase was transformed to beta-Ca3(PO4)2 , alpha-Ca3(PO4)2 and CaZrO3 phases on the surface of both composites. Cell culture indicated that the HA/ZrO2 composites supported cell attachment. Neither ALP expression nor mRNA expression of collagen I, osteocalcin or osteopontin from RT-PCR results showed significant deviation among four groups. CONCLUSION: Among these four composites, the graded HA/ZrO2 composite promotes the MSCs proliferation and the osteogenic differentiation to a certain extent.

Salvianolic acid B reverses the epithelial-to-mesenchymal transition of HK-2 cells that is induced by transforming growth factor-ß.

Salvianolic acid B (Sal B) is the most abundant bioactive molecule from Radix Salviae Miltiorrhizae, and has recently been used for treating renal fibrosis in traditional Chinese medicine. Here we investigated the ability reversal of Sal B to reverse the transdifferentiation of human kidney proximal tubular epithelial cells that was induced by transforming growth factor-beta 1 (TGF-ß1). The effects of Sal B on HK-2 cell morphology were observed by phase contrast microscopy, while alpha smooth muscle actin and E-cadherin were studied by immunocytochemistry and real-time reverse transcription polymerase chain reaction, respectively. Exposure of HK-2 cells to TGF-ß1 for 72 h induced a complete conversion of the epithelial cells to myofibroblasts. When HK-2 cells were co-incubated with Sal B and TGF-ß1 for a further 72 h, the morphology of myofibroblasts returned to that of proximal tubular epithelial cells, whereas the myofibroblast phenotype was maintained after exposure of cells to TGF-ß1 for 144 h. Sal B reduced alpha smooth muscle actin levels and increased E-cadherin levels compared with their epithelial-to-mesenchymal transition controls. The reversal effect of Sal B was dose-dependent. That Sal B reverses the epithelial-to-mesenchymal transition in vitro suggests that it could possibly facilitate the repair of tubular epithelial structures and the regression of renal fibrosis in injured kidneys.

Synthesis and characterization of new liver targeting 5-fluorouracil-cholic acid conjugates.

The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results were compared with those of the controls, which was a group of mice orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were remarkably increased after oral administration of the prodrugs, and were much larger than if only orally administered 5-FU. The results suggested the feasibility to improve therapeutic efficiency of liver targeting treatments by using cholic acid as the vector of drugs.

Investigation of the prevalence of CKD in 13,383 Chinese hospitalised adult patients.

BACKGROUND: There is an increase prevalence of chronic kidney disease (CKD)worldwide. However, the exact incidence of CKD in China is still uncertain. In this cross-sectional study, we retrospectively investigated the prevalence and distribution of CKD in Chinese hospitalised adult patients. METHODS: Totally, 13,383 adults patients who were hospitalised at our hospital were included in this study. They included 6215 males and 7168 females. Patients' gender, age, blood pressure, serum creatinine, blood urea nitrogen, uric acid, triglyceride, total cholesterol, albumin, hemoglobin, hemotocrit, urine protein, and history of hypertension, diabetes, and smoking were investigated. CKD was defined as eGFR<60 ML/ MIN PER 1.73 m(2) and/or proteinuria, GFR was estimated by using of the simplified MDRD equation. RESULTS: The prevalence rate of CKD was 14.82% in our group, which was respectively distributed from 1 to stage 5 at the following percentage, 3.33% (stage 1), 2.49% ( stage 2), 7.07% (stage 3), 1.08% (stage 4), and 0.86% (stage 5). Elderly patients (age >65 y) accounted for 53.07%, which had a higher CKD prevalence (29.47%) than middle and young-aged patients (9.49%). It was noted that 39.06% patients at stage 1-3 were undiagnosed with CKD during their hospitalization. The common etiology for CKD was hypertension (29.49%), diabetes (11.64%) and primary glomerulonephritis (4.39%). Hypertension, diabetes and ages were main associated factors for CKD. CONCLUSIONS: CKD is a very common disease among the hospitalised patients in China. With the increasing of aging population, elderly people will be the highest risk group for CKD. More strategies have to be made for its early detection and prevention.

[Analysis of 94 cases of IgA nephropathy in children].

OBJECTIVE: To evaluate the clinical and pathological features of 94 children suffering from IgA nephropathy (IgAN) while estimating the prevalent situation in Hunan province. METHODS: To summarize the annual number of hospitalized children, those with kidney diseases, those accepted biopsy, and those confirmed as IgAN in both Xiangya Hospital and Second Xiangya Hospital undertaking kidney biopsy in Hunan province during 1995 and 2004. RESULTS: In the past 10 years, as the hospitalized population in both hospitals accrued to 9.98% each year. The rate of 7.5% was seen in those with kidney diseases. Among whom 56.3% accepted kidney biopsy and 94 of them were confirmed as IgAN. Hematuria was the main clinical presentation, seen in 71 cases, accounting to 76%, and even to 98% after excluding those with nephrotic syndrome and isolating proteinuria type of IgAN. Inflammation infiltration (91%), renal tubule degeneration (81%), and renal interstitial fibrosis (31%) were the major pathological features of 94 children, especially in nephrotic syndrome IgAN. CONCLUSION: The number of children with IgAN synchronously accrues as hospitalized population, those with kidney diseases, and those by kidney biopsy. Hematuria is the major symptom. To routinely perform urine analysis and kidney biopsy in asymptomatic hematuria may improve the diagnosis. Inflammation infiltration, renal tubule degeneration, and renal interstitial fibrosis are the major pathological features in IgAN children, especially in nephrotic syndrome IgAN, probably relating to continuous proteinuria. Early control of proteinuria may delay or decrease renal tubule fibrosis.