The appearance and duration of the Jehol Biota: Constraint from SIMS U-Pb zircon dating for the Huajiying Formation in northern China.

The Lower Cretaceous Huajiying Formation of the Sichakou Basin in northern Hebei Province, northern China contains key vertebrate taxa of the early Jehol Biota, e.g., Protopteryx fengningensis, Archaeornithura meemannae, Peipiaosteus fengningensis, and Eoconfuciusornis zhengi This formation arguably documents the second-oldest bird-bearing horizon, producing the oldest fossil records of the two major Mesozoic avian groups Enantiornithes and Ornithuromorpha. Hence, precisely determining the depositional ages of the Huajiying Formation would advance our understanding of the evolutionary history of the Jehol Biota. Here we present secondary ion mass spectrometry (SIMS) U-Pb zircon analysis results of eight interbedded tuff/tuffaceous sandstone samples from the Huajiying Formation. Our findings, combined with previous radiometric dates, suggest that the oldest enantiornithine and ornithuromorph birds in the Jehol Biota are ∼129-131 Ma, and that the Jehol Biota most likely first appeared at ∼135 Ma. This expands the biota's temporal distribution from late Valanginian to middle Aptian with a time span of about 15 My.

Low-Dose IL-2 Attenuated Depression-like Behaviors and Pathological Changes through Restoring the Balances between IL-6 and TGF-ß and between Th17 and Treg in a Chronic Stress-Induced Mouse Model of Depression.

Microglia activation, increased IL-6 and decreased TGF-ß were found in depressed patients or in animal models of depression. IL-6 enhances T helper 17 cell differentiation, thereby causing an imbalance between Th17 and Treg cells, which induces neuroinflammation and neuronal dysfunction. However, whether imbalances between IL-6 and TGF-ß and between Th17 and Treg occur in depression and whether depression can be improved upon restoring these imbalances are unknown. Treg promoter IL-2 (1500UI/0.1 mL/day) was used to treat a mouse model of depression induced by chronic unpredictable mild stress (CUMS). The behavior and concentrations of IL-6, TGF-ß, Th17, IL-17A, IL-17Rc, Treg-related factors (helios and STAT5), astrocyte A1 phenotype S100ß, microglia M1 phenotype Iba-1, indoleamine-2,3-dioxygenase (IDO) enzyme, corticosterone (CORT) and neurotransmitters were evaluated. When compared to controls, CUMS reduced sucrose preference, the number of entries into and the time spent in the open arms of the elevated plus maze and the exploration in the "open field", while it increased the immobility time in tail suspension, which was ameliorated by IL-2 treatment. RoRα, S100ß, IL-17A, IL-17Rc, IL-6, Iba-1, IDO enzyme and CORT concentrations were significantly increased, and Helios, FoxP3+, STAT5 and TGF-ß were significantly decreased by CUMS, which were significantly attenuated by IL-2 when compared to the CUMS group. The NE, DA and 5-HT contents and those of their metabolites were decreased by CUMS, which returned to control levels after IL-2 treatment. The study demonstrated that imbalances between IL-6 and TGF-ß and between Th17and Treg occurred in the hippocampus of the depression model. IL-2 attenuated depression- and anxiety-like behaviors and normalized the neurotransmitter concentration and the activity of the IDO enzyme, astrocytes and microglia through restoring both balances, but it did not decrease the CORT concentration.

A bizarre Jurassic maniraptoran theropod with preserved evidence of membranous wings.

The wings of birds and their closest theropod relatives share a uniform fundamental architecture, with pinnate flight feathers as the key component. Here we report a new scansoriopterygid theropod, Yi qi gen. et sp. nov., based on a new specimen from the Middle-Upper Jurassic period Tiaojishan Formation of Hebei Province, China. Yi is nested phylogenetically among winged theropods but has large stiff filamentous feathers of an unusual type on both the forelimb and hindlimb. However, the filamentous feathers of Yi resemble pinnate feathers in bearing morphologically diverse melanosomes. Most surprisingly, Yi has a long rod-like bone extending from each wrist, and patches of membranous tissue preserved between the rod-like bones and the manual digits. Analogous features are unknown in any dinosaur but occur in various flying and gliding tetrapods, suggesting the intriguing possibility that Yi had membranous aerodynamic surfaces totally different from the archetypal feathered wings of birds and their closest relatives. Documentation of the unique forelimbs of Yi greatly increases the morphological disparity known to exist among dinosaurs, and highlights the extraordinary breadth and richness of the evolutionary experimentation that took place close to the origin of birds.

Vascular endothelial growth factor enhances tendon-bone healing by activating Yes-associated protein for angiogenesis induction and rotator cuff reconstruction in rats.

Local angiogenesis following rotator cuff reconstruction is crucial for tendon-bone healing. The current research on the mechanism underlying angiogenesis that promotes tendon-bone healing is scarce. This study investigates the mechanism underlying vascular endothelial growth factor (VEGF)-Hippo signaling pathway's involvement in tendon-bone healing following rotator cuff reconstruction. Verteporfin, the inhibitor of the Yes-associated protein (YAP), was used to mechanically test and analyze two groups of tensile-failure loads following rotator cuff reconstruction and to detect collagen and angiogenesis-related marker expressions in the tendon. The interaction mechanism of the VEGF-Hippo signaling pathway was assessed using human umbilical vein endothelial cells (HUVECs). The diameter of the supraspinatus tendon reduced following verteporfin treatment. Mechanical tests revealed that verteporfin significantly reduces the tensile-failure load of the supraspinatus tendon. Verteporfin significantly reduces collagen 1 (Col 1), Col 3, Angiopoietin 2, CD31, Von Willebrand factor, CTGF, and CYR61 expressions. In HUVECs, VEGF activates VEGF receptors and inhibits LATS and YAP phosphorylation. YAP is then transferred to the nucleus to further activate downstream pathways. Therefore, verteporfin can inhibit VEGF-induced YAP pathway activation by inhibiting YAP activity. Angiogenesis in tendon-bone healing following rotator cuff reconstruction requires VEGF-Hippo signaling pathway synergy.

Fossilized melanosomes and the colour of Cretaceous dinosaurs and birds.

Spectacular fossils from the Early Cretaceous Jehol Group of northeastern China have greatly expanded our knowledge of the diversity and palaeobiology of dinosaurs and early birds, and contributed to our understanding of the origin of birds, of flight, and of feathers. Pennaceous (vaned) feathers and integumentary filaments are preserved in birds and non-avian theropod dinosaurs, but little is known of their microstructure. Here we report that melanosomes (colour-bearing organelles) are not only preserved in the pennaceous feathers of early birds, but also in an identical manner in integumentary filaments of non-avian dinosaurs, thus refuting recent claims that the filaments are partially decayed dermal collagen fibres. Examples of both eumelanosomes and phaeomelanosomes have been identified, and they are often preserved in life position within the structure of partially degraded feathers and filaments. Furthermore, the data here provide empirical evidence for reconstructing the colours and colour patterning of these extinct birds and theropod dinosaurs: for example, the dark-coloured stripes on the tail of the theropod dinosaur Sinosauropteryx can reasonably be inferred to have exhibited chestnut to reddish-brown tones.

Hyperoside nanocrystals for HBV treatment: process optimization, in vitro and in vivo evaluation.

The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box-Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384 ± 21 nm and PDI of 0.172 ± 0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced Cmax (7.42 ± 0.73 versus 3.80 ± 0.66 mg/L) and AUC0 - t (193.61 ± 16.30 versus 91.92 ± 17.95 mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp.

Risk factors for post-ERCP pancreatitis: A systematic review and meta-analysis.

BACKGROUND AND AIM: Pancreatitis is the most common and serious complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Prevention strategies targeting risk factors could be important to reduce the rate of post-ERCP pancreatitis. However, the risk factors for post-ERCP pancreatitis (PEP) are still debated. This systematic review and meta-analysis was performed to identify risk factors for PEP. METHODS: Medline (PubMed and Ovid), Cochrane Central Register of Controlled trials & Database of Systematic Reviews, Embase, Scopus, ScienceDirect, Springer links and WEB OF SCIENCE were searched for published studies in all languages. Inclusion and exclusion criteria were defined a priori. Eighteen probable risk factors were evaluated, and outcomes were expressed in the case of dichotomous variables, as an odds ratio (OR) (with a 95% confidence interval, (CI)). RESULTS: When patient-related risk factors were analyzed, the ORs for female gender was 1.46 (95%CI: 1.30-1.64); for previous pancreatitis 2.03 (95%CI: 1.31-3.14); for previous PEP was 2.90 (95%CI: 1.87-4.48); for Sphincter of Oddi dysfunction (SOD) was 2.04 (95%CI: 1.73-2.33) and for Intraductal papillary mucinous neoplasm (IPMN) was 3.01 (95%CI: 1.34-6.77). Four endoscopy-related factors were confirmed: the OR for difficult cannulation was 3.49 (95%CI: 1.364-8.925); for endoscopic sphincterotomy (EST) it was 1.39 (95%CI: 1.09-1.79); for precut sphincterotomy it was 2.25 (95%CI: 1.70_2.96); and for main pancreatic duct injection it was 1.58 (95%CI: 1.21-2.08). CONCLUSIONS: Female gender, previous pancreatitis, previous PEP, SOD, IPMN, difficult cannulation, EST, precut sphincterotomy and main pancreatic duct injection are risk factors for post-ERCP pancreatitis.

Evaluation of early interventional treatment opportunity of the elderly & high-risk patients with non-ST segment elevation acute myocardial infarction.

OBJECTIVE: To investigate the effect of treatment on prognosis of patients with different timing of early interventional treatment for non-ST segment elevation acute myocardial infarction (NSTEMI). METHODS: Forty two cases above 75 years old, diagnosed with high-risk on NSTEMI, were selected in cardiology department of Xinxiang central hospital. They were randomly divided into two groups: 22 in group A and 20 in group B. Group A was performed PCI surgery within 12 hours after the onset while group B from 12 to 24 hour after the onset. Major adverse cardiovascular events (including death, heart failure readmission rates after ischemia, malignant arrhythmias, again target vessel revascularization) and bleeding data were recorded at the three terms of hospitalization, one month after the onset and six months after the onset. RESULTS: Angina, malignant arrhythmia and heart failure during hospitalization can be reduced after interventional treatment carried out within 12 hours after the onset. Readmission rates after ischemia, heart failure and the incidence of death can be significantly reduced after interventional treatment carried out during 1-6 month after the onset with no significant increase in bleeding rate. CONCLUSION: In the treatment of elderly patients with NSTEMI, early interventional treatment is safe and effective.

A bizarre Jurassic maniraptoran from China with elongate ribbon-like feathers.

Recent coelurosaurian discoveries have greatly enriched our knowledge of the transition from dinosaurs to birds, but all reported taxa close to this transition are from relatively well known coelurosaurian groups. Here we report a new basal avialan, Epidexipteryx hui gen. et sp. nov., from the Middle to Late Jurassic of Inner Mongolia, China. This new species is characterized by an unexpected combination of characters seen in several different theropod groups, particularly the Oviraptorosauria. Phylogenetic analysis shows it to be the sister taxon to Epidendrosaurus, forming a new clade at the base of Avialae. Epidexipteryx also possesses two pairs of elongate ribbon-like tail feathers, and its limbs lack contour feathers for flight. This finding shows that a member of the avialan lineage experimented with integumentary ornamentation as early as the Middle to Late Jurassic, and provides further evidence relating to this aspect of the transition from non-avian theropods to birds.