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Abstract: Numerous taxa show ancient intertropical disjunct distributions. Many can be explained by well-known processes of historical vicariance, such as the breakup of Gondwanaland. Others, such as Asian–Neotropical divergences are not as well understood. To clarify the phylogenetic position and understand biogeographic and temporal origins of the geographically disjunct and morphologically unique genera of hinged-teeth snakes, Scaphiodontophis (n =1) and Sibynophis (n =9; Colubridae), we inferred a time-calibrated phylogeny with additional 107 taxa representing the superfamily Colubroidea using four genes (c-mos, cyt-b, ND2, RAG-1; 3085bp). We used this tree to estimate ancestral areas for the group. The results show that Scaphiodontophis is sister to Sibynophis, both originated in the late Eocene/Oligocene in Asia and likely dispersed through Beringia to the New World, but unlike other snake groups left no extant species in temperate North America. Current recognition of Scaphiodontophiinae renders Colubrinae paraphyletic, and we resurrect the previously named subfamily Sibynophiinae to encompass both genera and use the tribes Sibynophiini (Sibynophis) and Scaphiodontophiini (Scaphiodontophis) to highlight the geographically distinct areas occupied by these taxa. These results suggest that intercontinental dispersal with extinction in intermediate areas can explain puzzling patterns of ancient intertropical disjunct distributions. [Copyright &y& Elsevier]

Background: Taiwan has the highest incidence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. Chinese herbal medicine (CHM) has been linked to CKD/ESRD in Taiwan. The specific effects and frequency of CHM on the risk of CKD are unknown. Methods: A hospital-based case‐control study was performed from August 2006 through December 2009. The cases were consecutive nephrology outpatients 20years of age or older, with a first-time diagnosis of CKD, and without cancer or pre-existing renal disease. The controls were randomly selected outpatients that did not have CKD and were matched 1:1 to cases for age, gender and date of outpatient visit. Results: Four hundred and twenty-four patients were recruited. Among 212 cases, 23.6% took non-prescribed CHM, compared to 6.6% among the controls (p<0.001). Multivariate analysis showed that illiteracy [odds ratio (OR) 6.3, 95% confidence interval (CI) 2.4–16.6], hypertension (OR 5.4, 95% CI 2.9–9.8) and occasional use of non-prescribed CHM (OR 6.2, 95% CI 1.8–21.6) were positively associated with CKD, whereas regular exercise was inversely associated with CKD (OR 0.5, 95% CI 0.3–0.9). Conclusion: Occasional use of non-prescribed CHM was associated with the risk of CKD in Taiwan. [Copyright &y& Elsevier]

Abstract: We conducted phylogenetic analyses to identify the closest related living relatives of the Xizang and Sichuan hot-spring snakes (T. baileyi and T. zhaoermii) endemic to the Tibetan Plateau, using mitochondrial DNA sequences (cyt b, ND4) from eight specimens, together with sequences from 95 additional caenophidian and five henophidian genera that were downloaded from GenBank. Phylogenetic trees were obtained using Bayesian Inference and Maximum likelihood methods. Results suggest that hot-spring snakes, which are adapted to high and cold environments, were clustered in the monophyletic Xenodontinae. Xenodontinae is one of the largest subfamilies of colubrid snakes, with about 90 genera and more than 500 species known, and are primarily tropical snakes previously thought to be restricted to the New World. Our data failed to provide any evidence that the New World xenodontines diverged from Thermophis and dispersed into the New World, also failed to suggest a colonization of Asia by New World xenodontines by dispersal from the New World. An alternative plausible scenario may be that Thermophis and the New World xenodontines evolved independently in Asia and America, respectively, after the divergence of their common ancestor. The divergence of the two species in Thermophis was caused by the barrier of the Hengduan Mountains, and the speciation had almost occurred when Tibetan Plateau attained present elevation. [Copyright &y& Elsevier]

Abstract: Using phylogenetic and population genetic approaches, the present study reports the phylogeographic structure of the sharp-snouted pitviper (Deinagkistrodon acutus), a threatened snake species with commercial and medicinal importance in China. The entire mitochondrial ND2 gene (NADH dehydrogenase subunit 2) sequences of 86 individuals of D. acutus from 14 localities across its range in China were determined. Based on the results of phylogenetic analyses, distribution of diagnostic sites, haplotype network, and AMOVA hierarchical analysis, an east–west division of the whole D. acutus population could be observed. Geographically, a line formed by a lake, river, and mountain chain (the Poyang Lake, Gan River to the southern end of the Wuyi Mountains), results in vicariance and approximately vertically splits the range into two and the whole population into two main lineages (western and eastern). The bifurcating tree suggested generally west to east dispersal trend. The data fit the isolation by distance (IBD) model well. Star-like clusters in haplotype network, significantly negative values of Fs statistics, and unimodal mismatch distributions all suggest recent demographic expansions in four areas. The results show that isolation, dispersal, bottleneck, and expansion jointly constitute the history of D. acutus. In a haplotype network, the excessive predominance of central haplotypes, few medium-frequency haplotypes, predominance (73.1%) of the singletons among the derived haplotypes, most of which are connected to the central haplotype by only one mutational step, unsymmetrical campanulate unimodal curve of mismatch distributions and leftwards shift of the peaks, all suggest that the whole D. acutus population is a young population with low genetic diversity. Based on the data, the first priority for conservation action should be given to the Huangshan unit. [Copyright &y& Elsevier]

The aim of the study was to evaluate the safety of flavonoid fraction of Lithocarpus polystachyus Rehd (Sweet Tea-F, ST-F) in mice and rats through acute and sub-chronic toxicity studies respectively. For acute toxicity study, a single dose of 5000 mg/kg of ST-F was given orally to healthy KM mice. The mice were observed mortality and toxic symptoms for 24 h, then once a day up to 14 days. In the sub-chronic toxicity study, ST-F was administered orally at doses of 0, 70, 140, 560 mg/kg/day to rats for 26 weeks. Body weight and food intake were recorded weekly. Hematological, biochemical, coagulation and organ parameters were analyzed at the end of 26 weeks administration. Vital organs were evaluated by histopathology. In the acute toxicity study, ST-F caused neither significant toxic symptoms, nor mortality in mice. In sub-chronic toxicity study, daily oral administration of ST-F at the dose of 70 mg/kg resulted in a significant increase ( P < 0.05) in the relative body weight at the 10-week, and the same situation brought at the dose of 140 mg/kg/day at the 22-week. Hematological and biochemical showed significant changes ( P < 0.01 or P < 0.05 ) in WBC, GLU, ALP, AST and serum electrolytes levels at the dose of 560 mg/kg/day. The amount of RBC decreased significantly ( P < 0.05 ) while the content of PLT slightly increased ( P < 0.05 ) at the dose of 140 mg/kg/day. In additional, no obvious histological changes were observed in vital organs of ST-F treated animals compared to control group. The ST-F may be exit slight side effects at the dose of 560 mg/kg/day in rats. Thus, the overall results show that the no-observed adverse effect level (NOAEL) of ST-F was considered to be 140 mg/kg for male SD rats. [ABSTRACT FROM AUTHOR]

Abstract: Mesenchymal stem cells (MSCs) transplantation has been proposed as a promising means for ischemic heart disease. Vascular endothelial growth factor (VEGF) has been demonstrated to play an important role in MSCs transplantation. Angiotensin II (AngII), the most important effector peptide of the renin–angiotensin system (RAS), is also an angiogenesis factor. However, the effects of AngII on VEGF expression in MSCs and the related signaling cascades were unknown. In this experiment, we first demonstrated that incubation of MSCs with AngII-induced a rapid increase in VEGF mRNA expression and protein synthesis. However, these effects were abolished by prior treatment with AngII type 1 (AT1) receptor antagonist losartan while not AngII type 2 (AT2) receptor antagonist PD123319. The addition of either the extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor U0126 or Akt inhibitor LY294002 also led to a marked inhibition of the AngII-induced VEGF mRNA and protein production. Taken together, these results suggested that AngII stimulated the synthesis of VEGF in MSCs through ERK1/2 and Akt pathway via AT1 receptor. [Copyright &y& Elsevier]

In response to digestion complex environments, protein's ability to bind bile salts (BS) will be altered. This study aimed to assess the different effects of in vitro digestion on the BS-binding capacity of fermentation-organic acid compound-modified and unmodified WPI. According to the results, modified WPI can increase the degree of hydrolysis, reduce the sulfhydryl group content, and expose aromatic amino acids during digestion, indicating that the BS-binding ability of WPI is dependent on the hydrogen bond content. The more residual of surface hydrophobicity and β-sheet and β-turn contents suggested that exposure of hydrophobic groups of modification would promote BS-binding with hydrophobic of modified WPI in simulated digestion, consistent with the change in sulfhydryl content and surface hydrophobicity. This further confirms the higher binding ability of WPI for BS through hydrophobic interactions. In addition, the apparent viscosity and viscoelasticity of modified WPI were increased, which contributed to improved BS binding. Further, the modification enhanced the content of fragmented polymers with a molecular weight less than or equal to 3.3 kDa after digestion. Based on peptidomics, it was concluded that FLPYPYYAKP and ALKALPMHIRL were polypeptides with strong cholesterol-lowering effects, with a significant difference between modified and unmodified WPI. • Residual tyrosine and tryptophan side chains of modified WPI promoted BS binding. • Viscosity and viscoelasticity of the modified WPI was beneficial to BS binding. • Modification enriched the content of fragmented polymers (≤3.3 kDa MW) and hydrophobic amino acids after digestion. • Cholesterol-lowering peptides of FLPYPYYAKP and ALKALPMHIRL were improved by modification after in vitro digestion. [ABSTRACT FROM AUTHOR]

Background Current global surgery initiatives focus on increasing surgical workforce; however, it is unclear whether this approach would be helpful globally, as patients in low-resource countries may not be able to reach hospitals in a timely fashion without formal Emergency Medical Services (EMS). We hypothesize that increased surgical workforce correlates with decreased road traffic deaths (RTDs) only in countries with EMS. Methods Estimated RTDs were obtained from the Global Status Report on Road Safety 2013, which estimated the RTD rate in 2010 (RTD 2010). The classification of EMS was defined by the Global Status Report on Road Safety 2009. The density of surgeons, anesthesiologists, and obstetricians (SAO density) and 2010 income classification were accessed from the World Bank. Multivariable regression analysis was performed adjusting for different countries, income levels, and trauma system characteristics. Sensitivity analysis was performed. Results One-fourth of the countries reported not having formal EMS ( n = 41, 23.4%). On adjusted analysis, SAO density was not associated with changes in RTD 2010 in countries without EMS ( n = 25, P = 0.50). However, in countries with EMS, each increase in SAO density per 100,000 population decreased RTDs by 0.079 per 100,000 population ( n = 97, P <0.001). Income was the only other factor resulting in reduced mortality rates ( P = 0.004). Sensitivity analysis confirmed these findings. Conclusions Increases in surgical workforce reduce RTDs only when EMS exist. Surgical workforce and EMS must be seen as part of the same system and developed together to maximize their effect in reducing RTDs. Global health initiatives should be tailored to individual country need. Level of Evidence Level II (Ecological study). [ABSTRACT FROM AUTHOR]

As a useful formalism tool, graph grammars provide a rigorous but intuitive way to specify visual languages. This paper, based on the existing Edge-based Graph Grammar (EGG), proposes a new context-sensitive graph grammar formalism called the Temporal Edge-based Graph Grammar, or TEGG. TEGG introduces some temporal mechanisms to grammatical specifications, productions, operations and so on in order to tackle time-related issues. In the paper, formal definitions of TEGG are provided first. Then, a new parsing algorithm with a decidability proof is proposed to check the correctness of a given graph's structure, to analyze operations’ timing when needed, and to make the computer simulation of the temporal sequence in the graph available. Next, the complexity of the parsing algorithm is analyzed. Finally, a case study on an application with temporal requirements is provided to show how the parsing algorithm of TEGG works. [ABSTRACT FROM AUTHOR]

Highlights: [•] Euprepiophis perlaceus is a valid species based on multi-locus markers. [•] Coalescent-based species delimitation methods support the validity of E. perlaceus. [•] Species trees show E. perlaceus is sister to E. mandarinus despite gene tree conflict. [Copyright &y& Elsevier]

Abstract: New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productive infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent. [Copyright &y& Elsevier]

Highlights: [•] GRP78/Bip as trigger of UPR signaling was expressed in normal mouse testis. [•] One cycle testicular hyperthermia induced UPR signaling activation in spermatocyte. [•] Repetitive cycles hyperthermia induced ER-stress mediated spermatocyte apoptosis. [•] Our results suggest a link between UPR signaling pathway and testicular hyperthermia. [ABSTRACT FROM AUTHOR]

Abstract: Background: In traumatic brain injury animal models, sham or naïve control groups are often used for the analysis of injured animals; however, the existence and/or significance of differences in the control groups has yet to be studied. In addition, recent controversies regarding the decompressive craniectomy trial in which decompressive craniectomies in patients with severe traumatic brain injury and refractory increased intracranial pressure remains unsettled. Although the report demonstrated that the procedure may result in less favorable long-term outcomes despite the decrease in intracranial pressure and shorter length of intensive care unit stay, the study has been criticized, and the debate is still inconclusive partly because of a lack of mechanistic explanation. We have recently discovered epithelial and endothelial tyrosine kinase (Etk) to exhibit upregulation after traumatic neural injury and will compare the effects of craniectomy procedure with those of other procedures inducing different levels of severity. Materials and methods: Four groups of rats receiving different procedures (controlled cortical impact, craniectomy, bicortical drilling, and unicortical drilling [UD]) were compared. Polymerase chain reaction, Western blot analysis, and immunoflorescence staining of Etk, S100, and glial fibrillary acidic protein levels were used to analyze the results and compare the different groups. Results: Etk upregulation was statistically significant between craniectomy and UD groups. The level of change for glial fibrillary acidic protein and S100 was only significant when cortex was impacted. Conclusions: UD may be preferable as a sham control procedure over craniectomy or bicortical drilling. Increases in the expression of Etk in the craniectomy group suggest a possible mechanism by which unfavorable outcome occurs in patients receiving craniectomy procedures. [Copyright &y& Elsevier]

Abstract: Angiogenesis is essential for transplantation of mesenchymal stem cells (MSCs). Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors identified to date. Elevated VEGF levels in MSCs correlate with the potential of MSCs transplantation. As an indirect angiogenic agent, transforming growth factor-β1 (TGF-β1) plays a pivotal role in the regulation of vasculogenesis and angiogenesis. However, the effect of TGF-β1 on VEGF synthesis in MSCs is still unknown. Besides, the intracellular signaling mechanism by which TGF-β1 stimulates this process remains poorly understood. In this article, we demonstrated that exposure of MSCs to TGF-β1 stimulated the synthesis of VEGF. Meanwhile, TGF-β1 stimulated the phosphorylation of Akt and extracellular signal-regulated kinase 1/2 (ERK1/2). Moreover, Ly 294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K)/Akt significantly attenuated the VEGF synthesis stimulated by TGF-β1. Additionally, U0126, a specific inhibitor of ERK1/2, also significantly attenuated the TGF-β1-stimulated VEGF synthesis. These results indicated that TGF-β1 enhanced VEGF synthesis in MSCs, and the Akt and ERK1/2 activation were involved in this process. [Copyright &y& Elsevier]

Abstract: Inactivated severe acute respiratory syndrome-associated coronavirus (SARS-CoV) has been tested as a candidate vaccine against the re-emergence of SARS. In order to understand the efficacy and safety of this approach, it is important to know the antibody specificities generated with inactivated SARS-CoV. In the current study, a panel of twelve monoclonal antibodies (mAbs) was established by immunizing Balb/c mice with the inactivated BJ01 strain of SARS-CoV isolated from the lung tissue of a SARS-infected Chinese patient. These mAbs could recognize SARS-CoV-infected cells by immunofluorescence analysis (IFA). Seven of them were mapped to the specific segments of recombinant spike (S) protein: six on S1 subunit (aa 12–798) and one on S2 subunit (aa 797–1192). High neutralizing titers against SARS-CoV were detected with two mAbs (1A5 and 2C5) targeting at a subdomain of S protein (aa 310–535), consistent with the previous report that this segment of S protein contains the major neutralizing domain. Some of these S-specific mAbs were able to recognize cleaved products of S protein in SARS-CoV-infected Vero E6 cells. None of the remaining five mAbs could recognize either of the recombinant S, N, M, or E antigens by ELISA. This study demonstrated that the inactivated SARS-CoV was able to preserve the immunogenicity of S protein including its major neutralizing domain. The relative ease with which these mAbs were generated against SARS-CoV virions further supports that subunit vaccination with S constructs may also be able to protect animals and perhaps humans. It is somewhat unexpected that no N-specific mAbs were identified albeit anti-N IgG was easily identified in SARS-CoV-infected patients. The availability of this panel of mAbs also provided potentially useful agents with applications in therapy, diagnosis, and basic research of SARS-CoV. [Copyright &y& Elsevier]

• A unified multilocus marker system for snake systematics was developed. • A comprehensive systematic framework of the snakes in China was constructed. • The marker system enables better understanding of the snake evolutionary histories. • The snake divergence times were estimated with the substantial new molecular data. Snakes are one of the most diverse groups of terrestrial vertebrates, with approximately 3500 extant species. A robust phylogeny and taxonomy of snakes is crucial for us to know, study and protect them. For a large group such as snakes, broad-scale phylogenetic reconstructions largely rely on data integration. Increasing the compatibility of the data from different researches is thus important, which can be facilitated by standardization of the loci used in systematic analyses. In this study, we proposed a unified multilocus marker system for snake systematics by conflating 5 mitochondrial markers, 19 vertebrate-universal nuclear protein coding (NPC) markers and 72 snake-specific noncoding intron markers. This marker system is an addition to the large squamate conserved locus set (SqCL) for studies preferring a medium-scale data set. We applied this marker system to over 440 snake samples and constructed the currently most comprehensive systematic framework of the snakes in China. Robust snake phylogenetic relationships were recovered at both deep and shallow evolutionary depths, demonstrating the usefulness of this multilocus marker system. Discordance was revealed by a parallel comparison between the snake tree based on the multilocus marker system and that based on only the mitochondrial loci, highlighting the necessity of using multiple types of markers to better understand the snake evolutionary histories. The divergence times of different snake groups were estimated with the nuclear data set. Our comprehensive snake tree not only confirms many important nodes inferred in previous studies but also contributes new insights into many snake phylogenetic relationships. Suggestions are made for the current Chinese snake taxonomy. [ABSTRACT FROM AUTHOR]

Intact epithelial barrier and mucosal immune system are crucial for maintaining intestinal homeostasis. Previous study indicated that Dendrobium officinale polysaccharides (DOPS) can regulate immune responses and inflammation to alleviate experimental colitis. However, it remains largely unknown whether DOPS can suppress AOM/DSS-induced colorectal cancer (CRC) model through its direct impact on intestinal barrier function and intestinal mucosal immunity. Here, we demonstrated the therapeutic action of DOPS for CRC model and further illustrated its underlying mechanisms. Treatment with 5-aminosalicylic acid (5-ASA) and DOPS significantly improved the clinical signs and symptoms of chronic colitis, relieve colon damage, suppress the formation and growth of colon tumor in CRC mice. Moreover, administration of DOPS effectively preserved the intestinal barrier function via reducing the loss of zonula occludens-1 (ZO-1) and occludin in adjacent tissues and carcinomatous tissues. Further studies demonstrated that DOPS improved the metabolic ability of tumor infiltrated CD8+ cytotoxic T lymphocytes (CTLs) and reduced the expression of PD-1 on CTLs to enhance the anti-tumor immune response in the tumor microenvironments (TME). Together, the conclusions indicated that DOPS restore intestinal barrier function and enhance intestinal anti-tumor immune response to suppress CRC, which may be a novel strategy for the prevention and treatment of CRC. [ABSTRACT FROM AUTHOR]