Bats, rodents, and shrews are the most important animal sources of human infectious diseases. However, the evolution and transmission of viruses among them remain largely unexplored. Through the ...meta-transcriptomic sequencing of internal organ and fecal samples from 2,443 wild bats, rodents, and shrews sampled from four Chinese habitats, we identified 669 viruses, including 534 novel viruses, thereby greatly expanding the mammalian virome. Our analysis revealed high levels of phylogenetic diversity, identified cross-species virus transmission events, elucidated virus origins, and identified cases of invertebrate viruses in mammalian hosts. Host order and sample size were the most important factors impacting virome composition and patterns of virus spillover. Shrews harbored a high richness of viruses, including many invertebrate-associated viruses with multi-organ distributions, whereas rodents carried viruses with a greater capacity for host jumping. These data highlight the remarkable diversity of mammalian viruses in local habitats and their ability to emerge in new hosts.
Display omitted
•A large number of novel viruses were identified in wild small mammals from China•Some were of evolutionary significance or had the ability to jump species boundaries•Shrews carried the most viruses in total and in a single animal species•Rodents harbored most viruses with the potential be transmitted to new host species
A large study of the mammalian virome identifies differences across rodents, bats, and shrews, revealing insights into host range, transmission, and potential pathogens with the ability to jump across species.
Display omitted
•Cadinane- and drimane-type sesquiterpenoids were isolated from Paecilomyces sp.•Compounds 1 and 2 represent novel examples of cadinane-type sesquiterpenoids.•Compounds 5 and 6 showed ...promising activities against acetylcholinesterase (AChE).•Docking analysis revealed the importance of the hydroxyl group at C-6 in 5 and 6.
Sesquiterpenoids with diverse skeleton types are regarded as potential lead compounds in pharmacological and other applications. Herein, we report the discovery of two new cadinane-type sesquiterpenoids, paecilacadinol A (1) and B (2); two new drimane-type sesquiterpenoids, ustusol D (3) and ustusol E (4); and six known analogs (5–10) from the endophytic fungus Paecilomyces sp. TE-540, enriching the structural diversity of naturally occurring sesquiterpenoids. Their planar structures were determined on the basis of detailed interpretation of 1D and 2D NMR spectroscopy and HRESIMS data, while their stereochemical structures were established by X-ray crystallographic analyses for 1 and 3–8 and theoretical calculations for 2. Notably, compounds 1 and 2 represent novel examples of cadinane-type sesquiterpenoids with ether bonds formed by intramolecular dehydration. Compounds 5 and 6 showed moderate activities against acetylcholinesterase (AChE), with IC50 values of 43.02 ± 6.01 and 35.97 ± 2.12 μM, respectively. Docking analysis predicted that 5 bound well in the catalytic pocket of AChE via hydrophobic interactions with Trp84, Gly117, Ser122, and Tyr121 residues, while 6 was located with Asp72 and Ser122 residues.
α-Fetoprotein is commonly used in the diagnosis of hepatocellular carcinoma. However, the diagnostic significance of α-fetoprotein has been questioned because a number of patients with hepatocellular ...carcinoma are α-fetoprotein negative. It is therefore necessary to develop novel noninvasive techniques for the early diagnosis of hepatocellular carcinoma, particularly when α-fetoprotein level is low or negative. The current study aimed to evaluate the diagnostic efficiency of hematological parameters to determine which can act as surrogate markers in α-fetoprotein–negative hepatocellular carcinoma. Therefore, a retrospective study was conducted on a training set recruited from Zhongnan Hospital of Wuhan University—including 171 α-fetoprotein–negative patients with hepatocellular carcinoma and 102 healthy individuals. The results show that mean values of mean platelet volume, red blood cell distribution width, mean platelet volume–PC ratio, neutrophils–lymphocytes ratio, and platelet count–lymphocytes ratio were significantly higher in patients with hepatocellular carcinoma in comparison to the healthy individuals. Most of these parameters showed moderate area under the curve in α-fetoprotein–negative patients with hepatocellular carcinoma, but their sensitivities or specificities were not satisfactory enough. So, we built a logistic regression model combining multiple hematological parameters. This model presented better diagnostic efficiency with area under the curve of 0.922, sensitivity of 83.0%, and specificity of 93.1%. In addition, the 4 validation sets from different hospitals were used to validate the model. They all showed good area under the curve with satisfactory sensitivities or specificities. These data indicate that the logistic regression model combining multiple hematological parameters has better diagnostic efficiency, and they might be helpful for the early diagnosis for α-fetoprotein–negative hepatocellular carcinoma.
Objective: The purpose of this study was to assess the effect of long-term deprivation of gonadal hormone on brain aging in mice to develop a model of gonadectomy-accelerated brain aging.
Methods: ...Male and female mice at 2 months old were orchiectomized (ORX) or ovarectomized (OVX) bilaterally or sham operated, and then they were fed for 10 months. The spatial learning and memory ability was tested using Morris Water Maze. The biomarkers of brain neuropathology were examined by Western blotting and immunohistochemistry.
Results: Ovarectomy mildly impaired spatial learning and memory of mice, while the impairment in ORX-mice was not significant. The amount of Nissl bodies decreased in the hippocampus and cortex of gonadectomied mice. The expression of beta-amyloid (Aβ), beta-site APP cleaving enzyme 1 and phosphorylated-Tau increased in gonadectomied mice. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) decreased in the brain of OVX-mice, but neurotrophin-3 (NT-3) showed no change. We detected no decrease of NGF, BDNF or NT-3 in ORX-mice. TrkA expression decreased and p75
NTR
increased in the brain of gonadectomied mice. In all the above tests, there were no significant differences between young (2 months old) and sham operated (12 months old) mice. Alternations in the brain aging parameters were more obvious in OVX-mice than in ORX-mice.
Conclusion: Long-term gonadal hormone deprivation by young-age gonadectomy accelerated mouse brain aging, which could serve as a valuable mouse model to study brain aging and aging-related pathological changes.
To evaluate the clinical value in diagnosis and treatment of lens subluxation using ultrasound biomicroscopy (UBM).
This study comprised 29 patients (32 eyes) that had cataract with subluxated lenses ...due to different causes admitted into our hospital between November 2000 and January 2002. All eyes received UBM examination preoperatively and postoperatively. Capsular tension ring (CTR) implantations were performed using different technique according to UBM examination. Then all patients received phacoemulsification and intraocular lens (IOL) implantation. The location of IOL and CTR and complications were evaluated postoperatively.
Different kinds of subluxated lens shown different manifestations in UBM. The degree of zonular defect can be evaluated with UBM preoperatively. With UBM examination preoperatively, extent of lens subluxation less than 1/2 quadrant in 19 eyes while more than 1/2 quadrant in other 13 eyes were observed. Postoperative UBM examination in this series shown that CTRs were holding in pla
Aim： To identify novel small compound inhibitor of p53 protein. Methods： Mouse embryonic fibroblasts （MEF） and mouse embryonic stem （ES） cells were tested. Cell proliferation rate was determined ...using a Cell Proliferation Kit. The mRNA and protein levels of p53-related genes were measured using real-time PCR and Western blotting, respectively. Global response in the p53 signaling network was analyzed using Illumina whole-genome expression BeadChips. Results： Treatment of MEF cells with a small molecule 1,4-bis-4-（3-phenoxy-propoxy）-but-2-ynyl-piperazine （G5） at 10 pmol/L for 24 h markedly reduced the mRNA and protein levels of the p53 downstream genes MDM2 and p21. In G5-treated ES cells, a total of 372 differentially expressed genes were identified, and 18 among them were direct downstream genes of p53; 6 out of 9 p53-repressed genes were upregulated, and 5 out of 9 p53-activated genes were downregulated. In both MEF cells and ES cells, treatment of with G5 （10 μmol/L） up to 48 h neither affected the proliferation rate nor caused morphological alterations. Conclusion： G5 inhibits p53 activity and simultaneously preserves the normal growth and proliferation of cells, therefore is a new compound for studies of p53-mediated cell manipulation.
Abnormal oocytes are one of the major causes of reproductive failure, and also limit the efficiency of assisted reproduction 1. The generation of functional oocytes either by differentiation of ...pluripotent stem cells 2 or in vitro culturing of the embryonic genital ridges 3 has not yet been achieved. Recently, we and other groups have reported that live fertile mice could be successfully produced by injecting androgenetic haploid embryonic stem （ahES） cells that carry some paternal imprints into oocytes in place of sperm 4, 5.
It is now widely accepted that carbon emission from human activities is an important driving force in global warming, and global change has a deep impact on sustainable development of human society. ...To meet the challenges of global change, the international community has reached a consensus that developed countries take strict actions in emission reduction, whereas developing countries take spontaneous efforts in reducing emissions under the guiding principle of common but differentiated responsibilities, with an agreed goal to restrict global surface temperature increase due to human activities to within 2°C of pre-industrial levels. However, there is no clear pathway to reach this goal. A number of related questions must be addressed on principles to be followed, research emphasis and policy measures. Here we argue that response policies to address global change issues must be based on balanced development at regional and international levels, and on advancements in science and technology. This requires consideration of harmony not only between humans and nature but also within human societies, to properly deal with the relationship between global change and sustainable development. We must make equal efforts toward carbon emission reduction and carbon sequestration, and toward mitigation and adaptation. There should be more research support to reduce uncertainties in our understanding of global change. Addressing the challenges of global change creates great opportunities for the development of human society. This will facilitate transformation of energy use structure, improve and restore ecological functioning of the earth environment, transform production modes and ways of living in human society, and promote harmonic and balanced development at regional and international levels.
Zinc induces protein phosphatase 2A （PP2A） inactivation and tau hyperphosphorylation through PP2A （tyrosine 307） phosphorylation in cells and the brain, but whether Zn2＋ has a direct inhibitory ...effect on PP2A is not clear. Here we explored the effect of Zn2＋ on PP2A and their direct interaction in vitro. The results showed that Zn2＋ mimicked the inhibitory effect of okadaic acid on protein phosphatase and prevented tau dephosphorylation in N2a cell lysates. PP2A activity assays indicated that a low concentration （10 pmol/L） of Zn2＋ inhibited PP2A directly. Further Zn2＋-IDA-agarose affinity binding assays showed that Zn2＋ bound to and inhibited PP2Ac（51l-270） but not PP2Ac（1.50） or PP2Ac（27.309）. Taken together, Zn2＋ inhibits PP2A directly through binding to PP2Ac（51-270） in vitro.
PDF
