Newcastle disease virus activates diverse signaling pathways via Src to facilitate virus entry into host macrophages.

As an intrinsic cellular mechanism responsible for the internalization of extracellular ligands and membrane components, caveolae-mediated endocytosis (CavME) is also exploited by certain pathogens for endocytic entry [e.g., Newcastle disease virus (NDV) of paramyxovirus]. However, the molecular mechanisms of NDV-induced CavME remain poorly understood. Herein, we demonstrate that sialic acid-containing gangliosides, rather than glycoproteins, were utilized by NDV as receptors to initiate the endocytic entry of NDV into HD11 cells. The binding of NDV to gangliosides induced the activation of a non-receptor tyrosine kinase, Src, leading to the phosphorylation of caveolin-1 (Cav1) and dynamin-2 (Dyn2), which contributed to the endocytic entry of NDV. Moreover, an inoculation of cells with NDV-induced actin cytoskeletal rearrangement through Src to facilitate NDV entry via endocytosis and direct fusion with the plasma membrane. Subsequently, unique members of the Rho GTPases family, RhoA and Cdc42, were activated by NDV in a Src-dependent manner. Further analyses revealed that RhoA and Cdc42 regulated the activities of specific effectors, cofilin and myosin regulatory light chain 2, responsible for actin cytoskeleton rearrangement, through diverse intracellular signaling cascades. Taken together, our results suggest that an inoculation of NDV-induced Src-mediated cellular activation by binding to ganglioside receptors. This process orchestrated NDV endocytic entry by modulating the activities of caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPases and downstream effectors. IMPORTANCE: In general, it is known that the paramyxovirus gains access to host cells through direct penetration at the plasma membrane; however, emerging evidence suggests more complex entry mechanisms for paramyxoviruses. The endocytic entry of Newcastle disease virus (NDV), a representative member of the paramyxovirus family, into multiple types of cells has been recently reported. Herein, we demonstrate the binding of NDV to induce ganglioside-activated Src signaling, which is responsible for the endocytic entry of NDV through caveolae-mediated endocytosis. This process involved Src-dependent activation of the caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPase and downstream effectors, thereby orchestrating the endocytic entry process of NDV. Our findings uncover a novel molecular mechanism of endocytic entry of NDV into host cells and provide novel insight into paramyxovirus mechanisms of entry.

[Spatio-temporal characteristics of the matching degree of water, soil, and heat resources based on ecosystem services in Central Asia]. / åŸºäºŽç”Ÿæ€ç³»ç»ŸæœåŠ¡çš„ä¸­äºšæ°´åœŸçƒ­èµ„æºåŒ¹é åº¦æ—¶ç©ºå˜åŒ–ç‰¹å¾.

The status of matching degree among water, soil, and heat resources determines ecosystem stability and sustainability. Under the framework of ecosystem services related to human well-being, we constructed the matching index of water, soil, and heat resources in Central Asia by the vegetation net primary productivity (NPP) index method based on remote sensing data. We analyzed the spatio-temporal characteristics of the matching degree in Central Asia, and correlations between the matching degree and climatic factors, water use efficiency using trend analysis and the Hurst index. The results showed that the matching degree of water, soil, and heat resources was generally low in Central Asia with a mean value of 9.3. There were obvious differences in the mat-ching degree in different biomes, with the order of alpine forest region > alpine meadow region > typical steppe region > desert steppe region > lake > desert region. From 2000 to 2015, the matching degree of water, soil, and heat resources in each biome and in the whole Central Asia showed a fluctuating downward trend. However, the matching degree changed slightly, with relatively poor persistence. There was a large difference and misalignment of spatial variation in temperature and precipitation, which was the main cause of low matching degree of water, soil, and heat resources. The effect of precipitation on the matching degree of water, soil, and heat resources in Central Asia was stronger than that of the temperature. There was a strong correlation between the matching degree and water use efficiency in Central Asia.

Naked-Eye Enumeration of Single Chlamydia pneumoniae Based on Light Scattering of Gold Nanoparticle Probe.

Chlamydia pneumoniae is a spherical zoonotic pathogen with a diameter of ∼200 nm, which can lead to a wide range of acute and chronic diseases in human body. Early and reliable on-site detection of C. pneumoniae is the key step to control the spread of the pathogen. However, the lack of a current technology with advantages of rapidity, ultrasensitivity, and convenience limits the implementation of traditional techniques for on-site detection of C. pneumoniae. Herein, we developed a naked-eye counting of C. pneumoniae based on the light scattering properties of gold nanoparticle (GNP) under dark-field microscopy (termed "GNP-labeled dark-field counting strategy"). The recognition of single C. pneumoniae by anti-C. pneumoniae antibodies-functionalized GNP probes with size of 15 nm leads to the formation of wreath-like structure due to the strong scattered light resulted from hundreds of GNP probes binding on one C. pneumoniae under dark-field microscopy. Hundreds of GNP probes can bind to the surface of C. pneumoniae due to the high stability and specificity of the nucleic acid immuno-GNP probes, which generates by the hybridization of DNA-modified GNP with DNA-functionalized antibodies. The limit of detection (LOD) of the GNP-labeled dark-field counting strategy for C. pneumoniae detection in spiked samples or real samples is down to four C. pneumoniae per microliter, which is about 4 times more sensitive than that of quantitative polymerase chain reaction (qPCR). Together with the advantages of the strong light scattering characteristic of aggregated GNPs under dark-field microscopy and the specific identification of functionalized GNP probes, we can detect C. pneumoniae in less than 30 min using a cheap and portable microscope even if the sample contains only a few targets of interest and other species at high concentration. The GNP-labeled dark-field counting strategy meets the demands of rapid detection, low cost, easy to operate, and on-site detection, which paves the way for early and on-site detection of infectious pathogens.

Surgical treatment of recurrent dislocation after total hip arthroplasty: the algorithmic approach and clinical outcome / 中华外科杂志

<p><b>OBJECTIVES</b>To study the surgical techniques and clinical outcomes of the revision surgery to treat recurrent dislocation after total hip arthroplasty.</p><p><b>METHODS</b>From March 1997 to November 2010, 12 patients (12 hips) with revision total hip arthroplasty for recurrent dislocation were reviewed. There were 5 male and 7 female, aged from 20 to 73 years (mean age 52.7 years), whose body mass index (BMI) were 14.8-30.0 kg/m2 (mean 23.6 kg/m2). The Harris score and WOMAC score were registered and analyzed before surgery and at the time of latest follow-up. Any episode of dislocation and other complications such as deep infection, deep vein thrombosis and pulmonary embolism (DVT-PE) events, periprosthetic fracture, or early aseptic loosening were recorded.</p><p><b>RESULTS</b>Twelve patients were successfully followed for 1.0-12.7 years (mean 4.0 years). No further dislocation episodes reported and all the hips were stable at the time of follow-up. No one complicated as deep infection, DVT-PE events, periprosthetic fracture, or early aseptic loosening. The Harris score was greatly improved from 38±21 before surgery to 81±9 at the time of last follow-up with statistic significance (t=-8.616, P<0.05) accompany with the WOMAC score elevation from 54±21 to 82±12 significantly (t=-6.200, P<0.05).</p><p><b>CONCLUSION</b>With a reasonable algorithmic approach, the recurrent dislocated total hip arthroplasty can be treated with a relatively high success rate.</p>

T-type calcium channel gene-CACNA1H is a susceptibility gene to childhood absence epilepsy / 中华儿科杂志

<p><b>OBJECTIVE</b>Childhood absence epilepsy (CAE) is one of the most frequently recognized syndromes among the idiopathic generalized epilepsies (IGEs). It is considered to be a hereditary disease. The possible inheritance pattern of CAE is polygenic. The genes responsible for CAE, however, have not yet been identified. The aim of this study was to further investigate based on the authors' recent work whether or not T-type calcium channel gene-CACNA1H is a susceptibility gene to childhood absence epilepsy.</p><p><b>METHODS</b>The authors conducted the mutation screening of the exons 6-12 and the nearby partial introns of the CACNA1H gene using the method of direct sequencing of PCR products in 48 newly found CAE patients.</p><p><b>RESULTS</b>The authors found 13 single nucleotide polymorphisms (SNPs). They also found 4 mutations which only existed in CAE patients. Both G773D and H515Y mutations were heterozygous. The mutation of H515Y has never been reported previously. The patient inherited the mutation from his mother. The authors found two CAE patients with the mutation of G773D previously. This is the third time that the authors found one more CAE family with this G773D mutation, and the patient with the mutation G773D inherited the mutation from his father.</p><p><b>CONCLUSION</b>T-type calcium channel gene-CACNA1H might be a susceptibility gene to childhood absence epilepsy.</p>

Effect of fuzheng jianpi recipe on content of trace element and immune function in children with spleen deficiency anorexia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and prospect of Fuzheng Jianpi Recipe (FZJPR) in treating children's Spleen deficiency anorexia (CSDA) by means of observing its effect on trace element content and immune function.</p><p><b>METHODS</b>One hundred and thirty cases of CSDA were treated with FZJPR, one dose per day in decoction, orally taken, 30 days for one therapeutic course. Levels of T-lymphocyte subsets, IL-2R, immunoglobulin and trace elements were determined before and after treatment, and compared with those in the control group consisted of 60 healthy children.</p><p><b>RESULTS</b>In the treated group, abnormal figures were shown in T-lymphocyte subsets, especially in lowering of CD3 and CD4 count before treatment, and IgG content was reduced also. After treatment, CD3, CD4, CD4/CD8 ratio as well as IgG and IgA were improved significantly (P < 0.01), IL-2R percentage approached normal. Moreover, the levels of Zn and Fe changed significantly (P < 0.01).</p><p><b>CONCLUSION</b>FZJPR could improve the trace elements content and immune function in CSDA children, so it is effective in treating CSDA.</p>