Sap-sucking insects often transmit plant viruses but also carry insect viruses, which infect insects but not plants. The impact of such insect viruses on insect host biology and ecology is largely unknown. Here, we identified a novel insect-specific virus carried by brown citrus aphid (Aphis citricidus), which we tentatively named Aphis citricidus picornavirus (AcPV). Phylogenetic analysis discovered a monophyletic cluster with AcPV and other unassigned viruses, suggesting that these viruses represent a new family in order Picornavirales. Systemic infection with AcPV triggered aphid antiviral immunity mediated by RNA interference, resulting in asymptomatic tolerance. Importantly, we found that AcPV was transmitted horizontally by secretion of the salivary gland into the feeding sites of plants. AcPV influenced aphid stylet behavior during feeding and increased the time required for intercellular penetration, thus promoting its transmission among aphids with plants as an intermediate site. The gene expression results suggested that this mechanism was linked with transcription of salivary protein genes and plant defense hormone signaling. Together, our results show that the horizontal transmission of AcPV in brown citrus aphids evolved in a manner similar to that of the circulative transmission of plant viruses by insect vectors, thus providing a new ecological perspective on the activity of insect-specific viruses found in aphids and improving the understanding of insect virus ecology.
在威胁中老年人身体健康的疾病中,心梗、脑梗以其隐匿性高、发病突然而极具杀伤力,中老年人应该提前了解其罪魁祸首,做好预防,防患于未然.
采用变量法精确确定了吨钢入炉铁水量调整后转炉系统的热量亏空,通过优化调整转炉造渣物料结构,减少强冷却效果物料的使用量,配加反应速度快、升温效率高的碳-硅质发热剂,稳定解决了吨钢铁水量降低所带来的转炉系统热量不足的问题,提高了入炉废钢比.在工业生产顺行的基础上,80 t转炉入炉铁水量由860 kg/t钢降低到800 kg/t钢.
A feasible one-pot synthesis method for the preparation of copper nanoparticles under ambient atmosphere is put forward. Copper oxide and D-isoascorbic acid were chosen as the copper precursor and mild reducing agent, respectively. Oleylamine and octylamine were selected as the capping agents. The effects of the amount and alkyl chain length of capping agent on the synthesis of copper nanoparticles were studied. Antioxidised copper nanoparticles were prepared successfully without the protection of inert atmosphere. The minimum average size of obtained copper nanoparticles was 149 ± 11 nm.
The corrosion behavior of super vacuum die-cast AM60B magnesium alloys immersed in a 5 wt% NaCl solution was investigated by slow positron beam technique, XRD, XPS, SEM and potentiodynamic polarization tests. The XRD and XPS results indicated that Mg(OH)(2) was main corrosion product in the salt solution. With prolonging the immersion time, a significant decrease of Doppler-broadened annihilation line-width parameter near the surface after corrosion was observed and interpreted that the pre-existing interfacial voids between oxide film and matrix might promote the formation of Mg(OH)2 corrosion layer. Polarization tests found that Mg(OH)(2) could provide a temporary protection. (C) 2016 Elsevier Ltd. All rights reserved.
BACKGROUND:Apoptosis plays an important role in renal ischemia/reperfusion (IR) injury. Evidence has shown that erythropoietin (EPO) has an antiapoptotic effect. Therefore, this study aimed to explore the effect and potential mechanism of EPO in renal IR injury.METHODS:Kidney IR injury in rats was established by clamping the left renal artery for 30 minutes followed by 24 hours of reperfusion, along with contralateral nephrectomy. Renal function, renal histology, and expression of EPOR, p-EPOR, ERK, p-ERK, p-p53, p53, Bcl-2, Bcl-xl, Bad, and Bax were examined.RESULTS:Pretreatment with EPO significantly reduced renal dysfunction, pathologic change, and expression of Bad and Bax. Furthermore, EPO treatment enhanced the expression of p-ERK, p-p53, Bcl-2, and Bcl-xl with no influence on the expression of EPOR, ERK, and p53.CONCLUSIONS:These findings demonstrated that EPO pretreatment can attenuate renal IR injury by inhibiting apoptosis by promoting activation of the ERK/p53 signaling.
Evolutionarily conserved signaling intermediate in Toll pathways (Ecsit) is reported to play an essential role in innate immunity, embryogenesis, and assembly or stability of the mitochondrial complex I. In this study, the full-length cDNA of Ecsit was cloned from the spinyhead croaker Collichthys lucidus based on the expressed sequence tags from our cDNA library constructed using the SMART technique. The cDNA was 1669 bp long, including a 5'-terminal untranslated region (UTR) of 121 bp, a 3'-terminal UTR of 183 bp, and an open reading frame of 1365 bp encoding a 454-amino acid polypeptide. The estimated molecular weight of C. lucidus Ecsit (ClEcsit) was 52.50 kDa with an isoelectric point of 6.14, and contained a typical Ecsit domain that is conserved in other Ecsits. Multiple alignment of ClEcsit with other selected Ecsits suggested that some amino acid residues were highly conserved. Phylogenetic analysis indicated that ClEcsit was more similar to its identities in Sciaenidae and grouped with Ecsits from other Perciformes. Quantitative real-time reverse transcription PCR analysis revealed broad expression of ClEcsit and the transcript was strongly expressed in the gill and weakly expressed in other tissues.
OBJECTIVE To explore the changing trend and clinical significance of disease spectrum of biliary surgery among 30 years in PLA General Hospital. METHODS We retrospectively analyzed the clinical data of 21 189 consecutive patients with biliary diseases in PLA General Hospital between January 1985 and December 2014 according to the inclusion criteria. Taking 5 years as a research group, all patients were divided into 6 groups, and then the 30 years of the disease spectrum of biliary surgery was described. RESULTS (1) From January 1985 to December 2014, the PLA General Hospital performed 21 189 cases of patients with biliary surgery diseases, including 9 460 cases of male, 11 729 cases of female (female∶male=1.24∶1). The average age was 52.1±13.5 years old (6-98 years). (2) Of the all cases, the most patients was cholelithiasis, accounting for 65.26%, and gallbladder stones accounting for 53.61%. The following disease was cholangiocarcinoma, accounting for 12.79%, and hilar cholangiocarcinoma accounting for 5.95%. (3) From the perspective of disease spectrum changing trend, the proportion of patients with cholelithiasis were decreased gradually, from 74.9% to 65.2%, while the proportion of patients with cholangiocarcinoma showed a gradual upward trend, rising from 6% to 14% (P<0.05); and the proportion of bile duct cystic dilatation and gallbladder carcinoma shared a gradual increase(P<0.05), however, the variation of proportion of gallbladder polyps and biliary stricture were not statistically significant (P>0.05). (4) In patients with cholelithiasis, the proportion of patients with gallbladder stones increased gradually from 71.9% to 82%, while the proportion of patients with bile duct stones decreased gradually from 28.1% to 18%. There was no statistical significance in the proportion of different types of cholangiocarcinoma patients (P>0.05) (40% of the patients with hilar cholangiocarcinoma, 25% of the intrahepatic cholangiocarcinoma, and 35% of the extrahepatic cholangiocarcinoma). CONCLUSION With the time changing, the disease spectrum of biliary surgery has also changed. The proportion of patients with cholelithiasis, especially the patients with bile duct stones, was declining gradually, and the proportion of patients with cholangiocarcinoma was increasing gradually.
Cardiotoxicity is the major dose-limiting factor in the chemotherapeutic use of doxorubicin (Dox). A delivery vehicle that can be triggered to release its payload in the tumoral microvasculature but not in healthy tissue would help improve the therapeutic window of the drug. Delivery strategies combining liposomal encapsulated Dox (LDox), microbubbles (MBs), and ultrasound (US) have been shown to improve therapeutic efficacy of LDox, but much remains to be known about the mechanisms and the US conditions that maximize cytotoxicity using this approach. In this study, we compared different US pulses in terms of drug release and acute toxicity. Drug uptake and proliferation rates using low-intensity US were measured in squamous cell carcinoma cells exposed to LDox conjugated to or coinjected with polymer MBs. The aims of this study were: (1) to compare the effects of low- and high-pressure US on Dox release kinetics; (2) to evaluate whether conjugating the liposome to the MB surface (DoxLPX) is an important factor for drug release and cytotoxicity; and (3) to determine which US parameters most inhibit cell proliferation and whether this inhibition is mediated by drug release or the MB/US interaction with cells. Low-pressure US (170 kPa) at high duty cycle (stable cavitation) released up to ∼ 70% of the encapsulated Dox from the DoxLPX, thus improving Dox bioavailability and cellular uptake and leading to a significant reduction in cell proliferation at 48 h. Flow cytometry showed that US generating stable oscillations of DoxLPX significantly increased cellular Dox uptake at 4 h after US exposure compared to LDox. Drug uptake was correlated with cytotoxicity at 48 h. Our results demonstrate that Dox-containing liposomes conjugated to polymer MBs can be triggered to release ∼ 70% of their payload using noninertial US. Following release, Dox became bioavailable to the cells and induced significantly higher cytotoxicity compared to nonreleased encapsulated drug. Our findings show promise for targeted drug delivery using this theranostic delivery platform at low US intensities.
Ultrasound-microbubble mediated therapies have been investigated to restore perfusion and enhance drug/gene delivery, using both short (~μs) and long (~ms) ultrasound tone-bursts. Microbubble oscillation behavior can be observed with ultra-high speed microscopy; however, due to the high frame rate required and limited number of frames available, microbubble dynamic behavior can only be observed for a few acoustic cycles (~μs). In this report, the fate of microbubbles throughout long tone-burst ultrasound exposures (5 ms) was explored via direct microscopic optical observation in conjunction with passive cavitation detection, over a range of acoustic pressures (0.25, 0.5, 1.0, and 1.5 MPa) and microbubble concentrations (2e6, 2e7, and 2e8 MB/ml). The ultrasound system was triggered from UPMC Cam, the ultra-high speed camera system at the University of Pittsburgh Medical Center, such that microbubble activity at various time points (0–5 ms) within the long tone-burst was captured. Microbubbles first underwent stable or inertial cavitation depending on the acoustic pressure used, and then formed gas-filled clusters that continued to oscillate, break up, and form new clusters. Cavitation detection confirmed continued, albeit diminishing acoustic activity throughout the 5 ms ultrasound excitation. This discovery suggests that persisting cavitation activity during long tone-bursts may confer additional therapeutic effect for ultrasound-microbubble mediated therapies.
Objective:hTe investigate the inhibitory effect of the adenovirus-mediated CD/TK double suicide gene system driven by KDR promoter (Ad-KDRP-CD/TK) combined with survivin gene interference on the growth of hepatocellular carcinoma (HCC) cells in nude mice. Methods:Twenty nude mice were equally randomized into model group (subcutaneous implantation of HCC BEL-7402 cells to establish xenogratf tumor without other additional treatment), double suicide gene transfection group (subcutaneous implantation of BEL-7402 cells transfected with Ad-KDRP-CD/TK, followed by intratumor injection with the prodrug gancilovir and 5-lfuorocytosine atfer tumor formation), survivin siRNA transfection group (subcutaneous implantation of BEL-7402 cells, followed by intratumor injection with survivin siRNA/Lip-DMEM transfection complex atfer tumor formation), and combination transfection group (double suicide gene transfection plus survivin siRNA transfection). Two weeks atfer transfection treatment, mice in each group were sacriifced, tumor weight and tumor inhibition rate were measured, the microvessel density (MVD), and survivin mRNA and protein expressions in the tumor tissues were determined. Results: In each treatment group compared with model group, the tumor weight was signiifcantly reduced, with the maximum tumor inhibition in combination transfection group (all P<0.05);the MVD, and the expression levels of survivin mRNA and protein were signiifcantly decreased, with the maximum decreasing amplitude in combination transfection group (all P<0.05). Conclusion:Double suicide gene combined with survivin gene interference is an effective method to inhibit the growth of HCC cells in vivo.
In this work, the structural dynamics of liquid Al80Cu20 is systematically investigated in terms of the evolution of its atomic structure, diffusivity, viscosity and fragility through ab initio molecular dynamics simulations. In addition to using pair correlation functions and coordination numbers, the various local ordered clusters are characterized comprehensively by Honeycutt-Anderson bond pairs and Voronoi polyhedra. Compared to the self diffusivity of pure liquid Cu, the tracer diffusion coefficients of Cu in liquid Al80Cu20 are increased, in agreement with the results measured by quasielastic neutron-scattering (QENS). Although the interdiffusion coefficients predicted by Darken’s equation match well to those obtained from the viscosity measurements via the Stokes-Einstein relation, they are smaller than those measured by QENS or X-ray radiography, indicative of an anomalous nature of the structural dynamics, dominated by the local ordered clusters in liquid Al80Cu20. Furthermore, Vogel–Fulcher–Tammann fitting results indicate that the liquid Al80Cu20 can be classified into a strong liquid. The deformation electron density shows that the intrinsic tetrahedral-type bonds in FCC Al and Cu are transformed into an amorphous type in liquid Al80Cu20. The present work provides insights into the understanding of structural dynamics and the kinetic properties of such metallic melts.
Objective: Background: Adrenal venous sampling (AVS) is an invasive and cost procedure, not all the medical centers can perform it. Considering the prevalence of incidentalomas increases with age, current primary aldosteronism (PA) diagnosis and treatment guideline and the AVS expert consensus both recommended that PA patients younger than age 40 are not necessary to have AVS before adrenalectomy if they have a typical PA profile and a clear unilateral adrenal adenoma on CT scan. To study the necessity of AVS in PA patients younger than age 45. Design and method: This is a retrospective study. 106 patients younger than age 45 who were diagnosed PA in the Department of Hypertension in Ruijin Hospital between 2006 and 2014 were analyzed. PA was confirmed either by fludrocortisone test or saline infusion test. Patients received unilateral adrenalectomy guided by AVS result or by the typical adenoma appearance on adrenal CT image. They were followed after surgery. Group 1 included 39 patients who received successful lateralized AVS. Group 2 had 67 patients including 53 without AVS, 10 with nonlateralized AVS and 4 with unsuccessful AVS. Results: The baseline clinical characters, including age, gender, hypertension duration, 24 hour systolic and diastolic blood pressure, hypokalemia history, the number of antihypertensive medications and the length of follow-up after surgery were not different, respectively, between two groups. Group 2 had significantly higher standing plasma aldosterone and urinary aldosterone level than that of group 1(298.71 ± 153.71 vs 399.67 ± 269.06 (pg/ml), 23.45 ± 14.61 vs 31.52 ± 21.16 ug/24hour, respectively, all P < 0.05), but there were no difference considering plasma renin activity and renin to aldosterone ratio. The adenoma diameter measured from adrenal CT image was different between two groups (1.2 ± 0.72 cm vs 1.5 ± 0.74 cm, P < 0.05). 59% patients in group 1 and 62.7% patients in group 2 had PA cured respectively after surgery (P > 0.05). Conclusions: In this small retrospective study, PA patients younger than age 45 had similar adrenalectomy outcome no matter they received AVS or not. It is suggested therefore that AVS might not be necessary in typical PA patients younger than 45.
Cachexia or muscle wasting is a common condition that occurs in many chronic diseases. The wasting conditions are characterized by increased levels of TNF-α which was also known as cachectin in the past. But how TNF-α exerts its cachetic effects remains controversial. To clarify this issue, we investigated the impact of TNF-α on C2C12 cell myogenic differentiation. Our results demonstrate that myotube formation was completely inhibited by TNF-α when added to differentiating C2C12 myoblasts. The inhibitory effect of TNF-α on differentiation was accompanied by activation of NF-κB and down regulation of myogenin and Akt. Importantly, TNF-α's effect on differentiation was abolished when IGF-1 was added to the culture. IGF-1 treatment also inhibited NF-κB reporter activity and restored Akt levels. Our data suggest that TNF-α inhibits myogenic differentiation through NF-κB activation and impairment of IGF-1 signaling pathway. The reversal of TNF-α induced inhibition of myogenesis by IGF-1 may have significant therapeutic potential.
Transforming growth factor-beta 1 (TGF-beta 1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-beta 1 causes MCP-1 over-expression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-beta 1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-kappa B (NF-kappa B), which upregulated expression of MCP-1. Incubating cultures with TGF-beta 1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (alpha-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-beta 1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-beta 1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-kappa B pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work.