Isolation, characterization, and circulation sphere of a filovirus in fruit bats.

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus, suggesting its classification as the prototype of a new genus within the family Filoviridae. The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region.

Sugar conundrum in plant-pathogen interactions: roles of invertase and sugar transporters depend on pathosystems.

It has been increasingly recognized that CWIN (cell wall invertase) and sugar transporters including STP (sugar transport protein) and SWEET (sugar will eventually be exported transporters) play important roles in plant-pathogen interactions. However, the information available in the literature comes from diverse systems and often yields contradictory findings and conclusions. To solve this puzzle, we provide here a comprehensive assessment of the topic. Our analyses revealed that the regulation of plant-microbe interactions by CWIN, SWEET, and STP is conditioned by the specific pathosystems involved. The roles of CWINs in plant resistance are largely determined by the lifestyle of pathogens (biotrophs versus necrotrophs or hemibiotrophs), possibly through CWIN-mediated salicylic acid or jasmonic acid signaling and programmed cell death pathways. The up-regulation of SWEETs and STPs may enhance or reduce plant resistance, depending on the cellular sites from which pathogens acquire sugars from the host cells. Finally, plants employ unique mechanisms to defend against viral infection, in part through a sugar-based regulation of plasmodesmatal development or aperture. Our appraisal further calls for attention to be paid to the involvement of microbial sugar metabolism and transport in plant-pathogen interactions, which is an integrated but overlooked component of such interactions.

Activated microglia promote invasion and barrier dysfunction of brain endothelial cells via regulating the CXCL13/CXCR5 axis.

The blood brain barrier (BBB) is a protective border that prevents noxious substances from gaining access to the central nervous system (CNS). CXCL13 is a chemokine from the CXC chemokine family, which has been shown to destroy the barrier function of umbilical vein endothelial cells with its receptor CXCR5. Here, we aimed to investigate the role of CXCL13/CXCR5 signaling axis in BBB. The invasive ability of bEnd.3 cells was determined by the Transwell invasion assay. The barrier integrity of bEnd.3 cells was assessed by detecting trans-endothelial electrical resistance, the permeability to fluorescein isothiocyanate-dextran, and the expression levels of the tight junction protein E-cadherin. Lipopolysaccharide (LPS)-activated microglia promoted invasion and barrier dysfunction, and upregulated CXCR5 and p-p38 expression levels in cocultured bEnd.3 cells. However, the effects of activated microglia were alleviated by knocking down CXCR5 in cocultured bEnd.3 cells. Furthermore, recombinant CXCL13 promoted invasion and barrier dysfunction, and upregulated the expression levels of p-p38 in bEnd.3 cells; however, its effects were abolished by treating bEnd.3 cells with the p38 inhibitor SB203580. Our data tentatively demonstrated that LPS-activated microglial cells may promote invasion and barrier dysfunction in bEnd.3 cells by regulating the CXCL13/CXCR5 axis and p38 signaling.

Rapid detection of sweepoviruses through lateral flow dipstick-based recombinase polymerase amplification.

Sweepoviruses represent a phylogenetic group of begomoviruses that cause significant sweet potato (Ipomoea batatas) production losses in various countries across the world. For rapid identification of sweepoviruses, we developed a technique based on isothermal recombinase polymerase amplification in conjunction with lateral flow dipsticks (RPA-LFD). The optimum reaction conditions for the RPA were 20 min incubation at 37°C. The RPA-LFD specifically detected distinct sweepovirus species, with no other viruses infecting sweet potato causing a cross-reaction. The detection limit of the RPA-LFD was 1.0×104 copies of the target DNA molecule per reaction, and it exhibited a 10-fold greater sensitivity than the conventional PCR. Furthermore, when coupled with an alkaline polyethylene glycol-based crude genomic DNA extraction, the entire procedure was completed in 30 min without the use of any special instruments other than a water bath. Therefore, the RPA-LFD technique is a potential sweepovirus diagnostic tool that can be used in the field with fewer available resources. Keywords: detection; sweepoviruses; recombinase polymerase amplification; lateral flow dipstick.

Physiology and Molecular Breeding in Sustaining Wheat Grain Setting and Quality under Spring Cold Stress.

Spring cold stress (SCS) compromises the reproductive growth of wheat, being a major constraint in achieving high grain yield and quality in winter wheat. To sustain wheat productivity in SCS conditions, breeding cultivars conferring cold tolerance is key. In this review, we examine how grain setting and quality traits are affected by SCS, which may occur at the pre-anthesis stage. We have investigated the physiological and molecular mechanisms involved in floret and spikelet SCS tolerance. It includes the protective enzymes scavenging reactive oxygen species (ROS), hormonal adjustment, and carbohydrate metabolism. Lastly, we explored quantitative trait loci (QTLs) that regulate SCS for identifying candidate genes for breeding. The existing cultivars for SCS tolerance were primarily bred on agronomic and morphophysiological traits and lacked in molecular investigations. Therefore, breeding novel wheat cultivars based on QTLs and associated genes underlying the fundamental resistance mechanism is urgently needed to sustain grain setting and quality under SCS.

Impact of glycemic control on the association of endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND: We investigated whether glycemic control affects the relation between endothelial dysfunction and coronary artery disease in patients with type 2 diabetes mellitus (T2DM). METHODS: In 102 type 2 diabetic patients with stable angina, endothelial function was evaluated using brachial artery flow-mediated dilation (FMD) with high-resolution ultrasound, and significant stenosis of major epicardial coronary arteries (≥ 50% diameter narrowing) and degree of coronary atherosclerosis (Gensini score and SYNTAX score) were determined. The status of glycemic control was assessed by blood concentration of glycated hemoglobin (HbA1c). RESULTS: The prevalence of significant coronary artery stenosis (67.9% vs. 37.0%, P = 0.002) and degree of coronary atherosclerosis (Gensini score: 48.99 ± 48.88 vs. 15.07 ± 21.03, P < 0.001; SYNTAX score: 15.88 ± 16.36 vs. 7.28 ± 10.54, P = 0.003) were higher and FMD was lower (6.03 ± 2.08% vs. 6.94 ± 2.20%, P = 0.036) in diabetic patients with poor glycemic control (HbA1c ≥ 7.0%; n = 56) compared to those with good glycemic control (HbA1c < 7.0%; n = 46). Multivariate regression analysis revealed that tertile of FMD was an independent determinant of presence of significant coronary artery stenosis (OR = 0.227 95% CI 0.056-0.915, P = 0.037), Gensini score (ß = - 0.470, P < 0.001) and SYNTAX score (ß = - 0.349, P = 0.004) in diabetic patients with poor glycemic control but not for those with good glycemic control (P > 0.05). CONCLUSION: Poor glycemic control negatively influences the association of endothelial dysfunction and coronary artery disease in T2DM patients.

CircRNA circ-ITCH improves renal inflammation and fibrosis in streptozotocin-induced diabetic mice by regulating the miR-33a-5p/SIRT6 axis.

Diabetic nephropathy (DN) seriously affects the people's life and health in China. This study aimed to investigate the effect of circRNA circ-ITCH on improving DN by regulating the miR-33a-5p/SIRT6 axis and the possible mechanism of action. High glucose (HG)-induced rat mesangial cells (RMCs) were used to simulate the DN in vitro. Reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis were conducted to detect the gene or protein expression. Cell Counting Kit-8 (CCK-8) and wound healing assays were performed to estimate the cell viability and migration capability. Immunofluorescence and enzyme-linked immunosorbent assay (ELISA) were used to detect the α-Smooth Muscle Actin (α-SMA) expression and levels of inflammatory factors. The potential associations between circ-ITCH and miR-33a-5p, miR-33a-5p and SIRT6 in RMCs were measured via dual-luciferase reporter assay. Streptozotocin (STZ) was used to induce the diabetic mice. Blood glucose and serum insulin of mice were determined by corresponding kits, and blood urea nitrogen (BUN) and serum creatinine (SCr) were measured using an automatic biochemical analyzer. Hematoxylin and eosin (H&E) staining and periodic acid-Schiff (PAS) staining were applied to observe the degree of pathological injury and fibrosis of renal tissues. The results of the present study revealed that circ-ITCH expression was obviously decreased in HG-induced RMCs. In addition, circ-ITCH overexpression inhibited the viability, migration, fibrosis and inflammatory response of HG-induced RMCs. Further experiments confirmed that miR-33a-5p may be a direct target of circ-ITCH and SIRT6 may be a direct target of miR-33a-5p. Notably, the miR-33a-5p mimic or shRNA-SIRT6 were discovered to reverse the inhibitory effects of circ-ITCH on the proliferation, migration, fibrosis and inflammatory response of HG-induced RMCs. Furthermore, circ-ITCH overexpression ameliorated renal inflammation and fibrosis in STZ-induced diabetic mice. In conclusion, circ-ITCH alleviated renal inflammation and fibrosis in STZ-induced diabetic mice by regulating the miR-33a-5p/SIRT6 axis.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [ChunYang] Last name [Xu]. Author 2 Given name: [DingBo] Last name [Xu]. Author 3 Given name: [YongHua] Last name [Liu]. Author 4 Given name: [Juanjuan] Last name [Jiang]. Also, kindly confirm the details in the metadata are correct.ok.

Emergent chikungunya fever and vertical transmission in Yunnan Province, China, 2019.

During the dengue epidemic in Yunnan Province, China, during 2019, a concurrent outbreak of chikungunya occurred in the city of Ruili, which is located in the southwest of the province, adjacent to Myanmar. As part of this outbreak, three neonatal cases of infection with indigenous chikungunya virus from mother-to-child (vertical) transmission were observed. Isolates of chikungunya virus were obtained from 37 serum samples of patients with chikungunya during this outbreak, and a phylogenetic analysis of these isolates revealed that they belong to the Indian Ocean subclade of the East/Central/South African genotype. The E1 genes of these viruses did not harbor the A226V mutation.

Using circulating O-sulfotyrosine in the differential diagnosis of acute kidney injury and chronic kidney disease.

BACKGROUND: Sulfation of tyrosine, yielding O-sulfotyrosine, is a common but fixed post-translational modification in eukaryotes. Patients with increased circulating O-sulfotyrosine levels experience a faster decline in renal function with progression to end-stage renal disease (ESRD). In the present study, we measured serum O-sulfotyrosine levels in individuals with chronic kidney disease (CKD) and acute kidney injury (AKI) to explore its ability to differentiate AKI from CKD. METHODS: A total of 135 patients (20 with AKI and 115 with CKD) were recruited prospectively for liquid chromatography-mass spectrometry assessment of circulating O-sulfotyrosine. We also studied C57BL/6 mice with CKD after 5/6 nephrectomy (Nx). Blood samples were drawn from the tail vein on Day 1, 3, 5, 7, 14, 30, 60, and 90 after CKD. Serum separation and characterization of creatinine, blood urea nitrogen (BUN), and O-sulfotyrosine was performed. Thus, the time-concentration curves of the O-sulfotyrosine level demonstrate the variation of kidney dysfunction. RESULTS: The serum levels of O-sulfotyrosine were markedly increased in patients with CKD compared with AKI. Median O-sulfotyrosine levels in CKD patients versus AKI, respectively, were as follows:243.61 ng/mL(interquartile range [IQR] = 171.90-553.86) versus 126.55 ng/mL (IQR = 48.19-185.03, P = 0.004). In patients with CKD, O-sulfotyrosine levels were positively correlated with creatinine, BUN, and Cystatin C (r = 0.63, P < 0.001; r = 0.49, P < 0.001; r = 0.61, P < 0.001, respectively) by the multivariate linear regression analysis (ß = 0.71, P < 0.001; ß = 0.40, P = 0.002; ß = 0.73, P < 0.001, respectively). However, this association was not statistically significant in patients with AKI (r = - 0.17, P = 0.472; r = 0.11, P = 0.655; r = 0.09, P = 0.716, respectively). The receiver operating characteristic (ROC) analysis illustrated that the area under the curve was 0.80 (95% confidence interval [CI] 0.71-0.89; P < 0.001) and the optimal cut-off value of serum O-sulfotyrosine suggesting AKI was < 147.40 ng/mL with a sensitivity and specificity of 80.90 and 70.00% respectively. In animal experiments, serum levels of O-sulfotyrosine in mice were elevated on Day 7 after 5/6 nephrectomy (14.89 ± 1.05 vs. 8.88 ± 2.62 ng/mL, P < 0.001) until Day 90 (32.65 ± 5.59 vs. 8.88 ± 2.62 ng/mL, P < 0.001). CONCLUSION: Serum O-sulfotyrosine levels were observed correlated with degrading renal function and in CKD patients substantially higher than those in AKI patients. Thus serum O-sulfotyrosine facilitated the differential diagnosis of AKI from CKD.

Synthesis and in vitro activity of asymmetric indole-based bisamidine compounds against Gram-positive and Gram-negative pathogens.

A series of new asymmetric bisamidine was designed, synthesized, and tested for their in-vitro antibacterial activity using a range of Gram-positive and Gram-negative pathogens. Most compounds demonstrated powerful antibacterial activity, and interestingly, some displayed better activity against several Gram-negative strains than the lead compound 1. The most potent bisamidine 8l exhibited 4-fold more potent activity against E. coli, K. pneumonia, P. aeruginosa, and C. freundii than compound 1. Especially 8l exhibited a powerful activity against K. pneumonia secreting NDM-1 enzyme with a minimum inhibitory concentration (MIC) of 2 µg/mL, while levofloxacin and vancomycin displayed resistance, with MICs > 128 µg/mL.

Anti-inflammatory effects of rosuvastatin treatment on coronary artery ectasia patients of different age groups.

BACKGROUND: Coronary artery ectasia (CAE) is an angiographic finding of abnormal coronary dilatation. Inflammation plays a major role in all phases of atherosclerosis. We investigated the relationship between CAE and serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels to test our hypothesis that patient age is associated with the efficacy of anti-inflammatory therapy for CAE. METHODS: We conducted a prospective analysis of 217 patients with CAE treated at the Department of Cardiology, Shanghai East Hospital, Ji'an Campus and the Baoshan People's Hospital, from January 1, 2015 to July 30, 2019. Baseline data of patients, including sex; age; and history of hypertension, hyperlipidemia, and diabetes, were collected from patient medical records. Study participants were grouped by age as follows: CAE-A (n = 60, age ≤ 50 years), CAE-B (n = 83, 50 years 70). Additionally, there was a control (NC) group (n = 73) with normal coronary arteries. RESULTS: All patients received oral rosuvastatin therapy (10 mg, QN quaque nocte) when they were diagnosed with CAE and maintained good follow-up, with a loss rate of 0.0% at the end of the 6-month follow-up. The NC group received regular symptom-relieving treatments and rosuvastatin therapy. Of these four groups, the inflammatory markers, hs-CRP and IL-6, were significantly higher in patients with CAE than in the NCs (p < 0.05). Post-hoc tests showed that hs-CRP and Il-6 levels had significant differences between the CAE-A and CAE-C groups (P = 0.048, P = 0.025). Logistic regression analysis showed that hs-CRP (OR = 1.782, 95% CI: 1.124-2.014, P = 0.021) and IL-6 (OR = 1.584, 95% CI: 1.112-1.986, P = 0.030) were independent predictors of CAE. The inflammatory markers were higher in the CAE-A group than in the CAE-B group and higher in the CAE-B group than in the CAE-C group. Follow-up after 6 months of rosuvastatin therapy showed a significantly greater reduction in hs-CRP and IL-6 levels in the CAE-A group than in the CAE-B group, which again were greater in the CAE-B group than in the CAE-C group. CONCLUSIONS: Anti-inflammatory therapy using rosuvastatin was more effective in younger CAE patients, indicating the need for early statin therapy in CAE.

Coupling coumarin to gold nanoparticles by DNA chains for sensitive detection of DNase I.

A kind of coumarin-modified gold nanoparticle by the bridge of dsDNA chains was designed and synthesized for sensitive detection of DNase I. The fluorescence of coumarin 343 at emission wavelengths of 491 nm excited at 440 nm was quenched by the gold nanoparticles due to the energy transfer process after the coumarin 343 was connected on the gold nanoparticles by DNA chains. When dsDNA chains were cut off by DNase I, the coumarin 343 molecules were released from gold nanoparticles and the fluorescence of coumarin 343 would be restored. The DNase I activity could be detected by this fluorescence assay with a high sensitivity based on the change of the energy transfer efficiency. The intensity of restored fluorescence is linearly related to the quantity of DNase I in the range from 1.0 to 40 mU/mL with a detection limit of 0.22 mU/mL. This design idea could render a useful way to develop similar molecular or enzyme sensor in analytical or biological fields.

Vasodilator-stimulated phosphoprotein-guided Clopidogrel maintenance therapy reduces cardiovascular events in atrial fibrillation patients requiring anticoagulation therapy and scheduled for percutaneous coronary intervention: a prospective cohort study.

BACKGROUND: In a previous study, we found that titrating clopidogrel maintenance doses (MDs) according to vasodilator-stimulated phosphoprotein (VASP) monitoring minimised the rate of major adverse cardiovascular and cerebral events (MACCE) after percutaneous coronary intervention (PCI) without increasing bleeding in patients with high on-treatment platelet reaction to clopidogrel. This study aimed to investigate whether VASP-guided clopidogrel MD could reduce thromboembolism and bleeding in atrial fibrillation (AF) patients requiring anticoagulation and scheduled for PCI. METHODS: AF patients scheduled for PCI were recruited between July 2014 and July 2016. These patients were allocated into VASP-guided (n = 250) and control (n = 253) groups depending on the clopidogrel MD profile. In the VASP-guided group, clopidogrel MD was titrated by the platelet reactivity index (PRI), whereas in the control group, clopidogrel MD was fixed at 75 mg per day. The primary endpoint was MACCE and secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding 1 year after PCI. RESULTS: Five hundred and three patients were included in the present study, with 1-year data available for 95.6% patients. The average CHA2DS2-VASc score of the whole population was 3.7 ± 0.7 and the average HAS-BLED score was 3.2 ± 0.4. MACCE was less in the VASP-guided group than in the control group (2.5% vs. 5.0%, P = 0.02). The incidence of major bleeding was comparable between both groups (3.0% vs. 2.8%, P = 0.72) and minor bleeding was higher in the VASP-guided group than in the control group (15.3% vs. 9.7%, P = 0.03). Kaplan-Meier analysis indicated that there was no difference in survival between both groups (log-rank test, P = 0.68). CONCLUSIONS: In AF patients requiring anticoagulation and scheduled for PCI, VASP-guided antiplatelet therapy reduced major cardiovascular and cerebral adverse events, accompanied by increased minor bleeding events. TRIAL REGISTRATION: The present study was retrospectively registered in the Chinese Clinical Trial Registry, A Primary Registry of the International Clinical Trial Registry Platform, World Health Organisation (Registration no: ChiCTR-IOR-17013854 ). The registered date was December 11, 2117.

Voltammetric determination of DNA based on regulation of DNA strand displacement using an allosteric DNA toehold.

An electrochemical biosensor for determination of DNA is described that is based on the reaction of regulated DNA (reg-DNA) first with substrated DNA (subs-DNA) to form a reaction intermediate. The intermediate binds target DNA (T) by hybridization and initiates a branch migration leading to the production of complex of substrated DNA and target DNA (TC). Once TC is produced, it reacts with assisted DNA (ass-DNA) through a toehold exchange mechanism, yielding the product complex of substrated DNA and assisted DNA (CS). The target is then released back into the solution and and catalyzes the next cycle of toehold-exchange with the reaction intermediate of substrated DNA and regulated DNA (CPR). Unlike in a conventional DNA toehold that is hardwired with the branch migration domain, the allosteric DNA toehold is designed into a reg-DNA which is independent of the branch migration domain. Under the optimal experimental conditions and at a working potential as low as 0.18 V, response to DNA is linear in the 1 fM to 1000 pM concentration range, and the detection limit is 0.83 fM. The assay is highly specific and can discriminate target DNA even from a single-base mismatch. It was applied to the analysis of DNA spiked plasma samples. Graphical abstract Schematic illustration of the electrochemical strategy for target DNA detection based on regulation of DNA strand displacement using an allosteric DNA toehold strategy. It can be used to analyze DNA-spiked plasma samples and has a low detection limit of 0.83 fM.

Cell Wall Invertase Promotes Fruit Set under Heat Stress by Suppressing ROS-Independent Cell Death.

Reduced cell wall invertase (CWIN) activity has been shown to be associated with poor seed and fruit set under abiotic stress. Here, we examined whether genetically increasing native CWIN activity would sustain fruit set under long-term moderate heat stress (LMHS), an important factor limiting crop production, by using transgenic tomato (Solanum lycopersicum) with its CWIN inhibitor gene silenced and focusing on ovaries and fruits at 2 d before and after pollination, respectively. We found that the increase of CWIN activity suppressed LMHS-induced programmed cell death in fruits. Surprisingly, measurement of the contents of H2O2 and malondialdehyde and the activities of a cohort of antioxidant enzymes revealed that the CWIN-mediated inhibition on programmed cell death is exerted in a reactive oxygen species-independent manner. Elevation of CWIN activity sustained Suc import into fruits and increased activities of hexokinase and fructokinase in the ovaries in response to LMHS Compared to the wild type, the CWIN-elevated transgenic plants exhibited higher transcript levels of heat shock protein genes Hsp90 and Hsp100 in ovaries and HspII17.6 in fruits under LMHS, which corresponded to a lower transcript level of a negative auxin responsive factor IAA9 but a higher expression of the auxin biosynthesis gene ToFZY6 in fruits at 2 d after pollination. Collectively, the data indicate that CWIN enhances fruit set under LMHS through suppression of programmed cell death in a reactive oxygen species-independent manner that could involve enhanced Suc import and catabolism, HSP expression, and auxin response and biosynthesis.

Upregulated Expression of TRIM32 Is Involved in Schwann Cell Differentiation, Migration and Neurite Outgrowth After Sciatic Nerve Crush.

Tripartite motif containing 32 (TRIM32), a member of the tripartite motif (TRIM) family, plays an indispensable role in myoblast proliferation. It also regulates neuron and skeletal muscle stem cell differentiation. Although it is of great importance, we know little about the roles of TRIM32 during peripheral nervous system injury. Here, we examined the dynamic changes of TRIM32 in acute sciatic nerve crush (SNC) model. After crush, TRIM32 rapidly increased and reached the climax at 1 week but then gradually declined to the normal level at 4 weeks post-injury. Meanwhile, we observed similar changes of Oct-6. What is more, we found co-localization of TRIM32 with S100 and Oct-6 in 1-week-injured tissues using double immunofluorescent staining. In further vitro experiments, enhancive expression of TRIM32 was detected during the process of cyclic adenosine monophosphate (cAMP)-induced Schwann cell differentiation and nerve growth factor (NGF)-induced PC12 cell neurite outgrowth. More interestingly, specific si-TRIM32-transfected RSC96 cells exhibited obvious reduction in the ability of migration. Taken together, we inferred that upregulated TRIM32 was not only involved in the differentiation and migration of Schwann cells but the neurite elongation after SNC.

The Expression of IGFBP6 after Spinal Cord Injury: Implications for Neuronal Apoptosis.

IGFBP6, a member of the insulin-like growth factor-binding proteins family that contains six high affinity IGFBPs, modulates insulin-like growth factor (IGF) activity and also showed an independent effect of IGF, such as growth inhibition and apoptosis. However, the role of IGFBP6 in spinal cord injury (SCI) remains largely elusive. In this study, we have performed an acute SCI model in adult rats and investigated the dynamic changes of IGFBP6 expression in the spinal cord. Our results showed that IGFBP6 was upregulated significantly after SCI, which was paralleled with the levels of apoptotic proteins p53 and active caspase-3. Immunofluorescent labeling showed that IGFBP6 was co-localizated with active caspase-3 and p53 in neurons. To further investigate the function of IGFBP6, an apoptosis model was established in primary neuronal cells. When IGFBP6 was knocked down by specific short interfering RNA (siRNA), the protein levels of active caspase-3 and Bax as well as the number of apoptotic primary neurons were significantly decreased in our study. Taken together, our findings suggest that the change of IGFBP6 protein expression plays a key role in neuronal apoptosis after SCI.

Novel carbazole sulfonamide derivatives of antitumor agent: Synthesis, antiproliferative activity and aqueous solubility.

The current optimization of IG-105 (3) on the carbazole-ring provided a series of new carbazole sulfonamides derivatives 13a-13m. All of the compounds have been evaluated against HepG2 cells (hepatoma cancer) for antiproliferative activity. Compounds that showed activity better or comparable to that of 3 versus HepG2 were evaluated against MCF-7 (breast cancer), MIA PaCa-2 (pancreatic cancer), and Bel-7402 (hepatoma/liver cancer) for antiproliferative activity. Of the seven compounds selected for further study five (13b, 13g, 13j, 13k and 13l) were found to give IC50 values against the four cell lines comparable to those for 3. Two compounds (13f and 13i) were more active than 3 and their activity against HepG2 and MCF-7 (IC50:0.01-0.07µM) approached that of the positive controls podophyllotoxin (podo) and CA-4. Most of compounds showed aqueous solubility (0.11-19.60µg/mL at pH 7.4 and 2.0) better than 3. These promising results warrant further development of new compounds 13f and 13i as potential potent antitumor drug candidates.

Synthesis and in vitro activity of dicationic indolyl diphenyl ethers as novel potent antibiotic agents against drug-resistant bacteria.

A series of 4,4'-bis-[2-(6-N-substituted-amidino)indolyl] diphenyl ether have been synthesized and tested for their in vitro antibacterial activity including a range of Gram-positive and Gram-negative pathogens and cytotoxicity. Most of these compounds have mainly shown anti-Gram positive bacteria activities especially against drug resistant bacterial strains MRSA, MRSE and VRE. The anti-MRSA and anti-MRSE activities of compound 7a and 7j were more potent than that of the lead compound 2, levofloxacin and vancomycin. Interestingly, 7j had greatly improved anti negative bacterial activity, especially for the producing NDM-1 Klebsiella pneumonia strain and less toxic than that of the lead compound 2.

Epidemiological and molecular characteristics of emergent dengue virus in Yunnan Province near the China-Myanmar-Laos border, 2013-2015.

BACKGROUND: Yunnan Province is located in southwestern China and neighbors the Southeast Asian countries, all of which are dengue-endemic areas. In 2000-2013, sporadic imported cases of dengue fever (DF) were reported almost annually in Yunnan Province. During 2013-2015, we confirmed that a large-scale indigenous DF outbreak emerged in cities of Yunnan Province near the China-Myanmar-Laos border. METHODS: Epidemiological characteristics of DF in Yunnan Province during 2013-2015 were evaluated by retrospective analysis. A total of 232 dengue virus (DENV)-positive sera were randomly collected for sequence analysis of the capsid/premembrane region of DENV from patients with DF in Yunnan Province. The envelope gene of DENV isolates was also amplified and sequenced. Phylogenetic analyses were performed using the neighbor-joining method with the Tajima-Nei model. RESULTS: Phylogenetically, all DENV-positive samples could be classified into DENV-1 genotype I and DENV-2 Asian I genotype during 2013-2015 and DENV-4 genotype I in 2015 from Ruili City; and DENV-3 genotype II in 2013 and DENV-2 Cosmopolitan genotype in 2015 from Xishuangbanna Prefecture. CONCLUSIONS: Our results indicated that imported DF from patients from Laos and Myanmar was the primary cause of the DF epidemic in Yunnan Province. Additionally, DENV strains of all four serotypes were identified in indigenous cases in Yunnan Province during the same time period, while the dengue epidemic pattern observed in southwestern Yunnan showed characteristics of a hypoendemic nature: circulation of DENV-1 and DENV-2 over consecutive years.