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Excess cadmium (Cd) in agricultural soils can be taken up by rice plants and concentrated in the grain, presenting a human health risk. In this study, we field tested the effects of three foliar treatments (zinc (Zn) alone, or combined with manganese (ZnMn) or phosphorus (ZnP)) on the Cd concentration and grain yield of six rice cultivars (C Liangyou 7, Fengyuanyou 272, Xiangwanxian 12, Tianyouhuazhan, Xiangwanxian 13, and Jinyou 284) at the grain filling stage. Our results showed that rice yield and Cd, Zn, Mn, P, and K concentrations were significantly different among the cultivars (p < 0.05); for example, Jinyou 284 recorded lower Cd levels than any other cultivar. Application of Zn, ZnMn, and ZnP had no significant effect on rice yield and Mn, P, and K concentrations for all cultivars. Compared with the control, Cd concentrations after treatment with Zn, ZnMn, and ZnP decreased by 19.03-32.55%, 36.63-55.78% (p < 0.05), and 25.72-49.10%, respectively, while Zn concentrations increased by 11.02-29.38%, 10.63-32.67%, and 11.97-36.82%, respectively. There was a significant negative correlation between Cd and Zn concentrations (p < 0.01). All three treatments increased Zn and reduced Cd concentration in rice grains, though ZnMn was most effective. Therefore, cultivar selection and Zn fertilizer application are effective strategies to minimize Cd concentration in rice grains. However, the lowest result still exceeded the Chinese Cd safety limit (0.2 mg Cd kg -1 ) by a factor of 2.6, demonstrating that additional effective measures should be simultaneously used to further reduce the accumulation of Cd in rice grains.

Lipids play numerous indispensable cellular functions and are involved in multiple steps in the replication cycle of viruses. Infections by human-pathogenic coronaviruses result in diverse clinical outcomes, ranging from self-limiting flu-like symptoms to severe pneumonia with extrapulmonary manifestations. Understanding how cellular lipids may modulate the pathogenicity of human-pathogenic coronaviruses remains poor. To this end, we utilized the human coronavirus 229E (HCoV-229E) as a model coronavirus to comprehensively characterize the host cell lipid response upon coronavirus infection with an ultra-high performance liquid chromatography-mass spectrometry (UPLC⁻MS)-based lipidomics approach. Our results revealed that glycerophospholipids and fatty acids (FAs) were significantly elevated in the HCoV-229E-infected cells and the linoleic acid (LA) to arachidonic acid (AA) metabolism axis was markedly perturbed upon HCoV-229E infection. Interestingly, exogenous supplement of LA or AA in HCoV-229E-infected cells significantly suppressed HCoV-229E virus replication. Importantly, the inhibitory effect of LA and AA on virus replication was also conserved for the highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV). Taken together, our study demonstrated that host lipid metabolic remodeling was significantly associated with human-pathogenic coronavirus propagation. Our data further suggested that lipid metabolism regulation would be a common and druggable target for coronavirus infections., Competing Interests: J.F.-W.C. has received travel grants from Pfizer Corporation Hong Kong and Astellas Pharma Hong Kong Corporation Limited, and was an invited speaker for Gilead Sciences Hong Kong Limited and Luminex Corporation. The other authors declared no conflict of interest. The funding sources had no role in study design, data collection, analysis or interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Human respiratory syncytial virus (HRSV) infection is a significant cause of morbidity and mortality, particularly among the children and the elderly. Despite extensive efforts, there is currently no formally approved vaccine and effective antiviral options against HRSV infection are limited. The development of vaccines and antiviral strategies for HRSV was partly hampered by the lack of an efficient lethal mouse model to evaluate the efficacy of the candidate vaccines or antivirals. In this study, we established a lethal HRSV mouse model by consecutively passaging a clinical HRSV isolate, GZ08-0. GZ08-18 was isolated from mouse bronchioalveolar lavage fluids at the 50 th passage of GZ08-0. Importantly, all GZ08-18-inoculated mice succumbed to the infection by day 7 post infection, whereas all GZ08-0-inoculated mice recovered from the infection. Subsequent investigations demonstrated that GZ08-18 replicated to a higher titer in mouse lungs, induced more prominent lung pathology, and resulted in higher expression levels of a number of key pro-inflammatory cytokines including IFN-γ, MIP-1α, and TNF-α in comparison to that of GZ08-0. The cyclophosphamide pretreatment rendered the mice more susceptible to a lethal outcome with less rounds of virus inoculation. Full genome sequencing revealed 17 mutations in GZ08-18, some of which might account for the dramatically increased pathogenicity over GZ08-0. In addition, by using ribavirin as a positive control, we demonstrated the potential application of this lethal mouse model as a tool in HRSV investigations. Overall, we have successfully established a practical lethal mouse model for HRSV with a mouse-adapted virus, which may facilitate future in vivo studies on the evaluation of candidate vaccines and drugs against HRSV., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Soybean seeds contain higher concentrations of oil (triacylglycerol) and fatty acids than do cereal crop seeds, and the oxidation of these biomolecules during seed storage significantly shortens seed longevity and decreases germination ability. Here, we report that diethyl aminoethyl hexanoate (DA-6), a plant growth regulator, increases germination and seedling establishment from aged soybean seeds by increasing fatty acid metabolism and glycometabolism. Phenotypic analysis showed that DA-6 treatment markedly promoted germination and seedling establishment from naturally and artificially aged soybean seeds. Further analysis revealed that DA-6 increased the concentrations of soluble sugars during imbibition of aged soybean seeds. Consistently, the concentrations of several different fatty acids in DA-6-treated aged seeds were higher than those in untreated aged seeds. Subsequently, quantitative PCR analysis indicated that DA-6 induced the transcription of several key genes involved in the hydrolysis of triacylglycerol to sugars in aged soybean seeds. Furthermore, the activity of invertase in aged seeds, which catalyzes the hydrolysis of sucrose to form fructose and glucose, increased following DA-6 treatment. Taken together, DA-6 promotes germination and seedling establishment from aged soybean seeds by enhancing the hydrolysis of triacylglycerol and the conversion of fatty acids to sugars.

Objective: To analyze the correlation between lymph node metastasis of thoracic esophageal squamous cell carcinoma (ESCC) and clinical and pathological factors, and to provide a reference for the outline of clinical target volume., Methods: The pathological characteristics of 1034 thoracic ESCC patients after surgery were described, and the correlations between clinical and pathological factors and lymph node metastasis were studied by univariate and Logistic multivariate analyses., Results: Lymph node metastasis was significantly correlated with tumor length, invasion depth and differentiation degree (P<0.01), but not gender, age, tumor site or pathological type (P>0.05). Logistic multivariate analysis showed that tumor length, invasion depth and differentiation degree were independent risk factors for thoracic ESCC. The lymph node metastasis rates of mid-thoracic ESCC in the middle mediastinum, lower-thoracic ESCC in the lower mediastinum and abdominal cavity were 18.5%, 35.3% and 19.7% respectively in the T1-T2 stage. In the T3-T4 stage, the lymph node metastasis rates of mid-thoracic ESCC in the middle mediastinum and abdominal cavity were 39.6% and 17.4% respectively, and those of lower-thoracic ESCC in middle and lower mediastina and abdominal cavity were 21.1%, 43.4% and 29.8% respectively. Highly/moderately differentiated mid-thoracic ESCC in the middle mediastinum, lower-thoracic ESCC in middle and lower mediastina and abdominal cavity had the lymph node metastasis rates of 34.7%, 15.1%, 33.5% and 23.7% respectively. Lowly differentiated mid-thoracic ESCC in the middle mediastinum and abdominal cavity had the lymph node metastasis rates of 46.9% a 29.6% respectively, and those of lower-thoracic ESCC in middle and lower mediastina and abdominal cavity were 25.5%, 49.1% and 27.3% respectively., Conclusion: During the outline of radiotherapy target volume for thoracic ESCC, tumor length, invasion depth and differentiation degree should be comprehensively considered to selectively irradiate the regions prone to lymph node metastasis., Competing Interests: Conflicts of Interest: None.

Exploring high-rate electrode materials with excellent kinetic properties is imperative for advanced sodium-storage systems. Herein, novel cubic-like XFe (X = Co, Ni, Mn) Prussian blue analogs (PBAs), as cathodes materials, are obtained through as-tuned ionic bonding, delivering improved crystallinity and homogeneous particles size. As expected, Ni-Fe PBAs show a capacity of 81 mAh g -1 at 1.0 A g -1 , mainly resulting from their physical-chemical stability, fast kinetics, and "zero-strain" insertion characteristics. Considering that the combination of elements incorporated with carbon may increase the rate of ion transfer and improve the lifetime of cycling stability, they are expected to derive binary metal-selenide/nitrogen-doped carbon as anodes. Among them, binary Ni 0.67 Fe 0.33 Se 2 coming from Ni-Fe PBAs shows obvious core-shell structure in a dual-carbon matrix, leading to enhanced electron interactions, electrochemical activity, and "metal-like" conductivity, which could retain an ultralong-term stability of 375 mAh g -1 after 10 000 loops even at 10.0 A g -1 . The corresponding full-cell Ni-Fe PBAs versus Ni 0.67 Fe 0.33 Se 2 deliver a remarkable Na-storage capacity of 302.2 mAh g -1 at 1.0 A g -1 . The rational strategy is anticipated to offer more possibilities for designing advanced electrode materials used in high-performance sodium-ion batteries., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unlike zero-dimensional quantum dots, one-dimensional nanowires/nanorods, and three-dimensional networks or even their bulk counterparts, the charge carriers in two-dimensional (2D) materials are confined along the thickness while being allowed to move along the plane. They have distinct characteristics like strong quantum confinement, tunable thickness, and high specific surface area, which makes them a promising candidate in a wide range of applications such as electronics, topological spintronic devices, energy storage, energy conversion, sensors, biomedicine, catalysis, and so on. After the discovery of the extraordinary properties of graphene, other graphene-like 2D materials have attracted a great deal of attention. Like graphene, to realize their potential applications, high efficiency and low cost industrial scale methods should be developed to produce high-quality 2D materials. The electrochemical methods usually performed under mild conditions are convenient, controllable, and suitable for mass production. In this review, we introduce the latest and most representative investigations on the fabrication of 2D monoelemental Xenes, 2D transition-metal dichalcogenides, and other important emerging 2D materials such as organic framework (MOF) nanosheets and MXenes through electrochemical exfoliation. The electrochemical exfoliation conditions of the bulk layered materials are discussed. The numerous factors which will affect the quality of the exfoliated 2D materials, the possible exfoliating mechanism and potential applications are summarized and discussed in detail. A summary of the discussion together with perspectives and challenges for the future of this emerging field is also provided in the last section.

Zika virus (ZIKV) is a human-pathogenic flavivirus that has recently emerged as a global public health threat. ZIKV infection may be associated with congenital malformations in infected fetuses and severe neurological and systemic complications in infected adults. There are currently limited treatment options for ZIKV infection. AR-12 (OSU-03012) is a celecoxib derivative cellular kinase inhibitor that has broad-spectrum antiviral activities. In this study, we investigated the antiviral activity and mechanism of AR-12 against ZIKV. We evaluated the in vitro anti-ZIKV activity of AR-12, using cell protection and virus yield reduction assays, in multiple clinically relevant cell lines, and the in vivo treatment effects of AR-12 in a lethal mouse model using type I interferon receptor-deficient A129 mice. AR-12 inhibited ZIKV strains belonging to both the African and Asian/American lineages in Huh-7 and/or neuronal cells. AR12's IC 50 against ZIKV was consistently <2 μM in these cells. ZIKV-infected A129 mice treated with intraperitoneally or orally administered AR-12 had significantly higher survival rate (50.0%-83.3% vs 0%, P < 0.05), less body weight loss, and lower blood and tissue ZIKV RNA loads than untreated control A129 mice. These anti-ZIKV effects were likely the results of down-regulation of the PI3K/Akt pathway by AR-12. Clinical trials using the clinically available and broad-spectrum AR-12 as an empirical treatment should be considered especially for patients residing in or returning from areas endemic of ZIKV and other arboviral infections who present with an acute undifferentiated febrile illness., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Emerging evidence suggests that the stress hormone abscisic acid (ABA) is also involved in the floral transition control. The transcription factors ABA INSENSITIVE4 (ABI4) and ABI5 negatively regulate flowering by directly promoting FLOWERING LOCUS C expression, and ABI3 also negatively regulates the floral transition. However, the genetic relationships between ABI4 and both ABI5 and ABI3 remain elusive. Here, we generated transgenic plants overexpressing ABI4 in the abi5 (OE-ABI4::abi5) and abi3 backgrounds (OE-ABI4::abi3). The flowering phenotypic analysis demonstrated that OE-ABI4::abi5 and OE-ABI4::abi3 plants exhibited delayed flowering. These findings suggest that ABI4 independently regulates floral transition but not through ABI5 and ABI3 cascades.

Objective: To understand the professional theory, prevention and control practice, experimental diagnosis and other technical skills of parasitic diseases among technicians of all levels of disease control and prevention institutions, so as to provide the evidence for strengthening the capacity building of Chinese professional personnel., Methods: According to the method of recommendation at all levels, the subjects from disease control and prevention institutions at province, prefecture or county levels were chosen to assess the theory of parasitic diseases and test operation skills by using the method of answering the questions together with on-site operations in China. A database was built consisting of subjects' basic information and assessment scores. By using the method of hierarchical classification, the scores by gender, age, professional title, institutions and places of participants were analyzed., Results: A total of 124 professions in prevention and treatment of parasitic diseases in 31 provinces (cities and regions) were evaluated in China. The average total score of all the subjects was 125.0 ± 35.2, with a passing rate of 54.8%. The average scores of male subjects and female subjects were 120.8 ± 34.2 and 126.6 ± 35.4 respectively; the average scores of the subjects aged under 30 years, between 30 and 40 years, and above 40 years were 125.6 ± 33.6, 124.9 ± 35.8, and 119.3 ± 45.9 respectively; the average scores of persons with junior, intermediate and senior professional titles were 119.8 ± 35.8, 136.0 ± 32.5 and 127.1 ± 40.9 respectively. The average theoretical assessment score of all the subjects was 67.4 ± 15.6, with a passing rate of 68.5%. The average practical skill assessment score of all the subjects was 57.6 ± 21.8, with a passing rate of 46.0%. The average detection rates of Plasmodium falciparum , P. vivax , P. ovale and P. malariae in endemic and non-endemic areas were 64.1%, 72.8%, 57.0%, 58.3% and 35.9%, 46.9%, 33.3%, 43.8%, respectively. The detection ability of professionals in endemic areas was significantly higher than that in non-endemic areas ( χ 2 = 767.10, 462.12, 134.97 and 360.80, respectively, all P < 0.01). The total detection rate of schistosome eggs was 48.7%, and the detection rates of schistosome eggs were 67.4% and 36.8% in endemic and non-endemic areas, respectively. The detection ability of professionals in endemic areas was significantly higher than that in non-endemic areas ( χ 2 = 817.74, P < 0.01). The detection rates of Ascaris lumbricoides , Trichuris trichiura , and Enterobius vermicularis were 85.7%, 78.6%, 91.7%, and 61.8%, 23.5% and 74.4% in the technicians in southern region and northern region of China, showing significant differences ( χ 2 = 622.58, 301.70 and 588.71, respectively, all P < 0.01)., Conclusions: The overall results of the subjects are good, but the technical operation capability of them is relatively low. Therefore, the specific training based on daily work needs should be enhanced. In addition, we should attach importance to talent cultivation and technical reserve, and strengthen the construction of the team, so as to meet the needs of the prevention and control of parasitic diseases.

Transition metal sulfides (TMSs) have been extensively studied as electrode materials for sodium-ion batteries by virtue of their high theoretical capacity. However, the poor cyclability limits the practical application of TMSs in sodium ion batteries. In this study, N-rich carbon-coated Co 3 S 4 ultrafine nanocrystal (Co 3 S 4 @NC) was prepared by utilizing ZIF-67 as a precursor through continuous carbonization and sulfuration processes, exhibiting ultrafine nanocrystals with a diameter of about 5 nm. When utilized as the anode for sodium ion batteries, the nanohybrid material exhibits remarkable cycling performance with a high specific capacity of 420.9 mA h g -1 at the current density of 100 mA g -1 after 100 cycles, indicating that the cycling performance is strengthened by the nitrogen-doped carbon coating. Impressively, the obtained material shows good rate performances with reversible specific capacities of 386.7, 284.0, and 151.2 mA h g -1 at 400, 1000, and 1400 mA g -1 , respectively, due to the high surface-capacitance contribution and porous structure inherited from the precursor, which finally results in the increase in infiltration of electrolyte and the accelerating diffusion rate of Na + . This study sheds light on the routes to improve the performance of TMSs@nitrogen-doped carbon nanohybrid materials for sodium ion batteries.

Background: Transversus abdominis plane (TAP) block can provide effective analgesia for abdominal surgery. However, many randomized controlled trials (RCTs) have shown controversial results in hysterectomy. We conducted a meta-analysis of RCTs to investigate the effectiveness of TAP block after hysterectomy., Methods: Studies were gathered from PubMed, MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov databases up to March 2018. RCTs involving TAP blocks in women undergoing hysterectomy were selected. The primary outcome of mean 24 hours morphine consumption and other outcomes, such as time to first request for analgesic, rest, and pain scores on movement at different times, and rates of nausea and vomiting, were compared between TAP block and no or sham block groups., Results: A total of 841 participants were included in the 13 selected RCTs. Compared with no or sham blocks, TAP block reduced mean 24-hour morphine consumption in abdominal hysterectomy (AH) (weighted mean difference [WMD] -10.77 mg, P =0.04) but not in laparoscopic hysterectomy (LH)/robotic-assisted hysterectomy (RH) (WMD -1.39 mg, P =0.24). TAP block in AH prolonged analgesic time and reduced nausea and vomiting rates. TAP block also reduced the postoperative pain score at rest and on movement at different times in the AH subgroup, but it did not significantly reduce the postoperative pain score at rest, 6-8, and 24 hours, as well as the pain score on movement at 2, 6-8, and 24 hours in the LH/RH subgroup., Conclusion: TAP block is an effective analgesic for AH. TAP block can reduce postoperative morphine consumption in AH and pain scores at rest and on movement for AH without increasing side effects. However, TAP block has limited analgesic effects for women undergoing LH/RH, as it does not reduce postoperative morphine consumption and pain scores at rest and on movement., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Coronavirus tropism is predominantly determined by the interaction between coronavirus spikes and the host receptors. In this regard, coronaviruses have evolved a complicated receptor-recognition system through their spike proteins. Spikes from highly related coronaviruses can recognize distinct receptors, whereas spikes of distant coronaviruses can employ the same cell-surface molecule for entry. Moreover, coronavirus spikes can recognize a broad range of cell-surface molecules in addition to the receptors and thereby can augment coronavirus attachment or entry. The receptor of Middle East respiratory syndrome coronavirus (MERS-CoV) is dipeptidyl peptidase 4 (DPP4). In this study, we identified membrane-associated 78-kDa glucose-regulated protein (GRP78) as an additional binding target of the MERS-CoV spike. Further analyses indicated that GRP78 could not independently render nonpermissive cells susceptible to MERS-CoV infection but could facilitate MERS-CoV entry into permissive cells by augmenting virus attachment. More importantly, by exploring potential interactions between GRP78 and spikes of other coronaviruses, we discovered that the highly conserved human GRP78 could interact with the spike protein of bat coronavirus HKU9 (bCoV-HKU9) and facilitate its attachment to the host cell surface. Taken together, our study has identified GRP78 as a host factor that can interact with the spike proteins of two Betacoronaviruses , the lineage C MERS-CoV and the lineage D bCoV-HKU9. The capacity of GRP78 to facilitate surface attachment of both a human coronavirus and a phylogenetically related bat coronavirus exemplifies the need for continuous surveillance of the evolution of animal coronaviruses to monitor their potential for human adaptations., (© 2018 Chu et al.)

Limited efficacy of current antivirals and antiviral-resistant mutations impairs anti-influenza treatment. Here, we evaluate the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Viral replication is significantly reduced in cell lines transfected with DIG-3. Mice treated with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus, respectively, have significantly better survivals (80% and 50%) than control mice (0%). We further develop a dual-functional peptide TAT-P1, which delivers DIG-3 with high efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification. TAT-P1/DIG-3 is more effective than jetPEI/DIG-3 in treating A(H7N7) or A(H1N1)pdm09-infected mice and shows potent prophylactic protection on A(H7N7) or A(H1N1)pdm09-infected mice. The addition of P1 peptide, which prevents endosomal acidification, can enhance the protection of TAT-P1/DIG-3 on A(H1N1)pdm09-infected mice. Dual-functional TAT-P1 with DIG-3 can effectively protect or treat mice infected by avian and seasonal influenza virus.

Objective: To understand the risk factors of cystic echinococcosis in Tibetan population, so as to provide the reference for development of prevention and control strategies., Methods: Four cystic echinococcosis highly-prevalent townships were selected from Naqu County of Tibet and Shiqu County of Sichuan Province, which had similar environmental and altitude conditions, from August to September, 2017. Applying the 1∶1 case-control study, a household survey was conducted to investigate the risk factors of echinococcosis in humans., Results: A total of 378 residents were investigated, of which the numbers of cases and non-cases were both 189. The univariate analysis showed that the years of keeping dogs ( OR = 1.032, P < 0.05), the number of keeping dogs ( OR = 1.260, P < 0.05), the way of raising dogs ( OR = 1.434, P < 0.05), feeding with raw viscera ( OR = 1.531, P < 0.05), and there being stray dogs around ( OR = 1.946, P < 0.05) were the risk factors of echinococcosis. As a result of the multivariate logistic regression analysis, only three risk factors, feeding with raw viscera, there being stray dogs around, and drinking water resource, were included in the regression model., Conclusions: Feeding with raw viscera, there being stray dogs around, and drinking water resource are the risk factors of echinococcosis in humans.

Cysteine-X-cysteine ligand 8 (CXCL8) was originally discovered as a proinflammatory chemokine. Recently, CXCL8 has been shown to act as an oncogene in several types of human cancers. However, the clinical and prognostic significance of CXCL8 in cervical cancer is poorly understood. In our study, we found that CXCL8 was highly expressed in cervical cancer tissues compared with normal cervical tissues in microarray datasets (GSE9750 and GSE7803). CXCL8 mRNA and protein expressions were increased in cervical cancer tissues and cell lines compared with normal cervical tissues and cervical epithelial cell lines. CXCL8 protein expression was significantly correlated with clinical stage, distant metastasis, histological type, and histological grade. CXCL8 high expression was a poor independent prognostic parameter for cervical cancer patients. In conclusion, CXCL8 is highly expressed in cervical cancer tissues and cell lines, and correlated with malignant status and prognosis in cervical cancer patients., (© 2017 The Author(s).)

Auxin is an important phytohormone which mediates diverse development processes in plants. Published research has demonstrated that auxin induces seed dormancy. However, the precise mechanisms underlying the effect of auxin on seed germination need further investigation, especially the relationship between auxins and both abscisic acid (ABA) and gibberellins (GAs), the latter two phytohormones being the key regulators of seed germination. Here we report that exogenous auxin treatment represses soybean seed germination by enhancing ABA biosynthesis, while impairing GA biogenesis, and finally decreasing GA 1 /ABA and GA 4 /ABA ratios. Microscope observation showed that auxin treatment delayed rupture of the soybean seed coat and radicle protrusion. qPCR assay revealed that transcription of the genes involved in ABA biosynthetic pathway was up-regulated by application of auxin, while expression of genes involved in GA biosynthetic pathway was down-regulated. Accordingly, further phytohormone quantification shows that auxin significantly increased ABA content, whereas the active GA 1 and GA 4 levels were decreased, resulting insignificant decreases in the ratiosGA 1 /ABA and GA 4 /ABA.Consistent with this, ABA biosynthesis inhibitor fluridone reversed the delayed-germination phenotype associated with auxin treatment, while paclobutrazol, a GA biosynthesis inhibitor, inhibited soybean seed germination. Altogether, exogenous auxin represses soybean seed germination by mediating ABA and GA biosynthesis.

Aims: Two-thirds of early pregnancy failures present with reduced trophoblast invasion, and SLIT2/ROBO1 signalling is considered to play an important role in trophoblast function during pregnancy. We investigated SLIT2/ROBO1 signalling associated with missed and threatened miscarriage during early gestation., Methods and Results: Human placenta samples were collected from women with missed miscarriage (n = 25), threatened miscarriage (n = 22) and termination of pregnancy controls (n = 32). Corresponding decreases in beta human chorionic gonadotrophin (β-hCG) levels and shallow trophoblast invasion were observed in patients with missed and threatened miscarriage, immunohistological staining revealed abnormal Slit2 and Robo1, as well as E-cadherin and activating protein-2 alpha (AP-2α) expression in villi and extravillous trophoblasts, and the expression of these proteins were confirmed in villi and decidua of miscarriage material by Western blotting. Using HTR8/SVneo cells, blocking SLIT2/ROBO1 signalling promoted cell migration, proliferation and suppressed differentiation. Moreover, blocking SLIT2/ROBO1 signalling in HTR8/SVneo cells altered trophoblast differentiation-related and angiogenesis-related gene mRNA expression, which also occurred in the tissues of missed and threatened miscarriage., Conclusions: SLIT2/ROBO1 signalling may regulate trophoblast differentiation and invasion causing restricting β-hCG production, shallow trophoblast invasion and inhibiting placental angiogenesis in missed and threatened miscarriage during the first trimester., (© 2017 John Wiley & Sons Ltd.)

Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA) while positively mediating abscisic acid (ABA) biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN), an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde) level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA 1 , GA 3 , and GA 4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA 1 /ABA, GA 3 /ABA, and GA 4 /ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

Objective: To report the integrated progress of the hydatid disease information management system, and to provide the reference for further system improvements by analysis of results on simulation test feedback., Methods: The work of institutional code matching by collecting fundamental and integrated information of the system in epidemic areas of hydatid disease was carried out, and professional control agencies were selected to carry out the simulation test., Results: The results of agencies code matching at stage indicated the average completion rate was 94.30% on administrative agencies, 69.94% on registered professional agencies and 56.40% on professional institutions matching related to hydatid disease prevention and control implements in seven provinces (autonomous regions) and Xinjiang Production and Construction Corps. Meanwhile, the response rate of open-ended proposals was 93.33% on fifteen feedbacks, and the statistics showed 21.43% believed the system was low fluency, 64.29% considered the system was inconvenience for data inputs and 42.86% considered it would be improved on system statistics functions, of which 27.78% were provincial users, 22.22% were the city users and 50.00% were the county users., Conclusions: The hydatid disease prevention information management system meets the fundamental needs of the majority agencies in hyperendemic areas of echinococcosis, it needs to develop the further test with more agencies joining after the work of the institutional code matching completion and the system service improvement in the next stage.

Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group ( P  < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC.

Substitutions in the PA N-terminus (PAN) of influenza A viruses are associated with viral pathogenicity. During our previous study, which identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing the substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase and endonuclease activities when compared with those of the wild-type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 influenza A virus.

Seed germination and early seedling establishment are critical stages during a plant's life cycle. These stages are precisely regulated by multiple internal factors, including phytohormones and environmental cues such as light. As a family of small molecules discovered in wildfire smoke, karrikins (KARs) play a key role in various biological processes, including seed dormancy release, germination regulation, and seedling establishment. KARs show a high similarity with strigolactone (SL) in both chemical structure and signaling transduction pathways. Current evidence shows that KARs may regulate seed germination by mediating the biosynthesis and/or signaling transduction of abscisic acid (ABA), gibberellin (GA) and auxin [indoleacetic acid (IAA)]. Interestingly, KARs regulate seed germination differently in different species. Furthermore, the promotion effect on seedling establishment implies that KARs have a great potential application in alleviating shade avoidance response, which attracts more and more attention in plant molecular biology. In these processes, KARs may have complicated interactions with phytohormones, especially with IAA. In this updated review, we summarize the current understanding of the relationship between KARs and SL in the chemical structure, signaling pathway and the regulation of plant growth and development. Further, the crosstalk between KARs and phytohormones in regulating seed germination and seedling development and that between KARs and IAA during shade responses are discussed. Finally, future challenges and research directions for the KAR research field are suggested.

The relationship between the Pro12Ala polymorphism of PPARγ and the risk of gestational diabetes mellitus remains unresolved. Here, we attempted to resolve this inconsistency. Case-control studies pertaining to the effect of the Pro12Ala polymorphism in the PPARγ protein and risk of gestational diabetes mellitus were extracted from the HuGE, PubMed, Web of Science, CNKI, and SinoMed databases after an extensive literature search. The studies were statistically analyzed using STATA (v.12.0) software. Twelve case-control studies composed of 2968 GDM cases and 5576 controls that fulfilled the inclusion criteria were included in this meta-analysis. We identified no significant relation between the Pro12Ala polymorphism of PPAR-γ and risk of GDM, when analyzed by the allele [G vs C: odds ratio (OR) = 0.85; 95% confidence interval (CI): 0.71-1.01] and dominant (CG+GG vs CC: OR = 0.86; 95% CI: 0.72-1.03) models. Subgroup analysis by ethnicity revealed that East Asian and Middle Eastern females expressing the A allele showed reduced susceptibility to GDM. Additionally, we observed significant differences between the East Asian, Middle Eastern, and Caucasian females (P = 0.008) with respect to GDM susceptibility. The results of this meta-analysis indicated the influence of ethnicity in determining GDM susceptibility, in the presence of a Pro12Ala polymorphism in PPARγ.

To evaluate the pathogenicity, a highly pathogenic avian influenza H7N7 virus (A/Netherlands/219/03) isolated from human was passaged in mice. A mutant virus (mH7N7) with attenuated virulence was isolated from mouse lung, which had a 3-log higher MLD50 than the wild-type virus (wH7N7). Sequence analysis and reverse genetics study revealed that mutations in PA account for the compromised viral replication in mammalian cells and mice. A mini-genome assay demonstrated that PA mutations P103H and S659L can cooperatively decrease polymerase activity. Actually, PA with double mutation P103H-S659L cannot sustain the generation of live virus by reverse genetics. Interestingly, the prior infection of mH7N7 virus provided mice with cross-protection against lethal challenge of other subtypes of influenza A virus including H1N1, H5N1 and H7N9. In conclusion, we demonstrated that PA mutations P103H and S659L can cooperatively reduce polymerase activity and viral replication in mammalian cells and attenuate pathogenicity in mice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The islets of Langerhans contain different types of endocrine cells, which are crucial for glucose homeostasis. β- and α-cells that release insulin and glucagon, respectively, are most abundant, whereas somatostatin-producing δ-cells and particularly pancreatic polypeptide-releasing PP-cells are more scarce. Studies of islet cell function are hampered by difficulties to identify the different cell types, especially in live-cell imaging experiments when immunostaining is unsuitable. The aim of the present study was to create a set of vectors for fluorescent protein expression with cell-type-specific promoters and evaluate their applicability in functional islet imaging. We constructed six adenoviral vectors for expression of red and green fluorescent proteins controlled by the insulin, preproglucagon, somatostatin, or pancreatic polypeptide promoters. After transduction of mouse and human islets or dispersed islet cells, a majority of the fluorescent cells also immunostained for the appropriate hormone. Recordings of the sub-plasma membrane Ca(2+) and cAMP concentrations with a fluorescent indicator and a protein biosensor, respectively, showed that labeled cells respond to glucose and other modulators of secretion and revealed a striking variability in Ca(2+) signaling among α-cells. The measurements allowed comparison of the phase relationship of Ca(2+) oscillations between different types of cells within intact islets. We conclude that the fluorescent protein vectors allow easy identification of specific islet cell types and can be used in live-cell imaging together with organic dyes and genetically encoded biosensors. This approach will facilitate studies of normal islet physiology and help to clarify molecular defects and disturbed cell interactions in diabetic islets., Competing Interests: Compliance with ethical standards Ethical approval All procedures for animal handling and islet isolation were approved by the Uppsala animal ethics committee, and all experiments with human islets were approved by the Uppsala human ethics committee. Conflict of interest The authors declare that they have no conflict of interest.

Although Sapovirus (Caliciviridae) has been accepted as one of the causes of acute gastroenteritis worldwide, little is known about the genetic characteristics of the whole genome of sapoviruses in China, especially those that infect humans. Here we report the complete genome sequence of a sapovirus strain, Human/Zhejiang1/2015/China, obtained from a child with acute gastroenteritis in Hangzhou, Zhejiang Province, China. Samples were collected and delivered to the CDC laboratories and were detected by RT-PCR. Sanger sequencing was used to obtain the full genome and molecular characterization of the genome was determined. A phylogenetic analysis of the genome was also performed. The results indicated that Human/Zhejiang1/2015/China belongs to Genogroup I. No recombination events were detected. This is the first complete sequence from a child to be reported in China. The sequence information is important for surveillance of this emerging gastrointestinal infection., Competing Interests: The authors declare that they have no competing interests. Ethics statement This study was approved by the ethics committee of the Zhejiang Provincial Center for Disease Control and Prevention (ZJCDC), China. This study was done in accordance with the Declaration of Helsinki, Good Clinical Practice, and Chinese regulatory requirements.

Human umbilical cord mesenchymal stem cells (UCMSCs) have recently been shown to hold great therapeutic potential for the treatment of spinal cord injury (SCI). However, the number of engrafted cells has been shown to decrease dramatically post-transplantation. Physioxia is known to enhance the paracrine properties and immune modulation of stem cells, a notion that has been applied in many clinical settings. We therefore hypothesized that preconditioning of UCMSCs in physioxic environment would enhance the regenerative properties of these cells in the treatment of rat SCI. UCMSCs were pretreated with either atmospheric normoxia (21% O2, N-UCMSC) or physioxia (5% O2, P-UCMSC). The MSCs were characterized using flow cytometry, immunocytochemistry, and real-time polymerase chain reaction. Furthermore, 10(5) N-UCMSC or P-UCMSC were injected into the injured spinal cord immediately after SCI, and locomotor function as well as cellular, molecular and pathological changes were compared between the groups. We found that N-UCMSC and P-UCMSC displayed similar surface protein expression. P-UCMSC grew faster, while physioxia up-regulated the expression of trophic and growth factors, including hepatocyte growth factor (HGF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor(VEGF), in UCMSCs. Compared to N-UCMSC, treatment with P-UCMSC was associated with marked changes in the SCI environment, with a significant increase in axonal preservation and a decrease in the number of caspase-3+ cells and ED-1+ macrophages. These changes were accompanied by improved functional recovery. Thus, the present study indicated that preculturing UCMSCs under 5% lowered oxygen physioxic conditions prior to transplantation improves their therapeutic potential for the treatment of SCI in rats., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Karrikins (KAR) are a class of signal compounds, discovered in wildfire smoke, which affect seed germination. Currently, numerous studies have focused on the model plant Arabidopsis in the KAR research field, rather than on crops. Thus the regulatory mechanisms underlying KAR regulation of crop seed germination are largely unknown. Here, we report that KAR delayed soybean seed germination through enhancing abscisic acid (ABA) biosynthesis, while impairing gibberellin (GA) biogenesis. Interestingly, KAR only retarded soybean seed germination under shaded conditions, rather than under dark and white light conditions, which differs from in Arabidopsis. Phytohormone quantification showed that KAR enhanced ABA biogenesis while impairing GA biosynthesis during the seed imbibition process, and subsequently, the ratio of active GA4 to ABA was significantly reduced. Further qRT-PCR analysis showed that the transcription pattern of genes involved in ABA and GA metabolic pathways are consistent with the hormonal measurements. Finally, fluridone, an ABA biogenesis inhibitor, remarkably rescued the delayed-germination phenotype of KAR-treatment; and paclobutrazol, a GA biosynthesis inhibitor, inhibited soybean seed germination. Taken together, these evidences suggest that KAR inhibit soybean seed germination by mediating the ratio between GA and ABA biogenesis.

Automatic liver segmentation not only plays an important role in the analysis of liver disease, but also reduces the cost and humanity's impact in segmentation. In addition, liver segmentation is a very challenging task due to countless anatomical variations and technical difficulties. Many methods have been designed to overcome these challenges, but these methods still need to be improved to obtain the desired segmentation precision. In this paper, a fast algorithm is proposed for liver extraction from CT images with single-block linear detection. The proposed method does not require iteration; thus, the computational time and complexity are decreased enormously. In addition, the initialization is not crucial in the algorithm, so the algorithm's robustness and specificity are improved. The experimental evaluation of the proposed method revealed effective segmentation in normal and abnormal (liver hemangioma and liver cancer) abdominal CT images. The average sensitivity, accuracy, and specificity for liver cancer are 96.59%, 98.65%, and 99.03%, respectively. The results of image segmentation approximate the manual segmentation results by the technical doctor. Moreover, our method shows superior flexibility to newly published method with comparable performance. The advantage of our method is verified with experimental results, which is described in detail.

Oxidative damage to the constituents of the eye lens is a major mechanism in the initiation and development of cataract. Lunasin, a 43-amino acids chemoprevention peptide, has been proved to possess potent anti-oxidative activity other than its established anticancer activities. Herein, we explored whether lunasin has preventative effects on d-galactose-induced experimental cataract in rat. After modeling, SD rats were administrated by instillation, 80 µM of lunasin eye drops to each eye thrice daily and consecutively for 30 days. As a result, lunasin treatment effectively inhibited the progression of d-galactose-induced experimental cataract, and protected the lenses of rats from oxidative damage and attenuated the lipid peroxidation through up-regulation of antioxidant enzymes, and inhibited the activation of polyol pathway by decreasing AR activity. Additionally, in vitro studies proved that lunasin treatment could protect human lens epithelial cells (hLECs) against d-galactose induced cell damage and apoptosis, and up-regulate antioxidant enzymes. This is the first demonstration that lunasin could inhibit d-galactose-induced experimental cataract in rats by protecting against oxidative damage and inhibiting the activation of polyol pathway.

Amino acid residues in the N-terminal of the PA subunit (PAN) of the influenza A virus polymerase play critical roles in endonuclease activity, protein stability, and viral RNA (vRNA) promoter binding. In addition, PAN is highly conserved among different subtypes of influenza virus, which suggests PAN to be a desired target in the development of anti-influenza agents. We selected DNA aptamers targeting the intact PA protein or the PAN domain of an H5N1 virus strain using systematic evolution of ligands by exponential enrichment (SELEX). The binding affinities of selected aptamers were measured, followed by an evaluation of in vitro endonuclease inhibitory activity. Next, the antiviral effects of enriched aptamers against influenza A virus infections were examined. A total of three aptamers targeting PA and six aptamers targeting PAN were selected. Our data demonstrated that all three PA-selected aptamers neither inhibited endonuclease activity nor exhibited antiviral efficacy, whereas four of the six PAN-selected aptamers inhibited both endonuclease activity and H5N1 virus infection. Among the four effective aptamers, one exhibited cross-protection against infections of H1N1, H5N1, H7N7, and H7N9 influenza viruses, with a 50% inhibitory concentration (IC50) of around 10 nM. Notably, this aptamer was identified at the 5th round but disappeared after the 10th round of selection, suggesting that the identification and evaluation of aptamers at early rounds of selection may be highly helpful for screening effective aptamers. Overall, our study provides novel insights for screening and developing effective aptamers for use as anti-influenza drugs., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Chronic palmitate exposure impairs glucose-stimulated insulin secretion and other aspects of β-cell function, but the underlying mechanisms are not known. Using various live-cell fluorescence imaging approaches, we show here that long-term palmitate treatment influences cAMP signaling in pancreatic β-cells. Glucose stimulation of mouse and human β-cells induced oscillations of the subplasma-membrane cAMP concentration, but after 48 h exposure to palmitate, most β-cells failed to increase cAMP in response to glucose. In contrast, GLP-1-triggered cAMP formation and glucose- and depolarization-induced increases in cytoplasmic Ca2+ concentration were unaffected by the fatty acid treatment. Insulin secretion from control β-cells was pulsatile, but the response deteriorated after long-term palmitate exposure. Palmitate-treated mouse islets showed reduced expression of adenylyl cyclase 9, and knockdown of this protein in insulinoma cells reduced the glucose-stimulated cAMP response and insulin secretion. We conclude that impaired glucose-induced generation of cAMP is an important determinant of defective insulin secretion after chronic palmitate exposure., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

The aim of this study was to determine whether double labelling of human umbilical cord mesenchymal stem cells (hUCMSCs) with gadolinium-diethylene triamine penta-acetic acid (Gd-DTPA) and PKH26 influences their biological characteristics. A tissue adherence technique was used to separate and purify the hUCMSCs and flow cytometry was performed to detect the surface markers expressed on them. Gd-DTPA and PKH26 were used to label the stem cells and MRI and fluorescence microscopy were used to detect the double-labelled hUCMSCs. A MTT assay was used to delineate the growth curve. Transmission electron microscopy (TEM) and atomic force microscopy were used to demonstrate the ultrastructural features of the hUCMSCs. Flow cytometry showed that hUCMSCs highly expressed CD29, CD90, CD44 and CD105. No expression of CD31, CD34 and CD45 was detected. Very low expression of HLA-DR and CD40 was detected. Atomic force microscopy showed these cells were long, spindle shaped, and the cytoplasm and nucleus had clear boundaries. After double labelling, TEM showed Gd particles aggregated in the cytoplasm in a cluster pattern. The proliferation activity, cell cycle, apoptosis and differentiation of the stem cells were not influenced by double labelling. Thus a tissue adherence technique is helpful to separate and purify hUCMSCs effectively; and Gd-DTPA and PKH26 are promising tracers in the investigation of migration and distribution of hUCMSCs in vivo., (© 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.)

Saw palmetto extract can induce the apoptosis of prostate cancer cells. The aim of the present study was to investigate the effect of saw palmetto extract on the phosphatidylinositol 3-kinase (PI3K)/Akt signaling transduction pathway in human glioma U87 and U251 cell lines. Suspensions of U87 and U251 cells in a logarithmic growth phase were seeded into six-well plates at a density of 10 4 cells/well. In the experimental group, 1 μl/ml saw palmetto extract was added, while the control group was cultured without a drug for 24 h. The expression levels of PI3K, B-cell lymphoma-extra large (Bcl-xL) and p53 were evaluated through western blot analysis. In the experimental group, the U87 and U251 cells exhibited a lower expression level of PI3K protein as compared with the control group (t=6.849; P<0.001). In addition, the two cell lines had a higher expression level of p53 protein in the experimental group as compared with the control group (t=40.810; P<0.001). Protein expression levels of Bcl-xL decreased significantly in the experimental group as compared with the control group (t=19.640; P=0.000). Therefore, saw palmetto extract induces glioma cell growth arrest and apoptosis via decreasing PI3K/Akt signal transduction.

A RP-high-performance liquid chromatography (HPLC) method was developed for quality control of Chinese propolis by simultaneous analysis of 12 flavonoids and 8 phenolic acids. The results showed that vanillic acid, rutin, myricetin, and luteolin were not detected in all of the analyzed propolis and poplar tree gum samples. The caffeic acid, ferulic acid and p-coumaric acid were not detected in poplar tree gum but were detected in propolis, which suggest that they are practical indexes of distinguishing propolis from poplar tree gum. The flavonoid profiles of poplar tree gum were found to be similar to those of propolis, which are dominated by pinobanksin, pinocembrin, 3-O-acetylpinobanksin, chrysin, and galangin. Therefore, the proposed method could be applied to exclude poplar tree gum from propolis with cafferic acid, ferulic acid, and p-coumaric acid as qualitative markers, and distinguish poplar source resin from other illegal substances, and evaluate the quality grading of poplar-type propolis with pinobanksin, pinocembrin, 3-O-acetylpinobanksin, chrysin, and galangin as qualitative and quantitative markers., (© 2014 Institute of Food Technologists®)

Owing to the growing global environmental problems, demands for environmentally friendly, fully biodegradable sustainable composites have substantially increased across various industries. Inspired by the composite structure of cocoon silk, we fabricated a fully green composite fiber (GCF) that is based on the lotus fiber (LF) and a biodegradable polymer, namely poly(vinyl alcohol) (PVA). After the formation of cross-linkages between the LF and PVA, the mechanical properties of this bioinspired GCF had substantially improved. In particular, the specific mechanical properties are superior to those of cocoon silk and other natural fibers. These findings suggest that LFs may be used as reinforcement materials for the fabrication of bulk green materials for various industries, such as the textile, medical, automobile, and aerospace industries., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Stromal cell-derived factor-1 (SDF-1) is a chemokine and plays an important role in cell migration, whereas its role in diabetic nephropathy has not been illustrated distinctly. We hypothesized that SDF-1α may have an effect on extracellular matrix (ECM) accumulations in mesangial cells exposed to transforming growth factor-β1 (TGF-β1) or high glucose in vitro. The exogenous SDF-1α was added into rat mesangial cells incubated with TGF-β1 or high glucose in the medium. The expression of fibronectin (FN) was quantitated by real-time RT-PCR, and the change of Akt and Smad3 measured by western blotting. SDF-1α, its receptor C-X-C chemokine receptor type 4 (CXCR4) and FN mRNA were expressed in rat mesangial cells. Both TGF-β1 and high glucose raised the mRNA expressions of CXCR4 and FN in the cells. SDF-1α inhibited the elevated FN mRNA expression induced by TGF-β1 and high glucose through CXCR4 and PI3K/Akt signaling pathway, as the effect of SDF-1α was reversed by CXCR4 antagonist AMD3100 and PI3K inhibitor LY294002. Correspondingly, TGF-β1 induced Smad3 phosphorylation was suppressed when PI3K/Akt signaling pathway was activated by SDF-1α. Based on these findings, we conclude that SDF-1α ameliorates TGF-β1/high glucose induced ECM accumulations in mesangial cells, which may mediate through PI3K/Akt pathway. This novel mechanism may bring a new insight to our understandings of diabetic nephropathy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

People with type 2 diabetes (T2DM) mellitus are high risk for dementia and Alzheimer's disease (AD) via several plausible pathways. However, the underlying mechanisms have been still unclear, and the relation of immune injury to the pathogenesis of T2DM-related AD is not yet completely understood. Our present study aimed to elucidate the possible role of immunoglobulin IgG in the immune process of AD associated with T2DM in db/db mice. Hippocampi of 20 db/db mice and 20 C57BL/6 mice were subjected to immunohistochemistry and immunofluorescence assays. The phosphorylation of tau, glycogen synthase kinase (GSK)-3β and AKT activity was examined by Western blot analysis. IgG purified from the sera of IgG deposit-positive db/db mice was stereotaxically injected into the hippocampi of another 12 db/db mice and 12 C57BL/6 mice. The phosphorylation of tau, Abeta, GSK-3β and AKT activity was analyzed. Compared with the C57BL/6 control, 13 of the 20 db/db mice exhibited high levels of IgG deposits in the hippocampus. Treatment with IgG triggered tau hyperphosphorylations and Abeta deposition, which are likely major factors in AD. Meanwhile, IgG inhibited AKT phosphorylation and promoted GSK-3β activity. The IgG deposits observed in some db/db mice were possibly related to the impairment of T2DM-related AD development. Some autoimmune processes may be involved in AD in type 2 diabetes mellitus development at the level of the hippocampus., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Specificity and versatility in cyclic AMP (cAMP) signalling are governed by the spatial localisation and temporal dynamics of the signal. Phosphodiesterases (PDEs) are important for shaping cAMP signals by hydrolyzing the nucleotide. In pancreatic β-cells, glucose triggers sub-plasma-membrane cAMP oscillations, which are important for insulin secretion, but the mechanisms underlying the oscillations are poorly understood. Here, we investigated the role of different PDEs in the generation of cAMP oscillations by monitoring the concentration of cAMP in the sub-plasma-membrane space ([cAMP](pm)) with ratiometric evanescent wave microscopy in MIN6 cells or mouse pancreatic β-cells expressing a fluorescent translocation biosensor. The general PDE inhibitor IBMX increased [cAMP](pm), and whereas oscillations were frequently observed at 50 µM IBMX, 300 µM-1 mM of the inhibitor caused a stable increase in [cAMP](pm). The [cAMP](pm) was nevertheless markedly suppressed by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine, indicating IBMX-insensitive cAMP degradation. Among IBMX-sensitive PDEs, PDE3 was most important for maintaining a low basal level of [cAMP](pm) in unstimulated cells. After glucose induction of [cAMP](pm) oscillations, inhibitors of PDE1, PDE3 and PDE4 inhibitors the average cAMP level, often without disturbing the [cAMP](pm) rhythmicity. Knockdown of the IBMX-insensitive PDE8B by shRNA in MIN6 cells increased the basal level of [cAMP](pm) and prevented the [cAMP](pm)-lowering effect of 2',5'-dideoxyadenosine after exposure to IBMX. Moreover, PDE8B-knockdown cells showed reduced glucose-induced [cAMP](pm) oscillations and loss of the normal pulsatile pattern of insulin secretion. It is concluded that [cAMP](pm) oscillations in β-cells are caused by periodic variations in cAMP generation, and that several PDEs, including PDE1, PDE3 and the IBMX-insensitive PDE8B, are required for shaping the sub-membrane cAMP signals and pulsatile insulin release.

Aim: Occlusion of the middle ferebral artery in rats may cause secondary injury that is not associated with middle ferebral artery feeding zone. This entity has been investigated very rarely., Material and Methods: HE staining method observed the changes of cerebellar cortex after MCAO operation. Electron Microscopy and TUNEL methods observed the apoptosis of neural cells of cerebellar cortex after MCAO in rats. Immunohistochemical analyses method observed the caspase-3 in neural cells of cerebellar cortex., Results: The results of HE staining indicated that no ischemia-necrosis changes of cerebellar cortex tissue were observed after MCAO operation by HE staining. Further experiments by Electron Microscopy and TUNEL assay revealed that the apoptosis of neural cells of cerebellar cortex were induced after MCAO in rats. Furthermore, immunohistochemical analyses showed that caspase-3 played an important role on MCAO-induced apoptosis of neural cells of cerebellar cortex., Conclusion: These data showed for the first time that the role of caspase-3 in the mechanism of secondary injury of separated infarction in cerebellar cortex after middle cerebral artery occlusion in rats and it might give a new treatment strategy for individuals with human ischemic stroke.

Objective: Erythropoietin (EPO) is a cytokine that regulates the proliferation, differentiation, and survival of erythroid progenitor cells. EPO has recently been demonstrated to have a tissue-protective role by mediating anti-apoptotic signals through the erythropoietin receptor (EPOR) in various tissues, including brain, liver, and heart. We have previously examined pancreatic β-cell line NIT-1 cells for the expression of EPOR by real-time PCR and determined that these cells were protected by EPO against cytokine-induced apoptosis. The precise underlying anti-apoptotic mechanisms in pancreatic β-cells are poorly understood. The purpose of this study is to examine erythropoietin receptor expression in the NIT-1 pancreatic beta-cell line and the intracellular pathway related with its anti-apoptosis effect in NIT-1 cells., Methods: we examined the expression of EPOR by western blot. We investigate the role of erythropoietin in the survival of these cells, and whether the PI3K/AKT pathway is involved in this protective process., Results: NIT-1 cells expressed EPOR and, in the presence of certain cytokines, exposure of NIT-1 cells to recombinant human erythropoietin (rhEPO) significantly improved the impaired insulin secretion and inhibited cytokine-induced apoptosis. RhEPO caused a rapid activation of Akt and increased expression of Bcl-2. The protective anti-apoptotic effect of rhEPO was significantly abolished by a specific phosphatidylinositol 3-kiniase (PI3K) inhibitor, LY294002., Conclusions: Our findings indicate that EPOR is expressed in pancreatic β-cell line NIT-1 cells and suggest that EPO may act as a survival factor requiring the PI3K/Akt pathway.

In order to explore the expression of erythropoietin receptor (EPOR) in pancreatic cell line NIT-1 and its effect on cell apoptosis after binding with erythropoietin (EPO), NIT-1 cells were cultured and expanded. The expression of EPOR was detected using electrophoresis. NIT-1 apoptosis was induced by cytokines and their effects on cell apoptosis and cell insulin secretion were assayed after binding of EPO to EPOR. The results showed that EPOR was expressed in NIT-1 cells. Recombinant human EPO (rHuEPO) had no effect on cell apoptosis but significantly inhibited apoptosis induced by cytokines. rHuEPO had no effect on cell insulin secretion but significantly improved insulin secretion inhibited by cytokines. From these findings, it was concluded that EPOR was expressed in NIT-1 cells and EPO could protect NIT-1 cells from apoptosis induced by cytokines.

Objective: To evaluate the risk factors associated with pathogenesis of cerebral palsy (CP) in young children., Methods: A cross-sectional survey on the prevalence of CP was conducted in young children aged one to six years in Leshan area, Sichuan Province. Cluster sampling and a 1:2 case-control design were used to investigate the risk factors for pathogenesis of CP., Results: Totally, 148,723 children were surveyed, in which 308 (2.07 per thousand ) were diagnosed as CP. Low birth weight, twins and premature birth were associated with significantly increased prevalence of CP, 16.32, 4.16 and 22.21 times as that in normal birth weight, single birth and full-term birth, respectively. Simple factor analysis showed varied factors involved in pathogenesis of CP. The multivariate analysis revealed that delivery at home, low Apgar score in five minutes, illness during the first month of life, maternal "cold" with fever in their early gestation, low protein (meat and egg) intake during pregnancy and lower education level of mother were risk factors for CP., Conclusions: Prevalence and clinical features of CP in Leshan was comparable to those in the developed countries. Relevant risk factors could be seen primarily in gestational and perinatal periods, which might involve in mothers, children, environment and heredity, etc. To attach more importance in gestational and perinatal care for mothers and babies will be crucial measures to reduce occurrence of CP in young children.

The rhizomes and roots of Curcuma are commonly used as Traditional Chinese Drugs. In this paper, a new species of Genus Curcuma from Sichuan, viz. Curcuma chuanyujin is reported, it is similar to C. aromatica, but differs from the dispersion of downs and the colour of bracts.

In this paper the relationship of Tibetan Huanglian and Yunnan Huanglian with Coptis teeta has been studied. The distribution and taxonomic features of Tibetan Huanglian are just the same as Coptis teeta, but quite different from Yunnan Huanglian. The results reveal that Tibetan Huanglian and Yunnan Huanglian are different in botanical origin.

The rhizomes of Coptis, known as Huang-Lian, are commonly used as traditional Chinese drugs. Two new species, viz., Coptis linearisepala, C. gulinensis and a new variety, viz., C. chinensis var. unguiculata are reported and the descriptions of the new species and new variety are presented in the present paper.

Quantitative determination of berberine, coptisine, palmatine, jatrorrhizine and epiberberine in Coptis chinensis, C. deltoidea, C. teetoides, C. omeiensis, C. chinensis var. brevisepala, C. linearisepala, C. gulinensis, C. chinensis var. unguiculata, C. teeta and 5 different samples of C. chinensis was made by thin layer chromatography-densitometry.