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Pulmonary arterial hypertension (PAH) is a progressive disease with a complex aetiology and high mortality. Functional and structural changes in the small pulmonary arteries lead to elevated pulmonary arterial pressure, resulting in right heart failure. The pathobiology of PAH is not fully understood, and novel treatment targets in PAH are desperately needed. The renin-angiotensin system is critical for maintaining homeostasis of the cardiovascular system. The system consists of the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang-(1–7)-Mas receptor axis. The former, the ACE-Ang II-AT1R axis, is involved in vasoconstrictive and hypertensive actions along with cardiac and vascular remodelling. The latter, the ACE2-Ang-(1–7)-Mas axis, generally mediates counterbalancing effects against those mediated by the ACE-Ang II-AT1R axis. Based on established functions, the ACE2-Ang-(1–7)-Mas axis may represent a novel target for the treatment of PAH. This review focuses on recent advances in pulmonary circulation science and the role of the ACE2-Ang-(1–7)-Mas axis in PAH.

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Flood control initiated Chinese civilization. Chinese civilization has a long history, and Chinese ancestors invented “aquatic engineering technology” for flood control and water management, including the Fascine body, as early as two thousand years ago. The Fascine body is a structure used to protect the bank and prevent breaching of an ancient Chinese flood control project. Excavation of the Shahe ancient bridge ruins in Xi’an City, Shaanxi Province, China led to discovery of a Fascine body structure. Through 14C dating, fibre, slice observations, infrared spectroscopy, X-ray diffraction, thermogravimetric analyses and SEM energy spectrum analyses of the fascine material, microbes in the structure and the surrounding soil were identified, the dominant microbial community was analyzed, and microbial diseases were controlled in a targeted manner. Research on the fascine bank ruins identified the width and length boundaries of the Shahe ancient bridge, determined the exact age of the Shahe ancient bridge, provided important materials for research on ancient bridges, river embankments and other ruins, and provided important clues for the traffic and layout around Chang’an during the Qin and Han Dynasties of Chinese history.

The endothelial dysfunction and the consequent attenuated pulmonary vasodilatation are the major causes of elevated pulmonary arterial resistance and pressure in pulmonary arterial hypertension (PAH). Current study aimed to explore the effects of a TOR2A gene product, salusin-β, on endothelium-dependent vascular relaxation and the progression of PAH in monocrotaline (MCT)-induced PAH rats as well as the relevant signaling pathway.Acetylcholine (ACh)-induced dose-dependent relaxation was used to evaluate the endothelium-dependent vasodilatation function.The salusin-β level in plasma and pulmonary artery (PA) in MCT-PAH rats were significantly increased, while the ACh-induced endothelium-dependent vasodilatation was attenuated. After salusin-β incubation or overexpression of salusin-β gene, the endothelium-dependent relaxation was further deteriorated, while anti-salusin-β IgG incubation or knockdown of salusin-β improved it in PAH rats. The superoxide anions scavenger NAC or the antioxidant apocynin inhibited the effect of salusin-β, while the SOD inhibitor DETC further enhanced it. The nitric oxide (NO) synthase inhibitor L-NAME almost blocked the effect of anti-salusin-β IgG. Silencing of salusin-β in PAH rats decreased right ventricular (RV) systolic pressure, RV hypertrophy index, NAD(P)H oxidase activity and ROS level, and increased the eNOS activity and NO level of PA. Overexpression of salusin-β played opposite roles.The elevated saluisn-β level in PAH rats plays important roles in the reduction of endothelium-dependent vasodilatation and participates in the progression of PAH through stimulating NAD(P)H oxidase-ROS production and inhibiting eNOS-NO release.

The research aimed to study the effect of dexmedetomidine combined with bundle strategy on the cardiac function of patients with severe sepsis through pyramid speckle tracking algorithm-based echocardiography, expected to provide reference for its clinical treatment. 98 patients with severe sepsis or septic shock admitted to the hospital were selected as the research subjects, and they were equally divided into experimental group (dexmedetomidine + bundle strategy) and control group (dexmedetomidine + routine nursing), with 49 in each. Ultrasonic cardiogram examination was performed on patients before and after treatment, and the pyramid-based speckle tracking (PST) algorithm was designed and used. The results showed that the running time of the PST algorithm (105.25 s) was less than that of the BM algorithm (336.41 s), and the difference was statistically significant ( P < 0.05 ), and the systolic blood pressure, diastolic blood pressure, left ventricular wall, and heart rate of the experimental group before treatment were not significantly different from those of the control group ( P > 0.05 ). The ultrasound index results found that the ejection fraction (EF) and fractional shortening (FS) of the two groups of patients showed a downward trend over time (1–7 days), while the E/A ratio showed an upward trend, and the E/A ratio of the experimental group was significantly greater than the control group ( P < 0.05 ). The systolic blood pressure, diastolic blood pressure, left ventricular wall, and heart rate of the two groups of patients showed a downward trend over time (1–7 days), and the systolic blood pressure, diastolic blood pressure, left ventricular wall, and heart rate of the experimental group were significantly lower than those of the control group ( P < 0.05 ). The 28-day mechanical ventilation time (6.97 ± 3.11 days), intensive care unit (ICU) stay time (9.18 ± 2.86 days), and the 28-day mortality rate (15.31%) of the experimental group were lower than those of the control group (6.97 ± 3.11 days; 13.08 ± 2.53 days; 31.95%) ( P < 0.05 ). In conclusion, the PST algorithm can effectively improve the quality of echocardiography and assist physicians in clinical evaluation, and dexmedetomidine combined with bundle strategy can stabilize the heart rate and reduce myocardial oxygen consumption in severe sepsis, while effectively shortens the recovery time and improves the overall prognosis.

Activation of transient receptor potential vanilloid 4 (TRPV4) induces neuronal injury. TRPV4 activation enhances inflammatory response and promotes the proinflammatory cytokine release in various types of tissue and cells. Hyperneuroinflammation contributes to neuronal damage in epilepsy. Herein, we examined the contribution of neuroinflammation to TRPV4-induced neurotoxicity and its involvement in the inflammation and neuronal damage in pilocarpine model of temporal lobe epilepsy in mice. Icv. injection of TRPV4 agonist GSK1016790A (GSK1016790A-injected mice) increased ionized calcium binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) protein levels and Iba-1-positive (Iba-1+) and GFAP-positive (GFAP+) cells in hippocampi, which indicated TRPV4-induced microglial cell and astrocyte activation. The protein levels of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome components NLRP3, apoptosis-related spotted protein (ASC) and cysteinyl aspartate-specific protease-1 (caspase-1) were increased in GSK1016790A-injected mice, which indicated NLRP3 inflammasome activation. GSK1016790A also increased proinflammatory cytokine IL-1β, TNF-α and IL-6 protein levels, which were blocked by caspase-1 inhibitor Ac-YVAD-cmk. GSK1016790A-induced neuronal death was attenuated by Ac-YVAD-cmk. Icv. injection of TRPV4-specific antagonist HC-067047 markedly increased the number of surviving cells 3 d post status epilepticus in pilocarpine model of temporal lobe epilepsy in mice (pilocarpine-induced status epilepticus, PISE). HC-067047 also markedly blocked the increase in Iba-1 and GFAP protein levels, as well as Iba-1+ and GFAP+ cells 3 d post-PISE. Finally, the increased protein levels of NLRP3, ASC and caspase-1 as well as IL-1β, TNF-α and IL-6 were markedly blocked by HC-067047. We conclude that TRPV4-induced neuronal death is mediated at least partially by enhancing the neuroinflammatory response, and this action is involved in neuronal injury following status epilepticus.

Colorectal carcinoma (CRC) is one of the most common malignant tumors. The present study aimed to investigate a non-invasive molecular marker that can evaluate the diagnosis and potential molecular mechanism of CRC. Microarray assays and reverse transcription-quantitative PCR analysis demonstrated that microRNA (miR)-325-3p expression was significantly increased in both tissues and serum samples of patients with CRC. In addition, miR-325-3p expression in the tissues and serum was significantly associated with differentiation, TNM stage and lymph node metastasis. The results of the dual-luciferase reporter assay and western blot analysis revealed that cytokeratin 18 (CK18) is a target gene of miR-325-3p. Furthermore, treatment with transforming growth factor (TGF)-β increased miR-325-3p expression in a time-dependent manner. Conversely, TGF-β decreased CK18 expression at 48 and 72 h. Western blot analysis demonstrated that TGF-β1 significantly decreased the expression of the epithelial marker, CK18, and increased the expression of the mesenchymal markers, α-SMA and vimentin. Notably, these effects were reversed following inhibition of miR-325-3p expression. Taken together, the results of the present study suggest that miR-325-3p is a key regulator of TGF-β-induced CK18 downregulation. Thus, elevated levels of miR-325-3p is an important factor affecting epithelial-to-mesenchymal transition, and is likely to be a molecular marker in the progression of CRC and act as a potential therapeutic target.

Background. Although accumulating evidence suggested that a molecular signature panel may be more effective for the prognosis prediction than routine clinical characteristics, current studies mainly focused on colorectal or colon cancers. No reports specifically focused on the signature panel for rectal cancers (RC). Our present study was aimed at developing a novel prognostic signature panel for RC. Methods. Sequencing (or microarray) data and clinicopathological details of patients with RC were retrieved from The Cancer Genome Atlas (TCGA-READ) or the Gene Expression Omnibus (GSE123390, GSE56699) database. A weighted gene coexpression network was used to identify RC-related modules. The least absolute shrinkage and selection operator analysis was performed to screen the prognostic signature panel. The prognostic performance of the risk score was evaluated by survival curve analyses. Functions of prognostic genes were predicted based on the interaction proteins and the correlation with tumor-infiltrating immune cells. The Human Protein Atlas (HPA) tool was utilized to validate the protein expression levels. Results. A total of 247 differentially expressed genes (DEGs) were commonly identified using TCGA and GSE123390 datasets. Brown and yellow modules (including 77 DEGs) were identified to be preserved for RC. Five DEGs (ASB2, GPR15, PRPH, RNASE7, and TCL1A) in these two modules constituted the optimal prognosis signature panel. Kaplan-Meier curve analysis showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. Receiver operating characteristic (ROC) curve analysis demonstrated that this risk score had high predictive accuracy for unfavorable prognosis, with the area under the ROC curve of 0.915 and 0.827 for TCGA and GSE56699 datasets, respectively. This five-mRNA classifier was an independent prognostic factor. Its predictive accuracy was also higher than all clinical factor models. A prognostic nomogram was developed by integrating the risk score and clinical factors, which showed the highest prognostic power. ASB2, PRPH, and GPR15/TCL1A were predicted to function by interacting with CASQ2/PDK4/EPHA67, PTN, and CXCL12, respectively. TCL1A and GPR15 influenced the infiltration levels of B cells and dendritic cells, while the expression of PRPH was positively associated with the abundance of macrophages. HPA analysis supported the downregulation of PRPH, RNASE7, CASQ2, EPHA6, and PDK4 in RC compared with normal controls. Conclusion. Our immune-related signature panel may be a promising prognostic indicator for RC.

BackgroundThe white-backed planthopper (WBPH),Sogatella furcifera(Horváth) (Hemiptera, Delphacidae), is a migratory pest of rice in Asia. Shandong Province, in northern China, is located on the migration pathway of WBPH between southern and northeast China. The potential sources of WBPH in northern China are poorly understood. We studied the sources of WBPH in Shandong Province by determining the population genetic structure of WBPH in 18 sites distributed in Shandong and in six regions of the Greater Mekong Subregion (GMS). We used mitochondrial gene and single-nucleotide polymorphism (SNP) markers for analysis.ResultsAll of the WBPH populations studied in the seven regions had low genetic diversity. Pairwise FSTvalues based on mtDNA ranged from − 0.061 to 0.285, while FSTbased on SNP data ranged from − 0.007 to 0.009. These two molecular markers revealed that 4.40% (mtDNA) and 0.19% (SNP) genetic variation could be explained by the interpopulation variation, while the rest came from intrapopulation variation. The populations in the seven geographic regions comprised four hypothetical genetic clusters (K = 4) not associated with geographic location. Eighty-four of 129 individuals distributed across the given area were designated as recent migrants or of admixed ancestry. Although the substantial migration presented, a weak but significant correlation between genetic and geographic distances was found (r = 0.083, P = 0.004).ConclusionThe Greater Mekong Subregion was the main genetic source of WBPH in Shandong, while other source populations may also exist. The genetic structure of WBPH is shaped by both migration and geographic barriers.These results help clarify the migration route and the source of WBPH in northern China.

PurposeSalusin-β, a multifunctional vasoactive peptide, has a potentially important function in the pathological development of hypertension. However, the exact functional role of salusin-β and the underlying mechanism in this process are still not fully understood. The current study aimed to investigate the effects of silencing salusin-β on vascular function and vascular remodeling, as well as its signaling pathways in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY).MethodsSilencing salusin-β was performed by caudal vein injection of adenovirus expressing salusin-β short hairpin RNA (shRNA). Acetylcholine (ACh)-induced endothelium-dependent relaxation was used to evaluate vasodilator function, and high K+ solution-induced constriction was used to evaluate vasoconstriction function.ResultsSalusin-β levels in plasma and its protein expression in mesenteric artery (MA), coronary artery (CA), and pulmonary artery (PA) of SHR were higher than those in WKY. The salusin-β level and expression were decreased effectively by salusin-β shRNA. Knockdown of salusin-β decreased arterial blood pressure (ABP) and high K+ solution-induced vascular constrictions, and improved the endothelium-dependent relaxation and vascular remodeling in SHR. The improved effect of silencing salusin-β on ACh-induced relaxation in SHR was almost blocked by the nitric oxide synthase (NOS) inhibitor L-NAME. Compared to WKY, the endothelial NOS (eNOS) activity and level, and nitric oxide (NO) level were decreased, while NAD(P)H oxidase activity and reactive oxygen species (ROS) levels in MA, CA, and PA of SHR were increased, which were all redressed by salusin-β knockdown.ConclusionThese results indicate that knockdown of salusin-β improves endothelium-dependent vascular relaxation and vascular remodeling and decreases ABP and vasoconstriction in SHR, which might be accomplished by increasing eNOS activation and NO release while inhibiting NAD(P)H oxidase derived-ROS generation. Scavenging salusin-β improves vascular function and then prevents the development and progression of vasculopathy of hypertension.

Salusin-β is a biologically active peptide with 20 amino acids that exerts several cardiovascular activity-regulating effects, such as regulating vascular endothelial function and the proliferation of vascular smooth muscle cells. However, the regulatory effects of salusin-β in myocardial infarction-induced chronic heart failure (CHF) are still unknown. The current study is aimed at investigating the effects of silencing salusin-β on endothelial function, cardiac function, vascular and myocardial remodeling, and its underlying signaling pathways in CHF rats induced by coronary artery ligation. CHF and sham-operated (Sham) rats were subjected to tail vein injection of adenoviral vectors encoding salusin-β shRNA or a control-shRNA. The coronary artery (CA), pulmonary artery (PA), and mesenteric artery (MA) were isolated from rats, and isometric tension measurements of arteries were performed. Compared with Sham rats, the plasma salusin-β, leptin and visfatin levels and the salusin-β protein expression levels of CA, PA, and MA were increased, while the acetylcholine- (ACh-) induced endothelium-dependent vascular relaxation of CA, PA, and MA was attenuated significantly in CHF rats and was improved significantly by salusin-β gene knockdown. Salusin-β knockdown also improved cardiac function and vascular and myocardial remodeling, increased endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) levels, and decreased NAD(P)H oxidase activity, NOX-2 and NOX-4 expression, and reactive oxygen species (ROS) levels in arteries in CHF rats. The effects of salusin-β knockdown in CHF rats were attenuated significantly by pretreatment with the NOS inhibitor L-NAME. These results indicate that silencing salusin-β contributes to the improvement of endothelial function, cardiac function, and cardiovascular remodeling in CHF by inhibiting NAD(P)H oxidase-ROS generation and activating eNOS-NO production.

Background The white-backed planthopper (WBPH), Sogatella furcifera (Horváth) (Hemiptera, Delphacidae), is a migratory pest of rice in Asia. Shandong Province, in northern China, is located on the migration pathway of WBPH between southern and northeast China. The potential sources of WBPH in northern China are poorly understood. We studied the sources of WBPH in Shandong Province by determining the population genetic structure of WBPH in 18 sites distributed in Shandong and in six regions of the Greater Mekong Subregion (GMS). We used mitochondrial gene and single-nucleotide polymorphism (SNP) markers (2b-RAD sequencing) for analysis.Results All of the WBPH populations studied in the seven regions had low genetic diversity. Pairwise FST values ranged from − 0.061 to 0.285, while FST based on SNP data ranged from − 0.007 to 0.009. These two molecular markers revealed that 4.40% (mtDNA) and 0.19% (SNP) genetic variation could be explained by the interpopulation variation, while the rest came from intrapopulation variation. The populations in the seven geographic regions comprised four hypothetical genetic clusters (K = 4) not associated with geographic location. Eighty-four of 129 individuals distributed across the given area were designated as recent migrants or of admixed ancestry. Although the substantial migration presented, a weak but significant correlation between genetic and geographic distances was found (r = 0.083, P = 0.004).Conclusion GMS was the main source of WBPH in Shandong, while other source populations may also exist. The genetic structure of WBPH is shaped by both migration and geographic barriers. These results help clarify the migration route and the source of WBPH in northern China.

IAV regulates inflammatory signaling via glucose metabolism., In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)–associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in influenza A virus (IAV)–induced cytokine storm. O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, mediated IAV-induced cytokine production. Upon investigating the mechanisms driving this event, we determined that IAV induced OGT to bind to interferon regulatory factor–5 (IRF5), leading to O-GlcNAcylation of IRF5 on serine-430. O-GlcNAcylation of IRF5 is required for K63-linked ubiquitination of IRF5 and subsequent cytokine production. Analysis of clinical samples revealed that IRF5 is O-GlcNAcylated, and higher levels of proinflammatory cytokines correlated with higher levels of blood glucose in IAV-infected patients. We identified a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates IRF5 function during IAV infection, highlighting the importance of glucose metabolism in IAV-induced cytokine storm.

A laboratory bioassay was conducted to determine the allelopathic potentials of aqueous extracts from either roots or leaves of seventeen sweet potato [Ipomoea batatas L. (Lam)] cultivars (SP0, SP1, SP2, SP3, SP4, SP5, SP6, SP7, SP9, SP10, SP11, SP13, SP14, SP15, SP16, SP18, and SP19). Most inhibitory rates on Lactuca sativa calculated for leaf or root extracts from the seventeen sweet potato cultivars exhibited positive values and significantly increased with increasing concentration. Germination was totally inhibited at a concentration of 0.05 g·mL−1 for leaf water extracts of SP13, SP15, SP18 and at a concentration of 0.05 g·mL−1 for both leaf and root water extracts of SP19. Inhibition of root length was clearly greater than inhibition of shoot length for both leaf and root water extracts. Biomass inhibition increased with increasing concentration, but some cultivars showed stimulatory effects at low concentrations, and inhibition was generally more pronounced for root water extracts than for leaf water extracts. Moreover, most synthetical inhibitory rates for both leaf and root water extracts from the seventeen cultivars exhibited positive values and significantly increased with increasing concentration. Comparing the synthetical inhibitory rates for both leaf and root water extracts among the seventeen cultivars, SP19, SP6, SP11, and SP7 had the highest allelopathic inhibition. The inhibitory activity on germination index was the greatest, followed by germination rate, root length, biomass, and shoot length in all bioassays. Inhibition by leaf water extracts was generally greater than inhibition by root water extracts, except in the case of shoot length or biomass. Overall, we conclude that all seventeen sweet potato cultivars have strong inhibitory effects on L. sativa, but that these effects vary with cultivar and plant part, with SP19, SP6, SP11, and SP7 exhibiting the highest rates of allelopathic inhibition.

Additional file 1: Figure S1. (A) Delta k value of data across 10 replicates of STRUCTURE, where k = 4 is shown as the best fit of the data for the highest level of hierarchical genetic structure. (B) The mean lnP(D|K) and SD for each k where the model of k = 2, 3 or 4 is indicated as the best fit. Table S1. Assignment test for Sogatella furcifera individuals in the seven geographic populations. Individuals are presented in rows according to their sampling locations as individuals assigned to their own population (self) and those assigned to other putative source population. Individuals in CN_YN were randomly selected as 20 individuals participated the analysis.

Background and aims Major vault protein (MVP) is up-regulated during infections with hepatitis B virus (HBV) and hepatitis C virus (HCV). Here, we found that MVP deficiency inhibited hepatocellular carcinoma (HCC) development induced by diethylnitrosamine, hepatitis B X protein, and HCV core. Approach and results Forced MVP expression was sufficient to induce HCC in mice. Mechanistic studies demonstrate that the ubiquitin ligase human double minute 2 (HDM2) forms mutual exclusive complexes either with interferon regulatory factor 2 (IRF2) or with p53. In the presence of MVP, HDM2 is liberated from IRF2, leading to the ubiquitination of the tumor suppressor p53. Mouse xenograft models showed that HBV and HCV promote carcinogenesis through MVP induction, resulting in a loss of p53 mediated by HDM2. Analyses of clinical samples from chronic hepatitis B, liver cirrhosis, and HCC revealed that MVP up-regulation correlates with several hallmarks of malignancy and associates with poor overall survival. Conclusions Taken together, through the sequestration of IRF2, MVP promotes an HDM2-dependent loss of p53 that promotes HCC development.

Glucose metabolism and innate immunity evolved side-by-side. It is unclear if and how the two systems interact with each other during hepatitis B virus (HBV) infections and, if so, which mechanisms are involved. Here, we report that HBV activates glycolysis to impede retinoic acid-inducible gene I (RIG-I)-induced interferon production. We demonstrate that HBV sequesters MAVS from RIG-I by forming a ternary complex including hexokinase (HK). Using a series of pharmacological and genetic approaches, we provide in vitro and in vivo evidence indicating that HBV suppresses RLR signaling via lactate dehydrogenase-A-dependent lactate production. Lactate directly binds MAVS preventing its aggregation and mitochondrial localization during HBV infection. Therefore, we show that HK2 and glycolysis-derived lactate have important functions in the immune escape of HBV and that energy metabolism regulates innate immunity during HBV infection., RIG-I is a cytosolic antiviral nucleic acid sensor that signals via MAVS to produce type 1 interferons. Here the authors show that hepatits B virus can repress this pathway by activating glycolysis and lactate production, enabling accumulated lactate to bind MAVS and prevent its mitochondrial localization.

Activation of transient receptor potential vanilloid 4 (TRPV4) induces neuronal injury. TRPV4 activation enhances inflammatory response and promotes the proinflammatory cytokine release in various types of tissue and cells. Hyperneuroinflammation contributes to neuronal damage in epilepsy. Herein, we examined the contribution of neuroinflammation to TRPV4-induced neurotoxicity and its involvement in the inflammation and neuronal damage in pilocarpine model of temporal lobe epilepsy in mice. Icv. injection of TRPV4 agonist GSK1016790A (GSK1016790A-injected mice) increased ionized calcium binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) protein levels and Iba-1-positive (Iba-1

Nowadays, it is a growing need for energy shortage and environmental protection, and therefore the development of air conditioning and cooling system with ice slurry system has an important significance and broad application prospect. The ice-making using sub-cooling water has become one of the most stressed dynamic ice-making methods because of its simple structure, high heat transfer efficiency and high ice-making efficiency. However, the ice blockage occurs too frequently, resulting in a discontinuous ice-making and reducing the efficiency of the system. Aiming at dealing with the ice blockage, the experiment with the super-hydrophobic sub-cooler has been carried out, which provides theoretical and experimental basis for the optimum design of the ice-making system. It was found that a large sub-cooling degree and a long lasting time of sub-cooling state can be obtained with the super-hydrophobic sub-cooler, increasing the yield of ice slurry. As a result, the efficiency of the ice-making system is improved, achieving the purpose of energy saving.

Hepatitis B virus X protein (HBx) critically contributes to the development of hepatocellular carcinoma (HCC). However, the mechanisms by which HBx promotes HCC remain unclear. In the present study, using a combination of gene expression profiling and immunohistochemistry, we found higher levels of SH2 domain–containing 5 (SH2D5) in liver tissue from HBV-associated HCC (HBV-HCC) patients than in adjacent nontumor tissues. Moreover, HBV infection elevated SH2D5 levels, and we observed that HBx plays an important role in SH2D5 induction. We also found that HBx triggers SH2D5 expression through the NF-κB and c-Jun kinase pathways. Employing SH2D5 overexpression or knockdown, we further demonstrate that SH2D5 promotes HCC cell proliferation both in vitro and in vivo. While investigating the mechanism of SH2D5-mediated stimulation of HCC cell proliferation, we noted that HBV induces SH2D5 binding to transketolase (TKT), a pentose phosphate pathway enzyme, thereby promoting an interaction between and signal transducer and activator of transcription 3 (STAT3). Furthermore, HBx stimulated STAT3 phosphorylation at Tyr-705 and promoted the activity and downstream signaling pathway of STAT3 via the SH2D5–TKT interaction. Taken together, our results suggest that SH2D5 is an HBV-induced protein capable of binding to TKT, leading to induction of HCC cell proliferation.

Background and objectives Sweet potato [Ipomoea batatas (L.) Lam] is an important locally grown cash crop in China; it was demonstrated to suppress the invasive plant Mikania micrantha (M. micrantha) H.B.K through strong competitiveness, but its allelopathic effects on this weed were unknown. The present study aimed to explore the allelopathic potential of sweet potato on M. micrantha. Materials and methods The allelopathic effects of water extracts and soil incorporation from leaves of three sweet potato cultivars (SP1, SP0 and SP9) on the sprout seedling growth of invasive plant M. micrantha in Yunnan Province, China, were studied under laboratory and greenhouse conditions. Results Stem length, root biomass, aboveground biomass and total biomass of M. micrantha were significantly reduced with increasing concentration in both leaf water extracts and leaf soil incorporation of three sweet potato cultivars. Among these, SP1 had the strongest inhibition and the next highest impact was from SP0 with the lowest effect from SP9. The highest inhibition rates were seen for root biomass, followed by total biomass, whereas the lowest impact was on aboveground biomass. The strong correspondence between results for both leaf water extracts and leaf soil incorporation provided a good demonstration that compounds produced by sweet potato have allelopathic effects on M. micrantha. The general inhibition of M. micrantha by sweet potato followed the order among the three sweet potato cultivars tested as SP1, SP0 and SP9. Moreover, the synthetical allelopathic indices of leaf soil incorporation of three cultivars on M. micrantha were generally higher than these of leaf water extracts. Conclusion Competition and allelopathy have primarily been seen as separate ecological weed management tools, but as these have demonstrated in the case of sweet potato where both mechanisms inhibit weed growth, there is potential for synergism between competition and allelopathy in the reduction of weed infestations.

Numerous microRNAs (miRNA/miRs) have been reported to be associated with the initiation and progression of non‑small cell lung cancer (NSCLC). The aim of the present study was to examine the expression and biological role of miR‑939 in human NSCLC, in vitro. Reverse transcription‑quantitative polymerase chain reaction analysis was used to evaluate the expression of miR‑939 in NSCLC tissues. Cell Counting Kit‑8, 5‑ethynyl‑29‑deoxyuridine and Transwell assays were also used to determine the effects of miR‑939 on tumor cell proliferation and invasion in two human NSCLC cell lines (H1299 and SPCA1). Furthermore, tissue inhibitor of metalloproteinases 2 (TIMP2) was confirmed to be a target of miR‑939 by luciferase reporter assay, western blotting and bioinformatics analysis. Following downregulation of miR‑939 expression, cell proliferative and invasive abilities were significantly suppressed. Collectively, these findings indicated that the knockdown of miR‑939 may inhibit cell proliferation and invasion by regulating the expression of TIMP2 in NSCLC cells. Thus, miR‑939 may be a potential target in the treatment of NSCLC, although this requires further investigation.

Key points Chronic subcutaneous infusion of Ang II causes a progressive increase in blood pressure (BP) associated with significant increases in angiotensin type 1 receptor (AT1R) and mineralocorticoid receptor (MR) expression in hypothalamic nuclei. Intra-paraventricular nucleus (PVN) infusion of AAV- AT1aR-siRNA or of AAV-MR-siRNA markedly knockdown AT1a-R or MR expression in the PVN but not in the subfornical organ; or supraoptic nucleus, and prevent most of the increase in BP. These findings indicate that increased MR and AT1R activation in the PVN play a critical role in Ang II-induced hypertension in rats on regular salt intake. Abstract Circulating Ang II activates an aldosterone-mineralocorticoid receptor (MR) – angiotensin II (Ang II) – angiotensin type 1 receptor (AT1R) pathway in the hypothalamus. To obtain insights into the actual neuronal projections involved, adeno-associated virus carrying small interfering RNA against either AT1aR (AAV-AT1aR-siRNA) or MR (AAV-MR-siRNA) were infused into the paraventricular nucleus (PVN) in Wistar rats. Intra-PVN infusion of AAV-AT1aR-siRNA or AAV-MR-siRNA decreased AT1R or MR expression in the PVN but not in the subfornical organ (SFO) or supraoptic nucleus (SON). Subcutaneous infusion of Ang II at 500 ng kg−1 min−1 for 2 weeks increased mean arterial pressure by 60–70 mmHg, and increased AT1R and MR expression in the SFO, SON and PVN. Intra-PVN AT1aR-siRNA prevented the Ang II-induced increase in AT1R but not MR expression in the PVN, and MR-siRNA prevented MR but not AT1R expression in the PVN. The increases in AT1R and MR expression in both the SFO and the SON were not changed by the two AAV-siRNAs. Specific knockdown of AT1R or MR in the PVN by AAV-siRNA each prevented most of the Ang II-induced hypertension. Prevention of the subcutaneous Ang II-induced increase in MR but not the increase in AT1R by knockdown of MR and vice versa suggests an independent regulation of MR and AT1R expression in the PVN. Both AT1R and MR activation in the PVN play a critical role in Ang II-induced hypertension in rats.

Key points Central mineralocorticoid receptor (MR) and angiotensin II type 1 receptor (AT1R) activation play a critical role in sympathetic hyperactivity and progressive left ventricle (LV) remodelling and dysfunction after a myocardial infarction (MI). Intra-paraventricular nucleus (PVN) infusion of adeno-associated virus (AAV) carrying small interfering RNA (siRNA) against MR (AAV-MR-siRNA) markedly decreases both MR and AT1R expression in the PVN post MI, whereas AAV-AT1aR-siRNA only decreases AT1R expression. Both AAVs largely prevent sympathetic hyperactivity and inhibit part of LV remodelling and dysfunction post MI. These findings indicate that enhanced MR–AT1R signalling in the PVN is critical for sympathetic hyperactivity post MI, and contributes to part of LV dysfunction post MI. Abstract Intracerebroventricular infusion of a mineralocorticoid receptor (MR) or angiotensin II type 1 receptor (AT1R) blocker in rats attenuates sympathetic hyperactivity and progressive left ventricular (LV) dysfunction post myocardial infarction (MI). The present study examined whether knockdown of MRs or AT1Rs specifically in the paraventricular nucleus (PVN) contributes to these effects, and compared cardiac effects with those of systemic treatment with the β1-adrenergic receptor blocker metoprolol. The PVN of rats was infused with adeno-associated virus carrying small interfering RNA against either MR (AAV-MR-siRNA) or AT1R (AAV-AT1R-siRNA), or as control scrambled siRNA. At 4 weeks post MI, AT1R but not MR expression was increased in the PVN, excitatory renal sympathetic nerve activity and pressor responses to air stress were enhanced, and arterial baroreflex function was impaired; LV end-diastolic pressure (LVEDP) was increased and LV peak systolic pressure (LVPSP), ejection fraction (EF) and dP/dtmax decreased. AAV-MR-siRNA and AAV-AT1R-siRNA both normalized AT1R expression in the PVN, similarly ameliorated sympathetic and pressor responses to air stress, largely prevented baroreflex desensitization, and improved LVEDP, EF and dP/dtmax as well as cardiac interstitial (but not perivascular) fibrosis. In a second set of rats, metoprolol at 70 or 250 mg kg−1 day−1 in the drinking water for 4 weeks post MI did not improve LV function except for a decrease in LVEDP at the lower dose. These results suggest that in rats MR-dependent upregulation of AT1Rs in the PVN contributes to sympathetic hyperactivity, and LV dysfunction and remodelling post MI. In rats, normalizing MR–AT1R signalling in the PVN is a more effective strategy to improve LV dysfunction post MI than systemic β1 blockade.

This study determined the accuracy and biases associated with retrieved Moderate Resolution Imaging Spectroradiometer (MODIS) total precipitable water (TPW) data, and it investigated the impact of these data on severe weather simulations using the Weather Research and Forecast (WRF) model. Comparisons of MODIS TPW with the global positioning system (GPS) TPW and radiosonde-derived TPW were carried out. The comparison with GPS TPW over the United States showed that the root-mean-square (RMS) differences between these two datasets were about 5.2 and 3.3 mm for infrared (IR) and near-infrared (nIR) TPW, respectively. MODIS IR TPW data were overestimated in a dry atmosphere but underestimated in a moist atmosphere, whereas the nIR values were slightly underestimated in a dry atmosphere but overestimated in a moist atmosphere. Two cases, a severe thunderstorm system (2004) over land and Hurricane Isidore (2002) over ocean, as well as conventional observations and Special Sensor Microwave Imager (SSM/I) retrievals were used to assess the impact of MODIS nIR TPW data on severe weather simulations. The assimilation of MODIS data has a slightly positive impact on the simulated rainfall over Oklahoma for the thunderstorm case, and it was able to enhance Isidore’s intensity when the storm track was reasonably simulated. The use of original and bias-corrected MODIS nIR TPW did not show significant differences from both case studies. In addition, SSM/I data were found to have a positive impact on both severe weather simulations, and the impact was comparable to or slightly better than that of MODIS data.

Background As a means of biologically controlling Mikania micrantha H.B.K. in Yunnan, China, the influence of sweet potato [Ipomoea batatas (L.) Lam.] on its reproductive characteristics was studied. The trial utilized a de Wit replacement series incorporating six ratios of sweet potato and M. micrantha plants in 25 m2 plots over 2 years. Results Budding of M. micrantha occurred at the end of September; flowering and fruiting occurred from October to February. Flowering phenology of M. micrantha was delayed (P

Activation of angiotensinergic pathways and central aldosterone (aldo)-MR-ENaC-endogenous ouabain (EO)-AT 1 R pathway play a critical role in Ang II associated hypertension. The SFO contains both MR and AT 1 R and can relay the signals of circulating Ang II to downstream nuclei such as the PVN, SON and RVLM. We evaluated the effect of knockdown of MR and AT 1 R specific in the SFO on reactive oxygen species (ROS) production in downstream nuclei. Wistar rats were intra SFO infused with AAV-MR- or AT 1a R-siRNA and after 7 days received a sc infusion of Ang II at 500 ng/min/kg for 2 weeks. MR and AT 1 R expression were measured by real-time qPCR and western blotting. ROS was assessed by DHE staining. Ang II increased AT 1 R mRNA expression in the SFO. Both MR- and AT 1 R-siRNA in the SFO prevented this increase. Ang II decreased MR mRNA but increased protein expression in the SFO. Both MR- and AT 1 R-siRNA further decreased MR mRNA expression. Ang II significantly increased ROS in the SFO, magno- and parvocellular parts of the PVN, SON and RVLM. Both MR- and AT 1 R-siRNA in the SFO prevented ROS increases in the PVN and RVLM. In contrast, MR- but not AT 1 R-siRNA in the SFO prevented the Ang II-induced ROS in the SON. Both MR- and AT 1 R-siRNA in the SFO prevented most of the Ang II-induced hypertension. These results suggest that aldo-MR signaling in the SFO is needed for the activation of Ang II-AT 1 R signaling from the SFO to the PVN and RVLM. Considering that only MR-siRNA in the SFO prevents circulating Ang II induced ROS in the SON, activation of aldo-MR signaling from the SFO to the SON may via EO enhance AT 1 R dependent activation of pre-sympathetic neurons in the PVN, and thereby to Ang II-hypertension.

Background There are a variety of ways of increasing crop diversity to increase agricultural sustainability and in turn having a positive influence on nearby natural ecosystems. Competitive crops may provide potent management tools against invasive plants. To elucidate the competitive mechanisms between a sweet potato crop (Ipomoea batatas) and an invasive plant, mile-a-minute (Mikania micrantha), field experiments were carried out in Longchuan County of Yunnan Province, Southwest China, utilizing a de Wit replacement series. The trial incorporated seven ratios of sweet potato and mile-a-minute plants in 25 m2 plots. Results In monoculture, the total biomass, biomass of adventitious root, leafstalk length, and leaf area of sweet potato were all higher than those of mile-a-minute, and in mixed culture the plant height, branch, leaf, stem node, adventitious root, flowering and biomass of mile-a-minute were suppressed significantly (P