Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation.

Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

An endophytic fungus Schizophyllum commune isolated from Panax ginseng enhances hairy roots growth and ginsenoside biosynthesis.

Using endophytic fungal elicitors to increase the accumulation of valuable secondary metabolites in plant tissue culture is an effective biotechnology strategy. In this study, a collection of 56 strains of endophytic fungi were isolated from different organs of cultivated Panax ginseng, of which seven strains can be symbiotically co-cultured with the hairy roots of P. ginseng. Further experiments observed that strain 3R-2, identified as endophytic fungus Schizophyllum commune, can not only infect hairy roots but also promote the accumulation of specific ginsenosides. This was further verified because S. commune colonization significantly affected the overall metabolic profile of ginseng hairy roots. By comparing the effects of S. commune mycelia and its mycelia extract (EM) on ginsenoside production in P. ginseng hairy roots, the EM was confirmed to be a relatively better stimulus elicitor. Additionally, the introduction of EM elicitor can significantly enhance the expressions of key enzyme genes of pgHMGR, pgSS, pgSE, and pgSD involved in the biosynthetic pathway of ginsenosides, which was deemed the most relevant factor for promoting ginsenosides production during the elicitation period. In conclusion, this study is the first to show that the EM of endophytic fungus S. commune can be considered as an effective endophytic fungal elicitor for increasing the biosynthesis of ginsenosides in hairy root cultures of P. ginseng.

Transcriptome sequencing and signal transduction for the enhanced tanshinone production in Salvia miltiorrhiza hairy roots induced by Trichoderma atroviride D16 polysaccharide fraction.

Salvia miltiorrhiza Bunge. is commonly used to treat vascular diseases because of its activity ingredients, phenolic acids, and tanshinones. Polysaccharide fraction (PSF) extracted from Trichoderma atroviride D16 could promote tanshinone accumulation in S. miltiorrhiza hairy roots. Transcriptome sequencing was conducted to describe the global gene expression of PSF-treatment hairy roots, and data analyses showed enzymes of tanshinone biosynthetic pathways were up-regulated, and genes associated to signal molecules and transcription factors were responsive. Endogenous H2O2, abscisic acid, and nitric oxide contents were measured after PSF treatment, while tanshinone accumulations were measured with treatment of exogenous H2O2 or H2O2 inhibitor on PSF-treatment S. miltiorrhiza hairy roots. The results showed H2O2 was important in tanshinone biosynthesis caused by PSF and nitric oxide might be the downstream molecules of H2O2. Taken together, the study indicates that D16 PSF enhances the accumulation of tanshinones through enzymes of tanshinone biosynthetic pathways, signal molecules, and transcription factors.

Biomechanical analysis of stress around the tilted implants with different cantilever lengths in all-on-4 concept.

BACKGROUND: Many clinical studies have reported the high success rate of the All-on-4 concept. In the present study, we aimed to compare the stress distribution with different tilted distal implants and cantilever lengths in an All-on-4 system using the two-dimensional photoelastic method and to establish the All-on-4 implant photoelastic model by computer-aided design (CAD) and rapid prototyping (RP).  METHODS: The data of the human edentulous mandible were acquired by computed tomography (CT). Three human edentulous mandible All-on-4 implant models with different distally inclined implant holes were fabricated using Mimic, Geomagic Studio software, and a light solidifying fast shaping machine. Then the final photoelastic models were established through the traditional method. Each of the three models had four NobelSpeedy Replace implants between the interforaminal regions. The two posterior implants were placed 0, 15, and 45 degrees distally before the mental foramen. The four implants were splinted by wrought cobalt-chromium alloy frameworks. Each of the three photoelastic models was submitted to a 150 N vertical load at five points on the framework: the central fossa of the mandibular first molar, and 0 mm, 5 mm, 10 mm, and 15 mm of the cantilever length. The stress produced in the models was photographed with a digital camera, and the highest value of the stressed fringe pattern was recorded. RESULTS: The All-on-4 implant photoelastic model established by CAD and RP was highly controllable and easy to modify. The position and inclination of implants were accurate, and the frameworks could be passively emplaced. The stress values were higher around a single tilted implant compared with the distal implant in All-on-4 with the same inclination. The 0-degree distal implant and 45-degree distal implant demonstrated the highest and lowest stress when loading at the central fossa of the mandibular first molar, respectively. With the same inclination of distal implant, the peri-implant bone stress increased as the length of cantilever increased. CONCLUSION: The method of establishing the All-on-4 implant photoelastic model by CAD and RP was highly controllable, convenient, fast, and accurate. The tilted implants splinted in the fully fixed prosthesis with reduced cantilever lengths did not increase the stress level compared with the vertical distal implants.And this illustrated that the influence of cantilever on stress distribution was greater than the influence of implant inlination.

[Puerarin Inhibits the Proliferation,Invasion,and Migration of Non-small Cell Lung Cancer Cells through Regulating miR-490/Denticleless E3 Ubiquitin Protein Ligase].

Objective To explore the mechanism of puerarin inhibiting the proliferation,invasion,and migration of non-small cell lung cancer cells. Methods A549 cells were cultured and treated with different concentrations of puerarin.The inhibition rate (IR) on cell proliferation was detected by CCK-8,and qRT-PCR was performed to detect the mRNA levels of miR-490 and denticleless E3 ubiquitin protein ligase(DTL).Double luciferase reporter assay was employed to identify the targets of miR-490 and DTL based on the establishment of NC mimic group,miR-490 mimic group,NC inhibitor group,and miR-490 inhibitor group.The cells treated by 20 µmol/L puerarin were classified into six groups:DMSO,puerarin,puerarin+NC inhibitor,puerarin+miR-490 inhibitor,puerarin+miR-490 inhibitor+Si-NC,and puerarin+miR-490 inhibitor+Si-DTL.Transwell was used to detect cell migration and invasion.Western blotting was performed to detect the protein levels of epithelial-mesenchymal transition-related markers E-cadherin,N-cadherin,and Vimentin. Results With the increase in puerarin concentration,the IR gradually elevated (F=105.375,P<0.001),miR-490 expression gradually increased (F=32.919,P<0.001),and DTL expression gradually decreased (F=116.120,P<0.001).Compared with NC mimic group,miR-490 mimic group had decreased luciferase activity (t=7.762,P=0.016),raised miR-490 mRNA level (t=13.319,P<0.001),and declined DTL mRNA level (t=7.415,P=0.002).Compared with those in NC inhibitor group,miR-490 demonstrated decreased mRNA level (t=9.523,P=0.001) and DTL presented increased mRNA level (t=11.305,P<0.001) in miR-490 inhibitor group.Western blotting showed that the protein level of DTL was higher in NC mimic group (t=7.953,P=0.001) than in miR-490 mimic group and higher in miR-490 inhibitor group than in NC inhibitor group (t=10.552,P<0.001).Compared with DMSO group,puerarin group showed up-regulated mRNA level of miR-490 (t=10.255,P=0.001) while down-regulated mRNA level of DTL (t=6.682,P=0.003).Compared with those in puerarin+NC inhibitor group,the mRNA level of miR-490 declined (t=10.995,P<0.001) while that of DTL raised (t=12.478,P<0.001) in puerarin+miR-490 inhibitor group.The mRNA level of miR-490 had no significant difference between puerarin+miR-490 inhibitor+Si-NC group and puerarin+miR-490 inhibitor+Si-DTL group (t=1.081,P=0.341),and that of DTL was lower in the latter group (t=14.321,P<0.001).The protein level of DTL was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=11.423,P<0.001),and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=12.080,P<0.001).Compared with DMSO group,puerarin group showed inhibited cell proliferation (F=129.27,P<0.001).The activity of cell proliferation was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (F=75.12,P<0.001),and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (F=52.59,P<0.001).Compared with DMSO group,puerarin group had suppressed cell migration (t=8.963,P=0.001).The cell migration ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=12.117,P<0.001) and higher in puerarin+miR-490 inhibitor+Si-NC group than in puerarin+miR-490 inhibitor+Si-DTL group (t=12.934,P<0.001).Puerarin group showed weakened cell invasion ability compared with DMSO group (t=4.710,P=0.009).The cell invasion ability was higher in puerarin+miR-490 inhibitor group than in puerarin+NC inhibitor group (t=13.264,P<0.001) and lower in puerarin+miR-490 inhibitor+Si-DTL group than in puerarin+miR-490 inhibitor+Si-NC group (t=13.476,P<0.001).Compared with DMSO group,puerarin group showed up-regulated protein level of E-cadherin (t=7.137,P=0.002) while down-regulated protein levels of N-cadherin (t=8.828,P=0.001) and vimentin (t=6.594,P=0.003).Compared with those in puerarin+NC inhibitor group,the protein level of E-cadherin (t=12.376,P<0.001) decreased while those of N-cadherin (t=13.436,P<0.001) and vimentin (t=11.467,P<0.001) increased in puerarin+miR-490 inhibitor group.Compared with puerarin+miR-490 inhibitor+Si-NC group,puerarin+miR-490 inhibitor+Si-DTL group up-regulated the protein level of E-cadherin (t=13.081,P<0.001) while down-regulated the protein levels of N-cadherin (t=10.835,P<0.001) and vimentin (t=11.862,P<0.001). Conclusion Puerarin could inhibit the proliferation,invasion,and migration of non-small cell lung cancer cells by up-regulating miR-490 and down-regulating DTL.

Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx.

BACKGROUND & AIMS: Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional silencing of cccDNA is a crucial curative strategy that may be achieved by targeting the viral protein HBx. METHODS: We screened 2,000 small-molecule compounds for their ability to inhibit HiBiT-tagged HBx (HiBiT-HBx) expression by using a HiBiT lytic detection system. The antiviral activity of a candidate compound and underlying mechanism of its effect on cccDNA transcription were evaluated in HBV-infected cells and a humanised liver mouse model. RESULTS: Dicoumarol, an inhibitor of NAD(P)H:quinone oxidoreductase 1 (NQO1), significantly reduced HBx expression. Moreover, dicoumarol showed potent antiviral activity against HBV RNAs, HBV DNA, HBsAg and HBc protein in HBV-infected cells and a humanised liver mouse model. Mechanistic studies demonstrated that endogenous NQO1 binds to and protects HBx protein from 20S proteasome-mediated degradation. NQO1 knockdown or dicoumarol treatment significantly reduced the recruitment of HBx to cccDNA and inhibited the transcriptional activity of cccDNA, which was associated with the establishment of a repressive chromatin state. The absence of HBx markedly blocked the antiviral effect induced by NQO1 knockdown or dicoumarol treatment in HBV-infected cells. CONCLUSIONS: Herein, we report on a novel small molecule that targets HBx to combat chronic HBV infection; we also reveal that NQO1 has a role in HBV replication through the regulation of HBx protein stability. LAY SUMMARY: Current antiviral therapies for hepatitis B are not curative because of their inability to eliminate covalently closed circular DNA (cccDNA), which persists in the nuclei of infected cells. HBV X (HBx) protein has an important role in regulating cccDNA transcription. Thus, targeting HBx to silence cccDNA transcription could be an important curative strategy. We identified that the small molecule dicoumarol could block cccDNA transcription by promoting HBx degradation; this is a promising therapeutic strategy for the treatment of chronic hepatitis B.

SIRT7 restricts HBV transcription and replication through catalyzing desuccinylation of histone H3 associated with cccDNA minichromosome.

Chronic hepatitis B virus (HBV) infection is a significant public health burden worldwide. HBV covalently closed circular DNA (cccDNA) organized as a minichromosome in nucleus is responsible for viral persistence and is the key obstacle for a cure of chronic hepatitis B (CHB). Recent studies suggest cccDNA transcription is epigenetically regulated by histone modifications, especially histone acetylation and methylation. In the present study, we identified transcriptionally active histone succinylation (H3K122succ) as a new histone modification on cccDNA minichromosome by using cccDNA ChIP-Seq approach. Silent mating type information regulation 2 homolog 7 (SIRT7), as an NAD+-dependent histone desuccinylase, could bind to cccDNA through interaction with HBV core protein where it catalyzed histone 3 lysine 122 (H3K122) desuccinylation. Moreover, SIRT7 acts cooperatively with histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1) and SET domain containing 2 (SETD2) to induce silencing of HBV transcription through modulation of chromatin structure. Our data improved the understanding of histone modifications of the cccDNA minichromosome, thus transcriptional silencing of cccDNA may represent a novel antiviral strategy for the prevention or treatment of HBV infection.

[Effect of pertussis vaccination on clinical manifestations of infants and young children with pertussis].

OBJECTIVE: To study the effect of pertussis vaccination on the clinical manifestations of infants and young children with pertussis. METHODS: A retrospective analysis was performed to investigate the differences in clinical manifestations and peripheral blood cell levels between pertussis children with different pertussis vaccination status. RESULTS: A total of 1 083 children with pertussisat at age of < 3 years were enrolled, with 551 children in the unvaccinated group and 532 in the vaccinated group. Of all the children, 392 had an age of onset of < 3 months (372 were unvaccinated and 20 were vaccinated) and 691 children had an age of onset of ≥ 3 months (179 were unvaccinated and 512 were vaccinated). Compared with the vaccinated group, the unvaccinated group had a longer length of hospital stay and a higher incidence rate of respiratory failure (P < 0.05). Among the children ≥ 3 months of age, the incidence of severe pneumonia in the unvaccinated group was higher than that in the vaccinated group (P < 0.05), and the incidence of severe pneumonia was the highest in the unvaccinated group (10.6%) and the lowest in the 4-dose vaccination group (1.2%). Among the 101 patients with severe pneumonia, 80 (79.2%) were observed in the unvaccinated group and only 21 (20.8%) in the four different doses vaccination groups. For the children with an age of onset of ≥ 3 months, the unvaccinated group had higher white blood cell count, absolute value of lymphocytes, and platelet count than the vaccinated group (P < 0.05). CONCLUSIONS: Pertussis vaccination can reduce the incidence of severe pneumonia and respiratory failure and alleviate the severity of respiratory complications in infants and young children with pertussis.

Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy.

Diabetic retinopathy (DR) is a microvascular complication of diabetes and one of the most common causes of blindness in active stage. This study is performed to explore the effects of microRNA-21 (miR-21) on retinal vascular endothelial cell (RVEC) viability and angiogenesis in rats with DR via the phosphatidylinositiol 3-kinase/protein kinase B (PI3K/Akt)/vascular endothelial growth factor (VEGF) signaling pathway by binding to phosphatase and tensin homolog (PTEN). Sprague Dawley (SD) rats were used for establishment of DR models. Target relationship between miR-21 and PTEN was assessed by bioinformatics prediction in combination with dual-luciferase reporter gene assay. Identification of expression of miR-21, PTEN and PI3K/Akt/VEGF signaling pathway-related genes in the retinal tissues was then conducted. In order to assess the contributory role of miR-21 in DR, the RVECs were transfected with mimic or inhibitor of miR-21, or siRNA-PTEN, followed by the detection of expression of PTEN and PI3K/Akt/VEGF-related genes, as well as the measurement of cell viability, cell cycle and apoptosis. Increased expression of miR-21 and PI3K/Akt/VEGF related genes, along with a reduced expression of PTEN was observed in the retinal tissues of DR rats. PTEN was targeted and negatively regulated by miR-21, while the PI3K/Akt/VEGF signaling pathway was activated by miR-21. RVECs transfected with miR-21 inhibitor exhibited promoted viability and angiogenesis, and inhibited apoptosis. To conclude, our results indicated that miR-21 overexpression could potentially stimulate RVEC viability and angiogenesis in rats with DR through activation of the PI3K/Akt/VEGF signaling pathway via repressing PTEN expression, highlighting the potential of miR-21 as a target for DR treatment.

C2-Symmetric 1,2-Diphenylethane-1,2-diamine-Derived Primary-Tertiary Diamine-Catalyzed Asymmetric Mannich Addition of Cyclic N-Sulfonyl Trifluoromethylated Ketimines.

A simple chiral primary-tertiary diamine derived from C2-symmetric 1,2-diphenylethane-1,2-diamine as the organocatalyst in combination with the trifluoroacetic acid additive for the asymmetric Mannich reaction of cyclic N-sulfonyl trifluoromethylated ketimines and methyl ketones afforded the desired product with high enantioselectivity (73-96% ee). The reactions proceeded well for a variety of different substituted cyclic N-sulfonyl trifluoromethyl ketimines and various alkyl methyl ketones, providing access to diverse enantioenriched benzo-fused cyclic sulfamidate N-heterocycles bearing a trifluoromethylated α-tetrasubstituted carbon stereocenter. This study also investigated the diastereoselective reduction of the carbonyl group and ring cleavage reduction of the sulfamidate group of the corresponding Mannich product.

MicroRNA-183 inhibition exerts suppressive effects on diabetic retinopathy by inactivating BTG1-mediated PI3K/Akt/VEGF signaling pathway.

Diabetic retinopathy (DR) is a serious diabetic complication caused by both environmental and genetic factors. Molecular mechanisms of DR may lead to the discovery of reliable prognostic indicators. The current study aimed to clarify the mechanism of microRNA-183 (miR-183) in DR in relation to the PI3K/Akt/VEGF signaling pathway. Microarray-based gene expression profiling of DR was used to identify the differentially expressed genes. Sprague-Dawley rats were used for the establishment of DR models, and then miR-183 was altered by mimic or inhibitor or BTG1 was downregulated by siRNA to explore the regulatory mechanism of miR-183 in DR. Furthermore, the expression of miR-183, CD34, endothelial nitric oxide synthase (eNOS), BTG1 and the PI3K/Akt/VEGF signaling pathway-related genes as well as reactive oxygen species (ROS) level was determined, and the relationship between miR-183 and BTG1 was also verified. Cell growth, cell apoptosis, and angiogenesis were determined. Microarray analysis revealed the involvement of miR-183 in DR via the PI3K/Akt/VEGF signaling pathway by targeting BTG1. Upregulated miR-183 and downregulated BTG1 were observed in retinal tissues of DR rats. miR-183 overexpression activated the PI3K/Akt/VEGF signaling pathway, upregulated CD34, eNOS, and ROS, and inhibited BTG1. BTG1 was confirmed as a target gene of miR-183. miR-183 overexpression or BTG1 knockdown promoted cell growth and tube formation while it suppressed cell apoptosis of vascular endothelial cells in DR rats. In this study, we demonstrated that miR-183 silencing inhibiting cell growth and tube formation in vascular endothelial cells of DR rats via the PI3K/Akt/VEGF signaling pathway by upregulating BTG1.

MicroRNA-200c plays an oncogenic role in nasopharyngeal carcinoma by targeting PTEN.

Recent studies suggested that microRNA-200 family microRNAs play critical roles in cancer initiation and metastasis. The underlying mechanism remained elusive. In this study, we show that microRNA-200c is upregulated in nasopharyngeal carcinoma cells. Manipulation of microRNA-200c levels affected cell growth, migration, and invasion in nasopharyngeal carcinoma cell lines. Furthermore, PTEN was identified as a direct target of microRNA-200c. Overexpression of PTEN resulted in similar effects to those of anti-microRNA-200c transfection. In vivo suppression of microRNA-200c level reduced tumor growth in mice. Overall, our data suggest that microRNA-200c plays an oncogenic role in nasopharyngeal carcinoma by targeting PTEN.

Effects of Intraoperative Hemodynamics on Incidence of Postoperative Delirium in Elderly Patients: A Retrospective Study.

BACKGROUND: Postoperative delirium (POD) is a common complication in the elderly. This retrospective study investigated the effect of intraoperative hemodynamics on the incidence of POD in elderly patients after major surgery to explore ways to reduce the incidence of POD. MATERIAL/METHODS: Based on the incidence of POD, elderly patients (81±6 y) were assigned to a POD (n=137) or non-POD group (n=343) after elective surgery with total intravenous anesthesia. POD was diagnosed based on the guidelines of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the confusion assessment method. The hemodynamic parameters, such as mean arterial pressure, were monitored 10 min before anesthesia (baseline) and intraoperatively. The incidence of intraoperative hypertension, hypotension, tachycardia, and bradycardia were calculated. RESULTS: At 30 min and 60 min after the initiation of anesthesia and at the conclusion of surgery, the monitored hemodynamic parameter values of the POD group, but not those of the non-POD group, were significantly higher than at baseline. Multivariate logistic regression analysis showed that intraoperative hypertension and tachycardia were significantly associated with POD. CONCLUSIONS: Intraoperative hypertension and tachycardia were significantly associated with POD. Maintaining intraoperative stable hemodynamics may reduce the incidence of POD in elderly patients undergoing surgery.

ANAC005 is a membrane-associated transcription factor and regulates vascular development in Arabidopsis.

Vascular tissues are very important for providing both mechanical strength and long-distance transport. The molecular mechanisms of regulation of vascular tissue development are still not fully understood. In this study we identified ANAC005 as a membrane-associated NAC family transcription factor that regulates vascular tissue development. Reporter gene assays showed that ANAC005 was expressed mainly in the vascular tissues. Increased expression of ANAC005 protein in transgenic Arabidopsis caused dwarf phenotype, reduced xylem differentiation, decreased lignin content, repression of a lignin biosynthetic gene and genes related to cambium and primary wall, but activation of genes related to the secondary wall. Expression of a dominant repressor fusion of ANAC005 had overall the opposite effects on vascular tissue differentiation and lignin synthetic gene expression. The ANAC005-GFP fusion protein was localized at the plasma membrane, whereas deletion of the last 20 amino acids, which are mostly basic, caused its nuclear localization. These results indicate that ANAC005 is a cell membrane-associated transcription factor that inhibits xylem tissue development in Arabidopsis.

Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting transcription factor AP-1.

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Nevertheless, the molecular mechanism of HBV replication remains elusive. SIRT1 is a class III histone deacetylase that is a structure component of the HBV cccDNA minichromosome. In this study, we found by using microarray-based gene expression profiling analysis that SIRT1 was upregulated in HBV-expressing cells. Gene silencing of SIRT1 significantly inhibited HBV DNA replicative intermediates, 3.5-kb mRNA, and core protein levels. In contrast, the overexpression of SIRT1 augmented HBV replication. Furthermore, SIRT1 enhanced the activity of HBV core promoter by targeting transcription factor AP-1. The c-Jun subunit of AP-1 was bound to the HBV core promoter region, as demonstrated by using a chromatin immunoprecipitation assay. Mutation of AP-1 binding site or knockdown of AP-1 abolished the effect of SIRT1 on HBV replication. Finally, SIRT1 inhibitor sirtinol also suppressed the HBV DNA replicative intermediate, as well as 3.5-kb mRNA. Our study identified a novel host factor, SIRT1, which may facilitate HBV replication in hepatocytes. These data suggest a rationale for the use of SIRT1 inhibitor in the treatment of HBV infection.

Spectral properties of the temporal evolution of brain network structure.

The temporal evolution properties of the brain network are crucial for complex brain processes. In this paper, we investigate the differences in the dynamic brain network during resting and visual stimulation states in a task-positive subnetwork, task-negative subnetwork, and whole-brain network. The dynamic brain network is first constructed from human functional magnetic resonance imaging data based on the sliding window method, and then the eigenvalues corresponding to the network are calculated. We use eigenvalue analysis to analyze the global properties of eigenvalues and the random matrix theory (RMT) method to measure the local properties. For global properties, the shifting of the eigenvalue distribution and the decrease in the largest eigenvalue are linked to visual stimulation in all networks. For local properties, the short-range correlation in eigenvalues as measured by the nearest neighbor spacing distribution is not always sensitive to visual stimulation. However, the long-range correlation in eigenvalues as evaluated by spectral rigidity and number variance not only predicts the universal behavior of the dynamic brain network but also suggests non-consistent changes in different networks. These results demonstrate that the dynamic brain network is more random for the task-positive subnetwork and whole-brain network under visual stimulation but is more regular for the task-negative subnetwork. Our findings provide deeper insight into the importance of spectral properties in the functional brain network, especially the incomparable role of RMT in revealing the intrinsic properties of complex systems.

[Study on anti-inflammation effect and involved mechanism of Guizhi Fuling capsule and its active complex].

The aim of this study was to investigate the anti-inflammatory effect of Guizhi Fuling capsule and its active complex (consistent of 15 active compounds) on LPS-induced RAW264. 7 cells. The effect of Guizhi Fuling capsule and its active complex on cell viability in RAW264. 7 cells were determined by MTT assay. The inhibitory effect of Guizhi Fuling capsule and active complex on the releasing of IL-1ß, TNF-α and PGE2 induced by LPS in RAW264. 7 cells was detected by ELISA assay. The expression of IL-1ß and mPGES-1 in Guizhi Fuling capsule or active complex treated RAW264. 7 cells was examined by Western blot assay. Guizhi Fuling capsule and active complex showed no significant effect on the cell viability in RAW264. 7 cells at doses range from 12.5 to 400 mg x L(-1). Compared with LPS treated group, Guizhi Fuling capsule and active complex dose dependently reduced the releasing of IL-1ß, TNF-α and PGE2 induced by LPS in RAW264. 7 cells. Moreover, the expression of IL-1ß and mPGES-1 was decreased after Guizhi Fuling capsule and active complex treatment, which might contribute to the inhibitory effect of Guizhi Fuling capsule in the releasing of IL-1ß, TNF-α and PGE2. This study provided the evidence that Guizhi Fuling capsule and active complex remarkably inhibited the releasing of IL-1ß, TNF-α and PGE2induced by LPS in RAW264. 7 cells by reducing the expression IL-1ß and mPGES-1. This study provided an experimental basis of Guizhi Fuling capsule for the treatment of inflammation and a theoretical basis for the development of effective compounds of Guizhi Fuling capsule.

[Adjunctive treatment of GnRHa combined wenshen xiaozheng decoction in treating endometriosis after laparoscopy: a clinical observation].

OBJECTIVE: To observe the therapeutic efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined Wenshen Xiaozheng Decoction (WXD) in auxiliary treating endometriosis after laparoscopy. METHODS: One hundred and thirty-four endometriosis patients with confirmative pathological diagnosis were assigned to three groups depending on whether they would receive adjuvant therapy or Chinese medicine treatment, i.e., the control group, the observation 1 group, and the observation 2 group. The 22 patients in the control group received no adjuvant therapy after laparoscopy. The 42 patients in the observation 1 group were treated with GnRHa 3.6 mg by subcutaneous injection starting from the 1st day to the 5th day of menstruation, once per 28 days. The 70 patients in the observation 2 group were treated with GnRHa 3.6 mg by subcutaneous injection in combination with WXD starting from the 1st day to the 5th day of menstruation, once per 28 days. They also took WXD for 7 doses, one cycle per every 28 days. The treatment lasted for three to six months. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cancer antigen 125 (CA125), as well as clinical efficacy, and adverse drug reactions were observed before and after treatment. RESULTS: There was statistical difference in serum levels of E2, FSH, or LH between the control group and the observation 1 and 2 groups (P < 0.05). There was no statistical difference in serum levels of E2, FSH, or LH between the observation 1 group and the observation 2 group (P > 0.05). There was statistical difference in the clinical efficiency among the 3 groups (P < 0.05). There was statistical difference in the pre-post difference of CA125 levels among the three groups (P < 0.01). Compared with the control group, there was no statistical difference in the pre-post difference of CA125 levels between the observation 1 group and the observation 2 group (P > 0.05). No obvious adverse reaction occurred during the treatment. CONCLUSIONS: GnRHa combined WXD showed confirmative clinical efficacy in treating endometriosis after laparoscopy. It also could lower serum levels of E2, FSH, and LH levels. So it was an ideal solution for treatment of endometriosis.

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling.

BACKGROUND: Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. METHODS: By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9-mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. RESULTS: Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155-3375 region of the 3'UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. CONCLUSIONS: Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.