Allosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea.

c-di-AMP is an essential and widespread nucleotide second messenger in bacterial signaling. For most c-di-AMP synthesizing organisms, c-di-AMP homeostasis and the molecular mechanisms pertaining to its signal transduction are of great concern. Here we show that c-di-AMP binds the N-acetylglucosamine (GlcNAc)-sensing regulator DasR, indicating a direct link between c-di-AMP and GlcNAc signaling. Beyond its foundational role in cell-surface structure, GlcNAc is attractive as a major nutrient and messenger molecule regulating multiple cellular processes from bacteria to humans. We show that increased c-di-AMP levels allosterically activate DasR as a master repressor of GlcNAc utilization, causing the shutdown of the DasR-mediated GlcNAc signaling cascade and leading to a consistent enhancement in the developmental transition and antibiotic production in Saccharopolyspora erythraea. The expression of disA, encoding diadenylate cyclase, is directly repressed by the regulator DasR in response to GlcNAc signaling, thus forming a self-sustaining transcriptional feedback loop for c-di-AMP synthesis. These findings shed light on the allosteric regulation by c-di-AMP, which appears to play a prominent role in global signal integration and c-di-AMP homeostasis in bacteria and is likely widespread in streptomycetes that produce c-di-AMP.

Enantioselective Total Synthesis of (-)-Daphenylline.

A concise enantioselective total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation of olefin and CuBr2-catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens' photoredox-catalyzed hydrocarboxylation was used twice, and Friedel-Crafts acylation thrice.

Protein acylation links metabolism and the control of signal transduction, transcription regulation, growth, and pathogenicity in Actinobacteria.

Actinobacteria have a complex life cycle, including morphological and physiological differentiation which are often associated with the biosynthesis of secondary metabolites. Recently, increased interest in post-translational modifications (PTMs) in these Gram-positive bacteria has highlighted the importance of PTMs as signals that provide functional diversity and regulation by modifying proteins to respond to diverse stimuli. Here, we review the developments in research on acylation, a typical PTM that uses acyl-CoA or related metabolites as donors, as well as the understanding of the direct link provided by acylation between cell metabolism and signal transduction, transcriptional regulation, cell growth, and pathogenicity in Actinobacteria.

Prevalence of prolonged grief disorder and its symptoms in Chinese parents who lost their only child: A systematic review and meta-analysis.

Background: Parents who lost their only child and cannot have a second child ("Shidu") have been a large population in China. Prolonged grief disorder (PGD) in Shidu parents is of clinical and public health concern but the reported PGD prevalence varies widely. To facilitate the planning of grief counseling services, this meta-analysis estimated prevalence of PGD and its symptoms and identified subgroups at elevated risk for PGD. Methods: We searched English and Chinese literature databases to identify cross-sectional surveys reporting prevalence of PGD or PGD symptoms in Chinese Shidu parents. The Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data ("JBI") was used to assess risk of bias of included studies. Results: Seven studies with a total of 2,794 Shidu parents were included and their JBI scores ranged from five to eight. The pooled prevalence of PGD and PGD symptoms was 20.9% and 75.0%, respectively. Greater risk of PGD was observed in mothers [vs. fathers, OR (odds ratio) = 1.89, P = 0.001] and in parents with religious beliefs (vs. without religious beliefs, OR = 1.65, P = 0.040). More severe PGD symptoms were presented in parents whose only child died from accidents [vs. illness, MD (mean difference) = 3.99, P < 0.001]. Deceased children of PGD parents were older than those of non-PGD parents (MD = 1.64, P = 0.035) and PGD parents had a shorter duration since the loss than non-PGD parents (MD = -3.26, P = 0.013). Conclusions: PGD is prevalent among Shidu parents. Grief counseling services for Shidu parents would be more effective if they target those who are mothers and have religious beliefs and those whose children died from accidents, lost children are older, and loss occurs more recently.

Synthesis and antibacterial activity studies in vitro of indirubin-3'-monoximes.

Multi-drug-resistant microbial pathogens are a serious global health problem. New compounds with antibacterial activity serve as good candidates for developing novel antibacterial drugs which is very urgent and important. In this work, based on the unique scaffold of indirubin, an active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan, we synthesized 29 indirubin-3'-monoximes and preliminarily evaluated their antibacterial activities. The antibacterial activity results demonstrated that the synthesized indirubin-3'-monoximes 5a-5z and 5aa-5ad displayed good potency against S. aureus ATCC25923 (MIC = 0.4-25.6 µg mL-1). Among them, we found that the 5-F, 5-Cl and 7-CF3 substituted indirubin-3'-monoximes 5r, 5s and 5aa also showed better antibacterial efficiency for S. aureus (MICs up to 0.4 µg mL-1) than the prototype natural product indirubin (MIC = 32 µg mL-1). More importantly, indirubin-3'-monoxime 5aa has certain synergistic effect with levofloxacin against clinic multidrug-resistant S. aureus (fractional inhibitory concentration index: 0.375). In addition, relevant experiments including electron microscopy observations, PI staining and the leakage of extracellular potassium ions and nucleic acid (260 nm) have been performed after treating S. aureus with indirubin-3'-monoxime 5aa, and the results revealed that indirubin-3'-monoximes could increase the cell membrane permeability of S. aureus. Although indirubin-3'-monoxime 5aa showed some cytotoxicity toward SH-SY5Y cells relative to compounds 5r and 5s, the skin irritation test of male mice after shaving showed that compound 5aa at a concentration of 12.8 µg mL-1 had no toxicity to mouse skin, and it could be used as a leading compound for skin antibacterial drugs.

Prevalence and correlates of suspected dementia in older adults receiving primary healthcare in Wuhan, China: A multicenter cross-sectional survey.

Background: Integrating the management of dementia into primary healthcare is a cost-effective way to reduce the burden of dementia but the clinical epidemiology of dementia in primary healthcare settings remains unclear. This study investigated the prevalence and correlates of suspected dementia in Chinese older adults receiving primary healthcare. Methods: In this multicenter cross-sectional survey, a total of 773 older adults (≥65 years) were consecutively recruited from seven urban and six rural primary care clinics in Wuhan, China, and interviewed with the validated Chinese version of the Brief Community Screening Instrument for Dementia (BCSI-D). Participants with suspected dementia were those who were screened positive on the BCSI-D. Results: The prevalence of suspected dementia in older primary healthcare adults was 26.8%. Factors significantly associated with suspected dementia were female sex (OR = 1.95, P < 0.001), age-group of 75+ (OR = 1.68, P = 0.004), poor financial status (OR = 4.79, P < 0.001), rural residence (OR = 1.47, P = 0.032), no regular physical exercise (OR = 1.74, P = 0.002), and stroke and other cerebrovascular diseases (OR = 1.97, P = 0.015). Conclusions: Chinese older adults receiving primary healthcare are at high risk of suspected dementia. Screening and intervention efforts for dementia in primary healthcare settings may be more useful to target older adults who are women, are 75 years and above, have poor economic status, are rural residents, have no exercise habit, and suffer from cerebrovascular diseases.

Selective recruitment of stress-responsive mRNAs to ribosomes for translation by acetylated protein S1 during nutrient stress in Escherichia coli.

The chemical modification of ribosomes plays an important regulatory role in cellular translation adaptation in response to environmental stresses. Nevertheless, how the modified ribosome reprograms the translation machinery for the preferential expression of the specific mRNAs encoding stress-responsive proteins to stress remains poorly understood. Here, we find that AcP-induced acetylation of K411 and K464 in ribosomal protein S1 during carbon-nitrogen imbalance, which in turn impacts its binding with distinct mRNAs. S1 acetylation shows differential selectivity for recruiting subsets of mRNAs to ribosomes. Using the RNC-Seq method, we find that mimic acetylated S1 prefers transcripts related with the formation of flagella/biofilms, two-component systems, nitrogen assimilation, amino acid degradation, and lipopolysaccharide biosynthesis, whereas inhibits the translation of mRNAs involved in amino acid biosynthesis and most ribosomal proteins. Importantly, further characterization of S1-binding site (SBS) sequences of mRNAs with different translation efficiencies indicated that the presence of a conserved motif allows coordinated regulation of S1 acetylation-driven translation reprogramming for cell survival during nitrogen starvation. These findings expand the repertoire of ribosome heterogeneity to the acetylation level of S1 at specific sites and its role in the ribosome-mediated regulation of gene expression as a cellular response at the translational level to stress.

Prevalence and correlates of suicidal ideation among older adults attending primary care clinics in Wuhan, China: A multicenter cross-sectional study.

Background: Primary care represents an ideal setting for screening for and managing suicidal older adults but the clinical epidemiology of suicidal ideation in Chinese older primary care patients remains unclear. This study investigated the prevalence and correlates of suicidal ideation in older Chinese adults receiving primary care. Methods: This multicenter cross-sectional survey included a total of 769 older adults (≥65 years) from seven urban and six rural primary care clinics in Wuhan, China. The presence of depressive symptoms and suicidal ideation was assessed with the Geriatric Depression Scale and a single-item question "In the past 12 months, did you think about ending your life?," respectively. Results: The 12-month prevalence of suicidal ideation in older primary care patients was 16.6%. Significant correlates of suicidal ideation were poor economic status (vs. good, OR = 2.80, P = 0.008), heart disease (OR = 2.48, P = 0.005), chronic gastric ulcer (OR = 3.55, P = 0.012), arthritis (OR = 2.10, P = 0.042), and depressive symptoms (OR = 11.29, P < 0.001). Conclusions: Suicidal ideation is common among older adults attending Chinese primary care clinics. It is necessary to integrate psychological crisis intervention into primary care to prevent late-life suicide.

A novel molybdenum disulfide nanosheet loaded Titanium/Zirconium bimetal oxide affinity probe for efficient enrichment of phosphopeptides in A549 cells.

In this paper, we developed a facile route for the preparation of a novel bimetal oxide affinity chromatography (MOAC) material. The TiO2/ZrO2@MoS2 was constructed by the electrostatic interaction between titanium oxide/zirconia (w:w, 10:1) and molybdenum disulfide nanosheet. The nanocomposite has the large specific surface area (186.30 m2⋅g-1) and pore volume (0.37 cm3⋅g-1). Compared with single-metal probes, the combination of bimetallic oxides probe (TiO2/ZrO2) and hydrophilicity MoS2 support offered multitudinous affinity sites for phosphopeptides capturing from tryptic digests of protein samples under 50% acetonitrile-1% trifluoroacetate conditions. Singnificant feasibility of the TiO2/ZrO2@MoS2 nanomaterial for the enrichment of phosphopeptides under optimal conditions was proved via the bovine serum albumin (BSA) and the mixtures of ß-casein. The phosphopeptide expression was identified using ultra-performance liquid chromatography (uHPLC) separation and-linear ion trap mass spectrometry (MSn). With these affinity characters of TiO2/ZrO2@MoS2, it exhibited higher binding capacity (25 mg⋅g-1), better selectivity for phosphopeptides from ß-casein/BSA (1:2000) tryptic digests, high sensitivity (1 fmol⋅µL-1) towards phosphopeptides from ß-casein tryptic digests, and great reusability of 8 cycles test for capturing phosphopeptides. In addition, the TiO2/ZrO2@MoS2 with high sensitivity and selectivity was successfully applied to enriching phosphopeptides from nonfat milk and human serum samples. More importantly, the TiO2/ZrO2@MoS2 was further successfully applied to multi-phosphopeptides enrichment, 1779 serine, threonine and tyrosine phosphosites can be identified in A549 cell protein tryptic digest. Compared with commercial TiO2 from enrichening 416 phosphopeptide from A549 cell lysates, the successful locating of 44 phosphosites were overlapped.

Development and application of an indirect ELISA to detect antibodies to Neospora caninum in cattle based on a chimeric protein rSRS2-SAG1-GRA7.

Neospora caninum is an important apicomplexan parasite causing neosporosis in cattle. The disease is recognized as one of the most important cause of reproductive problems and abortion in cattle worldwide. In this context, we developed an indirect enzyme-linked immunosorbent assays (ELISA) with chimeric protein rSRS2-SAG1-GRA7 to diagnose antibodies to Neospora-infection. This indirect ELISA was compared to indirect fluorescent antibody test (IFAT) and western blotting (WB), and the sensitivity and specificity results of ELISA were calculated to be 86.7 and 96.1%, respectively. The overall coincidence rate was 92.6% using IFAT and WB. Additionally, 329 aborting dairy cattle serum samples were tested using this ELISA to evaluate the prevalence of N. caninum in Ningxia, China. The positive rate of N. caninum in these farms was from 19.05 to 57.89%, and the mean rate was 41.64% (±11.01%), indicating that infection with N. caninum may be one of the important causes of cattle abortion in this region. This established rSRS2-SAG1-GRA7 indirect ELISA is capable for detecting the antibodies against N. caninum, and it could be a useful screening tool for monitoring the epidemiology of neosporosis in cattle.

A comparison of perioperative outcomes between extraperitoneal robotic single-port and multiport radical prostatectomy with the da Vinci Si Surgical System.

To evaluate outcomes between extraperitoneal robotic single-port radical prostatectomy (epR-spRP) and extraperitoneal robotic multiport radical prostatectomy (epR-mpRP) performed with the da Vinci Si Surgical System, comparison was performed between 30 single-port (SP group) and 26 multiport (MP group) cases. Comparisons included operative time, estimated blood loss (EBL), hospital stay, peritoneal violation, pain scores, scar satisfaction, continence, and erectile function. The median operation time and EBL were not different between the two groups. In the SP group, the median operation time of the first 10 patients was obviously longer than that of the latter 20 patients (P < 0.001). The median postoperative hospital stay in the SP group was shorter than that in the MP group (P < 0.001). The rate of peritoneal damage in the SP group was less than that in the MP group (P = 0.017). The pain score and overall need for pain medications in the SP group were lower than those in the MP group (P < 0.001 and P = 0.015, respectively). Patients in the SP group were more satisfied with their scars than those in the MP group 3 months postoperatively (P = 0.007). At 3 months, the cancer control, recovery of erectile function, and urinary continence rates were similar between the two groups. It is safe and feasible to perform epR-spRP using the da Vinci Si surgical system. Therefore, epR-spRP can be a treatment option for localized prostate cancer. Although epR-spRP still has a learning curve, it has advantages for postoperative pain and self-assessed cosmesis. In the absence of the single-port robotic surgery platform, we can still provide minimally invasive surgery for patients.

Facile synthesis of magnetic molybdenum disulfide@graphene nanocomposite with amphiphilic properties and its application in solid-phase extraction for a wide polarity of insecticides in wolfberry samples.

A novel magnetic molybdenum disulfide@graphene (Fe3O4/MoS2@G) nanocomposite with amphiphilic properties was prepared via a co-mixing solvothermal method. To demonstrate the feasibility of Fe3O4/MoS2@G as a sorbent during sample preparation, it was employed for the magnetic solid phase extraction (MSPE) of ten pyrethroids, three triazoles and two acaricide pyridaben and picoxystrobin in an emulsified aqueous solution. Dichloromethane was used as the extractant to form an emulsified aqueous solution. Subsequently, the Fe3O4/MoS2@G sorbent with amphiphilic properties was used to retrieve 15 wide polarity insecticides from dichloromethane via MSPE. The proposed method has the advantage of being applicable to different polar pesticides, strengthening the capacity of enrichment and purification of target analytes. The π-π interaction between the hydrophilic and hydrophobic moieties of Fe3O4/MoS2@G and the aromatic rings of target analytes were responsible for the efficient sorption. Thus, a reliable, convenient, and efficient method for the analysis of 15 insecticides with wide polarity in wolfberry samples was established by coupling Fe3O4/MoS2@G nanocomposite MSPE with gas chromatography-mass spectrometry (GC-MS) analysis. The obtained linearity of this method was in the range from 1 to 5000 ng mL-1 for 15 analytes, with determination coefficients (R2) ≥0.9907. The limit of detection (LOD) for 15 insecticides was in the range from 0.1 to 5.0 ng g-1. The recoveries of 15 insecticides from spiked wolfberry samples were in the range from 71.41% to 110.53%, and RSD was less than 14.8%.

A comparison of perioperative outcomes between extraperitoneal robotic single-port and multiport radical prostatectomy with the da Vinci Si Surgical System / 亚洲男科学杂志(英文版)

To evaluate outcomes between extraperitoneal robotic single-port radical prostatectomy (epR-spRP) and extraperitoneal robotic multiport radical prostatectomy (epR-mpRP) performed with the da Vinci Si Surgical System, comparison was performed between 30 single-port (SP group) and 26 multiport (MP group) cases. Comparisons included operative time, estimated blood loss (EBL), hospital stay, peritoneal violation, pain scores, scar satisfaction, continence, and erectile function. The median operation time and EBL were not different between the two groups. In the SP group, the median operation time of the first 10 patients was obviously longer than that of the latter 20 patients (P < 0.001). The median postoperative hospital stay in the SP group was shorter than that in the MP group (P < 0.001). The rate of peritoneal damage in the SP group was less than that in the MP group (P = 0.017). The pain score and overall need for pain medications in the SP group were lower than those in the MP group (P < 0.001 and P = 0.015, respectively). Patients in the SP group were more satisfied with their scars than those in the MP group 3 months postoperatively (P = 0.007). At 3 months, the cancer control, recovery of erectile function, and urinary continence rates were similar between the two groups. It is safe and feasible to perform epR-spRP using the da Vinci Si surgical system. Therefore, epR-spRP can be a treatment option for localized prostate cancer. Although epR-spRP still has a learning curve, it has advantages for postoperative pain and self-assessed cosmesis. In the absence of the single-port robotic surgery platform, we can still provide minimally invasive surgery for patients.

Overexpression of grapevine VvNAC08 enhances drought tolerance in transgenic Arabidopsis.

NAC [No apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), Cup-shaped cotyledon (CUC)] transcription factors (TFs) play an important role in plant growth and response to various environmental stress. Drought stress is the primary factor limiting the growth and fruit quality of grapevines worldwide. However, the biological function of the NAC family members in grapevine is not clear. In this study, we reported that VvNAC08, a novel NAC transcription factor gene, was expressed after drought, salicylic acid (SA) and abscisic acid (ABA), jasmonic acid (JA) and melatonin (MT) treatments in grapevine. VvNAC08 was expressed in various tissues. The open reading frame (ORF) of VvNAC08 was 792 bp, encoding 263 amino acids. The VvNAC08 protein could bind to NACRS [CGTA/CACG] in yeast. When subjected to drought and dehydration stress, VvNAC08-overexpression (OE) Arabidopsis had a higher survival rate and a lower water loss rate than wild type (WT) plants. Under drought conditions, transgenic Arabidopsis overexpressing VvNAC08 had a lower malondialdehyde (MDA), H2O2 contents, but a higher peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) activities as well as more proline content. Moreover, the expressions of marker genes, including ABI5, AREB1, COR15A, COR47, P5CS, RD22, and RD29A, were up-regulated in VvNAC08-overexpression lines when subjected to drought treatments. The results suggest that the transgenic Arabidopsis overexpressing VvNAC08 enhances resistance to drought while up-regulating the expressions of ABA- and stress-related genes.

A Hallmark-Based Six-Gene Expression Signature to Assess Colorectal Cancer and Its Recurrence Risk.

Purpose: As part of the effort to establish a general profile for solid tumors, the aim of this study was to develop a real-time polymerase chain reaction (RT-PCR)-based assay to assess colorectal cancer (CRC) and its recurrence risk utilizing the limited amounts of tissues available from biopsies through colonoscopy. Materials and Methods: Six candidate genes, reflecting the hallmarks of cancer cells, were identified by analyzing the gene expression profiles of primary invasive tumors in the public database. The expression of these genes in CRC and noncancerous colon tissues was quantified by RT-quantitative PCR. Classifiers were then generated to distinguish the tumors from the normal colon tissues, and to assess the risk of CRC recurrence based on the disease-free survival time, overall survival time, and metastatic status of the patients. Results: The expression profile of a five-gene panel was utilized to build a model that is capable of distinguishing CRC cancer tissues from noncancerous colorectal tissues (p < 0.0001). A classifier based on the expression signature of four genes, three of which were included in the five-gene panel, was then developed for assessing the tumor recurrence risk. This classifier could correctly identify those with a poor likelihood of survival (high risk of recurrence) >80% of time. There was a significant difference in disease-free survival time between patients in the low recurrence group and those in the high-risk group. Conclusion: The expression signatures of the six genes that reflect the genetic hallmarks of cancer cells could serve as a biomarker for identifying CRC and assessing the risk of recurrence with high sensitivity and specificity.

Anti-tumor activity and mechanism of oligoclonal hepatocellular carcinoma tumor-infiltrating lymphocytes in vivo and in vitro.

Objective: To explore a method for culturing hepatocellular carcinoma and tumor-infiltrating lymphocytes (HCC-TIL) and investigate the mechanism of TIL in killing tumors. Methods: The distribution of regulatory T cells (Treg) in HCC was detected by immunohistochemistry. Conventional TIL and oligoclonal TIL were isolated by the traditional method of enzyme digestion combined with mechanical treatment for whole HCC and micro HCC tissue block culturing method. MTT was used to compare the killing activity of TIL. Flow cytometry was used to analyze the proportion of CD8+ T cells and Treg cells in TIL. Tumor-bearing mice were established, and TIL adoptive immunotherapy was performed. Results: Treg cells were mainly distributed in the stroma of HCC. In vitro experiments showed oligoclonal TIL had higher cytotoxicity to tumor cells which negatively correlated with the proportion of Treg cells. In vivo experiments showed oligoclonal TIL had a higher anti-tumor effect. IFN-γ in peripheral blood and the positive rate of intratumoral lymphocytic infiltration in oligoclonal TIL group were both higher. TGF-ß and IL-10 in peripheral blood and the positive rate of intratumoral FoxP3 and IL-17 were both lower than those in conventional TIL group. Conclusion: The oligoclonal TIL culture method could obtain TIL with higher purity, and cytotoxicity to tumor cells was associated with Treg cells. The oligoclonal TIL had cytotoxicity to autologous HCC cells and significant inhibitory effect on the growth of transplanted tumors. The mechanism might be associated with the inhibition of Treg cells proliferation, increase of IFN-γ secretion, and decrease of TGF-ß, IL-10, and IL-17 secretion.

Robust analysis of novel mRNA-lncRNA cross talk based on ceRNA hypothesis uncovers carcinogenic mechanism and promotes diagnostic accuracy in esophageal cancer.

BACKGROUND: ceRNAs have emerged as pivotal players in the regulation of gene expression and play a crucial role in the physiology and development of various cancers. Nevertheless, the function and underlying mechanisms of ceRNAs in esophageal cancer (EC) are still largely unknown. METHODS: In this study, profiles of DEmRNAs, DElncRNAs, and DEmiRNAs between normal and EC tumor tissue samples were obtained from the Cancer Genome Atlas database using the DESeq package in R by setting the adjusted P<0.05 and |log2(fold change)|>2 as the cutoff. The ceRNA network (ceRNet) was initially constructed to reveal the interaction of these ceRNAs during carcinogenesis based on the bioinformatics of miRcode, miRDB, miRTarBase, and TargetScan. Then, independent microarray data of GSE6188, GSE89102, and GSE92396 and correlation analysis were used to validate molecular biomarkers in the initial ceRNet. Finally, a least absolute shrinkage and selection operator logistic regression model was built using an oncogenic ceRNet to diagnose EC more accurately. RESULTS: We successfully constructed an oncogenic ceRNet of EC, crosstalk of hsa-miR372-centered CADM2-ADAMTS9-AS2 and hsa-miR145-centered SERPINE1-PVT1. In addition, the risk-score model -0.0053*log2(CADM2)+0.0168*log2(SERPINE1)-0.0073*log2(ADAMTS9-AS2)+0.0905*log2(PVT1)+0.0047*log2(hsa-miR372)-0.0193*log2(hsa-miR145), (log2[gene count]) could improve diagnosis of EC with an AUC of 0.988. CONCLUSION: We identified two novel pairs of ceRNAs in EC and its role of diagnosis. The pairs of hsa-miR372-centered CADM2-ADAMTS9-AS2 and hsa-miR145-centered SERPINE1-PVT1 were likely potential carcinogenic mechanisms of EC, and their joint detection could improve diagnostic accuracy.

Hsa_circ_0007534/miR-761/ZIC5 regulatory loop modulates the proliferation and migration of glioma cells.

Increasing evidences demonstrate the essential roles of circular RNAs (circRNAs) in human cancers. However, the study about the functions of circRNAs in glioma remains very limited. In the present study, we found that circRNA hsa_circ_0007534 was highly expressed in glioma tissues compared to normal brain tissues. Furthermore, we found that knockdown of hsa_circ_0007534 significantly inhibited the proliferation and migration of glioma cells. In mechanism, we showed that hsa_circ_0007534 could sponge miR-761 to repress its availability in glioma cells. We found that inhibition of miR-761 could rescue the suppressed proliferation and migration of glioma cells by hsa_circ_0007534 knockdown. Moreover, we explored the downstream mechanism and found that ZIC5 was a target of miR-761. We showed that hsa_circ_0007534 promoted the expression of ZIC5 by inhibiting miR-761 in glioma cells. And restoration of ZIC5 expression significantly reversed the effects of hsa_circ_0007534 knockdown on glioma cell proliferation and migration. In summary, our results demonstrated that hsa_circ_0007534 serves as an oncogene in glioma via promoting ZIC5 expression by repressing miR-761 availability. Our results suggested that hsa_circ_0007534/miR-761/ZIC5 regulatory loop might be a promising therapeutic target for glioma treatment.

Effect of Fructus Ligustri Lucidi on osteoblastic like cell-line MC3T3-E1.

UNLABELLED: Fructus Ligustri Lucidi, fruits of Ligustrum lucidum Ait. (Oleaceae), has the effects of tonifying the liver and the kidney and strengthening the bones and muscles. In ancient times, Fructus Ligustri Lucidi can be prepared in ethanol or in water. Some active compounds have been found in Fructus Ligustri Lucidi, like Oleanolic acid and Ursolic acid, and Ursolic acid were proved to have osteogenic effects. METHODS AND RESULTS: To prove that Fructus Ligustri Lucidi water extract have osteogenic effects on MC3T3-E1 cells and how these effects work, we used CCK-8 (cell counting kit-8), ELISA (enzyme-linked immunosorbent assay), FQ-PCR (realtime fluorescence quantitative PCR) and western blot assays. After treatment with Fructus Ligustri Lucidi for 48h, 72h, 96h, the cell viability was marked increased, on concentration-dependently and time-dependently pattern. High and low concentrations of Fructus Ligustri Lucidi promoted differentiation of cells. Fructus Ligustri Lucidi could up-regulate OPG and RANKL protein in supernatant at 48h and 72h except for highest concentration (10(-1)mg/ml). Fructus Ligustri Lucidi promote OPG and RANKL mRNA expression at 48h and 72h, while the level of promoting at 72 was higher than 48h. 10(-5)mg/ml of Fructus Ligustri Lucidi up-regulates OPG protein expression and down-regulates RANKL protein expression. After treatment with Fructus Ligustri Lucidi water extract, inhibitors, Fructus Ligustri Lucidi water extract with inhibitors for 72h, inhibitors PD 98059, SB 203580, SP600125 and LY 294002 showed Fructus Ligustri Lucidi-induced cell proliferation and the leakage of OPG proteins effects. Fructus Ligustri Lucidi promoted the protein levels of ERK, p-ERK, p-JNK, p38, pp38, AKT and p-AKT, and inhibited the protein levels of JNK. CONCLUSIONS: Fructus Ligustri Lucidi water extract promoted cell proliferation and differentiation, mRNA and protein expression of OPG and RANKL on MC3T3-E1 cells. The effects of cell proliferation and leakage of OPG related to MAPK and AKT signaling pathways in different ways.

[Cost-effectiveness of schistosomiasis comprehensive control in Lushan County from 2007 to 2012].

OBJECTIVE: To evaluate the cost-effectiveness of comprehensive control strategy which mainly controls the schistosomiasis infection source in Lushan County from 2007 to 2012. METHODS: The data of the schistosomiasis endemic, Oncomelania hupensis snail status, control technology, and funding were collected and analyzed statistically in the endemic villages of Lushan County from 2007 to 2012. RESULTS: The schistosome infection rate of the residents decreased from 0.04% in 2007 to 0 in 2012. The numbers of advanced schistosomiasis patients decreased from 128 in 2007 to 121 in 2012. No acute schistosomiasis patients were found. The average density of living snails decreased from 0.06 snial/0.1 m2 to 0.05 snail/0.1 m2, with the decreased rate of 16.67%, and no schistosome infected snails were found. However, the snail area increased from 15.84 hm2 in 2007 to 52.12 hm2 in 2012, with the rise rate of 229.04%. The year per capita was 200.48 yuan, the cost of the infection rate decreasing by 1% was 949,900 yuan, and the cost of living snail density decreasing by 1% was 5,698,200 yuan. CONCLUSION: The cost-effectiveness of comprehensive control strategy which mainly controls the schistosomiasis infection source is relatively good in Lushan County from 2007 to 2012.