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In this study, we investigated the effect of three-dimensional of naringin/gelatin microspheres/nano-hydroxyapatite/silk fibroin (NG/GMs/nHA/SF) scaffolds on repair of a critical-size bone defect of lumbar 6 in osteoporotic rats. In this work, a cell-free scaffold for bone-tissue engineering based on a silk fibroin (SF)/nano-hydroxyapatite (nHA) scaffold was developed. The scaffold was fabricated by lyophilization. Naringin (NG) was loaded into gelatin microspheres (GMs), which were encapsulated in the nHA/SF scaffolds. The materials were characterized using x ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy and thermogravimetric analysis. Moreover, the biomechanics, degradation, and drug-release profile of the scaffold were also evaluated. In vitro, the effect of the scaffold on the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was evaluated. In vivo, at 3 months after ovariectomy, a critical-size lumbar defect was indued in the rats to evaluate scaffold therapeutic potential. A 3-mm defect in L6 developed in 60 SD rats, which were randomly divided into SF scaffold, nHA/SF scaffold, NG/nHA/SF scaffold, NG/GMs/nHA/SF scaffold, and blank groups (n = 12 each). At 4, 8, 12, and 16 weeks postoperatively, osteogenesis was evaluated by X-ray, micro-computed tomography, hematoxylin-eosin staining, and fast green staining, and by analysis of BMP-2, Runx2, and Ocn protein levels at 16 weeks. In our results, NG/GM/nHA/SF scaffolds exhibited good biocompatibility, biomechanical strength, and promoted BMSC adhesion, proliferation, and calcium nodule formation in vitro. Moreover, NG/GMs/nHA/SF scaffolds showed greater osteogenic differentiation potential than the other scaffolds in vitro. In vivo, gradual new bone formation was observed, and bone defects recovered by 16 weeks in the experimental group. In the blank group, limited bone formation was observed, and the bone defect was obvious. In conclusion, NG/GMs/nHA/SF scaffolds promoted repair of a lumbar 6 defect in osteoporotic rats. Therefore, the NG/GMs/nHA/SF biocomposite scaffold has potential as a bone-defect-filling biomaterial for bone regeneration.

Decompressive craniectomy is widely used to treat medically refractory intracranial hypertension. There were still few studies focusing on the complications between titanium cranioplasty with non-titanium materials cranioplasty. Our systematic review and meta-analysis aimed to assess the complications following titanium cranioplasty and to make a comparison with nontitanium materials. A systematic review was used to review titanium cranioplasty characters in recent articles. A systematic literature review and meta-analysis were performed by using PubMed/MEDLINE, Scopus, the Cochrane databases and Embase for studies reporting on cranioplasty procedures that compared complication outcomes between titanium with non-titanium materials. The final 15 studies met inclusion criteria and represented 2258 cranioplasty procedures (896 titanium, 1362 nontitanium materials). Overall complications included surgical site infection, hematoma, implant exposure, seizure, cerebrospinal fluid leak, imprecise fitting. Titanium cranioplasty was associated with a significant decrease in overall complications rate (OR, 0.72; P = 0.007), hematoma rate (OR, 0.31; P = 0.0003) and imprecise fitting rate (OR, 0.35; P = 0.04). However, it also suggested that titanium cranioplasty can be greatly increased implant exposure rate (OR, 4.11; P 0.00001). Our results confirmed the advantages of titanium cranioplasty in reducing complications including hematoma, imprecise fitting, and also suggested that clinicians should pay more attention to postoperative implant exposure. With new synthetic materials emerging, it would also be interesting to study the cost-effect and functional outcomes associated with cranioplasty materials.

To evaluate the efficacy and safety of foraminoplasty using percutaneous transforaminal endoscopic discectomy (PTED) (performed with the aid of an endoscopic drill) to treat patients with axillary disc herniations.From October 2016 to October 2018, 83 patients with single segmental axillary disc herniations diagnosed via magnetic resonance imaging who had undergone PTED were retrospectively evaluated. Of these, 38 and 45 underwent foraminoplasty using a trephine and an endoscopic drill, respectively. The 2 groups did not differ significantly in terms of age, sex, the herniated segment, the preoperative visual analog score (VAS), or the Oswestry disability index (ODI) (all P0.05). Foraminoplasty-related index scores were recorded.We found no significant between-group difference in the VAS and ODI scores at any time after surgery; in contrast, the scores improved significantly compared with those before surgery (both P0.05). Compared with the trephine group, the fluoroscopy time was shorter in the endoscopic drill group but the foraminoplasty and total operation times were longer.Foraminoplasty featuring endoscopic drilling can be used to treat axillary-type lumbar disc herniations. The radiation exposure time is less than that of the trephine approach, but the drilling approach is less efficient. The short-term clinical outcomes afforded by the 2 methods do not differ.

EGFRvⅢ is an established target for immunotherapy of glioblastoma (GBM). Current study aims to explore the efficacy of EGFRvⅢ-targeted immunotoxin combined with temozolomide (TMZ) or T cell-engaged bispecific antibody for the treatment of GBM. We generated three rabbit monoclonal antibodies (R1, R2, and R6) that specifically bound to EGFRvⅢ, but not EGFR, with high affinity. Immunotoxins were made by fusing the scFv of these antibodies with engineered Pseudomonas exotoxin PE24. The in vitro cytotoxicity and specificity of the immunotoxins was rigorously validated by EGFRvⅢ and EGFR-expressed cell lines. The in vivo efficacy of immunotoxin monotherapy and in combination with TMZ or EGFRvⅢ-targeted bispecific antibody was evaluated in orthotopic and subcutaneous xenograft mouse models. EGFRvⅢ immunotoxins potently killed U87, U251 and GL261 cells that were forcefully expressing EGFRvⅢ, with IC

Listeria monocytogenes, as a food-associated pathogen, is able to develop biofilms on different surfaces of food contact, which seriously threatens food safety. Phenyllactic acid (PLA) exhibits excellent inhibitory effects on many bacterial strains including L. monocytogenes. Our study aimed to investigate effects of PLA on L. monocytogenes biofilms and its growth in milk and on spiced beef. Biofilm biomass was measured by the microplate method and biofilm structure was observed by electron microscopy. Growth of L. monocytogenes in food samples was determined by colony counting. Results from the agar dilution method demonstrated that L. monocytogenes 10403S had a PLA minimum inhibitory concentration (MIC) value of 6 mg/ml. Sub-inhibitory concentrations of PLA could inhibit biofilm formation by reducing the secretion of exopolysaccharides and extracellular proteins in L. monocytogenes. PLA at concentrations above 1/2MIC could destroy mature biofilms of L. monocytogenes by decreasing the exopolysaccharides and extracellular proteins in the biofilm framework. Both swimming and swarming motilities of L. monocytogenes were inhibited by PLA. The hemolytic activity of L. monocytogenes was inactivated by PLA. However, the capacity to attach and invade Caco-2 cells was not affected by PLA. The results displayed that PLA had no effect on the expression of genes associated with motility, but reduced the expression level of the hly gene encoding Listeria hemolysin. When added to ultra-high temperature (UHT) whole and pasteurized milk, PLA at 3 mg/ml inhibited L. monocytogenes growth through 14 days of storage at 4 °C. PLA at concentrations ≥3 mg/ml significantly reduced L. monocytogenes counts on spiced beef samples during storage. PLA has potential as an alternative antimicrobial to control L. monocytogenes contamination and its biofilms in food industry.

Objective The current standard treatment of malignant glioma is maximal resection followed by chemotherapy and radiotherapy. Temozolomide (TMZ) has been the first-line chemotherapeutic agent used, although to achieve a satisfactory clinical effect. TMZ chemoresistance could result from glioblastoma stem cells, which are critical for tumor initiation, recurrence, and therapeutic resistance and are potential targets. Moreover, signals mediated by the dopamine D2 receptor (DRD2) can positively regulate proliferation and tumorigenesis of glioma cells. Results To enhance TMZ's antitumor effect, we treated glioma cells with combinations of TMZ and DRD2 antagonists (DDRAs). The combined application of TMZ and DDRAs (haloperidol or risperidone) had synergistic effects and inhibited proliferation of glioma cells more significantly than did monotherapy. The combined treatment increased the levels of γH2AX (a marker of DNA damage) more significantly than did TMZ alone, although DDRAs alone had no effect on γH2AX levels. Moreover, the expression of DRD2 transcripts in U251 glioma cells and glioblastoma stem cells were significantly elevated after TMZ treatment, suggesting crosstalk between TMZ- and DRD2-mediated signaling. To explore the underlying mechanisms, we measured the expression of prosurvival proteins after treatment with either TMZ or DDRAs alone or combined. The results showed that DDRAs could inhibit the extracellular signal-related kinase signaling pathway and block TMZ-induced protective autophagy, which could explain why DDRAs increased the cytotoxicity of TMZ. Conclusions We have provided evidence showing the synergistic effects of TMZ and DDRAs on suppressing glioma cell growth. Our study has provided novel insights on enhancing the effectiveness of chemotherapy against malignant glioma and eventually improving the clinical outcomes of patients with glioblastoma multiforme.

Recent studies have reported that microRNA-155 (miR-155) is linked to the clinical outcomes of many tumors. However, its role in prognosis of gliomas remains unclear. This meta-analysis aims to evaluate the prognostic value of miR-155 in the survival of patients with gliomas. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) were pooled with random effects or fixed effects models on the basis of heterogeneity. Subgroup analysis and sensitivity analysis were performed to elucidate the possible confounding factors and investigate the source of heterogeneity. In addition, we assessed publication bias using the Begg's funnel plots, Egger's test, and Begg's test. Only non-laboratory studies were considered for our analysis. 9 studies from 6 articles containing 1259 glioma patients were included. The pooled HR of elevated miR-155 for OS in patients with gliomas was 1.40 (95%CI [1.19-1.63], P 0.001) (I-squared = 52.4%, P = 0.032) suggesting that miR-155 might be a promising biomarker for the prognosis of gliomas in future clinical applications.

Background: Meningioma invasion can be pre-operatively recognized by radiomic features, which significantly contributes to treatment decision-making. Here, we aimed to evaluate the comparative performance of radiomic signatures derived from varying regions of interests(ROIs) in predicting BI and ascertaining the optimal width of the peritumoral regions needed for accurate analysis. Methods: 505 patients from Wuhan Union Hospital (internal cohort) and 214 cases from Taihe Hospital (external validation cohort) that pathologically diagnosed as meningioma were included in our study. Feature selection was performed from 1015 radiomic features respectively obtained from nine different ROIs[brain-tumor interface(BTI)2-5mm; whole tumor; the amalgamation of the two regions] on contrast-enhancement T1-weighted imaging using least absolute shrinkage and selection operator and random forest. Principal component analysis with varimax-rotation was employed for feature reduction. Receiver operator curve was utilized for assessing discrimination of the classifier. Furthermore, clinical index was used to detect the predictive power. Findings: Model obtained from BTI4mm ROI has the maximum AUC in the training set (0.98(0.97-0.99)), internal validation set (0.97(0.93-1)), and external validation set (0.72(0.62-0.81)) and displayed statistically significant results between nine radiomics models. The most predictive radiomic features are almost entirely generated from GLCM and GLDM statistics. The addition of PEV to radiomic features(BTI4mm) enhanced model discrimination of invasive meningiomas. Interpretation: The combined model(radiomic classifier with BTI4mm ROI + PEV) had greater diagnostic performance than other models, and may contribute to clinical application for meningioma patients. Funding: This study has received funding from National Natural Science Foundation of China (81974390). Declaration of Interest: The authors declare no potential conflicts of interest. Ethical Approval: The Wuhan Union Hospitals' Ethics Committees approved this research (NO. 2021-0098-01).

Objective An outbreak of 2019 coronavirus disease (COVID-19) occurred in Wuhan (Hubei, China) in December, 2019. Facing this largescale infectious public health event, everyone is under great psychological pressure. The aim was to investigate the psychological status of people affected by the COVID-19 outbreak in China. Methods The online cross-sectional study involving 922 participants (656 medical staff and 266 general population) was conducted in China between February and March, 2020. The psychological status was evaluated using the Symptom Check List 90 Revised (SCL-90). Linear and logistic regression analysis were used to examine the effect in the study. Results Of the 922 participants, approximately 18.3% had psychological health problems. The score of the SCL-90 was significant higher in medical staff (mean = 1.49) than that in general population (mean = 1.36). In addition, the participants enrolled in March were less likely to have psychological health problems than in February (odds ratio = 0.42, 95% confidence interval [CI] = 0.30 to 0.59). Female had a 1.44-fold risk of psychological health problems than male (95% CI = 1.01 to 2.03). Conclusions In the study, 18.3% had psychological health problems during the outbreak of COVID-19 epidemic. With the remission of the epidemic, the psychological health status of participants has been improved. Medical staff were likely to have higher SCL-90 scores than general population and female had more psychological problems than male. Our findings can be used to formulate psychological interventions for improving the mental health of vulnerable groups during the COVID-19 epidemic., Highlights • The participant in March have less psychological health problems than in February. • Medical staff were likely to have higher SCL-90 scores than general population. • Female was likely to have more psychological health problems than male.

Background: Last winter, a new coronavirus-induced pneumonia, COVID-19, broke out in Wuhan, China, and spread rapidly throughout the country due to its high inf

Background: Despite large populations with osteoporosis worldwide, no comprehensive study on the risk factors for different bone loss stages exists. We therefore assessed bone health status and the prevalence of and risk factors for the different bone loss stages. Methods: This cross-sectional study included a representative sample of postmenopausal women and elderly men aged ≥50 years (N=1,412: 1,031 women, 381 men) recruited from eight communities in Guangzhou. All participants underwent measurement of bone mineral density of the lumbar vertebrae and left hip and an assessment of serum bone metabolism parameters. Demographic, clinical, and laboratory data were compared among patients with different bone loss stages. We used univariable and multivariable logistic regression models to explore the risk factors associated with osteopenia or osteoporosis. Findings: The prevalence of osteopenia and osteoporosis was 48·7% and 36·5% in women and 58·3% and 22·3% in men, respectively. For postmenopausal women with normal bone mass, a higher risk of osteoporosis was associated with older age, menstruation duration

Background: Development of strategies for mitigating COVID-19 outbreak in a hospital setting is a public health priority. Methods: We developed an individual-based model for COVID-19 transmission among healthcare workers (HCWs) in a hospital setting. We calibrated the model using data of a COVID-19 outbreak in a hospital unit in Wuhan. The calibrated model was used to simulate different intervention scenarios and estimate the impact of different interventions on outbreak size and workday loss. Findings: We estimated that work-related stress increases susceptibility to COVID-19 infection among HCWs by 52% (90% CrI: 16·4% - 93·0%). The use of high efficacy facial masks was shown to be able to reduce infection cases and workday loss by 80% (90% CrI: 73·1% - 85·7%) and 87% (CrI: 80·0% - 92·5%), respectively. The use of social distancing alone, through reduced contacts between HCWs, had a marginal impact on the outbreak. A strict quarantine policy with isolation of symptomatic cases and a high fraction of pre-symptomatic cases (via contact tracing or high test rate), could only prolong outbreak duration with minimal impact on the outbreak size. Our results indicated that a quarantine policy should be coupled with other interventions to achieve its effect. The effectiveness of all these interventions was shown to increase with their early implementation. Interpretation: Our analysis shows that a COVID-19 outbreak in a hospital’s non-COVID-19 unit can be controlled or mitigated by the use of existing non-pharmaceutical measures. Funding Statement: This work was supported by the National Science Foundation RAPID Award [grant number DEB-2028631 to QH, AM, and DG], the National Science Foundation RAPID Award [grant number DEB-2028632 to MN], and the Fundamental Research Funds for the Central Universities [grant number 2020kfyXGYJ010 to XJ]. Declaration of Interests: All authors declare no competing interests.

Background: There had been a preliminary occurrence of human-to-human transmissions between healthcare workers (HCWs), but risk factors in the susceptibility for COVID-19, and infection patterns among HCWs have largely remained unknown. Methods: Retrospective data collection on demographics, lifestyles, contact status with infected subjects for 118 HCWs (include 12 COVID-19 HCWs) from a single-center. Sleep quality and working pressure were evaluated by Pittsburgh Sleep Quality Index (PSQI) and The Nurse Stress Index (NSI), respectively. Follow-up duration was from Dec 25, 2019, to Feb 15, 2020. Risk factors and transmission models of COVID-19 among HCWs were analyzed and constructed. Findings: A high proportion of COVID-19 HCWs had engaged in night shift-work (75.0% vs. 40.6%) and felt they were working under pressure (66.7% vs. 32.1%) than uninfected HCWs. COVID-19 HCWs had higher total scores of PSQI and NSI than uninfected HCWs. Furthermore, these scores were both positively associated with COVID-19 risk. An individual-based model (IBM) estimated the outbreak duration among HCWs in a non-typical COVID-19 ward at 62-80 days and the basic reproduction number =1.27 [1.06, 1.61]. By reducing the average contact rate per HCW by a 1.35 factor and susceptibility by a 1.40 factor, we can avoid an outbreak of the basic case among HCWs. Interpretation: Poor sleep quality and high working pressure were positively associated with high risks of COVID-19. A novel IBM of COVID-19 transmission is suitable for simulating different outbreak patterns in a hospital setting. Funding Statement: This work was supported by the Fundamental Research Funds for the Central Universities (grant 2020kfyXGYJ010 to Dr. X. Jiang). Declaration of Interests: None. Ethics Approval Statement: This study was approved by the institutional ethics board of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (No. 20200029).

Study Design A retrospective study. Objectives Anterior cervical fusion surgery is widely used procedure in cervical spondylosis. When considering the blood reinfusion strategies of cervical fusion surgery, the amount of blood loss is one of the key elements. We usually calculate the blood loss according to the surgical bleeding plus the postoperative drainage; however, this method ignores the possibility that there may be hidden blood loss (HBL). Methods We performed a retrospective study to determine the risk factors for HBL in patients who underwent anterior cervical fusion surgery for degenerative spine from 2013 to 2016. The Pearson correlation, Spearman correlation, and multivariate liner analysis were used to find association between patient characteristics and HBL. Results A total of 107 consecutive patients who underwent anterior cervical fusion surgery for degenerative spine in our hospital were reviewed. The amount of HBL was 261 mL, or 50% of the total blood loss. According to the model of multiple linear regression analysis, patient sex ( P = 0.028) and American Society of Anesthesiologists physical status classification ( P = 0.029) were independent risk factors contributing to HBL, but preoperative hematocrit was not ( P = 0.741). Conclusions We concluded that sex and American Society of Anesthesiologists physical status classification were independent risk factors of HBL in anterior cervical fusion surgery. In addition, there was a high proportion of HBL in anterior cervical fusion. When considering the strategies of transfusion, we should pay attention to the risk factors for HBL.

Cyanobacterial blooms pose great threats to water environment safety and human health due to the release of microcystins, and flocculation is an effective way to control cyanobacterial blooms. In this study, Aspergillus niger 7806F3 exhibited high flocculation activity on Microcystis aeruginosa species, and the addition of calcium ion could cause lysis of algal cells. Meanwhile, the combined effect of strain 7806F3 and calcium ion was conducive to reducing extracellular microcystins. The supernatant of strain 7806F3 induced by calcium ion possessed algicidal activity, which could be inhibited by calcium/calmodulin dependent protein kinase (CaMK) inhibitor, suggesting that calcium ion, as signal molecules, can activate CaMK activity, thus regulating a series of algicidal activities. The disturbance induced by 7806F3 and calcium ion on the bacterial community was not obvious, which indicated that the algicidal activity of Aspergillus niger induced by calcium ion cannot significantly affect the bacterial community dynamics. All these results confirm for the first time that calcium ion, as signal molecules, induce the algicidal activity of Aspergillus niger, which can provide a novel choice for controlling cyanobacterial blooms.

Ethnopharmacological relevance Plastrum testudinis (PT) has been used in traditional Chinese medicine to treat bone diseases such as senile osteoporosis (SOP) for thousands of years. However, the underlying mechanisms remain largely unknown. Aim of the study This study aims to investigate the possible molecular mechanism of PT in the treatment of SOP using an integrated strategy of network pharmacology and experimental validation. Materials and methods The compounds of PT and its targets were identified through the BATMAN-TCM database. The SOP-related targets were retrieved from the GeneCards database. Protein-protein interaction information was obtained by inputting the intersection targets into the STRING database. Cytoscape software was used to construct a protein-protein interaction network and a PT-compound-target-SOP network. Using Cytoscape and R software, we conducted GO function and KEGG pathway enrichment analyses. We also conducted in vivo and in vitro experiments to verify the network pharmacology findings. Results In total, 6 active compounds and 342 targets of PT were screened, of which 57 common targets were related to SOP. The GO biological process enrichment analysis identified 880 entries, mainly relating to the regulation of hormone response, the cell apoptotic process, the apoptotic signaling pathway, NF-kappaB transcription factor activity, fatty acid transportation, osteoclast differentiation, macrophage activation, and inflammatory response. The KEGG pathway enrichment analysis identified 52 entries, including 14 related signaling pathways, which mainly involved the TNF, MAPK, IL-17, AGE-RAGE, estrogen, relaxin, and other signaling pathways. Our in vivo experiments confirmed that PT alleviates SOP, while the in vitro experiments demonstrated that PT exerts a suppressive effect on osteoclast differentiation and bone resorption in a concentration-dependent manner. Furthermore, we observed that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway. Conclusion Through network pharmacology and experimental validation, this study is the first to report that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway, thus exerting a suppressive effect on osteoclast differentiation and bone resorption, which may be the molecular mechanism for PT treatment of SOP.

Ethnopharmacological relevance Plastrum testudinis (PT) is a kind of single traditional Chinese medicine that can tonify kidney and strengthen bone. Plastrum testudinis extract (PTE) has been approved to promote the osteogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro. However, the mechanism by which PTE reduces osteoclast differentiation has not yet been reported. Aim of the study To explore the potential of PTE as a therapeutic treatment for bone loss caused by senile osteoporosis (SOP). Materials and methods We evaluated whether PTE could inhibit RANKL-induced osteoclast differentiation both in vitro and in vivo, and investigated PTE-induced phenotypes of human peripheral blood monocytes. Results We found that PTE inhibited osteoclast differentiation and bone resorption in vitro in a concentration-dependent manner and that PTE treatment is most effective during the early stages of osteoclastogenesis. Moreover, we found that PTE could block the NF-κB signaling pathway in vitro, leading to the down-regulation of osteoclast-specific genes including C-FOS and NFATC1. The results from our in vivo mouse study suggest that PTE treatment suppresses osteoclast formation and mitigates bone loss caused by SOP. Notably, we also found that PTE inhibited RANKL-induced osteoclast differentiation in human peripheral blood monocytes. Conclusion Our results suggest that PTE treatment suppresses osteoclastogenesis and ameliorates bone loss caused by SOP by selectively blocking the nuclear translocation of NF-κB/p50.

Background Early diagnosis of intracranial aneurysm (IA) is arduous in the current situation, and no biomarker is available for the screening of IA. We here systematically evaluate the diagnostic value of circulating non-coding RNA (ncRNA) for the diagnosis of IA. Methods We searched PubMed, Web of Science, Embase, Scopus and Cochrane Library databases from inception to June 2020. We included studies that investigated the diagnostic performance of circulating ncRNAs for the diagnosis of IA. We performed Random-effect meta-analyses for the diagnostic test accuracy to calculate pooled estimates. Subgroup analyses and sensitivity analyses were conducted to explore the source of heterogeneity. Results Thirteen studies, including 1,105 patients and 28 ncRNAs, were included. The pooled sensitivity and specificity were 0.80 (95% confidence interval [CI], 0.76–0.83) and 0.80 (95% CI, 0.76-0.84), respectively, and the area under the hierarchical summary receiver operating characteristic curve was 0.87 (95% CI, 0.84-0.89). The pooled positive and negative likelihood ratios were 3.97 (95% CI, 3.17-4.98) and 0.25 (95% CI, 0.21-0.31), corresponding with a diagnostic odds ratio of 15.63 (95% CI, 10.41-23.47). Subgroup analyses revealed that the diagnostic accuracy of miRNA, lncRNA and circRNA were not significantly different (p > 0.05). Circulating ncRNAs showed higher diagnostic accuracy for patients with unruptured IA than those with ruptured IA (p = 0.0122). Conclusion Current evidence suggests that the circulating ncRNA test could be an effective method for universal IA screening. Future clinical studies need to confirm the diagnostic role of specific ncRNAs.

The aim of this study was to examine the presence of genes responsible for resistance to quaternary ammonium compounds (QACs) and the association of qac genes with class 1 integrons in Escherichia coli isolated from retail meats. Among the 179 E. coli isolates tested, the minimum inhibitory concentrations (MICs) of benzalkonium chloride (BC) ranged from 4 to 64μg/mL. PCR assays indicated that QAC-resistance genes sugE(c), ydgE/ydgF, mdfA, emrE and qacEΔ1 were commonly present (40.2%-88.3%) in these isolates, but qacE, qacF, qacH and sugE(p) were less prevalent (2.2%-28.5%). Seven different gene cassette arrangements were identified in 31 intI1-positive isolates. Three types of qacH-sul3-associated non-classic integrons were observed in four isolates: dfrA12-orfF-aadA2-cmlA1-aadA1-qacH-IS440-sul3, aadA2-cmlA1-aadA1-qacH-IS440-sul3 and dfrA1-aadA1-qacH-IS440-sul3. Non-classic class 1 integrons were located on plasmids of 100-150kb in these four isolates. Our results demonstrated that the qacH-associated integrons located on 100 kb plasmids in two isolates could be transferred to an E. coli recipient, indicating the co-existence and co-dissemination of disinfectant and antimicrobial resistance genes among bacterial species.

Background: Forkhead box protein f1 (Foxf1) is associated with cell differentiation, and may act as a key player in bone homeostasis. However, the effect of Foxf1 on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) and ovariectomized-induced bone loss, as well as its clinical implication, remains largely unknown. Methods: By qRT-PCR and western bloting analysis, we first test Foxf1 expression level in bone tissues, BMSCs, and BMMs, derived from ovariectomized (OVX) mice, then further investigate its expression during osteogenic differentiation and osteoclast differentiation. Using loss-offunction approach (small interfere RNA [siRNA]-mediated knockdown) in vitro, we examined whether Foxf1 regulated osteoblast differentiation of BMSCs via Wnt/β-catenin signaling pathway. Furthermore, we assessed the anabolic action of Foxf1 knockdown (siFoxf1) in OVX mice in vivo. Clinically, we investigated the expression of Foxf1 in bone tissues derived from postmenopausal osteoporosis (PMOP) patients and the connection between Foxf1 expression and bone mineral density (BMD). Finally, we examined the role of Foxf1 knockdown on the osteoblastic differentiation of human BMSCs. Findings: Foxf1 expression was significantly increased in bone extracts and BMSCs derived from OVX mice and gradually decreased during osteoblast differentiation BMSCs, whereas no significant difference in Foxf1 expression was observed in OVX mice-derived BMMs and during osteoclast differentiation. In vitro, Foxf1 knockdown markedly increased osteoblast specific gene expression, alkaline phosphatase (ALP) activity, and mineral potential. Moreover, Wnt/β-catenin signaling pathway was activated with siFoxf1 treatment. The increased osteogenic differentiation induced by siFoxf1 treatment was partly rescued by an Wnt signaling inhibitor (DKK1). In the OVX mice model, Foxf1 siRNA delivery in vivo significantly improved the bone loss through enhancing bone formation. Clinically, Foxf1 expression was increased in bone tissues derived from PMOP patients and was continuously increased along with the decreasing BMD. Also, Foxf1 knockdown significantly promoted the osteogenesis of human BMSCs. Interpretation: These findings indicated that Foxf1 is a novel molecular that its knockdwn promotes BMSCs osteogenesis and prevents OVX-induced bone loss. Foxf1 could be an osteogenic biomarker and a potential therapeutic target for PMOP. Funding Statement: This work was supported in part by the following grants: National Natural Science Foundation of China [81503591, 81774338, 81674000]; Natural Science Foundation of Guangdong Province [2016A030313645]; Science and Technology Projects of Guangdong Province [2016A020226006]; Special Research Project for the Construction of the National TCM Clinical Research Base of the State Administration of Traditional Chinese Medicine [JDZX2015078]; Excellent Young Scholars Project of China Association of Traditional Chinese Medicine [CACM-2017-QNRC1-01]; Excellent Doctor Project of the First School of Clinic Medicine of Guangzhou University of Chinese Medicine [YB201702]; Scientific Research Project of Guangdong Traditional Chinese Medicine Bureau [20180330134046]; Excellent Young Scholars Project of the First Affiliated Hospital of Guangzhou University of Chinese Medicine [2015QN03, 2017TD08, 2017QN08]. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All animal experiments were approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. All protocols performed on patients were approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine.

Zeolitic imidazole frameworks (ZIFs) create broad platforms to study electrochemical energy storage for their numerous advantages (e.g., their high surface area, hierarchical porous structures and flexibility templates). In the present study, metal-coordinated ZIF-derived Bimetal-Organic Framework exhibiting a well-defined morphology of rhombic dodecahedron was facilely synthesized through the addition of a certain molar ratio Ni2+ or Mg2+ when ZIF-67 was being grown. Via pyrolysis, the bimetallic composite materials, i.e., NiCo2O4@C and MgCo2O4@C were produced, exhibiting bimetallic active sites, large surface area and conductive carbon frameworks. When acting as the anode materials in lithium-ion batteries, the produced composite materials displayed excellent durability and greater specific capacity. The mentioned excellent electrochemical performances were contributed to by the stable carbon frameworks because of their greater electronic conductivity and higher electrochemical activity. Moreover, the present study presented novel ideas to synthesize the identical type of MOFs materials and can broaden their applications.

Lithium-ion batteries have progressively taken the place of conventional power sources and been extensively employed in our daily lives. In this study, a simple hydrothermal method was adopted to develop the two-dimensional layered MoSe2 into three-dimensional porous microspheres and nanosphere structures hydrangea-like via directional polymerization, self-assembly and Ostwald maturation. Subsequently, the dopamine hydrochloride was polymerized and carbonized to modify the curd-shaped MoSe2 by N-doped carbon coating. The modified MoSe2@N-C anode material exhibited a larger specific capacity, better stability and a higher rate at high current density than MoSe2 anode material. The modified negative electrode material achieved the specific capacity of 553 mAh/g at a current density of 1 A/g and 300.8 mAh/g at 10 A/g. Under high current density, the long-cycle charge-discharge performance test was performed, and the modified material exhibited a significantly large specific capacity and high stability performance. Its electrochemical performance was enhanced due to the N-doped carbon coating layer on the surface that increased the material conductivity and reduced the shuttle effect of polyselenide.

The strong adsorption of intermediates such as OH* and H* species on the surface of ruthenium (Ru) significantly impedes its electrocatalytic activity for hydrogen evolution reaction (HER) in alkaline media. Here, we propose the introduction of cobalt phosphide (CoP) to efficiently regulate the electronic configuration of Ru. The resultant CoP nanowire array decorated with ultrafine Ru nanoparticles on a conductive carbon cloth substrate (denoted as Ru–CoP/CC) displays comparable catalytic performance to the state-of-the-art Pt/C catalyst for HER in 1 M KOH solution, requiring an extremely low overpotential of only ~21 mV to achieve a current density of 10 mA cm−2, exhibiting a Tafel slope as low as ~49 mV/dec, and maintaining excellent stability over 24 h of electrolysis. Density functional theory calculations on the simulated charge distribution reveal that the regulation of the surface electronic structure of Ru by CoP decreases the adsorption energy of OH* and H* intermediates on the surface of Ru and ultimately contributes to the outstanding electrocatalytic activity of the Ru–CoP/CC electrode for HER.

Human clinically non-functioning pituitary adenomas (NFAs) account for approximately 40% of diagnosed pituitary tumors. Epigenetic mutations in tumor suppressive genes play an important role in NFA development. Maternally expressed gene 3 (MEG3) is a long non-coding RNA (lncRNA) and we hypothesized that it is a candidate tumor suppressor whose epigenetic silencing is specifically linked to NFA development. In this study, we introduced MEG3 expression into PDFS cells, derived from a human NFA, using both inducible and constitutively active expression systems. MEG3 expression significantly suppressed xenograft tumor growth in vivo in nude mice. When induced in culture, MEG3 caused cell cycle arrest at the G1 phase. In addition, inactivation of p53 completely abolished tumor suppression by MEG3, indicating that MEG3 tumor suppression is mediated by p53. In conclusion, our data support the hypothesis that MEG3 is a lncRNA tumor suppressor in the pituitary and its inactivation contributes to NFA development.

Background Glucocorticoid (GC) administration is the most common cause of secondary osteoporosis. Previous studies investigated GCs dose and frequency correlated positively with the side effects of glucocorticoid on bone health, however the impaired effect of various types of GCs on bone has not yet been reported. Purpose The aim is to compare the effect of long-acting (dexamethasone) and relatively short-acting glucocorticoid (methylprednisolone) on rat lumbar spine and try to explore the associated mechanism. Method Sprague Dawley rats ( N = 48) were randomly divided into four groups: baseline group (BL), control group (CON), methylprednisolone group (MP) and dexamethasone group (DEXA). BL rats were euthanized to remain as baseline (M0) at the beginning of experiment. CON group were injected daily with vehicle, while the other groups were given a daily subcutaneous injection of 1 mg/kg methylprednisolone and were given a subcutaneous injection of 0.6 mg/kg dexamethasone per 3 days, respectively. CON, MP and DEXA groups were monitored at 4th week (M1), 8th week (M2) and 12th week (M3) after intervention. Dual-energy X-ray, micro-computed tomography, compressive test, enzyme-linked immunosorbent assay have been used for bone mineral density, microarchitecture, biomechanical property of vertebrae and levels of estrogen, PINP and β-CTX, respectively. mRNA expression analysis of Biglycan, Col1a1, MMP9, Cathepsin K, Runx2, OPG, LRP5, Sclerostin were performed. Result We found that the bone mineral density (BMD) was significantly lower in DEXA rats at M3 compared with MP rats. The relative surface and trabecular number were significantly lower in DEXA group than that in MP group at M2, while trabecular separation was significantly higher in DEXA group than that in MP group at the same point. The compressive strength was significantly lower in L4 of DEXA than that in MP rats at M2 and M3. The levels of both PINP and estradiol in DEXA group were lower than MP group at M3, even though without statistical significance. The expression of bone formation marker Runx2 was significantly down-regulated at M3 in DEXA group compared with MP, CON and BL groups, while the expression of Col1a1 was significantly up-regulated and biglycan, LRP-5, OPG were significantly down-regulated in GCs intervention groups compared with CON and BL groups. There were no statistical differences in MMP9, Cathepsin K, Sclerostin among CON, MP and DEXA groups. Conclusion These results indicate that dexamethasone, the long-acting glucocorticoid, generates more serious osteoporosis of rat lumbar spine than methylprednisolone, which is relatively short-acting glucocorticoid. The discrepancy between the two GCs inducing osteoporosis may be mainly caused by a decrease in bone formation. RUNX2 and Col1a1 may be the two of critical genes inducing the discrepant impairment.

Background According to some clinical studies, insufficient cement distribution (ID) in the fractured area and asymmetrical cement distribution around the fractured area were thought to be the reasons for unrelieved pain and recollapse after percutaneous vertebral augmentation (PVA) in the treatment of symptomatic osteoporotic vertebral compression fractures. Methods Finite element methods were used to investigate the biomechanical variance among three patterns of cement distribution (ID and sufficient cement distribution in the fractured area and asymmetrical cement distribution around the fractured area including upward [BU] and downward [BD] cement distribution). Results Compared with fractured vertebra before PVA, distribution of von Mises stress in the cancellous bone was transferred to be concentrated at the cancellous bone surrounding cement after PVA, whereas it was not changed in the cortical bone. Compared with sufficient cement distribution group, maximum von Mises stress in the cancellous bone and cortical bone and maximum displacement of augmented vertebra increased significantly in the ID group, whereas asymmetrical cement distribution around the fractured area in BU and BD groups mainly increased maximum von Mises stress in the cancellous bone significantly. Similar results could be seen in all loading conditions. Conclusions ID in the fractured area may lead to unrelieved pain after PVA in the treatment of symptomatic osteoporotic vertebral compression fractures as maximum displacement of augmented vertebral body increased significantly. Both ID in the fractured area and asymmetrical cement distribution around the fractured area are more likely to induce recollapse of augmented vertebra because they increased maximum von Mises stress in the cancellous bone and cortical bone of augmented vertebra significantly.

Antimicrobial resistance in Escherichia coli has increased in recent years in China. Antimicrobial resistant isolates and resistance genes of E. coli can be transferred to humans through the food chain and this presents a public health risk. However, few studies have investigated the prevalence of antimicrobial resistance-encoding genes in E. coli isolated from food samples in China. The aim of this study was to investigate the presence of quinolone resistance genes (QRGs) and extended-spectrum beta-lactamases (ESBLs) in E. coli isolated from cooked meat products in Henan, China. A total of 75 E. coli isolates (12.1%) were detected from 620 samples. High rates of resistance to the following drugs were observed: tetracycline (56.0%), trimethoprim/sulfamethoxazole (41.3%), streptomycin (29.3%), ampicillin (26.7%) and nalidixic acid (14.7%). Of the 75 isolates, QRGs were present in 10 isolates (13.3%), with qnr and aac(6')-Ib-cr detected alone or in combination in five (6.7%) and eight isolates (10.7%). The qnr genes detected in this study included qnrS (n = 3) and qnrA (n = 2). The qepA gene was absent among these isolates. Three types of beta-lactamase genes were identified in the five ESBL-producing E. coli isolates: bla(CTX-M-1) and bla(CTX-M-9) and bla(TEM-1). The qnrS gene was found to be co-transferred with bla(CTX-M-1) and bla(TEM-1) one isolate. Our data suggest that cooked meat products may act as reservoirs for multi-resistant bacteria and facilitate the dissemination of antimicrobial resistance genes. (C) 2014 Elsevier B.V. All rights reserved.

The aim of this study was to investigate the antimicrobial resistance to tetracycline and trimethoprim/sulfamethoxazole and the prevalence of corresponding resistant genes of aerobic bacteria isolated from cooked meat products in Guangzhou. Among the 169 tested isolates, 55 (32.5%) exhibited resistance to tetracycline and 40 (23.7%) were resistant to trimethoprim/sulfamethoxazole. Among tetracycline resistance genes, tetM (14.2%) was found in the highest frequency followed by tetA (10.1%), tetS (5.9%), and tetB (2.9%). Among trimethoprim/sulfamethoxazole resistant genes, sulI (10.6%) was observed in the highest frequency which was twofold higher than sulII (5.3%). Multiple antimicrobial resistance genes were detected in 19 of 169 (11.2%) bacteria. One strain of Citrobacter freundii and one strain of Escherichia coli contained five antimicrobial resistance genes. The presence of resistance genes in isolates from cooked meats indicate that these bacteria may act as a reservoir of antimicrobial resistance genes and could play a role in the dissemination of resistant genes along the food chain.

The purpose of the present study was to evaluate the therapeutic efficacy of glioma lysate-pulsed DCs in combination with plasmid DNA vector encoding the murine interferon-induced protein of 10kDa (IP-10 or CXCL10) gene. Mouse models of brain glioma (GL261) were treated with combining glioma lysate-pulsed DCs with direct intratumoral injection of a nonviral plasmid DNA vector encoding the murine IP-10 gene. The survival of mice bearing GL261 glioma was observed. Enzyme-linked immuno-spot assay was used to determine the frequency of brain-infiltrating lymphocytes (BILs) capable of responding to GL261. Cytolytic T lymphocyte (CTL) response was measured by cytotoxic assay, vessel density and tumor cell proliferation were observed by immunostaining, and tumor apoptosis was determined by TUNEL staining. The results revealed that the combination therapy groups showed more significantly enhanced anti-tumor activity, attraction of lymphocytes into tumor tissues, apoptosis of tumor cells, and reduced neovascularization, cell proliferation, and developed a strong CTL response in these mice. In summary, the therapy of glioma lysate-pulsed DCs combined with the IP-10 gene has significant synergistic effect against glioma.

The purpose of the present study was to evaluate the anti-vasculature effects and the anti-tumor effects of attenuated Salmonella typhimurium vaccine strain encoding murine vascular endothelial growth factor (VEGF) receptor-2 (flk1) in combination with plasmid DNA vector encoding the murine interferon-induced protein of 10kDa (IP-10 or CXCL10) gene. Mouse models of malignant melanoma (B16-F10) were treated with combining orally given attenuated S. typhimurium vaccine strain encoding flk1 with direct intratumoral injection of a non-viral plasmid DNA vector encoding the murine IP-10 gene. The volumes of tumors and survival of mice bearing B16-F10 tumors were observed. Cytolytic T lymphocyte (CTL) response was measured by cytotoxic assay, vessel density and tumor-cell proliferation were observed by immunostaining, and tumor apoptosis was determined by TUNEL staining. The results revealed the combination therapy groups showed more significantly inhibited tumor growth, apoptosis of tumor cells, and reduced neovascularization, cell proliferation, and developed a strong CTL response in these mice. In summary, the therapy of attenuated S. typhimurium vaccine strain encoding flk1 combined with the IP-10 gene has significant synergistic effect against tumors.

The interleukin (IL) 13 receptor alpha2 (IL-13Ralpha2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. This study reported a novel approach for targeting malignant glioma with IL-13Ralpha2-specific allo-restricted cytotoxic T cells (CTLs) induced from the peripheral blood lymphocytes (PBLs) of HLA-A2-negative healthy donors by multiple stimulations with artificial antigen-presenting cells (aAPCs) made by coating HLA-A2/pIL-13Ralpha2(345-354) tetrameric complexes, anti-CD28 antibody and CD83 molecules to cell-sized latex beads. The induced allo-restricted CTLs exhibited specific lysis against T2 cells pulsed with the peptide pIL-13Ralpha2(345-354) and HLA-A2+ glioma cells expressing IL-13Ralpha2(345-354), while HLA-A2- glioma cell lines that express IL-13Ralpha2(345-354) could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-HLA class I monoclonal antibody. These results suggested the induced allo-restricted CTLs specific for IL-13Ralpha2(345-354) peptide could be a potential target of specific immunotherapy for HLA-A2+ patients with malignant glioma.

Hhex encodes a homeodomain-containing protein that functions as both a transcriptional repressor and activator, and is necessary for normal embryonic development. We previously reported that a null mutation of Hhex leads to abnormalities in vasculogenesis and have focused on identifying the transcriptional targets of Hhex necessary for vascular development. Here we report that the expression of ESM-1 , a cysteine-rich protein expressed in the endothelium, is increased in Hhex −/− embryos. Overexpression of Hhex in endothelial cells down-regulates ESM-1. The results from transient cotransfection assay, electrophoretic-mobility shift assay, site-directed mutagenesis, and chromatin immunoprecipitation assay demonstrate that Hhex can directly bind to and repress ESM-1 via an evolutionarily conserved Hhex response element (HRE) 1. These findings indicate that ESM-1 is a direct target of Hhex and that Hhex functions as a transcriptional repressor of ESM-1 . We speculate that Hhex-mediated repression of ESM-1 is critical for the normal function of the vascular endothelium and for tumor vasculogenesis.

Mouse embryos lacking the retinoic acid (RA) receptors RARalpha1 and RARbeta suffer from a failure to properly septate (divide) the early outflow tract of the heart into distinct aortic and pulmonary channels, a phenotype termed persistent truncus arteriosus. This phenotype is associated with a failure in the development of the cardiac neural crest cell lineage, which normally forms the aorticopulmonary septum. In this study, we examined the fate of the neural crest lineage in RARalpha1/RARbeta mutant embryos by crossing with the Wnt1-cre and conditional R26R alleles, which together constitute a genetic lineage marker for the neural crest. We find that the number, migration, and terminal fate of the cardiac neural crest is normal in mutant embryos; however, the specific function of these cells in forming the aorticopulmonary septum is impaired. We furthermore show that the neural crest cells themselves do not utilize retinoid receptors and do not respond to RA during this process, but rather that the phenotype is cell non-autonomous for the neural crest cell lineage. This suggests that an alternative tissue in the vicinity of the outflow tract of the heart responds directly to RA, and thereby induces or permits the neural crest cell lineage to initiate aorticopulmonary septation.