Comparison of anesthesia methods for intra-arterial therapy of patients with acute ischemic stroke: an updated meta-analysis and systematic review.

OBJECTIVES: Currently, there remains debate regarding the optimal anesthesia approach for patients undergoing intra-arterial therapy for acute ischemic stroke. Therefore, we conducted a comparative analysis to assess the effects of general anesthesia versus non general anesthesia on patient outcomes. METHODS: The research methodology entailed comprehensive searches of prominent databases such as the Cochrane Library, PubMed, Scopus, and Web of Science, covering the period from January 1, 2010, to March 1, 2024. Data synthesis employed techniques like risk ratio or standardized mean difference, along with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024523079). RESULTS: A total of 27 trials and 12,875 patients were included in this study. The findings indicated that opting for non-general anesthesia significantly decreased the risk of in-hospital mortality (RR, 1.98; 95% CI: 1.50 to 2.61; p<0.00001; I2 = 20%), as well as mortality within three months post-procedure (RR, 1.24; 95% CI: 1.15 to 1.34; p<0.00001; I2 = 26%), while also leading to a shorter hospitalization duration (SMD, 0.24; 95% CI: 0.15 to 0.33; p<0.00001; I2 = 44%). CONCLUSION: Ischemic stroke patients who undergo intra-arterial treatment without general anesthesia have a lower risk of postoperative adverse events and less short-term neurological damage. In routine and non-emergency situations, non-general anesthetic options may be more suitable for intra-arterial treatment, offering greater benefits to patients. In addition to this, the neuroprotective effects of anesthetic drugs should be considered more preoperatively and postoperatively.

Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines.

A copper(I)-catalyzed protocol is developed for the synthesis of various 2,3-diaroylquinolines starting from achiral ammonium salts and anthranils through [4+1+1] annulation. Using copper(I) chloride as the sole catalyst, this reaction is featured with easily available starting materials, broad substrate scope, good yields and simple reaction conditions.

Injectable hydrogel harnessing foreskin mesenchymal stem cell-derived extracellular vesicles for treatment of chronic diabetic skin wounds.

Chronic skin wounds are a serious complication of diabetes with a high incidence rate, which can lead to disability or even death. Previous studies have shown that mesenchymal stem cells derived extracellular vesicles (EVs) have beneficial effects on wound healing. However, the human foreskin mesenchymal stem cell (FSMSCs)-derived extracellular vesicle (FM-EV) has not yet been isolated and characterized. Furthermore, the limited supply and short lifespan of EVs also hinder their practical use. In this study, we developed an injectable dual-physical cross-linking hydrogel (PSiW) with self-healing, adhesive, and antibacterial properties, using polyvinylpyrrolidone and silicotungstic acid to load FM-EV. The EVs were evenly distributed in the hydrogel and continuously released. In vivo and vitro tests demonstrated that the synergistic effect of EVs and hydrogel could significantly promote the repair of diabetic wounds by regulating macrophage polarization, promoting angiogenesis, and improving the microenvironment. Overall, the obtained EVs-loaded hydrogels developed in this work exhibited promising applicability for the repair of chronic skin wounds in diabetes patients.

Benzodiazepine Use and the Risk of Dementia in the Elderly Population: An Umbrella Review of Meta-Analyses.

The prevalence of dementia among the elderly is high, and it is the leading cause of death globally. However, the relationship between benzodiazepine use and dementia risk has produced inconsistent results, necessitating an updated review of the evidence. To address this, we conducted an umbrella review of meta-analyses to summarize the available evidence on the association between benzodiazepine use and dementia risk and evaluate its credibility. We systematically evaluated the meta-analyses of observational studies that examined the connection between benzodiazepine use and dementia risk. For each meta-analysis, we collected the overall effect size, heterogeneity, risk of bias, and year of the most recent article and graded the evidence based on pre-specified criteria. We also used AMSTAR, a measurement tool to evaluate systematic reviews, to assess the methodological quality of each study. Our review included five meta-analyses encompassing 30 studies, and the effect size of the association between benzodiazepine use and dementia risk ranged from 1.38 to 1.78. Nonetheless, the evidence supporting this relationship was weak, and the methodological quality of the studies included was low. In conclusion, our findings revealed limited evidence of a link between benzodiazepine use and dementia risk, and more research is required to determine a causal connection. Physicians should only prescribe benzodiazepine for appropriate indications.

Artificial Intelligence in Dementia: A Bibliometric Study.

The applications of artificial intelligence (AI) in dementia research have garnered significant attention, prompting the planning of various research endeavors in current and future studies. The objective of this study is to provide a comprehensive overview of the research landscape regarding AI and dementia within scholarly publications and to suggest further studies for this emerging research field. A search was conducted in the Web of Science database to collect all relevant and highly cited articles on AI-related dementia research published in English until 16 May 2023. Utilizing bibliometric indicators, a search strategy was developed to assess the eligibility of titles, utilizing abstracts and full texts as necessary. The Bibliometrix tool, a statistical package in R, was used to produce and visualize networks depicting the co-occurrence of authors, research institutions, countries, citations, and keywords. We obtained a total of 1094 relevant articles published between 1997 and 2023. The number of annual publications demonstrated an increasing trend over the past 27 years. Journal of Alzheimer's Disease (39/1094, 3.56%), Frontiers in Aging Neuroscience (38/1094, 3.47%), and Scientific Reports (26/1094, 2.37%) were the most common journals for this domain. The United States (283/1094, 25.86%), China (222/1094, 20.29%), India (150/1094, 13.71%), and England (96/1094, 8.77%) were the most productive countries of origin. In terms of institutions, Boston University, Columbia University, and the University of Granada demonstrated the highest productivity. As for author contributions, Gorriz JM, Ramirez J, and Salas-Gonzalez D were the most active researchers. While the initial period saw a relatively low number of articles focusing on AI applications for dementia, there has been a noticeable upsurge in research within this domain in recent years (2018-2023). The present analysis sheds light on the key contributors in terms of researchers, institutions, countries, and trending topics that have propelled the advancement of AI in dementia research. These findings collectively underscore that the integration of AI with conventional treatment approaches enhances the effectiveness of dementia diagnosis, prediction, classification, and monitoring of treatment progress.

Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies.

Previous epidemiological studies have raised the concern that the use of proton pump inhibitors (PPIs) is associated with an increased risk of kidney diseases. To date, no comprehensive meta-analysis has been conducted to assess the association between PPIs and the risk of chronic kidney disease (CKD). Therefore, we conducted a systematic review and meta-analysis to address the association between PPIs and CKD. The primary search was conducted in the most popular databases, such as PubMed, Scopus, and Web of Science. All observational studies evaluated the risk of CKD among PPI users, and non-users were considered for inclusion. Two reviewers conducted data extraction and assessed the risk of bias. Random-effect models were used to calculate pooled effect sizes. A total of 6,829,905 participants from 10 observational studies were included. Compared with non-PPI use, PPI use was significantly associated with an increased risk of CKD (RR 1.72, 95% CI: 1.02-2.87, p = 0.03). This updated meta-analysis showed that PPI was significantly associated with an increased risk of CKD. Association was observed in the same among moderate-quality studies. Until further randomized control trials (RCTs) and biological studies confirm these results, PPI therapy should not stop patients with gastroesophageal reflux disease (GERD). However, caution should be used when prescribing to patients with high-risk kidney disease.

A novel strategy for active compound efficacy status identification in multi-tropism Chinese herbal medicine (Scutellaria baicalensis Georgi) based on multi-indexes spectrum-effect gray correlation analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Bioactive substance identification is always the focal point and the main challenge in Chinese herbal medicine (CHM). Most CHM present multiple efficacies and multiple tropisms, which has improved the application accuracy of CHM, and is worthy of further study. In this article, the concept of "multi-tropism efficacy of CHM" has been proposed for the first time. In addition, it is hypothesized that the different components in CHM can be classified based on their efficacy status. AIM OF THE STUDY: The spectrum-effect relationship between the fingerprint and efficacy was established to identify the efficacy status of components. This provided a practical, efficient and accurate way to identify the bioactive substances from a complex CHM system. MATERIALS AND METHODS: The network pharmacology approach was applied to preliminarily analyze the potential antibacterial compounds and mechanisms of HQ. Furthermore, its chemical fingerprint was established and the characteristic peaks were identified by LC-MS/MS. The antibacterial and anti-inflammatory bioactivities of HQ were determined to evaluate its pharmacological effect of heat-clearing and detoxification, and its anticoagulation activity was determined to evaluate its heat-clearing and tocolysis effects. The spectrum-effect relationships were assessed by gray correlation analysis to discriminate the status of active components in HQ with different efficacies. RESULTS: Network pharmacology analysis revealed apigenin, wogonin, baicalein, acacetin, ß-sitosterol, baicalin, eugenol, moslosooflavone, palmitic acid, oroxylin-A 7-O-glucuronide, and scutevulin as the potential active compounds responsible for the efficacy of HQ against both E. coli and S. aureus. The spectrum-effect relationship was utilized to reveal the orientation activities, with the results as follows: 1) The main basic-efficacy components in HQ with antibacterial, anti-inflammatory, and anticoagulant effects were P5, P8, P9, P15, P18, P19, P20; while the general basic-efficacy components were P2, P3, P6, P7, P11, P14, P21, P22, P28. 2) The main efficacy-oriented components in HQ with antibacterial effects on E. coli were P1, P12, P17, while the general efficacy-oriented compound was P10, P24, P25, P26, P27; the main efficacy-oriented in HQ with antibacterial effects on S. aureus were P14 and the general efficacy-oriented components were P1, P12, P26, P29, P30, respectively. 3) The main efficacy-oriented components with anti-inflammatory activity were P14, P24, P25, P27, and P30, while the general efficacy-oriented components were P13, P23, P26. 4) The main efficacy-oriented compounds in HQ with effects on anticoagulation were P6 and P22; these acted by prolonging APTT through the intrinsic coagulation pathway and PT through the extrinsic coagulation pathway, respectively. 5) The pharmacodynamic status classification of Scutellaria baicalensis ingredients were confirmed by nine reference compounds exemplarily. CONCLUSION: This work established a novel strategy for active compound efficacy status identification in multi-tropism Chinese herbal medicine (Scutellaria baicalensis Georgi) based on multi-indexes spectrum-effect gray correlation analysis, the method is scientific feasible and can be applied to the effective substances identification and quality control of other CHM.

Cardiovascular Risk Factors in Hospital Workers during the COVID-19 Pandemic: A Hospital-Based Repeated Measures Study.

Although many studies have investigated burnout, stress, and mental health issues among health care workers (HCWs) during the COVID-19 pandemic, few have linked these relationships to chronic physiological illnesses such as cardiovascular diseases. This study assessed changes in cardiovascular risk factors in HCWs and other hospital workers during the COVID-19 pandemic and identified vulnerable groups at a higher risk of increased adverse cardiovascular conditions. Five hundred and fourteen hospital employees ≥ 20 years of age underwent physical examinations and laboratory testing once before and once after the first wave of the pandemic in Taiwan during 2020 and 2021. Their sociodemographic characteristics and cardiovascular risk factors, including blood pressure, blood biochemical parameters, and body mass index, were collected. The differences between pre- and post-pandemic measurements of their biophysical and blood biochemical parameters were analyzed using pairwise tests. The post-pandemic increases in their parameter levels and cardiovascular risk as a function of underlying factors were estimated from multivariate regressions. HCWs showed significant increases in levels and abnormal rates of BMI, blood pressure, plasma glucose, and total cholesterol after the pandemic. Post-pandemic increases in BMI, waist circumference, and blood pressure were higher in females than in males. Workers with higher levels of education or longer job tenure had greater increases in BMI, triglyceride, and total cholesterol levels than other workers. Females had a higher incidence of abnormal BMI and hypertension than males (adjusted odds ratios [AORs] of 8.3 and 2.9, respectively). Older workers' incidence of hypertension was higher than younger workers' (AOR = 3.5). Preventive strategies should be implemented for HCWs susceptible to cardiovascular diseases during emerging infectious disease outbreaks.

Factors Associated with the Patient/Client Use of Report Cards, Physician Rating Websites, Social Media, and Google for Hospital and Physician Selection: A Nationwide Survey.

OBJECTIVE: To explore the factors associated with the different uses of report cards, physician rating websites, social media, and Google, including awareness, physician finding, and decision-making based on reviews from the patient/client perspective. METHODS: We used computer-assisted telephone interviews to conduct a nationwide representative survey in Taiwan. RESULTS: The urbanization level of the area, income, and long-term health conditions were not associated with the three kinds of usage of the websites studied. Seeking health information was an important factor in the three kinds of website use. The employment industry was associated with awareness, and education level was associated with physician seeking and actions based on reviews. CONCLUSIONS: Different factors influenced the three kinds of usage: awareness, actual use (i.e., finding an appropriate physician), and decision-making based on reviews. Seeking health information is of primary importance regardless of how the websites are used. PRACTICAL IMPLICATIONS: Policy-makers should focus on educating individuals working outside the health care sector to increase awareness of these websites and to assist individuals with low levels of education in increasing their use of these websites.

Gastrectomy with omentum preservation versus gastrectomy with omentectomy for locally advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Omentectomy has been traditionally a part of standard radical gastrectomy. Its clinical benefit for locally advanced gastric cancer (LAGC) remains controversial. This study aimed at evaluating the impact of gastrectomy with omentum preservation (GOP) on survival, recurrence, surgical outcomes and postoperative complications by comparing with gastrectomy with omentum resection (GOR). METHODS: Original studies comparing GOP with GOR in LAGC were searched. Meta-analysis was performed using RevMan 5.4. RESULTS: Seven studies involving 1879 patients were analyzed. Compared with GOR, GOP achieved significantly better overall survival (HR = 0.75 [0.60, 0.95], P = 0.01), with similar relapse-free survival (HR = 0.84 [0.68, 1.03], P = 0.10). The two groups had similar total recurrence rate (OR = 0.86 [0.68, 1.08], P = 0.19) and no significant differences in rates of peritoneal, hematogenous, locoregional or distant lymph node recurrences. GOP had significantly less blood loss (MD = -83 [-139, -28] ml, P = 0.003) and tended to have shorter operation time (MD = -28 [-58, 2] min, P = 0.06), with similar harvested number of lymph nodes (MD = -0.4 [-2.6, 1.8], P = 0.70). The incidences of total all grade and major complications were similar in GOP and GOR (all grade: 31.8% vs. 30.3%, OR = 1.08 [0.79, 1.46], P = 0.64; major: 9.2% vs. 10.1%, OR = 1.14 [0.55, 2.34], P = 0.73). There were no significant differences in incidences of complication or postoperative mortality. CONCLUSIONS: Omentum preservation did not affect curability or survival in LAGC. These findings require validation in randomized controlled trials with large sample sizes.

[Preparation of nanoemulsion spray from Moslae Herba volatile oil and its antibacterial activity].

Moslae Herba is a commonly used aromatic Chinese medicinal with volatile oil as the main effective component and exhibits broad-spectrum antibacterial and antiviral effects. However, the irritation and instability of Moslae Herba volatile oil necessitate the preparation into a specific dosage form. In this study, the steam distillation method was employed to extract the Moslae Herba volatile oil. The content of thymol and carvacrol in Moslae Herba volatile oil was determined by HPLC as(0.111 9±0.001 0) and(0.235 4±0.004 7) mg·mL~(-1), respectively. Pseudo-ternary phase diagrams and surfactants compounding were applied in the selection of the optimal excipients(surfactant and cosurfactant). On this basis, a nanoemulsion was prepared from the Moslae Herba volatile oil and then loaded into pressure vessels to get sprays, whose stability and antibacterial activity were evaluated afterward. With clarity, viscosity, smell and body feeling as comprehensive indexes, the optimal formulation of the Moslae Herba volatile oil nanoemulsion was determined as follows: Moslae Herba volatile oil∶peppermint oil∶cremophor EL∶absolute ethanol∶distilled water 7.78∶1.58∶19.26∶6.15∶65.23. The as-prepared nanoemulsion was a light yellow transparent liquid, with Tyndall effect shown under the irradiation of parallel light. It has the pH of 5.50, conductivity of 125.9 µS·cm~(-1), average particle size of 15.45 nm, polydispersity index(PDI) of 0.156, and Zeta potential of-17.9 mV. Under a transmission electron microscope, the Moslae Herba volatile oil nanoemulsion was presented as regular spheres without adhesion and agglomeration. Stability test revealed that the Moslae Herba volatile oil nanoemulsion was stable at 4-55 ℃, which was free from demulsification and stratification within 30 days. After the centrifugation at 12 000 r·min~(-1) for 30 min, there was no stratification either. The nanoemulsion had good inhibitory effects on Escherichia coli, Staphylococcus aureus and resistant S. aureus strains, with the minimum inhibitory concentrations of 0.39, 3.12 and 1.56 mg·mL~(-1), respectively. The above results demonstrated that the nanoemulsion was prepared feasibly and showed stable physical and chemical properties and good antibacterial effects. This study provides a practicable technical solution for the development of anti-epidemic and anti-infection products from Moslae Herba volatile oil.

Presenilin1 inhibits glioblastoma cell invasiveness via promoting Sortilin cleavage.

BACKGROUND: Alzheimer's disease (AD) and glioblastoma are the most common and devastating diseases in the neurology and neurosurgery departments, respectively. Our previous research reports that the AD-related protein Presenilin1 represses cell proliferation by inhibiting the Wnt/ß-catenin pathway in glioblastoma. However, the function of Presenilin1 and the underlying mechanism need to be further investigated. METHODS: The correlations of two genes were conducted on the R2 microarray platform and CGGA. Wound healing, Transwell assays and glioblastoma transplantation were performed to detect invasion ability. Phalloidin staining was employed to show cell morphology. Proximity ligation assays and protein docking assays were employed to detect two protein locations. We also employed western blotting to detect protein expression. RESULTS: We found that Presenilin1 clearly repressed the migration, invasion and mesenchymal transition of glioblastoma cells. Intriguingly, we observed that the expression of Presenilin1 was positively correlated with Sortilin, which is identified as a pro-invasion molecule in glioma. Furthermore, Presenilin1 interacted with Sortilin at the transmembrane domain and repressed Sortilin expression by cleaving it in glioblastoma cells. First, we found that Sortilin introduced the function of Presenilin1 in phosphorylating ß-catenin and repressing invasion in glioblastoma cells. Last, Presenilin1 stimulation sharply suppressed the invasion and mesenchymal transition of glioblastoma in mouse subcutaneous and intracranial transplantation models. CONCLUSIONS: Our study reveals that Sortilin mediates the regulation of ß-catenin by Presenilin1 and transduces the anti-invasive function of Presenilin1, which may provide novel therapeutic targets for glioblastoma treatment. Video Abstract.

[Unity and separation of lifting-thrusting and twirling reinforcing-reducing manipulation].

To analyze the collaborative use and separation reasons of lifting-thrusting and twirling reinforcing and reducing manipulation. Lifting-thrusting manipulation and twirling manipulation are two important contents of acupuncture methods. In traditional acupuncture and moxibustion, the two methods were used in reinforcing and reducing concert, which was mainly related to the therapeutic thought guided by the qi-blood theory and the influence of the human body structure on the technique manipulation. After the Republic of China, the separation of lifting-thrusting manipulation and twirling manipulation gradually appeared. It was related to the widespread use of "scientific acupuncture method" in later generations and the integration of neuroscience into the acupuncture treatment system.

Laparoscopic versus open transhiatal approach for adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Laparoscopic transhiatal approach (LTH) has gained growing popularity in the treatment of AEG. However, its safety and efficacy need to be evaluated. METHODS: Original studies comparing LTH with open transhiatal approach (OTH) were searched. Meta-analysis was performed using RevMan 5.3. RESULTS: Nine studies involving 2149 patients were eligible. Compared with OTH, LTH was associated with longer operation time (mean difference [MD] = 31min, 95%CI [20,41], P < 0.001) while less blood loss (MD = -103ml [-135, -72], P < 0.001), and harvested similar number of lymph nodes (MD = 0.1 [-1.2, 1.4], P = 0.89). There were no differences in time to ambulation (MD = -0.79 days [-1.77, 0.20], P = 0.12) or time to first flatus (MD = -0.82 days [-1.76, 0.11], P = 0.08); however, LTH was associated with shorter postoperative hospital stay (MD = -1.70 days [-2.34, -1.05], P < 0.001). The mortality after surgery was comparable for LTH and OTH (risk difference [RD] = -0.00 [-0.01, 0.01], P = 0.55). The incidence of total major complications was similar in LTH (6.1%) and OTH (8.4%) (RD = -0.02 [-0.05, 0.01], P = 0.12); there were no significant differences in the incidence of each complication. Furthermore, LTH achieved similar 2-year overall survival (OS) rate (risk ratio [RR] = 1.17 [0.86, 1.60], P = 0.31) while higher 5-year OS rate (RR = 1.43 [1.18, 1.73], P = 0.0003) and significant improvement of OS (univariable hazard ratio = 0.65 [0.50, 0.84], P = 0.0009; multivariable hazard ratio = 0.59 [0.44, 0.80], P = 0.0006). CONCLUSIONS: LTH is feasible and safe for AEG, and may provide more favorable short-term outcomes and potential long-term survival benefit, which needs to be confirmed by randomized trials.

TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions.

The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in malignant glioma compared to normal brain and low-grade glioma, and TRPV4 expression was negatively correlated with the prognosis of glioma patients. Functionally, stimulation of TRPV4 promoted glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal protein-F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4-regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in glioblastoma cells and influences the invasion-growth phenotype of glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients.

Presenilin1 exerts antiproliferative effects by repressing the Wnt/ß-catenin pathway in glioblastoma.

BACKGROUND: Glioblastoma and Alzheimer's disease (AD) are the most common and devastating diseases in the central nervous system. The dysfunction of Presenilin1 is the main reason for AD pathogenesis. However, the molecular function of Presenilin1 and its relative mechanism in glioblastoma remain unclear. METHODS: Expression of presenilin1 in glioma was determined by IHC. CCK-8, colony formation, Flow cytometry, Edu staining were utilized to evaluate functions of presenilin1 on glioblastoma proliferation. The mechanism of above process was assessed by Western blotting and cell immunofluorescence. Mouse transplanting glioblastoma model and micro-MRI detection were used to verified presenilin1 function in vivo. RESULTS: In this study, we found that all grades of glioma maintained relatively low Presenilin1 expression and that the expression of Presenilin1 in high-grade glioma was significantly lower than that in low-grade glioma. Moreover, the Presenilin1 level had a positive correlation with glioma and glioblastoma patient prognosis. Next, we determined that Presenilin1 inhibited the growth and proliferation of glioblastoma cells by downregulating CDK6, C-myc and Cyclin D1 to arrest the cell cycle at the G1/S phase. Mechanistically, Presenilin1 promoted the direct phosphorylation of ß-catenin at the 45 site and indirect phosphorylation at the 33/37/41 site, then decreased the stabilized part of ß-catenin and hindered its translocation from the cytoplasm to the nucleus. Furthermore, we found that Presenilin1 downregulation clearly accelerated the growth of subcutaneous glioblastoma, and Presenilin1 overexpression significantly repressed the subcutaneous and intracranial transplantation of glioblastoma by hindering ß-catenin-dependent cell proliferation. CONCLUSION: Our data implicate the antiproliferative effect of Presenilin1 in glioblastoma by suppressing Wnt/ß-catenin signaling, which may provide a novel therapeutic agent for glioblastoma. Video Abstract.

Progress in the synthesis of imide-based N-type polymer semiconductor materials.

Based on the development situation and challenge of organic photovoltaics (OPVs) and organic field-effect transistors (OFETs), it is necessary to develop N-type polymer building blocks with specific structures and performance. After decades of development, some excellent polymer receptor building blocks have been developed to construct N-type organic semiconductors, which have been applied in OFETs and OPVs. In this paper, four kinds of imide (bisthiophene imide BTI, bisthiazolimide BTz, naphthalimide NDI, and perylene imide PDI)-based N-type polymer semiconductor materials are introduced, and their applications in OFETs and OPVs are analyzed, too. The molecular structure design and the performance of corresponding materials are summarized to provide further guidance and reference for the design and development of high performance N-type polymer semiconductors.

A new method to investigate almost periodic solutions for an Nicholson's blowflies model with time-varying delays and a linear harvesting term.

In this paper, a delayed Nicholson's blowflies model with a linear harvesting term is investigated. By transforming the model into an equivalent integral equation, and applying a fixed point theorem inc ones, we establish a sufficient condition which ensure the existence of positive almost periodic solutions for the Nicholson's blowflies model. The results of this paper are completely new and complement those of the previous studies. The approach is new.

Sortilin promotes glioblastoma invasion and mesenchymal transition through GSK-3ß/ß-catenin/twist pathway.

High aggressiveness is a hallmark of glioblastoma and predicts poor prognosis of patients with glioblastoma. The expression level of sortilin has been preliminarily reported to be elevated in high-grade glioma; however, the potential significance of sortilin in glioblastoma progression has not been elucidated. In this study, we investigated the oncogenic effect of sortilin in glioblastoma. Increased levels of sortilin were noted in the mesenchymal subtype of glioblastoma and highly aggressive subtypes of glioblastoma tissues and cell lines. In addition, high levels of sortilin predicted poor prognoses in patients with glioblastoma. Sortilin knockdown or inhibition with AF38469 (an orally bioavailable inhibitor of sortilin) significantly suppressed migration and invasion by inhibiting EMT-like mesenchymal transition in glioblastoma cells. Furthermore, we proved that sortilin promoted cell invasion mainly via Glycogen synthase kinase 3 beta (GSK-3ß)/ß-catenin/Twist-induced EMT-like mesenchymal transition in glioblastoma. Taken together, our results demonstrate a critical role of sortilin in glioblastoma invasion and EMT-like mesenchymal transition, indicating that sortilin contributes to glioblastoma progression. These data also highlight the dramatic antitumor effects of AF38469 in glioblastoma, suggesting that AF38469 is a potentially powerful antitumor agent for sortilin-overexpressing human glioblastoma.

TLR4 gene polymorphisms rs11536889 is associated with intracranial aneurysm susceptibility.

Intracranial aneurysm (IA) is a common lesion which often present asymptomatic until the time of rupture and result in subarachnoid hemorrhage (SAH). The pathogenesis of IA formation is complex and is influenced by both genetic and environmental risk factors. For exploring the detailed molecular and cellular mechanisms involved in the pathogenesis of IA, recent studies indicated inflammatory pathways and their genetic variants may as potential biomarkers. In this study, functionally relevant polymorphisms in the toll-like receptor 4 (TLR4) were screened in 330 IA patients and 313 controls from a Han Chinese population. Eight single nucleotide gene polymorphisms (SNPs) genotyped by the Improved Multiple Ligase Detection Reaction (iMLDR) method. Our results indicated that the presence of the minor allele (C) of the TLR4 SNP rs11536889 was associated with a decreased risk of IA (C vs. G, OR = 0.731; 95% CI 0.567-0.943; P = 0.017). This association was also present at the genotype level in a codominant model (GC vs. GG, OR = 0.447; 95% CI 0.226-0.884; P = 0.020) and a recessive model (CC vs. GG + GC, OR = 0.489; 95% CI 0.250-0.955; P = 0.035). In summary, we firstly found that the TLR4 SNP rs11536889 was significantly associated with the susceptibility of IA. Our results indicated TLR4 SNP rs11536889 may be a marker for IA risk, though the exact functional roles of TLR4 SNP rs11536889 in IA formation are still not very clear.