Inflammatory factors mediated the effect of air pollution on ischemic stroke: a two-step, mediation Mendelian randomization study.

OBJECTIVE: Numerous investigations have indicated a correlation between air pollution (AP) and an elevated ischemic stroke (IS) likelihood. The existing literature does not provide a consensus about the possible link between AP and IS. A two-sample Mendelian randomization (MR) analysis was utilized to systematically measure the causal link between AP and ischemic stroke. Furthermore, the mediating impact of inflammatory factors was also performed by a two-step MR. MATERIALS AND METHODS: A two-sample MR analysis was utilized to examine the AP impact on the incidence of IS. Additionally, a two-step MR approach was carried out to account for possible mediating variables. The indirect impact was determined by employing the product approach, which included multiplying the AP impact on inflammatory factors by the inflammatory factors' impacts on IS. The MR effect was identified through inverse variance-weighted (IVW) meta-analysis of each Wald Ratio. Additionally, complementary studies were conducted using the weighted median and MR-egger approaches. RESULTS: The IVW method with random effects showed that the per unit increase in genetically predicted PM2.5 was linked to the 0.362-fold elevated ischemic stroke risk (OR: 1.362, 95% CI: 1.032-1.796, p=0.029). Furthermore, the IVM technique, incorporating random effects, demonstrated that the per unit increase in genetically predicted PM2.5 was related to an elevated Interleukin (IL)-1ß risk (OR: 1.529, 95% CI: 1.191-1.963, p=0.001), IL-6 (OR: 1.498, 95% CI: 1.094-2.052, p=0.012) and IL-17 (OR: 1.478, 95% CI: 1.021-2.139, p=0.038). IL-1ß, IL-6, and IL-17 modulated the PM2.5 impact on ischemic stroke, while the proportion mediated by them was 59.5%. CONCLUSIONS: A positive correlation between genetically predicted PM2.5 levels and elevated ischemic stroke risk is mediated by IL-1ß, IL-6, and IL-17.

[Research advances on the mechanism of nerve regeneration-related protein in skin fibrosis].

The healing process after skin injury is a dynamic process of interaction between various cells, cytokines, and extracellular matrix. Fibrosis is one of the main ways of skin injury repair. The process of fibrosis involves the regulation of many factors. Studies have shown that nerve regeneration-related protein (NREP) plays a key role in the fibrosis of skin tissue and organs. Based on the mechanism of skin fibrosis, this paper discusses the construction of tertiary structure of NREP, summarizes the effects of NREP and different cells in the skin on skin fibrosis and the research progress of mechanism of NREP in skin fibrosis, thus providing new ideas for the treatment of skin fibrosis diseases.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

Application value of transcranial contrast-enhanced ultrasonography in evaluating middle cerebral artery stenosis.

OBJECTIVE: To detect the display rate and flow velocity of intracranial circle of Willis (anterior, middle, and posterior cerebral arteries) with transcranial contrast-enhanced transcranial color-coded sonography (CE-TCCS), using digital subtraction angiography (DSA) as the golden diagnostic standard. PATIENTS AND METHODS: We collected data from 104 patients with suspected stroke treated in our hospital between December 2019 and October 2021. The detection rate of the intracranial circle of Willis, anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) were analyzed based on routine TCCS and CE-TCCS data. Based on digital subtraction angiography (DSA) data, the degree of MCA stenosis was divided into mild stenosis (<50%), moderate stenosis (50-69%), severe stenosis (70-99%), and bilateral middle cerebral artery CE-TCCS examinations were performed. We evaluated MCA color blood flow on CE-TCCS, and recorded the peak systolic velocity (PSV), end-diastolic velocity (EDV), and mean flow velocity (MFV). RESULTS: The display rates of ACA, MCA, and PCA were significantly improved on the CE-TCCS, and the PSV, EDV and MFV of the MCA stenosis group were higher than those of the normal group. The flow velocity of each stenosis subgroup was increased compared to the normal group. The optimal cutoff values of normal and stenosis under the receiver operating characteristic (ROC) curve were PSV = 168.5 cm/s, EDV = 61.5 cm/s, and MFV = 110.5 cm/s. The optimal cutoff values for mild and moderate stenosis and for moderate and severe stenosis were PSV = 201.5 cm/s and 249.5 m/s, EDV = 95.2 cm/s and 141.5 cm/s, and MFV = 137.6 cm/s and 160.5 cm/s, respectively. PSV and MFV had the most significant sensitivity, specificity, and accuracy. CONCLUSIONS: Transcranial contrast-enhanced ultrasonography can improve the display rate of intracranial blood vessels and can accurately diagnose MCA stenosis.

The influence of the shock-absorbing restorative materials on the stress distributions of short dental implant rehabilitations.

OBJECTIVE: Polymer materials with shock-absorbing ability may offer better stress distribution with short dental implants (SDI). The present study aimed to evaluate the effect of abutment and crown materials on the stress distributions in short implant-prosthesis-complex (6 mm) and standard implant-prosthesis-complex (10 mm) using 3D finite element analysis (FEA). MATERIALS AND METHODS: Two FEA models were designed to simulated single implant restoration of mandibular first molar, one each for short implant (6 mm) (Group S) and standard implant (10 mm) (Group C). In each group, two abutment materials were used, Polyetheretherketone (PEEK) and Zirconia (Zr), with two types of crowns, PEEK and Polymer-infiltrated ceramic-network (PICN). A vertical force of 200 N was applied to each central fossa. Stress distribution was evaluated via the von Mises stress analysis. RESULTS: Using the PEEK abutment, the stress was better dispersed with PEEK crowns, as compared to PICN crowns. The stress was concentrated on the platforms of Ti-bases and the head and middle part of abutment screws. In zirconia abutment, the stress was greatly concentrated on the axial angle regions when placed with the PEEK crowns, while the stress was dispersed when placed with PICN crowns. The stress was concentrated on the connector regions of Ti-bases and the middle part of abutment screws. For implants, the stress was concentrated on the neck of the two implants, regardless of crown materials and abutment materials. The PEEK materials were found to be suitable for the hybrid-retained prostheses of SDI. CONCLUSIONS: Our study indicates that the PEEK material is more suitable for the hybrid restorations of SDI. If the Zr abutment is used, the PICN crown would be better. Further, in-vivo clinical trials comparing these materials are needed to strengthen evidence.

MiR-92b inhibits proliferation and invasion of lung cancer by targeting EZH2.

OBJECTIVE: To verify that miR-92b inhibits proliferation and invasion of lung cancer by targeting EZH2. MATERIALS AND METHODS: The expression levels of miR-92b and EZH2 in human bronchial epithelial cell line BEAS-2B and human lung cancer cell line (A549, NCI-H23, NCI-H358, NCI-H1975, PC-9) were detected, and miR-92b mimic, sh-EZH2 expression vector, and plasmid blank vector (blank group) were constructed. Blank group, miR-92b mimic, miR-92b mimic+sh-EZH2 group (combined group) were set up, MTT and transwell were used to detect the proliferation and invasion ability of A549 and NCI-H23 cells, and fluorescein report verified the regulatory relationship of miR-92b to EZH2. RESULTS: The expression level of miR-92b in A549, NCI-H23, NCI-H358, NCI-H1975, and PC-9 cells was lower than that in BEAS-2B cells (p<0.05). The expression level of EZH2 was higher than that of BEAS-2B cells (p<0.05). A549 and NCI-H23 cells were selected for transfection. After that, the expression level of miR-92 in miR-92b mimic, combined group A549 and NCI-H23 cells was higher than that in blank group (p<0.05), and miR-92b mimic had no difference with joint group (p>0.05). The expression level of EZH2 in cells of miR-92b mimic, blank group A549, and NCI-H23 was lower than that of combined group (p<0.05), and miR-92b mimic was lower than that of blank group (p<0.05). After the overexpression of miR-92b, pmirGLO-EZH2-3'UT Wt luciferase activity decreased significantly (p<0.05) but had no effect on pmirGLO-EZH2-3'UTR Mut Luciferase activity (p>0.05). Cell proliferation ability and invasion ability of A549 cells and NCI-H23 cells in miR-92b mimic group were lower than those in blank group (p<0.05), while those in combined group were higher than those in miR-92b mimic group (p<0.05). CONCLUSIONS: MiR-92b inhibits proliferation and invasion of lung cancer cells through targeted inhibition of EZH2, which is a potential target for future treatment of lung cancer.

[Clinical effect of nasal endoscope combined with supporting laryngoscope surgery in the treatment of polyps of vocal cord and its influence on voice function of patients].

Objective:To explore the clinical value of nasal endoscope combined with supporting laryngoscope surgery in the treatment of polyps of vocal cord. Method:Ninety-four patients with vocal cord polyps were randomly divided into the control group (47 cases) and the observation group (47 cases). The patients in the control group were treated with simply supporting laryngoscope surgery while the patients in the observation group were treated with nasal endoscope combined with supporting laryngoscope. The therapeutic effects, voice function changes before and after operation, complications and recurrence of the two groups were observed. Result:The total effective rate was 93.62% in the observation group, compared to 78.72% in the control group, the difference was statistically significant (P<0.05). The incidence of postoperative complications in the observation group was 8.51%, compared with 25.53% in the control group, the difference was statistically significant (P<0.05). Six months after operation, there was no recurrence in the observation group, but the recurrence rate in the control group was 4.26%. There was no significant difference between the two groups (P>0.05). 12 months after operation, the recurrence rate of the observation group was 2.13%, compared with 14.89% of the control group, the difference was statistically significant (P<0.05). Conclusion:Nasal endoscope combined with supporting laryngoscope for vocal cord polyps has a definite effect and can significantly improve the voice function of patients with high safety and low recurrence rate, which is worthy of promotion..

Highly expressed miR-182-5p can promote preeclampsia progression by degrading RND3 and inhibiting HTR-8/SVneo cell invasion.

OBJECTIVE: The role of miR-182-5p in preeclampsia was studied, and its mechanism was also explored. PATIENTS AND METHODS: Fifty patients with preeclampsia were assigned to the study group and 50 normal pregnant women to the control group. The age, weight, blood pressure, urinary protein, and weight of newborns were compared between the two groups. The placental tissues of the above-mentioned subjects were collected, and quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) assay was used to detect the expression of miR-182-5p. MiR-182-5p was overexpressed or knocked down using a cell transfection assay in HTR-8/SVneov cell, which is a kind of human chorionic trophoblast cell. Changes in cell migration and invasiveness before and after transfection were determined by wound healing test and transwell assay, respectively. Western blot was performed to analyze the change of RND3 protein level before and after transfection. The biological prediction of the relationship between miR-182-5p and RND3 was performed and a dual luciferase reporter gene experiment was designed to verify the results. Finally, a rescue experiment was conducted to investigate whether RND3 could affect the role of miRNA-182-5p in the capacity of cell migration and invasion. RESULTS: Preeclampsia patients had higher systolic blood pressure, diastolic blood pressure, and urinary protein than normal pregnant women, while neonatal weight decreased compared with normal pregnant women. MiRNA-182-5p was highly expressed in placental tissues of patients with preeclampsia. After miRNA-182-5p was overexpressed, the migration and invasion of HTR-8/SVneo cells were significantly attenuated, and the mRNA and protein levels of RND3 were markedly downregulated, and vice versa. The dual luciferase reporting assay confirmed that miRNA-182-5p could bind to 3'UTR of RND3. In addition, the results of rescue experiment showed that overexpressing miRNA-182-5p could markedly inhibit the migration and invasion of HTR-8/SVneo cells; however, when RND3 was simultaneously overexpressed, the inhibitory effect of miRNA-182-5p was partially reversed. CONCLUSIONS: The highly expressed miRNA-182-5p in patients with preeclampsia promoted the development of preeclampsia, the possible mechanism of which might be that the increased miRNA-182-5p expression could inhibit the migratory and invasive ability of trophoblast cells through targeted degrading RND3 protein.

LINC01116 promotes the progression of epithelial ovarian cancer via regulating cell apoptosis.

OBJECTIVE: To explore the biological function of LINC01116 in epithelial ovarian cancer (EOC) and its underlying mechanism. PATIENTS AND METHODS: The expression level of LINC01116 in 60 EOC tissues, 30 normal ovarian tissues and EOC cells were detected by qRT-PCR (quantitative real-time polymerase chain reaction). Disease-free survival (DFS) and overall survival (OS) of enrolled EOC patients were recorded. The correlation between LINC01116 expression, DFS and OS of EOC patients was analyzed using ROC curve. Influencing factors for DFS and OS were analyzed by univariable and multivariable Cox regression model. For in vitro experiments, the effect of LINC01116 knockdown on proliferation, invasion and apoptosis of EOC cells were detected by CCK-8 (cell counting kit-8), transwell assay and flow cytometry, respectively. Protein expressions of apoptosis-related genes in EOC cells transfected with pc-DNA-LINC01116 or si-LINC01116 were detected by Western blot. RESULTS: LINC01116 was overexpressed in EOC tissues than that of paracancerous tissues. DFS and OS in EOC patients with higher expression of LINC01116 were remarkably shorter than those with lower expression. FIGO (International Federation of Gynecology and Obstetrics) clinical stage and LINC01116 expression were the independent factors that affected DFS and OS of EOC patients. Besides, LINC01116 expression was positively correlated to the diagnostic sensitivity of EOC patients. In vitro experiments found that LINC01116 overexpression promoted proliferation and invasion of EOC cells. Overexpressed LINC01116 resulted in upregulated Bcl-2, and downregulated cleaved Caspase-3 and cleaved Caspase-9 in EOC cells. CONCLUSIONS: Overexpressed LINC01116 promotes EOC progression via increasing proliferation and migration, and inhibiting cell apoptosis.

Blood-derived amyloid-ß protein induces Alzheimer's disease pathologies.

The amyloid-ß protein (Aß) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aß deposited in the brain originates from the brain tissue itself. However, Aß is generated in both brain and peripheral tissues. Whether circulating Aß contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aß originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aß plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aß accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aß can enter the brain, form the Aß-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aß metabolism in both the brain and the periphery.

Urea free synthesis of chitin-based acrylate superabsorbent polymers under homogeneous conditions: Effects of the degree of deacetylation and the molecular weight.

In order to understand the chemical structure of chitin-based acrylate superabsorbent polymers (SAP), chitin was dissolved in NaOH aqueous solution via freezing-thawing cyclic treatment without urea, subsequently, a transparent hydrogel was prepared by copolymerizing the alkali-chitin solution and acrylic acid directly. The effects of the degree of deacetylation (DDA) and the molecular weight (Mw) of chitin on the properties of SAP were investigated in detail. With increasing the DDA and Mw, the yield improved while the water absorbency decreased, yet the effect of DDA is insignificant if the Mw is smaller enough. The structures were characterized by FT-IR, XRD, TG, DSC, XPS, solid-state 13C NMR and elemental analyses. The results indicated that the poly(acrylic acid) chains were successfully grafted onto the chitin backbones, and the reaction sites were the NH2 on the chitosan units. The possible mechanism was further discussed, which was similar to that suggested for chitosan-g-poly(acrylic acid) SAP.

Association between single nucleotide polymorphisms in AKT1 and the risk of prostate cancer in the Chinese Han population.

AKT1, also known as v-akt murine thymoma viral oncogene homolog 1, is involved in the regulation of cell-survival and anti-apoptotic activities, which may affect the pathogenesis of various cancers. However, the association between genetic variants of AKT1 and the risk of developing prostate cancer has not been investigated before. This study investigated the associations between three polymorphisms (rs1130214, rs3730358, and rs2494732) in AKT1 and the risk of development of prostate cancer in the Chinese Han population. Sequenom MassARRAY & iPLEX technology were used to genotype these polymorphisms in 493 Chinese Han patients with prostate cancer and 309 age-matched healthy individuals. Compared to the CC genotype of the rs3730358 polymorphism, the CT genotype of the same polymorphism was strongly associated with a decreased risk of prostate cancer (OR = 0.617, 95%CI = 0.390-0.976, P = 0.037). However, there was no significant difference between the allele frequency of the rs3730358 polymorphism and those of the other two polymorphisms (P > 0.05). Moreover, no significant difference was found in the haplotype analysis (P > 0.05). Our study found that the variant genotype CT of rs3730358 of AKT1 was associated with a decreased risk of prostate cancer, which suggested that this polymorphism could play an important role in the development of the disease.

[Metformin's effect on 5-fluorouracil,cisplatin,paclitaxel in laryngocarcinoma Hep-2 cells].

Objective:To investigate metformin's effect on chemosensitivity of chemotherapeutic drug 5-fluorouracil in laryngocarcinoma Hep-2 cells. Investigate the variation trend of protein expression of AMPK pathway in the combined effect.Method:Laryngocarcinoma Hep-2 cells were treated with different concentrations of 5-fluorouracil in vitro together with or without metformin for 72 h. Use MTT assay to investigate the influence on the inhibition rate to Hep-2 cells. Hep-2 cells were treated with cisplatin, 5-fluorouracil or paclitaxel with or without metformin. Use Western blot assay to investigate the expression level of AMPKα, P21 or Cyclin D1 protein. Result:5-fluorouracil and metformin could inhibit the proliferation of Hep-2 cells. 5-fluorouracil in low concentration combined with metformin could increase the proliferation inhibition rate of Hep-2 cells. In the circumstances of using 5-fluorouracil in high concentration with metformin , the cell proliferation inhibition rate of combining group makes no differences with the single-drug group. The combination of metformin and 5-fluorouracil produced an antagonism action in Hep-2 cells.Western blot assay showed that metformin, cisplatin, 5-fluorouracil could have caused the increase of expression level of AMPK-α, P21 and Cyclin D1 in Hep-2 cells while Paclitaxel could have cause the decrease of expression level of Cyclin D1. Using combined drug could cause the change of protein expression. Conclusion:5-fluorouracil has been found to inhibit the proliferation of Hep-2 cells. Metformin has an antagonism on the anticancer effect to 5-fluorouracil in Hep-2 cells, and this antagonistic effect occurred partially through molecular signal pathways of AMPK-α, P21 and Cyclin D1 and it's significantly related to the cell cycle arrest.

TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway.

We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK-STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK-STAT signaling pathway.

The impact of the thermal conductivity of a dielectric layer on the self-heating effect of a graphene transistor.

The self-heating effect of a graphene transistor on the transport properties was studied. Different dielectric layers, SiO2 and AlN, which have different thermal conductivities, were used to tune the thermal dissipation of the graphene transistor. An obvious change in channel resistance and a shift of charge neutrality point were observed during the operation of the transistor with SiO2, while the change is slight when AlN is the dielectric layer. This observation is considered to be related to the temperature determined desorption rate of p-type dopants in graphene.

Phylogeography of Chinese cherry (Prunus pseudocerasus Lindl.) inferred from chloroplast and nuclear DNA: insights into evolutionary patterns and demographic history.

Chinese cherry (Prunus pseudocerasus Lindl.) is a commercially valuable fruit crop in China. In order to obtain new insights into its evolutionary history and provide valuable recommendations for resource conservation, phylogeographic patterns of 26 natural populations (305 total individuals) from six geographic regions were analyzed using chloroplast and nuclear DNA fragments. Low levels of haplotype and nucleotide diversity were found in these populations, especially in landrace populations. It is likely that a combined effect of botanical characteristics impact the effective population size, such as inbreeding mating system, long life span, as well as vegetative reproduction. In addition, strong bottleneck effect caused by domestication, together with founder effect after dispersal and subsequent demographic expansion, might also accelerate the reduction of the genetic variation in landrace populations. Interestingly, populations from Longmen Mountain (LMM) and Daliangshan Mountain (DLSM) exhibited relatively higher levels of genetic diversity, inferring the two historical genetic diversity centers of the species. Moreover, moderate population subdivision was also detected by both chloroplast DNA (GST = 0.215; NST = 0.256) and nuclear DNA (GST = 0.146; NST = 0.342), respectively. We inferred that the episodes of efficient gene flow through seed dispersal, together with features of long generation cycle and inbreeding mating system, were likely the main contributors causing the observed phylogeographic patterns. Finally, factors that led to the present demographic patterns of populations from these regions and taxonomic varieties were also discussed.

Effects of fixed pattern noise on single molecule localization microscopy.

The newly developed scientific complementary metal oxide semiconductor (sCMOS) cameras are capable of realizing fast single molecule localization microscopy without sacrificing field-of-view, benefiting from their readout speed which is significantly higher than that of conventional charge-coupled device (CCD) cameras. However, the poor image uniformity (suffered from fixed pattern noise, FPN) is a major obstruction for widespread use of sCMOS cameras in single molecule localization microscopy. Here we present a quantitative investigation on the effects of FPN on single molecule localization microscopy via localization precision and localization bias. We found that FPN leads to almost no effect on localization precision, but introduces a certain amount of localization bias. However, for a commercial Hamamatsu Flash 4.0 sCMOS camera, such localization bias is usually <2 nm and thus can be neglected for most localization microscopy experiments. This study addresses the FPN concern which worries researchers, and thus will promote the application of sCMOS cameras in single molecule localization microscopy.

5-HT3A receptors are required in long-term depression and AMPA receptor internalization.

5-Hydroxytrytamine (serotonin) type 3A receptors (5-HT3ARs), as the only ligand-gated ion channels in the serotonin receptor family, are known to regulate neuronal excitation and release of GABA in hippocampal interneurons. However, their physiological role in glutamatergic synaptic plasticity remains unclear. Here, we show that deletion of the 5-HT3AR gene in transgenic mice abolished N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) induced by low-frequency stimulation (LFS) in hippocampal CA1 synapses in slices, whereas the metabotropic glutamate receptor (mGluR)-dependent LTD did not change in the 5-HT3AR knockout mice. In addition, 5-HT3ARs disruption inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) internalization, without altering basal surface levels of AMPARs. However, the deletion of 5-HT3ARs did not lead to loss of synapses and structural alteration of dendritic spines. Furthermore, the concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus were not affected by the deletion of 5-HT3ARs. These observations revealed an important role of 5-HT3ARs in NMDAR-dependent long-term depression, which is critical for learning behaviors.

Orexin A activates hypoglossal motoneurons and enhances genioglossus muscle activity in rats.

BACKGROUND AND PURPOSE: Orexins have been demonstrated to play important roles in many physiological processes. However, it is not known how orexin A affects the activity of the hypoglossal motoneuron (HMN) and genioglossus (GG) muscle. EXPERIMENTAL APPROACH: GG muscle electromyograms (GG-EMG) were recorded in anaesthetized adult rats after orexin A or orexin receptor antagonists were applied to the hypoglossal nucleus, and in adult rats in which orexin neurons were lesioned with the neurotoxin orexin-saporin (orexin-SAP). HMN membrane potential and firing were recorded from neonatal rat brain slices using whole-cell patch clamp after an infusion of orexin A or orexin receptor antagonists. KEY RESULTS: Unilateral micro-injection of orexin A (50, 100 or 200 µM) into the hypoglossal nucleus significantly enhanced ipsilateral GG activity in adult rats. Orexin A (4, 20, 100 or 500 nM) depolarized the resting membrane potential and increased the firing rate of HMNs in a dose-dependent manner in the medullary slices of neonatal rats. Both SB 334867, a specific OX1 receptor antagonist and TCS OX2 29, a specific OX2 receptor antagonist not only blocked the depolarized membrane potential and the increased firing rate of HMNs by orexin A in the neonatal model but also attenuated GG-EMG in the adult model. A significant decrease in GG-EMG was observed in adult orexin neuron-lesioned rats compared with sham animals. CONCLUSION AND IMPLICATIONS: Orexin A activates OX1 and OX2 receptors within the hypoglossal motor pool and promotes GG activity, indicating that orexin A is involved in controlling respiratory motor activity.

Trends in cancer mortality in China: an update.

BACKGROUND: Cancer deaths of China with the world population nearly a quarter will have a severe impact on global cancer trend and burden. The study aims to provide a comprehensive overview of long-term trends in cancer mortality in China. MATERIALS AND METHODS: We used joinpoint analysis to detect changes in trends and generalized additive models to study birth cohort effect of risk factors between 1987 and 2009. RESULTS: Mortality of all cancers declined steadily in urban areas, but not in rural areas. Decreasing mortality from cancers of the stomach, esophagus, nasopharynx, and cervix uteri was observed, while lung and female breast cancer mortality increased. Mortality from leukemia remained relatively stable, and cancer of liver, colorectal, and bladder had different trends between the rural and urban areas. Generational risks peaked in the cohorts born around 1925-1930 and tended to decline in successive cohorts for most cancers except for leukemia, whose relative risks were rising in the very recent cohorts. CONCLUSION: The observed trends primarily reflect dramatic changes in socioeconomic development and lifestyle in China over the past two decades, and mortality from cancers of lung and female breast still represents a major public health priority for the government.