Anomalous intense coherent secondary photoemission from a perovskite oxide.

Photocathodes-materials that convert photons into electrons through a phenomenon known as the photoelectric effect-are important for many modern technologies that rely on light detection or electron-beam generation1-3. However, current photocathodes are based on conventional metals and semiconductors that were mostly discovered six decades ago with sound theoretical underpinnings4,5. Progress in this field has been limited to refinements in photocathode performance based on sophisticated materials engineering1,6. Here we report unusual photoemission properties of the reconstructed surface of single crystals of the perovskite oxide SrTiO3(100), which were prepared by simple vacuum annealing. These properties are different from the existing theoretical descriptions4,7-10. In contrast to other photocathodes with a positive electron affinity, our SrTiO3 surface produces, at room temperature, discrete secondary photoemission spectra, which are characteristic of efficient photocathode materials with a negative electron affinity11,12. At low temperatures, the photoemission peak intensity is enhanced substantially and the electron beam obtained from non-threshold excitations shows longitudinal and transverse coherence that differs from previous results by at least an order of magnitude6,13,14. The observed emergence of coherence in secondary photoemission points to the development of a previously undescribed underlying process in addition to those of the current theoretical photoemission framework. SrTiO3 is an example of a fundamentally new class of photocathode quantum materials that could be used for applications that require intense coherent electron beams, without the need for monochromatic excitations.

PET imaging for the early evaluation of ocular inflammation in diabetic rats by using [18F]-DPA-714.

Ocular complications of diabetes mellitus (DM) are the leading cause of vision loss. Ocular inflammation often occurs in the early stage of DM; however, there are no proven quantitative methods to evaluate the inflammatory status of eyes in DM. The 18 kDa translocator protein (TSPO) is an evolutionarily conserved cholesterol binding protein localized in the outer mitochondrial membrane. It is a biomarker of activated microglia/macrophages; however, its role in ocular inflammation is unclear. In this study, fluorine-18-DPA-714 ([18F]-DPA-714) was evaluated as a specific TSPO probe by cell uptake, cell binding assays and micro positron emission tomography (microPET) imaging in both in vitro and in vivo models. Primary microglia/macrophages (PMs) extracted from the cornea, retina, choroid or sclera of neonatal rats with or without high glucose (50 mM) treatment were used as the in vitro model. Sprague-Dawley (SD) rats that received an intraperitoneal administration of streptozotocin (STZ, 60 mg/kg once) were used as the in vivo model. Increased cell uptake and high binding affinity of [18F]-DPA-714 were observed in primary PMs under hyperglycemic stress. These findings were consistent with cellular morphological changes, cell activation, and TSPO up-regulation. [18F]-DPA-714 PET imaging and biodistribution in the eyes of DM rats revealed that inflammation initiates in microglia/macrophages in the early stages (3 weeks and 6 weeks), corresponding with up-regulated TSPO levels. Thus, [18F]-DPA-714 microPET imaging may be an effective approach for the early evaluation of ocular inflammation in DM.

The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons.

Dopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.

The effects of bitter melon (Momordica charantia) on anthropometric indices in adults: A systematic review and meta-analysis of randomized controlled trials.

There is controversial data on the impacts of bitter melon (Momordica charantia) supplementations on anthropometric indices. Thus, we aimed to clarify this role of bitter melon through a systematic review, and meta-analysis of the trials. All clinical trials conducted on the impact of bitter melon on anthropometric indices were published until August 2023 in PubMed, Web of Sciences, Scopus, Embase, and Cochrane Library web databases included. Overall, 10 studies with 448 individuals were included in the meta-analysis. Meta-analysis of 10 trials with 448 participants revealed no significant reductions in body weight (BW) (WMD: 0.04 Kg; 95 %CI: -0.16-0.25; P =0.651), body mass index (BMI) (WMD: -0.18 kg/m2; 95 %CI: -0.43-0.07; P =0.171), waist circumference (WC) (WMD: -0.95 cm; 95 % CI: -3.05-1.16; p =0.372), and percentage of body fat (PBF) (WMD: -0.99; 95 % CI: -2.33-0.35; p =0.141) following bitter melon supplementation. There was no significant impact of bitter melon supplementation on BW, BMI, WC, and PBF. More large-scale and high-quality RCTs are necessary to confirm these results.

Tanshinone I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC.

BACKGROUND: Abnormal activation of NLRP3 inflammasome is related to a series of inflammatory diseases, including type 2 diabetes, gouty arthritis, non-alcoholic steatohepatitis (NASH), and neurodegenerative disorders. Therefore, targeting NLRP3 inflammasome is regarded as a potential therapeutic strategy for many inflammatory diseases. A growing number of studies have identified tanshinone I (Tan I) as a potential anti-inflammatory agent because of its good anti-inflammatory activity. However, its specific anti-inflammatory mechanism and direct target are unclear and need further study. METHODS: IL-1ß and caspase-1 were detected by immunoblotting and ELISA, and mtROS levels were measured by flow cytometry. Immunoprecipitation was used to explore the interaction between NLRP3, NEK7 and ASC. In a mouse model of LPS-induced septic shock, IL-1ß levels in peritoneal lavage fluid and serum were measured by ELISA. Liver inflammation and fibrosis in the NASH model were analyzed by HE staining and immunohistochemistry. RESULTS: Tan I inhibited the activation of NLRP3 inflammasome in macrophages, but had no effect on the activation of AIM2 or NLRC4 inflammasome. Mechanistically, Tan I inhibited NLRP3 inflammasome assembly and activation by targeting NLRP3-ASC interaction. Furthermore, Tan I exhibited protective effects in mouse models of NLRP3 inflammasome-mediated diseases, including septic shock and NASH. CONCLUSIONS: Tan I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC, and exhibits protective effects in mouse models of LPS-induced septic shock and NASH. These findings suggest that Tan I is a specific NLRP3 inhibitor and may be a promising candidate for treating NLRP3 inflammasome-related diseases.

Targeting a thrombopoietin-independent strategy in the discovery of a novel inducer of megakaryocytopoiesis, DMAG, for the treatment of thrombocytopenia.

Thrombocytopenia is a thrombopoietin (TPO)-related disorder with very limited treatment options, and can be lifethreatening. There are major problems with typical thrombopoietic agents targeting TPO signaling, so it is urgent to discover a novel TPO-independent mechanism involving thrombopoiesis and potential druggable targets. We developed a drug screening model by the multi-grained cascade forest (gcForest) algorithm and found that 3,8-di-O-methylellagic acid 2- O-glucoside (DMAG) (10, 20 and 40 µM) promoted megakaryocyte differentiation in vitro. Subsequent investigations revealed that DMAG (40 mM) activated ERK1/2, HIF-1b and NF-E2. Inhibition of ERK1/2 blocked megakaryocyte differentiation and attenuated the upregulation of HIF-1b and NF-E2 induced by DMAG. Megakaryocyte differentiation induced by DMAG was inhibited via knockdown of NF-E2. In vivo studies showed that DMAG (5 mg/kg) accelerated platelet recovery and megakaryocyte differentiation in mice with thrombocytopenia. The platelet count of the DMAG-treated group recovered to almost 72% and 96% of the count in the control group at day 10 and 14, respectively. The platelet counts in the DMAG-treated group were almost 1.5- and 1.3-fold higher compared with those of the irradiated group at day 10 and 14, respectively. Moreover, DMAG (10, 25 and 50 mM) stimulated thrombopoiesis in zebrafish. DMAG (5 mg/kg) could also increase platelet levels in c-MPL knockout (c-MPL-/-) mice. In summary, we established a drug screening model through gcForest and demonstrated that DMAG promotes megakaryocyte differentiation via the ERK/HIF1/NF-E2 pathway which, importantly, is independent of the classical TPO/c-MPL pathway. The present study may provide new insights into drug discovery for thrombopoiesis and TPO-independent regulation of thrombopoiesis, as well as a promising avenue for thrombocytopenia treatment.

Effects of Atorvastatin on Bile Acid Metabolism in High-fat Diet-fed ApoE -/- Mice.

ABSTRACT: Statins are considered as the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease, where pleiotropic effects are thought to contribute greatly in addition to the lipid-lowering effect. Bile acid metabolism has been gradually reported to be involved in the antihyperlipidemic and antiatherosclerotic effects of statins, but with inconsistent results and few studies carried out on animal models of atherosclerosis. The study aimed to examine the possible role of bile acid metabolism in the lipid-lowering and antiatherosclerotic effects of atorvastatin (ATO) in high-fat diet-fed ApoE -/- mice. The results showed that the levels of liver and faecal TC as well as ileal and faecal TBA were significantly increased in mice of the model group after 20 weeks of high-fat diet feeding compared with the control group, with significantly downregulated mRNA expression of liver LXR-α, CYP7A1, BSEP, and NTCP. ATO treatment further increased the levels of ileal and faecal TBA and faecal TC, but no obvious effect was observed on serum and liver TBA. In addition, ATO significantly reversed the mRNA levels of liver CYP7A1 and NTCP, and no obvious changes were observed in the expression of LXR-α and BSEP. Our study suggested that statins may enhance the synthesis of bile acids and facilitate the reabsorption of bile acids from the ileum via portal into the liver, possibly through the upregulation of the expression of CYP7A1 and NTCP. The results are helpful in enriching the theoretical basis for the clinical use of statins and have good translational value.

APP in the Neuromuscular Junction for the Development of Sarcopenia and Alzheimer's Disease.

Sarcopenia, an illness condition usually characterized by a loss of skeletal muscle mass and muscle strength or function, is often associated with neurodegenerative diseases, such as Alzheimer's disease (AD), a common type of dementia, leading to memory loss and other cognitive impairment. However, the underlying mechanisms for their associations and relationships are less well understood. The App, a Mendelian gene for early-onset AD, encodes amyloid precursor protein (APP), a transmembrane protein enriched at both the neuromuscular junction (NMJ) and synapses in the central nervous system (CNS). Here, in this review, we highlight APP and its family members' physiological functions and Swedish mutant APP (APPswe)'s pathological roles in muscles and NMJ. Understanding APP's pathophysiological functions in muscles and NMJ is likely to uncover insights not only into neuromuscular diseases but also AD. We summarize key findings from the burgeoning literature, which may open new avenues to investigate the link between muscle cells and brain cells in the development and progression of AD and sarcopenia.

Targeting Energy Protection as a Novel Strategy to Disclose Di'ao Xinxuekang against the Cardiotoxicity Caused by Doxorubicin.

Doxorubicin (DOX) can induce myocardial energy metabolism disorder and further worsen heart failure. "Energy protection" is proposed as a new cardiac protection strategy. Previous studies have found that Di'ao Xinxuekang (DXXK) can improve doxorubicin-induced cardiotoxicity in mice by inhibiting ferroptosis. However, there are very few studies associating DXXK and energy protection. This study aims to explore the "energy protection" effect of DXXK on cardiotoxicity induced by DOX. A DOX-induced cardiotoxicity model established in rats and H9c2 cells are used to analyze the therapeutic effects of DXXK on serum indexes, cardiac function indexes and cardiac histopathology. The metabonomic methods were used to explore the potential mechanism of DXXK in treating DOX-induced cardiotoxicity. In addition, we also observed the mitochondrial- and autophagy-related indicators of myocardial cells and the mRNA expression level of the core target regulating energy-metabolism-related pathways. Our results indicated that DXXK can improve cardiac function, reduce myocardial enzymes and alleviate the histological damage of heart tissue caused by DOX. In addition, DXXK can improve mitochondrial damage induced by DOX and inhibit excessive autophagy. Metabonomics analysis showed that DOX can significantly affects the pathways related to energy metabolism of myocardial cells, which are involved in the therapeutic mechanism of DXXK. In conclusion, DXXK can treat DOX-induced cardiotoxicity through the AMPK-mediated energy protection pathway.

Study on the Preparation and Performance of Silicone-Modified Phenolic Resin Binder for Rail Grinding Wheels.

A scheme for manufacturing heavy-duty rail grinding wheels with silicone-modified phenolic resin (SMPR) as a binder in the field of rail grinding is presented to improve the performance of grinding wheels. To optimize the heat resistance and mechanical performance of rail grinding wheels, an SMPR for industrial production of rail grinding wheels was prepared in a two-step reaction using methyl-trimethoxy-silane (MTMS) as the organosilicon modifier by guiding the occurrence of the transesterification and addition polymerization reactions. The effect of MTMS concentration on the performance of silicone-modified phenolic resin for application in rail grinding wheels was investigated. The molecular structure, thermal stability, bending strength, and impact strength values of the SMPR were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and mechanical property testing, and the effect of MTMS content on the resin properties was investigated. The results indicated that MTMS successfully improved the performance of the phenolic resin. The thermogravimetric weight loss temperature of the SMPR modified by MTMS with 40% phenol mass at 30% weight loss is 66% higher than that of common phenolic resin (UMPR), exhibiting the best thermal stability; in addition, its bending strength and impact strength were enhanced by approximately 14% and 6%, respectively, compared with those of common UMPR. This study utilized an innovative Bronsted acid as a catalyst and simplified several intermediate reactions in the conventional silicone-modified phenolic resin technology. This new investigation of the synthesis process decreases the manufacturing cost of the SMPR, liberates it from the restrictions of grinding applications, and enables the SMPR to maximize its performance in the rail grinding industry. This study serves as a reference for future work on resin binders for grinding wheels and the development of rail grinding wheel manufacturing technology.

Opportunities and hurdles to European market access for multi-herbal traditional Chinese medicine products: An analysis of EU regulations for combination herbal medicinal products.

TCM herbal remedies are popular among European patients. However, a very limited number of TCM products have been approved as herbal medicinal products (HMPs) in Europe. Multi-herbal TCM products, the most prevalent form of medication in TCM practice, are even rare. This indicates multi-herbal TCM products are facing considerable obstacles in the access to EU market. To further identify such obstacles, we make a systematic analysis of current advances in both EU herbal monographs and combination HMPs granted in member states and present main features of the regulation as well as challenges for multi-herbal TCM products. The results show the EU is open to combination HMPs based on TCM or other non-European traditions. The regulation allows appropriate flexibility in the range of drug extraction rations, variation in concentrations of extraction solvent and number of herbal drugs presented in the product, if plausible pharmacological effects could be justified. Meanwhile, to guarantee the safety and efficacy based on medicinal usage, especially to justify the rationale or plausibility of the combination, is the key element for well-established use or traditional use combination HMPs. Additionally, EU herbal monographs also have great value in their marketing procedure. Nonetheless, there are many challenges in the European market access of multi-herbal TCM products which lies in quality control, safety and efficacy evaluation and others e.g., practical standard for full marketing authorization. Enforced scientific research and communication among research institutions, industries and authorities are necessary to further facilitate the access of multi-herbal TCM products to EU market. The results of this article may provide guidance for HMPs based on TCM or other non-European traditions with intention to entering EU market.

Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway.

Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway, and MG may be a promising therapeutic agent for UC treatment.

Prevalence of persistent vegetative state compared to recovery, disability, and death in subjects with severe traumatic brain injury: A meta-analysis.

BACKGROUND: The persistent vegetative state has drawn considerable attention since it is the poorest result apart from mortality in subjects with severe traumatic brain injury. This meta-analysis was performed to evaluate its prevalence compared to recovery, disability, and death 6 months post severe traumatic brain injury. METHODS: A systematic-literature search up to May 2020 was performed and 19 studies were detected with 10 368 subjects. They contained data about the subject's status 6 months post severe traumatic brain injury (recovery, disability, persistent vegetative state, and death). Odds ratio (OR) with 95% confidence intervals (CIs) was calculated comparing the prevalence of persistent vegetative state to that of recovery, disability, and death; 6 months post severe traumatic brain injury using the dichotomous method with a random- or fixed-effect model. RESULTS: Significantly higher prevalence was found of recovery (OR, 0.08; 95% CI, 0.03-0.20, P < .001); disability (OR, 0.09; 95% CI, 0.06-0.15, P < .001); and death (OR, 0.07; 95% CI, 0.04-0.11, P < .001) compared to the prevalence of persistent vegetative state. The prevalence of persistent vegetative state was variable over time. Also, the prevalence of persistent vegetative states in developing countries was much higher than in developed countries. CONCLUSIONS: However, persistent vegetative state is the poorest result apart from mortality in subjects with severe traumatic brain injury. Its prevalence is lower than the recovery, disability, and death even in developing counties with its lower healthcare services. The prevalence was variable over time and higher in developing countries. This relationship forces us to recommend improving healthcare services to the extent that a persistent vegetative state could be avoided as much as possible.

Case Report: Acute Retinal Necrosis after Intravitreal Ranibizumab for Exudative Macular Degeneration.

SIGNIFICANCE: Acute retinal necrosis (ARN) may occur after intravitreal ranibizumab (IVR) treatment for patients with exudative age-related macular degeneration (AMD). Awareness of this unusual but devastating complication after IVR is needed. Early identification may help provide timely antiviral treatment and prevent irreversible visual loss. PURPOSE: This study aimed to report a case of ARN after IVR in a patient with exudative AMD. CASE REPORT: A 67-year-old male patient complained of blurred vision in his left eye for 1 month. The patient was diagnosed with exudative AMD after detailed ophthalmic clinical evaluations. He received IVR once in his left eye. Three days after IVR, he developed varicella-zoster virus-associated ARN, which was treated with systemic and intravitreal antiviral therapy. Because of progressive inflammation, the patient underwent 25G pars plana vitrectomy with silicone oil tamponade. Seven months later, the patient was administered intravitreal aflibercept once in his left eye. Three months after intravitreal aflibercept, he underwent removal of silicone oil, and retinal detachment occurred 2 weeks after the surgery because of low IOP, and the patient eventually discontinued treatment. CONCLUSIONS: This study reports the first case of varicella-zoster virus-associated ARN after IVR. Early ARN may be very difficult to distinguish from intraocular inflammation after IVR. Therefore, early detection of viral DNA in the intraocular fluid using polymerase chain reaction is recommended. Immediate antiviral treatment may be beneficial to prevent severe visual loss.

Clinical efficacy and safety of Tanreqing injection combined with antibiotics versus antibiotics alone in the treatment of pulmonary infection patients after chemotherapy with lung cancer: A systematic review and meta-analysis.

This study aimed to evaluate the efficacy and safety of Tanreqing injection (TRQi) in the treatment of pulmonary infection after chemotherapy in patients with lung cancer. Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VMIS, Wan-Fang, and CBM databases were comprehensively searched from established to March 2020. randomized controlled trials (RCTs) of TRQi were selected. The evaluation manual of Cochrane RCT was used to evaluate the methodological quality of all included studies, Stata 13.0 and Review Manager 5.3 software was used for meta-analysis. This study is registered with PROSPERO (CRD42020175533). Eighteen RCTs with a total of 1,438 patients were met the inclusion criteria. Meta-analysis showed that compared with antibiotics alone, TRQi plus antibiotics could significantly improve the clinical efficacy, defervescence time, lung rale disappearance time, cough disappearance time, and average hospitalization time, reduce white blood cell, C-reactive protein, and procalcitonin levels, and adverse reactions. However, due to the small sample size and low quality of the study, more rigorous and more RCTs are needed for further verification. In conclusion, this study provides useful evidence for the efficacy and safety of TRQi combined with antibiotics in the treatment of pulmonary infection after chemotherapy with lung cancer.

Therapeutic effects of higenamine combined with [6]-gingerol on chronic heart failure induced by doxorubicin via ameliorating mitochondrial function.

Higenamine (HG) is a natural benzylisoquinoline alkaloid isolated from Aconitum with positive inotropic and chronotropic effects. This study aimed to investigate the possible cardioprotective effects of HG combined with [6]-gingerol (HG/[6]-GR) against DOX-induced chronic heart failure (CHF) by comprehensive approaches. DOX-induced cardiotoxicity model in rats and H9c2 cells was established. Therapeutic effects of HG/[6]-GR on haemodynamics, serum indices and histopathology of cardiac tissue were analysed. Cell mitochondrial energy phenotype and cell mitochondrial fuel flex were measured by a Seahorse XFp analyser. Moreover, UHPLC-Q-TOF/MS was performed to explore the potential metabolites affecting the therapeutic effects and pathological process of CHF. To further investigate the potential mechanism of HG/[6]-GR, mRNA and protein expression levels of RAAS and LKB1/AMPK/Sirt1-related pathways were detected. The present data demonstrated that the therapeutic effects of HG/[6]-GR combination on CHF were presented in ameliorating heart function, down-regulation serum indices and alleviating histological damage of heart tissue. Besides, HG/[6]-GR has an effect on increasing cell viability of H9c2 cells, ameliorating DOX-induced mitochondrial dysfunction and elevating mitochondrial OCR and ECAR value. Metabolomics analyses showed that the therapeutic effect of HG/[6]-GR combination is mainly associated with the regulation of fatty acid metabolites and energy metabolism pathways. Furthermore, HG/[6]-GR has an effect on down-regulating RAAS pathway-related molecules and up-regulating LKB1/AMPKα/Sirt1-related pathway. The present work demonstrates that HG/[6]-GR prevented DOX-induced cardiotoxicity via the cardiotonic effect and promoting myocardial energy metabolism through the LKB1/AMPKα/Sirt1 signalling pathway, which promotes mitochondrial energy metabolism and protects against CHF.

FoxM1 affects adhesive, migratory, and invasive abilities of human retinoblastoma Y-79 cells by targeting matrix metalloproteinase 2.

Forkhead box protein M1 (FoxM1) is an important transcription factor involved in various pathological processes including tumor metastasis. The changes of adhesive, migratory, and invasive abilities are considered as crucial events in tumor metastasis progression. In this study, we aimed to investigate the correlation between FoxM1 and retinoblastoma (Rb) metastasis and to explore the detailed mechanism. Wound healing, cell adhesion, and invasion assays showed that FoxM1 overexpression induced epithelial-mesenchymal transition in Y-79 cells and inhibited adhesion and subsequently promoted metastasis of Y-79 cells, while FoxM1 knockdown showed the opposite effects. A luciferase reporter assay and chromatin immunoprecipitation assay provided evidence that FoxM1 promoted matrix metalloproteinase 2 (MMP2) transcription by directly binding to and promoting MMP2 promoter. MMP2 knockdown by siRNA transfection attenuated cell metastasis of Y-79 cells induced by FoxM1 overexpression. Furthermore, the FoxM1-binding site mapped between -1167 and -1161 bp of the MMP2 promoter was identified. Our results suggested that the FoxM1-MMP2 axis plays an important role in Rb metastasis, which may be a novel target for designing therapeutic regimen to control Rb metastasis.

Plasmonic optical trapping of nanoparticles with precise angular selectivity.

In this paper, a plasmonic trapping scheme including a polystyrene nanoparticle with gold cap and a metal tip tweezers was proposed. We numerically investigated the optical trapping behavior of the metal tip to this asymmetric particle. The results show that the metal tip can capture the particle at the position of the gold cap due to the strong plasmonic interaction, while other positions of the particle cannot be captured by metal tip. Furthermore, the trapping angle of the nanoparticle can be adjusted by changing the incident wavelength. Precisely controlling the trapping angle of the nanoparticles in our study has important potential applications of optical tweezers, such as in single molecule manipulation.

ErbB4 Receptors in the Medial Habenula Regulate Contextual Fear Memory.

The Medial Habenular (MHb) and the Lateral Habenular nuclei are 2 main parts of the habenular complex (Hb). Recent studies showed that MHb plays an important role in memory, and in the expression of ErbB4. However, the expression of MHb ErbB4 receptor and its role in fear memory is not well understood. In this study, western blotting and quantitative real-time polymerase chain reaction were used to assess the protein and mRNA levels of ErbB4 in the process of contextual fear conditioning. A pharmacological approach was used to block and stimulate the ErbB4 receptor. Contextual fear conditioning tests induced a significant increase on the expression of ErbB4 at various times in the Hb and the MHb. Moreover, the blockade and stimulation of MHb ErbB4 receptors did not affect the fear formation but impaired and improved the contextual-dependent fear expression. Furthermore, in vitro electrophysiological recordings showed that the blockade of the MHb ErbB4 receptor reduced the presynaptic gamma-amino butyric acid release. ErbB4 is a susceptible gene for schizophrenia and the above findings may provide new insights into the mechanisms of fear-related responses.

Dorsomedial prefrontal cortex 5-HT6 receptors regulate anxiety-like behavior.

The dorsomedial prefrontal cortex (dmPFC) plays a very important role in decision-related and anxiety-related information processing. It has enriched 5-HT6 receptors; however, the precise role of dmPFC 5-HT6 receptors in anxiety remains to be fully investigated. In this study, we injected dmPFC with the 5-HT6 receptor agonist EMD 386088 and antagonist SB 271046 using stereotactic technology. 5-HT6 receptor activation in mice increased time spent in the center area on the open-field test, increased exploration of the open arms on the elevated plus maze test, and increased ratio on the social interaction test. 5-HT6 receptor inactivation induced the opposite effects. In brain slices, EMD 386088 decreased both spontaneous inhibitory postsynaptic currents (sIPSC) and spontaneous excitatory postsynaptic currents (sEPSC), while SB 271046 only increased sEPSC. These effects of EMD 386088 and SB 271046 could be reversed by the GABAA receptor antagonist bicuculline (BMI) and positive allosteric modulator clonazepam (CLZ), respectively. Our results suggest that neurotransmission in the dmPFC by 5-HT6 receptor activation and inhibition may play an important role in anxiety-like behavior, and may provide new insight into the pathological mechanism and potential target of anxiety disorders.