Molecular Plasmonics with Metamaterials.

Molecular plasmonics, the area which deals with the interactions between surface plasmons and molecules, has received enormous interest in fundamental research and found numerous technological applications. Plasmonic metamaterials, which offer rich opportunities to control the light intensity, field polarization, and local density of electromagnetic states on subwavelength scales, provide a versatile platform to enhance and tune light-molecule interactions. A variety of applications, including spontaneous emission enhancement, optical modulation, optical sensing, and photoactuated nanochemistry, have been reported by exploiting molecular interactions with plasmonic metamaterials. In this paper, we provide a comprehensive overview of the developments of molecular plasmonics with metamaterials. After a brief introduction to the optical properties of plasmonic metamaterials and relevant fabrication approaches, we discuss light-molecule interactions in plasmonic metamaterials in both weak and strong coupling regimes. We then highlight the exploitation of molecules in metamaterials for applications ranging from emission control and optical modulation to optical sensing. The role of hot carriers generated in metamaterials for nanochemistry is also discussed. Perspectives on the future development of molecular plasmonics with metamaterials conclude the review. The use of molecules in combination with designer metamaterials provides a rich playground both to actively control metamaterials using molecular interactions and, in turn, to use metamaterials to control molecular processes.

Model Selection for Exponential Power Mixture Regression Models.

Finite mixture of linear regression (FMLR) models are among the most exemplary statistical tools to deal with various heterogeneous data. In this paper, we introduce a new procedure to simultaneously determine the number of components and perform variable selection for the different regressions for FMLR models via an exponential power error distribution, which includes normal distributions and Laplace distributions as special cases. Under some regularity conditions, the consistency of order selection and the consistency of variable selection are established, and the asymptotic normality for the estimators of non-zero parameters is investigated. In addition, an efficient modified expectation-maximization (EM) algorithm and a majorization-maximization (MM) algorithm are proposed to implement the proposed optimization problem. Furthermore, we use the numerical simulations to demonstrate the finite sample performance of the proposed methodology. Finally, we apply the proposed approach to analyze a baseball salary data set. Results indicate that our proposed method obtains a smaller BIC value than the existing method.

[Research progress on strontium isotope-traced plant remains production areas and implications for traceability of Dao-di herbs in Forbidden City of the Qing Dynasty].

Strontium isotope(~(87)S/~(86)Sr) tracing technology has been widely used in animal remains and origin of modern food origin sources. However, due to the problems of sample contamination and cleaning, this technology has been applied less frequently in the tracing of plant remains. The Palace Museum preserves more than 1 000 relics of medicinal materials from the Forbidden City of the Qing Dynasty, which are rare precious materials for the study of Dao-di herbs. The well-preserved environment of these medicinal materials in the Forbidden City of the Qing Dynasty helps avoid external strontium contamination, making it possible to introduce strontium isotope technology in their tracing research. On this basis, this study discussed the principle of strontium isotope tracing technology and summarized the current research progress on tracing plant remains using strontium isotope. In addition, this study discussed three key problems and their respective solutions encountered when applying strontium isotope technology to the tracing research on medicinal materials from the Forbidden City of the Qing Dynasty: creating strontium isotope ratio maps, dealing with the wide range of traceable results, and addressing the sample contamination and cleaning challenges. The literature and historical materials of the Qing Dynasty are the important basis for understanding the distribution and application of Dao-di herbs in the Qing Dynasty. Based on literature research, the use of strontium isotope to trace the producing area of medicinal materials in the Forbidden City of the Qing Dynasty can provide physical evidence for relevant research. The combined evidence of historical materials and medicinal relics is expected to provide a new perspective for the study of Dao-di herbs in the Qing Dynasty and also provide a reference for the study of the revolution of Dao-di herbs producing areas.

[Inheritance of Yunling and rise of Anling: producing areas of Fuling in local chronicles of the Qing Dynasty].

There are abundant local chronicles in the Qing Dynasty, which provide rich literature for the research on the production of medicinal materials. This paper collates the contents of Fuling in the local chronicles of the Qing Dynasty to reveal the distribution of Fuling in China at that time. The distribution of Fuling in the local chronicles of the Qing Dynasty involved 318 county-level regions in 23 provinces. The distribution records were mainly found in Yunnan, Anhui, Hunan, Zhejiang, Fujian, Jiangxi, Shaanxi, and Hubei. The local chronicles of the Qing Dynasty showed that Yunnan was the Dao-di producing area of Fuling, which was consistent with the materia medica of the Ming and Qing Dynasties. In the Qing Dynasty, the quality of Fuling in Dabie Mountains of Anhui was excellent, and it was called "Anling". The development of Anling benefited from the introduction of planting technology from Yunnan and the development of characteristic cultivation technology, with the formation of a complete industrial chain covering planting, processing, and sales. The abundant historical materials of Fuling in the local chronicles of the Qing Dynasty provide not only a documentary basis for revealing the changes of the Dao-di producing areas but also a historical context for the development of modern Fuling-producing areas such as Fujian, Jiangxi, and Hunan. In addition to the information of producing areas, the local records recorded the quality, commodity evaluation, and cultivation techniques of Fuling, filling the gaps in ancient materia medica books and providing detailed historical materials for understanding the producing areas and application of Fuling in the Qing Dynasty.

Use of random integration to test equality of high dimensional covariance matrices.

Testing the equality of two covariance matrices is a fundamental problem in statistics, and especially challenging when the data are high-dimensional. Through a novel use of random integration, we can test the equality of high-dimensional covariance matrices without assuming parametric distributions for the two underlying populations, even if the dimension is much larger than the sample size. The asymptotic properties of our test for arbitrary number of covariates and sample size are studied in depth under a general multivariate model. The finite-sample performance of our test is evaluated through numerical studies. The empirical results demonstrate that our test is highly competitive with existing tests in a wide range of settings. In particular, our proposed test is distinctly powerful under different settings when there exist a few large or many small diagonal disturbances between the two covariance matrices.

Plasmonic Metamaterials for Nanochemistry and Sensing.

Plasmonic nanostructures were initially developed for sensing and nanophotonic applications but, recently, have shown great promise in chemistry, optoelectronics, and nonlinear optics. While smooth plasmonic films, supporting surface plasmon polaritons, and individual nanostructures, featuring localized surface plasmons, are easy to fabricate and use, the assemblies of nanostructures in optical antennas and metamaterials provide many additional advantages related to the engineering of the mode structure (and thus, optical resonances in the given spectral range), field enhancement, and local density of optical states required to control electronic and photonic interactions. Focusing on two of the many applications of plasmonic metamaterials, in this Account, we review our work on the sensing and nanochemistry applications of metamaterials based on the assemblies of plasmonic nanorods under optical, as well as electronic interrogation. Sensors are widely employed in modern technology for the detection of events or changes in their local environment. Compared to their electronic counterparts, optical sensors offer a combination of high sensitivity, fast response, immunity to electromagnetic interference, and provide additional options for signal retrieval, such as optical intensity, spectrum, phase, and polarization. Owing to the ability to confine and enhance electromagnetic fields on subwavelength scales, plasmonics has been attracting increasing attention for the development of optical sensors with advantages including both nanometer-scale spatial resolution and single-molecule sensitivity. Inherent hot-electron generation in plasmonic nanostructures under illumination or during electron tunneling in the electrically biased nanostructures provides further opportunities for sensing and stimulation of chemical reactions, which would otherwise not be energetically possible. We first provide a brief introduction to a metamaterial sensing platform based on arrays of strongly coupled plasmonic nanorods. Several prototypical sensing examples based on this versatile metamaterial platform are presented. Record-high refractive index sensitivity of gold nanorod arrays in biosensing based on the functionalization of the nanorod surface for selective absorption arises because of the modification of the electromagnetic coupling between the nanorods in the array. The capabilities of nanorod metamaterials for ultrasound and hydrogen sensing were demonstrated by precision coating of the nanorods with functional materials to create core-shell nanostructures. The extension of this metamaterial platform to nanotube and nanocavity arrays, and metaparticles provides additional flexibility and removes restrictions on the illumination configurations for the optical interrogation. We then discuss a nanochemical platform based on the electrically driven metamaterials to stimulate and detect chemical reactions in the tunnel junctions constructed with the nanorods by exploiting elastic tunneling for the activation of chemical reactions via generated hot-electrons and inelastic tunneling for the excitation of plasmons facilitating optical monitoring of the process. This represents a new paradigm merging electronics, plasmonics, photonics and chemistry at the nanoscale, and creates opportunities for a variety of practical applications, such as hot-electron-driven nanoreactors and high-sensitivity sensors, as well as nanoscale light sources and modulators. With a combination of merits, such as the ability to simultaneously support both localized and propagating modes, nanoporous texture, rapid and facile functionalization, and low cost and scalability, plasmonic nanorod metamaterials provide an attractive and versatile platform for the development of optical sensors and nanochemical platforms using hot-electrons with high performance for applications in fundamental research and chemical and pharmaceutical industries.

Dual-agonist occupancy of orexin receptor 1 and cholecystokinin A receptor heterodimers decreases G-protein-dependent signaling and migration in the human colon cancer cell line HT-29.

The orexin (OX1R) and cholecystokinin A (CCK1R) receptors play opposing roles in the migration of the human colon cancer cell line HT-29, and may be involved in the pathogenesis and pathophysiology of cancer cell invasion and metastasis. OX1R and CCK1R belong to family A of the G-protein-coupled receptors (GPCRs), but the detailed mechanisms underlying their functions in solid tumor development remain unclear. In this study, we investigated whether these two receptors heterodimerize, and the results revealed novel signal transduction mechanisms. Bioluminescence and Förster resonance energy transfer, as well as proximity ligation assays, demonstrated that OX1R and CCK1R heterodimerize in HEK293 and HT-29 cells, and that peptides corresponding to transmembrane domain 5 of OX1R impaired heterodimer formation. Stimulation of OX1R and CCK1R heterodimers with both orexin-A and CCK decreased the activation of Gαq, Gαi2, Gα12, and Gα13 and the migration of HT-29 cells in comparison with stimulation with orexin-A or CCK alone, but did not alter GPCR interactions with ß-arrestins. These results suggest that OX1R and CCK1R heterodimerization plays an anti-migratory role in human colon cancer cells.

Heterodimerization of the kappa opioid receptor and neurotensin receptor 1 contributes to a novel ß-arrestin-2-biased pathway.

Together with its endogenous ligands (dynorphin), the kappa opioid receptor (KOR) plays an important role in modulating various physiological and pharmacological responses, with a classical G protein-coupled pathway mediating analgesia and non-G protein-dependent pathway, especially the ß-arrestin-dependent pathway, eliciting side effects of dysphoria, aversion, drug-seeking in addicts, or even relapse to addiction. Although mounting evidence has verified a functional overlap between dynorphin/KOR and neurotensin/neurotensin receptor 1 (NTSR1) systems, little is known about direct interaction between the two receptors. Here, we showed that KOR and NTSR1 form a heterodimer that functions as a novel pharmacological entity, and this heterodimer, in turn, brings about a switch in KOR-mediated signal transduction, from G protein-dependent to ß-arrestin-2-dependent. This was simultaneously verified by analyzing a KOR mutant (196th residue) that lost the ability to dimerize with NTSR1. We also found that dual occupancy of the heterodimer forced the ß-arrestin-2-dependent pathway back into Gi protein-dependent signaling, according to KOR activation. These data provide new insights into the interaction between KOR and NTSR1, and the newly discovered role of NTSR1 acting as a switch between G protein- and ß-arrestin-dependent pathways of KOR also suggests a new approach for utilizing pathologically elevated dynorphin/KOR system into full play for its analgesic effect with limited side effects.

Dynamics of apelin receptor/G protein coupling in living cells.

During our research on apelin receptor (APJ) signalling in living cells with BRET and FRET, we demonstrated that apelin-13 stimulation can lead to the activation of Gαi2 or Gαi3 through undergoing a molecular rearrangement rather than dissociation in HEK293 cells expressing APJ. Furthermore, Gαo and Gαq also showed involvement in APJ activation through a classical dissociation model. However, both FRET signal and BRET ratio between fluorescent Gαi1 subunit and Gßγ subunits demonstrated little change after apelin-13 stimulation. These results demonstrated that stimulation of APJ with apelin-13 causes activation of Gαi2, Gαi3, Gαo, Gαq; among which Gαi2, Gαi3 were activated through a novel rearrangement process. These results provide helpful data for understanding APJ mediated G-protein signalling.

Heterodimerization of apelin receptor and neurotensin receptor 1 induces phosphorylation of ERK(1/2) and cell proliferation via Gαq-mediated mechanism.

Dimerization of G protein-coupled receptors (GPCRs) is crucial for receptor function including agonist affinity, efficacy, trafficking and specificity of signal transduction, including G protein coupling. Emerging data suggest that the cardiovascular system is the main target of apelin, which exerts an overall neuroprotective role, and is a positive regulator of angiotensin-converting enzyme 2 (ACE2) in heart failure. Moreover, ACE2 cleaves off C-terminal residues of vasoactive peptides including apelin-13, and neurotensin that activate the apelin receptor (APJ) and neurotensin receptor 1 (NTSR1) respectively, that belong to the A class of GPCRs. Therefore, based on the similar mode of modification by ACE2 at peptide level, the homology at amino acid level and the capability of forming dimers with other GPCRs, we have been suggested that APJ and NTSR1 can form a functional heterodimer. Using co-immunoprecipitation, BRET and FRET, we provided conclusive evidence of heterodimerization between APJ and NTSR1 in a constitutive and induced form. Upon agonist stimulation, hetrodimerization enhanced ERK(1/2) activation and increased proliferation via activation of Gq α-subunits. These novel data provide evidence for a physiological role of APJ/NTSR1 heterodimers in terms of ERK(1/2) activation and increased intracellular calcium and induced cell proliferation and provide potential new pharmaceutical targets for cardiovascular disease.

Nonparametric two-sample tests of high dimensional mean vectors via random integration.

Testing the equality of the means in two samples is a fundamental statistical inferential problem. Most of the existing methods are based on the sum-of-squares or supremum statistics. They are possibly powerful in some situations, but not in others, and they do not work in a unified way. Using random integration of the difference, we develop a framework that includes and extends many existing methods, especially in high-dimensional settings, without restricting the same covariance matrices or sparsity. Under a general multivariate model, we can derive the asymptotic properties of the proposed test statistic without specifying a relationship between the data dimension and sample size explicitly. Specifically, the new framework allows us to better understand the test's properties and select a powerful procedure accordingly. For example, we prove that our proposed test can achieve the power of 1 when nonzero signals in the true mean differences are weakly dense with nearly the same sign. In addition, we delineate the conditions under which the asymptotic relative Pitman efficiency of our proposed test to its competitor is greater than or equal to 1. Extensive numerical studies and a real data example demonstrate the potential of our proposed test.

Fuling production areas in China: climate and distribution changes (A.D. 618-2100).

Through a meticulous analysis of ancient Chinese literature, this study comprehensively documents the geographical distribution of Fuling, a traditional Chinese medicinal material, during the Tang, Song, Ming, and Qing dynasties spanning from the seventh to the twentieth century in China. Based on the contemporary distribution information of Fuling, we utilized the maximum entropy (MaxEnt) model to simulate the suitable distribution areas of Fuling under both present-day conditions and in the future (2081~2100). The findings reveal that climate change has influenced the distribution of Fuling production areas. The shifts in Fuling's origin during different periods in ancient and modern times align with climate fluctuations and concurrent societal development. During the Tang and Song dynasties, Fuling primarily originated in northern China. However, it migrated southward during the Little Ice Age (LIA) and has recently shown a slight northward shift, in line with the climate fluctuations of the LIA and contemporary global warming trends. This study offers a comprehensive analysis of the changes in the distribution and production areas of Fuling over a 1500-year period, encompassing ancient, modern, and future periods. The results provide critical insights for adjusting Fuling cultivation areas in response to climate change and for further exploration of the mechanisms through which climate impacts the growth of Fuling.

Heterodimerization of apelin and opioid receptor-like 1 receptors mediates apelin-13-induced G protein biased signaling.

The apelin receptor (APJ) and the opioid-related nociceptin receptor 1 (ORL1) are family A G protein-coupled receptors that participate in a variety of physiological processes. The distribution and function of APJ and ORL1 in the nervous system and peripheral tissues are similar; however, the detailed mechanism of how these two receptors modulate signaling and physiological effects remains unclear. Here, we examined whether APJ and ORL1 form dimers, and investigated signal transduction pathways. The endogenous co-expression of APJ and ORL1 in SH-SY5Y cells was confirmed by western blotting and RT-PCR. Bioluminescence and fluorescence resonance energy transfer assays, as well as a proximity ligation assay and co-immunoprecipitation experiments, demonstrated that APJ and ORL1 heterodimerize in HEK293 cells. We found that the APJ-ORL1 heterodimer is selectively activated by apelin-13, which causes the dimer to couple to Gαi proteins and reduce the recruitment of GRKs and ß-arrestins to the dimer. We showed that the APJ-ORL1 dimer exhibits biased signaling, in which G protein-dependent signaling pathways override ß-arrestin-dependent signaling pathways. Our results demonstrate that the structural interface of the APJ-ORL1 dimer switches from transmembrane domain TM1/TM2 in the inactive state to TM5 in the active state. We used mutational analysis and BRET assays to identify key residues in TM5 (APJ L2185.55, APJ I2245.61, and ORL1 L2295.52) responsible for the receptor-receptor interaction. These results provide important information on the APJ-ORL1 heterodimer and may assist the design of new drugs targeting biased signaling pathways for treatment of pain and cardiovascular and metabolic diseases.

The regulatory effects of the apelin/APJ system on depression: A prospective therapeutic target.

Depression is a debilitating neuropsychological disorder characterized by high incidence, high recurrence, high suicide, and high disability rates, which poses serious threats to human health and imposes heavy psychological and economic burdens on family and society. The pathogenesis of depression is extremely complex, and its etiology is multifactorial. Mounting evidence suggests that apelin and apelin receptor APJ, which compose the apelin/APJ system, are related to the development of depression. However, the specific mechanism is still unclear, and research in this area in human is still insufficient. Acceleration of research into the regulatory effects and underlying mechanisms of the apelin/APJ system in depression may identify attractive therapeutic targets and contribute to the development of novel intervention strategies against this devastating psychological disorder. In this review, we mainly discuss the regulatory effects of apelin/APJ system on depression and its potential therapeutic applications.

Study on the Evolution and Optimization of the Spatial Structure of the Oasis in the Arid Area: A Case Study of the Aksu River Basin in China.

To achieve high-quality sustainable development in arid areas based on the concept of ecological civilization, it is necessary to deeply study the territorial spatial structure characteristics. Taking the Aksu River Basin, an important ecological security barrier in northwest China, as an example, this paper follows the research idea of "feature analysis-suitability evaluation-conflict identification analysis-optimization" and constructs a comprehensive model based on the AHP-entropy weight comprehensive evaluation method, ArcGIS spatial identification analysis, variance coefficient-TOPSIS method, and NRCA. A comprehensive model based on the AHP-entropy power integrated evaluation method, ArcGIS spatial identification analysis, variance coefficient-TOPSIS method, and NRCA was constructed to guide the optimization of the territorial spatial layout by exploring the characteristics of territorial spatial pattern, the suitability of territorial spatial development, the identification of territorial spatial conflicts, and the efficiency and functional advantage of territorial spatial utilization in the study area. The results show that: (1) The spatial type of territorial space in the Aksu River Basin from 2000 to 2020 is dominated by ecological space, agricultural space, and urban space, and the three spatial boundaries are irregularly interlaced. (2) The spatial utilization conflict pattern of the Aksu River Basin has formed, and the general conflict area is overgrowing. (3) The overall efficiency of territorial utilization in the Aksu River Basin is low, with significant differences among county administrative units. (4) After optimization, the three types of space in the watershed are adjusted and refined into six functional areas: basic farmland protection area, rural development area, ecological protection red line area, ecological control area, urban development area, and industrial supporting construction area.

A robust and efficient variable selection method for linear regression.

Variable selection is fundamental to high dimensional statistical modeling, and many approaches have been proposed. However, existing variable selection methods do not perform well in presence of outliers in response variable or/and covariates. In order to ensure a high probability of correct selection and efficient parameter estimation, we investigate a robust variable selection method based on a modified Huber's function with an exponential squared loss tail. We also prove that the proposed method has oracle properties. Furthermore, we carry out simulation studies to evaluate the performance of the proposed method for both pn. Our simulation results indicate that the proposed method is efficient and robust against outliers and heavy-tailed distributions. Finally, a real dataset from an air pollution mortality study is used to illustrate the proposed method.

Efficacy and safety of Xuefu Zhuyu Granules combined with western medicine in the treatment of angina pectoris of coronary heart disease: A study protocol of a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Despite advances in treatment strategies for coronary heart disease, angina pectoris remains a major cardiovascular disease causing death worldwide. For patients with angina pectoris of coronary heart disease, new or adjuvant treatment regimens are needed. The available evidence suggests that Xuefu Zhuyu Granules combined with Western medicine has advantages in the treatment of angina pectoris of coronary heart disease, but whether its efficacy has a placebo effect and whether it can be used as an adjuvant regimen for the treatment of angina pectoris of coronary heart disease remains controversial. METHODS: This is a prospective, randomized, double-blind, placebo-controlled trial to study the efficacy and safety of Xuefu Zhuyu Granules combined with Western medicine in the treatment of angina pectoris of coronary heart disease. Participants will be randomly divided into a treatment group or a control group, and all patients will receive Western medicine treatment based on guideline recommendations. On this basis, the treatment group orally takes Xuefu Zhuyu Granules and the control group orally takes Xuefu Zhuyu Granules mimic, and are followed up for 24 weeks after 12 weeks of continuous treatment. The observation indexes include: cardiac function parameters (left ventricular end-diastolic diameter; left ventricular end-systolic diameter; left ventricular ejection fraction, blood lipid levels (total cholesterol; triacylglycerol; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol), the number of angina attacks per week, total amount of nitroglycerin tablets taken, and adverse reactions. Finally, SPSS22.0 (IBM Company, New York, NY) software will be used for statistical analysis of the data. DISCUSSION: This study will evaluate the efficacy and safety of Xuefu Zhuyu Granules combined with Western medicine in the treatment of angina pectoris of coronary heart disease. The results of this study will verify whether the efficacy of Xuefu Zhuyu Granules in the treatment of angina pectoris of coronary heart disease belongs to the placebo effect, which will also provide a reference for the clinical use of Xuefu Zhuyu Granules as a supplementary scheme for the treatment of angina pectoris of coronary heart disease.

Photoelectrochemical Detection of Calcium Ions Based on Hematite Nanorod Sensors.

α-Fe2O3 (hematite) thin films have been shown to be a robust sensor substrate for photoelectrochemical imaging with good stability and high spatial resolution. Herein, one-dimensional (1D) hematite nanorods (NRs) synthesized via a simple hydrothermal method are proposed as a substrate which provides nanostructured surfaces with enhanced photocurrent responses compared to previously described hematite films, good stability, and excellent spatial resolution for potential imaging applications. The photoelectrochemical sensing capability of hematite NRs was demonstrated by a high pH sensitivity without modification. The modification of the hematite NRs with a thin poly(vinyl chloride) (PVC)-based ion-selective film allowed highly reversible amperometric detection of calcium ions with sensor materials traditionally employed in potentiometric devices.

Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo.

G protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of depression. Increasing evidence supports the importance of serotonergic and orexin-producing neurons in numerous physiological processes, possibly via a crucial interaction between 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 1 (OX1R). However, little is known about the function of 5-HT1AR/OX1R heterodimers. It is unclear how the transmembrane domains (TMs) of the dimer affect its function and whether its modulation mediates antidepressant-like effects. Here, we examined the mechanism of 5-HT1AR/OX1R dimerization and downstream G protein-dependent signaling. We found that 5-HT1AR and OX1R form constitutive heterodimers that induce novel G protein-dependent signaling, and that this heterodimerization does not affect recruitment of ß-arrestins to the complex. In addition, we found that the structural interface of the active 5-HT1AR/OX1R dimer transforms from TM4/TM5 in the basal state to TM6 in the active conformation. We also used mutation analyses to identify key residues at the interface (5-HT1AR R1514.40, 5-HT1AR Y1985.41, and OX1R L2305.54). Injection of chronic unpredictable mild stress (CUMS) rats with TM4/TM5 peptides improved their depression-like emotional status and decreased the number of endogenous 5-HT1AR/OX1R heterodimers in the rat brain. These antidepressant effects may be mediated by upregulation of BDNF levels and enhanced phosphorylation and activation of CREB in the hippocampus and medial prefrontal cortex. This study provides evidence that 5-HT1AR/OX1R heterodimers are involved in the pathological process of depression. Peptides including TMs of the 5-HT1AR/OX1R heterodimer interface are candidates for the development of compounds with fast-acting antidepressant-like effects.

Prophylactically injection of Nicorandil to reduce no-reflow phenomenon during PCI in acute STEMI patients: Protocol of a double-blinded, randomized, placebo-controlled trial.

INTRODUCTION: An acute ST-elevation myocardial infarction (STEMI) is a very serious type of heart attack and a profoundly life-threatening medical emergency, and percutaneous coronary intervention (PCI) is the preferred strategy. However, in patients undergoing primary PCI, 30% to 40% may suffer the no-reflow phenomenon (NRP), and it could expand the myocardial infarction area and accompanied with high rehospitalization rate and fatality rate. In this study, we try to conduct a double blinded, randomized, placebo-controlled trial to observe whether the prophylactically intracoronary administration of Nicorandil could reduce the occurrence of NRP in STEMI patients undergoing PCI. METHODS: Simple randomization in a 1:1 ratio will be made in blocks of variable size according to a random numbers generated by Excel 2010 to divide the patients to treatment group (Nicorandil) and control group (Saline). The outcomes are the occurrence of NRP, levels of interleukin-6 and HS-CRP, cTnT, and CK-MB before, and every 4 hours following PCI, and major adverse cardiovascular events at day 30. SPSS 23.0 (IBM, Chicago, IL) will be used, and P-value < .05 will be considered statistically significant. CONCLUSIONS: The findings will determine the efficacy of prophylactically intracoronary administration of Nicorandil to reduce the occurrence of NRP during PCI in acute STEMI patients. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/QPF3V.