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The kappa opioid receptor (KOR) and its endogenous agonist dynorphin have been implicated in multiple psychiatric conditions including psychotic disorders. We tested the hypotheses that kappa expression is elevated and associated with psychotic symptoms in schizophrenia. We measured kappa expression in unmedicated patients with schizophrenia (7 female, 6 male) and matched controls (7 female, 6 male) with positron emission tomography (PET). We also acquired a measurement of cumulative dopamine activity over the life span in the same subjects using neuromelanin sensitive MRI. We hypothesized that neuromelanin accumulation would be higher in patients than controls and that in patients there would be a positive association between KOR availability and neuromelanin accumulation. Fourteen patients and thirteen controls were enrolled. Whole brain dynamic PET imaging data using the KOR selective tracer [ 18 F]LY245998 were acquired. Distribution volume ( V T ) was measured with region of interest analysis in 14 brain regions. Neuromelanin accumulation in midbrain dopaminergic nuclei was assessed in the same subjects. Positive and negative symptoms were measured by a clinical psychologist. We did not observe group level differences in KOR expression, neuromelanin accumulation or relationships of these to positive symptoms. Unexpectedly, we did observe strong positive associations between KOR expression and symptoms of anhedonia in the patients (Pearson r  > 0.7, uncorrected p  < 0.01 in 8 cortical brain regions). We also observed moderate associations between KOR expression and neuromelanin levels in patients. In conclusion, we did not observe a relationship between kappa and symptoms of psychosis but the observed relationship to the negative symptom of anhedonia is in line with recent work testing kappa antagonism as a therapy for anhedonia in depression.

Nicotine acts on the brain cholinergic system to drive the rewarding effects of cigarettes and perpetuate smoking. Prior studies in human smokers have used positron emission tomography (PET) to characterize differences in postsynaptic nicotinic acetylcholine receptors (nAChRs). However, preclinical studies indicate that nicotine also modulates presynaptic cholinergic targets that have implications for transmission, including the vesicular acetylcholine transporter (VAChT). To date, there is a paucity of studies imaging presynaptic targets in human smokers. We conducted an initial PET neuroimaging study with [18F]VAT, which indexes VAChT availability (presynaptic marker of cholinergic tone), in 12 healthy smokers and 13 demographically-matched healthy non-smokers. We tested for group differences in VAChT availability, measured as total distribution volume (VT), in the striatum (main region of interest) and in multiple cortical and subcortical extrastriatal regions. Within smokers, we also tested correlations between VAChT availability and indices of smoking chronicity and tobacco self-administration. Smokers had higher [18F]VAT VT than non-smokers in multiple cortical and subcortical regions (p < 0.05uncorrected). There were no group differences in the striatum. Within smokers, VT in the dorsolateral prefrontal and temporal cortices was positively correlated with smoking chronicity (p < 0.05corrected). This study provides first-line evidence of presynaptic cholinergic differences between smokers and non-smokers, such that VAChT is upregulated in smokers and associated with chronicity. Future studies with larger samples are needed to verify these initial effects. With confirmation, these findings could inform the development of new VAChT-targeting therapeutics that could potentially benefit smokers who have been unable to quit with currently available treatments.Nicotine acts on the brain cholinergic system to drive the rewarding effects of cigarettes and perpetuate smoking. Prior studies in human smokers have used positron emission tomography (PET) to characterize differences in postsynaptic nicotinic acetylcholine receptors (nAChRs). However, preclinical studies indicate that nicotine also modulates presynaptic cholinergic targets that have implications for transmission, including the vesicular acetylcholine transporter (VAChT). To date, there is a paucity of studies imaging presynaptic targets in human smokers. We conducted an initial PET neuroimaging study with [18F]VAT, which indexes VAChT availability (presynaptic marker of cholinergic tone), in 12 healthy smokers and 13 demographically-matched healthy non-smokers. We tested for group differences in VAChT availability, measured as total distribution volume (VT), in the striatum (main region of interest) and in multiple cortical and subcortical extrastriatal regions. Within smokers, we also tested correlations between VAChT availability and indices of smoking chronicity and tobacco self-administration. Smokers had higher [18F]VAT VT than non-smokers in multiple cortical and subcortical regions (p < 0.05uncorrected). There were no group differences in the striatum. Within smokers, VT in the dorsolateral prefrontal and temporal cortices was positively correlated with smoking chronicity (p < 0.05corrected). This study provides first-line evidence of presynaptic cholinergic differences between smokers and non-smokers, such that VAChT is upregulated in smokers and associated with chronicity. Future studies with larger samples are needed to verify these initial effects. With confirmation, these findings could inform the development of new VAChT-targeting therapeutics that could potentially benefit smokers who have been unable to quit with currently available treatments.

The human striatum is a collection of subcortical nuclei that serves as a critical node in an information processing network. Recent studies have established a clear topographical and functional organization of projections to and from striatal regions that involves detailed and complex subdivisions of the striatum. Manual segmentation of these functional subdivisions is labor-intensive and time-consuming, yet automated methods have also been a challenging computational problem. Recently, deep learning has emerged as a powerful tool for various tasks, including semantic segmentation. Multi-Task Learning (MTL) is a machine learning technique that allows latent representations between related tasks to be shared during model prediction of multiple tasks with better accuracy. We utilized MTL to segment subregions of the striatum consisting of pre-commissural putamen (prePU), pre-commissural caudate (preCA), post-commissural putamen (postPU), post-commissural caudate (postCA), and ventral striatum (VST). Dice similarity coefficients (DSC) demonstrate excellent spatial agreement between manual and MTL-generated segmentations (> 0.72 across all striatal subregions). Further quantitative task-based analysis was also conducted. Binding potential values, BPND, of [11C]raclopride PET, and ROI time-series and whole-brain connectivity using fMRI images were compared between results generated from manual segmentations and MTL-generated segmentations. BPND values from MTL-generated segmentations were shown to correlate well with manual segmentations with R2 > 0.91 in all caudate and putamen subregions, and R2=0.69 in VST. Mean Pearson correlation coefficients of the fMRI data between MTL-generated and manual segmentations were also high in time-series (>0.86) and whole-brain connectivity (>0.89) across all subregions. We conclude that the MTL approach is a fast, robust and reliable method for 3D striatal subregion segmentation with results comparable to manually segmented ROIs. Competing Interest Statement The authors have declared no competing interest.

COPD is characterized by chronic bronchitis, chronic airway obstruction, and emphysema, leading to a progressive and irreversible decline in lung function. Inflammation is central for the development of COPD. Chronic inflammation in COPD mainly involves the infiltration of neutrophils, macrophages, lymphocytes, and other inflammatory cells into the small airways. The contribution of resident airway structural cells to the inflammatory process is also important in COPD. Airway remodeling consists of detrimental changes in structural tissues and cells including airway wall thickening, epithelial metaplasia, goblet cell hypertrophy, and smooth muscle hyperplasia. Persistent airway inflammation might contribute to airway remodeling and small airway obstruction. However, the underlying mechanisms remain unclear. In this review, we will provide an overview of recent insights into the role of major immunoinflammatory cells in COPD airway remodeling.

Regulator of G protein signaling 1 (RGS1) is known to be highly expressed in various tumors, but its specific effects and regulatory mechanism in ovarian cancer (OC) progression are not well understood. To delve into the tumor biology, a predictive risk model for OC was developed, incorporating RGS1, PRKG2, CD24, and ABCB1, with RGS1 exhibiting the strongest correlation. The model’s reliability and validity were confirmed through Kaplan-Meier analysis, receiver operating characteristic (ROC) curve, and principal component analysis (PCA). The risk score was validated as an independent indicator of overall survival, and a nomogram model was created to predict overall survival. Moreover, RGS1 expression was found to be up-regulated and associated with a poor prognosis in OC. Functional studies revealed that deleting RGS1 inhibited OC cell proliferation both in vitro and in vivo, while overexpression of RGS1 enhanced cell proliferation. Additionally, blocking the NF-kB pathway was shown to impede RGS1-induced proliferation, and overexpression of p65 partially reversed the effects of RGS1 deletion, promoting the tumorigenic properties of OC cells. These findings suggest that RGS1 could be a valuable biomarker for predicting prognosis and a potential novel therapeutic target for OC treatment.

Planar-chiral cyclophanes have gained considerable concerns for drug discovery due to their unique conformational strain and 3D structure. However, the enantioselective synthesis of planar-chiral cyclophanes is a long-standing challenge for the synthetic community. We herein describe an N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of planar-chiral cyclophanes. This transformation occurs through a dynamic kinetic resolution (DKR) process to convert racemic substrates into planar-chiral macrocycle scaffolds in good to high yields with high to excellent enantioselectivities. The ansa chain length and aromatic ring substituent size is crucial to achieve the DKR approach. Controlled experiments and DFT calculations were performed to clarify the DKR process. Planar-chiral cyclophanes are important for drug discovery but the enantioselective synthesis of planar-chiral cyclophanes remains challenging. Here the authors describe an N-heterocyclic carbene-catalyzed asymmetric construction of planar-chiral cyclophanes.

To clarify the relationship between GNSS (Global Navigation Satellite System) crustal deformation and the preparation of strong earthquakes in the western Chinese Mainland, a series of methods including velocity field, strain rate field, and strain parameter time series are adopted based on the GNSS observation data from the CMONOC (Crustal Movement Observation Network of China). The abnormal characteristics of crustal deformation movement before the M  ≥ 5 earthquakes in the area since 1999 are studied. The corresponding variety of the crustal movement before earthquakes is discussed in combination with the seismogenic structure of earthquakes. The abnormalities of the GNSS velocity field, strain field, and strain parameter time series before earthquakes with different magnitudes are proposed. Finally, the anomaly criterion before medium-strong-large earthquakes in the western Chinese Mainland is proposed according to the GNSS and its combination with the characteristics of geological structure. The results can provide a basis for the forecasting of the trend and location of medium-strong-large earthquakes in the western Chinese Mainland.

Portulaca oleracea L. (purslane) is a widely distributed plant with a long history of cultivation and consumption. Notably, polysaccharides obtained from purslane exhibit surprising and satisfactory biological activities, which explain the various benefits of purslane on human health, including anti-inflammatory, antidiabetic, antitumor, antifatigue, antiviral and immunomodulatory effects. This article systematically reviews the extraction and purification methods, chemical structure, chemical modification, biological activity and other aspects of polysaccharides from purslane collected in the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar and CNKI databases in the last 14 years, using the keywords “Portulaca oleracea L. polysaccharides” and “purslane polysaccharides”. The application of purslane polysaccharides in different fields is also summarized, and its application prospects are also discussed. This paper provides an updated and deeper understanding of purslane polysaccharides, which will provide useful guidance for the further optimization of polysaccharide structures and the development of purslane polysaccharides as a novel functional material, as well as a theoretical basis for its further research and application in human health and manufacturing development.

Objective To investigate the correlation between non‐invasive cardiac function monitoring indexes and recent adverse prognosis in patients with STEMI. The hemodynamic indexes with high diagnostic value were selected to construct a new risk prediction model combined with GRACE scores, and the efficiency of the new prediction model was evaluated. Methods STEMI patients who met the inclusion and exclusion criteria were selected. All patients were followed for 6 months of major adverse cardiovascular events (MACE). The non‐invasive cardiac function monitoring indexes were analyzed by univariate and multivariate logistic regression. The ROC curve was used to evaluate the accuracy of non‐invasive cardiac function indexes predicting MACE. Then, a new risk prediction model was established and its prediction efficiency was evaluated by ROC curve. Results Patients were divided into MACE group (N = 69) and non‐MACE group (N = 173), stroke volume (SV), cardiac output (CO), cardiac index (CI), cardiac time intervals (CTI), early diastolic filling rate (EDFR), end‐diastolic volume (EDV), and systemic vascular resistance (SVR) were found to be significant predictors of recent MACE events in STEMI patients. Multivariate logistic regression analysis confirmed that indicators of noninvasive cardiac function were independent predictors. In addition, the combination of SV and CTI with the GRACE score has the potential to enhance the predictive accuracy for MACE. Conclusion Non‐invasive hemodynamic indicators SV, CO, CI, CTI, EDFR, EDV and SVR can not only independently predict the risk of recent MACE in patients with STEMI, but can also be used as joint indicators to significantly improve the predictive ability of GRACE score. This study systematically analyzed non‐invasive cardiac function monitoring indicators and proved that non‐invasive hemodynamic indicators not only have the ability to independently predict the short‐term MACE risk of STEMI patients, but also can be used as combined indicators to significantly improve the predictive ability of GRACE score.

(Thunb.) Nakai- (Lamb.) Hook. based agroforestry systems achieved high understory space utilization rate and economic values in southern China and more subtropical areas. To better understand the soil physio-chemical properties and nutrients/chemical components of under pure and mixed forests, the growth status, soil properties and some specific components (flavonoids and phenolic acids) of were determined under pure forest (CS system), Hook. f. mixed forest (CIS system) and Hook. f. & Thomson ex Miq. mixed forest (CQS system). under CQS system had the best growth status, while it showed lower growth and nutrient status under CIS system. Nutrient accumulation of leaves was dominant among organs, C and K accumulated more in CIS and CQS than CS system, while N and P were opposite. As for medicinal properties, in CIS system had the highest total flavonoid and chlorogenic acid contents, while isofraxidin and rosmarinic acid contents reached the maxima in CQS system. Non-rhizosphere soil under CIS system had higher moisture-holding capacity and less porosity than the other two systems, CQS and CIS systems had higher medicinal value of seedlings and C, P content in rhizosphere soil than in non-rhizosphere soil. There were negative correlations between chemical components and most of the plant nutrient contents, while positive correlations existed between different chemical component contents, speculating that CQS systems could be recommended for maximizing yield and some specific phenolic acids, while CIS systems was suitable for flavonoid accumulation. The yield, nutrient accumulation and medicinal quality of under mixed forest should be balanced by proper intercropping and cultivation methods.