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STUDY QUESTION: Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles? SUMMARY ANSWER: The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO2) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy. WHAT IS KNOWN ALREADY: Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods. STUDY DESIGN SIZE DURATION: This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study. PARTICIPANTS/MATERIALS SETTING METHODS: Daily average levels of six air pollutants (fine particulate matter (PM2.5), inhalable particulate matter (PM10), SO2, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations. MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM2.5 during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70-0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69-0.98), and SO2 in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86-0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were observed with dual air pollution models. In the multi-pollution analysis, QG-C indicated a 12% reduction in clinical pregnancy rates per IQR increment of mixed pollutants during specific exposure Period 3 (aOR = 0.89, 95% CI: 0.79-0.99). Among these pollutants, SO2 (33.40%) and NO2 (33.40%) contributed the most to the negative effects. The results from BKMR and QG-C were consistent. Stratified analysis revealed increased susceptibility to ambient air pollution among individuals who underwent transfer of two embryos, those with BMI ≥ 24 kg/m2 and those under 35 years old. LIMITATIONS REASONS FOR CAUTION: Caution was advised in interpreting the results due to the retrospective nature of the study, which was prone to selection bias from non-random sampling. Smoking and alcohol, known confounding factors in IVF/ICSI-ET, were not accounted for. Only successful cycles that reached the hCG test were included, excluding a few patients who did not reach the ET stage. While IDW was used to estimate pollutant concentrations at residential addresses, data on participants' work locations and activity patterns were not collected, potentially affecting the accuracy of exposure prediction. WIDER IMPLICATIONS OF THE FINDINGS: Exposure to a mixture of pollutants, spanning from ET to the serum hCG test (Period 3), appeared to be correlated with a diminished probability of achieving clinical pregnancy. This association suggested a potential impact of mixed pollutants on the interaction between embryos and the endometrium, as well as embryo implantation during this critical stage, potentially contributing to clinical pregnancy failure. This underscored the importance of providing women undergoing ART with comprehensive information to comprehend the potential environmental influences and motivating them to adopt suitable protective measures when feasible, thereby mitigating potential adverse effects of contaminants on reproductive health. STUDY FUNDING/COMPETING INTERESTS: This work received support from the National Key Research and Development Program of China (No. 2023YFC2705900), the National Natural Science Foundation of China (Nos. 82171664, 81971391, 82171668), the Natural Science Foundation of Chongqing Municipality of China (Nos. CSTB2022NSCQ-LZX0062, CSTB2023TIAD-KPX0052) and the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (No. 2021KFKT013). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

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Background: The Chinese herbal compound Lian-Gui-Ning-Xin-Tang (LGNXT), composed of 9 herbs, has a significant antiarrhythmic effect. Previous studies have confirmed that preventing intracellular Ca2+ overload and maintaining intracellular Ca2+ homeostasis may be the important antiarrhythmic mechanisms of LGNXT. Recent studies are focused on elucidating the mechanisms and pharmacodynamic substances of LGNXT. Purpose: 1) To investigate the antiarrhythmic mechanisms of LGNXT; 2) to explore the association of pharmacodynamics (PD) and pharmacokinetics (PK) of the potential pharmacodynamic substances in LGNXT to further verify the mechanisms of action. Methods: First, pharmacodynamic studies were conducted to determine the effect of LGNXT in arrhythmia at the electrophysiological, molecular, and tissue levels, and the "effect-time" relationship of LGNXT was further proposed. Next, an HPLC-MS/MS method was established to identify the "dose-time" relationship of the 9 potential compounds. Combining the "effect-time" and "dose-time" curves, the active ingredients closely related to the inhibition of inflammation, oxidative stress, and energy metabolism were identified to further verify the mechanisms and pharmacodynamic substances of LGNXT. Results: Pretreatment with LGNXT could delay the occurrence of arrhythmias and reduce their duration and severity. LGNXT exerted antiarrhythmic effects by inhibiting MDA, LPO, IL-6, and cAMP; restoring Cx43 coupling function; and upregulating SOD, Ca2+-ATPase, and Na+-K+-ATPase levels. PK-PD association showed that nobiletin, methylophiopogonanone A, trigonelline, cinnamic acid, liquiritin, dehydropolisic acid, berberine, and puerarin were the main pharmacodynamic substances responsible for inhibiting the inflammatory response in arrhythmia. Methylophiopogonanone A, dehydropalingic acid, nobiletin, trigonelline, berberine, and puerarin in LGNXT exerted antiarrhythmic effects by inhibiting oxidative stress. Dehydropalingic acid, berberine, cinnamic acid, liquiritin, puerarin, trigonelline, methylophiopogonanone A, nobiletin, and tetrahydropalmatine exerted antiarrhythmic effects by inhibiting the energy-metabolism process. Conclusions: LGNXT had a positive intervention effect on arrhythmias, especially ventricular tachyarrhythmias, which could inhibit inflammation, oxidative stress, and energy metabolism; positively stabilize the structure, and remodify the function of myocardial cell membranes. Additionally, the PD-PK association study revealed that methylophiopogonanone A, berberine, trigonelline, liquiritin, puerarin, tetrahydropalmatine, nobiletin, dehydropachymic acid, and cinnamic acid directly targeted inflammation, oxidative stress, and energy metabolism, which could be considered the pharmacodynamic substances of LGNXT. Thus, the antiarrhythmic mechanisms of LGNXT were further elucidated.

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BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

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Glioma is a central nervous system (CNS) malignant tumor with high heterogeneity and mortality, which severely threatens the health of patients. The overall survival of glioma patients is relatively short and it is critical to identify new molecular targets for developing effective treatment strategies. UBE2K is a ubiquitin conjugating enzyme with oncogenic function in several malignant tumors. However, whether UBE2K participates in gliomas remains unknown. Herein, in glioma cells, UBE2K was found highly expressed in U87 and U251 cells. Subsequently, U87 and U251 cells were transfected with si-UBE2K to silence UBE2K, with the si-NC transfection as the negative control. In both U87 and U251 cells, the cell viability was sharply reduced by transfecting si-UBE2K for 48 and 72 h. Markedly decreased colony number, reduced number of migrated cells and invaded cells, and declined relative wound healing rate were observed in si-UBE2K transfected U87 and U251 cells. Moreover, the Bcl-2 level was markedly reduced, while the Bax and cleaved-caspase-3 levels were sharply increased in U87 and U251 cells after the si-UBE2K transfection. Furthermore, the p62 level was signally declined, while the Beclin-1 and LC-3 II/I levels were greatly increased in U87 and U251 cells by the si-UBE2K transfection. Furthermore, the facilitating effect of si-UBE2K on the apoptosis and autophagy in U87 and U251 cells was abolished by the coculture of 3-MA, an inhibitor of autophagy. Collectively, UBE2K facilitated the in vitro growth of glioma cells, possibly by inhibiting the autophagy-related apoptosis, which might be a promising target for treating glioma.

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Exercise can induce brain plasticity. Functional near-infrared spectroscopy (fNIRS) is a functional neuroimaging technique that exploits cerebral hemodynamics and has been widely used in the field of sports psychology to reveal the neural mechanisms underlying the effects of exercise. However, most existing fNIRS studies are cross-sectional and do not include exercise interventions. In addition, attributed to differences in experimental designs, the causal relationship between exercise and brain functions remains elusive. Hence, this systematic review aimed to determine the effects of exercise interventions on alterations in brain functional activity in healthy individuals using fNIRS and to determine the applicability of fNIRS in the research design of the effects of various exercise interventions on brain function. Scopus, Web of Science, PubMed, CNKI, Wanfang, and Weipu databases were searched for studies published up to June 15, 2021. This study was performed in accordance with the PRISMA guidelines. Two investigators independently selected articles and extracted relevant information. Disagreements were resolved by discussion with another author. Quality was assessed using the Cochrane risk-of-bias method. Data were pooled using random-effects models. A total of 29 studies were included in the analysis. Our results indicated that exercise interventions alter oxygenated hemoglobin levels in the prefrontal cortex and motor cortex, which are associated with improvements in higher cognitive functions (e.g., inhibitory control and working memory). The frontal cortex and motor cortex may be key regions for exercise-induced promotion of brain health. Future research is warranted on fluctuations in cerebral blood flow during exercise to elucidate the neural mechanism underlying the effects of exercise. Moreover, given that fNIRS is insensitive to motion, this technique is ideally suited for research during exercise interventions. Important factors include the study design, fNIRS device parameters, and exercise protocol. The examination of cerebral blood flow during exercise intervention is a future research direction that has the potential to identify cortical hemodynamic changes and elucidate the relationship between exercise and cognition. Future studies can combine multiple study designs to measure blood flow prior to and after exercise and during exercise in a more in-depth and comprehensive manner.

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The quantitative analysis of spatio-temporal variations of vegetation cover and its correlation with climate are of great significance for understanding of ecological environment, ecological civilization construction, and sustainable development in semi-arid areas. We investigated the spatio-temporal variations of normalized difference vegetation index (NDVI) and its response to climate change during 2000-2020 in Xilin Gol, Inner Mongolia, by using trend analysis, regression analysis and partial correlation analysis based on the data of MODIS-NDVI, tempe-rature, precipitation, digital elevation model. The results showed that vegetation cover in Xilin Gol had been increased from 2000 to 2020, which generally included three phases, i.e., stable fluctuation, rapid growth, and steady growth. The mean NDVI showed a zonal increasing distribution from southwest to northeast, and had a strong correlation with elevation and population density in Xilin Gol region. The high values of NDVI were mainly in the east, with a significant increasing trend, and the low values were in the southwest, with a local degradation. The sensitivity of vegetation cover to climate change showed spatial and temporal variations. The spatial variation of vegetation was more sensitive to temperature and the interannual variation was sensitive to annual precipitation. In summary, vegetation cover improved overall in Xilin Gol, but there was degradation in some areas. We should formulate differentiated and precise vegetation restoration and ecological environmental protection policies.

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A rapid and accurate COVID-19 diagnosis is a prerequisite for blocking the source of infection as soon as possible and taking the appropriate medical action. Herein, we developed GeneClick, a device for nucleic acid self-testing of SARS-CoV-2, consisting of three modules: a sampling kit, a microfluidic chip-based disposable cartridge, and an amplification reader. In addition, we evaluated the clinical performance of GeneClick using 2162 nasal swabs collected at three medical institutions, using three commercial RT-qPCR kits and an antigen self-test as references. Compared to RT-qPCR, the sensitivity and specificity of the GeneClick assay were 97.93% and 99.72%, respectively, with a kappa value of 0.979 (P â€‹< â€‹0.01). Of the 2162 samples, 2076 were also tested for SARS-CoV-2 antigens. Among the 314 positive samples identified by GeneClick assay, 63 samples were undetected by antigen tests. Overall, the GeneClick nucleic acid self-test demonstrated higher accuracy than the antigen-based detection. Based on the additional features, including simple operation, affordable price, portable device, and reliability of smartphone APP-driven sampling and result reporting, GeneClick offers a powerful tool for field-based SARS-CoV-2 detection in primary healthcare institutions or at-home use.

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Sample pretreatment technology plays a vital role in the analysis of complex samples and is key to the entire analytical process. Its main purpose is to separate the substance to be measured from the sample matrix or interfering substances in the sample and to achieve a state in which the instrument can be analyzed and detected. Traditional sample pretreatment techniques include liquid-liquid extraction, liquid-solid extraction, precipitation separation, solvent volatilization-rotary evaporation, filtration, and centrifugation. However, the applications of these methods are limited by their low extraction efficiency, complicated operation, long time consumption, unstable recovery, use of large amounts of organic solvents, and large error rates. Several new sample pretreatment techniques, including solid-phase extraction, magnetic solid-phase extraction, solid-phase microextraction, and dispersive solid-phase extraction, have been developed and rapidly applied to various fields to overcome the shortcomings of traditional sample pretreatment methods. However, the development of adsorbent materials with high selectivity and enrichment capability remains a challenge in sample pretreatment technology, in which adsorbents with excellent adsorption performance are crucial. In recent years, various nanomaterials with remarkable properties have been introduced and applied to sample pretreatment, and numerous nano-extraction materials with diverse functions and high selectivity and enrichment capability have been developed. Hollow nanomaterials are nanoparticles with large voids in their solid shells. Owing to their advantageous properties, which include a large effective surface area, abundant internal space, low density, variety of preparation methods, structural and functional tailorability, short mass transmission path, and high carrying capacity, hollow nanomaterials show great application potential in sample pretreatment. The extraction mechanism of these materials is based on the synergistic effects of π-π stacking, electrostatic, hydrogen-bonding, and hydrophobic interactions to achieve the efficient separation and enrichment of the target analytes. Given their noteworthy physicochemical properties, hollow nanomaterials have gained wide attention in various research fields and are considered a research frontier in the field of materials science. Changing the structure or surface properties of the core and shell can lead to various hollow nanomaterials with unique properties. Such changes can create synergy between the physicochemical properties and structural function of the original core-shell material, leading to novel materials with superior performance compared with the starting materials and broad application prospects in sample pretreatment. Nevertheless, only a few hollow nanomaterials with diverse structures and functions are currently used for sample pretreatment, and their adsorption capacity for target analytes is often unsatisfactory. Consequently, enhancing the adsorption selectivity of these materials toward various analytes is the most important step in sample pretreatment. First, hollow nanomaterials with a large specific surface area and suitable pore size can be designed to achieve the specific adsorption of target analytes of varying sizes. The combination of hollow nanomaterials with other materials presenting desirable adsorption properties could also lead to synergistic effects and enhance the performance of composite hollow nanomaterials. In addition, more green methods to prepare hollow nanomaterials with outstanding selectivity can be explored to achieve the superior adsorption of a specific target analyte. Efforts to synthesize hollow nanomaterials have been met with great success, but the available synthesis methods still suffer from complicated steps, high costs, relatively harsh conditions, and the use of highly toxic substances. This paper summarizes the main types of hollow nanomaterials, their synthesis methods, and research progress on sample pretreatment technologies (solid-phase extraction, solid-phase microextraction, magnetic solid-phase extraction, and dispersive solid-phase extraction) and describes the challenges encountered in the synthesis of hollow nanomaterials. The applications and developments of hollow nanomaterials in sample pretreatment are also discussed.

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BACKGROUND: Accumulating evidence indicates that intervertebral disc degeneration (IDD) is associated with diabetes mellitus (DM), while the underlying mechanisms still remain elusive. Herein, the current study sought to explore the potential molecular mechanism of IDD in diabetic rats based on transcriptome sequencing data. METHODS: Streptozotocin (STZ)-induced diabetes mellitus type 1 (T1DM) rats were used to obtain the nucleus pulposus tissues for transcriptome sequencing. Next, differentially expressed genes (DEGs) in transcriptome sequencing data and GSE34000 microarray dataset were obtained and intersected to acquire the candidate genes. Moreover, GO and KEGG enrichment analyses were performed to analyze the cellular functions and molecular signaling pathways primarily regulated by candidate DEGs. RESULTS: A total of 35 key genes involved in IDD of T1DM rats were mainly enriched in the extracellular matrix (ECM) and cytokine adhesion binding-related pathways. NLRP3 inflammasome activation promoted the pyroptosis of nucleus pulposus cells (NPCs). Besides, BMP7 could affect the IDD of T1DM rats by regulating the inflammatory responses. Additionally, NPCs were isolated from STZ-induced T1DM rats to illustrate the effects of BMP7 on IDD of T1DM rats using the ectopic expression method. Both in vitro and in vivo experiments validated that BMP7 alleviated IDD of T1DM rats by inhibiting NLRP3 inflammasome activation and pyroptosis of NPCs. CONCLUSION: Collectively, our findings provided novel mechanistic insights for understanding of the role of BMP7 in IDD of T1DM, and further highlighted BMP7 as a potential therapeutic target for preventing IDD in T1DM.

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BACKGROUND AND PURPOSE: Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. METHODS: Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. RESULTS: The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC] = 0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC = 0.85, 95% CI = 0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. CONCLUSIONS: Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

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Ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, is implicated in intervertebral disc degeneration (IDD). The current study explored the role of Fer-1 in IDD via the toll-like receptor 4 (TLR4)/NF-κB signaling pathway. IDD-related gene expression microarray GSE124272 and high-throughput sequencing data set GSE175710 were obtained through the Gene Expression Omnibus database. Differentially expressed genes in IDD were identified, followed by implementation of protein-protein interaction network analysis and receiver operating characteristic curve analysis. The main pathways in IDD were obtained through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses, and target genes of Fer-1 were obtained through PubChem and PharmMapper websites. Finally, GPX4, FTH, and TLR4 expression was determined in a IDD rat model. Three key co-expression modules involved in IDD were obtained through Weighted Gene Co-Expression Network Analysis. Thirteen differentially expressed genes were found to be associated with IDD, and eight key genes (TLR4, BCL2A1, CXCL1, IL1R1, NAMPT, SOCS3, XCL1, and IRAK3) were found to affect IDD. These eight key genes had the diagnostic potential for IDD. The NF-κB signaling pathway was shown to play a predominant role in IDD development. Network pharmacologic analysis indicated a role of Fer-1 in suppressing ferroptosis and ameliorating IDD via the TLR4/NF-κB signaling pathway, which was verified by an in vivo animal experiment. The study showed that Fer-1 down-regulates TLR4 to inactivate NF-κB signaling pathway, suppressing ferroptosis and ultimately alleviating IDD in rats.

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OBJECTIVE: To understand the facial emotion recognition of male veterans with chronic schizophrenia and the relationship between facial emotion recognition and interpersonal communication to provide a reference for designing social skills training programmes. METHOD: Fifty-six eligible male patients with chronic schizophrenia who were admitted to our hospital from October 2020 to April 2021 were selected, and 24 healthy people were selected as controls. Facial emotion recognition, social communication skills and self-perceived interpersonal disturbance were assessed using a facial emotion recognition stimulus manual, the Social Skills Checklist (SSC) and the Interpersonal Relationship Integrative Diagnostic Scale (IRIDS). Disease status was assessed using the Positive and Negative Syndrome Scale. RESULTS: Both the control group and the patient group had the highest recognition accuracy for neutral faces. The recognition rate for neutral expression was higher in the control group than in the patient group (p = 0.008). The rate of neutral expressions identified as happiness was higher in the patient group than in the control group (p = 0.001). The identification of anger as happiness was higher in the control group than in the patient group (p = 0.026), and the pattern of misidentification was similar between the control group and the patient group. The accuracy of facial emotion recognition was negatively associated with the age of onset (p < 0.05). The recognition accuracy for happiness was negatively associated with negative symptoms, general pathological symptoms and total scale scores (p < 0.05). The total score for expression recognition was negatively associated with the negative symptom subscale scores (p < 0.05), and there was no correlation between expression recognition and positive symptoms (p > 0.05). The recognition accuracy for happiness was negatively correlated with the IRIDS conversation factor (p < 0.05). The recognition accuracy for happiness and anger and the total scores for facial emotion recognition were negatively correlated with the SSC subscale score and the total score (p < 0.05 and p < 0.01, respectively). The main influencing factors on facial emotion recognition were the SSC total score (p < 0.001) and the positive factor score (p = 0.039). CONCLUSION: Veterans with chronic schizophrenia have facial emotion recognition impairments affected by negative symptoms. There is a correlation between facial emotion recognition and interpersonal communication. HIGHLIGHTS: 1. There are extensive facial expression recognition disorders in schizophrenia. 2. The pattern of misidentification was similar in both the control group and the patient group, with the tendency for happiness to be identified as a neutral emotion, anger as happiness, and fear as neutral emotion and anger. 3. Based on the comprehensive assessment of social cognitive impairment in patients with schizophrenia, prospective studies of standardised interventions are designed to provide support for clinical practice.

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Chemical fractionation of the EtOH extract of the roots of a traditional Chinese herb, Morinda officinalis, afforded an array of methyl 2-naphthoate derivatives (1-9) including four pairs of enantiomers (1-4), two pimarane diterpenes and two ursane triterpenoids. Among them, eight compounds (1a/1b-3a/3b, 11 and 13) were reported in the current work for the first time. The structures of the new compounds, including their absolute configurations, were defined by spectroscopic analyses in combination with quantum chemical electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR calculations. All the isolates were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, and the enantiomers 1a and 3b exhibited moderate activity with IC50 values of 41.9 and 26.2 µM. Meanwhile, compound 3b also dose-dependently inhibited the secretion of two pro-inflammatory cytokines TNF-α and IL-6 in the same cell model.

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A unique ring C-expanded angucyclinone, oxemycin A (1), and seven new ring-cleavage derivatives (2-5 and 9-11) were isolated from the marine actinomycete Streptomyces pratensis KCB-132, together with eight known analogues (6-8 and 12-16). Their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffractions, and NMR and ECD calculations. Among these atypical angucyclinones, compound 1 represented the first seven-membered ketoester in the angucyclinone family, which sheds light on the origin of fragmented angucyclinones with C-ring cleavage at C-12/C-12a in the Baeyer-Villiger hypothesis, such as 2-4, while the related "nonoxidized" analogues 5-8 seem to originate from a diverse pathway within the Grob fragmentation hypothesis. Additionally, we have succeeded in the challenging separation of elmenols E and F (12) into their four stereoisomers, which remained stable in aprotic solvents but rapidly racemized under protic conditions. Furthermore, the absolute configurations of LS1924 and its isomers (14 and 15) were assigned by ECD calculations for the first time. Surprisingly, these two bicyclic acetals are susceptible to hydrolysis in solution, resulting in fragmented derivatives 17 and 18 with C-ring cleavage between C-6a and C-7. Compared with ring C-modified angucyclinones, ring A-cleaved 11 was more active to multiple resistant "ESKAPE" pathogens with MIC values ranging from 4.7 to 37.5 µg/mL.

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Background: Parkinson's disease (PD), with either rapid eye movement sleep behavior disorder (RBD) or olfactory dysfunction (OD), has been associated with disease progression. However, there is currently heterogeneity in predicting prognosis. Objectives: To identify whether the concurrent presence of OD and probable RBD (pRBD) in PD (Dual hit in PD, PD-DH) is associated with disease progression. Methods: We included 420 patients with de novo PD from the Parkinson's Progression Markers Initiative: 180 PD only (PD), 82 PD with OD (PD-OD), 94 PD with pRBD (PD-pRBD), and 64 PD with both OD and pRBD (PD-DH). Participants underwent motor and nonmotor evaluations, dopamine transporter imaging, and cerebrospinal fluid (CSF) assessment. Data were analyzed with generalized estimating equations and Cox proportional hazards analysis. Results: The PD-DH subtype was associated with higher scores and faster progression rates in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) Parts II and III. Also, patients in PD-DH group had faster deterioration in nonmotor symptoms, including MDS-UPDRS Part I score, Montreal Cognitive Assessment, Hopkins Verbal Learning Test-Revised, Wechsler Memory Scale-Third edition (WMS-III) Letter Number Sequencing score, Symbol Digit Modalities Test, and Scales for Outcomes in PD-Autonomic scores, with all P values <0.002. Moreover, the PD-DH subtype had a higher mild cognitive impairment risk (hazard ratio = 1.756, 95% confidence interval [CI] = 1.132-2.722; P = 0.012), faster decline in caudate standard uptake values (ß = -0.03, 95% CI = -0.06 to -0.008, P = 0.012), and CSF α-synuclein levels (ß = -77, 95% CI = -149 to -5, P = 0.034) than the PD group. Conclusion: Coexisting pRBD and OD in patients with PD may be associated with faster progressions in motor measurements and in cognitive and autonomic symptoms, indicating PD-DH as a more aggressive subtype for PD.

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BACKGROUND AND PURPOSE: The insidious onset of Parkinson's disease (PD) makes early diagnosis difficult. Notably, idiopathic rapid eye movement sleep behavior disorder (iRBD) was reported as a prodrome of PD, which may represent a breakthrough for the early diagnosis of PD. However, currently there is no reliable biomarker for PD diagnosis. Considering that α-synuclein (α-Syn) and neuroinflammation are known to develop prior to the onset of clinical symptoms in PD, it was hypothesized that plasma total exosomal α-Syn (t-exo α-Syn), neural-derived exosomal α-Syn (n-exo α-Syn) and exosomal apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) may be potential biomarkers of PD. METHODS: In this study, 78 PD patients, 153 probable iRBD patients (pRBD) and 63 healthy controls (HCs) were recruited. α-Syn concentrations were measured using a one-step paramagnetic particle-based chemiluminescence immunoassay, and ASC levels were measured using the Ella system. RESULTS: It was found that t-exo α-Syn was significantly increased in the PD group compared to the pRBD and HC groups (p < 0.0001), whilst n-exo α-Syn levels were significantly increased in both the PD and pRBD groups compared to HCs (p < 0.0001). Furthermore, although no difference was found in ASC levels between the PD and pRBD groups, there was a positive correlation between ASC and α-Syn in exosomes. CONCLUSIONS: Our results suggest that both t-exo α-Syn and n-exo α-Syn were elevated in the PD group, whilst only n-exo α-Syn was elevated in the pRBD group. Additionally, the adaptor protein of inflammasome ASC is correlated with α-Syn and may facilitate synucleinopathy.

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PURPOSE: The paper holds the research purpose of confirming the long-term results of trans-scaphoid perilunate fracture dislocations (TSPFD) under the treatment of open reduction and internal fixation. METHODS: Anteroposterial-lateral radiographs of the patient's wrist were taken before and after surgery. We use a dorsal approach for all cases. Postoperative clinical and radiographic assessments were performed routinely. The scapholunate angle (SLA), estradiol angle (RLA), as well as lunotriquetral distance (LTD) assisted in the radiographic assessment. Clinical assessment was performed using the Krimmer score, modified Mayo wrist score (MWS), active flexion extension arc (FEA), radial deviation and ulnar deviation arc (RUDA) and grip strength. A visual analog scale (VAS) assisted in the pain evaluation, the VAS score ranges from 0 to 10. RESULTS: Twenty-two TSPFD patients due to the wrist trauma received operative treatment and we retrospectively analyzed the surgical results, together with evaluating their clinical and radiological follow-up. These patients held a mean age of 30 years old. Herzberg's perilunate fracture-dislocation classification was taken into account to find that 19 males and 3 females suffered dorsal dislocation. The fellow-up time lasted 98.3 months on average. All cases obtained sufficient union after open reduction and internal fixation. The last follow-up found the median of grip strength was 20.00 (interquartile range, 20.00-21.25), which was 84.5% of the normal side. The modified Mayo wrist score evaluation scale considered 12 cases as excellent, and 10 good. The median of VAS and Krimmer scores at the final follow-up were 1.50 (interquartile range, 0.75-2.00) and 100.00 (interquartile range, 100.00-100.00), respectively, higher relative to the pre-operation (P < 0.001). No patients showed nerve damage preoperatively or postoperatively, or pin tract infection in any of the patient. CONCLUSIONS: It is necessary to diagnose such complicated biomechanical damage in early stage and adopt the open reduction and stable fixation for treatment; appropriate treatment can contribute to a functionally adequate and anatomically integrated wrist.

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Ribose plays an important role in the process of life. Excessive ribose in the human cerebrospinal fluid or urine can be used as an early diagnostic marker of leukoencephalopathy. Fluorinated phenylboronic acid combined with 19F NMR spectroscopy was a powerful method for molecular recognition. However, phenylboronic acid-based sensors for selective detection of ribose are rarely reported in the literature. In this study, the rapid and highly selective recognition of ribose was studied by 19F NMR and 2-fluorophenylboric acid. It was found that 2-fluoro-phenylboric acid was an appropriate 19F NMR-based sensor molecule for the determination of ribose under physiological conditions with high selectivity and robust anti-interference ability. When 2-fluorophenylboric acid was used for the detection of ribose in human urine without any sample pretreatment, a limit of detection of 78 µM was obtained at room temperature under given 19F NMR experimental conditions (400 MHz, 512 scans, ca. 12 min), which can well meet the needs of practical application.

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The relationship between cardiovascular diseases and iron disorders has gained increasing attention; however, the effects of hypotensive drugs on iron metabolic alterations in hypertension are not well understood. The purpose of this study was to investigate iron metabolic changes after prazosin treatment of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Our second objective was to examine the effects of hypertension and anti-hypertensive drugs on bone formation and resorption. SHRs and WKY rats were randomized into either prazosin-treated groups (WKY + PZ and SHR + PZ) or untreated groups (WKY and SHR). After 7 days of intragastric prazosin administration, the rats were sacrificed for analysis; blood samples and organs (the duodenum, liver, kidneys, spleen, and femur) were collected. Both WKY + PZ and SHR groups exhibited iron deficiency in the serum and liver. Prazosin increased the iron levels in the bone tissue of SHRs. Prazosin stimulated the expression of hepcidin mRNA in the liver of SHRs and inhibited the expression of this iron-regulatory hormone in WKY rats. FPN1 expression in the duodenum was increased significantly in SHRs, however markedly decreased after prazosin treatment. The expression of TLR4 and Ctsk was enhanced in the bone tissue of SHRs, whereas CLC-7 expression was inhibited. Both hypotension and hypertension can lead to iron deficiency. Treatment with prazosin restored iron homeostasis in SHRs. The inverse impacts of prazosin on hepatic hepcidin expression in SHRs versus WKY rats indicates differing iron regulatory mechanisms between hypertensive and normal animals. The osteoclast activity was found to be enhanced in SHRs. Further study is needed to address whether the changes in osteoblast and osteoclast activity in SHRs correlates with the effects on iron metabolism.

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[This retracts the article DOI: 10.1016/j.omtn.2019.06.010.].