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Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Background: Stroke, which is the main element of cerebrovascular disease (CVD), has become the foremost reason for death and disability on a global scale. The systemic inflammation response index (SIRI), a newly developed and comprehensive indicator, has demonstrated promise in forecasting clinical results for diverse ailments. Nevertheless, the uncertainty surrounding the assessment and prediction of clinical outcomes for stroke patients by SIRI persists, and the conflicting findings from the limited studies conducted on this matter further complicate the situation. Consequently, we performed a thorough systematic review and meta-analysis to explore the correlation between SIRI and the clinical results in individuals suffering from stroke., Methods: This research was registered in PROSPERO and carried out following the PRISMA guidelines. A thorough investigation was carried out on PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. Furthermore, we conducted a manual search in Chinese databases, such as China national Knowledge Infrastructure (CNKI), WanFang, VIP, and China Biology Medicine (CBM). We assessed the potential for bias in the studies included by utilizing the Newcastle-Ottawa Scale (NOS) tool. Adverse clinical outcomes were the main focus of the study, with secondary endpoints including mortality, the predictive value of SIRI, SIRI values across various endpoints, and clinical parameters associated with subarachnoid hemorrhage (SAH) in relation to low and high SIRI group., Results: Following rigorous evaluation, a grand total of 22 investigations, encompassing a populace of 12,737 individuals, were considered suitable for incorporation in the final analysis. The findings from our meta-analysis indicate a strong and consistent correlation between elevated SIRI levels and adverse functional outcomes, irrespective of the method used to evaluate unfavorable outcomes. Furthermore, increased SIRI values have a strong correlation with mortality rates in both the short and long term. Besides, SIRI is a useful indicator of the severity of SAH. SIRI demonstrates strong predictive ability in identifying unfavorable outcomes and stroke-related pneumonia (SAP), as higher SIRI values are typically linked to negative endpoints. Nevertheless, the meta-analysis indicated that there was no significant increase in the risk of early neurological deterioration (END) and acute hydrocephalus (AHC) in high SIRI group when comparing to low SIRI., Conclusion: This study could potentially pave the way for groundbreaking insights into the relationship between SIRI and stroke patient outcomes, as it appears to be the first meta-analysis to explore this association. Given the critical role of the inflammatory response in stroke recovery, closely monitoring patients with high SIRI levels could represent a promising strategy for mitigating brain damage post-stroke. Thus, further investigation into SIRI and its impact on clinical outcomes is essential. While our initial findings offer valuable insights into this area, continued research is necessary to fully elucidate the potential of SIRI, ideally through dynamic monitoring and large-scale, multi-center studies. Ultimately, this research has the potential to inform clinical decision-making and improve patient outcomes following stroke., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/ ; Identifier CRD42023405221., (© 2023. The Author(s).)

Background: Non-traumatic subarachnoid hemorrhage (SAH), primarily due to the rupture of intracranial aneurysms, contributes significantly to the global stroke population. A novel biomarker, pan-immune-inflammation value (PIV) or called the aggregate index of systemic inflammation (AISI), linked to progression-free survival and overall survival in non-small-cell lung cancer and mortality in Coronavirus Disease 2019 (COVID-19) patients, has surfaced recently. Its role in non-traumatic SAH patients, however, remains under-researched. This study aims to determine the relationship between PIV and all-cause mortality in non-traumatic SAH patients., Methods: A retrospective analysis was conducted using data from the Medical Information Mart for Intensive Care (MIMIC-IV) database to examine the association between PIV and all-cause mortality in critically ill patients with non-traumatic SAH. PIV measurements were collected at Intensive Care Unit (ICU) admission, and several mortality measures were examined. To control for potential confounding effects, a 1:1 propensity score matching (PSM) method was applied. The optimal PIV cutoff value was identified as 1362.45 using X-tile software that is often used to calculate the optimal cut-off values in survival analysis and continuous data of medical or epidemiological research. The relationship between PIV and short- and long-term all-cause mortality was analyzed using a multivariate Cox proportional hazard regression model and Kaplan-Meier (K-M) survival curve analysis. Interaction and subgroup analyses were also carried out., Results: The study included 774 non-traumatic SAH patients. After PSM, 241 pairs of score-matched patients were generated. The Cox proportional hazard model, adjusted for potential confounders, found a high PIV (≥ 1362.45) independently associated with 90-day all-cause mortality both pre- (hazard ratio [HR]: 1.67; 95% confidence intervals (CI): 1.05-2.65; P = 0.030) and post-PSM (HR: 1.58; 95% CI: 1.14-2.67; P = 0.042). K-M survival curves revealed lower 90-day survival rates in patients with PIV ≥ 1362.45 before (31.1% vs. 16.1%%, P < 0.001) and after PSM (68.9% vs. 80.9%, P < 0.001). Similarly, elevated PIV were associated with increased risk of ICU (pre-PSM: HR: 2.10; 95% CI: 1.12-3.95; P = 0.02; post-PSM: HR: 2.33; 95% CI: 1.11-4.91; P = 0.016), in-hospital (pre-PSM: HR: 1.91; 95% CI: 1.12-3.26; P = 0.018; post-PSM: 2.06; 95% CI: 1.10-3.84; P = 0.034), 30-day (pre-PSM: HR: 1.69; 95% CI: 1.01-2.82; P = 0.045; post-PSM: 1.66; 95% CI: 1.11-2.97; P = 0.047), and 1-year (pre-PSM: HR: 1.58; 95% CI: 1.04-2.40; P = 0.032; post-PSM: 1.56; 95% CI: 1.10-2.53; P = 0.044) all-cause mortality. The K-M survival curves confirmed lower survival rates in patients with higher PIV both pre- and post PSM for ICU (pre-PSM: 18.3% vs. 8.4%, P < 0.001; post-PSM:81.7 vs. 91.3%, P < 0.001), in-hospital (pre-PSM: 25.3% vs. 12.8%, P < 0.001; post-PSM: 75.1 vs. 88.0%, P < 0.001), 30-day (pre-PSM: 24.9% vs. 11.4%, P < 0.001; post-PSM:74.7 vs. 86.3%, P < 0.001), and 1-year (pre-PSM: 36.9% vs. 20.8%, P < 0.001; P = 0.02; post-PSM: 63.1 vs. 75.1%, P < 0.001) all-cause mortality. Stratified analyses indicated that the relationship between PIV and all-cause mortality varied across different subgroups., Conclusion: In critically ill patients suffering from non-traumatic SAH, an elevated PIV upon admission correlated with a rise in all-cause mortality at various stages, including ICU, in-hospital, the 30-day, 90-day, and 1-year mortality, solidifying its position as an independent mortality risk determinant. This study represents an attempt to bridge the current knowledge gap and to provide a more nuanced understanding of the role of inflammation-based biomarkers in non-traumatic SAH. Nevertheless, to endorse the predictive value of PIV for prognosticating outcomes in non-traumatic SAH patients, additional prospective case-control studies are deemed necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Zhang, Li and Yin.)

Whey protein powder (PP), which is mainly derived from bovine milk, is rich in milk fat globule membrane (MFGM). The MGFM has been shown to play a role in promoting neuronal development and cognition in the infant brain. However, its role in Alzheimer's disease (AD) has not been elucidated. Here, we showed that the cognitive ability of 3×Tg-AD mice (a triple-transgenic mouse model of AD) could be improved by feeding PP to mice for 3 mo. In addition, PP ameliorated amyloid peptide deposition and tau hyperphosphorylation in the brains of AD mice. We found that PP could alleviate AD pathology by inhibiting neuroinflammation through the peroxisome proliferator-activated receptor γ (PPARγ)-nuclear factor-κB signaling pathway in the brains of AD mice. Our study revealed an unexpected role of PP in regulating the neuroinflammatory pathology of AD in a mouse model., (© 2023, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Purpose: To systematically review the different types of irrigation fluid and the different temperatures of irrigation fluid on postoperative recurrence rates in the evacuation of chronic subdural hematoma (CSDH)., Methods: We conducted a comprehensive search of electronic databases, including PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), WanFang, the Chinese VIP Information (VIP), and China Biology Medicine (CBM), and reference lists of relevant studies to identify all eligible studies. Two reviewers independently screened the titles and abstracts for inclusion, and the full-text articles were assessed for eligibility based on predetermined inclusion and exclusion criteria. Data were extracted using a standardized form, and the quality of the studies was assessed using a risk of bias tool. Meta-analyses were performed using a fixed-or random-effects model, and heterogeneity was assessed using the I2 statistic. The primary endpoint was the postoperative recurrence rate., Results: After stringent screening, a total of 11 studies were identified, including six English publications, four Chinese publications, and one Japanese publication, involving a population of 29,846 patients. Our meta-analysis provides evidence that artificial cerebrospinal fluid (ACF) could decrease the post-operative recurrence rate by 47% after the evacuation of CSDH when compared to normal saline (NS) [(odds ratio) OR 0.53, 95% confidence intervals (CI): 0.31-0.90, p  = 0.02, I 2  = 67%]. Besides, the irrigation fluid at body temperature could decrease the postoperative recurrence rate of CSDH by 64% when compared to room temperature (OR = 0.36, 95% CI = 0.22-0.59, p  < 0.0001, I 2  = 0%)., Conclusion: Our analysis revealed significant difference in the choice of irrigation fluid for CSDH surgery. Notably, we found that irrigation with fluid at body temperature demonstrated superiority over irrigation with fluid at room temperature, resulting in fewer instances of recurrence. This straightforward technique is both safe and widely available, providing an opportunity to optimize outcomes for patients with CSDH. Our findings suggest that the use of body-temperature NS or ACF of room temperature during operation should be considered a standard of procedure in CSDH surgery. Nevertheless, whether the different temperature of ACF could be considered a standard of procedure in CSDH surgery still need high-quality RCTs to further identify., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/; Identifier CRD42023424344., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Li and Yin.)

Objective: Intracranial aneurysms (IAs) are a prevalent form of vascular disease that can lead to fatal outcomes upon rupture. Mirror intracranial aneurysms (MIAs) are a specific type of multiple aneurysms situated symmetrically on both sides of the parent arteries. The factors contributing to the risk of MIA rupture, based on morphological and hemodynamic parameters, are currently controversial. Thus, we conducted a systematic review and meta-analysis to investigate the risk factors for MIA rupture., Methods: The study performed an electronic search of Chinese and English databases, including China national Knowledge Infrastructure (CNKI), WanFang, VIP, PubMed, Embase, Web of Science, Scopus, and the Cochrane Library databases, and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The morphological parameters (IA size, aspect ratio [AR], size ratio [SR], bottleneck factor [BNF], height-width ratio [HWR], irregular shape) and hemodynamic parameters (wall shear stress [WSS], low WSS area [LSA], oscillatory shear index [OSI]) were analyzed for their significance in determining the risk of MIA rupture., Results: The analysis comprised 18 retrospective studies involving 647 patients, with a total of 1294 IAs detected, including 605 ruptured and 689 unruptured. The meta-analysis revealed that IA size, AR, SR, and irregular shape exhibited significant differences between the ruptured and unruptured groups, but HWR did not. In terms of hemodynamic parameters, WSS, OSI, and LSA were found to have significant differences between the two groups., Conclusions: Our results demonstrate that larger IAs, higher AR, SR, and BNF are associated with a higher risk of rupture in patients with MIAs, regardless of their location. there is no significant difference in HWR between the ruptured and unruptured groups. These preliminary findings offer valuable insights for clinical decision-making and a more comprehensive comprehension of the current MIA status. Nevertheless, larger and multi-center studies are indispensable for corroborating these findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/ identifier: CRD42022345587., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Stroke is a major global health concern and is ranked as the second leading cause of death worldwide, with the third highest incidence of disability. Intracerebral hemorrhage (ICH) is a devastating form of stroke that is responsible for a significant proportion of stroke-related morbidity and mortality worldwide. Hematoma expansion (HE), which occurs in up to one-third of ICH patients, is a strong predictor of poor prognosis and can be potentially preventable if high-risk patients are identified early. In this review, we provide a comprehensive summary of previous research in this area and highlight the potential use of imaging markers for future research studies., Recent Advances: Imaging markers have been developed in recent years to aid in the early detection of HE and guide clinical decision-making. These markers have been found to be effective in predicting HE in ICH patients and include specific manifestations on Computed Tomography (CT) and CT Angiography (CTA), such as the spot sign, leakage sign, spot-tail sign, island sign, satellite sign, iodine sign, blend sign, swirl sign, black hole sign, and hypodensities. The use of imaging markers holds great promise for improving the management and outcomes of ICH patients., Conclusion: The management of ICH presents a significant challenge, and identifying high-risk patients for HE is crucial to improving outcomes. The use of imaging markers for HE prediction can aid in the rapid identification of such patients and may serve as potential targets for anti-HE therapies in the acute phase of ICH. Therefore, further research is needed to establish the reliability and validity of these markers in identifying high-risk patients and guiding appropriate treatment decisions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Huang, Li and Yin.)

Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc-gamma-receptor type I (FcγRI) of the dorsal root ganglion (DRG) mediates antigen-specific pain. However, the mechanisms of neuronal FcγRI in neuropathic pain remain to be explored. Here, it is found that the activation of FcγRI-related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal FcγRI-related signaling in the DRG, and conditional knockout (CKO) of the FcγRI-encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C-reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal FcγRI-related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal FcγRI. These results indicate that the activation of neuronal CRP/FcγRI-related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Objective: Cardiovascular disease (CVD) and cerebrovascular disease are the leading cause of death around the world all the time. A novel marker described as the stress hyperglycemia ratio (SHR) can reflect the acute hyperglycemic status and is associated with poor outcomes in patients with acute illness, such as stroke and myocardial infarction (MI). Our previous study has shown that SHR was strongly related to the clinical outcomes of stroke patients. Nevertheless, the association between SHR and clinical outcomes in patients with CVD is still unclear and controversial. Consequently, in the current study, we analyzed the association of SHR and clinical outcomes in CVD patients by systematic review and meta-analysis., Materials and Methods: We searched the electronic databases to identify SHR studies of patients who met the eligibility criteria for CVD. We performed our study complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We utilized a ten terms tool to assess the potential bias of included studies. Major adverse cardiovascular and cerebrovascular events (MACCEs), all-cause death, left ventricular ejection fraction (LVEF), and other exciting outcome data were extracted for statistical analysis. Moreover, we used the DerSimonian and Laird random-effects model to perform the meta-analysis and conducted subgroup analyses to identify factors associated with substantial heterogeneity., Results: The study cohort included nine studies comprising 32,292 patients with CVD. Our meta-analysis found that MACCEs in the high SHR group were 1.68 folds compared with that in the low SHR group [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.41-2.00, p < 0.00001]. Besides, all-cause death in the high SHR group was 1.52 folds compared with that in the low SHR group (OR 1.52, 95% CI 1.15-2.01, p < 0.00001). Higher SHR meant the lower LVEF (mean difference [MD] -2.03, 95% CI [-3.28-0.79], p = 0.001). The risk of cardiogenic shock and stroke were 2.47 and 1.53 folds in the high SHR group, respectively, compared with the low SHR group. Yet, no statistically significant difference was observed for revascularization (OR 0.88, 95% CI 0.77-1.01, p = 0.08), recurrent MI (OR 1.27, 95% CI 0.69-2.33, p = 0.44), and left ventricular end-diastolic diameter (LVEDD) (MD 0.61, 95% CI [-1.65, 2.87], p = 0.60) between the two groups. Subgroup analyses identified that different study design was associated with heterogeneity about MACCEs and LVEF. Besides, studies from different countries were associated with heterogeneity about all-cause death., Conclusions: Higher SHR significantly increases the occurrence of MACCEs and all-cause death and decreases LVEF. Moreover, Higher SHR means a higher risk of cardiogenic shock and stroke. Nevertheless, SHR had no relationship with revascularization, recurrent MI, and LVEDD. As a novel and non-invasive marker, SHR should be paid more attention to in clinical practice. Future investigation should focus on the diagnostic value of SHR in CVD and the early control of stress hyperglycemia. Although no randomized, double-blind studies have been conducted, the available massive sample studies reflect the actual situation in the clinic and assist clinical decision-making.

Objective: Intracoronary injection of pro-urokinase (Pro-UK) during percutaneous coronary intervention (PCI) seems to be a promising treatment in improving myocardial perfusion. In this systematic review and meta-analysis, we aimed at investigating the efficacy and safety of intracoronary Pro-UK injection during PCI in ST elevation myocardial infarction (STEMI) patients., Materials and Methods: A comprehensive literature searched on PubMed, Embase, Cochrane, Ovid-MEDLINE, Ovid-Embase, Ovid-Cochrane Databases and ClinicalTrials.gov from inception until June 1, 2022, in English only. The primary outcome was myocardial perfusion, including thrombolysis in myocardial infarction (TIMI) grades, corrected TIMI frame count (CTFC), TIMI myocardial perfusion grades (TMPG). The secondary outcomes were ST-segment resolution (STR), major adverse cardiovascular events (MACE), myocardial marker, cardiac function and hemorrhagic complications., Results: We identified 5 studies (all RCTs) involving 761 participants. Under PCI procedure, compared with placebo, intracoronary Pro-UK injection may improve myocardial perfusion, including increasing the TIMI grades [odd ratio (OR) 0.46; 95% confidence interval (CI) 0.28-0.75; p = 0.002; I2 = 0%] , CTFC (OR -3.47; 95% CI [-5.60, -1.33]; p = 0.001; I2 = 0%) and TMPG (OR 0.17; 95% CI [0.06-0.44]; p = 0.0003; I2 = 0%), increase the rate of STR (OR 2.25; 95% CI [1.56-3.26]; p < 0.0001; I2 = 0%), reduce the incidence of MACE (OR 0.51; 95% CI [0.33-0.81]; p = 0.004; I2 = 0%) and reduce myocardial infarct size (CK, standardized mean difference [SMD] -0.45; 95% [CI] [-0.62, -0.28]; p < 0.00001; I2 = 10%. CK-MB, [SMD] -0.43; 95% CI [-0.68, -0.18]; p = 0.0007; I2 = 60%. cTnI, [SMD] -0.31; 95% CI [-0.46, -0.17]; p < 0.0001; I2 = 0%). Moreover, the treatment may improve the cardiac functions (LVFE, pooled mean difference [MD] 1.23; 95% CI [0.66-1.79]; p < 0.0001; I2 = 24%. LVEDd, pooled MD -0.13; 95% CI [-0.17, -0.09]; p < 0.00001; I2 = 0%). But there is no statistically significant difference between the Pro-UK group and placebo in the occurrence of hemorrhagic complications (OR 1.19; 95% CI [0.75-1.87]; p = 0.46; I2 = 0%)., Conclusions: Intracoronary Pro-UK injection during PCI in STEMI patients is an effective and safe treatment to perform. The treatment may improve myocardial perfusion and rate of STR, as well as decreasing the incidence of MACE and myocardial infarct size. Importantly, the treatment may improve the cardiac functions and life quality. In the future, more multi-centered and massive sample studies are required.

Objective: Surgery is the mainstay of treatment for chronic subdural hematoma (CSDH). However, the best surgical method is still controversial. Three different methods including burr hole craniostomy (BHC), minicraniotomy (MC), and twist drill craniostomy (TDC) are commonly utilized. Besides, large craniotomy, trephine craniotomy [TC (single or double)], small craniotomy, and endoscopic removal are befittingly used in some situations, too. Hence, we performed a systematic review and meta-analysis to compare the effects between BHC and MC for surgical treatment in CSDH., Materials and Methods: A literature research was conducted according to the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that directly compared BHC and MC for CSDH. The following endpoints were compared between BHC and MC: recurrence rate, reoperation rate, duration of operation, days of hospital treatment, postoperative complications, mortality, and rate of good outcome., Results: Thirteen papers [n = 3,559 (3,580 operation sites), BHC: 1,936 operation sites, MC: 1,644 operation sites] met the inclusion criteria. The recurrence rate (OR: 0.56, 95% CI: 0.34-0.91, p = 0.02; I2 = 66%) was lower and the reoperation rate was also significantly lower (OR: 0.45, 95% CI: 0.25-0.81, p = 0.008; I2 = 72%) in the BHC group compared with the MC group. The duration of operation (MD: -20.15 min, 95% CI: -28.99 to -11.31, p < 0.00001; I2 = 0%) was significantly shorter in the BHC group compared with the MC group. Nevertheless, there was no statistically significant difference between the two groups in mortality (OR: 1.22, 95% CI: 0.92-1.61, p = 0.16; I2 = 38%), postoperative complications (OR: 0.68, 95% CI: 0.033-1.37, p = 0.28; I2 = 82%), days of hospital treatment (MD: 1.59, 95% CI: -10.44 to 13.62, p = 0.14; I2 = 85%) and rate of good outcome (OR: 1.40, 95% CI: 0.94-2.08, p = 0.10; I2 = 0%)., Conclusions: A systematic review and meta-analysis of the included literature showed that BHC reduces the recurrence rate, reoperation rate and duration of operation compared to MC. BHC is much more minimal invasive when compared to MC. More invasions may signify more post-operative complications, which may cause the increasing rate of recurrence and reoperation. No significant difference in mortality, post-operative complications, days of hospital treatment and rate of good outcome was observed between the two groups.

Social memory enables one to recognize and distinguish specific individuals. It is fundamental to social behaviors that can be mediated by the oxytocin receptor (OXTR), such as forming relationships. We investigated the molecular regulation and function of OXTR in animal behavior involving social memory. We found that Ser 261 in OXTR was phosphorylated by protein kinase D1 (PKD1). Neuronal Ca 2+ signaling and behavior analyses revealed that rats expressing a mutated form of OXTR that cannot be phosphorylated at this residue (OXTR S261A) in the medial amygdala (MeA) exhibited impaired long-term social memory (LTSM). Blocking the phosphorylation of wild-type OXTR in the MeA using an interfering peptide in rats or through conditional knockout of Pkd1 in mice reduced social memory retention, whereas expression of a phosphomimetic mutant of OXTR rescued it. In HEK293A cells, the PKD1-mediated phosphorylation of OXTR promoted its binding to G q protein and, in turn, OXTR-mediated phosphorylation of PKD1, indicating a positive feedback loop. In addition, OXTR with a single-nucleotide polymorphism found in humans (rs200362197), which has a mutation in the conserved recognition region in the PKD1 phosphorylation site, showed impaired activation and signaling in vitro and in HEK293A cells similar to that of the S216A mutant. Our findings describe a phosphoregulatory loop for OXTR and its critical role in social behavior that might be further explored in associated disorders.

Indole 2,5-diketopiperazines (DKPs) are an important type of metabolic cyclic dipeptides containing a tryptophan (Trp) unit possessing a range of interesting biological activities. The intriguing structural features and divergent activities have stimulated tremendous efforts towards their efficient synthesis. Herein, we report the development of a unified strategy for the synthesis of three Trp-containing DKPs, namely tryprostatin A, and maremycins A and B, via a sequential C-H activation strategy. The key Trp skeletons were synthesized from the inexpensive, readily available alanine via a Pd(ii)-catalyzed β-methyl C(sp 3 )-H monoarylation. A subsequent C2-selective prenylation of the resulting 6-OMe-Trp by Pd/norbornene-promoted C-H activation led to the total synthesis of tryprostatin A in 12 linear steps from alanine with 25% overall yield. Meanwhile, total syntheses of maremycins A and B were successfully accomplished using a sequential Pd-catalyzed methylene C(sp 3 )-H methylation as the key step in 15 linear steps from alanine., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Rapid, green and efficient extraction of active compounds followed by fast analysis is always pursued in the field of food analysis and/or industry. Herein, a green and highly efficient extraction of four active flavonoids from the seeds of Oroxylum indicum using a combination of natural deep eutectic solvents (DESs) and tissue-smashing extraction (TSE) technique was applied and a UPLC method was developed for their sensitive and selective quantification. RSM coupled with BBD procedure was used to optimize the extraction conditions based on single factors, such as liquid-solid ratios, extraction speed and extraction time. Compared with other conventional methods, the TSE greatly shortens extraction time, obviously raises the extraction production, and decreases energy consumption. By combination of the DES-based TSE and UPLC, the analysis of flavonoids was accomplished within only 6 min, providing an ultra-rapid, environmentally friendly and promising choice for extraction and analysis of active compounds in natural products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

With the shifting role of placebos, there is a need to develop animal models of placebo analgesia and elucidate the mechanisms underlying the effect. In the present study, male Sprague-Dawley rats with chronic inflammatory pain caused by complete Freund's adjuvant (CFA) underwent a series of conditioning procedures, in which morphine was associated with different cues, but they failed to induce placebo analgesia. Then, conditioning with the conditioned place preference apparatus successfully induced analgesic expectancy and placebo analgesia in naïve rats but only induced analgesic expectancy and no analgesic effect in CFA rats. Subsequently, we found enhanced c-fos expression in the nucleus accumbens and reduced expression in the anterior cingulate cortex in naïve rats while c-fos expression in the anterior cingulate cortex in CFA rats was not altered. In summary, the behavioral conditioning model demonstrated the difficulty of establishing a placebo analgesia model in rats with a pathological condition.

There is an increasing interest in screening and developing natural tyrosinase inhibitors widely applied in medicinal and cosmetic products, as well as in the food industry. In this study, an approach by ultrafiltration LC-MS and molecular docking was used to screen and identify tyrosinase inhibitors from Semen Oroxyli extract. The samples were first incubated with the tyrosinase to select the optimal binding conditions including tyrosinase concentration, incubation time and the molecular weight of ultrafiltration membrane. By comparison of the chromatographic profiles of the extracts after ultrafiltration with activated and inactivated tyrosinase, the potential inhibitors were obtained and then identified by LC-MS. The relative binding affinities of the potential inhibitors were also calculated based on the decrease of peak areas of those. As a result, seven compounds were fished out as tyrosinase inhibitors by this assay. Among them, oroxin A and baicalein showed higher tyrosinase inhibitory than resveratrol as positive drug, and their binding mode with enzyme was further verified via the molecular docking analysis. The test results showed that the proposed method was a simple, rapid, effective, and reliable method for the discovery of natural bioactive compounds, and it can be extended to screen other bioactive compounds from traditional Chinese medicines., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Space-time template matching is considered as a promising approach for human action recognition. However, a major drawback of template-based methods is computational overhead due to matching in spatial domain. Recently, space-time correlation-based action filters have been proposed for recognizing human actions in frequency domain. These action filters present reduction in time complexity as Fourier transform-based matching is faster than spatial template matching. However, the utility of such action filters is challenged due to a number of factors: 1) inability to deal with view variations due to implicit lack of support for view-invariance; 2) these filters can be trained only for one action class at a time, and separate filters are required for each action class with increased computational overhead; 3) these filters simply take average of similar action instances and behave no better than average filters; and 4) slightly misaligned action data sets create problems as these filters are not shift-invariant. In this paper, we try to address these shortcomings by proposing an advanced space-time filtering framework for recognizing human actions despite large viewpoint variations. Rather than using crude intensity values, we use 3D tensor structure at each pixel, which characterizes the most common local motion in action sequences. Discrete tensor Fourier transform is then applied to achieve frequency domain representations. Then, we form view clusters from multiple view action data and use space-time correlation filtering to achieve discriminative view representations. These representations are used in an innovative way to achieve action recognition despite viewpoint variations. Extensive experimentation is performed on well-known multiple view action data sets, including IXMAS, WVU, and N-UCLA action data set. A detailed performance comparison with the existing view-invariant action recognition techniques indicates that our approach works equally well for RGB and RGB-D video data with increased accuracy and efficiency.

Rh(iii)-catalyzed cascade C-H activation/annulation/lactonization of quinoline-4-ols and alkynes has been reported. A broad range of tetracyclic pyrano[2,3,4-de]quinolines have been prepared in one-step with good functional group tolerance, excellent site selectivity, and high efficiency.

Pd-Catalyzed sequential monoarylation/amidation of C(sp 3 )-H bonds of alanine enabled by a removable 5-methoxyquinolin-8-amine (MQ) auxiliary is described. This process is highly efficient and compatible with a variety of functional groups, providing a general and practical access to various α-amino-β-lactams. The synthetic potential of this protocol is further demonstrated by the stereoselective synthesis of orthogonally protected anti-α,β-diamino acids.

Several examples on Pd-catalysed carbonylation of methyl C(sp 3 )-H bonds with gaseous CO via Pd(II)/Pd(0) catalysis have been reported. However, methylene C(sp 3 )-H carbonylation remains a great challenge, largely due to the lack of reactivity of C-H bonds and the difficulty in CO migratory insertion. Herein, we report the stereoselective alkoxycarbonylation of both methyl and methylene C(sp 3 )-H bonds with alkyl chloroformates through a Pd(II)/Pd(IV) catalytic cycle. A broad range of aliphatic carboxamides and alkyl chloroformates are compatible with this protocol. In addition, this process is scalable and the directing group could be easily removed under mild conditions with complete retention of configuration., Competing Interests: B.-F.S., G.L. and X.-S.Y. are the co-inventors on a patent application: ‘A highly efficient method to the synthesis of aspartate derivatives' CN application number 201610147639.1. The remaining authors declare no competing financial interests.

A palladium-catalyzed arylation of unactivated γ-methylene C(sp(3) )H and remote δ-CH bonds by using an oxazoline-carboxylate directing group has been developed. Arylation occurs with a broad substrate scope and high tolerance of functional groups (i.e., halogen, nitro, cyano, ether, trifluoromethyl, amine, and ester). The oxazoline-type auxiliary can be removed under acidic conditions., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A catalyst-controlled vicinal amino- versus oxy-acetoxylation of alkenes with PhI(OAc)2 as the oxidant is described. The divergent synthesis of cyclic ureas and isoureas was achieved in good yields under mild conditions employing ambident urea nucleophiles. Both terminal and internal alkenes are compatible with this reaction protocol.

The synthesis of fluorinated complex molecules via direct C(sp(3))-H fluorination is attractive yet remains challenging. Here we describe the Pd(II)-catalyzed fluorination of unactivated methylene C(sp(3))-H bonds by an inner-sphere mechanism. This method allows the site- and diastereoselective fluorination of β-methylene C(sp(3))-H bonds of α-amino acid derivatives. A range of substrates containing both aliphatic and benzylic C(sp(3))-H bonds were compatible with this protocol, leading to an array of β-fluorinated α-amino acids. Stoichiometric fluorination of an isolated palladacycle intermediate takes place rapidly under very mild reaction conditions (room temperature, 5-10 min). Data from preliminary mechanistic studies are consistent with direct C-F reductive elimination from a high-valent intermediate.

A copper/silver-mediated oxidative ortho-ethynylation of unactivated aryl C-H bonds with terminal alkyne has been developed. The reaction uses the removable PIP directing group and features broad substrate scope, high functional-group tolerance, and compatibility with a wide range of heterocycles, providing an efficient synthesis of aryl alkynes. This procedure highlights the potential of copper catalysts to promote unique, synthetically enabling C-H functionalization reactions that lie outside of the current scope of precious metal catalysis., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A Pd(II)-catalyzed arylation of methylene C(sp(3))-H bonds in aliphatic amides directed by our newly developed PIP directing group with aryl iodides/bromides has been achieved. Arylation occurs efficiently with a broad range of aryl halides and amides.

Inflammatory mediators are closely associated with the pathogenesis of neurodegenerative changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Osteopontin (OPN) is a proinflammatory cytokine that has been shown to play an important role in various neuroinflammatory diseases. However, the function of OPN in AD and MCI progression is not well defined. Cerebrospinal fluid (CSF) and plasma samples were obtained from 35 AD patients, 31 MCI patients, and 20 other noninflammatory neurologic diseases (OND). Concentrations of OPN in the CSF and plasma were determined by enzyme-linked immunosorbent assay. During a 3-year clinical followup, 13 MCI patients converted to AD (MCI converters), and 18 were clinically stable (MCI nonconverters). CSF OPN concentrations were significantly increased in AD and MCI converters compared to OND, and increased levels of OPN in AD were associated with MMSE score; OPN protein levels both in the CSF and plasma of newly diagnosed AD patients were higher than that of chronical patients. In MCI converters individuals tested longitudinally, both plasma and CSF OPN concentrations were significantly elevated when they received a diagnosis of AD during followup. Further wide-scale studies are necessary to confirm these results and to shed light on the etiopathogenic role of osteopontin in AD.

The ventri-yellow pigmentation mouse (temporarily named VY(Slac)) arose spontaneously in the C57BL/6J inbred mouse strain, found and bred by Shanghai SLAC Laboratory Animal Co., Ltd. VY(Slac) presented a special phenotype marked by yellow coat on the ventral surface of neck and trunk that was without melanin deposition but maintained a normal structure. The number of melanocytes in epidermis and melanin in hair follicle of the abdominal skin of the mutant mouse were less than that of their background strain, while there was no significant difference between the dorsal skins of the two strains. This mutant phenotype was inherited as single-gene dominant inheritance, confirmed by genetic experiment, and there was no significant difference between VY(Slac) and B(6) for other biological parameters such as weight, anatomic and histological structures of major organs and blood physiology. When the linkage relationship between the genomic DNA samples of F(2) 48 mice (VY(Slac)D(2)F(1)×D(2)) and mutant phenotype were evaluated, the mutant gene was confirmed on chromosome 2 near D2Mit229. New microsatellite and SNP markers were selected to amplify genomic DNA samples of 196 F(2) mice and the mutant gene was narrowed down to 5.3 Mb region between rs13476833 and rs27310903 on chromosome 2. The preliminary results of our phenotype analysis and gene location provides a solid basis for further identification of this mutant gene.

Li(8)ZrO(6) contains a high lithium content and may bear a great ability of CO(2) absorption, yet the reports about the properties of CO(2) absorption on Li(8)ZrO(6) are few to date for its difficulty in production. In this paper, high-purity Li(8)ZrO(6) is synthesized via a three-step calcination method combined with an effective lithium source and a suitable initial Li/Zr molar ratio. The produced Li(8)ZrO(6) possesses a great CO(2) absorption capacity of about 53.98 wt % at 998 K, which could be well-maintained in a wide range of CO(2) partial pressures of 0.1-1.0 bar although it decreased gradually during the multicycle process of CO(2) absorption-desorption in a 10% CO(2) feed stream because of the high working temperature. These properties imply that Li(8)ZrO(6) may be a new option for high-temperature CO(2) capture applied in industrial processes such as a steam methane reformer.

Objective: To analyze the extent of myocardium and coronary artery lesion post atrioventricular ring radiofrequency catheter ablation with different tip catheters., Methods: Twenty-one healthy dogs were randomly divided into 64 degrees C/50 W/100 s, 64 degrees C/100 W/100 s, 45 degrees C/45 W/100 s groups and ablated by 4 mm tip catheter, 8 mm tip catheter and irrigated tip catheter respectively. Left atrioventricular ring and right atrioventricular ring ablation were performed in all dogs. After ablation, myocardium lesion volume was calculated as 1/6pi x length x width x depth. Histological examinations were performed at the myocardium tissue at ablation sites., Results: The lesion depths post 8 mm tip catheter ablation (7.18 +/- 1.72) mm and irrigated tip catheter ablation (7.99 +/- 1.77) mm were similar and significantly deeper than that post 4 mm tip catheter ablation (4.54 +/- 1.38) mm, P < 0.01. Similar results were found in terms of lesion volume [(356.76 +/- 94.44) mm(3) post 8 mm tip catheter ablation, (391.69 +/- 109.54) mm(3) post irrigated tip catheter ablation and (191.34 +/- 74.52) mm(3) post 4 mm tip catheter ablation]. Five (5/42, 11.9%) transmural myocardium necrosis and 8 (8/42, 19%) coronary artery lesions were observed post ablations., Conclusion: The extents of post ablation myocardium and coronary artery lesion were significantly higher induced by 8 mm tip catheter and irrigate tip catheter compared those by 4 mm tip catheter.

Spinel-type ternary LiMn(2)O(4) oxide precursor was synthesized by direct hydrothermal synthesis of Mn(NO(3))(2), LiOH, and H(2)O(2) at 383 K for 8 h, a better technique for controlling the nanocrystalline structure with well-defined pore size distribution and high surface area than the traditional solid state reaction method. The final low-dimensional MnO(2) nanorod ion-sieve with a lithium ion selective adsorption property was further prepared by an acid treatment process to completely extract lithium ions from the Li-Mn-O lattice. The effects of hydrothermal reaction conditions on the nanostructure, chemical stability, and ion-exchange property of the LiMn(2)O(4) precursor and MnO(2) ion-sieve were systematically examined via powder X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), selected-area electron diffraction (SAED), and lithium ion selective adsorption measurements. The results show that this new kind of low-dimensional MnO(2) nanorod can be used for lithium extraction from aqueous environments, including brine, seawater, and waste water.

RNA interference (RNAi) has been extensively used for sequence-specific silencing of gene function in C. elegans, Drosophila, mouse and rat. The generation of RNAi transgenic mice made it possible to knock down gene expression at the whole organism level in mammalian species. In this review we described the design strategy of RNAi vectors, compared the difference of gene knock-down from knock-out, and summarized the advantages and unresolved issues concerning RNAi transgenic mice. The contribution of RNAi transgenic mice to functional genomics and of its prospect for application were also discussed.

Aim: In order to elucidate the relationship between homocysteine (Hcy) and the fibrinolytic system, we examined the effect of Hcy on tissue- type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) gene expression in human umbilical vein endothelial cells (HUVEC) in vitro., Methods: Total RNA was extracted from HUVEC exposed to physical and pathological concentrations of Hcy (0, 10, 50, 200, 500 micromol/L ) for 24 hours, using the guanidinium isothiocyanate method. The semi-quantification of tPA and PAI-1 mRNA in HUVEC was carried out by reverse transcriptase-polymerase chain reaction (RT-PCR)., Results: PAI-1 mRNA levels was enhanced by Hcy at concentrations of 500 micromol/L of Hcy, compared with that of 0 micromol/L Hcy (P < 0.05). The mRNA expression of tPA, however, was significantly decreased at concentrations of 500 micromol/L Hcy, compared with that of 10 micromol/L Hcy (P < 0.05), but compared with the control group, the tPA level of 10 micromol/L Hcy was much higher (P < 0.05)., Conclusion: Hyperhomocysteinemia increases the incidence of cardio cerebral vascular disease, which may be caused by decreasing the activity of fibrinolytic system, whereas, the physiological concentration of Hcy may be decreased the incidence by enhancing the activity of fibrinolytic system.

Malting-quality barley samples of the varieties Harrington, Manley, and TR118, each from two locations in Saskatchewan, were collected directly from the producers and sent to China for storage. At regular intervals samples were shipped back to Canada for analysis consisting of germination studies, alpha-amylase tests, magnetic resonance imaging (MRI), and magnetic relaxation (NMR) studies. Samples showing a decrease in germinative energy and elevated levels of alpha-amylase also showed a rapid uptake of water in the area between the embryo and the endosperm as observed by MRI. Using NMR relaxation experiments, viable and nonviable barley samples could be distinguished after 2 h of imbibition.

Complete and reliable data of mortality rate of malignant tumors from 1973 to 1982 in Yangzhong County, Jiangsu Province, China are reported. The annual mortality rate was 271.38/100,000 which is the highest of all counties in China. Among the malignant tumors, the mortality rates of esophageal, stomach, liver and intestinal cancers are 100.77/100,000, 90.25/100,000, 31.25/100,000 and 11.95/100,000, respectively. Moreover, the mortality rates of lung, cervical cancers and leukemia are also rather high. The mortality rate of esophageal cancer in the female is higher than that in the male. There have been no obvious changes in the mortality rates of some chief malignant tumors in the past ten years. For the high mortality rates of various malignancies in Yangzhong county, epidemiological factors should be further investigated.

Data are presented for the amino acid and sugar compositions of gum talha (tahl), i.e. the exudate from Acacia seyal Del., and for four sequential Smith-degradation (SD) products (0.10, 0.19, 0.38, 1.60 and 2.22% N respectively). Gum talha, which is not permitted as a food additive, is liable to occur as a contaminant of shipments of legitimate gum arabic (Acacia senegal (L.) Willd.). The molar polysaccharide/protein ratio in the whole gum (113:1) decreased to 58:1, 27:1, 5.5:1 and 4:1 in the first, second, third and fourth SD products respectively. From previous studies, SD-IV is known to be a branched galactan; hydroxyproline, aspartic acid, serine, valine, proline, and leucine account jointly for 70% of its amino acids. The first SD eliminated large amounts of sugars (ca 50%, including all of the rhamnose and glucuronic acid present) but only very small amounts of amino acids (molar ratio 807/1). The second and third degradations eliminated all of the arabinose and 99% of the galactose originally present. The very small yield of the final SD product is an established characteristic of dextrorotatory Acacia exudates of the A. seyal type (Bentham's Gummiferae). Overall (four SD stages), 99.7% of the original sugars but only 91.3% of the amino acids were eliminated. Hydroxyproline accounts for ca 25% of the low amino acid content of A. seyal gum and each of its SD products; the proteinaceous enrichment of the branched galactan core also involves aspartic acid, glutamic acid and iso-leucine.(ABSTRACT TRUNCATED AT 250 WORDS)