A boryl radical-triggered C–H functionalization of aliphatic ethers/amines or DMF with isocyanides is developed to deliver diverse phenanthridine derivatives in good to excellent yields. The ...substrate scope is broad, and a wide range of functional groups are tolerated under the standard conditions. The rapid removal of HBPin species by 4-cyanopyridine 1-oxide provides the driving force for this reaction. This new method should make boryl radicals widely applicable in organic synthesis.
If a dialogue system can predict the personality of a user from dialogue, it will enable the system to adapt to the user's personality, leading to better task success and user satisfaction. In a ...recent study, personality prediction was performed using the Myers-Briggs Type Indicator (MBTI) personality traits with a task-oriented human-machine dialogue using an end-to-end (neural-based) system. However, it is still not clear whether such prediction is generally possible for other types of systems and user personality traits. To clarify this, we recruited 378 participants, asked them to fill out four personality questionnaires covering 25 personality traits, and had them perform three rounds of human-machine dialogue with a pipeline task-oriented dialogue system or an end-to-end task-oriented dialogue system. We also had another 186 participants do the same with an open-domain dialogue system. We then constructed BERT-based models to predict the personality traits of the participants from the dialogues. The results showed that prediction accuracy was generally better with open-domain dialogue than with task-oriented dialogue, although Extraversion (one of the Big Five personality traits) could be predicted equally well for both open-domain dialogue and pipeline task-oriented dialogue. We also examined the effect of utilizing different types of dialogue on personality prediction by conducting a cross-comparison of the models trained from the task-oriented and open-domain dialogues. As a result, we clarified that the open-domain dialogue cannot be used to predict personality traits from task-oriented dialogue, and vice versa. We further analyzed the effects of system utterances, task performance, and the round of dialogue with regard to the prediction accuracy.
•VPA alleviates SNL-induced mechanical allodynia.•VPA ameliorates neuroinflammatory response.•VPA inhibits spinal microgliosis and mediates microglia polarization following SNL.•VPA suppresses ...SNL-induced spinal cell apoptosis.•VPA modulates SNL-induced the STAT1/NF-κB and JAK2/STAT3 signaling pathways.
Spinal inflammation is a pathophysiological state of neuropathic pain (NP). The subsequent microglial activation and neuroinflammatory response are contributing factors for long-lasting behavioral hypersensitivity. Valproic acid (VPA), a histone deacetylase inhibitor, has promising anti-inflammatory and neuroprotective properties for clinical use in the treatment of neurological disorders. However, the underlying mechanisms of its effects on NP have not been determined. This study aimed to clarify the possible mechanisms by which VPA alleviates NP in rat models induced by spinal nerve ligation (SNL).
Intraperitoneal injection of VPA (300 mg/kg) efficiently attenuated mechanical allodynia in rats with NP. VPA exerted anti-inflammatory effects by downregulating proinflammatory cytokines (tumor necrosis factor-α, cytokines interleukin-1β, cytokines interleukin-6; TNF-α, IL-1β, and IL-6) and upregulating anti-inflammatory cytokines (transforming growth factor-β, cytokines interleukin-10, cytokines interleukin-4; TGF-β, IL-10 and IL-4). Additionally, VPA suppressed spinal microgliosis and promoted the polarization of microglia towards the M2 phenotype to further ameliorate spinal neuroinflammation. VPA also exerted neuroprotective effects by decreasing spinal cell apoptosis. The anti-inflammatory and neuroprotective effects may have depended on changes in nuclear histone deacetylase 3 (HDAC3) expression following VPA treatment. Moreover, VPA treatment inhibited nuclear factor-κB (NF-κB) p65 nuclear expression and upregulated acetylated the signal transducer and activator of transcription 1 (STAT1). In addition, VPA suppressed SNL-induced phosphorylation of Janus Kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Taken together, our results demonstrate that VPA is a promising anti-inflammatory agent suitable for NP therapy that regulates microglial function and suppresses spinal neuroinflammation via the STAT1/NF-κB and JAK2/STAT3 signaling pathways.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due ...to acinar‐to‐ductal metaplasia (ADM). Baicalein has been shown to exert anti‐inflammatory and anti‐tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines‐induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα‐induced AR42J cells switched their phenotype from dominantly amylase‐positive acinar cells to dominantly cytokeratin 19‐positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes‐1, a Notch target, was up‐regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes‐1. Baicalein inhibited NF‐κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium‐treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS‐activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα‐induced ADM of AR42J cells by inhibiting NF‐κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC.
Chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar‐to‐ductal metaplasia (ADM). Baicalein, an active compound isolated from the roots of Scutellaria baicalensis Georgi, exert anti‐inflammatory and anti‐tumor effects for CP or PDAC. Our research showed that baicalein could suppress the acinar‐to ductal metaplasia (ADM) of pancreatic acinar cell AR42J via inhibition of NF‐κB activation. Furthermore, Baicalein also suppressed the inflammatory response of LPS‐activated macrophages, thereby inhibited ADM of AR42J through an altered microenvironment. Together, our study may provide new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC.
Aim of this study was to evaluate the association between multiple essential microelements exposure and the aggressive clinicopathologic characteristics of papillary thyroid carcinoma (PTC). The ...concentrations of 10 essential microelements in urine cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), strontium (Sr), zinc (Zn), and iodine (I) were measured in 608 patients newly diagnosed with PTC, including 154 males and 454 females. Chi square test and Wilcoxon rank sum test were used to compare general characteristics among males and females. Multivariate logistic regression was used to evaluate the associations between essential microelements and PTC clinicopathologic characteristics in single- and multi-microelement models. In this study, we only observed that the frequency of lymph node metastasis in males was higher than in females, and males had higher levels of zinc than females, but males had lower levels of iodine than females. It was found that high levels of Fe were associated with decreased risk of PTC tumor size > 1 cm, capsular invasion, and advanced T stage (T3/4a/4b). High levels of Co and Mo were associated with decreased risk of capsular invasion and lymph node metastasis, respectively. However, high levels of Mn and Sr were associated with increased risk of capsular invasion and multifocality respectively, and both were associated with increased risk of advanced T stage (T3/4a/4b). These findings indicated that certain essential microelements might have potential effects on PTC progression and aggressiveness. Further studies are required to confirm these findings.
When a gravitational wave or a graviton travels through an electric or magnetic background, it could convert into a photon with some probability. In this paper, a dipole magnetic field is considered ...as this kind of background in both the Minkowski spacetime and the curved spacetime in the near-zone of a neutron star. In the former case, we find that the graviton traveling vertically rather than parallel to the background magnetic field could be more effectively converted into an electromagnetic radiation field. In the latter case, we focus on the situation, in which the graviton travels along the radial direction near a neutron star. The radius of a neutron star is about ten kilometers, so the gravitational wave with long wavelength or low frequency may bypass neutron stars by diffraction. For high frequency gravitational wave, the conversion probability is proportional to the distance square as that in the static electric or magnetic background case. The smaller the inclination angle between the dipole field and the neutron star north pole is, the larger magnetic amplitude will be. The term that described curved spacetime will slightly enhance this kind of probability. We estimate that this value is about the order of ∼10−14−10−10. Therefore, it is expectable that this kind of conversion process may have a potential to open a window for observing high frequency gravitational waves.
In signal array processing, high-resolution direction-of-arrival (DOA) estimation algorithms work well on the assumption that the system models are perfect. However, in practicality, there are ...imperfect system models in which sensor gain-and-phase errors are considered. In this paper, we propose a novel framework that can effectively solve direction-of-arrival estimation tasks in the presence of sensor gain-and-phase errors. In contrast to existing approaches based on phase retrieval, our method eliminates gain errors by using the compensated covariance matrix. Meanwhile, we propose a data preprocessing method by taking only one column of the compensated covariance matrix without losing any magnitude information. Additionally, the phase retrieval problem is formed by the proposed data preprocessing method. Furthermore, the phase retrieval problem is solved by the recently proposed sparse feasible point pursuit algorithm, and DOA estimates are obtained. To prevent the model from ambiguities, we employ the known DOA to place reference sources. Numerical results show that the proposed scheme achieves better performance compared to state-of-the-art approaches.
Thyroid cancer (TC) has inflicted huge threats to the health of mankind. Chlorophenols (CPs) were persistent organic pollutant and can lead to adverse effects in human health, especially in thyroid. ...However, epidemiological studies have revealed a rare and inconsistent relationship between internal exposure to CPs and TC risk. The purpose of this study was to investigate the correlation between urinary CPs and TC risk in Chinese population. From June 2017 to September 2019, a total of 297 histologically confirmed TC cases were recruited. Age- and gender-matched controls were enrolled at the same time. Gas chromatography-mass spectrometry (GC-MS) was used to determine the levels of three CPs in urine. Conditional logistic regression models were adopted to assess the potential association. Restricted cubic spline function was used to explore the non-liner association. After adjusting for confounding factors, multivariate analysis showed that, compared with the first quartile, the fourth quartile concentrations of 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP), and pentachlorophenol (PCP) were associated with TC risk (odds ratio (OR)
2,4-DCP
=2.28, 95% confidence interval (CI): 1.24–4.18; OR
2,4,6-TCP
=3.09, 95% CI: 1.66–5.77; OR
PCP
=3.30, 95% CI: 1.71–6.36, respectively), when CPs were included in the multivariate model and restricted cubic spline function as continuous variables, presenting significant dose-response relationships. Meanwhile, whether in the TC group with tumor diameter > 1 cm or metastatic TC, the changes of 2,4,6 TCP and PCP concentrations were positively correlated with the risk of TC. Our study suggests that higher concentrations of urinary CPs are associated with increased TC risks. Moreover, 2,4,6-TCP and PCP have certain effects on the invasiveness of thyroid cancer. Targeted public health policies should be formulated to reduce the CP pollution. These findings need further in-depth studies to confirm and relevant mechanism also needed to be clarified.
The traditional Chinese medicine Shen-ling-bai-zhu-san (SLBZS) is described in “Tai Ping Hui Min He Ji Ju Fang.” SLBZS has been shown to be effective against many gastrointestinal diseases. The ...present study aimed to investigate the effect of SLBZS on experimental colitis in mice and to define the potential mechanisms. Our data suggest that compared to the model group, SLBZS treatment increases mouse body weight and colon length, decreases the DAI score, and improves colonic injury. SLBZS reduces the production of cytokines (IL-1β, IL-18, and TNF-α) in colon tissue and mouse colonic mucosal epithelial (MCME) cells. Mechanistically, SLBZS inhibits inflammation by inhibiting the MAPK and NF-κB signaling pathways. Further mechanistic analyses showed that SLBZS attenuates the expression levels of pyroptosis-related genes, including NLRP3, ASC, and GSDMD-N in the colons of mice. In addition, SLBZS restores the levels of the colon tight junction proteins ZO-1 and occludin, suggesting that it protects colonic barrier integrity and ameliorates the progression of colitis. In this paper, we demonstrate that SLBZS attenuates DSS-induced ulcerative colitis injury in mice
via
the MAPK/NF-κB and pyroptosis signaling pathway. These results indicate that SLBZS is a potential drug for the treatment of UC.
Background:
Probiotics have been associated with the treatment of depression and anxiety. However, the results reported in the literature have been inconsistent, and no meta-analysis specifically ...reported probiotics used on participants with varying levels of emotional state.
Methods:
This meta-analysis aimed to study the effectiveness of probiotics on anxious or depressive symptomatology for participants under stress conditions or with a depressive or anxiety disorder diagnosis. Medline, PubMed, EMBASE, and the Cochrane Library were searched through December 2019 for randomized controlled trials (RCTs). The primary outcomes were depression and anxiety scores. Main inclusion criteria: RCTs of probiotics for participants with a mood or emotional disorder diagnosis or under stress situations; and all participants were adults (age ≥16 years); Assessed by the modified Jadad assessment scale found seven high-quality studies and three low-quality studies.
Results:
Ten clinical trials (
n
= 685 total participants) were included based on the inclusion and exclusion criteria. All studies were assessed as low or moderate risk of bias. The meta-analysis showed that probiotics could significantly reduce the depression scale for patients with anxiety and depression, and healthy participants under stress. However, there was no significant difference between the probiotics and placebo groups in the reduction of patient anxiety scores, even if they are depressive or anxious patients or healthy participants under stress. Subgroup analysis revealed that probiotics had significant effect on depressive symptoms just in patients with depression, and no significant change in anxiety in patients, and no improvement in participant performance under stress.
Conclusions:
Probiotics could alleviate depressive symptoms in patients with a depression diagnosis or depression scores also in anxiety disorder diagnosis, and suggesting that probiotics may be adjunct therapies for mood or emotional disorders. Therefore, it is essential that probiotics could be more involved in the treatment of patients with depression in the future. The evidence of probiotics successfully treating depression is still insufficient, and more high-quality studies on patients with depression are still needed.
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