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Objectives: The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed‐based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting‐state functional magnetic resonance imaging (MRI). Methods: The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well‐matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations. Results: Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus‐central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area‐parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016). Conclusions: Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions. [ABSTRACT FROM AUTHOR]

Aims: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus, is an effective therapy for patients with drug‐resistant epilepsy, yet, its mechanism of action remains elusive. Adenosine kinase (ADK), a key negative regulator of adenosine, is a potential modulator of epileptogenesis. DBS has been shown to increase adenosine levels, which may suppress seizures via A1 receptors (A1Rs). We investigated whether DBS could halt disease progression and the potential involvement of adenosine mechanisms. Methods: Control group, SE (status epilepticus) group, SE‐DBS group, and SE‐sham‐DBS group were included in this study. One week after a pilocarpine‐induced status epilepticus, rats in the SE‐DBS group were treated with DBS for 4 weeks. The rats were monitored by video‐EEG. ADK and A1Rs were tested with histochemistry and western blot, respectively. Results: Compared with the SE group and SE‐sham‐DBS group, DBS could reduce the frequency of spontaneous recurrent seizures (SRS) and the number of interictal epileptic discharges. The DPCPX, an A1R antagonist, reversed the effect of DBS on interictal epileptic discharges. In addition, DBS inhibited the overexpression of ADK and the downregulation of A1Rs. Conclusion: The findings indicate that DBS can reduce SRS in epileptic rats via inhibition of ADK and activation of A1Rs. A1Rs might be a potential target of DBS for the treatment of epilepsy. [ABSTRACT FROM AUTHOR]

Aims: Mesial temporal lobe epilepsy without hippocampal sclerosis (no‐HS MTLE) refers to those MTLE patients who have neither magnetic resonance imaging (MRI) lesions nor definite pathological evidence of hippocampal sclerosis. They usually have resistance to antiepileptic drugs, difficulties in precise seizure location and poor surgical outcomes. Adenosine is a neuroprotective neuromodulator that acts as a seizure terminator in the brain. The role of adenosine in no‐HS MTLE is still unclear. Further research to explore the aetiology and pathogenesis of no‐HS MTLE may help to find new therapeutic targets. Methods: In surgically resected hippocampal specimens, we examined the maladaptive changes of the adenosine system of patients with no‐HS MTLE. In order to better understand the dysregulation of the adenosine pathway in no‐HS MTLE, we developed a rat model based on the induction of focal cortical lesions through a prenatal freeze injury. Results: We first examined the adenosine system in no‐HS MTLE patients who lack hippocampal neuronal loss and found ectopic expression of the astrocytic adenosine metabolising enzyme adenosine kinase (ADK) in hippocampal pyramidal neurons, as well as downregulation of neuronal A1 receptors (A1Rs) in the hippocampus. In the no‐HS MTLE model rats, the transition of ADK from neuronal expression to an adult pattern of glial expression in the hippocampus was significantly delayed. Conclusions: Ectopic expression of neuronal ADK might be a pathological hallmark of no‐HS MTLE. Maladaptive changes in adenosine metabolism might be a novel target for therapeutic intervention in no‐HS MTLE. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is one of the important long-term sequelae of neonatal hypoxic-ischemic encephalopathy (HIE) and is typically characterized by drug resistance and poor surgical outcomes. Vagus nerve stimulation (VNS) is a promising neuromodulation therapy for refractory epilepsy. Objectives: The present study aimed to first evaluate the effectiveness of VNS in patients with refractory HIE-induced epilepsy and scrutinize potential clinical predictors. Methods: We retrospectively collected the outcomes of VNS in all patients with refractory HIE-induced epilepsy and at least 2 years of follow-up. Subgroups were classified as responders and nonresponders according to the effectiveness of VNS (⩾50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS effectiveness. Results: A total of 55 patients with refractory HIE-induced epilepsy who underwent VNS therapy were enrolled. Responders represented 56.4% of patients, and 12.7% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time with rates of 23.6%, 38.2%, 50.9%, and 56.4% at the 3-, 6-, 12- and 24-month follow-ups, respectively. After multivariate analysis, neonatal seizure was identified as a negative predictor (OR: 4.640, 95% CI: 1.129–19.066), and a predominant seizure type of generalized onset was identified as a positive predictor (OR: 0.261, 95% CI: 0.078–0.873) of VNS effectiveness. Conclusion: VNS therapy was effective in patients with refractory HIE-induced epilepsy and was well tolerated over a 2-year follow-up period. VNS therapy demonstrated better effectiveness in patients without neonatal seizures or with a predominant seizure type of generalized onset. [ABSTRACT FROM AUTHOR]

Uranium contamination has become a nonnegligible global health problem. Inhalation of particulate uranium is one of the predominant routes of occupational and environmental exposure. Uranium particle is a complex two-phase flow of matter that is both particulate and flowable. This particular physicochemical property may alter its biological activity. Epidemiological studies from occupationally exposed populations in the uranium industry have concluded that there is a possible association between lung cancer risk and uranium exposure, while the evidence for the risk of other tumors is not sufficient. The toxicological effects of particulate uranium exposure to animals have been shown in laboratory tests to focus on respiratory and central nervous system damage. Fibrosis and tumors can occur in the lung tissue of the respiratory tract. Uranium particles can also induce a concentration-dependent increase in cytotoxicity, targeting mitochondria. The understanding of the health risks and potential toxicological mechanisms of particulate uranium contamination is still at a preliminary stage. The diversity of particle parameters has limited the in-depth exploration. This review summarizes the current evidence on the toxicology of particulate uranium and highlights the knowledge gaps and research prospects. [ABSTRACT FROM AUTHOR]

Probiotics are beneficial microorganisms existing in nature and animals and can be used in livestock and poultry breeding. Here, 240 1-day-old Arbor Acre (AA) broilers were used to study the effects of compound probiotics (CP) on antioxidant capacity, intestinal barrier function and caecum microorganisms. 2‰, 3‰ or 4‰ CP were added to the basal diet. Blood, jejunum, caecum and caecum contents of broilers were collected on day 60, and the jejunum histopathological observation, oxidative stress state evaluation, intestinal barrier function mRNA level and caecum microflora composition were carried out. The results showed that CP significantly improved the growth performance of broilers in 1-30 days. Moreover, CP supplementation increased superoxide dismutase (SOD) activity, reduced malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents in serum, and increased the mRNA levels of zona occludens 1 (ZO-1), claudin-1 and occludin in the jejunum of broilers. 3‰ CP observably increased the ratio of villus height to crypt depth, and the abundance of the genus Rikenellaceae_RC9_gut_group and Phascolarctobacterium, decreased the abundance of the genus Ruminococcaceae_UCG-014, together with regulation of several genes that are responsible for signaling pathways involved in carbohydrate metabolism, amino acid metabolism and endocrine and metabolic diseases. Taken together, the supplementation of CP could reduce oxidative stress levels, increase the mRNA expression levels of tight junction (TJ)-related genes and the colonization of beneficial bacteria in the caecum, which has a promoting effect on the growth performance in broilers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Clausena lansium (Lour.) Skeels, belonging to the genus Clausena of the family Rutaceae, has a wide range of medical and agricultural activities. Previous studies on agricultural activities have shown that C. lansium extracts and some components have obvious herbicidal activities. In order to study systematically herbicidal activity of this plant, we studied the herbicidal effect of ethyl acetate (EtOAc) extract from the stems and leaves of this plant and further isolated the active compounds. RESULTS: The EtOAc extract inhibited the growth of roots and shoots of Echinochloa crus‐galli (L.) Beauv., and the inhibitory effect of the EtOAc extract on roots were stronger than those on shoots with half maximal inhibitory concentration (IC50) values of 420.45 and 585.05 mg L−1, respectively. Fifteen compounds were subsequently isolated and identified from the stems and leaves of C. lansium, including nine O‐monoterpenoid furanocoumarins and six cinnamamides. Our results showed that most compounds exhibited varying degrees of herbicidal activities to E. crus‐galli. Among them, compounds 3, 8, and 13–15 showed the best inhibitory activities on the growth of E. crus‐galli roots, with inhibition rate values ranging from 70% to 83% at a concentration of 300 mg L−1. Compounds 1 and 2 are two new compounds, and their structures were established as 5‐O‐monoterpenoid furanocoumarin and 8‐O‐monoterpenoid furanocoumarin, and named as claulansicoumarin‐A and ‐B, respectively. CONCLUSION: The EtOAc extract and pure compounds showed noticeable herbicidal activities against E. crus‐galli and indicated a great potential for these natural compounds to be developed as a herbicide. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Conventional switching table‐based direct power control (DPC) usually suffers from higher power ripples due to the heuristic nature of the switching table. This study presents a novel model predictive DPC (MPDPC) strategy for grid‐connected three‐level inverters. In the proposed MPDPC strategy, a new synchronous frame‐based predictive model is first developed and the conjugate of the complex power is then chosen as the control variable to simplify the analysis. Based on the newly developed predictive model, new principles of the voltage vector selection are further derived with the strict analytical proof to match all the control requirements, including the active and reactive power control, neutral point potential balance control, as well as the avoidance of the high voltage jumps. Finally, experimental results are provided to support the theoretical study and confirm the effectiveness of the proposed MPDPC strategy, as well as to demonstrate better performance in both steady‐state and dynamic responses over the conventional DPC. [ABSTRACT FROM AUTHOR]

Two new oleanane derivatives, leonuronins A and B (1 and 2), along with three known oleanane triterpenes (3-5) were isolated from the fruits of Leonurus japonicus. Their structures were elucidated on the basis of NMR, MS, IR and UV spectroscopic data. The new compounds were tested for cytotoxic activities against A549 and Hela cancer cell lines. Compounds 1 and 2 exhibited weak cytotoxicity with IC50 values ranging from 6.97 to 18.13 μM. [ABSTRACT FROM AUTHOR]

Abstract: As a γ-secretase inhibitor, DAPT has been widely used to evaluate the biological behaviors and Notch signaling pathway in various cells. This study was aimed to examine the effects of DAPT on the growth and vitamin D3 induced osteogenesis in adipose derived stem cells (ASCs). The cells were treated with or without DAPT and induced to osteoblastic lineage in the presence of vitamin D3. Alizarin red staining and real-time PCR results indicated that the addition of DAPT to vitamin D3 treatments enhanced osteogenesis in ASCs. According to the fold increase and colony-forming unit assay results, the cells cultured in DAPT exhibited lower proliferation rate than those cultured in control medium. Hey1, expressed in the nucleus of ASCs to act as a transcriptional repressor, was downregulated when Notch signaling was inhibited by DAPT. Whereas the expression of Runx2 increased in the nucleus of osteogenic induced ASCs after DAPT treatment. This study demonstrated that DAPT reduced the proliferation and enhanced the osteogenesis in ASCs via regulation of Notch and Runx2 expression. [Copyright &y& Elsevier]

Clausena lansium Lour. Skeels (Rutaceae) is widely distributed in South China and has historically been used as a traditional medicine in local healthcare systems. Although the characteristic components (carbazole alkaloids and coumarins) of C. lansium have been found to possess a wide variety of biological activities, little attention has been paid toward the other components of this plant. In the current study, phytochemical analysis of isolates from a water-soluble stem and leaf extract of C. lansium led to the identification of 12 compounds, including five aromatic glycosides, four sesquiterpene glycosides, two dihydrofuranocoumarin glycosides, and one adenosine. All compounds were isolated for the first time from the genus Clausena, including a new aromatic glycoside (1), a new dihydrofuranocoumarin glycoside (6), and two new sesquiterpene glycosides (8 and 9). The phytochemical structures of the isolates were elucidated using spectroscopic analyses including NMR and MS. The existence of these compounds demonstrates the taxonomic significance of C. lansium in the genus Clausena and suggests that some glycosides from this plant probably play a role in the anticancer activity of C. lansium to some extent. [ABSTRACT FROM AUTHOR]