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Background: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). Methods: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein–protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. Results: We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10–6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets—FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3—that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). Conclusions: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments. [ABSTRACT FROM AUTHOR]

Objective: To delineate the structural connectome alterations in patients with chronic migraine (CM), episodic migraine (EM), and healthy controls (HCs). Background: The pathogenesis of migraine chronification remains elusive, with structural brain network changes potentially playing a key role. However, there is a paucity of research employing graph theory analysis to explore changes in the whole brain structural networks in patients with CM and EM. Methods: The individual structural brain connectome of 60 patients with CM, 34 patients with EM, and 39 healthy control participants were constructed by using deterministic diffusion-tensor tractography. Graph metrics including global efficiency, characteristic path length, local efficiency, clustering coefficient, and small-world parameters were evaluated to describe the topologic organization of the white matter structural networks. Additionally, nodal clustering coefficient and efficiency were considered to assess the regional characteristics of the brain connectome. A graph-based statistic was used to assess brain network properties across the groups. Results: Graph theory analysis revealed significant disruptions in the structural brain networks of CM patients, characterized by reduced global efficiency, local efficiency, and increased characteristic path length compared to HCs. Additionally, CM patients exhibited significantly lower local efficiency than EM patients. Notably, the CM group demonstrated marked reductions in local clustering coefficient and nodal local efficiency in the frontal and temporal regions compared with the healthy control group and EM group. Nodal local efficiency can effectively distinguish CM from EM and HCs. Moreover, the disrupted topologic efficiency was significantly associated with attack frequency and MIDAS score in patients with migraine after Bonferroni correction. Conclusion: Decreased structural connectivity in the frontal and temporal regions may serve as a neuroimaging marker for migraine chronification and disease progression, providing valuable insights into the pathophysiology of chronic migraine. [ABSTRACT FROM AUTHOR]

The obtainment of the neutron multiplicity distribution is the precondition of the neutron coincidence or multiplicity measurement. In related measurements, the calibration of the detector and the optimization of the analysis parameters prefer acquiring the neutron multiplicity distribution through the offline time-correlation analysis of the measured time stamps, while the usual measurement tasks tend to get it online. To meet with the demands of online and offline obtainment of the neutron multiplicity distribution, an online time-correlation analysis method on the basis of list-mode data acquisition technique is proposed in present work. The reliability of the obtained neutron multiplicity distribution is verified through the experiments carried out with a strong and a weak 252Cf neutron sources. [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]

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]

Background: New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. Specific abnormalities in gray matter and white matter structure are associated with pain, but have not been well studied in NDPH. The objective of this work is to explore the fiber tracts and structural connectivity, which can help reveal unique gray and white matter structural abnormalities in NDPH. Methods: The regional radiomics similarity networks were calculated from T1 weighted (T1w) MRI to depict the gray matter structure. The fiber connectivity matrices weighted by diffusion metrics like fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) were built, meanwhile the fiber tracts were segmented by anatomically-guided superficial fiber segmentation (Anat-SFSeg) method to explore the white matter structure from diffusion MRI. The considerable different neuroimaging features between NDPH and healthy controls (HC) were extracted from the connectivity and tract-based analyses. Finally, decision tree regression was used to predict the clinical scores (i.e. pain intensity) from the above neuroimaging features. Results: T1w and diffusion MRI data were available in 51 participants after quality control: 22 patients with NDPH and 29 HCs. Significantly decreased morphological similarity was found between the right superior frontal gyrus and right hippocampus. The superficial white matter (SWM) showed significantly decreased FA in fiber tracts including the right superficial-frontal, left superficial-occipital, bilateral superficial-occipital-temporal (Sup-OT) and right superficial-temporal, meanwhile significant increased RD was found in the left Sup-OT. For the fiber connectivity, NDPH showed significantly decreased FA in the bilateral basal ganglion and temporal lobe, increased MD in the right frontal lobe, and increased RD in the right frontal lobe and left temporal-occipital lobe. Clinical scores could be predicted dominantly by the above significantly different neuroimaging features through decision tree regression. Conclusions: Our research indicates the structural abnormalities of SWM and the neural pathways projected between regions like right hippocampus and left caudate nucleus, along with morphological similarity changes between the right superior frontal gyrus and right hippocampus, constitute the pathological features of NDPH. The decision tree regression demonstrates correlations between these structural changes and clinical scores. [ABSTRACT FROM AUTHOR]

Background: New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. Methods: This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson's correlation analysis between the NODDI indicators and clinical characteristics. Results: Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. Conclusions: Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH. [ABSTRACT FROM AUTHOR]

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]

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]

Scintillators with n - γ discrimination property are widely used in the measurement of neutrons. In sub MeV region, the n - γ discrimination property will be greatly deteriorated so that the neutron and γ -ray events can't be accurately discriminated. As a result, the determination of the proportions of neutron and γ -ray events beyond the discrimination threshold is important if scintillators are applied to measure the low energy neutrons. In the present work, a method based on the time-of-flight technique is proposed to calibrate the proportions of neutron and γ -ray events beyond the discrimination threshold. After the calibration, the numbers of the measured neutron and γ -ray events can be separately determined even if the neutron and γ -ray events can't be perfectly discriminated. • A method was proposed to calibrate the proportions of neutron and γ-ray events beyond the discrimination threshold. • The numbers of the neutron and γ-ray events can be separately determined even if they can't be accurately classified. • After the calibration, a lower detection threshold can be adopted to improve the detection efficiency of the scintillators. [ABSTRACT FROM AUTHOR]

For the reconstructed image of transmission computed tomography, the linear attenuation coefficients of the diagnosed object may improve the image quality by adding additional constraint besides the projection data. In the present work, an image reconstruction method with the constraint of the linear attenuation coefficients is developed and two models including a classical numerical Shepp-Logan model and a Monte Carlo model are used to show the corresponding benefits. The results indicate that the number of the projection angles is potentially decreased to 1/3 of itself while the quality of the reconstructed image is not deteriorated. • An image reconstruction method with the constraint of the linear attenuation coefficients is developed. • The method can decrease the number of the projection angles to 1/3 of itself while the image quality is not deteriorated. • The present method can prevent the image quality from decreasing with the increase of loop iteration. [ABSTRACT FROM AUTHOR]

• Landscape affects parasitoid body size in species-specific manner. • Body size of M. russata and E. sinicus was positive to water bodies. • ITD and body mass of E. sinicus was negative to landscape diversity. • Gregarious parasitoid of C. chilonis have nothing to do with landscape variable. • Solitary parasitoids were more sensitive to variation in habitat resource-availability. The top-down effect of natural enemies on pests is a crucial ecosystem service supporting integrated pest management. However, the variation in morphological traits of parasitoids in different landscape contexts and the differences in parasitoid emergence rate caused by this variation are still poorly known. We measured the inter-tegular distance (ITD) and body mass of three parasitoids– Cotesia chilonis (Munakata), Eriborus sinicus (Holmgren) , and Microgaster russata Haliday – on overwintering larvae of Chilo suppressalis (Walker), the rice stem borer (RSB), collected from 20 rice paddies along a landscape heterogeneity gradient. Our objectives were to assess how landscape composition and landscape diversity affect functional traits (ITD and body mass) of species-specific parasitoid, and individual body size for its impact on biological control. From a total of 5002 sampled individuals of the three parasitoids, regression analysis revealed that (1) the presence of water bodies within the landscape respectively positive affected the ITD of E. sinicus and M. russata at 2000 m scales, landscape factors had yet no discernible effects on either the body size (ITD or body mass) of C. chilonis , (2) habitats with high landscape diversity had a negative effect on body size (ITD and body mass) of the solitary parasitoids E. sinicus at 200 m scales, and (3) a significantly negative correlation was found between the parasitoid emergence rate and ITD of E. sinicus. Our findings suggest that parasitoids' body sizes may respond differently among species to landscape features. Solitary parasitoids in our study were more sensitive to variation in habitat resource-availability than was the gregarious parasitoid. We conclude that landscape habitat changes can affect the body size and parasitism of parasitoids, modifying their biocontrol services against pests. [ABSTRACT FROM AUTHOR]

Considering the difficulties of the low signal-to-noise ratio in weak radioactive source detections, this study proposes an abandon Gaussian tails method based on the analysis of the characteristic information denoted by the full-energy peak of the gamma spectrum of a gamma-emitting radioactive source. Based on the study of the signal-to-background ratio and the statistical fluctuations in the signal of the weak radioactive source, a factor ζ, incorporating the statistical fluctuations of signal and background and the signal-to-background ratio, is suggested to characterize the sensitivity of a radioactive source detection. When ζ reaches its maximum value, the optimal counting window around the centroid of the full-energy peak can be obtained. To evaluate the effectiveness of the proposed approach, comparisons between the proposed abandon Gaussian tails, the conventional full-energy counting, and other experiential methods were performed. The results show that the sensitivity can be significantly improved. Further, experiments with different intensity of radiation sources and duplicated experiments were conducted to examine the stability of the proposed method. • A method to enhance the sensitivity for weak radioactive source detection is presented. • A factor, ζ, is suggested for characterizing the sensitivity of the presence of a radioactive source. • The detection sensitivity of the source search can be improved when the factor ζ is at its maximized value. [ABSTRACT FROM AUTHOR]

Rasmussen's encephalitis (RE) is a rare, progressive disease characterized by unilateral cerebral hemisphere atrophy. Studies showed that inflammatory response and overexpressed chemokines were present in RE patients. The present study aims to determine whether caspase-1- mediated neuronal pyroptosis occurred in RE. Immunohistochemistry and Western blotting analysis were used to examine the expression of Gasdermin D (GSDMD), NOD-like receptor protein 1 (NLRP1), NOD-like receptor protein 3 (NLRP3), caspase-1, and pro-caspase-1 in RE and control cortical specimens (n = 14). Perilesional tissue specimens from six focal cortical dysplasia (FCD) cases were used as controls. Double staining showed the colocalization of GSDMD, NLRP1, NLRP3 and caspase-1. Enzyme-linked immunosorbent assay (ELISA) was used to quantify the amount of interleukin (IL)−1β and IL-18 in RE cortical specimens. Compared with the control cortex, we found higher GSDMD expression in the cytoplasm of neurons in RE cortex but no detectable expression in astrocytes and microglia. Further analysis revealed that NLRP1, NLRP3, caspase-1 and its precursor pro-caspase-1 were also upregulated in the RE, and predominantly localized in the cytoplasm of the neurons. In addition, significantly higher levels of IL-1β and IL-18 were present in the RE group compared with the control group. Our results suggest that pyroptosis represents an important pathway for neuronal loss in the pathological processes associated with RE, and that targeting the canonical inflammasome pathway of pyroptosis may provide potential therapeutic value for RE. • The expression of NLRP1, NLRP3, caspase-1, and GSDMD were increased in the brain specimens of RE. • The pyroptosis represents an important pathway for neuronal loss in the pathological processes associated with RE. • Targeting the canonical inflammasome pathway of pyroptosis may provide potential therapeutic value for RE. [ABSTRACT FROM AUTHOR]

It is of great significance to develop facile and economical strategies for on-site detection and treatment of toxic metal ions. Stimulus-responsive DNA hydrogel materials have been increasingly used for convenient detection of metal ions due to their advantages such as simplicity, portability, and ease of storage. However, these methods still require encapsulation of signal tags by labeling or embedding. In this paper, a one-step preparation of Pb2+-responsive pure DNA hydrogel material was designed to realize a new label-free strategy for Pb2+ biosensing. The Pb2+-dependent DNAzyme strand and substrate strand were introduced to fabricate the DNA hydrogel. The presence of Pb2+ in the sample activates the enzyme strand in the hydrogel skeleton and triggers the cleavage of the substrate, thereby destroy the hydrogel structure. DNA fragments released by the collapsed hydrogel were readily measured as signal output for quantifying Pb2+ concentrations with a minimum detection limit of 7.7 nM. We successfully eliminated the need for embedding or labeling of signal molecules by using the DNA molecules that construct hydrogels as the signal output. And the newly developed method for label-free detection of Pb2+ based on pure DNA hydrogel is simple, easy readout, and cost-effective. By adjusting the DNAzyme and substrate sequences, label-free analysis of other metal ions can also be achieved. We expect that our strategy can be applied to the field detection of toxic metal ions. [Display omitted] • A one-step preparation of Pb2+-responsive pure DNA hydrogel was designed to realize label-free detection of lead ion. • This strategy successfully eliminated the need for embedding or tagging extra signal molecules. • The developed label-free method based on pure DNA hydrogel is facile, easy readout, and cost-effective. [ABSTRACT FROM AUTHOR]

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]