Selection signatures and landscape genomics analysis to reveal climate adaptation of goat breeds.

Goats have achieved global prominence as essential livestock since their initial domestication, primarily owing to their remarkable adaptability to diverse environmental and production systems. Differential selection pressures influenced by climate have led to variations in their physical attributes, leaving genetic imprints within the genomes of goat breeds raised in diverse agroecological settings. In light of this, our study pursued a comprehensive analysis, merging environmental data with single nucleotide polymorphism (SNP) variations, to unearth indications of selection shaped by climate-mediated forces in goats. Through the examination of 43,300 SNPs from 51 indigenous goat breeds adapting to different climatic conditions using four analytical methods: latent factor mixed models (LFMM), F-statistics (Fst), Extended haplotype homozygosity across populations (XPEHH), and spatial analysis method (SAM), A total of 74 genes were revealed to display clear signs of selection, which are believed to be influenced by climatic conditions. Among these genes, 32 were consistently identified by at least two of the applied methods, and three genes (DENND1A, PLCB1, and ITPR2) were confirmed by all four approaches. Moreover, our investigation yielded 148 Gene Ontology (GO) terms based on these 74 genes, underlining pivotal biological pathways crucial for environmental adaptation. These pathways encompass functions like vascular smooth muscle contraction, cellular response to heat, GTPase regulator activity, rhythmic processes, and responses to temperature stimuli. Of significance, GO terms about endocrine regulation and energy metabolic responses, key for local adaptation were also uncovered, including biological processes, such as cell differentiation, regulation of peptide hormone secretion, and lipid metabolism. These findings contribute to our knowledge of the genetic structure of climate-triggered adaptation across the goat genome and have practical implications for marker-assisted breeding in goats.

Surface-enhanced photoluminescence and Raman spectroscopy of single molecule confined in coupled Au bowtie nanoantenna.

Optical nanoantennas possess broad applications in the fields of photodetection, environmental science, biosensing and nonlinear optics, owing to their remarkable ability to enhance and confine the optical field at the nanoscale. In this article, we present a theoretical investigation of surface-enhanced photoluminescence spectroscopy for single molecules confined within novel Au bowtie nanoantenna, covering a wavelength range from the visible to near-infrared spectral regions. We employ the finite element method to quantitatively study the optical enhancement properties of the plasmonic field, quantum yield, Raman scattering and fluorescence. Additionally, we systematically examine the contribution of nonlocal dielectric response in the gap mode to the quantum yield, aiming to gain a better understanding of the fluorescence enhancement mechanism. Our results demonstrate that altering the configuration of the nanoantenna has a significant impact on plasmonic sensitivity. The nonlocal dielectric response plays a crucial role in reducing the quantum yield and corresponding fluorescence intensity when the gap distance is less than 3 nm. However, a substantial excitation field can effectively overcome fluorescence quenching and enhance the fluorescence intensity. By optimizing nanoantenna configuration, the maximum enhancement of surface-enhanced Raman can be turned to 9 and 10 magnitude orders in the visible and near-infrared regions, and 3 and 4 magnitude orders for fluorescence enhancement, respectively. The maximum spatial resolutions of 0.8 nm and 1.5 nm for Raman and fluorescence are also achieved, respectively. Our calculated results not only provide theoretical guidance for the design and application of new nanoantennas, but also contribute to expanding the range of surface-enhanced Raman and fluorescence technology from the visible to the near-infrared region.

Inhibitory Neurons in Nucleus Tractus Solitarius Are Involved in Decrease of Heart Rate Variability and Development of Depression-Like Behaviors in Temporal Lobe Epilepsy.

BACKGROUND: Diminished heart rate variability (HRV) has been observed in epilepsy, especially in epilepsy with depressive disorders. However, the underlying mechanism remains elusive. METHODS: We studied HRV, spontaneous recurrent seizures, and depression-like behaviors in different phases of pilocarpine-induced temporal lobe epilepsy (TLE) in mice. Single-cell RNA sequencing analysis was used to identify various nerve cell subsets in TLE mice with and without depression. Differentially expressed gene (DEG) analysis was performed in epilepsy, depression, and HRV central control-related brain areas. RESULTS: We found decreased HRV parameters in TLE mice, and alterations were positively correlated with the severity of depression-like behaviors. The severity of depression-like behaviors was correlated with the frequency of spontaneous recurrent seizure. Characteristic expression of mitochondria-related genes was significantly elevated in mice with depression in glial cells, and the enrichment analysis of those DEGs showed an enriched GABAergic synapse pathway in the HRV central control-related brain area. Furthermore, inhibitory neurons in the nucleus tractus solitarius, which is an HRV central control-related brain area, were specifically expressed in TLE mice combined with depression compared with those in mice without depression. A significantly enriched long-term depression pathway in DEGs from inhibitory neurons was found. CONCLUSIONS: Our study reported correlations between HRV and epilepsy-depression comorbidity in different phases of TLE. More importantly, we found that HRV central control-related inhibitory neurons are involved in the development of depression in TLE, providing new insights into epilepsy comorbid with depression.

Enhancement and quenching of plasmon-enhanced spectroscopy of single molecule confined in metallic nanoparticle dimers.

We present a theoretical analysis of plasmon-enhanced fluorescence (PEF) and Raman scattering (PERS) spectroscopy of a single molecule confined in the laser-irradiated metallic nanoparticles (NPs) dimer, focusing on the origin of the spectral enhancement and quenching effects. The theoretical method ofD-parameters has been used to calculate the dimer distance-dependent nonlocal dielectric effect in Ag and Au NPs. Meanwhile, other damping rates and electric field enhancements are quantitatively computed by finite element method. Moreover, PEF and PERS spectra of rhodamine 6G are obtained within the density-functional theory. Our calculated results show that the PERS mainly depend on the excitation and emission field enhancements, and thus it occurs at the narrower dimer gap due to the stronger localized plasmon coupling. The PEF is related to fluorescence rate caused by the competition between excitation electric field and quantum efficiency, and the increase of former may enhance the fluorescence intensity while the lower latter lead to reduce the intensity as decreasing the dimer distance. The contribution of nonlocal dielectric effect can significantly reduce the quantum efficiency at smaller distance so that it overcomes the excitation field enhancement, leading to the fluorescence quenching for Au NPs dimer. Furthermore, by optimizing the dimer distance and NPs size, the maximum PERS and PEF cross sections reach 10-14and 10-15under 2.45 eV laser excitation for Ag NPs dimer, and 10-18for Au NPs. Our study finely explains the experiment results showed either fluorescence enhancement or quenching with the change of molecule-NPs distance, and better guidance for optimizing the experiments.

Crystal Structure of Allantoinase from Escherichia coli BL21: A Molecular Insight into a Role of the Active Site Loops in Catalysis

Allantoinase (ALLase; EC 3.5.2.5) possesses a binuclear metal center in which two metal ions are bridged by a posttranslationally carbamylated lysine. ALLase acts as a key enzyme for the biogenesis and degradation of ureides by catalyzing the conversion of allantoin into allantoate. Biochemically, ALLase belongs to the cyclic amidohydrolase family, which also includes dihydropyrimidinase, dihydroorotase, hydantoinase (HYDase), and imidase. Previously, the crystal structure of ALLase from Escherichia coli K-12 (EcALLase-K12) was reported; however, the two active site loops crucial for substrate binding were not determined. This situation would limit further docking and protein engineering experiments. Here, we solved the crystal structure of E. coli BL21 ALLase (EcALLase-BL21) at a resolution of 2.07 Å (PDB ID 8HFD) to obtain more information for structural analyses. The structure has a classic TIM barrel fold. As compared with the previous work, the two missed active site loops in EcALLase-K12 were clearly determined in our structure of EcALLase-BL21. EcALLase-BL21 shared active site similarity with HYDase, an important biocatalyst for industrial production of semisynthetic penicillin and cephalosporins. Based on this structural comparison, we discussed the functional role of the two active site loops in EcALLase-BL21 to better understand the substrate/inhibitor binding mechanism for further biotechnological and pharmaceutical applications.

Timing matters: there are significant differences in short-term outcomes between two time points of status epilepticus.

BACKGROUND: In 2015, the International League Against Epilepsy proposed a new conceptual definition of status epilepticus (SE) with two operational dimensions (t1 and t2) to guide emergency treatment. The purpose of this study was to compare clinical characteristics and prognoses of patients at these two different time points. METHODS: We conducted a prospective observational cohort study of consecutive adults diagnosed with SE. In case of convulsive SE, t1 is 5 min and t2 is 30 min, whereas in case of focal SE with impaired consciousness, t1 is 10 min, t2 is 60 min. Data on clinical characteristics, including age, gender, history of prior seizures, neuroimaging, semiology, duration, and etiology of SE, were collected. The primary outcome was mortality, with seizure recurrence as a secondary measure, and functional status as tertiary outcome of enrolled patients at 3 months after SE onset. RESULTS: We screened one hundred patients with SE, with a median age of 66 years and 61% were male. Fifty-six (56.0%) patients reached t1 of SE, while 44 (44.0%) reached t2 of SE. Convulsive SE (52.0%, n = 52) was more common than focal SE with impaired consciousness (48.0%, n = 48). Status epilepticus secondary to an acute symptomatic process was the most common (50%, n = 50). Patients meeting t2 of SE demonstrated a remarkably increased risk of mortality (unadjusted analysis-RR 3.606, 95%CI 1.552-8.376, p = 0.003; adjusted analysis-RR 2.924, 95%CI 1.221-7.003, p = 0.016) and unfavorable functional status (unadjusted analysis-RR 1.803, 95%CI 1.280-2.539, p = 0.001; adjusted analysis-RR 1.664, 95%CI 1.184-2.340, p = 0.003) at 3 months compared to those who only reached t1 of SE. Patients reaching t2 of SE were more likely to experience seizure recurrence, however, there was no significant difference between the two cohorts. CONCLUSIONS: Our study provides strong support for the new definition of SE. Patients meeting t2 of SE tend to have a remarkably increased risk of mortality and unfavorable functional outcomes compared to those who only reached t1 of SE. Furthermore, patients were likely to experience seizure recurrence after undergoing an episode of SE. Physicians must be educated about prompt recognition and appropriate management of SE.

Development of emergent ferroelectric nematic liquid crystals with highly fluorinated and rigid mesogens.

The emerging ferroelectric nematic liquid crystals have been attracting broader interests in new liquid crystal physics and their unique material properties. One big challenge for the ferroelectric nematic research is to enrich the material choice, which is now limited to RM734 and DIO families as representatives, in sharp contrast to the enormously diverse variety of the traditional apolar nematic liquid crystals. Here, we report a design of novel ferroelectric nematic materials with highly fluorinated and rigid mesogens. Noteworthily, they show distinct chemical structural features compared with previous aromatic ester-based molecules. The ferroelectric nematic phase was identified and confirmed through rigorous experiments. The bulk polarization was found to become purely along the long axis director, creating giant dielectric anisotropy. This work demonstrates a great potential for expanding ferroelectric nematic material diversity and will accelerate the corresponding application research and technology innovation.

Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model.

PURPOSE: This study aimed to investigate whether 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor with anti-inflammatory effects, could alleviate spontaneous recurrent seizures (SRS) and epilepsy-associated depressive behaviours in the lithium chloride (LiCl)-pilocarpine-induced post-status epilepticus (SE) rat model. METHODS: The rats were intraperitoneally (IP) injected with LiCl (127 mg/kg) and pilocarpine (40 mg/kg) to induce SE. A video surveillance system was used to monitor SRS in the post-SE model for 6 weeks (from the onset of the 2nd week to the end of the 7th week after SE induction). TPPU (0.1 mg/kg/d) was intragastrically given for 4 weeks from the 21st day after SE induction in the SRS + 0.1 TPPU group. The SRS + PEG 400 group was given the vehicle (40% polyethylene glycol 400) instead, and the control group was given LiCl and PEG 400 but not pilocarpine. The sucrose preference test (SPT) and forced swim test (FST) were conducted to evaluate the depression-like behaviours of rats. Immunofluorescent staining, enzyme-linked immunosorbent assay, and western blot analysis were performed to measure astrocytic and microglial gliosis, neuronal loss, and levels of soluble epoxide hydrolase (sEH), cytokines [tumour necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6], and cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB). RESULTS: The frequency of SRS was significantly decreased at 6 weeks and 7 weeks after SE induction in the 0.1TPP U group compared with the SRS + PEG 400 group. The immobility time (IMT) evaluated by FST was significantly decreased, whereas the climbing time (CMT) was increased, and the sucrose preference rate (SPR) evaluated by SPT was in an increasing trend. The levels of sEH, TNF-α, IL-1ß, and IL-6 in the hippocampus (Hip) and prefrontal cortex (PFC) were all significantly increased in the SRS + PEG 400 group compared with the control group; neuronal loss, astrogliosis, and microglial activation were also observed. The astrocytic and microglial activation and levels of the pro-inflammatory cytokines in the Hip and PFC were significantly attenuated in the TPPU group compared with the SRS + PEG 400 group; moreover, neuronal loss and the decreased CREB expression were significantly alleviated as well. CONCLUSION: TPPU treatment after SE attenuates SRS and epilepsy-associated depressive behaviours in the LiCl-pilocarpine induced post-SE rat model, and it also exerts anti-inflammatory effects in the brain. Our findings suggest a new therapeutic approach for epilepsy and its comorbidities, especially depression.

Different behavioral and pathological changes between epilepsy-associated depression and primary depression models.

PURPOSE: Comorbid depression is common in patients with epilepsy. However, the epilepsy-associated depression is generally atypical and has not been fully recognized by neurologists. This study aimed to compare the behavioral and pathological changes between the chronic lithium chloride-pilocarpine rat epilepsy model (Licl-pilocarpine model) and the Chronic Unpredictable Mild Stress rat depression model (CUMS model), to evaluate for differences between epilepsy-associated depression and primary depression. METHODS: The Licl-pilocarpine model and the CUMS model were established respectively and simultaneously. Spontaneous seizures were recorded by video monitoring. Forced swim test (FST) and sucrose consumption test (SCT) were performed to test depressive behaviors. Immobility time (IMT) and climbing time (CMT) in FST, sucrose preference rate (SPR) in SCT, and weight gain rate (WGR) were adopted to represent severity of depressive behaviors in rats. Immunofluorescent staining was conducted to measure expressions of neuronal specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), and cluster of differentiation molecule 11b (CD11b) in the hippocampus of Licl-pilocarpine model, CUMS model, and Control group. RESULTS: Significantly, more prolonged IMT was observed in both the Licl-pilocarpine model (p<0.05) and the CUMS model (p<0.01) than Control group. But decreased WGR was only seen in the CUMS model. The percentage of rats with CMT greater than 100s was significantly higher in the Licl-pilocarpine model than the CUMS model (p<0.05). Increased CMT was observed in the Licl-pilocarpine model with mild depression subgroup (EMD, IMT≤100s) even compared with the Control group. Neuronal loss was both found in the Licl-pilocarpine model and the CUMS model when comparing with the Control group (p<0.05). However, the number of GFAP and CD11b staining cells was both greater in the Licl-pilocarpine model than the CUMS model and the Control group (p<0.05). CONCLUSION: There were some different depressive behavioral and hippocampal pathological changes between the Licl-pilocarpine and the CUMS models except for some common features. Gliosis and microglial activation might be more involved in the pathophysiology of epilepsy-associated depression than primary depression.

Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments.

Global climate change has a significant effect on extreme environments and a profound influence on species survival. However, little is known of the genome-wide pattern of livestock adaptations to extreme environments over a short time frame following domestication. Sheep (Ovis aries) have become well adapted to a diverse range of agroecological zones, including certain extreme environments (e.g., plateaus and deserts), during their post-domestication (approximately 8-9 kya) migration and differentiation. Here, we generated whole-genome sequences from 77 native sheep, with an average effective sequencing depth of ∼5× for 75 samples and ∼42× for 2 samples. Comparative genomic analyses among sheep in contrasting environments, that is, plateau (>4,000 m above sea level) versus lowland (<100 m), high-altitude region (>1500 m) versus low-altitude region (<1300 m), desert (<10 mm average annual precipitation) versus highly humid region (>600 mm), and arid zone (<400 mm) versus humid zone (>400 mm), detected a novel set of candidate genes as well as pathways and GO categories that are putatively associated with hypoxia responses at high altitudes and water reabsorption in arid environments. In addition, candidate genes and GO terms functionally related to energy metabolism and body size variations were identified. This study offers novel insights into rapid genomic adaptations to extreme environments in sheep and other animals, and provides a valuable resource for future research on livestock breeding in response to climate change.

Postictal generalized EEG suppression and respiratory dysfunction following generalized tonic-clonic seizures in sleep and wakefulness.

OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is a common cause of death in epilepsy and frequently occurs following generalized tonic-clonic seizures (GTCS) in sleep. Postictal generalized electroencephalography (EEG) suppression (PGES), postictal immobility, and periictal respiratory dysfunction are potential risk factors for SUDEP. We sought to determine whether there was a difference in respiratory dysfunction, PGES, and postictal immobility for GTCS occurring during wakefulness or sleep. METHODS: We retrospectively analyzed video-EEG telemetry data in the epilepsy-monitoring unit. Patients' state at seizure onset and seizure characteristics were identified. Respiratory parameters and heart rate were recorded. Presence and duration of PGES and time to first postictal nonrespiratory movement were recorded. RESULTS: There were 165 seizures in 67 patients. There was no significant difference in the duration of postictal immobility in GTCS occurring out of wakefulness or sleep (p = 0.280). Oxygen desaturation nadir (p = 0.572) and duration of oxygen desaturation were not significantly different for GTCS starting during sleep or wakefulness (p = 0.992). PGES occurred more frequently when seizure onset was in sleep than in wakefulness (p = 0.004; odds ratio [OR] 2.760). There was no difference in the duration of PGES between the two groups. SIGNIFICANCE: PGES occurs more commonly after GTCS in sleep than in wakefulness but, in the epilepsy-monitoring unit (EMU), a patient's state at seizure onset does not affect the degree of respiratory dysfunction or duration of postictal immobility. In sleep, outside the hospital setting, GTCS are likely to go unnoticed. Postictal immobility in prone patients prevents head repositioning and unimpeded air exchange. A positive feedback cycle ensues with increasing respiratory distress, potentiating postictal immobility and PGES and eventually leading to asystole. Our findings suggest that the high incidence of nocturnal SUDEP may be related to the unsupervised environment during sleep rather than the severity of sleep-related respiratory dysfunction or PGES duration in the immediate postictal period.

Mitogenomic Meta-Analysis Identifies Two Phases of Migration in the History of Eastern Eurasian Sheep.

Despite much attention, history of sheep (Ovis aries) evolution, including its dating, demographic trajectory and geographic spread, remains controversial. To address these questions, we generated 45 complete and 875 partial mitogenomic sequences, and performed a meta-analysis of these and published ovine mitochondrial DNA sequences (n = 3,229) across Eurasia. We inferred that O. orientalis and O. musimon share the most recent female ancestor with O. aries at approximately 0.790 Ma (95% CI: 0.637-0.934 Ma) during the Middle Pleistocene, substantially predating the domestication event (∼8-11 ka). By reconstructing historical variations in effective population size, we found evidence of a rapid population increase approximately 20-60 ka, immediately before the Last Glacial Maximum. Analyses of lineage expansions showed two sheep migratory waves at approximately 4.5-6.8 ka (lineages A and B: ∼6.4-6.8 ka; C: ∼4.5 ka) across eastern Eurasia, which could have been influenced by prehistoric West-East commercial trade and deliberate mating of domestic and wild sheep, respectively. A continent-scale examination of lineage diversity and approximate Bayesian computation analyses indicated that the Mongolian Plateau region was a secondary center of dispersal, acting as a "transportation hub" in eastern Eurasia: Sheep from the Middle Eastern domestication center were inferred to have migrated through the Caucasus and Central Asia, and arrived in North and Southwest China (lineages A, B, and C) and the Indian subcontinent (lineages B and C) through this region. Our results provide new insights into sheep domestication, particularly with respect to origins and migrations to and from eastern Eurasia.

Y chromosome haplotype diversity of domestic sheep (Ovis aries) in northern Eurasia.

Variation in two SNPs and one microsatellite on the Y chromosome was analyzed in a total of 663 rams representing 59 breeds from a large geographic range in northern Eurasia. SNPA-oY1 showed the highest allele frequency (91.55%) across the breeds, whereas SNPG-oY1 was present in only 56 samples. Combined genotypes established seven haplotypes (H4, H5, H6, H7, H8, H12 and H19). H6 dominated in northern Eurasia, and H8 showed the second-highest frequency. H4, which had been earlier reported to be absent in European breeds, was detected in one European breed (Swiniarka), whereas H7, which had been previously identified to be unique to European breeds, was present in two Chinese breeds (Ninglang Black and Large-tailed Han), one Buryatian (Transbaikal Finewool) and two Russian breeds (North Caucasus Mutton-Wool and Kuibyshev). H12, which had been detected only in Turkish breeds, was also found in Chinese breeds in this work. An overall low level of haplotype diversity (median h = 0.1288) was observed across the breeds with relatively higher median values in breeds from the regions neighboring the Near Eastern domestication center of sheep. H6 is the dominant haplotype in northwestern and eastern China, in which the haplotype distribution could be explained by the historical translocations of the H4 and H8 Y chromosomes to China via the Mongol invasions followed by expansions to northwestern and eastern China. Our findings extend previous results of sheep Y chromosomal genetic variability and indicate probably recent paternal gene flows between sheep breeds from distinct major geographic regions.

A cancer-associated fibroblasts related risk score (CAFscore) helps to guide prognosis and personal treatment for Glioblastoma.

BACKGROUND: Recent studies have identified the presence of cancer-associated fibroblasts (CAFs) within glioblastoma (GBM), yet their biological roles and underlying mechanisms remain poorly understood. This study aimed to construct a CAF-related prognostic model to guide patient prognosis and treatment strategies. METHOD: We employed various bioinformatics methods, including enrichment analysis, Weighted Gene Co-expression Network Analysis (WGCNA), Lasso regression analysis, and machine learning techniques such as XGBoost and Random Forest, to develop a novel risk index termed CAFscore. Patients were stratified into high and low CAFscore groups for subsequent survival analysis. The area under the curve (AUC) and concordance index (C-index) for CAFscore were calculated and compared against other clinical characteristics and existing prognostic models. Drug sensitivity assessments were conducted using the Oncopredict package. Functional validation of key genes was performed through scratch and invasion assays in GBM cells. RESULTS: Our analyses revealed four core CAF-related genes, leading to the establishment of CAFscore. Notably, patients in the high CAFscore group exhibited significantly reduced survival and exhibited enrichment in epithelial-mesenchymal transition (EMT) and inflammation response pathways. Furthermore, CAFscore showed a significant negative correlation with the sensitivity to irinotecan and its analogs, while demonstrating a positive correlation with sensitivity to 505,124 (a TGFßRI inhibitor). LRP10 emerged as a central gene within the CAFscore, displaying markedly elevated expression in GBM and a strong association with CAF infiltration. Silencing LRP10 significantly inhibited the invasive capabilities of GBM cells. CONCLUSION: This study presented the first CAF related prognostic model (CAFscore) in GBM, and demonstrated that the model could effectively guide patient prognosis and potentially inform personalized treatment strategies. The core gene of CAFscore, LRP10, was significantly overexpressed in GBM and might play a pivotal role in regulating CAF infiltration as well as tumor invasion and metastasis, highlighting LRP10 as a promising therapeutic target for GBM management.

Synthesis of High-Performance Colorless Polyimides with Asymmetric Diamine: Application in Flexible Electronic Devices.

Colorless polyimides (CPIs) are widely used as high-performance materials in flexible electronic devices. From a molecular design standpoint, the industry continues to encounter challenges in developing CPIs with desired attributes, including exceptional optical transparency, excellent thermal stability, and enhanced mechanical strength. This study presents and validates a method for controlling 2-substituents, with a specific emphasis on examining how these substituents affect the thermal, mechanical, optical, and dielectric characteristics of CPIs. The presence of two CF3 groups on the same side of the diamine structure ensured the transmittance of the film. The charge transfer effect and the molecular distance are dynamically regulated by changing the 2-substituent (-OCH3/-CH3/H/F). The polyimide exhibited a well-maintained equilibrium between transparency and thermal stability, with a T500nm value ranging from 86.2 to 89.6% in the visible region, and a glass transition temperature (Tg) ranging from 358.6 to 376.0 °C. Additionally, the 6FDA-2-MTFMB compound, when combined with methyl, excels as a protective layer and base material, exhibiting excellent performance in various aspects. It has been verified as an appropriate option for flexible photodetectors and wearable piezoresistive sensors. In summary, this systematic investigation will provide a comprehensive and demonstrative methodology for developing CPIs that are capable of adapting to flexible electronic devices.

Interaction between Dietary Lactoferrin and Gut Microbiota in Host Health.

The gut microbiota are known to play an important role in host health and disease. Alterations in the gut microbiota composition can disrupt the stability of the gut ecosystem, which may result in noncommunicable chronic diseases (NCCDs). Remodeling the gut microbiota through personalized nutrition is a novel therapeutic avenue for both disease control and prevention. However, whether there are commonly used gut microbiota-targeted diets and how gut microbiota-diet interactions combat NCCDs and improve health remain questions to be addressed. Lactoferrin (LF), which is broadly used in dietary supplements, acts not only as an antimicrobial in the defense against enteropathogenic bacteria but also as a prebiotic to propagate certain probiotics. Thus, LF-induced gut microbiota alterations can be harnessed to induce changes in host physiology, and the underpinnings of their relationships and mechanisms are beginning to unravel in studies involving humans and animal models.

Interictal interleukin-17A levels are elevated and correlate with seizure severity of epilepsy patients.

Interleukin 17A (IL-17A) is implicated in the pathogenesis of several neuroimmunologic diseases. We aimed to evaluate the relationship between IL-17A and seizure severity in patients with epilepsy. Seventy patients with probable symptomatic epilepsy and 68 healthy controls were included. Interictal serum IL-17A and related cytokine (IL-23, IL-6, IL-1ß, interferon gamma (IFN-γ), and IL-10) levels were measured. The relationship between seizure severity and cytokine concentrations was assessed by Spearman correlation and multivariate linear regression test. IL-17A levels in the cerebrospinal fluid (CSF) were tested in 30 additional patients with epilepsy, either in the postictal or interictal period and 15 patients with idiopathic inflammatory demyelinating diseases (IIDDs). Interictal serum IL-17A levels were significantly elevated in patients with epilepsy compared to controls. IL-6, IFN-γ, and IL-1ß levels were also markedly elevated. Spearman correlation analysis revealed positive correlation between IL-17A, IL-6 levels and Veterans Administration Seizures Frequency and Severity Rating Scale score(VA score); IFN-γ, IL-10 levels, and National Hospital Seizure Severity Scale (NHS3) score. In addition, IL-17A levels correlated significantly with seizure frequency. Multivariate linear regression test showed that only IL-17A levels were independently positively correlated with VA scores (B = 0.288, p = 0.027). Postictal IL-17A levels in the CSF were significantly elevated compared to interictal patients and patients with IIDDs. Our results suggest that interictal IL-17A levels correlated highly with seizure severity.

Increased ratio of glutamate/glutamine to creatine in the right hippocampus contributes to depressive symptoms in patients with epilepsy.

PURPOSE: Our study aimed to investigate whether the glutamatergic system in the hippocampus is correlated with depressive symptoms in patients with epilepsy. METHODS: Fifty patients with epilepsy were recruited and divided into three groups on the basis of their Hamilton Depression Rating Scale (HAMD) scores. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) was carried out. Pearson correlation analysis and multiple linear regression analysis were performed to investigate any correlation between the variables of hippocampal metabolites and HAMD scores. RESULTS: Proton magnetic resonance spectroscopy analysis showed that the ratio of glutamate/glutamine to creatine (Glx/Cr) in the right hippocampus was significantly increased in patients with moderate depression and correlated positively with HAMD scores. Multiple linear regression analysis showed that the ratio of Glx/Cr in the right hippocampus was an independent risk factor relating to depressive symptoms in patients with epilepsy. CONCLUSION: A disturbance of the hippocampal glutamatergic system may be involved in the pathogenesis of depression in epilepsy.

Complexed Crystal Structure of the Dihydroorotase Domain of Human CAD Protein with the Anticancer Drug 5-Fluorouracil.

Dihydroorotase (DHOase) is the third enzyme in the pathway used for the biosynthesis of pyrimidine nucleotides. In mammals, DHOase is active in a trifunctional enzyme, CAD, which also carries out the activities of carbamoyl phosphate synthetase and aspartate transcarbamoylase. Prior to this study, it was unknown whether the FDA-approved clinical drug 5-fluorouracil (5-FU), which is used as an anticancer therapy, could bind to the DHOase domain of human CAD (huDHOase). Here, we identified huDHOase as a new 5-FU binding protein, thereby extending the 5-FU interactome to this human enzyme. In order to investigate where 5-FU binds to huDHOase, we solved the complexed crystal structure at 1.97 Å (PDB ID 8GVZ). The structure of huDHOase complexed with malate was also determined for the sake of comparison (PDB ID 8GW0). These two nonsubstrate ligands were bound at the active site of huDHOase. It was previously established that the substrate N-carbamoyl-L-aspartate is either bound to or moves away from the active site, but it is the loop that is extended towards (loop-in mode) or moved away (loop-out mode) from the active site. DHOase also binds to nonsubstrate ligands via the loop-out mode. In contrast to the Escherichia coli DHOase model, our complexed structures revealed that huDHOase binds to either 5-FU or malate via the loop-in mode. We further characterized the binding of 5-FU to huDHOase using site-directed mutagenesis and the fluorescence quenching method. Considering the loop-in mode, the dynamic loop in huDHOase should be a suitable drug-targeting site for further designing inhibitors and clinical chemotherapies to suppress pyrimidine biosynthesis in cancer cell lines.

Interictal Heart Rate Variability as a Biomarker for Comorbid Depressive Disorders among People with Epilepsy.

Depressive disorders are common among people with epilepsy (PwE). We here aimed to report an unbiased automatic classification of epilepsy comorbid depressive disorder cases via training a linear support vector machine (SVM) model using the interictal heart rate variability (HRV) data. One hundred and eighty-six subjects participated in this study. Among all participants, we recorded demographic information, epilepsy states and neuropsychiatric features. For each subject, we performed simultaneous electrocardiography and electroencephalography recordings both in wakefulness and non-rapid eye movement (NREM) sleep stage. Using these data, we systematically explored the full parameter space in order to determine the most effective combinations of data to classify the depression status in PwE. PwE with depressive disorders exhibited significant alterations in HRV parameters, including decreased time domain and nonlinear domain values both in wakefulness and NREM sleep stage compared with without depressive disorders and non-epilepsy controls. Interestingly, PwE without depressive disorder showed the same level of HRV values as the non-epilepsy control subjects. The SVM classification model of PwE depression status achieved a higher classification accuracy with the combination of HRV parameters in wakefulness and NREM sleep stage. Furthermore, the receiver operating characteristic (ROC) curve of the SVM classification model showed a satisfying area under the ROC curve (AUC: 0.758). Intriguingly, we found that the HRV measurements during NREM sleep are particularly important for correct classification, suggesting a mechanistic link between the dysregulation of heart rate during sleep and the development of depressive disorders in PwE. Our classification model may provide an objective measurement to assess the depressive status in PwE.