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Thanks to the precise astrometric measurements of proper motions by the Gaia mission, a new tidal stellar stream has been discovered in the northern hemisphere. The distribution of star count shows that the stream is approximately 80° long and 1.°70 wide. Observations of 21 member stars, including 14 RR Lyrae stars, indicate that the stream has an eccentric and retrograde orbit with e = 0.58. The low metallicity, high total energy, and large angular momentum suggest that it is associated with the merging event Sequoia. This discovery suggests the possibility of finding more substructures with high eccentricity orbits, even in the inner halo. [ABSTRACT FROM AUTHOR]

Objectives: In physiological situations, the anterior cingulate cortex (ACC) and anterior insular cortex (AIC) are prone to coactivation. The functional connectivity and interaction between ACC and AIC in the context of epilepsy remain unclear. This study aimed to investigate the dynamic coupling between these two brain regions during seizures. Methods: Patients who underwent stereoelectroencephalography (SEEG) recording were included in this study. The SEEG data were visually inspected and quantitatively analyzed. The narrowband oscillations and aperiodic components at seizure onset were parameterized. The frequency‐specific non‐linear correlation analysis was applied to the functional connectivity. The excitation/inhibition ratio (E:I ratio) reflected by the aperiodic slope was performed to evaluate the excitability. Results: Twenty patients were included in the study, with 10 diagnosed with anterior cingulate epilepsy and 10 with anterior insular epilepsy. In both types of epilepsy, the correlation coefficient (h2) between the ACC and AIC at seizure onset exhibited a significantly higher value than that during interictal and preictal periods (p < 0.05). The direction index (D) showed a significant increase at seizure onset, serving as an indicator for the direction of information flow between these two brain regions with up to 90% accuracy. The E:I ratio increased significantly at seizure onset, with the seizure‐onset zone (SOZ) demonstrating a more pronounced increase compared to non‐SOZ (p < 0.05). For seizures originating from AIC, the E:I ratio was significantly higher in the AIC than in the ACC (p = 0.0364). Conclusions: In the context of epilepsy, the ACC and AIC are dynamically coupled during seizures. The functional connectivity and excitability exhibit a significant increase at seizure onset. By analyzing connectivity and excitability, the SOZ in ACC and AIC can be identified. The direction index (D) serves as an indicator for the direction of information flow from SOZ to non‐SOZ. Notably, the excitability of SOZ changes more significantly than that of non‐SOZ. [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]

Helium variations are common features of globular clusters (GCs) with multiple stellar populations. All the formation scenarios predict that secondary population stars are enhanced in helium, but the exact helium content depends on the polluters. Therefore, searching for helium variations in a star cluster is a straightforward method to understand whether it hosts multiple populations or not and to constrain the formation scenario. Although this topic has been well explored for Galactic GCs, GCs beyond the Milky Way are challenging to study because of their large distances. This work studies the helium distribution of GK-type main-sequence (MS) dwarfs in an old (∼12.5 Gyr) GC in the Large Magellanic Cloud, NGC 2210, using the deep photometry observed by the Hubble Space Telescope. We compare the observed morphology of the MS with that of synthetic populations with different helium distributions. We confirm that NGC 2210 dwarfs have a helium spread, with an internal dispersion of δ Y ∼ 0.06–0.07. The fraction of helium-enriched stars depends on the δ Y distribution. A continuous δ Y distribution would indicate that more than half of MS stars are helium enriched (∼55%). If the δ Y distribution is discrete (bimodal), a fraction of ∼30% enriched stars is able to explain the observed morphology of the MS. We also find that the He-enriched population stars are more centrally concentrated than He-normal stars. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a hereditary skeletal disorder that is mainly caused by variants in COL1A1/2. So far, no specific treatment has been developed to correct its underlying etiology. We aimed to gain a better understanding of the pathological mechanisms of OI and develop gene therapies to correct OI‐causing variants. A de novel cis‐double‐variant c.[175C>T; 187T>A] in COL1A1 was identified from a 5‐year‐old OI patient by whole‐exome sequencing (WES). Three peptide nucleic acids (PNAs) were designed and then transfected patient‐derived fibroblasts. PNA2 affected the translational strand and induced an optimal interfering effect at 0.25μM concentration, proved by Sanger sequencing, qPCR, Western blot, and immunostaining. Additionally, induced pluripotent stem cells (iPSCs) were cultured from patient‐derived fibroblasts. Clones of iPSCs with c.187T>A variant and those with both variants largely restored their osteogenic capacities after CRISPR/Cas9 gene editing, which corrected the variants. Importantly, correcting c.187T>A variant alone in CRISPR‐edited iPSCs was sufficient to alleviate OI phenotypes, as indicated by increased levels of COL1A1, COL1A2, ALP mRNAs, and COL1A1 protein. Our findings suggest that c.187T>A is the dominant variant of cis‐double‐variant in COL1A1 that led to OI, and PNA interference and CRISPR/Cas9 gene editing may be new therapeutic tools for OI treatment. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background: Mycoplasma hyopneumoniae, the primary pathogen responsible for porcine enzootic pneumonia, reduces average daily weight gain and causes substantial economic losses to the pig industry worldwide. Vaccination is the most common strategy to control this disease but offers partial protection. Therefore, developing next‐generation vaccines by screening protective antigens is crucial. Objectives: The aim of this study was to evaluate the antibody response to 33 recombinant proteins in pigs naturally infected with M. hyopneumoniae. Methods: The genes encoding 33 (hypothetical) membrane proteins or secretory proteins were ligated into pGEX‐6P‐1, pGEX‐6P‐2, pGEX‐5X‐3 or pGEX‐4T‐3 vectors and transformed into Escherichia coli BL21(DE3) or E. coli XL‐1 Blue to construct recombinant bacteria and to express the recombinant proteins. The recombinant bacteria expressing the target proteins reacted with porcine convalescent sera and negative sera to screen immunodominant proteins by ELISA. Then, recombinant bacteria expressing immunodominant proteins were used to identify the discriminating immunodominant proteins that were recognised by convalescent sera nut not hyperimmune sera. Results: All recombinant bacteria could express the target recombinant proteins in soluble form. Twenty‐one proteins were shown to present immunodominant antigens, and four proteins were not recognised by convalescent sera. Moreover, six proteins were considered discriminating and reacted with convalescent sera but not with hyperimmune sera. Conclusions: The identified immunodominant proteins were antigenic and expressed during bacterial infection, suggesting that these proteins, especially those capable of discriminating between sera, can be used to identify protective antigens with the view to develop more effective vaccines against M. hyopneumoniae infection. [ABSTRACT FROM AUTHOR]

Context: Ischemic stroke is the most common type of acute cerebrovascular disease. Carnosol is a polyphenol compound extracted from rosemary. Objective: This study aimed to explore the effects of carnosol on the oxygen-glucose deprivation (OGD) treated BV2 microglia cells. Materials and methods: MTT and EdU assays were used to detect the cell viability and proliferation. Flow cytometry was conducted to measure the apoptosis rates. Additionally, the protein expression was determined by western blot. The inflammatory factors and antioxidant indexes were detected by corresponding kits. Results and discussion: Carnosol promoted the proliferation and inhibited the apoptosis of the OGD treated BV2 cells. What's more, the protein expressions of PCNA and Bcl-2 were up-regulated, the Bax expression was down-regulated after carnosol treatment. In addition, carnosol decreased the levels of MDA, LPO, TNF-α, IL-1β and IL-6, and increased the levels of GSH, SOD, IL-4 and IL-10 in the OGD treated BV2 cells. Furthermore, the PI3K/AKT/mTOR signaling pathway was activated after carnosol treatment and inhibition of the PI3K/AKT/mTOR signaling pathway reversed the carnosol effects. Conclusions: Carnosol promotes the proliferation, inhibits the apoptosis, relieves the oxidative damage and inflammation of OGD treated cells through regulating the PI3K/AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs), as a novel platform for the synthesis of metal nanoparticles, display abundant properties of adjustable porosity, high crystallinity and large surface area. In particular, three-dimensional (3D)-COFs are unique skeletons with greater surface areas, numerous easily accessible active sites and interpenetrating channels compared to 2D-COFs. These eminent properties of 3D-COFs are very beneficial for anchoring metal nanoparticles, and effectively restrict the size and growth of nanoparticles, enhancing the catalytic performance. In this study, we prepare hybrid nano-materials (denoted as AgNPs-3D-COF) based on Ag nanoparticles and a hydroxy functional 3D-COF. The strong coordination between OH groups and metal Ag and finite aperture generate uniform and small size Ag nanoparticles. When applied to the catalytic reduction of 4-nitrophenol and the degradation of organic dyes, namely methylene blue and Congo red, AgNPs-3D-COF delivers high activity and enduring cycling stability. We expect that this study can offer a strategy for constructing advanced heterogeneous metal nanoparticle catalysts and accelerate the advancements of 3D-COFs. [ABSTRACT FROM AUTHOR]

Saxifraga species are widely distributed in alpine and arctic regions in the Northern hemisphere. Highly morphological diversity within this genus brings great difficulties for species identification, and their typical highland living properties make it interesting how they adapt to the extreme environment. Here, we newly generated the chloroplast (cp) genomes of two Saxifraga species and compared them with another five Saxifraga cp genomes to understand the characteristics of cp genomes and their potential roles in highland adaptation. The genome size, structure, gene content, GC content, and codon usage pattern were found to be highly similar. Cp genomes ranged from 146,549 bp to 151,066 bp in length, most of which comprised 130 predicted genes. Yet, due to the expansion of IR regions, the second copy of rps19 in Saxifraga stolonifera was uniquely kept. Through sequence divergence analysis, we identified seven hypervariable regions and detected some signatures of regularity associated with genetic distance. We also identified 52 to 89 SSRs and some long repeats among seven Saxifraga species. Both ML and BI phylogenetic analyses confirmed that seven Saxifraga species formed a monophyletic clade in the Saxifragaceae family, and their intragenus relationship was also well supported. Additionally, the ndhI and ycf1 genes were considered under positive selection in species inhabiting relatively high altitudes. Given the conditions of intense light and low CO2 concentration in the highland, the products of these two genes might participate in the adaptation to the extreme environment. [ABSTRACT FROM AUTHOR]

Despite much attention on the history of goat evolution, information on origin, demographic history, and expansion route remains controversial. To address these questions, we collected 4,189 published goat DNA sequences including 1,228 sequences from 57 breeds in China and 2,961 sequences including 193 goat breeds from 71 other countries and carried out an integrated analysis. We found goat breeds from South China had the highest genetic diversity of lineage B, and subclades B2 only were found in Southwest China, suggesting that lineage B (particularly, subclade B2) probably originated from Southwest China and its surrounding areas. In addition, in this study, we found that lineage A from South China also presented higher genetic diversity and earlier expansion time (10, 606 years ago), even earlier than breeds from the Middle East. Hence, we speculated that South China and surrounding areas were the origin of lineage B and also the transportation hub for lineage A spreading to North China and Southwest Asia. Furthermore, according to the analysis of correlation between genetic differentiation value λ1 and λ2 and geographical distance, we further confirmed two phases of migration in goat breeds of North China. These results will contribute to a better understanding of the origin and migration history of domestic goat. [ABSTRACT FROM AUTHOR]

The color–magnitude diagrams of young star clusters show that, particularly at ultraviolet wavelengths, their upper main sequences (MSs) bifurcate into a sequence comprising the bulk population and a blue periphery. The spatial distribution of stars is crucial to understanding the reasons for these distinct stellar populations. This study uses high-resolution photometric data obtained with the Hubble Space Telescope to study the spatial distributions of the stellar populations in seven Magellanic Cloud star clusters. The cumulative radial number fractions of blue stars within four clusters are strongly anticorrelated with those of the high mass ratio binaries in the bifurcated region, with negative Pearson coefficients <−0.7. Those clusters are generally young or in an early dynamical evolutionary stage. In addition, a supporting N-body simulation suggests that the increasing percentage of blue MS stars from the cluster centers to their outskirts may be associated with the dissolution of soft binaries. This study provides a different perspective to explore the MS bimodalities in young clusters and adds extra puzzles. A more comprehensive study combined with detailed simulations is needed in the future. [ABSTRACT FROM AUTHOR]

Background: Ischemia/reperfusion (I/R)-induced stroke is a long-lasting disability. Numerous reports have demonstrated that inflammation is the major cause of ischemic cerebral injury. Therefore, it is important to develop an effective anti-inflammatory agent for the attenuation of I/R-induced brain injury. Objective: In this study, we examined the therapeutic role of kirenol against I/R-induced neuronal damage by inhibiting inflammation in Sprague-Dawley (SD) rats. Materials and Methods: I/R was induced in SD rats and subsequently were administered with 10 and 20 mg/kg of kirenol. Then, we assessed the neurological score, brain water content, and infarct size. The level of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione, and acetylcholinesterase, as well as the levels of malondialdehyde, was measured by using standard methods. The level of tumor necrosis factor (TNF)-α interleukin (IL)-1 β, IL-4, IL-6, and IL-10; and vascular endothelial growth factor was measured using standard kits. The targeted messenger RNA expression (NLRP3, NLRP4, TLR-4, TNF-α, caspase-1, ASC, and IL-1β) was quantified by polymerase chain reaction technique. Histopathological analysis of the brain tissue was performed. Results: According to our results, kirenol decreased the neurological deficit score, ameliorated the motor function, suppressed oxidative stress, reduced inflammation, and mediated the inhibition of TLR4/NLRP3-mediated inflammatory pathway. Conclusion: In conclusion, these findings demonstrate the protective effects of kirenol against I/R-induced cerebral injury. The mechanism of action is associated with the inhibition of inflammation through halting the TLR4/NLRP3 signaling pathway. In summary, kirenol is a potentially new compound which can be used to improve therapeutic strategies for stroke treatments. [ABSTRACT FROM AUTHOR]

Finger citron (FC) is one of many traditional Chinese herbs that have been used to treat obesity. The aim of this study was to elucidate the pharmacological effects and mechanisms of FC on obese rats. Rats were fed with a high-fat diet as a model of obesity and treated with FC at three different dosages for 6 weeks. Pathology in liver tissue was observed. Glucose levels, lipids levels, and inflammatory indicators in serum were evaluated by enzyme‐linked immunosorbent assay. Furthermore, the expression of G protein-coupled receptor 5 (TGR5) pathway genes in rat colon tissue was detected by reverse transcription-polymerase chain reaction analysis (RT-PCR). Our result revealed that FC alleviates obesity by reducing body weight (BW) and waist circumference, managing inflammation and improving glycolipid metabolism, liver function, and liver lipid peroxidation in vivo. In addition, the mechanism of FC on obesity is possibly the stimulation of glucagon-like peptide-1 (GLP-1) secretion by activating the TGR5 pathway in intestinal endocrine cells. Our studies highlight the obesity reduction effects of FC and one of the mechanisms may be the activation of the TGR5 pathway in intestinal endocrine cells. [ABSTRACT FROM AUTHOR]

Multiple stellar populations (MPs) with different chemical compositions are not exclusive features of old globular clusters (older than 10 Gyr). Indeed, recent studies reveal that younger clusters (∼2–6 Gyr-old) in the Magellanic Clouds also exhibit star-to-star chemical variations among evolved stars. However, whether MPs are present among less-evolved dwarfs of these intermediate-age clusters is still unclear. In this work, we search for chemical variations among GK-type dwarfs in the ∼2 Gyr old cluster NGC 1978, which is the youngest cluster with MPs. We exploit deep ultraviolet and visual observations from the Hubble Space Telescope to constrain the nitrogen (N) and oxygen (O) variations among main-sequence (MS) stars. To do this, we compare appropriate photometric diagrams that are sensitive to N and O with synthetic diagrams of simple stellar populations and MPs. We conclude that the G- and K-type MS stars in NGC 1978 host MPs. Our statistical analysis shows that the fraction of N-rich stars ranges from ∼40% to ∼80%, depending on the detailed distributions of N and O. [ABSTRACT FROM AUTHOR]

Osteogenesis imperfecta (OI) is a rare heritable skeletal disorder which is mainly caused by defected type I collagen. Autosomal recessive OI (AR-OI) is caused by mutations of genes that are responsible for type I collagen modification and folding, and is often associated with more severe phenotypes. Due to the limited number of recessive OI patients, it has been difficult to study the mutation spectrum as well as the correlation of genotype and phenotype. This study recruited a Chinese cohort of 74 AR-OI families, aiming to establish the mutation spectrum and to examine the genotypic and phenotypic correlation. We identified 82 variants including 25 novel variants and 57 HGMD reported variants in these AR-OI patients, using whole exome sequencing/panel sequencing combined with Sanger sequencing. Pathogenic mutations were found at WNT1 (n = 30, 40.54%), SERPINF1 (n = 22, 29.73%), FKBP10 (n = 10, 13.51%), CRTAP (n = 3, 4.05%), P3H1 (n = 3, 4.05%), SERPINH1 (n = 2, 2.70%), SEC24D (n = 3, 4.05%), and PLOD2 (n = 1, 1.35%) respectively. Thus, WNT1 represents the most frequent pathogenic gene of AR-OI in Chinese population. The most common clinical manifestations of AR-OI patients include walking problem (72.86%), scoliosis (65.28%) and frequent fractures (fractures ≥2/year) (54.05%). Interestingly, ptosis represents a unique phenotype of patients carrying WNT1 variants, and it was rare in patients harboring other pathogenic genes. Our study expanded the mutation spectrum of AR-OI and enriched the knowledge of genotypic and phenotypic correlation in Chinese cohort with AR-OI. [ABSTRACT FROM AUTHOR]

Sterculia nobilis Smith pericarp is a by-product of tropical and subtropical fruit Sterculia nobilis Smith, the functional activity and phytochemical composition of which have not been widely reported. In this work, LC-ESI-MS/MS-MRM technique was used for the qualitative and quantitative analysis of 16 phenolic compounds in the ethyl acetate fraction of Sterculia nobilis Smith pericarp extract (EAF). Luteolin-7-O-glucoside, epicatechin gallate and apigetrin were the principal phenolics in the EAF. The hypoglycemic activity of EAF was examined by α-glucosidase and α-amylase inhibition models. EAF inhibited both α-glucosidase and α-amylase activities reversibly and uncompetitively with half-inhibitory concentration (IC 50) values of 69.390 ± 1.410 μg/mL and 2.151 ± 0.044 mg/mL, respectively. Enzyme inhibition mechanism of EAF was studied by spectroscopic methods. The results showed that EAF altered the secondary structure and microenvironment of tyrosine and tryptophan residues of the enzymes. This research demonstrates that Sterculia nobilis Smith pericarp is a potential raw material for production of functional foods at low cost. • Sixteen phenolics were identified in Sterculia nobilis Smith pericarp. • EAF had better inhibitory effects on α-glucosidase than α-amylase. • EAF inhibited both α-glucosidase and α-amylase in uncompetitive manner. • EAF exhibited different fluorescence quenching mechanisms for α-glucosidase and α-amylase. • EAF can decrease postprandial blood sugar levels by delaying the digestion of carbohydrates. [ABSTRACT FROM AUTHOR]