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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]

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]

• Severe inflammation induces prolonged cognitive impairment among C57/BL6 mice. • Prolonged upsurge in hippocampal IL-1β levels exacerbates extended cognitive dysfunction following severe inflammation in C57/BL6 mice. • TRPM2 serves as a mediator of IL-1β's impact on the persistent cognitive impairment resulting from severe inflammation in C57/BL6. • IL-1β expedites astrocyte apoptosis by upregulating TRPM2 activity. Sepsis could lead to chronic cognitive impairment by unclear molecular mechanisms. Transient receptor potential melastatin-2 (TRPM2) is essential against immunity-related activities and inflammation. Our study attempted to decipher the relationship between cognitive impairment caused by severe inflammation and TRPM2 expression levels. Severe inflammation was induced by intraperitoneally injecting C57/BL6 mice with a high dosage (5 mg kg−1) of Lipopolysaccharide (LPS). Fear conditioning and a Morris water maze test were performed to examine the cognitive abilities of the mice. Moreover, the signaling and expression of pro-inflammatory cytokines and TRPM2 were measured using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry and immunofluorescence staining helped to determine the astrocyte apoptosis rate. Severe inflammation can lead to long-term cognitive impairment in C57/BL6 mice. The interleukin-1 beta (IL-1β) levels intra-hippocampus were significantly elevated until P14 post-LPS introduction. At both P7 and P14, there is an up-regulation of TRPM2 expression within hippocampus. Administration of recombinant IL-1β to astrocytes results in a significant up-regulation of TRPM2 expression. IL-1β or TRPM2 level knockdown helped counter the cognitive impairment caused by significant inflammation. A continuous increase in IL-1β levels within the hippocampus can lead to cognitive impairment by enhancing TRPM2 levels caused by severe inflammation. [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]

Background: Enterocytozoon bieneusi, Encephalitozoon spp., Cryptosporidium spp., and Giardia duodenalis (G. intestinalis) are enteric pathogens that cause diarrhea in pigs. This study aimed to determine the prevalence of these enteric parasites and their coinfection with E. bieneusi in diarrheic pigs in Southwest China (Chongqing and Sichuan) using nested polymerase chain reaction (nPCR) based methods. Results: A total of 514 fecal samples were collected from diarrheic pigs from 14 pig farms in Chongqing (five farms) and Sichuan (nine farms) Provinces. The prevalence of Encephalitozoon spp., Cryptosporidium spp. and G. duodenalis was 16.14% (83/514), 0% (0/514), and 8.95% (46/514), respectively. Nested PCR revealed 305 mono-infections of E. bieneusi, six of E. cuniculi, two of E. hellem, and nine of G. duodenalis and 106 concurrent infections of E. bieneusi with the other enteric pathogens. No infections of E. intestinalis and Cryptosporidium species were detected. The highest coinfection was detected between E. bieneusi and E. cuniculi (10.5%, 54/514), followed by E. bieneusi and G. duodenalis (5.8%, 30/514) and E. bieneusi and E. hellem (2.9%, 15/514). E. bieneusi was the most frequently detected enteric pathogen, followed by E. cuniculi, G. duodenalis and E. hellem. There was a significant age-related difference in the prevalence of E. cuniculi in fattening pigs (χ2 = 15.266, df = 3, P = 0.002) and G. duodenalis in suckling pigs (χ2 = 11.92, df = 3, P = 0.008) compared with the other age groups. Sequence analysis of the ITS region of Encephalitozoon species showed two genotypes (II and III) for E. cuniculi and one (TURK1B) for E. hellem. Only G. duodenalis assemblage A was identified in all nested PCR-positive samples. E. bieneusi was found more often than other enteric pathogens. Conclusions: This study showed that E. bieneusi, Encephalitozoon spp. [E. cuniculi and E. hellem] and G. duodenalis were common enteric parasites in diarrheic pigs in Chongqing and Sichuan Provinces. In case of both mono-infection and coinfection, E. bieneusi was the most common enteric pathogen in diarrheic pigs. Thus, it may be a significant cause of diarrhea in pigs. Precautions should be taken to prevent the spread of these enteric parasites. [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]

Sulfonated carbon nanotubes (sCNTs) were prepared by reacting concentrated sulfuric acid with carbon nanotubes (CNTs) on the defect sites. Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) were used to characterize the morphology and structure of sCNTs, respectively. Subsequently, polyaniline (PANI)/nickel hexacyanoferrate (NiHCF)/sCNT interconnected composite films were electrodeposited on the platinum electrode by the one-step co-polymerization using cyclic voltammetry in an aqueous dispersion containing sCNTs. The effect of concentration of NiSO and KFe(CN) in the prepared solution on the morphology and structure of PANI/NiHCF/sCNTs composite films was studied by scanning electron microscopy (SEM), FTIR spectroscopy, and X-ray diffraction (XRD), respectively. The effect of concentration of NiSO and KFe(CN) in the prepared solution on polymerization and electrochemical performance was investigated by cyclic voltammetry (CV), galvanostatic charge/discharge tests, and electrochemical impedance spectroscopy (EIS). One-step electrodeposition mechanism was discussed deeply. It was found that sulfonic acid groups had been attached to surface of CNTs, and sCNTs had higher dispersibility than CNTs in an aqueous dispersion. The morphology of PANI/NiHCF/sCNTs interconnected composite films was remarkably influenced by the concentration of NiSO and KFe(CN). The tubular packing structure appeared with the low concentration of NiSO and KFe(CN) in prepared solution, while the beautiful coral-like interconnected structure exhibited with 0.04 mol L NiSO and 0.04 mol L KFe(CN), which was mainly attributed to the π-π* electron stacking effect among sCNTs, NiHCF, and PANI. The specific capacitance and electroactivity of PANI/NiHCF/sCNTs composite films increased markedly with the increase of concentration of NiSO and KFe(CN) in prepared solution. The specific capacitance of PANI/NiHCF/sCNTs composite film was 430.77 F g with 0.04 mol L NiSO and 0.04 mol L KFe(CN) due to self-doping effect of sCNT in composite films. The cycle stability of PANI/NiHCF/sCNTs composite films was enhanced with the increase of NiSO and KFe(CN) in prepared solution. [ABSTRACT FROM AUTHOR]

Background: Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K+-Cl- co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development.Methods: Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg-1) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift.Results: Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1β) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (EGABA) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1β mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized EGABA at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1β or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation.Conclusions: Sustained elevation of IL-1β in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development. [ABSTRACT FROM AUTHOR]

The study of a linear regression model with an interval-censored covariate, which was motivated by an acquired immunodeficiency syndrome (AIDS) clinical trial, was first proposed by Gómez et al. They developed a likelihood approach, together with a two-step conditional algorithm, to estimate the regression coefficients in the model. However, their method is inapplicable when the interval-censored covariate is continuous. In this article, we propose a novel and fast method to treat the continuous interval-censored covariate. By using logspline density estimation, we impute the interval-censored covariate with a conditional expectation. Then, the ordinary least-squares method is applied to the linear regression model with the imputed covariate. To assess the performance of the proposed method, we compare our imputation with the midpoint imputation and the semiparametric hierarchical method via simulations. Furthermore, an application to the AIDS clinical trial is presented. [ABSTRACT FROM PUBLISHER]

To explore the dependences of morphology and electrochemical performance of polyaniline/nickel hexacyanoferrate (PANI/NiHCF) nanogranules on pH value of the reaction system, electrodeposition of PANI/NiHCF nanogranules was performed across a pH range from 0 to 7 on carbon nanotubes (CNTs)-modified platinum substrate by cyclic voltammetry in a mixture of 0.002 mol L NiSO, 0.25 mol L NaSO, 0.002 mol L KFe(CN), and 0.01 mol L aniline solutions. The morphology and structure of PANI/NiHCF nanogranules were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy, respectively. The supercapacitive performances of the nanogranules were investigated with cyclic voltammetry (CV), charge/discharge tests, and electrochemical impedance spectroscopy (EIS). The results showed that the nanogranules with different morphology and sizes were obtained with the change of pH values from 0 to 7, which could control the mechanism of homogeneous or heterogeneous nucleation directly. The nanogranules were dispersed in matrix uniformly at pH 0 and pH 1, while the size of which decreased with the increase of pH values. The smooth cross-linking network structure was found from pH 2 to 7. The structure of PANI/NiHCF nanogranules had slightly changed from pH 0 to 7. PANI/NiHCF nanogranules had good electrochemical performance from pH 0 to 7 in a mixture of 0.5 mol L HSO and 0.5 mol L KNO solutions, and the highest specific capacitance value of 274 F g was obtained at current densities of 2 mA cm in neutral medium. PANI/NiHCF nanogranules had high stability in neutral medium after 2,000 cycles by CV. [ABSTRACT FROM AUTHOR]

For time series nonparametric regression models with discontinuities, we propose to use polynomial splines to estimate locations and sizes of jumps in the mean function. Under reasonable conditions, test statistics for the existence of jumps are given and their limiting distributions are derived under the null hypothesis that the mean function is smooth. Simulations are provided to check the powers of the tests. A climate data application and an application to the US unemployment rates of men and women are used to illustrate the performance of the proposed method in practice. [ABSTRACT FROM AUTHOR]

Highlights: [•] Gene expression profile in microglial cell line BV2 infected with RABV was analyzed. [•] Infection of rabies virus modulates gene expression in BV2. [•] Regulated genes were mainly involved in innate immune responses. [•] Microglia might regulate immune responses in the CNS after rabies virus infection. [ABSTRACT FROM AUTHOR]

Chronic cerebral ischemia (CCI) refers to long-term hypoperfusion of cerebral blood flow with the main clinical manifestations of progressive cognitive impairment. The pathological mechanism of CCI is complex, and there is a lack of effective treatments. Salvianolic acid A (SalA) is a neuroprotective extract of Salvia miltiorrhiza with the effects of anti-inflammation and anti-apoptosis. In this study, the effect of SalA on cognitive function and Drd2/Cryab/NF-κB signaling pathway in rats with CCI was investigated. Morris water maze and open field test were used to observe the effects of SalA on the cognitive function of CCI rats. The pathological changes in the brain were observed by HE, Nissl, and LFB staining. TUNEL staining, enzyme-linked immunosorbent assay, and western blot analysis were used to detect the inflammatory and apoptosis in the cortex and hippocampus. The expression of Drd2/Cryab/NF-κB pathway-related molecules and Drd2 localization were detected by western blotting and dual immunofluorescence, respectively. SH-SY5Y cells were exposed to chronic hypoglycemic and hypoxic injury in vitro, and Drd2 inhibitor haloperidol was used to verify the involved pathway. The results showed that SalA could improve the cognitive function of CCI rats, reduce pathological damage of cortex and hippocampus, inhibit neuroinflammation and apoptosis, and suppress the activation of NF-κB by regulating Drd2/Cryab pathway. And SalA inhibited NF-κB activation and nuclear translocation in SH-SY5Y cells by upregulating Drd2/Cryab pathway, which was reversed by haloperidol interference. In conclusion, SalA could relieve CCI-induced cognitive impairment in rats, at least partly through the Drd2/Cryab/NF-κB pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

For nonparametric time series regression, we propose to apply polynomial splines to squared residuals to develop the variance function estimation. Furthermore, we obtain and use simultaneous confidence bands to detect certain parametric forms for entire variance curves. The proposed method is extremely fast. Asymptotic results are established under the assumption that observations are from a strictly stationary $\alpha$-mixing process. Simulations and a financial data set application are provided to illustrate the performance of the proposed method numerically. [ABSTRACT FROM AUTHOR]

• The allopolyploid Isoetes sinensis is only distributed in the plain, but has a plateau parent Isoetes yunguiensis. • The strong ultraviolet radiation (UV) might be major stress for I. sinensis in the plateau adaptation. • Crassulacean acid metabolism (CAM) intensity of I. sinensis might positively associate with the altitude. Relatively high frequencies of polyploidy are generally found in high-altitude regions. However, more diploid than polyploid species of Isoetes are distributed in plateau environments in China. The low-altitude species Isoetes sinensis originates from the allopolyploidization between a plateau parent and another low altitude species. To study potential ecological adaptation to plateau environments in the allopolyploid I. sinensis , we transplanted individuals of I. sinensis to different altitudes. RNA sequencing was performed to elucidate the molecular response of this species' ecological adaptation to plateaus. More unique differentially expressed genes (DEGs) were detected in individuals transplanted to the Qinghai–Tibet Plateau (QTP) than elsewhere, such as genes for ribosomal proteins (RPs) and succinate dehydrogenase (SDH), which helped them adapt to higher altitudes under both terrestrial and submerged conditions. In both terrestrial and submerged conditions, the expression of a large number of genes changed to help plants adapt to exposure to the high levels of ultraviolet (UV) radiation on plateaus, such as the genes associated with the accumulation of flavonoids, decreasing chlorophyll content, and reducing light harvesting activity. The expression of vacuolar-type H+-transporting ATPase (V-ATPase) and phosphoenolpyruvate carboxylase (PEPC) increased with altitude, revealing that the intensity of the crassulacean acid metabolism (CAM) of I. sinensis might be positively associated with altitude. In general, our results reveal that although I. sinensis only lives at low altitudes, it can still adapt to plateau stress by regulating the expression of certain key genes. The potential ecological adaptation to plateau environments in the allopolyploid I. sinensis may have been inherited from the plateau parent. [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]

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]

Computed tomography (CT) scans of acute cerebral hemorrhage are often characterized by high-density imaging with occasional mixed density and low-density imaging features. Possible reasons for this are a lack of blood coagulation, extravasation of cerebrospinal fluid, and brain tissue edema. It is rarely due to the accumulation of lipid components associated with hyperlipidemia. In the present case, preoperative lipid tests and the intraoperative finding of a large amount of milky white fluid surrounding the hematoma confirmed that the low-density imaging surrounding the hematoma visible on the CT scan represented a rare case of lipid accumulation. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is overexpressed in a wide range of solid tumors. In this study, we exploited a high-affinity EGFR-antagonistic affibody (Z EGFR) coupled to a doxorubicin loaded pegylated liposome (LS-Dox) for concurrent passive and active targeting of EGFR+ A431 tumor cells in vitro and in vivo. The in vitro studies revealed that the Dox liposomes coupled with Z EGFR (AS-Dox) showed a higher Dox uptake than LS-Dox in EGFR+ A431 cells but not in EGFR− B16F10 cells, resulting in a selectively enhanced cytotoxicity. In vivo , AS-Dox confirmed its long circulation time and efficient accumulation in tumors. This targeted chemotherapy achieved greater tumor suppression. Further, this low-dose but effective targeted treatment reduced systemic toxicity such as body weight loss and organ injury demonstrated by H&E staining. Thus, selective targeting of LS-Dox coupled with Z EGFR enhanced antitumor effects and improved systemic safety. These results demonstrated that LS-Dox coupled with Z EGFR might be developed as a potential tool for therapy of EGFR+ tumors. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is an efficient target for cancer therapy. In this study, a high-affinity EGFR-antagonistic affibody (Z EGFR) molecule coupled with cisplatin-loaded PEGylated liposomes (LS-DDP) was applied to actively target EGFR+ A431 tumor cells in vitro and in vivo. The LS-DDP coupled with Z EGFR (AS-DDP) had an average size of 140.01 ± 0.84 nm, low polydispersity, a zeta potential of -13.40 ± 0.8 mV, an acceptable encapsulation efficiency of 17.30 ± 1.35%, and released cisplatin in a slow-controlled manner. In vitro , AS-DDP demonstrated a higher amount of platinum intracellular uptake by A431 cells than LS-DDP. The IC50 value of AS-DDP (9.02 ± 1.55 μg/ml) was much lower than that of LS-DDP (16.44 ± 0.87 μg/ml), indicating that the anti-tumor effects of AS-DDP were remarkable due to the modification of Z EGFR. In vivo , the concentration of AS-DDP in the tumor site increased more than 1.76-fold, while an increase in apoptotic cells at 48 h compared to the LS-DDP was also observed, illustrating that AS-DDP possessed excellent tumor-targeting efficiency. As a result, the targeted nano-liposomes achieved greater tumor suppression. Therefore, selective targeting of LS-DDP coupled with Z EGFR enhanced the anti-tumor effects and appeared to be a promising strategy for the treatment of EGFR+ tumors. [ABSTRACT FROM AUTHOR]

Good's syndrome (GS) is an immunodeficiency characterized by thymoma, hypogammaglobulinemia, and impaired T-cell function. Progressive multifocal encephalopathy (PML), an infection caused by JC virus (JCV), usually occurs in patients infected with human immunodeficiency virus (HIV), or in patients on treatment with immunosuppressive or immunomodulatory drugs. There were few reports of PML due to GS, especially with the comorbidity of peripheral neuropathy. We describe a case of an uncommon presentation of PML and peripheral neuropathy in a male who presented with blurred vision, cognitive changes, limb weakness, and numbness over a 4-month period due to GS. To the best of our knowledge, this is the first report of PML and peripheral neuropathy due to GS. This case aims to highlight that it is necessary to consider the possibility of PML due to GS in patients with thymoma and intracranial lesions, and we should focus not only on opportunistic infections of the central nervous system, such as PML, but also on peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: White clover (Trifolium repens L.) is an excellent leguminous cool-season forage with a high protein content and strong nitrogen-fixing ability. Despite these advantages, its growth and development are markedly sensitive to environmental factors. Indole-3-acetic acid (IAA) is the major growth hormone in plants, regulating plant growth, development, and response to adversity. Nevertheless, the specific regulatory functions of Aux/IAA genes in response to abiotic stresses in white clover remain largely unexplored. Results: In this study, we identified 47 Aux/IAA genes in the white clover genome, which were categorized into five groups based on phylogenetic analysis. The TrIAAs promoter region co-existed with different cis-regulatory elements involved in developmental and hormonal regulation, and stress responses, which may be closely related to their diverse regulatory roles. Collinearity analysis showed that the amplification of the TrIAA gene family was mainly carried out by segmental duplication. White clover Aux/IAA genes showed different expression patterns in different tissues and under different stress treatments. In addition, we performed a yeast two-hybrid analysis to investigate the interaction between white clover Aux/IAA and ARF proteins. Heterologous expression indicated that TrIAA18 could enhance stress tolerance in both yeast and transgenic Arabidopsis thaliana. Conclusion: These findings provide new scientific insights into the molecular mechanisms of growth hormone signaling in white clover and its functional characteristics in response to environmental stress. [ABSTRACT FROM AUTHOR]

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]

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]

Key message: Positive selection genes are related to metabolism, while differentially expressed genes are related to photosynthesis, suggesting that genetic adaptation and expression regulation may play independent roles in different gene classes. Genome-wide investigation of the molecular mechanisms for high-altitude adaptation is an intriguing topic in evolutionary biology. The Qinghai-Tibet Plateau (QTP) with its extremely variable environments is an ideal site for studying high-altitude adaptation. Here, we used transcriptome data of 100 individuals from 20 populations collected from various altitudes on the QTP to investigate the adaptive mechanisms of the aquatic plant Batrachium bungei at both the genetic and transcriptional level. To explore genes and biological pathways that may contribute to QTP adaptation, we employed a two-step approach, in which we identified positively selected genes and differentially expressed genes using the landscape genomic and differential expression approaches. The positive selection analysis showed that genes involved in metabolic regulation played a crucial role in B. bungei adaptation to the extreme environments of the QTP, especially intense ultraviolet radiation. Altitude-based differential expression analysis suggested that B. bungei could increase the rate of energy dissipation or reduce the efficiency of light energy absorption by down regulating the expression of photosynthesis-related genes to adapt to the strong ultraviolet radiation. Weighted gene co-expression network analysis identified ribosomal genes as hubs of altitude adaptation in B. bungei. Only a small part of genes (about 10%) overlapped between positively selected genes and differentially expressed genes in B. bungei, suggesting that genetic adaptation and gene expression regulation might play relatively independent roles in different categories of functional genes. Taken together, this study enriches our understanding of the high-altitude adaptation mechanism of B. bungei on the QTP. [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]

Background: Plant organelle genomes are a valuable resource for evolutionary biology research, yet their genome architectures, evolutionary patterns and environmental adaptations are poorly understood in many lineages. Rhodiola species is a type of flora mainly distributed in highland habitats, with high medicinal value. Here, we assembled the organelle genomes of three Rhodiola species (R. wallichiana, R. crenulata and R. sacra) collected from the Qinghai-Tibet plateau (QTP), and compared their genome structure, gene content, structural rearrangements, sequence transfer and sequence evolution rates. Results: The results demonstrated the contrasting evolutionary pattern between plastomes and mitogenomes in three Rhodiola species, with the former possessing more conserved genome structure but faster evolutionary rates of sequence, while the latter exhibiting structural diversity but slower rates of sequence evolution. Some lineage-specific features were observed in Rhodiola mitogenomes, including chromosome fission, gene loss and structural rearrangement. Repeat element analysis shows that the repeats occurring between the two chromosomes may mediate the formation of multichromosomal structure in the mitogenomes of Rhodiola, and this multichromosomal structure may have recently formed. The identification of homologous sequences between plastomes and mitogenomes reveals several unidirectional protein-coding gene transfer events from chloroplasts to mitochondria. Moreover, we found that their organelle genomes contained multiple fragments of nuclear transposable elements (TEs) and exhibited different preferences for TEs insertion type. Genome-wide scans of positive selection identified one gene matR from the mitogenome. Since the matR is crucial for plant growth and development, as well as for respiration and stress responses, our findings suggest that matR may participate in the adaptive response of Rhodiola species to environmental stress of QTP. Conclusion: The study analyzed the organelle genomes of three Rhodiola species and demonstrated the contrasting evolutionary pattern between plastomes and mitogenomes. Signals of positive selection were detected in the matR gene of Rhodiola mitogenomes, suggesting the potential role of this gene in Rhodiola adaptation to QTP. Together, the study is expected to enrich the genomic resources and provide valuable insights into the structural dynamics and sequence divergences of Rhodiola species. [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]

Background: Atelectasis is the primary cause of hypoxemia during general anesthesia. This study aimed to evaluate the impact of the combination of recruitment maneuvers (RM) and positive end-expiratory pressure (PEEP) on the incidence of atelectasis in adult women undergoing gynecologic laparoscopic surgery using pulmonary ultrasound. Methods: In this study, 42 patients with healthy lungs undergoing laparoscopic gynecologic surgery were randomly divided into the recruitment maneuver group (RM group; 6 cm H2O PEEP and RM) or the control group (C group; 6 cm H2O PEEP and no RM), 21 patients in each group. Volume-controlled ventilation was used in all selected patients, with a tidal volume of 6–8 mL·kg−1 of ideal body weight. When atelectasis was detected, patients in the RM group received ultrasound-guided RM, while those in the C group received no intervention. The incidence and severity of atelectasis were determined using lung ultrasound scores. Results: A total of 41 patients were investigated. The incidence of atelectasis was lower in the RM group (40%) than in the C group (80%) 15 min after arrival in the post-anesthesia care unit (PACU). Meanwhile, lung ultrasound scores (LUSs) were lower in the RM group compared to the C group. In addition, the differences in the LUS between the two groups were mainly due to the differences in lung ultrasound scores in the posterior regions. However, this difference did not persist after 24 h of surgery. Conclusions: In conclusion, the combination of RM and PEEP could reduce the incidence of atelectasis in patients with healthy lungs 15 min after arrival at the PACU; however, it disappeared within 24 h after surgery. Trial registration: (Prospectively registered): ChiCTR2000033529. Registered on 4/6/2020. [ABSTRACT FROM AUTHOR]

Stroke is one of the leading causes of death worldwide. Hemorrhagic transformation (HT) is a common serious complication of ischemic stroke (IS) and is related to poor prognosis. Hyperglycemia after stroke is associated with the occurrence of HT and seriously affects the clinical treatment of stroke. Our previous experiments demonstrated that the Xiao-Xu-Ming decoction effective components group (XXMD), which is a Chinese medicine formula reconstituted by active ingredients, has multiple pharmacological effects in the treatment of IS. However, the effects of XXMD on HT after IS remain unclear. Thus, we investigated the preventive effects of XXMD on hyperglycemia-induced HT and further explored the underlying mechanism. Acute hyperglycemia combined with the electrocoagulation cerebral ischemia model was used to establish the HT model. XXMD (37.5, 75, 150 mg/kg/d) was given by gavage for 5 days. Network pharmacology was used to predict potential targets and pathways of XXMD in HT occurrence, and further studies confirmed the related targets. The results showed that hyperglycemia aggravated neurological deficits and blood-brain barrier (BBB) disruption, leading to intracerebral hemorrhage. Pretreatment with XXMD improved neurological function and BBB integrity and inhibited HT occurrence. Network pharmacology revealed that AGE-RAGE-mediated neuroinflammation may be associated with hyperglycemia-induced HT. Further studies confirmed that hyperglycemia activated the AGE-RAGE signaling pathway, increased the expression of HMGB1, TLR4 and p-p65, and induced the release of inflammatory factors and neutrophil infiltration, leading to HT. XXMD could inhibit AGE-RAGE-mediated neuroinflammation. These findings indicated that pretreatment with XXMD alleviated hyperglycemia-induced HT, which may be associated with the inhibition of AGE-RAGE-mediated neuroinflammation. Therefore, XXMD may be a potential therapeutic drug for HT. [Display omitted] • HT is a common and serious complication after ischemic stroke. • Hyperglycemia promotes the occurrence of HT and worsens prognosis of stroke. • Pretreatment with XXMD alleviates BBB disruption and the incidence of HT. • Pretreatment with XXMD inhibits AGE-RAGE-mediated neuroinflammation. [ABSTRACT FROM AUTHOR]

Background: As one of the most common chronic diseases in the world, osteoporosis occurs especially in postmenopausal women. Circular RNAs (circRNAs) are emerging as major drivers in human disease. The aim of the present study was to analyse circRNA expression profiles in osteoporosis and to explore the clinical significance and the regulatory molecular mechanism of hsa_circ_0006859 during osteoporosis. Methods: Exosomes were isolated from clinically collected serum samples. A circRNA microarray was performed to screen differentially expressed circRNAs. Quantitative real-time PCR (qRT-PCR) and western blot were performed to analyse target gene mRNA expression and protein expression. Alizarin red staining (ARS) was performed to evaluate the mineralization ability of human bone marrow mesenchymal stem cells (hBMSCs). Oil Red O staining was performed to evaluate the lipid droplet formation ability of hBMSCs. Bioinformatics analysis and the luciferase reporter assay were performed to investigate the interaction between two genes. Results: Hsa_circ_0006859 was identified as one of the most upregulated circRNAs in the microarray analysis. Hsa_circ_0006859 in exosomes was upregulated in osteoporosis patients compared to healthy controls. Hsa_circ_0006859 differentiated osteopenia or osteoporosis patients from healthy controls with high sensitivity and specificity. Hsa_circ_0006859 suppressed osteoblastic differentiation and promoted adipogenic differentiation of hBMSCs. Hsa_circ_0006859 directly bound to miR-431-5p, and ROCK1 was identified as a novel target gene of miR-431-5p. Hsa_circ_0006859 is a competing endogenous RNA (ceRNA) of miR-431-5p that promotes ROCK1 expression. Hsa_circ_0006859 suppressed osteogenesis and promoted adipogenesis by sponging miR-431-5p to upregulate ROCK1. Conclusions: Exosomal hsa_circ_0006859 is a potential biomarker for postmenopausal osteoporosis and controls the balance between osteogenesis and adipogenesis in hBMSCs by sponging miR-431-5p. [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]

Graphical abstract Highlights • The main problem addressed in this study is the anti-inflammatory effects of Magnolol-a natural extract and the main bioactive component from Magnolia. • U937 LO-2 cells culture and DSS-treated experimental mice were utilized to analyze inflammatory cytokines, proteins activation in MAPK, NF-κB signal pathways regulation, the phagocytosis immunoregulatory effects in vitro and in vivo with that permits analysis of Magnolol contributors to the inflammatory bowel diseases. • By studying living human cell lines, we identified Magnolol previously unknown contributions of enhancement of phagocytosis, specific pro-inflammatory factors IL-6 and IL-1β significantly depression, p-JNK, p-P38, p-IκBα and p-P65 were down-regulation. • We provide experimental evidence to show that Magnolol as a drug could be used to improve human inflammatory bowel disease and gain new insights into the mechanisms involved phagocytosis immunoregulatory effects, MAPK and NF-κB signal pathways. Abstract Magnolol is a natural extract and the main bioactive component from Chinese medicine-Magnolia. We speculate that it's functional action might be associated with the anti-inflammatory effects of magnolol. Herein, the main purpose was to elucidate the phagocytic immune function and anti-inflammatory activities associated. The toxicity of magnolol on U937 and LO-2 cells was assayed by MTT, flow cytometry and laser scanning confocal microscope was utilized to detect the phagocytosis effect on U937 cells, C57BL/6 mice and the follow-up hematoxylin-eosin staining methods were used to evaluate its bioactivity in vivo. The results showed that magnolol had dose dependent effects on enhancement of phagocytosis ability and significantly inhibited the NO production at the concentration range from10 to 40 μM. Furthermore, Magnolol significantly reduced the gene expression and protein release of IL-1β and TNF-α. However, the p-ERK1/2 in MAPK signaling pathway was not significantly affected by magnolol, whereas p-JNK and p-P38 were down-regulated. Magnolol also inhibited the expression of p-IκBα and p-P65 of NF-κB signaling pathways. The loss of body weight and the shorter length of colon were significantly improved in DSS-treated colitis C57BL/6 mice after the administration of magnolol. The cytokines of pro-inflammatory factors TNF-α, IL-6 and IL-1β attenuated significantly in a concentration dependent manner. The histopathological manifestations of 5–20 mg/kg after the treatment magnolol were markedly improved in the DSS-treated mice. These findings showed that magnolol exerted an anti-inflammatory effect through immunoregulatory phagocytosis, MAPK and NF-κB signaling pathways. Our results provide experimental evidence and theory basis for research on anti-inflammatory effects for magnolol as a potentially anti-inflammatory drug candidate. [ABSTRACT FROM AUTHOR]

Background: It has been shown that intracranial atherosclerotic stenosis (ICAS) has heterogeneous features in terms of plaque instability and vascular remodeling. Therefore, quantitative information on the changes of intracranial atherosclerosis and lenticulostriate arteries (LSAs) may potentially improve understanding of the pathophysiological mechanisms underlying stroke and may guide the treatment and work-up strategies. Our present study aimed to use a novel whole-brain high-resolution cardiovascular magnetic resonance imaging (WB-HRCMR) to assess both ICAS plaques and LSAs in recent stroke patients. Methods: Twenty-nine symptomatic and 23 asymptomatic ICAS patients were enrolled in this study from Jan 2015 through Sep 2017 and all patients underwent WB-HRCMR. Intracranial atherosclerotic plaque burden, plaque enhancement volume, plaque enhancement index, as well as the number and length of LSAs were evaluated in two groups. Enhancement index was calculated as follows: ([Signal intensity (SI)plaque/SInormal wall on post-contrast imaging] − [SIplaque/SInormal wall on matched pre-contrast imaging])/(SIplaque / SInormal wall on matched pre-contrast imaging). Logistic regression analysis was used to investigate the independent high risk plaque and LSAs features associated with stroke. Results: Symptomatic ICAS patients exhibited larger enhancement plaque volume (20.70 ± 3.07 mm3 vs. 6.71 ± 1.87 mm3P = 0.001) and higher enhancement index (0.44 ± 0.08 vs. 0.09 ± 0.06 P = 0.001) compared with the asymptomatic ICAS. The average length of LSAs in symptomatic ICAS (20.95 ± 0.87 mm) was shorter than in asymptomatic ICAS (24.04 ± 0.95 mm) (P = 0.02). Regression analysis showed that the enhancement index (100.43, 95% CI − 4.02-2510.96; P = 0.005) and the average length of LSAs (0.80, 95% CI − 0.65-0.99; P = 0.036) were independent factors for predicting of stroke. Conclusion: WB-HRCMR enabled the comprehensive quantitative evaluation of intracranial atherosclerotic lesions and perforating arteries. Symptomatic ICAS had distinct plaque characteristics and shorter LSA length compared with asymptomatic ICAS. [ABSTRACT FROM AUTHOR]

Timely and accurate detection of SARS-CoV-2 variants of concern (VOCs) is urgently needed for pandemic surveillance and control. Great efforts have been made from a mass of scientists in increasing the detection sensitivity and operability, and reducing the turn-around time and cost. Here, we report a nucleic acid testing-based method aiming to detect and discriminate SARS-CoV-2 mutations by combining RT-RPA and CRISPR-Cas12a detecting assays (RRCd). With a detection limit of 10 copies RNA/reaction, RRCd was validated in 194 clinical samples, showing 89% positive predictive agreement and 100% negative predictive agreement, respectively. Critically, using specific crRNAs, representatives of single nucleotide polymorphisms and small deletions in SARS-CoV-2 VOCs including N501Y, T478K and ΔH69-V70 were discriminated by RRCd, demonstrating 100% specificity in clinical samples with C t < 33. The method completes within 65 min and could offer visible results without using any electrical devices, which probably facilitate point-of-care testing of SARS-CoV-2 variants and other epidemic viruses. • A SARS-CoV-2 detection method (RRCd) was developed. • RRCd can detect and discriminate SARS-CoV-2 mutations. • RRCd was validated in 194 clinical samples showing high accuracy and sensitivity. • RRCd is independent of bulk and electrical devices. [ABSTRACT FROM AUTHOR]

6 hsa circ 0006859 suppresses osteogenesis and promotes adipogenesis by sponging miR-431-5p to upregulate ROCK1. a Relative miR-431-5p expression in hBMSCs after transfection with miR-431 M or miR-431I. b ALP activity in hBMSCs after transfection with miR-431 M or miR-431I. c Alizarin red staining was used to detect the mineralization ability of hBMSCs after transfection with miR-431 M or miR-431I. d Oil Red O staining of hBMSCs after transfection with miR-431 M or miR-431I. e Relative ROCK1 mRNA expression in hBMSCs after transfection with OE-ROCK1, si-ROCK1 #1, si-ROCK1 #2, or si-ROCK1 #3. f Western blot analysis of ROCK1 expression in hBMSCs after transfection with OE-ROCK1, si-ROCK1 #1, si-ROCK1 #2, or si-ROCK1 #3. g Alizarin red staining of hBMSCs after transfection with OE-ROCK1 or si-ROCK1. h Oil Red O staining of hBMSCs after transfection with OE-ROCK1 or si-ROCK1. i Alizarin red staining of hBMSCs after transfection with si-NC+EV, si-NC+OE-circ, si-ROCK1+EV, or si-ROCK1+OE-circ. j Oil Red O staining of hBMSCs after transfection with si-NC+EV, si-NC+OE-circ, si-ROCK1+EV, or si-ROCK1+OE-circ Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Correction: Exosomal hsa circ 0006859 is a potential biomarker for postmenopausal osteoporosis and enhances adipogenic versus osteogenic differentiation in human bone marrow mesenchymal stem cells by sponging miR-431-5p Feng Zhi and Yi Ding contributed equally to this work Correction: Stem Cell Res Ther 12, 157 (2021) https://doi.org/10.1186/s13287-021-02214-y Following publication of the original article [[1]], the authors identified that there are image overlap in the Alizarin red staining experiment in Fig. [Extracted from the article]

Natural polysaccharides and their modified derivatives are crucial supplements to the prevention of inflammation. This study aimed to evaluate the effect of sulfated modification on the anti-inflammatory and anti-oxidative activities of Cyclocarya paliurus polysaccharides (CP). A sulfated CP, S-CP1-4 was obtained using chlorosulfonic acid-pyridine method. The chemical components and FT-IR spectrum confirmed that sulfated group was synthesized to the polysaccharide chains successfully. S-CP1-4 was found to inhibit nitric oxide production, phagocytic activity and the release of interleukin (IL)-6 and IL-1β in lipopolysaccharide-treated macrophage cells, RAW 264.7. S-CP1-4 significantly decreased the secretion of IL-6 and TNF-α and the thymus and spleen indexes, and increased the production of IL-10 in lipopolysaccharide-treated mice. S-CP1-4 could better protect the liver by inhibiting the activities of alanine aminotransferase and aspartate aminotransferase, and malondialdehyde level while increasing the superoxide dismutase activity and total anti-oxidative capacity. These results suggested that S-CP1-4 may be an effective anti-inflammatory agent, and sulfated modification may be a reliable method for the development of food supplements. [ABSTRACT FROM AUTHOR]

Inflammation is now believed to be responsible for coronary heart disease (CHD). This belief has stimulated the evaluation of various inflammatory markers for predicting CHD. This study was designed to investigate the association between four inflammatory cytokines (CD121a, interleukin [IL]-1β, IL-8, and IL-11) and CHD. Here, we evaluated 443 patients with CHD and 160 CHD-free controls who underwent coronary angiography. Cytokines were evaluated using flow cytometry, and statistical analyses were performed to investigate the association between cytokine levels and the risk of CHD. Patients with CHD had significantly higher levels of CD121a. The odds ratios for CHD according to increasing CD121a quartiles were 1.00, 1.47 [95% confidence interval (CI): 0.79–2.72], 2.67 (95% CI: 1.47–4.84), and 4.71 (95% CI: 2.65–8.37) in an age- and sex-adjusted model, compared to 1.00, 1.48 (95% CI: 0.70–3.14), 2.25 (95% CI: 1.10–4.62), and 4.39 (95% CI: 2.19–8.79) in a model that was adjusted for multiple covariates. A comparison of the stable angina, unstable angina, and acute myocardial infarction (AMI) subgroups revealed that patients with AMI had the highest CD121a levels, although IL-1β levels were similar across all groups. IL-8 levels were also increased in AMI patients, and IL-11 levels were higher in CHD patients than in non-CHD patients. Correlation analysis revealed a positive association between CD121a, IL-8, and the Gensini score. Together, the significant increase in CD121a levels among CHD patients suggests that it may be a novel inflammatory marker for predicting CHD. [ABSTRACT FROM AUTHOR]

Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18 mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6 h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-α, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-α, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect. [ABSTRACT FROM AUTHOR]

This study investigated the dynamic and long-term efficacy of vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE) induced by tuberous sclerosis complex (TSC). In addition, the impact of VNS on cognition and emotion after a one-year follow-up was evaluated. A total of 17 patients diagnosed with DRE induced by TSC were retrospectively recruited between 2008 and 2019. Dynamic changes in seizure frequency were observed in the responders (≥50% reduction of seizure frequency at last follow-up) and non-responders. Clinical characteristics and seizure outcomes were comprehensively analyzed to determine factors associated with seizure outcomes. The Wechsler intelligence scale was applied in a subgroup of six pediatric patients, whereas the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) were assessed in a subgroup of nine patients to determine the impact of VNS therapy on cognitive performance and emotional state. The follow-up duration for the 17 patients who underwent VNS treatment ranged from 0.5 to 10 years (mean ± SD: 4.1 ± 3.2 years). Monthly seizures decreased significantly from three months to four years post-treatment (p < 0.05). At the last follow-up, 70.6% of the patients achieved at least a 50% reduction in seizure frequency, and three patients were completely seizure free. Comparatively, non-responder patients experienced deterioration of seizure frequency after the first year. Notably, after one-year follow-up the mean standard score of full-scale intelligence quotient increased from 67.33 to 69.5 (p = 0.078) while the mean, standard score of SDS decreased from 49.22 to 45.67 (p = 0.003) compared to preoperative neuropsychological evaluation results. VNS is a safe and effective treatment for patients with DRE caused by TSC. Although early outcomes were encouraging, a follow-up of at least one-year was required to predict long-term outcomes in patients receiving VNS treatment. Moreover, VNS may improve depressive mood in patients with DRE caused by TSC. Further investigations are needed to validate the present results. [ABSTRACT FROM AUTHOR]

A new strategy for preparing amphibious ZnO quantum dots (QDs) with blue fluorescence within hyper-branched poly(ethylenimine)s (HPEI) was proposed in this paper. By changing [Zn2+]/[OH−] molar ratio and heating time, ZnO QDs with a quantum yields (QY) of 30% in ethanol were obtained. Benefiting from the amphibious property of HPEI, the ZnO/HPEI nanocomposites in ethanol could be dissolved in chloroform and water, acquiring a QY of 53%, chloroform and 11% in water. By this strategy, the ZnO/HPEI nano-composites could be applied in not only in optoelectronics, but also biomedical fields (such as bio-imaging and gene transfection). The bio-imaging application of water-soluble ZnO/HPEI nanocomposites was investigated and it was found that they could easily be endocytosed by the COS-7 cells, without transfection reagent, and they exhibited excellent biological imaging behavior. [ABSTRACT FROM AUTHOR]

A new strategy for nanocrystal encapsulation, release and application based on pH-sensitive covalent dynamic hyperbranched polymers is described. The covalent dynamic hyperbranched polymers, with multi-arm hydrophobic chains and a hydrophilic hyperbranched poly(amidoamine) (HPAMAM) core connected with pH-sensitive imine bonds (HPAMAM–DA), could encapsulate CdTe quantum dots (QDs) and Au nanoparticles (NPs). Benefiting from its pH response property, CdTe QDs and Au NPs encapsulated by HPAMAM–DA could be released to aqueous phase after imine hydrolysis. The released CdTe/HPAMAM and Au/HPAMAM nanocomposites exhibited excellent biological imaging behavior and high catalytic activities on p-nitrophenol hydrogenation, respectively. [ABSTRACT FROM AUTHOR]