Resting-state neural correlates of individual differences in ignored experience and its deleterious effect.

Uncovering the neural mechanisms of ostracism experience (including its subclasses of excluded and ignored experiences) is important. However, the resting-state functional brain substrates responsible for individual differences in ostracism experience and its negative effects remain largely undefined. This study explored these issues in a sample of 198 Chinese college students by assessing the amplitude of low-frequency fluctuations and functional connectivity. The findings indicated a positive correlation between ignored experience and the amplitude of low-frequency fluctuations in the right superior frontal gyrus and the functional connectivity between the right superior frontal gyrus and left cerebellum posterior lobe. Additionally, a negative correlation was found between ignored experience and the functional connectivity between the right superior frontal gyrus and the bilateral insula as well as the bilateral inferior parietal lobule. Moreover, the mediation analysis demonstrated that the effects of the functional connectivities of right superior frontal gyrus-left cerebellum posterior lobe and right superior frontal gyrus-right inferior parietal lobule on revenge intention were mediated by ignored experience. Our study offers novel insights into the neural correlates of both individual variations in ignored experience and its typical deleterious effect. These results could deepen our understanding of individual differences in negative experiences and inspire the development of targeted interventions for social stress from the perspective of the brain.

Not exclusively the activity, but the sweet spot: a dehydrogenase point mutation synergistically boosts activity, substrate tolerance, thermal stability and yield.

Catalytic activity is undoubtedly a key focus in enzyme engineering. The complicated reaction conditions hinder some enzymes from industrialization even though they have relatively promising activity. This has occurred to some dehydrogenases. Hydroxysteroid dehydrogenases (HSDHs) specifically catalyze the conversion between hydroxyl and keto groups, and hold immense potential in the synthesis of steroid medicines. We underscored the importance of 7α-HSDH activity, and analyzed the overall robustness and underlying mechanisms. Employing a high-throughput screening approach, we comprehensively assessed a mutation library, and obtained a mutant with enhanced enzymatic activity and overall stability/tolerance. The superior mutant (I201M) was identified to harbor improved thermal stability, substrate susceptibility, cofactor affinity, as well as the yield. This mutant displayed a 1.88-fold increase in enzymatic activity, a 1.37-fold improvement in substrate tolerance, and a 1.45-fold increase in thermal stability when compared with the wild type (WT) enzyme. The I201M mutant showed a 2.25-fold increase in the kcat/KM ratio (indicative of a stronger binding affinity for the cofactor). This mutant did not exhibit the highest enzyme activity compared with all the tested mutants, but these improved characteristics contributed synergistically to the highest yield. When a substrate at 100 mM was present, the 24 h yield by I201M reached 89.7%, significantly higher than the 61.2% yield elicited by the WT enzyme. This is the first report revealing enhancement of the catalytic efficiency, cofactor affinity, substrate tolerance, and thermal stability of NAD(H)-dependent 7α-HSDH through a single-point mutation. The mutated enzyme reached the highest enzymatic activity of 7α-HSDH ever reported. High enzymatic activity is undoubtedly crucial for enabling the industrialization of an enzyme. Our findings demonstrated that, when compared with other mutants boasting even higher enzymatic activity, mutants with excellent overall robustness were superior for industrial applications. This principle was exemplified by highly active enzymes such as 7α-HSDH.

The mediating role of sleep problems and depressed mood between psychological abuse/neglect and suicidal ideation in adolescent childhood: a multicentred, large sample survey in Western China.

BACKGROUND: Adolescent suicidal ideation are associated with factors including psychological abuse/neglect, sleep problems, and depressed mood, but the systematic effects of these factors on suicidal ideation remain unclear, which is a research gap this work aims to fill. METHODS: A multi-center, the cluster sampling method was employed to collect general demographic data, such as age, gender, the experience of being left behind, and parents' marital status, from 12,192 students across 17 secondary schools in China. The Child Psychological Abuse and Neglect Scale (CPANS), Pittsburgh Sleep Quality Index (PSQI), the Chinese version of the Depressed mood, Anxiety and Stress Scale - 21 Items (DASS-21) and Chinese version of Positive and Negative Suicide Ideation Inventory (PANSI) were utilized. Data were analyzed using t-tests, chi-square tests, correlation analyses, and structural equation modeling mediation analyses. RESULTS: The prevalence of psychological abuse/neglect and adolescent suicidal ideation was 34.8% and 13%, respectively. This mediation analysis suggests that, in the relationship between psychological abuse/neglect and suicidal ideation, sleep problems and depressed mood play both parallel and sequential mediating roles. CONCLUSION: Sleep problems and depressed mood play a mediating role in the development of suicidal ideation in adolescents. Good sleep habits and depressed mood interventions help reduce the risk of suicidal ideation in adolescents who experience psychological neglect/abuse.

Bioactive polysaccharides in different plant parts of Aconitum carmichaelii.

BACKGROUND: Aconitum carmichaelii is an industrially cultivated medicinal plant in China and its lateral and mother roots are used in traditional Chinese medicine due to the presence of alkaloids. However, the rootlets and aerial parts are discarded after collection of the roots, and the non-toxic polysaccharides in this plant have attracted less attention than the alkaloids and poisonous features. In this study, five neutral and 14 acidic polysaccharide fractions were isolated systematically from different plant parts of A. carmichaelii, and their structural features and bioactivity were studied and compared. RESULTS: The neutral fraction isolated from the rootlets differed from those isolated from the lateral and mother roots. It consisted of less starch and more possible mannans, galactans, and/or xyloglucans, being similar to those of the aerial parts. Pectic polysaccharides containing homogalacturonan and branched type-I rhamnogalacturonan (RG-I) were present in all plant parts of A. carmichaelii. However, more arabinogalactan (AG)-II side chains in the RG-I backbone were present in the aerial parts of the plants, while more amounts of arabinans were found in the roots. Various immunomodulatory effects were observed, determined by complement fixation activity and anti-inflammatory effects on the intestinal epithelial cells of all polysaccharide fractions. CONCLUSION: This study highlighted the diversity of polysaccharides present in A. carmichaelii, especially in the unutilized plant parts, and showed their potential medicinal value. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Serial Cascade Effects of Relative Deprivation and Anger Rumination on the Development of Social Aggression Over 2.5 Years in Emerging Adults.

Although the mechanisms of development of aggression have been focused on day by day, the complicated effects of distal and proximal factors on the development of social aggression in emerging adults have not been uncovered. A serial cascade model of aggression was proposed to address this issue. A longitudinal investigation over 2.5 years was conducted to test this model by exploring the serial cascade effects of relative deprivation (a representative of distal factors) and anger rumination (a representative of proximal factors) on the development of social aggression. A total of 1113 Chinese university students (Mage = 18.95 ± 0.96, 63.10% female) from six universities in five areas participated in this study. The results suggest that developmental trajectories and longitudinal changes in anger rumination mediate the relationship between developmental trajectories and longitudinal changes in relative deprivation and social aggression, and developmental trajectories and changes in relative deprivation mediate the longitudinal relationship between anger rumination and social aggression. These findings support the serial cascade effects of distal and proximal factors on the development of aggression and expand upon the general aggression model (GAM).

Health-related quality of life and associated factors in Chinese menstrual migraine patients: a cross-sectional study.

BACKGROUND: Menstrual migraine is a particular form of migraine with a significant impact on the quality of life for women afflicted. Presently, no study has reported the quality of life in menstrual migraine patients. This work aims to assess the health-related quality of life and identify its associated factors among Chinese menstrual migraine patients. METHODS: The cross-sectional study group consisted of 109 patients with menstrual migraine, and the control group consisted of 397 female patients with non-menstrual migraine. In total, 506 patients completed questionnaires for demographic and clinical information, the Self-rating Idea of Suicide Scale, the Hamilton Depression Scale, the Hamilton Anxiety Scale, the Headache Impact Test-6, the Perceived Social Support Scale, the Pittsburgh Sleep Quality Index. Health-related quality of life was measured using the 36-Item Short Form Survey. RESULTS: Compared with non-menstrual migraine patients, five dimensions of health-related quality of life were all found to be significantly impaired in menstrual migraine patients. Headache frequency (ß = - 0.218, P = 0.014), the impact of headache on daily life (ß = - 0.270, P = 0.002), depression symptoms (ß = - 0.345, P < 0.001) were significantly associated with physical component summary, depression symptoms (ß = - 0.379, P < 0.001), social support (ß = 0.270, P < 0.001), suicidal ideation (ß = - 0.344, P < 0.001) were closely related to mental component summary. CONCLUSION: Menstrual migraine patients had a significantly poorer health-related quality of life in many domains than non-menstrual migraine patients. Headache frequency, the impact of headache on daily life, depression symptoms, social support, and suicidal ideation were significantly associated with health-related quality of life in menstrual migraine patients. TRIAL REGISTRATION: ChiCTR1800014343. This study was registered prospectively on 7 January 2018 at Chinese Clinical Trial registry. http://www.chictr.org.cn/showproj.aspx?proj=24526.

Comparisons of the energy efficiency and intraocular safety of two torsional phacoemulsification tips.

BACKGROUND: During cataract phacoemulsification surgery, an Intrepid® balanced (IB) tip can achieve a larger amplitude, which may lead to higher energy efficiency than a Kelman (K) tip when paired with a torsional phaco platform. In this retrospective cohort study, we compared their energy efficiency and damage to the cornea under a new energy setting. METHODS: The medical records of 104 eyes of 79 patients were reviewed, with 47 eyes belonging to the IB group and 57 eyes belonging to the K group. All surgeries were performed on an Alcon Centurion® platform with gravity infiltration. Surgical parameters, visual outcome, central corneal thickness (CCT) changes, and endothelial cell density (ECD) loss rate were recorded and calculated. RESULTS: No significant differences in postoperative best corrected visual acuity (BCVA), intraocular pressure (IOP), total ultrasound time, estimated fluid aspirated, CCT changes, or ECD loss rate were observed between the two groups. We divided the included eyes into soft nucleus and hard nucleus subgroups and found lower cumulative dissipated energy (CDE, 8.15 ± 8.02 vs 14.82 ± 14.16, P = 0.023), cumulative torsional energy (CTE, 8.06 ± 7.87 vs 14.13 ± 13.02, P = 0.027), and cumulative longitudinal energy (CLE, 0.09 ± 0.17 vs 0.69 ± 1.37, P = 0.017) in the IB group than in the K group, implying less energy used and higher energy efficiency of the IB tip. CONCLUSION: Lower CLE in the IB group indicates fewer phaco tip obstructions and a significantly higher capability to conquer hard nuclei with IB tips with statistical significance. With an ultra-perfusion cannula, the balanced tip does not cause more corneal damage.

Expression of L-phosphinothricin synthesis enzymes in Pichia pastoris for synthesis of L-phosphinothricin.

With the ban of highly toxic herbicides, such as paraquat and glyphosate, phosphinothricin (PPT) is becoming the most popular broad-spectrum and highly effective herbicide. The current PPT products in the market are usually a racemic mixture with two configurations, the D-type and L-type, of which only the L-PPT has the herbicidal activity. The racemic product is not atom economic, more toxic and may cause soil damage. Asymmetric synthesis of L-PPT has become a research focus in recent years, while biological synthesis methods are preferred for its character of environmental friendly and requiring less reaction steps when being compared to the chemical methods. We have developed a biological synthesis route to produce optically pure L-PPT from D,L-PPT in two steps using 2-carbonyl-4- (hydroxymethyl phosphonyl) butyric acid as the intermediate. In this study, we expressed the glutamate dehydrogenase and glucose dehydrogenase using Pichia pastoris as the first time. After a series of optimization, the total L-PPT yield reached 84%. The developed synthesis system showed a high potential for future industrial application. Compare to the previous plasmid-carrying-E. coli expression system, the established method may avoid antibiotic usage and provided an alternative way for industrial synthesis of optically pure L-PPT.

Recent advances in the improvement of enzyme thermostability by structure modification.

Thermostability is considered to be an important parameter to measure the feasibility of enzymes for industrial applications. Generally, higher thermostability makes an enzyme more competitive and desirable in industry. However, most natural enzymes show poor thermostability, which restricts their application. Protein structure modification is a desirable method to improve enzyme properties. In recent years, tremendous progress has been achieved in protein thermostability engineering. In this review, we provide a systemic overview on the approaches of protein structure modification for the improvement of enzyme thermostability during the last decade. Structure modification approaches, including the introduction of non-covalent interactions and covalent bonds, increase of proline and/or decrease in glycine, reinforcement of subunit-subunit interactions, introduction of glycosylation sites, truncation and cyclization have been highlighted.

Mitigation of nitrous oxide emissions from acidic soils by Bacillus amyloliquefaciens, a plant growth-promoting bacterium.

Nitrous oxide (N2 O) is a long-lived greenhouse gas that can result in the alteration of atmospheric chemistry and cause accompanying changes in global climate. To date, many techniques have been used to mitigate the emissions of N2 O from agricultural fields, which represent one of the most important sources of N2 O. In this study, we designed a greenhouse pot experiment and a microcosmic serum bottle incubation experiment using acidic soil from a vegetable farm to study the effects of Bacillus amyloliquefaciens (BA) on plant growth and N2 O emission rates. The addition of BA to the soil promoted plant growth enhanced the soil pH and increased the total nitrogen (TN) contents in the plants. At the same time, it decreased the concentrations of ammonium (NH4+ ), nitrate (NO3- ) and TN in the soil. Overall, the addition of BA resulted in a 50% net reduction of N2 O emissions compared with the control. Based on quantitative PCR and the network analysis of DNA sequencing, it was demonstrated that BA partially inhibited the nitrification process through the significant reduction of ammonia oxidizing bacteria. Meanwhile, it enhanced the denitrification process, mainly by increasing the abundance of N2 O-reducing bacteria in the treatment with BA. The results of our microcosm experiment provided evidence that strongly supported the above findings under more strictly controlled laboratory conditions. Taken together, the results of our study evidently demonstrated that BA has dual effects on the promotion of plant growth and the dramatic reduction of greenhouse emissions, thus suggesting the possibility of screening beneficial microbial organisms from the environment that can promote plant growth and mitigate greenhouse trace gases.

Modulation of electronic and magnetic properties in InSe nanoribbons: edge effect.

Quite recently, the two-dimensional (2D) InSe nanosheet has become a hot material with great promise for advanced functional nano-devices. In this work, for the first time, we perform first-principles calculations on the structural, electronic, magnetic and transport properties of 1D InSe nanoribbons with/without hydrogen or halogen saturation. We find that armchair ribbons, with various edges and distortions, are all nonmagnetic semiconductors, with a direct bandgap of 1.3 (1.4) eV for bare (H-saturated) ribbons, and have the same high electron mobility of about 103 cm2V-1s-1 as the 2D InSe nanosheet. Zigzag InSe nanoribbons exhibit metallic behavior and diverse intrinsic ferromagnetic properties, with the magnetic moment of 0.5-0.7 µ B per unit cell, especially for their single-edge spin polarization. The edge spin orientation, mainly dominated by the unpaired electrons of the edge atoms, depends sensitively on the edge chirality. Hydrogen or halogen saturation can effectively recover the structural distortion, and modulate the electronic and magnetic properties. The binding energy calculations show that the stability of InSe nanoribbons is analogous to that of graphene and better than in 2D InSe nanosheets. These InSe nanoribbons, with novel electronic and magnetic properties, are thus very promising for use in electronic, spintronic and magnetoresistive nano-devices.

Large numbers of interleukins-22- and -17A-producing T helper cells in cholangiocarcinoma related to liver fluke infection.

Cholangiocarcinoma (CCA) associated with liver fluke infection involves inflammatory and immune processes; however, whether these involve the proinflammatory cytokine IL-17A and proliferative cytokine IL-22 remains unclear. Here, numbers of IL-22- and IL-17A-producing Th cells and cytokine concentrations in 30 patients with CCA and long-term liver fluke infection, 40 patients with liver-fluke infection but not CCA, and 16 healthy controls were compared. Analyses were performed using immunohistochemistry, flow cytometry, ELISA and RT-PCR. Immunohistochemical staining showed weaker expression of IL-22 and IL-17A in patients with CCA with than in those without liver fluke infection (P < 0.01). Flow cytometry revealed significantly greater median proportions of IL-22-producing T helper cells in patients with CCA (2.2%) than in those without it (0.69%) or controls (0.4%, P < 0.001). Similar results were obtained for IL-17A-producing T helper cells. ELISA revealed plasma concentrations of IL-22 were 1.3-fold higher in patients with CCA than in those without it and 4.6-fold higher than in controls (P < 0.001). Plasma concentrations of IL-17A were 2.5-fold higher in patients with CCA than in those without it, and 21-fold higher than in controls (P < 0.001). Amounts of IL-22 and IL-17A mRNAs in blood were significantly higher in patients with CCA than in the other two groups. Proportions of CD4+ CD45RO+ T cells producing IL-22 correlated with proportions producing IL-17A (r = 0.759; P < 0.001), and plasma concentrations of IL-22 correlated with those of IL-17A (r = 0.726; P < 0.001). These results suggest that both IL-17A and IL-22 affect development of CCA related to liver fluke infection.

Combined metabolomics and proteomics to reveal the mechanism of S. oneidensis MR-1 degradation malathion enhanced by FeO/C.

Iron oxide @ biochar (FeO/C) promotes bacterial growth and facilitates electron transfer, thereby effectively promoting malathion degradation by Shewanella oneidensis MR-1 (S. oneidensis MR-1). This study elucidated the underlying mechanism of FeO/C-enhanced malathion degradation by S. oneidensis MR-1 through a combination of metabolomics and proteomics analysis. The kinetic fitting results from the degradation experiment indicated that 0.1 g/L FeO/C exerted the most significant enhancement effect on malathion degradation by S. oneidensis MR-1. Observations from Scanning Electron Microscopy and Laser Scanning Confocal Microscopy, along with physiological and biochemical analysis, showed that FeO/C enhanced the growth and oxidative response of S. oneidensis MR-1 under malathion stress. In addition, metabolomics and proteomics analysis revealed an increase in certain electron transfer related metabolites, such as coenzymes, and the upregulation of proteins, including coenzyme A, sdhD, and petC. Overall, spectroscopic analysis suggested that Fe2+, which was reduced from Fe3+ by S. oneidensis MR-1 in FeO/C, promoted electron transfer in S. oneidensis MR-1 to enhance the degradation of malathion. This study offers enhanced strategies for efficient removal of malathion contaminants.

Development of a yeast cell based method for efficient screening of high yield tacrolimus production strain.

Tacrolimus (FK506) is a widely used and clinically important immunosuppressant drug that can be produced by fermentation of Streptomyces tsukubaensis. The industrial strains are typically obtained through multiple rounds of mutagenesis and screening, a labor-intensive process. We have established an efficient yeast cell based screening method for the evolutionary process of high-FK506-yielding strain. The S. tsukubaensis strains of different FK506 yields were tested for zone of growth inhibition of the wild type and calcineurin mutant (cnb1∆) yeast strains. We found that different FK506 yields correspond well to altered yeast growth inhibitions. Based on the combinational inhibition effects of FK506 with different antifungals that have been frequently reported, we also tested the zone of inhibition by addition of fluconazole, amphotericin B and caspofungin to the medium. In the end, for the best screening performance, we systemically evaluated the strategy when different yeast strains and different antifungals were used according to the clarity, size, and divergence of the inhibition circles. Using different yeast strains and antifungals, we successfully broadened the screening spectrum. An efficient high-FK506-yield S. tsukubaensis screening method has been established and optimized. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03870-y.

Intergenerational or intragenerational learning? The relationship between interpersonal neural synchrony and older adult's learning acquisition.

OBJECTIVES: Lifelong learning facilitates active ageing, and intragenerational learning-the process by which older adults learn from their peers-is an effective means of achieving this goal. The present research aims to elucidate the mechanisms and differences between intergenerational and intragenerational learning models for older adults as evidenced by brain-to-brain synchrony. METHODS: Fifty-six instructor-learner dyads completed a study comparing intergenerational and intragenerational learning models, as well as task difficulty. The study utilized a block puzzle task and functional near-infrared spectroscopy (fNIRS) for hyperscanning. RESULTS: The instructor-learner dyads showed greater interpersonal neural synchrony (INS) and learning acquisition in the intragenerational learning model in the difficult task condition (t (54) = 3.49, p < 0.01), whereas the two learning models yielded similar results in the easy condition (t (54) = 1.96, p = 0.06). In addition, INS and self-efficacy mediated the association between learning models and learning acquisition in older adults (b = 0.14, SEM = 0.04, 95 % CI [0.01 0.16]). DISCUSSION: This study is the first to provide evidence of interbrain synchrony in an investigation of the intragenerational learning model in older adults. Our findings suggest that intra-learning is as effective as traditional inter-learning and may be more effective in certain contexts, such as difficult tasks. Encouraging intra-learning in community service or educational activities can effectively mitigate the challenge of limited volunteers and enhance learning acquisition among older adults.

The mediating role of impulsivity between sleep quality and suicidal ideation in adolescent population: a multicenter cross-sectional study in the northeastern Sichuan, China.

Introduction: Suicidal ideation is a critical early stage in the progression towards suicidal be havior. Prior research has established links between sleep quality, impulsivity, and suicidal tendencies, yet the interaction among these factors has been less explored. This study aims to explore the mediating role of impulsivity in the relationship between sleep quality and suicidal ideation in adolescents. Methods: Employing a cross-sectional study design, 6,974 questionnaires were distributed,including the Socio-demographic Characteristics Questionnaire, Barratt Impulsiveness Scale, the Positive and Negative Suicide Ideation Inventory,and the Pittsburgh Sleep Quality Index Scale. The participants were high school and middle school students from 33 schools in northeastern Sichuan, China, selected through random cluster sampling. Results: Of these 6,786 questionnaires were analyzed. The participant distribution included 47.2% male and 52.8% female students, with 68.3% from junior schools and 31.7% from senior schools. The prevalence of suicidal ideation was found to be 13.6%. The analysis, which involved correlation analysis and the construction of a structural equation model, revealed that sleep quality had a significant positive effect on impulsivity (ß:0.289,p < 0.05), and impulsivity, in turn, had a positive impact on suicidal ideation (ß:0.355,p < 0.05).Moreover, sleep quality was directly linked to suicidal ideation (ß:0.208,p < 0.05). Thus, sleep quality affects suicidal ideation both directly and indirectly through impulsivity. Discussion: The results of this study suggest that both sleep quality and impulsivity are significant direct influencers of suicidal ideation among adolescents in the region studied, with impulsivity also playing an indirect role in the relationship between sleep quality and suicidal ideation.

Prevalence and associated factors of adolescent psychological abuse, neglect in Western China a multi-center cross-sectional study.

Background: The western region of China has a dense population, relatively underdeveloped economy, and a significant number of left-behind children. Currently, the prevalence of adolescent psychological abuse, neglect, and the factors associated with these issues in the region remain unclear. This study aims to evaluate the current status of adolescent psychological abuse and neglect and its associated factors in this region.Methods: Data were collected from 50 schools in western China through cluster sampling to target adolescents aged 12 to 18. A comprehensive survey form was used to collect socio-demographic characteristics of adolescents. The Child Psychological Abuse and Neglect Scale was employed to assess the current psychological abuse and neglect of adolescents. Independent samples t-tests were used for inter-group comparisons. A Directed Acyclic Graph was constructed for controlling confounding variables. Subsequently, binary logistic regression analysis was performed, and a nomogram risk factors model was developed using R Studio.Results: This study included 12,743 teenagers, with an average age of 15.53(±1.39) years. Among them, 4,965 individuals, accounting for 39.0%, reported experiences of psychological abuse, while 4,167 individuals, accounting for 32.7%, reported experiences of neglect. The rates of psychological abuse and neglect in adolescents are influenced by gender, grade, left-behind experience, parental marital status, and living on campus (P < .05).Conclusion: Adolescents in western China exhibit higher rates of psychological abuse and neglect compared to those in the eastern and northern regions of China. Gender, grade, left-behind experience, and family factors significantly influence the psychological abuse and neglect of adolescents.

This study is the first large-scale, multi-centre, cross-sectional analysis of psychological abuse and neglect among youth in Western China, a region with relatively underdeveloped economic and social conditions.This article fills in the gap in the region's research on psychological abuse and neglect by addressing the issues of small sample size, limited coverage, and a lack of variables included.This provides a crucial theoretical foundation for enhancing the mental well-being of youth in this region and preventing psychological and mental illnesses among youth.

Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro.

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

Associations of polymorphisms in the genes of FGFR2, FGF1, and RBFOX2 with breast cancer risk by estrogen/progesterone receptor status.

Genetic polymorphisms of fibroblast growth factor receptor 2 (FGFR2) have been demonstrated to be associated with breast cancer risk, presumably through elevation of FGFR2 expression. Fibroblast growth factor 1 (FGF1) and RNA binding protein fox-1 homolog 2 (RBFOX2), which are functionally related to FGFR2, may also associate with breast cancer risk. We investigated the associations between breast cancer risk and the polymorphisms of FGFR2 rs2981582, FGF1 rs250108, and RBFOX2 rs2051579 among 839 incident breast cancer cases and 863 age-matched controls in the Guangzhou Breast Cancer Study. Stratified odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by estrogen receptor (ER)/progesterone receptor (PR) status using multivariate logistic regression. FGFR2 rs2981582 was confirmed to be significantly associated with the risk of ER-positive but not ER-negative breast cancer. In contrast, FGF1 rs250108 was significantly associated with the risk of ER-negative breast cancer (OR (95% CI) = 1.68 (1.20-2.35) for CT + TT vs. CC genotype) but not ER-positive breast cancer. CA + AA genotypes at RBFOX2 rs2051579 were associated with a reduced risk of ER-negative (0.71 (0.52-0.97)) but not ER-positive breast cancer compared to the CC genotype. Similar results were observed when differentiating breast cancer cases by PR status. Neither of the pairs between the three SNPs had a significant interaction on breast cancer risk. Our findings show a suggestively stronger association between FGFR2 rs2981582 and ER-positive breast cancer risk and suggest a greater association of FGF1 rs250108 and RBFOX2 rs2051579 with ER-negative compared to ER-positive breast cancer.