Toxoplasma gondii Causes Adverse Pregnancy Outcomes by Damaging Uterine Tissue-Resident NK Cells That Secrete Growth-Promoting Factors.

Vertical transmission of the intracellular parasite, Toxoplasma gondii can lead to adverse pregnancy outcomes especially when infection occurs in early pregnancy. Decidual natural killer (dNK) cells accumulate at the maternal-fetal interface in large numbers during early pregnancy. Their nutritional roles during infection with T. gondii remain poorly defined. In the present study, we demonstrated that a functional deficiency of the uterine tissue-resident NK (trNK) cells, a subset of dNK cells, contributes to the adverse pregnancy outcomes induced by T. gondii in early pregnancy. Adverse pregnancy outcomes could be ameliorated by adoptive transfer of trNK cells. Moreover, fetal growth restriction could be improved after supplementation of growth-promoting factors. In addition to the widely recognized disturbance of the immune balance at the interface between the mother and the fetus, our study reveals a novel mechanism in T. gondii that contributes to the adverse pregnancy outcomes.

Associations between metabolic syndrome and anxiety, and the mediating role of inflammation: Findings from the UK Biobank.

OBJECTIVES: To investigate the association between metabolic syndrome (MetS) and anxiety and to explore the mediating role of inflammation indicators in this relationship based on the UK Biobank prospective cohort. METHODS: This population-based retrospective cohort study analyzed data from 308,352 participants. MetS was defined according to criteria jointly developed by the American Heart Association, the National Heart, Lung, and Blood Institute, and the International Diabetes Federation. Anxiety was defined using ICD-10 codes. Cox proportional risk regression models were used to explore the hazard ratios (HRs) between MetS, components of MetS, number of MetS components, and anxiety. The mediating effect of inflammation on the association between MetS and anxiety was explored using longitudinal mediation analysis. RESULTS: A total of 308,352 participants were included in this study. Of these, 9471 (3.071 %) developed anxiety over a mean follow-up of 12.05 years. In the fully adjusted model, MetS increased the risk of anxiety by 13.6 % (HR: 1.136, 95 %CI: 1.085-1.189). All MetS components significantly increased the risk of anxiety, with HRs ranging from 1.066 to 1.165. When MetS was treated as a linear variable, the risk of anxiety increased by 6.5 % per component increment. Age-stratified results showed that the risk of MetS for anxiety was higher among those <55 years (HR: 1.23, 95 %CI: 1.13-1.33) than among those ≥55 years (HR: 1.12, 95 %CI: 1.06-1.18). The mediating effects of platelets, lymphocytes, neutrophils, C-reactive protein, leukocytes, and INFLA scores on the association between MetS and anxiety were significant, with mediating effects of 2.30 %, 7.20 %, 15.9 %, 20.7 %, 22.0 %, and 25.3 %, respectively, and a combined mediating effect of these inflammatory factors was 30.8 % (except for INFLA scores). CONCLUSIONS: MetS and its components significantly increased the risk of anxiety, which increased with the number of components. This association may be partially mediated by serum inflammatory indicators, suggesting that MetS may increase the risk of anxiety by elevating the level of chronic inflammation.

ADGRL1 variants: From developmental and epileptic encephalopathy to genetic epilepsy with febrile seizures plus.

AIM: To expand the phenotypic spectrum of ADGRL1 and explore the correlation between epilepsy and the ADGRL1 genotype. METHOD: We performed whole-exome sequencing in a cohort of 115 families (including 195 males and 150 females) with familial febrile seizure or epilepsy with unexplained aetiology. The damaging effects of variants was predicted using protein modelling and multiple in silico tools. All reported patients with ADGRL1 pathogenic variants were analysed. RESULTS: One new ADGRL1 variant (p.Pro753Leu) was identified in one family with genetic epilepsy with febrile seizures. Further analysis of 12 ADGRL1 variants in 16 patients revealed that six patients had epilepsy. Epilepsy types ranged from early-onset epileptic encephalopathy to genetic epilepsy with febrile seizures plus (GEFS+). All four variants associated with epilepsy were located in the non-helix or sheet region of ADGRL1. Three of the four epilepsy-associated variants were missense variants. Thus, all three variants located in the G-protein-coupled receptor autoproteolytic-inducing domain exhibited epilepsy. INTERPRETATION: We found one new missense variant of ADGRL1 in one family with GEFS+. ADGRL1 may be a potential candidate or susceptibility gene for epilepsy. ADGRL1-associated epilepsy ranged from benign GEFS+ to severe epileptic encephalopathy; the genotypes and variant locations may help explain the phenotypic heterogeneity of patients with the ADGRL1 variant.

Chlorogenic acid, rutin, and quercetin from Lysimachia christinae alleviate triptolide-induced multi-organ injury in vivo by modulating immunity and AKT/mTOR signal pathway to inhibit ferroptosis and apoptosis.

Drug-induced organ injury is one of the key factors causing organ failure and death in the global public. Triptolide (TP) is the main immunosuppressive component of Tripterygium wilfordii Hook. f. (Leigongteng, LGT) for the first-line management of autoimmune conditions, but it can cause serious multi-organ injury. Lysimachia christinae (Jinqiancao, JQC) is a detoxifying Chinese medicine and could suppress LGT's toxicity. It contains many immune enhancement and organ protection components including chlorogenic acid (CA), rutin (Rut), and quercetin (Que). This study aimed to explore the protection of combined treatments of these organ-protective ingredients of JQC on TP-induced liver, kidney, and heart injury and initially explore the mechanisms. Molecular docking showed that CA, Rut, and Que bounded protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway-related molecules intimately and might competitively antagonize TP. Corresponding in vivo results showed that the combination activated TP-inhibited protein of AKT/mTOR pathway, and reversed TP-induced excessive ferroptosis (excessive Fe 2+ and lipid peroxidation malondialdehyde accumulation, decreased levels of antioxidant enzymes catalase, glutathione peroxidase, glutathione-s transferase, reduced glutathione, and superoxide dismutase, and down-regulated P62/nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway), and apoptosis (activated apoptotic factor Fas and Bax and inhibited Bcl-2) in the organ of mice to varying degrees. In conclusion, the combined treatments of CA, Rut, and Que from JQC inhibited TP-induced multi-organ injury in vivo, and the mechanism may largely involve immunomodulation and activation of the AKT/mTOR pathway-mediated cell death reduction including ferroptosis and apoptosis inhibition.

Association of the Oxidative Balance Score and Cognitive Function and the Mediating Role of Oxidative Stress: Evidence from the National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Oxidative stress is possibly related to cognitive function decline. The oxidative balance score (OBS) that combines pro- and antioxidant components from diet and lifestyle has been reported to be associated with age-related diseases. OBJECTIVES: We aimed to investigate the association between OBS and cognitive function in older adults and explore whether oxidative stress mediated this relationship. METHODS: A total of 1745 adults aged ≥60 y were included in the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Cognitive function was measured using 4 tests: the immediate recall test, delayed recall test, animal fluency test (AFT), and digital symbol substitution test (DSST). Weighted multivariate linear regression and restricted cubic splines (RCS) analyses were used to evaluate the association between OBS and cognitive function, and mediation analysis was used to test the indirect effect of oxidative stress indicators on the association. RESULTS: The OBS was positively associated with AFT, DSST, and global cognitive function in older adults, and the beta estimates (95% CI) were 0.015 (0.008, 0.034), 0.009 (0.002, 0.025), and 0.030 (0.024, 0.074), moreover, RCS results suggested an approximately linear dose-response relationship between the OBS and these 3 tests. The highest quartiles of these 3 tests were also significantly correlated with OBS. Albumin, uric acid, and serum 25(OH)D concentrations were significant mediators of the relationship between OBS and cognitive function, and the overall mediation effect proportion was 36% when included in 1 model. CONCLUSIONS: OBS was positively correlated with cognitive function in older adults, and albumin, uric acid, and serum 25(OH)D concentrations could be the driving mediators of the association. The findings emphasize the importance of a healthy, antioxidant diet and lifestyle that contribute to cognitive function. J Nutr 20xx;x:xx.

Association between prenatal exposure to per- and polyfluoroalkyl substances and neurodevelopment in children: Evidence based on birth cohort.

BACKGROUND: Although numerous studies have examined the effect of prenatal per- and polyfluoroalkyl substances (PFAS) exposure on neurodevelopment in children, findings have been inconsistent. OBJECTIVE: To better understand the effects of PFAS exposure during pregnancy on offspring neurodevelopment, we conducted a systematic review of prenatal exposure to different types of PFAS and neurodevelopment in children. METHODS: A comprehensive search was conducted in the PubMed, Web of Science, and EMBASE electronic databases up to March 2023. Only birth cohort studies that report a specific association between PFAS exposure during pregnancy and neurodevelopment were included in this review. RESULTS: 31 birth cohort studies that met the inclusion criteria were qualitatively integrated. Among these, 14 studies investigated the impact of PFAS exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. Additionally, 4 studies explored the influence of PFAS on children's comprehensive development. CONCLUSION: Prenatal PFAS exposure was associated with poor neurodevelopment in children, including psychomotor development, externalizing behavior, and comprehensive development. However, conclusive evidence regarding its effects on other neurological outcomes remains limited. In addition, sex-specific effects on social behavior and sleep problems were identified.

Associations between urinary caffeine and caffeine metabolites and cognitive function in older adults.

BACKGROUND: The effects of caffeine on cognitive impairment have not been conclusively determined. This study aimed to objectively assess the correlation between the urinary caffeine and caffeine metabolites and cognitive decline in older adults. METHODS: Data on urinary caffeine and caffeine metabolites and the cognitive performance of participants aged 60 years and older were extracted from the National Health and Nutrition Examination Surveys 2011-2014. Binary logistic regression and restricted cubic splines (RCS) analyses were used to evaluate the association between urinary caffeine and caffeine metabolites and cognitive performance. RESULTS: Eight hundred twenty-seven individuals were enrolled in this cross-sectional study. We observed that 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, 1,7-dimethylxanthine, and 3,7-dimethylxanthine levels were significantly and inversely associated with cognitive decline. The RCS results suggested an approximately linear dose-response relationship between the aforementioned metabolites and cognitive performance. Moreover, the effects of urinary caffeine and caffeine metabolites on cognitive function assessed using the AFT were more evident in men. CONCLUSIONS: Our study suggested that urinary caffeine and caffeine metabolite levels were associated with a reduced risk of cognitive impairment in a linear manner, especially in men.

Experimental Realization of Two-Dimensional Weak Topological Insulators.

We report the experimental realization of a two-dimensional (2D) weak topological insulator (WTI) in spinless Su-Schrieffer-Heeger circuits with parity-time and chiral symmetries. Strong and weak Z2 topological indexes are adopted to explain the experimental findings that a Dirac semimetal (DSM) phase and four WTI phases emerge in turn when we modulate the centrosymmetric circuit deformations. In the DSM phase, it is found that the Dirac cone is highly anisotropic and that it is not pinned to any high-symmetry points but can widely move within the Brillouin zone, which eventually leads to the phase transition between WTIs. In addition, we observe a pair of flat-band domain wall states by designing spatially inhomogeneous node connections. Our work provides the first experimental evidence for 2D WTIs, which significantly advances our understanding of the strong and weak nature of topological insulators, the robustness of flat bands, and the itinerant and anisotropic features of Dirac cones.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Effects of HMGA2 on the epithelial-mesenchymal transition-related genes in ACHN renal cell carcinoma cells-derived xenografts in nude mice.

BACKGROUND: The architectural transcriptional regulator high-mobility group AT-hook 2 (HMGA2) is an oncofetal protein which has been reported to be ectopically expressed in a variety of cancers. A high expression of HMGA2 in human renal cell carcinoma (RCC) is related with tumor invasiveness and poor prognosis. Recent in vitro studies have shown that HMGA2 knockdown was able to decrease cell proliferation and migration, and regulate the gene expression related to epithelial-mesenchymal transition (EMT). METHODS: To understand the HMGA2's effect in vivo, HMGA2 expression was knocked down in ACHN cells using small hairpin RNA (shRNA), then the HMGA2-deficient ACHN cells were xenografted into the BALB/c nude mice. Tumor growth was monitored and the expression of EMT-related genes was analyzed. RESULTS: HMGA2 expression was confirmed to be knocked down in the cultured and xenografted ACHN cells. The xenograft tumor of HMGA2-deficient cells demonstrated a retarded growth pattern compared with the control. The expression of E-cadherin was increased, whereas N-cadherin and Snail were decreased in the HMGA2-deficient xenograft tumors. CONCLUSIONS: In conclusion, to the best of our knowledge, for the first time, we have successfully developed an in vivo experiment using HMGA2-silencing ACHN cells to be grown as xenografts in nude mice. Our findings show that HMGA2 deficiency was sufficient to suppress the xenograft tumor growth in vivo, which support our hypothesis that HMGA2-induced renal carcinogenesis occurs at least in part through the regulation of tumor associated EMT genes.

Catalpol Exerts Antidepressant-Like Effects by Enhancing Anti-oxidation and Neurotrophy and Inhibiting Neuroinflammation via Activation of HO-1.

Catalpol is an iridoid glycoside with rich content, rich nutrition, and numerous biological activities in Rehmanniae Radix contained in classic antidepressant prescriptions in Chinese clinical medicine. Catalpol has been confirmed previously its exact antidepressant-like effect involved heme oxygenase (HO)-1, but its antidepressant molecular targets and mechanism are still unclear. Here, catalpol's antidepressant-like molecular target was diagnosed and confirmed by ZnPP intervention [the antagonist of HO-1, (10 µg/rat), intracerebroventricular] for the first time, and its molecule mechanism network was determined through HO-1 related pathway and molecules in the hippocampus. Results showed that ZnPP significantly abolished catalpol's (10 mg/kg) reversal on depressive-like behaviors of chronic unpredictable mild stress rats, abolished catalpol's up-regulation on the phosphorylation level of extracellular regulated protein kinases (ERK)1/2 and brain-derived neurotrophic factor (BDNF)'s receptor tropomyosin-related kinase B (TrkB), the nuclear expression level of nuclear factor E 2-related factor 2 (Nrf2), the levels of anti-oxidant factors (such as HO-1, SOD, GPX, GST, GSH) and BDNF, and abolished catalpol's down-regulation on the levels of peroxide and neuroinflammation factors [cyclooxygenase-2 (COX-2), induced nitrogen monoxide synthase (iNOS), nitric oxide (NO)]. Thus, HO-1 could serve as an important potential molecular target for catalpol's antidepressant-like process, and the antidepressant-like mechanism of catalpol could at least involve the activation of HO-1 triggering the up-regulation of the ERK1/2/Nrf2/HO-1 pathway-related factors to enhance the anti-oxidant defense, triggering the down-regulation of the COX-2/iNOS/NO pathway-related factors to inhibit neuroinflammation, and triggering the up-regulation of the BDNF/TrkB pathway to enhance neurotrophy.

Association of body perception and dietary weight management behaviours among children and adolescents aged 6-17 years in China: cross-sectional study using CHNS (2015).

BACKGROUND: Obesity is rapidly globally increasing. Meanwhile, there is an increase in negative perception of the body image and, consequently, an increase in weight control management. Body perception plays an important mediating role between overweight or obesity and weight control behaviours. This study aims to examine whether body perception is associated with dietary weight management behaviours among Chinese children and adolescents. METHODS: Child body perception and health behaviours from Chinese Health and Nutrition Survey (2015) were assessed, and 729 boys and 640 girls who aged 6 to 17 years were included in this study. Variables assessed as covariates were sociodemographic, physical activity and body perception involving self-perceptive weight status and body image dissatisfaction (BID). Multivariate logistic regression was used to explore the association between dietary weight management behaviours and body perception. RESULTS: 60.77% students rightly matched their body mass index (BMI) with self-perceived weight. The prevalence of BID was 59.39%. After adjustment for sociodemographic information, physical activities and BMI, those whose self-perceived weight status as overweight/obesity were associated with an increased risk of dietary weight management behaviours comparing to those who have normal weight in boys (OR = 5.07; 95% CI = 1.86, 13.87; P < 0.001) and girls (OR = 14.28; 95%CI = 5.73, 35.56; P < 0.001). And those who desire to be thinner were strongly associated with dietary weight management behaviours (OR = 9.51; 95%CI = 3.47, 26.09; P < 0.001) comparing to those who were satisfied with their body image in girls. CONCLUSIONS: The results revealed that body perception had a significant association with dietary weight management behaviours and exited the discrepancy according to sex. It is necessary to promote healthy awareness of body perception and to establish self-motivation for improving basic health knowledge in school health education activities.

Association between the dietary literacy of children's daily diet providers and school-age children's nutritional status and eating behaviours: a cross-sectional study.

BACKGROUND: Overweight and obesity rates have increased rapidly in Chinese school-age children, and previous studies have indicated that poor dietary literacy can lead to unhealthy eating behaviours. However, few studies have investigated the association between the dietary literacy of daily diet providers and the eating behaviours and nutritional status of school-age children raised by the providers. Thus, we aimed to explore this association. METHODS: We collected data on the eating behaviours and nutritional status of children in two primary schools in Anhui Province, as well as the dietary literacy of their daily diet providers. T-tests, one-way ANOVA, chi-square tests, and multiple linear regression were used to analyse the association. RESULTS: We found significant differences in the scores on the Questionnaire of Children's Daily Diet Providers' Dietary Literacy (QCDDPDL) by region, relationship with the child, age, and educational level of the daily diet provider (all p < .05). Moreover, the children in the low QCDDPDL score group were inclined to engage in unhealthy eating behaviours such as emotional undereating and overeating (p < .05). In addition, the incidence of overweight and obesity was higher in the low QCDDPDL attitude score group than in the high score group (p = .006). CONCLUSIONS: Our study showed that the dietary literacy of diet providers may influence children's health and eating behaviours. Improving the dietary literacy of diet providers may promote the health status and eating behaviours of school-age children.

Graph Attention Interaction Aggregation Network for Click-Through Rate Prediction.

Click-through rate prediction is a critical task for computational advertising and recommendation systems, where the key challenge is to model feature interactions between different feature domains. At present, the main click-through rate prediction models model feature interactions in an implicit way, which leads to poor interpretation of the model, and the interaction between each pair of features may introduce noise into the model, thus limiting the predictive ability of the model. In response to the above problems, this paper proposes a click-through rate prediction model (GAIAN) based on the graph attention interactive aggregation network, which explicitly obtains cross features on the graph structure. Our specific method is to design a feature interactive selection mechanism to select cross features that are beneficial to model prediction, reducing model noise and reducing the risk of model overfitting. On this basis, the bilinear interaction function is integrated into the aggregation strategy of the graph neural network, and the fine-grained intersection features are extracted in a flexible and explicit way, which makes graph neural networks more suitable for modeling feature interactions and enhances the interpretability of the model. Compared with several other state-of-the-art models on the Criteo and Avazu datasets, the experimental results show the superiority of the model.

[Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway].

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

Realization of the Square-Root Higher-Order Topological Insulator in Electric Circuits.

Higher-order topological insulator (HOTI) represents a new phase of matter, the characterization of which goes beyond the conventional bulk-boundary correspondence and is attracting significant attention by the broad community. Using a square-root operation, it has been suggested that a square-root HOTI may emerge in a hybrid honeycomb-kagome lattice. Here, we report the first experimental realization of the square-root HOTI in topological LC circuits. We show theoretically and experimentally that the square-root HOTI inherits the feature of wave function from its parent with corner states pinned to nonzero energies. The topological feature is fully characterized by the bulk polarization. To directly measure the finite-energy corner modes, we introduce extra grounded inductors to each node, which shifts corner states to zero-energy without affecting their spatial distributions. Our results experimentally substantiate the emerging square-root HOTI and pave the way to realizing exotic topological phases that are challenging to observe in condensed matter physics.

[Processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae decoction].

On the basis of the previous work of the research group, the orthogonal design method was further used to optimize the processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae Decoction. A total of 9 processed products of T.wilfordii in L.christinae decoction were prepared by four factors and three levels orthogonal design table. The contents of triptolide in T.wilfordii were determined by high performance liquid chromatography(HPLC) before and after processing: 4.27, 3.92, 3.57, 2.75, 2.42, 2.66, 3.51, 1.87, 1.75, 2.03 µg·g~(-1). On this basis, the above processed products were orally given to mice for 28 days. 12 hours after the last administration, food fasting except water was provided, and 24 hours later, the eyeballs were taken for blood and liver tissue. Serum biochemical indexes, liver lipid peroxidation and antioxidant related indexes were detected by kit method. Twenty-eight days after oral administration of raw T.wilfordii, the levels of serum alanine aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and liver malondialdehyde(MDA) in mice increased by 91%(P<0.01), 46%(P<0.05), 73%(P<0.01) and 99%(P<0.01), while the liver antioxidant indexes such as superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GPX) and glutathione-S transferase(GST) significantly decreased(P<0.01). After administration of the processed products, the above indexes were significantly reversed(P<0.01 or P<0.05). Especially, the processing conditions of A_3B_2C_1D_3 had the best detoxification effect on T.wilfordii, which decreased the high levels of AST, ALT, ALP and MDA by 49%(P<0.01), 32%(P<0.01), 42%(P<0.01), and 17%(P<0.05). Therefore, the best processing conditions for T.wilfordii in L.christinae decoction were A_3B_2C_1D_3, namely "15% mass fraction of L.christinae, 1 h moistening time, 160 ℃ frying temperature, and 9 min frying time".

Tuning electronic structure of monolayer InP3 in contact with graphene or Ni: effect of a buffer layer and intrinsic In and P-vacancy.

Monolayer indium triphosphide (m-InP3), predicted theoretically to be a new 2D semiconducting material, exhibits a promising opportunity for applications in electronic and optoelectronic devices [N. H. Miao, et al., J. Am. Chem. Soc., 2017, 139, 11125-11131]. For these applications, excellent contact performance between m-InP3 and the electrodes is vital. In this work, by first-principles calculations, the electronic structures of m-InP3 in contact with graphene (G) and Ni are investigated and the contact characters are further tuned by inserting a buffer layer, e.g., a G or BN monolayer (m-BN) along with the introduction of intrinsic P- and In-vacancy defects. For m-InP3 in contact with G, inserting an m-BN can alter the contact character from an n-type to a p-type Schottky contact. This is consistent with the prediction of the Schottky-Mott rule, indicating that Fermi level pinning is removed in the interface. However, for the contact with Ni, if an m-BN or G is inserted into the interface, an n-type Ohmic contact is obtained, rather than the p-type Schottky one based on the Schottky-Mott rule. We attribute this inconsistency to the effect of electron transfer from m-BN or G to Ni, which leads to a decreased work function for Ni. Additionally, introducing In- and P-vacancy defects can reduce the Schottky barrier in the interfaces between m-InP3 and G or Ni. Moreover, if m-BN is inserted into these defect-containing interfaces, an n-type Ohmic contact could be achieved and dominate the contact character. Our results offer deeper insights into factors such as the Fermi level pinning on the band alignment of the interfaces between m-InP3 and G or Ni, and how the contact characters are improved by inserting a buffer layer along with the introduction of In- and P-vacancy defects.

[Research progress in mineral Chinese medicine realgar].

Realgar is a mineral traditional medicine with definite efficacy. The function of realgar is detoxicating, insecticiding, eliminating dampness and phlegm, etc. It is widely applied in clinical practice by compatibility medicines. However, the safety and scientificalness of clinical application are questioned because of the toxic effect caused by arsenic compounds. At present, there are still many problems in the research of realgar, which are mainly manifested in three areas: the expression of main components and effective substances are inconsistent; the anti-tumor mechanism is difficult to explain at the molecular level; the mechanism of compatibility is not clear. As a result, realgar and realgar-containing Chinese patent medicines are frequently prohibited from entering the international market, and the reputation of traditional Chinese medicine is also damaged. This paper would analyze the research status of realgar at home and abroad as well as its problems from its main components, effective substances, anti-tumor mechanism and compatibility mechanism. In view of these difficulties, quantum chemical calculation method is proposed to solve them, so as to make up for the shortcomings and limitations of experimental technology and experimental conditions, reduce the cost of realgar research and improve research efficiency. Moreover, it provides inspiration for research of other mineral medicine.