Danggui-Shaoyao San alleviates cognitive impairment via enhancing HIF-1α/EPO axis in vascular dementia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Invigorating blood circulation to remove blood stasis is a primary strategy in TCM for treating vascular dementia (VaD). Danggui-Shaoyao San (DSS), as a traditional prescription for neuroprotective activity, has been proved to be effective in VaD treatment. However, its precise molecular mechanisms remain incompletely understood. AIM OF THE STUDY: The specific mechanism underlying the therapeutic effects of DSS on VaD was explored by employing network pharmacology as well as in vivo and in viro experiment validation. MATERIALS AND METHODS: We downloaded components of DSS from the BATMAN-TCM database for target prediction. The intersection between the components of DSS and targets, PPI network, as well as GO and KEGG enrichment analysis were then performed. Subsequently, the potential mechanism of DSS predicted by network pharmacology was assessed and validated through VaD rat model induced by 2VO operation and CoCl2-treated PC12 cells. Briefly, the DSS extract were first quantified by HPLC. Secondly, the effect of DSS on VaD was studied using MWM test, HE staining and TUNEL assay. Finally, the molecular mechanism of DSS against VaD was validated by Western blot and RT-QPCR experiments. RESULTS: Through network analysis, 137 active ingredients were obtained from DSS, and 67 potential targets associated with DSS and VaD were identified. GO and KEGG analysis indicated that the action of DSS on VaD primarily involves hypoxic terms and HIF-1 pathway. In vivo validation, cognitive impairment and neuron mortality were markedly ameliorated by DSS. Additionally, DSS significantly reduced the expression of proteins related to synaptic plasticity and neuron apoptosis including PSD-95, SYP, Caspase-3 and BCL-2. Mechanistically, we confirmed DSS positively modulated the expression of HIF-1α and its downstream proteins including EPO, p-EPOR, STAT5, EPOR, and AKT1 in the hippocampus of VaD rats as well as CoCl2-induced PC12 cells. HIF-1 inhibitor YC-1 significantly diminished the protection of DSS on CoCl2-induced PC12 cell damage, with decreased HIF-1α, EPO, EPOR expression. CONCLUSION: Our results initially demonstrated DSS could exert neuroprotective effects in VaD. The pharmacological mechanism of DSS may be related to its positive regulation on HIF-1α/EPO pathway.

A 1-year analysis from a natural history study in Chinese individuals with Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is a disabling and life-threatening, X-linked recessive disorder caused by mutations in dystrophin. Natural history studies can inform the disease characteristics of DMD, and data from these studies can be used to plan and design clinical trials and as external controls for long-term studies. We report 12-month results from the largest natural history study of individuals with DMD in China receiving standard of care treatment. Methods: This ongoing, multicentre, prospective, single-cohort study (ClinicalTrials.gov: NCT03760029) was conducted in Chinese male participants with DMD (ambulatory aged <6 years [Group 1; n = 99]; ambulatory aged ≥6 years [Group 2; n = 177], and non-ambulatory of any age [Group 3; n = 36]. The follow-up period is ≥24 months, with some participants followed for 30 months. The primary endpoint was time to clinical milestones due to DMD disease progression, and motor, pulmonary, and cardiac function. Secondary endpoints were quality of life (QoL) assessments. Findings: Mean (standard deviation [SD]) age at screening was 3.4 (1.2), 8.6 (2.0), 12.3 (2.7) and 7.4 (3.5) years in Groups 1, 2, 3 and total respectively. Mean (SD) North Star Ambulatory Assessment (NSAA) total score at baseline was 21.2 (5.8) in Group 1, 19.5 (8.3) in Group 2 and 20.0 (7.7) in ambulatory total. Overall, the time to clinical milestones due to DMD disease progression was consistent with previous findings, in which loss of ambulation occurred at 13 years. There was a trend towards a decline over 12 months in NSAA and timed motor function from age 6 years, with the greatest reductions observed thereafter. There were no consistent trends in measures of QoL, although participants of any age generally had poorer outcomes at Month 12 versus their domain scores at baseline. Interpretation: This study improves the understanding of DMD progression according to the current standards of care in the Chinese DMD population and may inform selected endpoints and patient populations in clinical trials. Funding: Pfizer Inc.

The structural and electronic properties of (001) surface of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) with first-principles calculations.

CONTEXT: 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is a typical insensitive energetic material. It can be used in explosive formulations, such as PBX-9502 and LX-17-0. TATB is an intriguing and unusual explosive for another reason: it crystallizes into a wide array of planar hydrogen bonds, forming a graphite-like layered structure. Therefore, TATB is one of the important research objects, and its surface structure needs to be deeply understood. In this research work, the electronic and energetic properties of TATB (001) surface are explored. METHODS: In this paper, the structural, electronic, energetic properties and impact sensitivity of TATB (001) surface structure at 0 and -3 GPa along with x-axis were calculated in this study using the first-principles calculations. The calculations in this paper are performed in the CASTEP code, which is based on the density functional theory with the first-principles calculation method using the plan-wave pseudopotential approach. The exchange-correlation interaction was adopted by the generalized gradient approximation (GGA) with the Perdew-Burke-Ernzerhof (PBE) functional. The DFT-D method with the Grimme correction accurately models van der Waals interactions. To model the surface structures of TATB, the planar slab method was employed. We constructed TATB (001) periodic slabs including three layers with a 15-Å vacuum layer.

Association of body mass index with asthma occurrence and persistence in adolescents: A retrospective study of NHANES (2011-2018).

Objective: To investigate the association of body mass index (BMI) with asthma and analyze the risk factors of asthma persistence among overweight/obese adolescents and those with a high risk for obesity. Methods: In this cross-sectional study, adolescents aged 11-17 years with complete general information and asthma diagnoses were selected from the National Health and Nutrition Examination Survey database. For adolescents without self-reported asthma, we performed matching according to age and sex at a case-to-control ratio of 1:3. Logistic regression analysis was employed to identify independent predictors of asthma occurrence followed by constructing a nomogram and comparing its efficacy to independent factors in predicting asthma occurrence. Besides, associations of BMI with asthma occurrence and persistence were evaluated. Finally, we obtained risk factors for asthma persistence in overweight/obese individuals and those at a high risk for obesity. Results: Totally 753 adolescents with asthma and 2259 adolescents without asthma were included to analyze the occurrence of asthma. BMI and Hispanic Ethnicity were independent predictors of asthma occurrence and were included in nomogram construction. BMI had an efficiency comparable to that of the nomogram model in predicting asthma occurrence, which is superior to that of Hispanic Ethnicity. Of the 753 adolescents diagnosed with asthma, 464 were still diagnosed with asthma of at least a year's duration. Interestingly, BMI may have the ability to predict asthma persistence. Further, Hispanic Ethnicity and household income were significantly related to asthma occurrence among overweight/obese and high-risk obese individuals. Conclusions: High BMI could independently predict increased asthma occurrence. Additionally, BMI may play an essential role in predicting asthma persistence. This study may help improve the diagnosis and reduce the occurrence of asthma.

Peroxido-bridged chiral double-decker dysprosium macrocycles.

Lanthanide peroxides show high reactivity in oxidative coupling of methane (OCM). However, the number of isolated and structurally characterized molecular species remains relatively small. To the best of our knowledge, homochiral molecule-based lanthanide peroxides have not been reported. Herein, two pairs of side-on peroxido-bridged dinuclear hexaazamacrocyclic dysprosium enantiomers with formulas [Dy2(LES/R)2L2O2](BPh4)2·CH3OH·CH3CN (where LE is derived from the condensation reaction between (1S,2S)/(1R,2R)-1,2-diphenylethylenediamine and 2,6-diformylpyridine; HL = 2,6-diphenylphenol) (1/2) and [Dy2(LES/R)2Cl2O2](BPh4)2·2CH3CN (3/4) are specially designed and created with the help of hydrogen peroxide. The out-of-phase alternating-current magnetic susceptibility of 1/2 gives rise to frequency-dependent peaks between 6 and 32 K under a zero applied direct current (dc) field, while no peak at any temperature and frequency was observed for 3/4 implying the presence of a weak axial crystal field (CF).

[Effects of Microplastic Exposure on the Community Structure and Function of Symbiotic Bacteria in Sinularia microclavata].

Microplastics are widely distributed in the marine environment and are harmful to the health of marine organisms (including corals). However, studies on the impact of microplastics on coral have been very limited, and the specific mechanism of their impact is not clear. Therefore, in this study, microplastic PA, which is common in the marine environment, was selected to conduct a 7-day microplastic exposure experiment on Sinularia microclavata. The effects of microplastic exposure at different times on the diversity, community structure, and function of the symbiotic bacterial community of coral were analyzed using high-throughput sequencing technology. The α-diversity of the symbiotic bacterial community of coral first decreased and then increased with the exposure time of microplastics. The analysis of ß-diversity and microbial community composition showed that microplastic exposure caused significant changes in the symbiotic bacterial community of coral, and the bacterial community composition also changed with the exposure time. A total of 49 phyla, 152 classes, 363 orders, 634 families, and 1390 genera were detected. At the phylum level, Proteobacteria was the dominant taxa in all samples, but the relative abundance varied among samples. Microplastic exposure increased the abundance of Proteobacteria, Chloroflexi, Firmicutes, Actinobacteriota, Bacteroidota, and Acidobacteriota. At the genus level, Ralstonia, Acinetobacter, and Delftia were the dominant taxa of symbiotic bacteria of coral after microplastic exposure. PICRUSt functional prediction indicated that functions of the coral symbiotic bacterial community, including signal transduction, cellular community prokaryotes, xenobiotics biodegradation and metabolism, and cell motility, decreased after microplastic exposure on coral. BugBase phenotype predictions indicated that microplastic exposure altered three phenotypes (pathogenic, anaerobic, and oxidative stress-tolerant) of the coral symbiotic bacterial community. FAPROTAX functional predictions indicated that microplastic exposure caused significant changes in functions such as the symbiotic relationship between coral symbiotic bacteria and the host, carbon and nitrogen cycling, and photosynthesis. This study provided basic data on the mechanism of microplastic impacts on corals and microplastics ecotoxicology.

Three-component acyloxylation of diazo compounds with carboxylic acids and azadienes.

Despite many studies on benzofuran-derived azadiene being reported, multi-component studies have scarcely been reported on this heterocyclic skeleton. The first cascade three-component acyloxylation of diazos with acids and azadienes has been reported under mild conditions. The reaction is applicable to various (A/A) diazo compounds, generating diverse complex benzofuran derivatives.

Hsa_circ_0007460 affects the survival of intracellular Mycobacterium tuberculosis by regulating autophagy and apoptosis of macrophages.

Circular RNA (circRNA) is a category of non-coding RNAs characterized by the absence of a 5'-cap and 3'-poly(A) tail, and participates in the physiological processes of various human diseases. Nonetheless, the diagnostic and functional significance of circRNAs in active pulmonary tuberculosis (ATB) remains uncertain. Consequently, the purpose of this study is to investigate whether hsa_circ_0007460 can be employed as a potential diagnostic biomarker in ATB patients and explore its function. The result of real-time quantitative fluorescent PCR (RT-qPCR) validated a notable increase in the expression of hsa_circ_0007460 in the peripheral blood of 32 ATB patients, as well as in THP-1 human macrophages infected with Bacillus Calmette Guerin (BCG) which is an attenuated strain of Mycobacterium bovis. Additionally, the receiver operating curve (ROC) illustrated that the area under the ROC curve (AUC), sensitivity and specificity were 0.7474, 76.67%, and 78.13% respectively. RNase R, Actinomycin D and other experiments confirmed that hsa_circ_0007460 was stabler than its linear mRNA, indicating that hsa_circ_0007460 has potential as a diagnostic biomarker of ATB. Furthermore, Western blot (WB), Cell Counting Kit-8 (CCK-8), plate counting, and immunofluorescence experiments revealed that hsa_circ_0007460 could regulate apoptosis and autophagy of macrophages. The downstream miRNAs and mRNAs were subsequently predicted using bioinformatics, and the hsa circ 0007460/hsa-miR-3127-5p/PATZ1 axis was built. These above results suggest that hsa_circ_0007460 is substantially up-regulated in the peripheral blood of patients with ATB and can be utilized as a potential diagnostic biomarker. In addition, hsa_circ_0007460 can promote apoptosis of macrophages and inhibit autophagy of macrophages, thereby promoting the survival of BCG.

Status and associated factors of food and nutrition literacy among young adults aged 15-44 years in Shenzhen City, China.

Background: Food and nutrition literacy (FNL) plays an important role in young adults' dietary habits and nutrition. This study aimed to investigate FNL status and its associated factors among young adults aged 15-44 years in Shenzhen. Methods: A cross-sectional survey of 5,390 participants was conducted in June 2021. FNL was measured using the Food and Nutrition Literacy Questionnaire for Chinese Adults (FNLQ). A generalized linear model was employed to analyze the factors associated with FNL. Results: The median FNL score (total score = 100) was 68.00, which was below the adequate level of 80. FNL was divided into the two different domains of knowledge and skills, with significantly different scoring rate of 85.30 and 67.77%, respectively. The overall proportion of respondents with adequate FNL was 19.52%. The FNL score was significantly higher among the participants who were female (ß = 2.665; 95% confidence interval [CI]: 2.031-3.299) and with higher education levels (ß ranging from 5.632 [CI: 3.845-7.419] to 10.756 [CI: 8.973-12.538]), healthcare-related work experience (ß = 4.197; CI: 3.557-4.837) and a higher economic status (ß ranging from 0.753 [CI: 0.079-1.426] to 6.217 [CI: 5.208-7.227]). Those who were divorced or with an unknown marital status (ß = -8.438; CI: -9.701, -7.175), abnormal body mass index (thin [ß = -2.115; CI: -3.063, -1.166], overweight [ß = -1.427; CI: -2.254, -0.600]), and suffering from chronic diseases (single disease [ß = -3.483; CI: -4.485, -2.480], multimorbidity [ß = -5.119; CI: -5.912, -4.327]) had significantly lower FNL scores. Conclusion: Generally, the level of FNL among young adults in Shenzhen, China, was relatively low. Thus, nutrition education programs targeted at promoting improved FNL status call for additional emphasis, especially in subgroups with lower scores.

Five-Coordinated Dysprosium Single-Molecule Magnet Functionalized by the SMe Group.

A five-coordinate mononuclear Dy(III) complex with a C4v geometry (square-pyramid), [Dy(X)(DBP)2(TMG(H))2] [X = 3-(methylthio)-1-propoxide, DBP = 2,6-di-tert-butylphenoxide, and TMG(H) = 1,1,3,3-tetramethylguanidine] (1), was designed and synthesized. The complex displays a large anisotropy barrier of 432 cm-1 in the absence of a dc magnetic field benefiting from the strong interaction between the phenolate and Dy(III) ion. Ab initio calculations reveal that the most possible relaxation pathway is going through the second excited state. The terminal SMe group in the apical position furnishes the possibility of depositing it on the Au surface by the strong Au-S bond.

Industrial Process Monitoring Based on Dynamic Overcomplete Broad Learning Network.

Most industrial processes feature high nonlinearity, non-Gaussianity, and time correlation. Models based on overcomplete broad learning system (OBLS) have been successfully applied in the fault monitoring realm, which may relatively deal with the nonlinear and non-Gaussian characteristics. However, these models barely take time correlation into full consideration, hindering the further improvement of the monitoring accuracy of the network. Therefore, an effective dynamic overcomplete broad learning system (DOBLS) based on matrix extension is proposed, which extends the raw data in the batch process with the idea of "time lag" in this article. Subsequently, the OBLS monitoring network is employed to continue the analysis of the extended dynamic input data. Finally, a monitoring model is established to tackle the coexistence of nonlinearity, non-Gaussianity, and time correlation in process data. To illustrate the superiority and feasibility, the proposed model is conducted on the penicillin fermentation simulation platform, the experimental result of which illustrates that the model can extract the feature of process data more comprehensively and be self-updated more efficiently. With shorter training time and higher monitoring accuracy, the proposed model can witness an improvement of average monitoring accuracy by 3.69% and 1.26% in 26 process fault types compared to the state-of-the-art fault monitoring methods BLS and OBLS, respectively.

pH-Responsive DNA Motif: From Rational Design to Analytical Applications.

pH-responsive DNA motifs have attracted substantial attention attributed to their high designability and versatility of DNA chemistry. Such DNA motifs typically exploit DNA secondary structures that exhibit pH response properties because of the presence of specific protonation sites. In this review, we briefly summarized second structure-based pH-responsive DNA motifs, including triplex DNA, i-motif, and A+-C mismatch base pair-based DNA devices. Finally, the challenges and prospects of pH-responsive DNA motifs are also discussed.

Comparing rice production systems in China: Economic output and carbon footprint.

In recent years, many rotational and integrated rice production systems coupled with several greenhouse gas (GHG) emissions mitigation practices have been developed and adopted for demand of low carbon production. However, there have been only few studies about comparisons on the balance between high production and mitigation of GHG emissions in different rice production systems. We therefore aimed to evaluate economic output and carbon footprint of different rice production systems, based on several long-term experiments conducted by our lab. CH4 and N2O emission were measured by the same static chamber/gas chromatogram measurement procedure in different rice production systems, including rice-fallow, rice-rapeseed, rice-wheat, double rice, and integrated rice-crayfish production system. Then, we applied the DeNitrification DeComposition model to simulate CH4 and N2O emission over different years under the same condition for comparison. Carbon footprint was calculated following the process-based life cycle assessment (PLCA) methodology. The economic benefit of rice production systems was assessed by cost-benefit analysis. According to the analysis, the double-rice production system exhibited the highest intensity of carbon footprint (ICF = 4.14 kg CO2-eq yuan-1), rain-fed treatment in the rice-rapeseed system had the lowest (ICF = 0.68 kg CO2-eq yuan-1). The intensity of carbon footprint in different treatments in the integrated rice-crayfish production system was around 0.8 kg CO2-eq yuan-1. Overall, the results of this case study suggest: (1) the proposed practices in different rice production systems are no straw returning (rice-fallow), no-tillage without straw returning (rice-wheat), rain-fed farming (rice-rapeseed), no insect and no inoculation (double rice), and feeding with straw returning (rice-crayfish); (2) rotational and integrated systems can achieve high net output with low carbon emission; (3) reducing the amount of nitrogenous fertilizer application is the most important and effective GHG mitigation practice for rotational systems.

Air-Stable Chiral Single-Molecule Magnets with Record Anisotropy Barrier Exceeding 1800 K.

Design and synthesis of air-stable and easily tailored high-performance single-molecule magnets (SMMs) are of great significance toward the implementation of SMMs in molecular-based magneto-electronic devices. Here, by introducing electron-withdrawing fluorinated substituents on equatorial ligand, two chiral Dy(III) macrocyclic complexes, RRRR-Dy-D6hF12 (1) and SSSS-Dy-D6hF12 (2), with a record anisotropy barrier exceeding 1800 K and the longest relaxation time approaching 2500 s at 2.0 K for all known air-stable SMMs, were obtained. The nearly perfect axiality of the ground Kramers doublet (KD) enables the open hysteresis loops up to 20 K in the magnetically diluted sample. It is notable that they are structurally rigid with high thermal stability and the apical ligand can be tailored to carry proper surface-binding groups. This finding not only improves the magnetic properties for air-stable SMMs but also provides a new avenue for deposition of SMMs on surfaces.

Tetraphenylpyrazine-Based Luminescent Metal-Organic Framework for Chemical Sensing of Carcinoids Biomarkers.

A new non-interpenetrated three-dimensional (3D) pillared-layered TPP-based LMOF [Zn3(TPyTPP)0.5(BDC)3]·8DMF (denoted as Zn-MOF 1) was successfully prepared (TPyTPP = tetrakis(4-(pyridin-4-yl)phenyl)pyrazine and H2BDC = 1,4-benzenedicarboxylic acid). Zn-MOF 1 was characterized by single-crystal X-ray diffraction, PXRD, IR, N2 adsorption, thermogravimetric analysis, and luminescent spectrum. Impressively, luminescent sensing studies reveal that activated Zn-MOF 1 not only displays excellent luminescence-quenching efficiency with the values of high Ksv and low LODs toward 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA), respectively, but also possesses outstanding sensing characteristics in terms of fast response, high sensitivity, and specific selectivity. Zn-MOF 1 performs as efficient sensing of carcinoid biomarkers to provide a fresh detection platform for the diagnosis of carcinoids. In addition, the sensing mechanism was also explored on the basis of ultraviolet-visible (UV-vis) absorption, DFT calculations, and structural analysis.

[Detection of JAK2V617F and CALR Gene Mutations by Multiplex of Patients with Myeloproliferative Neoplasms PCR-Capillary Electrophoresis].

OBJECTIVE: To evaluate the proformance of multiplex PCR and capillary electrophoresis(MPCE) in the detection of JAK2V617F and CALR mutation in myeloproliferative neoplasms(MPN). METHODS: The specificity primers of JAK2617F gene mutation and the primers of CALR gene were designed at the same time. The JAK2V617F and CALR gene primers were labeled with Cy5 fluorescence, all the primers were mixed in one tube for multiplex PCR and the PCR prodcuts were analysised by capillary electrophoresis. Then detection limit and sensitivity of MPCE were evaluated, and compared with comercial diagnostic kit. RESULTS: JAK2V617F and CALR gene mutations could be detect by MPCE in one PCR test. JAK2V617F mutation could be detected at 0.01 ng genomic DNA, double positive JAK2V617F and CLAR gene mutations could be detected at 0.1 ng genomic DNA, at least 0.1% JAK2V617F positive mutation could be detected. The consistency between MPCE and commercial diagnostic gene mutation kit was 100%. CONCLUSION: It is developed that a new gene mutation detection method of JAK2 V617F and CLAR gene based on MPCE in our experiment and it can be used as a new reagent for molecular diagnosis of MPN patients.

LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway.

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

Network Pharmacology-Based Approach Uncovers the Mechanism of GuanXinNing Tablet for Treating Thrombus by MAPKs Signal Pathway.

BACKGROUND: GuanXinNing tablet (GXNT), a traditional Chinese patent medicine, has been found to have remarkable antithrombotic effects and can effectively inhibit pro-thrombotic factors in previous studies. However, the mechanism of its antithrombotic effects remains little known. METHODS: In this study, we first determined and identified the sources of each main compound in GXNT using liquid chromatography-mass spectrometry (LC-MS). Through the approach of network pharmacology, we predicted the action targets of the active components, mapped the target genes related to thrombus, and obtained potential antithrombotic targets for active ingredients. We then performed gene ontology (GO) enrichment analyses and KEGG signaling pathway analyses for the action targets, and constructed networks of active component-target and active component-target-pathway for GXNT. Additionally, we evaluated the pharmacodynamic effects of GXNT on thrombus using the rat thrombus model induced by FeCl3, observed the effects of antiplatelet aggregation via platelet assay, and further verified the results predicted by network pharmacology via Western blot. RESULTS: In total, 14 active ingredients were identified in GXNT, and 83 action targets were predicted, 17 of which are antithrombotic targets that potentially participate in processes including response to oxidative stress and positive regulation of blood vessel endothelial cell migration. KEGG pathway analyses revealed that the predicted action targets were involved in multiple signal pathways, such as MAPK, IL-17, and platelet activation. Pharmacodynamics study found that GXNT could significantly reduce the thrombus length and weight, lower platelet aggregation function, and decrease the levels of Fbg and PAI-1. In addition, GXNT could significantly increase 6-keto-PGF1α content and regulate the ratio of TXB2/6-keto-PGF1α, while not having dramatic effects on TXB2. GXNT was also observed to visibly inhibit maximum platelet aggregation. Herein, we further studied the thrombus-related MAPKs signaling pathway and found that GXNT could significantly reduce the phosphorylation levels of p38MAPK, ERK, and JNK proteins in platelet. CONCLUSIONS: This study revealed the pharmacodynamic material basis of GXNT and its potential multicomponent-multitarget-multipath pharmacological effects, confirmed the antithrombotic effects of GXNT, and showed that its mechanism may be related to inhibiting phosphorylation of p38, ERK, and JNK proteins in MAPKs signaling pathway, partially verifying the results from network pharmacology. The results from this study could provide a theoretical basis for the development and clinical application of GXNT.

A U-shaped Association of Breastfeeding Duration with Cognitive Impairment in Chinese Postmenopausal Women.

Breastfeeding is related to maternal health. However, the association of women's breastfeeding duration with cognitive function in their later life is limited and inconsistent. The aim of this study was to accurately evaluate the association in Chinese postmenopausal women. We analyzed the data from Zhejiang Ageing and Health Cohort Study including 5487 postmenopausal women. Cognitive impairment was assessed via the Mini-Mental State Examination. Data on breastfeeding duration was collected in the reproductive history section within the questionnaire. Generalized additive models (GAMs) and logistic regression models, controlled for an extensive range of potential confounders, were generated to examine the associations. A U-shaped association was identified between breastfeeding duration and cognitive impairment based on GAM. The nadir with lowest odds of cognitive impairment was ascertained by quadratic model as 12 months. The logistic models showed that compared with women breastfeeding 12 months per child, the fully adjusted odds ratios (ORs) were 1.50 (95% Confidence Interval (CI): 1.20-1.88), 1.58 (95% CI: 1.29-1.93), 1.33 (95% CI: 1.06-1.68), 2.08 (95% CI: 1.64-2.65) for those averagely breastfeeding <6, 6-<12,>12-18,>18 months, respectively. Furthermore, we did not observe significant effect modification of the association. Future longitudinal studies are needed to confirm the association.

Influence of Post-Annealing on the Structural and Nanomechanical Properties of Co Thin Films.

The correlations between the microstructure and nanomechanical properties of a series of thermal annealed Co thin films were investigated. The Co thin films were deposited on glass substrates using a magnetron sputtering system at ambient conditions followed by subsequent annealing conducted at various temperatures ranging from 300 C to 800 C. The XRD results indicated that for annealing temperature in the ranged from 300 C to 500 C, the Co thin films were of single hexagonal close-packed (hcp) phase. Nevertheless, the coexistence of hcp-Co (002) and face-centered cubic (fcc-Co (111)) phases was evidently observed for films annealed at 600 C. Further increasing the annealing temperature to 700 C and 800 C, the films evidently turned into fcc-Co (111). Moreover, significant variations in the hardness and Young's modulus are observed by continuous stiffness nanoindentation measurement for films annealed at different temperatures. The correlations between structures and properties are discussed.