Search

The grain characteristic and orientation were analyzed using the electron backscatter diffraction (EBSD) for AZ31 hot-rolled alloys. The corrosion initiation of the bimodal microstructure is revealed for the hot-rolled AZ31 alloys obtained by the quasi-in-situ EBSD, showing the preferential corrosion in the fine grain region. Meanwhile, the non-basal crystal plane grain is easier to corrode than the basal crystal plane grain. The adsorption energies of H2O molecule on the crystal planes of magnesium matrix were calculated by the density functional theory method, and a new insight into the corrosion anisotropy of crystal planes was proposed from the surface adsorption energy.

Prosocial behaviour is a bedrock of humane societies. Although previous studies have shown that parental style is an important contributing factor for children's prosocial behaviour, the psychological mechanism underlying this association in specific cultural background remains unclear. Based on the ecological systems theory, this study sought to explore the influence of parental warmth on children's prosocial behaviour, and the mediating effect of self-efficacy, as well as the moderating role of teachers' incentive evaluation in the link between self-efficacy and children's prosocial behaviour. This cross-sectional, survey-based study collected data from parents and teachers of 414 Chinese preschoolers (5–6 years old). Parents of these children finished questionnaires on the Chinese version of the short-form Egna minnen av. Barndoms uppfostran (s-EMBU-C), Child Behaviour Scale (CBS), and the revised General Self-efficacy Scale (GSES), while Incentive evaluation questionnaire was finished by their teachers. Results indicated that children who experience high parental warmth were more likely to act prosocially (b = 0.61, p

Based on the simulation results of ProCAST software for the filling and solidification process, the formation mechanism of the VIM electrode ingot's pipe and porosities and the influence of the casting process on the formation of electrode shrinkage were studied in detail. The research results indicate that the critical condition for the formation of 200 kg grade C650R heat-resistant alloy is verified to be G/R≤5.0 (K·s)0.5/cm. In addition to the alloy's inherent characteristics, the substantial height to diameter ratio (H/D) of the VIM electrode ingot is the primary factor contributing to the formation of deep pipe and severe porosities. Simply adjusting the casting time or casting speed alone does not significantly improve the solidification quality of the ingot. While the use of a hot top can eliminate pipe, its effectiveness is limited, as the alloy melt at the hot top location has minimal influence on the solidification process in the lower regions of the electrode ingot, thereby failing to effectively reduce the formation of porosities. Properly reducing the casting speed and casting superheat lead to the formation of a V-shaped melt at localized positions during the final stage of solidification. This enhances the ability of the liquid phase for further feeding, ultimately significantly decreasing both the depth of pipe and the porosity rate. The optimal casting process optimization solution for C650R alloy electrode ingot with a size of Φ130 mm × 1240 mm is the casting speed of 60 kg/min and the superheat of 40 °C.

Alzheimer’s disease (AD) is a progressive neurological disorder, with two main pathological hallmarks of senile plaques and neurofibrillary tangles accumulated of abnormally phosphorylated Tau. Ginkgolic acid (GA), as an inhibitor of SUMO-1, exhibits many biological activities, including neuroprotective effects. However, the efficacy of GA in AD treatment has not been sufficiently investigated. Therefore, the current study aimed to explore the function and the underlying molecular mechanisms of GA related to AD. Our study revealed that GA exerted protective effects on cognitive impairment of an Aβ-induced AD rat model, and suppressed the neuronal apoptosis and oxidative stress induced by Aβ1-42 both in vivo and in vitro. Of crucial importance, GA significantly inhibited Tau phosphorylation, and blocked the activation of the SUMO-1/GSK3β signaling pathway. Taken together, these observations demonstrated that GA improved cognitive ability and inhibited Tau phosphorylation through SUMO1/GSK3β pathway, indicating that GA is a potential drug for the preventing and treatment of AD.

Aiming at the problem of low efficiency at low flow in small hydropower stations, a permanent magnet direct-drive hydropower generation control system based on dual PWM converters is proposed to realize wide-range variable-speed constant-frequency hydropower generation of hydraulic turbine units and improve the comprehensive power generation efficiency of small hydropower stations. In this control system, the hydraulic turbine is coaxially connected to the permanent magnet synchronous generator(PMSG) through the flywheel, and the power grid is connected by back-to-back dual PWM converters, and the bidirectional energy flow is realized by the voltage space vector pulse width modulation method. The generator-side converter controls the rotating speed of hydraulic turbine units and tracks the optimal speed point of the hydraulic turbine units in real time to realize the maximum power output of hydraulic turbine units. The grid-side converter adopts active power and reactive power decomposition control method to stabilize the DC bus voltage and provide the reactive power required by the grid. Finally, the effectiveness of the proposed control system was proved by comparative experiments in a 400V/200kW/428rpm small hydropower station.

In this paper, the modular design is adopted to study the control strategy of photovoltaic system, energy storage system and flexible DC system, so as to achieve the design and control strategy research of the whole system of “photovoltaic + energy storage + DC + flexible DC”. This realizes the flexibility and diversity of networking. Due to space reasons, this article focuses on the detailed explanation of the photovoltaic energy storage system control strategy, including the maximum power tracking control strategy of photovoltaic power generation, photovoltaic power generation boost chopper circuit control strategy, photovoltaic power generation DC/AC converter control strategy, PCS device control strategy, PCS virtual impedance control algorithm, etc. Simulation experiments are carried out according to the specific case setting parameters. The simulation results prove that the proposed flexible DC system coordinated control strategy can ensure grid frequency stability and grid voltage stability, and improve the consumption capacity of distributed new energy.

Background: Growing competition in tight job market and academic excellence as a social norm in Asian culture have made Chinese college students burdened with immense academic stress. Objectives: This study aimed to explore the associations between academic stress and depression, and the mediating roles of negative affect and sleep quality, as well as the moderating role of social support in the relationship between negative affect and sleep quality. Methodology: A convenience sample of 221 male and 479 female college students aged between 17 and 25 completed questionnaires on academic stress, depression, negative affect, sleep quality and social support. Results: Results indicated that academic stress could not only directly affect depression (b = 0.31, p

Background: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. Objectives: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. Methods: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. Results: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: β = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: β = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 μg/L) increase of Se was positively associated with the MMSE score (β = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. Conclusions: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Precise diagnosis of early prostate cancer (PCa) is critical for preventing tumor progression. However, the diagnostic outcomes of currently used markers are far from satisfactory due to the low sensitivity or specificity. Here, we identified a diagnostic subpopulation in PCa tissue with the integrating analysis of single-cell and bulk RNA-seq. The representative markers of this subpopulation were extracted to perform intersection analysis with early-PCa-related gene module generated from weighted correlation network analysis (WGCNA). A total of 24 overlapping genes were obtained, the diagnostic roles of which were validated by distinguishing normal and tumorous prostate samples from the public dataset. A least absolute shrinkage and selection operator (LASSO) model was constructed based on these genes and the obtained 24-gene panel showed high sensitivity and specificity for PCa diagnosis, with better identifying capability of PCa than the commercially used gene panel of Oncotype DX. The top two risk factors, TRPM4 and PODXL2, were verified to be highly expressed in early PCa tissues by multiplex immunostaining, and PODXL2 was more sensitive and specific compared to TRPM4 and the pathologically used marker AMACR for early PCa diagnosis, suggesting a novel and promising pathology marker.

Background & Aims: Aflatoxin exposure increases the risk for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected individuals, particularly males. We investigated sex-based differences in the HCC genome and antitumor immunity. Methods: Whole-genome, whole-exome, and RNA sequencing were performed on 101 HCC patient samples (47 males, 54 females) that resulted from HBV infection and aflatoxin exposure from Qidong. Androgen on the expression of aflatoxin metabolism-related genes and nonhomologous DNA end joining (NHEJ) factors were examined in HBV-positive HCC cell lines, and further tested in tumor-bearing syngeneic mice. Results: Qidong HCC differed between males and females in genomic landscape and transcriptional dysfunction pathways. Compared with females, males expressed higher levels of aflatoxin metabolism-related genes, such as AHR and CYP1A1, and lower levels of NHEJ factors, such as XRCC4, LIG4, and MRE11, showed a signature of up-regulated type I interferon signaling/response and repressed antitumor immunity. Treatment with AFB1 in HBV-positive cells, the addition of 2 nmol/L testosterone to cultures significantly increased the expression of aflatoxin metabolism-related genes, but reduced NHEJ factors, resulting in more nuclear DNA leakage into cytosol to activate cGAS-STING. In syngeneic tumor-bearing mice that were administrated tamoxifen daily via oral gavage, favorable androgen signaling repressed NHEJ factor expression and activated cGAS-STING in tumors, increasing T-cell infiltration and improving anti–programmed cell death protein 1 treatment effect. Conclusions: Androgen signaling in the context of genotoxic stress repressed DNA damage repair. The alteration caused more nuclear DNA leakage into cytosol to activate the cGAS-STING pathway, which increased T-cell infiltration into tumor mass and improved anti–programmed cell death protein 1 immunotherapy in HCCs.

Modular multi-level converter (MMC)-based multi-terminal dc (MTDC) grid (abbreviated as MMC-MTDC) is promising in the integration and transmission of bulk renewable energy. This paper analyzes the transient characteristic of large-scale power systems with the MMC-MTDC. First, the transient stability-electromagnetic transient (TS-EMT) model of the system is established. The corresponding simulation flowchart is also presented, where the MMC-MTDC grid dynamics are calculated by EMT simulation and the ac grid is simulated by the TS program. Second, based on the mathematical model of the MMC-MTDC grid, the transient characteristics during various faults are analyzed. Third, it analyzes the influences of the controller parameters on the transient characteristics. Test results on the North-China power system with Zhangbei MTDC verifies the correctness of the transient characteristic analyses.

The dynamic load of vehicles is the main cause of rutting on asphalt pavement. To study the magnitude of the rutting depth generated by the load frequency on asphalt pavement, the rutting test procedure was developed through a material test system (MTS). A rutting fixture for the MTS test system has been designed. Rutting tests were carried out on AC-13, AC-20, and SMA-13 modified asphalt mixtures at different temperatures and load frequencies. Track and detect rut deformation under different loading times. The finite element Abaqus was used for simulation analysis, and a paired sample t-test was performed between the finite element simulation results and the MTS rutting test results. Through multiple regression analysis of the MTS rutting test data, an indoor rutting prediction model for asphalt mixtures including load frequency parameters was established. The correlation between the rutting prediction model established in this study and the rutting prediction model Specifications for Design of Highway Asphalt Pavement (JTG D50-2017) reached 0.894. The researchers conducted the MTS rut loading test by adding AC-20 modified asphalt mixture. SPSS data analysis software was used to analyze the measured data and predicted data. The correlation coefficient between the predicted and measured values was 0.973. In the paired sample test, the significance probability P = 0.671 was much larger than 0.05, indicating that the data error of the two groups was small. It is verified that the rut prediction model established in this study has high accuracy.

Oncolytic viruses mediate antitumor responses through direct tumor cell lysis and induction of host antitumor immunity. However, the therapeutic efficacy of oncolytic viruses against malignant ascites has rarely been explored. This study aimed to evaluate the efficacy, safety, and immunomodulatory effect of an intraperitoneal injection of human type 5 recombinant adenovirus (called H101) against malignant ascites. Forty patients with malignant ascites were recruited and treated with intraperitoneal H101 in the Fudan University Shanghai Cancer Center. The 4-week clinical responses were determined by an objective assessment of ascites volume change. The ascites response rate and ascites control rate were 40% (16/40) and 75% (30/40), respectively. The major adverse events following intraperitoneal H101 administration were mild-to-moderate abdominal pain (8/40, 20.0%) and fever (11/40, 27.5%); no grade III/IV adverse events were observed. Mass cytometry and immunocytological analysis at baseline, and days 7 and 14 post-treatment showed that intraperitoneally injected H101 led to marked tumor cell depletion, increased dendritic cell and CD8+ T cell densities. H101-meditated tumor-specific immune activation on day 14 post-treatment was further identified by enzyme-linked immunospot assay. In conclusion, intraperitoneal H101 administration was well tolerated and effective in treating malignant ascites; thus, its immune activation ability may be a promising tool in combination with immunotherapy.

Background: The most common disease caused by biallelic AFG3L2 mutations is spastic ataxia type 5 (SPAX5). Identification of complex phenotypes resulting from biallelic AFG3L2 mutations has been increasing in recent years. Methods: A retrospective analysis was performed on a child with microcephaly and recurrent seizures. The child underwent physical and neurological examinations, laboratory tests, electroencephalography (EEG), and brain magnetic resonance imaging (MRI). Trio-whole-exome sequencing (trio-WES) was performed to identify possible causative mutations. Results: We described a child who exhibited early-onset and intractable epilepsy, developmental regression, microcephaly, and premature death. Neuroimaging revealed global cerebral atrophy (GCA) involving the cerebrum, cerebellum, corpus callosum, brainstem, cerebellar vermis, and basal ganglia. On trio-WES, two novel compound heterozygous mutations, c.1834G > T (p.E612*) and c.2176-6T > A in the AFG3L2 gene, were identified in this patient. Conclusions: Our findings have expanded the mutation spectrum of the AFG3L2 gene and identified a severe neurodegenerative phenotype of global cerebral atrophy caused by biallelic AFG3L2 mutations.

Summary: Background: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease affecting multiple organs and tissues with high cellular heterogeneity. CD8+ T cell activity is involved in the SLE pathogenesis. However, the cellular heterogeneity and the underlying mechanisms of CD8+ T cells in SLE remain to be identified. Methods: Single-cell RNA sequencing (scRNA-seq) of PBMCs from a SLE family pedigree (including 3 HCs and 2 SLE patients) was performed to identify the SLE-associated CD8+ T cell subsets. Flow cytometry analysis of a SLE cohort (including 23 HCs and 33 SLE patients), qPCR analysis of another SLE cohort (including 30 HCs and 25 SLE patients) and public scRNA-seq datasets of autoimmune diseases were employed to validate the finding. Whole-exome sequencing (WES) of this SLE family pedigree was used to investigate the genetic basis in dysregulation of CD8+ T cell subsets identified in this study. Co-culture experiments were performed to analyze the activity of CD8+ T cells. Findings: We elucidated the cellular heterogeneity of SLE and identified a new highly cytotoxic CD8+ T cell subset, CD161−CD8+ TEMRA cell subpopulation, which was remarkably increased in SLE patients. Meanwhile, we discovered a close correlation between mutation of DTHD1 and the abnormal accumulation of CD161−CD8+ TEMRA cells in SLE. DTHD1 interacted with MYD88 to suppress its activity in T cells and DTHD1 mutation promoted MYD88-dependent pathway and subsequently increased the proliferation and cytotoxicity of CD161−CD8+ TEMRA cells. Furthermore, the differentially expressed genes in CD161−CD8+ TEMRA cells displayed a strong out-of-sample prediction for case–control status of SLE. Interpretation: This study identified DTHD1-associated expansion of CD161−CD8+ TEMRA cell subpopulation is critical for SLE. Our study highlights genetic association and cellular heterogeneity of SLE pathogenesis and provides a mechanistical insight into the diagnosis and treatment of SLE. Fundings: Stated in the Acknowledgements section of the manuscript.

Summary: CCR7-triggered DC migration toward draining lymph nodes is critical for the initiation of protective immunity and maintenance of immune tolerance. How to promote CCR7-mediated DC migration to determine T cell responses under inflammatory and homeostatic conditions remains poorly understood. Here we demonstrate that the Extl1 (Exostosin like glycosyltransferase 1) promotes CCR7-triggered DC migration in a heparan sulfate proteoglycans (HSPG)-dependent manner. Mechanistically, Extl1 mediates HSPG production via its glycosyltransferase domain to inhibit C1q expression. Extl1/HSPG axis relieves C1q-mediated restriction of CCR7 surface expression and internalization, and thus enhances CCR7-dependent migratory signaling activation. Consequently, Extl1 is required for DC-mediated Th1 and Th17 responses in immune defense against bacterial infection and for Treg cell development in the prevention of autoimmunity. Our study adds mechanistic insights to the regulation of CCR7-triggered DC migration in immunity and tolerance and provides a potential target for the treatment of infectious and autoimmune diseases.

Background: Epidemiological studies have reported an association between traffic-related pollution with risk of metabolic syndrome (MetS). However, evidence from prospective studies on the association of walkability and nitrogen dioxide (NO2) with MetS is still scarce. We, therefore, aimed to evaluate the association of long-term exposure to NO2 and walkability with hazards of incident MetS. Methods: A total of 17,965 participants without MetS diagnosed within one year at baseline were included in our study from a population-based prospective cohort in Yinzhou District, Ningbo, Zhejiang Province, China. Participants were followed up by the regional Health Information System (HIS) until December 15, 2021. MetS was defined based on the criteria of Chinese Diabetes Society (CDS2004). We used walkscore tools, calculating with amenity categories and decay functions, and spatial–temporal land-use regression (LUR) models to estimate walkability and NO2 concentrations. We used Cox proportional hazards regression models to examine the association of walkability and NO2 with hazards of MetS incidence reporting with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Overall, we followed up 77,303 person-years and identified 4040 incident cases of MetS in the entire cohort. Higher walkability was inversely associated with incident MetS (HR = 0.94, 95 % CI: 0.91–0.99), whereas NO2 was positively associated with MetS incidence (HR = 1.07, 95 %CI: 1.00–1.15) per interquartile range increment in two-exposure models. Furthermore, we found a significant multiplicative interaction between walkability and NO2. Stronger associations were observed for NO2 and incident MetS among men, smokers, drinkers and participants who aged

Identification of clinically applicable molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) is crucial to improving patient outcomes. However, the traditional tissue-dependent transcriptional subtyping strategies are invasive and not amenable to routine clinical evaluation. In this study, we developed a circulating extracellular vesicle (cEV) long RNA (exLR)-based PDAC subtyping method and provided exLR-derived signatures for predicting immunogenic features and clinical outcomes in PDAC. We enrolled 426 individuals, among which 227 PDACs served as an internal cohort, 118 PDACs from two other medical centers served as an independent validation cohort, and 81 healthy individuals served as the control. ExLR sequencing was performed on all plasma samples. We found that PDAC could be categorized into three subtypes based on plasma exLR profiles. Each subpopulation showed its own molecular features and was associated with patient clinical prognosis. The immunocyte-derived cEV fractions were altered among PDAC subtypes and interconnected with tumor-infiltrating lymphocytes in cancerous tissue. Additionally, we found a significant concordance of immunoregulators between tissue and blood EVs, and we harvested potential PDAC therapeutic targets. Most importantly, we constructed a nine exLR-derived, tissue-applicable signature for prognostic assessment of PDAC. The circulating exLR-based features may offer an attractive platform for personalized treatment and predicting patient outcomes in multiple types of cancer.

Background: Some studies have reported to use some predictors before extracorporeal membrane oxygenation (ECMO) initiation to predict the acute kidney injury (AKI) risk. However, injury during the ECMO operation and the response of patients to ECMO may significantly influence the prognosis, and they are unpredictable before ECMO initiation. This study aims to develop a potential model based clinical characteristics at the 2-hour time point during ECMO for the early prediction of AKI in patients receiving ECMO. Methods: 139 patients who underwent ECMO were enrolled in this study. The clinical characteristics and the laboratory examinations at 2-hour time point during ECMO were recorded. The least absolute shrinkage and selection operator (LASSO) regression method was performed to select predictors, and logistic regression and a nomogram were used to establish the prediction model. The area under curve (AUC) of the receiver operating characteristic and calibration curve were used to analyze the discrimination and calibration of the model. K-fold cross-validation method was performed to validate the accuracy of this model. Results: Among the 139 patients receiving ECMO, 106 participants (76.26%) developed AKI. Four predictive variables including ECMO model, serum creatinine (Scr-2h), uric acid(UA-2h), and serum lactate (Lac-2h) at the 2-hour time point during ECMO were filtered from 39 clinical parameters by LASSO regression. These four predictors were incorporated to develop a model for predicting AKI risk using logistic regression. The AUC of the model was 0.905 (0.845–0.965), corresponding to 81.1% sensitivity, 90.9% specificity and 83.5% accuracy. Moreover, this model showed good consistency between observed and predicted probability based on the calibration curve (P > 0.05). The validation performed by K-fold cross-validation method showed that the accuracy was 0.874 ± 0.006 in training sets, 0.827 ± 0.053 in test sets, indicating a good capability for AKI risk prediction. Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusion: The nomogram incorporating Scr-2h,Lac-2h, UA-2h, and ECMO model may facilitate the individualized prediction of the AKI risk among patients undergoing ECMO.

With the rapid increase in vehicles, the load on the asphalt pavement increases, which aggravates the appearance of rutting disease. In order to establish an effective rutting depth prediction model, this study carried out accelerated loading tests (ALT) of asphalt pavement at three different temperature environments of 60 °C, 45 °C, and 30 °C for Ji-Qing Expressway at the end of service. The rutting depth of the test was measured using a Lr-70/700 laser rut measuring instrument, and the relationship between the rutting depth of asphalt pavement and the temperature change was examined. At the ambient temperature of 60 °C, three different loading speeds of 3.5 km/h, 4.5 km/h, and 5.5 km/h were tested to analyze the influence of load frequency on rutting depth. With the SPSS analysis software, the regression analysis of the collected test data was carried out to modify the rutting prediction model established by the indoor improved MTS test. The results show that when the loading speed is increased from 3.5 km/h to 4.5 km/h, the rutting depth can be reduced by 11%. When the loading speed increases from 4.5 km/h to 5.5 km/h, the rut depth can be reduced by 15.8%. When the loading temperature increases from 30 °C to 45 °C, the rut depth increases by 2.15 times. When the loading temperature increased from 45 °C to 60 °C, the rutting depth increased by 0.46 times.

As the core of the secondary part of the high voltage direct current transmission (hereinafter referred to as HVDC) transmission system, HVDC protection is the first line of defense for the safe and reliable operation of the HVDC transmission system. Its reliability directly determines the safety of the HVDC transmission equipment and the stable operation of the power grid. Therefore, it is necessary to evaluate the reliability of the HVDC protection system. Based on the operating data of the converter station, this paper puts forward relevant evaluation indicators, and uses the mixed weighting method of interval analytic hierarchy process and interval entropy weight method to evaluate the converter station’s HVDC protection system and protection equipment. The evaluation results qualitatively and quantitatively judge the operating status of the equipment and verify the effectiveness and feasibility of the method. Using this method can scientifically and reasonably evaluate and analyze the operation of the HVDC protection system and various equipment, and judge the operation status of various equipment. This method can provide important guidance for the selection of new station equipment, the operation, maintenance, and overhaul of the HVDC transmission protection system of the converter station.

Summary: Background: Multiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder. Methods: We performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted UPLC-MS. A four-day food diary was recorded to capture the habitual dietary pattern of study participants. Findings: Together with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. The microbiome and metabolome profiles remained stable over six months in MS and control individuals. Interpretation: Our study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker. Funding: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Background: There has been a great deal of evidence indicating that cytokines participate in meningeal inflammation. Different cytokine profiles may be presented in central nervous system (CNS) infection due to different pathogens. We have attempted to investigate cytokine profiles in cerebrospinal fluid (CSF) of patients with CNS infection. Methods: Forty-three patients with CNS infection including tuberculous meningitis, purulent meningitis and cryptococcal meningitis were enrolled and 11 patients with normal CSF were enrolled as control group. The concentrations of Th1-, Th2- and Th17-type cytokines in CSF were detected using multiplex cytokine assay. Furthermore, the correlation between CSF cytokines and CSF parameters in CNS infection was analyzed. Results: The CSF levels of IL-1β, IL-4, IL-6, IL-10, IL-17, IL-23, IL-33, IFN-γ, TNF-α and sCD40L among the patients with CNS infection were all higher than control group (all P

A position-sensitive CsI(Tl) crystal array coupled with the multi-anode position sensitive photomultiplier tube (PS-PMT), Hamamatsu H8500C, has been developed at the Institute of Modern Physics. An effective, fast, and economical readout circuit based on discretized positioning circuit (DPC) bridge was designed for the 64-channel multi-anode flat panel PSPMT. The horizontal and vertical position resolutions are 0.58 mm and 0.63 mm respectively for the 1.0 × 1.0 × 5.0 mm3 CsI(Tl) array, and the horizontal and vertical position resolutions are 0.86 mm and 0.80 mm respectively for the 2.0 × 2.0 × 10.0 mm3 CsI(Tl) array. These results show that the CsI(Tl) crystal array with low cost could be applied in the fields of medical imaging and high-resolution gamma camera. Keywords: CsI(Tl), Crystal array, DPC, Discretized positioning circuit, IQSP518 system

The wetting behaviour of Al alloys (i.e., 6061 Al and 4043 Al alloys) on the surface of pure titanium was studied by sessile drop method at temperatures of 873–973 K under high vacuum with ˜10−4 Pa. All wetting processes were divided into two stages: in the nonlinear stage, the formation of a compact intermetallic layer (Ti7Al5Si12) blocked the mass transfer at solid/liquid (S/L) interface and deteriorated wetting, while the formation of loose phase (Al3Ti) at triple line region can removed the oxide film and improved wettability. The wetting activation energy (56 kJ/mol for a 6061Al/Ti system, and 71 kJ/mol for a 4043Al/Ti system) corresponded to the sum of the difference in surface energy per molar area between α-Ti and TiO2 (27.2 kJ/mol), and the Gibbs energy of formation for Al3Ti (30 kJ/mol) or the decomposition energy for Ti7Al5Si12 (48 kJ/mol). In the near-linear stage, the droplet spread on the surface of intermetallic compound (IMC). The spreading dynamics for 6061 alloy satisfied the Jiang’s empirical equation, and for 4043 alloy satisfied the viscous dissipation-limited model. The interfacial reaction had little effected on a droplet spreading, while the viscous friction drove the spread of 4043 alloy on precursor film in the near-linear stage. Keywords: Interfacial mass transfer, Reactive wettability, Activation energy, Al-Ti

To investigate the genetic variation and molecular epidemiology characteristics of Human Respiratory Syncytial Virus (HRSV) in Guizhou Province, nasopharyngeal aspirates were collected from patients with acute respiratory infection (ARI) in Guizhou Provincial People's Hospital, from December 2017 to March 2018, and inoculated to Hep-2 cells to isolate HRSV. Cells that showed cytopathic effect (CPE) were then confirmed by indirect immunofluorescence assay and reverse transcription. The sequence of the PCR products was determined for HRSV isolates, and the genetic variation was analyzed. Out of 196 nasopharyngeal aspirate samples, HRSV were isolated in 39. The second hypervariable region at the 3′ terminal of glycoprotein gene (HVR2) sequence analysis showed that subgroup A was dominant. Seventy-nine percent of the isolates belonged to subgroup A, ON1 genotype, and 21 % belonged to subgroup B, BA9 genotype, which indicates that the dominant HRSV circulating in Guizhou Province was subgroup A, genotype ON1, co-circulating with a less prevalent subgroup B, genotype BA9. Keywords: Human respiratory syncytial virus, Virus isolation, RT-PCR, HVR2, Phylogenetic analysis, Molecular epidemiology

The pathology of cerebrovascular disorders takes an important role in traumatic brain injury (TBI) by increasing intracranial pressure. Fibroblast growth factor 20 (FGF20) is a brain-derived neurotrophic factor, that has been shown to play an important role in the survival of dopaminergic neurons and the treatment of Parkinson's disease (PD). However, little is known about the role of FGF20 in the treatment of TBI and its underlying mechanism. The purpose of this study was to evaluate the protective effect of recombinant human FGF20 (rhFGF20) on protecting cerebral blood vessels after TBI. In this study, we indicated that rhFGF20 could reduce brain edema, Evans blue penetration and upregulated the expression of blood-brain barrier (BBB)-related tight junction (TJ) proteins, exerting a protective effect on the BBB in vivo after TBI. In the TBI repair phase, rhFGF20 promoted angiogenesis, neurological and cognitive function recovery. In tumor necrosis factor-α (TNF-α)-induced human brain microvascular endothelial cells (hCMEC/D3), an in vitro BBB disruption model, rhFGF20 reversed the impairment in cell migration and tube formation induced by TNF-α. Moreover, in both the TBI mouse model and the in vitro model, rhFGF20 increased the expression of β-catenin and GSK3β, which are the two key regulators in the Wnt/β-catenin signaling pathway. In addition, the Wnt/β-catenin inhibitor IWR-1-endo significantly reversed the effects of rhFGF20. These results indicate that rhFGF20 may prevent vascular repair and angiogenesis through the Wnt/β-catenin pathway.

Summary: Diffuse large B cells in the cerebrospinal fluid (CSF-DLBCs) have offered great promise for the diagnostics and therapeutics of central nervous system lymphoma (CNSL) leptomeningeal involvement. To explore the phenotypic states of CSF-DLBCs, we analyzed the transcriptomes of more than one thousand CSF-DLBCs from six patients with CNSL diffuse large B-cell lymphoma (DLBCL) using Smart-seq2 single-cell RNA sequencing. CSF-DLBCs were defined based on abundant expression of B-cell markers, the active cell proliferation and energy metabolism properties, and immunoglobulin light chain restriction. We identified inherent heterogeneity of CSF-DLBCs, which were mainly manifested in cell cycle state, cancer-testis antigen expression, and classification based on single-cell germinal center B-cell signature. In addition, the 16 upregulated genes in CSF-DLBCs compared to various normal B cells showed great possibility in the homing effect of the CNS-DLBCL for the leptomeninges. Our results will provide insight into the mechanism research and diagnostic direction of CNSL-DLBCL leptomeningeal involvement.

Summary: Development of highly sensitive, stable, and repeatable surface-enhanced Raman scattering (SERS) substrates is crucial for analytical detection, which is a challenge for traditional metallic structures. Here, by exploiting the high surface activity of the 1T′ transition metal telluride, we fabricate high-density gold nanoparticles (AuNPs) that are prepared spontaneously in situ on the 1T′ MoTe2 atomic layers, forming a plasmonic-2D material hybrid SERS substrate. This AuNP formation is unique to the 1T′ phase, which is repressed in 2H MoTe2 with lower surface activity. The hybrid structure generates coupling effects of electromagnetic and chemical enhancements, as well as excellent molecule adsorption, leading to ultrasensitive (4 × 10−17 M) and reproducible detection. Flexible SERS tapes are demonstrated in practical applications. Our approach facilitates ultrasensitive SERS detection by a facile method, as well as an enhanced mechanistic understanding of SERS beyond plasmonic effects.

Artemisinin and its derivatives (ARTs) were reported to display heme-dependent antitumor activity. On the other hand, histone deacetylase inhibitors (HDACi) were known to be able to promote heme synthesis in erythroid cells. Nevertheless, the effect of HDACi on heme homeostasis in non-erythrocytes remains unknown. We envisioned that the combination of HDACi and artesunate (ARS) might have synergistic antitumor activity through modulating heme synthesis. In vitro studies revealed that combination of ARS and HDACi exerted synergistic tumor inhibition by inducing cell death. Moreover, this combination exhibited more effective antitumor activity than either ARS or HDACi monotherapy in xenograft models without apparent toxicity. Importantly, mechanistic studies revealed that HDACi coordinated with ARS to increase 5-aminolevulinate synthase (ALAS1) expression, and subsequent heme production, leading to enhanced cytotoxicity of ARS. Notably, knocking down ALAS1 significantly blunted the synergistic effect of ARS and HDACi on tumor inhibition, indicating a critical role of ALAS1 upregulation in mediating ARS cytotoxicity. Collectively, our study revealed the mechanism of synergistic antitumor action of ARS and HDACi. This finding indicates that modulation of heme synthesis pathway by the combination based on ARTs and other heme synthesis modulators represents a promising therapeutic approach to solid tumors. Keywords: Artesunate, HDAC inhibitor, Heme, ALAS1, Antitumor

In this paper, we propose and demonstrate a RoF system based on polarization multiplexing and carrier suppression to generate frequency eightfold millimeter-wave. The proposed scheme is based on one single drive Mach-Zehnder modulator and a polarization control system. By adjusting the modulation index, two-forth sidebands can be obtained. By controlling the polarization direction, our system can generate 80 GHz frequency eightfold millimeter-wave or recover optical carrier at the base station (BS). Finally, we verified the bit error rate (BER) of received optical power in the uplink and downlink. The received power penalty of uplink and downlink via 15 km single mode fiber (SMF) are 0.13 dBm and 0.34 dBm at the BER of 1 × 10-9 respectively. This technology opens a new path for developments in microwave photonics. Keywords: Millimeter wave, Microwave photonics, Optical carrier suppression, Polarization multiplexing

The main goal of this article is to study the friction coefficient of wheel/rail transient sliding thermal contact through a pendulum. A new method is firstly established to analyze the friction coefficient. The formula for calculating the friction coefficient is not dependent on material and thermal parameters of wheel/rail. The experiment measures the sliding contact time and friction coefficient at different wheel temperature. The results show that the sliding contact time is very short and the average sliding contact time is 8 ms. The friction coefficient slowly ascends before 500 °C and then gradually decreases from 500 °C to 1000 °C. From 1000 °C to 1200 °C, the friction coefficient quickly descends. The maximum friction coefficient is 0.388. With the increase of wheel temperature, the number of small pits gradually decreases, and the scratching on the wheel surface becomes more obvious. Keywords: Friction coefficient, Temperature, Sliding contact, Contact time

Background: Sleep disorders have been verified to be associated with adverse health outcomes. Recent studies have linked ambient air pollution to sleep disorders. However, evidence with large sample size and especially prospective studies is very limited. Methods: We used data from a prospective cohort study established from 2015 to 2018 in Ningbo, China. Participants were followed-up after baseline survey through linkage to the regional Health Information System (HIS). Sleep disorders were defined based on International Classification of Disease 10 (ICD-10). Spatial-temporal land-use regression (LUR) models were used to estimate the annual exposure to particulate matter with diameter ≤ 2.5 µm (PM2.5), ≤ 10 µm (PM10) and nitrogen dioxides (NO2). The associations between long-term exposure to air pollutants and prevalence of sleep disorders were examined using logistic regression models, and Cox regression models for the effects of air pollution on the incidence of sleep disorders. A generalized weighted quantile sum (gWQS) regression was used in the multipollutant analysis. Results: A total of 38,775 participants were included in the final analysis. Based on baseline data, we observed significant positive associations between air pollution exposure and increased odds of prevalent sleep disorders (Odds Ratio (OR)= 1.48, 95% confidence interval (CI): 1.41–1.55 for PM2.5; OR= 1.47,95%CI:1.38–1.57 for PM10; OR= 1.38, 95%CI:1.31–1.46 for NO2). In the longitudinal analysis, hazard ratios for incident sleep disorders associated with per interquartile range (IQR) increase in PM2.5, PM10 and NO2 were 1.14 (1.03, 1.25), 1.13 (1.01, 1.27) and 1.13 (1.04, 1.23), respectively. A gWQS regression analysis showed significant association between air pollution mixture and incident sleep disorders (OR=1.11, 95%CI: 1.03–1.20). Conclusions: Long-term exposure to PM2.5, PM10 and NO2 were associated with increased risk of sleep disorders in a Chinese population. Our findings could provide evidence for a more general role in the adverse health impact of air pollution.

Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 µg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain γ-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 μg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males.

Cumulative research on resistomes and microbiomes from aquatic environments has revealed that both integrated freshwater and monoculture freshwater aquaculture systems can cause the development and dissemination of antibiotic resistance genes (ARGs) and associated mobile genetic elements (MGEs). However, few studies have examined differences in resistomes between the different aquaculture modes, and those that do have focused on antibiotic residues or individual resistance genes. In the current study, we collected 44 environmental samples from two monoculture freshwater aquaculture farms and four integrated farms (two duck and fish farms, two laying duck and fish farms) in Guangdong, China, in 2018. After measuring the concentrations of antibiotic residues in the samples, we characterized MGEs and ARGs and examined their association with potential bacterial hosts in the microbial communities using high-throughput sequencing-based metagenomic and network analyses. We then compared the resistome profiles of the different aquaculture models. We found that the number and total relative abundance of ARG and MGE subtypes in the integrated (fish and duck/laying duck) farm samples were significantly higher than those in samples from monoculture freshwater aquaculture farms. Specifically, both the mobile colistin resistance genes mcr variants and tigecycline resistance gene tet(X) variants in integrated farms exhibited higher total relative abundance than that in monoculture farms. Moreover, the interrelationships among ARGs and microbial taxa, ARGs and MGEs, and MGEs and microbial taxa in the integrated farm samples were also more complex than those observed in monoculture freshwater aquaculture farm samples. Meanwhile, the species of Acinetobacter and Escherichia were identified to be the possible host of tet(X) and ESBL gene blaCTX-M in aquaculture, respectively. To the best of our knowledge, this is the first metagenomic study to analyze differences in resistome profiles between integrated and monoculture ponds. Overall, integrated aquaculture systems exhibited a higher prevalence of resistance genes compared with monoculture freshwater aquaculture farms. Therefore, additional antimicrobial resistance surveillance should be focused on this type of freshwater aquaculture system.

Objectives: There are little data on the long-term clinical outcomes of optimal medical therapy (OMT) compared with successful percutaneous coronary intervention (PCI) in patients with chronic total occlusions (CTOs). Methods: A total of 388 patients with ≥1 CTO were enrolled from January 2008 to December 2010. 62 patients were excluded, and 326 patients were divided into an OMT group (n = 125) and PCI group (n = 201) according to the initial treatment strategy. Propensity-score matching was also done to adjust for baseline characteristics. The primary outcome was major adverse cardiac event (MACE), included cardiac death, recurrent myocardial infarction, and repeated revascularization. Results: After a mean follow-up of 47.2 ± 20.0 months, there was no significant difference between the two groups with respect to the prevalence of MACE (successful PCI vs. OMT: 29.6% vs. 21.9%, unadjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.95–2.28, p=0.085). After multivariate analyses, there were significant differences in the prevalence of MACE (adjusted HR 1.76, 95% CI 1.09–2.28, p=0.02) and repeated revascularization (2.14; 1.18–3.90, 0.01). In the propensity score-matched population (80 pairs), there were no significant differences in the prevalence of MACE (adjusted HR 1.89, 95% CI 0.96–3.71, p=0.06) and cardiac death (1.30, 0.44–3.80, 0.63) between groups. Conclusion: In the treatment of patients with CTOs, successful PCI did not reduce the long-term risk of MACE compared with OMT. Keywords: Chronic total occlusions, Percutaneous coronary intervention, Optimal medical therapy, Outcome

Background: To investigate the effect of hydrogen peroxide (H2S) on myocardial clock gene Bmal1 in ischemic cardiomyocytes. Materials & methods: Quantitative PCR (qPCR) was used to detect the expression of Bmal1 at the mRNA level in H9C2 rat cardiomyocytes. The protein expressions of Bax and Bcl-2, PI3K/Akt, caspase-3 were measured by western blotting. The levels of reactive oxygen species (ROS) were determined by ELISA. Results: The expression level of clock gene Bmal1 demonstrated a clock rhythm of periodic oscillation within 24 h. Compared with the control group, H2S treatment maintained the rhythm of the clock gene in ischemic cardiomyocytes and increased the transcription and expression levels of Bmal1. H2S increased cell survival by activating PI3K/Akt signaling pathway, inhibiting mitochondrial apoptosis signaling, and reducing intracellular oxidative stress. PI3K/Akt and Bmal1 were demonstrated to be involved in H2S protection of cardiomyocyte ischemia. Knockout of Bmal1 gene affects the degree of phosphorylation of Akt and Erk proteins, and the level of ROS production, resulting in a decrease in the protective effects of H2S. Conclusion: The expression level of Bmal1 has effects on the function of cardiomyocytes such as ROS production. The potential mechanism by which H2S regulates clock genes may be related to the effect of clock genes on protein phosphorylation levels in ischemic cardiomyocytes.

DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER) and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability. Integrative analyses of melanoma cells reveal that MED23 controls the expression of a melanocyte master regulator, Mitf, by modulating its distal enhancer activity, leading to opposing effects on pigmentation and DNA repair. Collectively, the Mediator MED23/MITF axis connects DNA repair to pigmentation, thus providing molecular insights into the DNA damage response and skin-related diseases.

Sodium manganese periodate compounds were synthesized to serve as high capacity cathodes. The composition and morphology of resulting products were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray Diffraction (XRD) and thermogravimetric analysis (TGA). Composite cathodes made from the synthesized periodates were used to fabricate batteries with zinc anode and acetic acid electrolyte. Electrode formulations were optimized using nanocarbon conductive additives. For the full design and mechanism related to the sodium manganese periodate electrode with specific capacity as high as 750 mAh g−1, please refer to our research article “High Capacity Aqueous Periodate Batteries Featuring a Nine-Electron Transfer Process” [1]. Keywords: Periodate, Sodium manganese periodate, Battery, Carbon nanotube, Graphene oxide

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which synovial fibroblast-like cells (FLSs) play an important role in RA development and is known to be lack of effective therapy. Thus, novel therapeutic strategies are greatly needed for treatment of RA. Metformin, a first-line drug for the treatment of type 2 diabetes, has been reported to inhibit the proliferation of a variety of tumor cells. In this study, we demonstrated that metformin could inhibit the RA-FLS proliferation in dose- and time-dependent manner. Our cell viability MTT test and 5-ethynyl-2-deoxyuridine incorporation assay showed that metformin inhibited the RA-FLSs proliferation with a time- and concentration-dependent increase. More importantly, metformin induced G2/M cell cycle phase arrest in RA-FLS via the IGF-IR/PI3K/AKT/ m-TOR pathway and inhibited m-TOR phosphorylation through both the IGF-IR/PI3K/AKT signaling pathways thereby further upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation, respectively; however, metformin was found not to induce apoptosis in RA-FLSs. In summary, these results demonstrate that metformin can effectively inhibit RA-FLS proliferation through inducing cell cycle and upregulating and down-regulating p70s6k and 4E-BP1 phosphorylation. Moreover, IGF-IR/PI3K/AKT m-TOR signaling pathway can be regulated by metformin. Our results indicate that metformin may provide a new way of thinking for the treatment of RA.

The creep properties of 2.25Cr-1Mo steel samples, undoped and doped with Sb (0.05 wt%), are examined under different applied engineering stresses (150–400 MPa) and temperatures (773–873 K). The creep behavior follows a unified Monkman-Grant relation ε̇m×tr1.04=0.046 for both the undoped and Sb-doped steels, where ε̇m is the minimum creep rate in h−1 and tr is the rupture time in h. Under the same experimental conditions, the rupture time of the undoped steel is much longer than that of the Sb-doped steel, and meanwhile the minimum creep rate of the former is apparently smaller. Moreover, the threshold stress for creep is much lower for the Sb-doped steel than for the undoped one. This indicates that the impurity element Sb severely lowers the high temperature creep resistance of 2.25Cr-1Mo steel. As shown by boundary microanalysis, there is apparent grain or subgrain boundary segregation of Sb, which could promote the boundary sliding and the nucleation of cavities or microcracks, thereby leading to the creep property deterioration of the steel. Keywords: Creep properties, Cr-Mo steels, Impurities, Grain boundaries, Segregation

Objective: To find the target genes in combination of astragalus root (Astragalus membranaceus) and spindle tree wings (Euonymus alatus (THUNB.) SIEB.) (Qijian Heji) with the function of regulating blood glucose levels in kk mice by real-time fluorescence quantitative PCR (RT-PCR). To achieve the primary exploration on the material basis for Qijian Heji to improve the blood glucose levels of type 2 diabetic kk mice. Methods: We applied RT-PCR to detecting the expression of gene targets in kidney tissues of type 2 diabetes model kk mice. The detected gene targets were predicted by the network pharmacology method in the early stage of the project. Through the observation of the hypoglycemic effect of different ratios of Qijian Heji, the optimal proportion was determined and then used to conduct research of material basis. Results: Continuous administration of Qijian Heji (astragalus root: spindle tree wings = 3:1) for six weeks resulted in significantly lowering blood glucose levels in mice in the fourth week, dropping from 33.3 to 21.9 mmol/L; this lower level was maintained in the fifth to sixth weeks. Blood glucose values in the positive drug group decreased from 33.3 to 21.85 mmol/L in the fourth week and maintained steady decreasing in the fifth and sixth weeks. Conclusion: Qijian Heji, with proportion of 3:1, could significantly reduce the blood glucose values in kk mice, animal experiment results verified the accurate prediction of network pharmacology, and at the same time, it is verified there was a certain therapeutic effect about the combination of the two herbs on reducing the glucose value. Animal experiments and RT-PCR results showed that Qijian Heji conducted a hypoglycemic effect by modulating estrogen receptor (ESR1) and renin (REN) expression.

Carbon sequestration in agricultural soils is a complex process controlled by farming practices, climate and some other environment factors. Since purple soils are unique in China and used as the main cropland in Sichuan Basin of China, it is of great importance to study and understand the impacts of different fertilizer amendments on soil organic carbon (SOC) changes with time. A research was carried out to investigate the relationship between soil carbon sequestration and organic carbon input as affected by different fertilizer treatments at two long-term rice-based cropping system experiments set up in early 1980s. Each experiment consisted of six identical treatments, including (1) no fertilizer (CK), (2) nitrogen and phosphorus fertilizers (NP), (3) nitrogen, phosphorus and potassium fertilizers (NPK), (4) fresh pig manure (M), (5) nitrogen and phosphorus fertilizers plus manure (MNP), and (6) nitrogen, phosphorus and potassium fertilizers plus manure (MNPK). The results showed that annual harvestable carbon biomass was the highest in the treatment of MNPK, followed by MNP and NPK, then M and NP, and the lowest in CK. Most of fertilizer treatments resulted in a significant gain in SOC ranging from 6.48 to 29.13% compared with the CK, and raised soil carbon sequestration rate to 0.10–0.53 t ha−1 yr−1. Especially, addition of manure on the basis of mineral fertilizers was very conducive to SOC maintenance in this soil. SOC content and soil carbon sequestration rate under balanced fertilizer treatments (NPK and MNPK) in the calcareous purple soil (Suining) were higher than that in the acid purple soil (Leshan). But carbon conversion rate at Leshan was 11.00%, almost 1.5 times of that (7.80%) at Suining. Significant linear correlations between soil carbon sequestration and carbon input were observed at both sites, signifying that the purple soil was not carbon-saturated and still had considerable potential to sequestrate more carbon.

Background: Validating the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder (BP) may help enable early intervention strategies. Methods: We followed up with 44 offspring of parents with BP, subdividing into the HR and UHR categories. The offspring were aged 8–28 years and were free of any current DSM-IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM) volumes, brain network connectivity, neuropsychological performance, and clinical outcomes. Findings: Compared with the healthy controls (HCs) (n = 33), the HR offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex. Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM volumes in four regions. Both the HR and UHR offspring displayed abnormalities in the inferior occipital cortex regarding the measures of degree and centrality, reflecting the connections and roles of the region, respectively. In the UHR versus the HR offspring, the UHR offspring exhibited upwards-shifted small world topologies that reflect high clustering and efficiency in the brain networks. Compared with the HCs, the UHR offspring had significantly lower assortativity, which was suggestive of vulnerability. Finally, processing speed, visual–spatial, and general function were impaired in the UHR offspring but not in the HR offspring. Interpretation: The abnormalities observed in the HR offspring appear to be inherited, whereas those associated with the UHR offspring represent stage-specific changes predisposing them to developing the disorder.

The greatest concern over DDT exposure in China arose since the early 1990s for the rising breast cancer incidence, and the cause still remains to be elucidated. An extensive survey of DDT background in agricultural soils, covered the entire region of China, was conducted. DDT at concentrations greater than 100 ng/g (the China’s Farmland Environmental Quality Evaluation Standards for Edible Agricultural Products) was found to impact 42.3 million Chinese population. Considering the geographical differences with diverse DDT contributions and different diet products and habits, the average daily dietary intake was modeled and estimated to be 0.34 μg/kg p,pʹ-DDE (the main bioactive constituent in DDT). Population attributable fraction derived from a case–control study from 78 women with breast cancer and 72 controls was used to assess the DDT exposure risk to breast cancer. Based on the estimated population attributable fraction with a median value of 0.6% (IQR 0.23–2.11%), the excess annual breast cancer incidence rate attributable to p,p′-DDE exposure averaged 0.06 × 10−5 with significant spatial variations varying from 0.00021 × 10−5 to 11.05 × 10−5 in Chinese females. Exposure to DDT is a contributor to breast cancer, but the overall limited relative risk and population attributable fraction imply confounding factors for breast cancer in Chinese females. Exposure risk in a regional scale helps understand the cause and prevention of breast cancer. Our mapping and modeling method could be used to assess other environmental carcinogens and related cancer diseases. Keywords: DDT exposure, Dietary intake, Health risk, Breast cancer

Background: The capacity of toll-like receptor (TLR) 7/8 agonist-conjugated hepatitis B virus (HBV) proteins (HBV-Ag) to overcome established hepatitis B surface antigen (HBsAg)-specific immune tolerance was explored. Methods: A TLR7/8 agonist, CL097, was conjugated with alum-absorbed HBsAg and hepatitis B core antigen (HBcAg), as confirmed by ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS). Mice from two independently generated HBV-transgenic (HBV-Tg) colonies, C57BL/6J-TgN (AlblHBV) 44Bri/J mice and C57BL/6-HBV-1.3 genome-eq mice, were immunized with CL097-conjugated HBV-Ag every 2 weeks, four times. Results: After immunization, 8/11 (72.7%) of the AlblHBV mice and 10/13 (76.9%) of the HBV-1.3 genome-eq mice generated serum detectable antibodies against HBsAg (anti-HBs). HBsAg-specific interferon gamma (IFN-γ)-producing CD4+ and CD8+ T-cells were detected in splenocytes from these mice. Naïve normal mice receiving splenocytes from the mice immunized with CL097-conjugated HBV-Ag generated immediate recall immune responses, e.g., the mice that received CD4+CD25+-depleted splenocytes generated anti-HBs on day 3 after HBsAg challenge while those receiving cells from sham-immunized mice did not. Conclusions: Immunization with CL097-conjugated HBV-Ag reversed immune tolerance in HBV-Tg mice and induced antigen-specific immune responses. TLR7/8 agonists appear to be potent adjuvants for the induction of antigen-specific Th1 responses in an immune tolerant state.