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In the present work, the diffusion behavior of the Ag–Cu–Ni alloys was comprehensively studied for the first time. Twelve solid-solid diffusion couples were prepared and annealed at 1023, 1123, and 1223K, respectively. Based on the measured composition-distance profiles, the interdiffusion coefficients in FCC Ag–Cu–Ni alloys at different temperatures were then calculated by both the Matano-Kirkaldy (MK) and numerical inversion (NI) methods. The atomic mobilities of the Ag–Cu–Ni alloys were also optimized. The results indicate that the model-predicted diffusion behavior shows reasonable agreement with the experimental data, validating the reliability of the two versions of atomic mobility obtained in this work and demonstrating the accuracy and efficiency of the NI method. Ag diffuses faster than Ni in the Cu matrix alloy. The pre-exponential factor D0Ag and the activation energy QAgAgCu show a slight change with the Ag, but significantly increase with the Ni. The variation of the pre-exponential factor D0Ni and the activation energy QNiNiCu with the concentration of Ag and Ni were presented with a 3-D planes and discussed in detail. The accurate diffusivities and atomic mobilities of FCC Ag–Cu–Ni alloys obtained in this work will provide crucial input for the development and design of multi-component low-Ag brazing filler metals.

BackgroundIt is unclear whether patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are allowed variable low levels of alcohol. This study aimed to evaluate the effect of mild-moderate alcohol consumption on the biochemical and histological characteristics of patients with MASLD.MethodsAlcohol consumption was assessed in 713 patients with steatotic liver disease (SLD) who underwent liver biopsy. Non-drinking, mild-moderate drinking, and excessive drinking were defined as 0 g/day, 1-20 g/day for women and 0 g/day, 1-30 g/day for men, respectively. Liver biopsies were scored according to the NASH CRN system.ResultsA total of 713 participants (median age 39.0 years and 77.1% male) with biopsy-proven SLD were enrolled, including 239 nondrinkers, 269 mild-moderate drinkers and 205 excessive drinkers. Excessive drinking was associated with increased risks for lobular inflammation and liver fibrosis compared to nondrinkers and mild-moderate drinkers. Compared with non-drinkers, mild-moderate drinkers had significantly lower odds for steatosis (OR = 0.60, 95% CI = 0.38–0.93, p = 0.025), hepatocellular ballooning (OR = 0.52, 95% CI = 0.29–0.91, p = 0.020) and fibrosis (OR = 0.50, 95% CI = 0.31–0.81, p = 0.005). However, in non-excessive drinkers with type 2 diabetes mellitus (T2DM), there was no association between mild-moderate alcohol consumption and liver fibrosis (OR = 0.562, 95% CI = 0.207–1.530, p = 0.257).ConclusionsMild-moderate alcohol consumption might be protective against liver fibrosis in MASLD patients, which is modified by the presence of T2DM. However, further longitudinal studies are needed to determine the effect of ongoing alcohol consumption on disease severity.

The maximum clique problem in graph theory is a well-known challenge that involves identifying the complete subgraph with the highest number of nodes in a given graph, which is a problem that is hard for nondeterministic polynomial time (NP-hard problem). While finding the exact application of the maximum clique problem in the real world is difficult, the relaxed clique model quasi-clique has emerged and is widely applied in fields such as bioinformatics and social network analysis. This study focuses on the maximum quasi-clique problem and introduces two algorithms, NF1 and NR1. These algorithms make use of previous iteration information through an information feedback model, calculate the information feedback score using fitness weighting, and update individuals in the current iteration based on the benchmark algorithm and selected previous individuals. The experimental results from a significant number of composite and real-world graphs indicate that both algorithms outperform the original benchmark algorithm in dense instances, while also achieving comparable results in sparse instances.

Abstract Background Hepatic inflammation is the major risk factor of hepatocellular carcinoma (HCC). However, the underlying mechanism by which hepatic inflammation progresses to HCC is poorly understood. This study was designed to investigate the role of ETS translocation variant 4 (ETV4) in linking hepatic inflammation to HCC. Methods Quantitative real‐time PCR and immunoblotting were used to detect the expression of ETV4 in HCC tissues and cell lines. RNA sequencing and luciferase reporter assays were performed to identify the target genes of ETV4. Hepatocyte‐specific ETV4‐knockout (ETV4fl/fl, alb‐cre) and transgenic (ETV4Hep‐TG) mice and diethylnitrosamine‐carbon tetrachloride (DEN‐CCL4) treatment experiments were applied to investigate the function of ETV4 in vivo. The Cancer Genome Atlas (TCGA) database mining and pathological analysis were carried out to determine the correlation of ETV4 with tumor necrosis factor‐alpha (TNF‐α) and mitogen‐activated protein kinase 11 (MAPK11). Results We revealed that ETV4 was highly expressed in HCC. High levels of ETV4 predicted a poor survival rate of HCC patients. Then we identified ETV4 as a transcription activator of TNF‐α and MAPK11. ETV4 was positively correlated with TNF‐α and MAPK11 in HCC patients. As expected, an increase in hepatic TNF‐α secretion and macrophage accumulation were observed in the livers of ETV4Hep‐TG mice. The protein levels of TNF‐α, MAPK11, and CD68 were significantly higher in the livers of ETV4Hep‐TG mice compared with wild type mice but lower in ETV4fl/fl, alb‐cre mice compared with ETV4fl/fl mice as treated with DEN‐CCL4, indicating that ETV4 functioned as a driver of TNF‐α/MAPK11 expression and macrophage accumulation during hepatic inflammation. Hepatocyte‐specific knockout of ETV4 significantly prevented development of DEN‐CCL4‐induced HCC, while transgenic expression of ETV4 promoted growth of HCC. Conclusions ETV4 promoted hepatic inflammation and HCC by activating transcription of TNF‐α and MAPK11. Both the ETV4/TNF‐α and ETV4/MAPK11 axes represented two potential therapeutic targets for highly associated hepatic inflammation and HCC. ETV4+TNF‐α were potential prognostic markers for HCC patients.

This study evaluated the quality attributes of tomato sour soup marinade and investigated the effects of ultrasound-assisted marination on the physicochemical properties, microstructure, texture, sensory quality, and flavour profile of beef. The results showed that tomato sour soup significantly increased the marinade absorption rate and improved beef tenderloin’s physicochemical properties, texture, and flavour attributes compared to static brine (P

Surface-attached micro- and nanobubbles are known for their resistance to external forces. This study experimentally and theoretically investigates their response to strong ultrasonic fields. Surface-attached micro- and nanobubbles with contact radii from 2 μm to 20 μm are generated in a microchannel and exposed to ultrasound through a vibrating glass substrate. At a driving frequency over 200 kHz up to 2 MHz tested, no significant response from the micro- and nanobubbles is observed. By contrast, at 100 kHz–200 kHz, ultrasonic cavitation bubbles appear in the microchannel and migrate toward the surface micro- and nanobubbles. Then the surface micro- and nanobubbles merge with the ultrasonic cavitation bubbles, detach from the substrate, and become free gaseous nuclei susceptible to further cavitation. Notably, the removal process leaves no observable residue. Theoretical analysis suggests that the directional migration of cavitation bubbles is driven by mutual acoustic radiation forces. This work demonstrates that ultrasonic fields can effectively remove surface micro- and nanobubbles, transforming them into free gaseous cavitation nuclei.

Background & Aims: The expression of HBsAg from integrated HBV DNA limits the achievement of functional cure for chronic hepatitis B. Thus, characterising the unique expression and secretion of HBsAg derived from integrated HBV DNA is of clinical significance. Methods: A total of 563 treatment-naive patients and 62 functionally cured patients were enrolled, and HBsAg and HBcAg immunohistochemistry of their liver biopsy tissues was conducted followed by semi-quantitative analysis. Then, based on stratified analysis of HBeAg-positive and -negative patients, long-read RNA sequencing analysis, as well as an in vitro HBV integration model, we explored the HBsAg secretion characteristics of integrated HBV DNA and underlying mechanisms. Results: In contrast to the significantly lower serum HBsAg levels, no significant decrease of intrahepatic HBsAg protein was observed in HBeAg-negative patients, as compared with HBeAg-positive patients. The results of long-read RNA sequencing of liver tissues from patients with chronic HBV infection and in vitro studies using integrated HBV DNA mimicking dslDNA plasmid revealed that, the lower HBsAg secretion efficiency seen in HBeAg-negative patients might be attributed to an increased proportion of preS1 mRNA derived from integrated HBV DNA instead of covalently closed circular DNA. The latter resulted in an increased L-HBsAg proportion and impaired HBsAg secretion. Enhancer 1 (EnhI) in integrated HBV DNA could retarget preS1 (SP1) and preS2 (SP2) promoters to disrupt their transcriptional activity balance. Conclusions: The secretion of HBsAg originating from integrated HBV DNA was impaired. Mechanistically, functional deficiency of core promoter leads to retargeting of EnhI and thus uneven activation of the SP1 over the SP2 promoter, resulting in an increase in the proportion of L-HBsAg. Impact and implications: Integrated hepatitis B virus (HBV) DNA can serve as an important reservoir for HBV surface antigen (HBsAg) expression, and this limits the achievement of a functional cure. This study revealed that secretion efficiency is lower for HBsAg derived from integrated HBV DNA than HBsAg derived from covalently closed circular DNA, as determined by the unique sequence features of integrated HBV DNA. This study can broaden our understanding of the role of HBV integration and shed new light on antiviral strategies to facilitate a functional cure. We believe our results are of great general interest to a broad audience, including patients and patient organisations, the medical community, academia, the life science industry and the public.

We experimentally, numerically, and theoretically investigate the dynamics of cavitation bubbles in viscous liquids in a tube during a transient process. In experiments, cavitation bubbles are generated by a modified tube-arrest setup, and the bubble evolution is captured with high-speed imaging. Numerical simulations using OpenFOAM are employed to validate our quasi-one-dimensional theoretical model, which effectively characterizes the bubble dynamics. We find that cavitation onset is minimally affected by the liquid viscosity. However, once cavitation occurs, various aspects of bubble dynamics, such as the maximum bubble length, bubble lifetime, collapse time, and collapse speed, are closely related to the liquid viscosity. We further establish that normalized bubble dynamics are solely determined by the combination of the Reynolds number and the Euler number. Moreover, we also propose a new dimensionless number, Ca2, to predict the maximum bubble length, a critical factor in determining the occurrence of liquid column separation.

ABSTRACTIt is urgently needed to evaluate the necessity and benefits of booster vaccination against the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron to facilitate clinical decision-making for 2019 coronavirus disease (COVID-19) convalescents. We conducted a multicenter, prospective clinical trial (registration number: ChiCTR2100045810) in the first patients with COVID-19 from 28 January 2020 to 20 February 2020 to assess the long-term durability of neutralizing antibodies against live Omicron BA.5 and further assess the efficiency and safety of CoronaVac in the convalescent group. A total of 96 COVID-19 convalescents were enrolled in this study. Neutralizing antibody titers in convalescents were significantly reduced in 9–10 months. A dose-refreshing vaccination in 28 convalescents with an antibody titer below 96 significantly induced neutralizing antibodies against live Omicron by 4.84-fold. Meanwhile, the abundance of naive T cells increased dramatically, and TEMRA and TEM cells gradually decreased after vaccination. Activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes. One-dose booster vaccination was effective in inducing a robust antibody response against SARS-CoV-2 Omicron in COVID-19 convalescents with low antibody titers. However, vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.IMPORTANCEThe globally dominant coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron variant raises the possibility of repeat infections among 2019 coronavirus disease (COVID-19) convalescents with low neutralizing antibody titers. The importance of this multicenter study lies in its evaluation of the long-term durability of neutralizing antibodies in COVID-19 convalescents and the efficacy of a booster vaccination against the live Omicron. The findings suggest that a one-dose booster vaccination is effective in inducing a robust antibody response against SARS-CoV-2 Omicron in convalescents with low antibody titers. However, the study also highlights the potential detrimental effects on the antiviral response due to vaccine-mediated T-cell consumption and regeneration patterns. These results are crucial for facilitating clinical decision-making for COVID-19 convalescents and informing public health policies regarding booster vaccinations.

Abstract The pregenomic RNA (pgRNA) of hepatitis B virus (HBV) serves not only as a bicistronic message RNA to translate core protein (Cp) and DNA polymerase (Pol), but also as the template for reverse transcriptional replication of viral DNA upon packaging into nucleocapsid. Although it is well known that pgRNA translates much more Cp than Pol, the molecular mechanism underlying the regulation of Cp and Pol translation efficiency from pgRNA remains elusive. In this study, we systematically profiled HBV nucleocapsid- and pgRNA-associated cellular proteins by proteomic analysis and identified TIA-1-related protein (TIAR) as a novel cellular protein that binds pgRNA and promotes HBV DNA replication. Interestingly, loss- and gain-of-function genetic analyses showed that manipulation of TIAR expression did not alter the levels of HBV transcripts nor the secretion of HBsAg and HBeAg in human hepatoma cells supporting HBV replication. However, Ribo-seq and PRM-based mass spectrometry analyses demonstrated that TIAR increased the translation of Pol but decreased the translation of Cp from pgRNA. RNA immunoprecipitation (RIP) and pulldown assays further revealed that TIAR directly binds pgRNA at the 5’ stem-loop (ε). Moreover, HBV replication or Cp expression induced the increased expression and redistribution of TIAR from the nucleus to the cytoplasm of hepatocytes. Our results thus imply that TIAR is a novel cellular factor that regulates HBV replication by binding to the 5’ ε structure of pgRNA to tip the balance of Cp and Pol translation. Through induction of TIAR translocation from the nucleus to the cytoplasm, Cp indirectly regulates the Pol translation and balances Cp and Pol expression levels in infected hepatocytes to ensure efficient viral replication.

Background: Acute severe hepatitis with unknown aetiology in children (ASHep-UA) has become a global health alert. This article reported clinicopathological characteristics of 3 probable ASHep-UA cases. Methods: We respectively collected serological data and liver biopsies of 3 suspected cases of ASHep-UA. Neutralizing antibodies titer for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants were determined by virus neutralization test (VNT). Histological assessment, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for cytomegalovirus (CMV), Epstein-Barr virus (EBV), human adenoviruses (HAdV), adeno-associated virus (AAV2), human herpes virus type 6 (HHV-6) were performed to identify possible aetiologies. Results: Remarkable elevation of transaminase (median ALT level, 1100 IU/liter; median AST level, 500 IU/liter) were revealed with undetectable hepatitis A-E and non-hepatotropic virus in both sera and tissues. Weakness, jaundice, pale stools and splenomegaly were observed. Interestingly, two individuals had SARS-CoV-2 Omicron variants infection. Histologically, moderate or severe lobular necroinflammation, active interface hepatitis and portal inflammatory infiltrate with lymphocytic, plasma cells, neutrophils and eosinophilic cells were noted. Conclusions: The exact aetiology of ASHep-UA was still unknown. By reporting the 3 probable cases, we expect to enrich the clinical experience in diagnosis and treatment of ASHep-UA as well as the pathological characteristics.

The invasiveness of ground-glass nodules (GGNs) is difficult to characterize through morphological examination. Multiple studies have independently detected a close relationship between mean computed tomography value and invasiveness of GGNs, however, their relative diagnostic accuracy is uncertain. Here, we performed a meta-analysis to validate whether the mean computed tomography value can predict the invasiveness of GGNs. Briefly, we searched the Web of Science, Embase, PubMed, Cochrane, Google Scholar, CNKI, VIP, Wanfang and SinoMed databases. The sensitivity, specificity, 95% confidence interval (CI), symmetric receiver operating characteristic curve (SROC curve) and the area under curve (AUC) were obtained using STATA 16.0 to evaluate the predictive value of the mean computed tomography value for GGNs. The presence of heterogeneity was assessed using fixed effects sensitivity analysis and I2 statistics. We used the Deek's funnel plot to evaluate the possibility of publication bias. Thirteen studies encompassing 1564 GGNs were included in our meta-analysis. Six of these studies revealed that using the mean computed tomography value for the diagnosis of pre-invasive and invasive lesions had a sensitivity and specificity of 0.75 (95% CI: 0.61–0.85) and 0.81 (95% CI: 0.74–0.86), respectively. The optimal critical value was −557 Hu. Later, eight studies were examined for the use of the mean CT value for patients with minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC); the results showed that the sensitivity was 0.78 (95% CI: 0.66–0.86) and the specificity was 0.81 (95% CI: 0.68–0.89), and the optimal critical value was −484 Hu. Therefore, the mean computed tomography value assessed via CT scan could be a significant predictor of the invasiveness of GGNs as well as a good surgical treatment guide in patients diagnosed with lung cancer. Prospero registration number: CRD42020177125.

Gastric cancer is a common and highly malignant tumor of the digestive system, which seriously threatens human health. The benefit of surgical treatment is limited. The effect of radiotherapy and chemotherapy is not significant, and the toxic and side effects are large. Although the diagnosis and treatment modes of molecular targeting and multidisciplinary cooperation have also been further developed and applied, a relatively unified comprehensive treatment standard scheme has not been formed. Traditional Chinese medicine (TCM), as complementary and alternative medicine, has unique advantages in the development of diagnosis and treatment of diseases in China. Therefore, the Chinese Association of Integrative Medicine formed “Expert Consensus for Diagnosis and Treatment of Gastric Cancer with Integrated Traditional Chinese and Western Medicine” on the basis of clinical practice and experience. In this article, the consensus is interpreted from the perspective of nursing, focusing on the pathogenesis, high-risk factors, characteristic therapies of TCM, and nursing of integrated traditional Chinese and Western medicine for gastric cancer, to provide a reference for front-line medical personnel in the roots in the future nursing care of gastric cancer.

PurposeThis study evaluates the association between habitual physical activity (HPA) and the outcomes of patients with myocardial infarction (MI).MethodsPatients newly diagnosed with MI were divided into two groups based on whether they engaged in HPA, defined as an aerobic activity with a duration of no less than 150 min/week, before the index admission. The primary outcomes included major adverse cardiovascular events (MACEs), cardiovascular (CV) mortality, and cardiac readmission rate 1 year following the index date of admission. A binary logistic regression model was applied to analyze whether HPA was independently associated with 1-year MACEs, 1-year CV mortality, and 1-year cardiac readmission rate.ResultsAmong the 1,266 patients (mean age 63.4 years, 72% male), 571 (45%) engaged in HPA, and 695 (55%) did not engage in HPA before MI. Patients who participated in HPA were independently associated with a lower Killip class upon admission (OR = 0.48: 95% CI, 0.32–0.71, p

Article highlights A novel type of loading strut is applied in the cable supported portal frame structure. The screw is rotated in the middle of the strut to elongate the strut, so the strand prestress is applied. The strut is found to be simple to operate and could indirectly tension the steel strand to achieve loading.

Abstract Spectrally diverse fluorescent proteins (FPs) provide straightforward means for multiplexed imaging of biological systems. Among FPs fitting standard color channels, blue FPs (BFPs) are characterized by lower brightness compared to other spectral counterparts. Furthermore, available BFPs were not systematically characterized for imaging in cultured mammalian cells and common model organisms. Here we introduce a pair of new BFPs, named Electra1 and Electra2, developed through hierarchical screening in bacterial and mammalian cells using a novel dual-expression vector. We performed systematic benchmarking of Electras against state-of-art BFPs in cultured mammalian cells and demonstrated their utility as fluorescent tags for structural proteins. The Electras variants were validated for multicolor neuroimaging in Caenorhabditis elegans, zebrafish larvae, and mice in comparison with one of the best in the class BFP mTagBFP2 using one-photon and two-photon microscopy. The developed BFPs are suitable for multicolor imaging of cultured cells and model organisms in vivo. We believe that the described dual-expression vector has a great potential to be adopted by protein engineers for directed molecular evolution of FPs.

Abstract Identifying cohesive subgraphs is an important topic in graph theory and complex network analysis. The quasi‐clique, as a generalization of clique, can be used to identify the functional and structural properties of various networks. In this paper, the authors study the maximum weighted quasi‐clique problem and propose a local search algorithm for solving the problem. In the algorithm, an iterated local search method is used as the search framework. To find the quasi‐clique with the maximum total weights, hybrid vertex selection strategies are proposed and incorporated into the authors’ algorithm. The hybrid strategies utilize a probability‐based mechanism for choosing sub‐strategies in each round of the local search. The authors conduct experiments on synthetic networks and real‐world networks to show the effectiveness of the authors’ algorithm. The results indicate that hybrid strategies perform better than existing methods, and thus the authors’ algorithm has a good ability to tackle various networks.

Lung cancer is a malignant tumor with the highest incidence and mortality in China, which seriously affects the quality of life of patients. Traditional Chinese medicine (TCM) plays a unique advantage in the treatment and rehabilitation of lung cancer. In order to standardize TCM diagnosis and treatment and disease management of clinical medical workers, the Chinese Association of Integrative Medicine issued the “Expert Consensus on the Diagnosis and Treatment of Lung Cancer by Integrated Traditional Chinese and Western Medicine” in August 2021. Experts' recommendations were made on the clinical staging and syndrome differentiation and classification of lung cancer, characteristic TCM therapies, and nursing care of integrated traditional Chinese and Western medicine. This article interpreted the Consensus on the above aspects from a nursing perspective, hoping to provide references for clinical medical workers in the treatment and nursing care of lung cancer.

Refining the α-Al grain size and controlling the morphology of intermetallic phases during solidification of Al alloys using ultrasonic melt processing (USMP) and Al-Ti-B have been extensively used in academic and industry. While, their synergy effect on the formation of these phases has not yet clearly demonstrated. In this paper, the influence of USMP and Al-Ti-B on the solidified microstructure of multicomponent Al-4.5Cu-0.5Mn-0.5Mg-0.2Si-xFe alloys (x = 0.7, and 1.2 wt%) has been comparatively studied. The results show that the USMP + Al-Ti-B method produce a more profound refinement effect than the individual methods. In addition, the area of single Fe-rich phases in both alloys with USMP + Al-Ti-B are also refined compared with conventional methods. A mechanism is proposed for the refinement, which are the deagglomerated TiB2 parties induced by USMP providing more effective nucleation sites for α-Al, and the refined interdendritic regions limited the growth of Fe-rich phases in the following eutectic reaction. Finally, the application of combined USMP + Al-Ti-B methods is feasible in microstructural refinement, resulting in the improving the casting soundness and mechanical properties of alloys.

BackgroundThis study primarily explored the role of paeonol in doxorubicin (DOX)-induced chronic heart failure (CHF), considering the cardioprotective effect of paeonol on an epirubicin-induced cardiac injury.MethodsDOX-induced CHF-modeled rats were treated with paeonol. Cardiac function and myocardial damage in rats were evaluated by using the multifunction instrument, and the histopathology, apoptosis, and the expression of miR-21-5p and S-phase kinase-associated protein 2 (SKP2) in myocardium were detected. The target gene of miR-21-5p was confirmed by a dual-luciferase reporter assay. After the required transfection or paeonol treatment, the viability, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) of the DOX-induced cardiomyocytes were determined. Reverse-transcription quantitative-PCR (RT-qPCR) and Western blot were performed to quantify the expressions of miR-21-5p, SKP2, and apoptosis-related factors.ResultsPaeonol improved cardiac function and also ameliorated the cardiac damage of CHF-modeled rats, where the downregulation of abnormally elevated myocardial damage markers, including brain natriuretic peptide, lactate dehydrogenase, renin, angiotensin II, aldosterone, and endothelin 1, was observed. Paeonol alleviated the histopathological injury and suppressed the apoptosis in CHF-modeled rats, inhibited miR-21-5p expression, and upregulated SKP2 expression in vitro and in vivo. miR-21-5p targeted SKP2. Paeonol and SKP2 increased the viability and MMP, but reduced apoptosis and ROS in the DOX-induced cardiomyocytes. miR-21-5p exerted effects opposite to PAE and SKP2, and it downregulated the expression of Bcl-2 and mitochondrion-Cytochrome c (Cyt c) and upregulated the expression of Bax, C-caspase-3, and cytoplasm-Cyt c. miR-21-5p reversed the effects of paeonol, and its effects were further reversed by SKP2.ConclusionPaeonol shows a cardioprotective effect on DOX-induced CHF via regulating the miR-21-5p/SKP2 axis.

In order to eliminate capital chaos in the Education And Training (EAT) industry and ease parents' and students' excessive attention to subject achievements over physical quality, China government has launched the “Double Reduction” (“DR”) policy which promotes students' Sports Participation (SP) in the Compulsory Education (CE) stage concerning students' physical and mental health. Firstly, based on the actual situation of students' SP before and after releasing the “DR” policy, this paper understands the exact needs of parents and children. Secondly, following empirical research and mathematical statistics, it analyzes the structure and characteristics of students' SP before and after the release of the “DR” policy. Mainly, the experiment focuses on the frequency, project types, and off-campus class expenditure. It also considers students' SP motivation in on-campus and off-campus sports classes before and after the “DR” policy proposal. Additionally the general curriculum resource utilization of PE teachers are surveyed in order to find out the current status of on-campus PE classes. Eventually, the strategies are put forward to optimize students' SP under the “DR” from the perspectives of family, school, and society. The results show that after the release of “DR”, parents and schools gradually pay attention to student's physical health and better understand students' physical exercise in school. The consumption expenditure on sports off-campus classes has increased significantly. Meanwhile, family income and the father's occupation significantly impact the children's SP frequency in off-campus sports classes. Overall, “DR” is a protracted war. The existing difficulties need to be solved by families, schools, and the government. The research provides a practical basis for extending and managing on-campus sports classes and training. It helps timely uncover the problems in policy implementation. It guides the formulation of PE policy in the next stage of CE.

Evidence from epidemiological studies suggests that chronic arsenic exposure may be associated with a higher incidence of hypertension in the population. However, the effect of arsenic exposure on blood pressure remains unexplored in different populations, regions, and regarding arsenic biomarkers. This study investigated 233 arsenicosis patients and 84 participants from a non-arsenic-exposed area to explore the relationship between arsenic exposure and blood pressure and the occurrence of hypertension and wide pulse pressure (WPP) in patients with coal-burning arsenicosis. The results show that arsenic exposure is related to an increased incidence of hypertension and WPP in the arsenicosis population, primarily due to an induced increase in systolic blood pressure (SBP) and pulse pressure (PP) (OR = 1.47, 1.65, all p < 0.05). The dose–effect relationships between monomethylated arsenicals (MMA), trivalent arsenic (As3+), hypertension, and WWP were characterized following trend analyses (all p-trend < 0.05) in the coal-burning arsenicosis population. After adjusting for age, gender, body mass index (BMI), smoking, and alcohol usage, compared with low-level exposure, the high level of MMA exposure increases the risk of hypertension by 1.99 times (CI: 1.04–3.80) and the WPP by 2.42 times (CI: 1.23–4.72). Similarly, the high level of As3+ exposure increases the hypertension risk by 3.68 times (CI: 1.86–7.30) and the WPP by 3.84 times (CI: 1.93–7.64). Together, the results revealed that urinary MMA and As3+ levels are mainly associated with increased SBP and induce a higher incidence of hypertension and WPP. This study provides preliminary population evidence that cardiovascular-related adverse events such as hypertension and WPP ought to be noticed in the coal-burning arsenicosis population.

Vasomotion is the spontaneous time-dependent contraction and relaxation of micro arteries and the oscillating frequency is about 0.01–0.1 Hz. The physiological mechanism of vasomotion has not been thoroughly understood. From the dynamics point of view, the heartbeat is the only external loading exerted on the vascular system. We speculate that the nonlinear vascular system and the variable period of the heartbeat might induce the low-frequency vasomotion. In this study, the laser Doppler flowmeter is used to measure the time series of radial artery blood flow and reconstructed modified time series that has the same period as the measured time series but different heartbeat curves. We measured the time series of radial artery blood flow in different conditions by adding different noise disturbances on the forearm, and we decomposed the experiment pulse signal by Hilbert–Huang transform. The wavelet spectral analyses showed that the low-frequency components were induced by the variable period but independent of the shape of the heartbeat curve. Furthermore, we simulated the linear flow in a single pipe and the nonlinear flow in a piping network and found that the nonlinear flow would generate low-frequency components. From the results, we could deduce that the variable period of heartbeat and the nonlinearity of the vascular system induce vasomotion. The noise has effects on the blood signals related to the respiratory activities (∼0.3 Hz) but little influence on that related to the cardiac activities (∼1 Hz). Adding white noise and then stopping would induce an SNR increase in the frequency band related to vasomotion (∼0.1 Hz).

A thermodynamic model Mgx(Xs, Mg)6(Xl, Mg)8 (Xs and Xl are elements smaller and larger than Mg) for long-period stacking ordered phases (LPSOs) was proposed based on two key factors: the Xs6Xl8-type L12 clusters and the variation of chemical compositions. In general, all available LPSOs can be described with this model. As a representative system, Mg-Y-Zn with three LPSOs was investigated using the CALPHAD (calculation of phase diagram) approach aided with first-principles calculations. Two new three-phase equilibria were predicted and were validated by key experiments. The model-based descriptions will be the basis for the research and development of magnesium alloys.

In order to solve the problem that it is difficult to complete the full period contact characteristic control of the intersecting cross-axis gear based on the traditional conjugate surfaces meshing theory， a design and analysis method of the intersecting cross-axis gear based on conjugate curves is proposed. In this method， differential geometry and gear kinematics and the conjugate curves meshing theory are applied to deduce the general mathematical model of the conjugate curves intersecting cross-axis gear. The tooth surface curvature analysis and meshing analysis of gear model is carried out and an example is given. The research results have certain guiding significance for the design and manufacture of overload and high-efficiency intersecting cross-axis gear.

Abstract CCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo‐ovarian high‐grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high‐level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut‐off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high‐level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut‐off for IHC to predict CCNE1 high‐level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high‐level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high‐level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38–2.26, p

The elastic stress and the plastic zone are the important mechanical parameters to determine the tunnel support design. Based on Muskhelishvili’s complex variable function, the analytical solution for the elastic stress around a deeply buried noncircular tunnel under the nonhydrostatic pressure is firstly derived. The shape and size of the plastic zone of the surrounding rock mass are then determined by substituting the elastic stresses into the Drucker-Prager yield criterion. Finally, taking a horseshoe-shaped tunnel as an example, the analytical solutions of elastic stress distribution and plastic zone shape around the tunnel under different lateral pressure coefficients are in good agreement with ANSYS numerical solutions. The calculation results show that if the vertical in situ stress exceeds the critical value, with increasing lateral pressure coefficient, the hoop stress at the roof and floor of the tunnel increases significantly and the shape and size of the plastic zone change obviously.

ABSTRACT: A selected yeast fraction (SYF) was tested for the purpose of preventing pullorum disease and fowl typhoid in breeder chickens. In a challenge-protection experiment, commercial Three-Yellow breeder chicks were initially divided into groups A, B (challenged, treated), C (challenged, untreated), and D (unchallenged, untreated). The group A diet was supplemented with SYF and group B was supplemented with Acidipure via drinking water. At 7 D, birds of groups A, B, and C were divided into 2 equal subgroups (A1-A2, B1-B2, and C1-C2). Subgroups A1, B1, and C1 were challenged with Salmonella pullorum (SP), while subgroups A2, B2, and C2 were challenged with Salmonella gallinarum (SG). Clinical signs and mortality were recorded daily. At intervals, antibodies against SP and SG were detected by a plate agglutinate test (PAT). At 42 D, all birds were weighed and necropsied, lesions were recorded and challenge pathogens were isolated. Results showed that SP and SG isolation positive rates of groups A1-A2 were significantly lower (P < 0.05) than those of B1-B2 and C1-C2, respectively. The average body weight (BW) of groups A1-A2 was significantly higher (P < 0.05) than that of B1-B2 and C1-C2, respectively. In the field trial, chicks were randomly divided into 3 groups. Group 1 birds were fed a diet supplemented with SYF, group 2 diet was supplemented with Acidipure via drinking water, and group 3 was fed the same but un-supplemented diet as the control group. Antibodies against SP and SG were detected by PAT at 120 D. The antibodies positive rate of group 1 was significantly lower (P < 0.05) than those of groups 2 and 3, while no significant difference (P > 0.05) was found between groups 2 and 3. The results demonstrated that SYF supplementation could significantly decrease SP and SG infection rates, improve the BW of birds challenged with SP and SG, and was more effective than Acidipure via drinking water.

Large-scale modifications to urban underlying surfaces owing to rapid urbanization have led to stronger urban heat island (UHI) effects and more frequent urban heat wave (HW) events. Based on observations of automatic weather stations in Beijing during the summers of 2014–2020, we studied the interaction between HW events and the UHI effect. Results showed that the UHI intensity (UHII) was significantly aggravated (by 0.55°C) during HW periods compared to non-heat wave (NHW) periods. Considering the strong impact of unfavorable weather conditions and altered land use on the urban thermal environment, we evaluated the modulation of HW events and the UHI effect by wind speed and local climatic zones (LCZs). Wind speeds in urban areas were weakened due to the obstruction of dense high-rise buildings, which favored the occurrence of HW events. In detail, 35 HW events occurred over the LCZ1 of a dense high-rise building area under low wind speed conditions, which was much higher than that in other LCZ types and under high wind speed conditions (< 30 HW events). The latent heat flux in rural areas has increased more due to the presence of sufficient water availability and more vegetation, while the increase in heat flux in urban areas is mainly in the form of sensible heat flux, resulting in stronger UHI effect during HW periods. Compared to NHW periods, lower boundary layer and wind speed in the HW events weakened the convective mixing of air, further expanding the temperature gap between urban and rural areas. Note that LCZP type with its high-density vegetation and water bodies in the urban park area generally exhibited, was found to have a mitigating effect on the UHI, whilst at the same time increasing the frequency and duration of HW events during HW periods. Synergies between HWs and the UHI amplify both the spatial and temporal coverage of high-temperature events, which in turn exposes urban residents to additional heat stress and seriously threatens their health. The findings have important implications for HWs and UHII forecasts, as well as for scientific guidance on decision-making to improve the thermal environment and to adjust the energy structure.

Previous studies on the impact of urbanization on the diurnal temperature range (DTR) have mainly concentrated on the intra-seasonal and interannual–decadal scales, while relatively fewer studies have considered synoptic scales. In particular, the modulation of DTR by different synoptic weather patterns (SWPs) is not yet fully understood. Taking the urban agglomeration of the Yangtze River Delta region (YRDUA) in eastern China as an example, and by using random forest machine learning and objective weather classification methods, this paper analyzes the characteristics of DTR and its urban–rural differences (DTRU–R) in summer from 2013 to 2016, based on surface meteorological observations, satellite remote sensing, and reanalysis data. Ultimately, the influences of urbanization-related factors and different large-scale SWPs on DTR and DTRU–R are explored. Results show that YRDUA is controlled by four SWPs in the 850-hPa geopotential height field in summer, and the DTRs in three sub-regions are significantly different under the four SWPs, indicating that they play a role in regulating the DTR in YRDUA. In terms of the average DTR for each SWP, the southern sub-region of the YRDUA is the highest, followed by the northern sub-region, and the middle sub-region is the lowest, which is most significantly affected by high-level urbanization and high anthropogenic heat emission. The DTRU–R is negative and differs under the four different SWPs with variation in sunshine and rainfall. The difference in anthropogenic heat flux between urban and rural areas is one of the potentially important urbanization-related drivers for DTRU–R. Our findings help towards furthering our understanding of the response of DTR in urban agglomerations to different SWPs via the modulation of local meteorological conditions.

Background: Whether achieving sustained virological response (SVR) in patients with hepatitis C attains complete elimination of hepatitis C virus (HCV) is unknown, because occult HCV infection (OCI), defined as the detection of HCV-RNA in hepatocytes or peripheral blood mononuclear cells (PBMC) in absence of serum HCV-RNA, may occur. We thus investigated the prevalence and clinical relevance of OCI. Methods: Subjects from three hospitals who had achieved serum HCV clearance, including 60 of Direct-acting antiviral agents (DAAs) induced SVR, 50 of pegylated interferon plus ribavirin (PR) induced SVR, and 30 of spontaneous resolution, were subjected to detect HCV-RNA in liver by robust RNAscope assay and PBMC by qPCR. Paired liver biopsies at baseline and at SVR24 were analyzed. Results: OCI was detected in 16 of 140 subjects (11.4%), with 15.0% in DAA-based group, 10.0% in PR group and 6.7% in spontaneously resolved group. In DAA-based subgroups, the incidence of OCI was gradually increased in group of solely DAA(s) therapy, combining DAA and PR therapy and combining DAA and ribavirin therapy. OCI is more frequent in patients with genotype 3. No correlation between baseline viral load, interleukin-28B genotype, baseline transaminases, post-SVR transaminases and OCI were found. However, OCI was significantly linked with severity of fibrosis and active inflammation at post-SVR, even considering basal fibrosis status. In addition, both the magnitude and the frequency of fibrosis regression were lower in patients with OCI than in those without OCI. In the multivariate analysis, PR therapy was identified an independent negative prognostic factor for both hepatic inflammation (P = .022) and fibrosis regression (P = .015). Importantly, we found HCV relapse in one of the OCI patients at 48 weeks after the end of PR treatment. Conclusions: HCV-RNA can persist in hepatocytes and/or PBMC in a certain of patients who achieved spontaneous or treatment-induced HCV RNA clearance from serum and associated with persistent histological abnormality. Our findings provide new insights into cure of HCV and could influence the following-up scenario after SVR. Keywords: Occult hepatitis C, Direct-acting antiviral agents, RNAscope assay, Liver fibrosis, Hepatic pathology

ABSTRACTHepatocyte proliferation could result in the loss of covalently closed circular DNA (cccDNA) and the emergence of cccDNA-cleared nascent hepatocytes, which appear refractory to hepatitis B virus (HBV) reinfection with unknown mechanism(s). Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for HBV entry. In this study, down-regulation of cell membrane localized NTCP expression in proliferating hepatocytes was found to prevent HBV infection in HepG2-NTCP-tet cells and in liver-humanized mice. In patients, lower NTCP protein expression was correlated well with higher levels of hepatocyte proliferation and less HBsAg expression in HBV-related focal nodular hyperplasia (FNH) tissues. Clinically, significantly lower NTCP protein expression was correlated with more active hepatocyte proliferation in CHB patients with severe active necroinflammation and better antiviral treatment outcome. Mechanistically, the activation of cell cycle regulatory genes p53, S-phase kinase-associated protein 2 (SKP2) and cyclin D1 during cell proliferation, as well as proliferative and inflammatory cytokine Interleukin-6 (IL-6) could transcriptionally down-regulate NTCP expression. From these aspects, we conclude that within the milieu of hepatocyte proliferation, down-regulation of cell membrane localized NTCP expression level renders nascent hepatocytes resistant to HBV reinfection. This may accelerate virus clearance during immune-mediated cell death and compensatory proliferation of survival hepatocytes.

The self-oscillation of the cavitating vortices is one of the dangerous phenomena of hydraulic turbine operation near full-load conditions. This work is an attempt to generalize data and expand insight on the phenomenon of self-excited oscillations by comparing the experimental results obtained on a simplified turbine and scaled-down pump–turbine models. In both cases, a series of high-speed imaging was carried out, which made it possible to study these phenomena with high temporal resolution. The high-speed imaging data was subjected to additional processing such as binarization, cropping, and scaling. For a simplified turbine model, the volume of the vapor cavity was calculated based on the assumption of the axial symmetry of the cavity, after which fast Fourier transform (FFT) analysis was carried out. A proper orthogonal decomposition (POD) analysis was also performed to examine individual modes in the original digital imaging data. For the pump–turbine, visualization data on the cavitation cavity oscillations were supplemented by pressure measurements in the draft tube cone to determine the frequency characteristics. Based on obtained experimental data, an improved one-dimensional model describing the oscillations of the cavitation cavity arising behind the hydraulic turbine runner is proposed.

Ovarian Clear Cell Carcinoma (OCCC) displays distinctive clinical and molecular characteristics and confers the worst prognosis among all ovarian carcinoma histotypes when diagnosed at advanced stage, because of the lack of effective therapy. IGF2BP3 is an RNA binding protein that modulates gene expression by post-transcriptional action. In this study, we investigated the roles of IGF2BP3 in the progression of OCCC. We used 328 OCCCs from the AOVT (the Alberta Ovarian Tumor Type study) and the COEUR (the Canadian Ovarian Experimental Unified Resource) cohorts to elucidate the associations between IGF2BP3 expression and clinicopathological parameters, with positive IGF2BP3 expression defined as diffuse block staining, being more frequently observed at stage III (P = 0.0056) and significantly associated with unfavorable overall survival (HR = 1.59, 95% CI 1.09–2.33) in multivariate analysis. IGF2BP3 mRNA gene expression was markedly increased in OCCC cell lines compared to normal tissues such as ovarian surface epithelium. We chose two IGF2BP3-overexpressing cell lines ES2 and OVMANA for in vitro and in vivo knockdown experiments. The proliferation and viability of both cell lines were significantly inhibited by two IGF2BP3 siRNAs and similar suppression was observed in cell migration and invasion by Wound Healing and Transwell assays. The percentage of apoptotic cancer cells was enhanced by both IGF2BP3 siRNAs. In vivo experiments showed significantly reduced sizes of tumors when treated with IGF2BP3 siRNA compared to controls. Furthermore, cancer metastasis-indicators MMP2 and MMP9 proteins were down-regulated. In conclusion, our study shows that IGF2BP3 expression is a promising biomarker for prognostication of women diagnosed with OCCC with multiple effects on key cell functions, supporting its role as an important cellular regulator with potential oncogenic activity, and as a potential target for future intervention strategies.

Synoptic weather conditions can modulate short-term variations in the marine biophysical environment. However, the impact of large-scale synoptic circulation patterns (LSCPs) on variations in chlorophyll-a (chl-a) and sea surface temperature (SST) in the South China Sea (SCS) remains unclear. Using a T-mode principal component analysis method, four types of LSCP related to the Northwest Pacific subtropical high are objectively identified over the SCS for the summers of 2015–2018. Type 1 exhibits a lower chl-a concentration of −3 offshore of southern Vietnam with respect to the other three types. For Type 2, the high chl-a concentration zone (>0.3 mg m−3) along the coast of Guangdong exhibits the widest areas of coverage. The offshore chl-a bloom jet (>0.3 mg m−3) formed in southern Vietnam is the most obvious under Type 3. Under Type 4, the high chl-a concentration zone along the coast of Guangdong is the narrowest, while the chl-a concentration in the middle of the SCS is the lowest (−3). These type differences are mostly caused by the various monsoon circulations, local ocean mesoscale processes and resultant differences in localized precipitation, wind vectors, photosynthetically active radiation and SST. In particular, precipitation over land helps to transport nutrients from the land to the shore, which is conducive to the increase of chl-a. However, precipitation over ocean will dilute the upper seawater and reduce chl-a. Typhoons pump the deeper seawater with nutrients to the surface, and therefore make a positive contribution to chl-a in most offshore areas; however, they also disturb shallower water and hinder the growth of phytoplankton, making a negative contribution near the coast of Guangdong. In general, our findings will provide a better understanding of wind pump impact: the responses of marine biophysical environments to LSCPs.

Thermal conductivity and phase identification of Mg-RE (Rare-Earth) alloy (Mg-La, Mg-Ce, Mg-Nd, Mg-Sm) in both as-cast and annealed states were investigated. The thermal conductivity was measured by the laser flash method in the composition range of 4 wt.% to 12 wt.% RE and the temperature range of 298 K to 673 K. Results demonstrated that homogenization treatment can increase its thermal conductivity. The thermal conductivity increases with the increasing temperature in two states, which is inconsistent with the pure magnesium, and the thermal conductivity of Mg-RE alloys decreases with the alloy additions. Compared with the atomic radius, valence, and intermetallic compounds, the solid solubility of the above four RE elements in α-Mg plays a vital role in the thermal conductivity of Mg-RE binary alloy. The reduction of thermal conductivity caused by the addition of Nd and Sm, which show observable solid solubility in α-Mg, is significantly greater than the addition of La and Ce with negligible solid solubility in α-Mg.

Low-level jet (LLJ) significantly affects the synoptic-scale hydrometeorological conditions in the South China Sea, although the impact of LLJs on the marine ecological environment is still unclear. We used multi-satellite observation data and meteorological reanalysis datasets to study the potential impact of LLJs on the marine biophysical environment over the Beibuwan Gulf (BBG) in summer during 2015–2019. In terms of the summer average, the sea surface wind vectors on LLJ days became stronger in the southwesterly direction relative to those on non-LLJ days, resulting in enhanced Ekman pumping (the maximum upwelling exceeds 10 × 10−6 m s−1) in most areas of the BBG, accompanied by stronger photosynthetically active radiation (increased by about 20 μmol m−2 s−1) and less precipitation (decreased by about 3 mm day−1). These LLJ-induced hydrometeorological changes led to an increase of about 0.3 °C in the nearshore sea surface temperature and an increase of 0.1–0.5 mg m−3 (decrease of 0.1–0.3 mg m−3) in the chlorophyll-a (chl-a) concentrations in nearshore (offshore) regions. Intraseasonal and diurnal changes in the incidence and intensity of LLJs potentially resulted in changes in the biophysical ocean environment in nearshore regions on intraseasonal and semi-diurnal timescales. The semi-diurnal peak and amplitude of chl-a concentrations on LLJ days increased with respect to those on non-LLJ days. Relative to the southern BBG, LLJ events exhibit greater impacts on the northern BBG, causing increases of the semi-diurnal peak and amplitude with 1.5 mg m−3 and 0.7 mg m−3, respectively. This work provides scientific evidence for understanding the potential mechanism of synoptic-scale changes in the marine ecological environment in marginal seas with frequent LLJ days.

Phase equilibria of the Mg-Sn-Ag system in Mg-rich corner at 320 and 400 °C were experimentally investigated with nine ternary alloys subjected to electron probe microanalysis and X-ray diffraction techniques. No ternary compounds were observed at both isothermal sections. Two three-phase triangles, i.e. hcp (Mg) + Mg2Sn + Mg3Ag and Mg2Sn + Mg3Ag + MgAg (bcc_B2), were both observed at 320 and 400 °C. A new three-phase region of Ag3Sn + Mg2Sn + MgAg (bcc_B2) was additionally observed at 320 °C, which implied that the binary phase Ag3Sn has a considerable solubility of Mg in the ternary system at the temperature. And the maximal solubility of Mg in Ag3Sn was measured to be 27.2 at.%. This result is not consistent with the thermodynamic calculated isothermal section at 350 °C from Wang et al. [11] and put forward a new requirement or refinement for the optimization of the Mg-Sn-Ag ternary system. At 400 °C, the maximal solubility of Sn in the Mg3Ag phase was determined to be about 3.0 at.% Sn, and the solubility of Ag in Mg2Sn was negligible. The temperature of ternary eutectic reaction at Mg-rich corner (L↔hcp (Mg) + Mg54Ag17 + Mg2Sn) was measured by differential scanning calorimetry. The partial isothermal sections in Mg-rich corner of the ternary system at 320 and 400 °C were then constructed based on the above experimental data. Keywords: Mg-Sn-Ag system, X-ray diffraction techniques, Electron probe microanalysis, Differential scanning calorimetry, Isotheromal sections

An overview about one thermodynamic database of multi-component Mg alloys is given in this work. This thermodynamic database includes thermodynamic descriptions for 145 binary systems and 48 ternary systems in 23-component (Mg–Ag–Al–Ca–Ce–Cu–Fe–Gd–K–La–Li–Mn–Na–Nd–Ni–Pr–Si–Sn–Sr–Th–Y–Zn–Zr) system. First, the major computational and experimental tools to establish the thermodynamic database of Mg alloys are briefly described. Subsequently, among the investigated binary and ternary systems, representative binary and ternary systems are shown to demonstrate the major feature of the database. Finally, application of the thermodynamic database to solidification simulation and selection of heat treatment schedule is described.

Cryptotanshinone (CTs), an active component isolated from the root of Salvia miltiorrhiza (SM), has been shown to exert potent neuroprotective property. We here established an oxygen-glucose deprivation/recovery (OGD/R)-injured Neurovascular Unit (NVU) model in vitro to observe the neuroprotective effects of CTs on cerebral ischemia/reperfusion injury (CIRI), and explore the underlying mechanisms. CTs was observed to significantly inhibit the OGD/R-induced neuronal apoptosis, and decease the activation of Caspase-3 and the degradation of poly-ADP-ribose polymerase (PARP), as well as the increase of Bax/Bcl-2 ratio in neurons under OGD/R condition. The inhibitory effects of CTs on neuron apoptosis were associated with the blocking of mitogen-activated protein kinase (MAPK) signaling pathway. CTs also remarkably ameliorated OGD/R-induced reduction of transepithelial electrical resistance (TEER) values and the increase of transendothelial permeability coefficient (Pe) of sodium fluorescein (SF) by upregulating the expression of ZO-1, Claudin-5, and Occludin in brain microvascular endothelial cells (BMECs), which might be related to the down-regulation of matrix metalloproteinase (MMP)-9 expression. Based on these findings, CTs may play a neuroprotective role in OGD/R injure in NVU models in vitro by inhibiting cell apoptosis and alleviating the damage of blood-brain barrier (BBB).

In order to provide specific references and suggestions for the design and operation of underground pumping stations, in this paper, an experimental model of an underground pumping station, including 4 pumps and 2 pump intakes (primary and secondary), was obtained through similitude of fluid mechanics. The phase diagrams of various vortices, in terms of different dimensionless numbers are presented, which can reveal their appearance and evolution process. Three specific cases with different vortex flows were analyzed. The experiment results may provide a reference for the current design guidelines for underground pumping stations.

In order to investigate the pharmacokinetics of a combination of diazepam and dexamethasone under hypoxic conditions, a novel, sensitive and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of diazepam and dexamethasone in rat plasma was developed and validated. The chromatographic separation of analytes was successfully achieved on an XTerra® MS C18 column using a gradient elution of methanol and water containing 0.1% formic acid at a flow rate of 0.5 mL/min. This method demonstrated good linearity and no endogenous material interferences. The linear ranges were 1.0–100 ng/mL for diazepam and 2.0–200 ng/mL for dexamethasone. The intra- and inter-day precision for the two compounds in plasma were lower than 10.0%, and the accuracy was between −7.9% and 11.5%. Our method was then successfully applied in a pharmacokinetic comparison between normoxic and hypoxic rats. The results indicated that there were significant differences in the main pharmacokinetics parameters of diazepam and dexamethasone between normoxic and hypoxic rats. The results provide the important and valuable information for discovering and developing novel anti-hypoxia drug combinations, as well as a better understanding of the safety and efficacy of these drugs.

Ventricular assist device has been increasingly used in the treatment of end-stage heart failure, with a high incidence of hemolysis in clinical use, which is a serious problem to be solved. In this study, a complete set of continuous-flow ventricular assist device in vitro test platform for hydraulic performance and hemolysis was established. A self-developed continuous-flow ventricular assist device was employed, with the impeller being chamfered or unchamfered, respectively, to undergo the hydraulic performance and in vitro hemolysis tests, using computational fluid dynamics and a rheometer to investigate the influences of the shear stress on hemolysis. Computational fluid dynamics results showed that the shear stress of continuous-flow ventricular assist device with chamfered impeller was significantly decreased; as a result, the normalized index of hemolysis of the chamfered was reduced, demonstrating that lowering the shear stress of the impeller could significantly reduce hemolysis. Moreover, it was further confirmed by a fixed shear stress test. When the shear stress was greater than 100 Pa, the hemolytic effects were increased significantly. In standard operating conditions, lowering the impeller’s shear stress to less than 100 Pa could effectively reduce the hemolytic effects of ventricular assist device.

The positive slope on the pump performance curve of pump-turbines suggests potential operational instabilities in pump mode. Previous research has indicated that the increase of the hydraulic loss caused by sudden changes of flow patterns in pump-turbines is responsible for the positive slope, however its detailed flow mechanism is still unclear. A low specific speed model pump-turbine was numerically investigated against experiments in the present study, by applying unsteady RANS (Reynolds-Averaged Navier–Stokes equations) simulations with a v2-f turbulence model. The mechanism of occurrence of the positive slope on the pump performance curve was discussed regarding the energy balance, as this region appears when the value of ∂ P u ∂ Q is larger than the critical value P u Q . An unsteady local loss analysis, derived from the energy equation, was conducted to illustrate the contribution of local flow patterns to the loss in corresponding hydraulic components. The variation of the kinetic energy of the mean flow was taken into account for the first time so that this method can be applied to highly time dependent flow patterns, e.g., a rotating stall in the present study. The investigations on the flow patterns revealed that some guide vane channels stalled with a larger discharge coefficient than the positive slope region. Several guide vane channels near the stalled channels were stalling with minor decrease of the discharge coefficient, leading to sudden increases of the input power and the loss. When the discharge coefficient slightly decreased in further, the pump-turbine operated into the positive slope region, and the rotating stall with 3 stall cells appeared, proven by the FFT (Fast Fourier Transform) and cross-phase analysis on the pressure fluctuations.

First-principles evolutionary algorithms are employed to shed light on the phase stability of Al–Nb intermetallics. While the tetragonal Al3Nb and AlNb2 structures are correctly identified as stable, the experimentally reported Laves phase of AlNb3 yields soft phonon modes implying its dynamical instability at 0 K. The soft phonon modes do not disappear even upon elevating the temperature in the simulation up to 1500 K. X-Ray diffraction patterns recorded for our powder-metallurgically produced arc cathodes, however, clearly show that the AlNb3 phase exists. We propose that AlNb3 is dynamically stabilised by ordered antisite defects at the Al sublattice, leading also to a shift of the Nb content from 75 to ∼81 at.%. Unlike the defect-free AlNb3, the antisite-stabilised variant hence falls into the compositional range consistent with our CALPHAD-based phase diagram as well as with the previous reports.

Microstructure and corrosion behavior of the Mg-3Al-xMn (x = 0, 0.12, 0.21, 0.36, 0.45) (hereafter in wt.%) alloys were experimentally investigated by electron probe microanalysis (EPMA), scanning electron microscope equipped with energy dispersive X-ray spectroscopy (SEM/EDX), X-ray diffraction (XRD), electrochemical, and hydrogen evolution tests. A new self-constructed Mg-Al-Mn-Fe thermodynamic database was used to predict the solidification paths of the alloys. The addition of Mn showed no grain refinement in the cast Mg-3Al alloys. According to the microstructure observation, Al-Fe phases were observed in the non-Mn-added alloy, while Al8Mn5(LT) (Al8Mn5 in low temperature) became the main intermetallic phase in the Mn-added alloys, and the amount increased gradually with the Mn addition. The τ–Al0.89Mn1.11 phase with lower Al/(Fe + Mn) ratio was observed in the alloys with 0.36 and 0.45 wt.% Mn content. According to the electrochemical tests, all five alloys showed localized corrosion characteristics in 3.5 wt.% NaCl solution. Compared with the Mg-3Al alloy, the corrosion resistance of Mn-added alloys were significantly improved and increased gradually with the Mn addition, which was due to the variation of Al-containing intermetallic compounds. The present experimental investigations and thermodynamic calculations confirmed the mechanism that the increasing amount of Al8Mn5(LT) with Mn addition could encapsulate the B2-Al(Mn,Fe) phase with higher Fe. Therefore, it could prevent this detrimental phase from contacting magnesium matrix, thus suppressing micro-galvanic corrosion and improving corrosion resistance gradually.

As there are frequent needs to install a micro wind turbine generator in a residential area, we have developed such a downwind-type turbine rotor having the following specifications: The rotor has the tip diameter of 1.5 m and three two-dimensional NACA0018 blades of 0.15 m chord whose material is light, soft and pliable foam plastic for perfect safety. From the wind tunnel test under the wind speed less than 14 m/s, it is clarified that the downwind turbine generator having soft blades has the low noise and the self-output-control characteristics, which are regarded as favorable for its actual operation. The latter feature is primarily attributed to bending and torsional elastic-deformation of the soft blade. The remarkable aerodynamic performances are summarized in this paper.

In pump-turbines, high pressure fluctuation is one of the crucial instabilities, which is harmful to the stable and effective operation of the entire unit. Extensive studies have been carried out to investigate pressure fluctuations (amplitude and frequency) at specific locations. However, limited research was conducted on the distribution of pressure fluctuations in turbine mode in a pump-turbine, as well as the influence of the number of runner blades on pressure fluctuations. Hence, in this study, three dimensional numerical simulations were performed to predict the distribution of pressure fluctuations with different numbers of runner blades in a prototype pump-turbine in turbine mode using the shear stress transport (SST) k-ω turbulence model. Three operating points with the same hydraulic head and different mass flow rates were simulated. The distribution of pressure fluctuation components of blade passing frequency and its harmonics in the direction along the whole flow path, as well as along the circumferential direction, was presented. The mass flow rate and number of runner blades have great influence on the distribution of pressure fluctuations, especially at blade passing frequency along circumferential direction. The mass flow rate mainly affects the position of peak pressure fluctuations, while the number of runner blades mainly changes the number of peak pressure fluctuations. Additionally, the number of runner blades influences the dominant frequencies of pressure fluctuations especially in the spiral casing and draft tube.

Leading-edge protuberances on airfoils or hydrofoils have been considered as a viable passive method for flow separation control recently. In this article, the hydrodynamic performance of a NACA 63 4 -021 (baseline) foil and two modified foils with leading-edge protuberances was numerically investigated using the Spalart–Allmaras turbulence model. It was found that modified foils performed worse than the baseline foil at pre-stall angles, while the lift coefficients at high angles of attack of the modified foils were increased. Both the deterioration of pre-stall and the improvement of post-stall performance were enhanced with larger amplitude of protuberance. Near-wall flow visualizations showed that the leading-edge protuberances worked in pairs at high angles of attack, producing different forms of streamwise vortices. An attached flow along some valley sections was observed, leading to a higher local lift coefficient at post-stall angles. The leading-edge protuberances were considered as sharing a similar mechanism as delta wings, increasing nonlinear lift at large angles of attack. The specific stall characteristics of this leading-edge modification could provide some guidelines for the design of some special hydrofoils or airfoils.

Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.