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This paper explores the principle of deep reinforcement learning algorithm application and constructs the digital teaching model of Civics through the recurrent neural network, Markov decision process, Actor-Critic algorithm and collaborative filtering recommendation algorithm. On this basis, the state representation model and decision-making model are invoked to improve the diversity optimization recommendation of the deep reinforcement learning algorithm. Aiming at the problems existing in the practical application of the OBE concept, the model constructed in this paper is utilized to propose a multi-platform integration of the Civics digital learning model. The objective of empirical and simulation experiments is to confirm the model’s implementation and recommendation effects, respectively. In the validation of hyperparameter d and N values, the DQN model achieves the optimal recommendation effect when the d values are 65 and 63 on the HetRec and MovieTweetings datasets. During the implementation of the digital teaching evaluation of the course Civics, more than 60% of the students rated the teacher’s feedback session higher. Overall, the 6 dimensions were rated higher, and the number of students who chose to be fully compliant and conforming was more than 200.

The ETV6::PDGFRB fusion gene is commonly reported in chronic myelomonocytic leukemia with eosinophilia, yet patients with ETV6::PDGFRB presenting myeloid and lymphoid neoplasms successively have not been reported. Here, we report the first case of a 35-year-old man with myeloid and lymphoid neoplasms harboring an ETV6::PDGFRB fusion gene who demonstrated poor response to imatinib. The patient was diagnosed with an ETV6::PDGFRB fusion gene myeloid neoplasm on initial diagnosis at our hospital. After 5 months of treatment with imatinib, he was diagnosed with T-cell lymphoblastic lymphoma. ETV6::PDGFRB turned negative after increasing the dose of imatinib, but enlarged superficial lymph nodes reappeared the following year. Notably, the patient exhibited a worse response to imatinib treatment. This study describes this rare case and speculates on a possible mechanism. [ABSTRACT FROM AUTHOR]

In recent years, Zn and its alloys have become some of the most promising degradable metals as in vivo implants due to their acceptable biocompatibility and more suitable degradation rate compared with Mg-based and Fe-based alloys. However, the degradation rate of Zn-based materials after implantation in the body for orthopedic applications is relatively slow, leading to long-term retention of the implants after fulfilling their missions. Moreover, the excessive release of Zn2+ during the degradation process of Zn-based implants usually leads to high cytotoxicity and delayed osseointegration. To provide a feasible solution to the problem faced by Zn-based implants, a Zn-Ca composite was fabricated by an air pressure infiltration method in this work. The XRD pattern of the composite suggests that the composite is fully composed of Zn-Ca intermetallic compounds. The degradation tests in vitro show that the composite has a much higher degradation rate than pure Zn, and the high Ca content regions in the composite can preferentially degrade as sacrificial anodes. In addition, the composite can efficiently induce Ca-P deposition during immersion tests in Hank's solution. Cytotoxicity tests indicate that L-929 cells exhibit around 82% cell viability (Grade 1) even after being cultured in the 100% extract prepared from the Zn-Ca composite for 1 day and show excellent cell viability. [ABSTRACT FROM AUTHOR]

Aluminum and its alloys are widely used in packaging, transportation, electrical materials, and many other fields because of their abundance, light weight, good mechanical properties, suitable corrosion resistance, excellent electrical conductivity, and other advantages. Grain refinement achieved by adding inoculant is important not only to reduce the segregation and thermal cracking of alloy castings but also to improve the mechanical properties of alloy castings. Therefore, fine equiaxed grain structure has always been one of the goals pursued by the aluminum alloy casting industry. For this reason, the selection and development of effective inoculants for aluminum alloy is a key technology in the aluminum processing industry. This paper summarizes the development history of inoculants for aluminum alloy, including Al-Ti-C, Al-Ti-B, Al-Ti, Al-Ti-B-(C)-Ce, Al-Sc, and the Fe-rich phase of Al-Si alloy. At the same time, the advantages and disadvantages of common inoculants are introduced and prospective future applications are reviewed. [ABSTRACT FROM AUTHOR]

Climate change alters hydrological processes in cold regions. However, the mechanisms of runoff component variation remain obscure. We implemented a WEP-N model to estimate monthly runoff in the Songhua River Basin (SRB) between 1956 and 2018. All flow simulations were accurate (NSE > 0.75 and RE < 5%). The annual runoff was attenuated in 1998, and the hydrological series (1956–2018) was divided into base and change periods in that year. Relative to the BS (base scenario), annual production flow reduction was −28.2% under climate change and water use. A multifactor attribution analysis showed that climate change and water use contributed 77.0% and 23.0% to annual runoff reduction, respectively. Decreases in annual surface and base flow explained 62.1% and 35.7% of annual production flow reduction, respectively. The base flow increased by 8.5% and 6.5% during the freezing and thawing periods, respectively. Relative to the BS, groundwater recharge increased by 9.2% and 4.1% during the freezing and thawing periods, respectively, under climate change conditions. Climate change was the dominant factor attenuating production flow. The change in production flow occurred mainly during the non-freeze-thaw period. The decrease in total production flow in the SRB was caused mainly by the decrease in the surface flow, where the reduction in base flow accounted for a relatively small proportion. Production flow attenuation aggravated water shortages. The utilization rate of groundwater resources is far below the internationally recognized alarm line. Therefore, attention should be directed towards certain areas of the SRB and other regions with minimal groundwater exploitation. [ABSTRACT FROM AUTHOR]

Cancer‐associated fibroblasts (CAFs) as a predominant cell component in the tumour microenvironment (TME) play an essential role in tumour progression. Our earlier studies revealed oxidized ATM activation in breast CAFs, which is independent of DNA double‐strand breaks (DSBs). Oxidized ATM has been found to serve as a redox sensor to maintain cellular redox homeostasis. However, whether and how oxidized ATM in breast CAFs regulates breast cancer progression remains poorly understood. In this study, we found that oxidized ATM phosphorylates BNIP3 to induce autophagosome accumulation and exosome release from hypoxic breast CAFs. Inhibition of oxidized ATM kinase by KU60019 (a small‐molecule inhibitor of activated ATM) or shRNA‐mediated knockdown of endogenous ATM or BNIP3 blocks autophagy and exosome release from hypoxic CAFs. We also show that oxidized ATM phosphorylates ATP6V1G1, a core proton pump in maintaining lysosomal acidification, leading to lysosomal dysfunction and autophagosome fusion with multi‐vesicular bodies (MVB) but not lysosomes to facilitate exosome release. Furthermore, autophagy‐associated GPR64 is enriched in hypoxic CAFs‐derived exosomes, which stimulates the non‐canonical NF‐κB signalling to upregulate MMP9 and IL‐8 in recipient breast cancer cells, enabling cancer cells to acquire enhanced invasive abilities. Collectively, these results provide novel insights into the role of stromal CAFs in promoting tumour progression and reveal a new function of oxidized ATM in regulating autophagy and exosome release. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are considered the roots of cancer metastasis and recurrence (CSCs), due in part to their self‐renewal and therapy resistance properties. However, the underlying mechanisms for the regulation of CSC stemness are poorly understood. Recently, increasing evidence shows that long non‐coding RNAs (lncRNAs) are critical regulators for cancer cell function in various malignancies including breast cancer, but how lncRNAs regulate the function of breast cancer stem cells (BCSCs) remains to be determined. Herein, using lncRNA/mRNA microarray assays, a novel lncRNA (named lnc030) is identified, which is highly expressed in BCSCs in vitro and in vivo, as a pivotal regulator in maintaining BCSC stemness and promoting tumorigenesis. Mechanistically, lnc030 cooperates with poly(rC) binding protein 2(PCBP2) to stabilize squalene epoxidase (SQLE) mRNA, resulting in an increase of cholesterol synthesis. The increased cholesterol in turn actives PI3K/Akt signaling, which governs BCSC stemness. In summary, these findings demonstrate that a new, lnc030‐based mechanism for regulating cholesterol synthesis and stemness properties of BCSCs. The lnc030‐SQLE‐cholesterol synthesis pathway may serve as an effective therapeutic target for BCSC elimination and breast cancer treatment. [ABSTRACT FROM AUTHOR]

The World Health Organization guidelines recommend lopinavir/ritonavir (LPV/r) as a second-line antiretroviral therapy (ART) for HIV-infected adults in middle-income and low-income countries as a protease inhibitor boost based on clinical trials; however, the real-world safety and efficacy remain unknown. Therefore, we conducted a large-scale, multicenter retrospective cohort study to evaluate the efficacy and safety of LPV/r-based ART among HIV-infected adults in China in whom first-line therapy failed. The data were obtained from a national database covering 17 clinics in China for six years of follow-up from 2009 to 2016. Failure of first-line treatment was determined according to a viral load at least 400 copies/ml at week 48, non-completers at week 48 for any reason, and those who switched ART before week 48 for any reason such as side effects. Treatment effectiveness was assessed by the rate of CD4+T cell recovery, defined as >500 cells/mm3, and the proportion of patients achieving viral suppression, defined as <400 or <50 copies/ml according to the methods used during treatment. Safety was assessed by rates of LPV/r-related adverse events (AEs), including lipid disorder, severe abnormal liver function, myelosuppression, and renal function. Between 2009 and 2016, 1196 participants (median, 36 years old; IQR, 30–43 years) were ultimately enrolled. All patients had been on LPV/r-based second-line ART treatment for more than one year after failure of any first-line ART regimen. Overall CD4+T cell counts increased from 138 cells/mm3 to 475 cells/mm3 and 37.2% of all participants reached CD4 recovery. Viral suppression rates dramatically increased at the end of the first year (<400 copies/ml, 88.8%; <50 copies/ml, 76.7%) and gradually increased during follow-up (<400 copies/ml, 95.8%; <50 copies/ml, 94.4%). The most frequently reported AEs were LPV/r-induced lipid disorders with no obvious increase on LDL-C at follow-up visits. This is the first real-world LPV/r-based second-line treatment study to cover such a large population in China. These results provide strong clinical evidence that LPV/r-based second-line ART is effective in increasing CD4+T cell counts and viral suppression rates with tolerable side effects in HIV-infected adults in China in whom first-line treatment had failed. [ABSTRACT FROM AUTHOR]

Background: Arterial stiffness independently predicts cardiovascular disease. However, few studies have evaluated the associations of central and peripheral pulse wave velocity (PWV) with biomarkers of both myocardial stress (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin-T [hs-cTnT]) among persons without cardiac disease. Methods: We examined 3,348 participants (67–90 years) without prevalent cardiac disease in the Atherosclerosis Risk in Communities (ARIC) Study (2011–13). The cross-sectional associations of PWV quartiles for central arterial segments (carotid-femoral, heart-carotid, heart-femoral) and peripheral artery (femoral-ankle) with NT-proBNP and hs-cTnT were evaluated accounting for potential confounders. Results: Most PWV measures demonstrated J- or U-shaped associations with the two cardiac biomarkers. The highest (Q4) vs. second lowest (Q2) quartile of central PWV measures (carotid-femoral, heart-carotid, heart-femoral PWV) were associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were less evident for hs-cTnT. These associations were attenuated after adjusting for traditional cardiovascular risk factors, but the heart-carotid PWV-NT-proBNP relationship remained borderline significant (difference in log-NT-proBNP = 0.08 [-0.01, 0.17] in Q4 vs. Q2, p = 0.07). Peripheral PWV demonstrated inverse associations. Higher values of NT-proBNP were seen in the lowest vs. second lowest quartile of all PWV measures. Conclusions: Central stiffness measures showed stronger associations with cardiac biomarkers (particularly NT-proBNP) than peripheral measures among older adults without cardiac disease. Our findings are consistent with the concept of ventricular-vascular coupling and suggest that central rather than peripheral arterial hemodynamics are more closely related to myocardial stress rather than damage. [ABSTRACT FROM AUTHOR]

Background/Aims: The ataxia-telangiectasia mutated (ATM) protein kinase is critical for the maintenance of genomic stability and acts as tumor suppressor. Although evidence shows that a DNA damage-independent ATM (oxidized ATM) may be involved in cancer progression, the underlying mechanism is still unclear. Methods: Immunohistochemistry, immunofluorescence and western blotting were applied to detect the levels of oxidized ATM. Transwell assay was used to detect the cell migration and invasion abilities in different treatments. Quantitative phosphoproteome analysis was performed using hypoxic BT549 cells, in the presence or absence of Ku60019, a specific inhibitor of ATM kinase. The phosphorylated cortactin, the target protein of oxidized ATM, was confirmed by immunoprecipitation-western blots and in vitro kinase assay. The functions of phosphorylated cortactin were studied by specific short hairpin RNA, site-directed mutation, transwell assay, and actin polymerization assay. Results: Enhanced oxidized ATM proteins were present not only in the advanced and invasive breast tumor tissues but also malignant hypoxic breast cancer cells, in the absence of DNA damage. Loss of ATM expression or inhibiting oxidized ATM kinase activity reduced breast cancer cell migration and invasion. Using quantitative phosphoproteomics approach, 333 oxidized ATM target proteins were identified, some of these proteins govern key signaling associated with gap junction, focal adhesion, actin cytoskeleton rearrangement. Cortactin, one of the biggest changed phospho-protein, is a novel oxidized ATM-dependent target in response to hypoxia. Mechanically, we reveal that hypoxia-activated ATM can enhance the binding affinity of cortactin with Arp2/3 complex by phosphorylating cortactin at serine 113, and as a result, in favor of breast cancer cell migration and invasion. Conclusion: Oxidized ATM can phosphorylate cortactin at serine 113, playing a critical role in promoting breast tumor cell mobility and invasion via actin polymerization. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression continue to be significant comorbidities for people with HIV infection. We investigated the prevalence of and factors associated with anxiety and depression among adult HIV-infected patients across China. Methods: In this cross-sectional study, we described clinical and psychosocial variables related to depression and anxiety in 4103 HIV-infected persons. Doctors assessed anxiety and depression by asking patients whether they had experienced anxiety or depression in the prior month. Patients also self-administered the Hospital Anxiety and Depression (HAD) scale; those with score ≥8 on HAD-A/D were considered to be at high risk of anxiety or depression. Results: Associations between socio-demographic, psychosocial, and ART-related clinical factors and risk of depression or anxiety were investigated using multivariable logistic regression. Among patients assessed between 9/2014 and 11/2015, 27.4% had symptoms of anxiety, 32.9% had symptoms of depression, and 19.0% had both. Recentness of HIV diagnoses (P = 0.046) was associated with elevated odds of anxiety. Older age (P = 0.004), higher educational attainment (P < 0.001), employment (P = 0.001), support from family / friends (P < 0.001), and sleep disturbance (P < 0.001), and number of ART regimen switches (P = 0.046) were associated with risk of depression, while neither sex nor transmission route showed any associations. There were no significant associations with HIV-specific clinical factors including current CD4+ T cell count and current viral load. Conclusions: Prevalence of symptoms of anxiety and depression is high in this cohort of treatment-experienced HIV patients. Psychological and social-demographic factors, rather than HIV disease status, were associated with risk of depression and anxiety. This finding highlights the need to deliver interventions to address the mental health issues affecting HIV-infected persons with fully successful immune restoration across China. [ABSTRACT FROM AUTHOR]

In situ CeB 6 /Al composite has been proven to be an effective refiner for commercial pure aluminum, however, it remains unclear as to the mechanisms of synthesis and grain refinement. We use low-temperature alloying and high-speed melt spinning to optimize the microstructure of CeB 6 . It is found that in situ CeB 6 /Al composite shows controllable microstructure and its refining effect is obviously dependent on the size of CeB 6 particle/cluster. As nano-CeB 6 particles self-assemble into submicron clusters, the inoculant shows significantly enhanced refining effect, reducing the grain size of pure aluminum to ∼110 μm. The refining mechanism is attributed to the combining effect of the cluster structure in submicron scale and the excellent crystallography matching relationship of CeB 6 and Al. Mechanical properties of pure aluminum are also improved by addition of in situ CeB 6 /Al composite inoculant due to collaboration effect of dispersion strengthening and grain refining strengthening. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of maternal death on the health of the index child, the health and educational attainment of the older children, and the mental health and quality of life of the surviving husband. Methods: A cohort study including 183 households that experienced a maternal death matched to 346 households that experienced childbirth but not a maternal death was conducted prospectively between June 2009 and October 2011 in rural China. Data on household sociodemographic characteristics, physical and mental health were collected using a quantitative questionnaire and medical examination at baseline and follow-up surveys. Multivariate linear regression, logistic regression models and difference-in-difference (DID) were used to compare differences of outcomes between two groups. Findings: The index children who experienced the loss of a mother had a significantly higher likelihood of dying, abandonment and malnutrition compared to children whose mothers survived at the follow-up survey. The risk of not attending school on time and dropping out of school among older children in the affected group was higher than those in the control group during the follow-up. Husbands whose wife died had significantly lower EQ-5D index and EQ-VAS both at baseline and at follow-up surveys compared to those without experiencing a wife’s death, suggesting an immediate and sustained poorer mental health quality of life among the surviving husbands. Also the prevalence of posttraumatic stress disorder (PTSD) was 72.6% at baseline and 56.2% at follow-up among husbands whose wife died. Conclusions: Maternal death has multifaceted and spillover effects on the physical and mental health of family members that are sustained over time. Programmes that reduce maternal mortality will mitigate repercussions on surviving family members are critical and needed. [ABSTRACT FROM AUTHOR]

The fabrication of AlN/Al composites through nitrogen-bearing gas (NH3) bubbling method into Al melts or Al–Mg melts was once experimentally and analytically studied. The experimental results show that Mg addition greatly enhanced the nitridation rate and volume fraction of AlN. However, a detailed characterization of these changes is still incomplete. This paper presents results of an extensive experimental study and theoretical analysis carried out to investigate the profound effect of the formation of AlN with Mg addition. X-ray diffraction, scanning electron microscopy, and energy dispersive spectroscopy were used to characterize the microstructure. The edge-to-edge matching crystallographic model which applied to the three common crystal structures (body-centered cubic, face-centered cubic, and hexagonal close packed) was used to analyze and investigate this notable phenomenon. The calculation and analysis of theoretical model manifested that AlN is formed by the direct interfacing of pure Al or Al–Mg and NH3 with active nitrogen, instead of forming into the precursor Mg3N2 first and then the precursor transformed to AlN. [ABSTRACT FROM AUTHOR]

The mechanical properties of iron-rich Al–Si alloy is limited by the existence of plenty of the iron-rich phase (β-Al5FeSi), whose unfavorable morphology not only splits the matrix but also causes both stress concentration and interface mismatch with the Al matrix. The effect of the cooling rate on the tensile properties of Fe-rich Al–Si alloy was studied by the melt spinning method at different rotating speeds. At the traditional casting cooling rate of ~10 K/s, the size of the needle-like β-Al5FeSi phase is about 80 μm. In contrast, the size of the β-Al5FeSi phase is reduced to 500 nm and the morphology changes to a granular morphology with the high cooling rate of ~104 K/s. With the increase of the cooling rate, the morphology of the β-Al5FeSi phase is optimized, meanwhile the tensile properties of Fe-rich Al–Si alloy are greatly improved. The improved tensile properties of the Fe-rich Al-Si alloy is attributed to the combination of Fe-rich reinforced particles and the granular silicon phase provided by the high cooling rate of the melt spinning method. [ABSTRACT FROM AUTHOR]

An in situ TiC–TiB2/Al composite inoculant is prepared by melt spinning the sintered mixture of Al powder, Ti powder, B4C particles, and graphene nanoplates (GNPs). To increase the degree of dispersion of the particles, the GNPs are coated on the surface of the B4C particles by high‐energy ball milling before sintering. The as‐spun inoculant ribbons are added to the melt of a typical Al–Si alloy to verify its effect of refining the grains on aluminum alloys. It is found that the columnar grains of the as‐cast Al–Si alloy sample are refined to finely approximate equiaxed grains, with an addition level of 0.6 wt% of the inoculant ribbons. The mechanical properties of the as‐inoculated Al–Si alloys also improve significantly, and show a remarkable strengthening and toughening effect. It can be attributed to the grain refinement and the dispersion strengthening by the introduction of TiC and TiB2 particles in the Al matrix. The results show that the newly developed composite inoculant ribbons using GNPs can significantly meliorate the overall mechanical performance of typical Al–Si alloys. [ABSTRACT FROM AUTHOR]