Search

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]

Background: Cancer stem cells (CSCs) are considered as the major cause to tumor initiation, recurrence, metastasis, and drug resistance, driving poor clinical outcomes in patients. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in cancer development and progression. However, limited lncRNAs involved in CSCs have been reported. Methods: The novel lncROPM (a regulator of phospholipid metabolism) in breast CSCs (BCSCs) was identified by microarray and validated by qRT-PCR in BCSCs from breast cancer cells and tissues. The clinical significance of lncROPM was evaluated in two breast cancer cohorts and TANRIC database (TCGA-BRCA, RNAseq data). Gain- and loss-of-function assays were performed to examine the role of lncROPM on BCSCs both in vitro and in vivo. The regulatory mechanism of lncROPM was investigated by bioinformatics, RNA FISH, RNA pull-down, luciferase reporter assay, and actinomycin D treatment. PLA2G16-mediated phospholipid metabolism was determined by UHPLC-QTOFMS system. Cells' chemosensitivity was assessed by CCK8 assay. Results: LncROPM is highly expressed in BCSCs. The enhanced lncROPM exists in clinic breast tumors and other solid tumors and positively correlates with malignant grade/stage and poor prognosis in breast cancer patients. Gain- and loss-of-function studies show that lncROPM is required for the maintenance of BCSCs properties both in vitro and in vivo. Mechanistically, lncROPM regulates PLA2G16 expression by directly binding to 3'-UTR of PLA2G16 to increase the mRNA stability. The increased PLA2G16 significantly promotes phospholipid metabolism and the production of free fatty acid, especially arachidonic acid in BCSCs, thereby activating PI3K/AKT, Wnt/β-catenin, and Hippo/YAP signaling, thus eventually involving in the maintenance of BCSCs stemness. Importantly, lncROPM and PLA2G16 notably contribute to BCSCs chemo-resistance. Administration of BCSCs using clinic therapeutic drugs such as doxorubicin, cisplatin, or tamoxifen combined with Giripladib (an inhibitor of cytoplasmic phospholipase A2) can efficiently eliminate BCSCs and tumorigenesis. Conclusions: Our study highlights that lncROPM and its target PLA2G16 play crucial roles in sustaining BCSC properties and may serve as a biomarker for BCSCs or other cancer stem cells. Targeting lncROPM-PLA2G16 signaling axis may be a novel therapeutic strategy for patients with breast cancer. [ABSTRACT FROM AUTHOR]

The corrosion resistance of 5083 aluminum alloy after refining with nano-CeB 6 /Al inoculant was investigated by 3.5 wt% NaCl solution, compared with that of as-cast alloy and cold-rolled alloy. It was found that nano-CeB 6 /Al inoculant showed significant grain-refining effect on 5083 alloy and the corrosion resistance of 5083 Al alloy was improved as well. The results of potentiodynamic polarization tests showed that the polarization resistance of refined alloy was higher than that of as-cast alloy and cold-rolled alloy, together with more positive breakdown potential value. The corrosion rate was dependent on the grain size following a power law type relationship, which was attributed to the reduced precipitate on the grain boundary. Unlabelled Image • CeB 6 inoculant can effectively refine 5083 aluminum alloy and improve its corrosion resistance. • The corrosion rate was dependent on the grain size following a power law type relationship. • Refined intergranular precipitates reduce the pitting tendency of aluminum. [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]

Assembly and packaging technology is one of the most critical factors that restrict the development of microelectromechanical systems (MEMS), including chips and other devices. Dispensing robot is a key high-end equipment in MEMS packaging. Its core component, WC-Co impact needle, is limited by fretting wear and deformation, leading to reduced service accuracy and life, which is the most important cause of failure. Impact fretting wear frequently occurs in micro-nano mechanical systems and has been widely studied. However, the combined high frequency (∼300 HZ) and micro impact amplitude (∼120 μm) wear behaviors such as WC-Co impact needle with ultrafine grain (∼100 nm) is rarely concerned. To further understand the influence of impact frequency and impact velocity on the wear rate of impact needle, dispensing experiments were designed and the wear mechanism was investigated. Results indicated that the impact velocity has more influence on the wear rate of impact needle than the impact frequency. In addition, a high-current pulsed electron beam (HCPEB) surface treatment method which can effectively increase the wear resistance of impact needle was proposed. After HCPEB treatment, the abrasion loss was reduced by 44% compared to the untreated one at the same impact frequency and different impact velocities, while the abrasion loss was reduced by 52% compared to the untreated one at the same impact velocity and different frequencies. These can be attributed to the fact that HCPEB treatment decreased the grain size of WC-Co cemented carbide impact needle and promoted WC phase transition, leading to an increase in microhardness. • High-current pulsed electron beam (HCPEB) was employed to WC-Co impact needle. • Impact velocity has a significant effect on impact fretting wear resistance of impact needle than impact frequency. • The microhardness of HCPEB treated impact needle being 1.4 times compared to untreated one. • Impact wear resistance improvement attributed to the WC phase transition and surface grain refinement. [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]

The CeB 6 /Al inoculant with variable sizes of CeB 6 particles were prepared by arc-melting and controlled by melt-spinning and then verified the refining efficacy in pure aluminum. It was found that the grain refining efficacy can be significantly improved by controlling the CeB 6 particle size. The pure aluminum can be refined from a grain size grade of 870 ± 25 μm to 150 ± 35 μm by addition of CeB 6 /Al ribbon with a very small ratio of 0.4% in weight. Thereafter, the mechanical properties of the pure aluminum, including the tensile strength, yield strength and microhardness, were obviously improved by the addition of the CeB 6 /Al ribbon. The excellent grain refining can be attributed to the nano-sized refiner particles and the well-banded particle/matrix interface which are benefit for the nucleation of aluminum during solidification. It is suggested that the CeB 6 /Al inoculant ribbon is a promising inoculants for aluminum alloy. [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]

Objective To analyze the clinic value of application of percutaneous endoscopic gastrostomy by Introducer in critically-illed patients. Methods A retrospective analysis from January 2009 to December 2013 of this hospital was conducted in clinic data of 96 critically-illed patients with the percutaneous endoscopic gastrostomy. The observation group (50 cases) was adopted percutaneous endoscopic gastrostomy by Introducer while the control group (46 cases) with percutaneous endoscopic gastrostomy by line pull. The patients' tolerance, operation time, general indicators change before and after surgery, postoperative complications and the length of time were compared between the two groups. Results The surgery of the two groups were successful, reported no deaths. The operation time in the observation group was shorter than that of the control group, whose difference was statistically significant (P<0.01). Among the patients, 75% expressed that it was hard to beat line pull method after the operation. 12% think it was unbearable for Introducer method. The serum prealbumin, hemoglobin, albumin 1 month after the surgery were significantly increased than those of before the surgery. The difference had statistical significance (P<0.05). There was no statistical difference in the length of hospitalization between the two groups (P>0.05). There was no complications in the observation group and 10 cases in the control group, including 7 cases colostomy mouth infection, 3 cases abdominal infection. The observation group as access to direct replacement of fistula in vitro, while the control group should be operated guided by gastroscope with original colostomy method. conclusion The percutaneous endoscopic gastrostomy by Introducer is safe, reliable and convenient, which is suitable for critical patients and the gastrointestinal nutrition is more simple, safe and fewer complications. [ABSTRACT FROM AUTHOR]

Hybrid aluminum matrix composites have received widespread attention because of their superior performance to single-phase reinforced aluminum matrix composites. In situ VB 2 –AlN–Al 4 C 3 –VSi 2 /Al ribbons with polyphasic and multi-scale reinforcement particles were prepared by powder metallurgy method and controlled by melt-spinning and then verified the reinforcement efficacy in Al–12Si alloy. It was found that the addition of VB 2 –AlN–Al 4 C 3 –VSi 2 /Al ribbons not only refined the grain of α-Al, but also optimized the morphology of eutectic silicon for Al–12Si matrix composite. Thereafter, the mechanical properties of the VB 2 –AlN–Al 4 C 3 –VSi 2 /Al–12Si composite, including the tensile strength, ductility and hardness were increased by 36.2%, 82.2% and 33.4%, respectively, with the addition of VB 2 –AlN–Al 4 C 3 –VSi 2 /Al ribbons. The excellent mechanical properties can be attributed to the micron-sized VSi 2 particles, nano-sized AlN, VB 2 , and Al 4 C 3 as well as the well-bonded particle/matrix interface. In addition, multiple strengthening mechanisms have also made outstanding contributions to the improvement of the mechanical properties, including (1) Orowan strengthening; (2) Coefficient of thermal expansion (CTE) mismatch strengthening; (3) the Hall-Petch effect caused by grain refinement. The present experimental results provide an insight into the understanding of polyphasic and multi-scale reinforcement particles, and extend the effort for the development of Al–Si composite. • In situ polyphasic and multi-scale particles was prepared by PM and melt-spinning. • Inoculant ribbons refine the α-Al grain and optimize the morphology of eutectic silicon. • VB 2 –AlN–Al 4 C 3 –VSi 2 /Al interface is clean and well lattice-matched. • The VB 2 –AlN–Al 4 C 3 –VSi 2 /Al–12Si composite exhibit excellent mechanical properties. [ABSTRACT FROM AUTHOR]

Sc alloying is usually carried out by adding a small amount of Sc in typical aluminum alloys to improve the mechanical properties, however, the effect of high-Sc content on the microstructure and properties of aluminum alloys is rarely concerned. To further understand the role of Sc alloying, several Al–Sc binary alloys with high-Sc content are designed and the relationship between the Sc content and mechanical properties were investigated. It is found that the mechanical properties of Al–Sc binary alloy is determined by both the Sc content and the cooling rate. The addition amount of Sc shows relatively small effect on the mechanical properties at low cooling rate, but higher at high cooling rate, because cooling rate turns the size and distribution of Al 3 Sc particles. Through the high Sc content alloy design and melt spinning rapid cooling technology, the densely distributed Al 3 Sc precipitate of about 250 nm can be located inside the α-Al grains, resulting in the intracsystalline reinforcement. The combination of high tensile strength (344 MPa) and good plasticity (5.7%) were achieved at a grain size of ~500 nm in the hypereutectic Al–Sc binary alloys ribbons. The significant strengthening could be attributed to multiple strengthening mechanisms including (1) Orowan strengthening; (2) coefficient of thermal expansion (CTE) mismatch strengthening; (3) the Hall-Petch effect caused by grain refinement; (4) solid solution strengthening. When the cooling rate is increased, the effects of thermal mismatch strengthening and Orowan mechanism are more prominent, significantly improving the strength of the Al–Sc alloy. The present experimental results provide an insight into the understanding of microstructural evolution of nanoparticles, and extend the effort for the development of hypereutectic Al–Sc alloys as a member of high-strength structural materials. • Addition of too much Sc fails to enhancement by traditional casting. • Melt spinning causes uniform distribution of Al 3 Sc nanoparticles. • The prepared Al–Sc ribbons exhibit excellent mechanical properties. • Fast cooling and high Sc synergy strengthen Orowan mechanism. [ABSTRACT FROM AUTHOR]

Purpose: The metallic alloys and their components fabricated via laser powder bed fusion (LPBF) suffer from the microvoids formed inevitably due to the extreme solidification rate during fabrication, which are impossible to be removed by heat treatment. This paper aims to remove those microvoids in as-built AlSi10Mg alloys by hot forging and enhance their mechanical properties. Design/methodology/approach: AlSi10Mg samples were built using prealloyed powder with a set of optimized LPBF parameters, viz. 350 W of laser power, 1,170 mm/s of scan speed, 50 µm of layer thickness and 0.24 mm of hatch spacing. As-built samples were preheated to 430°C followed by immediate pressing with two different thickness reductions of 10% and 35%. The effect of hot forging on the microstructure was analyzed by means of X-ray diffraction, scanning electron microscopy, electron backscattered diffraction and transmission electron microscopy. Tensile tests were performed to reveal the effect of hot forging on the mechanical properties. Findings: By using hot forging, the large number of microvoids in both as-built and post heat-treated samples were mostly healed. Moreover, the Si particles were finer in forged condition (∼150 nm) compared with those in heat-treated condition (∼300 nm). Tensile tests showed that compared with heat treatment, the hot forging process could noticeably increase tensile strength at no expense of ductility. Consequently, the toughness (integration of tensile stress and strain) of forged alloy increased by ∼86% and ∼24% compared with as-built and heat-treated alloys, respectively. Originality/value: Hot forging can effectively remove the inevitable microvoids in metals fabricated via LPBF, which is beneficial to the mechanical properties. These findings are inspiring for the evolution of the LPBF technique to eliminate the microvoids and boost the mechanical properties of metals fabricated via LPBF. [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]

Background: Intramural pregnancy is an uncommon type of ectopic pregnancy, where the gestational sac is completely encircled by myometrium and unconnected with endometrial cavity, fallopian tubes or round ligament. Owing to its potentially life-threatening hemorrhage and uterine rupture, early diagnosis and management are urgently required. We present a case of a woman undergoing zigzag medical procedures, which featured non-consensus preoperative diagnosis of intramural and interstitial pregnancy and an intramural ectopic pregnancy ultimately confirmed and successfully removed by emergency laparoscopy. Additionally, we present a review of the related literature and discuss its varied clinical features, imageological characters, diagnosis, differential diagnosis and multiple treatments.Methods: A comprehensive bibliographic search through PubMed, using keywords: intramural ectopic pregnancy. Relevant literatures published from January 2013 to April 2019 were reviewed.Results: Twenty-four cases in total for intramural ectopic pregnancy including this report were reviewed. Diagnoses were mainly made by ultrasound images. Most patients had a history of uterine surgery or intrauterine operation and had been surgically resected. None of the mothers were in danger, but only one case had live birth at 37 weeks of gestation.Conclusion: Non-specific clinical presentation and non-uniform ultrasound criteria pose a challenge for us to make timely and accurate management. Integrated radiological examinations and communication and cooperation between sonographers and gynecologists play a vital role in diagnostic accuracy and selecting the optimal therapeutic method of an intramural pregnancy. [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]

Introduction: Current guidelines recommend amphotericin B as the preferred drug for induction therapy; however, amphotericin B is not available in certain settings. Induction therapy with amphotericin B deoxycholate or voriconazole has been shown to be an effective treatment for talaromycosis. However, prospective clinical trials comparing these two antifungal drugs are absent from the literature. Methods: In this open-labeled, multicenter, prospective controlled trial, we enrolled patients at 15 hospitals in China from 2019 to 2020. Participants received induction treatment with either amphotericin B deoxycholate intravenously at a dose of 0.5 to 0.7 mg per kilogram per day or voriconazole at a dose of 6 mg/kg intravenously twice daily for the first day, followed by 4 mg/kg intravenously twice daily for 3 days, and then voriconazole was given either intravenously (4 mg/kg intravenously twice daily) or orally (200 mg twice daily) for the remaining 10 days. The primary outcome was all-cause mortality during 48 weeks after baseline. Secondary outcomes were mortality at week 2 or week 24, clinical resolution of talaromycosis, and fungal clearance at week 2. A propensity score (PS) matching analysis was performed to control confounding factors. Results: We observed no difference in the risk of death at week 2, at week 24, or at week 48 in either the unmatched cohort or the matched cohort. Both in the unmatched and the matched cohorts, logistic regression analysis revealed a significantly lower odds ratio of clinical resolution (OR 0.450, 95% CI 0.291–0.696, p < 0.001; OR 0.443, 95% CI 0.261–0.752, p = 0.003) and fungal clearance (OR 0.514, 95% CI 0.333–0.793, p = 0.003; OR 0.542, 95% CI 0.318–0.923, p = 0.024) in voriconazole users compared to amphotericin B deoxycholate users over the course of 2 weeks. In the induction therapy without ART subgroup patients in the amphotericin B deoxycholate group showed a significantly higher rate of clinical resolution and fungal clearance than those in the voriconazole group (56.1% vs. 30.4%, 95% CI 13.4–36.5, p = 0.000; 63.8% vs. 40.4%, 95% CI 11.1–34.7, p = 0.000), whereas there was no significant difference in clinical resolution and fungal clearance in the induction therapy combined with ART subgroup. Conclusions: Induction therapy using voriconazole had a similar efficacy, in terms of all-cause mortality rate, to induction therapy using amphotericin B deoxycholate in HIV-infected patients with talaromycosis over a 48-week observation period. Amphotericin B deoxycholate contributed to earlier fungal clearance and earlier clinical resolution of symptoms in the induction therapy without ART subgroup, whereas amphotericin B deoxycholate use did not contribute to a significant difference in clinical resolution and fungal clearance in the induction therapy combination with ART subgroup. Trial Registration: ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362. [ABSTRACT FROM AUTHOR]

JUP, a homologue of β-catenin, is a cell-cell junction protein involved in adhesion junction and desmosome composition. JUP may have a controversial role in different malignancies dependence of its competence with or collaboration with β-catenin as a transcription factor. In this study, we focused on the role of JUP in tumor progress and metastasis of GC. We investigated whether that the function of JUP is related to its cellular location in GC development process from epithelium-like, low malignant GC to advanced EMT-phenotypic GC. Gradual loss of membrane and/or cytoplasm JUP was closely correlated with GC malignancy and poor prognostics. Knockdown of JUP in epithelium-like GC cells causes EMT and promotes GC cell migration and invasion. Ectopic expression of wild JUP in malignant GC cells led to an attenuated malignant phenotype such as reduced cell invasive potential. In mechanism, loss of membrane and/or cytoplasm JUP abolished the restrain of JUP to EGFR at cell membrane and resulted in increased p-AKT levels and AKT/GSK3β/β-catenin signaling activity. In addition, nuclear JUP interacts with nuclear β-catenin and TCF4 and played a synergistic role with β-catenin in promoting TCF4 transcription and its downstream target MMP7 expression to fuel GC cell invasion. [ABSTRACT FROM AUTHOR]

Drosha-dependent canonical microRNAs (miRNAs) play a crucial role in the biological functions and development of cancer. However, the effects of Drosha-independent non-canonical miRNAs remain poorly understood. In our previous work, we found a set of aberrant miRNAs, including some upregulated miRNAs, called Drosha-independent noncanonical miRNAs, in Drosha-knockdown gastric cancer (GC) cells. Surprisingly, Drosha-silenced GC cells still retained strong malignant properties (e.g., proliferation ability and cancer stem cell (CSC) characteristics), indicating that aberrantly upregulated non-canonical miRNAs may play an important role in the maintenance of the malignant properties in GC cells that express low Drosha levels. Here, we report that miR-6778-5p, a noncanonical miRNA, acts as a crucial regulator for maintenance of CSC stemness in Drosha-silenced GC cells. MiR-6778-5p belongs to the 5'-tail mirtron type of non-canonical miRNAs and is transcript splice-derived from intron 5 of SHMT1 (coding cytoplasmic serine hydroxymethyltransferase). It positively regulates expression of its host gene, SHMT1, via targeting YWHAE in Drosha-knockdown GC cells. Similar to its family member SHMT2, SHMT1 plays a crucial role in folate-dependent serine/glycine inter-conversion in one-carbon metabolism. In Drosha wild type GC cells, SHMT2 mediates a mitochondrial-carbon metabolic pathway, which is a major pathway of one-carbon metabolism in normal cells and most cancer cells. However, in Drosha-silenced or Drosha low-expressing GC cells, miR-6778-5p positively regulates SHMT1, instead of SHMT2, thus mediating a compensatory activation of cytoplasmic carbon metabolism that plays an essential role in the maintenance of CSCs in gastric cancer (GCSCs). Drosha wild type GCSCs with SHMT2 are sensitive to 5-fluorouracil; however, Drosha low-expressing GCSCs with SHMT1 are 5-FU-resistant. The loss of miR-6778-5p or SHMT1 notably mitigates GCSC sphere formation and increases sensitivity to 5-fluorouracil in Drosha-knockdown gastric cancer cells. Thus, our study reveals a novel function of Drosha-independent noncanonical miRNAs in maintaining the stemness of GCSCs. [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]

Study Design: Retrospective comparative study.Objective: The purpose of this study is to compare functional outcomes, hospital resource utilization, and spine-related costs during 2 years in patients who had undergone primary or revision surgery for adult spinal deformity (ASD).Summary Of Background Data: After surgery for ASD, patients may require revision for pseudarthrosis, implant complications, or deformity progression. Data evaluating cost-effectiveness of primary and, in particular, revision surgery, for ASD are sparse.Methods: We retrospectively reviewed records for 119 consecutive patients who had undergone primary or revision surgery for ASD. Two-year total spine-related medical costs were derived from hospital charge data. Functional outcome scores were extracted from prospectively collected patient data. Cost utility ratios (cost/quality-adjusted life-year [QALY]) at 2 years were calculated and assessed against a threshold of $154,458/QALY gained (three times the 2015 US per-capita gross domestic product).Results: The primary surgery cohort (n = 56) and revision cohort (n = 63) showed significant improvements in health-related quality-of-life scores at 2 years. Median surgical and spine-related 2-year follow-up costs were $137,990 (interquartile range [IQR], $84,186) for primary surgery and $115,509 (IQR, $63,753) for revision surgery and were not significantly different between the two groups (P = 0.12). We report 2-year QALY gains of 0.36 in the primary surgery cohort and 0.40 in the revision group (P = 0.71). Primary instrumented fusion was associated with a median 2-year cost per QALY of $197,809 (IQR, $187,350) versus $129,950 (IQR, $209,928) for revision surgery (P = 0.31).Conclusion: Revision surgery had lower total 2-year costs and higher QALY gains than primary surgery for ASD, although the differences were not significant. Although revision surgery for ASD is known to be technically challenging and to have a higher rate of major complications than primary surgery, revision surgery was cost-effective at 2 years. The cost/QALY ratio for primary surgery for ASD exceeded the threshold for cost effectiveness at 2 years.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

For the development of high-performance aluminum (Al) matrix composites reinforced with carbon nanotubes (CNTs), high energy ball milling (HEBM) is the most prevalent method to disperse CNTs in Al powder. However, the dispersion mechanism of CNTs in Al powder is still unclear, mainly because it is difficult to characterize CNTs when they are buried inside Al powder particles. Herein, focused-ion-beam-assisted transmission electron microscopy observation of CNTs in Al powder via HEBM with various milling times was conducted. Results showed that with increasing HEBM time, CNTs clusters were firstly broken up to be dispersed shorter-lengthed CNTs on the surface of Al flakes with gradually reduced thickness. Afterward, cold-welding of Al flakes was the predominant phenomenon, which resulted in re-spheroidization of Al powders and homogeneously dispersed CNTs. This study may provide guidance for controlling and optimizing the HEBM process to disperse CNTs in Al matrix towards the development of high-performance CNTs/Al composites. [Display omitted] • CNT dispersion mechanism in Al matrix during ball milling process was elucidated. • Focused ion beam-assisted transmission electron microscopy observation was adopted. • Homogeneous CNT dispersion was obtained after 28 h ball milling process. • Dislocations and stacking faults in matrix enhanced powder modulus and hardness. [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]

In this paper, an efficient route that combined addition of excessive Mg (3.6 wt.%) and a trace of La (0.5 wt.%) as well as subsequent T6 heat treatment has been first proposed to modify the detrimental platelet-like β-Al 5 FeSi Fe-rich intermetallic to valuable granular-like π-Al 8 Mg 3 FeSi 6 phase in eutectic Al–Si die alloys. The results of the DSC analysis revealed that majority of Mg play the leading role for precipitation of large script-like π-phase while rare earth La has the significant effect on modifying the eutectic Si phase simultaneously. A new phenomenon has been found that the morphology of the π-phase transformed from the script-like to fine granular-like by two main stages, including fragmentation and growth during solution treatment. By calculation, the coarsening rate coefficient of the segmented π-phase was about 2.9 × 10 − 19 m 3 /h during growth stage. The tensile testing measurements showed that the ultimate tensile strength (UTS), yield strength (YS), elongation to fracture (EI) and the quality index (Q) of T6 treated eutectic Al–Si die alloys alloying with 3.6 wt.% Mg and 0.5 wt.% La can reach 312 MPa, 270 MPa, 4.28% and 406 MPa respectively, and the enhanced mechanical properties corresponding to the evolution of the microstructure. [ABSTRACT FROM AUTHOR]

• The SARAX code system was extended for full-range spectrum adaptability. • The assembly calculation is based on the improved Tone's method with MOC solver. • The high-efficient 2-D hyperfine group method was developed. For better self-shielded cross-section generation in advanced reactor analysis with full-range spectrum adaptability, the 2-D subassembly calculation capability has been recently developed with several new methods in the SARAX code system. The improved Tone's method was implemented in the 2-D resonance self-shielding by incorporating the MOC to accurately estimate the heterogeneity effect. The 2-D hyperfine group method with on-the-fly collision probability and the adjacent region flux approximation was developed to perform the 2-D slowing-down spectrum calculation. For better consideration of spectral transition effects due to different mean free path of neutrons, the local super-subassembly model and the whole-core equivalent model can be built with the super-homogenization technique. Verification results showed that for different subassembly calculations, the eigenvalue and self-shielded cross-sections of major actinides agreed with the OpenMC solutions. For core calculations of TRIGA and the reactor with irradiation tunnel, the k-effective and power distribution also agreed well with the OpenMC. [ABSTRACT FROM AUTHOR]

• The behaviors of 1 2 ¯ 1 0 -oriented crack in twinning boundaries and basal/prismatic (BP) interface of Mg are studied. • The brittleness and ductility are governed by the competition of dislocation emission and cleavage at crack tips for twins. • BP transformation dominates the initial plastic deformation for BP bicrystal with a pre-crack under tensile loading. • The brittle-ductile transition can be observed with the increased temperature. In this study, 1 2 ¯ 1 0 -oriented interfacial crack behaviors and mechanical properties of Mg bicrystal subjected to uniaxial tensile deformation are systematically studied by molecular dynamic (MD) simulation. According to the simulation results, the behaviors of 1 2 ¯ 1 0 -oriented crack associated with { 1 0 1 ¯ 1 } twin boundary (TB), { 1 0 1 ¯ 2 } TB and basal/prismatic (BP) interface show a strong dependence on the crystalline orientation of Mg. For the bicrystals with TB, the brittle and ductile fracture rely on the competition of dislocation emission and cleavage at the crack-tip under low temperature. The brittle-ductile transition can be observed with the increased temperature. Interestingly, the BP transformation dominates the initial plastic deformation for Mg bicrystal with BP interface which accompanies the boundary migration under tension. The boundary migration mechanism is revealed to influence on the interfacial cracking behavior and the correlative mechanical property of materials. [ABSTRACT FROM AUTHOR]

• TiN-AlN/Al inoculant was prepared by melt-spinning with Si 3 N 4 as a nitrogen source. • HRTEM shows that an orientation difference of 17° 11′ between (1 1 1) TiN and (1 1 1) Al. • Mechanical properties of pure Al improved by adding AlN-TiN/Al after sonication. A new in-situ TiN-AlN/Al composite inoculant with submicron structure was developed by arc melting and melt spinning method using Si 3 N 4 as nitrogen source. Under ultrasonic condition, the as-spun inoculant ribbon shows significant refining effect for pure Al, leading to an obviously reduced grain size from 780 μm to 140 μm and increased tensile strength from 57 MPa to 140 MPa. It is found that an obvious crystal orientation difference of 17° 11′ is presented between the TiN crystal and the Al matrix, which helps to form a coherent interface. It is proved that TiN can be used as an effective heterogeneous substrate for nucleation of Al crystals. [ABSTRACT FROM AUTHOR]