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BACKGROUND: Permanent epicardial pacing is the primary choice for neonates and infants with bradyarrhythmia. We reviewed mid-term outcomes after epicardial permanent pacemaker (EPPM) implantation in this age group. METHODS: From Dec 1, 2008 to Dec 1, 2019, children who underwent EPPM implantation within the first year of life were included in our study. Patients were followed up for as long as 12 years, until Jun 11, 2021, for all-cause mortality and pacemaker reoperation. Kaplan-Meier and log-rank tests were used for analysis. RESULTS: Of 31 consecutive patients [18 boys (58.1%) and 2 neonates (6.5%)] included in this study, 30 (96.8%) were discharged alive and assessed at a median follow-up of 3.9 years [interquartile range (IQR) 4.7]. The median age and weight of the patients were 156 days (IQR 217) and 5.3 kg (IQR 3.5), respectively, at the time of their operation. Twenty-five (80.6%) patients had congenital heart disease, and the main indication for pacing was postoperative atrioventricular block (AVB) in 21 (67.7%) patients. During follow-up, 3 (9.7%) patients died and there were a total of 9 pacing lead failures in 7 (22.6%) patients. The median longevity of leads (unipolar steroid-eluting) was 2.9 years (IQR 3.6). Freedom from lead reoperation was 90.3%, 72.0%, 65.5% and 49.1% at 1, 3, 5, and 8 years, respectively. The median longevity of the pacing generators was 3.3 years (IQR 2.8). Freedom from generator reoperation was 90.3%, 75.6%, 52.4% and 43.6% at 1, 3, 5 and 6 years, respectively. CONCLUSIONS: The mid-term outcome of EPPM implantation in neonates and infants was acceptable. Neonates and infants with EPPM implants face the risk of repeated reoperations and all-cause death. A patient’s prognosis can depend on regular follow-up, type of pacing lead and the presence of congenital heart malformations, especially complex congenital heart disease.

This retrospective study aimed to derive the clinical phenotypes of ventilated ICU patients to predict the outcomes on the first day of ventilation. Clinical phenotypes were derived from the eICU Collaborative Research Database (eICU) cohort via cluster analysis and were validated in the Medical Information Mart for Intensive Care (MIMIC-IV) cohort. Four clinical phenotypes were identified and compared in the eICU cohort (n = 15,256). Phenotype A (n = 3112) was associated with respiratory disease, had the lowest 28-day mortality (16%), and had a high extubation success rate (~80%). Phenotype B (n = 3335) was correlated with cardiovascular disease, had the second-highest 28-day mortality (28%), and had the lowest extubation success rate (69%). Phenotype C (n = 3868) was correlated with renal dysfunction, had the highest 28-day mortality (28%), and had the second-lowest extubation success rate (74%). Phenotype D (n = 4941) was associated with neurological and traumatic diseases, had the second-lowest 28-day mortality (22%), and had the highest extubation success rate (>80%). These findings were validated in the validation cohort (n = 10,813). Additionally, these phenotypes responded differently to ventilation strategies in terms of duration of treatment, but had no difference in mortality. The four clinical phenotypes unveiled the heterogeneity of ICU patients and helped to predict the 28-day mortality and the extubation success rate.

Laser powder bed fusion (LPBF) is a powder-based Additive Manufacturing (AM) technology, where the quality control of powder feedstock is critical as the particle packing on the powder bed and laser–particle interaction during laser melting influence the quality of the final parts. In this work, two AlSi10Mg powder batches with satellite particles and non-satellite particles were used to fabricated LPBF AlSi10Mg samples, and the influences of the different powder properties on the defect, microstructure, and surface morphology were quantified. The satellite and agglomeration of powder leads to the formation of the large powder cluster and poor powder flowability and subsequently forms the inter-particle gap left in the powder bed. In the LPBF process, these powder properties can cause uneven recoating and rough surface, which continues to accumulate, eventually forming internal defects such as lack-of-fusion or unfilled irregular shaped defects in parts.

BACKGROUND: The modification of N(6)-methyladenosine (m(6)A) is a dynamic and reversible course that might play a role in cardiovascular disease. However, the mechanisms of m(6)A modification in myocardial ischemia/reperfusion injury (MIRI) remain unclear. METHODS: A mouse model of MIRI and a cell model of oxygen-glucose deprivation/reperfusion (OGD/R) HL-1 cells were employed. In an in vivo study, the total RNA m(6)A modification levels were determined by dot blot, and the key genes related to m(6)A modification were screened by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In an in vitro study, the effects of AlkB homolog 5 (ALKBH5), an RNA demethylase, on cell proliferation, cell injury, and apoptosis were detected by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, lactate dehydrogenase (LDH) and cardiac troponin-I (cTnI) levels, and flow cytometry. Besides, the m(6)A modification-changed and differentially expressed messenger RNA (mRNA) were determined by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) in ALKBH5-overexpressed HL-1 cells. Finally, the mRNA levels of the promising targeted gene were examined by RT-qPCR and its m(6)A modification levels were examined by MeRIP-qPCR. RESULTS: Our results showed that RNA m(6)A modification was involved in MIRI, in which ALKBH5 was downregulated. Functionally, by overexpressing or silencing ALKBH5 in experimental cells, we verified its protective properties on cell proliferation, cell injury, and apoptosis in the process of MIRI. Besides, we provided a mass of latent different mRNAs with m(6)A modification variation in ALKBH5-overexpressed HL-1 cells. Mechanistically, we further screened the most potential targeted mRNAs and suggested that triple functional domain (Trio) mRNA could be upregulated by ALKBH5 by reducing m(6)A level of Trio. CONCLUSIONS: This study demonstrated that the downregulated ALKBH5 might contribute to MIRI process by increasing the m(6)A modification of Trio mRNA and downregulating Trio.

TiB, TiC and La2O3 hybrid-reinforced Ti-6Al-4V matrix composites were fabricated by common casting and processed by the following forging and isothermal extrusion. The texture evolution, dynamic recrystallization (DRX) behavior and mechanical properties of the as-extruded composites were investigated. The results show that DRXed regions and deformed regions formed during extrusion, strong 〈0001〉α, $$ \left\langle {10\bar{1}0} \right\rangle_{\alpha } $$ and weak $$ \left\langle { 1 0 {\bar{\text{1}}\text{1}}} \right\rangle_{\alpha } $$ fiber textures parallel to extrusion direction were formed due to the selection of slip system in α phase and inheritance from phase transformation according to Burgers orientation relationship. Additionally, the orientation of α grain in DRXed regions became randomized in comparison with the deformed regions. Micro-sized TiB short fibers not only acted as source to generated dislocations, but hindered dislocation slip to cause pile-ups around TiB, which is beneficial to stimulate dynamic recrystallization. Submicro-sized La2O3 particles distributed at the triple junction of grain boundaries could pin grain boundaries and hinder grain growth. Tensile test results show that the ultimate tensile strength got a 9.8 pct enhancement, from 834.3 ± 10 to 916.0 ± 10.6 MPa, accompanied by simultaneous improvement of elongation from 5.4 ± 0.6 to 12.2 ± 0.7 pct at room temperature. The simultaneous increase of strength and ductility was principally attributed to TiB fracture modes and grain refinement after extrusion.

Titanium matrix composites (TMCs) reinforced with different TiBw and La2O3p content were successfully processed by equal channel angular pressing (ECAP), and the role of reinforcements on the microstructure and mechanical properties were investigated. The results show that the addition of reinforcements accelerates continuous dynamic recrystallization (CDRX) and promotes the formation of new ultrafine grains (200 to 500 nm) in ECAPed TMCs. Micron-scale TiBw accelerates recrystallization by particle-stimulated nucleation and the increasing effective strain. CDRX occurs more easily near TiBw tips due to the load-bearing effect. By contrast, nano-scaled La2O3p retards the migration of grain boundaries through Zener drag effect and promotes the evolution of CDRX. The strength of ECAPed TMCs is improved significantly and reinforcements enhance the contribution of grain-refinement strengthening. The TMCs with 1.2 vol pct reinforcements exhibited the largest improvement in total strength, which is 5 times and 3 times of those with 0 vol pct and 2.4 vol pct, respectively. The elongations of both forged and ECAPed TMCs decrease with increasing reinforcement content owing to TiB whisker fracture and interface debonding and the diminishing strain hardening capacity.

Hepatocellular carcinoma (HCC) has high morbidity and mortality. MicroRNAs (miRNAs), which could be regulated by cancer-derived exosomes, play critical regulatory roles in the initiation and development of cancer. However, the expressions, effects, and mechanisms of abundant miRNAs regulated by HCC cancer-derived exosomes in HCC remain largely unclear. Exosomes of HepG2 cells under heat shock, TGF-β1, doxorubicin, acid and hypoxia/reoxygenation (H/R) conditions, and exosomes were successfully identified by transmission electron microscopy and Western blot analysis. The identified exosomes were then applied to evaluate the miRNA expression profiles by RNA sequencing. Mechanically, we discovered that doxorubicin was upregulated, TGF-β1 downregulated the expressions of Vps4A, Rab27A, Alix, and Hrs in HepG2 cells and exosomes, and Vps4A and Rab27A, as target genes for miR-4454, could also be downregulated by miR-4454. Functionally, we revealed that miR-4454 inhibitor and miR-4454 inhibitor-mediated exosomes could markedly suppress proliferation, migration, invasion, and vascularization and accelerate cycle arrest, apoptosis, and ROS of HepG2 cells. This study provided many potential HCC cancer-derived exosome-mediated miRNAs in HCC under 5 different stimulus conditions. Meanwhile, we certified that miR-4454 in exosomes could provide a novel and effective mechanism for HCC function.

Aorto-oesophageal fistula is a rare but fatal disease. Open surgical repair or endotube repair of aorta and oesophagus save patients from circulatory deterioration, major haematemesis and severe infection. Here we present a rare case of an aorto-oesophageal fistula in the right hemi-arch caused by a fish bone treated with an alternative surgical strategy. Total aortic arch repair using the frozen elephant trunk procedure combined with oesophageal repair were performed. No aortic fistula, oesophageal fistula or artificial graft infection occurred in the follow-up.

Emerging evidence has shown that exosome microRNAs (miRNAs) regulate the development of hepatocellular carcinoma (HCC). Here, the influences of miR-4800-3p on the progression of HCC were explored.The expression of miR-4800-3p in the exosome derived by transforming growth factor beta 1 (TGF-β1)-treated HCC cells and the serum exosome isolated from HCC patients were identified by real-time PCR. The effects of TGF-β1 and the influences of Huh7-secreted exosomes and the effects of miR-4800-3p combined with/without STK25 on cell functions were explored using the EdU assay cloning experiments, wound healing assay, and Transwell assay. The corresponding molecular mechanisms were further detected using Western blot and real-time PCR assays. The combination of miR-4800-3p and STK25 was verified by the dual-luciferase and RNA pulldown assays. The influences of miR-4800-3p on the growth and epithelial-mesenchymal transformation (EMT) of implanted tumors were testedThe miR-4800-3p expression was highly expressed in both exosomes derived by TGF-β1-treated HCC cells and the serum exosomes of HCC patients. In the cases of treatment with both Huh7-derived exosomes, the level of miR-4800-3p expression was highest, and the treatment of TGF-β1 could greatly promote the proliferation, stemness, migration, and invasion of HCC cellsExosomal miR-4800-3p could accelerate HCC development by regulating the Hippo signal by targeting STK25, which could be used as a new therapeutic target for HCC treatment.

BACKGROUND: Mechanical ventilation (MV) is an important lifesaving method in intensive care unit (ICU). Prolonged MV is associated with ventilator associated pneumonia (VAP) and other complications. However, premature weaning from MV may lead to higher risk of reintubation or mortality. Therefore, timely and safe weaning from MV is important. In addition, identification of the right patient and performing a suitable weaning process is necessary. Although several guidelines about weaning have been reported, compliance with these guidelines is unknown. Therefore, the aim of this study is to explore the variation of weaning in China, associations between initial MV reason and clinical outcomes, and factors associated with weaning strategies using a multicenter cohort. METHODS: This multicenter retrospective cohort study will be conducted at 17 adult ICUs in China, that included patients who were admitted in this 17 ICUs between October 2020 and February 2021. Patients under 18 years of age and patients without the possibility for weaning will be excluded. The questionnaire information will be registered by a specific clinician in each center who has been evaluated and qualified to carry out the study. DISCUSSION: In a previous observational study of weaning in 17 ICUs in China, weaning practices varies nationally. Therefore, a multicenter retrospective cohort study is necessary to be conducted to explore the present weaning methods used in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) (No. ChiCTR2100044634).

In this study, X-ray micro computed tomography (X-ray microCT) was utilized to study the qualities of GH3536 part specimens produced by additive manufacturing. The results showed that all the specimens had high density of inclusions. Based on the location of the inclusion within the specimen, one of the inclusion was exposed to the surface by grind. The scanning electron microscope (SEM) showed that the mostly spherical particles were embedded in the specimen, and the energy dispersive spectrum (EDS) revealed that the inclusion was tungsten particle. In order to find the root source of the inclusion, the powder specimen used for printing the part specimen was characterized, and it was found that the trace amount of tungsten inclusion found in GH3536 powder specimen can only be certified by X-ray microCT, while other commonly used method for powder characterization failed to detect the contaminant.

Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-oxidant effects. Oxidative stress plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation during endotoxemia. Whether and how DHQ regulates inflammatory responses in endotoxemia remains elusive. Here we show DHQ pretreatment effectively reduced the Ten-day mortality in bacterial endotoxin lipopolyssacharide (LPS)-challenged mice, suppressing LPS-induced inflammatory responses reflected by impaired production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the serum of mice. In Raw 264.7 cells, DHQ pretreatment significantly inhibited the transcriptional upregulation of TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10) and toll-like receptor 4 (TLR-4) after LPS stimulation. Additionally, knockdown of heme oxygenase-1 (HO-1), one of the most important DHQ induced antioxidant genes, cancelled the inhibition of DHQ treatment on LPS induced TNF-α, IFN-γ production. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and AMP-activated protein kinase (AMPK) phosphorylation were both enhanced by DHQ in Raw 264.7 cells, indicating a DHQ induced AMPK/Nrf2/HO-1 signal axis. In conclusion, DHQ pretreatment could protect mice against the inflammation and mortality associated with endotoxemia.

Dexmedetomidine is widely used for sedating patients in operation rooms or intensive care units. Its protective functions against oxidative stress, inflammation reaction, and apoptosis have been widely reported. In present study, we explored the effects of dexmedetomidine on monocyte-endothelial adherence. We built lipopolysaccharide- (LPS-) induced monocyte-endothelial adherence models with U937 monocytes and human umbilical vein endothelial cells (HUVECs) and observed the effects of dexmedetomidine on U937-HUVEC adhesion. Specific siRNA was designed to knock-down Connexin43 (Cx43) expression in U937 monocytes. Gö6976, GSK2795039, and NAC were used to inhibit PKC-α, NOX2, and ROS, respectively. Then, we detected whether dexmedetomidine could downregulate Cx43 expression and its downstream PKC-α/NOX2/ROS signaling pathway activation and ultimately result in the decrease of U937-HUVEC adhesion. The results showed that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), could inhibit adhesion of molecule expression (VLA-4 and LFA-1) and U937-HUVEC adhesion. Simultaneously, it also attenuated Cx43 expression in U937 monocytes. With the downregulation of Cx43 expression, the activity of PKC-α and its related NOX2/ROS signaling pathway were reduced. Inhibiting PKC-α/NOX2/ROS signaling pathway with Gö6976, GSK2795039, and NAC, respectively, VLA-4, LFA-1 expression, and U937-HUVEC adhesion were all decreased. In summary, we concluded that dexmedetomidine, at its clinically relevant concentrations (0.1 nM and 1 nM), decreased Cx43 expression in U937 monocytes and PKC-α associated with carboxyl-terminal domain of Cx43 protein. With the downregulation of PKC-α, the NOX2/ROS signaling pathway was inhibited, resulting in the decrease of VLA-4 and LFA-1 expression. Ultimately, U937-HUVEC adhesion was reduced.

In this study, the laser repairing (LR) method is applied to 12Cr12Mo stainless steel, and the corresponding microstructural evolution, texture characteristic, and hardness variation are investigated. A 50/50 uniaxial tensile-test is conducted, and the mechanical failure mechanism is investigated using scanning electron microscope and transmission electron microscopy. The results show that the microstructure consists mainly of martensite and tiny M23C6 carbide particles in the deposited zone (DZ), while the substrate contains tempered martensite and coarse M23C6 carbide. The high laser-power generates a cubic texture in the DZ, while the substrate maintains a texture-free matrix. From the substrate to the DZ, the hardness increases sharply at the fusion line and then decreases gradually along the building direction. The tensile-test result indicates that the overall mechanical properties of LRed 12Cr12Mo stainless steel are comparable to wrought parts. Moreover, the microvoid-coalescence fracture indicates good plasticity of the LRed samples. Using this approach, we successfully repaired a 17th-stage stator cascade of a gas turbine, which indicates that LR can be used for the type of steel investigated in this study.

To determine whether erythromycin is non-inferior to metoclopramide in facilitating post-pyloric placement of self-propelled spiral nasoenteric tubes (NETs) in critically ill patients. A prospective, multicenter, open-label, parallel, and non-inferiority randomized controlled trial was conducted comparing erythromycin with metoclopramide in facilitating post-pyloric placement of spiral NETs in critically ill patients admitted to intensive care units (ICUs) of eight tertiary hospitals in China. The primary outcome was procedure success defined as post-pyloric placement (spiral NETs reached the first portion of the duodenum or beyond confirmed by abdominal radiography 24 h after tube insertion). A total of 5688 patients were admitted to the ICUs. Of these, in 355 patients there was a plan to insert a nasoenteric feeding tube, of whom 332 were randomized, with 167 patients assigned to the erythromycin group and 165 patients assigned to the metoclopramide group. The success rate of post-pyloric placement was 57.5% (96/167) in the erythromycin group, as compared with 50.3% (83/165) in the metoclopramide group (a difference of 7.2%, 95% CI − 3.5% to 17.9%), in the intention-to-treat analysis, not including the prespecified margin of − 10% for non-inferiority. The success rates of post-D1 (reaching the second portion of the duodenum or beyond), post-D2 (reaching the third portion of the duodenum or beyond), post-D3 (reaching the fourth portion of the duodenum or beyond), and proximal jejunum placement and the incidence of any adverse events were not significantly different between the groups. Erythromycin is non-inferior to metoclopramide in facilitating post-pyloric placement of spiral NETs in critically ill patients. The success rates of post-D1, post-D2, post-D3, and proximal jejunum placement were not significantly different.

Epileptic seizures are the main clinical manifestation of low-grade astrocytoma. Voltage-gated sodium channels (VGSCs) play a crucial role in epilepsy. Until now, the role of VGSCs and the relationships between calmodulin (CaM)/CaM-dependent protein kinase II (CaMKII) and VGSCs in low-grade astrocytoma have not been demonstrated. In our study, the protein expression of NaV1.3, NaV1.6 and CaM was significantly increased in the tumor compared to control tissue, while the level of p-CaMKII/CaMKII was significantly decreased in the tumor group as determined by Western Blotting and immunohistochemistry. Furthermore, double-labeling immunofluorescence results showed that NaV1.3/NaV1.6 and CaM co-localization was significantly increased in the tumor group compared to control tissue. This study represents the first evidence of the abnormal changes in VGSCs subtypes and CaM/CaMKII pathway in human brain low-grade astrocytoma, providing new potential targets for molecular therapies of this disease.

The selective laser-melted (SLM) Inconel 718(IN718) specimens were heat-treated with different solution regimes after the hot isostatic pressing (HIP). The results show that δ phase forms at grain boundary and presents needle-like pattern, and the size and volume fraction of δ phase increase with the increase of holding time and the decrease of solution temperature. The equilibrium volume fraction of needle-like δ phase in SLM-built IN718 is higher than that of short rod-like δ phase in forged-IN718 under the same heat treatment. The SLM-built IN718 specimen without δ phase at grain boundary has the best stress rupture properties, while the specimen with the largest volume fraction of δ phase at grain boundary exhibits the worst stress rupture properties. This is attributed to that the needle-like δ phase at grain boundary promotes the nucleation of void-formed cracks and accelerates the deformation damage. The analysis of the responses to the coordinated deformation capacity of grain orientation and grain size indicates that there exist the heterogeneous deformation and stress/strain concentration at grain boundary. The existence of δ phase influences the coordinated deformation capacity and promotes the stress/strain concentration around grain boundary region. Especially, the needle-like δ phase at grain boundary leads to the more detrimental effect on the rupture life and ductility of SLM-built IN718 alloy on compared with the forged-IN718 alloy.

A two-dimensional finite element model is used to explore the fracture parameter in the tip region of stress corrosion crack (SCC) of AA6082 alloy. Based on the ABAQUS code, we investigate the effect of oxide film’s yield stress on the Mises stress and equivalent plastic strain (PEEQ) in the crack tip. The results show that as the yield strength of oxide film increases, the Mises stress and PEEQ of base alloy in crack tip area both decrease, and the stress of oxide film in crack tip also reduces, but the strain increases. This is because the oxide film bears more load, so the load on the base alloy of the crack tip becomes smaller, resulting in a reduction in the stress and strain on the base.

// Xinbing Sui 1, 2, * , Liming Lei 5, * , Liuxi Chen 6, * , Tian Xie 1, 2 and Xue Li 3 , 4 1 Department of Medical Oncology Holistic Integrative Oncology Institutes and Holistic Integrative Pharmacy Institutes, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, China 2 Department of Medical Oncology Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China 3 Departments of Urology and Pathology, Boston Children's Hospital, Boston, MA, USA 4 Department of Surgery, Harvard Medical School, Boston, MA, USA 5 Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou, China 6 Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China * These authors have contributed equally to this work Correspondence to: Tian Xie, email: hzzju@aliyun.com Xue Li, email: sean.li@childrens.harvard.edu Keywords: inflammation, tumorigenesis, development, bladder cancer Received: April 25, 2017 Accepted: September 08, 2017 Published: October 06, 2017 ABSTRACT Accumulating evidence suggests the idea that chronic inflammation may play a critical role in various malignancies including bladder cancer and long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is significantly effective in reducing certain cancer incidence and mortality. However, the molecular mechanisms leading to malignant transformation and the progression of bladder cancer in a chronically inflammatory environment remain largely unknown. In this review, we will describe the role of inflammation in the formation and development of bladder cancer and summarize the possible molecular mechanisms by which chronic inflammation regulates cell immune response, proliferation and metastasis. Understanding the novel function orchestrating inflammation and bladder cancer will hopefully provide us insights into their future clinical significance in preventing bladder carcinogenesis and progression.

Complete transposition of the great arteries (TGA) is the most frequent cyanotic heart defect diagnosed in neonates. However, the exact etiology of TGA is unknown. The aim of the present study was to assess the association of TGA pathogenesis with single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs)-1 and 3a- in Chinese children. We genotyped 5 SNPs (rs16999593, rs16999358, and rs2228611 in DNMT1; and rs2276599 and rs2276598 in DNMT3A) in 206 patients with complete TGA and 252 healthy children. Statistical analysis was performed to explore the association of the 5 SNPs with complete TGA susceptibility. Compared with the T/T and C/C genotypes, the heterozygous genotype C/T of rs16999593 correlated with a decreased risk for complete TGA under codominant (OR=0.46; 95% CI=0.29-0.72), dominant (OR=0.58; 95% CI=0.38-0.88), and overdominant (OR=0.44; 95% CI=0.28-0.68) models. In contrast, the genotype C/C of rs16999593 correlated with a higher risk for TGA under a recessive model (OR=3.15; 95% CI=1.14-8.68) compared with the T/T and C/T genotypes. Furthermore, the TGC, TGT, CGC, and CGT haplotypes of DNMT1 did not differ significantly between the two groups, whereas the frequency of the TAC haplotype was lower in the case group (OR

The microstructures and mechanical properties of Inconel 718 (IN718) alloy fabricated by selective laser melting (SLM) are evaluated in as-built, direct aging (DA), and homogenization + aging (HA) conditions on considering the effect of applied loading direction. The results show that the microstructure of as-built and DA specimens consist of the intracrystalline fine degenerated dendritic structures (0.6–1 μm in spacing) with a high density of dislocations (1013–1014 m−2). Fine dendritic structures disappear after HA treatment, and the average geometrically necessary dislocation (GND) density decreases to 1012 m−2. A quantitative analysis of strengthening mechanisms is established by taking into consideration the grain boundary, solid solution, precipitation and dislocation strengthening. For the as-built and DA specimens, the contribution to the yield strength by dislocation strengthening is ~85 MPa in vertical deposition and ~170 MPa in horizontal deposition, respectively, and the Laves phases provide approximately 100–110 MPa. The contribution of precipitation strengthening to the strength increment in the DA and HA specimens is 590–600 and 830–850 MPa, respectively. The precipitation strengthening is mainly contributed by shearing mechanisms among which coherency strengthening plays dominant effect rather than order strengthening. For as-built, DA, and HA regimes, the specimens always exhibit higher strength along the horizontal direction than that along the vertical direction. The anisotropy of yield strength in the as-built and DA specimens is mainly attributed to the difference in dislocation density and effective grain size, and the anisotropy of yield strength in the HA specimens is mainly caused by the difference in effective grain size and Taylor factor.

Four types of scanning strategies, i.e. 0°, 90°, 67° hatch angle and a chessboard with 67° hatch angle strategy (CB + 67°), were adopted to study the microstructure and mechanical anisotropy of Hastelloy X superalloy produced by Laser Powder Bed Fusion (LPBF). The tensile tests show that all the horizontal specimens perform higher yield strength and lower elongation than the vertical counterparts, indicating that tensile anisotropy appears in as-fabricated Hastelloy X. According to the electron backscatter diffraction (EBSD) analysis, there are more grain boundaries and geometrically necessary dislocations (GNDs) hindering dislocation motion when tested along the horizontal direction. Therefore, various degrees of grain boundary strengthening and dislocation strengthening effect are responsible for yield strength anisotropy. Because highly ordered microcracks along the building direction are much more detrimental to horizontal plasticity, the elongation anisotropy can be ascribed to different crack sensitivity along with two tensile directions. Besides, specimens produced using diverse scanning strategies exhibit varying extent of anisotropy, as well as yield strength and elongation. The yield strength of the 0° and CB + 67° specimen is lower than the 90° and 67° one regardless of the tensile direction. Among all horizontal specimens, the 0° specimen shows the lowest elongation and the CB + 67° one performs the highest.

Optimizing the microstructure to enhance the high temperature stress rupture properties of Inconel 718 (IN718) alloy fabricated via selective laser melting (SLM) is an urgent issue. In this study, SLM-built IN718 specimens were heat-treated with hot isostatic pressing, solution and aging treatment, and their microstructure and high temperature stress rupture properties were investigated, focusing on the influence of grain structure and precipitates. The results show that the coarsening of γ″ precipitate with the aging time at 720 °C follows the Lifshitz-Slyozov-Wagner theory. As the γ″ precipitate size increases, the rupture life gradually increases, area reduction gradually decreases, and the uniform elongation first increases and then decreases. Furthermore, a wide distribution of grain size results in the fine grains regions with much higher geometrically necessary dislocations compared with coarse grain regions during deformation. Hence, the micro-cracks preferentially initiate and propagate along fine-grain boundary. The main deformation mechanisms of specimens aged at 720 °C for 4 h (HSA4) and 8 h (HSA8) with the small γ″ precipitate are dislocation slipping and micro-twinning mode during stress rupture test, while those of specimen aged at 720 °C for 32 h (HSA32) with relatively large γ″ precipitate are dislocation slipping and isolated faulting mode. The HSA8 specimen with the best comprehensive stress rupture properties has the average life of 130 h and uniform elongation of 7.5%, meeting the standard specification for wrought IN718. Finally, some potential strategies for further improving the stress rupture properties of SLM-built IN718 were proposed by comparing to forged-IN718.

Superior superplasticity of 682% was newly-achieved in an as-rolled 2.5 vol. % TiB reinforced near-α Ti matrix composite with 0001 11 2 ¯ 0 > and { 11 2 ¯ 0 } 10 1 ¯ 0 > texture components, which was attributed to dynamic globularization/recrystallization. Microstructure characterization shows that the dominant mechanism of dynamic globularization was associated with the following progress. First, the low-angle grain boundaries (LAGBs) divided the elongated α grain into two equiaxed sub-grains. Then, the LAGBs gradually evolved to HAGBs impelled by grain boundary sliding. Finally, switching and rotation of these neighboring grains occurred, which accelerated the formation of equiaxed grain. In addition, it was found that TiB can not only induce dynamic globularization by hindering dislocation gliding and promoting the formation of sub-grain boundaries, but also induce discontinuous dynamic recrystallization by the particle stimulated nucleation mechanisms. The most interesting, nano-scale (Zr,Ti)5Si3 particles with special arrangement induced dynamic globularization/recrystallization were discovered.

In this paper, the temperature sensitivity of mechanical properties and microstructure of the additive manufactured Ti-6Al-4V alloy via selective laser melting was investigated in the deformation temperature range between room temperature (RT) and 550 °C. Mechanical properties and microstructure were characterized by the means of tensile testing, optical microscope, scanning electron microscope and transmission electron microscope. The results show that the ultimate tensile strength (UTS) of the experimental Ti-6Al-4V alloy exhibits two-stage temperature sensitivity, which is reflected in the fact that the temperature sensitivity of UTS below 500 °C is conventional, whereas, the UTS decreases drastically from 834 MPa to 562 MPa as the temperature increases from 500 °C to 550 °C. Compared with the Ti-6Al-4V alloys prepared by conventional processing methods and other additive manufacturing methods, this experimental Ti-6Al-4V alloy exhibits a competitive strength below 500 °C and possesses excellent comprehensive mechanical properties at RT. The analysis shows that the microstructure is composed of α′ martensite with plenty of twinning structures when the as-built samples are deformed below 500 °C. However, above 500 °C, martensite gradually transformed into equilibrium α phase, the microstructure changed from acicular to lamellar, and β and α2 (Ti3Al) appear due to the elemental distribution homogenization and martensite decomposition, which account for the dramatic decrease of the tensile strength of the experimental Ti-6Al-4V alloy above 500 °C.

Tensile properties of GH4169 fabricated by selective laser melting under stripe and chessboard scanning strategies were investigated. The results show that the GH4169 specimens fabricated by the chessboard scanning strategy have higher tensile strengths and more evident tensile anisotropy than that of the specimens fabricated by the stripe scanning strategy. The strain hardening ability of the chessboard specimens superior to that of the stripe specimen is mainly attributed to the difference in residual stress magnitude arising from different scanning strategies and the unique processing-induced heterogeneous grain structure in the chessboard specimens.

BACKGROUND: Progressive dilatation is responsible for significant mortality and morbidity in patients with thoracic aortic aneurysms (TAAs). Studies have shown that the development and progression of TAAs are closely related to immune regulatory pathways and genes. Therefore, it is important to understand the immune regulatory mechanisms and biomarkers of TAA dilatation. METHODS: Systematic bioinformatics analysis was applied, including linear models for microarray data (LIMMA) differential expression analyses, principal component analysis (PCA), immunocyte identification, and genetic function enrichment analysis. RESULTS: Our results showed that both aortic intima-media (AMed) and outer aortic adventitia (AAdv) tissues were closely associated with T cell activation during the process of tricuspid aortic valve (TAV)-associated TAA dilation. Additionally, the degree of infiltration of resting memory CD4+ T cells was linked to both AAdv and AMed vascular dilation. The core regulators PPTRC, IL1B, CD4, CD3G, and IL2RA were also identified and are closely related to resting memory CD4+ T cell infiltration in this pathological process. CONCLUSIONS: The candidate genes PPTRC, IL1B, CD4, CD3G, and IL2RA were involved in the regulation of resting memory CD4 T cell tissue infiltration, which is closely related to the process of AAdv and AMed vascular dilation in TAV patients.