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Ultrasonic spot welding has recently garnered significant attention as a method for joining metal sheets. Numerical simulation plays an important role in understanding the principles of this process and improving the quality of the ultrasonic spot welded joint. This paper aims to summarises the critical parameters in the finite element model of ultrasonic spot welding, including the friction coefficient, thermal field, acoustic and thermal softening, meshing and boundary conditions. Additionally, it provides a detailed review of the research status related to the simulation results, such as welding interface temperature, stress distribution, plastic strain, intermetallic compounds, macrostructure, dynamic recrystallisation and interfacial diffusion. Furthermore, this paper discusses the remaining challenges and the development trend of the numerical simulation.

Ultrasonic spot welding has recently garnered significant attention as a method for joining metal sheets. Numerical simulation plays an important role in understanding the principles of this process and improving the quality of the ultrasonic spot welded joint. This paper aims to summarises the critical parameters in the finite element model of ultrasonic spot welding, including the friction coefficient, thermal field, acoustic and thermal softening, meshing and boundary conditions. Additionally, it provides a detailed review of the research status related to the simulation results, such as welding interface temperature, stress distribution, plastic strain, intermetallic compounds, macrostructure, dynamic recrystallisation and interfacial diffusion. Furthermore, this paper discusses the remaining challenges and the development trend of the numerical simulation.

ABSTRACTWith increasing clamping pressure, the bond density increases, the effective thickness decreases, and the plastic deformation at the Cu side near the welding interface regions below the sonotrode tip peak and valley increases; the maximum lap shear tensile load is obtained at the clamping pressure of 0.5 MPa. In the case of the Cu/Ni joint prepared at the clamping pressure of 0.5 MPa, evident mutual diffusion and nanoscale wave-like pattern appear in the Cu/Ni interfacial area, bonding between Cu and Ni sheets is formed by the interdiffusion of the parent elements. Plastic strain distribution and temperature on weld cross-section were simulated employing finite element analysis.

With increasing clamping pressure, the bond density increases, the effective thickness decreases, and the plastic deformation at the Cu side near the welding interface regions below the sonotrode tip peak and valley increases; the maximum lap shear tensile load is obtained at the clamping pressure of 0.5?MPa. In the case of the Cu/Ni joint prepared at the clamping pressure of 0.5?MPa, evident mutual diffusion and nanoscale wave-like pattern appear in the Cu/Ni interfacial area, bonding between Cu and Ni sheets is formed by the interdiffusion of the parent elements. Plastic strain distribution and temperature on weld cross-section were simulated employing finite element analysis.

As a solid state joining process, ultrasonic spot welding has been proven to be a promising technique for joining copper alloys. However, challenges still remain in employing ultrasonic spot welding to join copper alloys. This article comprehensively reviews the current state of ultrasonic spot welding of copper alloys with a number of critical issues including materials flow, plastic deformation, temperature distribution, vibration, relative motion, vertical displacement, interface friction coefficient, online monitoring technique, coupled with the macrostructure and microstructure, the mechanical properties and electrical conductivity. In addition, the future trends in this field are provided.

As a solid state joining process, ultrasonic spot welding has been proven to be a promising technique for joining copper alloys. However, challenges still remain in employing ultrasonic spot welding to join copper alloys. This article comprehensively reviews the current state of ultrasonic spot welding of copper alloys with a number of critical issues including materials flow, plastic deformation, temperature distribution, vibration, relative motion, vertical displacement, interface friction coefficient, online monitoring technique, coupled with the macrostructure and microstructure, the mechanical properties and electrical conductivity. In addition, the future trends in this field are provided.

Correlating electromechanical and dielectric properties with nanometre-scale order is the defining challenge for the development of piezoelectric oxides. Current lead (Pb)-based relaxor ferroelectrics can serve as model systems with which to unravel these correlations, but the nature of the local order and its relation to material properties remains controversial. Here we employ recent advances in diffuse scattering instrumentation to investigate crystals that span the phase diagram of PbMg1/3Nb2/3O3-xPbTiO3(PMN-xPT) and identify four forms of local order. From the compositional dependence, we resolve the coupling of each form to the dielectric and electromechanical properties observed. We show that relaxor behaviour does not correlate simply with ferroic diffuse scattering; instead, it results from a competition between local antiferroelectric correlations, seeded by chemical short-range order, and local ferroic order. The ferroic diffuse scattering is strongest where piezoelectricity is maximal and displays previously unrecognized modulations caused by anion displacements. Our observations provide new guidelines for evaluating displacive models and hence the piezoelectric properties of environmentally friendly next-generation materials. How local order affects the excellent piezoelectric properties of Pb-based relaxor ferroelectrics is unclear, but neutron diffuse scattering shows that non-relaxor distortions are implicated, indicating the important role of oxygen atoms.

To clarify the interfacial reaction mechanism between multi-component oxides and solid Mn- and Si-deoxidised alloys during heat treatment, five diffusion couples with different compositions of Fe–Mn–Si alloy and CaO–SiO2–Al2O3–MgO–MnO oxide were produced using a confocal scanning laser microscope. The changes in the chemical compositions of the oxide and alloy by heat treatment at 1273 and 1473 K were investigated. The mechanisms of the ‘solid–solid’ and ‘solid–liquid’ interfacial reactions and the diffusion of elements between the alloy and oxide were revealed thermodynamically and are discussed. The results show that counter-diffusion occurring between Mn and Si in the alloy and oxide was the main reaction in the diffusion couples. The MnO content of the oxide and the Si content of the alloy are the driving forces of the interfacial reactions.

To clarify the interfacial reaction mechanism between multi-component oxides and solid Mn- and Si-deoxidised alloys during heat treatment, five diffusion couples with different compositions of Fe–Mn–Si alloy and CaO–SiO2–Al2O3–MgO–MnO oxide were produced using a confocal scanning laser microscope. The changes in the chemical compositions of the oxide and alloy by heat treatment at 1273 and 1473 K were investigated. The mechanisms of the ‘solid–solid’ and ‘solid–liquid’ interfacial reactions and the diffusion of elements between the alloy and oxide were revealed thermodynamically and are discussed. The results show that counter-diffusion occurring between Mn and Si in the alloy and oxide was the main reaction in the diffusion couples. The MnO content of the oxide and the Si content of the alloy are the driving forces of the interfacial reactions.

Imetelstat (GRN163L) is a specific telomerase inhibitor that has demonstrated clinical activity in patients with myeloproliferative neoplasms (MPN) and in patients with solid tumors. The antitumor effects were associated with the development of thrombocytopenia, one of the common side effects observed in patients treated with imetelstat. The events underlying these adverse effects are not apparent. In this report, we investigated the potential mechanisms that account for imetelstat’s beneficial effects in MPN patients and the manner by which imetelstat treatment leads to a reduction in platelet numbers. Using a well-established system of ex vivomegakaryopoiesis, we demonstrated that imetelestat treatment affects normal megakaryocyte (MK) development by exclusively delaying maturation of MK precursor cells. By contrast, additional stages along MPN MK development were affected by imetelstat resulting in reduced numbers of assayable colony-forming unit MK and impaired MK maturation. In addition, treatment with imetelstat inhibited the secretion of fibrogenic growth factors by malignant but not by normal MK. Our results indicate that the delay observed in normal MK maturation may account for imetelstat-induced thrombocytopenia, while the more global effects of imetelstat on several stages along the hierarchy of MPN megakaryopoiesis may be responsible for the favorable clinical outcomes reported in MPN patients.

W–Y–N coatings with yttrium content ranging from 0 to 8.2 at.-% were deposited by reactive magnetron sputtering technique. The influence of yttrium content on the structure, oxidation resistance and mechanical properties was investigated. The results show that yttrium atoms substitute tungsten atoms forming the solid solution W–Y–N coatings. All the coatings exhibit a single-phase face-centered cubic structure and the preferred orientation changes from (200) to (111) with yttrium addition. The grain size of W–Y–N coatings decreases with the increase of yttrium content. The oxidation resistance temperature of W–Y–N coatings increases from 500°C at 0 at.-% Y to 730°C at 8.2 at.-% Y. All coatings are in compressive stress state. The hardness, elastic modulus and compressive stress of W–Y–N coatings increase gradually from 28.0, 320 and 1.1 GPa at 0 at.-% Y to 36.0, 385 and 2.1 GPa at 8.2 at.% Y, respectively. The improvement of hardness was attributed to the effect of solid solution strengthening and the grain refinement. In addition, the addition of yttrium content into WN coating also improves its resistance against elastic strain and plastic deformation to failure.

We address propagation of light in nonlinear twisted multicore fibers with alternating amplifying and absorbing cores that are arranged into the parity-time (PT)-symmetric structure. In this structure, the coupling strength between neighboring cores and global energy transport can be controlled not only by the nonlinearity, but also by gain and losses and by the fiber twisting rate. The threshold level of gain/losses, at which PT-symmetry breaking occurs, is a non-monotonic function of the fiber twisting rate, and it can be reduced nearly to zero or, instead, notably increased just by changing this rate. Nonlinearity usually leads to the monotonic reduction of the symmetry-breaking threshold in such fibers.

W–Y–N coatings with yttrium content ranging from 0 to 8.2 at.-% were deposited by reactive magnetron sputtering technique. The influence of yttrium content on the structure, oxidation resistance and mechanical properties was investigated. The results show that yttrium atoms substitute tungsten atoms forming the solid solution W–Y–N coatings. All the coatings exhibit a single-phase face-centered cubic structure and the preferred orientation changes from (200) to (111) with yttrium addition. The grain size of W–Y–N coatings decreases with the increase of yttrium content. The oxidation resistance temperature of W–Y–N coatings increases from 500°C at 0 at.-% Y to 730°C at 8.2 at.-% Y. All coatings are in compressive stress state. The hardness, elastic modulus and compressive stress of W–Y–N coatings increase gradually from 28.0, 320 and 1.1 GPa at 0 at.-% Y to 36.0, 385 and 2.1 GPa at 8.2 at.% Y, respectively. The improvement of hardness was attributed to the effect of solid solution strengthening and the grain refinement. In addition, the addition of yttrium content into WN coating also improves its resistance against elastic strain and plastic deformation to failure.

Recently, two genome-wide association studies (GWASs) of schizophrenia (SCZ) in Han Chinese identified several susceptibility loci. Replication efforts aiming to validate the GWAS findings were made and focused on the top hits. We conducted a more extensive follow-up study in an independent sample of 1471 cases and 1528 matched controls to verify 26 genetic variants by including nine top single-nucleotide polymorphisms (SNPs) that reached genome-wide significance and 17 promising SNPs nominated in the initial discovery phase. rs8073471 in an intron of tubulin-folding cofactor D (TBCD) obtained nominal significance (P<0.01) in single SNP analysis. Logistic regression identified significant interaction between rs3744165 (5’-untranslated region variant of exon 2 of zinc finger protein 750 (ZNF750), and in an intron of TBCD) and rs8073471 (Deviance test P-value=2.77 × 10-34). Both SNPs are located at 17q25, an interesting region that has been implicated in SCZ. By using the Genotype-Tissue Expression (GTEx) data set, we implemented an expression quantitative trait loci epistasis analysis to explore the association between the genotype combinations of the two SNPs and gene expression levels in 13 areas of human central nervous system. We observed that rs3744165 × rs8073471 interaction modulated the expression profile of TEAD3 (P=1.87 × 10-8), SH3TC2 (P=2.00 × 10-8), KCNK9 (P=5.20 × 10-7) and PPDPF (P=1.13 × 10-6) in postmortem cortex tissue; EFNA1 (P=7.26 × 10-9), RNU4ATAC (P=2.32 × 10-8) and NUPL2 (P=6.79 × 10-8) in cerebellum tissue. To the best of our knowledge, our study is the first one that links TBCD and ZNF750 mutations to SCZ susceptibility and to the transcript levels in human brain tissues. Further efforts are needed to understand the role of those variants in the pathogenesis of SCZ.

Soluble antigen-based cancer vaccines have poor retention in tissues along with suboptimal antigen processing by dendritic cells. Multiple booster doses are often needed, leading to dose-limiting systemic toxicity. A versatile, immunomodulatory, self-assembly protein nanogel vaccine is reported that induces robust immune cell response at lower antigen doses than soluble antigens, an important step towards biomaterials-based safer immunotherapy approaches.

The WCN films with different C contents were deposited under different substrate bias by a sputtering system. The composition, structure and mechanical properties were characterised by X-ray photoelectron spectroscopy, X-ray diffraction, high resolution transmission electron microscopy, scanning electron microscopy, atomic force microscopy and nanoindentation. Results showed that the WCN films consisted of WCN, W2N, amorphous C and CNx phases. With the incorporation of C content, the growth pattern changed from continuous columnar to discontinuous columnar due to grain refinement. By applying substrate bias to the films, the growth pattern changed from discontinuous columnar to fine grained structure because the bias could enhance the mobility of impinging ions or atoms leading to film densification. As increasing the C content, the hardness first increased and then decreased due to the effect of solid solution strengthening and grain refinement. However, the substrate bias had little influence on the hardness because of the co-action of the dense structure and residual stress induced by bias.

The WCN films with different C contents were deposited under different substrate bias by a sputtering system. The composition, structure and mechanical properties were characterised by X-ray photoelectron spectroscopy, X-ray diffraction, high resolution transmission electron microscopy, scanning electron microscopy, atomic force microscopy and nanoindentation. Results showed that the WCN films consisted of WCN, W2N, amorphous C and CNx phases. With the incorporation of C content, the growth pattern changed from continuous columnar to discontinuous columnar due to grain refinement. By applying substrate bias to the films, the growth pattern changed from discontinuous columnar to fine grained structure because the bias could enhance the mobility of impinging ions or atoms leading to film densification. As increasing the C content, the hardness first increased and then decreased due to the effect of solid solution strengthening and grain refinement. However, the substrate bias had little influence on the hardness because of the co-action of the dense structure and residual stress induced by bias.

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvβ3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvβ3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.

The interaction of lymphoid tumor cells with components of the extracellular matrix via integrin αvβ3 allows tumor survival and growth. This integrin was demonstrated to be the membrane receptor for thyroid hormones (THs) in several tissues. We found that THs, acting as soluble integrin αvβ3 ligands, activated growth-related signaling pathways in T-cell lymphomas (TCLs). Specifically, TH-activated αvβ3 integrin signaling promoted TCL proliferation and angiogenesis, in part, via the upregulation of vascular endothelial growth factor (VEGF). Consequently, genetic or pharmacologic inhibition of integrin αvβ3 decreased VEGF production and induced TCL cell death in vitro and in human xenograft models. In sum, we show that integrin αvβ3 transduces prosurvival signals into TCL nuclei, suggesting a novel mechanism for the endocrine modulation of TCL pathophysiology. Targeting this mechanism could constitute an effective and potentially low-toxicity chemotherapy-free treatment of TCL patients.

To investigate the failure behaviour of thermal barrier coatings (TBCs) on diesel engine piston, YSZ TBCs were sprayed onto the 2A70 aluminium by atmospheric plasma spray. Finite element model was employed to estimate the temperature and stress distributions in TBCs on piston. Both the temperature and stress distributions were affected by the thickness of TBCs. The simulation results indicated that the bond coat/substrate interface was the weak region due to large interfacial stress. The thermal cycling performance of TBCs was evaluated by a burner rig test facility. The phase transformation of weak region during thermal cycling was analysed. After about 2000 cycles, the cracks along bond coat/substrate interface and the oxidation of the heat affected zone (HAZ) were visible. The TBCs spalled after about 4000 cycles, which is mainly attributed to the large thermal mismatch stress at bond coat/substrate interface and severe oxidation of HAZ.

YSZ thermal barrier coatings (TBCs) were sprayed onto 2A70 aluminium by atmospheric plasma spray. To relieve the thermal stress between TBCs and aluminium substrate, Ni–P and Ni–Cu–P electroless plating (EP) were deposited onto aluminium as interlayers. The fabricated Ni–P and Ni–Cu–P EPs exhibited amorphous structure and their crystallisation temperatures were 346·4 and 356·4°C, respectively. Deposition of the interlayers did not degrade much the bonding strength of the TBCs. The thermal shock lifetimes of TBCs with Ni–P interlayer and Ni–Cu–P interlayer were approximately 600 and 200 cycles, respectively, which were enhanced compared to that of the conventional TBCs (58 cycles). The failure of the TBCs with Ni–Cu–P interlayer was mainly caused by the thermal mismatch stress induced during the thermal shock, while the TBCs with Ni–P interlayer failed due to the interdiffusion between the interlayer and the substrate and the relatively poor ductility of the Ni–P interlayer.

Increases in ligand binding to integrins (activation) play critical roles in platelet and leukocyte function. Integrin activation requires talin and kindlin binding to integrin β cytoplasmic tails. Research has focused on the conserved GFFKR motif in integrin αIIbtails, integrin β cytoplasmic tails and the binding partners of β tails. However, the roles of αIIbtail distal of GFFKR motif are unexplored.

Self-assembled peptide materials have received considerable interest for a range of applications, including 3D cell culture, tissue engineering, and the delivery of cells and drugs. One challenge in applying such materials within these areas has been the extreme stability of β-sheet fibrillized peptides, which are resistant to proteolysis, degradation, and turnover in biological environments. In this study, we designed self-assembling depsipeptides containing ester bonds within the peptide backbone. Beta-sheet fibrillized nanofibers were formed in physiologic conditions, and two of these nanofiber-forming depsipeptides produced hydrogels that degraded controllably over the course of days-to-weeks viaester hydrolysis. With HPLC, TEM, and oscillating rheometry, we show that the rate of hydrolysis can be controlled in a straightforward manner by specifying the amino acid residues surrounding the ester bond. In 3D cell cultures, depsipeptide gels softened over the course of several days and permitted considerably more proliferation and spreading of C3H10T1/2 pluripotent stem cells than non-degradable analogs. This approach now provides a reliable and reproducible means to soften or clear β-sheet fibrillized peptide materials from biological environments.

Integrins are cell surface adhesion and signaling receptors important for cell adhesion, survival and migration. Integrins are known to be regulated by signals from inside the cells. Such inside‐out regulation modulates affinities of integrins for their extracellular matrix ligand and is critical for thrombosis, haemostasis and immune response. Talin and kindlin, two integrin binding proteins, have been shown to be important regulators of integrin function. In this review, we will focus on the molecular mechanism of integrin regulation that has emerged from recent structural, biochemical and genetic studies.

This prospective, randomized study compared the outcomes of hand-assisted laparoscopic surgery (HALS) with open surgery for the resection of rectal cancer. The main outcome measures were procedure time, blood loss, post-operative pain, time to oral intake, return of bowel function, length of hospital stay, morbidity and functional recovery. Patients in each group were similar with regard to general status, procedure types and the histopathological features of tumours. Procedure times were significantly longer with HALS versus open surgery. Analgesic requirements, surgical blood loss, time to first passing flatus, time to first oral fluids and postoperative hospital stay length were all significantly shorter in the HALS group. At a median follow-up of 16.3 months, local recurrence of tumour was not observed in either group. In this study, the HALS approach for curative resection of rectal cancer was safe and effective and may offer several potential advantages to patients in their post-operative recovery.

Background: The receptor for advanced glycation end products (RAGE) plays an important role in the pathogenesis of diabetic complications. The aim of this study is to investigate the association of the 1704 G/T and G82S polymorphisms in the RAGEgene with diabetic retinopathy (DR). Methods: The 1704G/T and G82S polymorphisms were genotyped in 340 Type 2 diabetes (T2DM) without DR subjects (DR-group); 166 T2DM with DR subjects (DR+ group), and 182 normal glucose tolerant subjects (NGT group). The genotypes were detected by the methods of ligase detection reaction coupled PCR. Results: There was no evident difference in the 1704G/T and G82S genotypic and allelic frequencies distribution between NGT and T2DM subjects. However, the frequences of G/A+AA genotypes (60.6%) and A allele (36.4%) of G82S were significantly higher in DR+ group than those (38.4%; 20.9%, respectively) in DR-group (p=0.01 and p=0.007, respectively). Furthermore, haplotype analysis revealed that the frequency of G-A haplotype containing 1704G and 82S allele in DR+ group was significantly higher than that in DR-group (33.5% vs19.6%, p=0.01). The multiple logistic regression analysis indicated that the G82S polymorphism [odds ratio (OR): 2.964, 95% confidence interval (CI): 1.013–5.46, p=0.029] and diabetes duration (OR: 1.013, 95% CI: 1.007–1.02, p<0.001) were independent risk factors for DR. Conclusions: G82S polymorphism in the RAGEgene is associated with DR and G-A haplotype containing 1704G and 82S allele might be a genetic marker of DR in Chinese T2DM patients.

Immune checkpoint inhibitor (ICI) therapy continues to revolutionize melanoma treatment, but only a subset of patients respond. Major efforts are underway to develop minimally invasive predictive assays of ICI response. Using single-cell transcriptomics, we discovered a unique CD8 T cell blood/tumor-shared subpopulation in melanoma patients with high levels of oxidative phosphorylation (OXPHOS), the ectonucleotidases CD38 and CD39, and both exhaustion and cytotoxicity markers. We called this population with high levels of OXPHOS “CD8+ TOXPHOS cells.” We validated that higher levels of OXPHOS in tumor- and peripheral blood–derived CD8+ TOXPHOS cells correlated with ICI resistance in melanoma patients. We then developed an ICI therapy response predictive model using a transcriptomic profile of CD8+ TOXPHOS cells. This model is capable of discerning responders from nonresponders using either tumor or peripheral blood CD8 T cells with high accuracy in multiple validation cohorts. In sum, CD8+ TOXPHOS cells represent a critical immune population to assess ICI response with the potential to be a new target to improve outcomes in melanoma patients.