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Cancer is the second leading cause of death worldwide. Traditional approaches, such as surgery, chemotherapy, and radiotherapy have been the main cancer therapeutic modalities in recent years. Cancer immunotherapy is a novel therapeutic modality that potentiates the immune responses of patients against malignancy. Immune checkpoint proteins expressed on T cells or tumor cells serve as a target for inhibiting T cell overactivation, maintaining the balance between self-reactivity and autoimmunity. Tumors essentially hijack the immune checkpoint pathway in order to survive and spread. Immune checkpoint inhibitors (ICIs) are being developed as a result to reactivate the anti-tumor immune response. Recent advances in nanotechnology have contributed to the development of successful, safe, and efficient anticancer drug systems based on nanoparticles. Nanoparticle-based cancer immunotherapy overcomes numerous challenges and offers novel strategies for improving conventional immunotherapies. The fundamental and physiochemical properties of nanoparticles depend on various cancer therapeutic strategies, such as chemotherapeutics, nucleic acid-based treatments, photothermal therapy, and photodynamic agents. The review discusses the use of nanoparticles as carriers for delivering immune checkpoint inhibitors and their efficacy in cancer combination therapy.

Fucoidan is a sulfated polysaccharide, derived from various marine brown seaweeds, that has immunomodulatory effects. In this study, we analyzed the effects of five different fucoidans, which were extracted from Ascophyllum nodosum, Undaria pinnatifida, Macrocystis pyrifera, Fucus vesiculosus, and Ecklonia cava, on natural killer (NK) cell activation in mice. Among these, E. cava fucoidan (ECF) promoted an increase in the number of NK cells in the spleen and had the strongest effect on the activation of NK cells. Additionally, we observed that DC stimulation was required for NK cell activation and that ECF had the most potent effect on splenic dendritic cells (DC). Finally, ECF treatment effectively prevented infiltration of CT-26 carcinoma cells in the lungs of BALB/c mice in an NK cell dependent manner. Collectively, these results suggest that ECF could be a suitable candidate for enhancing NK cell-mediated anti-cancer immunity.

Astragalus membranaceus (A. membranaceus) is commonly used in various herbal formulations to treat several human and animal diseases. Polysaccharides, which are the major bioactive components in the A. membranaceus, exhibit various bioactive properties. However, the ability of A. membranaceus polysaccharides (APS) to activate the mucosal immune response has not been examined. We examined the effect of intranasal administration of APS on mucosal immune cell activation and the growth-inhibitory activity against pulmonary metastatic melanoma in mice by combination treatment with immune checkpoint blockade. The intranasal treatment of APS increased the number of lineage-CD11c+ dendritic cell (DCs) in the mesenteric lymph nodes (mLN) through the upregulation of CC-chemokine receptor 7 expression. Moreover, intranasal treatment of APS activated DCs, which further stimulated natural killer (NK) and T cells in the mLN. The APS/anti-PD-L1 antibody combination inhibited the pulmonary infiltration of B16 melanoma cells. The depletion of NK cells and CD8 T cells in mice mitigated the anti-cancer effect of this combination, thereby highlighting the critical role of NK cells and CD8 T cells in mediating anti-cancer immunity. These findings demonstrated that APS could be used as a topical mucosal adjuvant to enhance the immune check point inhibitor anti-cancer effect.

Brown seaweed is an important source of fucoidan, which displays immunomodulatory effects by activating various immune cells. However, these effects of fucoidans from various sources of brown seaweed have not yet been explored in human blood dendritic cells. We studied fucoidans extracted from Ecklonia cava, Macrocystis pyrifera, Undaria pinnatifida, and Fucus vesiculosus for their effects on human monocyte-derived dendritic cells (MODC) and human peripheral blood DC (PBDC) activation. Ecklonia cava fucoidan (ECF) strongly upregulated co-stimulatory molecules, major histocompatibility complex class I and II, and the production of proinflammatory cytokines in MODCs and PBDCs compared to those by the other three fucoidans. Moreover, ECF elicited the strongest effect in the induction of syngeneic T cell proliferation and IFN-γ production compared to those of other fucoidans. These results suggest that ECF could be a suitable candidate molecule for enhancing immune activation in humans compared to that with the other three fucoidans.

The focus of this article is to review the complex determinants of gender assignment in a child with a disorder of sex development using four different clinical cases. While the care of patients with DSD may be shared across several specialties and opinions regarding their management may vary, this may be further complicated by psychosocial, cultural and economic factors. In this regard, access to behavioral health specialists with experience and specialization in the treatment of patients with DSD should be a foundational component of the standard of care and can greatly assist in the complex decision-making regarding gender assignment. We recommend an individualized approach by a multidisciplinary team utilizing a range of evolving strategies, including outcome data (or lack thereof) to support families during the decision-making process.

Summary Introduction/background Many parents of infants born with a DSD describe the process of initial sex assignment at birth as highly stressful. Parents of children with a DSD also note high distress when their children engage in behaviors that are not considered typical for their gender. Objective The goal of this article is to provide members of the health care team a brief overview of psychosocial facets of gender and gender identity particularly relevant to DSD for the purposes of enhancing shared decision-making and optimizing support for individuals with a DSD and their families. Discussion Gender identity is a multidimensional construct involving related but distinct concepts such as gender typicality, gender contentedness and felt pressure for gender differentiation, and can be assessed via standardized measures. Gender dysphoria is associated with poor psychological adjustment, and is mitigated by family and peer support. Family influences on gender identity include parental modeling of gender behavior and family composition (e.g., same-sex children vs both sons and daughters in a family). Cultural factors that may influence sex assignment include societal views on gender, and gender-related differential resource allocation within a society. In addition, religious beliefs and the presence of a “third-sex” category within a culture may also influence parental gender ideology. Clinical application Health care providers who work with patients with a DSD must have a strong grasp on the construct of gender identity, and must be able to clearly and consistently communicate with patients and families about gender beliefs in order to optimize family support and gender-related decisions.

A key technique for controlling solidification microstructures is magneto-hydrodynamics (MHD), resulting from imposing a magnetic field to solidifying metals and alloys. Applications range from bulk stirring to flow control and turbulence damping via the induced Lorentz force. Over the past two decades the Lorentz force caused by the interaction of thermoelectric currents and a magnetic field, a MHD phenomenon known as Thermoelectric Magnetohydrodynamics (TEMHD), was also shown to drive inter-dendritic flow altering microstructural evolution. In this contribution, high-speed synchrotron X-ray tomography and high-performance computational simulation are coupled to reveal the evolution, dynamics and mechanisms of solidification within a magnetic field, resolving the complex interplay and competing flow effects arising from Lorentz forces of different origins. The study enabled us to reveal the mechanisms disrupting the traditional columnar dendritic solidification microstructure, ranging from an Archimedes screw-like structure, to one with a highly refined dendritic primary array. We also demonstrate that alloy composition can be tailored to increase or decrease the influence of MHD depending on the Seebeck coefficient and relative density of the primary phase and interdendritic liquid. This work paves the way towards novel computational and experimental methods of exploiting and optimising the application of MHD in solidification processes, together with the calculated design of novel alloys that utilise these forces.

Acute kidney recovery (AKR) is a recently described phenomenon observed after transcatheter aortic valve replacement (TAVR) and is more frequent than acute kidney injury (AKI). To determine the incidence and predictors of AKR between surgical aortic valve replacement (SAVR) and TAVR, we examined patients with chronic kidney disease and severe aortic stenosis who underwent SAVR or TAVR procedure between 2007 and 2017; excluding age65 or90, dialysis, endocarditis, non-aortic valve stenosis, or patients died within 48-hours postprocedure. AKR was defined as an increase of estimated glomerular filtration rate (eGFR)25% and AKI as decrease in eGFR25% at discharge. Stroke, mortality, major bleeding, transfusion, and length of stay were examined. Multivariate logistic regression analysis was used to examine predictors of AKR. There were 750 transcatheter and 1,062 surgical patients and 319 pairs after propensity matching. AKR was observed in 26% TAVR versus 23.2% SAVR, p = 0.062. Highest recovery was in patients with eGFR30 for both TAVR (33.7%) and SAVR (34.5%) patients. Independent predictors of AKR were ejection fraction50% (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.02 to 2.71, p = 0.042), female gender (OR 1.66, 95% CI 1.1 to 2.5, p = 0.015), and obesity (OR 1.5, 95% CI 1.04-2.3, p = 0.032). Diabetes was a negative predictor of AKR (OR 0.55, 95% CI 0.36 to 0.84, p = 0.005). AKR was associated with improved secondary clinical outcomes compared with AKI. In conclusion, AKR is a generalizable phenomenon occurring frequently and similarly among transcatheter or surgical aortic valve patients. Diabetes is a negative predictor of AKR, possibly indicative of less reversible kidney disease.

Magnetic fields have been widely used to control solidification processes. Here, high-speed synchrotron X-ray tomography was used to study the effect of magnetic fields on solidification. We investigated vertically upward directional solidification of an Al-Si-Cu based W319 alloy without and with a transverse magnetic field of 0.5 T while the sample was rotating. The results revealed the strong effect of a magnetic field on both the primary α-Al phase and secondary β-Al5FeSi intermetallic compounds (IMCs). Without the magnetic field, coarse primary α-Al dendrites were observed with a large macro-segregation zone. When a magnetic field is imposed, much finer dendrites with smaller primary arm spacing were obtained, while macro-segregation was almost eliminated. Segregated solutes were pushed out of the fine dendrites and piled up slightly above the solid/liquid interface, leading to a gradient distribution of the secondary β-IMCs. This work demonstrates that rotating the sample under a transversal magnetic field is a simple yet effective method to homogenise the temperature and composition distributions, which can be used to control the primary phase and the distribution of iron-rich intermetallics during solidification.

Ti-containing micro-alloyed steels are often alloyed with molybdenum (Mo) to reduce nano-precipitate coarsening, although the mechanism is still disputed. Using small angle neutron scattering we characterised the precipitate composition and coarsening of Ti-alloyed and Ti-Mo-alloyed steels. The results demonstrate ~25 at.% of Ti is substituted by Mo in the (Ti, Mo)C precipitates, increasing both the precipitate volume percent and average size. Mo alloying did not retard precipitation coarsening, but improved lattice misfit between precipitate and matrix, contributing to better ageing resistance of the Ti-Mo-alloyed steel. This new understanding opens opportunities for designing ageing-resistant micro-alloyed steels with lean alloying elements.

Rylene dyes exhibit superior photophysical properties including outstanding chemical and photochemical stabilities as well as high fluorescence quantum yields (FQYs). However, the rylene chromophores have some limitations, such as high hydrophobicity and low solubility in aqueous solution, as a fluorescent tag for biological system. Herein, we present a general method to load the rylene dyes into triblock copolymer nanoparticles (NPs) and stabilize the core. The rylene dyes in confined hydrophobic core fairly preserve their FQYs in aqueous environment. Lumogen probe nanoparticles (PNPs) were prepared with four different commercial rylenes (Lumogen Violet, Yellow, Orange and Red) in the spectral region of visible and infrared (400–750 nm) and their photophysical properties were characterized. They exhibited enhanced photostability compared to commercial fluorescent dyes. Also the internalization of Lumogen PNPs in HeLa cell was confirmed by cell uptake test. These results indicate the Lumogen PNPs can be widely applicable in fluorescence detection and imaging such as flow cytometry and fluorescence microscopy.

Microstructures and pore systems in shales are key to understanding the role of shale in many energy applications. This study proposes a novel multi-stage upscaling procedure to comprehensively investigate the heterogeneous and complex microstructures and pore systems in a laminated and microfractured shale, utilizing 3D multi-scale imaging data. Five imaging techniques were used for characterisation from sub-nanoscale to macroscale (core-scale), spanning four orders of magnitude. Image data collected using X-ray tomography, Focused Ion Beam, and Electron Tomography techniques range in voxel size from 0.6 nm to 13 μm.Prior to upscaling, a novel two-step analysis was performed to ensure sub-samples were representative. Following this, a three-step procedure, based on homogenising descriptors and computed volume coefficients, was used to upscale the quantified microstructure and pore system. At the highest resolution (nanoscale), four distinct pore types were identified. At the sub-micron scale equations were derived for three pore-associated phases. At the microscale, the volume coefficients were recalculated to upscale the pore system to the macroscale (millimetre). The accuracy of the upscaling methodology was verified, predicting the total porosity within 7.2% discrepancy. The results provide a unique perspective to understand heterogeneous rock types, breaking though prior scale limitations in the pore system.

Pluronic® triblock copolymers, which spontaneously form nano-sized aggregates in water, have been considered as promising carriers for bioimaging and drug delivery. However, their use for applications in pharmacology and diagnostics is hindered by instability of polymer aggregates which are easily dissociated into unimers. Here we report a general method for stabilizing Pluronic® F127 micelles via semi-interpenetrating network (sIPN). The formation of sIPN within a core stabilizes the micelle upon temperature and concentration changes. We determined optimized methods for the preparation of F127 sIPN in the regime of chemical components. Importantly, F127 sIPNs are able to load various organic fluorescence probes, covering a panchromatic range of photoluminescence (350–850 nm; entire UV–Vis-NIR), without compromising their photophysical properties. Moreover, efficient cellular uptake of the fluorescence probes loaded sIPN is observed in human and mouse cells. After intravenous injection into mice, an infrared dye-loaded sIPNs are incorporated in multiple organs and have longer lifetime than a commercially available imaging probe. With the improvement of stability, Pluronic micelles with sIPN can be a powerful tool for building functional nanoprobes and in vivo fluorescence imaging for cancer cells and live animals.

In our latest update of the evidence on smoking bans and heart disease we summarize 59 studies. We take account of the underlying trends in incidence rates as far as possible by using control data in eight studies, and by adjustment based on observed trends in cases pre- and post-ban in 40 studies, being unable to make an adjustment in the remaining 11 studies. Overall, based on 62 independent estimates from the 59 studies, we estimate that bans reduce incidence by 5.0% (95% CI 3.2-6.8%), though this estimate reduces to 2.9% (0.01-5.6%) when we exclude regional estimates where national estimates are available, and studies where trend adjustment is not possible. For 25 of the studies, quadratic rather than linear adjustment is possible, but this hardly affects the overall estimates. Ban effects are somewhat greater when the pre-ban period studied is relatively short, and in smaller studies. We compare our findings with those in other recent reviews, one of which totally ignored underlying trends and results from control populations. We discuss reasons why we believe there is likely to be a true small effect of smoking bans, and weaknesses in the data which preclude reaching any very confident conclusion.

Many soft tissues, such as the intervertebral disc (IVD), have a hierarchical fibrous composite structure which suffers from regional damage. We hypothesise that clinical injury patterns in these tissues occur in localised regions where there is an integrated requirement for both marked compliance and significant load transfer. Here we used synchrotron computed tomography (sCT) to resolve collagen fibre bundles (~5μm width) in 3D throughout an intact native rat lumbar IVD under increasing compressive load. Using intact samples meant that tissue boundaries (such as endplate-disc or nucleus-annulus) and residual strain were preserved; this is vital for characterising both the inherent structure and structural changes upon loading in tissue regions functioning in a near-native environment. Nano-scale displacement measurements along >10,000 individual fibres were tracked, and fibre orientation, curvature and strain changes were compared between the failure-prone posterior-lateral region and the more robust anterior region. These methods can be widely applied to other soft tissues, to identify fibre structures which cause tissue regions to be more susceptible to injury and degeneration. Our results demonstrate for the first time that highly-localised changes in fibre orientation, curvature and strain indicate differences in regional strain transfer and mechanical function (e.g. tissue compliance), correlating directly with locations clinically at risk of damage. This included decreased fibre reorientation at higher loads, specific tissue morphology which reduced capacity for flexibility and high strain at the disc-endplate boundary.

The feasibility and advantages of synchrotron imaging have been demonstrated to effectively characterise fracture initiation and propagation in shales during indentation tests. These include 1) fast (minute-scale) and high-resolution (μm-scale) imaging of fracture initiation, 2) concurrent spatial and temporal information (4D) about fracture development, 3) quantification and modelling of shale deformation prior to fracture. Imaging experiments were performed on four shale samples with different laminations and compositions in different orientations, representative of three key variables in shale microstructure. Fracture initiation and propagation were successfully captured in 3D over time, and strain maps were generated using digital volume correlation (DVC). Subsequently, post-experimental fracture geometries were characterised at nano-scale using complementary SEM imaging. Characterisation results highlight the influence of microstructural and anisotropy variations on the mechanical properties of shales. The fractures tend to kink at the interface of two different textures at both macroscale and microscale due to deformation incompatibility. The average composition appears to provide the major control on hardness and fracture initiation load; while the material texture and the orientation of the indentation to bedding combine to control the fracture propagation direction and geometry. This improved understanding of fracture development in shales is potentially significant in the clean energy applications.

Porosity and high surface roughness can be detrimental to the mechanical performance of laser powder bed fusion (LPBF) additive manufactured components, potentially resulting in reduced component life. However, the link between powder layer thickness on pore formation and surface undulations in the LPBF parts remains unclear. In this paper, the influence of processing parameters on Ti-6Al-4 V additive manufactured thin-wall components are investigated for multilayer builds, using a custom-built process replicator and in situ high-speed synchrotron X-ray imaging. In addition to the formation of initial keyhole pores, the results reveal three pore phenomena in multilayer builds resulting from keyhole melting: (i) healing of the previous layers' pores via liquid filling during remelting; (ii) insufficient laser penetration depth to remelt and heal pores; and (iii) pores formed by keyholing which merge with existing pores, increasing the pore size. The results also show that the variation of powder layer thickness influences which pore formation mechanisms take place in multilayer builds. High-resolution microcomputed tomography images reveal that clusters of pores form at the ends of tracks, and variations in the layer thickness and melt flow cause irregular remelting and track height undulations. Extreme variations in height were found to lead to lack of fusion pores in the trough regions. It is hypothesised that the end of track pores were augmented by soluble gas which is partitioned into the melt pool and swept to track ends, supersaturating during end of track solidification and diffusing into pores increasing their size.

The architecture of bone scaffolds, such as pore dimensions, connectivity and orientation can regulate osteogenic defect repair, as can their rate of degradation. Synthetic bone grafts have historically been developed with foam structures to mimic trabecular bone. Now, Additive Manufacturing techniques enable production of open and regular pore architectures with improved compressive strengths. Here, we compare two types of bioactive glass scaffolds, made of the highly biodegradable ICIE16 composition, with distinctively different architectures but matched interconnect sizes (~150 µm), produced via two different techniques: gel-cast foaming and direct ink writing. A rabbit lateral femoral defect model was used to compare the effect of their architecture on in vivo bone regeneration, relative to a defect only control group, after 4 and 10 weeks of implantation. 3D X-ray microcomputed tomography (micro-CT), correlated to histology and back-scatter electron microscopy (BS-SEM) permitted quantitative evaluation of new bone ingrowth and degradation of the scaffolds. Both foam and printed scaffolds showed equal or higher bone ingrowth compared to the control group. After 4 weeks, the foam group showed the highest osteogenesis, with 51% more bone ingrowth than the defect only controls, but after 10 weeks the defect treated with the printed scaffold had the most bone ingrowth (40% more than the empty defect). Energy dispersive X-ray (EDS) mapping revealed degradation of the glass and calcium-phosphate deposition. The foam group showed more rapid degradation than the printed group, due to higher total porosity (even though interconnected pore size was equivalent). The foam scaffold appeared to allow rapid bone ingrowth and cancellous bone formation, whereas the printed scaffold seemed to provoke cortical-like bone formation, while remaining in place for longer than the 10 week study. While the foam's concave architectures promote initial bone ingrowth, the higher strength open pore channels of the printed scaffolds are beneficial for scaffolds made of highly degradable bioactive glasses.

Four-dimensional fast synchrotron X-ray tomography has been used to investigate the semi-solid deformation of nano- and micro-particle reinforced aluminum-copper composites (Al-10 wt% Cu alloy with ~1.0 wt% Al2O3 nano and ~1.0 wt% Al2O3 micro particles). Quantitative image analysis of the semi-solid deformation behavior of three alloys (base, nano- and micro-particle reinforced) revealed the influence of the particulate size on both microstructural formation and dominant deformation mechanisms. The results showed that initial void closure and incubation period were present in the particle-free and nano-particle reinforced Al-Cu composite during semi-solid compression, while the micro-particle reinforced alloy only showed continual void growth and coalescence into cracks. The results suggest that the nano-particle reinforced composite has the best hot-tearing resistance amongst the three alloys. Improved hot-tear performance with nano-particulate reinforcement was attributed to the small liquid channel thickness, fine grain size which alters the distribution/morphology of the liquid channels, more viscous inter-dendritic liquid, and fewer initial voids. National Key Research and Development Program of China (No. 2017YFA0403803); National Natural Science Foundation of China (Nos. 51901034, 51525401, 51927801, 51974058); LiaoNing Revitalization Talents Program (No. XLYC1808005); ExoMet Project funded by the European Commission in the 7th Framework Programme (Contract FP7-NMP3-LA-2012– 280421); EPSRC-funded project UltraMelt2 (EP/R011001/1); EPSRC (EP/I02249X/1); Royal Academy of Engineering (CiET1819/10).

In the “internet plus” era, online healthcare platforms provide an effective way of easing the demand for hospitals, and their popularity among patients has been increasing sharply in recent years. Such platforms' effectiveness depends on whether there are adequate interactions between patients and doctors through multiple online consultations. Nonetheless, compared with face-to-face consultations, online patients' trust to the doctors and switching costs are often lower. Thus, many of them (in particular, those with chronic diseases) may terminate their cases after the very first consultation, jeopardizing the effectiveness of the online platforms. We adopt a trust development perspective to examine how doctors' online consultation behaviours can reduce patients' switching of doctors and how they enhance patient satisfaction, thereby offering insights to make such healthcare platforms more efficient and effective. By analyzing 77,248 patients' behaviours on an online healthcare platform covering the period 2014–2015, we find that the response time, the depth of interaction, and service content during the first consultation influence the patients' subsequent consultation behaviours significantly. Also, the effects of doctor response time, service content, and depth of interaction on patient satisfaction are different in different periods. Our findings offer managerial insights on managing patients' continuous consultation behaviours and enhancing their satisfaction by considering the time scope and service type. Also, they offer important insights into how online medical care can be delivered more effectively, so relieving the demand for traditional healthcare system capacity.

In our previous study, we showed that Rehmannia glutinosa polysaccharide (RGP) treatment induced activation of dendritic cells (DCs) in human and mouse subjects. In this study, we evaluated the effect of RGP as a mucosal adjuvant for inducting activation of DCs in the mediastinal lymph node (mLN) in the mouse. The C57BL/6 mice were intranasally (i.n.) treated with RGP and activation of DC in the mLN was analyzed. The treatment with RGP induced a substantial increase in the number of DCs in the mLN due to the up-regulation of C-C motif chemokine receptor 7 (CCR7) in the DCs. Moreover, the expression of co-stimulatory molecules in the mLN DCs and the concentration of pro-inflammatory cytokines in the lung were up-regulated by RGP treatment. Also, RGP treatment induced interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production in the mLN T cells. The combination treatment of RGP and ovalbumin (OVA) induced OVA-specific TCR transgenic I (OT-I) and OT-II cell proliferation in the mLN. Finally, the combination treatment of RGP and tyrosinase-related protein 2 (TRP2) peptide, a melanoma self-antigen, protected mice from melanoma challenge. Thus, these data demonstrated that RGP can be used as a mucosal adjuvant for inducing activation of immune responses in the lung.

A robotic cloud laboratory driven by a state-of-the-art unified laboratory operating system integrates automated hardware, humans, and sensors. This lab of the future system enables researchers to transparently and collaboratively create, optimize, and organize biological experiments to achieve more reproducible results, perform around-the-clock experimentation, and more efficiently navigate the vast parameter space of biology.

Dendritic microstructural evolution during the solidification of Mg-Zn alloys was investigated as a function of Zn concentration using in situ synchrotron X-ray tomography. We reveal that increasing Zn content from 25 wt% to 50 wt% causes a Dendrite Orientation Transition (DOT) from a six-fold snow-flake structure to a hyper-branched morphology and then back to a six-fold structure. This transition was attributed to changes in the anisotropy of the solid-liquid interfacial energy caused by the increase in Zn concentration. Further, doublon, triplon and quadruplon tip splitting mechanisms were shown to be active in the Mg-38 wt%Zn alloy, creating a hyper-branched structure. Using the synchrotron tomography datasets, we quantify, for the first time, the evolution of grain structures during the solidification of these alloys, including dendrite tip velocity in the mushy zone, solid fraction, and specific surface area. The results are also compared to existing models. The results demonstrate the complexity in dendritic pattern formation in hcp systems, providing critical input data for the microstructural models used for integrated computational materials engineering of Mg alloys.

The deformation responses at 77 and 293 K of a FeCoNiCr high-entropy alloy, produced by a powder metallurgy route, are investigated using in situ neutron diffraction and correlative transmission electron microscopy. The strength and ductility of the alloy are significant improved at cryogenic temperatures. The true ultimate tensile strength and total elongation increased from 980 MPa to 45% at 293 K to 1725 MPa and 55% at 77 K, respectively. The evolutions of lattice strain, stacking fault probability, and dislocation density were determined via quantifying the in situ neutron diffraction measurements. The results demonstrate that the alloy has a much higher tendency to form stacking faults and mechanical twins as the deformation temperature drops, which is due to the decrease of stacking fault energy (estimated to be 32.5 mJ/m2 and 13 mJ/m2 at 293 and 77 K, respectively). The increased volume faction of nano-twins and twin-twin intersections, formed during cryogenic temperature deformation, has been confirmed by transmission electron microscopy analysis. The enhanced strength and ductility at cryogenic temperatures can be attributed to the increased density of dislocations and nano-twins. The findings provide a fundamental understanding of underlying governing mechanistic mechanisms for the twinning induced plasticity in high entropy alloys, paving the way for the development of new alloys with superb resistance to cryogenic environments.

Notwithstanding the availability of a substantial body of literature on corporate social responsibility (CSR), the term has remained controversial and ambiguous in terms of its meaning, use, and usefulness. Specifically, the impact of CSR on tangible and intangible returns to Chinese manufacturers has remained uncertain. Drawing on stakeholder theory and CSR literature, we empirically develop an exploratory taxonomy of CSR practices in China's manufacturing industries. By surveying the manufacturers operating in China's food, pharmaceutical, automotive, and clothing industries, we identify three CSR clusters and examine how they are related to their financial, operational, reputational, and social capital performances. Our findings deepen the understanding of CSR adoption patterns by clarifying the consequences of CSR adoption in China's manufacturing industry.

Direct ink writing (DIW) or Robocasting, is an additive manufacturing technique that offers the opportunity to create patient specific bioactive glass scaffolds and high strength scaffolds for bone repair. The original 45S5 Bioglass® composition crystallises during sintering and until now, robocast glass scaffolds contained at least 51.9 mol% SiO2 or B2O3 to maintain their amorphous structure. Here, ICIE16 and PSrBG compositions, containing

The free energy is central to statistical mechanics and thermodynamics, and its accurate calculation via. computational modelling is important for a large number of applications, especially when its experimental value is hard to obtain. Several established and general methods for calculating the Helmholtz free energy across different length scales, including continuum, atomistic and quantum mechanical, are compared and analyzed. A computational approach is then proposed to calculate the temperature dependences of internal energy and absolute Helmholtz free energy for solid and liquid phases with the coupling of thermodynamic integration (TI) and harmonic approximation calculations from both classical molecular dynamics (MD) and density functional theory (DFT). We use the Lennard-Jones system as an example (i.e. argon) for the demonstration of the approach. It is observed that the free energy transits smoothly from being describable by the harmonic approximation to including anharmonic effects at a transition temperature around 0.56 Tm; below this temperature, the quantum behavior of atoms is important. At higher temperatures (T > 0.56 Tm), the TI and harmonic approximation results for the Helmholtz free energy functions become increasingly divergent with the increase of temperature. This work demonstrates that a multiscale approach employing TI, MD, and DFT can provide accurate calculations of the temperature dependence of absolute Helmholtz free energy for both solid and liquid phases.

The thermal conductivity (λ) of glass foams is thought to depend on pore size. We report on the impact of pore size, determined using X-ray microtomography, and percentage porosity on the λ of glass foams. Glass foams were prepared by heating powder mixtures of obsolete cathode ray tube (CRT) panel glass, Mn 3O 4 and carbon as foaming agents, and K 3PO 4 as additive, to a suitable temperature above T g, and subsequent cooling. Here, we report for the first time a correlation between λ and pore size in the range 0.10–0.16 mm showing a decrease from 57 to 49 mW m −1 K −1 with increasing the pore size for glass foams with porosities of 87–90%. This indicates that the pore structure should be optimized in order to improve the insulating performance of glass foams.

Purpose Single agent PD-1 inhibitors have yielded durable responses in a minority of gastroesophageal cancers. Radiation therapy has been recognized to promote antitumor immune responses and may synergize with anti-PD-1 agents. We sought to evaluate if combining palliative radiation therapy with pembrolizumab can augment antitumor immune responses in gastroesophageal cancer. Methods and Materials Patients had metastatic gastroesophageal cancer with indication for palliative radiation therapy with ≥2 disease sites outside of the radiation field assessable for abscopal response and biopsies for laboratory correlative analyses. Palliative radiation was delivered to a dose of 30 Gy over 10 fractions. Pembrolizumab, 200 mg, was administered concurrently intravenously every 3 weeks until disease progression, unacceptable toxicity, or study withdrawal, for up to 2 years. Endpoints included PD-L1 expression in pre- and posttreatment biopsies and abscopal objective response rate per Response Evaluation Criteria in Solid Tumors. Results Of 14 enrolled patients, the objective response rate was 28.6% (95% confidence interval, 8.4%-58.1%), and the median duration of response was not reached (95% confidence interval, 6.9-NR months). Overall, 2 patients had treatment-related grade 3 to 4 adverse events with no grade 5 events. One patient discontinued therapy due to grade 4 colitis. We did not observe an association between radiation and abscopal changes in PD-L1 expression via assessment of an analogous PD-L1 Combined Positive Score, Tumor Proportion Score, Mononuclear Immune Cell Density Score, or proportion of PD-L1-expressing immune cells between pre- and posttreatment tumor biopsies. Conclusions Combining palliative radiation therapy and pembrolizumab provided promising durable responses in this patient population but we were unable to definitively distinguish abscopal biologic changes. Biomarker analyses beyond PD-L1 expression are needed to better understand putative mechanisms and identify patients who will benefit from this approach.

In specialised solidification processing techniques such as High Pressure Die Casting, Twin-Roll Casting and others, an additional external deformation load is applied to achieve the required shape, leading to the formation of microstructural features such as shear bands. The mechanism for forming these features is believed to be dependent on dynamically evolving strain fields, which are dependent on the local solid fraction, applied strain rates and casting geometry. To investigate this, a semisolid ( ∼ 50 % solid fraction) Al-10 wt.% Cu alloy is isothermally injected into a bespoke die using a custom-designed thermo-mechanical rig. The semisolid deformation, formation of Cu-rich dilatant bands and subsequent pore nucleation and growth are captured using fast synchrotron X-ray radiography. The local normal and shear strains acting on the mush are quantified using digital image correlation to identify the dilatant shear bands and the dominant local strain component. Correlating the radiographs with strain maps reveals that gas pores within the dilated interstices grow, while those in compressed regions are squeezed out. A linear correlation between accumulated volumetric strain and porosity volume fraction demonstrates that higher dilations give rise to a local increase in both gas and shrinkage porosity.

Ductile cast irons (DCIs) are of increasing importance in the renewable energy and transportation sectors. The distribution and morphology of the graphite nodules, in particular the formation of degenerate features during solidification, dictate the mechanical performance of DCIs. In situ high-speed synchrotron X-ray tomography was used to capture the evolution of graphite nodules during solidification of DCI, including degenerate features and the effect of the carbon concentration field. The degeneration of nodules is observed to increase with re-melting cycles, which is attributed to Mg-loss. The dendritic primary austenite and carbon concentration gradients in the surrounding liquid phase were found to control nodule morphology by locally restricting and promoting growth. A coupled diffusion-mechanical model was developed, confirming the experimentally informed hypothesis that protrusions form through liquation cracking of the austenite shell and subsequent localised growth. These results provide valuable insights into the solidification kinetics of cast irons, supporting the design of advanced alloys.

Cancer stem cells (CSCs) initiate tumor formation and are known to be resistant to chemotherapy. A metabolic alteration in CSCs plays a critical role in stemness and survival. However, the association between mitochondrial energy metabolism and the redox system remains undefined in colon CSCs. In this study, we assessed the role of the Sulfiredoxin-Peroxiredoxin (Srx-Prx) redox system and mitochondrial oxidative phosphorylation (OXPHOS) in maintaining the stemness and survival of colon CSCs. Notably, Srx contributed to the stability of PrxI, PrxII, and PrxIII proteins in colon CSCs. Increased Srx expression promoted the stemness and survival of CSCs and was important for the maintenance of the mitochondrial OXPHOS system. Furthermore, Nrf2 and FoxM1 led to OXPHOS activation and upregulated expression of Srx-Prx redox system-related genes. Therefore, the Nrf2/FoxM1-induced Srx-Prx redox system is a potential therapeutic target for eliminating CSCs in colon cancer., Graphical abstract Image 1, Highlights • CSCs initiate tumor formation and are known to be resistant to chemotherapy. • We assessed the role of the Srx-Prx redox system and OXPHOS in colon CSCs. • Srx contributed to the stability of PrxI, PrxII, and PrxIII proteins in colon CSCs. • Nrf2 and FoxM1 upregulated Srx-Prx redox system-related gene expression. • Nrf2/FoxM1-induced Srx-Prx redox system is a target to eliminate CSCs in colon cancer.

The additive manufacturing (AM) of metals is becoming an increasingly important production process with the potential to replace traditional techniques such as casting. Laser Powder Bed Fusion (LPBF) is used in many applications to print metal parts from powder. The metal powder is heated locally with sufficient laser radiation that the liquid melt easily reaches its boiling temperature, which leads to a metallic vapour jet that can entrain both powder bed particles and molten droplets. The small size of laser-matter interaction site makes a detailed experimental analysis of the process challenging. Synchrotron X-ray imaging experiments are one of the few methods which can capture the dynamic melting and solidification processes. Comparing such experiments with computer simulations of the process is an important approach in order to better understand the manufacturing process and to analyse the influence of process parameters on the evaporated gas jet and the subsequent impact on particle ejection, leading to potentially reduced AM component quality. The melting and solidification of the metal powder is simulated using an Eulerian multiphase approach based on a control volume discretization of powder bed and substrate and a volume of liquid separation from melt and gas phase. The gas phase modelled as an ideal gas reaches velocities up to 100 m/s. Lagrangian particle tracking in the simulation demonstrates that the velocity fields calculated by the Eulerian multi-phase approach in combination with a standard drag-force model lead to particle accelerations in good agreement with those measured experimentally. In order to avoid numerical laborious Lagrangian calculations, a direct method to compare an Eulerian multiphase simulation with synchrotron X-ray experiments was introduced and validated. This approach is used to analyse the influence of process parameters including laser power and laser speed on the maximal acceleration of particles from the melt pool area. While the particle acceleration increases linearly with line energy in the conduction mode, a linear decrease of the acceleration with increasing line energy can be found in the transition mode before the acceleration increases again with line energy in the keyhole mode.