A dual porous hierarchical coating of TiO2 nanotubes (50 nm diameter) on the nanoscale and large (1 to 20 mum) pores on the micro-scale can be fabricated on the surface of Ti by anodic oxidation. ...This unique coating may have potential applications as bioactive coatings for Ti bone implants. This paper details several important aspects of the coating microstructure. TiO2 coatings were fabricated by anodic oxidation in 1 M H2SO4 + 0.1 M NaF solution. Microstructure characterization was carried out using scanning electron microscopy. We also report on the observation of precipitates which form as both a continuous surface layer and of a conical geometry. The mechanism for nanotube formation, precipitate layer formation, and microscopic pitting was discussed. The effect of processing variables (i.e. time, temperature, pH) on the TiO2 microstructure was studied. Anodization time was found to affect nanotube length and also pit size and density. Lowering the electrolyte pH decreased the nanotube length and microscopic pit density. Increasing electrolyte temperature decreased nanotube length and increased pit/pore and precipitate density. Microscopic pitting, in the nanotube coating was found to occur above grain boundaries in the Ti substrate and above Ti grains with (0 0 0 1) orientation.
The global burden of hepatocellular carcinoma (HCC), one of the frequent causes of cancer-related deaths worldwide, is rapidly increasing partly due to the limited treatment options available for ...this disease and recurrence due to therapy resistance. Immune checkpoint inhibitors that are proved to be beneficial in the treatment of advanced melanoma and other cancer types are currently in clinical trials in HCC. These ongoing trials are testing the efficacy and safety of a few select checkpoints in HCC. Similar to observations in other cancers, these immune checkpoint blockade treatments as monotherapy may benefit only a fraction of HCC patients. Studies that assess the prevalence and distribution of other immune checkpoints/modulatory molecules in HCC have been limited. Moreover, robust predictors to identify which HCC patients will respond to immunotherapy are currently lacking. The objective of this study is to perform a comprehensive evaluation on different immune modulators as predictive biomarkers to monitor HCC patients at high risk for poor prognosis. We screened publically available HCC patient databases for the expression of previously well described immune checkpoint regulators and evaluated the usefulness of these immune modulators to predict high risk, patient overall survival and recurrence. We also identified the immune modulators that synergized with known immune evasion molecules programmed death receptor ligand-1 (PD-L1), programmed cell death protein-1 (PD-1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and correlated with worse patient outcomes. We evaluated the association between the expression of epithelial-to-mesenchymal transition (EMT) markers and PD-L1 in HCC patient tumors. We also examined the relationship of tumor mutational burden with HCC patient survival. Notably, expression of immune modulators
, and
were independently associated with worse prognosis, while
, and
predicted low recurrence-free survival. Moreover, the prognosis of patients expressing high
with high
, and
expression was significantly worse. Interestingly,
expression in HCC patients in the high-risk group was closely associated with EMT marker expression and prognosticates poor survival. In HCC patients, high tumor mutational burden (TMB) predicted worse patient outcomes than those with low TMB.
This study investigates the microstructure evolution of as-atomized 7075 aluminum powder during high pressure cold spray deposition. The as-received powder and the deposition were characterized via ...scanning electron microscopy, electron backscatter diffraction, and transmission electron microscopy. The as-received powder was composed of two different particle types, differentiated by their grain boundary structure and solute element distribution. Significant solute element segregation was observed at grain boundaries for both particle types. The powder also contained nanoscale subgrain and dislocation structures. High pressure cold spray resulted in the formation of a high quality deposition with limited porosity and inter-particle voids. The deposition was characterized by two distinct regions: particle/particle boundaries and particle interiors. Particle/particle boundaries showed a high degree of deformation resulting in the formation of an ultra-fine grain structure and a low density of low angle grain boundaries. The formation of the ultra-fine grain structure is attributed to dynamic recrystallization and recovery processes. Particle interiors were characterized by larger grains containing a high density of low angle grain boundaries and dislocation structure. Large grains in the deposition contained precipitates distributed both within the grain interior and at grain boundaries. Precipitates in small grains were distributed primarily at grain boundaries. The effect of these precipitates on the microstructure evolution was also discussed.
•Powder/deposition microstructure relationship study via different techniques•High dislocation density, recovery and recrystallization in the deposition•Various microstructural features in different areas of the deposition•The main and possible recrystallization mechanisms of the observed UFG structures•Various spatial distributions of precipitates in grains with different sizes
Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer‐related death worldwide. Activated hepatic stellate cells (HSCs) are key ...components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of growth factors and cytokines. Current treatment modalities that include chemotherapy, radiotherapy and ablation are able to activate HSCs and remodel the tumor microenvironment. Growing evidence has demonstrated that the complex interaction between activated HSCs and tumor cells can facilitate cancer chemoresistance and metastasis. Therefore, therapeutic targeting of activated HSCs has emerged as a promising strategy to improve treatment outcomes for HCC. This review summarizes the molecular mechanisms of HSC activation triggered by treatment modalities, the function of activated HSCs in HCC, as well as the crosstalk between tumor cells and activated HSCs. Pathways of activated HSC reduction are discussed, including inhibition, apoptosis, and reversion to the inactivated state. Finally, we outline the progress and challenges of therapeutic approaches targeting activated HSCs in the development of HCC treatment.
Summary
Background
Symptomatic breakthrough in proton pump inhibitor (PPI)‐treated gastro‐oesophageal reflux disease (GERD) patients is a common problem with a range of underlying causes. The ...nonsystemic, raft‐forming action of alginates may help resolve symptoms.
Aim
To assess alginate‐antacid (Gaviscon Double Action, RB, Slough, UK) as add‐on therapy to once‐daily PPI for suppression of breakthrough reflux symptoms.
Methods
In two randomised, double‐blind studies (exploratory, n=52; confirmatory, n=262), patients taking standard‐dose PPI who had breakthrough symptoms, assessed by Heartburn Reflux Dyspepsia Questionnaire (HRDQ), were randomised to add‐on Gaviscon or placebo (20 mL after meals and bedtime). The exploratory study endpoint was change in HRDQ score during treatment vs run‐in. The confirmatory study endpoint was “response” defined as ≥3 days reduction in the number of “bad” days (HRDQ heartburn/regurgitation >0.70) during treatment vs run‐in.
Results
In the exploratory study, significantly greater reductions in HRDQ scores (heartburn/regurgitation) were observed in the Gaviscon vs placebo (least squares mean difference 95% CI −2.10 −3.71 to −0.48; P=.012). Post hoc “responder” analysis of the exploratory study also revealed significantly more Gaviscon patients (75%) achieved ≥3 days reduction in “bad” days vs placebo patients (36%), P=.005. In the confirmatory study, symptomatic improvement was observed with add‐on Gaviscon (51%) but there was no significant difference in response vs placebo (48%) (OR (95% CI) 1.15 (0.69‐1.91), P=.5939).
Conclusions
Adding Gaviscon to PPI reduced breakthrough GERD symptoms but a nearly equal response was observed for placebo. Response to intervention may vary according to whether symptoms are functional in origin.
Linked ContentThis article is linked to Katz and Coyle and Bytzer papers. To view these articles visit https://doi.org/10.1111/apt.14120 and https://doi.org/10.1111/apt.14151.
Cold spray deposition is well known to produce a highly deformed microstructure with large strain gradients across the individual particles composing the deposited layer. This study investigates the ...relationship between the as-deposited cold spray microstructure and the resulting local and coating-scale mechanical properties of 7075 aluminum powder deposited onto wrought 7075 aluminum substrates via high pressure cold spray. Local mechanical property variations were probed using nanoindentation and correlated with microstructural characterization conducted via various microscopy techniques. 7075 Aluminum powder particles experienced high deformation rates during impact, resulting in local microstructural variations, specifically grain size and dislocation densities, between particle interfaces and their interiors. Consequently, an average 0.5GPa increase in nanohardness was observed in particle interface regions. This increase in hardness was concluded to be primarily the result of grain refinement promoted by local dynamic recrystallization, rather than from an increase in local dislocation density causing strain hardening behavior. Examination of the coating revealed a decrease in hardness and an increase in local grain size with increasing distance from the substrate. The effects of these microstructural variations on the quality of the deposition were also evaluated by tensile pull-off and three lug shear testing.
An efficient synthetic route to 2‐ and 2,7‐substituted pyrenes is described. The regiospecific direct CH borylation of pyrene with an iridium‐based catalyst, prepared in situ by the reaction of ...{Ir(μ‐OMe)cod}2 (cod=1,5‐cyclooctadiene) with 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine, gives 2,7‐bis(Bpin)pyrene (1) and 2‐(Bpin)pyrene (2, pin=OCMe2CMe2O). From 1, by simple derivatization strategies, we synthesized 2,7‐bis(R)‐pyrenes with R=BF3K (3), Br (4), OH (5), B(OH)2 (6), and OTf (7). Using these nominally nucleophilic and electrophilic derivatives as coupling partners in Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig cross‐coupling reactions, we obtained 2,7‐bis(R)‐pyrenes with R=(4‐CO2C8H17)C6H4 (8), Ph (9), C≡CPh (10), C≡C{4‐B(Mes)2}C6H4 (11), C≡CTMS (12), C≡C(4‐NMe2)C6H4 (14), C≡CH (15), N(Ph)(4‐OMe)C6H4 (16), and R=OTf, R′=C≡CTMS (13). Lithiation of 4, followed by reaction with CO2, yielded pyrene‐2,7‐dicarboxylic acid (17), whilst borylation of 2‐tBu‐pyrene gave 2‐tBu‐7‐Bpin‐pyrene (18) selectively. By similar routes (including Negishi cross‐coupling reactions), monosubstituted 2‐R‐pyrenes with R=BF3K (19), Br (20), OH (21), B(OH)2 (22), 4‐B(Mes)2C6H4 (23), B(Mes)2 (24), OTf (25), C≡CPh (26), C≡CTMS (27), (4‐CO2Me)C6H4 (28), C≡CH (29), C3H6CO2Me (30), OC3H6CO2Me (31), C3H6CO2H (32), OC3H6CO2H (33), and O(CH2)12Br (34) were obtained from 2. These derivatives are of synthetic and photophysical interest because they contain donor, acceptor, and conjugated substituents. The crystal structures of compounds 4, 5, 7, 12, 18, 19, 21, 23, 26, and 28–31 have also been obtained from single‐crystal X‐ray diffraction data, revealing a diversity of packing modes, which are described in the Supporting Information. A detailed discussion of the structures of 1 and 2, their polymorphs, solvates, and co‐crystals is reported separately.
The point of catalytic CH borylation! Regioselective iridium‐catalyzed borylation of pyrene takes place at the 2‐ and 2,7‐positions. The resulting mono‐ and bisboronate esters can be readily converted into both nucleophilic and electrophilic cross‐coupling partners and serve as useful precursors to a wide range of pyrene derivatives of significant photophysical and structural interest, which are otherwise difficult to prepare (see scheme).
PurposeThose travelling overseas for work or leisure including male expatriates, longer-term and frequent travellers (ELoFTs) may be at heightened risk for a range of health and wellbeing issues. ...Social support may mediate this risk. However, from a public health perspective, little is written about how ELoFTs access health information and support and the role of their social networks in facilitating health and wellbeing outcomes. This research was part of a study examining social network processes of Australian male ELoFTs travelling, living, or working in Southeast Asia (SEA).MethodsSymbolic Interactionism and Grounded Theory were the conceptual framework and methodology supporting semi-structured, in-depth interviews (n = 25) conducted in Australia and Thailand with Australian male ELoFTs to SEA, aged 18 years or older.ResultsFindings highlight supports that assist ELoFT transition and adjustment to country of destination or manage their transnational experience. Influential places, people, and points in the migration journey mediated engagement with social support.ConclusionsELoFT social networks and the support provided within them may provide a mechanism for intervention across a range of public health issues. Findings may support the development of policy and practice across industries charged with supporting successful ELoFT adjustment.
While liver transplantation remains the sole treatment option for patients with end-stage liver disease, there are numerous limitations to liver transplantation including the scarcity of donor livers ...and a rise in livers that are unsuitable to transplant such as those with excess steatosis. Fatty livers are susceptible to ischaemia-reperfusion (IR) injury during transplantation and IR injury results in primary graft non-function, graft failure and mortality. Recent studies have described new cell death pathways which differ from the traditional apoptotic pathway. Necroptosis, a regulated form of cell death, has been associated with hepatic IR injury. Receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL) are thought to be instrumental in the execution of necroptosis. The study of hepatic necroptosis and potential therapeutic approaches to attenuate IR injury will be a key factor in improving our knowledge regarding liver transplantation with fatty donor livers. In this review, we focus on the effect of hepatic steatosis during liver transplantation as well as molecular mechanisms of necroptosis and its involvement during liver IR injury. We also discuss the immune responses triggered during necroptosis and examine the utility of necroptosis inhibitors as potential therapeutic approaches to alleviate IR injury.
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