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Transformational advances in additive manufacturing combined with the unique functional behavior of shape memory alloys (SMAs) has propelled the field of 4D printing “smart” materials. In this study, we leverage multiple processing pathways with additive manufacturing to design and fabricate SMA components capable of precise, self-guided shape change that could actuate large-scale (up to 25 × 25 × 33 cm3) structures under external thermal stimuli. The dual benefits of minor alloy doping (

Additive manufacturing (AM) has transformed the process of shaping refractory metals into complex form factors. This study was undertaken to investigate the AM processing parameters for pure tantalum (Ta) and to understand their influence on the attendant properties. Computational fluid dynamics simulations informed a subset of AM laser parameters that were manufactured and characterized for their porosity and mechanical response. Manufacturing with high energy densities (350-470 J/mm3) increased material density and mechanical strength, but dramatically reduced the ductility owing to the prolific formation of pre-existing edge cracks. While low porosity is typically a key metric for success in AM, the results presented here elucidate that a balance between maximizing bulk material density and minimizing steep thermal gradients during processing is needed to optimize the strength-ductility tradeoff.

Achieving microscopy with large space-bandwidth products plays a key role in diagnostic imaging and is widely significant in the overall field of clinical practice. Among quantitative microscopy techniques, Fourier Ptychography (FP) provides a wide field of view and high-resolution images, suitable to the histopathological field, but onerous in computational terms. Artificial intelligence can be a solution in this sense. In particular, this research delves into the application of Generative Adversarial Networks (GAN) for the dual-channel complex FP image enhancement of human kidney samples. The study underscores the GANs' efficacy in promoting biological architectures in FP domain, thereby still guaranteeing high resolution and visibility of detailed microscopic structures. We demonstrate successful GAN-based enhanced reconstruction through two strategies: cross-explainability and expert survey. The cross-explainability is evaluated through the comparison of explanation maps for both real and imaginary components underlining its robustness. This comparison further shows that their interplay is pivotal for accurate reconstruction without hallucinations. Secondly, the enhanced reconstruction accuracy and effectiveness in a clinical workflow are confirmed through a two-step survey conducted with nephrologists., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors M.V., V.B., L.M., P.M., P.Fe., P.Fi., F.B., and R.T. declare no financial or any other competing interest associated with the present manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Extremely low-frequency electromagnetic fields (ELF-MF) can modify the cell viability and regulatory processes of some cell types, including breast cancer cells. Breast cancer is a multifactorial disease where a role for ELF-MF cannot be excluded. ELF-MF may influence the biological properties of breast cells through molecular mechanisms and signaling pathways that are still unclear. This study analyzed the changes in the cell viability, cellular morphology, oxidative stress response and alteration of proteomic profile in breast cancer cells (MDA-MB-231) exposed to ELF-MF (50 Hz, 1 mT for 4 h). Non-tumorigenic human breast cells (MCF-10A) were used as control cells. Exposed MDA-MB-231 breast cancer cells increased their viability and live cell number and showed a higher density and length of filopodia compared with the unexposed cells. In addition, ELF-MF induced an increase of the mitochondrial ROS levels and an alteration of mitochondrial morphology. Proteomic data analysis showed that ELF-MF altered the expression of 328 proteins in MDA-MB-231 cells and of 242 proteins in MCF-10A cells. Gene Ontology term enrichment analysis demonstrated that in both cell lines ELF-MF exposure up-regulated the genes enriched in "focal adhesion" and "mitochondrion". The ELF-MF exposure decreased the adhesive properties of MDA-MB-231 cells and increased the migration and invasion cell abilities. At the same time, proteomic analysis, confirmed by Real Time PCR, revealed that transcription factors associated with cellular reprogramming were upregulated in MDA-MB-231 cells and downregulated in MCF-10A cells after ELF-MF exposure. MDA-MB-231 breast cancer cells exposed to 1 mT 50 Hz ELF-MF showed modifications in proteomic profile together with changes in cell viability, cellular morphology, oxidative stress response, adhesion, migration and invasion cell abilities. The main signaling pathways involved were relative to focal adhesion, mitochondrion and cellular reprogramming., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Micron size fiber fragments (MFFs), both natural and synthetic, are ubiquitous in our life, especially in textile clothes, being necessary in modern society. In the Earth's aquatic ecosystem, microplastic fibers account for ~91% of microplastic pollution, thus deserving notable attention as one of the most alarming ecological problems. Accurate automatic identification of MFFs discharges in specific upstream locations is highly demanded. Computational microscopy based on Digital Holography (DH) and machine learning has been demonstrated to identify microplastics in respect to microalgae. However, DH is a non-specific optical tool, meaning it cannot distinguish different types of plastic materials. On the other hand, materials-specific assessments are pivotal to establish the environmental impact of different textile products and production processes. Spectroscopic assays can be employed to identify microplastics for their intrinsic specificity, although they are generally low-throughput and require large concentrations to enable effective measurements. Conversely, MFFs are usually finely dispersed within a water sample. Here we rely on a polarization-resolved holographic flow cytometer in a Lab-on-Chip (LoC) platform for analysing MFFs. We demonstrate that two important objectives can be achieved, i.e. adding material specificity through polarization analysis while operating in a microfluidic stream modality. Through a machine learning numerical pipeline, natural fibers (i.e. cotton and wool) can be clearly separated from synthetic microfilaments, namely PA6, PA6.6, PET, PP. Moreover, the proposed system can accurately distinguish between different polymers under investigation, thus fulfilling the specificity goal. We extract and select different features from amplitude, phase and birefringence maps retrieved from the digital holograms. These are shown to typify MFFs without the need for sample pre-treatment or large concentrations. The simplicity of the DH method for identifying MFFs in LoC-based flow cytometers could promote the use of polarization resolved field-portable analysis systems suitable for studying pollution caused by washing processes of synthetic textiles., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study is to assess Blood oxygenation level dependent Magnetic Resonance Imaging (BOLD-MRI) and Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) in the differentiation of benign and malignant breast lesions., Methods: Fifty-nine breast lesions (26 benign and 33 malignant lesions) pathologically proven in 59 patients were included in this retrospective study. As BOLD parameters were estimated basal signal S 0 and the relaxation rate R2*, diffusion and perfusion parameters were derived by DWI (pseudo-diffusion coefficient (Dp), perfusion fraction (fp) and tissue diffusivity (Dt)). Wilcoxon-Mann-Whitney U test and Receiver operating characteristic (ROC) analyses were calculated and area under ROC curve (AUC) was obtained. Moreover, pattern recognition approaches (linear discrimination analysis (LDA), support vector machine, k-nearest neighbours, decision tree) with least absolute shrinkage and selection operator (LASSO) method and leave one out cross validation approach were considered., Results: A significant discrimination was obtained by the standard deviation value of S0, as BOLD parameter, that reached an AUC of 0.76 with a sensitivity of 65%, a specificity of 85% and an accuracy of 76%. No significant discrimination was obtained considering diffusion and perfusion parameters. Considering LASSO results, the features to use as predictors were all extracted parameters except that the mean value of R2* and the best result was obtained by a LDA that obtained an AUC = 0.83, with a sensitivity of 88%, a specificity of 77% and an accuracy of 83%., Conclusions: Good performance to discriminate benign and malignant lesions could be obtained using BOLD and DWI derived parameters with a LDA classification approach. However, these findings should be proven on larger and several dataset with different MR scanners., (Copyright © 2020 Elsevier Inc. All rights reserved.)

MiR-222 and miR-126 are associated with asbestos exposure and the ensuing malignancy, but the mechanism(s) of their regulation remain unclear. We evaluated the mechanism by which asbestos regulates miR-222 and miR-126 expression in the context of cancer etiology. An 'in vitro' model of carcinogen-induced cell transformation was used based on exposing bronchial epithelium BEAS-2B cells to three different carcinogens including asbestos. Involvement of the EGFR pathway and the role of epigenetics have been investigated in carcinogen-transformed cells and in malignant mesothelioma, a neoplastic disease associated with asbestos exposure. Increased expression of miR-222 and miR-126 were found in asbestos-transformed cells, but not in cells exposed to arsenic and chrome. Asbestos-mediated activation of the EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation, which was reversed by EGFR inhibition. Conversely, asbestos-induced miR-126 expression was affected neither by EGFR modulation nor inflammation. Rather than methylation of the miR-126 host gene EGFL7, epigenetic mechanism involving DNMT1- and PARP1-mediated chromatin remodeling was found to upregulate of miR-126 in asbestos-exposed cells, while miR-126 was downregulated in malignant cells. Analysis of MM tissue supported the role of PARP1 in miR-126 regulation. Therefore, activation of the EGFR pathway and the PARP1-mediated epigenetic regulation both play a role in asbestos-induced miRNA expression, associated with in asbestos-induced carcinogenesis and tumor progression., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Novel water-soluble 4-aminonaphthalimides were synthesised and their cellular fluorescent imaging, cytotoxicity and ability to induced apoptosis evaluated. The lead compound 1 was designed from the cross-fertilisation of the basic hydrophilic amino pharmacophore of mitoxantrone, and an aminonaphthalimide scaffold of the drug candidate, amonafide. The compounds are also fluorescent pH probes based on photoinduced electron transfer (PET) and internal charge transfer (ICT). The compounds are sensitive to solvent polarity with large Stoke shifts (>90 nm) and provide emissive-coloured solutions (blue to yellow). Excited state pK a s of 9.0-9.3 and fluorescence quantum yields of 0.47-0.58 were determined in water. The cytotoxicity and cellular fluorescent imaging properties of the compounds were tested on human cancer cell lines K562 and MCF-7 by the MTT assay, phase contrast and fluorescence microscopy. Compounds 1 and 3 with flexible aminoalkyl chains exhibited GI 50 comparable to amonafide, while 2 and 4 with a rigid piperazine moiety and butyl chain are less cytotoxic. Fluorescence microscopy with 1 allowed for the visualization of the intracellular microenvironment exemplifying the potential utility of such hybrid molecules as anticancer and fluorescent cellular imaging agents., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To prevent opioid-related mortality, the Veterans Health Administration (VHA) developed a national Opioid Overdose Education and Naloxone Distribution (OEND) program., Setting: VHA's OEND program sought national implementation of OEND across all medical facilities (n = 142)., Practice Description: This paper describes VHA's efforts to facilitate nationwide health care system-based OEND implementation, including the critical roles of VHA's national pharmacy services and academic detailing services., Practice Innovation: VHA is the first large health care system in the United States to implement OEND nationwide. Launching the national program required VHA to translate a primarily community-based public health approach to OEND into a health care system-based approach that distributed naloxone to patients with opioid use disorders as well as to patients prescribed opioid analgesics. Key innovations included developing steps to implement OEND, pharmacy developing standard naloxone rescue kits, adding those kits to the VHA National Formulary, centralizing kit distribution, developing clinical guidance for issuing naloxone kits, and supporting OEND as a focal campaign of academic detailing. Other innovations included the development of patient and provider education resources (e.g., brochures, videos, accredited training) and implementation and evaluation resources (e.g., technical assistance, clinical decision support tools)., Evaluation: Clinical decision support tools that leverage VHA national data are available to clinical staff with appropriate permissions. These tools allow staff and leaders to evaluate OEND implementation and provide actionable next steps to help them identify patients who could benefit from OEND., Results: Through fiscal year 2016, VHA dispensed 45,178 naloxone prescriptions written by 5693 prescribers to 39,328 patients who were primarily prescribed opioids or had opioid use disorder. As of February 2, 2016, there were 172 spontaneously reported opioid overdose reversals with the use of VHA naloxone prescriptions., Conclusion: VHA has successfully translated community-based OEND into health care system-based OEND targeting 2 patient populations. There is a tremendous amount that can be learned from VHA's experience implementing this novel health care innovation nationwide., (Published by Elsevier Inc.)

Due to the toxic effect of asbestos, other materials with similar chemical-physical characteristics have been introduced to substitute it. We evaluate the angiogenic effect of certain asbestos substitute fibres such as glass fibres (GFs), ceramic fibres (CFs) and wollastonite fibres (WFs) and then compare angiogenic responses to those induced by crocidolite asbestos fibres (AFs). An in vitro model using human endothelial cells in small islands within a culture matrix of fibroblasts (Angio-Kit) was used to evaluate vessel formation. The release of IL-6, sIL-R6, IL-8, VEGF-A and their soluble receptors, sVEGFR-1, sVEGFR-2, was determined in the conditioning medium of Angio-Kit system after fibre treatment. ROS formation and cell viability were evaluated in cultured endothelial cells (HUVEC). To evaluate the involvement of intracellular mechanisms, EGFR signalling, ROS formation and nuclear factor-κB (NFκB) pathway were then inhibited by incubating HUVEC cells with AG1478, NAC and PDTC respectively, and the cytokine and growth factor release was analyzed in the culture medium after 7 days of fibre incubation. Among the mineral fibres tested, WFs markedly induced blood vessel formation which was associated with release of IL-6 and IL-8, VEGF-A and their soluble receptors. ROS production was observed in HUVEC after WFs treatment which was associated with cell cytotoxicity. The EGFR-induced ERK phosphorylation and ROS-mediated NFκB activation were involved in the cytokine and angiogenic factor release. However, only the EGFR activation was able to induce angiogenesis. The WFs are potential angiogenic agents that can induce regenerative cytokine and angiogenic factor production resulting in the formation of new blood vessels., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Epidemiological studies have shown that mortality from malignant mesothelioma (MM) and lung cancer have increased with increasing cumulative exposure to asbestos. To investigate whether tumour-related biomarkers can contribute towards the evaluation of the carcinogenic risk in populations exposed to asbestos, the DNA adduct 8-hydroxy-2'-deoxyguanosine (80HdG), interleukine-6 (IL-6), platelet-derived growth factor (PDGF-BB), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGFbeta) and soluble mesothelin-related peptides (SMRPs) were analysed in a cohort of workers differently exposed to asbestos fibres at the workplace. To document biomarker levels in an unexposed population, 54 age-matched subjects were enrolled. A total of 119 subjects with a history of occupational exposure to asbestos underwent clinical examination and were interviewed by trained personnel, responding to a detailed questionnaire related to duration of asbestos exposure, smoking, and occupational task. According to the occupational tasks, asbestos-exposed subjects were analysed for their asbestos cumulative dose and the association with the biomarkers was evaluated. Among the occupational groups, maintenance workers, pipe fitters and electricians were exposed to a higher cumulative dose of asbestos fibres. Exposure to asbestos significantly increased the steady-state content of 80HdG in DNA. Elevated levels of 80HdG and IL-6 best reflected a high level of SMRPs, which is related to cell transformation. Subjects heavily exposed to asbestos [> 60(ff/cm3) x years] showed also a higher level of angiogenic factors. A combination of angiogenic biomarkers with a specific mesothelioma-biomarker such as SMRPs could be used for close surveillance of workers with a history of asbestos exposure.

The evidence for HLA-Cw antigens' involvement in the modulation of the immune response in bone marrow transplantation, NK alloreactivity and the susceptibility and follow-up for different diseases has been growing in the recent years, but very few data on HLA-Cw distribution in healthy Italian subjects are available to date. This report presents an updated description of HLA-Cw frequencies in Italy, comparing data from the northern (Lombardia) and southern (Campania and Puglia) parts of the country. A total of 1101 healthy subjects of Italian origin were genotyped, and the results showed that HLA-Cw*04, Cw*07, Cw*12, and, in particular, Cw*0401, Cw*0701, Cw*1203, were the most frequent alleles found in all three regions analysed. Nevertheless, statistically significant differences were observed in Cw*07 distribution, which was more frequent in the southern than in the northern part of Italy (28.8% vs 22.4%; p=0.001; OR: 1.4; 95%CI: 1.14-1.73), and in Cw*12 distribution, which was more frequent in the north than the south (17.0% vs 12.4%; p=0.007, OR: 1.4; 95%CI: 1.10-1.91). These results, which give an improved pattern of distribution of HLA-Cw alleles in the Italian population, would be useful in bone marrow transplantation and anthropological studies. Moreover, due to the important role of HLA-Cw antigens in modulation of the immune response and NK alloreactivity, these data would be of interest in studies on susceptibility, follow-up and/or protection against different diseases.

Lymphocyte differentiation, maturation and peripheral functions are affected by the thymic protein hormone thymulin. Mercury at very low concentrations has been seen to impair some lymphocytic functions causing subclinical manifestations in exposed workers. The present study was performed to test in vitro the effect of mercury on the production kinetics of thymulin using cultures of whole thymuses from young mice. Exposure to mercury (10(-8) M and 10(-6) M) added to the cultures, reduced kinetic thymulin production at all time intervals considered (1, 2, 4, 5 and 6 h) as compared to kinetic thymulin production of thymuses from young control mice. After the first hour the inhibition is more evident at the highest mercury concentration. Thymulin production decreased by 70, 74, 82 and 86% and by 55, 66, 73 and 81% for mercury concentrations of 10(-6) M and 10(-8) M, respectively, after 2, 4, 5 and 6 h. Mercury toxic effect on thymulin kinetics may be directly exerted to thymulin synthesis in epithelial cells, although it is less dramatic than that of cycloheximide (CHX), known as a potent inhibitor of protein synthesis in such cells. The toxic effect of mercury on thymic endocrine activity might cause the subclinical effects on cell-mediated immunological status observed in mercury exposed workers.

Our previous research (Soleo L, Vacca A, Vimercati L et al. Occup Environ Med 1997;54:437-442) showed a reduction in tumor necrosis factor-alpha (TNF-alpha) serum levels in workers with prolonged exposure to low doses of inorganic mercury, suggesting an in vivo functional defect of the monocyte-macrophage system. On this basis, here we wondered whether workers exposed to lower doses of metallic mercury displayed possible changes in the monocyte-macrophage system. In this particular cohort of workers, we also sought for the effects of the exposure on the polymorphonuclear leukocytes (PMNL) chemotaxis. The monocyte-macrophage system and the natural killer (NK) cells were examined in 19 exposed workers and in 25 unexposed workers, as the control group (controls). Specifically, the circulating monocyte-macrophage cells and their CD13, CD15 and CD33 subsets, serum cytokines (IL-8, GM-CSF and TNF-alpha) and the NK cells were analyzed. In seven exposed and seven controls randomly chosen workers the PMNL chemotaxis was also assessed. The selected indicator of mercury exposure were the levels of mercury in the urine (U-Hg), that was significantly higher in exposed workers than the controls (9.7 +/- 5.5 microg/l and 2.4 +/- 1.2 microg/l, respectively). None of the exposed workers had shown signs of either acute or chronic inorganic mercury toxicity or any form of hypersensitivity. Several immunological variables tested, monocyte-macrophage cells and their subsets, NK cells and serum cytokines overlapped between the exposed and the control workers. When the workers were considered as a whole (exposed plus controls), no correlation was found between current U-Hg and all immunological parameters. However, when exposed workers were studied separately, an inverse correlation was disclosed between cumulative U-Hg and cells (as percentage) expressing the CD13 (r = -0.599; P = 0.007) and CD15 (r = -0.614; P = 0.005) molecules, and NK cells (r = -0.455; P = 0.05). Moreover, a significant impairment in the PMNL chemotaxis (t = 3.70; P = 0.003) was observed in the exposed workers. The results of our study suggest that the exposure to very low levels of metallic mercury led to subtle impairment of circulating monocyte and NK cells (as percentages) according to the increase in U-Hg levels, as well as of the PMNL chemotactic function in this particular group of workers, even though they remain clinically asymptomatic. Therefore, we suggest that impairment of these parameters provide a sensitive indicator of metallic mercury and other chemical contaminants present in the environment.

This review deals with some of our contributions to the use of chemotaxis, as a tool in evaluating effects of industrial xenobiotics on PMN, either in vitro or ex vivo. In vitro experiments have shown that lead, arsenic, styrene and 2,5-hexanedione, a major neurotoxicant metabolite of n-hexane, reduce chemotaxis. The most important results of ex vivo experiments have confirmed those obtained in vitro with styrene and 2,5-hexanedione: a significant reduction of chemotaxis was indeed observed in PMN harvested from workers exposed to low levels of n-hexane or styrene who did not show any sign of biochemical or clinical alteration. After 3 weeks under non-exposed conditions, the chemotactic indexes were markedly increased in most of the workers which were exposed to styrene and in all the workers exposed to n-hexane, all of whom have shown a reduced chemotaxis at the first blood sampling. Moreover chemotaxis was found to be significantly reduced at relative low levels of lead: results of the in vitro and ex vivo experiments show a comparable ranking of midpoint inhibition concentrations. We are only at the dawn of the understanding of the relation between occupational xenobiotics and PMN chemotaxis. This research area is still promising for the future, since PMN chemotaxis seems to be adequate and it must therefore enter in well-defined study protocols for investigating the potential immunotoxicity of occupational chemicals to which humans are exposed at low levels.

The fluorescence decay of 1,6-diphenyl-1,3,5-hexatriene has been used to characterize the structural organization of erythrocyte membranes. At 37 degrees C a large fraction of the decay (0.96) is associated with a lifetime value of 11.31 ns, while a minor fraction has a short lifetime of 2.63 ns. The distribution analysis approach has shown that the 11 ns component can be described using a Lorentzian distribution function having a full width at half maximum of 0.27 ns. The width of this component is associated with the membrane structural organization since liposomes from erythrocyte total lipid extract exhibit a narrower width. Moreover the distribution width is sensitive to different treatments of erythrocyte membrane.

Although the phenomenon of stimulus-response coupling in polymorphonuclear leukocytes involves a series of membrane events the influence of stimulation on membrane fluidity is to clarify. In our experiments we have used 1-(4-trimethylaminophenyl) 6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene fluorescence polarization technique to evaluate membrane fluidity in living polymorphonuclear leukocytes after stimulation with N-formyl-methyonil-leucyl-phenylalanine peptide which has a well defined membrane receptor on the plasma membrane. We report that polymorphonuclear leukocytes stimulation increases 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene polarization, only when colcemid, a microtubule disrupting drug, is added to polymorphonuclear leukocytes. This can be viewed as an indirect evidence that microtubules are involved in the control of polymorphonuclear leukocytes membrane fluidity. On the contrary no changes have been observed with 1,6-diphenyl-1,3,5-hexatriene. This study indicates the potential use of 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene to evaluate the involvement of plasma membrane physical state during intact cell activity.

Since lead impairs in vitro the functions of macrophagic cells, we have studied the chemotactic activity of polymorphonuclear leukocytes (PMNs) obtained from lead acid battery workers who were removed from exposure one month before, because they had an abnormal lead absorption. Controls were 18 age matched subjects without any history of occupational lead exposure. Both lead acid battery workers and controls had no alterations of the blood haematological and metabolic parameters. Chemotaxis was carried on in Boyden chambers using zymosan activated serum as chemotactic stimulus. The chemotactic indexes are 56.4 +/- 8.7 in acid battery workers and 75.6 +/- in controls. The difference, which is statistically significant, shows that lead workers have an impairment of PMNs chemotactic activity.