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Background: Pulmonary involvement in systemic juvenile idiopathic arthritis (SJIA) is a rare but dangerous complication. The main risk factors are already known, such as macrophage activation syndrome, a refractory course of systemic juvenile arthritis, infusion reaction to interleukin 1 and/or interleukin 6 blockers, trisomy 21, and eosinophilia. However, information about respiratory system involvement (RSI) at the onset of SJIA is scarce. Our study aimed to evaluate the specific features of children with SJIA with RSI and their outcomes. Methods: In a single-center retrospective cohort study, we compared the information from the medical records of 200 children with SJIA according to ILAR criteria or SJIA-like disease (probable/possible SJIA) with and without signs of RSI (dyspnea, shortness of breath, pleurisy, acute respiratory distress syndrome, and interstitial lung disease (ILD)) at the disease onset and evaluated their outcomes (remission, development of chronic ILD, clubbing, and pulmonary arterial hypertension). Results: A quarter (25%) of the SJIA patients had signs of the RSI at onset and they more often had rash; hepato- and splenomegaly; heart (pericarditis, myocarditis), central nervous system, and kidney involvement; hemorrhagic syndrome; macrophage activation syndrome (MAS, 44.4% vs. 9.0%, p = 0.0000001); and, rarely, arthritis with fewer active joints, compared to patients without RSI. Five patients (10% from the group having RSI at the onset of SJIA and 2.5% from the whole SJIA cohort) developed fibrosing ILD. All of them had a severe relapsed/chronic course of MAS; 80% of them had a tocilizumab infusion reaction and further switched to canakinumab. Unfortunately, one patient with Down's syndrome had gone. Conclusion: Patients with any signs of RSI at the onset of the SJIA are required to be closely monitored due to the high risk of the following fibrosing ILD development. They required prompt control of MAS, monitoring eosinophilia, and routine checks of night oxygen saturation for the prevention/early detection of chronic ILD.

Understanding of DNA interaction with carbonaceous surfaces (including graphite, graphene and carbon nanotubes) is important for the development of DNA-based biosensors and other biotechnological devices. Though many issues related to DNA adsorption on graphitic surfaces have been studied, some important aspects of DNA interaction with graphite remain unclear. In this work, we use atomic force microscopy (AFM) equipped with super-sharp cantilevers to analyze the morphology and conformation of relatively long DNA molecule adsorbed on a highly oriented pyrolytic graphite (HOPG) surface. We have revealed the effect of DNA embedding into an organic monolayer of N,N'-(decane-1,10-diyl)-bis(tetraglycinamide) (GM), which may "freeze" DNA conformation on a HOPG surface during drying. The dependence of the mean squared point-to-point distance on the contour length suggests that DNA adsorbs on a bare HOPG by a "kinetic trapping" mechanism. For the first time, we have estimated the unfolded fraction of DNA upon contact with a HOPG surface (24 ± 5 %). The obtained results represent a novel experimental model for investigation of the conformation and morphology of DNA adsorbed on graphitic surfaces and provide with a new insight into DNA interaction with graphite., 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 © 2024 Elsevier B.V. All rights reserved.)

We propose a sparse computation method for optimizing the inference of neural networks in reinforcement learning (RL) tasks. Motivated by the processing abilities of the brain, this method combines simple neural network pruning with a delta-network algorithm to account for the input data correlations. The former mimics neuroplasticity by eliminating inefficient connections; the latter makes it possible to update neuron states only when their changes exceed a certain threshold. This combination significantly reduces the number of multiplications during the neural network inference for fast neuromorphic computing. We tested the approach in popular deep RL tasks, yielding up to a 100-fold reduction in the number of required multiplications without substantial performance loss (sometimes, the performance even improved)., (© 2023. The Author(s).)

Although the World Health Organization has declared the end of the COVID-19 pandemic, doctors continue to register new cases of the disease among both adults and children. Unfortunately, the course of COVID-19 in children can have a severe form, with death being a potential outcome. The absence of published works discussing the pathological morphology of COVID-19 in children prevents the objective analysis of the disease's pathogenesis, including among the adult population. In this vein, the objective of our study is to identify the morphological features of the lungs' involvement and evaluate virus-host interactions in the case of COVID-19 in patients at a pediatric medical practice. We present the results of the study of the lungs of three children who died due to COVID-19, highlighting the predominant involvement of their respiratory organs at different stages of the disease (5, 21, and 50 days). This article presents data obtained from histopathological and immunohistochemical investigations, taking into account the results of clinical and laboratory indicators and intravital and postmortem SARS-CoV-2 PCR investigations. The common finding of all of the examined COVID-19 cases is the involvement of the endothelium in microcirculation vessels, which are considered to be a primary target of various pathogenic influencing factors. We also discuss both the significance of apoptosis as a result of virus-host interactions and the most likely cause of endothelium cell destruction. The results of this study could be useful for the development of endothelium-protective therapy to prevent the progression of disseminated intravascular coagulation syndrome.

Nanoplastics have been widely studied as environmental pollutants, which can accumulate in the human body through the food chain or direct contact. Research has shown that nanoplastics can affect the immune system and mitochondrial function, but the underlying mechanisms are unclear. Lungs and macrophages have important immune and metabolic functions. This study explored the effects of 100 nm PS-NPs on innate immunity, mitochondrial function, and cellular metabolism-related pathways in lung (BEAS-2B) cells and macrophages (RAW264.7). The results had shown that PS-NPs exposure caused a decrease in mitochondrial membrane potential, intracellular ROS accumulation, and Ca 2+ overload, and activated the cGAS-STING signaling pathway related to innate immunity. These changes had been observed at concentrations of PS-NPs as low as 60 μg/mL, which might have been comparable to environmental levels. Non-target metabolomics and Western Blotting results confirmed that PS-NPs regulated prostaglandin B1 and other metabolites to cause cell damage through the cGAS-STING pathway. Supplementation of prostaglandin B1 alleviated the immune activation and metabolic disturbance caused by PS-NPs exposure. This study identified PS-NPs-induced innate immune activation, mitochondrial dysfunction, and metabolic toxicity pathways, providing new insights into the potential for adverse outcomes of NPs in human life., 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 Elsevier Ltd. All rights reserved.)

NMDA excitotoxicity, as a part of glutamate excitotoxicity, has been proposed to contribute significantly to many retinal diseases. Therefore, understanding mechanisms of NMDA excitotoxicity will provide further insight into the mechanisms of many retinal diseases. To study mechanisms of NMDA excitotoxicity in vivo, we used an animal model in which NMDA (20 mM, 2 µL) was injected into the vitreous of mice. We also used high-throughput expression profiling, various animals with reduced expression of target genes, and animals treated with the oral iron chelator deferiprone. We found that the expression of many genes involved in inflammation, programmed cell death, free radical production, oxidative stress, and iron and calcium signaling was significantly increased 24 h after NMDA treatment. Meanwhile, decreased activity of the pro-inflammatory TNF signaling cascade and decreased levels of ferrous iron (Fe 2+ , required for free radical production) led to significant neuroprotection in NMDA-treated retinas. Since increased TNF signaling activity and high Fe 2+ levels trigger regulated necrosis, which, in turn, lead to inflammation, we proposed an important role in NMDA excitotoxicity of a positive feedback loop in which regulated necrosis promotes inflammation, which subsequently triggers regulated necrosis., (© 2023. The Author(s).)

The acquisition of reliable knowledge about the mechanism of short laser pulse interactions with semiconductor materials is an important step for high-tech technologies towards the development of new electronic devices, the functionalization of material surfaces with predesigned optical properties, and the manufacturing of nanorobots (such as nanoparticles) for bio-medical applications. The laser-induced nanostructuring of semiconductors, however, is a complex phenomenon with several interplaying processes occurring on a wide spatial and temporal scale. In this work, we apply the atomistic-continuum approach for modeling the interaction of an fs-laser pulse with a semiconductor target, using monolithic crystalline silicon (c-Si) and porous silicon (Si). This model addresses the kinetics of non-equilibrium laser-induced phase transitions with atomic resolution via molecular dynamics, whereas the effect of the laser-generated free carriers (electron-hole pairs) is accounted for via the dynamics of their density and temperature. The combined model was applied to study the microscopic mechanism of phase transitions during the laser-induced melting and ablation of monolithic crystalline (c-Si) and porous Si targets in a vacuum. The melting thresholds for the monolithic and porous targets were found to be 0.32 J/cm 2 and 0.29 J/cm 2 , respectively. The limited heat conduction mechanism and the absence of internal stress accumulation were found to be involved in the processes responsible for the lowering of the melting threshold in the porous target. The results of this modeling were validated by comparing the melting thresholds obtained in the simulations to the experimental values. A difference in the mechanisms of ablation of the c-Si and porous Si targets was considered. Based on the simulation results, a prediction regarding the mechanism of the laser-assisted production of Si nanoparticles with the desired properties is drawn.

The production of non-toxic and homogeneous colloidal solutions of nanoparticles (NPs) for biomedical applications is of extreme importance nowadays. Among the various methods for generation of NPs, pulsed laser ablation in liquids (PLAL) has proven itself as a powerful and efficient tool in biomedical fields, allowing chemically pure silicon nanoparticles to be obtained. For example, laser-synthesized silicon nanoparticles (Si NPs) are widely used as contrast agents for bio visualization, as effective sensitizers of radiofrequency hyperthermia for cancer theranostics, in photodynamic therapy, as carriers of therapeutic radionuclides in nuclear nanomedicine, etc. Due to a number of complex and interrelated processes involved in the laser ablation phenomenon, however, the final characteristics of the resulting particles are difficult to control, and the obtained colloidal solutions frequently have broad and multimodal size distribution. Therefore, the subsequent fragmentation of the obtained NPs in the colloidal solutions due to pulsed laser irradiation can be utilized. The resulting NPs' characteristics, however, depend on the parameters of laser irradiation as well as on the irradiated material and surrounding media properties. Thus, reliable knowledge of the mechanism of NP fragmentation is necessary for generation of a colloidal solution with NPs of predesigned properties. To investigate the mechanism of a laser-assisted NP fragmentation process, in this work, we perform a large-scale molecular dynamics (MD) modeling of FS laser interaction with colloidal solution of Si NPs. The obtained NPs are then characterized by their shape and morphological properties. The corresponding conclusion about the relative input of the properties of different laser-induced processes and materials to the mechanism of NP generation is drawn.

The COVID-19 pandemic has illustrated the unprecedented challenges of ensuring the continuity of operations in a supply chain as suppliers' and their suppliers stop producing due the spread of infection, leading to a degradation of downstream customer service levels in a ripple effect. In this paper, we contextualize a dynamic approach and propose an optimal control model for supply chain reconfiguration and ripple effect analysis integrated with an epidemic dynamics model. We provide supply chain managers with the optimal choice over a planning horizon among subsets of interchangeable suppliers and corresponding orders; this will maximize demand satisfaction given their prices, lead times, exposure to infection, and upstream suppliers' risk exposure. Numerical illustrations show that our prescriptive forward-looking model can help reconfigure a supply chain and mitigate the ripple effect due to reduced production because of suppliers' infected workers. A risk aversion factor incorporates a measure of supplier risk exposure at the upstream echelons. We examine three scenarios: (a) infection limits the capacity of suppliers, (b) the pandemic recedes but not at the same pace for all suppliers, and (c) infection waves affect the capacity of some suppliers, while others are in a recovery phase. We illustrate through a case study how our model can be immediately deployed in manufacturing or retail supply chains since the data are readily accessible from suppliers and health authorities. This work opens new avenues for prescriptive models in operations management and the study of viable supply chains by combining optimal control and epidemiological models., (© 2023 Elsevier B.V. All rights reserved.)

Background: p53 wild-type lung cancer cells can develop radiation resistance. Circular RNA (circRNA) consists of a family of transcripts with exclusive structures. circRNA is critical in tumorigenesis and is a potential biomarker or therapeutic target. It is uncertain how circRNA expression and functions are regulated post-radiation in p53 wild-type cancer cells., Methods: A549 or H1299 cells were divided into p53 -wt and p53 -KO groups by CRISPR/Cas9; both groups were subjected to 4 Gy ionizing radiation (IR: p53 -wt -IR and p53 -KO -IR). RNA-seq, CCK8, cell cycle, and other functional and mechanism experiments were performed in vivo. p53 gene knockout mice were generated to test the cell results in vitro., Results: circRNAs were found in differential groups. circRNA_0006420 (IRSense) was upregulated in p53 -wt cells but had the same expression level as p53 -KO cells after radiation, indicating that p53 silencing prevents its upregulation after IR. In the presence of p53, upregulated IRSense post-radiation induces G2/M arrest by regulating DNA damage repair (DDR) pathway-related proteins. Meanwhile, upregulated IRSense post-radiation aggravates the radiation-induced epithelial-mesenchymal transition (EMT). Interestingly, in the presence of p53, it promotes IRSense/HUR/PTBP1 complex formation resulting in the promotion of the radiation-induced EMT. Moreover, c-Jun regulates the upregulation of p53 transcription after radiation treatment. For these lung cancer cells with p53, upregulated IRSense aggravates lung cancer cell proliferation and increases radiation resistance by interacting with HUR (ElAV-like protein 1) and PTBP1 (polypyrimidine tract-binding protein 1) in the nucleus., Conclusions: Lung cancer cells retaining p53 may upregulate circRNA_0006420 (IRSense) expression post radiation to form an IRSense/HUR/PTBP1 complex leading to radiotherapy resistance. This study furthers our understanding of the roles of circRNA in regulating the effect of radiotherapy and provides novel therapeutic avenues for effective clinical lung cancer therapies., 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. Production and hosting by Elsevier B.V.)

Retinal ischemia-reperfusion (IR)-which ultimately results in retinal ganglion cell (RGC) death-is a common cause of visual impairment and blindness worldwide. IR results in various types of programmed cell death (PCD), which are of particular importance since they can be prevented by inhibiting the activity of their corresponding signaling cascades. To study the PCD pathways in ischemic RGCs, we used a mouse model of retinal IR and a variety of approaches including RNA-seq analysis, knockout animals, and animals treated with an iron chelator. In our RNA-seq analysis, we utilized RGCs isolated from retinas 24 h after IR. In ischemic RGCs, we found increased expression of many genes that regulate apoptosis, necroptosis, pyroptosis, oxytosis/ferroptosis, and parthanatos. Our data indicate that genetic ablation of death receptors protects RGCs from IR. We showed that the signaling cascades regulating ferrous iron (Fe 2+ ) metabolism undergo significant changes in ischemic RGCs, leading to retinal damage after IR. This data suggests that the activation of death receptors and increased Fe 2+ production in ischemic RGCs promote the simultaneous activation of apoptosis, necroptosis, pyroptosis, oxytosis/ferroptosis, and parthanatos pathways. Thus, a therapy is needed that concurrently regulates the activity of the multiple PCD pathways to reduce RGC death after IR.

DcAFF (discontinuous aligned fibre filament) is a novel material for fused filament fabrication (FFF) 3D printing made of highly aligned discontinuous fibres produced using high performance discontinuous fibre (HiPerDiF) technology. It reinforces a thermoplastic matrix to provide high mechanical performance and formability. Accurate printing of DcAFF poses a challenge, especially for complex geometries, because: (i) there is a discrepancy between the path where the filament experiences the adhering pressure from the filleted nozzle and the nozzle path; and (ii) the rasters display poor adhesion to the build platform immediately after deposition, which causes the filament to be dragged when the printing direction changes. This paper explains the implication of these phenomena on steering capabilities and examines the techniques for improving DcAFF printing accuracy. In the first approach, the machine parameters were adjusted to improve the quality of the sharp turning angle without changing the desired path, but this showed insignificant effects in terms of precision improvements. In the second approach, a printing path modification with a compensation algorithm was introduced. The nature of the inaccuracy of the printing at the turning point was studied with a first-order lag relationship. Then the equation to describe the deposition raster inaccuracy was determined. A proportional-integral (PI) controller was added to the equation to calculate the nozzle movement in order to bring the raster back to the desired path. The applied compensation path is shown to give an accuracy improvement in curvilinear printing paths. This is particularly beneficial when printing larger circular diameter curvilinear printed parts. The developed printing approach can be applied with other fibre reinforced filaments to achieve complex geometries.

Currently, the chemistry of self-healing polymers is aimed not only at obtaining materials with high self-healing efficiency, but also at improving their mechanical performance. This paper reports on a successful attempt to obtain self-healing copolymers films of acrylic acid, acrylamide and a new metal-containing complex of cobalt acrylate with a 4'-phenyl-2,2':6',2″-terpyridine ligand. Samples of the formed copolymer films were characterized by ATR/FT-IR and UV-vis spectroscopy, elemental analysis, DSC and TGA, SAXS, WAXS and XRD studies. The incorporation of the metal-containing complex directly into the polymer chain results in an excellent tensile strength (122 MPa) and modulus of elasticity (4.3 GPa) of the obtained films. The resulting copolymers demonstrated self-healing properties both at acidic pH (assisted by HCl healing) with effective preservation of mechanical properties, and autonomously in a humid atmosphere at room temperature without the use of initiators. At the same time, with a decrease in the content of acrylamide, a decrease in the reducing properties was observed, possibly due to an insufficient amount of amide groups to form hydrogen bonds through the interface with terminal carboxyl groups, as well as a decrease in the stability of complexes in samples with a high content of acrylic acid.

Investigation of hyaluronic acid (HA) morphology and mechanical properties at a single-molecule level is important for the development of HA based biomaterials. We have developed the atomic force microscopy (AFM) based approach for quantitative characterization of conformation of HA molecules. HA molecules adsorbed on a modified graphitic surface form oriented linear segments. Conformation of HA molecules can be considered as two-dimensional quasi-projection of a three-dimensional conformation locally straightened by a substrate. The persistence length and Young's modulus of biomolecules estimated using wormlike chain model decrease from 15.7 to 9.9 nm, and from ∼21 to ∼13 GPa, respectively, when KCl concentration increases from 0 to 100 mM. The dependence of the persistence length on ionic strength supports the Odijk-Skolnick-Fixman model of polyelectrolyte stiffening in electrolyte solution. The obtained results represent a new insight into the conformation and mechanical characteristics of HA molecules and complement the characterization of this biopolymer by bulk methods., 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 Ltd. All rights reserved.)

This paper explores the use of Discontinuous Aligned Fibre Filament (DcAFF), a novel discontinuous fibre reinforced thermoplastic filament for 3D printing, to produce structural complex parts. Compared to conventional composite manufacturing, 3D printing has great potential in steering fibres around small structural features. In this current study, the initial thin carbon fibre (CF)-poly(L-lactic acid) (PLA) tape, produced with the High Performance Discontinuous Fibre (HiPerDiF) technology, is now reshaped into a circular cross-section filament, the DcAFF, using a bespoke machine designed to be scalable to high production rates rather than using a labour-intensive manual moulding method as in previous work. The filaments are then fed to a general-purpose 3D printer. Tensile and open-hole tensile tests were considered in this paper for mechanical and processability of DcAFF. The 3D printed specimens fabricated with the DcAFF show superior tensile properties compared to other PLA-based 3D printed composites, even those containing continuous fibres. Curvilinear open-hole tensile test samples were fabricated to explore the processability and performances of such material in complex shapes. The mechanical performance of the produced specimens was benchmarked against conventionally laid-up specimens with a cut hole. Although the steered specimens produced have lower strength than the fully consolidated samples, the raster generated by the printing path has turned the failure mechanism of the composite from brittle to ductile.

Ischemia-reperfusion (IR) injury is implicated in a large array of pathological conditions in the retina. Increasing experimental evidence suggests that programmed necrosis makes a significant contribution to inflammation and retinal damage triggered by IR. Since there are many types of programmed necrosis, it is important to identify those involved in retinal IR to determine the correct treatment. To this end, we used a mouse model of retinal IR and a variety of approaches including RNA-seq data analysis. Our RNA-seq data revealed the rapid development of ischemic pathology in the retina during the first 24 h after reperfusion. We found that at least four types of programmed necrosis including necroptosis, pyroptosis, oxytosis/ferroptosis, and parthanatos are simultaneously involved in retinal IR. Our data suggest that the high activity of the TNF pathway at the early stage of retinal IR leads to early activation of necroptosis while significant activity of other types of programmed necrosis appears later. Our results indicate that TNF, glutamate, and ferrous iron generated by Steap3 may be key players concurrently triggering at least necroptosis, oxytosis/ferroptosis, and parthanatos in ischemic retinal ganglion cells (RGCs). Thus, multiple signaling cascades involved in programmed necrosis should be synchronously targeted for therapeutic purposes to treat retinal IR., (© 2022. The Author(s).)

Modern artificial intelligence (AI) systems, based on von Neumann architecture and classical neural networks, have a number of fundamental limitations in comparison with the mammalian brain. In this article we discuss these limitations and ways to mitigate them. Next, we present an overview of currently available neuromorphic AI projects in which these limitations are overcome by bringing some brain features into the functioning and organization of computing systems (TrueNorth, Loihi, Tianjic, SpiNNaker, BrainScaleS, NeuronFlow, DYNAP, Akida, Mythic). Also, we present the principle of classifying neuromorphic AI systems by the brain features they use: connectionism, parallelism, asynchrony, impulse nature of information transfer, on-device-learning, local learning, sparsity, analog, and in-memory computing. In addition to reviewing new architectural approaches used by neuromorphic devices based on existing silicon microelectronics technologies, we also discuss the prospects for using a new memristor element base. Examples of recent advances in the use of memristors in neuromorphic applications are also given., Competing Interests: DI, MK, and DL were employed by the company Cifrum. 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 © 2022 Ivanov, Chezhegov, Kiselev, Grunin and Larionov.)

Background: Previously we demonstrated that in patients with preeclampsia elevated levels of endogenous Na/K-ATPase inhibitor, marinobufagenin, cause inhibition of Friend leukemia virus integration 1 (Fli1), a negative regulator of collagen-1 synthesis. We hypothesized that in vitro silencing of Fli1 in healthy human umbilical arteries would be associated with an increase in collagen-1 output, similar to the effect of preeclampsia in rat and human tissues., Methods: The isolated segments of healthy human umbilical arteries were tested for sensitivity to MBG and Fli1 silencing with Fli1 siRNA or control siRNA., Results: Following 24-hour incubation of arteries with nanomolar concentrations of marinobufagenin, Fli1 expression was inhibited 5-fold (P < 0.001), and synthesis of collagen-1 increased 3 times (P < 0.01). Twenty-four-hour incubation of umbilical artery fragments with Fli1 siRNA caused a dramatic decrease of Fli1 (7-fold; P < 0.001) and cytoplasmic PKC δ (4-fold; P < 0.001) expression in comparison to control siRNA or untreated control, followed by elevation in procollagen (3-fold; P < 0.001) and collagen-1 (3-fold; P < 0.001) levels in vascular tissue., Conclusions: Our results show that after silencing the Fli1 gene in healthy human umbilical arteries a new phenotype emerges which is typical for preeclampsia and is associated with vascular fibrosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This article investigates the impacts of the COVID-19 pandemic and their proactive mediation by adaptive operational decisions in different network design structures in anticipation of and during the pandemic. In generalized terms, we contribute to the understanding of the effect of preparedness and recovery decisions in a pandemic setting on supply chain operations and performance. In particular, we examine the impact of inventory pre-positioning in anticipation of a pandemic and the adaptation of production-ordering policy during the pandemic. Our model combines three levels, which is not often seen jointly in operations management literature, i.e., pandemic dynamics, supply chain design, and operational production-inventory control policies. The analysis is performed for both two- and three-stage supply chains and different scenarios for pandemic dynamics (i.e., uncontrolled propagation or controlled dispersal with lockdowns). Our findings suggest that two-stage supply chains exhibit a higher vulnerability in disruption cases. However, they are exposed to a lower system inertia and show positive effects at the recovery stage. Supply chain adaptation ahead of a pandemic is more advantageous than during the pandemic when specific operational recovery policies are deployed. We show that it is instructive to avoid simultaneous changes in structural network design and operational policies since that can destabilize the production-inventory system and result in higher product shortages., (© 2022 Elsevier Ltd. All rights reserved.)

Increased electricity consumption along with the transformations of the energy systems and interruptions in energy supply can lead to a blackout, i.e., the total loss of power in an area (or a set of areas) of a longer duration. This disruption can be fatal for production, logistics, and retail operations. Depending on the scope of the affected areas and the blackout duration, supply chains (SC) can be impacted to different extent. In this study, we perform a simulation analysis using anyLogistix digital SC twin to identify potential impacts of blackouts on SCs for scenarios of different severity. Distinctively, we triangulate the design and evaluation of experiments with consideration of SC performance, resilience, and viability. The results allow for some generalizations. First, we conceptualize blackout as a special case of SC risks which is distinctively characterized by a simultaneous shutdown of several SC processes, disruption propagations (i.e., the ripple effect), and a danger of viability losses for entire ecosystems. Second, we demonstrate how simulation-based methodology can be used to examine and predict the impacts of blackouts, mitigation and recovery strategies. The major observation from the simulation experiments is that the dynamics of the power loss propagation across different regions, the blackout duration, simultaneous unavailability of supply and logistics along with the unpredictable customer behavior might become major factors that determine the blackout impact and influence selection of an appropriate recovery strategy. The outcomes of this research can be used by decision-makers to predict the operative and long-term impacts of blackouts on the SCs and viability and develop mitigation and recovery strategies. The paper is concluded by summarizing the most important insights and outlining future research agenda toward SC viability, reconfigurable SC, multi-structural SC dynamics, intertwined supply networks, and cross-structural ripple effects., (© The Author(s) 2022.)

The COVID-19 pandemic has wreaked havoc across supply chain (SC) operations worldwide. Specifically, decisions on the recovery planning are subject to multi-dimensional uncertainty stemming from singular and correlated disruptions in demand, supply, and production capacities. This is a new and understudied research area. In this study, we examine, SC recovery for high-demand items (e.g., hand sanitizer and face masks). We first developed a stochastic mathematical model to optimise recovery for a three-stage SC exposed to the multi-dimensional impacts of COVID-19 pandemic. This allows to generalize a novel problem setting with simultaneous demand, supply, and capacity uncertainty in a multi-stage SC recovery context. We then developed a chance-constrained programming approach and present in this article a new and enhanced multi-operator differential evolution variant-based solution approach to solve our model. With the optimisation, we sought to understand the impact of different recovery strategies on SC profitability as well as identify optimal recovery plans. Through extensive numerical experiments, we demonstrated capability towards efficiently solving both small- and large-scale SC recovery problems. We tested, evaluated, and analyzed different recovery strategies, scenarios, and problem scales to validate our approach. Ultimately, the study provides a useful tool to optimise reactive adaptation strategies related to how and when SC recovery operations should be deployed during a pandemic. This study contributes to literature through development of a unique problem setting with multi-dimensional uncertainty impacts for SC recovery, as well as an efficient solution approach for solution of both small- and large-scale SC recovery problems. Relevant decision-makers can use the findings of this research to select the most efficient SC recovery plan under pandemic conditions and to determine the timing of its deployment., (© The Author(s) 2022.)

Retinitis pigmentosa and related photoreceptor dystrophies (RPRPD) are rare retinal diseases caused by hereditary gene mutations resulting in photoreceptor death, followed by vision loss. While numerous genes involved in these diseases have been identified, many cases have still not been associated with any gene, indicating that new mechanisms may be involved in the pathogenesis of these photoreceptor dystrophies. Many genes associated with RPRPD regulate photoreceptor specification and maturation in the developing retina. Since retinal development begins with a population of equivalent, proliferating retinal progenitor cells (RPCs) having a specific "competence" in generating all types of retinal neurons, including cone and rod photoreceptors, we tested the epigenetic changes in promoters of genes required for photoreceptor development and genes associated with RPRPD during RPC differentiation into cone and rod photoreceptors. We found that promoters of many of these genes are epigenetically repressed in RPCs but have no epigenetic restrictions in photoreceptors. Our findings also suggest that DNA methylation as an epigenetic mark, and DNA demethylation as a process, are more important than other epigenetic marks or mechanisms in the pathogenesis of these diseases. Most notably, irregularities in the DNA demethylation process during the RPC-to-photoreceptor transition may significantly contribute to retinitis pigmentosa (RP) pathogenesis since genes with hypermethylated promoters in RPCs account for at least 40% of autosomal recessive RP cases and at least 30% of autosomal dominant RP cases. Thus, we proposed an epigenetic model according to which unsuccessful demethylation of regulatory sequences (e.g., promoters, enhancers) of genes required for photoreceptor development, maturation, and function during the RPC-to-photoreceptor transition may reduce or even eliminate their activity, leading to RPRPD without any inheritable mutations in these genes., Competing Interests: The 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 © 2022 Dvoriantchikova, Lypka and Ivanov.)

Objective: To study burnout of Russian physicians in the conditions of COVID-19 pandemic and how their work with coronavirus-infected patients influenced it. According to a three-factor model of burnout developed by Maslach and Jackson, this syndrome includes emotional exhaustion, depersonalization, and reduction of personal accomplishment. Design: A cross-sectional survey study. Setting: Large medical practice. Participants: Physicians of different specialties. Methods: Data collection was conducted from June 23 to July 12, 2020. We developed a Google form including a questionnaire and psychological inventories and placed it in a medical portal. Maslach Burnout Inventory - Human Services Survey for Medical Personnel was used to study burnout; the Hospital Anxiety and Depression Scale was used to determine anxiety and depression. Results: Of all the physicians who took part in the study (N = 599), 31.2 % worked with coronavirus-infected patients. Of the medical personnel who treated COVID-19 patients, 63.6% noted increased workload during the pandemic. Compared to other physicians, they more often had a high degree of emotional exhaustion (43.3 % vs 33.0 %, φ* = 2.404, P ≤ 0.01) and depersonalization (41.7 % vs 34, 0%, φ* = 1.803, P ≤ 0.05). An overwhelming majority of physicians, without any dependence on work with infected patients, had an absence of anxiety and depression. The identified interrelations between the symptoms of burnout, anxiety, depression; age and career stage in medical personnel were identical, except for weak correlations between age and emotional exhaustion (rs = -0.097, P ≤ 0.05), as well as career stage and personal accomplishment (rs = 0.102, P ≤ 0.05) in those physicians who worked with COVID-19 patients. The structure of burnout was identical in all physicians and did not depend on interaction with the infected patients. Conclusion: Public health authorities should reduce the workload on physicians involved in treating infected patients against the backdrop of the pandemic. Psychotherapeutic measures focused on preventing burnout should reduce its number among physicians interacting with patients infected with the coronavirus., (© 2022 Marshfield Clinic Health System.)

Much attention has been recently drawn to studying melatonin - a hormone whose synthesis was first found in the epiphysis (pineal gland). This interest can be due to discovering the role of melatonin in numerous physiological processes. It was the discovery of melatonin synthesis in endocrine organs (pineal gland), neural structures (Purkinje cells in the cerebellum, retinal photoreceptors), and immunocompetent cells (T lymphocytes, NK cells, mast cells) that triggered the evolution of new approaches to the unifield signal regulation of homeostasis, which, at the turn of the 21st century, lead to the creation of a new integral biomedical discipline - neuroimmunoendocrinology. While numerous hormones have been verified over the last decade outside the "classical" locations of their formation, melatonin occupies an exclusive position with regard to the diversity of locations where it is synthesized and secreted. This review provides an overview and discussion of the major data regarding the role of melatonin in various physiological and pathological processes, which affords grounds for considering melatonin as the "cornerstone" on which neuroimmunoendocrinology has been built as an integral concept of homeostasis regulation.

Viability is the ability of a supply chain (SC) to maintain itself and survive in a changing environment through a redesign of structures and replanning of performance with long-term impacts. In this paper, we theorize a new notion-the viable supply chain (VSC). In our approach, viability is considered as an underlying SC property spanning three perspectives, i.e., agility, resilience, and sustainability. The principal ideas of the VSC model are adaptable structural SC designs for supply-demand allocations and, most importantly, establishment and control of adaptive mechanisms for transitions between the structural designs. Further, we demonstrate how the VSC components can be categorized across organizational, informational, process-functional, technological, and financial structures. Moreover, our study offers a VSC framework within an SC ecosystem. We discuss the relations between resilience and viability. Through the lens and guidance of dynamic systems theory, we illustrate the VSC model at the technical level. The VSC model can be of value for decision-makers to design SCs that can react adaptively to both positive changes (i.e., the agility angle) and be able to absorb negative disturbances, recover and survive during short-term disruptions and long-term, global shocks with societal and economical transformations (i.e., the resilience and sustainability angles). The VSC model can help firms in guiding their decisions on recovery and re-building of their SCs after global, long-term crises such as the COVID-19 pandemic. We emphasize that resilience is the central perspective in the VSC guaranteeing viability of the SCs of the future. Emerging directions in VSC research are discussed., (© The Author(s) 2020.)

The coronavirus (COVID-19) outbreak shows that pandemics and epidemics can seriously wreak havoc on supply chains (SC) around the globe. Humanitarian logistics literature has extensively studied epidemic impacts; however, there exists a research gap in understanding of pandemic impacts in commercial SCs. To progress in this direction, we present a systematic analysis of the impacts of epidemic outbreaks on SCs guided by a structured literature review that collated a unique set of publications. The literature review findings suggest that influenza was the most visible epidemic outbreak reported, and that optimization of resource allocation and distribution emerged as the most popular topic. The streamlining of the literature helps us to reveal several new research tensions and novel categorizations/classifications. Most centrally, we propose a framework for operations and supply chain management at the times of COVID-19 pandemic spanning six perspectives, i.e., adaptation, digitalization, preparedness, recovery, ripple effect, and sustainability. Utilizing the outcomes of our analysis, we tease out a series of open research questions that would not be observed otherwise. Our study also emphasizes the need and offers directions to advance the literature on the impacts of the epidemic outbreaks on SCs framing a research agenda for scholars and practitioners working on this emerging research stream., (© The Author(s) 2020.)

Graphitic materials including graphene, carbon nanotubes and fullerenes, are promising for use in nanotechnology and biomedicine. Non-covalent functionalization by peptides and other organic molecules allows changing the properties of graphitic surfaces in a controlled manner and represents a big potential for fundamental research and applications. Recently described oligopeptide-hydrocarbon derivative N,N'-(decane-1,10-diyl)bis(tetraglycineamide) (GM) is highly prospective for the development of graphitic interfaces in biosensor application as well as in structural biology for improving the quality of high-resolution atomic force microscopy (AFM) visualization of individual biomacromolecules. However, molecular organization of GM on graphitic surfaces is still unknown. In this work, the molecular model of GM at the water/highly oriented pyrolytic graphite (HOPG) interface has been developed basing on the high-resolution AFM and full-atom molecular modeling data. This model explains two periodicities observed in AFM images by GM self-assembly on a HOPG surface with formation of the stacks with the lateral shifts. The obtained results reveal the particular patterns and dynamics of GM molecules adsorbed on graphite and unravel the puzzle of peptide self-assembly on graphitic surfaces., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sudden infant death syndrome (SIDS) is one of the primary causes of death of infants in the first year of life. According to the WHO's data, the global infant mortality rate is 0.64-2 per 1,000 live-born children. Molecular and cellular aspects of SIDS development have not been identified so far. The purpose of this paper is to verify and analyze the expression of melatonin 1 and 2 receptors, serotonin (as a melatonin precursor), and CD34 molecules (as hematopoietic and endothelial markers of cardiovascular damage) in the medulla, heart, and aorta in infants who died from SIDS. An immunohistochemical method was used to investigate samples of medulla, heart, and aorta tissues of infants 3 to 9 months of age who died from SIDS. The control group included children who died from accidents. It has been shown that the expression of melatonin receptors as well as serotonin and CD34 angiogenesis markers in tissues of the medulla, heart, and aorta of infants who died from SIDS is statistically lower as compared with their expression in the same tissues in children who died from accidents. The obtained data help to clarify in detail the role of melatonin and such signaling molecules as serotonin and CD34 in SIDS pathogenesis, which can open new prospects for devising novel methods for predictive diagnosis of development and targeted prophylaxis of SIDS., Competing Interests: The authors have declared that no competing interests exist.

In this study, we examine the impact of the COVID-19 pandemic on food retail supply chains (SCs) and their resilience. Based on real-life pandemic scenarios encountered in Germany, we develop and use a discrete-event simulation model to examine SC operations and performance dynamics with the help of anyLogistix digital SC twin. The computational results show that food retail SC resilience at the upheaval times is triangulated by the pandemic intensity and associated lockdown/shutdown governmental measures, inventory-ordering dynamics in the SC, and customer behaviours. We observe that surges in demand and supplier shutdowns have had the highest impact on SC operations and performance, whereas the impact of transportation disruptions was rather low. Transportation costs have spiked because of chaotic inventory-ordering dynamics leading to more frequent and irregular shipments. On bright side, we observe the demand growth and utilization of online sales channels yielding higher revenues. We propose several directions and practical implementation guidelines to improve the food retail SC resilience. We stress the importance of SC digital twins and end-to-end visibility along with resilient demand, inventory, and capacity management. The outcomes of our study can be instructive for enhancing the resilience of food retail SCs in preparation for future pandemics and pandemic-like crises., (© 2021 Elsevier Ltd. All rights reserved.)

A local disruption can propagate to forward and downward through the material flow and eventually influence the entire supply chain network (SCN). This phenomenon of ripple effect, immensely existing in practice, has received great interest in recent years. Moreover, forward and backward disruption propagations became major stressors for SCNs during the COVID-19 pandemic triggered by simultaneous and sequential supply and demand disruptions. However, current literature has paid less attention to the different impacts of the directions of disruption propagation. This study examines the disruption propagation through simulating simple interaction rules of firms inside the SCN. Specifically, an agent-based computational model is developed to delineate the supply chain disruption propagation behavior. Then, we conduct multi-level quantitative analysis to explore the effects of forward and backward disruption propagation, moderated by network structure, network-level health and node-level vulnerability. Our results demonstrate that it is practically important to differentiate between forward and backward disruption propagation, as they are distinctive in the associated mitigation strategies and in the effects on network and individual firm performance. Forward disruption propagation generally can be mitigated by substitute and backup supply and has greater impact on firms serving the assembly role and on the supply/assembly networks, whereas backward disruption propagation is normally mitigated by flexible operation and distribution and has bigger impact on firms serving the distribution role and on distribution networks. We further analyze the investment strategies in a dual-focal supply network under disruption propagation. We provide propositions to facilitate decision-making and summarize important managerial implications., (© 2020 Elsevier B.V. All rights reserved.)

There has been an increased interest in optimizing pricing and sourcing decisions under supplier competition with supply disruptions. In this paper, we conduct an analytical game-theoretical study to examine the effects of supply capacity disruption timing on pricing decisions for substitute products in a two-supplier one-retailer supply chain setting. We investigate whether the timing of a disruption may significantly impact the optimal pricing strategy of the retailer. We derive the optimal pricing strategy and ordering levels with both disruption timing and product substitution. By exploring both the Nash and Stackelberg games, we find that the order quantity with the disrupted supplier depends on price leadership and it tends to increase when the non-disrupted supplier is the leader. Moreover, the equilibrium market retail prices are higher under higher levels of disruption for the Nash game, compared to the Stackelberg game. We also uncover that the non-disrupted supplier can always charge the highest wholesale price if a disruption occurs before orders are received. This highlights the critical role of order timing. The insights can help operations managers to proper design risk mitigation ordering strategies and re-design the supply contracts in the presence of product substitution under supply disruptions., (© 2020 Elsevier Ltd. All rights reserved.)

Embryogenesis is a complex multi-stage process regulated by various signaling molecules including pineal and extrapineal melatonin (MT). Extrapineal MT is found in the placenta and ovaries, where it carries out local hormonal regulation. MT is necessary for normal development of oocytes, fertilization and subsequent development of human, animal and avian embryos. This review discusses the role of MT as a regulator of preimplantation development of the embryo and its implantation into endometrial tissue, followed by histo-, morpho- and organogenesis. MT possesses pronounced antioxidant properties and helps to protect the embryo from oxidative stress by regulating the expression of the NFE2L2, SOD1 , and GPX1 genes. MT activates the expression of the ErbB1, ErbB4, GJA1, POU5F1, and Nanog genes which are necessary for embryo implantation and blastocyst growth. MT induces the expression of vascular endothelial growth factor (VEGF) and its type 1 receptor (VEGF-R1) in the ovaries, activating angiogenesis. Given the increased difficulties in successful fertilization and embryogenesis with age, it is of note that MT slows down ovarian aging by increasing the transcription of sirtuins. MT administration to patients suffering from infertility demonstrates an increase in the effectiveness of in vitro fertilization. Thus, MT may be viewed as a key factor in embryogenesis regulation, including having utility in the management of infertility.

Entering the COVID-19 pandemic wreaked havoc on supply chains. Reacting to the pandemic and adaptation in the "new normal" have been challenging tasks. Exiting the pandemic can lead to some after-shock effects such as "disruption tails." While the research community has undertaken considerable efforts to predict the pandemic's impacts and examine supply chain adaptive behaviors during the pandemic, little is known about supply chain management in the course of pandemic elimination and post-disruption recovery. If capacity and inventory management are unaware of the after-shock risks, this can result in highly destabilized production-inventory dynamics and decreased performance in the post-disruption period causing product deficits in the markets and high inventory costs in the supply chains. In this paper, we use a discrete-event simulation model to investigate some exit strategies for a supply chain in the context of the COVID-19 pandemic. Our model can inform managers about the existence and risk of disruption tails in their supply chains and guide the selection of post-pandemic recovery strategies. Our results show that supply chains with postponed demand and shutdown capacity during the COVID-19 pandemic are particularly prone to disruption tails. We then developed and examined two strategies to avoid these disruption tails. First, we observed a conjunction of recovery and supply chain coordination which mitigates the impact of disruption tails by demand smoothing over time in the post-disruption period. Second, we found a gradual capacity ramp-up prior to expected peaks of postponed demand to be an effective strategy for disruption tail control., (© The Author(s) 2021.)

Supply chain viability (SCV) is an emerging concept of growing importance in operations management. This paper aims to conceptualize, develop, and validate a measurement scale for SCV. SCV is first defined and operationalized as a construct, followed by content validation and item measure development. Data have been collected through three independent samplings comprising a total of 558 respondents. Both exploratory and confirmatory factor analyses are used in a step-wise manner for scale development. Reliability and validity are evaluated. A nomological model is theorized and tested to evaluate nomological validity. For the first time, our study frames SCV as a novel and distinct construct. The findings show that SCV is a hierarchical and multidimensional construct, reflected in organizational structures, organizational resources, dynamic design capabilities, and operational aspects. The findings reveal that a central characteristic of SCV is the dynamic reconfiguration of SC structures in an adaptive manner to ensure survival in the long-term perspective. This research conceptualizes and provides specific, validated dimensions and item measures for SCV. Practitioner directed guidance and suggestions are offered for improving SCV during the COVID-19 pandemic and future severe disruptions., (© The Author(s) 2021.)

The review summarizes the results of experimental and clinical studies aimed at elucidating the causes and pathophysiological mechanisms of the development of endocrine pathology in children. The modern data on the role of epigenetic influences in the early ontogenesis of unfavorable factors that violate the patterns of the formation of regulatory mechanisms during periods of critical development of fetal organs and systems and contribute to the delayed development of pathological conditions are considered. The mechanisms of the participation of melatonin in the regulation of metabolic processes and the key role of maternal melatonin in the formation of the circadian system of regulation in the fetus and in the protection of the genetic program of its morphofunctional development during pregnancy complications are presented. Melatonin, by controlling DNA methylation and histone modification, prevents changes in gene expression that are directly related to the programming of endocrine pathology in offspring. Deficiency and absence of the circadian rhythm of maternal melatonin underlies violations of the genetic program for the development of hormonal and metabolic regulatory mechanisms of the functional systems of the child, which determines the programming and implementation of endocrine pathology in early ontogenesis, contributing to its development in later life. The significance of this factor in the pathophysiological mechanisms of endocrine disorders determines a new approach to risk assessment and timely prevention of offspring diseases even at the stage of family planning.

The COVID-19 pandemic unveils unforeseen and unprecedented fragilities in supply chains (SC). A primary stressor of SCs and their subsequent shocks derives from disruption propagation (i.e., the ripple effect) through related networks. In this paper, we conceptualize current state and future research directions on the ripple effect for pandemic context. We scrutinize the existing OR (Operational Research) studies published in international journals dealing with disruption propagation and structural dynamics in SCs. Our study pursues two major contributions in relation to two research questions. First, we collate state-of-the-art research on disruption propagation in SCs and identify a methodical taxonomy along with theories displaying their value and applications for coping with the impacts of pandemics on SCs. Second, we reveal and systemize managerial insights from theory used for operating (adapting) amid a pandemic and during times of recovery, along with becoming more resistant to future pandemics. Streamlining the literature allowed us to reveal several new research tensions and novel categorizations and classifications. The outcomes of our study show that methodical contributions and the resulting managerial insights can be categorized into three levels, i.e., network, process, and control. Our analysis reveals that adaptation capabilities play the most crucial role in managing the SCs under pandemic disruptions. Our findings depict how the existing OR methods can help coping with the ripple effect at five pandemic stages (i.e., Anticipation; Early Detection; Containment; Control and Mitigation; and Elimination) following the WHO classification. The outcomes and findings of our study can be used by industry and researchers alike to progress the decision-support systems guiding SCs amid the COVID-19 pandemic and toward recovery. Suggestions for future research directions are offered and discussed., (© 2020 Elsevier B.V. All rights reserved.)

Aging is a complex biological process, a major aspect of which is the accumulation of somatic changes throughout life. Cellular senescence is a condition in which cells undergo an irreversible cell cycle arrest in response to various cellular stresses. Once the cells begin to senesce, they become more resistant to any mutagens, including oncogenic factors. Inflammaging (inflammatory aging) is an age-related, chronic, and systemic inflammatory condition realized by cells with the Senescence-Associated Secretory Phenotype (SASP). These recently recognized senescent phenotypes associated with aging have been reported to promote better wound healing, embryonic development, as well as stimulation and extension of the tumor process. It is assumed that cellular senescence contributes to the age-related decline of reproductive function due to the association of senescent cells with aging and age-related diseases. Thus, SASPs have both positive and negative effects, depending on the biological context. SASP cell accumulation in tissues contributes to an age-related functional decline of the tissue and organ state. In this review, the term "cellular senescence" is used to refer to the processes of cells irreversible growth inhibition during their viable state, while the term "aging" is used to indicate the deterioration of tissues due to loss of function. Late reproductive age is associated with infertility and possible complications of the onset and maintenance of pregnancy. Senescent cells express pro-inflammatory cytokines, growth factors, and matrix metalloproteinases and some other molecules collectively called the Senescence-Associated Secretory Phenotype (SASP)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the broad sense, the Bayesian networks (BN) are probabilistic graphical models that possess unique methodical features to model dependencies in complex networks, such as forward and backward propagation (inference) of disruptions. BNs have transitioned from an emerging topic to a growing research area in supply chain (SC) resilience and risk analysis. As a result, there is an acute need to review existing literature to ascertain recent developments and uncover future areas of research. Despite the increasing number of publications on BNs in the domain of SC uncertainty, an extensive review on their application to SC risk and resilience is lacking. To address this gap, we analyzed research articles published in peer-reviewed academic journals from 2007 to 2019 using network analysis, visualization-based scientometric analysis, and clustering analysis. Through this study, we contribute to literature by discussing the challenges of current research, and, more importantly, identifying and proposing future research directions. The results of our survey show that further debate on the theory and application of BNs to SC resilience and risk management is a significant area of interest for both academics and practitioners. The applications of BNs, and their conjunction with machine learning algorithms to solve big data SC problems relating to uncertainty and risk, are also discussed., Competing Interests: 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., (© 2020 Elsevier Ltd. All rights reserved.)

We present a new approach to femtosecond direct laser writing lithography to pattern nanocavities in ferromagnetic thin films. To demonstrate the concept, we irradiated 300 nm thin nickel films by single intense femtosecond laser pulses through glass substrate. Using a fluence above the ablation threshold, the process is destructive, leading to the formation of an ablation crater. By progressively lowering the laser fluence, the formation of closed spallation cavities below the ablation threshold is achieved. Systematic studies by the electron and optical interferometric microscopies, supported by molecular dynamics simulations, enabled us to gain an understanding of the thermo-mechanical spallation mechanism at the solid-molten interface. We achieved the fabrication of periodic arrangements of closed spallation nanocavities. Due to their topology, closed magnetic nanocavities can support unique couplings of multiple excitations (magnetic, optical, acoustic, spintronic). Thereby, they offer a unique physics playground for emerging fields in magnetism, magneto-photonic, and magneto-acoustic applications.

A direct comparison of simulation and experimental results of UV laser-induced surface nanostructuring of gold is presented. Theoretical simulations and experiments are performed on an identical spatial scale. The experimental results have been obtained by using a laser wavelength of 248 nm and a pulse length of 1.6 ps. A mask projection setup is applied to generate a spatially periodic intensity profile on a gold surface with a sinusoidal shape and periods of 270 nm, 350 nm, and 500 nm. The formation of structures at the surface upon single pulse irradiation is analyzed by scanning and transmission electron microscopy (SEM and TEM). For the simulations, a hybrid atomistic-continuum model capable of capturing the essential mechanisms responsible for the nanostructuring process is used to model the interaction of the laser pulse with the gold target and the subsequent time evolution of the system. The formation of narrow ridges composed of two colliding side walls is found in the simulation as well as in the experiment and the structures generated as a result of the material processing are categorized depending on the range of applied fluencies and periodicities.

Traumatic optic neuropathy (TON) can occur following blunt trauma to the orbit and can lead to permanent vision loss. In this study, we investigated the effectiveness of elamipretide (MTP-131), a small mitochondrially-targeted tetrapeptide, in conjunction with etanercept, a tumor necrosis factor (TNF) inhibitor, as neuroprotective agents of retinal ganglion cells (RGCs) after optic nerve trauma with sonication-induced TON (SI-TON) in mice. Treatment with intravitreal MTP-131 and subcutaneous etanercept and MTP-131 showed a 21% increase (p < 0.01) in RGC survival rate compared to PBS-treated control eyes. Subcutaneous etanercept and MTP-131 had an 11% increase (p < 0.05) in RGC survival compared to controls. Subcutaneous etanercept only group showed 20% increase (p < 0.01) in RGC survival compared to controls, while subcutaneous MTP-131 alone showed a 17% increase (p < 0.01). Surprisingly, we did not observe a synergistic effect between the two drugs in the group receiving both etanercept and MTP-131. One possible explanation for the absence of a synergistic effect is that MTP-131 and etanercept may be acting on different portions of the same pathway., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). We demonstrated that MBG induces fibrosis via mechanism involving inhibition of Fli1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. We hypothesized that PE blockade of increased MBG with antibody would lessen the fibrosis of umbilical arteries and lower the blood pressure in rats with PE., Methods: We tested 36 pregnant Sprague-Dawley rats in which 12 were made hypertensive by 1.8% Na supplementation (days 6-19 of gestation), 12 pregnant rats served controls. At day 19, PE rats received one intraperitoneal injection of polyclonal anti-MBG-4 antibody (0.5 ug/ml) for 4 hours., Results: PE was associated with higher blood pressure (117 ± 2 vs. 107 ± 2 mm Hg; P < 0.01), plasma MBG levels (1.54 ± 0.34 vs. 0.49 ± 0.11 nmol/L; P < 0.01), protein excretion (26 vs. 12 mg/24 hours), sFlt-1 (3-fold), decrease in Fli1 (7-fold) and increase in collagen-1 in aorta (4-fold) vs. control rats (all P < 0.01). In 12 rats treated with polyclonal anti-MBG-4 antibody blood pressure dropped (93 ± 3 mm Hg) and Fli1 was decreased much less (2-fold; P < 0.01 vs. nontreated rats)., Conclusions: These results demonstrate that in experimental PE elevated MBG level is implicated in umbilical fibrosis via suppression of Fli1., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. This article reviews the role of melatonin in the prenatal modulation of offspring obesity. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin's effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Epidemic outbreaks are a special case of supply chain (SC) risks which is distinctively characterized by a long-term disruption existence, disruption propagations (i.e., the ripple effect), and high uncertainty. We present the results of a simulation study that opens some new research tensions on the impact of COVID-19 (SARS-CoV-2) on the global SCs. First, we articulate the specific features that frame epidemic outbreaks as a unique type of SC disruption risks. Second, we demonstrate how simulation-based methodology can be used to examine and predict the impacts of epidemic outbreaks on the SC performance using the example of coronavirus COVID-19 and anyLogistix simulation and optimization software. We offer an analysis for observing and predicting both short-term and long-term impacts of epidemic outbreaks on the SCs along with managerial insights. A set of sensitivity experiments for different scenarios allows illustrating the model's behavior and its value for decision-makers. The major observation from the simulation experiments is that the timing of the closing and opening of the facilities at different echelons might become a major factor that determines the epidemic outbreak impact on the SC performance rather than an upstream disruption duration or the speed of epidemic propagation. Other important factors are lead-time, speed of epidemic propagation, and the upstream and downstream disruption durations in the SC. The outcomes of this research can be used by decision-makers to predict the operative and long-term impacts of epidemic outbreaks on the SCs and develop pandemic SC plans. Our approach can also help to identify the successful and wrong elements of risk mitigation/preparedness and recovery policies in case of epidemic outbreaks. The paper is concluded by summarizing the most important insights and outlining future research agenda., (© 2020 Elsevier Ltd. All rights reserved.)

Muller glia are the predominant glial cell type in the retina, and they structurally and metabolically support retinal neurons. Wnt/β-catenin signaling pathways play essential roles in the central nervous system, including glial and neuronal differentiation, axonal growth, and neuronal regeneration. We previously demonstrated that Wnt signaling activation in retinal ganglion cells (RGC) induces axonal regeneration after injury. However, whether Wnt signaling within the adjacent Muller glia plays an axongenic role is not known. In this study, we characterized the effect of Wnt signaling in Muller glia on RGC neurite growth. Primary Muller glia and RGC cells were grown in transwell co-cultures and adenoviral constructs driving Wnt regulatory genes were used to activate and inhibit Wnt signaling specifically in primary Muller glia. Our results demonstrated that activation of Wnt signaling in Muller glia significantly increased RGC average neurite length and branch site number. In addition, the secretome of Muller glia after induction or inhibition of Wnt signaling was characterized using protein profiling of conditioned media by Q Exactive mass spectrometry. The Muller glia secretome after activation of Wnt signaling had distinct and more numerous proteins involved in regulation of axon extension, axon projection and cell adhesion. Furthermore, we showed highly redundant expression of Wnt signaling ligands in Muller glia and Frizzled receptors in RGCs and Muller glia. Therefore, this study provides new information about potential neurite growth promoting molecules in the Muller glia secretome, and identified Wnt-dependent target proteins that may mediate the axonal growth., (© 2020 Wiley Periodicals, Inc.)

Gold nanoparticles (NPs) have a wide range of applications in various fields. Here, we present high-order nonlinear optical studies of the plasmas produced from ablation of Au bulk targets and Au NP films deposited on paper and glass substrates. Experimentally, we analyze high-order harmonic generation (HHG) from gold NPs-containing plasmas. The HHG is produced by 35-fs pulses at 800 and 400 nm, while the plasmas are produced by femtosecond (35 fs, 800 nm), picosecond (200 ps, 800 nm), and nanosecond (5 ns, 1064 nm) pulses, respectively. High-order harmonics produced from ablated Au NPs on paper were 40 times stronger than the HHG from that ablated from the Au bulk targets. Through molecular dynamic simulations, we investigate the formation of gold NPs during laser ablation of a metal surface under different conditions.

We present a framework based on the atomistic continuum model, combining the Molecular Dynamics (MD) and Two Temperature Model (TTM) approaches, to characterize the growth of metal nanoparticles (NPs) under ultrashort laser ablation from a solid target in water ambient. The model is capable of addressing the kinetics of fast non-equilibrium laser-induced phase transition processes at atomic resolution, while in continuum it accounts for the effect of free carriers, playing a determinant role during short laser pulse interaction processes with metals. The results of our simulations clarify possible mechanisms, which can be responsible for the observed experimental data, including the presence of two populations of NPs, having a small (5-15 nm) and larger (tens of nm) mean size. The formed NPs are of importance for a variety of applications in energy, catalysis and healthcare.