Failure Of Defense Research Articles

Defensive responses of most antioxidant genes in the freshwater dinoflagellate Palatinus apiculatus to cadmium stress and their implications

Photosynthetic dinoflagellates are one of the major microalgal taxa, playing essential roles in biogeochemical cycles and food webs in aquatic environments. Some freshwater dinoflagellates are known to be sensitive to environmental conditions, like water quality and contaminants; however, their molecular toxicological responses are insufficiently discovered. In the present study, we evaluated the physiological and transcriptomic responses of the freshwater dinoflagellate Palatinus apiculatus exposed to cadmium (Cd), focusing on stress-responsive genes. The cell number of P. apiculatus decreased significantly at Cd concentrations above 0.25 mg/L after 72 h, with an estimated EC50 value of 1.35 mg/L. In addition, we constructed 87,207 transcriptomic contigs from the P. apiculatus cells exposed to the Cd. Differential expression gene analysis showed that 21.0 % of total contigs were statistically significant, including 8647 up-regulated and 4195 down-regulated genes. Gene Ontology enrichment results revealed that genes responsive to stress and external stimuli were highly expressed in Cd-treated cells. Moreover, Cd significantly induced reactive oxygen species (ROS) production in P. apiculatus cells, and their patterns were similar to the expressions of certain antioxidant genes. Among the selected genes, GR expression levels were down-regulated, which may lead to the failure of cell defense against heavy metals. These results showed molecular defense pathways of the freshwater dinoflagellate P. apiculatus against the heavy metal that could be served as potential sensitive biomarkers for evaluating molecular toxicity in freshwater ecosystems.

Water, not carbon, drives drought-constraints on stem terpene defense against simulated bark beetle attack in Pinus edulis.

Drought predisposes forest trees to bark beetle-induced mortality, but the physiological mechanisms remain unclear. While drought-induced water and carbon limitations have been implicated in defensive failure and tree susceptibility, evidence demonstrating how these factors interact is scarce. We withheld water from mature, potted Pinus edulis and subsequently applied a double-stem girdle to inhibit carbohydrate transport from the crown and roots. Within this isolated segment we then elicited a defense response by inoculating trees with a bark beetle-fungal symbiont (Ophiostoma sp.). We quantified local mono- and sesquiterpenes (MST), nonstructural carbohydrates (NSC), and pressure potential of the inner bark. Both drought-stressed and watered trees had similar NSC concentrations just before inoculation and depleted NSC similarly following inoculation, yet MST induction (i.e. increased concentration and altered composition) was constrained only in drought-stressed trees. Thus, NSC consumption was largely unrelated to de novo MST synthesis. Instead, stoichiometric calculations show that induction originated largely from stored resin. Watered trees experiencing higher pressure potentials consistently induced higher MST concentrations. We demonstrate the importance of preformed resin toward an induced MST response in a semi-arid conifer where drought-constraints on defense occurred through biophysical limitations (i.e. reduced turgor hindering resin transport) rather than through substrate limitation.

Effects of parenteral nutrition supplemented with beta-hydroxy-beta-methylbutyrate on gut-associated lymphoid tissue and morphology in mice.

Parenteral nutrition (PN) without enteral nutrition (EN) leads to marked atrophy of gut-associated lymphoid tissue (GALT), causing mucosal defense failure in both the gut and the extraintestinal mucosal system. We evaluated the effects of beta-hydroxy-beta-methylbutyrate (HMB) on GALT and gut morphology in PN-fed mice. Experiment 1: male Institute of Cancer Research mice were assigned to the Chow (n = 12), Control (standard PN: n = 10), or H600 and H2000 (PN containing 600 mg/kg or H2000 mg/kg body weight of Ca-HMB: n = 12 and 10, respectively) groups. After 5 days of dietary manipulation, all mice were killed and the whole small intestine was harvested. GALT lymphocyte cell numbers and phenotypes of Peyer patch (PP), intraepithelial space, and lamina propria lymphocytes were evaluated. Experiment 2: 47 mice (Chow: n = 12; Control: n = 14; H600: n = 11; and H2000: n = 10) were fed for 5 days as in experiment 1. Proliferation and apoptosis of gut immune cells and mucosa, and protein expressions (mammalian target of rapamycin [mTOR], caspase-3, and Bcl2) were evaluated in the small intestine. Compared with the Controls, the Chow and HMB groups showed significantly higher PP cell numbers, prevented gut mucosal atrophy, inhibited apoptosis of gut cells, and increased their proliferation in association with increased mTOR activity and Bcl2 expression. HMB-supplemented PN is a potentially novel method of preserving GALT mass and gut morphology in the absence of EN.

#1955 Ferroptotic proteins ACSL4 and ALOX15 as therapeutic targets in AKI

Abstract Background and Aims Ferroptosis is a regulated form of necrosis which is dependent on cellular iron and is characterized by the accumulation of lipid peroxides and failure of cellular antioxidant defences. We have previously described in vivo that ferroptosis is the primary cause of folic acid-induced acute kidney injury (FA-AKI) and that necroinflammation secondary to ferroptosis may further worsen kidney injury, since ferroptosis inhibition improved kidney function and decreased tubular cell death and oxidative stress. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is involved in the incorporation of polyunsaturated fatty acid (PUFA) into membranes, while 15-Lipoxygenase (Alox15) catalyzes the regio- and enantioselective peroxidation of membrane-esterified PUFAs, forming the ultimate peroxidized species that induce ferroptosis. In the present work, we aim to explore the potential of both proteins as therapeutic targets in AKI, as well as the molecular characterization of kidney ferroptosis in cultured tubular cells. Method Animal model: Female 12- to 14-week-old C57BL/6J wild type mice received a single intraperitoneal (i.p) injection of folic acid or vehicle and were sacrificed 48 hours later. Troglitazone was intravenously administered for in vivo ACSL4 inhibition, and Compound 1 was i.p administered for in vivo ALOX15 inhibition. In vitro characterization of ferroptosis: HK2 human tubular kidney cells were incubated with arachidonic acid (AA) prior to sublethal RSL3 administration for sensitization to ferroptosis. We used Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lpx-1) as inhibitors of ferroptosis. The thiazolidinedione family members Rosiglitazone, Pioglitazone and Troglitazone were used as pharmacological inhibitors of ACSL4. We also performed transcriptional silencing of ACSL4 using a specific siRNA. Compound 1 and PD1646 were administered for in vitro Alox15 inhibition. Cellular lipid peroxidation was analyzed by flow cytometry with Bodipy 581/591 staining. To characterize the lipid signature of ferroptotic cells, supernatants were collected and 15-HETEs levels were measured by ELISA. Oxido-lipidomic analysis of ferroptotic cells was performed by LC-MS. Real Time PCR and Western Blot of whole kidneys and cultured cells were performed for the detection and quantification of ACSL4 and ALOX15. Cell death was assessed by measurement of cell viability (MTT assay) and cytotoxicity (LDH assay). Tissue cell death was assessed by TUNEL. Results Kidney transcriptomics identified Acsl4 as the most upregulated member of Acsl family during FA-AKI. This was validated at mRNA and protein levels. Supplementation with AA, the preferred ACSL4 substrate, sensitized HK2 tubular cells to ferroptosis under sublethal RSL3 conditions, and this was prevented with specific ferroptosis inhibitors Fer-1 and Lpx-1. Pharmacological inhibition of ACSL4 with Troglitazone and a specific siRNA protected from cell death and lipid peroxidation induced by co-stimulation of AA and RSL3 in HK2 cells. Likewise, ALOX15 proteins levels were also increased in FA-AKI at 48 hours. PD1646 and Compound 1, both used to inhibit ALOX15, protected from ferroptotic cell death and lipid peroxidation in HK2 cells. Lipidomic analysis on HK2 tubular cells stimulated with AA+RSL3 uncovered an increased content of key peroxidized lipid species involved in ferroptosis execution, which was alleviated by targeting ACSL4 or ALOX15. Additionally, renal function of FA-AKI in mice was improved by ACSL4 pharmacological inhibition with Troglitazone and with ALOX15 inhibition with Compound 1. Conclusion Our preliminary results suggest therapeutic potential of ACSL4 and ALOX15 as ferroptotic targes during AKI. High PUFA content sensitizes human tubular HK2 cells to cell death and lipid peroxidation in the presence of sublethal ferroptotic triggers, and this was prevented by targeting ACSL4 or ALOX15 both in vitro and in vivo in FA-AKI. Closely related lipid peroxide species were decreased by ACSL4 or ALOX15 inhibitors.

Deriving optimal defensive resource deployment of complex system-of-systems for risk response considering cascading effect

As disruptions happen with increasing frequency, over-deployment or insufficient deployment can lead to inefficiency or defensive failure for security risk management. Therefore, it is necessary to deploy appropriate defensive resources so as to defend a complex system-of-systems (SoS). Component heterogeneity and cascade effect must be considered in the high-risk environment. To that end, a novel security defensive deployment decision model is proposed in this research considering cooperation and non-cooperation. We formulate a maximum utility model to figure out the optimal defensive deployment of component in the case of independent defence. In addition, the complex SoS’s optimal defensive behaviour is calculated under all components work together to fulfil the demand and complete the mission. We also compare two scenarios and draw that the utility of coordinated defence is greater than that of independent defence in a SoS. The proposed model is employed in a weapon equipment SoS, elaborating how the SoS operators should operate against disruptive events.

Detection and Defense of Unlearnable Examples

Privacy preserving has become increasingly critical with the emergence of social media. Unlearnable examples have been proposed to avoid leaking personal information on the Internet by degrading the generalization abilities of deep learning models. However, our study reveals that unlearnable examples are easily detectable. We provide theoretical results on linear separability of certain unlearnable poisoned dataset and simple network-based detection methods that can identify all existing unlearnable examples, as demonstrated by extensive experiments. Detectability of unlearnable examples with simple networks motivates us to design a novel defense method. We propose using stronger data augmentations coupled with adversarial noises generated by simple networks, to degrade the detectability and thus provide effective defense against unlearnable examples with a lower cost. Adversarial training with large budgets is a widely-used defense method on unlearnable examples. We establish quantitative criteria between the poison and adversarial budgets, which determine the existence of robust unlearnable examples or the failure of the adversarial defense.

Avoidance behaviour and toxicological impact of sunscreens in the teleost Chelon auratus

There is increasing evidence that sunscreen, more specifically the organic ultra-violet filters (O-UVFs), are toxic for aquatic organisms. In the present study, we simulated an environmental sunscreen exposure on the teleost fish, Chelon auratus. The first objective was to assess their spatial avoidance of environmental concentrations of sunscreen products (i.e. a few μg.L−1 of O-UVFs). Our results showed that the fish did not avoid the contaminated area. Therefore, the second objective was to evaluate the toxicological impacts of such pollutants after 35 days exposure to concentrations of a few μg.L−1 of O-UVFs. At the individual level, O-UVFs increased the hepatosomatic index which could suggest pathological alterations of the liver or the initiation of the detoxification processes. At the cellular level, a significant increase of malondialdehyde was measured in the muscle of fish exposed to O-UVFs which suggests a failure of antioxidant defences and/or an excess of reactive oxygen species.

The Possible Protective effect of Daflon 500mg on Cisplatin Induce Nephrotoxicity in Experimental Rats

Background: Drug-induced nephrotoxicity is one of the most common causes of acute kidney injury. Cisplatin is one of the most effective and potent anticancer drugs, induces a reduction in the antioxidant, leading to a failure of the antioxidant defense against free-radical damage generated by antitumor drug. Objectives: This study was conducted to examine the possible ameliorative activity of Daflon against Cis-induce acute kidney injury. Materials and methods: Animals divided into six groups, group Ӏ: received NaCl on a daily; group ӀӀ: received Cisplatin (7.5mg/kg) single dose; group ӀӀӀ: received Daflon mini dose (50mg/kg) for 15 successive days, group IV: received Daflon max dose (100mg/kg/day) for 15 successive days; group V: received Daflon mini dose (50mg/kg) for 15 successive days and a single IP dose of Cisplatin (7.5mg/kg) to be injected on day 15, group VI : received Daflon max dose (100mg/kg) for 15 successive days and a single IP dose of Cisplatin (7.5mg/kg) to be injected on day 15, Finally, after euthanization of each animal by diethyl ether, the samples were collected for analysis. Serum MDA, Serum GSH and Tumor Necrosis Factor (TNF-α) had been used as an indicator for the protective effect of Daflon. Conclusion: The results show that administration of Daflon for 15 days had significant protective effect against cisplatin induced nephrotoxicity.

Innate immune side of STAT1 GOF

STAT1 gain-of-function (GOF) mutations underlie an inborn error of immunity hallmarked by chronic mucocutaneous candidiasis (CMC). Beyond the fungal susceptibility, attributed to Th17 failure, over half of the reported patients suffer from autoimmune manifestations, which remain mechanistically unexplained. Surprisingly, little is known about the biological consequences of augmented STAT1 signaling in innate immune cells. Considering the importance of innate immune mechanisms in antifungal defense and autoimmune complications, we examined the phenotype and function of monocytes and dendritic cells in a cohort of patients with STAT1 GOF.We demonstrated that human ex vivo STAT1 GOF monocytes are characterized by proinflammatory phenotype and strong inflammatory skew of their secretory cytokine profile. The distribution of monocytes subpopulations’ is altered and they exhibit various functional abnormalities, which might represent a contributing mechanism in the pathogenesis of STAT1 GOF-associated autoimmunity, e.g., a selectively enhanced responsiveness to TLR7/8 stimulation, but not to other TLR ligands. Importantly, some of these features extend to STAT1 GOF myeloid dendritic cells, suggesting that the alterations observed in monocytes are, in fact, intrinsic due to STAT1 mutation, and not mere secondary consequence of the chronic inflammatory milieu.To follow up on the ex vivo data, we employed an in vitro model of monocyte-derived DC (moDC) and tolerogenic DC (tDC). Functional and signaling studies, co-culture experiments and RNA sequencing demonstrated that STAT1 GOF DCs were profoundly altered in their phenotype and functions, characterized by loss of tolerogenic functions, proinflammatory skew and decreased capacity to induce Th17. Cytokine signaling, autophagy and metabolic processes were identified as the most prominently altered cellular processes.In conclusion, we present first-ever data implying a direct involvement of monocytes and DCs in the STAT1 GOF-associated immune pathology, possibly contributing to both autoimmune manifestations and the failure of antifungal defense. Our work thus highlights a yet understudied innate immune background in STAT1 GOF which should be dissected in details by future research.

In Situ Molecular Ecological Analyses Illuminate Distinct Factors Regulating Formation and Demise of a Harmful Dinoflagellate Bloom.

The development and demise of a harmful algal bloom (HAB) are generally regulated by multiple processes; identifying specific critical drivers for a specific bloom is important yet challenging. Here, we conducted a whole-assemblage molecular ecological study on a dinoflagellate bloom to address the hypothesis that energy and nutrient acquisition, defense against grazing and microbial attacks, and sexual reproduction are critical to the rise and demise of the bloom. Microscopic and molecular analyses identified the bloom-causing species as Karenia longicanalis and showed that the ciliate Strombidinopsis sp. was dominant in a nonbloom plankton community, whereas the diatom Chaetoceros sp. dominated the after-bloom community, along with remarkable shifts in the community structure for both eukaryotes and prokaryotes. Metatranscriptomic analysis indicated that heightened energy and nutrient acquisition in K. longicanalis significantly contributed to bloom development. In contrast, active grazing by the ciliate Strombidinopsis sp. and attacks by algicidal bacteria (Rhodobacteracea, Cryomorphaceae, and Rhodobacteracea) and viruses prevented (at nonbloom stage) or collapsed the bloom (in after-bloom stage). Additionally, nutrition competition by the Chaetoceros diatoms plausibly contributed to bloom demise. The findings suggest the importance of energy and nutrients in promoting this K. longicanalis bloom and the failure of antimicrobial defense and competition of diatoms as the major bloom suppressor and terminator. This study provides novel insights into bloom-regulating mechanisms and the first transcriptomic data set of K. longicanalis, which will be a valuable resource and essential foundation for further elucidation of bloom regulators of this and related species of Kareniaceae in the future. IMPORTANCE HABs have increasingly occurred and impacted human health, aquatic ecosystems, and coastal economies. Despite great efforts, the factors that drive the development and termination of a bloom are poorly understood, largely due to inadequate in situ data about the physiology and metabolism of the causal species and the community. Using an integrative molecular ecological approach, we determined that heightened energy and nutrient acquisition promoted the bloom, while resource allocation in defense and failure to defend against grazing and microbial attacks likely prevented or terminated the bloom. Our findings reveal the differential roles of multiple abiotic and biotic environmental factors in driving the formation or demise of a toxic dinoflagellate bloom, suggesting the importance of a balanced biodiverse ecosystem in preventing a dinoflagellate bloom. The study also demonstrates the power of whole-assemblage metatranscriptomics coupled to DNA barcoding in illuminating plankton ecological processes and the underlying species and functional diversities.

Neutrophil defect and lung pathogen selection in cystic fibrosis.

Cystic fibrosis is a life-threatening genetic disorder caused by mutations in the CFTR chloride channel. Clinically, over 90% of patients with cystic fibrosis succumb to pulmonary complications precipitated by chronic bacterial infections, predominantly by Pseudomonas aeruginosa and Staphylococcus aureus. Despite the well-characterized gene defect and clearly defined clinical sequelae of cystic fibrosis, the critical link between the chloride channel defect and the host defense failure against these specific pathogens has not been established. Previous research from us and others has uncovered that neutrophils from patients with cystic fibrosis are defective in phagosomal production of hypochlorous acid, a potent microbicidal oxidant. Here we report our studies to investigate if this defect in hypochlorous acid production provides P. aeruginosa and S. aureus with a selective advantage in cystic fibrosis lungs. A polymicrobial mixture of cystic fibrosis pathogens (P. aeruginosa and S. aureus) and non-cystic fibrosis pathogens (Streptococcus pneumoniae, Klebsiella pneumoniae, and Escherichia coli) was exposed to varied concentrations of hypochlorous acid. The cystic fibrosis pathogens withstood higher concentrations of hypochlorous acid than did the non-cystic fibrosis pathogens. Neutrophils derived from F508del-CFTR HL-60 cells killed P. aeruginosa less efficiently than did the wild-type counterparts in the polymicrobial setting. After intratracheal challenge in wild-type and cystic fibrosis mice, the cystic fibrosis pathogens outcompeted the non-cystic fibrosis pathogens and exhibited greater survival in the cystic fibrosis lungs. Taken together, these data indicate that reduced hypochlorous acid production due to the absence of CFTR function creates an environment in cystic fibrosis neutrophils that provides a survival advantage to specific microbes-namely, S. aureus and P. aeruginosa-in the cystic fibrosis lungs.

Erosion time scale in pipes below dikes for turbulent and laminar flow

ABSTRACT This article discusses the piping erosion time, where pipes start to erode in aquifers underneath dikes and dams until they reach their critical values. The magnitude of the piping erosion time significantly determines the risk of failure of water defences. The time-scale equation is based on a sediment mass balance equation and appropriate bedload transport predictors, assuming the erosion process to be continuous. We argue that the flow is laminar for pipes in sandy aquifers and turbulent for pipes in gravel aquifers. We then account for aquifer composition in examining pipe erosion by discussing different bedload transport predictors for each flow regime. To estimate the turbulence intensity, we have used and modified the Einstein bedload transport theory. The time-scale relation includes the effects of meander bends and has been tested for some experiments on a small scale and on a large scale.

Participatory risk assessment of pluvial floods in four towns of Niger

Intense rainfalls in Sub-Saharan Africa are increasing in frequency. Land degradation, watercourses siltation, and flood defence failure turn these events into disastrous floods. Over the last decade flood risk assessments have been prepared to face these disasters. However, they have frequent limitations in design, accuracy, and completeness. The objectives of this study are (i) to integrate local and scientific knowledge into a participated pluvial flood risk assessment (ii) to identify assets and (iii) to estimate the potential impact and efficiency of risk-reduction measures. The assessment is developed in four rapidly expanding towns of Niger, flooded several times in recent years. Flood-prone areas and assets are identified according four flood scenarios using local knowledge, 2D hydraulic modelling, and visual photointerpretation of very-high-resolution satellite images. Risk-reduction measures are singled-out through public participation. The residual risk and benefit/cost analyses provide a decision-making tool to accept or treat risk. During the last decade the expansion of the four towns has been more rapid in flood-prone zones than in safe areas. Nowadays more than half of the housing stock could be flooded by rainfalls with 20 years return period. Catchment treatment and building retrofitting can reduce risk. from 100 to 29–82. Nevertheless, the benefit/cost of risk reduction is high for towns settled in small catchments only.

Aberrant tolerogenic functions and proinflammatory skew of dendritic cells in STAT1 gain-of-function patients may contribute to autoimmunity and fungal susceptibility

STAT1 gain-of-function (GOF) mutations underlie an inborn error of immunity hallmarked by chronic mucocutaneous candidiasis (CMC). Beyond the fungal susceptibility, attributed to Th17 failure, over half of the reported patients suffer from autoimmune manifestations, mechanism of which has not been explained yet. We hypothesized that the STAT1 mutations would affect dendritic cells' (DCs) properties and alter their inflammatory and tolerogenic functions. To test the hypothesis, we generated monocyte-derived DCs (moDCs) and tolerogenic DCs (tDCs). Functional and signaling studies, co-culture experiments and RNA sequencing demonstrated that STAT1 GOF DCs were profoundly altered in their phenotype and functions, characterized by loss of tolerogenic functions, proinflammatory skew and decreased capacity to induce Th17. Cytokine signaling, autophagy and metabolic processes were identified as the most prominently altered cellular processes. The results suggest that DCs are directly involved in STAT1 GOF-associated immune pathology, possibly contributing to both autoimmune manifestations and the failure of antifungal defense.

Immunoprofiling of monocytes in STAT1 gain-of-function chronic mucocutaneous candidiasis.

Patients with STAT1 gain-of-function (GOF) mutations suffer from an inborn error of immunity hallmarked by chronic mucocutaneous candidiasis (CMC). The pathogenesis behind this complex and heterogeneous disease is still incompletely understood. Beyond the well-recognized Th17 failure, linked to the STAT1/STAT3 dysbalance-driven abrogation of antifungal defense, only little is known about the consequences of augmented STAT1 signaling in other cells, including, interestingly, the innate immune cells. STAT1-mediated signaling was previously shown to be increased in STAT1 GOF CD14+ monocytes. Therefore, we hypothesized that monocytes might represent important co-orchestrators of antifungal defense failure, as well as various immunodysregulatory phenomena seen in patients with STAT1 GOF CMC, including autoimmunity. In this article, we demonstrate that human STAT1 GOF monocytes are characterized by proinflammatory phenotypes and a strong inflammatory skew of their secretory cytokine profile. Moreover, they exhibit diminished CD16 expression, and reduction of classical (CD14++C16-) and expansion of intermediate (CD14++16+) subpopulations. Amongst the functional aberrations, a selectively enhanced responsiveness to TLR7/8 stimulation, but not to other TLR ligands, was noted, which might represent a contributing mechanism in the pathogenesis of STAT1 GOF-associated autoimmunity. Importantly, some of these features extend to STAT1 GOF monocyte-derived dendritic cells and to STAT1 GOF peripheral myeloid dendritic cells, suggesting that the alterations observed in monocytes are, in fact, intrinsic due to STAT1 mutation, and not mere bystanders of chronic inflammatory environment. Lastly, we observe that the proinflammatory bias of STAT1 GOF monocytes may be ameliorated with JAK inhibition. Taken together, we show that monocytes likely play an active role in both the microbial susceptibility and autoimmunity in STAT1 GOF CMC.

Multi-objective Optimization Model for C-UAS Sensor Placement in Air Base

Recently, there are an increased the number of reports on the misuse or malicious use of an UAS. Thus, many researchers are studying on defense schemes for UAS by developing or improving C-UAS sensor technology. However, the wrong placement of sensors may lead to a defense failure since the proper placement of sensors is critical for UAS defense. In this study, a multi-object optimization model for C-UAS sensor placement in an air base is proposed. To address the issue, we define two objective functions: the intersection ratio of interested area and the minimum detection range and try to find the optimized placement of sensors that maximizes the two functions. C-UAS placement model is designed using a NSGA-II algorithm, and through experiments and analyses the possibility of its optimization is verified.

Sleep Deprivation, Immune Suppression and SARS-CoV-2 Infection.

Sleep health and its adaptation to individual and environmental factors are crucial to promote physical and mental well-being across animal species. In recent years, increasing evidence has been reported regarding the relationship between sleep and the immune system and how sleep disturbances may perturb the delicate balance with severe repercussions on health outcomes. For instance, experimental sleep deprivation studies in vivo have reported several major detrimental effects on immune health, including induced failure of host defense in rats and increased risk for metabolic syndrome (MetS) and immune suppression in humans. In addition, two novel risk factors for dysregulated metabolic physiology have recently been identified: sleep disruption and circadian misalignment. In light of these recent findings about the interplay between sleep and the immune system, in this review, we focus on the relationship between sleep deprivation and immunity against viruses, with a special interest in SARS-CoV-2 infection.

Defending against adversarial attacks using spherical sampling-based variational auto-encoder

Although deep neural networks achieve outstanding performance in many tasks, adding very imperceptible perturbations to clean images can easily fool the deep neural network. In this paper, we propose a new defence model: Adversarial Memory Variational AutoEncoder(AdMVAE), that can be used to transform adversarial images into clean images. At inference time, it finds an output that is similar to a given image in a high probability region of the manifold space. And the memory module uses normal features to reconstruct the image in the process of reconstruction. It can effectively prevent the reconstruction of malicious perturbations and avoid defense failure. Our approach is a pre-processing module that does not change the results of the classifier. Therefore, it can be combined with other defence models to jointly improve the performance robustness of the classifier. The experimental results on three benchmark datasets including Fashion-MNIST, CIFAR10 and Imagenet show that the proposed method outperforms the state-of-the-art defense methods.

Ferroptotic stress promotes macrophages against intracellular bacteria.

Rational: Intracellular bacterial survival is a major factor causing chronic or recurrent infection, leading to the failure of both host defense and/or antibiotic treatment. However, the elimination of intracellular bacteria is challenging as they are protected from antibiotics and host immune attack. Recent studies have indicated that iron helps macrophages against intracellular bacteria, contradictory to traditional “nutritional immunity”, in which iron is considered a key nutrient for bacterial survival in host cells. However, how iron facilitates intracellular bacterial death has not been fully clarified. In this study, we found that ferroptotic stress can help macrophages suppress intracellular bacteria by reversing the importation of ferrous iron into bacterial vacuoles via ferroportin and thereby inducing in situ ferroptosis-like bacterial death.Methods: A macrophage model of bacterial invasion was established to monitor dynamic changes in ferroptotic hallmarks, including ferrous iron and lipid peroxidation. Ferroptosis inducers and inhibitors were added to the model to evaluate the relationship between ferroptotic stress and intracellular bacterial survival. We then determined the spatiotemporal distributions of ferroportin, ferrous iron, and lipid peroxidation in macrophages and intracellular bacteria. A bacterial infection mouse model was established to evaluate the therapeutic effects of drugs that regulate ferroptotic stress.Results: Ferrous iron and lipid peroxidation increased sharply in the early stage of bacterial infection in the macrophages, then decreased to normal levels in the late stage of infection. The addition of ferroptosis inducers (ras-selective lethal small molecule 3, sulfasalazine, and acetaminophen) in macrophages promoted intracellular bacterial suppression. Further studies revealed that ferrous iron could be delivered to the intracellular bacterial compartment via inward ferroportin transportation, where ferrous iron induced ferroptosis-like death of bacteria. In addition, ferroptotic stress declined to normal levels in the late stage of infection by regulating iron-related pathways in the macrophages. Importantly, we found that enhancing ferroptotic stress with a ferroptosis inducer (sulfasalazine) successfully suppressed bacteria in the mouse infection models.Conclusions: Our study suggests that the spatiotemporal response to ferroptosis stress is an efficient pathway for macrophage defense against bacterial invasion, and targeting ferroptosis may achieve therapeutic targets for infectious diseases challenged by intracellular pathogens.

Cytokines and progressive chronic kidney disease in children

The problem of chronickidney disease is one of the urgent problems in nephrology. There is data on the multifaceted participation of cytokines in the development and prognosis of pathological conditions. The recent studies are focusedon the mechanismsoflocal inflammation with the analysis of interleukins level in the urine. Cytokines are mediators between nonspecific defense reactions and specificimmunity. Being synthesized in the focus of inflammation, cytokines influence almost all cells involvedin inflammation. In case of local defense failure, cytokines enterthe circulation and act at the systemic level, developing an acutephaseresponse in the body. The review presents data on the cytokine status in chronic kidney disease in children and its rolein the progression oft he disease. The authors emphasize the scientific and practical significance of studies of the cytokine status in chronic kidney diseases.