Damage To System Research Articles

Reliability sensitivity analysis for water hammer-induced stress failure of fluid-conveying pipe

The water hammer, resulting from sudden valve closures or similar operations, is a primary cause of leakage and damage in fluid-conveying pipe systems. This work aims to investigate the reliability sensitivity of fluid-conveying pipes under the water hammer. A reliability model for the fluid-conveying straight pipe, involving uncertainty and fluid-structure interaction, is developed based on the stress-strength interference theory. Then the method of characteristics is employed to analyze the nonlinear behaviors of the pipe. To avoid excessive model evaluations, the Kriging surrogate strategy is used to evaluate rapidly the statistics of nonlinear responses. Furthermore, the Kriging model coupled with the single-loop Monte Carlo simulation is presented for estimating reliability sensitivity indices. The accuracy of results is verified by the Monte Carlo simulation. The results reveal that the proposed method is feasible for the reliability sensitivity analysis of fluid-conveying pipe under the water hammer. Moreover, the wall thickness has the most obvious influence on stress failure, followed by the inner radius, while the pipe length, Young's modulus, density of the pipe material, and Poisson ratio show a low effect. This work can not only guide the safety design of pipe but also enrich the theory and application of statistical analysis and reliability sensitivity evaluation for liquid-conveying pipe systems.

Living in a dynamic environment: The effects of multi-ways temperature variation on embryo and newborn juveniles of a shallow-water octopus (Amphioctopus fangsiao)

Shallow waters are characterized by fluctuating environmental conditions, modulating marine life cycles and biological phenomena. Multiple variations in water temperature could affect eggs and embryos during spawning events of many marine invertebrate species, yet most of the findings on embryonic development in invertebrates come from experiments based on the constant temperature. In this study, to examine the effects of temperature variation on octopus embryos, Amphioctopus fangsiao, a common shallow-water octopus along the coast of China, was exposed to the constant temperature (18 °C, in situ temperature of the seawater in Lianyungang), ramping temperatures (from 18 to 24 °C), diel oscillating temperatures (18 °C and 20 °C for 12 h each day), and acute increasing temperatures (the temperature increased sharply from 18 °C to 24 °C at embryonic development stage XIX) for 47 days (from embryogenesis to settlement). The results demonstrated that the temperature variations accelerated the development time of A. fangsiao embryos. Temperature fluctuations could cause embryonic oxidative damage and disorder of glycolipid metabolism, thereby affecting the growth performance of embryos and the survival rate of hatchings. Through transcriptome sequencing, the mechanistic adaption of the embryo to environmental temperature variations was revealed. The pathways involved in the TCA cycle, DNA replication and repair, protein synthesis, cell signaling, and nervous system damage repair were significantly enriched, indicating that the embryo could improve heat tolerance to thermal stress by regulating gene expression. Moreover, acute warming temperatures posed the most detrimental effects on A. fangsiao embryos, which could cause embryos to hatch prematurely from the vegetal pole, further reducing the survival of hatchings. Meanwhile, the diel oscillating temperature was observed to affect the normal morphology of the embryo, resulting in embryo deformities. Thus, the constant temperature is critical for balanced growth and defense status in octopuses by maintaining metabolism homeostasis. For the first time, this study evaluates the effects of multiple temperature fluctuations on embryos of A. fangsiao, providing new insights into the physiological changes and molecular responses of cephalopod embryos following dynamic temperature stress.

Oral subacute polypropylene microplastics administration effect on potential immunotoxicity in ICR mice

ABSTRACT Exposure to microplastics may be associated with damage of immune system. Polypropylene microplastics (PP-MPs) with a wide range of beneficial applications have not been extensively studied with respect to the immune system. The aim of this investigation is to examine the influence of two different sizes of PP-MPs (5.2 and 23.9 μm diameter) on immune system components in ICR mice. PP-MPs were administered orally to female and male mice at 0 (corn oil vehicle), 500, 1000, or 2000 mg/kg/d for single and daily for 4-week repeated toxicity test, respectively. No significant differences were observed in number of thymic CD4+, CD8+, CD4+CD8+ T lymphocytes, splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-γ to interleukin-4 in culture supernatants from activated splenocytes ex vivo (48 hr) was lower in females which were repeatedly administered with PP-MPs compared to vehicle irrespective of PP-MPs size and dose. In contrast, the opposite trend was observed in males. Production of tumor necrosis factor-α was upregulated in females that were repeatedly exposed to PP-MPs. The serum IgG2a/IgG1 ratio was lowered in female receiving large-size PP-MPs. Data suggest that immune disturbances resulting in predominant type-2 helper T cell reactivity may occur in mice, especially in females, when repeatedly exposed to PP-MPs. Further investigations with longer exposure periods are necessary to determine the immunotoxicities attributed to PP-MPs.

Strategies for Organochlorine/Organobromine Removal from Aqueous Environment Using Nanotechnology: A Review

Organohalogens have been discovered since the 1930s and have been used for many applications ever since. The rapid development of industrial activities and reliance on organochlorine/organobromine compounds have further increased their production, ultimately leading to their leakage into our natural environment, where they circulate indefinitely. Exposure to these persistent organic pollutants (POPs) not only results in detrimental effects on human health, such as various cancers, nervous system damage, and liver damage, in addition to fetal and infant growth defects, but also affects fauna, such as bird populations, by depriving them of the ability to reproduce successfully, and farm livestock. The direct consumption of the latter or its derivatives will also lead to the bioaccumulation of POPs in the human body. The POP treatment methods discussed in this review include granular activated carbon (GAC) adsorption, magnetic nanospheres coated with polystyrene, hydrogen peroxide (H2O2), UV, as well as O3 ozonation. The mechanisms, along with the advantages and drawbacks of these methods, were thoroughly discussed. Finally, challenges faced in reducing organochlorine/organobromine pollution were discussed, such as the lack of updates on water quality standards and the list of dangerous pollutants, and the failure to control illegal disposal issues.

Minimalist Deployment of Neural Network Equalizers in a Bandwidth-Limited Optical Wireless Communication System with Knowledge Distillation.

An equalizer based on a recurrent neural network (RNN), especially with a bidirectional gated recurrent unit (biGRU) structure, is a good choice to deal with nonlinear damage and inter-symbol interference (ISI) in optical communication systems because of its excellent performance in processing time series information. However, its recursive structure prevents the parallelization of the computation, resulting in a low equalization rate. In order to improve the speed without compromising the equalization performance, we propose a minimalist 1D convolutional neural network (CNN) equalizer, which is reconverted from a biGRU with knowledge distillation (KD). In this work, we applied KD to regression problems and explain how KD helps students learn from teachers in solving regression problems. In addition, we compared the biGRU, 1D-CNN after KD and 1D-CNN without KD in terms of Q-factor and equalization velocity. The experimental data showed that the Q-factor of the 1D-CNN increased by 1 dB after KD learning from the biGRU, and KD increased the RoP sensitivity of the 1D-CNN by 0.89 dB with the HD-FEC threshold of 1 × 10-3. At the same time, compared with the biGRU, the proposed 1D-CNN equalizer reduced the computational time consumption by 97% and the number of trainable parameters by 99.3%, with only a 0.5 dB Q-factor penalty. The results demonstrate that the proposed minimalist 1D-CNN equalizer holds significant promise for future practical deployments in optical wireless communication systems.

Sickle cell disease and increased adverse maternal and perinatal outcomes in different genotypes

BackgroundSickle cell disease (SCD) comprises a heterogeneous group of inherited hemolytic disorders that increases the risk of maternal and perinatal complications due to chronic systemic inflammatory response, endothelial damage and vaso-occlusion. The contribution of genotypes to the severity of outcomes during pregnancy is not completely established. MethodsA retrospective study of medical charts was performed to compare maternal and perinatal outcomes in Hb SS, Hb SC disease and sickle-beta thalassemia (Hb Sβ) pregnancies followed at a high-risk antenatal care unit over a 6-year period. A descriptive analysis of morphological findings was performed of the placenta when pathology reports were available. ResultsSixty-two SCD pregnant women [25 Hb SS (40 %), 29 Hb SC (47 %) and 8 Hb Sβ (13 %)] were included. Overall, SCD was associated with maternal complications (77 %), preterm birth (30 %), cesarean section (80 %) and a need of blood transfusion. In general there were no statistically significant differences between genotypes. The only significant difference was the hemoglobin level at first antenatal care visit which was lower for the homozygous genotype (7.7 g/dL) compared to Hb SC and Hb Sβ (9.7 g/dL and 8.4 g/dL, respectively; p-value = 0.01). Ten of 15 evaluated placentas showed abnormal morphological findings ConclusionSCD, regardless of the underlying genotype, is associated with increased adverse maternal and perinatal outcomes and placental abnormalities associated with maternal vascular malperfusion.

QTc Prolongation to Predict Mortality in Patients Admitted with COVID-19 Infection: An Observational Study.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), characterized by pulmonary infection ranging from asymptomatic forms to respiratory insufficiency and death. Evidence of cardiac involvement in COVID-19 is increasing, and systemic inflammation or direct heart damage by SARS-CoV-2 can prolong the corrected QT interval (QTc). In this observational study, a total of 333 consecutive patients admitted to the Covid Center of Verona University Hospital from November 2020 to April 2021 were included. Patients with bundle branch block, pacemaker-controlled heart rhythm and heart rate >120 beats/min were excluded. A complete electrocardiogram (ECG) was performed at admission, and QTc values of ≥440 ms for males and ≥460 ms for females were considered prolonged. Overall, 153 patients had prolonged QTc (45.5%). In multivariate logistic regression analysis, male sex (odds ratio (OR)=6.612, p=0.046), troponin (OR=1.04, p=0.015) and lymphocyte count (OR=3.047, p=0.019) were independently associated with QTc prolongation. Multivariate logistic regression showed that QTc was independently associated with mortality (OR=4.598, p=0.036). Age, sex, the ratio between the partial pressure of oxygen (PaO2) and the fraction of inspired oxygen (FiO2) (P/F), and fibrosis-4 index for liver fibrosis (FIB-4) were also independently associated with mortality. QTc interval prolongation appears to be a frequent finding in patients with COVID-19. Moreover, prolonged QTc may be predictive of more severe forms of COVID-19 and worse outcome.

Fingolimod improves diffuse brain injury by promoting AQP4 polarization and functional recovery of the glymphatic system.

Diffuse brain injury (DBI) models are characterized by intense global brain inflammation and edema, which characterize the most severe form of TBI. In a previous experiment, we found that fingolimod promoted recovery after controlled cortical impact injury (CCI) by modulating inflammation around brain lesions. However, it remains unclear whether fingolimod can also attenuate DBI because of its different injury mechanisms. Furthermore, whether fingolimod has additional underlying effects on repairing DBI is unknown. The impact acceleration model of DBI was established in adult Sprague-Dawley rats. Fingolimod (0.5 mg/kg) was administered 0.5, 24, and 48 h after injury for 3 consecutive days. Immunohistochemistry, immunofluorescence analysis, cytokine array, and western blotting were used to evaluate inflammatory cells, inflammatory factors, AQP4 polarization, apoptosis in brain cells, and the accumulation of APP after DBI in rats. To evaluate the function of the glymphatic system (GS), a fluorescent tracer was injected into the cistern. The neural function of rats with DBI was evaluated using various tests, including the modified neurological severity score (mNSS), horizontal ladder-crossing test, beam walking test, and tape sensing and removal test. Brain water content was also measured. Fingolimod administration for 3 consecutive days could reduce the levels of inflammatory cytokines, neutrophil recruitment, microglia, and astrocyte activation in the brain following DBI. Moreover, fingolimod reduced apoptotic protein expression, brain cell apoptosis, brain edema, and APP accumulation. Additionally, fingolimod inhibited the loss of AQP4 polarization, improved lymphatic system function, and reduced damage to nervous system function. Notably, inhibiting the GS weakened the therapeutic effect of fingolimod on the neurological function of rats with DBI and increased the accumulation of APP in the brain. In brief, these findings suggest that fingolimod alleviates whole-brain inflammation and GS system damage after DBI and that inhibiting the GS could weaken the positive effect of fingolimod on nerve function in rats with DBI. Thus, inhibiting inflammation and regulating the GS may be critical for the therapeutic effect of fingolimod on DBI.

Study on the underlying molecular mechanism of benzene-induced nervous system damage in mice based on tandem mass tag (TMT) proteomics.

Benzene is known to be a common toxic industrial chemical, and prolonged benzene exposure may cause nervous system damage. At present, there were few studies on benzene-induced neurological damage. This research aimed to identify the protein biomarkers to explore the mechanism of nervous system damage caused by benzene. We established a benzene poisoning model of C57 mice by gavage of benzene-peanut oil suspension and identified differentially expressed proteins (DEPs) in brain tissue using tandem mass tag (TMT) proteomics. The results showed a significant weight loss and decrease in leukocyte and neutrophil counts in benzene poisoning mice compared to the control group. We also observed local cerebral oedema and small vessel occlusion in the cerebral white matter of benzene poisoning mice. TMT proteomic results showed that a total 6,985 proteins were quantified, with a fold change (FC)>1.2 (or<1/1.2) and P value <0.05 were considered as DEPs. Compared with the control group, we identified 43 DEPs, comprising 14 upregulated and 29 downregulated proteins. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis results showed that the candidate proteins were mainly involved in cholesterol metabolism, complement and coagulation cascades, african trypanosomiasis, PPAR signaling pathway, and vitamin digestion and absorption. Three proteins, 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (UGT8), Apolipoprotein A-I (APOA1) and Complement C3 (C3) were validated using immunoblotting and immunohistochemical. In conclusion, our study preliminarily investigated the mechanism of benzene toxicity to the nervous system by analyzing DEPs changes in the brain.

Adult-onset Krabbe disease manifesting as Charcot- Marie-Tooth disease

Krabbe disease (KD) is a progressive lysosomal storage disorder characterized by the deficiency of β-galactocerebrosidase (GALC). It mainly manifests as central nervous system involvement, but peripheral nervous system damage is also found. Although it can appear as a widespread neuropathy, it is very rare to manifest in a form similar to Charcot-Marie-Tooth disease (CMT). A 34-year-old woman presented with progressive gait disturbance and foot deformity. There were no other medical or family history of abnormalities. Nerve conduction studies showed demyelinating neuropathy, and brain MRI showed white matter hyperintensities. Sequencing of PMP22 gene was normal, followed by next-generation sequencing (NGS). Potential compound heterozygous variants in the GALC gene were found; additionally a decrease in GALC enzymatic activity was confirmed, and KD was diagnosed. Although CMT has been previously diagnosed through a single genetic test, since the introduction of NGS, various genetic mutations have been identified in patients suspected of having CMT. In addition to the phenotypes mainly found in KD, other unusual phenotypes have also been found. In this case, we identified a unique clinical phenotype similar to CMT in a KD patient. We also confirmed the clinical usefulness of NGS by demonstrating in a KD patient diagnosed through NGS, who was not identified by conventional genetic mutation testing.

Neutrophil-Associated Proteins as Novel Biomarkers Elevated in Cerebrospinal Fluid of Patients With Neurosyphilis.

The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges. We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 patients with non-neurosyphilis and 10 with neurosyphilis. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 patients with non-neurosyphilis, 51 with untreated neurosyphilis, and 31 posttreatment for neurosyphilis were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve. A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis positively correlated with white blood cell counts, rapid plasma regain (RPR) titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an area under the curve of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR. CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis.

Bioprospecting of Polyhydroxy butyrate (PHB) from Bacillus thuringiensis KUMBNGBT-41 by using Agro-industrial wastes

The diverse group of chemicals used in making of plastic is known to be highly toxic and poses a serious threat to the biosphere. These substances besides hitting hard to ecosystem cause an array of problems like birth defects, cancer, damage of nervous and immune systems. The present research work was aimed to isolate and characterize PHB producing bacteria from landfill soil sample collected from Sanehally, Chitradurga district and qualitatively screened by using viable staining techniques. Quantitative estimation was examined by using solvent extraction method. The PHB producing bacteria were characterized based on morphological, biochemical and molecular identification and confirmed as Bacillus thuringiensis strain KUMBNGBT-41 (Accession No. MW040075). Growth parameters were optimized for biomass production using various conditions such as media-nutrient broth, incubation time-72hrs, temperature-37˚C, pH-7.0, carbon source-glucose, nitrogen source-ammonium chloride and carbon to nitrogen ratio as 4:1. The low-cost production media was used for PHB production by cheaper substrates in submerged fermentation. PHB was analysed and quantified by using UV-Visible spectrophotometer at 200-600nm.

Progress in the Treatment of Central Nervous System Diseases Based on Nanosized Traditional Chinese Medicine.

Traditional Chinese Medicine (TCM) is widely used in clinical practice to treat diseases related to central nervous system (CNS) damage. However, the blood-brain barrier (BBB) constitutes a significant impediment to the effective delivery of TCM, thus substantially diminishing its efficacy. Advances in nanotechnology and its applications in TCM (also known as nano-TCM) can deliver active ingredients or components of TCM across the BBB to the targeted brain region. This review provides an overview of the physiological and pathological mechanisms of the BBB and systematically classifies the common TCM used to treat CNS diseases and types of nanocarriers that effectively deliver TCM to the brain. Additionally, drug delivery strategies for nano-TCMs that utilize in vivo physiological properties or in vitro devices to bypass or cross the BBB are discussed. This review further focuses on the application of nano-TCMs in the treatment of various CNS diseases. Finally, this article anticipates a design strategy for nano-TCMs with higher delivery efficiency and probes their application potential in treating a wider range of CNS diseases.

MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques.

MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 108 infectious units of the MVA-BN-EEEV or MVA-BN-WEV vaccine by the intramuscular route rapidly developed robust levels of neutralizing antibodies to EEEV that persisted at high levels until challenge at day 84 via small particle aerosol delivery with a target inhaled dose of 107 PFU of EEEV FL93-939. Robust protection was observed, with 7/8 animals receiving MVA-BN-EEEV and 100% (8/8) animals receiving MVA-BN-WEV surviving while only 2/8 mock vaccinated controls survived lethal challenge. Complete protection from viremia was afforded by both vaccines, with near complete protection from vRNA loads in tissues and any pathologic evidence of central nervous system damage. Overall, the results indicate both vaccines are effective in eliciting an immune response that is consistent with protection from aerosolized EEEV-induced disease.

NEAR-INFRARED DYE IR-780 ALLEVIATES HEMATOPOIETIC SYSTEM DAMAGE BY PROMOTING HEMATOPOIETIC STEM CELLS INTO QUIESCENCE.

Potential radiation exposure is a general concern, but there still lacks radioprotective countermeasures. Here, we found a small molecular near-infrared dye IR-780, which promoted hematopoietic stem cells (HSCs) into quiescence to resist stress. When mice were treated with IR-780 before stress, increased HSC quiescence and better hematopoietic recovery were observed in mice in stress conditions. However, when given after radiation, IR-780 did not show obvious benefit. Transplantation assay and colony-forming assay were carried out to determine self-renewal ability and repopulation capacity of HSCs. Furthermore, IR-780 pretreatment reduced the generation of reactive oxygen species (ROS) and DNA damage in HSCs after radiation. In homeostasis, the percentage of Lineage - , Sca-1 + , and c-Kit + cells and long-term HSCs (LT-HSCs) were improved, and more HSCs were in G0 state after administration of IR-780. Further investigations showed that IR-780 selectively accumulated in mitochondria membrane potential high LT-HSCs (MMP-high LT-HSCs). Finally, IR-780 promoted human CD34 + HSC reconstruction ability in NOD-Prkdc scid Il2rg null mice after transplantation and improved repopulation capacity in vitro culture. Our research showed that IR-780 selectively entered MMP-high LT-HSCs and promoted them into dormancy, thus reducing hematopoietic injury and improving regeneration capacity. This novel approach might hold promise as a potential countermeasure for radiation injury.

Clinical characteristics of 4,520 paediatric patients infected with the SARS-CoV-2 omicron variant, in Xi'an, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has broad tissue tropism and high transmission, which are likely to perpetuate the pandemic. The study aim to analyze the clinicopathogenic characteristics in paediatric patients. In this single-centre study, we retrospectively included all confirmed cases infected by SARS-CoV-2 infection at Xi'an Children's Hospital, China, from 1 December to 31 December 2022. The demographic, clinical, laboratory, and radiological features of the patients were analysed. A total of 4,520 paediatric patients with SARS-CoV-2 omicron variant infections were included. Of these, 3,861 (85.36%) were outpatients, 659 (14.64%) were hospitalised patients, and nine patients (0.20%) died. Of the nine patients who died, five were diagnosed with acute necrotising encephalopathy (ANE). The most common symptoms were fever in 4,275 (94.59%) patients, cough in 1,320 (29.20%) patients, convulsions in 610 (13.50%) patients, vomiting in 410 (9.07%) patients, runny nose/coryza in 277 (6.13%) patients, hoarseness of voice in 273 (6.04%) patients. A blood cell analysis showed a slight elevation of monocytes (mean: 11.14 ± 0.07%). The main diagnoses for both outpatients and inpatients were respiratory infection with multisystem manifestations. A high incidence of convulsions is a typical characteristic of children infected with SARS-CoV-2. Five of the nine COVID-19 fatalities were associated with ANE. This indicates that nervous system damage in children with SARS-CoV-2 infection is more significant.

Поражение ЦНС у новорожденных вследствие гипо- и гипергликемии

Carbohydrate metabolism plays an enormous role in the vital functions of a child’s body. Glucose is the main energy source for the development of the central nervous system starting from the intrauterine development period. This bibliographical review is devoted to such pathological conditions of newborns as hypo- and hyperglycemias and namely to the mechanisms of the influence of the named metabolic disorders on the central nervous system, the topography of the brain damages and clinical consequences. The analysis revealed that dysglycaemia is more common in children with an aggravated ante- and perinatal history, is combined with damage of brain structures and leads, even in subclinical form, to short- and long-term consequences of neuropsychiatric development, and therefore requires predictive and timely verification and correction taking into account individual characteristics.

Implications of tolerance to iron toxicity on root system architecture changes in rice (Oryza sativa L.)

IntroductionToxicity due to excess soil iron (Fe) is a significant concern for rice cultivation in lowland areas with acidic soils. Toxic levels of Fe adversely affect plant growth by disrupting the absorption of essential macronutrients, and by causing cellular damage. To understand the responses to excess Fe, particularly on seedling root system, this study evaluated rice genotypes under varying Fe levels.MethodsSixteen diverse rice genotypes were hydroponically screened under induced Fe levels, ranging from normal to excess. Morphological and root system characteristics were observed. The onset of leaf bronzing was monitored to identify the toxic response to the excess Fe. Additionally, agronomic and root characteristics were measured to classify genotypes into tolerant and sensitive categories by computing a response stability index.ResultsOur results revealed that 460 ppm of Fe in the nutrient solution served as a critical threshold for screening genotypes during the seedling stage. Fe toxicity significantly affected root system traits, emphasizing the consequential impact on aerial biomass and nutrient deprivation. To classify genotypes into tolerant and sensitive categories, leaf bronzing score was used as a major indicator of Fe stress. However, the response stability index provided a robust basis for classification for the growth performance. Apart from the established tolerant varieties, we could identify a previously unrecognized tolerant variety, ILS 12–5 in this study. Some of the popular mega varieties, including BPT 5204 and Pusa 44, were found to be highly sensitive.DiscussionOur findings suggest that root system damage, particularly in root length, surface area, and root volume, is the key factor contributing to the sensitivity responses under Fe toxicity. Tolerant genotypes were found to retain more healthy roots than the sensitive ones. Fe exclusion, by reducing Fe2+ uptake, may be a major mechanism for tolerance among these genotypes. Further field evaluations are necessary to confirm the behavior of identified tolerant and sensitive lines under natural conditions. Insights from the study provide potential scope for enhancement of tolerance through breeding programs as well as throw light on the role root system in conferring tolerance.

TGFβ1-induced hedgehog signaling suppresses the immune response of brain microvascular endothelial cells elicited by meningitic Escherichia coli

BackgroundMeningitic Escherichia coli (E. coli) is the major etiological agent of bacterial meningitis, a life-threatening infectious disease with severe neurological sequelae and high mortality. The major cause of central nervous system (CNS) damage and sequelae is the bacterial-induced inflammatory storm, where the immune response of the blood-brain barrier (BBB) is crucial.MethodsWestern blot, real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and dual-luciferase reporter assay were used to investigate the suppressor role of transforming growth factor beta 1 (TGFβ1) in the immune response of brain microvascular endothelial cells elicited by meningitic E. coli.ResultIn this work, we showed that exogenous TGFβ1 and induced noncanonical Hedgehog (HH) signaling suppressed the endothelial immune response to meningitic E. coli infection via upregulation of intracellular miR-155. Consequently, the increased miR-155 suppressed ERK1/2 activation by negatively regulating KRAS, thereby decreasing IL-6, MIP-2, and E-selectin expression. In addition, the exogenous HH signaling agonist SAG demonstrated promising protection against meningitic E. coli-induced neuroinflammation.ConclusionOur work revealed the effect of TGFβ1 antagonism on E. coli-induced BBB immune response and suggested that activation of HH signaling may be a potential protective strategy for future bacterial meningitis therapy.BxeG5o_KFymqkvc8v8uqghVideo

Non-stenotic fibro-calcific aortic valve as a predictor of myocardial infarction recurrence.

Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk. To stratify subgroups of AMI patients with specific probabilities of recurrent AMI and to evaluate the importance of AVSc in this setting. Consecutive AMI patients (n = 2530) were admitted at Centro Cardiologico Monzino (2010-2019) and followed up for 5 years. Patients were divided into study (n = 1070) and test (n = 966) cohorts. Topological data analysis (TDA) was used to stratify patient subgroups, while Kaplan-Meier and Cox regressions analyses were used to evaluate the significance of baseline characteristics. TDA identified 11 subgroups of AMI patients with specific baseline characteristics. Two subgroups showed the highest rate of reinfarction after 5 years from the indexed AMI with a combined hazard ratio (HR) of 3.8 (95%CI: 2.7-5.4) compared to the other subgroups. This was confirmed in the test cohort (HR = 3.1; 95%CI: 2.2-4.3). These two subgroups were mostly men, with hypertension and dyslipidemia, who exhibit higher prevalence of AVSc, higher levels of high-sensitive c-reactive protein and creatinine. In the year-by-year analysis, AVSc, adjusted for all confounders, showed an independent association with the increased risk of reinfarction (odds ratio of ∼2 at all time-points), in both the study and the test cohorts (all p < 0.01). AVSc is a crucial variable for identifying AMI patients at high risk of recurrent AMI and its presence should be considered when assessing the management of AMI patients. The inclusion of AVSc in risk stratification models may improve the accuracy of predicting the likelihood of recurrent AMI, leading to more personalized treatment decisions.