Pathophysiologically, the classification of acute kidney injury (AKI) can be divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal. Emerging evidence supports the involvement ...of renal tubular epithelial cells and the innate and adaptive arms of the immune system in the pathogenesis of intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen-associated molecular patterns, hypoxia inducible factors, toll-like receptors, complement system, oxidative stress, adhesion molecules, cell death, resident renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural killer T cells, cytokines, and secreted chemokines contribute to the immunopathogenesis of AKI. However, other immune cells and pathways such as M2 macrophages, regulatory T cells, progranulin, and autophagy exhibit anti-inflammatory properties and facilitate kidney tissue repair after AKI. Thus, therapies for AKI include agents such as anti-inflammatory (e.g., recombinant alkaline phosphatase), antioxidants (iron chelators), and apoptosis inhibitors. In preclinical toxicity studies, drug-induced kidney injury can be seen after exposure to a nephrotoxicant test article due to immune mechanisms and dysregulation of innate, and/or adaptive cellular immunity. The focus of this review will be on intrinsic AKI, as it relates to the immune and renal systems cross talks focusing on the cellular and pathophysiologic mechanisms of AKI.
Anatomically, the kidneys are paired, bean-shaped (in most mammals), excretory organs that lie in the retroperitoneum. High blood flow to the kidneys, together with high oxygen consumption, makes ...them more vulnerable to exposure, via the circulation, and subsequent injury related to high concentrations of xenobiotics and chemicals. In preclinical drug development and safety assessment of new investigational drugs, changes in kidney structure and/or function following drug administration in experimental laboratory animals need to be put in context with interspecies differences in kidney functional anatomy, physiology, spontaneous pathologies, and toxicopathological responses to injury. In addition, translation to human relevance to avoid premature drug termination from development is vital. Thus, detection and characterization of kidney toxicity in preclinical species and human relevance will depend on the preclinical safety testing strategy and collective weight-of-evidence approach including new investigational drug mechanism of action (MOA), preclinical and clinical interspecies differences, and MOA relevance to humans. This review describes kidney macroscopic and microscopic functional anatomy, physiology, pathophysiology, toxicology, and drug-induced kidney toxicities in safety risk assessment and drug development.
We report first-principles calculations, using the full potential linear augmented plane wave method, on six lead halide semiconductors, namely, CH3NH3PbI3, CH3NH3PbBr3, CsPbX3 (X = Cl, Br, I), and ...RbPbI3. Exchange is modeled using the modified Becke–Johnson potential. With an appropriate choice of the parameter that defines this potential, an excellent agreement is obtained between calculated and experimental band gaps of the six compounds.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic class in clinical medicine. These are sub-divided based on their selectivity for inhibition of cyclooxygenase ...(COX) isoforms (COX-1 and COX-2) into: (1) non-selective (ns-NSAIDs), and (2) selective NSAIDs (s-NSAIDs) with preferential inhibition of COX-2 isozyme. The safety and pathophysiology of NSAIDs on the renal and cardiovascular systems have continued to evolve over the years following short- and long-term treatment in both preclinical models and humans. This review summarizes major learnings on cardiac and renal complications associated with pharmaceutical inhibition of COX-1 and COX-2 with focus on preclinical to clinical translatability of cardio-renal data.
New technique is presented for modeling total cross section of proton-proton (p-p) collision from low to ultra-high energy regions using gene expression programming (GEP). GEP, as a machine learning ...technique is usually used for modeling physical phenomena by discovering a new function σ T ( s ) . In case of modeling the p-p interactions at the Large Hadron Collider (LHC), GEP is used to simulate and predict the total cross-section which is a function of total center-of-mass from low to high energy √s. The discovered function shows a good match as compared with the other models. The predicted values of total cross section are in good agreement with Particle Data Group (PDG).
This study was aimed to investigate the synergistic effects of selenium (Se-NP) and zinc oxide (ZnO-NP) nanoparticles on growth performance, hemato-biochemical profile, immune and oxidative stress ...responses, and intestinal morphometry of Nile tilapia (
Oreochromis niloticus
)
.
Monosex Nile tilapia (12.50 ± 1.03 g,
N
= 180) were randomly allocated into 4 groups in triplicates. Fish were fed diet supplemented with 0 Se-NP and Zn-NP (control group, CG), while fish in the other experimental groups were fed diet supplemented with 1 mg/kg diet Se-NP (Se-NP group), 10 mg/kg diet ZnO-NP (Zn-NP group), and a mixture of 1 and 10 mg/kg diet Se-NP and Zn-NP, respectively (Se/Zn-NP group) for 60 days. Fish fed diet containing Se-NP, Zn-NP, and Se/Zn-NP showed higher final body weight, weight gain, weight gain rate, specific growth rate, and lower feed conversion ratio with respect to CG (
P
<0.05) with the highest being in fish fed with Se/Zn-NP. Fish fed with Se/Zn-NP showed higher hemoglobin, red blood cells, and globulin (
P
<0.05). The highest phagocytic activity, phagocytic index, lysozyme activity, and immunoglobulin M was recorded in fish that received Se/Zn-NP followed by Se-NP, Zn-NP, and the lowest in CG (
P
<0.05). Fish that received diet supplemented with Se-NP, Zn-NP, and Se/Zn-NP significantly (
P
<0.05) increased superoxide dismutase and catalase while reduced malonaldehyde activity compared to CG. Intestinal morphometry revealed significantly (
P
<0.05) increased villi length and goblet cells number in fish fed with Se-NP and/or Zn-NP. In conclusion, dietary supplementation of Nile tilapia with Se-NP and Zn-NP induces synergistic effects that improve growth performance, blood health, and intestinal histomorphology.
As well known, the solar distiller is one of the introduced solutions to the freshwater shortage problem, but it is demerited by the low freshwater output. In this paper, a design modification that ...includes the use of a convex dish absorber instead of a flat absorber liner was proposed. Also, a circular stepped surface was used instead of the flat absorber surface. The modified solar distiller is nominated by dish solar distiller and abbreviated by DSD. In addition, a cotton wick was used as a wetting material for facilitating the evaporation process inside the distiller. Besides, the effect of different water heights in the steps was investigated for 0.50, 1, 1.50, 2, and 3 cm. Finally, the space under the dish absorber is filled with a phase change material (PCM) of paraffin wax mixed with CuO nanoparticles. Experimental results revealed that the best water depth over the steps absorber of DSD that provided the highest freshwater productivity was 1.50 cm, where the average daily yields of DSD (at 1.50 cm) and conventional distillers were reported as 6525 and 2800 mL/m².day, respectively. Then, the productivity of DSD was improved by around 133% over that of the conventional distiller. In addition, when using the phase change material, the average daily distillate of stepped DSD was improved by approximately 178% compared to that of the conventional solar still, where the distillate of conventional still and DSD with PCM at 1.50 cm water depth over the steps absorber of DSD was 2950 and 8200 mL/m².day, respectively. The water productivity of the three established solar distillers has been predicted using machine learning algorithms. Besides, the maximum thermal efficiency of DSD was obtained when using PCM at 1.5 cm water depth over the steps absorber of DSD, where it was 67.62% compared to 31.71% for the conventional distiller. The proposed machine learning algorithms succeeded in predicting water productivity with a high correlation coefficient of 0.99.
Lean premixed combustion mode has become attractive for utilization in industrial gas turbines due to its ability to meet strict emissions regulations without compromising engine efficiency. In this ...combustion mode, the mixing process is the key player that affect the flame structure and stability, as well as the generated emissions. Many studies have investigated the aspects that influence premixed flames, including the effects of turbulence, combustor geometry, and level of partial premixing, while mostly using conventional natural gas fuel represented by methane. Recently, ammonia, a sustainable energy source, has been considered in gas turbines due to its carbon-free fuel producing no CO2. Utilizing 100% ammonia or a blend of methane and ammonia alters the combustion performance of a premixed flame due to the variation associated with the physical and chemical properties of ammonia. Thus, investigating the coupling between blend ratios and mixing length of methane-ammonia on flame stability and emissions is an essential step toward implementing ammonia in industrial gas turbines. In this study, the influence of various methane-ammonia blends, from 0 (pure methane) to XNH3 = 75%, and mixing lengths on the flame performance were studied. The mixing length was altered by delaying the injection (i.e., partially premixing) of the ammonia while using a fixed injection location for the reference methane-air mixture. This was done by using three fuel ports located at three different heights upstream of the combustion chamber. The results showed that the flame stability is negatively influenced by increasing (decreasing) ammonia fraction (mixing length ratio) and is more sensitive to the ammonia fraction than to the mixing length. At a constant equivalence ratio, the CO and NOx performances improved positively by increasing the ammonia volume fractions (especially at XNH3 = 75% compared to XNH3 = 25% and 50%) and the mixing length.
Aeromonas hydrophila is a ubiquitous fish pathogen and an opportunistic human pathogen. It is mostly found in aquatic habitats, but it has also been isolated from food and bottled mineral waters. It ...causes hemorrhagic septicemia, ulcerative disease, and motile Aeromonas septicemia (MAS) in fish and other aquatic animals. Moreover, it might cause gastroenteritis, wound infections, and septicemia in humans. Different variables influence A. hydrophila virulence, including the virulence genes expressed, host susceptibility, and environmental stresses. The identification of virulence factors for a bacterial pathogen will help in the development of preventive and control measures. 95 Aeromonas spp. genomes were examined in the current study, and 53 strains were determined to be valid A. hydrophila. These genomes were examined for pan- and core-genomes using a comparative genomics technique. A. hydrophila has an open pan-genome with 18,306 total genes and 1620 genes in its core-genome. In the pan-genome, 312 virulence genes have been detected. The effector delivery system category had the largest number of virulence genes (87), followed by immunological modulation and motility genes (69 and 46, respectively). This provides new insight into the pathogenicity of A. hydrophila. In the pan-genome, a few distinctive single-nucleotide polymorphisms (SNPs) have been identified in four genes, namely: D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphatase, chemoreceptor glutamine deamidase, Spermidine N (1)-acetyltransferase, and maleylpyruvate isomerase, which are present in all A. hydrophila genomes, which make them molecular marker candidates for precise identification of A. hydrophila. Therefore, for precise diagnostic and discrimination results, we suggest these genes be considered when designing primers and probes for sequencing, multiplex-PCR, or real-time PCR.
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