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Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Responses were studied in C57BL/6J mice in the maternal immune activation (MIA) model and controls. Basal metabolic rates and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Intraperitoneal eATP dropped basal metabolic rate measured by whole body oxygen consumption by 74% ± 6% (mean ± SEM) and rectal temperature by 6.2˚ ± 0.3˚C in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. Breathomics showed an increase in exhaled carbon monoxide, dimethylsulfide, and isoprene. Metabolomics revealed an acute increase in lactate, citrate, purines, urea, dopamine, eicosanoids, microbiome metabolites, oxidized glutathione, thiamine, niacinamide, and pyridoxic acid, and decreased folate-methylation-1-carbon intermediates, amino acids, short and medium chain acyl-carnitines, phospholipids, ceramides, sphingomyelins, cholesterol, bile acids, and vitamin D similar to some children with ASD. MIA animals were hypersensitive to postnatal exposure to eATP or poly(IC), which produced a rebound increase in body temperature that lasted several weeks before returning to baseline. Acute hyperpurinergia produced metabolic and behavioral changes in mice. The behaviors and metabolic changes produced by ATP injection were associated with mitochondrial functional changes that were profound but reversible.

BACKGROUND: More than 230,000 veterans-about 1/3 of US personnel deployed in the 1990-1991 Persian Gulf War-developed chronic, multi-symptom health problems now called Gulf War illness (GWI), for which mechanisms and objective diagnostic signatures continue to be sought. METHODS: Targeted, broad-spectrum serum metabolomics was used to gain insights into the biology of GWI. 40 male participants, included 20 veterans who met both Kansas and CDC diagnostic criteria for GWI and 20 nonveteran controls without similar symptoms that were 1:1 matched to GWI cases by age, sex, and ethnicity. Serum samples were collected and archived at -80° C prior to testing. 358 metabolites from 46 biochemical pathways were measured by hydrophilic interaction liquid chromatography and tandem mass spectrometry. RESULTS: Veterans with GWI, compared to healthy controls, had abnormalities in 8 of 46 biochemical pathways interrogated. Lipid abnormalities accounted for 78% of the metabolic impact. Fifteen ceramides and sphingomyelins, and four phosphatidylcholine lipids were increased. Five of the 8 pathways were shared with the previously reported metabolic phenotype of males with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, 4 of the 5 shared pathways were regulated in opposite directions; key pathways that were up-regulated in GWI were down-regulated in ME/CFS. The single pathway regulated in the same direction was purines, which were decreased. CONCLUSIONS: Our data show that despite heterogeneous exposure histories, a metabolic phenotype of GWI was clearly distinguished from controls. Metabolomic differences between GWI and ME/CFS show that common clinical symptoms like fatigue can have different chemical mechanisms and different diagnostic implications. Larger studies will be needed to validate these findings.

The Named Data Networking (NDN) is currently an important future network framework, and the mobility issue of producers within NDN is a primary challenge. However, in environments characterized by frequent producers mobility, traditional producer mobility support schemes still encounter issues such as excessive consumer delays and interest packet loss. With the development of The 6th generation communication technology (6G), integrating ground networks with satellites has emerged as a potential solution to address the aforementioned problems. In this paper, we propose an NDN producer mobility support scheme based on multi-satellite data depot, named MsDD. The proposed scheme proactively caches producer data into a data depot built on a low-earth orbit satellite constellation to minimize the impact of NDN producer mobility on network performance. We design data depot construction strategy, in-network caching strategy, and routing strategy based on forwarding hint to facilitate effective communication in satellite networks. Experimental results using ndnSIM demonstrate that compared with other existing schemes, MsDD can effectively shield the impact of producer mobility on consumer delay, delivery ratio, and signaling overhead, and MsDD has a clear advantage in terms of consumer delay and delivery ratio. [ABSTRACT FROM AUTHOR]

Proposed is a Satellite network cache placement strategy (PNCCP) based on popularity and node cooperation to address the issue of significant delays in end-to-end connectivity due to instability among satellites. Initially, the strategy employs spectral clustering algorithm to partition the satellite network's topology, limiting the retrieval scope of content and reducing unnecessary propagation delays. Within each partition, a cache collaboration open mechanism among satellites is devised to share cache resources, utilizing the proximity of neighboring nodes to share popular content and cache space. Furthermore, the data naming network (NDN) cache model is enhanced and integrated with the open mechanism, with an update mechanism designed to address the invalidation caused by the dynamic nature of satellite networks. Finally, aiming to minimize users' average retrieval delay, the artificial bee colony algorithm is employed to solve the optimal cache placement problem. Simulation results demonstrate that compared to three contrasting cache strategies, the proposed strategy reduces user content retrieval delays, improves cache hit rates, and holds an advantage in reducing request hop counts. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is among the top ten most common forms of cancer and is the most common malignancy of the kidney. Clear cell renal carcinoma (cc-RCC), the most common type of RCC, is one of the most refractory cancers with an incidence that is on the rise. Screening of plant extracts in search of new anti-cancer agents resulted in the discovery of englerin A, a guaiane sesquiterpene with potent cytotoxicity against renal cancer cells and a small subset of other cancer cells. Though a few cellular targets have been identified for englerin A, it is still not clear what mechanisms account for the cytotoxicity of englerin A in RCC, which occurs at concentrations well below those used to engage the targets previously identified. Unlike any prior study, the current study used a systems biology approach to explore the mechanism(s) of action of englerin A. Metabolomics analyses indicated that englerin A profoundly altered lipid metabolism by 24 h in cc-RCC cell lines and generated significant levels of ceramides that were highly toxic to these cells. Microarray analyses determined that englerin A induced ER stress signaling and an acute inflammatory response, which was confirmed by quantitative PCR and Western Blot analyses. Additionally, fluorescence confocal microscopy revealed that englerin A at 25 nM disrupted the morphology of the ER confirming the deleterious effect of englerin A on the ER. Collectively, our findings suggest that cc-RCC is highly sensitive to disruptions in lipid metabolism and ER stress and that these vulnerabilities can be targeted for the treatment of cc-RCC and possibly other lipid storing cancers. Furthermore, our results suggest that ceramides may be a mediator of some of the actions of englerin A. Lastly, the acute inflammatory response induced by englerin A may mediate anti-tumor immunity.

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis. [ABSTRACT FROM AUTHOR]

ObjectiveHead and neck squamous cell carcinoma (HNSCC) accounts for more than 5% of all cancers worldwide. The mortality rate of HNSCC has remained unchanged (approximately 50%) over the last few decades. Ubiquitous overexpression of wild type EGFR in many solid tumors has led to the development of EGFR targeted therapies. EGFR can be constitutively activated via several mechanisms including the truncated, EGFR variant III isoform (EGFRvIII). EGFRvIII lacks exons 2-7 and has been reported to be present in up to 20-40% of HNSCC. EGFRvIII has been shown to contribute to cetuximab resistance. The mechanisms leading to EGFRvIII expression in HNSCC are unknown. The present investigation was undertaken to determine the etiology of EGFRvIII in HNSCC.Materials and methodsFixed HNSCC and glioma tissues were analyzed by fluorescence in situ hybridization for EGFR amplification. DNA and RNA from fresh frozen specimens were used to determine the presence of EGFRvIII transcripts and the mechanisms of expression via PCR, RT-PCR and RNA sequencing.ResultsUnlike glioma, EGFRvIII expression in HNSCC did not correlate with EGFR amplification. We found evidence of genomic deletion of the exon 2-7 in 6 of 7 HNSCC cases examined, however, the presence of genomic deletion did not always result in mRNA expression of EGFRvIII. RNA sequencing with automated alignment did not identify EGFRvIII due to microhomology between intron 1 and exon 8. RNA sequencing analyzed by manual alignment methods did not correlate well with RT-PCR and PCR findings.ConclusionThese findings suggest that genomic deletion as well as additional regulatory mechanisms may contribute to EGFRvIII expression in HNSCC. Further, large scale automated alignment of sequencing are unlikely to identify EGFRvIII and an assay specifically designed to detect EGFRvIII may be necessary to detect this altered form of EGFR in HNSCC tumors.

In the background of the post-epidemic era, the consumption demand and market scale of cold chain logistics in China are expanding, but there is still an obvious gap with developed countries. To complete the balance between the supply and demand for aquatic products and the rational allocation of logistics resources and promote the rapid development trend of aquatic product cold chain logistics, it is particularly important to forecast and analyze the demand for aquatic product cold chain logistics. This article selects six main factors that affect the demand for aquatic products in cold chain logistics, uses the traditional grey model and the grey-BP neural network model to simulate and predict the demand for aquatic products in cold chain logistics in China from 2012 to 2021, and compares and analyzes the simulation results. Generally speaking, the demand for aquatic products from Chinese residents is on the rise. In the simulation prediction process, the prediction error of the grey-BP neural network is reduced compared to the traditional grey model, and the processing ability of the nonlinear system is ideal. The results show that the grey-BP neural network model is an effective method to predict the demand for cold chain logistics of aquatic products. Finally, suggestions are made on the future development of aquatic cold chain logistics in the post-epidemic era from the economic, social, and environmental aspects, which provide valuable decision-making reference for the development of marine aquaculture enterprises and cold chain logistics industry. [ABSTRACT FROM AUTHOR]

Flood-based hydrodynamic damage to check dam systems on the Loess Plateau of China occurs frequently, and there is a strong desire to carry out risk assessments of such check dam systems. This study proposes a weighting method that combines the analytic hierarchy process, entropy method, and TOPSIS to assess the risk of check dam systems. The combined weight-TOPSIS model avoids weight calculation only considers the influence of subjective or objective preference and the bias of the single weighting method. The proposed method is capable of multi-objective risk ranking. It is applied to the Wangmaogou check dam system located in a small watershed on the Loess Plateau. The result of risk ranking matches the reality of the situation. The gray correlation theory model is utilized to rank the risks in the same research area and compared with the results of the combined weight-TOPSIS model. The combined weight-TOPSIS model is more favorable to risk assessment than the gray correlation theory model. The resolution level and decisive judgment of the combined weight-TOPSIS model are more advantageous. These results are in line with the actual conditions. It proves that the combined weight-TOPSIS model can provide a technical reference for the risk assessment of check dam systems in small watersheds. [ABSTRACT FROM AUTHOR]

This study aimed to compare the intrinsic foot muscle (IFM) morphology and isometric strength among runners with habitual rearfoot strike (RFS) and non-rearfoot strike (NRFS) patterns. A total of 70 recreational male runners were included in this study (32 RFS and 38 NRFS), an ultrasound device and hand-held dynamometry were used to measure IFM morphology and isometric strength. Results indicated that the RFS runners had significantly thicker tibialis anterior (P = 0.01, ES = 0.64, 95% CI [0.01–0.07]) in IFMs morphology and higher Toe2345 flexion strength in IFMs strength (P = 0.04, ES = 0.50, 95% CI [0.01–0.27]) than NRFS runners, the cross-sectional area of flexor digitorum brevis was positively correlated with T2345 flexion strength (r = 0.33, p = 0.04), T12345 (r = 0.37, p = 0.02) and Doming (r = 0.36, p = 0.03) for runners with NRFS. IFMs morphology and isometric strength were associated with foot strike pattern, preliminary findings provide new perspectives for NRFS runners through the simple measurement of IFMs morphological characteristics predicting IFMs strength, future studies could adopt IFMs training to compensate the muscle strength defects and prevent foot-related injuries. [ABSTRACT FROM AUTHOR]