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Due to the extreme temperatures inside the combustion chambers of liquid propellant rocket engines, the walls of the combustion chamber and the nozzle are cooled by either the fuel or the oxidizer in what is known as regenerative cooling. This study presents an indigenous computational tool developed for the analysis of heat transfer in regenerative cooling of such rocket engines. The developed tool incorporates a one-dimensional (1-D) combustion analysis to calculate the thermophysical properties of the combustion gas. Basic engine properties were calculated and used to generate a thrust chamber profile based on a bell-shaped nozzle. The hot gas side was analyzed using 1-D isentropic flow assumptions, along with heat transfer correlations. The coolant side was evaluated using the hydraulic analysis in the axial direction and the heat transfer analysis in the radial direction. Thermophysical properties and the phase of the coolant were determined using the given property tables and the instantaneous state of the coolant. This flexible and computationally less demanding tool was used to analyze two small-scale engines utilizing liquid hydrocarbon fuels, which are used in modern rocket propulsion. The wall cooling analyses of a liquid oxygen (LOX)/liquid methane (LCH4) engine and a liquid oxygen (LOX)/liquid propane (LC3H8) engine are presented. Fuel and oxidizer were used separately as coolants for both engines, and both of them experienced phase change. Results reveal the advantage of the high mass flow rate of the oxidizer in cooling performance. In addition, the results of this study show that the cooling of the LOX/LC3H8 engine is somewhat more challenging compared to the LOX/LCH4 engine.

The lysyl oxidase (LOX) family, consisting of LOX and LOX-like proteins 1–4 (LOXL1–4), is responsible for the covalent crosslinking of collagen and elastin, thus maintaining the stability of the extracellular matrix (ECM) and functioning in maintaining connective tissue function, embryonic development, and wound healing. Recent studies have found the aberrant expression or activity of the LOX family occurs in various types of cancer. It has been proved that the LOX family mainly performs tumor microenvironment (TME) remodeling function and is extensively involved in tumor invasion and metastasis, immunomodulation, proliferation, apoptosis, etc. With relevant translational research in progress, the LOX family is expected to be an effective target for tumor therapy. Here, we review the research progress of the LOX family in tumor progression and therapy to provide novel insights for future exploration of relevant tumor mechanism and new therapeutic targets.

Studies in multiple species indicate that reducing growth hormone (GH) action enhances healthy lifespan. In fact, GH receptor knockout (GHRKO) mice hold the Methuselah prize for the world's longest‐lived laboratory mouse. We previously demonstrated that GHR ablation starting at puberty (1.5 months), improved insulin sensitivity and female lifespan but results in markedly reduced body size. In this study, we investigated the effects of GHR disruption in mature‐adult mice at 6 months old (6mGHRKO). These mice exhibited GH resistance (reduced IGF‐1 and elevated GH serum levels), increased body adiposity, reduced lean mass, and minimal effects on body length. Importantly, 6mGHRKO males have enhanced insulin sensitivity and reduced neoplasms while females exhibited increased median and maximal lifespan. Furthermore, fasting glucose and oxidative damage was reduced in females compared to males irrespective of Ghr deletion. Overall, disrupted GH action in adult mice resulted in sexual dimorphic effects suggesting that GH reduction at older ages may have gerotherapeutic effects. Attenuation of growth hormone action in mice at a mature adult age (6‐months) extends lifespan, reduces protein oxidation and glomerulonephritis in females while improving insulin sensitivity and decreasing lipid peroxidation, glomerulonephritis, and neoplasms in males.

Tamoxifen (TAM) is required for gene recombination in the inducible Cre/lox system. The TAM‐enriched diet is considered safe, with negligible impact on animal wellbeing. However, studies reporting the long‐term effects of the TAM diet and its potential impact on experimental outcomes are scarce. We conducted a longitudinal study on mice exposed to a 4‐week dietary TAM citrate supplementation. Several parameters were recorded, such as body weight, body composition, mortality, and cardiac function. The collagen1a2 (Col1a2) transgenic mouse was used to assess TAM‐induced recombination in vivo in cardiac fibroblasts followed by myocardial infarction (MI). The impact of TAM on the MI outcome was also evaluated. The recombination efficiency and cytotoxic effect of the TAM active metabolite, 4‐hydroxy‐tamoxifen (4‐OHT), were assessed in vitro. Mice exposed to a TAM diet showed body weight loss and a 10% increase in mortality (P = 0.045). The TAM diet decreased cardiac function and induced cardiac remodeling, indicated by decreased fractional shortening from 32.23% to 19.23% (P = 0.001) and left ventricular (LV) wall thinning. All measured parameters were reversed to normal when mice were returned to a normal diet. Infarcted Col1a2‐CreER mice on the TAM regimen showed gene recombination in fibroblasts, but it was associated with a substantial increase in mortality post‐surgery (2.5‐fold) compared to the controls. In vitro, 4‐OHT induced gene editing in fibroblasts; however, cell growth arrest and cytotoxicity were observed at high concentrations. In conclusion, prolonged exposure to the TAM diet can be detrimental and necessitates careful model selection and interpretation of the results. What is the central question of this study? Tamoxifen is used to induce Cre‐mediated gene editing, but high doses used in intraperitoneal injection can be toxic and tamoxifen‐enriched food has emerged as an alternative: what is the impact of long‐term exposure to the tamoxifen diet in mice? What is the main finding and its importance? Prolonged exposure to the tamoxifen diet induced severe weight loss, weakness, and impaired cardiac function. Mice exposed to long‐term tamoxifen‐enriched diet are more likely to succumb to further interventions. Investigators planning to use inducible mouse models should be aware of the potential problems that can be avoided with careful experimental design.

In order to investigate the acoustic oscillation characteristics of gas–liquid pintle rocket engines and elucidate the path by which spray combustion process provides energy to the combustor pressure oscillation, a LOX/GCH 4 pintle engine with rectangular combustor was designed. By adding transverse velocity disturbance for the first time, the acoustic response of spray combustion process was simulated, and the effect of excitation amplitude on acoustic response was researched. Numerical results show that the adopted transverse velocity disturbance can excite the first-order transverse acoustic oscillation with same excitation frequency in the engine combustor. The acoustic response maintenance mechanism under extrinsic excitation is summarized for pintle engines. Besides, the temperature distribution inside the engine combustor tends to be uniform, and the low-frequency oscillation caused by the flame transverse swing gradually disappears. The amplitude of combustor pressure oscillation is dominated by excitement amplitude and phase difference between the pressure and heat release in combustion reaction region. In addition, the time-averaged combustor pressure can be amplified mainly by transverse velocity disturbance. The research work can provide a reference for related fire tests on the acoustic response of a subscale gas–liquid pintle engine.

Conditional gene expression is a powerful tool for genetic analysis of biological phenomena. In the widely used “lox-stop-lox” approach, insertion of a stop cassette consisting of a series of stop codons and polyadenylation signals flanked by lox sites into the 5′ untranslated region (UTR) of a gene prevents expression until the cassette is excised by tissue-specific expression of Cre recombinase. Although lox-stop-lox and similar approaches using other site-specific recombinases have been successfully used in many experimental systems, this design has certain limitations. Here, we describe the Floxed exon (Flexon) approach, which uses a stop cassette composed of an artificial exon flanked by artificial introns, designed to cause premature termination of translation and nonsense-mediated decay of the mRNA and allowing for flexible placement into a gene. We demonstrate its efficacy in Caenorhabditis elegans by showing that, when promoters that cause weak and/or transient cell-specific expression are used to drive Cre in combination with a gfp(flexon) transgene, strong and sustained expression of green fluorescent protein (GFP) is obtained in specific lineages. We also demonstrate its efficacy in an endogenous gene context: we inserted a flexon into the Argonaute gene rde-1 to abrogate RNA interference (RNAi), and restored RNAi tissue specifically by expression of Cre. Finally, we describe several potential additional applications of the Flexon approach, including more precise control of gene expression using intersectional methods, tissue-specific protein degradation, and generation of genetic mosaics. The Flexon approach should be feasible in any system where a site-specific recombination-based method may be applied.

Carcinoma-associated fibroblasts (CAFs) exhibit significant heterogeneity and are closely associated with progression, resistance to anticancer therapies, and poor prognosis in head and neck squamous cell carcinoma (HNSCC). However, the specific functional role of CAFs in HNSCC has been inadequately explored. In this study, we utilized a single-cell RNA sequencing dataset from HNSCC (GSE103322) to recluster CAFs via the Seurat pipeline. On the basis of the reported markers, we identified two CAF subtypes, LOX-myCAFs and LOX + iCAFs, and generated signature markers for each. Through unsupervised consensus clustering, we identified and characterized two molecular subtypes of HNSCC-TCGA, each exhibiting distinct dysregulated cancer hallmarks, immunological tumor microenvironments, and stemness characteristics. The robustness of the LOX + iCAF-related signature clustering, particularly in terms of prognosis and prediction of immunotherapeutic response, was validated in an ANOVA cohort via a GEO dataset (GSE159067) consisting of 102 HNSCC patients. A positive correlation was validated between the expression of LOX and that of CD86, a marker of M1 macrophage polarization. Further experiments involving the coculture of conditioned medium derived from LOX-silenced CAFs with CAL-27 and UM-SCC-1 cell lines revealed that LOX silencing led to decreased proliferation and migration of these cancer cells, which was mediated by epithelial-mesenchymal transition (EMT) through IL-34- induced CSF1R/Akt signaling. In summary, our single-cell and bulk RNA sequencing analyses revealed a LOX + iCAF-related signature that can predict the prognosis and response to immunotherapy in HNSCC patients. Additionally, the LOX gene was identified as a promising therapeutic target for HNSCC treatment.

This review offers a systematic understanding about how polyphenols target multiple inflammatory components and lead to anti-inflammatory mechanisms. It provides a clear understanding of the molecular mechanisms of action of phenolic compounds. Polyphenols regulate immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. They inactivate NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and modulate mitogen-activated protein Kinase (MAPk) and arachidonic acids pathways. Polyphenolic compounds inhibit phosphatidylinositide 3-kinases/protein kinase B (PI3K/AkT), inhibitor of kappa kinase/c-Jun amino-terminal kinases (IKK/JNK), mammalian target of rapamycin complex 1 (mTORC1) which is a protein complex that controls protein synthesis, and JAK/STAT. They can suppress toll-like receptor (TLR) and pro-inflammatory genes’ expression. Their antioxidant activity and ability to inhibit enzymes involved in the production of eicosanoids contribute as well to their anti-inflammation properties. They inhibit certain enzymes involved in reactive oxygen species ROS production like xanthine oxidase and NADPH oxidase (NOX) while they upregulate other endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione (GSH) peroxidase (Px). Furthermore, they inhibit phospholipase A2 (PLA2), cyclooxygenase (COX) and lipoxygenase (LOX) leading to a reduction in the production of prostaglandins (PGs) and leukotrienes (LTs) and inflammation antagonism. The effects of these biologically active compounds on the immune system are associated with extended health benefits for different chronic inflammatory diseases. Studies of plant extracts and compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation such as diabetes, obesity, neurodegeneration, cancers, and cardiovascular diseases, among other conditions.

This study aimed to analyze the serum and salivary levels of copper (Cu), zinc (Zn), iron (Fe), chromium (Cr), manganese (Mn) and the Cu/Zn ratio and investigate the association between LOX gene variants (rs18800449 and rs2288393) and oral submucosal fibrosis (OSMF). A total of 250 subjects were included in the study: OSMF patients (n = 50), areca nut chewers without OSMF (n = 100) and controls (n = 100). Trace metals were measured using an atomic absorption spectrophotometer, while LOX gene variants were genotyped using the tetra primer amplification refractory mutation system (tetra ARMS) polymerase chain reaction (PCR) method. The results showed significant variations in serum and salivary Cu, Zn, Fe and Cr levels and serum Mn concentrations among the three groups (p < 0.0001). Serum Cu levels were significantly higher in OSMF patients, while serum Zn levels were significantly lower. Both serum and salivary Cu/Zn ratios demonstrated a statistically significant difference (p < 0.0001) and diagnostic potential to differentiate OSMF from chewers and controls. However, LOX gene variants did not show an association between OSMF and chewers, except for rs1800449 genotypes, which showed a significant and increased risk with the AA genotype in OSMF patients compared to controls (OR = 7.58; 95%CI 2.30–24.97). The study suggests that trace elements and genetic variants may impact the etiology of OSMF. The findings may aid in early diagnosis, suitable treatment, and as a prognostic indicator for disease progression.

Inflammation is a natural process that is connected to various conditions and disorders such as arthritis, psoriasis, cancer, infections, asthma, etc. Based on the fact that cyclooxygenase isoenzymes (COX-1, COX-2) are responsible for the production of prostaglandins that play an important role in inflammation, traditional treatment approaches include administration of non-steroidal anti-inflammatory drugs (NSAIDs), which act as selective or non-selective COX inhibitors. Almost all of them present a number of unwanted, often serious, side effects as a consequence of interference with the arachidonic acid cascade. In search for new drugs to avoid side effects, while maintaining high potency over inflammation, scientists turned their interest to the synthesis of dual COX/LOX inhibitors, which could provide numerous therapeutic advantages in terms of anti-inflammatory activity, improved gastric protection and safer cardiovascular profile compared to conventional NSAIDs. Τhiazole and thiazolidinone moieties can be found in numerous biologically active compounds of natural origin, as well as synthetic molecules that possess a wide range of pharmacological activities. This review focuses on the biological activity of several thiazole and thiazolidinone derivatives as COX-1/COX-2 and LOX inhibitors.