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To address the hypothesis that maternal uteroplacental insufficiency (UPI) increases severity of retinopathy of prematurity, we developed a composite rat model of UPI and oxygen-fluctuations and removed premature birth as a confounding factor. Timed-pregnant Sprague-Dawley dams underwent bilateral uterine artery ligation or anesthesia (control) at e19.5. Full-term pups developed in room air (RA) or an oxygen-induced retinopathy (OIR) model. Isolectin-stained retinal flat-mounts were analyzed for percent of areas of avascular/total retina (AVA) and of intravitreal neovascular/total retina (IVNV). Pup weights and serum and mRNA of liver and kidney VEGF, IGF-1, and erythropoietin (EPO) were determined. Multivariable mixed effects linear regressions and Pearson correlations were performed using STATA14. Postnatal growth restriction occurred in pups in UPI/RA, but not in UPI/OIR. Weight gain was similar between UPI/OIR and control/OIR pups. AVA was reduced and a trend toward reduced IVNV was seen in UPI/OIR compared to control/OIR. No difference in birth weights of UPI/OIR vs. control/OIR pups occurred. Serum and renal IGF-1 and EPO were significantly increased in UPI/OIR compared to control/OIR pups. In the absence of prematurity, UPI increased angiogenic factors in association with reduced OIR severity, suggesting that ischemia from UPI could yield protective angiogenic effects by offspring.

Intrauterine growth restriction (IUGR) and exposure to a high‐fat diet (HFD) independently increase the risk of cardiovascular disease (CVD) and hyperlipidemia. In our previous studies, IUGR increased blood pressure and promoted vascular remodeling and stiffness in early life, a finding that persisted and was augmented by a maternal HFD through postnatal day (PND) 60. The impact of these findings with aging and the development of hyperlipidemia and atherosclerosis remain unknown. We hypothesized that the previously noted impact of IUGR on hypertension, vascular remodeling, and hyperlipidemia would persist. Adult female rats were fed either a regular diet (RD) or high fat diet (HFD) prior to conception through lactation. IUGR was induced by uterine artery ligation. Offspring were weaned to either RD or HFD through PND 365. For both control (C) and IUGR (I) and rats, this resulted in the following six groups per sex: offspring from RD dams weaned to an RD (CRR and IRR), or offspring from HFD dams weaned to either an RD (CHR and IHR) or to an HFD (CHH and IHH). IHH male and female rats had increased large artery stiffness, a suggestion of fatty streaks in the aorta, and persistent decreased elastin and increased collagen in the aorta and carotid arteries. Post‐weaning HFD intake increased blood lipids regardless of IUGR status. IUGR increased HFD‐induced mortality. We speculate that HFD‐induced risk of CVD and mortality is potentiated by developmental programming of the ECM. We report that intrauterine growth restriction impacts on early vascular aging persists and induces fatty streaks in the systemic vasculature in a rat model of maternal and offspring high‐fat diet consumption. Our study shows the importance of maternal and early life intervention to modify cardiovascular risk throughout life.

Currently, hypersonic vehicles are confronted with severe aerodynamic heating challenges, imposing strict demands on the thermal insulation and other characteristics of vehicle thermal protection materials. C/SiC composites have emerged as one of the favored materials for aircraft thermal protection, owing to their outstanding ablation resistance, oxidation resistance, and other properties. In this paper, a thermochemical ablation model was developed to elucidate the ablation mechanism of C/SiC composites. The dimensionless ablation rates of C/SiC under different pressures and material ratios were comparatively examined, and the total and linear ablation rates of C/SiC composites over 50 seconds were determined. The simulation results were contrasted with existing experimental data, and the error was within 10%.

Background Low levels of insulin-like growth factor-1 (IGF-1) protein in preterm human infants are associated with bronchopulmonary dysplasia (BPD). We used our preterm lamb model of BPD to determine (1) dosage of recombinant human (rh) IGF-1 bound to binding protein-3 (IGFBP-3) to reach infant physiologic plasma levels; and (2) whether repletion of plasma IGF-1 improves pulmonary and cardiovascular outcomes. Methods Group 1: normal, unventilated lambs from 128 days gestation through postnatal age 5 months defined normal plasma levels of IGF-1. Group 2: continuous infusion of rhIGF-1/rhIGFBP-3 (0.5, 1.5, or 4.5 mg/kg/day; n  = 2) for 3 days in mechanically ventilated (MV) preterm lambs determined that 1.5 mg/kg/day dosage attained physiologic plasma IGF-1 concentration of ~125 ng/mL, which was infused in four more MV preterm lambs. Results Group 1: plasma IGF-1 protein increased from ~75 ng/mL at 128 days gestation to ~220 ng/L at 5 months. Group 2: pilot study of the optimal dosage (1.5 mg/kg/day rhIGF-1/rhIGFBP-3) in six MV preterm lambs significantly improved some pulmonary and cardiovascular outcomes ( p  < 0.1) compared to six MV preterm controls. RhIGF-1/rhIGFBP-3 was not toxic to the liver, kidneys, or lungs. Conclusions Three days of continuous iv infusion of rhIGF-1/rhIGFBP-3 at 1.5 mg/kg/day improved some pulmonary and cardiovascular outcomes without toxicity. Impact Preterm birth is associated with rapid decreases in serum or plasma IGF-1 protein level. This decline adversely impacts the growth and development of the lung and cardiovascular system. For this pilot study, continuous infusion of optimal dosage of rhIGF-1/rhIGFBP-3 (1.5 mg/kg/day) to maintain physiologic plasma IGF-1 level of ~125 ng/mL during mechanical ventilation for 3 days statistically improved some structural and biochemical outcomes related to the alveolar formation that would favor improved gas exchange compared to vehicle-control. We conclude that 3 days of continuous iv infusion of rhIGF-1/rhIGFBP-3 improved some physiological, morphological, and biochemical outcomes, without toxicity, in mechanically ventilated preterm lambs.

Phthalonitrile–polyhedral oligomeric silsesquioxane (POSS) copolymers were prepared by adding two different POSS cage mixtures: epoxycyclohexyl POSS (EP0408) and N-phenylaminopropyl POSS (AM0281). The cure behavior and properties of these polymers were analyzed and compared using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), Fourier transform far infrared (FTIR) measurements, and rheometric studies. The POSS-containing polymers showed higher chemical reactivity, better thermal stability and better mechanical performance in comparison to their unmodified counterparts. All the polymers showed water absorption below 1.5%. As revealed by FTIR measurements, the polymerization products contained triazine ring structures that were responsible for the superior thermal properties exhibited by these POSS-containing polymers.

Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. Proliferative diabetic retinopathy (PDR) and end stage renal disease (ESRD) are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. However, the precise gene(s) and genetic variant(s) involved remain largely unknown. Erythropoietin (EPO) is a potent angiogenic factor observed in the diabetic human and mouse eye. By a combination of case-control association and functional studies, we demonstrate that the T allele of SNP rs1617640 in the promoter of the EPO gene is significantly associated with PDR and ESRD in three European-American cohorts [Utah: P = 1.91 x 10⁻³; Genetics of Kidneys in Diabetes (GoKinD) Study: P = 2.66 x 10⁻⁸; and Boston: P = 2.1 x 10⁻²]. The EPO concentration in human vitreous body was 7.5-fold higher in normal subjects with the TT risk genotype than in those with the GG genotype. Computational analysis suggests that the risk allele (T) of rs1617640 creates a matrix match with the EVI1/MEL1 or AP1 binding site, accounting for an observed 25-fold enhancement of luciferase reporter expression as compared with the G allele. These results suggest that rs1617640 in the EPO promoter is significantly associated with PDR and ESRD. This study identifies a disease risk-associated gene and potential pathway mediating severe diabetic microvascular complications.

Intrauterine growth restriction (IUGR) and maternal consumption of a high‐saturated‐fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD. HFD‐fed dams consumed the same kilocalories as regular diet‐fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low‐density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non‐IUGR offspring both from regular diet‐ and HFD‐fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation. Two disparate perinatal insults, intrauterine growth restriction and maternal consumption of a high‐fat diet, frequently occur together and increase the risk of developing hyperlipidemia in the offspring. Our findings show that the combination of intrauterine growth restriction and a maternal high‐fat diet in rats increases offspring hepatic cholesterol, low‐density lipoprotein receptor protein levels, and low‐density lipoprotein receptor activity at birth and at postnatal day 14.

This study investigates small-scale pretraining for Small Language Models (SLMs) to enable efficient use of limited data and compute, improve accessibility in low-resource settings and reduce costs. To enhance long-context extrapolation in compact models, we focus on Infini-attention, which builds a compressed memory from past segments while preserving local attention. In our work, we conduct an empirical study using 300M-parameter LLaMA models pretrained with Infini-attention. The model demonstrates training stability and outperforms the baseline in long-context retrieval. We identify the balance factor as a key part of the model performance, and we found that retrieval accuracy drops with repeated memory compressions over long sequences. Even so, Infini-attention still effectively compensates for the SLM's limited parameters. Particularly, despite performance degradation at a 16,384-token context, the Infini-attention model achieves up to 31% higher accuracy than the baseline. Our findings suggest that achieving robust long-context capability in SLMs benefits from architectural memory like Infini-attention.

To address the inefficiencies and limited spatial resolution of traditional single-point monitoring techniques, this study proposes a multi-scale analysis method that integrates the Multi-Scale Model-to-Model Cloud Comparison (M3C2) algorithm with least-squares plane fitting. This approach employs the M3C2 algorithm for qualitative full-field deformation detection and utilizes least-squares plane fitting for quantitative feature extraction. When applied to the approach span of a cross-river bridge in Hubei Province, China, this method leverages dense point clouds (greater than 500 points per square meter) acquired using a Leica RTC360 scanner. Data preprocessing incorporates curvature-adaptive cascade denoising, achieving over 98% noise removal while retaining more than 95% of structural features, along with octree-based simplification. By extracting multi-level slice features from bridge decks and piers, this method enables the simultaneous analysis of global trends and local deformations. The results revealed significant deformation, with an average settlement of 8.2 mm in the left deck area. The bridge deck exhibited a deformation trend characterized by left and higher right in the vertical direction, while the bridge piers displayed noticeable tilting, particularly with the maximum offset of the rear pier columns reaching 182.2 mm, which exceeded the deformation of the front pier. The bridge deck’s micro-settlement error was ±1.2 mm, and the pier inclination error was ±2.8 mm, meeting the Chinese Highway Bridge Maintenance Code (JTG H11-2004) and the American Association of State Highway and Transportation Officials (AASHTO) standards, and the multi-scale algorithm achieved engineering-level accuracy. Utilizing point cloud densities >500 pt/m2, the M3C2 algorithm achieved a spatial resolution of 0.5 mm, enabling sub-millimeter full-field analysis for complex scenarios. This method significantly enhances bridge safety monitoring precision, enhances the precision of intelligent systems monitoring, and supports the development of targeted systems as pile foundation reinforcement efforts and as improvements to foundations.

The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME. The tumor microenvironment can influence patient survival response to therapy. Here, the authors used single-cell sequencing to investigate the microenvironment of nasopharyngeal cancer and identify tumor-specific signatures in five stromal clusters of cells that may influence patient survival.