LC Resources (United States)

Introduction Osteoporosis of the femoral neck contributes significantly to hip fracture risk and remains challenging to treat due to the limitations of systemic pharmacotherapies. We investigated whether direct intra-medullary visualization of the femoral neck is feasible and could support localized therapeutic delivery. Methods Four cadaveric femoral specimens were evaluated. A guidewire was placed into the femoral neck under biplanar fluoroscopy, followed by canal access using a 5 mm reamer. A 4 mm standard arthroscope was inserted, and the cavity was irrigated and debrided using a 3.5 mm shaver and a radiofrequency probe. Tetracycline and Alizarin Red dyes were instilled and visualized under ultraviolet and green light, respectively. Results The intramedullary cavity of the femoral neck was easily accessed and visualized. Loose cancellous bone, fibrous, and adipose tissue were observed and removed. The inferior femoral neck appeared softer than the superior portion. Bi-portal access allowed effective irrigation, visualization, and working space maintenance. Fluorochrome-based imaging revealed patchy areas of fluorescence, demonstrating potential for localized labeling and future targeted delivery. No obstruction to fluid inflow or visualization was noted. Discussion Intraosseous visualization enabled both structural assessment and localized labeling of the femoral neck intramedullary canal. This approach may support novel future strategies to prevent fractures of the femoral neck from osteoporosis. Conclusion This pilot cadaveric study demonstrates that the femoral neck intramedullary canal can be accessed and visualized using standard arthroscopic tools. This approach allows for real-time visualization and cavity preparation, providing a potential route for targeted osteoporosis therapies. Further development of endoscopic imaging systems and localized delivery agents may enable biologic reconstruction of compromised bone while minimizing systemic exposure.

Aortic aneurysm/dissection (AAD) is a life-threatening disease lacking effective pharmacological treatment. Protein ubiquitination plays a pivotal role in cardiovascular diseases. However, the possible contribution of the E3 ubiquitin ligase March2 (membrane-associated RING [really interesting new gene] finger protein 2) to the cause of AAD remains elusive. Integrated single-cell RNA sequencing analysis was conducted in human AAD tissues. Based on the screening results, we generated a mouse line of smooth muscle cell-specific March2 knockout. β-Aminopropionitrile monofumarate was used to establish AAD. Cleavage under targets and tagmentation and cleavage under targets and tagmentation-quantitative polymerase chain reaction were performed to identify possible target genes for histone H3K18 lactylation. March2 expression was downregulated in aorta from patients with AAD or β-aminopropionitrile monofumarate-induced AAD mice. β-Aminopropionitrile monofumarate-induced AAD was significantly accentuated in March2 global (March2-/-) and vascular smooth muscle cell-specific deletion (March2fl/fl; TaglnCre) mice, whereas the AAD pathology was rescued by rAAV9-SM22α (smooth muscle 22α)-March2 (recombinant adeno-associated virus serotype 9 expressing Flag-tagged March2 under SM22α promoter). March2 interacted with PKM2 (pyruvate kinase M2) to promote K33-linked polyubiquitination. Deficiency of March2 lessened PKM2 dimer-to-tetramer conversion in AAD and overtly exacerbated AAD-induced histone H3K18 lactylation in vascular smooth muscle cells by fostering glucose metabolism reprogramming, thereby promoting p53-driven apoptotic transcriptional response-a hallmark of AAD pathogenesis. TEPP-46 (tetraethyl pyrophosphate), a PKM2-specific activator, pronouncedly alleviated March2 deficiency-deteriorated AAD pathology. Our findings demonstrated that March2 is a novel endogenous defender that prevents AAD by inhibiting vascular smooth muscle cell apoptosis, suggesting that March2 represents a potential therapeutic target for AAD.

Fiction that had Punic Carthage as subject was, until the beginning of the 19th century, exclusively based on the historic sources written by Greeks and Romans. Nevertheless, the first – rivals of Carthage, and second – their enemies, have necessarily proposed to their posterity a biased story, full of subjectivity, rivalry or even hate. The development of archeology as a field of research as well as an auxiliary science of history has allowed to confront the ancients texts with the material coming from the Punic civilization, and consequently questioned centuries old ingrained stereotypes about Carthage. The decolonization of two countries that were directly influenced by Punic Carthage – Tunisia and Lebanon – has then emerged new stakes: the ideology used historic information to support the national identity of these freshly born countries. In Salammbô the autor of the Dictionnaire des idées reçues paradoxically mentions the historic stereotype that nourished the existence of Moloch god. In Elegie à Carthage, Senghor use the Didon myth to support the Panafricanist ideology. Finally, the Tunisian Fawzi Mellah and the Libanese J-J Tabet both dispute Elyssa identity.

A two component three degree simplex lattice experimental design was employed to evaluate the impact of different mixing fractions of TiO2 and ZnO on an ordered mesoporous SBA-15 support for CO2 photoreduction. It was anticipated that the combined advantages of TiO2 and ZnO: low cost, non-toxicity and combined electronic properties would facilitate CO2 photoreduction. The fraction of ZnO had a statistically dominant impact on maximum CO2 adsorption (β2 = 22.65, p-value = 1.39 × 10−4). The fraction of TiO2 used had a statistically significant positive impact on CO (β1 = 9.71, p-value = 2.93 × 10−4) and CH4 (β1 = 1.43, p-value = 1.35 × 10−3) cumulative production. A negative impact, from the interaction term between the fractions of TiO2 and ZnO, was found for CH4 cumulative production (β3 = −2.64, p-value = 2.30 × 10−2). The systematic study provided evidence for the possible loss in CO2 photoreduction activity from sulphate groups introduced during the synthesis of ZnO. The decrease in activity is attributed to the presence of sulphate species in the ZnO prepared, which may possibly act as charge carrier and/or radical intermediate scavengers.

Structure identification in nontargeted metabolomics based on liquid-chromatography coupled to mass spectrometry (LC-MS) remains a significant challenge. Quantitative structure-retention relationship (QSRR) modeling is a technique capable of accelerating the structure identification of metabolites by predicting their retention, allowing false positives to be eliminated during the interpretation of metabolomics data. In this work, 191 compounds were grouped according to molecular weight and a QSRR study was carried out on the 34 resulting groups to eliminate false positives. Partial least squares (PLS) regression combined with a Genetic algorithm (GA) was applied to construct the linear QSRR models based on a variety of VolSurf+ molecular descriptors. A novel dual-filtering approach, which combines Tanimoto similarity (TS) searching as the primary filter and retention index (RI) similarity clustering as the secondary filter, was utilized to select compounds in training sets to derive the QSRR models yielding R2 of 0.8512 and an average root mean square error in prediction (RMSEP) of 8.45%. With a retention index filter expressed as ±2 standard deviations (SD) of the error, representative compounds were predicted with >91% accuracy, and for 53% of the groups (18/34), at least one false positive compound could be eliminated. The proposed strategy can thus narrow down the number of false positives to be assessed in nontargeted metabolomics.