bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caveolin‐3 loss linked with the P104L LGMD‐1C mutation modulates skeletal muscle mTORC1 signalling and cholesterol homeostasis
Authors: Shah Dinesh S. , Nisr Raid B. , Krasteva‐Christ Gabriela , Hundal Harinder S. 
Published: September 2023

AbstractBackgroundCaveolins are the principal structural components of plasma membrane caveolae. Dominant pathogenic mutations in the muscle‐specific caveolin‐3 (Cav3) gene isoform, such as the limb girdle muscular dystrophy type 1C (LGMD‐1C) P104L mutation, result in dramatic loss of the Cav3 protein and pathophysiological muscle weakness/wasting. We hypothesize that such muscle degeneration may be linked to disturbances in signalling events that impact protein turnover. Herein, we report studies assessing the effects of Cav3 deficiency on mammalian or mechanistic target of rapamycin complex 1 (mTORC1) signalling in skeletal muscle cells.MethodsL6 myoblasts were stably transfected with Cav3P104L or expression of native Cav3 was abolished by CRISPR/Cas9 genome editing (Cav3 knockout [Cav3KO]) prior to performing subcellular fractionation and immunoblotting, analysis of real‐time mitochondrial respiration or fixed cell immunocytochemistry. Skeletal muscle from wild‐type and Cav3−/− mice was processed for immunoblot analysis of downstream mTORC1 substrate phosphorylation.ResultsCav3 was detected in lysosomal‐enriched membranes isolated from L6 myoblasts and observed by confocal microscopy to co‐localize with lysosomal‐specific markers. Cav3P104L expression, which results in significant (~95%) loss of native Cav3, or CRISPR/Cas9‐mediated Cav3KO, reduced amino acid‐dependent mTORC1 activation. The decline in mTORC1‐directed signalling was detected by immunoblot analysis of L6 muscle cells and gastrocnemius Cav3−/− mouse muscle as judged by reduced phosphorylation of mTORC1 substrates that play key roles in the initiation of protein synthesis (4EBP1S65 and S6K1T389). S6K1T389 and 4EBP1S65 phosphorylation reduced by over 75% and 80% in Cav3KO muscle cells and by over 90% and 30% in Cav3−/− mouse skeletal muscle, respectively. The reduction in protein synthetic capacity in L6 muscle cells was confirmed by analysis of puromycylated peptides using the SUnSET assay. Cav3 loss was also associated with a 26% increase in lysosomal cholesterol, and pharmacological manipulation of lysosomal cholesterol was effective in replicating the reduction in mTORC1 activity observed in Cav3KO cells. Notably, re‐expression of Cav3 in Cav3KO myoblasts normalized lysosomal cholesterol content, which coincided with a recovery in protein translation and an associated increase in mTORC1‐directed phosphorylation of downstream targets.ConclusionsOur findings indicate that Cav3 can localize on lysosomal membranes and is a novel regulator of mTORC1 signalling in muscle. Cav3 deficiency associated with the Cav3P104L mutation impairs mTORC1 activation and protein synthetic capacity in skeletal muscle cells, which may be linked to disturbances in lysosomal cholesterol trafficking and contribute to the pathology of LGMD‐1C.
The extreme precipitation and added value of East Asia regional reanalysis system
Authors: Yang Linyun , Liang Xudong , Yin Jinfang , Xie Yanxin , Fan Huiyi 
Published: September 2023

AbstractIn the study, we evaluate extreme precipitation of the East Asia regional reanalysis system (EARS‐CMA), ERA‐Interim and ERA5 applying Tropical Rainfall Measuring Mission 3B42V7 (TRMM), Climate Prediction Center Morphing Method satellite‐gauge blended product (CMORPH) and CN05.1 over land‐only East Asia in 2008–2017. The added value of EARS‐CMA is also calculated to identify the small‐scale processes at different timescales and spatial resolutions. Compared to TRMM, CMORPH has a better agreement with CN05.1 for the annual, summer and winter spatial pattern and amplitude of most extreme precipitation indices. EARS‐CMA is capable to reproduce amplitude and locations of most extreme precipitation indices for annual and summertime precipitation over China mainland against CN05.1. For land‐only East Asia, ERA5 can reproduce the closest spatial features of various extreme precipitation indices to CMORPH for annual, summer and winter precipitation, followed by EARS‐CMA. All reanalysis datasets show worse skill on the spatial characteristics of duration indicators than on other extreme precipitation indices against CN05.1, but perform better than TRMM and CMORPH. The real added value, potential added value and relative added value of EARS‐CMA show that EARS‐CMA can capture the mesoscale processes over south China, Yangtze River basin, Tibetan Plateau and Indo‐China efficiently, especially the daily and subseasonal timescales over the Tibetan Plateau subregion, which benefits from fine‐scale topographical detail over the complex terrain region in the regional climate model. Also, higher extreme precipitation of aggregating EARS‐CMA than ERA‐Interim can be obtained at the same resolution, which implies that the added value obtained with EARS‐CMA is not merely the contribution of a higher resolution, but also the physical processes resolved by the dynamical downscaling technique.
Tumor size and survival in intrahepatic cholangiocarcinoma treated with surgical resection or ablation
Authors: Kanu Elishama N. , Rhodin Kristen E. , Masoud Sabran J. , Eckhoff Austin M. , Bartholomew Alex J. , Howell Thomas C. , Bao Jiayin , Befera Nicholas T. , Kim Charles Y. , Blazer Dan G. , Zani Sabino , Nussbaum Daniel P. , Allen Peter J. , Lidsky Michael E. 
Published: September 2023

AbstractObjectivesWe performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA).MethodsThe National Cancer Database was queried for patients with clinical stage I–III iCCA diagnosed during 2010–2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan–Meier and multivariable Cox proportional hazards methods.ResultsOf 2140 patients, 1877 (87.7%) underwent resection and 263 (12.3%) underwent ablation, with median tumor sizes of 5.5 and 3 cm, respectively. Overall, resection was associated with greater median OS (41.2 months (95% confidence interval [95% CI]: 37.6–46.2) vs. 28 months (95% CI: 15.9–28.6) on univariable analysis (p < 0.0001). There was no significant difference on multivariable analysis (p = 0.42); however, there was a significant interaction between tumor size and management. On subgroup analysis of patients with tumors <3 cm, there was no difference in OS between resection versus ablation. However, ablation was associated with increased mortality for tumors ≥3 cm.ConclusionAlthough resection is associated with improved OS for tumors ≥3 cm, we observed no difference in survival between management strategies for tumors < 3 cm. Ablation may be an alternative therapeutic strategy for small iCCA, particularly in patients at risk for high surgical morbidity.
Associations and ranging patterns of common bottlenose dolphins near Brunswick, Georgia, USA
Authors: Speakman Todd R. , Quigley Brian M. , Zolman Eric S. , Balmer Brian C. , Lane Suzanne M. , Martinson Ross A. , Kolkmeyer Trip , Takeshita Ryan , Caldwell Marthajane , Schwacke Lori H. 
Published: September 2023

AbstractThe Southern Georgia Estuarine System (SGES) stock of common bottlenose dolphins (Tursiops truncatus) resides in estuarine waters near Brunswick, Georgia, USA. There are concerns for this population due to the presence of anthropogenic stressors, particularly in the Turtle‐Brunswick River Estuary (TBRE), where polychlorinated biphenyl (PCB) concentrations in dolphins are >10 times higher relative to dolphins elsewhere in the southeastern United States. The goal of this study was to evaluate the association patterns and distribution of the SGES stock based on long‐term photo‐identification data (2010–2021) using analyses of social dynamics and spatial movements. Social analyses identified 5 distinct clusters, 3 of which were substantially larger and more well‐defined than the other 2. Spatial analyses indicated geographic partitioning among the 3 large clusters, with little overlap in their core ranges (50% utilization distributions) but shared ranges in their 95% utilization distributions. Despite having variable ranging patterns, all 3 large clusters used the TBRE in proximity to the Linden Chemicals and Plastics (LCP) Superfund site to a degree, suggesting that they have likely been exposed to high levels of PCBs. Given the spatial distinction and low connectivity between clusters, loss in any of the identified clusters has potential to further segment the population and lead to a decline in the SGES stock as a whole. The fine‐scale population structure should be considered in identifying effective conservation efforts at the appropriate scale.
Synthesis of Crosslinked Microparticles Based on Glycidyl Methacrylate and N‐Vinylimidazole
Authors: Trofin Marin‐Aurel , Racovita Stefania , Vasiliu Silvia , Bargan Alexandra , Bucatariu Florin , Vasiliu Ana‐Lavinia , Mihai Marcela 
Published: September 2023

AbstractIn this study, suspension polymerization technique is used to obtain 3D porous networks based on two monofunctional monomers (glycidyl methacrylate and N‐vinylimidazole) and one of the following difunctional monomers known as crosslinking agents: mono‐, di‐, and triethylene glycol dimethacrylate or divinylbenzene. The influence of various operational parameters like: monomer molar ratio, amount and type of crosslinkers, composition of stabilization system, stirring speed, amount of porogenic agent on the reaction yield, surface morphologies, particle size distribution, and porous characteristics are investigated in order to find the optimal conditions for the synthesis of microparticles possessing the desired properties for further chemical modification. Crosslinked porous microparticles are structurally characterized by Fourier transform inrared (FTIR) spectroscopy, X‐ray photoelectron spectroscopy, and elemental analysis by determination of nitrogen and epoxy groups. The microparticle morphologies as a function of investigated parameters are revealed by scanning electron microscopy, whereas the porous structure is highlighted by mercury porosimetry and dynamic water vapor sorption methods. All the crosslinked networks exhibit porous structures with different surface morphologies and specific surface area values (1.15–48.32 m2 g−1) depending on the operational parameters. These microparticles can be considered precursors for the preparation of various functional polymeric materials.
Bacteria‐Targeting Nanosilver‐Based Antibacterial Drugs for Efficient Treatment of Drug‐Resistant Bacterial‐Infected Keratitis
Authors: Zhang Yufei , Li Anran , Zhang Ye , Hong Shihao , Xue Yun , Song Xianhui , Li Jie , Huang Siyuan , Zhang Xinge 
Published: September 2023

AbstractKeratitis caused by drug‐resistant bacteria is a severe condition that can lead to corneal perforation and even blindness, making effective treatment a top priority amid growing antibiotic resistance. Eye drops for anti‐inflammatory treatment necessitate frequent administration of high doses throughout every day due to bacterial resistance resulting from antibiotic overuse and the low bioavailability of drugs. To overcome these issues, an antibacterial nanocomposite is prepared via conjugating random copolymers of galactose and 3‐(acrylamide)phenylboronic acid to the surface of silver nanoparticles. The customized nanocomposites trigger specific binding to bacteria, resulting in excellent retention of the drug on the ocular surface, resulting in rapid and powerful killing of bacteria and inhibition of bacterial proliferation. Due to its superior drug delivery capabilities to the ocular surface, the functionalized nanocomplex markedly amplifies the anti‐inflammatory efficacy, even at low doses. This effect is achieved by impeding immune cell infiltration and diminishing the synthesis of inflammatory mediators and cytokines, thereby suggesting enhanced healing properties for corneal inflammation. This study demonstrates a promising nanocomposite which is an effective and safe antibacterial strategy for bacterial keratitis with favorable prognostic and clinical conversion potential.
Reconstruction of circumferential fingertip defect using free superficial palmar branch of the radial artery flap: Report of two cases
Authors: Kim Ju Hee , Lee Kyeong‐Tae 
Published: September 2023

AbstractWide local excision of noninvasive malignant melanomas has been increasingly performed instead of digit amputation, which often results in extensive fingertip defects. Owing to the unique anatomical characteristics of the fingertips, achieving favorable outcomes in both function and cosmesis is challenging during reconstruction. The free superficial palmar branch of the radial artery (SPBRA) flap is advantageous for finger reconstruction. However, its application in circumferential fingertip defects has rarely been reported. In this report, we describe two cases of circumferential fingertip defect reconstruction using a free SPBRA flap after wide local excision of subungual melanoma. The patients were women aged 74 and 63 years at the time of surgery. They presented with subungual melanoma on the right fourth finger and left thumb, in which both biopsies confirmed malignant melanoma in situ (Tis N0 M0), Breslow thickness of 0 mm (noninvasive). After wide local excision, circumferential defects, sized 2.5 × 6 and 2.7 × 7 cm, were formed on their fingertips. A vertically designed free SPBRA flap measuring 2.7 × 6 and 3 × 6 cm was elevated from the unaffected palm in each patient. After performing microvascular anastomosis, the flap was inserted transversely, wrapping the exposed phalangeal bone in a conical shape. The donor site was primarily closed. All flaps survived, and postoperative complications did not develop. Neither local recurrence nor distant metastasis was detected at the latest follow‐up in either patient at 24 or 28 months postoperatively. The patients were satisfied with the natural contour of the reconstructed fingertip and recovered functions. In the evaluation of subjective sensory recovery using four scales (excellent, good, fair, and poor), they responded “fair” and “good,” respectively. We suggest that the free SPBRA flap could be a reliable reconstructive method for circumferential fingertip defects.
Polyphenols Cause Structure Dependent Effects on the Metabolic Profile of Human Hepatocarcinogenic Cells
Authors: Gerdemann Andrea , Broenhorst Melissa , Behrens Matthias , Humpf Hans‐Ulrich , Esselen Melanie 
Published: September 2023

ScopeAlthough many beneficial health effects are attributed to polyphenols their influence on the human metabolome has not been elucidated yet. The ubiquitous occurrence of polyphenols in the human diet demands comprehensive knowledge about physiological and toxicological effects of these compounds on human cells.Methods and resultsThe human hepatocarcinogenic cell line HepG2 is used to elucidate the effects of 13 polyphenols and three respective phenolic degradation products on the human metabolome using HPLC‐MS/MS. To investigate structure‐activity‐relationships, structurally related examples of polyphenols from different compound classes are selected. The analysis of catechins points toward a relation between the degree of hydroxylation and the extent of metabolic effects particularly on the urea cycle and the pentose phosphate pathway (PPP). A correlation between the modulation of the PPP and the stability of the compounds is demonstrated, which may be caused by reactive oxygen species (ROS). The incubation of flavones and alkenylbenzenes demonstrates reduced activity of methoxylated compounds and no impact of the B‐ring position.ConclusionIn general, polyphenols induce a multitude of metabolic effects, for example, on energy metabolism, PPP, and urea cycle. These metabolic alterations may be related to the widely reported bioactivity of these compounds such as the anticarcinogenic effects.
Concentrated Grape Powder Consumption Modulates Cholesterol Metabolism and Homeostasis in Healthy Subjects
Authors: Yang Jieping , Lee Rupo , Henning Susanne M. , Xing Emily , Huang Jianjun , Yang Scarlet , Garcia Michael C. , Surampudi Vijaya , Heber David , Li Zhaoping 
Published: September 2023

ScopeFour weeks’ of concentrated grape powder (GP) consumption reduces circulating cholesterol in healthy free‐living subjects consuming a low‐fiber/low‐polyphenol diet. Here, the study aims to investigate the underlying mechanisms for cholesterol reduction by evaluating biomarkers of cholesterol de novo biosynthesis, intestinal absorption, miRNA involved in transcriptional regulation of cholesterol metabolism, as well as cholesterol oxidation.Methods and resultsFasting plasma samples collected from 19 healthy free‐living subjects at baseline and week 4 of GP consumption are used in this study. Gas chromatography‐mass (GC‐MS) analysis of plasma samples shows that lathosterol, a precursor of cholesterol synthesis, is significantly decreased after GP consumption indicating reduced cholesterol de novo biosynthesis. Markers of intestinal absorption, campesterol, and β‐sitosterol are not changed. Realtime PCR shows that plasma exosomal miRNA‐1 is increased after GP consumption. GC‐MS also shows that GP consumption reduces the plasma cholesterol oxidation product 27‐hydroxycholesterol (27‐HC).ConclusionsThis study enhances the understanding of the mechanisms of the cholesterol lowering effects of GP, and provides new insights into the potential health benefits of grape consumption.
Coded aperture and Compton imaging for the development of 225Ac‐based radiopharmaceuticals
Authors: Frame Emily , Bobba Kondapa , Gunter Donald , Mihailescu Lucian , Bidkar Anil , Flavell Robert , Vetter Kai 
Published: September 2023

AbstractBackgroundTargeted alpha‐particle therapy (TAT) has great promise as a cancer treatment. Arguably the most promising TAT radionuclide that has been proposed is 225Ac. The development of 225Ac‐based radiopharmaceuticals has been hampered due to the lack of effective means to study the daughter redistribution of these agents in small animals at the preclinical stage.PurposeThe ability to directly image the daughters, namely 221Fr and 213Bi, via their gamma‐ray emissions would be a boon for preclinical studies. That said, conventional medical imaging modalities, including single photon emission computed tomography (SPECT) based on nonmultiplexed collimation, cannot be employed due to sensitivity limitations.MethodsAs an alternative, we propose the use of both coded aperture and Compton imaging with the former modality suited to the 218‐keV gamma‐ray emission of 221Fr and the latter suited to the 440‐keV gamma‐ray emission of 213Bi.ResultsThis work includes coded aperture images of 221Fr and Compton images of 213Bi in tumor‐bearing mice injected with 225Ac‐based radiopharmaceuticals.ConclusionsThese results are the first demonstration of visualizing and quantifying the 225Ac daughters in small animals through the application of coded aperture and Compton imaging.
Semi‐solid 3D printing of mesoporous silica nanoparticle‐incorporated xeno‐free nanomaterial hydrogels for protein delivery
Authors: Mahran Alaa , Özliseli Ezgi , Wang Qingbo , Özliseli Ilayda , Bhadane Rajendra , Xu Chunlin , Wang Xiaoju , Rosenholm Jessica M. 
Published: September 2023

AbstractMultifunctional biomaterial inks are in high demand for adapting hydrogels in biomedical applications through three‐dimensional (3D) printing. Our previously developed xeno‐free system consisting of anionic cellulose nanofibers (T‐CNF) and methacrylated galactoglucomannan (GGMMA) as a photo(bio)polymer provides high‐performance ink fidelity in extrusion‐based 3D printing. The fusion between nanoparticles and this biomaterial‐ink system is a promising yet challenging avenue worth exploring, due to the colloidal stability of T‐CNF being sensitive to electrostatic interactions. Mesoporous silica nanoparticles (MSNs), with their robust ceramic matrix and fine‐tunable surface chemistries, are well‐established nanocarriers for different biologicals. Here, we fabricated MSNs with different surface modifications resulting in a net surface charge ranging from highly negative to highly positive to develop printable MSNs‐laden nanocomposite biomaterial inks. We utilized rheology as a comprehensive tool to address the matrix interactions with differently surface‐charged MSNs. Fluorescently labeled bovine serum albumin (FITC‐BSA) was used as a model protein for MSN loading, whereby negatively or neutral‐charged MSNs were found suitable to formulate FITC‐BSA‐loaded biomaterial inks of T‐CNF/GGMMA. Depending on the particles’ surface charge, FITC‐BSA showed different release profiles and preserved its stability after release. Lastly, the proof‐of‐concept to deliver large‐sized biological cargo with MSN‐laden nanocomposite biomaterial inks was established via the 3D printing technique.
The effect of convexity in energy absorption of E‐glass reinforced epoxy composites under high velocity impact: An experimental and numerical investigation
Authors: Manesh Abolfazl Vaezi , Kazemian Amir Hossein , Rahmani Hossein 
Published: September 2023

AbstractComposite laminates have found extensive application in various industries, and numerous studies have been conducted to investigate their behavior in flat sheet configurations. The present study aims to extend this research by examining the behavior of convex composite specimens subjected to high velocity impact (HVI), and comparing their energy absorption and failure area to that of flat sheets made of glass fibers. Additionally, we seek to investigate the influence of curvature diameter on the energy absorption and fiber failure percentage of the composite specimens. Four series of composite laminates with distinct geometries, comprising a flat specimen and three convex composite specimens, were fabricated with nine layers each and diameters of 10, 15, and 20 cm. All specimens were fully clamped and subjected to empirical gas gun impact tests at three different velocities of 200, 250, and 300 m/s. The velocity values before and after the impact were measured using velocity sensors, and the energy absorption of the laminates was computed. Of the tested composite specimens, those with smaller diameters and greater curvature exhibited reduced fiber damage percentage and increased energy absorption. Compared to the flat specimens made of glass fibers, the convex specimens with a diameter of 10 cm exhibited an energy absorption increase of approximately 47%, while the specimens with diameters of 15 and 20 cm showed approximately energy absorption increases of 42% and 7%, respectively. The results were confirmed through simulation using finite element software ABAQUS/Explicit.Highlights
Curved E‐glass laminates studied under high velocity impact which is done experimentally and numerically.
Convexity increases energy absorption capacity of E‐glass reinforced epoxy composites.
The results show that convexity can absorb more energy compared to flat panels.
The damaged area of curved laminates are smaller than the flat one.
The findings suggest that convexity can be a useful design feature for improving impact resistance in various applications.