bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteogenesis-Related Long Noncoding RNA GAS5 as a Novel Biomarker for Osteonecrosis of Femoral Head
Authors: Liu Guanzhi , Luo Sen , Lei Yutian , Jiao Ming , Cao Ruomu , Guan Huanshuai , Tian Run , Wang Kunzheng , Yang Pei 
Published: March 2022

Background: The lack of effective biomarkers makes it difficult to achieve early diagnosis and intervention for osteonecrosis of the femoral head (ONFH). Hence, we aimed to identify novel long noncoding RNA (lncRNA) biomarkers for ONFH.Methods: High-throughput RNA sequencing was performed to detect lncRNA and mRNA expression levels in subchondral bone samples from three patients with ONFH and three patients with femoral neck fractures. Integrated bioinformatics analyses were conducted to identify lncRNAs associated with ONFH development and their potential functions and signaling pathways. A co-expression network was constructed based on the gene time-series expression data in GSE113253. After selecting lncRNA GAS5 as a novel biomarker for ONFH, bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation assays were performed to verify the association between lncRNA GAS5 and osteogenic differentiation. Alkaline phosphatase (ALP) staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to measure the osteogenic phenotype and lncRNA GAS5 expression. Finally, for further validation, ONFH rat models were established, and lncRNA GAS5 expression in subchondral bone was detected by RT-qPCR.Results: We identified 126 and 959 differentially expressed lncRNAs and genes, respectively. lncRNA GAS5 expression level was significantly downregulated in patients with ONFH compared to the control group patients. The BMSC osteogenic differentiation assays showed that ALP activity increased gradually from days 3 to 7, while the lncRNA GAS5 expression level was significantly upregulated in the osteogenic differentiation induction groups. Furthermore, in vivo experiments suggested that the bone volume/tissue volume value and trabecular thickness significantly decreased in the ONFH rat model group compared to the control group, whereas the trabecular space significantly increased in the ONFH group compared to the control group. In addition, the lncRNA GAS5 expression level significantly decreased in the ONFH rat model group.Conclusion: The lncRNA GAS5 expression level was highly associated with BMSC osteogenic differentiation and was significantly downregulated in both the subchondral trabecular bone tissue of ONFH patients and ONFH rat models. Therefore, lncRNA GAS5 can serve as an ONFH osteogenic biomarker to provide an effective target for early diagnosis and molecular therapy of ONFH.
The Mitochondria-Targeting Agent MitoQ Improves Muscle Atrophy, Weakness and Oxidative Metabolism in C26 Tumor-Bearing Mice
Authors: Pin Fabrizio , Huot Joshua R. , Bonetto Andrea 
Published: March 2022

Cancer cachexia is a debilitating syndrome characterized by skeletal muscle wasting, weakness and fatigue. Several pathogenetic mechanisms can contribute to these muscle derangements. Mitochondrial alterations, altered metabolism and increased oxidative stress are known to promote muscle weakness and muscle catabolism. To the extent of improving cachexia, several drugs have been tested to stimulate mitochondrial function and normalize the redox balance. The aim of this study was to test the potential beneficial anti-cachectic effects of Mitoquinone Q (MitoQ), one of the most widely-used mitochondria-targeting antioxidant. Here we show that MitoQ administration (25 mg/kg in drinking water, daily) in vivo was able to improve body weight loss in Colon-26 (C26) bearers, without affecting tumor size. Consistently, the C26 hosts displayed ameliorated skeletal muscle and strength upon treatment with MitoQ. In line with improved skeletal muscle mass, the treatment with MitoQ was able to partially correct the expression of the E3 ubiquitin ligases Atrogin-1 and Murf1. Contrarily, the anabolic signaling was not improved by the treatment, as showed by unchanged AKT, mTOR and 4EBP1 phosphorylation. Assessment of gene expression showed altered levels of markers of mitochondrial biogenesis and homeostasis in the tumor hosts, although only Mitofusin-2 levels were significantly affected by the treatment. Interestingly, the levels of Pdk4 and CytB, genes involved in the regulation of mitochondrial function and metabolism, were also partially increased by MitoQ, in line with the modulation of hexokinase (HK), pyruvate dehydrogenase (PDH) and succinate dehydrogenase (SDH) enzymatic activities. The improvement of the oxidative metabolism was associated with reduced myosteatosis (i.e., intramuscular fat infiltration) in the C26 bearers receiving MitoQ, despite unchanged muscle LDL receptor expression, therefore suggesting that MitoQ could boost β-oxidation in the muscle tissue and promote a glycolytic-to-oxidative shift in muscle metabolism and fiber composition. Overall, our data identify MitoQ as an effective treatment to improve skeletal muscle mass and function in tumor hosts and further support studies aimed at testing the anti-cachectic properties of mitochondria-targeting antioxidants also in combination with routinely administered chemotherapy agents.
Methotrexate-Lactoferrin Targeted Exemestane Cubosomes for Synergistic Breast Cancer Therapy
Authors: Mokhtar Sarah , Khattab Sherine N. , Elkhodairy Kadria A. , Teleb Mohamed , Bekhit Adnan A. , Elzoghby Ahmed O. , Sallam Marwa A. 
Published: March 2022

While the treatment regimen of certain types of breast cancer involves a combination of hormonal therapy and chemotherapy, the outcomes are limited due to the difference in the pharmacokinetics of both treatment agents that hinders their simultaneous and selective delivery to the cancer cells. Herein, we report a hybrid carrier system for the simultaneous targeted delivery of aromatase inhibitor exemestane (EXE) and methotrexate (MTX). EXE was physically loaded within liquid crystalline nanoparticles (LCNPs), while MTX was chemically conjugated to lactoferrin (Lf) by carbodiimide reaction. The anionic EXE-loaded LCNPs were then coated by the cationic MTX–Lf conjugate via electrostatic interactions. The Lf-targeted dual drug-loaded LCNPs exhibited a particle size of 143.6 ± 3.24 nm with a polydispersity index of 0.180. It showed excellent drug loading with an EXE encapsulation efficiency of 95% and an MTX conjugation efficiency of 33.33%. EXE and MTX showed synergistic effect against the MCF-7 breast cancer cell line with a combination index (CI) of 0.342. Furthermore, the Lf-targeted dual drug-loaded LCNPs demonstrated superior synergistic cytotoxic activity with a combination index (CI) of 0.242 and a dose reduction index (DRI) of 34.14 and 4.7 for EXE and MTX, respectively. Cellular uptake studies demonstrated higher cellular uptake of Lf-targeted LCNPs into MCF-7 cancer cells than non-targeted LCNPs after 4 and 24 h. Collectively, the targeted dual drug-loaded LCNPs are a promising candidate offering combinational hormonal therapy/chemotherapy for breast cancer.
Synthesis and Modification of Tetrahedron Li10.35Si1.35P1.65S12via Elemental Doping for All-Solid-State Lithium Batteries
Authors: Lin Yuanzhong , Chen Jian , Yan Jiawei , Zhuang Yanhua , Lu Hengyi , Zhao Chenyang 
Published: March 2022

Solid-state electrolyte (SSE), as the core component of solid-state batteries, plays a critical role in the performance of the batteries. Currently, the development of SSE is still hindered by its high price, low ionic conductivity, and poor interface stability. In this work, we report the tailored synthesis of a high ionic conductive and low cost sulfide SSE for all-solid-state lithium batteries. The Li10.35Si1.35P1.65S12 with favorable tetragonal structure was synthesis by increasing the concentration of Si4+, which shows an ionic conductivity of 4.28 × 10−3 S cm−1 and a wide electrochemical stability window of up to 5 V. By further modifying the composition of the electrolyte via ionic doping, the ionic conductivity of Li10.35Si1.35P1.65S12 can be further enhanced. Among them, the 1% Co4+-doped Li10.35Si1.35P1.65S12 shows the highest ionic conductivity of 6.91 × 10−3 S cm−1, 40% higher than the undoped one. This can be attributed to the broadened MS4− tetrahedrons and increased Li+ concentration. As a demonstration, an all-solid-state Li metal battery was assembled using TiS2 as the cathode and 1% Co4+-doped Li10.35Si1.35P1.65S12 as the electrolyte, showing capacity retention of 72% at the 110th cycle. This strategy is simple and can be easily extended for the construction of other high-performance sulfide SSEs.
Introduction of the Rapid Deployment Aortic Valve System Use in Elderly Patients With Endocarditis
Authors: Öner Alper , Hemmer Christoph , Alozie Anthony , Löser Benjamin , Dohmen Pascal M. 
Published: March 2022

IntroductionThe rapid-deployment valve system (RDVS) was introduced to facility minimally invasive aortic valve replacement. In this study we evaluate the potential benefits of RDVS in elderly high-risk patients with endocarditis of the aortic valve.Materials and MethodsSince the introduction of RDVS in our institution in December 2017 through October 2021, EDWARDS INTUITY rapid-deployment prosthesis (Model 8300A, Edwards Lifesciences, Irvine, CA, USA) has been implanted in a total of 115 patients for different indications by a single surgeon. Out of one-hundred and fifteen cases of RDVS implantation, seven patients with a median age of 77 yrs. (range 62–84yrs.), suffered from active infective endocarditis of the aortic valve. The median EuroSCORE II of these highly selected patient cohort was 77% (range 19–80%). Patient data were evaluated perioperatively including intra-operative data as well as in-hospital morbidity/mortality and follow-up after discharge from hospital.ResultsThree patients underwent previous cardiac surgery. Concomitant procedures were performed in six patients including, ascending aorta replacement (n = 3), mitral valve repair (n = 1), pulmonary valve replacement (n = 1), bypass surgery (n = 1), left atrial appendix resection (n = 1) and anterior mitral valve repair (n = 1). Median aortic cross-clamp and cardiopulmonary bypass time was 56 min (range 29–122 min) and 81 min (range 45–162 min.), respectively. Post-operative complications in these elderly high-risk patients were atrial fibrillation (n = 3) and re-exploration for pericardial effusion (n = 1). One pacemaker implantation was required on postoperative day 6 due to sick sinus syndrome. There was one in-hospital death (14%) and one during follow-up (14%).ConclusionRapid-deployment aortic valve system seems to be a viable option with acceptable morbidity and mortality in elderly high-risk patients with active infective endocarditis of the aortic valve.
Occlusion of Bilobulated Left Atrial Appendage Using the Dual-Watchman Technique: A Long-Term Follow-Up Study
Authors: Chen Tao , Wang Qing-song , Liu Ge , Lu Xu , Song Ting-ting , Shi Ming-yuan , Zhu Hang , Mu Yang , Guo Jun , Chen Yun-dai 
Published: March 2022

BackgroundPercutaneous left atrial appendage (LAA) occlusion has been considered an efficient alternative to oral anticoagulation to prevent embolic events in patients with non-valvular atrial fibrillation (NVAF). Due to the complexities and heterogeneous anatomy of the LAA structure, the single-device approach may not always fit a large bilobulated LAA. This study aimed to evaluate the feasibility and safety of one-stop dual Watchman implantation for patients with bilobulated LAA.MethodsIncluded in the analysis were patients who underwent complete LAA closure with dual Watchman devices between December 2015 and December 2021. The anatomic morphology, procedure characteristics, procedure safety, and procedural complications were analyzed. Cardiac CT or transesophageal ultrasound was obtained at 7 days, 6 months, 1 year, and 2 years post-operatively to evaluate the effect of occlusion.ResultsAmong the 330 patients who underwent LAA occlusion during the study period, 7 (2.1%) patients were occluded with one-stop implantation of the double Watchman strategy. Successful occlusion was achieved in all patients. One patient had the double-access sheath strategy for implantation, and 6 patients had only a single-access sheath strategy for implantation. Pericardial effusion occurred in one case during the 7-day perioperative period. There was no device embolization, thrombosis, or obvious peridevice leakage (≥l mm) during the 2-year follow-up, with the exception of two cases with 2 mm of incomplete LAA sealing.ConclusionThe one-stop implantation of a dual Watchman is feasible and safe and might provide a strategy to occlude a large bilobulated LAA when incomplete closure is inevitable with a single device.
Fluid Inclusion, Isotopic, and Elemental Geochemistry Studies of Cave-Filling Calcite in the Lower–Middle Ordovician Yingshan Formation of Tahe Oilfield, NW China: Implication for Karstification in Non-exposed Limestone
Authors: Zhang Yongmei , Zhang Shaonan , Huang Baiwen , Lu Ziye , Ye Ning , Zhu Bei , Hou Xianhai , Xie Fei , Bai Xiaoliang , Zhang Xinyan 
Published: March 2022

Improving the recognition of paleo-fluid circulation history is of great significance to reconstruct pore evolution during carbonate diagenesis. Integrated petrography, fluid inclusion, isotopic and elemental geochemistry (laser ablation inductively coupled plasma mass spectrometry) studies, calcites generated in paleocaves, and fractures were investigated. This study aims to reveal the paleo-fluid origin and karstification event within the nonexposed limestone of the Lower–Middle Ordovician Yingshan Formation in the Tarim Basin. The only generation of blocky calcite growing along the karst paleocave and fracture walls [cave-filling calcite (CFC)] crosscuts burial stylolites. The secondary fluid inclusions obtained from CFC are characterized by the coexistence of liquid-only and liquid-dominated aqueous inclusions with low salinities values (0–2.4 wt%), suggesting that the CFC has experienced a low-temperature environment (&lt;50°C). The depleted δ18O values (−15.32‰ to 12.45‰), seawater-like yttrium and rare earth element patterns, and low ΣREE (&lt;0.65 ppm) have recorded the major episode of meteoric water leaching the Yingshan limestone. This view was further confirmed by the calculated δ18Owater values of parent fluids (−14.3‰ to 2.2‰). The relatively higher 87Sr/86Sr ratios (0.70942–0.70994) are interpreted as the result of meteoric water interacting with the overlying Silurian detrital rock when percolated downward. The geochemical evidence recorded by CFC indicates that the karstification event for Yingshan nonexposed limestone possibly took place in the Early Hercynian period during the late Devonian. Therefore, meteoric water percolating downward along the fractures penetrating insoluble strata and/or migrating laterally along the permeable strata is deemed responsible for the karstification event, although the overlying thick insoluble strata in the coverage area.
CLCC1 c. 75C>A Mutation in Pakistani Derived Retinitis Pigmentosa Families Likely Originated With a Single Founder Mutation 2,000–5,000 Years Ago
Authors: Ma Yan , Wang Xun , Shoshany Nadav , Jiao Xiaodong , Lee Adrian , Ku Gregory , Baple Emma L. , Fasham James , Nadeem Raheela , Naeem Muhammad Asif , Riazuddin Sheikh , Riazuddin S. Amer , Crosby Andrew H. , Hejtmancik J. Fielding 
Published: March 2022

Background: A CLCC1 c. 75C &gt; A (p.D25E) mutation has been associated with autosomal recessive pigmentosa in patients in and from Pakistan. CLCC1 is ubiquitously expressed, and knockout models of this gene in zebrafish and mice are lethal in the embryonic period, suggesting that possible retinitis pigmentosa mutations in this gene might be limited to those leaving partial activity. In agreement with this hypothesis, the mutation is the only CLCC1 mutation associated with retinitis pigmentosa to date, and all identified patients with this mutation share a common SNP haplotype surrounding the mutation, suggesting a common founder.Methods: SNPs were genotyped by a combination of WGS and Sanger sequencing. The original founder haplotype, and recombination pathways were delineated by examination to minimize recombination events. Mutation age was estimated by four methods including an explicit solution, an iterative approach, a Bayesian approach and an approach based solely on ancestral segment lengths using high density SNP data.Results: All members of each of the nine families studied shared a single autozygous SNP haplotype for the CLCC1 region ranging from approximately 1–3.5 Mb in size. The haplotypes shared by the families could be derived from a single putative ancestral haplotype with at most two recombination events. Based on the haplotype and Gamma analysis, the estimated age of the founding mutation varied from 79 to 196 generations, or approximately 2,000–5,000 years, depending on the markers used in the estimate. The DMLE (Bayesian) estimates ranged from 2,160 generations assuming a population growth rate of 0–309 generations assuming a population growth rate of 2% with broad 95% confidence intervals.Conclusion: These results provide insight into the origin of the CLCC1 mutation in the Pakistan population. This mutation is estimated to have occurred 2000–5,000 years ago and has been transmitted to affected families of Pakistani origin in geographically dispersed locations around the world. This is the only mutation in CLCC1 identified to date, suggesting that the CLCC1 gene is under a high degree of constraint, probably imposed by functional requirements for this gene during embryonic development.
Extracellular HMGB1 Impairs Macrophage-Mediated Efferocytosis by Suppressing the Rab43-Controlled Cell Surface Transport of CD91
Authors: Wang Yao , Zhang Wen , Xu Yu , Wu Di , Gao Zhan , Zhou Jianchun , Qian Hang , He Binfeng , Wang Guansong 
Published: March 2022

High-mobility group box 1 (HMGB1) protein can impair phagocyte function by suppressing the macrophage-mediated clearance of apoptotic cells (ACs), thereby delaying inflammation resolution in the lungs and allowing the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the precise mechanism underlying this HMGB1-mediated inhibition of efferocytosis remains unknown. The aim of this study was to determine the effect of HMGB1 on macrophage-mediated efferocytosis. We discovered that HMGB1 prevented efferocytosis by bone marrow-derived macrophages (BMDMs) and suppressed the expression of Ras-related GTP-binding protein 43 (Rab43), a member of the Ras-associated binding (Rab) family. The downregulation of Rab43 expression resulted in impaired clearance of apoptotic thymocytes by BMDMs. Subsequent analysis of HMGB1-treated and Rab43-deficient BMDMs revealed the inhibited transport of cluster of differentiation 91 (CD91), a phagocyte recognition receptor, from the cytoplasm to the cell surface. Notably, Rab43 directly interacted with CD91 to mediate its intercellular trafficking. Furthermore, Rab43 knockout delayed the inflammation resolution and aggravated the lung tissue damage in mice with ALI. Therefore, our results provide evidence that HMGB1 impairs macrophage-mediated efferocytosis and delays inflammation resolution by suppressing the Rab43-regulated anterograde transport of CD91, suggesting that the restoration of Rab43 levels is a promising strategy for attenuating ALI and ARDS in humans.
Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell Inner Plexiform Layer in Progressive Myopia and Glaucoma Among Adolescents
Authors: Xiao Hui , Zhong Yimin , Ling Yunlan , Xu Xiaoyu , Liu Xing 
Published: March 2022

PurposeThis study aimed to investigate the differences in longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) caused by progressive myopia and glaucoma among adolescents.DesignThis was a retrospective observational study.MethodsA total of forty-seven and 25 eyes of 47 and 25 adolescents with myopia progression (MP) and glaucoma progression (GP), respectively, who were followed up at the Zhongshan Ophthalmic Center for at least 3 years, were included in the study. The pRNFL and GCIPL that measured at the initial and last visits were analyzed.ResultsThe median follow-up period was 5 years for both two groups. During follow-up, the whole, superior, and inferior pRNFL decreased in both the MP and GP groups, (p &lt; 0.001). Nasal pRNFL decreased in the MP group (p &lt; 0.001) but had no significant difference in the GP group (p = 0.19). Temporal pRNFL was increased in the MP group (p &lt; 0.001) but decreased in the GP group (p &lt; 0.001). The average and sectoral GCIPL decreased in both groups (p &lt; 0.001). The annual change rate of temporal pRNFL and pRNFL at 10-, 8-, 9-, and 7-clock-hour sectors and the inferotemporal GCIPL has better diagnostic value to differentiate glaucoma from myopia (the area under the receiver operating characteristic curve, AUC &gt; 0.85).ConclusionGlaucoma and MP could cause loss of the pRNFL and GCIPL in adolescents; however, the loss patterns were different between the two groups. The temporal quadrant and 7-, 8-, 9-, and 10-clock-hour sector pRNFL and the inferotemporal GCIPL can help distinguish pRNFL and GCIPL loss caused by glaucoma or MP.
Changes in Influenza Activity and Circulating Subtypes During the COVID-19 Outbreak in China
Authors: Zheng Luyan , Qi Jinjin , Wu Jie , Zheng Min 
Published: March 2022

BackgroundNon-pharmaceutical interventions (NPIs) to mitigate COVID-19 can impact the circulation of influenza viruses. There is a need to describe the activity of influenza and its subtypes during the COVID-19 pandemic to aid in the development of influenza prevention and control measures in the next influenza season.MethodData from pathogenic surveillance performed by the Chinese National Influenza Center from January 2016 to August 2021 were extracted and stratified by type and subtype for northern China and southern China. The distribution of influenza activity and circulating subtypes were described during the COVID-19 pandemic, and data from 2016 to 2019 were used for comparisons.ResultsInfluenza activity declined rapidly and then rose slowly during the COVID-19 pandemic in China. The distribution of influenza subtypes changed from A-dominant to B/Victoria-dominant after the COVID-19 outbreak.DiscussionWhether the B/Yamagata lineage has disappeared from China deserves more attention in future virologic monitoring programs. The influenza vaccination campaign in the 2021–2022 season is an important means by which to reduce the proportion of susceptible people and limit the damage that potentially greater and earlier circulation of the virus could cause.