bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryogenic 3D Printing of ß-TCP/PLGA Composite Scaffolds Incorporated With BpV (Pic) for Treating Early Avascular Necrosis of Femoral Head
Authors: Li Feng , Cao Zhifu , Li Kai , Huang Ke , Yang Chengliang , Li Ye , Zheng Chuanchuan , Ye Yulu , Zhou Tingjie , Peng Haoqiang , Liu Jia , Wang Chong , Xie Kegong , Tang Yujin , Wang Liqiang
Published: January 2022

Avascular necrosis of femoral head (ANFH) is a disease that is characterized by structural changes and collapse of the femoral head. The exact causes of ANFH are not yet clear, but small advances in etiopathogenesis, diagnosis and treatment are achieved. In this study, ß-tricalcium phosphate/poly lactic-co-glycolic acid composite scaffolds incorporated with bisperoxovanadium [bpV (pic)] (bPTCP) was fabricated through cryogenic 3D printing and were utilized to treat rat models with early ANFH, which were constructed by alcohol gavage for 6 months. The physical properties of bPTCP scaffolds and in vitro bpV (pic) release from the scaffolds were assessed. It was found that the sustained release of bpV (pic) promoted osteogenic differentiation and inhibited adipose differentiation of bone marrow-derived mesenchymal stem cells. Micro-computed tomography scanning and histological analysis confirmed that the progression of ANFH in rats was notably alleviated in bPTCP scaffolds. Moreover, it was noted that the bPTCP scaffolds inhibited phosphatase and tensin homolog and activated the mechanistic target of rapamycin signaling. The autophagy induced by bPTCP scaffolds could partially prevent apoptosis, promote osteogenesis and angiogenesis, and hence eventually prevent the progression of ANFH, suggesting that the bPTCP scaffold are promising candidate to treat ANFH.
Two Hits for Bone Regeneration in Aged Patients: Vertebral Bone Marrow Clot as a Biological Scaffold and Powerful Source of Mesenchymal Stem Cells
Authors: Salamanna Francesca , Contartese Deyanira , Borsari Veronica , Pagani Stefania , Barbanti Brodano Giovanni , Griffoni Cristiana , Ricci Alessandro , Gasbarrini Alessandro , Fini Milena
Published: January 2022

Recently, the use of a new formulation of bone marrow aspirate (BMA), the BMA clot, has been described. This product entails a naturally formed clot from the harvested bone marrow, which retains all the BMA components preserved in a matrix biologically molded by the clot. Even though its beneficial effects were demonstrated by some studies, the impact of aging and aging-associated processes on biological properties and the effect of BMA cell-based therapy are currently unknown. The purpose of our study was to compare selected parameters and properties of clotted BMA and BMA-derived mesenchymal stem cells (MSCs) from younger (<45 years) and older (>65 years) female donors. Clotted BMA growth factors (GFs) expression, MSCs morphology and viability, doubling time, surface marker expression, clonogenic potential, three-lineage differentiation, senescence-associated factors, and Klotho synthesis from younger and older donors were analyzed. Results indicated that donor age does not affect tissue-specific BMA clot regenerative properties such as GFs expression and MSCs morphology, viability, doubling time, surface antigens expression, colony-forming units, osteogenic and adipogenic differentiation, and Klotho and senescence-associated gene expression. Only few differences, i.e., increased platelet-derived growth factor-AB (PDGF-AB) synthesis and MSCs Aggrecan (ACAN) expression, were detected in younger donors in comparison with older ones. However, these differences do not interfere with all the other BMA clot biological properties. These results demonstrated that BMA clot can be applied easily, without any sample processing and avoiding potential contamination risks as well as losing cell viability, proliferation, and differentiation ability, for autologous transplantation in aged patients. The vertebral BMA clot showed two successful hits since it works as a biological scaffold and as a powerful source of mesenchymal stem cells, thus representing a novel and advanced therapeutic alternative for the treatment of orthopedic injuries.
Imaging Approaches for the Study of Metabolism in Real Time Using Genetically Encoded Reporters
Authors: Chandris Panagiotis , Giannouli Christina C. , Panayotou George
Published: January 2022

Metabolism comprises of two axes in order to serve homeostasis: anabolism and catabolism. Both axes are interbranched with the so-called bioenergetics aspect of metabolism. There is a plethora of analytical biochemical methods to monitor metabolites and reactions in lysates, yet there is a rising need to monitor, quantify and elucidate in real time the spatiotemporal orchestration of complex biochemical reactions in living systems and furthermore to analyze the metabolic effect of chemical compounds that are destined for the clinic. The ongoing technological burst in the field of imaging creates opportunities to establish new tools that will allow investigators to monitor dynamics of biochemical reactions and kinetics of metabolites at a resolution that ranges from subcellular organelle to whole system for some key metabolites. This article provides a mini review of available toolkits to achieve this goal but also presents a perspective on the open space that can be exploited to develop novel methodologies that will merge classic biochemistry of metabolism with advanced imaging. In other words, a perspective of “watching metabolism in real time.”
Exosomal miRNA Profiling is a Potential Screening Route for Non-Functional Pituitary Adenoma
Authors: Lyu Liang , Li Haiyan , Chen Cheng , Yu Yang , Wang Li , Yin Senlin , Hu Yu , Jiang Shu , Ye Feng , Zhou Peizhi
Published: January 2022

Non-functional pituitary adenomas (NFPAs) are one of the most prevalent pituitary adenoma subtypes. The lack of reliable screening approach for NFPAs for the insidious clinical course usually leads to delays in medical therapy and consequently worse prognosis. Hence, we employed a sequence cohort (patient: control, 6:2) and a validation cohort (patient: control, 22:8) to develop a serum exosomal miRNA profile-based method for NFPA screening and prognosis prediction. We found that a total of 1,395 kinds of human miRNA were detected. Compared with healthy donors, 18 up-regulated and 36 down-regulated miRNAs showed significant expression alterations in NFPA patients. Target genes of differentially expressed miRNAs are mainly enriched in axonogenesis and cancer-associated terms. After validation, hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p were promising biomarkers for NFPA, in which miR-486-5p was the most competent one. After a median of 33 months of prospective follow-up, exosomal hsa-miR-486-5p also was an efficient predictive biomarker for progression or relapse of NFPAs. By protein-protein interaction network construction of hsa-miR-486-5p targeted genes, the core modules revealed a high possibility that exosomal hsa-miR-486-5p regulated tumor progression by epigenetic regulation of MAPK signaling pathways. In conclusion, exosomal hsa-miR-486-5p, hsa-miR-151a-5p, hsa-miR-652-3p_R+1, and hsa-miR-1180-3p are candidate biomarkers for diagnosis and screening of NFPAs. More importantly, prospective follow-up reveals that hsa-miR-486-5p can be regarded as a significant predictor for prognosis of NFPAs.
Emerging Mechanisms and Disease Implications of Ferroptosis: Potential Applications of Natural Products
Authors: Ge Chun , Zhang Sujie , Mu Huiwen , Zheng Shaojun , Tan Zhaoyi , Huang Xintong , Xu Chen , Zou Jianjun , Zhu Yubing , Feng Dong , Aa Jiye
Published: January 2022

Ferroptosis, a newly discovered form of regulatory cell death (RCD), has been demonstrated to be distinct from other types of RCD, such as apoptosis, necroptosis, and autophagy. Ferroptosis is characterized by iron-dependent lipid peroxidation and oxidative perturbation, and is inhibited by iron chelators and lipophilic antioxidants. This process is regulated by specific pathways and is implicated in diverse biological contexts, mainly including iron homeostasis, lipid metabolism, and glutathione metabolism. A large body of evidence suggests that ferroptosis is interrelated with various physiological and pathological processes, including tumor progression (neuro)degenerative diseases, and hepatic and renal failure. There is an urgent need for the discovery of novel effective ferroptosis-modulating compounds, even though some experimental reagents and approved clinical drugs have been well documented to have anti- or pro-ferroptotic properties. This review outlines recent advances in molecular mechanisms of the ferroptotic death process and discusses its multiple roles in diverse pathophysiological contexts. Furthermore, we summarize chemical compounds and natural products, that act as inducers or inhibitors of ferroptosis in the prevention and treatment of various diseases. Herein, it is particularly highlighted that natural products show promising prospects in ferroptosis-associated (adjuvant) therapy with unique advantages of having multiple components, multiple biotargets and slight side effects.
Systematic kMC Study of Doped Hole Injection Layers in Organic Electronics
Authors: Özdemir Ali Deniz , Kaiser Simon , Neumann Tobias , Symalla Franz , Wenzel Wolfgang
Published: January 2022

Organic light emitting diodes (OLED) play an important role in commercial displays and are promising candidates for energy-efficient lighting applications. Although they have been continuously developed since their discovery in 1987, some unresolved challenges remain. The performance of OLEDs is determined by a multifaceted interplay of materials and device architectures. A commonly used technique to overcome the charge injection barrier from the electrodes to the organic layers, are doped injection layers. The optimization of doped injection layers is critical for high-efficiency OLED devices, but has been driven mainly by chemical intuition and experimental experience, slowing down the progress in this field. Therefore, computer-aided methods for material and device modeling are promising tools to accelerate the device development process. In this work, we studied the effect of doped hole injection layers on the injection barrier in dependence on material and layer properties by using a parametric kinetic Monte Carlo model. We were able to quantitatively elucidate the influence of doping concentration, material properties, and layer thickness on the injection barrier and device conductivity, leading to the conclusion that our kMC model is suitable for virtual device design.
Corrosion Behavior and Biocompatibility of Na2EDTA-Induced Nacre Coatings on AZ91D Alloys Prepared via Hydrothermal Treatment
Authors: He Meifeng , Lu Wenbing , Yu Dan , Wang Hao , Wang Shuai , Yuan Chenggong , Chen Aiying
Published: January 2022

An effective method for controlling the corrosion rate of Mg-based implants must be urgently developed to meet the requirements of clinical applications. As a naturally occurring osteoid material, nacre offers a strategy to endow biomedical Mg alloys with excellent biocompatibility, and corrosion resistance. In this study, pearl powder and NaH2PO4 were used as precursors to deposit coatings on AZ91D alloy substrates hydrothermally based on Na2EDTA-assisted induction. Na2EDTA-induced nacre coatings were fabricated at various pH values, and its chemical composition and microstructure were analyzed via energy-dispersive X-ray, scanning electron microscopy, and X-ray diffraction spectroscopy. The corrosion-resistant performance and cytocompatibility of the samples were evaluated via electrochemical measurements and in vitro cell experiments. Results showed that the samples hydrothermally treated under faint acid conditions present excellent corrosion resistance, whereas the samples treated under slight alkaline conditions demonstrate improved biocompatibility due to high Ca and P content and large Ca/P atomic ratio. This study provides substantial evidence of the potential value of nacre coatings in expanding the biological applications of implanted biomaterials.
Bacterial Vaginosis: What Do We Currently Know?
Authors: Abou Chacra Linda , Fenollar Florence , Diop Khoudia
Published: January 2022

The vaginal microbiome is a well-defined compartment of the human microbiome. It has unique conditions, characterized by the dominance of one bacterial species, the Lactobacilli. This microbiota manifests itself by a low degree of diversity and by a strong dynamic of change in its composition under the influence of various exogenous and endogenous factors. The increase in diversity may paradoxically be associated with dysbiosis, such as bacterial vaginosis (BV). BV is the result of a disturbance in the vaginal ecosystem; i.e., a sudden replacement of Lactobacilli by anaerobic bacteria such as Gardnerella vaginalis, Atopobium vaginae, Ureaplasma urealyticum, Mycoplasma hominis, and others. It is the most common cause of vaginal discharge in women of childbearing age, approximately 30% of all causes. The etiology of this dysbiosis remains unknown, but its health consequences are significant, including obstetrical complications, increased risk of sexually transmitted infections and urogenital infections. Its diagnosis is based on Amsel’s clinical criteria and/or a gram stain based on the Nugent score. While both of these methods have been widely applied worldwide for approximately three decades, Nugent score are still considered the “gold standard” of BV diagnostic tools. Given the limitations of these tools, methods based on molecular biology have been developed as alternative rational strategies for the diagnosis of BV. The treatment of BV aims at restoring the balance of the vaginal flora to stop the proliferation of harmful microorganisms. Prescription of antibiotics such as metronidazole, clindamycin, etc. is recommended. Faced with the considerable uncertainty about the cause of BV, the high rate of recurrence, the unacceptable treatment options, and clinical management which is often insensitive and inconsistent, research on this topic is intensifying. Knowledge of its composition and its associated variations represents the key element in improving the therapeutic management of patients with the most suitable treatments possible.
Variation of Serum Uric Acid Is Associated With Gut Microbiota in Patients With Diabetes Mellitus
Authors: Zhang Weifeng , Wang Ting , Guo Ruixue , Cui Wen , Yu Wei , Wang Zhihui , Jiang Yumin , Jiang Minghan , Wang Xiaojie , Liu Chao , Xiao Jing , Shang Jin , Wen Xuejun , Zhao Zhanzheng
Published: January 2022

Diabetes mellitus is a metabolic disease closely related to a disordered gut microbiome. Diabetic patients usually suffer from various metabolic disorders, such as increased serum uric acid levels. Although serum uric acid levels depend partially on intestine excretion, the relationship between uric acid and gut microbiome in diabetic patients remains unknown. We collected a total of 126 fecal samples from diabetic patients for 16S ribosomal RNA gene amplicon sequencing and recorded clinical data. We analyzed the correlation between clinical indicators and gut microbiota of diabetic patients using Spearman analysis. Since uric acid was the most prominent one, we classified diabetic patients based on their uric acid levels to find the microbiome associated with uric acid disturbance. We constructed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway profiles using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to identify variations between the different groups. Among all the clinical indicators, uric acid had the strongest correlation with gut microbiota. First, we divided the patients into three groups according to their uric acid levels. The two low uric acid groups were similar, while the elevated uric acid group had significant differences in gut microbiota and metabolic pathways. The elevated uric acid group had a significantly lower gut microbiota diversity. At the genus level, this group had remarkably higher Escherichia–Shigella amounts and notably lower Faecalibacterium, Oscillospiraceae_UCG−002, and Oscillospiraceae_UCG−005 amounts. The gut microbiota of the high uric acid group was predicted to be enriched in metabolism, human diseases, and lipopolysaccharide biosynthesis. Since the two low uric acid groups were similar, we regrouped and matched the abnormal uric acid patients with normal uric acid patients. The differences in gut microbiota and metabolic pathways related to nucleotide metabolism became more significant. The serum uric acid levels were associated with gut microbiome changes. This might be related to uric acid metabolism by gut microbes. Our study indicates that targeting the gut microbiome could help manage elevated uric acid levels.
Metabolic and Microbial Changes Associated With Diet and Obesity During Pregnancy: What Can We Learn From Animal Studies?
Authors: Dreisbach Caitlin , Morgan Hailey , Cochran Caroline , Gyamfi Adwoa , Henderson Wendy Ann , Prescott Stephanie
Published: January 2022

The intestinal microbiota changes throughout pregnancy and influences maternal metabolic adaptations to support fetal growth. Obesity induces alterations to the microbiota that include decreased microbial diversity and shifts in microbial composition, though specific species changes are inconsistent between published studies. In animal models, probiotics and exercise moderate maternal weight gain and partially correct the maternal microbiota. Supplemental Escherichia coli, however, exacerbate maternal obesity during the perinatal period, lending weight to the theory that inflammation-induced gut epithelial barrier leak influences metabolic dysregulation. Although birth weight is not always altered when offspring are exposed to an obesogenic diet during gestation, insulin resistance and lipid metabolism are impacted through adulthood in association with this exposure and can lead to increased body weight in adulthood. Postnatal offspring growth is accelerated in response to maternal overnutrition during lactation. Offspring microbiota, metabolism, and behavior are altered in response to early exposure to high fat and high sucrose diets. Consequences to this exposure include impaired glucose and insulin homeostasis, fatty liver, and neurobehavioral deficits that can be ameliorated by improving the microbial environment. In this mini review, we provide an overview of the use of translational animal models to understand the mechanisms associated with changes to the gastrointestinal microbiota due to maternal obesity and the microbial impact on the metabolic changes of pregnancy.
Association Between Preinfarction Angina and Culprit Lesion Morphology in Patients With ST-Segment Elevation Myocardial Infarction: An Optical Coherence Tomography Study
Authors: Wang Ying , Sheng Zhaoxue , Li Jiannan , Tan Yu , Zhou Peng , Liu Chen , Zhao Xiaoxiao , Zhou Jinying , Chen Runzhen , Song Li , Zhao Hanjun , Yan Hongbing
Published: January 2022

Background

Previous studies reported the cardiac protection effect of preinfarction angina (PIA) in patients with acute myocardial infarction (AMI). We sought to identify culprit-plaque morphology and clinical outcomes associated with PIA in patients with ST-segment elevation myocardial infarction (STEMI) using optical coherence tomography (OCT).

Methods and Results

A total of 279 patients with STEMI between March 2017 and March 2019 who underwent intravascular OCT of the culprit lesion were prospectively included. Of them, 153 (54.8%) patients were presented with PIA. No differences were observed in clinical and angiographic data between the two groups, except STEMI onset with exertion was significantly less common in the PIA group (24.2 vs. 40.5%, p = 0.004). Patients with PIA exhibited a significantly lower incidence of plaque rupture (40.5 vs. 61.9%, p < 0.001) and lipid-rich plaques (48.4 vs. 69.0%, p = 0.001). The thin-cap fibroatheroma (TCFA) prevalence was lower in the PIA group, presenting a thicker fibrous cap thickness, although statistically significant differences were not observed (20.3 vs. 30.2%, p = 0.070; 129.1 ± 92.0 vs. 111.4 ± 78.1 μm, p = 0.088; respectively). The multivariate logistic regression analysis indicated that PIA was an independent negative predictor of plaque rupture (odds ratio: 0.44, 95% CI: 0.268–0.725, p = 0.001). No significant differences in clinical outcomes were observed besides unplanned revascularization.

Conclusion

Compared with the non-PIA group, STEMI patients with PIA showed a significantly lower prevalence of plaque rupture and lipid-rich plaques in culprit lesion, implying different mechanisms of STEMI attack in these two groups.
MiR-29a Increase in Aging May Function as a Compensatory Mechanism Against Cardiac Fibrosis Through SERPINH1 Downregulation
Authors: Rusu-Nastase Evelyn Gabriela , Lupan Ana-Mihaela , Marinescu Catalina Iolanda , Neculachi Carmen Alexandra , Preda Mihai Bogdan , Burlacu Alexandrina
Published: January 2022

Deregulation of microRNA (miRNA) profile has been reportedly linked to the aging process, which is a dominant risk factor for many pathologies. Among the miRNAs with documented roles in aging-related cardiac diseases, miR-18a, -21a, -22, and -29a were mainly associated with hypertrophy and/or fibrosis; however, their relationship to aging was not fully addressed before. The purpose of this paper was to evaluate the variations in the expression levels of these miRNAs in the aging process. To this aim, multiple organs were harvested from young (2–3-months-old), old (16–18-months-old), and very old (24–25-months-old) mice, and the abundance of the miRNAs was evaluated by quantitative real-time (RT)-PCR. Our studies demonstrated that miR-21a, miR-22, and miR-29a were upregulated in the aged heart. Among them, miR-29a was highly expressed in many other organs, i.e., the brain, the skeletal muscle, the pancreas, and the kidney, and its expression was further upregulated during the natural aging process. Western blot, immunofluorescence, and xCELLigence analyses concurrently indicated that overexpression of miR-29a in the muscle cells decreased the collagen levels as well as cell migration and proliferation. Computational prediction analysis and overexpression studies identified SERPINH1, a specific chaperone of procollagens, as a potential miR-29a target. Corroborating to this, significantly downregulated SERPINH1 levels were found in the skeletal muscle, the heart, the brain, the kidney, and the pancreas harvested from very old animals, thereby indicating the role of the miR-29a-SERPINH1 axis in the aging process. In vitro analysis of miR-29a effects on fibroblast and cardiac muscle cells pointed toward a protective role of miR-29a on aging-related fibrosis, by reducing cell migration and proliferation. In conclusion, our study indicates an adaptive increase of miR-29 in the natural aging process and suggests its role as a transcriptional repressor of SERPINH1, with a potential therapeutic value against adverse matrix remodeling and aging-associated tissue fibrosis.
A Risk-Stratification Machine Learning Framework for the Prediction of Coronary Artery Disease Severity: Insights From the GESS Trial
Authors: Mittas Nikolaos , Chatzopoulou Fani , Kyritsis Konstantinos A. , Papagiannopoulos Christos I. , Theodoroula Nikoleta F. , Papazoglou Andreas S. , Karagiannidis Efstratios , Sofidis Georgios , Moysidis Dimitrios V. , Stalikas Nikolaos , Papa Anna , Chatzidimitriou Dimitrios , Sianos Georgios , Angelis Lefteris , Vizirianakis Ioannis S.
Published: January 2022

Our study aims to develop a data-driven framework utilizing heterogenous electronic medical and clinical records and advanced Machine Learning (ML) approaches for: (i) the identification of critical risk factors affecting the complexity of Coronary Artery Disease (CAD), as assessed via the SYNTAX score; and (ii) the development of ML prediction models for accurate estimation of the expected SYNTAX score. We propose a two-part modeling technique separating the process into two distinct phases: (a) a binary classification task for predicting, whether a patient is more likely to present with a non-zero SYNTAX score; and (b) a regression task to predict the expected SYNTAX score accountable to individual patients with a non-zero SYNTAX score. The framework is based on data collected from the GESS trial (NCT03150680) comprising electronic medical and clinical records for 303 adult patients with suspected CAD, having undergone invasive coronary angiography in AHEPA University Hospital of Thessaloniki, Greece. The deployment of the proposed approach demonstrated that atherogenic index of plasma levels, diabetes mellitus and hypertension can be considered as important risk factors for discriminating patients into zero- and non-zero SYNTAX score groups, whereas diastolic and systolic arterial blood pressure, peripheral vascular disease and body mass index can be considered as significant risk factors for providing an accurate estimation of the expected SYNTAX score, given that a patient belongs to the non-zero SYNTAX score group. The experimental findings utilizing the identified set of important risk factors indicate a sufficient prediction performance for the Support Vector Machine model (classification task) with an F-measure score of ~0.71 and the Support Vector Regression model (regression task) with a median absolute error value of ~6.5. The proposed data-driven framework described herein present evidence of the prediction capacity and the potential clinical usefulness of the developed risk-stratification models. However, further experimentation in a larger clinical setting is needed to ensure the practical utility of the presented models in a way to contribute to a more personalized management and counseling of CAD patients.
Fibroblast Growth Factor 1 Reduces Pulmonary Vein and Atrium Arrhythmogenesis via Modification of Oxidative Stress and Sodium/Calcium Homeostasis
Authors: Lu Yen-Yu , Cheng Chen-Chuan , Huang Shih-Yu , Chen Yao-Chang , Kao Yu-Hsun , Lin Yung-Kuo , Higa Satoshi , Chen Shih-Ann , Chen Yi-Jen
Published: January 2022

Rationale

Atrial fibrillation is a critical health burden. Targeting calcium (Ca2+) dysregulation and oxidative stress are potential upstream therapeutic strategies. Fibroblast growth factor (FGF) 1 can modulate Ca2+ homeostasis and has antioxidant activity. The aim of this study was to investigate whether FGF1 has anti-arrhythmic potential through modulating Ca2+ homeostasis and antioxidant activity of pulmonary vein (PV) and left atrium (LA) myocytes.

Methods

Patch clamp, western blotting, confocal microscopy, cellular and mitochondrial oxidative stress studies were performed in isolated rabbit PV and LA myocytes treated with or without FGF1 (1 and 10 ng/mL). Conventional microelectrodes were used to record electrical activity in isolated rabbit PV and LA tissue preparations with and without FGF1 (3 μg/kg, i.v.).

Results

FGF1-treated rabbits had a slower heart rate than that observed in controls. PV and LA tissues in FGF1-treated rabbits had slower beating rates and longer action potential duration than those observed in controls. Isoproterenol (1 μM)-treated PV and LA tissues in the FGF1-treated rabbits showed less changes in the increased beating rate and a lower incidence of tachypacing (20 Hz)-induced burst firing than those observed in controls. FGF1 (10 ng/mL)-treated PV and LA myocytes had less oxidative stress and Ca2+ transient than those observed in controls. Compared to controls, FGF1 (10 ng/mL) decreased INa−L in PV myocytes and lowered Ito, IKr−tail in LA myocytes. Protein kinase C (PKC)ε inhibition abolished the effects of FGF1 on the ionic currents of LA and PV myocytes.

Conclusion

FGF1 changes PV and LA electrophysiological characteristics possibly via modulating oxidative stress, Na+/Ca2+ homeostasis, and the PKCε pathway.
High-Resolution Imaging: An Approach by Compensating Absorption and Dispersion in Prestack Time Migration With Effective Q Estimation and Fresnel Zone Identification Based on Deep Learning
Authors: Wu Jizhong , Shi Ying , Guo Aihua , Lu Pengfei , Yang Qianqian
Published: January 2022

We have developed a migration scheme that can compensate absorption and dispersion with effective Q estimation and Fresnel zone identification based on deep learning. We use the U-Net neural network technology in deep learning to automatically identify Fresnel zones from compensated migrated dip-angle gathers and obtain the optimal aperture for migration, avoiding the tedious task of manually modifying the boundaries of Fresnel zones. Instead of the interval Q factor, we used an effective Q parameter to compensate absorption and dispersion. The effective Q is estimated using VSP well data and surface seismic velocity data. The proposed scheme can be incorporated into conventional seismic data processing workflow. A field data set was employed to validate the proposed scheme. Higher resolution imaging results with low noise levels are obtained.
Advancement of Megadunes and its Implications in the Badain Jaran Sand Sea
Authors: Dong Peng , Liang Aimin , Zhou Yali
Published: January 2022

The tallest megadunes on the Earth are developed in China’s Badain Jaran Sand Sea, as a result of which a prolonged curiosity exists with regards to the existence and migration of such large dunes. However, our present understanding of movement of aeolian bedforms is largely limited to dunes with height ranging from several to several tens of meters. Difficulties in understanding the movement of megadunes predominantly exists in the monitoring methods. This study presents the evidence of the megadune advancement and its rate in the Badain Jaran Sand Sea, estimated by optically stimulated luminescence (OSL) dating of sediments on the slipfaces of several megadunes. It is suggested that megadunes experience similar advancement as the commonly observed sand dunes; the rate of advancement of megadunes fits the rate-height relationship. The rate of advancement varies linearly with the reciprocal of megadune height, which has been confirmed for dunes, extending the advancement rate-height relationship to a previously blind range of dune size. In addition, the advancement rate of megadunes exhibits far-reaching implications for megadune formation. In combination with other morphometric evidences, it exemplifies the assumption that the development of megadunes is predominantly controlled by wind rather than other factors such as the underlying relief and ground water, as accepted by most researchers.
The Changes in Drainage Systems of Weihe Basin and Sanmenxia Basin Since Late Pliocene Give New Insights Into the Evolution of the Yellow River
Authors: Liu Jin , Wang Ping , Chen Xingqiang , Shi Wei , Song Lijun , Hu Jianmin
Published: January 2022

The formation of the Yellow River involved the draining of a series of ancestral local lakes along their course, substantially changing the regional, geomorphic, and paleoenvironmental evolution. However, the evolution of the Weihe-Sanmenxia Basin section of the Yellow River remains indistinct as previous studies regard the Weihe and Sanmenxia Basin as one integral basin of the Late Cenozoic. Here, we present the detrital zircon age spectra from the Pliocene-Pleistocene Sanmen Formation to clarify the drainage system evolution of the two basins since the Late Pliocene. The results reveal that these two basins belonged to different drainage systems in the Late Pliocene because no sediments from the marginal mountains of the Weihe Basin accumulated in the Sanmenxia Basin. At 2.8/2.6 Ma, the currents presented at the edge of the basins and transported the sediment of east Hua Mountain into the Sanmenxia Basin, where it was deposited. This integration likely leads to a mismatch between the deposition and regional paleoclimate in previous studies. At ∼1.0 Ma, the Sanmenxia Gorge was traversed and the Yellow River finally formed, depositing Jinshaan Gorge sediment into the Sanmenxia Basin and lower reaches of the Yellow River.
Aeromagnetic-Imaged Basement Fault Structure of the Eastern Tarim Basin and Its Tectonic Implication
Authors: Kuang Xingtao , Zhu Xiaoying , Ning Fangxin , Li Wei , Zheng Qifang , Li Bing , Zhou Daoqing
Published: January 2022

The property of the magnetic basement and the faults in the basement is significant for structural evolution, the Phanerozoic deposition, and oil resource exploration of the Tarim Basin. Based on the newly acquired aeromagnetic and industry seismic data, we mapped the distribution of basement faults by applying magnetic gradient-processing methods such as the horizontal gradient derivative, the first vertical derivative, the tilt derivative, and the upward continuation method. The dips of basement faults were confirmed and the susceptibilities of basement blocks were obtained by forward modeling of five profiles using the constraint of sedimentary strata depth and Moho topography. On the basis of comprehensive analysis of the magnetic anomalies, the distribution and inclination of basement faults, and susceptibilities differentiation obtained by forward modeling and field measurement, the property of the basement faults and their implication were discussed and interpreted. Our results show that the origin of the Central Highly Magnetic Anomaly Belt is highly magnetic Archean metamorphic rocks. The weakly magnetic Southeastern Domain and highly magnetic Central Tadong Domain assembled along the Tadong South Fault during the Paleoproterozoic. The Paleozoic Cherchen Fault is just an interior fault in the weakly magnetic Southeastern Domain although it presents a large vertical fault displacement. Considering the prominent variation of strikes of the Tadong North Fault system, and the moderately magnetic anomalies in the Northeastern Mangal Domain corresponding to the center of Neoproterozoic deposition, it is likely that the basement of the Northeastern Mangal Domain modified by the Neoproterozoic rifting could be originally the same as the basement of Central Highly Magnetic Anomaly Belt.
Horizontal Fracture Formation in the Cenozoic Mudstone of the Western Qaidam Basin
Authors: Li Jian , Li Qi , Zeng Lianbo , Zhu Zhenjun , Ding Xiaojun , Li Xianming
Published: January 2022

Fractures can provide valuable information on the tectonic evolution of the Earth’s crust. Our field observation data, rock core data, and thin section observations reveal several horizontal fractures in the Cenozoic mudstone strata in the western Qaidam Basin, Qinghai Province, China. These horizontal fractures have rough surfaces and are filled by gypsum. The fractures are mainly curved; however, some straight fractures are also found. There are many intersections between adjacent curved fractures, which often adjoin to form “T” shape fractures. Fracture apertures are mainly between 1 mm and 1 cm, with a maximum of 3 cm. Both the size and density of fractures decrease as strata denudation thickness decreases and depth of burial increases. Horizontal fractures are only found in a core area of anticlines with severe strata denudation. Accordingly, these fractures are related to vertical extension due to residual stress in the process of rapid uplift and denudation. The horizontal fractures cut earlier vertical tectonic fractures, indicating their formation after tectonic extrusion. Electron spin resonance (ESR) dating of fracture-filling materials revealed that horizontal fractures appeared in two stages. The first stage was approximately 1.8 Ma ago, while the second stage was approximately 0.3 Ma ago. The size and density of the later-stage horizontal fractures are markedly greater than the earlier-stage fractures. Based on the driving stress when fractures are formed, which is obtained from fracture parameters, the denudation rate in the later stage was approximately 2∼3-fold greater than that in the earlier stage. According to the evidence, during the Quaternary, the western Qaidam Basin experienced pulsating tectonic extrusion, producing uplift and denudation and an increase in tectonic activity. Such findings suggest a gradual increase in episodic tectonic activity in the entire Tibetan Plateau region during the Quaternary.
Place Value Understanding Explains Individual Differences in Writing Numbers in Second and Third Graders But Goes Beyond
Authors: Herzog Moritz , Fritz Annemarie
Published: January 2022

Recent studies have shown that children’s proficiency in writing numbers as part of the so-called transcoding correlates with math skills. Typically, children learn to write numbers up to 10,000 between Grade 1 and 4. Transcoding errors can be categorized in lexical and syntactical errors. Number writing is thus considered a central aspect of place value understanding. Children’s place value understanding can be structured by a hierarchical model that distinguishes five levels. The current study investigates to what extent a profound understanding of the place value system can explain individual differences in number writing. N = 266 s and third graders (126 girls) participated in the study. The children wrote down 28 verbal given numbers up to 10,000 and completed a place value test based on a hierarchical model to assess number writing skills and place value understanding. Second graders made more number writing errors than third graders and transcoding errors were mostly syntactical errors. In both grades, transcoding performance and place value understanding correlated substantially. In particular complex numbers were more often solved correctly by children with a more elaborated place value understanding. The effect of place value understanding on error rate was smaller regarding lexical errors than syntactical errors. This effect was also comparably small regarding inversion-related errors. The results underpin that writing numbers is an integral part of early place value understanding. Writing numbers can be assumed to be mostly based on the identification of the place values. However, variance in transcoding skills cannot totally be explained by place value understanding, because children with an elaborated place value understanding differed in transcoding performance, too. The differences between the grades indicate that children’s development of writing numbers is also driven by instruction in school. Thus, writing numbers and place value understanding overlap but exceed each other. We discuss how an understanding of the place value relations can be integrated in existing frameworks of place value processing. Since writing numbers is a basic skill in place value understanding, it might serve as an efficient screening method for children, who struggle severely with understanding the decimal place value system.
Impacts of the COVID-19 Pandemic on Elementary School Teachers’ Practices and Perceptions Across the Spring and Fall 2020 Semesters
Authors: Goodrich J. Marc , Hebert Michael , Namkung Jessica M.
Published: January 2022

Following the closure of schools in the spring 2020 semester due to the COVID-19 pandemic, we developed two surveys to understand how the pandemic affected elementary education in the U.S. First, we distributed a survey at the end of the spring 2020 semester to understand how school closures impacted delivery of instruction. Second, we conducted a follow up survey in November 2020 to determine the nature of instruction provided to students when schools did or did not re-open in Fall 2020 and understand teachers’ perceptions of student learning and achievement during the pandemic. Each survey was sent to a sample of over 9,000 teachers who were randomly selected to be representative of the population of the U.S. Results indicated that many students did not receive direct instruction in academic skills during the spring 2020 semester. Although by late fall 2020 teachers reported broad use of some form of in-person instructional model, teachers indicated that many of their students were not ready to transition to the next grade level and that achievement gaps were larger in fall 2020 than in typical years. These findings have important implications for practices during potential school closures in the future.
A Comparison of Two Hybrid Closed-Loop Systems in Italian Children and Adults With Type 1 Diabetes
Authors: Bassi Marta , Teliti Marsida , Lezzi Marilea , Iosca Arianna , Strati Marina Francesca , Carmisciano Luca , d’Annunzio Giuseppe , Minuto Nicola , Maggi Davide
Published: January 2022

Tandem Control-IQ and Minimed 780G represent the most Advanced Hybrid Closed Loop (AHCL) systems currently available in pediatric and adult subjects with Type 1 Diabetes (T1D). We retrospectively compared clinical and continuous glucose monitoring data from 51 patients who upgraded to Minimed 780G system and have completed 1-month observation period with data from 39 patients who upgraded to Tandem Control-IQ. Inverse probability weighting was used to minimize the basal characteristics imbalances. Both AHCL systems showed a significant improvement in glycemic parameters. Minimed 780G group achieved higher TIR increase (p= 0.004) and greater reduction of blood glucose average (p= 0.001). Tandem Control-IQ system significantly reduced the occurrence of TBR (p= 0.010) and the Coefficient of Variation of glucose levels (p= 0.005). The use of ACHL systems led to a significant improvement of glycemic control substantially reaching the International recommended glycemic targets. Minimed 780G appears to be more effective in managing hyperglycemia, while Tandem Control-IQ seems to be more effective in reducing time in hypoglycemia.
Distinct Community-Wide Responses to Forecasted Climate Change in Afrotropical Forests
Authors: Núñez Chase L. , Poulsen John R. , White Lee J. T. , Medjibe Vincent , Clark James S.
Published: January 2022

More refined knowledge of how tropical forests respond to changes in the abiotic environment is necessary to mitigate climate change, maintain biodiversity, and preserve ecosystem services. To evaluate the unique response of diverse Afrotropical forest communities to disturbances in the abiotic environment, we employ country-wide tree species inventories, remotely sensed climate data, and future climate predictions collected from 104 1-ha plots in the central African country of Gabon. We predict a 3–8% decrease in Afrotropical forest species richness by the end of the century, in contrast to the 30–50% loss of plant diversity predicted to occur with equivalent warming in the Neotropics. This work reveals that forecasts of community species composition are not generalizable across regions, and more representative studies are needed in understudied diverse biomes. This study serves as an important counterpoint to work done in the Neotropics by providing contrasting predictions for Afrotropical forests with substantially different ecological, evolutionary, and anthropogenic histories.
Systemic Immune Dysregulation Correlates With Clinical Features of Early Non-Small Cell Lung Cancer
Authors: Hao Zhixing , Lin Mingjie , Du Feng , Xin Zhongwei , Wu Dang , Yu Qun , Wu Yimin , Zhu Zhouyu , Li Wenshan , Chen Yongyuan , Chen Xiaoke , Chai Ying , Jin Shenghang , Wu Pin
Published: January 2022

Background

Systemic immune dysregulation correlates with cancer progression. However, the clinical implications of systemic immune dysregulation in early non-small cell lung cancer (NSCLC) remain unclear.

Methods

Using a panel of 9 markers to identify 12 parameters in the peripheral blood of 326 patients (34 in the discovery group and 292 in the validation group), we investigated systemic immune dysregulation in early NSCLC. Then, we analyzed the impact of surgery on the systemic immune state of these patients. Finally, we analyzed correlations between systemic immune dysregulation and the clinical features of early NSCLC.

Results

We found striking systemic immune dysregulation in the peripheral blood of early NSCLC patients. This dysregulation was characterized by a significant decrease in total lymphocytes, T cells, quiescent T cells, CD4+ T cells, and NKT cells. We also observed increased proportions of activated lymphocytes and activated T cells. Systemic immune dysregulation was increased after surgery. Furthermore, systemic immune dysregulation was correlated with multiple clinical features, such as sex, age, smoking history, pathological type, tumor stage, surgical approach, tumor differentiation, and epidermal growth factor receptor (EGFR) mutation. Finally, we observed that systemic immune dysregulation was correlated with complications and systemic inflammatory response syndrome (SIRS) in early NSCLC patients.

Conclusions

Our results reveal systemic immune dysregulation occurring in early NSCLC and demonstrate the correlation between these dysregulations and clinical features. Our findings suggest that systemic immune dysregulation is involved in cancer development and may be a promising candidate for high-risk screening and treatment strategies for early NSCLC.
Integrated Analysis of mRNA-Seq and MiRNA-Seq Reveals the Molecular Mechanism of the Intestinal Immune Response in Marsupenaeus japonicus Under Decapod Iridescent Virus 1 Infection
Authors: He Zihao , Zhong Yunqi , Hou Danqing , Hu Xianye , Fu Zhibin , Liu Luyao , Zhang Shuang , Sun Chengbo
Published: January 2022

The intestine is not only an important digestive organ but also an important immune organ for shrimp; it plays a key role in maintaining homeostasis. Decapod iridescent virus 1 (DIV1) is a new type of shrimp-lethal virus that has received extensive attention in recent years. To date, most studies of the shrimp intestinal immune response under viral infections have relied on single omics analyses; there is a lack of systematic multi-omics research. In the current study, intestinal mRNA-seq and microRNA (miRNA)-seq analyses of Marsupenaeus japonicus under DIV1 infection were performed. A total of 1,976 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs (DEMs) were identified. Among them, 21 DEMs were negatively correlated with 194 DEGs from a total of 223 correlations. Functional annotation analysis revealed that M. japonicus can regulate glycosaminoglycan biosynthesis (chondroitin sulfate, dermatan sulfate, and keratan sulfate), vitamin metabolism (retinol metabolism and ascorbate and aldarate metabolism), immune pathway activation (Toll and IMD signaling pathways, Wnt signaling pathway, IL-17 signaling pathway, and Hippo signaling pathway), immunity enzyme activity promotion (triose-phosphate isomerase), antimicrobial peptide (AMP) expression, reactive oxygen species (ROS) production, and cell apoptosis through miRNAs to participate in the host’s antiviral immune response, while DIV1 can influence Warburg effect-related pathways (pyruvate metabolism, glycolysis/gluconeogenesis, and citrate cycle), glycosphingolipid biosynthesis-related pathways (glycosphingolipid biosynthesis—globo and isoglobo series and glycosphingolipid biosynthesis—lacto and neolacto series), and the tight junction and adhesion junction of the intestinal mucosal epithelium through the host’s miRNAs and mRNA to promote its own invasion and replication. These results indicate that intestinal miRNAs play important roles in the shrimp immune response against DIV1 infection. This study provides a basis for further study of the shrimp intestinal antiviral immune response and for the formulation of effective new strategies for the prevention and treatment of DIV1 infection.