bluuebunny/crossref_metadata_2025 huggingface dataset:
Fretting Characteristics of Rubber X-Ring Exposed to High-Pressure Gaseous Hydrogen
Authors: Zhou Chilou , Zheng Yiran , Liu Xianhui
Published: September 2022

The rubber ring is an essential component of high-pressure hydrogen storage systems. However, the fretting damage can lead to the seal failure of the rubber ring, which may cause hydrogen leakage. Rubber X-ring has been proven to own excellent static sealing performance, while its fretting characteristics under high-pressure hydrogen remain unclear. In this study, a numerical model is developed to explore the fretting characteristics of the X-ring combined seal, in which the effect of hydrogen swelling is well considered. The stress distribution of the fretting seal and the effects of fretting amplitude, friction coefficient, hydrogen pressure, and pre-compression ratio on the fretting behavior of the X-ring are investigated. Moreover, the similarities and differences in the fretting performance of X-ring and O-ring under high-pressure hydrogen are discussed. It is shown that the evolution of the stress concentration zone inside the X-ring is closely linked to the cover’s drag direction and the wedge-ring’s blocking action. The X-ring enters the fretting cycle earlier with increased fretting amplitude, whereas the fretting period remains unchanged. Furthermore, increasing the hydrogen pressure and pre-compression ratio could enhance the fretting sealing performance. The friction coefficient and hydrogen pressure increase the possibility of failure due to cracks or elasticity. The fretting characteristics of the X-ring are superior to those of the O-ring, denoting that X-ring may be an alternative to the O-ring in the fretting seal structure. This work is of theoretical importance for the quantitative evaluation and reliable prevention of fretting damage to rubber rings and improving the safety of high-pressure hydrogen storage systems.
Autothermal Siberian Pine Nutshell Pyrolysis Maintained by Exothermic Reactions
Authors: Astafev Alexander , Shanenkov Ivan , Ibraeva Kanipa , Tabakaev Roman , Preis Sergei
Published: September 2022

The global energy industry works towards an increased use of carbon-neutral biomass. Nutshell represents a regional bio-waste, i.e., a bio-energy resource. Pyrolysis is a common method for processing biomass into valuable energy products. The heat demand, however, limits pyrolysis applications. Yet, such demand may be addressed via exothermic pyrolysis reactions under selected operation conditions. Making the pyrolysis of Siberian pine nutshell autothermic comprised the objective of the study. The study involved analytical methods together with a pyrolysis experiment. The analytical methods included a thermogravimetric analysis combined with differential scanning calorimetry and an integrated gas analyzer. Thermophysical characterization was executed using a thermal diffusivity analyzer with the laser flash method. At 650 °C, pyrolytic heat was released in the amount of 1224.6 kJ/kg, exceeding the heat demand of 1179.5 kJ/kg. Pyrolysis at a lower temperature of 550 °C remained endothermic, although the combusted gas product provided 847.7 kJ/kg of heat, which, together with exothermic release, covered the required heat demand for the pyrolysis process.
Identification and Functional Analysis of LncRNAs in Response to Seed Aging in Metasequoia glyptostroboides by Third Generation Sequencing Technology
Authors: Luo Yongjian , Le Jingyu , Zhang Yixin , Wang Ru , Li Qing , Lu Xinxiong , Liu Jun , Deng Zhijun
Published: September 2022

The seeds of Metasequia glyptostroboides Hu et Cheng, an endangered species, are susceptible to aging, making natural population renewal difficult and increasing the risk of extinction. LncRNAs play important roles in plant growth and development and biotic and abiotic stress responses, but the functions of lncRNAs in the aging process of M. glyptostroboides seeds are still unclear. In this study, we used single molecule real-time (SMRT) sequencing technology in combination with Illumina RNA-seq to analyze lncRNA changes during M. glyptostroboides seed aging. We identified 403 intergenic lncRNAs (lincRNAs), 29 intronic lncRNAs, and 25 antisense lncRNAs; screened 9000 differentially expressed mRNAs (DEGs) and 128 differentially expressed lncRNAs (DELs); and predicted 844 cis-target genes and 8098 trans-target genes. GO and KEGG functional annotation of target genes revealed that the regulation of the reactive oxygen species metabolic process, protein processing in the endoplasmic reticulum, and the MAPK signaling pathway and other pathways were significantly enriched, showing a high correlation with the mRNA enrichment results. In addition, we constructed a ceRNA network consisting of 18 lncRNAs, 38 miRNAs, and 69 mRNAs, in which some miRNAs and mRNAs related to seed aging were found. Among them, miR167(a,b,c,d) may compete with lncRNA_00185, which is related to plant aging, to regulate the expression of the RCD1(Radical-induced Cell Death1) gene, thus promoting the balance of seed reactive oxygen species and enhancing seed-aging resistance. These results will have significant reference value in elucidating the molecular mechanism of the seed aging of M. glyptostroboides sequoia, improving the storage capacity for crop seeds, and protecting rare germplasm resources.
Laterally Positioned Flap Procedure with Augmented or Nonaugmented Palatal Connective Tissue Grafts in the Treatment of Multiple Adjacent Gingival Recessions: A Two-Year Follow-Up Study
Authors: Bednarz Wojciech , Majer Jennifer , Pakuszyńska-Błaszczyk Justyna , Dominiak Marzena , Gedrange Tomasz , Zielińska-Pałasz Agata
Published: September 2022

The most commonly used technique for covering gingival recessions is the coronally advanced flap (CAF) technique due to its high success rate. In clinical situations where there is less keratinized tissue apical to the defect due to unfavorable anatomical conditions, a more advantageous technique for this situation should be considered, specifically the laterally positioned flap (LPF). The aim of this study was to compare the gingival thickness after gingival recession coverage using the laterally positioned flap supported by an augmented and non-augmented connective tissue graft (CTG). Thirty-four patients with 105 gingival recessions of Miller’s class I and/or II were enrolled in this study. The method of choice was the laterally positioned flap. The test group was treated with previously augmented CTG harvested from the palatal mucosa while the control group was treated with a non-augmented CTG. Clinical measurements were recorded at baseline, 6, 12 and 24 months after intervention. Clinical results showed a statistically more significant percentage of average and complete gingival recession coverage in the test group. The LPF in combination with an augmented CTG proves to be an effective alternative to the CAF. Greater improvement in gingival thickness was observed in the LPF with augmented CTG than in non-augmented CTG.
Variable-Scale Visualization of High-Density Polygonal Buildings on a Tile Map
Authors: Chen Zhixiong , Shen Yilang , Lv Xinlin , Qin Qiaolin , Chen Xin
Published: September 2022

To better satisfy user’s needs for the accurate visualization of massive amounts of geographic data, the variable-scale expression of map content based on multilevel data organization has attracted increasing attention. Traditional methods based on vector data usually cannot handle tile data in the form of a grid on the network. Therefore, this paper proposes a variable-scale visualization method for high-density buildings based on a raster tile map. First, the buildings on a tile map are typified on the basis of linear spectral clustering (LSC) superpixel segmentation to reduce the number of buildings. Then, the shapes of buildings are simplified using the minimum bounding rectangle method. Lastly, the designed focus + glue + context (F + G + C) variable-scale model is used for visual output. The OpenStreetMap tile data are used to perform experiments. Compared with traditional methods, the proposed variable-scale visualization method in this paper considers the spatial distribution, quantity, and shape characteristics of buildings, reduces the clutter of data, and has a better (average value of building quantity, area and density is 57%) visual effect. Variable-scale visualization can be applied to unstructured map data sources and extended to grid data sources to improve the readability and recognizability of high-density buildings.
Molecular and Morphological Characteristics of the De-Obstructed Rat Urinary Bladder—An Update
Authors: Uvelius Bengt , Andersson Karl-Erik
Published: September 2022

Many patients with outlet obstruction secondary to prostatic enlargement have lower urinary tract symptoms (LUTSs) and an increased frequency of micturition. The standard treatment is transurethral resection of the prostate (TURP), which alleviates obstruction and symptoms. However, after TURP, 20–40 percent of patients continue to experience LUTSs. The aim of the present study in rats was to identify the mechanisms that do not normalize after the removal of the obstruction and that could explain the persisting symptoms. We had microarray data from control, obstructed, and de-obstructed female rat bladders, which made it possible to study 14,553 mRNA expressions. We also had a bank of electron micrographs from similar detrusors. Microarrays: There were significant differences between the control and obstructed bladders for 1111 mRNAs. The obstructed and de-obstructed bladders differed significantly for 1059 mRNAs. The controls and the de-obstructed bladders differed significantly for 798 mRNAs. We observed many mRNAs that were increased in the obstructed bladder and then decreased to control levels after de-obstruction, and many mRNAs that were decreased in the obstructed bladder and then increased following de-obstruction. mRNAs that were significantly higher or lower in the de-obstructed bladder than in the control bladder were also found. Ultrastructure: The detrusor cells in the obstructed bladders had cross-sectional areas that were much larger than those in the controls. The control cells had smooth outlines and similar cross-sectional areas. The de-obstructed detrusor cells had larger cross-sectional areas than the controls, as well as corrugated surfaces. The cell areas varied, suggesting that the shrinkage of the de-obstructed cells was not even. We did not find any points of contact of the gap junction plaque type between the detrusor cells. There were abundant finger-like processes between the detrusor cells in the obstructed and in de-obstructed bladders, which were only occasionally found in the control detrusors. They are the only possible localization for gap junction channels. The de-obstructed rat bladder is not an organ with properties intermediate between those of the control and obstructed bladders. Instead, de-obstructed bladders have gene expressions, morphologies, and functional properties of the individual cells and their organization, which make them distinctly different from both control and obstructed bladders.
Photosynthetic Efficiency and Glyco-Metabolism Changes in Artificial Triploid Loquats Contribute to Heterosis Manifestation
Authors: Wang Lingli , Tu Meiyan , Li Jing , Sun Shuxia , Song Haiyan , Xu Zihong , Chen Dong , Liang Guolu
Published: September 2022

Previous studies indicated that extensive genetic variations could be generated due to polyploidy, which is considered to be closely associated with the manifestation of polyploid heterosis. Our previous studies confirmed that triploid loquats demonstrated significant heterosis, other than the ploidy effect, but the underlying mechanisms are largely unknown. This study aimed to overcome the narrow genetic distance of loquats, increase the genetic variation level of triploid loquats, and systematically illuminate the heterosis mechanisms of triploid loquats derived from two cross combinations. Here, inter-simple sequence repeats (ISSRs) and simple sequence repeats (SSRs) were adopted for evaluating the genetic diversity, and transcriptome sequencing (RNA-Seq) was performed to investigate gene expression as well as pathway changes in the triploids. We found that extensive genetic variations were produced during the formation of triploid loquats. The polymorphism ratios of ISSRs and SSRs were 43.75% and 19.32%, respectively, and almost all their markers had a PIC value higher than 0.5, suggesting that both ISSRs and SSRs could work well in loquat assisted breeding. Furthermore, our results revealed that by broadening the genetic distance between the parents, genetic variations in triploids could be promoted. Additionally, RNA-Seq results suggested that numerous genes differentially expressed between the triploids and parents were screened out. Moreover, KEGG analyses revealed that “photosynthetic efficiency” and “glyco-metabolism” were significantly changed in triploid loquats compared with the parents, which was consistent with the results of physiological indicator analyses, leaf micro-structure observations, and qRT-PCR validation. Collectively, our results suggested that extensive genetic variations occurred in the triploids and that the changes in the “photosynthetic efficiency” as well as “glyco-metabolism” of triploids might have further resulted in heterosis manifestation in the triploid loquats.
Enhanced Photocatalytic Activity of Anatase/Rutile Heterojunctions by Lanthanum and Tin Co-Doping
Authors: Zhu Xiaodong , Qin Fengqiu , He Lili , Jiao Yu , Feng Wei
Published: September 2022

Anatase/rutile heterojunctions were prepared using the sol–gel method and modified by La/Sn single doping and co-doping. Sn doping promoted the transformation from anatase to rutile, while La doping inhibited the phase transformation. La and Sn co-doping showed an inhibitory effect. The co-doping of La and Sn did not increase visible-light absorption, but exhibited a synergistic effect on inhibiting the recombination of photogenerated electrons and holes, which improved the photocatalytic activity on the basis of single-element modification. The first-order reaction rate constant of La/Sn co-doped sample was 0.027 min−1, which is 1.8 times higher than that of pure TiO2 (0.015 min−1). Meanwhile, the mechanism of photodegradation of methylene blue (MB) by La/Sn co-doped anatase/rutile heterojunctions was discussed through electrochemical measurements and free-radical trapping experiments.
Hydroxyapatite Biobased Materials for Treatment and Diagnosis of Cancer
Authors: De Lama-Odría María del Carmen , del Valle Luis J. , Puiggalí Jordi
Published: September 2022

Great advances in cancer treatment have been undertaken in the last years as a consequence of the development of new antitumoral drugs able to target cancer cells with decreasing side effects and a better understanding of the behavior of neoplastic cells during invasion and metastasis. Specifically, drug delivery systems (DDS) based on the use of hydroxyapatite nanoparticles (HAp NPs) are gaining attention and merit a comprehensive review focused on their potential applications. These are derived from the intrinsic properties of HAp (e.g., biocompatibility and biodegradability), together with the easy functionalization and easy control of porosity, crystallinity and morphology of HAp NPs. The capacity to tailor the properties of DLS based on HAp NPs has well-recognized advantages for the control of both drug loading and release. Furthermore, the functionalization of NPs allows a targeted uptake in tumoral cells while their rapid elimination by the reticuloendothelial system (RES) can be avoided. Advances in HAp NPs involve not only their use as drug nanocarriers but also their employment as nanosystems for magnetic hyperthermia therapy, gene delivery systems, adjuvants for cancer immunotherapy and nanoparticles for cell imaging.
Transcriptional Response of Circadian Clock Genes to an ‘Artificial Light at Night’ Pulse in the Cricket Gryllus bimaculatus
Authors: Levy Keren , Fishman Bettina , Barnea Anat , Ayali Amir , Tauber Eran
Published: September 2022

Light is the major signal entraining the circadian clock that regulates physiological and behavioral rhythms in most organisms, including insects. Artificial light at night (ALAN) disrupts the natural light–dark cycle and negatively impacts animals at various levels. We simulated ALAN using dim light stimuli and tested their impact on gene expression in the cricket Gryllus bimaculatus, a model of insect physiology and chronobiology. At night, adult light–dark-regime-raised crickets were exposed for 30 min to a light pulse of 2–40 lx. The relative expression of five circadian-clock-associated genes was compared using qPCR. A dim ALAN pulse elicited tissue-dependent differential expression in some of these genes. The strongest effect was observed in the brain and in the optic lobe, the cricket’s circadian pacemaker. The expression of opsin-Long Wave (opLW) was upregulated, as well as cryptochrome1-2 (cry) and period (per). Our findings demonstrate that even a dim ALAN exposure may affect insects at the molecular level, underscoring the impact of ALAN on the circadian clock system.
The Potential Connection between Molecular Changes and Biomarkers Related to ALS and the Development and Regeneration of CNS
Authors: Glavač Damjan , Mladinić Miranda , Ban Jelena , Mazzone Graciela L. , Sámano Cynthia , Tomljanović Ivana , Jezernik Gregor , Ravnik-Glavač Metka
Published: September 2022

Neurodegenerative diseases are one of the greatest medical burdens of the modern age, being mostly incurable and with limited prognostic and diagnostic tools. Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by the loss of motoneurons, with a complex etiology, combining genetic, epigenetic, and environmental causes. The neuroprotective therapeutic approaches are very limited, while the diagnostics rely on clinical examination and the exclusion of other diseases. The recent advancement in the discovery of molecular pathways and gene mutations involved in ALS has deepened the understanding of the disease pathology and opened the possibility for new treatments and diagnostic procedures. Recently, 15 risk loci with distinct genetic architectures and neuron-specific biology were identified as linked to ALS through common and rare variant association analyses. Interestingly, the quantity of related proteins to these genes has been found to change during early postnatal development in mammalian spinal cord tissue (opossum Monodelphis domestica) at the particular time when neuroregeneration stops being possible. Here, we discuss the possibility that the ALS-related genes/proteins could be connected to neuroregeneration and development. Moreover, since the regulation of gene expression in developmental checkpoints is frequently regulated by non-coding RNAs, we propose that studying the changes in the composition and quantity of non-coding RNA molecules, both in ALS patients and in the developing central nervous (CNS) system of the opossum at the time when neuroregeneration ceases, could reveal potential biomarkers useful in ALS prognosis and diagnosis.
Functional and Expressional Analyses Reveal the Distinct Role of Complement Factor I in Regulating Complement System Activation during GCRV Infection in Ctenopharyngodon idella
Authors: Liu Yi , Lv Zhao , Xiao Tiaoyi , Zhang Xuewen , Ding Chunhua , Qin Beibei , Xu Baohong , Liu Qiaolin
Published: September 2022

Complement factor I (CFI), a complement inhibitor, is well known for regulating the complement system activation by degrading complement component 3b (C3b) in animal serum, thus becoming involved in innate defense. Nevertheless, the functional mechanisms of CFI in the complement system and in host-pathogen interactions are far from being clarified in teleost fish. In the present study, we cloned and characterized the CFI gene, CiCFI, from grass carp (Ctenopharyngodon idella) and analyzed its function in degrading serum C3b and expression changes after grass carp reovirus (GCRV) infection. The open reading frame of CiCFI was found to be 2121 bp, encoding 706 amino acids with a molecular mass of 79.06 kDa. The pairwise alignments showed that CiCFI shared the highest identity (66.9%) with CFI from Carassius gibelio and the highest similarity (78.7%) with CFI from Danio rerio. The CiCFI protein was characterized by a conserved functional core Tryp_SPc domain with the catalytic triad and substrate binding sites. Phylogenetic analysis indicated that CiCFI and the homologs CFIs from other teleost fish formed a distinct evolutionary branch. Similar with the CFIs reported in mammals, the recombinant CiCFI protein could significantly reduce the C3b content in the serum, demonstrating the conserved function of CiCFI in the complement system in the grass carp. CiCFI mRNA and protein showed the highest expression level in the liver. After GCRV infection, the mRNA expressions of CiCFI were first down-regulated, then up-regulated, and then down-regulated to the initial level, while the protein expression levels maintained an overall downward trend to the late stage of infection in the liver of grass carps. Unexpectedly, the protein levels of CiCFI were also continuously down-regulated in the serum of grass carps during GCRV infection, while the content of serum C3b proteins first increases and then returns to the initial level, suggesting a distinct role of CiCFI in regulating complement activation and fish-virus interaction. Combining our previous results that complement factor D, a complement enhancer, shows continuously up-regulated expression levels in grass carps during GCRV infection, and this study may provide the further essential data for the full picture of complex complement regulation mechanism mediated by Df and CFI of the grass carp during pathogen infection.
Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice
Authors: Chung Chi-Li , Chen Jui-Hsuan , Huang Wei-Chieh , Sheu Joen-Rong , Hsia Chih-Wei , Jayakumar Thanasekaran , Hsia Chih-Hsuan , Chiou Kuan-Rau , Hou Shaw-Min
Published: September 2022

Platelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities (i.e., obesity and diabetes) and protects against CVDs and neuronal disorders. To the best of our knowledge, no studies have focused on glabridin’s effects on platelet activation. Therefore, we investigated these effects in humans and mice. Glabridin exhibited the highest inhibitory effects on collagen-stimulated platelet aggregation and moderate effects on arachidonic-acid-stimulated activation; however, no effects were observed for any other agonists (e.g., thrombin or U46619). Glabridin evidently reduced P-selectin expression, ATP release, and intracellular Ca2+ ([Ca2+]i) mobilization and thromboxane A2 formation; it further reduced the activation of phospholipase C (PLC)γ2/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β), mitogen-activated protein kinase (MAPK), and NF-κB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLCγ2/PKC cascade and prevents the activation of the PI3K/Akt/GSK3β and MAPK pathways; this leads to a reduction in [Ca2+]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders.
Citicoline Eye Drops Protect Trabecular Meshwork Cells from Oxidative Stress Injury in a 3D In Vitro Glaucoma Model
Authors: Vernazza Stefania , Passalacqua Mario , Tirendi Sara , Marengo Barbara , Domenicotti Cinzia , Sbardella Diego , Oddone Francesco , Bassi Anna Maria
Published: September 2022

Intraocular pressure (IOP) is considered an important modifiable risk factor for glaucoma, which is known as the second leading cause of blindness worldwide. However, lowering the IOP is not always sufficient to preserve vision due to other non-IOP-dependent mechanisms being involved. To improve outcomes, adjunctive therapies with IOP-independent targets are required. To date, no studies have shown the effect of citicoline on the trabecular meshwork (TM), even though it is known to possess neuroprotective/enhancement properties and multifactorial mechanisms of action. Given that reactive oxygen species seem to be involved in glaucomatous cascade, in this present study, an advanced millifluidic in vitro model was used to evaluate if citicoline could exert a valid TM protection against oxidative stress. To this end, the cellular behavior, in terms of viability, apoptosis, mitochondrial state, senescence and pro-inflammatory cytokines, on 3D human TM cells, treated either with H2O2 alone or cotreated with citicoline, was analyzed. Our preliminary in vitro results suggest a counteracting effect of citicoline eye drops against oxidative stress on TM cells, though further studies are necessary to explore citicoline’s potential as a TM-target therapy.
Mapping QTLs for Reproductive Stage Salinity Tolerance in Rice Using a Cross between Hasawi and BRRI dhan28
Authors: Mondal Sejuti , Septiningsih Endang M. , Singh Rakesh K. , Thomson Michael J.
Published: September 2022

Salinity stress is a major constraint to rice production in many coastal regions due to saline groundwater and river sources, especially during the dry season in coastal areas when seawater intrudes further inland due to reduced river flows. Since salinity tolerance is a complex trait, breeding efforts can be assisted by mapping quantitative trait loci (QTLs) for complementary salt tolerance mechanisms, which can then be combined to provide higher levels of tolerance. While an abundance of seedling stage salinity tolerance QTLs have been mapped, few studies have investigated reproductive stage tolerance in rice due to the difficulty of achieving reliable stage-specific phenotyping techniques. In the current study, a BC1F2 mapping population consisting of 435 individuals derived from a cross between a salt-tolerant Saudi Arabian variety, Hasawi, and a salt-sensitive Bangladeshi variety, BRRI dhan28, was evaluated for yield components after exposure to EC 10 dS/m salinity stress during the reproductive stage. After selecting tolerant and sensitive progeny, 190 individuals were genotyped by skim sequencing, resulting in 6209 high quality single nucleotide polymorphic (SNP) markers. Subsequently, a total of 40 QTLs were identified, of which 24 were for key traits, including productive tillers, number and percent filled spikelets, and grain yield under stress. Importantly, three yield-related QTLs, one each for productive tillers (qPT3.1), number of filled spikelets (qNFS3.1) and grain yield (qGY3.1) under salinity stress, were mapped at the same position (6.7 Mb or 26.1 cM) on chromosome 3, which had not previously been associated with grain yield under salinity stress. These QTLs can be investigated further to dissect the molecular mechanisms underlying reproductive stage salinity tolerance in rice.
Treatment Effect of Platelet Gel on Reconstructing Bone Defects and Nonunions: A Review of In Vivo Human Studies
Authors: Lin Che-Yu
Published: September 2022

In ideal circumstances, a fractured bone can heal properly by itself or with the aid of clinical interventions. However, around 5% to 10% of bone fractures fail to heal properly within the expected time even with the aid of clinical interventions, resulting in nonunions. Platelet gel is a blood-derived biomaterial used in regenerative medicine aiming to promote wound healing and regeneration of damaged tissues. The purpose of this paper is to review relevant articles in an attempt to explore the current consensus on the treatment effect of platelet gel on reconstructing bone defects and nonunions, hoping to provide a valuable reference for clinicians to make treatment decisions in clinical practice. Based on the present review, most of the studies applied the combination of platelet gel and bone graft to reconstruct bone defects and nonunions, and most of the results were positive, suggesting that this treatment strategy could promote successful reconstruction of bone defects and nonunions. Only two studies tried to apply platelet gel alone to reconstruct bone defects and nonunions, therefore a convincing conclusion could not be made yet regarding the treatment effect of platelet gel alone on reconstructing bone defects and nonunions. Only one study applied platelet gel combined with extracorporeal shock wave therapy to reconstruct nonunions, and the results were positive; the hypothetical mechanism of this treatment strategy is reasonable and sound, and more future clinical studies are encouraged to further justify the effectiveness of this promising treatment strategy. In conclusion, the application of platelet gel could be a promising and useful treatment method for reconstructing bone defects and nonunions, and more future clinical studies are encouraged to further investigate the effectiveness of this promising treatment method.
Molecular Advances in MAFLD—A Link between Sphingolipids and Extracellular Matrix in Development and Progression to Fibrosis
Authors: Kołakowski Adrian , Dziemitko Sylwia , Chmielecka Aleksandra , Żywno Hubert , Bzdęga Wiktor , Charytoniuk Tomasz , Chabowski Adrian , Konstantynowicz-Nowicka Karolina
Published: September 2022

Metabolic-Associated Fatty Liver Disease (MAFLD) is a major cause of liver diseases globally and its prevalence is expected to grow in the coming decades. The main cause of MAFLD development is changed in the composition of the extracellular matrix (ECM). Increased production of matrix molecules and inflammatory processes lead to progressive fibrosis, cirrhosis, and ultimately liver failure. In addition, increased accumulation of sphingolipids accompanied by increased expression of pro-inflammatory cytokines in the ECM is closely related to lipogenesis, MAFLD development, and its progression to fibrosis. In our work, we will summarize all information regarding the role of sphingolipids e.g., ceramide and S1P in MAFLD development. These sphingolipids seem to have the most significant effect on macrophages and, consequently, HSCs which trigger the entire cascade of overproduction matrix molecules, especially type I and III collagen, proteoglycans, elastin, and also tissue inhibitors of metalloproteinases, which as a result cause the development of liver fibrosis.
Comparative Physiological and Transcriptomic Analyses of Improved Heat Stress Tolerance in Celery (Apium Graveolens L.) Caused by Exogenous Melatonin
Authors: Li Mengyao , Zhou Jin , Du Jiageng , Li Xiaoyan , Sun Yue , Wang Zhuo , Lin Yuanxiu , Zhang Yunting , Wang Yan , He Wen , Wang Xiaorong , Chen Qing , Zhang Yong , Luo Ya , Tang Haoru
Published: September 2022

Melatonin (MT) is crucial in plant growth, development, and response to stress. Celery is a vegetable that grows in a cool climate, and a hot climate can deteriorate its growth, yield, and quality. This study investigates the effect of exogenous melatonin on celery physiology. Transcriptional levels were analyzed by spraying celery with exogenous MT before exposing it to high temperatures. The regulatory mechanism of exogenous MT-mediated heat tolerance was examined. The results show that the exogenous MT reduced the thermal damage state of celery seedlings, as well as the malondialdehyde (MDA) content and relative conductivity (REC), increasing the oxidase activity, the osmotic regulatory substances, and chlorophyll, enhancing the leaf transpiration and the light energy utilization efficiency. We examined the mechanism of exogenous MT in mitigating high-temperature damage using the transcriptome sequencing method. A total of 134 genes were expressed differently at high temperature in the celery treated with MT compared with the untreated celery. Functional annotation analysis revealed that the differentially expressed genes were abundant in the “pyruvate metabolism” pathway and the “peroxidase activity” pathway. According to the pathway-based gene expression analysis, exogenous MT can inhibit the upregulation of pyruvate synthesis genes and the downregulation of pyruvate consumption genes, preventing the accumulated pyruvate from rapidly upregulating the expression of peroxidase genes, and thereby enhancing peroxidase activity. RT-qPCR verification showed a rising encoding peroxidase gene expression under MT treatment. The gene expression pattern involved in pyruvate anabolism and metabolism agreed with the abundant transcriptome expression, validating the physiological index results. These results indicate that the application of exogenous MT to celery significantly enhances the ability of plant to remove reactive oxygen species (ROS) in response to heat stress, thereby improving the ability of plant to resist heat stress. The results of this study provide a theoretical basis for the use of MT to alleviate the damage caused by heat stress in plant growth and development.
Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021
Authors: Zhang Chunyan , Sun Caifang , Zhao Yabin , Wang Qiwen , Guo Jianlin , Ye Bingyu , Yu Guoying
Published: September 2022

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) about 22 nucleotides in size, which play an important role in gene regulation and are involved in almost all major cellular physiological processes. In recent years, the abnormal expression of miRNAs has been shown to be associated with human diseases including cancer. In the past ten years, the link between miRNAs and various cancers has been extensively studied, and the abnormal expression of miRNAs has been reported in various malignant tumors, such as lung cancer, gastric cancer, colorectal cancer, liver cancer, breast cancer, and prostate cancer. Due to the high malignancy grade of these cancers, it is more necessary to develop the related diagnostic and prognostic methods. According to the study of miRNAs, many potential cancer biomarkers have been proposed for the diagnosis and prognosis of diseases, especially cancer, thus providing a new theoretical basis and perspective for cancer screening. The use of miRNAs as biomarkers for diagnosis or prognosis of cancer has the advantages of being less invasive to patients, with better accuracy and lower price. In view of the important clinical significance of miRNAs in human cancer research, this article reviewed the research status of miRNAs in the above-mentioned cancers in 2021, especially in terms of diagnosis and prognosis, and provided some new perspectives and theoretical basis for the diagnosis and treatment of cancers.
Oxidative Stress and Mitochondrial Complex I Dysfunction Correlate with Neurodegeneration in an α-Synucleinopathy Animal Model
Authors: Morales-Martínez Adriana , Martínez-Gómez Paola A. , Martinez-Fong Daniel , Villegas-Rojas Marcos M. , Pérez-Severiano Francisca , Del Toro-Colín Miguel A. , Delgado-Minjares Karen M. , Blanco-Alvarez Víctor Manuel , Leon-Chavez Bertha Alicia , Aparicio-Trejo Omar Emiliano , Baéz-Cortés Mauricio T. , Cardenas-Aguayo Maria-del-Carmen , Luna-Muñoz José , Pacheco-Herrero Mar , Angeles-López Quetzalli D. , Martínez-Dávila Irma A. , Salinas-Lara Citlaltepetl , Romero-López José Pablo , Sánchez-Garibay Carlos , Méndez-Cruz Adolfo R. , Soto-Rojas Luis O.
Published: September 2022

The α-synucleinopathies constitute a subset of neurodegenerative disorders, of which Parkinson’s disease (PD) is the most common worldwide, characterized by the accumulation of misfolded α-synuclein in the cytoplasm of neurons, which spreads in a prion-like manner to anatomically interconnected brain areas. However, it is not clear how α-synucleinopathy triggers neurodegeneration. We recently developed a rat model through a single intranigral administration of the neurotoxic β-sitosterol β-D-glucoside (BSSG), which produces α-synucleinopathy. In this model, we aimed to evaluate the temporal pattern of levels in oxidative and nitrosative stress and mitochondrial complex I (CI) dysfunction and how these biochemical parameters are associated with neurodegeneration in different brain areas with α-synucleinopathy (Substantia nigra pars compacta, the striatum, in the hippocampus and the olfactory bulb, where α-syn aggregation spreads). Interestingly, an increase in oxidative stress and mitochondrial CI dysfunction accompanied neurodegeneration in those brain regions. Furthermore, in silico analysis suggests a high-affinity binding site for BSSG with peroxisome proliferator-activated receptors (PPAR) alpha (PPAR-α) and gamma (PPAR-γ). These findings will contribute to elucidating the pathophysiological mechanisms associated with α-synucleinopathies and lead to the identification of new early biomarkers and therapeutic targets.
Insights Gained from RNA Editing Targeted by the CRISPR-Cas13 Family
Authors: Liu Li , Pei De-Sheng
Published: September 2022

Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems, especially type II (Cas9) systems, have been widely developed for DNA targeting and formed a set of mature precision gene-editing systems. However, the basic research and application of the CRISPR-Cas system in RNA is still in its early stages. Recently, the discovery of the CRISPR-Cas13 type VI system has provided the possibility for the expansion of RNA targeting technology, which has broad application prospects. Most type VI Cas13 effectors have dinuclease activity that catalyzes pre-crRNA into mature crRNA and produces strong RNA cleavage activity. Cas13 can specifically recognize targeted RNA fragments to activate the Cas13/crRNA complex for collateral cleavage activity. To date, the Cas13X protein is the smallest effector of the Cas13 family, with 775 amino acids, which is a promising platform for RNA targeting due to its lack of protospacer flanking sequence (PFS) restrictions, ease of packaging, and absence of permanent damage. This study highlighted the latest progress in RNA editing targeted by the CRISPR-Cas13 family, and discussed the application of Cas13 in basic research, nucleic acid diagnosis, nucleic acid tracking, and genetic disease treatment. Furthermore, we clarified the structure of the Cas13 protein family and their molecular mechanism, and proposed a future vision of RNA editing targeted by the CRISPR-Cas13 family.
PD-L1, a Potential Immunomodulator Linking Immunology and Orthodontically Induced Inflammatory Root Resorption (OIIRR): Friend or Foe?
Authors: Yong Jiawen , Gröger Sabine , von Bremen Julia , Meyle Joerg , Ruf Sabine
Published: September 2022

Orthodontically induced inflammatory root resorption (OIIRR) is considered an undesired and inevitable complication induced by orthodontic forces. This inflammatory mechanism is regulated by immune cells that precede orthodontic tooth movement (OTM) and can influence the severity of OIIRR. The process of OIIRR is based on an immune response. On some occasions, the immune system attacks the dentition by inflammatory processes during orthodontic treatment. Studies on the involvement of the PD-1/PD-L1 immune checkpoint have demonstrated its role in evading immune responses, aiming to identify possible novel therapeutic approaches for periodontitis. In the field of orthodontics, the important question arises of whether PD-L1 has a role in the development of OIIRR to amplify the amount of resorption. We hypothesize that blocking of the PD-L1 immune checkpoint could be a suitable procedure to reduce the process of OIIRR during orthodontic tooth movement. This review attempts to shed light on the regulation of immune mechanisms and inflammatory responses that could influence the pathogenesis of OIIRR and to acquire knowledge about the role of PD-L1 in the immunomodulation involved in OIIRR. Possible clinical outcomes will be discussed in relation to PD-L1 expression and immunologic changes throughout the resorption process.
Betaine-Based Deep Eutectic Solvent as a New Media for Laccase-Catalyzed Template-Guided Polymerization/Copolymerization of Aniline and 3-Aminobenzoic Acid
Authors: Vasil’eva Irina , Morozova Olga , Shumakovich Galina , Yaropolov Alexander
Published: September 2022

Deep eutectic solvents (DESs) can compensate for some of the major drawbacks of traditional organic solvents and ionic liquids and meet all requirements of green chemistry. However, the potential of their use as a medium for biocatalytic reactions has not been adequately studied. In this work we used the DES betaine-glycerol with a molar ratio of 1:2 as co-solvent for enzymatic template-guided polymerization/copolymerization of aniline (ANI) and 3-aminobenzoic acid (3ABA). The laccase from the basidial fungus Trametes hirsuta and air oxygen served as catalyst and oxidant, respectively. Sodium polystyrene sulfonate (PSS) was used as template. Interpolyelectrolyte complexes of homopolymers polyaniline (PANI) and poly(3-aminobenzoic acid) (P3ABA) and copolymer poly(aniline-co-3-aminobenzoic acid) (P(ANI-3ABA)) were prepared and their physico-chemical properties were studied by UV-Vis and FTIR spectroscopy and cyclic voltammetry. According to the results obtained by atomic force microscopy, PANI/PSS had a granular shape, P(ANI-3ABA)/PSS had a spherical shape and P3ABA/PSS had a spindle-like shape. The copolymer showed a greater antimicrobial activity against Escherichia coli and Staphylcocus aureus as compared with the homopolymers. The minimal inhibitory concentration of the P(ANI-3ABA)/PSS against the gram-positive bacterium S. aureus was 0.125 mg mL−1.
Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients
Authors: Honfi Dániel , Gémes Nikolett , Szabó Enikő , Neuperger Patrícia , Balog József Á. , Nagy Lajos I. , Toldi Gergely , Puskás László G. , Szebeni Gábor J. , Balog Attila
Published: September 2022

Vaccination against SARS-CoV-2 to prevent COVID-19 is highly recommended for immunocompromised patients with autoimmune rheumatic and musculoskeletal diseases (aiRMDs). Little is known about the effect of booster vaccination or infection followed by previously completed two-dose vaccination in aiRMDs. We determined neutralizing anti-SARS-CoV-2 antibody levels and applied flow cytometric immunophenotyping to quantify the SARS-CoV-2 reactive B- and T-cell mediated immunity in aiRMDs receiving homologous or heterologous boosters or acquired infection following vaccination. Patients receiving a heterologous booster had a higher proportion of IgM+ SARS-CoV-2 S+ CD19+CD27+ peripheral memory B-cells in comparison to those who acquired infection. Biologic therapy decreased the number of S+CD19+; S+CD19+CD27+IgG+; and S+CD19+CD27+IgM+ B-cells. The response rate to a booster event in cellular immunity was the highest in the S-, M-, and N-reactive CD4+CD40L+ T-cell subset. Patients with a disease duration of more than 10 years had higher proportions of CD8+TNF-α+ and CD8+IFN-γ+ T-cells in comparison to patients who were diagnosed less than 10 years ago. We detected neutralizing antibodies, S+ reactive peripheral memory B-cells, and five S-, M-, and N-reactive T-cells subsets in our patient cohort showing the importance of booster events. Biologic therapy and <10 years disease duration may confound anti-SARS-CoV-2 specific immunity in aiRMDs.
Cold-Induced Nuclear Import of CBF4 Regulates Freezing Tolerance
Authors: Shi Wenjing , Riemann Michael , Rieger Sophie-Marie , Nick Peter
Published: September 2022

C-repeat binding factors (CBFs) are crucial transcriptional activators in plant responses to low temperature. CBF4 differs in its slower, but more persistent regulation and its role in cold acclimation. Cold acclimation has accentuated relevance for tolerance to late spring frosts as they have become progressively more common, as a consequence of blurred seasonality in the context of global climate change. In the current study, we explore the functions of CBF4 from grapevine, VvCBF4. Overexpression of VvCBF4 fused to GFP in tobacco BY-2 cells confers cold tolerance. Furthermore, this protein shuttles from the cytoplasm to the nucleus in response to cold stress, associated with an accumulation of transcripts for other CBFs and the cold responsive gene, ERD10d. This response differs for chilling as compared to freezing and is regulated differently by upstream signalling involving oxidative burst, proteasome activity and jasmonate synthesis. The difference between chilling and freezing is also seen in the regulation of the CBF4 transcript in leaves from different grapevines differing in their cold tolerance. Therefore, we propose the quality of cold stress is transduced by different upstream signals regulating nuclear import and, thus, the transcriptional activation of grapevine CBF4.
Vascular and Liver Homeostasis in Juvenile Mice Require Endothelial Cyclic AMP-Dependent Protein Kinase A
Authors: Nedvetsky Pavel I. , Cornelissen Ivo , Mathivet Thomas , Bouleti Claire , Ou Phalla , Baatsen Pieter , Zhao Xiaocheng , Schuit Frans , Stanchi Fabio , Mostov Keith E. , Gerhardt Holger
Published: September 2022

During vascular development, endothelial cAMP-dependent protein kinase A (PKA) regulates angiogenesis by controlling the number of tip cells, and PKA inhibition leads to excessive angiogenesis. Whether this role of endothelial PKA is restricted to embryonic and neonatal development or is also required for vascular homeostasis later on is unknown. Here, we show that perinatal (postnatal days P1–P3) of later (P28–P32) inhibition of endothelial PKA using dominant-negative PKA expressed under the control of endothelial-specific Cdh5-CreERT2 recombinase (dnPKAiEC mice) leads to severe subcutaneous edema, hypoalbuminemia, hypoglycemia and premature death. These changes were accompanied by the local hypersprouting of blood vessels in fat pads and the secondary enlargement of subcutaneous lymphatic vessels. Most noticeably, endothelial PKA inhibition caused a dramatic disorganization of the liver vasculature. Hepatic changes correlated with decreased gluconeogenesis, while liver albumin production seems to be unaffected and hypoalbuminemia is rather a result of increased leakage into the interstitium. Interestingly, the expression of dnPKA only in lymphatics using Prox1-CreERT2 produced no phenotype. Likewise, the mosaic expression in only endothelial subpopulations using Vegfr3-CreERT2 was insufficient to induce edema or hypoglycemia. Increased expression of the tip cell marker ESM1 indicated that the inhibition of PKA induced an angiogenic response in the liver, although tissue derived pro- and anti-angiogenic factors were unchanged. These data indicate that endothelial PKA is a gatekeeper of endothelial cell activation not only in development but also in adult homeostasis, preventing the aberrant reactivation of the angiogenic program.