bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Local Skeletal Muscle Blood Flow in Manipulative Therapy by Diffuse Correlation Spectroscopy
Authors: Matsuda Yasuhiro , Nakabayashi Mikie , Suzuki Tatsuya , Zhang Sinan , Ichinose Masashi , Ono Yumie
Published: January 2022

Manipulative therapy (MT) is applied to motor organs through a therapist’s hands. Although MT has been utilized in various medical treatments based on its potential role for increasing the blood flow to the local muscle, a quantitative validation of local muscle blood flow in MT remains challenging due to the lack of appropriate bedside evaluation techniques. Therefore, we investigated changes in the local blood flow to the muscle undergoing MT by employing diffuse correlation spectroscopy, a portable and emerging optical measurement technology that non-invasively measures blood flow in deep tissues. This study investigated the changes in blood flow, heart rate, blood pressure, and autonomic nervous activity in the trapezius muscle through MT application in 30 volunteers without neck and shoulder injury. Five minutes of MT significantly increased the median local blood flow relative to that of the pre-MT period (p < 0.05). The post-MT local blood flow increase was significantly higher in the MT condition than in the control condition, where participants remained still without receiving MT for the same time (p < 0.05). However, MT did not affect the heart rate, blood pressure, or cardiac autonomic nervous activity. The post-MT increase in muscle blood flow was significantly higher in the participants with muscle stiffness in the neck and shoulder regions than in those without (p < 0.05). These results suggest that MT could increase the local blood flow to the target skeletal muscle, with minimal effects on systemic circulatory function.
Local Application of Mineral-Coated Microparticles Loaded With VEGF and BMP-2 Induces the Healing of Murine Atrophic Non-Unions
Authors: Orth M. , Fritz T. , Stutz J. , Scheuer C. , Ganse B. , Bullinger Y. , Lee J. S. , Murphy W. L. , Laschke M. W. , Menger M. D. , Pohlemann T.
Published: January 2022

Deficient angiogenesis and disturbed osteogenesis are key factors for the development of nonunions. Mineral-coated microparticles (MCM) represent a sophisticated carrier system for the delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-2. In this study, we investigated whether a combination of VEGF- and BMP-2-loaded MCM (MCM + VB) with a ratio of 1:2 improves bone repair in non-unions. For this purpose, we applied MCM + VB or unloaded MCM in a murine non-union model and studied the process of bone healing by means of radiological, biomechanical, histomorphometric, immunohistochemical and Western blot techniques after 14 and 70 days. MCM-free non-unions served as controls. Bone defects treated with MCM + VB exhibited osseous bridging, an improved biomechanical stiffness, an increased bone volume within the callus including ongoing mineralization, increased vascularization, and a histologically larger total periosteal callus area consisting predominantly of osseous tissue when compared to defects of the other groups. Western blot analyses on day 14 revealed a higher expression of osteoprotegerin (OPG) and vice versa reduced expression of receptor activator of NF-κB ligand (RANKL) in bone defects treated with MCM + VB. On day 70, these defects exhibited an increased expression of erythropoietin (EPO), EPO-receptor and BMP-4. These findings indicate that the use of MCM for spatiotemporal controlled delivery of VEGF and BMP-2 shows great potential to improve bone healing in atrophic non-unions by promoting angiogenesis and osteogenesis as well as reducing early osteoclast activity.
A Novel Model Based on Necroptosis-Related Genes for Predicting Prognosis of Patients With Prostate Adenocarcinoma
Authors: Li Xin-yu , You Jian-xiong , Zhang Lu-yu , Su Li-xin , Yang Xi-tao
Published: January 2022

Background: Necroptosis is a newly recognized form of cell death. Here, we applied bioinformatics tools to identify necroptosis-related genes using a dataset from The Cancer Genome Atlas (TCGA) database, then constructed a model for prognosis of patients with prostate cancer.

Methods: RNA sequence (RNA‐seq) data and clinical information for Prostate adenocarcinoma (PRAD) patients were obtained from the TCGA portal (http://tcga-data.nci.nih.gov/tcga/). We performed comprehensive bioinformatics analyses to identify hub genes as potential prognostic biomarkers in PRAD u followed by establishment and validation of a prognostic model. Next, we assessed the overall prediction performance of the model using receiver operating characteristic (ROC) curves and the area under curve (AUC) of the ROC.

Results: A total of 5 necroptosis-related genes, namely ALOX15, BCL2, IFNA1, PYGL and TLR3, were used to construct a survival prognostic model. The model exhibited excellent performance in the TCGA cohort and validation group and had good prediction accuracy in screening out high-risk prostate cancer patients.

Conclusion: We successfully identified necroptosis-related genes and constructed a prognostic model that can accurately predict 1- 3-and 5-years overall survival (OS) rates of PRAD patients. Our riskscore model has provided novel strategy for the prediction of PRAD patients’ prognosis.
Reactive Oxygen Species (ROS)-Responsive Biomaterials for the Treatment of Bone-Related Diseases
Authors: Ren Xiaoxiang , Liu Han , Wu Xianmin , Weng Weizong , Wang Xiuhui , Su Jiacan
Published: January 2022

Reactive oxygen species (ROS) are the key signaling molecules in many physiological signs of progress and are associated with almost all diseases, such as atherosclerosis, aging, and cancer. Bone is a specific connective tissue consisting of cells, fibers, and mineralized extracellular components, and its quality changes with aging and disease. Growing evidence indicated that overproduced ROS accumulation may disrupt cellular homeostasis in the progress of bone modeling and remodeling, leading to bone metabolic disease. Thus, ROS-responsive biomaterials have attracted great interest from many researchers as promising strategies to realize drug release or targeted therapy for bone-related diseases. Herein, we endeavor to introduce the role of ROS in the bone microenvironment, summarize the mechanism and development of ROS-responsive biomaterials, and their completion and potential for future therapy of bone-related diseases.
Pharmacological Targeting of STING-Dependent IL-6 Production in Cancer Cells
Authors: Al-Asmari Sumaiah S. , Rajapakse Aleksandra , Ullah Tomalika R. , Pépin Geneviève , Croft Laura V. , Gantier Michael P.
Published: January 2022

Activation of the STING pathway upon genotoxic treatment of cancer cells has been shown to lead to anti-tumoral effects, mediated through the acute production of interferon (IFN)-β. Conversely, the pathway also correlates with the expression of NF-κB-driven pro-tumorigenic genes, but these associations are only poorly defined in the context of genotoxic treatment, and are thought to correlate with a chronic engagement of the pathway. We demonstrate here that half of the STING-expressing cancer cells from the NCI60 panel rapidly increased expression of pro-tumorigenic IL-6 upon genotoxic DNA damage, often independent of type-I IFN responses. While preferentially dependent on canonical STING, we demonstrate that genotoxic DNA damage induced by camptothecin (CPT) also drove IL-6 production through non-canonical STING signaling in selected cancer cells. Consequently, pharmacological inhibition of canonical STING failed to broadly inhibit IL-6 production induced by CPT, although this could be achieved through downstream ERK1/2 inhibition. Finally, prolonged inhibition of canonical STING signaling was associated with increased colony formation of MG-63 cells, highlighting the duality of STING signaling in also restraining the growth of selected cancer cells. Collectively, our findings demonstrate that genotoxic-induced DNA damage frequently leads to the rapid production of pro-tumorigenic IL-6 in cancer cells, independent of an IFN signature, through canonical and non-canonical STING activation; this underlines the complexity of STING engagement in human cancer cells, with frequent acute pro-tumorigenic activities induced by DNA damage. We propose that inhibition of ERK1/2 may help curb such pro-tumorigenic responses to DNA-damage, while preserving the anti-proliferative effects of the STING-interferon axis.
The Interaction Between Long Non-Coding RNAs and Cancer-Associated Fibroblasts in Lung Cancer
Authors: Ti Wenqi , Wang Jianbo , Cheng Yufeng
Published: January 2022

Despite great advances in research and treatment, lung cancer is still one of the most leading causes of cancer-related deaths worldwide. Evidence is mounting that dynamic communication network in the tumor microenvironment (TME) play an integral role in tumor initiation and development. Cancer-associated fibroblasts (CAFs), which promote tumor growth and metastasis, are the most important stroma component in the tumor microenvironment. Consequently, in-depth identification of relevant molecular mechanisms and biomarkers related to CAFs will increase understanding of tumor development process, which is of great significance for precise treatment of lung cancer. With the development of sequencing technologies such as microarray and next-generation sequencing, lncRNAs without protein-coding ability have been found to act as communicators between tumor cells and CAFs. LncRNAs participate in the activation of normal fibroblasts (NFs) to CAFs. Moreover, activated CAFs can influence the gene expression and secretion characteristics of cells through lncRNAs, enhancing the malignant biological process in tumor cells. In addition, lncRNA-loaded exosomes are considered to be another important form of crosstalk between tumor cells and CAFs. In this review, we focus on the interaction between tumor cells and CAFs mediated by lncRNAs in the lung cancer microenvironment, and discuss the analysis of biological function and molecular mechanism. Furthermore, it contributes to paving a novel direction for the clinical treatment of lung cancer.
May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression
Authors: Williams Donnell L. , Sikora Veronica Maria , Hammer Max A. , Amin Sayali , Brinjikji Taema , Brumley Emily K. , Burrows Connor J. , Carrillo Paola Michelle , Cromer Kirin , Edwards Summer J. , Emri Olivia , Fergle Daniel , Jenkins M. Jamal , Kaushik Krishangi , Maydan Daniella D. , Woodard Wrenn , Clowney E. Josephine
Published: January 2022

How does the information in the genome program the functions of the wide variety of cells in the body? While the development of biological organisms appears to follow an explicit set of genomic instructions to generate the same outcome each time, many biological mechanisms harness molecular noise to produce variable outcomes. Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is particularly evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation. These systems employ overlapping molecular strategies including allelic exclusion, gene silencing by constitutive heterochromatin, targeted double-strand breaks, and competition for limiting enhancers. Here, we describe and compare five stochastic molecular mechanisms that produce variety in pathogen coat proteins and in the cell surface receptors of animal immune and neuronal cells, with an emphasis on the utility of non-deterministic variation.
Synthesis of Hydrophilic Derivative Surfactants From Algae-Derived Unsaponifiable Lipids
Authors: Fioroni Gina , Katahira Rui , Van Wychen Stefanie , Rowland Steven M. , Christensen Earl D. , Dong Tao , Pienkos Philip T. , Laurens Lieve M. L.
Published: January 2022

In the context of decarbonizing the economy, the utilization of biologically sourced feedstocks to produce replacements for petroleum-derived materials is becoming more urgent. Improving renewable biomass production and utilization is imperative for commercializing future biorefineries. Algae-derived biomass is a particularly promising feedstock thanks to its attractive oil content and composition; specifically, the high-value products in the unsaponifiable lipids have not been included in a conversion process. Here we demonstrate surfactant synthesis from a complex oil fraction as the hydrophobic donor moieties, yielding products that are similar to commercially available surfactants such as the linear alkyl benzene sulfonates. Unsaponifiable lipids extracted from algae were derivatized to non-ionic surfactants using a green chemical synthesis route based on a double esterification with succinic acid and polyethylene glycol. The in-depth molecular and structural surfactant characterization is included and indicates that the resulting properties fall between those of pure cholesterol and phytol used as surrogates for the reaction synthesis demonstration. This is the first demonstration of an effective and potentially high-value synthesis of functional surfactants with properties that can be tailored based on the relative composition of the resulting hydrocarbon alcohol components in the mixture. This novel green chemistry synthesis approach provides a route to high-value product synthesis from algae.
Mono-/Bis-Alkenoic Acid Derivatives From an Endophytic Fungus Scopulariopsis candelabrum and Their Antifungal Activity
Authors: Tang Jun , Huang Xueshuang , Cao Ming-Hang , Wang Zhiyan , Yu Zhiyin , Yan Yijun , Huang Jian-Ping , Wang Li , Huang Sheng-Xiong
Published: January 2022

During a screening for antifungal secondary metabolites, six new mono-/bis-alkenoic acid derivatives (2–7) and one known alkenoic acid derivative (1) were isolated from an endophytic fungi Scopulariopsis candelabrum. Their chemical structures were identified by 1H-NMR, 13C-NMR, 2D NMR, and high-resolution mass spectrometry, as well as comparisons with previously reported literatures. Among them, fusariumesters C‒F (2–5) are bis-alkenoic acid derivatives dimerized by an ester bond, while acetylfusaridioic acid A (6) and fusaridioic acid D (7) are alkenoic acid monomers. All the isolates were submitted to an antifungal assay against Candida albicans and the corn pathogen Exserohilum turcicum using the filter paper agar diffusion method. As a result, only compound 1 decorating with β-lactone ring turned out to be active against these two tested fungi. The broth microdilution assay against Candida albicans showed the minimum inhibitory concentration (MIC) value of 1 to be 20 μg/ml, while the minimum inhibitory concentration value of the positive control (naystatin) was 10 μg/ml. And the half maximal inhibitory concentration (IC50) value (21.23 μg/ml) of 1 against Exserohilum turcicum was determined by analyzing its inhibition effect on the mycelial growth, using cycloheximide (IC50 = 46.70 μg/ml) as the positive control.
The Mini-Cross Prefenestration for Endovascular Repair of Aortic Arch Pathologies
Authors: Pei Yifei , Zhu Hongqiao , Xiao Yu , Zhou Jian , Jing Zaiping
Published: January 2022

Objective: To examine the feasibility, integrity, efficacy, and safety of endovascular repair of the aortic arch pathologies with the mini-cross prefenestration (MCPF) on stent grafts.

Methods: First, to prove the feasibility of the MCPF, an in-vitro prefenestration experiment was conducted. Second, to examine the integrity of the MCPF stent grafts, a fatigue test was conducted. Then, the membranes and metal structures of stent grafts were examined by light microscopy and scanning electron microscopy (SEM). Third, a clinical experiment was conducted to investigate the efficacy and safety of this novel technique (ClinicalTrials.gov Identifier: NCT04544579).

Results: All the 12 branch stents were successfully implanted and flared in vitro. After the fatigue test stimulating a 5-year cardiac cycle, no obvious disintegration or fracture was found in light microscopy or SEM. From December 2017 to February 2020, 26 patients with left subclavian arteries and/or left common carotid arteries involved received the novel technique. The endovascular repair with the MCPF was successfully performed on all the 26 (100%) patients. Eighteen (69.2%) patients underwent the reconstruction of the left subclavian artery (LSCA) only. The fenestrations of both the LSCA and left common carotid artery (LCCA) were conducted in 8 (30.8%) patients. Median operative time was 120 [interquartile range (IQR), 95–137.5] min and median revascularization time of the LSCA and LCCA was 30.5 (IQR, 22.8–42.0) s and 20.0 (IQR, 18.0–32.0) s separately. During the median follow-up duration of 38.9 (range, 18.8–44.2) months, one case needed an open surgery because of retrograde type A aortic dissection 3 months after implantation and no other complications or mortality occurred. The maximum aortic diameters were significantly decreased in patients with thoracic aortic dissection and thoracic aortic aneurysm (p < 0.05).

Conclusion: The existing evidence demonstrated the safety, rapid branch artery revascularization, and positive aortic remodeling of the novel technique. Long-term observation is warranted to prove the durability.
Bayesian Hierarchical Models can Infer Interpretable Predictions of Leaf Area Index From Heterogeneous Datasets
Authors: Stojanović Olivera , Siegmann Bastian , Jarmer Thomas , Pipa Gordon , Leugering Johannes
Published: January 2022

Environmental scientists often face the challenge of predicting a complex phenomenon from a heterogeneous collection of datasets that exhibit systematic differences. Accounting for these differences usually requires including additional parameters in the predictive models, which increases the probability of overfitting, particularly on small datasets. We investigate how Bayesian hierarchical models can help mitigate this problem by allowing the practitioner to incorporate information about the structure of the dataset explicitly. To this end, we look at a typical application in remote sensing: the estimation of leaf area index of white winter wheat, an important indicator for agronomical modeling, using measurements of reflectance spectra collected at different locations and growth stages. Since the insights gained from such a model could be used to inform policy or business decisions, the interpretability of the model is a primary concern. We, therefore, focus on models that capture the association between leaf area index and the spectral reflectance at various wavelengths by spline-based kernel functions, which can be visually inspected and analyzed. We compare models with three different levels of hierarchy: a non-hierarchical baseline model, a model with hierarchical bias parameter, and a model in which bias and kernel parameters are hierarchically structured. We analyze them using Markov Chain Monte Carlo sampling diagnostics and an intervention-based measure of feature importance. The improved robustness and interpretability of this approach show that Bayesian hierarchical models are a versatile tool for the prediction of leaf area index, particularly in scenarios where the available data sources are heterogeneous.
Detection Rate of Bird Species and What It Depends on: Tips for Field Surveys
Authors: Morelli Federico , Brlík Vojtěch , Benedetti Yanina , Bussière Raphaël , Moudrá Lucie , Reif Jiri , Svitok Marek
Published: January 2022

Bird counting inevitably suffers from imperfect detection, which varies across species, habitats, period of the day, and seasons. Although various modeling techniques have recently been developed to account for this phenomenon, the biological basis of natural variation in detection remains insufficiently known. This study examined the bird species’ detection rate throughout the day, considering their body mass and diet type, concerning the environment and weather characteristics. Species detection rates were significantly affected by the number of individuals of that species but were unrelated to body mass. Overall, species with the highest detection rate were Corn bunting, Blackbird, European robin, House sparrow and Common chiffchaff. Granivores-insectivores and insectivores showed significant differences in detection rates throughout the day among habitats, with higher detection rates in grasslands during the afternoon. Insectivores showed higher detection rates in farmland during midday (warmest time of the day). Granivores, omnivores and scavengers did not show changes in detection rates in different day periods. Such patterns in daily detection rates were significant even when considering abundance and total species richness in each community. Finally, cloudiness was unrelated to the overall detection rate of birds, while temperature and wind affected detection rates in some guilds. Our findings provide some advice for choosing a suitable ornithological sampling method by considering the avian communities composition in combination with the type of environment, the diet of bird species, and the period of the day.
Landscape Evolution as a Diversification Driver in Freshwater Fishes
Authors: Val Pedro , Lyons Nathan J. , Gasparini Nicole , Willenbring Jane K. , Albert James S.
Published: January 2022

The exceptional concentration of vertebrate diversity in continental freshwaters has been termed the “freshwater fish paradox,” with > 15,000 fish species representing more than 20% of all vertebrate species compressed into tiny fractions of the Earth’s land surface area (<0.5%) or total aquatic habitat volume (<0.001%). This study asks if the fish species richness of the world’s river basins is explainable in terms of river captures using topographic metrics as proxies. The River Capture Hypothesis posits that drainage-network rearrangements have accelerated biotic diversification through their combined effects on dispersal, speciation, and extinction. Yet rates of river capture are poorly constrained at the basin scale worldwide. Here we assess correlations between fish species density (data for 14,953 obligate freshwater fish species) and basin-wide metrics of landscape evolution (data for 3,119 river basins), including: topography (elevation, average relief, slope, drainage area) and climate (average rainfall and air temperature). We assess the results in the context of both static landscapes (e.g., species-area and habitat heterogeneity relationships) and transient landscapes (e.g., river capture, tectonic activity, landscape disequilibrium). We also relax assumptions of functional neutrality of basins (tropical vs. extratropical, tectonically stable vs. active terrains). We found a disproportionate number of freshwater species in large, lowland river basins of tropical South America, Africa, and Southeast Asia, under predictable conditions of large geographic area, tropical climate, low topographic relief, and high habitat volume (i.e., high rainfall rates). However, our results show that these conditions are only necessary, but not fully sufficient, to explain the basins with the highest diversity. Basins with highest diversity are all located on tectonically stable regions, places where river capture is predicted to be most conducive to the formation of high fish species richness over evolutionary timescales. Our results are consistent with predictions of several landscape evolution models, including the River Capture Hypothesis, Mega Capture Hypothesis, and Intermediate Capture Rate Hypothesis, and support conclusions of numerical modeling studies indicating landscape transience as a mechanistic driver of net diversification in riverine and riparian organisms with widespread continental distributions.
Seasonal Partitioning of Rainfall in Second-Growth Evergreen Temperate Rainforests in Chiloé Island, Southern Chile
Authors: Frêne Cristián , Núñez-Ávila Mariela , Castro Ben , Armesto Juan J.
Published: January 2022

Rainfall partitioning in secondary forests from southern Chile is relevant in the climate change scenario, in which a 30% reduction in summer precipitation has been projected for the temperate region. Logging and degradation of old-growth forests has resulted in extensive secondary forests, over large areas of the Chiloé Archipelago as well as the mainland. These secondary forests are simple tree communities, dominated by two broad-leaved tree species, evergreen Drimys winteri and Nothofagus nitida, and have the potential to provide multiple benefits to society, including water provision, soil protection, and wood-derived products. Here, we ask how southern South American secondary rainforests modulate rainwater redistribution considering precipitation partitioning. We evaluated the seasonality of throughfall and stemflow components of precipitation, to assess ecohydrological processes for water regulation in a climate change context, where summer droughts have been more frequent in the last decade. The partitioning of gross rainfall (TP) into throughfall (TH), stemflow (ST), and canopy interception (IN) in relation to forest structure, was assessed in four forest plots (400 m2 each) in Senda Darwin Biological Station, Chiloé. TH and ST were measured seasonally for 35 rainfall events from 2019 to 2021. IN water losses were estimated from the mass balance equation. Results indicate that the secondary rainforest intercepts 33% of TP (990 mm of the total monitored), where 59% of the volume corresponds to TH and 7% to ST, which taken together account for nearly 100% the rainwater that reaches the forest floor. Canopy IN varied seasonally from 25 to 40% of total rainfall, with maximum values occurring in the growing season (spring-summer). We found no statistical relation between ST and forest structural parameters (DBH, Basal Area). We explored the contribution of the two dominant tree species to ST and discuss the results in a climate change context. Finally, we propose to incorporate this hydrologic knowledge into adaptive forest management strategies to maximize ecosystem benefits to people. If these ecosystems were properly managed, they have the potential to provide multiple benefits to society within this century, such as water provision and soil protection in addition to carbon sequestration in biomass.
Design and Evaluation of Remote Driving Architecture on 4G and 5G Mobile Networks
Authors: den Ouden Jos , Ho Victor , van der Smagt Tijs , Kakes Geerd , Rommel Simon , Passchier Igor , Juza Jakub , Tafur Monroy Idelfonso
Published: January 2022

Despite the progress in the development of automated vehicles in the last decade, reaching the level of reliability required at large-scale deployment at an economical price and combined with safety requirements is still a long road ahead. In certain use cases, such as automated shuttles and taxis, where there is no longer even a steering wheel and pedals required, remote driving could be implemented to bridge this gap; a remote operator can take control of the vehicle in situations where it is too difficult for an automated system to determine the next actions. In logistics, it could even be implemented to solve already more pressing issues such as shortage of truck drivers, by providing more flexible working conditions and less standstill time of the truck. An important aspect of remote driving is the connection between the remote station and the vehicle. With the current roll-out of 5G mobile technology in many countries throughout the world, the implementation of remote driving comes closer to large-scale deployment. 5G could be a potential game-changer in the deployment of this technology. In this work, we examine the remote driving application and network-level performance of remote driving on a recently deployed sub-6-GHz commercial 5G stand-alone (SA) mobile network. It evaluates the influence of the 5G architecture, such as mobile edge computing (MEC) integration, local breakout, and latency on the application performance of remote driving. We describe the design, development (based on Hardware-in-the-Loop simulations), and performance evaluation of a remote driving solution, tested on both 5G and 4G mobile SA networks using two different vehicles and two different remote stations. Two test cases have been defined to evaluate the application and network performance and are evaluated based on position accuracy, relative reaction times, and distance perception. Results show the performance of the network to be sufficient for remote driving applications at relatively low speeds (<40 km/h). Network latencies compared with 4G have dropped to half. A strong correlation between latency and remote driving performance is not clearly seen and requires further evaluation taking into account the influence of the user interface.
Identification of Bovine miRNAs with the Potential to Affect Human Gene Expression
Authors: Myrzabekova Moldir , Labeit Siegfried , Niyazova Raigul , Akimniyazova Aigul , Ivashchenko Anatoliy
Published: January 2022

Milk and other products from large mammals have emerged during human evolution as an important source of nutrition. Recently, it has been recognized that exogenous miRNAs (mRNA inhibited RNA) contained in milk and other tissues of the mammalian body can enter the human body, which in turn have the ability to potentially regulate human metabolism by affecting gene expression. We studied for exogenous miRNAs from Bos taurus that are potentially contain miRNAs from milk and that could act postprandially as regulators of human gene expression. The interaction of 17,508 human genes with 1025 bta-miRNAs, including 245 raw milk miRNAs was studied. The milk bta-miR-151-5p, bta-miR-151-3p, bta-miRNA-320 each have 11 BSs (binding sites), and bta-miRNA-345-5p, bta-miRNA-614, bta-miRNA-1296b and bta-miRNA-149 has 12, 14, 15 and 26 BSs, respectively. The bta-miR-574-5p from cow’s milk had 209 human genes in mRNAs from one to 25 repeating BSs. We found 15 bta-miRNAs that have 100% complementarity to the mRNA of 13 human target genes. Another 12 miRNAs have BSs in the mRNA of 19 human genes with 98% complementarity. The bta-miR-11975, bta-miR-11976, and bta-miR-2885 BSs are located with the overlap of nucleotide sequences in the mRNA of human genes. Nucleotide sequences of BSs of these miRNAs in 5′UTR mRNA of human genes consisted of GCC repeats with a total length of 18 nucleotides (nt) in 18 genes, 21 nt in 11 genes, 24 nt in 14 genes, and 27–48 nt in nine genes. Nucleotide sequences of BSs of bta-miR-11975, bta-miR-11976, and bta-miR-2885 in CDS mRNA of human genes consisted of GCC repeats with a total length of 18 nt in 33 genes, 21 nt in 13 genes, 24 nt in nine genes, and 27–36 nt in 11 genes. These BSs encoded polyA or polyP peptides. In only one case, the polyR (SLC24A3 gene) was encoded. The possibility of regulating the expression of human genes by exogenous bovine miRNAs is discussed.
Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy
Authors: Ning Yujie , Hu Minhan , Diao Jiayu , Gong Yi , Huang Ruitian , Chen Sijie , Zhang Feiyu , Liu Yanli , Chen Feihong , Zhang Pan , Zhao Guanghui , Chang Yanhai , Xu Ke , Zhou Rong , Li Cheng , Zhang Feng , Lammi Mikko , Wang Xi , Guo Xiong
Published: January 2022

The mechanism of environmental factors in Kashin–Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin–responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin–responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.
Sea Anemones Responding to Sex Hormones, Oxybenzone, and Benzyl Butyl Phthalate: Transcriptional Profiling and in Silico Modelling Provide Clues to Decipher Endocrine Disruption in Cnidarians
Authors: Morgan Michael B. , Ross James , Ellwanger Joseph , Phrommala Rebecca Martin , Youngblood Hannah , Qualley Dominic , Williams Jacob
Published: January 2022

Endocrine disruption is suspected in cnidarians, but questions remain how occurs. Steroid sex hormones are detected in corals and sea anemones even though these animals do not have estrogen receptors and their repertoire of steroidogenic enzymes appears to be incomplete. Pathways associated with sex hormone biosynthesis and sterol signaling are an understudied area in cnidarian biology. The objective of this study was to identify a suite of genes that can be linked to exposure of endocrine disruptors. Exaiptasia diaphana were exposed to nominal 20ppb concentrations of estradiol (E2), testosterone (T), cholesterol, oxybenzone (BP-3), or benzyl butyl phthalate (BBP) for 4 h. Eleven genes of interest (GOIs) were chosen from a previously generated EST library. The GOIs are 17β-hydroxysteroid dehydrogenases type 14 (17β HSD14) and type 12 (17β HSD12), Niemann-Pick C type 2 (NPC2), Equistatin (EI), Complement component C3 (C3), Cathepsin L (CTSL), Patched domain-containing protein 3 (PTCH3), Smoothened (SMO), Desert Hedgehog (DHH), Zinc finger protein GLI2 (GLI2), and Vitellogenin (VTG). These GOIs were selected because of functional associations with steroid hormone biosynthesis; cholesterol binding/transport; immunity; phagocytosis; or Hedgehog signaling. Quantitative Real-Time PCR quantified expression of GOIs. In silico modelling utilized protein structures from Protein Data Bank as well as creating protein structures with SWISS-MODEL. Results show transcription of steroidogenic enzymes, and cholesterol binding/transport proteins have similar transcription profiles for E2, T, and cholesterol treatments, but different profiles when BP-3 or BBP is present. C3 expression can differentiate between exposures to BP-3 versus BBP as well as exposure to cholesterol versus sex hormones. In silico modelling revealed all ligands (E2, T, cholesterol, BBP, and BP-3) have favorable binding affinities with 17β HSD14, 17β HSD12, NPC2, SMO, and PTCH proteins. VTG expression was down-regulated in the sterol treatments but up-regulated in BP-3 and BBP treatments. In summary, these eleven GOIs collectively generate unique transcriptional profiles capable of discriminating between the five chemical exposures used in this investigation. This suite of GOIs are candidate biomarkers for detecting transcriptional changes in steroidogenesis, gametogenesis, sterol transport, and Hedgehog signaling. Detection of disruptions in these pathways offers new insight into endocrine disruption in cnidarians.
Autoregressive Modeling and Prediction of the Activity of Antihypertensive Peptides
Authors: Xie Xufen , Zhu Chuanchuan , Wu Di , Du Ming
Published: January 2022

Naturally derived bioactive peptides with antihypertensive activities serve as promising alternatives to pharmaceutical drugs. There are few relevant reports on the mapping relationship between the EC50value of antihypertensive peptide activity (AHTPA-EC50) and its corresponding amino acid sequence (AAS) at present. In this paper, we have constructed two group series based on sorting natural logarithm of AHTPA-EC50or sorting its corresponding AAS encoding number. One group possesses two series, and we find that there must be a random number series in any group series. The random number series manifests fractal characteristics, and the constructed series of sorting natural logarithm of AHTPA-EC50shows good autocorrelation characteristics. Therefore, two non-linear autoregressive models with exogenous input (NARXs) were established to describe the two series. A prediction method is further designed for AHTPA-EC50prediction based on the proposed model. Two dynamic neural networks for NARXs (NARXNNs) are designed to verify the two series characteristics. Dipeptides and tripeptides are used to verify the proposed prediction method. The results show that the mean square error (MSE) of prediction is about 0.5589 for AHTPA-EC50prediction when the classification of AAS is correct. The proposed method provides a solution for AHTPA-EC50prediction.
Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women
Authors: Yeo Kee Thai , Chia Wan Ni , Tan Chee Wah , Ong Chengsi , Yeo Joo Guan , Zhang Jinyan , Poh Su Li , Lim Amanda Jin Mei , Sim Kirsten Hui Zhi , Sutamam Nursyuhadah , Chua Camillus Jian Hui , Albani Salvatore , Wang Lin-Fa , Chua Mei Chien
Published: January 2022

Background

There is limited information on the functional neutralizing capabilities of breastmilk SARS-CoV-2-specific antibodies and the potential adulteration of breastmilk with vaccine mRNA after SARS-CoV-2 mRNA vaccination.

Methods

We conducted a prospective cohort study of lactating healthcare workers who received the BNT162b2 vaccine and their infants. The presence of SARS-CoV-2 neutralizing antibodies, antibody isotypes (IgG, IgA, IgM) and intact mRNA in serum and breastmilk was evaluated at multiple time points using a surrogate neutralizing assay, ELISA, and PCR, over a 6 week period of the two-dose vaccination given 21 days apart.

Results

Thirty-five lactating mothers, median age 34 years (IQR 32-36), were included. All had detectable neutralizing antibodies in the serum immediately before dose 2, with significant increase in neutralizing antibody levels 7 days after this dose [median 168.4 IU/ml (IQR 100.7-288.5) compared to 2753.0 IU/ml (IQR 1627.0-4712.0), p <0.001]. Through the two vaccine doses, all mothers had detectable IgG1, IgA and IgM isotypes in their serum, with a notable increase in all three antibody isotypes after dose 2, especially IgG1 levels. Neutralizing antibodies were detected in majority of breastmilk samples a week after dose 2 [median 13.4 IU/ml (IQR 7.0-28.7)], with persistence of these antibodies up to 3 weeks after. Post the second vaccine dose, all (35/35, 100%) mothers had detectable breastmilk SARS-CoV-2 spike RBD-specific IgG1 and IgA antibody and 32/35 (88.6%) mothers with IgM. Transient, low intact vaccine mRNA levels was detected in 20/74 (27%) serum samples from 21 mothers, and 5/309 (2%) breastmilk samples from 4 mothers within 1 weeks of vaccine dose. Five infants, median age 8 months (IQR 7-16), were also recruited - none had detectable neutralizing antibodies or vaccine mRNA in their serum.

Conclusion

Majority of lactating mothers had detectable SARS-CoV-2 antibody isotypes and neutralizing antibodies in serum and breastmilk, especially after dose 2 of BNT162b2 vaccination. Transient, low levels of vaccine mRNA were detected in the serum of vaccinated mothers with occasional transfer to their breastmilk, but we did not detect evidence of infant sensitization. Importantly, the presence of breastmilk neutralising antibodies likely provides a foundation for passive immunisation of the breastmilk-fed infant.
Oral Administration of Nanopeptide CMCS-20H Conspicuously Boosts Immunity and Precautionary Effect Against Bacterial Infection in Fish
Authors: Huo Xingchen , Wang Zhensheng , Xiao Xun , Yang Chunrong , Su Jianguo
Published: January 2022

Massive mortalities caused by bacterial infections in intensive aquaculture result in serious economic losses. In this study, a novel antimicrobial peptide gcIFN-20H was efficiently expressed in Pichia pastoris (GS115) and loaded on carboxylmethyl chitosan (CMCS) to prepare CMCS-20H nanoparticles. Through physical characterization assays (TEM, DLS, BCA, and Raman) and biological activity tests (antimicrobial activity and cytotoxicity), CMCS-20H nanopeptide was verified to be spherical nanoparticles with sustained release, antimicrobial activity, and negligible toxicity. CMCS-20H nanoparticles are more resistant to intestinal degradation than unloaded gcIFN-20H by indirect immunofluorescence assay. Oral administration was then carried out for 42 days. Complement C3 content, lysozyme, and total superoxide dismutase activities are highest in CMCS-20H group by serum biochemistry index assays. After challenge with Aeromonas hydrophila, the survival rate in CMCS-20H group is highest (46%), which is 64% higher than the control group (28%). Meanwhile, the tissue bacterial loads (intestine, spleen, head kidney, trunk kidney, hepatopancreas, muscle, and blood) in the CMCS-20H group are significantly lower than other groups. By PAS staining analysis, the number of intestinal villi goblet cells and the thickness of mucin in the CMCS-20H group obviously increased. CMCS-20H effectively enhances mRNA expressions of some important immune genes (IL-1β, IL-6, TNF-α, IL-2, IFN-γ2, and IgM). The minimal tissue lesions (Intestine, spleen, and trunk kidney) were seen in the CMCS-20H group by histopathological examination. 16S rRNA sequencing showed that oral CMCS-20H maintains the intestinal microbiome homeostasis in bacterial infection. The results indicate that the novel nanopeptide CMCS-20H as the immunopotentiator can remarkably boost fish immunity and precautionary effect by oral administration and address the theoretical mechanisms and insights into the promising application prospect in aquaculture.
A Framework for Simulating Ecosystem Effects in Data-Poor Small-Scale Fisheries Using Science-Based and Local Ecological Knowledge-Based Models
Authors: Zetina-Rejón Manuel J. , López-Ibarra Gladis A. , Rocha-Tejeda Lorena , Flores-Guzmán Alesa , López-Ercilla Inés , Rodríguez-Rodríguez Ellmi , Sandoval-Jiménez Sergio Antonio , Arreguín-Sánchez Francisco , Cisneros-Montemayor Andrés M.
Published: January 2022

The constant demand for seafood products and the undeniable effects of fishing on marine ecosystems make it urgent to implement an ecosystem approach, even in data-poor scenarios such as small-scale fisheries. Understanding the impacts of fishing is essential for promoting management strategies that prevent irreversible damage to marine ecosystems. Thus, ecosystem quantitative science-based models have been frequently used to evaluate the effects of fishing, although fishers’ local ecological knowledge (LEK) can aid the implementation of qualitative models, particularly in data-poor conditions. Here, we present a framework for simulating and assessing the effects of fishing following two strategies: (1) for both types of models, we simulated species removal scenarios, and (2) for quantitative science-based models, we fitted time series to dynamically assessed impacts. The impacts were analyzed through ecological indicators commonly used for quantitative models, and because these indicators cannot be easily estimated for qualitative models, we propose the use of topological indicators in both types of models. The approach was applied to three case studies of small-scale finfish fisheries in northwestern Mexico. We found that the ecosystem response to species removal was different in each case study and that the target species can play an important role in ecosystems, but their removal does not generate abrupt changes in the ecosystem structure. The quantitative science-based models were able to reproduce the historical catch trends, which allowed us to reveal that changes in ecosystems are indeed influenced by fishing effort but also by underlying primary productivity. Furthermore, topological and ecological indicators showed similar trends in the quantitative models, which suggests that the former could be useful when data-poor conditions allow only qualitative models. This result confirms the relevance of the participation of fishers in generating qualitative models and their decisive role in the discussion of co-management strategies and risk scenarios in a better-informed manner.
Liver Fibrosis—From Mechanisms of Injury to Modulation of Disease
Authors: Liedtke Christian , Nevzorova Yulia A. , Luedde Tom , Zimmermann Henning , Kroy Daniela , Strnad Pavel , Berres Marie-Luise , Bernhagen Jürgen , Tacke Frank , Nattermann Jacob , Spengler Ulrich , Sauerbruch Tilman , Wree Alexander , Abdullah Zeinab , Tolba René H. , Trebicka Jonel , Lammers Twan , Trautwein Christian , Weiskirchen Ralf
Published: January 2022

The Transregional Collaborative Research Center “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (referred to as SFB/TRR57) was funded for 13 years (2009–2021) by the German Research Council (DFG). This consortium was hosted by the Medical Schools of the RWTH Aachen University and Bonn University in Germany. The SFB/TRR57 implemented combined basic and clinical research to achieve detailed knowledge in three selected key questions: (i) What are the relevant mechanisms and signal pathways required for initiating organ fibrosis? (ii) Which immunological mechanisms and molecules contribute to organ fibrosis? and (iii) How can organ fibrosis be modulated, e.g., by interventional strategies including imaging and pharmacological approaches? In this review we will summarize the liver-related key findings of this consortium gained within the last 12 years on these three aspects of liver fibrogenesis. We will highlight the role of cell death and cell cycle pathways as well as nutritional and iron-related mechanisms for liver fibrosis initiation. Moreover, we will define and characterize the major immune cell compartments relevant for liver fibrogenesis, and finally point to potential signaling pathways and pharmacological targets that turned out to be suitable to develop novel approaches for improved therapy and diagnosis of liver fibrosis. In summary, this review will provide a comprehensive overview about the knowledge on liver fibrogenesis and its potential therapy gained by the SFB/TRR57 consortium within the last decade. The kidney-related research results obtained by the same consortium are highlighted in an article published back-to-back in Frontiers in Medicine.