bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Humidity Pretreatment Devices on the Loss of HCl Gas Emitted from Industrial Stacks
Authors: Gil Han-Nui , Dinh Trieu-Vuong , Lee Jee-Hyun , Park Byeong-Gyu , Choi In-Young , Lee Sang-Woo , Kim In-Young , Kim Jo-Chun
Published: December 2021

A high humidity at a high temperature presents a common challenge in monitoring the air pollutants emitted from stationary sources. Thus, humidity removal is a pivotal issue. In this study, the effect of humidity pretreatment devices (HPDs) on hydrogen chloride (HCl) gas emitted from an incinerator stack was investigated. A conventional cooler (HPD_CL), and poly-tube (HPD_NP) and single-tube (HPD_NS) Nafion™ dryers were used as HPDs in this study. HCl concentrations varied at five and 10 parts per million in volume (ppmv). Low (i.e., ~4%) and high (i.e., ~17%) humidities were generated at 180 °C. The removal efficiencies of humidity and the loss rates of HCl by the devices were determined. The removal efficiencies of humidity by HPD_CL and the two dryers were found to be similar, at approximately 85% at a low humidity and 95% at a high humidity. In terms of HCl loss rates, HPD_CL revealed the highest loss rates in all conditions (i.e., >95%), followed by HPD_NP and HPD_NS. At normal room temperature (i.e., 25 °C), the HCl loss rates of HPD_NP were >40% at a low humidity and >70% at a high humidity, while those of HPD_NS were >10% at a low humidity and >60% at a high humidity. The performance of the two dryers improved when they were heated to 80 °C. However, this temperature caused damage to the dryers, which reduced their lifetime.
Long-Term Observations of Schumann Resonances at Portishead (UK)
Authors: Pizzuti Andrea , Bennett Alec , Füllekrug Martin
Published: December 2021

Constructive interference of lightning-generated signals in the extremely low frequency (ELF) below 100 Hz is the source of a global electromagnetic phenomenon in the Earth’s atmosphere known as Schumann Resonances (SR). SR are excited at frequencies of 7.8, 14, 20, 26, … Hz, and their diurnal and seasonal intensity variations are largely dependent on changes in the location and magnitude of the major lightning centres in Southeast Asia, Africa, and South America. In the last five decades, extensive research has focused on reconstructing the spatial and temporal evolution in global lighting activity using SR measurements, and more recently on analysing the links to climate change, transient luminous events (TLE), and biological systems. In this study, a quasi-electrostatic antenna, primarily designed as a thunderstorm warning system, is for the first time applied to measure background variability in the SR band at an urban site in Southwest England. Data collected continuously from June 2015 for a 5-year period are suitably filtered and analysed showing that SR is the dominant contribution to the fair-weather displacement current measured by the sensor in the band 10–45 Hz. Diurnal and seasonal signal amplitude variations have been found to be consistent with previous studies and show the African-European lightning centre to prevail due to the shorter source-observer distance. Also, it is shown that long-term global changes in the ocean and land temperature, and the subsequent effect on the major lightning hotspots, may be responsible for the inter-annual variability of SR intensity, indicating that the largest increase occurred during the 2015–2016 super El-Niño episode.
Pattern Formation in One-Dimensional Polaron Systems and Temporal Orthogonality Catastrophe
Authors: Koutentakis Georgios M. , Mistakidis Simeon I. , Schmelcher Peter
Published: December 2021

Recent studies have demonstrated that higher than two-body bath-impurity correlations are not important for quantitatively describing the ground state of the Bose polaron. Motivated by the above, we employ the so-called Gross Ansatz (GA) approach to unravel the stationary and dynamical properties of the homogeneous one-dimensional Bose-polaron for different impurity momenta and bath-impurity couplings. We explicate that the character of the equilibrium state crossovers from the quasi-particle Bose polaron regime to the collective-excitation stationary dark-bright soliton for varying impurity momentum and interactions. Following an interspecies interaction quench the temporal orthogonality catastrophe is identified, provided that bath-impurity interactions are sufficiently stronger than the intraspecies bath ones, thus generalizing the results of the confined case. This catastrophe originates from the formation of dispersive shock wave structures associated with the zero-range character of the bath-impurity potential. For initially moving impurities, a momentum transfer process from the impurity to the dispersive shock waves via the exerted drag force is demonstrated, resulting in a final polaronic state with reduced velocity. Our results clearly demonstrate the crucial role of non-linear excitations for determining the behavior of the one-dimensional Bose polaron.
Banach Actions Preserving Unconditional Convergence
Authors: Banakh Taras , Kadets Vladimir
Published: December 2021

Let A,X,Y be Banach spaces and A×X→Y, (a,x)↦ax be a continuous bilinear function, called a Banach action. We say that this action preserves unconditional convergence if for every bounded sequence (an)n∈ω in A and unconditionally convergent series ∑n∈ωxn in X, the series ∑n∈ωanxn is unconditionally convergent in Y. We prove that a Banach action A×X→Y preserves unconditional convergence if and only if for any linear functional y*∈Y* the operator Dy*:X→A*, Dy*(x)(a)=y*(ax) is absolutely summing. Combining this characterization with the famous Grothendieck theorem on the absolute summability of operators from ℓ1 to ℓ2, we prove that a Banach action A×X→Y preserves unconditional convergence if A is a Hilbert space possessing an orthonormal basis (en)n∈ω such that for every x∈X, the series ∑n∈ωenx is weakly absolutely convergent. Applying known results of Garling on the absolute summability of diagonal operators between sequence spaces, we prove that for (finite or infinite) numbers p,q,r∈[1,∞] with 1r≤1p+1q, the coordinatewise multiplication ℓp×ℓq→ℓr preserves unconditional convergence if and only if one of the following conditions holds: (i) p≤2 and q≤r, (ii) 2<p<q≤r, (iii) 2<p=q<r, (iv) r=∞, (v) 2≤q<p≤r, (vi) q<2<p and 1p+1q≥1r+12.
Early Diagnosis of Alzheimer’s Disease Using Cerebral Catheter Angiogram Neuroimaging: A Novel Model Based on Deep Learning Approaches
Authors: Gharaibeh Maha , Almahmoud Mothanna , Ali Mostafa Z. , Al-Badarneh Amer , El-Heis Mwaffaq , Abualigah Laith , Altalhi Maryam , Alaiad Ahmad , Gandomi Amir H.
Published: December 2021

Neuroimaging refers to the techniques that provide efficient information about the neural structure of the human brain, which is utilized for diagnosis, treatment, and scientific research. The problem of classifying neuroimages is one of the most important steps that are needed by medical staff to diagnose their patients early by investigating the indicators of different neuroimaging types. Early diagnosis of Alzheimer’s disease is of great importance in preventing the deterioration of the patient’s situation. In this research, a novel approach was devised based on a digital subtracted angiogram scan that provides sufficient features of a new biomarker cerebral blood flow. The used dataset was acquired from the database of K.A.U.H hospital and contains digital subtracted angiograms of participants who were diagnosed with Alzheimer’s disease, besides samples of normal controls. Since each scan included multiple frames for the left and right ICA’s, pre-processing steps were applied to make the dataset prepared for the next stages of feature extraction and classification. The multiple frames of scans transformed from real space into DCT space and averaged to remove noises. Then, the averaged image was transformed back to the real space, and both sides filtered with Meijering and concatenated in a single image. The proposed model extracts the features using different pre-trained models: InceptionV3 and DenseNet201. Then, the PCA method was utilized to select the features with 0.99 explained variance ratio, where the combination of selected features from both pre-trained models is fed into machine learning classifiers. Overall, the obtained experimental results are at least as good as other state-of-the-art approaches in the literature and more efficient according to the recent medical standards with a 99.14% level of accuracy, considering the difference in dataset samples and the used cerebral blood flow biomarker.
MicroRNA Expression Profile Analysis of Chlamydomonas reinhardtii during Lipid Accumulation Process under Nitrogen Deprivation Stresses
Authors: Zhang Jingxian , Shi Jiping , Yuan Chenyang , Liu Xiangcen , Du Guilin , Fan Ruimei , Zhang Baoguo
Published: December 2021

Lipid accumulation in various microalgae has been found induced by nitrogen deprivation, and it controls many different genes expression. Yet, the underlying molecular mechanisms still remain largely unknown. MicroRNA (miRNAs) play a critical role in post-transcriptional gene regulation. In this study, miRNAs were hypothesized involved in lipid accumulation by nitrogen deprivation. A deep-sequencing platform was used to explore miRNAs-mediated responses induced by nitrogen deprivation in Chlamydomonas reinhardtii. The eukaryotic orthologous groups of proteins (KOG) function in the predicted target genes of miRNA with response to nitrogen deprivation were mainly involved in signal transduction mechanisms, including transcription, lipid transport, and metabolism. A total of 109 miRNA were predicted, including 79 known miRNA and 30 novel miRNA. A total of 29 miRNAs showed significantly differential expressions after nitrogen deprivation, and most of them were upregulated. A total of 10 miRNAs and their targeting genes might involve in lipid transport and metabolism biological process. This study first investigates nitrogen deprivation-regulated miRNAs in microalgae and broadens perspectives on miRNAs importance in microalgae lipid accumulation via nitrogen deprivation. This study provides theoretical guidance for the application of microalgae in bio-oil engineering production.
Identification and Effects of Skim Milk-Derived Bioactive Antihypertensive Peptides
Authors: Ahtesh Fatah B. , Stojanovska Lily , Mishra Vijay , Donkor Osaana , Feehan Jack , Bosevski Marijan , Mathai Michael , Apostolopoulos Vasso
Published: December 2021

Bioactive peptides are generated during milk fermentation or enzymatic hydrolysis. Lactobacillus (L) helveticus is commonly used to produce some types of fermented milk products. Fermented milk derived bioactive peptides are known to be beneficial in human health. Anti-hypertensive peptides play a dual role in the regulation of hypertension through the production of the vasoconstrictor angiotensin II and its inactivation of the vasodilator bradykinin. MALDI MS/MS, nano-LC/MS/MS and RP-HPLC were used to isolate peptides showing angiotensin converting enzyme inhibition (ACE-I) from 12% fermented skim milk using a combination of L. helveticus and Flavourzyme®. The fermentation procedure facilitated the identification of 133 anti-hypertensive peptides and 75% short chain amino acids, and the three with the highest ACE-I activity reduced blood pressure in a rat model of hypertension. The freeze- dried extract was supplemented in rodent chow. In this study 14-week-old male spontaneously hypertensive rats were fed for 10 weeks with the identified peptides added to chow and compared to controls supplemented with skim milk powder. Blood pressure (BP) decreased significantly (p < 0.05) from 6 to 10 weeks of FS groups (120/65 mmHg) compared with the NFS control groups, where the BP increased significantly (220/150 mmHg) (p < 0.05). The F6 fraction provided bioactive peptides with stronger antihypertensive properties than other fractions. Skim milk fermented by L. helveticus and Flavourzyme® generates several bioactive peptides which have a blood pressure lowering effect in hypertensive disease.
Effects of Resistance Training on Oxidative Stress Markers and Muscle Damage in Spinal Cord Injured Rats
Authors: Barros Natalie de Almeida , Aidar Felipe J. , Marçal Anderson Carlos , Santos Jymmys L. , de Souza Raphael Fabricio , Menezes Jainara Lima , Gomes Margarete Zanardo , de Matos Dihogo Gama , Neves Eduardo Borba , Carneiro André Luiz Gomes , de Almeida-Neto Paulo Francisco , de Araújo Tinoco Cabral Breno Guilherme , Belo Neto Reinaldo Viana , Knechtle Beat , Clemente Filipe Manuel , Camargo Enilton Aparecido
Published: December 2021

Background: Spinal cord injury (SCI) is a condition that affects the central nervous system, is characterized by motor and sensory impairments, and impacts individuals’ lives. The objective of this study was to evaluate the effects of resistance training on oxidative stress and muscle damage in spinal cord injured rats. Methodology: Forty Wistar rats were selected and divided equally into five groups: Healthy Control (CON), Sham (SHAM) SCI Untrained group (SCI-U), SCI Trained group (SCI- T), SCI Active Trained group (SCI- AT). Animals in the trained groups were submitted to an incomplete SCI at T9. Thereafter, they performed a protocol of resistance training for four weeks. Results: Significant differences in muscle damage markers and oxidative stress in the trained groups, mainly in SCI- AT, were found. On the other hand, SCI- U group presented higher levels of oxidative stress and biomarkers of LDH and AST. Conclusion: The results highlight that resistance training promoted a decrease in oxidative stress and a significative response in muscle damage markers.
Unexpected Terrain Induced Changes in Cortical Activity in Bipedal-Walking Rats
Authors: Liu Honghao , Li Bo , Zhang Minjian , Dai Chuankai , Xi Pengcheng , Liu Yafei , Huang Qiang , He Jiping , Lang Yiran , Tang Rongyu
Published: December 2021

Humans and other animals can quickly respond to unexpected terrains during walking, but little is known about the cortical dynamics in this process. To study the impact of unexpected terrains on brain activity, we allowed rats with blocked vision to walk on a treadmill in a bipedal posture and then walk on an uneven area at a random position on the treadmill belt. Whole brain EEG signals and hind limb kinematics of bipedal-walking rats were recorded. After encountering unexpected terrain, the θ band power of the bilateral M1, the γ band power of the left S1, and the θ to γ band power of the RSP significantly decreased compared with normal walking. Furthermore, when the rats left uneven terrain, the β band power of the bilateral M1 and the α band power of the right M1 decreased, while the γ band power of the left M1 significantly increased compared with normal walking. Compared with the flat terrain, the θ to low β (3–20 Hz) band power of the bilateral S1 increased after the rats contacted the uneven terrain and then decreased in the single- or double- support phase. These results support the hypothesis that unexpected terrains induced changes in cortical activity.
Clinical Trial on the Usefulness of On-Site Evaluation of Canine Fetal Fluids by Reagent Test Strip in Puppies at Elective Caesarean Section
Authors: Fusi Jasmine , Bolis Barbara , Probo Monica , Faustini Massimo , Carluccio Augusto , Veronesi Maria Cristina
Published: December 2021

The reagent urinary test strips (TS) marketed for urines represent the first-line diagnostic tool in many instances. Therefore, the aim of the study was to assess the usefulness of TS for the on-field evaluation of fetal fluids’ composition in newborn dogs at elective caesarean section. Of a total of 137 puppies born at term, 127 survived and 10 did not survive. One hundred and thirteen amniotic and 107 allantoic samples from surviving newborns were collected, and 8 amniotic and allantoic fluids were collected from the non-surviving newborns and assessed by strips. Significantly lower amounts of amniotic glucose and higher amounts of amniotic and allantoic nitrites, amniotic protein, allantoic urobilinogen, and amniotic bilirubin concentrations were found in non-surviving when compared to surviving newborns. In the surviving ones, higher specific gravity and bilirubin concentrations, and lower pH, were found in allantoic than in amniotic fluids. Higher amniotic and allantoic glucose concentrations, higher amniotic and allantoic pH, and lower amniotic and allantoic protein concentrations were found in medium/large- than in small-sized puppies. The TS allowed the quick evaluation of fetal fluids in puppies at birth. The differences between surviving and non-surviving puppies seem to suggest that the on-site analysis of fetal fluids’ composition by TS could represent a first-line diagnostic tool in the field of canine neonatology, allowing the quick recognition of puppies needing assistance as a complementary tool for clinical evaluation.
A Newly Discovered Forest of the Whip Coral Viminella flagellum (Anthozoa, Alcyonacea) in the Mediterranean Sea: A Non-Invasive Method to Assess Its Population Structure
Authors: Chimienti Giovanni , Aguilar Ricardo , Maiorca Michela , Mastrototaro Francesco
Published: December 2021

Coral forests are vulnerable marine ecosystems formed by arborescent corals (e.g., Anthozoa of the orders Alcyonacea and Antipatharia). The population structure of the habitat-forming corals can inform on the status of the habitat, representing an essential aspect to monitor. Most Mediterranean corals live in the mesophotic and aphotic zones, and their population structures can be assessed by analyzing images collected by underwater vehicles. This is still not possible in whip-like corals, whose colony lengths and flexibilities impede the taking of direct length measurements from images. This study reports on the occurrence of a monospecific forest, of the whip coral Viminella flagellum in the Aeolian Archipelago (Southern Tyrrhenian Sea; 149 m depth), and the assessment of its population structure through an ad-hoc, non-invasive method to estimate a colony height based on its width. The forest of V. flagellum showed a mean density of 19.4 ± 0.2 colonies m−2 (up to 44.8 colonies m−2) and no signs of anthropogenic impacts. The population was dominated by young colonies, with the presence of large adults and active recruitment. The new model proved to be effective for non-invasive monitoring of this near threatened species, representing a needed step towards appropriate conservation actions.
Harnessing Synergistic Biostimulatory Processes: A Plausible Approach for Enhanced Crop Growth and Resilience in Organic Farming
Authors: Sani Md. Nasir Hossain , Yong Jean W. H.
Published: December 2021

Demand for organically grown food crops is rising substantially annually owing to their contributions to human health. However, organic farm production is still generally lower compared to conventional farming. Nutrient availability, content consistency, uptake, assimilation, and crop responses to various stresses were reported as critical yield-limiting factors in many organic farming systems. In recent years, plant biostimulants (BSs) have gained much interest from researchers and growers, and with the objective of integrating these products to enhance nutrient use efficiency (NUE), crop performance, and delivering better stress resilience in organic-related farming. This review gave an overview of direct and indirect mechanisms of microbial and non-microbial BSs in enhancing plant nutrient uptake, physiological status, productivity, resilience to various stressors, and soil-microbe-plant interactions. BSs offer a promising, innovative and sustainable strategy to supplement and replace agrochemicals in the near future. With greater mechanistic clarity, designing purposeful combinations of microbial and non-microbial BSs that would interact synergistically and deliver desired outcomes in terms of acceptable yield and high-quality products sustainably will be pivotal. Understanding these mechanisms will improve the next generation of novel and well-characterized BSs, combining microbial and non-microbial BSs strategically with specific desired synergistic bio-stimulatory action, to deliver enhanced plant growth, yield, quality, and resilience consistently in organic-related cultivation.
A Rapid Method for Postmortem Vitreous Chemistry—Deadside Analysis
Authors: Zilg Brita , Alkass Kanar , Kronstrand Robert , Berg Sören , Druid Henrik
Published: December 2021

Vitreous fluid is commonly collected for toxicological analysis during forensic postmortem investigations. Vitreous fluid is also often analyzed for potassium, sodium, chloride and glucose for estimation of time since death, and for the evaluation of electrolyte imbalances and hyperglycemia, respectively. Obtaining such results in the early phase of a death investigation is desirable both in regard to assisting the police and in the decision-making prior to the autopsy. We analyzed vitreous fluid with blood gas instruments to evaluate/examine the possible impact of different sampling and pre-analytical treatment. We found that samples from the right and left eye, the center of the eye as well as whole vitreous samples gave similar results. We also found imprecision to be very low and that centrifugation and dilution were not necessary when analyzing vitreous samples with blood gas instruments. Similar results were obtained when analyzing the same samples with a regular multi-analysis instrument, but we found that such instruments could require dilution of samples with high viscosity, and that such dilution might impact measurement accuracy. In conclusion, using a blood gas instrument, the analysis of postmortem vitreous fluid for electrolytes and glucose without sample pretreatment produces rapid and reliable results.
Sexual Dimorphism in Metabolic Responses to Western Diet in Drosophila melanogaster
Authors: De Groef Sofie , Wilms Tom , Balmand Séverine , Calevro Federica , Callaerts Patrick
Published: December 2021

Obesity is a chronic disease affecting millions of people worldwide. The fruit fly (Drosophila melanogaster) is an interesting research model to study metabolic and transcriptomic responses to obesogenic diets. However, the sex-specific differences in these responses are still understudied and perhaps underestimated. In this study, we exposed adult male and female Dahomey fruit flies to a standard diet supplemented with sugar, fat, or a combination of both. The exposure to a diet supplemented with 10% sugar and 10% fat efficiently induced an increase in the lipid content in flies, a hallmark for obesity. This increase in lipid content was more prominent in males, while females displayed significant changes in glycogen content. A strong effect of the diets on the ovarian size and number of ma-ture oocytes was also present in females exposed to diets supplemented with fat and a combina-tion of fat and sugar. In both males and females, fat body morphology changed and was associ-ated with an increase in lipid content of fat cells in response to the diets. The expression of me-tabolism-related genes also displayed a strong sexually dimorphic response under normal condi-tions and in response to sugar and/or fat-supplemented diets. Here, we show that the exposure of adult fruit flies to an obesogenic diet containing both sugar and fat allowed studying sexual dimorphism in metabolism and the expression of genes regulating metabolism.
A Brief Analysis of Proteomic Profile Changes during Zebrafish Regeneration
Authors: Ulhaq Zulvikar Syambani , Tse William Ka Fai
Published: December 2021

Unlike mammals, zebrafish are capable to regenerate many of their organs, however, the response of tissue damage varies across tissues. Understanding the molecular mechanism behind the robust regenerative capacity in a model organism may help to identify and develop novel treatment strategies for mammals (including humans). Hence, we systematically analyzed the current literature on the proteome profile collected from different regenerated zebrafish tissues. Our analyses underlining that several proteins and protein families responsible as a component of cytoskeleton and structure, protein synthesis and degradation, cell cycle control, and energy metabolism were frequently identified. Moreover, target proteins responsible for the initiation of the regeneration process, such as inflammation and immune response were less frequently detected. This highlights the limitation of previous proteomic analysis and suggested a more sensitive modern proteomics analysis is needed to unfold the mechanism. This brief report provides a list of target proteins with predicted functions that could be useful for further biological studies.
Smell Detection Agent Optimisation Framework and Systems Biology Approach to Detect Dys-Regulated Subnetwork in Cancer Data
Authors: Sivan Suma L. , Sukumara Pillai Vinod Chandra S.
Published: December 2021

Network biology has become a key tool in unravelling the mechanisms of complex diseases. Detecting dys-regulated subnetworks from molecular networks is a task that needs efficient computational methods. In this work, we constructed an integrated network using gene interaction data as well as protein–protein interaction data of differentially expressed genes derived from the microarray gene expression data. We considered the level of differential expression as well as the topological weight of proteins in interaction network to quantify dys-regulation. Then, a nature-inspired Smell Detection Agent (SDA) optimisation algorithm is designed with multiple agents traversing through various paths in the network. Finally, the algorithm provides a maximum weighted module as the optimum dys-regulated subnetwork. The analysis is performed for samples of triple-negative breast cancer as well as colorectal cancer. Biological significance analysis of module genes is also done to validate the results. The breast cancer subnetwork is found to contain (i) valid biomarkers including PIK3CA, PTEN, BRCA1, AR and EGFR; (ii) validated drug targets TOP2A, CDK4, HDAC1, IL6, BRCA1, HSP90AA1 and AR; (iii) synergistic drug targets EGFR and BIRC5. Moreover, based on the weight values assigned to nodes in the subnetwork, PLK1, CTNNB1, IGF1, AURKA, PCNA, HSPA4 and GAPDH are proposed as drug targets for further studies. For colorectal cancer module, the analysis revealed the occurrence of approved drug targets TYMS, TOP1, BRAF and EGFR. Considering the higher weight values, HSP90AA1, CCNB1, AKT1 and CXCL8 are proposed as drug targets for experimentation. The derived subnetworks possess cancer-related pathways as well. The SDA-derived breast cancer subnetwork is compared with that of tools such as MCODE and Minimum Spanning Tree, and observed a higher enrichment (75%) of significant elements. Thus, the proposed nature-inspired algorithm is a novel approach to derive the optimum dys-regulated subnetwork from huge molecular network.
Co-Stimulatory Molecules during Immune Control of Epstein Barr Virus Infection
Authors: Münz Christian
Published: December 2021

The Epstein Barr virus (EBV) is one of the prominent human tumor viruses, and it is efficiently immune-controlled in most virus carriers. Cytotoxic lymphocytes strongly expand during symptomatic primary EBV infection and in preclinical in vivo models of this tumor virus infection. In these models and patients with primary immunodeficiencies, antibody blockade or deficiencies in certain molecular pathways lead to EBV-associated pathologies. In addition to T, NK, and NKT cell development, as well as their cytotoxic machinery, a set of co-stimulatory and co-inhibitory molecules was found to be required for EBV-specific immune control. The role of CD27/CD70, 4-1BB, SLAMs, NKG2D, CD16A/CD2, CTLA-4, and PD-1 will be discussed in this review. Some of these have just been recently identified as crucial for EBV-specific immune control, and for others, their important functions during protection were characterized in in vivo models of EBV infection and its immune control. These insights into the phenotype of cytotoxic lymphocytes that mediate the near-perfect immune control of EBV-associated malignancies might also guide immunotherapies against other tumors in the future.
Integrated Multi-Omics for Novel Aging Biomarkers and Antiaging Targets
Authors: Wu Lei , Xie Xinqiang , Liang Tingting , Ma Jun , Yang Lingshuang , Yang Juan , Li Longyan , Xi Yu , Li Haixin , Zhang Jumei , Chen Xuefeng , Ding Yu , Wu Qingping
Published: December 2021

Aging is closely related to the occurrence of human diseases; however, its exact biological mechanism is unclear. Advancements in high-throughput technology provide new opportunities for omics research to understand the pathological process of various complex human diseases. However, single-omics technologies only provide limited insights into the biological mechanisms of diseases. DNA, RNA, protein, metabolites, and microorganisms usually play complementary roles and perform certain biological functions together. In this review, we summarize multi-omics methods based on the most relevant biomarkers in single-omics to better understand molecular functions and disease causes. The integration of multi-omics technologies can systematically reveal the interactions among aging molecules from a multidimensional perspective. Our review provides new insights regarding the discovery of aging biomarkers, mechanism of aging, and identification of novel antiaging targets. Overall, data from genomics, transcriptomics, proteomics, metabolomics, integromics, microbiomics, and systems biology contribute to the identification of new candidate biomarkers for aging and novel targets for antiaging interventions.
Lipotoxicity Downstream of α-Synuclein Imbalance: A Relevant Pathomechanism in Synucleinopathies?
Authors: Tripathi Arati , Fanning Saranna , Dettmer Ulf
Published: December 2021

Neuronal loss in Parkinson’s disease and related brain diseases has been firmly linked to the abundant neuronal protein α-synuclein (αS). However, we have gained surprisingly little insight into how exactly αS exerts toxicity in these diseases. Hypotheses of proteotoxicity, disturbed vesicle trafficking, mitochondrial dysfunction and other toxicity mechanisms have been proposed, and it seems possible that a combination of different mechanisms may drive pathology. A toxicity mechanism that has caught increased attention in the recent years is αS-related lipotoxicity. Lipotoxicity typically occurs in a cell when fatty acids exceed the metabolic needs, triggering a flux into harmful pathways of non-oxidative metabolism. Genetic and experimental approaches have revealed a significant overlap between lipid storage disorders, most notably Gaucher’s disease, and synucleinopathies. There is accumulating evidence for lipid aberrations causing synuclein misfolding as well as for αS excess and misfolding causing lipid aberration. Does that mean the key problem in synucleinopathies is lipotoxicity, the accumulation of harmful lipid species or alteration in lipid equilibrium? Here, we review the existing literature in an attempt to get closer to an answer.
A Comprehensive Review on the Heavy Metal Toxicity and Sequestration in Plants
Authors: Riyazuddin Riyazuddin , Nisha Nisha , Ejaz Bushra , Khan M. Iqbal R. , Kumar Manu , Ramteke Pramod W. , Gupta Ravi
Published: December 2021

Heavy metal (HM) toxicity has become a global concern in recent years and is imposing a severe threat to the environment and human health. In the case of plants, a higher concentration of HMs, above a threshold, adversely affects cellular metabolism because of the generation of reactive oxygen species (ROS) which target the key biological molecules. Moreover, some of the HMs such as mercury and arsenic, among others, can directly alter the protein/enzyme activities by targeting their –SH group to further impede the cellular metabolism. Particularly, inhibition of photosynthesis has been reported under HM toxicity because HMs trigger the degradation of chlorophyll molecules by enhancing the chlorophyllase activity and by replacing the central Mg ion in the porphyrin ring which affects overall plant growth and yield. Consequently, plants utilize various strategies to mitigate the negative impact of HM toxicity by limiting the uptake of these HMs and their sequestration into the vacuoles with the help of various molecules including proteins such as phytochelatins, metallothionein, compatible solutes, and secondary metabolites. In this comprehensive review, we provided insights towards a wider aspect of HM toxicity, ranging from their negative impact on plant growth to the mechanisms employed by the plants to alleviate the HM toxicity and presented the molecular mechanism of HMs toxicity and sequestration in plants.
Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?
Authors: Migliaccio Silvia , Bimonte Viviana M. , Besharat Zein Mersini , Sabato Claudia , Lenzi Andrea , Crescioli Clara , Ferretti Elisabetta
Published: December 2021

The number of aged individuals is increasing worldwide, rendering essential the comprehension of pathophysiological mechanisms of age-related alterations, which could facilitate the development of interventions contributing to “successful aging” and improving quality of life. Cardiovascular diseases (CVD) include pathologies affecting the heart or blood vessels, such as hypertension, peripheral artery disease and coronary heart disease. Indeed, age-associated modifications in body composition, hormonal, nutritional and metabolic factors, as well as a decline in physical activity are all involved in the increased risk of developing atherogenic alterations that raise the risk of CVD development. Several factors have been reported to play a role in the alterations observed in muscle and endothelial cells and that lead to increased CVD, such as genetic pattern, smoking and unhealthy lifestyle. Moreover, a difference in the risk of these diseases in women and men has been reported. Interestingly, in the past decades attention has been focused on a potential role of several pollutants that disrupt human health by interfering with hormonal pathways, and more specifically in non-communicable diseases such as obesity, diabetes and CVD. This review will focus on the potential alteration induced by Endocrine Disruptors (Eds) in the attempt to characterize a potential role in the cellular and molecular mechanisms involved in the atheromatous degeneration process and CVD progression.
DNA Microarray-Based Global Gene Expression Profiling in Human Amniotic Epithelial Cells Predicts the Potential of Microalgae-Derived Squalene for the Nervous System and Metabolic Health
Authors: Ferdousi Farhana , Furuya Kinji , Sasaki Kazunori , Zheng Yun-Wen , Oda Tatsuya , Isoda Hiroko
Published: December 2021

In recent years, perinatal stem cells, such as human amniotic epithelial cells (hAECs), have attracted increasing interest as a novel tool of stem cell-based high-throughput drug screening. In the present study, we investigated the bioactivities of squalene (SQ) derived from ethanol extract (99.5%) of a microalgae Aurantiochytrium Sp. (EEA-SQ) in hAECs using whole-genome DNA microarray analysis. Tissue enrichment analysis showed that the brain was the most significantly enriched tissue by the differentially expressed genes (DEGs) between EEA-SQ-treated and control hAECs. Further gene set enrichment analysis and tissue-specific functional analysis revealed biological functions related to nervous system development, neurogenesis, and neurotransmitter modulation. Several adipose tissue-specific genes and functions were also enriched. Gene-disease association analysis showed nervous system-, metabolic-, and immune-related diseases were enriched. Altogether, our study suggests the potential health benefits of microalgae-derived SQ and we would further encourage investigation in EEA-SQ and its derivatives as potential therapeutics for nervous system- and metabolism-related diseases.
Inhibitory Effects of Astaxanthin on CML-HSA-Induced Inflammatory and RANKL-Induced Osteoclastogenic Gene Expression in RAW 264.7 Cells
Authors: Mamun-Or-Rashid A. N. M. , Lucy Tanzima Tarannum , Yagi Masayuki , Yonei Yoshikazu
Published: December 2021

Objective: Elevated levels of serum Nε-carboxymethyllysine (CML), a well-known advanced glycation end-product (AGE), were observed in patients with inflammation or osteoporosis. Astaxanthin was reported to possess anti-inflammatory and antioxidant effects. In the present study, we investigated the effects of commercially available dietary supplement AstaReal ACTR (ASR) capsule content as astaxanthin on CML-HSA-induced inflammatory and receptor activator of nuclear factor-kappa-Β ligand (RANKL)-induced osteoclastogenic gene expression. Methods: RAW 264.7 murine macrophage cells were stimulated with CML-HSA to trigger inflammatory gene expression and treated with either a vehicle control or varied concentrations of astaxanthin. Inflammatory gene expression was measured using an enzyme-linked immunosorbent assay (ELISA) or qPCR. We triggered osteoclastogenesis using RANKL, and osteoclastogenic gene expression was measured through tartrate-resistant acid phosphatase (TRAP) activity, staining, immunofluorescence, and qPCR analyses. Results: CML-HSA showed a stimulatory effect on inflammatory gene expression, and astaxanthin reduced the expression by at least two-fold. The levels of autoinflammatory gene expression were reduced by astaxanthin. The RANKL-induced osteoclastogenesis was significantly inhibited by astaxanthin, with reductions in the activation of nuclear factor-κB (NF-κB), the expression of NFATc1 (nuclear factor of activated T cells 1), multinucleated cell formation, and the expression of mature osteoclast marker genes. Conclusion: Astaxanthin has potential as a remedy for CML-HSA-induced inflammation and RANKL-induced excessive bone loss.
Differential iNKT and T Cells Activation in Non-Alcoholic Fatty Liver Disease and Drug-Induced Liver Injury
Authors: Caballano-Infantes Estefanía , García-García Alberto , Lopez-Gomez Carlos , Cueto Alejandro , Robles-Diaz Mercedes , Ortega-Alonso Aida , Martín-Reyes Flores , Alvarez-Alvarez Ismael , Arranz-Salas Isabel , Ruiz-Cabello Francisco , Lucena Isabel M. , García-Fuentes Eduardo , Andrade Raúl J. , García-Cortes Miren
Published: December 2021

Background: Non-alcoholic fatty liver disease (NAFLD) and idiosyncratic drug-induced liver injury (DILI) could share molecular mechanisms involving the immune system. We aimed to identify activation immunological biomarkers in invariant natural killer T (iNKT) and CD4/CD8+ T cells in NAFLD and DILI. Methods: We analyzed the activation profile (CD69, CD25, and HLA-DR) and natural killer group 2 member D (NKG2D) on iNKT cells, and CD4/CD8 T cells in peripheral blood mononuclear cells from NAFLD, with or without significant liver fibrosis, and DILI patients. Results: There was an increase in iNKT cells in NAFLD patients compared to DILI or control subjects. Regarding the cellular activation profile, NAFLD with significant liver fibrosis (F ≥ 2) displayed higher levels of CD69+iNKT cells compared to NAFLD with none or mild liver fibrosis (F ≤ 1) and control patients. CD69+iNKT positively correlated with insulin resistance, aspartate aminotransferase (AST) level, liver fibrosis-4 index (FIB4) and AST to Platelet Ratio Index (APRI). DILI patients showed an increase in CD69+ and HLA-DR+ in both CD4+ and CD8+ T cells, detecting the most relevant difference in the case of CD69+CD8+ T cells. Conclusions: CD69+iNKT may be a biomarker to assess liver fibrosis progression in NAFLD. CD69+CD8+ T cells were identified as a potential distinctive biomarker for distinguishing DILI from NAFLD.
Mice with Type 2 Diabetes Present Significant Alterations in Their Tissue Biomechanical Properties and Histological Features
Authors: Cruz Tânia B. , Carvalho Filomena A. , Matafome Paulo N. , Soares Raquel A. , Santos Nuno C. , Travasso Rui D. , Oliveira Maria J.
Published: December 2021

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease often associated with severe complications that may result in patient morbidity or death. One T2DM etiological agent is chronic hyperglycemia, a condition that induces damaging biological processes, including impactful extracellular matrix (ECM) modifications, such as matrix components accumulation. The latter alters ECM stiffness, triggering fibrosis, inflammation, and pathological angiogenesis. Hence, studying ECM biochemistry and biomechanics in the context of T2DM, or obesity, is highly relevant. With this in mind, we examined both native and decellularized tissues of obese B6.Cg-Lepob/J (ob/ob) and diabetic BKS.Cg-Dock7m+/+LeprdbJ (db/db) mice models, and extensively investigated their histological and biomechanical properties. The tissues analyzed herein were those strongly affected by diabetes—skin, kidney, adipose tissue, liver, and heart. The referred organs and tissues were collected from 8-week-old animals and submitted to classical histological staining, immunofluorescence, scanning electron microscopy, rheology, and atomic force microscopy. Altogether, this systematic characterization has identified significant differences in the architecture of both ob/ob and db/db tissues, namely db/db skin presents loose epidermis and altered dermis structure, the kidneys have clear glomerulopathy traits, and the liver exhibits severe steatosis. The distribution of ECM proteins also pinpoints important differences, such as laminin accumulation in db/db kidneys and decreased hyaluronic acid in hepatocyte cytoplasm in both obese and diabetic mice. In addition, we gathered a significant set of data showing that ECM features are maintained after decellularization, making these matrices excellent biomimetic scaffolds for 3D in vitro approaches. Importantly, mechanical studies revealed striking differences between tissue ECM stiffness of control (C57BL/6J), obese, and diabetic mice. Notably, we have unveiled that the intraperitoneal adipose tissue of diabetic animals is significantly stiffer (G* ≈ 10,000 Pa) than that of ob/ob or C57BL/6J mice (G* ≈ 3000–5000 Pa). Importantly, this study demonstrates that diabetes and obesity selectively potentiate severe histological and biomechanical alterations in different matrices that may impact vital processes, such as angiogenesis, wound healing, and inflammation.
Micro-RNA 92a as a Therapeutic Target for Cardiac Microvascular Dysfunction in Diabetes
Authors: Samak Mostafa , Kaltenborn Diana , Kues Andreas , Le Noble Ferdinand , Hinkel Rabea , Germena Giulia
Published: December 2021

Microvascular dysfunction is a pathological hallmark of diabetes, and is central to the ethology of diabetes-associated cardiac events. Herein, previous studies have highlighted the role of the vasoactive micro-RNA 92a (miR-92a) in small, as well as large, animal models. In this study, we explore the effects of miR-92a on mouse and human cardiac microvascular endothelial cells (MCMEC, HCMEC), and its underlying molecular mechanisms. Diabetic HCMEC displayed impaired angiogenesis and a pronounced inflammatory phenotype. Quantitative PCR (qPCR) showed an upregulation of miR-92a in primary diabetic HCMEC. Downregulation of miR-92a by antagomir transfection in diabetic HCMEC rescued angiogenesis and ameliorated diabetic endothelial bed inflammation. Furthermore, additional analysis of potential in silico-identified miR-92a targets in diabetic HCMEC revealed the miR-92a dependent downregulation of an essential metalloprotease, ADAM10. Accordingly, downregulation of ADAM10 impaired angiogenesis and wound healing in MCMEC. In myocardial tissue slices from diabetic pigs, ADAM10 dysregulation in micro- and macro-vasculature could be shown. Altogether, our data demonstrate the role of miR-92a in cardiac microvascular dysfunction and inflammation in diabetes. Moreover, we describe for the first time the metalloprotease ADAM10 as a novel miR-92a target, mediating its anti-angiogenic effect.
The Cardiovascular System in Space: Focus on In Vivo and In Vitro Studies
Authors: Baran Ronni , Marchal Shannon , Garcia Campos Sebastian , Rehnberg Emil , Tabury Kevin , Baselet Bjorn , Wehland Markus , Grimm Daniela , Baatout Sarah
Published: December 2021

On Earth, humans are subjected to a gravitational force that has been an important determinant in human evolution and function. During spaceflight, astronauts are subjected to several hazards including a prolonged state of microgravity that induces a myriad of physiological adaptations leading to orthostatic intolerance. This review summarises all known cardiovascular diseases related to human spaceflight and focusses on the cardiovascular changes related to human spaceflight (in vivo) as well as cellular and molecular changes (in vitro). Upon entering microgravity, cephalad fluid shift occurs and increases the stroke volume (35–46%) and cardiac output (18–41%). Despite this increase, astronauts enter a state of hypovolemia (10–15% decrease in blood volume). The absence of orthostatic pressure and a decrease in arterial pressures reduces the workload of the heart and is believed to be the underlying mechanism for the development of cardiac atrophy in space. Cellular and molecular changes include altered cell shape and endothelial dysfunction through suppressed cellular proliferation as well as increased cell apoptosis and oxidative stress. Human spaceflight is associated with several cardiovascular risk factors. Through the use of microgravity platforms, multiple physiological changes can be studied and stimulate the development of appropriate tools and countermeasures for future human spaceflight missions in low Earth orbit and beyond.
Preparation, Physicochemical Assessment and the Antimicrobial Action of Hydroxyapatite–Gelatin/Curcumin Nanofibrous Composites as a Dental Biomaterial
Authors: Sharifi Simin , Zaheri Khosroshahi Asma , Maleki Dizaj Solmaz , Rezaei Yashar
Published: December 2021

In this study, we prepared and evaluated hydroxyapatite–gelatin/curcumin nanofibrous composites and determined their antimicrobial effects against Escherichia coli, Staphylococcus aureus, and Streptococcus mutans. Hydroxyapatite–gelatin/curcumin nanofibrous composites were prepared by the electrospinning method. The prepared nanocomposites were then subjected to physicochemical studies by the light scattering method for their particle size, Fourier transmission infrared spectroscopy (FTIR) to identify their functional groups, X-ray diffraction (XRD) to study their crystallinity, and scanning electron microscopy (SEM) to study their morphology. For the microbial evaluation of nanocomposites, the disk diffusion method was used against Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The results showed that the nanofibers were uniform in shape without any bead (structural defects). The release pattern of curcumin from the nanocomposite was a two-stage release, 60% of which was released in the first two days and the rest being slowly released until the 14th day. The results of the microbial evaluations showed that the nanocomposites had significant antimicrobial effects against all bacteria (p = 0.0086). It seems that these nanocomposites can be used in dental tissue engineering or as other dental materials. Also, according to the appropriate microbial results, these plant antimicrobials can be used instead of chemical antimicrobials, or along with them, to reduce bacterial resistance.