bluuebunny/crossref_metadata_2025 huggingface dataset:
High Coverage Mitogenomes and Y-Chromosomal Typing Reveal Ancient Lineages in the Modern-Day Székely Population in Romania
Authors: Borbély Noémi , Székely Orsolya , Szeifert Bea , Gerber Dániel , Máthé István , Benkő Elek , Mende Balázs Gusztáv , Egyed Balázs , Pamjav Horolma , Szécsényi-Nagy Anna
Published: January 2023

Here we present 115 whole mitogenomes and 92 Y-chromosomal Short Tandem Repeat (STR) and Single Nucleotide Polymorphism (SNP) profiles from a Hungarian ethnic group, the Székelys (in Romanian: Secuii, in German: Sekler), living in southeast Transylvania (Romania). The Székelys can be traced back to the 12th century in the region, and numerous scientific theories exist as to their origin. We carefully selected sample providers that had local ancestors inhabiting small villages in the area of Odorheiu Secuiesc/Székelyudvarhely in Romania. The results of our research and the reported data signify a qualitative leap compared to previous studies since it presents the first complete mitochondrial DNA sequences and Y-chromosomal profiles of 23 STRs from the region. We evaluated the results with population genetic and phylogenetic methods in the context of the modern and ancient populations that are either geographically or historically related to the Székelys. Our results demonstrate a predominantly local uniparental make-up of the population that also indicates limited admixture with neighboring populations. Phylogenetic analyses confirmed the presumed eastern origin of certain maternal (A, C, D) and paternal (Q, R1a) lineages, and, in some cases, they could also be linked to ancient DNA data from the Migration Period (5th–9th centuries AD) and Hungarian Conquest Period (10th century AD) populations.
The Two-Faced Role of crAssphage Subfamilies in Obesity and Metabolic Syndrome: Between Good and Evil
Authors: Cervantes-Echeverría Melany , Gallardo-Becerra Luigui , Cornejo-Granados Fernanda , Ochoa-Leyva Adrian
Published: January 2023

Viral metagenomic studies of the human gut microbiota have unraveled the differences in phage populations between health and disease, stimulating interest in phages’ role on bacterial ecosystem regulation. CrAssphage is a common and abundant family in the gut virome across human populations. Therefore, we explored its role in obesity (O) and obesity with metabolic syndrome (OMS) in a children’s cohort. We found a significantly decreased prevalence, diversity, and richness of the crAssphage Alpha subfamily in OMS mainly driven by a decrease in the Alpha_1 and Alpha_4 genera. On the contrary, there was a significant increase in the Beta subfamily in OMS, mainly driven by an increase in Beta_6. Additionally, an overabundance of the Delta_8 genus was observed in OMS. Notably, a decreased abundance of crAssphages was significantly correlated with the overabundance of Bacilli in the same group. The Bacilli class is a robust taxonomical biomarker of O and was also significantly abundant in our OMS cohort. Our results suggest that a loss of stability in the Alpha subfamily of crAssphages is associated with O and OMS. Contrary, an overabundance of the Delta subfamily was found in OMS. Our study advises the importance of considering the dual role (good and evil) of crAssphage subfamilies and their participation in conditions such as O, where we suggest that Alpha loss and Delta gain are associated with obese individuals.
Inflammageing and Cardiovascular System: Focus on Cardiokines and Cardiac-Specific Biomarkers
Authors: Perrone Marco Alfonso , Aimo Alberto , Bernardini Sergio , Clerico Aldo
Published: January 2023

The term “inflammageing” was introduced in 2000, with the aim of describing the chronic inflammatory state typical of elderly individuals, which is characterized by a combination of elevated levels of inflammatory biomarkers, a high burden of comorbidities, an elevated risk of disability, frailty, and premature death. Inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and rapid progression to heart failure. The great experimental and clinical evidence accumulated in recent years has clearly demonstrated that early detection and counteraction of inflammageing is a promising strategy not only to prevent cardiovascular disease, but also to slow down the progressive decline of health that occurs with ageing. It is conceivable that beneficial effects of counteracting inflammageing should be most effective if implemented in the early stages, when the compensatory capacity of the organism is not completely exhausted. Early interventions and treatments require early diagnosis using reliable and cost-effective biomarkers. Indeed, recent clinical studies have demonstrated that cardiac-specific biomarkers (i.e., cardiac natriuretic peptides and cardiac troponins) are able to identify, even in the general population, the individuals at highest risk of progression to heart failure. However, further clinical studies are needed to better understand the usefulness and cost/benefit ratio of cardiac-specific biomarkers as potential targets in preventive and therapeutic strategies for early detection and counteraction of inflammageing mechanisms and in this way slowing the progressive decline of health that occurs with ageing.
Biosynthesis and Transfer of α-Elostearic Acid In Vivo in Momordica charantia L. Developing Seeds and In Vitro in Microsomal Fractions of These Seeds
Authors: Banaś Antoni , Jasieniecka-Gazarkiewicz Katarzyna , Klińska Sylwia
Published: January 2023

The research concerned the efficiency of biosynthesis and transfer to triacylglycerols (TAG) of α-eleostearic acid (αESA). The experiments were carried out on developing seeds of Momordica charantia L. and on microsomal fractions obtained from these seeds. The seeds from in vivo conditions were collected 20, 23, 26 and 33 days after pollination (DAP) and used for lipid extraction and further analyses. Microsomal fractions were prepared from seeds at 26 DAP. The most intensive lipid accumulation occurred between 20 and 26 DAP, but continued up to 33 DAP. The most abundant lipid fraction was TAG; up to 98% of total acyl lipids at 33 DAP. The synthesised in vivo αESA was very efficiently transferred to TAG and constituted about 60% of its total fatty acids in 33 DAP. The content of αESA in polar lipids (containing, among others, phosphatidylcholine—the place of αESA biosynthesis) was very low. The biosynthesis of αESA in vitro (assays with microsomal fractions and [14C]-labelled substrates) in the presence of NADPH was fairly intensive (about 60% of the corresponding intensity in vivo) when linolenic acid was used as a substrate. Contrary to the in vivo condition, most of the synthesised in vitro αESA remained in phosphatidylcholine.
Imaging of Indocyanine Green-Human Serum Albumin (ICG-HSA) Complex in Secreted Protein Acidic and Rich in Cysteine (SPARC)-Expressing Glioblastoma
Authors: Jang Hye Jung , Song Myung Geun , Park Cho Rong , Youn Hyewon , Lee Yun-Sang , Cheon Gi Jeong , Kang Keon Wook
Published: January 2023

Glioblastoma is the most common and fatal primary glioma and has a severe prognosis. It is a challenge for neurosurgeons to remove brain tumor tissues completely by resection. Meanwhile, fluorescence-guided surgery (FGS) is a technique used in glioma surgery to enhance the visualization of tumor edges to clarify the extent of tumor resection. Indocyanine green (ICG) is the only FDA-approved NIR fluorescent agent. It non-covalently binds to human serum albumin (HSA). Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein expressed in gliomas and binds to albumin, suggesting that it plays an important role in tumor uptake of the ICG-HSA complex. Here we demonstrate the binding properties of HSA or SPARC to ICG using surface plasmon resonance and saturation binding assay. According to in vitro and in vivo studies, the results showed that the uptake of ICG-HSA complex was higher in SPARC-expressing glioblastoma cell line and tumor region compared with the uptake of free ICG. Here, we visualized the SPARC-dependent uptake of ICG and ICG-HSA complex in U87MG. Our results demonstrated that the ICG-HSA complex is likely to be used as an efficient imaging agent targeting SPARC-expressing tumors, especially glioblastoma.
Inflammation in Urological Malignancies: The Silent Killer
Authors: Catalano Martina , Roviello Giandomenico , Santi Raffaella , Villari Donata , Spatafora Pietro , Galli Ilaria Camilla , Sessa Francesco , Conte Francesco Lupo , Mini Enrico , Cai Tommaso , Nesi Gabriella
Published: January 2023

Several studies have investigated the role of inflammation in promoting tumorigenesis and cancer progression. Neoplastic as well as surrounding stromal and inflammatory cells engage in well-orchestrated reciprocal interactions to establish an inflammatory tumor microenvironment. The tumor-associated inflammatory tissue is highly plastic, capable of continuously modifying its phenotypic and functional characteristics. Accumulating evidence suggests that chronic inflammation plays a critical role in the development of urological cancers. Here, we review the origins of inflammation in urothelial, prostatic, renal, testicular, and penile cancers, focusing on the mechanisms that drive tumor initiation, growth, progression, and metastasis. We also discuss how tumor-associated inflammatory tissue may be a diagnostic marker of clinically significant tumor progression risk and the target for future anti-cancer therapies.
The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors
Authors: Amagai Ryo , Takahashi Toshiya , Terui Hitoshi , Fujimura Taku , Yamasaki Kenshi , Aiba Setsuya , Asano Yoshihide
Published: January 2023

An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents.
Comprehensive Profiling of ceRNA (circRNA-miRNA-mRNA) Networks in Hypothalamic-Pituitary-Mammary Gland Axis of Dairy Cows under Heat Stress
Authors: Zeng Hanfang , Xia Haibin , Wang Xinling , Wang Yue , Fang Jian , Li Shujie , Zhai Yunfei , Han Zhaoyu
Published: January 2023

Heat stress (HS) is directly correlated with mammary gland dysfunction and the hypothalamic-pituitary-mammary gland (HPM) axis is involved in regulating stress responses and lactation in dairy cows. Circular RNAs (circRNAs) play major roles in regulating transcription and post-transcription but their expression in the HPM axis of dairy cows under HS is still unclear. In the present study, we performed RNA sequencing to identify diferentially expressed (DE) circRNAs, DE microRNAs(miRNAs) and DEmRNAs, and performed bioinformatics analysis on those in HPM axis-related tissues of heat-stressed and normal cows. A total of 1680, 1112 and 521 DEcircRNAs, 120, 493 and 108 DEmiRNAs, 274, 6475 and 3134 DEmRNAs were identified in the hypothalamic, pituitary, and mammary gland tissues, respectively. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses indicated that the MAPK signaling pathway is potentially a key pathway. Competitive endogenous RNA (ceRNA) networks related to HS response and lactation regulation were established in three tissues. In conclusion, our results indicate that HS induces differential circRNA expression profiles in HPM axis-related tissues, and the predicted ceRNA network provides a molecular basis for regulating the stress response and lactation regulation in heat-stressed dairy cows.
Metabolic Signature of Energy Metabolism Alterations and Excess Nitric Oxide Production in Culture Media Correlate with Low Human Embryo Quality and Unsuccessful Pregnancy
Authors: Pallisco Romina , Lazzarino Giacomo , Bilotta Gabriele , Marroni Francesca , Mangione Renata , Saab Miriam Wissam , Brundo Maria Violetta , Pittalà Alessandra , Caruso Giuseppe , Capoccia Elena , Lazzarino Giuseppe , Tavazzi Barbara , Bilotta Pasquale , Amorini Angela Maria
Published: January 2023

Notwithstanding the great improvement of ART, the overall rate of successful pregnancies from implanted human embryos is definitely low. The current routine embryo quality assessment is performed only through morphological criteria, which has poor predictive capacity since only a minor percentage of those in the highest class give rise to successful pregnancy. Previous studies highlighted the potentiality of the analysis of metabolites in human embryo culture media, useful for the selection of embryos for implantation. In the present study, we analyzed in blind 66 human embryo culture media at 5 days after in vitro fertilization with the aim of quantifying compounds released by cell metabolism that were not present as normal constituents of the human embryo growth media, including purines, pyrimidines, nitrite, and nitrate. Only some purines were detectable (hypoxanthine and uric acid) in the majority of samples, while nitrite and nitrate were always detectable. When matching biochemical results with morphological evaluation, it was found that low grade embryos (n = 12) had significantly higher levels of all the compounds of interest. Moreover, when matching biochemical results according to successful (n = 17) or unsuccessful (n = 25) pregnancy, it was found that human embryos from the latter group released higher concentrations of hypoxanthine, uric acid, nitrite, and nitrate in the culture media. Additionally, those embryos that developed into successful pregnancies were all associated with the birth of healthy newborns. These results, although carried out on a relatively low number of samples, indicate that the analysis of the aforementioned compounds in the culture media of human embryos is a potentially useful tool for the selection of embryos for implantation, possibly leading to an increase in the overall rate of ART.
Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men
Authors: García-González Pablo , de Rojas Itziar , Moreno-Grau Sonia , Montrreal Laura , Puerta Raquel , Alarcón-Martín Emilio , Quintela Inés , Orellana Adela , Andrade Victor , Adami Pamela V. Martino , Heilmann-Heimbach Stefanie , Gomez-Garre Pilar , Periñán María Teresa , Alvarez Ignacio , Diez-Fairen Monica , Nuñez Llaves Raul , Olivé Roig Claudia , Garcia-Ribas Guillermo , Menéndez-González Manuel , Martínez Carmen , Aguilar Miquel , Buongiorno Mariateresa , Franco-Macías Emilio , Saez Maria Eugenia , Cano Amanda , Bullido Maria J. , Real Luis Miguel , Rodríguez-Rodríguez Eloy , Royo Jose Luís , Álvarez Victoria , Pastor Pau , Piñol-Ripoll Gerard , Mir Pablo , Lara Miguel Calero , Padilla Miguel Medina , Sánchez-Juan Pascual , Carracedo Angel , Valero Sergi , Hernandez Isabel , Tàrraga Lluis , Ramirez Alfredo , Boada Mercé , Ruiz Agustín
Published: January 2023

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis.
A Bioengineering Strategy to Control ADAM10 Activity in Living Cells
Authors: Pastore Francesco , Battistoni Martina , Sollazzo Raimondo , Renna Pietro , Paciello Fabiola , Li Puma Domenica Donatella , Barone Eugenio , Dagliyan Onur , Ripoli Cristian , Grassi Claudio
Published: January 2023

A Disintegrin and Metalloprotease 10, also known as ADAM10, is a cell surface protease ubiquitously expressed in mammalian cells where it cuts several membrane proteins implicated in multiple physiological processes. The dysregulation of ADAM10 expression and function has been implicated in pathological conditions, including Alzheimer’s disease (AD). Although it has been suggested that ADAM10 is expressed as a zymogen and the removal of the prodomain results in its activation, other potential mechanisms for the ADAM10 proteolytic function and activation remain unclear. Another suggested mechanism is post-translational modification of the cytoplasmic domain, which regulates ADAM10-dependent protein ectodomain shedding. Therefore, the precise and temporal activation of ADAM10 is highly desirable to reveal the fine details of ADAM10-mediated cleavage mechanisms and protease-dependent therapeutic applications. Here, we present a strategy to control prodomain and cytosolic tail cleavage to regulate ADAM10 shedding activity without the intervention of small endogenous molecule signaling pathways. We generated a series of engineered ADAM10 analogs containing Tobacco Etch Virus protease (TEV) cleavage site (TEVcs), rendering ADAM10 cleavable by TEV. This strategy revealed that, in the absence of other stimuli, the TEV-mediated removal of the prodomain could not activate ADAM10. However, the TEV-mediated cleavage of the cytosolic domain significantly increased ADAM10 activity. Then, we generated ADAM10 with a minimal constitutively catalytic activity that increased significantly in the presence of TEV or after activating a chemically activatable TEV. Our results revealed a bioengineering strategy for controlling the ADAM10 activity in living cells, paving the way to obtain spatiotemporal control of ADAM10. Finally, we proved that our approach of controlling ADAM10 promoted α-secretase activity and the non-amyloidogenic cleavage of amyloid-β precursor protein (APP), thereby increasing the production of the neuroprotective soluble ectodomain (sAPPα). Our bioengineering strategy has the potential to be exploited as a next-generation gene therapy for AD.
Vitamin D, Gut Microbiota, and Cardiometabolic Diseases—A Possible Three-Way Axis
Authors: Sukik Ayah , Alalwani Joud , Ganji Vijay
Published: January 2023

Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases such as obesity, type-2 diabetes mellitus (T2DM), and cardiovascular diseases. Emerging evidence suggests that vitamin D deficiency links to cardiometabolic diseases through microbiota. A combination of poor vitamin D status and dysbiosis may contribute to the progression of cardiometabolic diseases. Therefore, in this review, we present the relationship among vitamin D, microbiota, and cardiometabolic diseases with a focus on MetSyn. We searched major databases for reports on vitamin D, microbiota, and MetSyn until June 2022. We reviewed 13 reports on the relation between vitamin D and MetSyn (6 randomized controlled and 7 cross-sectional studies) and 6 reports on the effect of vitamin D on the gut microbiome. Adequate vitamin D status has a beneficial effect on gut microbiota, therefore preventing the progression of MetSyn. Further, well-controlled studies are needed for a better understanding of the mechanisms of action involving vitamin D and microbiota in the pathogenesis of cardiometabolic diseases.
Chloride Channel Family in the Euhalophyte Suaeda altissima (L.) Pall: Cloning of Novel Members SaCLCa2 and SaCLCc2, General Characterization of the Family
Authors: Nedelyaeva Olga I. , Popova Larissa G. , Khramov Dmitrii E. , Volkov Vadim S. , Balnokin Yurii V.
Published: January 2023

CLC family genes, comprising anion channels and anion/H+ antiporters, are widely represented in nearly all prokaryotes and eukaryotes. CLC proteins carry out a plethora of functions at the cellular level. Here the coding sequences of the SaCLCa2 and SaCLCc2 genes, homologous to Arabidopsis thaliana CLCa and CLCc, were cloned from the euhalophyte Suaeda altissima (L.) Pall. Both the genes cloned belong to the CLC family as supported by the presence of the key conserved motifs and glutamates inherent for CLC proteins. SaCLCa2 and SaCLCc2 were heterologously expressed in Saccharomyces cerevisiae GEF1 disrupted strain, Δgef1, where GEF1 encodes the only CLC family protein, the Cl− transporter Gef1p, in undisrupted strains of yeast. The Δgef1 strain is characterized by inability to grow on YPD yeast medium containing Mn2+ ions. Expression of SaCLCa2 in Δgef1 cells growing on this medium did not rescue the growth defect phenotype of the mutant. However, a partial growth restoration occurred when the Δgef1 strain was transformed by SaCLCa2(C544T), the gene encoding protein in which proline, specific for nitrate, was replaced with serine, specific for chloride, in the selectivity filter. Unlike SaCLCa2, expression of SaCLCc2 in Δgef1 resulted in a partial growth restoration under these conditions. Analysis of SaCLCa2 and SaCLCc2 expression in the euhalophyte Suaeda altissima (L.) Pall by quantitative real-time PCR (qRT-PCR) under different growth conditions demonstrated stimulation of SaCLCa2 expression by nitrate and stimulation of SaCLCc2 expression by chloride. The results of yeast complementation assay, the presence of both the “gating” and “proton” glutamates in aa sequences of both the proteins, as well results of the gene expression in euhalophyte Suaeda altissima (L.) Pall suggest that SaCLCa2 and SaCLCc2 function as anion/H+ antiporters with nitrate and chloride specificities, respectively. The general bioinformatic overview of seven CLC genes cloned from euhalophyte Suaeda altissima is given, together with results on their expression in roots and leaves under different levels of salinity.
P. gingivalis-LPS Induces Mitochondrial Dysfunction Mediated by Neuroinflammation through Oxidative Stress
Authors: Verma Ambika , Azhar Gohar , Zhang Xiaomin , Patyal Pankaj , Kc Grishma , Sharma Shakshi , Che Yingni , Wei Jeanne Y.
Published: January 2023

Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis, is associated with neuroinflammation. Periodontal disease increases with age; 70.1% of adults 65 years and older have periodontal problems. However, the P. gingivalis- lipopolysaccharide (LPS)induced mitochondrial dysfunction in neurodegenerative diseases remains elusive. In this study, we investigated the possible role of P. gingivalis-LPS in mitochondrial dysfunction during neurodegeneration. We found that P. gingivalis-LPS treatment activated toll-like receptor (TLR) 4 signaling and upregulated the expression of Alzheimer’s disease-related dementia and neuroinflammatory markers. Furthermore, the LPS treatment significantly exacerbated the production of reactive oxygen species and reduced the mitochondrial membrane potential. Our study highlighted the pivotal role of P. gingivalis-LPS in the repression of serum response factor (SRF) and its co-factor p49/STRAP that regulate the actin cytoskeleton. The LPS treatment repressed the genes involved in mitochondrial function and biogenesis. P. gingivalis-LPS negatively altered oxidative phosphorylation and glycolysis and reduced total adenosine triphosphate (ATP) production. Additionally, it specifically altered the mitochondrial functions in complexes I, II, and IV of the mitochondrial electron transport chain. Thus, it is conceivable that P. gingivalis-LPS causes mitochondrial dysfunction through oxidative stress and inflammatory events in neurodegenerative diseases.
Structural Modifications of siRNA Improve Its Performance In Vivo
Authors: Chernikov Ivan V. , Ponomareva Ulyana A. , Chernolovskaya Elena L.
Published: January 2023

The use of small interfering RNA (siRNA) in the clinic gives a wide range of possibilities for the treatment of previously incurable diseases. However, the main limitation for biomedical applications is their delivery to target cells and organs. Currently, delivery of siRNA to liver cells is a solved problem due to the bioconjugation of siRNA with N-acetylgalactosamine; other organs remain challenging for siRNA delivery to them. Despite the important role of the ligand in the composition of the bioconjugate, the structure and molecular weight of siRNA also play an important role in the delivery of siRNA. The basic principle is that siRNAs with smaller molecular weights are more efficient at entering cells, whereas siRNAs with larger molecular weights have advantages at the organism level. Here we review the relationships between siRNA structure and its biodistribution and activity to find new strategies for improving siRNA performance.
Evaluation of Compressive and Permeability Behaviors of Trabecular-Like Porous Structure with Mixed Porosity Based on Mechanical Topology
Authors: Chao Long , He Yangdong , Gu Jiasen , Xie Deqiao , Yang Youwen , Shen Lida , Wu Guofeng , Wang Lin , Tian Zongjun
Published: January 2023

The mechanical properties and permeability properties of artificial bone implants have high-level requirements. A method for the design of trabecular-like porous structure (TLPS) with mixed porosity is proposed based on the study of the mechanical and permeability characteristics of natural bone. With this technique, the morphology and density of internal porous structures can be adjusted, depending on the implantation requirements, to meet the mechanical and permeability requirements of natural bone. The design parameters mainly include the seed points, topology optimization coefficient, load value, irregularity, and scaling factor. Characteristic parameters primarily include porosity and pore size distribution. Statistical methods are used to analyze the relationship between design parameters and characteristic parameters for precise TLPS design and thereby provide a theoretical basis and guidance. TLPS scaffolds were prepared by selective laser melting technology. First, TLPS under different design parameters were analyzed using the finite element method and permeability simulation. The results were then verified by quasistatic compression and cell experiments. The scaling factor and topology optimization coefficient were found to largely affect the mechanical and permeability properties of the TLPS. The corresponding compressive strength reached 270–580 MPa; the elastic modulus ranged between 6.43 and 9.716 GPa, and permeability was 0.6 × 10−9–21 × 10−9; these results were better than the mechanical properties and permeability of natural bone. Thus, TLPS can effectively improve the success rate of bone implantation, which provides an effective theory and application basis for bone implantation.
Physiological Regulation of Pulmonary Microcirculation under Mechanical Ventilation at Different Cardiac Outputs and Positive End-Expiratory Pressures in a Porcine Model
Authors: Pan Pan , Li Lina , Xie Fei , Hu Xingshuo , Guo Yinghua , Xie Lixin , Su Longxiang
Published: January 2023

This study was performed to visualize the hemodynamic effects of pulmonary microcirculation and ventilation/perfusion (V/Q) matching after mechanical ventilation under different cardiac outputs and positive end-expiratory pressures (PEEPs). Ten experimental pigs were randomly divided into high and low tidal volume groups, and ventilation/perfusion were measured by electrical impedance tomography (EIT) at different PEEPs. Then, all the pigs were redivided into high cardiac output (CO) and low CO groups and measured by EIT at different PEEP levels with a low tidal volume. Additionally, sidestream dark field (SDF) was used to measure pulmonary microcirculation. Hemodynamic parameters and respiratory mechanics parameters were recorded. As PEEP increased at high tidal volume, blood flow was impaired at a higher PEEP (20 cmH2O) compared with low tidal volume (shunt: 30.01 ± 0.69% vs. 17.95 ± 0.72%; V/Q ratio: 65.12 ± 1.97% vs. 76.57 ± 1.25%, p < 0.01). Low tidal volume combined with an appropriate PEEP is the best option from the match between ventilation and pulmonary blood flow. Increasing PEEP can solve the problem of excessive shunt at high CO, and the V/Q ratio tends to match. At low CO, the increased dead space can reach as high as 64.64 ± 7.13% when PEEP = 20 cmH2O. With increasing PEEP, the microcirculation index deteriorates, including total vessel density (TVD), proportion of perfused vessel (PPV), perfused vessel density (PVD), and microcirculatory flow index (MFI). The periodic collapse of pulmonary capillaries or interruption of blood flow obviously occurred with high PEEP. The hemodynamic parameters indicated that the transpulmonary capillary wall pressure (Pcap) of the low CO group was negative at PEEP = 5 cmH2O, which determines the opening and closing of the pulmonary microcirculation and controls lung perfusion and the production of extravascular lung water. Therefore, it is essential to couple macrocirculation and pulmonary microcirculation during mechanical ventilation by improving shunting and optimizing Pcap.
Exploring the Spatial Discrete Heterogeneity of Housing Prices in Beijing, China, Based on Regionally Geographically Weighted Regression Affected by Education
Authors: Wang Zengzheng , Zhang Fuhao , Zhao Yangyang
Published: January 2023

Spatial heterogeneity analysis of housing prices, in general, is crucial for maintaining high-quality economic development in China, especially in the post-COVID-19 pandemic context. Previous studies have attempted to explain the associated geographical evolution by studying the spatial non-stationary continuous heterogeneity; however, they ignored the spatial discrete heterogeneity caused by natural or policy factors, such as education, economy, and population. Therefore, in this study, we take Beijing as an example and consider educational factors in order to propose an improved local regression algorithm called the regionally geographically weighted regression affected by education (E-RGWR), which can effectively address spatial non-stationary discrete heterogeneity caused by education factors. Our empirical study indicates that the R2 and R2adj values of E-RGWR are 0.8644 and 0.8642, which are 10.98% and 11.01% higher than those of GWR, and 3.26% and 3.27% higher than those of RGWR, respectively. In addition, through an analysis of related variables, the quantitative impacts of greening rate, distance to market, distance to hospitals. and construction time on housing prices in Beijing are found to present significant spatial discrete heterogeneity, and a positive relationship between school districts and housing prices was also observed. The obtained evaluation results indicate that E-RGWR can explain the spatial instability of housing prices in Beijing and the spatial discrete heterogeneity caused by education factors. Finally, based on the estimation results of the E-RGWR model, regarding housing prices in Beijing, we analyze the relationships between enrollment policy, real estate sales policy, and housing prices, E-RGWR can provide policy makers with more refined evidence to understand the nature of the centralized change relationship of Beijing’s housing price data in a well-defined manner. The government should not only carry out macro-control, but also implement precise policies for different regions, refine social governance, promote education equity, and boost the economy.
Discussion of the Segregation and Low Hardness of Large-Diameter M3 High-Speed Steel Produced by Spray Forming
Authors: Liu Jihao , Chi Hongxiao , Wu Huibin , Ma Dangshen , Zhou Jian
Published: January 2023

As an advanced near-net-shape processing method in which directly preformed, semi-finished products are created from liquid metals, spray forming has become popular in the development and application of new materials and is supporting industrialization. However, as investigated in this work, the problems of segregation and low hardness exist in the actual industrialization process, particularly for large-diameter M3 high-speed steel. It was here found that the annual ring segregation morphologies were mostly distributed from the edge to 1/2R, with a large number of stripes primarily enriched in C, Mo, and Cr elements, and the degree of segregation was mild. The ring segregation was located at the 1/2R position, where the main elemental enrichments were C, W, Mo, Cr, and V, and the segregation degree was severe. The formation of segregation during deposition is described based on an equilibrium solidification model. A slow cooling rate and heat dissipation from the surface to the inside were judged to be the main factors causing segregation and changes in the carbide morphology. In terms of hardness, with the increase in the quenching temperature to 1230 °C, the tempering hardness increased significantly. The analysis shows that a faster cooling rate in the atomization stage caused the solidified droplets to exhibit rapid solidification characteristics, and there was a higher proportion of MC carbide in the deposited billet. MC carbides cannot be fully dissolved using the conventional heat treatment process, which decreases the C, Cr, Mo, and V contents in the solution and, thus, reduces the secondary hardening capability. The findings show that, when the spray forming process is used to prepare large-diameter materials, it should not be considered a rapid solidification technology simply because of its atomization stage. Moreover, more attention should be paid to the influence of microstructure transformation during atomization and deposition.
The Interaction of Anthracycline Based Quinone-Chelators with Model Lipid Membranes: 1H NMR and MD Study
Authors: Selyutina Olga Yu. , Mastova Anna V. , Polyakov Nikolay E.
Published: January 2023

Anthracycline antibiotics, e.g., doxorubicin, daunomycin, and other anthraquinones, are an important family of antitumor agents widely used in chemotherapy, which is currently the principal method for treating many malignancies. Thus, development of improved antitumor drugs with enhanced efficacy remains a high priority. Interaction of anthraquinone-based anticancer drugs with cell membranes attracts significant attention due to its importance in the eventual overcoming of multidrug resistance (MDR). The use of drugs able to accumulate in the cell membrane is one of the possible ways of overcoming MDR. In the present work, the aspects of interaction of anthraquinone 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione) (Q1) with a model membrane were studied by means of NMR and molecular dynamics simulations. A fundamental shortcoming of anthracycline antibiotics is their high cardiotoxicity caused by reactive oxygen species (ROS). The important feature of Q1 is its ability to chelate transition metal ions responsible for ROS generation in vivo. In the present study, we have shown that Q1 and its chelating complexes penetrated into the lipid membrane and were located in the hydrophobic part of the bilayer near the bilayer surface. The chelate complex formation of Q1 with metal ions increased its penetration ability. In addition, it was found that the interaction of Q1 with lipid molecules could influence lipid mobility in the bilayer. The obtained results have an impact on the understanding of molecular mechanisms of Q1 biological activity.
Effect of Light Emitting Diodes (LED) Exposure on Vitreous Metabolites-Rodent Study
Authors: Theruveethi Nagarajan , Joshi Manjunath B. , Jathanna Judith S. , Valiathan Manna , Kabekkodu Shama Prasada , Bhandarkar Manasa , Thomas R. Huban , Thangarajan Rajesh , Bhat Shailaja S. , Surendran Sudarshan
Published: January 2023

The exposure to blue and white Light emitting diodes (LED) light leads to damage in the visual system with short-term LED light exposure. Chronic exposure, adaptive responses to light, and self-protective mechanisms against LED light exposures need to be explored, and it would be essential to understand the repercussions of LED radiation on vitreous metabolites. A total of 24 male Wistar rats were used in this study, divided into four groups (n = 6 in each group). Three experimental groups of rats were exposed to either blue, white, or yellow LED light for 90 days (12:12 light-dark cycle routine) with uniform illumination (450–500 lux). Standard lab settings were used to maintain control rats. Vitreous fluids were subjected to untargeted metabolomics analysis using liquid chromatography-mass spectrometry (LC/MS). PLS-DA analysis indicated significant the separation of m metabolites among groups, suggesting that LED exposure induces metabolic reprogramming in the vitreous. Amino acids and their modifications showed significant alterations among groups which included D-alanine, D-serine (p < 0.05), lysine (p < 0.001), aspartate (p = 0.0068), glutathione (p = 0.0263), taurine (p = 0.007), and hypotaurine. In chronic light exposure, the self-protective or reworking system could be depleted, which may decrease the ability to compensate for the defending mechanism. This might fail to maintain the metabolomic structural integrity of the vitreous metabolites.
Copper/Zinc Ratio in Childhood and Adolescence: A Review
Authors: Escobedo-Monge Marlene Fabiola , Barrado Enrique , Parodi-Román Joaquín , Escobedo-Monge María Antonieta , Torres-Hinojal María Carmen , Marugán-Miguelsanz José Manuel
Published: January 2023

Both copper (Cu) and zinc (Zn) are crucial micronutrients for human growth and development. This literature review covered the last five years of available evidence on the Cu/Zn ratio in children and adolescents. We searched PubMed, Web of Science, Google Scholar, Cochrane Library, and Science Direct for publications between 2017 and 2022, especially in English, although publications in other languages with abstracts in English were included. The main terms used were “copper”, “zinc”, “copper-zinc”, and “zinc-copper” ratios. Cu and Zn determinations made in blood, plasma, or serum were included. This review comprises several cross-sectional and case–control studies with substantial results. The bibliographic search generated a compilation of 19 articles, in which 63.2% of the studies mostly reported a significantly higher Cu/Zn ratio, and 57.9% of them informed significantly lower levels of Zn. We conclude that children and adolescents with acute and chronic conditions are at greater risk of developing elevated Cu/Zn ratios, related to altered nutritional, infectious, and inflammatory status.
Development of an Automated Design Tool for FEM-Based Characterization of Solid and Hollow Microneedles
Authors: Lechuga Yolanda , Kandel Gregoire , Miguel Jose Angel , Martinez Mar
Published: January 2023

Microneedle design for biomedical applications, such as transdermal drug delivery, vaccination and transdermal biosensing, has lately become a rapidly growing research field. In this sense, finite element analysis has been extendedly used by microneedle designers to determine the most suitable structural parameters for their prototypes, and also to predict their mechanical response and efficiency during the insertion process. Although many proposals include computer-aided tools to build geometrical models for mechanical analysis, there is a lack of software utilities intended to automate the design process encompassing geometrical modeling, simulation setup and postprocessing of results. This work proposes a novel MATLAB-based design tool for microneedle arrays that permits personalized selection of the basic characteristics of a mechanical model. The tool automatically exports the selected options to an ANSYS batch file, including instructions to run a static and a linear buckling analysis. Later, the subsequent simulation results can be retrieved for on-screen display and potential postprocessing. In addition, this work reviews recent proposals (2018–2022) about finite element model characterization of microneedles to establish the minimum set of features that any tool intended for automating a design process should provide.
Percussion and PSO-SVM-Based Damage Detection for Refractory Materials
Authors: Yang Dan , Peng Yi , Zhou Ti , Wang Tao , Lu Guangtao
Published: January 2023

Refractory materials are basic materials widely used in industrial furnaces and thermal equipment. Their microstructure is similar to that of many heterogeneous high-performance materials used in micro/nanodevices. The presence of damage can reduce the mechanical properties and service life of refractory materials and even cause serious safety accidents. In this paper, a novel percussion and particle swarm optimization-support vector machine (PSO-SVM)-based method is proposed to detect damage in refractory materials. An impact is applied to the material and the generated sound is recorded. The percussion-induced sound signals are fed into a mel filter bank to generate time–frequency representations in the form of mel spectrograms. Then, two image descriptors—the local binary pattern (LBP) and histogram of oriented gradient (HOG)—are used to extract the texture information of the mel spectrogram. Finally, combining both HOG and LBP features, the fused features are input to the PSO-SVM algorithm to realize damage detection in refractory materials. The results demonstrated that the proposed method could identify five different degrees of damage of refractory materials, with an accuracy rate greater than 97%. Therefore, the percussion and PSO-SVM-based method proposed in this paper has high potential for field applications in damage detection in refractory material, and also has the potential to be extended to research on damage detection methods for other materials used in micro/nanodevices.
Metal and Oxide Sublimation from Lunar Regolith: A Kinetics Study
Authors: Shaw Matthew , Humbert Matthew , Brooks Geoffrey , Rhamdhani M. , Duffy Alan , Pownceby Mark
Published: January 2023

When considering the extraction of metals from lunar regolith for use in space, one reductive method of interest is vacuum thermal dissociation. Given the high vacuum environment on the Moon, the sub-liquidus operation of such a process, i.e., sublimation, warrants investigation. In the current work, the kinetics of the vacuum sublimation of the more volatile major oxides found in the lunar regolith, Na2O, K2O, and FeO, are evaluated. Two distinct factors are accounted for in the current work: the change in the evaporation flux due to temperature; and the reduction in available surface area for evaporation due to sintering of the feedstock. Surface area change due to the sintering of compressed LMS-1 regolith simulant pellets was quantified via a Brunauer–Emmett–Teller analysis. The surface area of the samples was measured to vary from 3.29 m2/g in the unsintered sample, to 1.04 m2/g in the samples sintered at 800 °C, and down to 0.09 m2/g in the sample sintered at 1150 °C. Evaporation flux was calculated using the Hertz–Knudsen–Langmuir equation using saturated vapor pressures predicted from the FactSage thermochemical package and verified against Knudsen Effusion Mass Spectroscopy data from tests conducted on lunar regolith sample #12022. The combination of these studies resulted in the conclusion that no local maxima in evaporation rate below the melting point was found for the current system, as such the highest rate of sublimation was determined to be 1200 °C for all species, at temperatures of 1200 °C and above, partial melting of the material occurs. The predicted maximum rate of sublimation for the species Fe, Na, and K at 1200 °C was 0.08, 1.38, and 1.02 g/h/g of regolith, respectively. It is noted that significant variation was seen between FactSage predictions of saturated vapor pressures and the measured values. Future work generating detailed thermochemical databases to predict the behavior of complex systems similar in composition to lunar regolith would benefit the accuracy of similar kinetic studies in the future.
Tunable Aryl Alkyl Ionic Liquid Supported Synthesis of Platinum Nanoparticles and Their Catalytic Activity in the Hydrogen Evolution Reaction and in Hydrosilylation
Authors: Woitassek Dennis , Strothmann Till , Biller Harry , Lerch Swantje , Schmitz Henning , Song Yefan , Roitsch Stefan , Strassner Thomas , Janiak Christoph
Published: January 2023

Tunable aryl alkyl ionic liquids (TAAILs) are ionic liquids (ILs) with a 1-aryl-3-alkylimidazolium cation having differently substituted aryl groups. Herein, nine TAAILs with the bis(trifluoromethylsulfonyl)imide anion are utilized in combination with and without ethylene glycol (EG) as reaction media for the rapid microwave synthesis of platinum nanoparticles (Pt-NPs). TAAILs allow the synthesis of small NPs and are efficient solvents for microwave absorption. Transmission electron microscopy (TEM) shows that small primary NPs with sizes of 2 nm to 5 nm are obtained in TAAILs and EG/TAAIL mixtures. The Pt-NPs feature excellent activity as electrocatalysts in the hydrogen evolution reaction (HER) under acidic conditions, with an overpotential at a current density of 10 mA cm−2 as low as 32 mV vs the reversible hydrogen electrode (RHE), which is significantly lower than the standard Pt/C 20% with 42 mV. Pt-NPs obtained in TAAILs also achieved quantitative conversion in the hydrosilylation reaction of phenylacetylene with triethylsilane after just 5 min at 200 °C.