bluuebunny/crossref_metadata_2025 huggingface dataset:
Early and late effects of hyperbaric oxygen treatment on oxidative stress parameters in diabetic patients
Authors: Gürdöl F , Cimşit M , Öner-İyidoğan YZ , Körpinar Ş , Yalçinkaya S , Koçak H
Published: April 2021

Exposure to hyperbaric oxygen leads to increased amount of
reactive oxygen species (ROS) that are derived from various
sources. After the discovery that ROS can function as signaling
molecules, the idea of ROS being hazardous to biological tissues
has been challenged. The aim of this study was to examine the
changes in oxidative stress parameters in diabetics undergoing
hyperbaric oxygen therapy (HBOT) due to foot ulcers. Twenty
patients, who received HBOT for diabetic foot ulcers, were
included in the study. Blood samples were taken before HBOT
and 30 min after exit from the chamber, on the day of the first
and the 15th HBOT sessions. They were used for the
determinations of malondialdehyde (MDA), 8-isoprostane and
advanced oxidation protein products (AOPPs). 8-Isoprostane and
AOPP levels were not altered significantly after the first HBOT
session, while both were increased on the fifteenth day (p<0.05).
MDA was significantly increased only after the first HBOT session,
and remained unchanged on the fifteenth day (within-day
variations). Plasma AOPP levels were lowered significantly after
fifteen consecutive HBOT sessions (between-day variations).
Decreased AOPP levels suggest that increased oxygenation of
tissues due to HBO therapy may activate some endogenous
factors that prevent hazardous effects of the disease itself.
The influence of COVID-19 on air quality in Brasov
Authors: Blaga Larisa , Savescu Dan
Published: April 2021

Population health and air quality represents the objective of nowadays. Environmental
pollution represents its deterioration and involves altering the chemical and structural
characteristics of the natural and anthropogenic components of the environment, diminishing the
diversity or biological productivity of natural ecosystems, affecting the natural environment with
effects on quality of life, mainly caused by pollution. Environmental monitoring becomes a
systematic and methodical concern, achieved through various measurement systems, in order to
ensure the efficient management of all social activities. The Covid-19 pandemic has left its mark
on air quality, reducing the amount of harmful compounds. Consequences of "lockdown" caused
by the COVID-19 have been studied in the city Brasov, from Romania country, where the amount
of suspended particles of 10 microns, respectively 25 microns.
The new European Union Strategic Framework for Roma Integration 2020-2030: Insights and recommendations for the national strategic frameworks
Authors: Ghimisi Andrei
Published: April 2021

The paper “The new European Union Strategic Framework for Roma Integration
2020-2030: Insights and recommendations for the national strategic frameworks” seeks to
present some of the most important elements that target specifically the Roma community in the new EU strategic framework. Moreover, after some crucial aspects of the strategy are presented, some key recommendations are presented for the upcoming national strategic frameworks..
“The Unreasonable Effectiveness of Mathematics”: A Universal Language of Contact?
Authors: Dolgikh Serge
Published: April 2021

In this essay we argue that the expectation that mathematics can serve as a universal foundation and conceptual framework for communication can be based on some implicit anthropocentric assumptions. In our view, the formation of foundations of mathematical thinking, including arithmetic and geometry can be determined to a large extent if not entirely, by the environment and the means of perception and processing of the sensory information about it, and for these reasons can be species-dependent and to a large degree, specific. The conclusion of this analysis is a form of semantic relativism in communication: that no absolute and universal frame of reference may exist for species attempting communication; and therefore, the success of such attempts is determined by finding or establishing a common conceptual frame of reference that is relative to them and specific to them.
Valorization of Enzymatic Hydrolysis Residues from Corncob into Lignin-Containing Cellulose Nanofibrils and Lignin Nanoparticles
Authors: Xu Rui , Du Haishun , Wang Hui , Zhang Meng , Wu Meiyan , Liu Chao , Yu Guang , Zhang Xinyu , Si Chuanling , Choi Sun-Eun , Li Bin
Published: April 2021

As a kind of biomass waste, enzymatic hydrolysis residues (EHRs) are conventionally burned or just discarded, resulting in environmental pollution and low economic benefits. In this study, EHRs of corncob residues (CCR) were used to produce high lignin-containing cellulose nanofibrils (LCNFs) and lignin nanoparticles (LNPs) through a facile approach. The LCNFs and LNPs with controllable chemical compositions and properties were produced by tuning the enzymolysis time of CCR and the followed homogenization. The morphology, thermal stability, chemical and crystalline structure, and dispersibility of the resultant LCNFs and LNPs were further comprehensively investigated. This work not only promotes the production of lignocellulose-based nanomaterials but also provides a promising utilization pathway for EHRs.
Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma
Authors: Yuan Tian , Zheng Rui , Zhou Xiang-min , Jin Peng , Huang Zhi-qun , Zi Xiao-xue , Wu Qing-wu , Wang Wei-hao , Deng Hui-yi , Kong Wei-feng , Qiu Hui-jun , Zhou Sui-zi , Chen Qian-min , Tu Yan-yi , Li Tao , Liu Jing , Tan Kai Sen , Ong Hsiao Hui , Shi Li , Chen Zhuang-gui , Huang Xue-kun , Yang Qin-tai , Wang De-yun
Published: April 2021

Background

Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them.

Methods

We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP’s role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP’s role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP.

Results

The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlated with proliferation and neutrophil infiltration in NIP. YAP expression was also significantly increased in NIP patients with adverse outcomes.

Conclusion

Abnormal expression of YAP/active YAP is associated with proliferation, differentiation, neutrophil infiltration, and adverse outcome in NIP and may present a novel target for diagnosis and intervention in NIP.
RIP1 Perturbation Induces Chondrocyte Necroptosis and Promotes Osteoarthritis Pathogenesis via Targeting BMP7
Authors: Cheng Jin , Duan Xiaoning , Fu Xin , Jiang Yanfang , Yang Peng , Cao Chenxi , Li Qi , Zhang Jiying , Hu Xiaoqing , Zhang Xin , Ao Yingfang
Published: April 2021

Osteoarthritis (OA) is a highly prevalent and debilitating joint disorder that characterized by progressive destruction of articular cartilage. There is no effective disease-modifying therapy for the condition due to limited understanding of the molecular mechanisms on cartilage maintenance and destruction. Receptor-interacting protein kinase 1 (RIP1)-mediated necroptosis plays a vital role in various diseases, but the involvement of RIP1 in OA pathogenesis remains largely unknown. Here we show that typical necrotic cell morphology is observed within human OA cartilage samples in situ, and that RIP1 is significantly upregulated in cartilage from both OA patients and experimental OA rat models. Intra-articular RIP1 overexpression is sufficient to induce structural and functional defects of cartilage in rats, highlighting the crucial role of RIP1 during OA onset and progression by mediating chondrocyte necroptosis and disrupting extracellular matrix (ECM) metabolism homeostasis. Inhibition of RIP1 activity by its inhibitor necrostatin-1 protects the rats from trauma-induced cartilage degradation as well as limb pain. More importantly, we identify bone morphogenetic protein 7 (BMP7) as a novel downstream target that mediates RIP1-induced chondrocyte necroptosis and OA manifestations, thereby representing a non-canonical regulation mode of necroptosis. Our study supports a model whereby the activation of RIP1-BMP7 functional axis promotes chondrocyte necroptosis and subsequent OA pathogenesis, thus providing a new therapeutic target for OA.
Relationship Between Autophagy and Metabolic Syndrome Characteristics in the Pathogenesis of Atherosclerosis
Authors: Xu Jing , Kitada Munehiro , Ogura Yoshio , Koya Daisuke
Published: April 2021

Atherosclerosis is the main cause of mortality in metabolic-related diseases, including cardiovascular disease and type 2 diabetes (T2DM). Atherosclerosis is characterized by lipid accumulation and increased inflammatory cytokines in the vascular wall, endothelial cell and vascular smooth muscle cell dysfunction and foam cell formation initiated by monocytes/macrophages. The characteristics of metabolic syndrome (MetS), including obesity, glucose intolerance, dyslipidemia and hypertension, may activate multiple mechanisms, such as insulin resistance, oxidative stress and inflammatory pathways, thereby contributing to increased risks of developing atherosclerosis and T2DM. Autophagy is a lysosomal degradation process that plays an important role in maintaining cellular metabolic homeostasis. Increasing evidence indicates that impaired autophagy induced by MetS is related to oxidative stress, inflammation, and foam cell formation, further promoting atherosclerosis. Basal and mild adaptive autophagy protect against the progression of atherosclerotic plaques, while excessive autophagy activation leads to cell death, plaque instability or even plaque rupture. Therefore, autophagic homeostasis is essential for the development and outcome of atherosclerosis. Here, we discuss the potential role of autophagy and metabolic syndrome in the pathophysiologic mechanisms of atherosclerosis and potential therapeutic drugs that target these molecular mechanisms.
Structure and Membrane Targeting of the PDZD7 Harmonin Homology Domain (HHD) Associated With Hearing Loss
Authors: Lin Lin , Wang Huang , Ren Decheng , Xia Yitian , He Guang , Lu Qing
Published: April 2021

Usher syndrome (USH) is the leading cause of hereditary hearing–vision loss in humans. PDZ domain-containing 7 (PDZD7) has been reported to be a modifier of and contributor to USH. PDZD7 co-localizes with USH2 proteins in the inner ear hair cells and is essential for ankle-link formation and stereocilia development. PDZD7 contains three PDZ domains and a low-complexity region between the last two PDZ domains, which has been overlooked in the previous studies. Here we characterized a well-folded harmonin homology domain (HHD) from the middle region and solved the PDZD7 HHD structure at the resolution of 1.49 Å. PDZD7 HHD adopts the same five-helix fold as other HHDs found in Harmonin and Whirlin; however, in PDZD7 HHD, a unique α1N helix occupies the canonical binding pocket, suggesting a distinct binding mode. Moreover, we found that the PDZD7 HHD domain can bind lipid and mediate the localization of PDZD7 to the plasma membrane in HEK293T cells. Intriguingly, a hearing-loss mutation at the N-terminal extension region of the HHD can disrupt the lipid-binding ability of PDZD7 HHD, suggesting that HHD-mediated membrane targeting is required for the hearing process. This structural and biochemical characterization of the PDZD7 HHD region provides mechanistic explanations for human deafness-causing mutations in PDZD7. Furthermore, this structure will also facilitate biochemical and functional studies of other HHDs.
Fibrillarin-GFP Facilitates the Identification of Meiotic Competent Oocytes
Authors: Wang Ting , Na Jie
Published: April 2021

The nucleolus undergoes significant functional changes and plays important roles during mammalian oocyte meiotic maturation. Fibrillarin (FBL) is the component of nucleolar small nuclear ribonucleoprotein (snRNP) particle and localizes to the dense fibrillar component (DFC) of the nucleolus. We found that FBL–GFP displays an uneven and cloudy localization in the nucleolus of non-surrounded nucleolus (NSN) oocytes, while it distributes evenly and to a few bright dots in the surrounded nucleolus (SN) oocytes. Accordingly, NSN oocytes showed active nascent RNA transcription, while the SN group was transcriptionally quiescent. NSN geminal vesicles also contained more DNA damage marker γH2AX foci. Based on different FBL–GFP patterns in live oocytes, the ones with superior meiotic maturation potential can be identified. Global transcriptome profiling revealed a significant difference in single SN and NSN oocytes. Thus, FBL–GFP can serve as a marker for nucleolus activity, which also correlates with transcription activity and the quality of oocytes.
Membrane Interactions of the Peroxisomal Proteins PEX5 and PEX14
Authors: Gaussmann Stefan , Gopalswamy Mohanraj , Eberhardt Maike , Reuter Maren , Zou Peijian , Schliebs Wolfgang , Erdmann Ralf , Sattler Michael
Published: April 2021

Human PEX5 and PEX14 are essential components of the peroxisomal translocon, which mediates import of cargo enzymes into peroxisomes. PEX5 is a soluble receptor for cargo enzymes comprised of an N-terminal intrinsically disordered domain (NTD) and a C-terminal tetratricopeptide (TPR) domain, which recognizes peroxisomal targeting signal 1 (PTS1) peptide motif in cargo proteins. The PEX5 NTD harbors multiple WF peptide motifs (WxxxF/Y or related motifs) that are recognized by a small globular domain in the NTD of the membrane-associated protein PEX14. How the PEX5 or PEX14 NTDs bind to the peroxisomal membrane and how the interaction between the two proteins is modulated at the membrane is unknown. Here, we characterize the membrane interactions of the PEX5 NTD and PEX14 NTD in vitro by membrane mimicking bicelles and nanodiscs using NMR spectroscopy and isothermal titration calorimetry. The PEX14 NTD weakly interacts with membrane mimicking bicelles with a surface that partially overlaps with the WxxxF/Y binding site. The PEX5 NTD harbors multiple interaction sites with the membrane that involve a number of amphipathic α-helical regions, which include some of the WxxxF/Y-motifs. The partially formed α-helical conformation of these regions is stabilized in the presence of bicelles. Notably, ITC data show that the interaction between the PEX5 and PEX14 NTDs is largely unaffected by the presence of the membrane. The PEX5/PEX14 interaction exhibits similar free binding enthalpies, where reduced binding enthalpy in the presence of bicelles is compensated by a reduced entropy loss. This demonstrates that docking of PEX5 to PEX14 at the membrane does not reduce the overall binding affinity between the two proteins, providing insights into the initial phase of PEX5-PEX14 docking in the assembly of the peroxisome translocon.
And Then There Were Three…: Extreme Regeneration Ability of the Solitary Chordate Polycarpa mytiligera
Authors: Gordon Tal , Upadhyay Arnav Kumar , Manni Lucia , Huchon Dorothée , Shenkar Noa
Published: April 2021

Extensive regenerative ability is a common trait of animals capable of asexual development. The current study reveals the extraordinary regeneration abilities of the solitary ascidianPolycarpa mytiligera. Dissection of a single individual into separate fragments along two body axes resulted in the complete regeneration of each fragment into an independent, functional individual. The ability of a solitary ascidian, incapable of asexual development, to achieve bidirectional regeneration and fully regenerate all body structures and organs is described here for the first time. Amputation initiated cell proliferation in proximity to the amputation line. Phylogenetic analysis demonstrated the close affinity ofP. mytiligerato colonial species. This evolutionary proximity suggests the ability for regeneration as an exaptation feature for colonial lifestyle.P. mytiligera’s exceptional regenerative abilities and phylogenetic position highlight its potential to serve as a new comparative system for studies seeking to uncover the evolution of regeneration and coloniality among the chordates.
Pannexin 1 Influences Lineage Specification of Human iPSCs
Authors: Noort Rebecca J. , Christopher Grace A. , Esseltine Jessica L.
Published: April 2021

Every single cell in the body communicates with nearby cells to locally organize activities with their neighbors and dysfunctional cell-cell communication can be detrimental during cell lineage commitment, tissue patterning and organ development. Pannexin channels (PANX1, PANX2, and PANX3) facilitate purinergic paracrine signaling through the passage of messenger molecules out of cells. PANX1 is widely expressed throughout the body and has recently been identified in human oocytes as well as 2 and 4-cell stage human embryos. Given its abundance across multiple adult tissues and its expression at the earliest stages of human development, we sought to understand whether PANX1 impacts human induced pluripotent stem cells (iPSCs) or plays a role in cell fate decisions. Western blot, immunofluorescence and flow cytometry reveal that PANX1 is expressed in iPSCs as well as all three germ lineages derived from these cells: ectoderm, endoderm, and mesoderm. PANX1 demonstrates differential glycosylation patterns and subcellular localization across the germ lineages. Using CRISPR-Cas9 gene ablation, we find that loss of PANX1 has no obvious impact on iPSC morphology, survival, or pluripotency gene expression. However, PANX1 gene knockout iPSCs exhibit apparent lineage specification bias under 3-dimensional spontaneous differentiation into the three germ lineages. Indeed, loss of PANX1 increases representation of endodermal and mesodermal populations in PANX1 knockout cells. Importantly, PANX1 knockout iPSCs are fully capable of differentiating toward each specific lineage when exposed to the appropriate external signaling pressures, suggesting that although PANX1 influences germ lineage specification, it is not essential to this process.
Formaldehyde Molecules Adsorption on Zn Doped Monolayer MoS2: A First-Principles Calculation
Authors: Li Huili , Fu Ling , He Chaozheng , Huo Jinrong , Yang Houyong , Xie Tingyue , Zhao Guozheng , Dong Guohui
Published: April 2021

Based on the first principles of density functional theory, the adsorption behavior of H2CO on original monolayer MoS2 and Zn doped monolayer MoS2 was studied. The results show that the adsorption of H2CO on the original monolayer MoS2 is very weak, and the electronic structure of the substrate changes little after adsorption. A new kind of surface single cluster catalyst was formed after Zn doped monolayer MoS2, where the ZnMo3 small clusters made the surface have high selectivity. The adsorption behavior of H2CO on Zn doped monolayer MoS2 can be divided into two situations. When the H-end of H2CO molecule in the adsorption structure is downward, the adsorption energy is only 0.11 and 0.15 eV and the electronic structure of adsorbed substrate changes smaller. When the O-end of H2CO molecule is downward, the interaction between H2CO and the doped MoS2 is strong leading to the chemical adsorption with the adsorption energy of 0.80 and 0.98 eV. For the O-end-down structure, the adsorption obviously introduces new impurity states into the band gap or results in the redistribution of the original impurity states. All of these may lead to the change of the chemical properties of the doped MoS2 monolayer, which can be used to detect the adsorbed H2CO molecules. The results show that the introduction of appropriate dopant may be a feasible method to improve the performance of MoS2 gas sensor.
Modular Approaches to Synthesize Activity- and Affinity-Based Chemical Probes
Authors: van der Zouwen Antonie J. , Witte Martin D.
Published: April 2021

Combinatorial and modular methods to synthesize small molecule modulators of protein activity have proven to be powerful tools in the development of new drug-like molecules. Over the past decade, these methodologies have been adapted toward utilization in the development of activity- and affinity-based chemical probes, as well as in chemoproteomic profiling. In this review, we will discuss how methods like multicomponent reactions, DNA-encoded libraries, phage displays, and others provide new ways to rapidly screen novel chemical probes against proteins of interest.
Free-Standing N-Doped Porous Carbon Fiber Membrane Derived From Zn–MOF-74: Synthesis and Application as Anode for Sodium-Ion Battery With an Excellent Performance
Authors: Xue Kaiwen , Si Yechen , Xie Shuya , Yang Jingxuan , Mo Yan , Long Baojun , Wei Wen , Cao Peiyu , Wei Huixian , Guan Hongyu , Michaelis Elizabeth G. , Guo George , Yue Yanfeng , Shan Changsheng
Published: April 2021

It is important to develop new energy storage and conversion technology to mitigate the energy crisis for the sustainable development of human society. In this study, free-standing porous nitrogen-doped carbon fiber (PN-CF) membranes were obtained from the pyrolysis of Zn–MOF-74/polyacrylonitrile (PAN) composite fibers, which were fabricated in situ by an electrospinning technology. The resulting free-standing fibers can be cut into membrane disks and directly used as an anode electrode without the addition of any binder or additive. The PN-CFs showed great reversible capacities of 210 mAh g−1 at a current density of 0.05 A g−1 and excellent cyclic stability of 170.5 mAh g−1 at a current density of 0.2 A g−1 after 600 cycles in sodium ion batteries (SIBs). The improved electrochemical performance of PN-CFs can be attributed to the rich porous structure derived by the incorporation of Zn–MOF-74 and nitrogen doping to promote sodium ion transportation.
MicroRNA Profiles in Normotensive and Hypertensive South African Individuals
Authors: Matshazi Don M. , Weale Cecil J. , Erasmus Rajiv T. , Kengne Andre P. , Davids Saarah F. G. , Raghubeer Shanel , Hector Stanton , Davison Glenda M. , Matsha Tandi E.
Published: April 2021

Hypertension has a complex pathogenesis and symptoms appear in advanced disease. Dysregulation of gene expression regulatory factors like microRNAs has been reported in disease development. Identifying biomarkers which could help understand the pathogenesis and prognosis of hypertension is essential. The study's objective was to investigate microRNA expression profiles according to participant blood pressure status. Next generation sequencing was used to identify microRNAs in the whole blood of 48 body mass index-, smoking- and age-matched normotensive (n = 12), screen-detected hypertensive (n = 16) and known hypertensive (n = 20) female participants. Quantitative reverse transcription polymerase chain reaction was used to validate the next generation sequencing findings in a larger, independent sample of 84 men and 179 women. Using next generation sequencing, 30 dysregulated microRNAs were identified and miR-1299 and miR-30a-5p were the most significantly differentially expressed. Both microRNAs were upregulated in known hypertensives or screen-detected hypertensives compared to the normotensives. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated possible involvement of platelet activation, calcium signaling and aldosterone synthesis pathways. Further validation of miR-1299 and miR-30a-5p using quantitative reverse transcription polymerase chain reaction confirmed sequencing results while yielding new findings. These findings demonstrate microRNA dysregulation in hypertension and their expression may be related to genes and biological pathways essential for blood pressure homeostasis.
Influence of Internal Structure on Breaking Process of Short-Lived Landslide Dams
Authors: Meng Chu-Ke , Chen Kun-Ting , Niu Zhi-Pan , Di Bao-Feng , Ye Yu-Jian
Published: April 2021

The diversity of the landslide dam structure will result in the difference in the dam body’s seepage. In this paper, based on two kinds of soil bodies of different particle gradations, fourteen groups of structures of the landslide dam are designed to generalize different seepage developments and breaking processes. The study shows that the saturation and seepage evolution characteristics of the landslide dam's seepage have a considerable influence on the landslide dam’s breaking characteristics. An empirical formula is fitted according to the time-seepage degree curve of the landslide dams of different breaking processes to predict the breaking forms of the landslide dams before the dam break. During the water storage process of the landslide dam, the seepage's saturation process inside the dam body reduces the stability of the landslide dam, thus affecting the evolution of the failure process after it has started. In the experiment, it is found that the growth rate of the seepage degree of the landslide dam is inversely proportional to the growth rate of the dam breach area. Although the internal penetration of landslide dams is usually undervalued, the result verifies that the study on the seepage process before the breaking of landslide dam is conductive for further understanding the breaking mechanism of the landslide dam.
Applicability and Variability of Chemical Weathering Indicators and Their Monsoon-Controlled Mechanisms in the Bay of Bengal
Authors: Li Jingrui , Liu Shengfa , Shi Xuefa , Zhang Hui , Cao Peng , Li Xiaoyan , Pan Hui-Juan , Khokiattiwong Somkiat , Kornkanitnan Narumol
Published: April 2021

To help understanding the potential relationship between chemical weathering and Indian summer monsoon (ISM) since the last glacial period a gravity core (BoB-56) was retrieved from the central Bay of Bengal (BoB). The data of chemical weathering indexes (CIA, WIP, and αAlNa) used in this study showed general synchronicity with the regional monsoon precipitation and temperature record on precessional scale, indicating existence of control from the ISM on weathering. Corresponding to alteration of warm/cold period during the last deglaciation, obvious simultaneously alteration of higher/lower values of the chemical weathering and terrestrial input proxies’ record support our hypothesis that the ISM driving chemical weathering on the millennial scale. However, a contradiction occurred during the Holocene period, when the ISM precipitation and temperature rose to a higher level, while the alternative indexes unanimously reflected a weaker chemical weathering conditions. In this study, we discussed the applicability of chemical weathering indexes in the BoB during the Holocene period. Besides the possible weakened monsoon during 6–3 ka, recorded by the stalagmite δ18O and Sea Surface Temperature (SST) reconstruction results in the northeastern Indian Ocean, other factors were responsible for this phenomenon, including the grain size effect and distinction between the mountain high land and floodplain low land. The chemical weathering records, during the last glaciation, indicated the presence of control from the ISM on weathering at precessional and millennial scales. While, during the Holocene, they failed to reflect the actual chemical weathering dynamics of the source area. Indeed, a mixture of physical erosion and chemical weathering seems to be representative of the chemical weathering dynamics in the area. Our findings emphasized on the tight connections between the chemical weathering evolution and global-regional climate conditions around the BoB, implying possible ISM-controlled mechanisms during different time scales.
Quantitative Measurement of Retained Oil in Organic-Rich Shale—A Case Study on the Chang 7 Member in the Ordos Basin, China
Authors: Hou Lianhua , Luo Xia , Lin Senhu , Zhao Zhongying , Li Yong
Published: April 2021

This study proposes a method to calculate the retained oil content (WO) in cores collected by a sealed tool from organic-rich shale with thermal maturity around%Ro = 0.8 in the Ordos Basin, China. Approaches such as soaking cores at low temperature, multiple extractions, multiple pyrolysis, and multiple chromatographic analyses were conducted and then the relationships between total retained oil content and mineral compositions were analyzed. The total retained oil content measured by the method proposed in this paper is 60–260% higher than that measured by a conventional pyrolysis method and 34–69% higher than the sum (WO) of two extractions with dichloromethane (WO3) and chloroform (WO4). After extractions with dichloromethane and chloroform (WO5), the oil retained in the organic-rich shale was 4.7–11.6%, which has not been extracted. Positive correlations exist between WO (i.e., WO3 + WO4) and total organic carbon (TOC) and S1 (absorbed hydrocarbon by rock pyrolysis), and WO has the highest correlation coefficient with the former. The method can provide important guidance for the objective analysis of retained oil in organic-rich shale, and it is reliable for the evaluation of shale oil reserves.
Black Hole-Inspired Optimal Design of Biomethane Liquefaction Process for Small-Scale Applications
Authors: He Tianbiao , Qyyum Muhammad Abdul , Zhou Zhongming , Ahmad Ashfaq , Rehan Mohammad , Nizami Abdul-Sattar , Lee Moonyong
Published: April 2021

Biomethane is regarded as a promising renewable energy source, with great potential to satisfy the growth of energy demands and to reduce greenhouse gas emissions. Liquefaction is a suitable approach for long distances and overseas transportation of biomethane; however, it is energy-intensive due to its cryogenic working condition. The major challenge is to design a high-energy efficiency liquefaction process with simple operation and configuration. A single mixed refrigerant biomethane liquefaction process adopting the cryogenic liquid turbine for small-scale production has been proposed in this study to address this issue. The optimal design corresponding to minimal energy consumption was obtained through the black-hole-based optimization algorithm. The effect of the minimum internal temperature approach (MITA) in the main cryogenic heat exchanger on the biomethane liquefaction process performance was investigated. The study results indicated that the specific energy consumption of modified case 2 with MITA of 2°C was 0.3228 kWh/kg with 21.01% reduction compared to the published base case. When the MITA decreased to 1°C, the specific power of modified case 1 reduced to 0.3162 kWh/kg, which was 24.96% lower than the base case. In terms of exergy analysis, the total exergy destruction of the modified cases 1, 2, and 3 was 31.28%, 22.27%, and 17.51% lower than the base case, respectively. This study’s findings suggested that introducing the cryogenic liquid turbine to the single mixed refrigerant-based biomethane liquefaction process could reduce the specific energy consumption and total exergy destruction significantly. Therefore, this study could provide a viable path for designing and improving the small-scale biomethane liquefaction process.
WingBank: A Wing Image Database of Mosquitoes
Authors: Virginio Flávia , Domingues Victor , da Silva Letícia Cecília Gomes , Andrade Lucas , Braghetto Kelly Rosa , Suesdek Lincoln
Published: April 2021

Mosquito-borne diseases affect millions of people and cause thousands of deaths yearly. Vaccines have been hitherto insufficient to mitigate them, which makes mosquito control the most viable approach. But vector control depends on correct species identification and geographical assignment, and the taxonomic characters of mosquitoes are often inconspicuous to non-taxonomists, which are restricted to a life stage and/or even damaged. Thus, geometric morphometry, a low cost and precise technique that has proven to be efficient for identifying subtle morphological dissimilarities, may contribute to the resolution of these types of problems. We have been applying this technique for more than 10 years and have accumulated thousands of wing images with their metadata. Therefore, the aims of this work were to develop a prototype of a platform for the storage of biological data related to wing morphometry, by means of a relational database and a web system named “WingBank.” In order to build the WingBank prototype, a multidisciplinary team performed a gathering of requirements, modeled and designed the relational database, and implemented a web platform. WingBank was designed to enforce data completeness, to ease data query, to leverage meta-studies, and to support applications of automatic identification of mosquitoes. Currently, the database of the WingBank contains data referring to 77 species belonging to 15 genera of Culicidae. From the 13,287 wing records currently cataloged in the database, 2,138 were already made available for use by third parties. As far as we know, this is the largest database of Culicidae wings of the world.
Sequence Read Depth Analysis of a Monophyletic Cluster of Y Chromosomes Characterized by Structural Rearrangements in the AZFc Region Resulting in DYS448 Deletion and DYF387S1 Duplication
Authors: Ravasini Francesco , D’Atanasio Eugenia , Bonito Maria , Bonucci Biancamaria , Della Rocca Chiara , Berti Andrea , Trombetta Beniamino , Cruciani Fulvio
Published: April 2021

The azoospermia factor c region (AZFc), located in the long arm of the human Y chromosome, is frequently involved in chromosome rearrangements, mainly due to non-allelic homologous recombination events that occur between the nearly identical sequences (amplicon) that comprises it. These rearrangements may have major phenotypic effects like spermatogenic failure or other pathologies linked to male infertility. Moreover, they may also be relevant in forensic genetics, since some of the Y chromosome short tandem repeats (Y-STRs) commonly used in forensic analysis are located in amplicons or in inter-amplicon sequences of the AZFc. In a previous study, we identified four phylogenetically related samples with a null allele at DYS448 and a tetrallelic pattern at DYF387S1, two Y-STRs located in the AZFc. Through NGS read depth analysis, we found that the unusual Y-STR pattern may be due to a 1.6 Mb deletion arising concurrently or after a 3.5 Mb duplication event. The observed large genomic rearrangement results in copy number reduction for the RBMY gene family as well as duplication of other AZFc genes. Based on the diversity of 16 additional Y-STRs, we estimated that the duplication/deletion event occurred at least twenty generations ago, suggesting that it has not been affected by negative selection.
Establishing a Risk Prediction Model for Atherosclerosis in Systemic Lupus Erythematosus
Authors: Xing Haiping , Pang Haiyu , Du Tian , Yang Xufei , Zhang Jing , Li Mengtao , Zhang Shuyang
Published: April 2021

Background and aims: Patients with systemic lupus erythematosus (SLE) have a significantly higher incidence of atherosclerosis than the general population. Studies on atherosclerosis prediction models specific for SLE patients are very limited. This study aimed to build a risk prediction model for atherosclerosis in SLE.

Methods: RNA sequencing was performed on 67 SLE patients. Subsequently, differential expression analysis was carried out on 19 pairs of age-matched SLE patients with (AT group) or without (Non-AT group) atherosclerosis using peripheral venous blood. We used logistic least absolute shrinkage and selection operator regression to select variables among differentially expressed (DE) genes and clinical features and utilized backward stepwise logistic regression to build an atherosclerosis risk prediction model with all 67 patients. The performance of the prediction model was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses.

Results: The 67 patients had a median age of 42.7 (Q1–Q3: 36.6–51.2) years, and 20 (29.9%) had atherosclerosis. A total of 106 DE genes were identified between the age-matched AT and Non-AT groups. Pathway analyses revealed that the AT group had upregulated atherosclerosis signaling, oxidative phosphorylation, and interleukin (IL)-17-related pathways but downregulated T cell and B cell receptor signaling. Keratin 10, age, and hyperlipidemia were selected as variables for the risk prediction model. The AUC and Hosmer–Lemeshow test p-value of the model were 0.922 and 0.666, respectively, suggesting a relatively high discrimination and calibration performance. The prediction model had a higher net benefit in the decision curve analysis than that when predicting with age or hyperlipidemia only.

Conclusions: We built an atherosclerotic risk prediction model with one gene and two clinical factors. This model may greatly assist clinicians to identify SLE patients with atherosclerosis, especially asymptomatic atherosclerosis.
AhR Ligands Modulate the Differentiation of Innate Lymphoid Cells and T Helper Cell Subsets That Control the Severity of a Pulmonary Fungal Infection
Authors: de Araújo Eliseu F. , Loures Flávio V. , Preite Nycolas W. , Feriotti Cláudia , Galdino Nayane AL , Costa Tânia A. , Calich Vera L. G.
Published: April 2021

In agreement with other fungal infections, immunoprotection in pulmonary paracoccidioidomycosis (PCM) is mediated by Th1/Th17 cells whereas disease progression by prevalent Th2/Th9 immunity. Treg cells play a dual role, suppressing immunity but also controlling excessive tissue inflammation. Our recent studies have demonstrated that the enzyme indoleamine 2,3 dioxygenase (IDO) and the transcription factor aryl hydrocarbon receptor (AhR) play an important role in the immunoregulation of PCM. To further evaluate the immunomodulatory activity of AhR in this fungal infection, Paracoccidioides brasiliensis infected mice were treated with two different AhR agonists, L-Kynurenin (L-Kyn) or 6-formylindole [3,2-b] carbazole (FICZ), and one AhR specific antagonist (CH223191). The disease severity and immune response of treated and untreated mice were assessed 96 hours and 2 weeks after infection. Some similar effects on host response were shared by FICZ and L-Kyn, such as the reduced fungal loads, decreased numbers of CD11c+ lung myeloid cells expressing activation markers (IA, CD40, CD80, CD86), and early increased expression of IDO and AhR. In contrast, the AhR antagonist CH223191 induced increased fungal loads, increased number of pulmonary CD11c+ leukocytes expressing activation markers, and a reduction in AhR and IDO production. While FICZ treatment promoted large increases in ILC3, L-Kyn and CH223191 significantly reduced this cell population. Each of these AhR ligands induced a characteristic adaptive immunity. The large expansion of FICZ-induced myeloid, lymphoid, and plasmacytoid dendritic cells (DCs) led to the increased expansion of all CD4+ T cell subpopulations (Th1, Th2, Th17, Th22, and Treg), but with a clear predominance of Th17 and Th22 subsets. On the other hand, L-Kyn, that preferentially activated plasmacytoid DCs, reduced Th1/Th22 development but caused a robust expansion of Treg cells. The AhR antagonist CH223191 induced a preferential expansion of myeloid DCs, reduced the number of Th1, Th22, and Treg cells, but increased Th17 differentiation. In conclusion, the present study showed that the pathogen loads and the immune response in pulmonary PCM can be modulated by AhR ligands. However, further studies are needed to define the possible use of these compounds as adjuvant therapy for this fungal infection.
Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation
Authors: Papp Gábor , Szabó Krisztina , Jámbor Ilona , Mile Marianna , Berki Alexandra Réka , Arany Attila Csaba , Makra Gabriella , Szodoray Peter , Csiki Zoltán , Balogh László
Published: April 2021

Age-related changes of the immune system lead to an increased morbidity and mortality due to enhanced vulnerability to infectious diseases and malignancies. Recent studies revealed the important effects of physical activity on immune functions, which may largely depend on the type of exercise, its intensity and duration. However, limited information is available regarding the immunological effects of sport activities in older ages. The aim of our study was to examine the changes in a wide spectrum of lymphocyte subtypes after regular workout among healthy elderly individuals. We enrolled 29 elderly women with sedentary lifestyle (mean age: 67.03 ± 3.74 years) to take part in a 6-week long functional conditioning gymnastic exercise program. The percentages of peripheral natural killer (NK), NKT cells, T and B lymphocyte subtypes (early-/late-activated T, naïve and memory T, cytotoxic T (Tc), T-helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), CD4+CD127lo/-CD25bright Treg, as well as naïve and memory B cells) were determined by flow cytometry. Evaluation of the changes in functional capability of Treg cells was based on in vitro functional assays. At the end of exercise program, in parallel with improvements in body composition and physical performance, significant changes in naïve and memory lymphocyte ratios were observed. Importantly, levels of naïve Tc cells elevated, ratios of effector memory Tc cells decreased and distribution of memory B cells rearranged as well. Additionally, proportions of late-activated HLA-DR+ T cells increased, while percentages of anti-inflammatory interleukin (IL)-10 producing Tr1 cells, as well as immunosuppressive CD4+CD127lo/-CD25bright Treg cells decreased following the exercise workout. Changes observed after the regular exercise program indicate an improvement in the age-related redistribution of certain naïve and memory cell proportions and a retuned immune regulation in older ages.
Mesenchymal Stromal Cell-Derived Extracellular Vesicles Restore Thymic Architecture and T Cell Function Disrupted by Neonatal Hyperoxia
Authors: Reis Monica , Willis Gareth R. , Fernandez-Gonzalez Angeles , Yeung Vincent , Taglauer Elizabeth , Magaletta Margaret , Parsons Teagan , Derr Alan , Liu Xianlan , Maehr Rene , Kourembanas Stella , Mitsialis S. Alex
Published: April 2021

Treating premature infants with high oxygen is a routine intervention in the context of neonatal intensive care. Unfortunately, the increase in survival rates is associated with various detrimental sequalae of hyperoxia exposure, most notably bronchopulmonary dysplasia (BPD), a disease of disrupted lung development. The effects of high oxygen exposure on other developing organs of the infant, as well as the possible impact such disrupted development may have on later life remain poorly understood. Using a neonatal mouse model to investigate the effects of hyperoxia on the immature immune system we observed a dramatic involution of the thymic medulla, and this lesion was associated with disrupted FoxP3+ regulatory T cell generation and T cell autoreactivity. Significantly, administration of mesenchymal stromal cell-derived extracellular vesicles (MEx) restored thymic medullary architecture and physiological thymocyte profiles. Using single cell transcriptomics, we further demonstrated preferential impact of MEx treatment on the thymic medullary antigen presentation axis, as evidenced by enrichment of antigen presentation and antioxidative-stress related genes in dendritic cells (DCs) and medullary epithelial cells (mTECs). Our study demonstrates that MEx treatment represents a promising restorative therapeutic approach for oxygen-induced thymic injury, thus promoting normal development of both central tolerance and adaptive immunity.
Opportunities and Challenges in Democratizing Immunology Datasets
Authors: Bhattacharya Sanchita , Hu Zicheng , Butte Atul J.
Published: April 2021

The field of immunology is rapidly progressing toward a systems-level understanding of immunity to tackle complex infectious diseases, autoimmune conditions, cancer, and beyond. In the last couple of decades, advancements in data acquisition techniques have presented opportunities to explore untapped areas of immunological research. Broad initiatives are launched to disseminate the datasets siloed in the global, federated, or private repositories, facilitating interoperability across various research domains. Concurrently, the application of computational methods, such as network analysis, meta-analysis, and machine learning have propelled the field forward by providing insight into salient features that influence the immunological response, which was otherwise left unexplored. Here, we review the opportunities and challenges in democratizing datasets, repositories, and community-wide knowledge sharing tools. We present use cases for repurposing open-access immunology datasets with advanced machine learning applications and more.
Genome-Wide Gene Expression Analysis of Mtb-Infected DC Highlights the Rapamycin-Driven Modulation of Regulatory Cytokines via the mTOR/GSK-3β Axis
Authors: Etna Marilena P. , Severa Martina , Licursi Valerio , Pardini Manuela , Cruciani Melania , Rizzo Fabiana , Giacomini Elena , Macchia Gianfranco , Palumbo Orazio , Stallone Raffaella , Carella Massimo , Livingstone Mark , Negri Rodolfo , Pellegrini Sandra , Coccia Eliana M.
Published: April 2021

In human primary dendritic cells (DC) rapamycin—an autophagy inducer and protein synthesis inhibitor—overcomes the autophagy block induced by Mycobacterium tuberculosis (Mtb) and promotes a Th1 response via IL-12 secretion. Here, the immunostimulatory activity of rapamycin in Mtb-infected DC was further investigated by analyzing both transcriptome and translatome gene profiles. Hundreds of differentially expressed genes (DEGs) were identified by transcriptome and translatome analyses of Mtb-infected DC, and some of these genes were found further modulated by rapamycin. The majority of transcriptome-associated DEGs overlapped with those present in the translatome, suggesting that transcriptionally stimulated mRNAs are also actively translated. In silico analysis of DEGs revealed significant changes in intracellular cascades related to cytokine production, cytokine-induced signaling and immune response to pathogens. In particular, rapamycin treatment of Mtb-infected DC caused an enrichment of IFN-β, IFN-λ and IFN-stimulated gene transcripts in the polysome-associated RNA fraction. In addition, rapamycin led to an increase of IL-12, IL-23, IL-1β, IL-6, and TNF-α but to a reduction of IL-10. Interestingly, upon silencing or pharmacological inhibition of GSK-3β, the rapamycin-driven modulation of the pro- and anti-inflammatory cytokine balance was lost, indicating that, in Mtb-infected DC, GSK-3β acts as molecular switch for the regulation of the cytokine milieu. In conclusion, our study sheds light on the molecular mechanism by which autophagy induction contributes to DC activation during Mtb infection and points to rapamycin and GSK-3β modulators as promising compounds for host-directed therapy in the control of Mtb infection.