bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic and Environmental Assessment of Plastic Waste Pyrolysis Products and Biofuels as Substitutes for Fossil-Based Fuels
Authors: Pacheco-López Adrián , Lechtenberg Fabian , Somoza-Tornos Ana , Graells Moisès , Espuña Antonio
Published: June 2021

The global economy is shifting toward more sustainable sources of energy. The transportation sector is a remarkable example of this fact, where biofuels have emerged as promising alternatives to traditional fossil fuels. This work presents a techno-economic and environmental assessment of existing liquid fuels in hard-to-decarbonize sectors and their emerging renewable substitutes. The comparison focuses on fossil-based, biomass-derived, and plastic waste-sourced fuel alternatives that can be used in spark-ignition (gasoline) and compression-ignition (diesel) engines. Results for diesel substitutes prove the superior performance of plastic waste pyrolysis oil in terms of production cost reduction (−25% compared to diesel) and “well-to-tank” life cycle impact reduction (−54% human health, −40% ecosystems, −98% resources). Consequently, research and development toward the conversion of plastic waste into fuels should be extended to make the technology more accessible and robust in terms of fuel quality. On the contrary, the results for gasoline alternatives are not as conclusive: bioethanol and ethanol from plastic pyrolysis have a considerably lower impact on resource scarcity than gasoline (−80% and −35% respectively) and higher on the other two life cycle endpoint categories, but they have higher production costs compared to gasoline (+57% and +130% respectively). While blends of gasoline with pyrolysis-sourced ethanol can reduce the impact on human health and ecosystems, blends with bioethanol have a lower impact on resource scarcity and increase economic profitability. This allows fuel providers to offer tradeoff solutions in the form of blends based on their priorities.
Come Rain, Come Shine: Peatland Carbon Dynamics Shift Under Extreme Precipitation
Authors: Barel Janna M. , Moulia Vincent , Hamard Samuel , Sytiuk Anna , Jassey Vincent E. J.
Published: June 2021

Precipitation patterns are becoming increasingly extreme, particularly at northern latitudes. Current climate models predict that this trend will continue in the future. While droughts have been repeatedly studied in many ecosystems over the last decades, the consequences of increasingly intense, but less frequent rainfall events, on carbon (C) cycling are not well understood. At northern latitudes, peatlands store one third of the terrestrial carbon and their functioning is highly dependent on water. Shifts in rainfall regimes could disrupt peatland C dynamics and speed-up the rates of C loss. How will these immense stocks of C be able to withstand and recover from extreme rainfall? We tested the resistance and resilience effects of extreme precipitation regimes on peatland carbon dioxide (CO2) and methane (CH4) fluxes, pore water dissolved organic carbon (DOC) and litter decomposition rates by exposing intact peat cores to extreme, spring-time rainfall patterns in a controlled mesocosm experiment. We find that more intense but less frequent rainfall destabilized water table dynamics, with cascading effects on peatland C fluxes. Decomposition and respiration rates increased with a deeper mean water table depth (WTD) and larger WTD fluctuations. We observed similar patterns for CO2 uptake, which were likely mediated by improved vascular plant performance. After a three-week recovery period, CO2 fluxes still displayed responses to the earlier WTD dynamics, suggesting lagged effects of precipitation regime shifts. Furthermore, we found that CH4 emissions decreased with deeper mean WTD, but this showed a high resilience once WTD dynamics stabilised. Not only do our results illustrate that shifting rainfall patterns translate in altered WTD dynamics and, consequentially, influence C fluxes, they also demonstrate that exposure to altered rainfall early in the growing season can have lasting effects on CO2 exchange. Even though the increased CO2 assimilation under extreme precipitation patterns signals peatland resistance under changing climatic conditions, it may instead mark the onset of vascular plant encroachment and the associated C loss.
Assessing Lignin Decomposition and Soil Organic Carbon Contents Across a Tropical Savannah-Rainforest Boundary in Guyana
Authors: Black Jasmine E. , Wagner Thomas , Abbott Geoffrey D.
Published: June 2021

The soils beneath the rainforest of Guyana have the potential to hold, and release, large stores of carbon under land use and climate change. Little is known about soil carbon stocks or molecular dynamics in this region. This study therefore aims to elucidate differences in the molecular (lignin and tannin) and bulk soil organic carbon (SOC) stocks in different ‘sub-environments’ along a rainforest-savannah boundary, setting a framework for further investigation into the soil carbon dynamics of the region. Bulk SOC analysis shows that Gleysols have the highest stocks, particularly those under rainforest vegetation (swamp and island forests surrounded by savannah), whereas Plinthosols have significantly lower SOC stocks. Texture and soil water content analysis indicates that predominantly clay soils play a role in high SOC stocks, whilst predominantly sandy soils prevent SOC stocks from accumulating. Clay and sand are present in both Gleysols and Plinthosols, to different extents. Analysis of lignin and tannin in surface soils of the sub-environments reveals clear differences in molecular composition. Heavily degraded lignin signatures in rainforest Gleysols suggests a surrounding physio-chemical environment which promotes their degradation. Conversely, Plinthosols beneath woodland within the savannah have the greatest amount of lignin and tannin products. The presence of the clay mineral kaolinite and iron oxide strengite in these soils indicates a low ability for protection or complexing of organic matter. Therefore, water content and microbial activity may play a more important role in the degradation of lignin and tannin, as well as the SOC stock. With the potential for future deforestation due to land use or climate change, the high lignin degradation of Gleysols indicates a vulnerability to savannah encroachment. Forest Islands isolated from the main forest biome are the most vulnerable to change, and could lose a significant proportion of their SOC stock in a transition to savannah.
Downregulated F-Box/LRR-Repeat Protein 7 Facilitates Pancreatic Cancer Metastasis by Regulating Snail1 for Proteasomal Degradation
Authors: Tang Liang , Ji Meng , Liang Xing , Chen Danlei , Liu Anan , Yang Guang , Shi Ligang , Fu Zhiping , Shao Chenghao
Published: June 2021

Pancreatic cancer (PCa) is one of the most aggressive lethal malignancies, and cancer metastasis is the major cause of PCa-associated death. F-box/LRR-repeat protein 7 (FBXL7) regulates cancer metastasis and the chemosensitivity of human pancreatic cancer. However, the clinical significance and biological role of FBXL7 in PCa have been rarely studied. In this study, we found that the expression of FBXL7 was down-regulated in PCa tissues compared with tumor-adjacent tissues, and the low expression of FBXL7 was positively associated with cancer metastasis. Functionally, overexpression of FBXL7 attenuated PANC1 cell invasion, whereas FBXL7 silencing promoted BxPC-3 cell invasion. Forced expression of FBXL7 upregulated the expression of epithelial markers (e.g., E-cadherin) and repressed the expression of mesenchymal markers (e.g., N-cadherin and Vimentin), indicating that FBXL7 negatively regulated the epithelial-mesenchymal transition (EMT) of PCa cells. Furthermore, we identified that FBXL7 repressed the expression of Snail1, a crucial transcription factor of EMT. Mechanistically, FBXL7 bound to Snail1 and promoted its ubiquitination and proteasomal degradation. In vivo studies demonstrated that FBXL7 inhibition promotes PCa metastasis. Taken together, our findings demonstrate that FBXL7 knockdown could efficiently enhance PCa metastasis by regulating Snail1-dependent EMT.
Identification of an EMT-Related Gene Signature for Predicting Overall Survival in Gastric Cancer
Authors: Dai Weiyu , Xiao Yizhi , Tang Weimei , Li Jiaying , Hong Linjie , Zhang Jieming , Pei Miaomiao , Lin Jianjiao , Liu Side , Wu Xiaosheng , Xiang Li , Wang Jide
Published: June 2021

Background

It has been widely reported that epithelial-mesenchymal transition (EMT) is associated with malignant progression in gastric cancer (GC). Integration of the molecules related to EMT for predicting overall survival (OS) is meaningful for understanding the role of EMT in GC. Here, we aimed to establish an EMT-related gene signature in GC.

Methods

Transcriptional profiles and clinical data of GC were downloaded from The Cancer Genome Atlas (TCGA). We constructed EMT-related gene signature for predicting OS by using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier analysis were performed to assess its predictive value. A nomogram combining the prognostic signature with clinical characteristics for OS prediction was established. And its predictive power was estimated by concordance index (C-index), time-dependent ROC curve, calibration curve and decision curve analysis (DCA). GSE62254 dataset from Gene Expression Omnibus (GEO) was used for external validation. Quantitative real-time PCR (qRT-PCR) was used to detected the mRNA expression of the five EMT-related genes in human normal gastric mucosal and GC cell lines. To further understand the potential mechanisms of the signature, Gene Set Enrichment Analysis (GSEA), pathway enrichment analysis, predictions of transcription factors (TFs)/miRNAs were performed.

Results

A novel EMT-related gene signature (including ITGAV, DAB2, SERPINE1, MATN3, PLOD2) was constructed for OS prediction of GC. With external validation, ROC curves indicated the signature’s good performance. Patients stratified into high- and low-risk groups based on the signature yielded significantly different prognosis. Univariate and multivariate Cox regression suggested that the signature was an independent prognostic variable. Nomogram for prognostication including the signature presented better predictive accuracy and clinical usefulness than the similar model without risk score to some extent with external validation. The qRT-PCR assays suggested that high expression of the five EMT-related genes could be found in human GC cell lines compared with normal gastric mucosal cell line. GSEA and pathway enrichment analysis revealed that focal adhesion and ECM-receptor interaction might be the two important pathways to the signature.

Conclusion

Our EMT-related gene signature may have practical application as an independent prognostic factor in GC.
SARS-CoV-2 in Pregnancy: Fitting Into the Existing Viral Repertoire
Authors: Rajput Roopali , Sharma Jitender
Published: June 2021

The risk of viral infection during pregnancy is well-documented; however, the intervention modalities that in practice enable maternal-fetal protection are restricted by limited understanding. This becomes all the more challenging during pandemics. During many different epidemic and pandemic viral outbreaks, worse outcomes (fetal abnormalities, mortality, preterm labor, etc.) seem to affect pregnant women than what has been evident when compared to non-pregnant women. The condition of pregnancy, which is widely understood as “immunosuppressed,” needs to be re-understood in terms of the way the immune system works during such a state. The immune system gets transformed to accommodate and facilitate fetal growth. The interference of such supportive conversion by viral infection and the risk of co-infection lead to adverse fetal outcomes. Hence, it is crucial to understand the risk and impact of potent viral infections likely to be encountered during pregnancy. In the present article, we review the effects imposed by previously established and recently emerging/re-emerging viral infections on maternal and fetal health. Such understanding is important in devising strategies for better preparedness and knowing the treatment options available to mitigate the relevant adverse outcomes.
Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation
Authors: Bongers Suzanne H. , Chen Na , van Grinsven Erinke , van Staveren Selma , Hassani Marwan , Spijkerman Roy , Hesselink Lilian , Lo Tam Loi Adèle T. , van Aalst Corneli , Leijte Guus P. , Kox Matthijs , Pickkers Peter , Hietbrink Falco , Leenen Luke P. H. , Koenderman Leo , Vrisekoop Nienke
Published: June 2021

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62Llow neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62Llow neutrophils appeared in the peripheral blood several days (>3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16low and CD62Llow subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16low or CD62Llow neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease.
Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer
Authors: Huang Bilian , Zhu Linjing , Wei Hongxia , Shi Haixia , Zhang Doudou , Yuan Huanyun , Luan Linlin , Zheng Nan , Xu Shijie , Nawaz Waqas , Hong Ying , Wu Xilin , Wu Zhiwei
Published: June 2021

Cervical cancer caused by human papillomavirus (HPV) infections is the fourth most common cancer in women worldwide. Current prophylactic HPV vaccines have achieved promising success in preventing HPV infection. However, still 570,000 new cases were reported in 2018. The current primary treatment for the patient with cervical cancer is either surgery or chemoradiotherapy. Cervical cancer still lacks standard medical therapy. HPV18 induced cervical cancer has the worst prognosis and high mortality compared to other HPV infections. The development of HPV18 related with cervical malignancy requires the persistent infection of cervical–vaginal epithelium by HPV18 subtype, which can take years to transform the epithelium. This period of repeated infection provides a window for therapeutic intervention. Neutralizing antibodies formulated as topical agents that inhibit HPV18 infection should reduce the chance of cervical malignancy. We previously demonstrated that potent neutralizing anti-sera against HPV18 infection were induced by HPV18 viral like particle (VLP) generated in mammalian cells. We, therefore, isolated two potent neutralizing antibodies, 2A12 and 8H4, from over 3,810 hybridomas prepared from mice immunized with HPV18 VLP. 2A12 and 8H4 exhibited excellent potency, with 50% virus-inhibitory concentrations (IC50) of 0.4 and 0.9 ng/ml, respectively. Furthermore, 2A12 and 8H4 recognized distinct and non-overlapping quaternary epitopes and bound specifically with HPV18. Humanized 2A12 (Hu2A12) retained comparable neutralizing activity against HPV18 infection in various acidic pH settings and in hydrogel formulation with IC50 values of 0.04 to 0.77 ng/ml, indicating that Hu2A12 will be a promising candidate for clinical development as a topical vaginal biopharmaceutical agent against HPV18 infection.
The Role of microRNAs and Long Non-Coding RNAs in the Regulation of the Immune Response to Mycobacterium tuberculosis Infection
Authors: Kundu Manikuntala , Basu Joyoti
Published: June 2021

Non-coding RNAs have emerged as critical regulators of the immune response to infection. MicroRNAs (miRNAs) are small non-coding RNAs which regulate host defense mechanisms against viruses, bacteria and fungi. They are involved in the delicate interplay between Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and its host, which dictates the course of infection. Differential expression of miRNAs upon infection with M. tuberculosis, regulates host signaling pathways linked to inflammation, autophagy, apoptosis and polarization of macrophages. Experimental evidence suggests that virulent M. tuberculosis often utilize host miRNAs to promote pathogenicity by restricting host-mediated antibacterial signaling pathways. At the same time, host- induced miRNAs augment antibacterial processes such as autophagy, to limit bacterial proliferation. Targeting miRNAs is an emerging option for host-directed therapies. Recent studies have explored the role of long non-coding RNA (lncRNAs) in the regulation of the host response to mycobacterial infection. Among other functions, lncRNAs interact with chromatin remodelers to regulate gene expression and also function as miRNA sponges. In this review we attempt to summarize recent literature on how miRNAs and lncRNAs are differentially expressed during the course of M. tuberculosis infection, and how they influence the outcome of infection. We also discuss the potential use of non-coding RNAs as biomarkers of active and latent tuberculosis. Comprehensive understanding of the role of these non-coding RNAs is the first step towards developing RNA-based therapeutics and diagnostic tools for the treatment of TB.
Regulatory Dendritic Cells Induced by Bendamustine Are Associated With Enhanced Flt3 Expression and Alloreactive T-Cell Death
Authors: Molina Megan S. , Hoffman Emely A. , Stokes Jessica , Kummet Nicole , Smith Kyle A. , Baker Forrest , Zúñiga Tiffany M. , Simpson Richard J. , Katsanis Emmanuel
Published: June 2021

The growth factor Flt3 ligand (Flt3L) is central to dendritic cell (DC) homeostasis and development, controlling survival and expansion by binding to Flt3 receptor tyrosine kinase on the surface of DCs. In the context of hematopoietic cell transplantation, Flt3L has been found to suppress graft-versus-host disease (GvHD), specifically via host DCs. We previously reported that the pre-transplant conditioning regimen consisting of bendamustine (BEN) and total body irradiation (TBI) results in significantly reduced GvHD compared to cyclophosphamide (CY)+TBI. Pre-transplant BEN+TBI conditioning was also associated with greater Flt3 expression among host DCs and an accumulation of pre-cDC1s. Here, we demonstrate that exposure to BEN increases Flt3 expression on both murine bone marrow-derived DCs (BMDCs) and human monocyte-derived DCs (moDCs). BEN favors development of murine plasmacytoid DCs, pre-cDC1s, and cDC2s. While humans do not have an identifiable equivalent to murine pre-cDC1s, exposure to BEN resulted in decreased plasmacytoid DCs and increased cDC2s. BEN exposure and heightened Flt3 signaling are associated with a distinct regulatory phenotype, with increased PD-L1 expression and decreased ICOS-L expression. BMDCs exposed to BEN exhibit diminished pro-inflammatory cytokine response to LPS and induce robust proliferation of alloreactive T-cells. These proliferative alloreactive T-cells expressed greater levels of PD-1 and underwent increased programmed cell death as the concentration of BEN exposure increased. Alloreactive CD4+ T-cell death may be attributable to pre-cDC1s and provides a potential mechanism by which BEN+TBI conditioning limits GvHD and yields T-cells tolerant to host antigen.
Glycogen Synthase Kinase 3 Gene Is Important in Growth and Molting of the Pacific White Shrimp Litopenaeus vannamei
Authors: Pang Ying , Zhang Xiaojun , Yuan Jianbo , Zhang Xiaoxi , Su Manwen , Li Fuhua
Published: June 2021

Glycogen synthase kinase 3 (GSK3) is a vital multifunctional molecule that is widely distributed in invertebrates and vertebrates. GSK3 is a highly conserved serine/threonine (Ser/Thr) protein kinase, which plays an important role in insulin, Wnt, and various signaling pathways. In this study, a GSK3 gene were identified in the genome of the Pacific white shrimp, Litopenaeus vannamei, and analyzed its gene structure, phylogeny, and expression profiles. The deduced LvGSK3 protein contains a highly conserved Ser/Thr protein kinase catalytic (S_TKc) domain, the LvGSK3 gene exhibited high expression in different early developmental stages, most adult tissues, and premolting stages. RNA interference of LvGSK3 significantly retarded the increment of body weight and affected the expressions of molting-related genes compared with control groups. These results will improve our understanding of the conserved structure and functions of the LvGSK3 gene and show potential applications of shrimp growth.
Occurrence and Habitat Characteristics of Aurelia sp. Polyps in a High-Latitude Fjord
Authors: Rekstad Matias Einer , Majaneva Sanna , Borgersen Åshild Løvas , Aberle Nicole
Published: June 2021

Causes and consequences of jellyfish bloom formation are subject to controversial discussions worldwide. While medusae have been studied to a broader extent, the knowledge on polyp stages of scyphozoans is limited thus hampering reliable prediction of jellyfish bloom formation. This study describes the occurrence, abundance, habitat characteristics and interactions of scyphozoan Aurelia sp. polyp colonies with other fouling organisms in intertidal and subtidal sectors of Trondheimsfjorden (Norway). In total, 982 polyps were found on 70 substrata of varying material types during a field survey in spring-summer 2018 along a longitudinal gradient within and outside Trondheimsfjorden. The polyps were identified as Aurelia sp. based on molecular species identification. Most polyps were found in bays with macroalgae canopy on the down facing side of artificial and natural substrata (rocks, concrete, iron) and inside rock cracks. Polyp microhabitats included the surface of Ascidia mentula (solitary ascidian), increments of Pomatoceros triqueter (polychete) tubes and dead Balanus balanoides (barnacle) shells. Based on the deployment of settling plates, abundance of Aurelia sp. polyps ranged from 1.2 (± 0.7) to 0.12 (± 0.07) polyps cm–2. Settlement occurred either directly on the PVC settling plates or as epibionts on the ascidian Ascidia mentula and on barnacle shells of Balanus balanoides. This study provides insights into the potential of local Aurelia sp. polyps contributing to the seasonal occurrence and abundance of Aurelia sp. in fjord systems, where intensive blooms occur annually.
Perspective for a New Bioinspired Permanent Adhesive for dry Conditions - Insights in the Glue Producing Japanese art of Defence System of the Oita Salamander Hynobius dunni
Authors: von Byern Janek , Farkaš Robert , Steinort Daniel , Greistorfer Sophie , Eckhard Margret , Cyran Norbert
Published: June 2021

Novel medical bioadhesives are proposed to fulfil numerous ideals as being biocompatible, non-toxic, include tissue healing and regeneration characteristics, have high mechanical properties onto different surfaces and other important key features. Mussel-inspired adhesives have provided the basis for many new applications under wet conditions. In contrast, the defence secretion system in amphibians may provide potential for novel fast-curing secretion able to adhere to surfaces under dry conditions. With the microanatomical and histochemical characterization of the endemic Japanese Oita salamanderHynobius dunnidetails on its anatomical organization, the nature of the chemical composition of both glue-producing glands and its divergence to the other well-characterized speciesPlethodon shermaniare discussed. The study shows that the cutaneous glands of both glue-producing salamanders (H. dunniandP. shermani) exhibit certain morphological and histochemical similarities. Nevertheless, clear differences exist between the two species, especially with regard to the sugar composition of the mucous glands and the pH level of the granular glands. Moreover, the adhesive secretions ofH. dunnishow a clear reactivity to Arnow staining (indicating the presence of L-DOPA), which is lacking inP. shermani. This is the first indication of the presence of L-DOPA in the adhesive secretions of a terrestrial vertebrate, which has thus far only been found for marine invertebrates, such as mussels and polychaetes.
Case Report: Analysis of Circulating Tumor Cells in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient
Authors: Rossi Tania , Palleschi Michela , Angeli Davide , Tebaldi Michela , Martinelli Giovanni , Vannini Ivan , Puccetti Maurizio , Limarzi Francesco , Maltoni Roberta , Gallerani Giulia , Fabbri Francesco
Published: June 2021

Circulating tumor cells (CTCs) are a rare population of cells found in the bloodstream and represent key players in the metastatic cascade. Their analysis has proved to provide further core information concerning the tumor. Herein, we aim at investigating CTCs isolated from a 32-year-old patient diagnosed with triple negative spindle-shaped metaplastic breast cancer (MpBC), a rare tumor poorly responsive to therapies and with a dismal prognosis. The molecular analysis performed on the primary tumor failed to underline effective actionable targets to address the therapeutic strategy. Besides the presence of round-shaped CTCs, cells with a spindle shape were present as well, and through molecular analysis, we confirmed their malignant nature. This aspect was coherent with the primary tumor histology, proving that CTCs are released regardless of their morphology. Copy number aberration (CNA) profiling and variant analysis using next-generation sequencing (NGS) showed that these cells did not harbor the alterations exhibited by the primary tumor (PIK3CA G1049A mutation, MYC copy number gain). However, despite the great heterogeneity observed, the amplification of regions involved in metastasis emerged (8q24.22–8q24.23). Our findings support the investigation of CTCs to identify alterations that could have a role in the metastatic process. To the best of our knowledge, this is the first examination of CTCs in an MpBC patient.
Recombinant Enzymatic Redox Systems for Preparation of Aroma Compounds by Biotransformation
Authors: Varga Viktor , Štefuca Vladimír , Mihálová Lenka , Levarski Zdenko , Struhárňanská Eva , Blaško Jaroslav , Kubinec Robert , Farkaš Pavel , Sitkey Vladimír , Turňa Ján , Rosenberg Michal , Stuchlík Stanislav
Published: June 2021

The aim of this study was to develop immobilized enzyme systems that reduce carbonyl compounds to their corresponding alcohols. The demand for natural aromas and food additives has been constantly growing in recent years. However, it can no longer be met by extraction and isolation from natural materials. One way to increase the availability of natural aromas is to prepare them by the enzymatic transformation of suitable precursors. Recombinant enzymes are currently being used for this purpose. We investigatedtrans-2-hexenal bioreduction by recombinantSaccharomyces cerevisiaealcohol dehydrogenase (ScADH1) with simultaneous NADH regeneration by recombinantCandida boidiniiformate dehydrogenase (FDH). In a laboratory bioreactor with two immobilized enzymes, 88% of thetrans-2-hexenal was transformed totrans-2-hexenol. The initial substrate concentration was 3.7 mM. The aldehyde destabilized ScADH1 by eluting Zn2+ions from the enzyme. A fed-batch operation was used and thetrans-2-hexenal concentration was maintained at a low level to limit the negative effect of Zn2+ion elution from the immobilized ScADH1. Another immobilized two-enzyme system was used to reduce acetophenone to (S)-1-phenylethanol. To this end, the recombinant alcohol dehydrogenase (RrADH) fromRhodococcus ruberwas used. This biocatalytic system converted 61% of the acetophenone to (S)-1-phenylethanol. The initial substrate concentration was 8.3 mM. All enzymes were immobilized by poly-His tag to Ni2+, which formed strong but reversible bonds that enabled carrier reuse after the loss of enzyme activity.
Systematic Review: Genetic, Neuroimaging, and Fluids Biomarkers for Frontotemporal Dementia Across Latin America Countries
Authors: Duran-Aniotz Claudia , Orellana Paulina , Leon Rodriguez Tomas , Henriquez Fernando , Cabello Victoria , Aguirre-Pinto María F. , Escobedo Tamara , Takada Leonel T. , Pina-Escudero Stefanie D. , Lopez Oscar , Yokoyama Jennifer S. , Ibanez Agustin , Parra Mario A. , Slachevsky Andrea
Published: June 2021

Frontotemporal dementia (FTD) includes a group of clinically, genetically, and pathologically heterogeneous neurodegenerative disorders, affecting the fronto-insular-temporal regions of the brain. Clinically, FTD is characterized by progressive deficits in behavior, executive function, and language and its diagnosis relies mainly on the clinical expertise of the physician/consensus group and the use of neuropsychological tests and/or structural/functional neuroimaging, depending on local availability. The modest correlation between clinical findings and FTD neuropathology makes the diagnosis difficult using clinical criteria and often leads to underdiagnosis or misdiagnosis, primarily due to lack of recognition or awareness of FTD as a disease and symptom overlap with psychiatric disorders. Despite advances in understanding the underlying neuropathology of FTD, accurate and sensitive diagnosis for this disease is still lacking. One of the major challenges is to improve diagnosis in FTD patients as early as possible. In this context, biomarkers have emerged as useful methods to provide and/or complement clinical diagnosis for this complex syndrome, although more evidence is needed to incorporate most of them into clinical practice. However, most biomarker studies have been performed using North American or European populations, with little representation of the Latin American and the Caribbean (LAC) region. In the LAC region, there are additional challenges, particularly the lack of awareness and knowledge about FTD, even in specialists. Also, LAC genetic heritage and cultures are complex, and both likely influence clinical presentations and may modify baseline biomarker levels. Even more, due to diagnostic delay, the clinical presentation might be further complicated by both neurological and psychiatric comorbidity, such as vascular brain damage, substance abuse, mood disorders, among others. This systematic review provides a brief update and an overview of the current knowledge on genetic, neuroimaging, and fluid biomarkers for FTD in LAC countries. Our review highlights the need for extensive research on biomarkers in FTD in LAC to contribute to a more comprehensive understanding of the disease and its associated biomarkers. Dementia research is certainly reduced in the LAC region, highlighting an urgent need for harmonized, innovative, and cross-regional studies with a global perspective across multiple areas of dementia knowledge.
Changes in EEG Brain Connectivity Caused by Short-Term BCI Neurofeedback-Rehabilitation Training: A Case Study
Authors: Wang Youhao , Luo Jingjing , Guo Yuzhu , Du Qiang , Cheng Qiying , Wang Hongbo
Published: June 2021

Background

In combined with neurofeedback, Motor Imagery (MI) based Brain-Computer Interface (BCI) has been an effective long-term treatment therapy for motor dysfunction caused by neurological injury in the brain (e.g., post-stroke hemiplegia). However, individual neurological differences have led to variability in the single sessions of rehabilitation training. Research on the impact of short training sessions on brain functioning patterns can help evaluate and standardize the short duration of rehabilitation training. In this paper, we use the electroencephalogram (EEG) signals to explore the brain patterns’ changes after a short-term rehabilitation training.

Materials and Methods

Using an EEG-BCI system, we analyzed the changes in short-term (about 1-h) MI training data with and without visual feedback, respectively. We first examined the EEG signal’s Mu band power’s attenuation caused by Event-Related Desynchronization (ERD). Then we use the EEG’s Event-Related Potentials (ERP) features to construct brain networks and evaluate the training from multiple perspectives: small-scale based on single nodes, medium-scale based on hemispheres, and large-scale based on all-brain.

Results

Results showed no significant difference in the ERD power attenuation estimation in both groups. But the neurofeedback group’s ERP brain network parameters had substantial changes and trend properties compared to the group without feedback. The neurofeedback group’s Mu band power’s attenuation increased but not significantly (fitting line slope = 0.2, t-test value p > 0.05) after the short-term MI training, while the non-feedback group occurred an insignificant decrease (fitting line slope = −0.4, t-test value p > 0.05). In the ERP-based brain network analysis, the neurofeedback group’s network parameters were attenuated in all scales significantly (t-test value: p < 0.01); while the non-feedback group’s most network parameters didn’t change significantly (t-test value: p > 0.05).

Conclusion

The MI-BCI training’s short-term effects does not show up in the ERD analysis significantly but can be detected by ERP-based network analysis significantly. Results inspire the efficient evaluation of short-term rehabilitation training and provide a useful reference for subsequent studies.
Proximal Disruption of Brain Energy Supply Raises Systemic Blood Glucose: A Systematic Review
Authors: Sprengell Marie , Kubera Britta , Peters Achim
Published: June 2021

This work joins a series that methodically tests the predictions of the Selfish-Brain theory. The theory postulates a vital ability of the mammalian brain, namely to give priority to its own energy metabolism. The brain behaves “selfishly” in this respect. For the cerebral artery occlusion studied here, the theory predicts an increase in blood glucose concentration, what becomes the hypothesis to be tested. We conducted a systematic review of cerebral-artery-occlusion papers to test whether or not the included studies could confirm this hypothesis. We identified 239 records, screened 231 works by title or abstract, and analyzed 89 by full text. According to strict selection criteria (set out in our PROSPERO preregistration, complying with PRISMA guidelines), 7 papers provided enough information to decide on the hypothesis. Our hypothesis could be fully confirmed for the 3 to 24 h after the onset of a transient 2 h or permanent occlusion. As for the mechanism, the theory predicts that the energy-deprived brain suppresses insulin secretion via the sympathoadrenal system, thereby preventing insulin-mediated glucose uptake into muscle and fat and, as a result, enhancing insulin-independent glucose uptake via the blood-brain barrier. Evidence from our included studies actually demonstrated cerebral insulin suppression. In all, the current work confirms the second major prediction of the Selfish-Brain theory that relates to a proximal bottleneck of the cerebral supply chain, cerebral artery occlusion. Its first major prediction relates to a distal supply bottleneck, caloric restriction, and is fulfilled as shown by our previous work, whereas the prediction of the long held gluco-lipostatic theory, which sees the brain as only passively supplied, is violated (Sprengell et al., 2021). The crucial point was that caloric restriction elicits smaller changes in mass (energy) in the brain than in the body. Taken together, the evidence from the current and previous work clearly shows that the most accurate predictions are possible with a theory that views the brain as an independently self-regulating energy compartment occupying a primary position in energy metabolism.
Identification of the Potential Gene Regulatory Networks and Therapeutics in Aged Mice With Postoperative Neurocognitive Disorder
Authors: Wu Wensi , Peng Yongpai , Zhou Jiaxin , Zhang Xiaojun , Cao Lin , Lin Wei-jye , Lu Yanan , Wen Jing , Wang Zhi
Published: June 2021

Postoperative neurocognitive disorder (PND) is one of the most common postoperative neurological complications in aged patients, characterized by mental disorder, anxiety, personality changes, and impaired memory. At present, the molecular mechanism of PND remains largely unclear, and the ideal biomarker for clinical diagnosis and prognosis are lacking. Circular RNA (circRNA) and microRNA (miRNA), as unique non-coding RNAs, affecting the regulation of miRNAs on genes and further intervening in the progression of diseases through the sponge action between the two. Besides, it could be served as novel biomarkers in various diseases. In order to detect the differential expression profiles of genes caused by PND, a total of 26 18-month-old male C57BL/6 mice were randomly assigned to control group and PND group. Behavioral tests showed that mice in the PND group had impaired cognitive function compared with the control group. Three mice in each group were randomly selected to harvest the brain for analysis the expressions of circRNAs, miRNAs, and mRNAs in the prefrontal cortex by next-generation sequencing (NGS) technology. Differentially expressed genes, including 1192 circRNAs, 27 miRNAs, and 266 mRNAs were identified, and its accuracy was further confirmed by qRT-PCR. Bioinformatics analysis results suggested that neuroinflammation was the main pathological mechanism of PND. The construction of competitive endogenous RNA (ceRNA) networks and the identification of hub genes provided possible therapeutic targets for PND. Cinnarizine and Clemastine were predicted to have the potential therapeutic effects on PND. This is the first study to explore the differential expression profiles of genes and their regulation mechanisms in PND, our results provided new clues and targets for the treatment of this refractory disease.
Role of the Dopaminergic System in the Striatum and Its Association With Functional Recovery or Rehabilitation After Brain Injury
Authors: Verduzco-Mendoza Antonio , Carrillo-Mora Paul , Avila-Luna Alberto , Gálvez-Rosas Arturo , Olmos-Hernández Adriana , Mota-Rojas Daniel , Bueno-Nava Antonio
Published: June 2021

Disabilities are estimated to occur in approximately 2% of survivors of traumatic brain injury (TBI) worldwide, and disability may persist even decades after brain injury. Facilitation or modulation of functional recovery is an important goal of rehabilitation in all patients who survive severe TBI. However, this recovery tends to vary among patients because it is affected by the biological and physical characteristics of the patients; the types, doses, and application regimens of the drugs used; and clinical indications. In clinical practice, diverse dopaminergic drugs with various dosing and application procedures are used for TBI. Previous studies have shown that dopamine (DA) neurotransmission is disrupted following moderate to severe TBI and have reported beneficial effects of drugs that affect the dopaminergic system. However, the mechanisms of action of dopaminergic drugs have not been completely clarified, partly because dopaminergic receptor activation can lead to restoration of the pathway of the corticobasal ganglia after injury in brain structures with high densities of these receptors. This review aims to provide an overview of the functionality of the dopaminergic system in the striatum and its roles in functional recovery or rehabilitation after TBI.
Effect of Almond Consumption on Metabolic Risk Factors—Glucose Metabolism, Hyperinsulinemia, Selected Markers of Inflammation: A Randomized Controlled Trial in Adolescents and Young Adults
Authors: Madan Jagmeet , Desai Sharvari , Moitra Panchali , Salis Sheryl , Agashe Shubhada , Battalwar Rekha , Mehta Anushree , Kamble Rachana , Kalita Soumik , Phatak Ajay Gajanan , Udipi Shobha A. , Vaidya Rama A. , Vaidya Ashok B.
Published: June 2021

A large percentage of the Indian population has diabetes or is at risk of pre-diabetes. Almond consumption has shown benefits on cardiometabolic risk factors in adults. This study explored the effect of almond consumption on determinants of metabolic dysfunction—blood glucose, lipids, insulin and selected inflammatory markers in adolescents and young adults aged 16–25 years from Mumbai city. This randomized controlled trial was conducted for a period of 90 days on individuals with impaired levels of fasting glucose levels between 100–125 mg/dL (5.6–6.9 mmol/L) and 2-h post-glucose value 140–199 mg/dL (7.8–11.0 mmol/L) and/or fasting insulin (≥15 mIU/ml)/stimulated insulin (≥80 mIU/ml). Of 1,313 individuals screened, 421 met the inclusion criteria, of which 275 consented to participate and 219 completed the trial. The trial was registered with Clinical Trials Registry India (CTRI) CTRI/2018/02/011927. The almonds group (n = 107) consumed 56 g almonds daily, the control group (n = 112) was provided an iso-caloric cereal-pulse based snack. At baseline and endline, blood glucose, insulin, HbA1c, LDL-c, HDL-c, total and ox-cholesterol, triglycerides, hs-CRP, IL-6, TNF-α, adiponectin, leptin were measured and HOMA-IR and FG:FI ratios were calculated. Dietary intakes were assessed. The anthropometric measurements, biochemical markers as well as macronutrient intakes did not differ significantly between the two groups at baseline. Almond consumption significantly decreased HbA1c, total cholesterol and LDL-c. Stimulated insulin decreased post-intervention in both groups, but the decrease was greater in the almonds group. Fasting glucose was reduced post intervention in the controls with no change in the almonds group. FG:FI ratio decreased in the almonds group. TNF-α and IL-6 decreased in the almonds group, while it increased in the control group. Our results showed that almonds reduced HbA1c, LDL-c and total cholesterol levels in just 12 weeks of consumption in these adolescents and young adults who were at risk for developing diabetes. Almonds can be considered as part of food-based strategies for preventing pre-diabetes.

Clinical Trial Registration:ClinicalTrials.gov, identifier: CTRI/2018/02/011927.
Exploratory Analysis of 18F-3’-deoxy-3’-fluorothymidine (18F-FLT) PET/CT-Based Radiomics for the Early Evaluation of Response to Neoadjuvant Chemotherapy in Patients With Locally Advanced Breast Cancer
Authors: Fantini Lorenzo , Belli Maria Luisa , Azzali Irene , Loi Emiliano , Bettinelli Andrea , Feliciani Giacomo , Mezzenga Emilio , Fedeli Anna , Asioli Silvia , Paganelli Giovanni , Sarnelli Anna , Matteucci Federica
Published: June 2021

Purpose

The objective of this study was to evaluate a set of radiomics-based advanced textural features extracted from 18F-FLT-PET/CT images to predict tumor response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (BC).

Materials and Methods

Patients with operable (T2-T3, N0-N2, M0) or locally advanced (T4, N0-N2, M0) BC were enrolled. All patients underwent chemotherapy (six cycles every 3 weeks). Surgery was performed within 4 weeks of the end of NCT. The MD Anderson Residual Cancer Burden calculator was used to evaluate the pathological response. 18F-FLT-PET/CT was performed 2 weeks before the start of NCT and approximately 3 weeks after the first cycle. The evaluation of PET response was based on EORTC criteria. Standard uptake value (SUV) statistics (SUVmax, SUVpeak, SUVmean), together with 148 textural features, were extracted from each lesion. Indices that are robust against contour variability (ICC test) were used as independent variables to logistically model tumor response. LASSO analysis was used for variable selection.

Results

Twenty patients were included in the study. Lesions from 15 patients were evaluable and analyzed: 9 with pathological complete response (pCR) and 6 with pathological partial response (pPR). Concordance between PET response and histological examination was found in 13/15 patients. LASSO logistic modelling identified a combination of SUVmax and the textural feature index IVH_VolumeIntFract_90 as the most useful to classify PET response, and a combination of PET response, ID range, and ID_Coefficient of Variation as the most useful to classify pathological response.

Conclusions

Our study suggests the potential usefulness of FLT-PET for early monitoring of response to NCT. A model based on PET radiomic characteristics could have good discriminatory capacity of early response before the end of treatment.
Loss of TARBP2 Drives the Progression of Hepatocellular Carcinoma via miR-145-SERPINE1 Axis
Authors: Li Li-Man , Chen Chang , Ran Ruo-Xi , Huang Jing-Tao , Sun Hui-Lung , Zeng Chang , Zhang Zhou , Zhang Wei , Liu Song-Mei
Published: June 2021

The clinical outcomes of hepatocellular carcinoma (HCC) remain dismal. Elucidating the molecular mechanisms for the progression of aggressive HCC holds the promise for developing novel intervention strategies. The transactivation response element RNA-binding protein (TRBP/TARBP2), a key component of microRNA (miRNA) processing and maturation machinery has been shown to play conflicting roles in tumor development and progression. We sought to investigate the expression of TARBP2 in HCC using well-characterized HCC cell lines, patient-derived tissues and blood samples. Additionally, the potential prognostic and diagnostic value of TARBP2 in HCC were analyzed using Kaplan-Meier plots and ROC curve. Cell counting kit‐8 (CCK‐8), wound healing and transwell assays examined the ability of TARBP2 to induce cell proliferation, migration, and invasion in HCC cell lines. RNA sequencing was applied to identify the downstream elements of TARBP2. The interaction of potential targets of TARBP2, miR‐145 and serpin family E member 1 (SERPINE1), was assessed using luciferase reporter assay. TARBP2 expression was down-regulated in HCC cell lines relative to normal hepatocyte cells, with a similar pattern further confirmed in tissue and blood samples. Notably, the loss of TARBP2 was demonstrated to promote proliferation, migration, and invasion in HCC cell lines. Interestingly, the reduction of TARBP2 was shown to result in the upregulation of SERPINE1, also known as plasminogen activator inhibitor (PAI-1), which is a vital gene of the HIF-1 signaling pathway. Knockdown of SERPINE1 rescued the TARBP2-lost phenotype. Moreover, TARBP2 depletion induced the upregulation of SERPINE1 through reducing the processing of miR-145, which directly targets SERPINE1. Finally, overexpression of miR-145 repressed SERPINE1 and rescued the functions in sh-TARBP2 HCC cells. Our findings underscore a linear TARBP2-miR-145-SERPINE1 pathway that drives HCC progression, with the potential as a novel intervention target for aggressive HCC.