bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Global Diversity of Candidatus Microthrix, a Troublesome Filamentous Organism in Full-Scale WWTPs
Authors: Nierychlo Marta , Singleton Caitlin M. , Petriglieri Francesca , Thomsen Lisette , Petersen Jette F. , Peces Miriam , Kondrotaite Zivile , Dueholm Morten S. , Nielsen Per H.
Published: June 2021

CandidatusMicrothrix is one of the most common bulking filamentous microorganisms found in activated sludge wastewater treatment plants (WWTPs) across the globe. One species,Ca.M. parvicella, is frequently observed, but global genus diversity, as well as important aspects of its ecology and physiology, are still unknown. Here, we use the MiDAS ecosystem-specific 16S rRNA gene database in combination with amplicon sequencing of Danish and global WWTPs to investigateCa.Microthrix spp. diversity, distribution, and factors affecting their global presence. Only two species were abundant across the world confirming low diversity of the genus: the dominantCa.M. parvicella and an unknown species typically present along withCa.M. parvicella, although usually in lower abundances. Both species were mostly found in Europe at low-to-moderate temperatures and their growth was favored in municipal WWTPs with advanced process designs. As no isolate is available for the novel species, we propose the name “CandidatusMicrothrix subdominans.” Ten high-quality metagenome-assembled genomes recovered from Danish WWTPs, including 6 representing the novelCa.M. subdominans, demonstrated high genetic similarity between the two species with a likely preference for lipids, a putative capability to reduce nitrate and nitrite, and the potential to store lipids and poly-P.Ca.M. subdominans had a potentially more versatile metabolism including additional sugar transporters, higher oxygen tolerance, and the potential to use carbon monoxide as energy source. Newly designed fluorescencein situhybridization probes revealed similar filamentous morphology for both species. Raman microspectroscopy was used to quantify thein situlevels of intracellular poly-P. Despite the observed similarities in their physiology (both by genomes andin situ), the two species showed different seasonal dynamics in Danish WWTPs through a 13-years survey, possibly indicating occupation of slightly different niches. The genomic information provides the basis for future research intoin situgene expression and regulation, while the new FISH probes provide a useful tool for further characterizationin situ. This study is an important step toward understanding the ecology ofCa.Microthrix in WWTPs, which may eventually lead to optimization of control strategies for its growth in this ecosystem.
Metabolic Control of Cell Elongation and Cell Division in Bacillus subtilis
Authors: Galinier Anne , Foulquier Elodie , Pompeo Frédérique
Published: June 2021

To survive and adapt to changing nutritional conditions, bacteria must rapidly modulate cell cycle processes, such as doubling time or cell size. Recent data have revealed that cellular metabolism is a central regulator of bacterial cell cycle. Indeed, proteins that can sense precursors or metabolites or enzymes, in addition to their enzymatic activities involved in metabolism, were shown to directly control cell cycle processes in response to changes in nutrient levels. Here we focus on cell elongation and cell division in the Gram-positive rod-shaped bacterium Bacillus subtilis and we report evidences linking these two cellular processes to environmental nutritional availability and thus metabolic cellular status.
SLC38A10 Transporter Plays a Role in Cell Survival Under Oxidative Stress and Glutamate Toxicity
Authors: Tripathi Rekha , Aggarwal Tanya , Fredriksson Robert
Published: June 2021

Graphical Abstract

SLC38A10 role in cells survival under stress.
Regulation of Eukaryotic RNAPs Activities by Phosphorylation
Authors: González-Jiménez Araceli , Campos Adrián , Navarro Francisco , Clemente-Blanco Andrés , Calvo Olga
Published: June 2021

Evolutionarily conserved kinases and phosphatases regulate RNA polymerase II (RNAPII) transcript synthesis by modifying the phosphorylation status of the carboxyl-terminal domain (CTD) of Rpb1, the largest subunit of RNAPII. Proper levels of Rpb1-CTD phosphorylation are required for RNA co-transcriptional processing and to coordinate transcription with other nuclear processes, such as chromatin remodeling and histone modification. Whether other RNAPII subunits are phosphorylated and influences their role in gene expression is still an unanswered question. Much less is known about RNAPI and RNAPIII phosphorylation, whose subunits do not contain functional CTDs. However, diverse studies have reported that several RNAPI and RNAPIII subunits are susceptible to phosphorylation. Some of these phosphorylation sites are distributed within subunits common to all three RNAPs whereas others are only shared between RNAPI and RNAPIII. This suggests that the activities of all RNAPs might be finely modulated by phosphorylation events and raises the idea of a tight coordination between the three RNAPs. Supporting this view, the transcription by all RNAPs is regulated by signaling pathways that sense different environmental cues to adapt a global RNA transcriptional response. This review focuses on how the phosphorylation of RNAPs might regulate their function and we comment on the regulation by phosphorylation of some key transcription factors in the case of RNAPI and RNAPIII. Finally, we discuss the existence of possible common mechanisms that could coordinate their activities.
Propofol Ameliorates ox-LDL-Induced Endothelial Damage Through Enhancing Autophagy via PI3K/Akt/m-TOR Pathway: A Novel Therapeutic Strategy in Atherosclerosis
Authors: Zhou Hongyi , Jiang Fan , Leng Yufang
Published: June 2021

Objective: Atherosclerosis (AS) represents a common age-associated disease, which may be accelerated by oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury. This study aimed to investigate the effects of Propofol on ox-LDL-induced endothelial damage and the underlying molecular mechanisms.

Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to ox-LDL to induce endothelial damage. HUVECs were pretreated with 0, 5, 25 and 100°μM Propofol, followed by exposure to 100°μg/ml ox-LDL for 24°h. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. The expression of autophagy- and apoptosis-related proteins was detected via western blot. Autophagosome was investigated under a transmission electron microscope. After co-treatment with autophagy inhibitor Bafilomycin A1 or si-Beclin-1, cell apoptosis was detected by flow cytometry. Furthermore, under cotreatment with PI3K activator 740Y-P, PI3K/Akt/m-TOR pathway- and autophagy-related proteins were examined by western blot.

Results: With a concentration-dependent manner, Propofol promoted the viability of HUVECs exposed to ox-LDL, and increased LC3-II/I ratio and Beclin-1 expression, and decreased P62 expression. The formation of autophagosome was enhanced by Propofol. Furthermore, Propofol treatment elevated Bcl-2/Bax ratio and lowered Caspase-3 expression. Bafilomycin A1 or si-Beclin-1 distinctly ameliorated the inhibitory effects of Propofol on apoptosis in ox-LDL-exposed HUVECs. Moreover, Propofol lowered the activation of PI3K/Akt/m-TOR pathway in HUVECs under exposure to ox-LDL. However, its inhibitory effects were weakened by 740Y-P.

Conclusion: Collectively, this study revealed that Propofol could ameliorate ox-LDL-induced endothelial damage through enhancing autophagy via PI3K/Akt/m-TOR pathway, which might offer a novel therapeutic strategy in AS.
Post-stroke Anxiety Analysis via Machine Learning Methods
Authors: Wang Jirui , Zhao Defeng , Lin Meiqing , Huang Xinyu , Shang Xiuli
Published: June 2021

Post-stroke anxiety (PSA) has caused wide public concern in recent years, and the study on risk factors analysis and prediction is still an open issue. With the deepening of the research, machine learning has been widely applied to various scenarios and make great achievements increasingly, which brings new approaches to this field. In this paper, 395 patients with acute ischemic stroke are collected and evaluated by anxiety scales (i.e., HADS-A, HAMA, and SAS), hence the patients are divided into anxiety group and non-anxiety group. Afterward, the results of demographic data and general laboratory examination between the two groups are compared to identify the risk factors with statistical differences accordingly. Then the factors with statistical differences are incorporated into a multivariate logistic regression to obtain risk factors and protective factors of PSA. Statistical analysis shows great differences in gender, age, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level between PSA group and non-anxiety group with HADS-A and HAMA evaluation. Meanwhile, as evaluated by SAS scale, gender, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level differ in the PSA group and the non-anxiety group. Multivariate logistic regression analysis of HADS-A, HAMA, and SAS scales suggest that hypertension, diabetes mellitus, drinking, high NIHSS score, and low serum HDL-C level are related to PSA. In other words, gender, age, disability, hypertension, diabetes mellitus, HDL-C, and drinking are closely related to anxiety during the acute stage of ischemic stroke. Hypertension, diabetes mellitus, drinking, and disability increased the risk of PSA, and higher serum HDL-C level decreased the risk of PSA. Several machine learning methods are employed to predict PSA according to HADS-A, HAMA, and SAS scores, respectively. The experimental results indicate that random forest outperforms the competitive methods in PSA prediction, which contributes to early intervention for clinical treatment.
Association Between Iron-Related Protein Lipocalin 2 and Cognitive Impairment in Cerebrospinal Fluid and Serum
Authors: das Neves Sofia Pereira , Taipa Ricardo , Marques Fernanda , Soares Costa Patrício , Monárrez-Espino Joel , Palha Joana A. , Kivipelto Miia
Published: June 2021

A worldwide increase in longevity is bringing novel challenges to public health and health care professionals. Cognitive impairment in the elderly may compromise living conditions and precede Alzheimer’s disease (AD), the most prevalent form of dementia. Therefore, finding molecular markers associated with cognitive impairment is of crucial importance. Lipocalin 2 (LCN2), an iron-related protein, has been suggested as a potential marker for mild cognitive impairment (MCI) and AD. This study aimed at investigating the association between LCN2 measured in serum and cerebrospinal fluid (CSF) with cognitive impairment. A cross-sectional design based on two aging cohorts was used: individuals diagnosed with subjective cognitive complaints (SCC), MCI, and AD from a Swedish memory clinic-based cohort, and individuals diagnosed with SCC and AD from a Portuguese cohort. Binary logistic [for the outcome cognitive impairment (MCI + AD) in the Swedish cohort and AD in the Portuguese cohort] and multinomial logistic (for the outcomes MCI and AD) regression analyses were used. No associations were found in both cohorts when controlling for sex, education, and age. This explanatory study suggests that the association between serum and CSF LCN2 concentrations with cognitive impairment reported in the literature must be further analyzed for confounders.
Altered Functional Connectivity of the Basal Nucleus of Meynert in Subjective Cognitive Impairment, Early Mild Cognitive Impairment, and Late Mild Cognitive Impairment
Authors: Xu Wenwen , Rao Jiang , Song Yu , Chen Shanshan , Xue Chen , Hu Guanjie , Lin Xingjian , Chen Jiu
Published: June 2021

Background: The spectrum of early Alzheimer's disease (AD) is thought to include subjective cognitive impairment, early mild cognitive impairment (eMCI), and late mild cognitive impairment (lMCI). Choline dysfunction affects the early progression of AD, in which the basal nucleus of Meynert (BNM) is primarily responsible for cortical cholinergic innervation. The aims of this study were to determine the abnormal patterns of BNM-functional connectivity (BNM-FC) in the preclinical AD spectrum (SCD, eMCI, and lMCI) and further explore the relationships between these alterations and neuropsychological measures.

Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate FC based on a seed mask (BNM mask) in 28 healthy controls (HC), 30 SCD, 24 eMCI, and 25 lMCI patients. Furthermore, the relationship between altered FC and neurocognitive performance was examined by a correlation analysis. The receiver operating characteristic (ROC) curve of abnormal BNM-FC was used to specifically determine the classification ability to differentiate the early AD disease spectrum relative to HC (SCD and HC, eMCI and HC, lMCI and HC) and pairs of groups in the AD disease spectrum (eMCI and SCD, lMCI and SCD, eMCI and lMCI).

Results: Compared with HC, SCD patients showed increased FC in the bilateral SMA and decreased FC in the bilateral cerebellum and middle frontal gyrus (MFG), eMCI patients showed significantly decreased FC in the bilateral precuneus, and lMCI individuals showed decreased FC in the right lingual gyrus. Compared with the SCD group, the eMCI group showed decreased FC in the right superior frontal gyrus (SFG), while the lMCI group showed decreased FC in the left middle temporal gyrus (MTG). Compared with the eMCI group, the lMCI group showed decreased FC in the right hippocampus. Interestingly, abnormal FC was associated with certain cognitive domains and functions including episodic memory, executive function, information processing speed, and visuospatial function in the disease groups. BNM-FC of SFG in distinguishing eMCI from SCD; BNM-FC of MTG in distinguishing lMCI from SCD; BNM-FC of the MTG, hippocampus, and cerebellum in distinguishing SCD from HC; and BNM-FC of the hippocampus and MFG in distinguishing eMCI from lMCI have high sensitivity and specificity.

Conclusions: The abnormal BNM-FC patterns can characterize the early disease spectrum of AD (SCD, eMCI, and lMCI) and are closely related to the cognitive domains. These new and reliable findings will provide a new perspective in identifying the early disease spectrum of AD and further strengthen the role of cholinergic theory in AD.
Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders
Authors: Manzanza Nelson de Oliveira , Sedlackova Lucia , Kalaria Raj N.
Published: June 2021

Lewy Body Disorders (LBDs) lie within the spectrum of age-related neurodegenerative diseases now frequently categorized as the synucleinopathies. LBDs are considered to be among the second most common form of neurodegenerative dementias after Alzheimer's disease. They are progressive conditions with variable clinical symptoms embodied within specific cognitive and behavioral disorders. There are currently no effective treatments for LBDs. LBDs are histopathologically characterized by the presence of abnormal neuronal inclusions commonly known as Lewy Bodies (LBs) and extracellular Lewy Neurites (LNs). The inclusions predominantly comprise aggregates of alpha-synuclein (aSyn). It has been proposed that post-translational modifications (PTMs) such as aSyn phosphorylation, ubiquitination SUMOylation, Nitration, o-GlcNacylation, and Truncation play important roles in the formation of toxic forms of the protein, which consequently facilitates the formation of these inclusions. This review focuses on the role of different PTMs in aSyn in the pathogenesis of LBDs. We highlight how these PTMs interact with aSyn to promote misfolding and aggregation and interplay with cell membranes leading to the potential functional and pathogenic consequences detected so far, and their involvement in the development of LBDs.
Treatment of Traumatic Intracranial Pseudoaneurysms: A Single-Center Experience
Authors: Shi Yingwu , Gao Yuan , Liu Yufei , Cui Wenxing , Zhou Gaoyang , Wang Liang , Yu Jia , Zhang Tao , Qu Yan , Deng Jianping , Ge Shunnan
Published: June 2021

Background and Purpose: As a rare lesion secondary to brain trauma, traumatic intracranial aneurysms (TICAs) lead to high mortality and morbidity, and multiple treatment modalities have been applied for TICAs. All patients diagnosed with TICAs in our institution from 2010 to 2020 were included in the report, and their clinical features, treatment, and outcomes are described in detail. The purpose of this study is to illustrate the characteristic of different therapeutic methods of TICAs, and focus on the endovascular treatment.

Methods: A total of 20 patients were included in this study. The 3 patients who declined treatment all died. Five of the other 17 patients were treated surgically, including clipping, wrapping, and trapping with or without EC-IC high-flow bypass, with only 1 case of parent artery preservation. Twelve patients underwent endovascular treatment, including bare coil embolization (1 case), stent-assisted coiling (2 cases), balloon-assisted coils/Onyx glue embolization (1 case) and covered stents (8 cases), with only 1 case of parent artery sacrifice.

Results: 20 patients were included in the present study with 17 males, and the mean of age on 27 years (IQR: 22, 44 years). Eight patients presented with epistaxis, followed by 5 patients with coma, 3 patients with visual defects and 2 patients with CSF leakage. There were 18 TICAs located at the internal carotid artery (ICA); The other 2 TICAs located at pericallosal artery and A1 segment anterior cerebral artery (ACA). One case of diplopia occurred due to sacrifice of the ICA. Occlusion of the ophthalmic artery occurred in 3 patients after placement of a covered stent, with 1 patient suffering an irreversible vision decrease. None of the other patients who underwent the treatment have experienced an aggravation of their symptoms since the treatment; During the imaging follow-up, 1 case of recurrence and 1 case of endoleak occurred in this case series.

Conclusions: TICAs are associated with significant morbidity and mortality, and endovascular treatment has emerged as a valuable option, which may be promising to improve the clinical outcomes due to their advantages of preserving the parent artery if occlusion of the side branch artery can be avoided.
Ethical Issues in Care and Treatment of Neuronal Ceroid Lipofuscinoses (NCL)–A Personal View
Authors: Kohlschütter Alfried
Published: June 2021

The management of Neuronal Ceroid Lipofuscinoses (NCL), a group of genetic neurodegenerative disorders mainly affecting brain and retinas, raises difficult questions for physicians and other professionals in research, pharmaceutical industry, and public health. Ethical problems in medicine cannot be solved by rational deliberation or by following formal rules. Two topics of ethical issues in the field of NCL are presented here. One group relates to the care of individual patients and centers on a life with dementia at a young age. Advanced care planning for the end of life and the use of life-prolonging measures require challenging assumptions in the best interest of a patient. A second group of questions relates to new treatments. Impressive novel putative causal therapies, such as enzyme replacement for CLN2 disease, may be only disease-modifying and carry the risk of changing a deadly disease of short duration into one with prolonged survival and poor quality of life. The wish for better therapeutic interventions in life-limiting diseases has to take such risks, but more experience is needed before definite conclusions can be drawn. The appropriateness of presymptomatic screening for a severe disease, e.g., must be carefully evaluated to avoid the disastrous experience made with the rash start of newborn screening for Krabbe disease. The ethical issues described and commented in the article reflect the personal experience of a pediatrician who has studied clinical and research questions in NCL for four decades. They should alert various professionals to the necessity of taking their own decisions in situations that are caused by rare progressive brain diseases of young persons, as typified by the NCL.
Development of a Low-Cost EEG-Controlled Hand Exoskeleton 3D Printed on Textiles
Authors: Araujo Rommel S. , Silva Camille R. , Netto Severino P. N. , Morya Edgard , Brasil Fabricio L.
Published: June 2021

Stroke survivors can be affected by motor deficits in the hand. Robotic equipment associated with brain–machine interfaces (BMI) may aid the motor rehabilitation of these patients. BMIs involving orthotic control by motor imagery practices have been successful in restoring stroke patients' movements. However, there is still little acceptance of the robotic devices available, either by patients and clinicians, mainly because of the high costs involved. Motivated by this context, this work aims to design and construct the Hand Exoskeleton for Rehabilitation Objectives (HERO) to recover extension and flexion movements of the fingers. A three-dimensional (3D) printing technique in association with textiles was used to produce a lightweight and wearable device. 3D-printed actuators have also been designed to reduce equipment costs. The actuator transforms the torque of DC motors into linear force transmitted by Bowden cables to move the fingers passively. The exoskeleton was controlled by neuroelectric signal—electroencephalography (EEG). Concept tests were performed to evaluate control performance. A healthy volunteer was submitted to a training session with the exoskeleton, according to the Graz-BCI protocol. Ergonomy was evaluated with a two-dimensional (2D) tracking software and correlation analysis. HERO can be compared to ordinary clothing. The weight over the hand was around 102 g. The participant was able to control the exoskeleton with a classification accuracy of 91.5%. HERO project resulted in a lightweight, simple, portable, ergonomic, and low-cost device. Its use is not restricted to a clinical setting. Thus, users will be able to execute motor training with the HERO at hospitals, rehabilitation clinics, and at home, increasing the rehabilitation intervention time. This may support motor rehabilitation and improve stroke survivors life quality.
Dendritic/Post-synaptic Tau and Early Pathology of Alzheimer’s Disease
Authors: Yin Xiaomin , Zhao Chenhao , Qiu Yanyan , Zhou Zheng , Bao Junze , Qian Wei
Published: June 2021

Microtubule-associated protein tau forms insoluble neurofibrillary tangles (NFTs), which is one of the major histopathological hallmarks of Alzheimer’s disease (AD). Many studies have demonstrated that tau causes early functional deficits prior to the formation of neurofibrillary aggregates. The redistribution of tau from axons to the somatodendritic compartment of neurons and dendritic spines causes synaptic impairment, and then leads to the loss of synaptic contacts that correlates better with cognitive deficits than amyloid-β (Aβ) aggregates do in AD patients. In this review, we discuss the underlying mechanisms by which tau is mislocalized to dendritic spines and contributes to synaptic dysfunction in AD. We also discuss the synergistic effects of tau and oligomeric forms of Aβ on promoting synaptic dysfunction in AD.
The Effect of Nutrition Intervention With Oral Nutritional Supplements on Ovarian Cancer Patients Undergoing Chemotherapy
Authors: Qin Nan , Jiang Guichun , Zhang Xu , Sun Di , Liu Meishuo
Published: June 2021

Background: Ovarian cancer is the third most common gynecological malignancy in the world and it is under a higher incidence of malnutrition. Chemotherapy is currently a common treatment for ovarian cancer, but the resulting side effects can exacerbate malnutrition. Our aim was to investigate the beneficial effects of oral nutrition supplements (ONS) on ovarian cancer patients undergoing chemotherapy.

Methods: Single-blinded randomized controlled trial. Patients with ovarian cancer receiving chemotherapy were randomly assigned either to the ONS or non-ONS groups via a simple randomization. The ONS group was given 250 mL ONS each time (1.06 kcal, 0.0356 g of protein per mL), three times a day, and nutrition education. Control group received nutrition education alone. The primary outcome was the nutritional risk of the patients as assessed by the Patient-Generated Subjective Global Assessment (PG-SGA). The secondary outcome was the results of the participants' biochemical tests at each measurement time point. Data were collected (T0) at baseline, (T1) post intervention at 3 weeks, (T2) 9-week follow-up, (T3) 15-week follow-up. Generalized estimating equation models were used to compare the changes in outcomes over time between groups.

Results: 60 participants (30 ONS, 30 controls) completed the trial, and data was analyzed. For baseline comparisons, no significant differences were found between the two groups. A progressive trend toward amelioration in PG-SGA scores over time was found within the ONS group, with scores decreasing from 9.27 ± 1.68 at baseline (T0) to 5.87 ± 2.06 after the intervention (T3). Furthermore, ONS group achieved a significantly greater reduction in PG-SGA score at the T1 (p = 0.03, confidence interval −2.23 to −0.11), T2 (p = 0.001, confidence interval −2.86 to −0.74) and T3 (p < 0.001, confidence interval −3.81 to −1.53), than the control group. In terms of biochemical test results, patients in the ONS group had better leukocytes, lymphocytes, Hemoglobin, Albumin and Total Protein than the control group at different time points, with statistical differences between the two groups (p < 0.05).

Conclusions: The present study demonstrated that ONS can significantly reduce the nutritional risk of patients undergoing chemotherapy for ovarian cancer. In addition, we also found that nutritional education seems to have a positive effect on reducing the nutritional risk of patients especially at the beginning of chemotherapy.
Promoting Sustainable and Healthy Diets to Mitigate Food Insecurity Amidst Economic and Health Crises in Lebanon
Authors: Hwalla Nahla , Jomaa Lamis , Hachem Fatima , Kharroubi Samer , Hamadeh Rena , Nasreddine Lara , Naja Farah
Published: June 2021

Introduction: Lebanon, a middle-income Eastern Mediterranean country, continues to face detrimental economic, health and socio-political challenges that are further exacerbated by the COVID-19 pandemic. In parallel, the country has been experiencing a remarkable nutrition transition that has contributed to the burden of malnutrition and non-communicable diseases, all imposing serious repercussions on people's livelihoods, food security, and health. Such circumstances have prodded public demand for guidance on affordable, healthy, and sustainable dietary choices to alleviate the burden to this emerging unfortunate situation.

Objective: The purpose of this study is to provide evidence-based sustainable and healthy dietary recommendations which balance the tradeoffs among the health, environmental footprint and cost dimensions of sustainability, while closely resembling the usual food consumption pattern.

Methodology: Data from the latest available national food consumption survey was used as the usual food consumption pattern of Lebanese adults. Optimized dietary patterns were calculated using the optimization model Optimeal which produced patterns most similar to the usual diet and simultaneously satisfying the three main sets of constraints: health, environmental footprints, and cost. The identified healthy and sustainable dietary options were vetted by multiple key stakeholders from the government, academia, international, and national non-governmental organizations.

Results: Compared to the usual intake, the optimized diet included higher intakes of whole grain bread, dark green vegetables, dairy products, and legumes, and lower intakes of refined bread, meat, poultry, added sugars, saturated fat, as compared to usual national mean consumption. The optimized dietary model resulted in a decrease in the associated environmental footprints: water use (−6%); and GHG (−22%) with no change in energy use. The cost of the optimized diet was not different from that of the usual intake.

Conclusion: An evidence-based sustainable and healthy diet was developed for Lebanon providing the population and policy makers with some answers to a complex situation. Findings highlight the need for the development of sustainable food based dietary guidelines for Lebanon to promote diets that are healthy, sustainable, culturally acceptable, and affordable and that can alleviate food insecurity among the general population.
NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers
Authors: Takatori Atsushi , Hossain MD. Shamim , Ogura Atsushi , Akter Jesmin , Nakamura Yohko , Nakagawara Akira
Published: June 2021

Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.
Targeting Long Non-Coding RNAs in Hepatocellular Carcinoma: Progress and Prospects
Authors: Lin Xinrong , Xiang Xiaosong , Feng Bing , Zhou Hao , Wang Ting , Chu Xiaoyuan , Wang Rui
Published: June 2021

Hepatocellular carcinoma is the fifth-ranked cancer worldwide with a relatively low five-year survival rate. Long non-coding RNAs are a group of RNAs with remarkable aberrant expression which could act on multiple bioprocesses and ultimately impact upon tumor proliferation, invasion, migration, metastasis, apoptosis, and therapy resistance in cancer cells including hepatocellular carcinoma cells. In recent years, long non-coding RNAs have been reported to be indispensable targets in clinical target therapy to stop the growth of cancer and prolong the lifespan of patients with hepatocellular carcinoma. In this review, we enumerate the signaling pathways and life activities affected by long non-coding RNAs in hepatocellular carcinoma cells to illustrate the role of long non-coding RNAs in the development and therapy resistance of hepatocellular carcinoma.
Exosomal miR-183-5p Shuttled by M2 Polarized Tumor-Associated Macrophage Promotes the Development of Colon Cancer via Targeting THEM4 Mediated PI3K/AKT and NF-κB Pathways
Authors: Zhang Shangxin , Li Deguan , Zhao Min , Yang Fei , Sang Changye , Yan Changhong , Wang Zhenjun , Li Yongxiang
Published: June 2021

Background

Abnormal accumulation of macrophages in the colon cancer (CC) contribute to its progression. miR-183-5p has been confirmed as an oncogene in CC and this article explores the effect and mechanism of exosomal miR-183-5p enriched by M2-polarized tumor-associated macrophages (TAM) on CC cells.

Methods

The human macrophage THP1 was induced to M2 polarization through IL-4 and IL-13 treatment. Exosomes in THP1 were isolated through ultracentrifugation, and the miR-183-5p expression in macrophages and exosomes was verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The miR-183-5p inhibitors and mimics were applied to down-regulate and upregulate miR-183-5p in macrophages, respectively. Meanwhile, CC cell lines LoVo and SW480 were treated with the macrophage conditioned medium and exosomes, respectively. CC cells’ proliferation, invasion, and apoptosis were tested by the cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry (FCM), Transwell assay, and xenograft assay, respectively. The profiles of thioesterase superfamily member 4 (THEM4), Akt, and NF-κB were compared by Western blotting (WB).

Results

The miR-183-5p level in M2-TAM and M2-TAM-derived exosomes was significantly increased. Meanwhile, M2-TAM and M2-TAM-derived exosomes significantly facilitated CC cell proliferation and invasion and dampened apoptosis. Overexpression of miR-183-5p in M2-TAM aggravated M2-TAM-mediated promotive effects on CC cells, with down-regulating miR-183-5p reversed M2-TAM-mediated tumor-promotive effects. Mechanically, miR-183-5p targeted THEM4 and inhibited its mRNA and protein expression. Overexpressing THEM4 abated miR-183-5p-mediated carcinogenic effects and inactivates Akt and NF-κB pathways in CC cells. Overall, this article elaborated that exosomal miR-183-5p shuttled by M2-TAM mediated Akt/NF-κB pathway to accelerate CC progression through targeting THEM4.
ARID1A Variations in Cholangiocarcinoma: Clinical Significances and Molecular Mechanisms
Authors: Zhao Shankun , Xu Youwen , Wu Weizhou , Wang Pan , Wang Yichao , Jiang Hao , Zhu Jie
Published: June 2021

Cholangiocarcinoma (CCA), a high mortality malignant carcinoma characterized by advanced disease and frequent recurrence, constitutes a major challenge for treatment and prognosis. AT-rich interaction domain 1A (ARID1A) variation is a distinct genetic entity in CCA, getting mounting concerns recently. Here, we comprehensively reviewed the clinical significance and molecular mechanisms of ARID1A alterations in CCA. Based on the independent data derived from 29 relevant studies, the variation rate of ARID1A in intrahepatic and extrahepatic CCA is reported at 6.9–68.2% and 5–55%, respectively. Most of the included studies (28/29, 96.6%) suggest that ARID1A serves as a tumor suppressor in CCA. ARID1A variation may be an important prognostic indicator to predict disease mortality, metastasis, and recurrence in patients with CCA. Multifactorial molecular mechanisms are involved in the relationship between ARID1A variations and the pathogenesis and pathophysiology of CCA, including disruption of the cell cycle, chromatin remodeling, oxidative stress damage, DNA hypermethylation, and the interaction of multiple genes being affected. This review describes that ARID1A variation might be a potential diagnostic and prognostic biomarker for CCA. Future diagnoses and treatments targeting ARID1A hint towards a precision medicine strategy in the management of CCA.
Prospective Evaluation of a Circulating Tumor Cell Sensitivity Profile to Predict Response to Cisplatin Chemotherapy in Metastatic Breast Cancer Patients
Authors: de Kruijff I. E. , Sieuwerts A. M. , Beije N. , Prager - van der Smissen W. J. C. , Angus L. , Beaufort C. M. , Van M. N. , Oomen - de Hoop E. , Jager A. , Hamberg P. , de Jongh F. E. , Kraan J. , Martens J. W. M. , Sleijfer S.
Published: June 2021

Background

Cisplatin (cDDP) has regained interest for metastatic breast cancer (MBC) patients, given the platinum sensitivity in subtypes and better manageable toxicity. Here, the primary aim was to determine whether molecular characteristics of circulating tumor cells (CTCs) could identify patients responding to cDDP and to describe the outcomes to cDDP monotherapy in a large group of MBC patients pretreated with anthracycline- and taxane-based treatments.

Methods

Based on cell line data, a CTC-cDDP-sensitivity profile was generated. Applying an A’Herns single-stage phase II design, further investigation was considered worthwhile if 5/10 patients with a favorable profile responded to cDDP. Patients received 70mg/m2 cDDP every three weeks, CTCs were enumerated and the CTC-cDDP-sensitivity profile was determined. In total, 65 heavily pretreated MBC patients (77% received ≥2 lines of previous chemotherapy for MBC) were eligible for the per-protocol analysis. Primary endpoint was response rate, secondary endpoints included best observed response, progression-free survival (PFS) and overall survival (OS).

Results

The best observed response during cDDP therapy was a partial response in 7% and stable disease in 56% of the patients. None of the patients with a favorable CTC-cDDP-sensitivity profile had a response. The median baseline CTC count was 8 (range 0-3254). Patients with <5 CTCs had a better PFS and OS than patients with ≥5 CTCs (median PFS 4.5 months (95%CI 2.38-6.62) vs. 2.1 months [(95%CI 1.34-2.80)(p=0.009)] and median OS 13.1 months (95%CI 9.89-16.33) vs. 5.6 months [(95%CI 3.60-7.64)(p=0.003)]. No other factors than CTC count were associated with outcome to cDDP therapy, including triple-negative breast cancer versus ER-positive tumors.

Conclusions

The CTC-cDDP-sensitivity profile was unable to select patients responding to cDDP monotherapy. In an unselected group of heavily pretreated MBC patients, cDDP yields outcomes comparable to other chemotherapeutic regimens for heavily pretreated MBC patients. CTC count was the only factor associated with outcome in these patients.

Clinical Trial Registration

(https://www.trialregister.nl/trial/3885, identifier NTR4046)
A Metabolomic Approach in Search of Neurobiomarkers of Perinatal Asphyxia: A Review of the Current Literature
Authors: Debuf Marie Julie , Carkeek Katherine , Piersigilli Fiammetta
Published: June 2021

Perinatal asphyxia and the possible sequelae of hypoxic-ischemic encephalopathy (HIE), are associated with high morbidity and mortality rates. The use of therapeutic hypothermia (TH) commencing within the first 6 h of life—currently the only treatment validated for the management of HIE—has been proven to reduce the mortality rate and disability seen at follow up at 18 months. Although there have been attempts to identify neurobiomarkers assessing the severity levels in HIE; none have been validated in clinical use to date, and the lack thereof limits the optimal treatment for these vulnerable infants. Metabolomics is a promising field of the “omics technologies” that may: identify neurobiomarkers, help improve diagnosis, identify patients prone to developing HIE, and potentially improve targeted neuroprotection interventions. This review focuses on the current evidence of metabolomics, a novel tool which may prove to be a useful in the diagnosis, management and treatment options for this multifactorial complex disease. Some of the most promising metabolites analyzed are the group of acylcarnitines: Hydroxybutyrylcarnitine (Malonylcarnitine) [C3-DC (C4-OH)], Tetradecanoylcarnitine [C14], L-Palmitoylcarnitine [C16], Hexadecenoylcarnitine [C16:1], Stearoylcarnitine [C18], and Oleoylcarnitine [C18:1]. A metabolomic “fingerprint” or “index,” made up of 4 metabolites (succinate × glycerol/(β-hydroxybutyrate × O-phosphocholine)), seems promising in identifying neonates at risk of developing severe HIE.
Traditional Chinese Medication Tongxinluo Attenuates Lipidosis in Ox-LDL-Stimulated Macrophages by Enhancing Beclin-1-Induced Autophagy
Authors: Chen Yifei , Yu Fangpu , Zhang Yu , Li Mengmeng , Di Mingxue , Chen Weijia , Liu Xiaolin , Zhang Yun , Zhang Mei
Published: June 2021

Tongxinluo (TXL), a traditional Chinese medication, plays a key role in the formation and progression of plaques in atherosclerosis. The formation of foam cells by macrophages accelerates the destabilisation of plaques. In previous research, we had found that TXL significantly inhibits ox-LDL-induced apoptosis in macrophages in vitro by improving the dissociation of the Beclin-1-Bcl-2 complex. Therefore, here, we explored the effect of TXL on lipid metabolism in macrophages and the mechanism involved. To evaluate the role of TXL in atherosclerotic plaques, we construct the atherosclerotic animal model with lentiviral injection and performed immunofluorescence staining analysis in vivo. Western blot, immunofluorescence staining and microscopy were performed to elucidate the mechanism underlying TXL-mediated regulation of autophagy in THP-1 macrophages in vitro. Immunofluorescence assay revealed that TXL treatment inhibited lipid deposition in advanced atherosclerotic plaques. In vitro TXL treatment inhibited lipid deposition in THP-1 macrophages by enhancing autophagy via Beclin-1. TXL reversed the high expression of class I histone deacetylases (HDACs) induced by ox-LDL (p < 0.05). Compared with the TXL + ox-LDL group, TXL failed to promote intracellular lipid droplet decomposition after the addition of the histone deacetylase agonist. We found that TXL attenuates the accumulation of lipids in macrophage by enhancing Beclin-1-induced autophagy, and additionally, it inhibits the inhibitory effect of class I HDAC on the expression of Beclin-1.
IIIM-941, a Stilbene Derivative Inhibits NLRP3 Inflammasome Activation by Inducing Autophagy
Authors: Ali Mehboob , Gupta Mehak , Wani Abubakar , Sharma Ankita , Abdullaha Mohd , Kour Dilpreet , Choudhary Sushil , Bharate Sandip B. , Singh Gurdarshan , Kumar Ajay
Published: June 2021

Aberrant activation of NLRP3 inflammasome has been implicated in several inflammatory diseases. Autophagy is one of the primary mechanisms that regulate NLRP3 inflammasome activity. In this study, we attempted to target NLRP3 inflammasome activity by a synthetic compound IIIM-941. We found that IIIM-941 inhibits ATP induced NLRP3 inflammasome by induction of autophagy through AMPK pathway in bone marrow derived macrophages (BMDMs) and J774A.1 cells. It was interesting to observe that IIIM-941 did not show any inhibitory activity against LPS induced pro-inflammatory cytokines TNF-α and IL-6. The anti-NLRP3 activity of IIIM-941 was significantly reversed when we attempted to block autophagy by using either pharmacological inhibitor bafilomycin A1or by using siRNA against AMPK. Further, we found that IIIM-941 downregulated the expression of NLRP3 and prevented the oligomerization of ASC to exert its anti-NLRP3 inflammasome effect in J774A.1 cells. We validated inhibitory activity of IIIM-941 against NLRP3 in three different mice models. The anti-inflammatory effect of IIIM-941 was highly significant in ATP induced peritoneal inflammation model. IIIM-941 was similarly effective in suppressing MSU induced IL-1β in the air pouch model of inflammation without affecting the levels of TNF-α and IL-6. Finally, oral efficacy of IIIM-941 was also proved in MSU indued foot paw edema model of inflammation in mice at 10 and 20 mg/kg (b.w.). The compounds like IIIM-941 can be explored further for the development of therapies against diseases such as Alzheimer’s disease and Parkinson’s disease, where hampered autophagy and NLRP3 activation play a crucial role in the pathological development.
Comparison of Energy Contributions and Workloads in Male and Female Badminton Players During Games Versus Repetitive Practices
Authors: Fu Yue , Liu Yu , Chen Xiaoping , Li Yongming , Li Bo , Wang Xinxin , Shu Yang , Shang Lei
Published: June 2021

Purpose

The aim of this study was to compare the energy contributions and workloads in men and women during badminton matches versus frequently used multi-ball smash practices.

Methods

Fourteen badminton players performed one badminton singles game and one session of smashing practice on separate days. The energy contributions were examined in terms of each individual’s three energy systems and substrate oxidation, while workloads included heart rate (HR), Player Load (PL), accelerations, decelerations, changes of direction, and jumps.

Results

(1) During games, male players exhibited higher adenosine triphosphate–phosphocreatine system contribution (EPCr, kJ) (p = 0.008) and average rate of carbohydrate oxidation (RCHO, g/min) (p = 0.044) than female players, while female players showed greater absolute PL (p = 0.029) and more accelerations (p = 0.005) than male players. Furthermore, players who lost performed higher relative PL (p = 0.017) than those who won. (2) Higher energy system contributions, including EPCr (kJ) (p = 0.028), EHLa (kJ) (p = 0.024), EAer (kJ) (p = 0.012), ETot (kJ) (p = 0.007), and RCHO (g/min) (p = 0.0002), were seen in male players during repetitive spike practices. Male players also made greater number of jumps (p = 0.0002). (3) Players exhibited higher aerobic energy contribution (p < 0.001), mean HR (p = 0.002), and HRmax (p = 0.029) during games, while exhibiting greater anaerobic energy contribution (p < 0.001) and relative PL (p = 0.001) during repetitive practices.

Conclusion

The similarities between male and female badminton players in proportional use of the three energy systems during games and repetitive spike training indicate similar relative energy demands for both genders. However, considering the need for higher aerobic capacity in competition, it might be advisable to design appropriate work:rest ratios for repetitive practices in daily training.
A Randomized Crossover Trial on the Acute Cardiovascular Demands During Flywheel Exercise
Authors: Zubac Damir , Ivančev Vladimir , Valić Zoran , Pišot Rado , Meulenberg Cécil J. W. , Trozić Irhad , Goswami Nandu , Šimunič Boštjan
Published: June 2021

In a randomized crossover trial, we examined whether age plays a role in the mean arterial pressure (MAP) response during a vigorous flywheel exercise of varying load. We hypothesized that the magnitude of increase in the MAP during the flywheel exercise would increase in proportion to advancing age, thereby imposing a significant challenge to the cardiovascular system. A total of 30 participants of both sexes (age range from 20–55 y, 37% women) underwent a detailed medical examination, and their maximal oxygen uptake was determined. They performed a squat exercise (2 sets × 7 repetitions) on a flywheel ergometer at three randomly assigned moments of inertia set at 0.025, 0.05, and 0.075 kg m2, while the cardiovascular response was continuously recorded via a Task force monitor. Compared to the resting values, robust rises in the MAP were observed during all three flywheel loads, reaching the highest value of 179 ± 4 mmHg (p = 0.001) during the highest load. In parallel, the cardiac index (cardiac output normalized by the body surface area) was two-fold greater during all the flywheel loads compared to rest, and at a high load, exclusively, the total peripheral resistance increased by 11% (p = 0.001). The rise in heart rate compensated for a load-dependent drop in the stroke index (stroke volume normalized by the body surface area). In our study population, no correlations were observed between the relative increase in the MAP and the participants’ age for the three flywheel loads. The present findings suggest that the larger moments of inertia impose a substantial burden to the cardiovascular system, without apparent associated age-differences of the relative magnitude of MAP rise throughout the exercise.