bluuebunny/crossref_metadata_2025 huggingface dataset:
Scalable Dual-Fluorescence Assay for Functional Interpretation of HNF-4α Missense Variants
Authors: Guo Yiming , Zhao Jing , Huang Rong , Xu Tao , Zhou Kaixin , Zheng Li
Published: February 2022

Aim

The study aimed to develop a scalable dual-fluorescence assay in cells to enable the functional interpretation of HNF-4α missense variants identified in exome sequencing, which can be used to guide clinical diagnosis.

Methods

Using mOrange2 and GFP fluorescence proteins to track the expression of HNF-4α (HNF-4α-mOrange2) and reporter activity under the control of the HNF-1α promoter (pHNF1A-GFP), respectively, we designed a dual-fluorescence assay to evaluate the expression level, cellular localization, and transcriptional function of HNF-4α simultaneously in live cells. To assess the scalable characteristic of the assay, a small library containing five previously reported mutations and wild-type HNF-4α was constructed. Cells infected with this library were sorted into different populations through fluorescence-activated cell sorting (FACS) according to the transcription activity and expression abundance. Cloning and Sanger sequencing were used to detect the mutations of the different groups. High content screening (HCS) assay was used for the validation of individual mutants in the function and expression point of view.

Results

HNF-4α-mOrange2 exhibited nuclear localization and transactivation capability on the HNF-1α promoter as physical HNF-4α does. The expression of HNF-4α-mOrange2 shows a 6-fold induction of GFP expression compared to the control without HNF-4α-mOrange2, which was significantly abolished by the known loss-of-function mutant M373R. The different performances of wild-type and mutant M373R made them distinguishable in the FACS system, empowering the scalable capability of this assay for classifying large numbers of variants combining functional stratification and sequencing. Further application of the assay in the small library showed that three cell populations were seen grouped as Normal (same transactivation as wild type), Reducedexp_nor (reduced transactivation with normal or higher expression), and Reducedexp_low (reduced transactivation with lower expression). Subsequently, Sanger sequencing showed that wild-type HNF-4α was in the Normal group, two mutations (M373R and G79C) were enriched in the Reducedexp_nor group, and three mutations (C115S, L272P, and F83C) belonged to the Reducedexp_low group. These results were validated by further imaging data using HCS assay for individual mutation.

Conclusions

Our study proposes a scalable and informative approach for the characterization of the variants in HNF-4α genes in a quantitative and high-throughput manner.
Exergetic Assessment of Waste Gas to Energy in a Novel Integrated NGL Recovery and Power Generation Plant
Authors: Aigba Peter Alenoghena , Emovon Ikuobase , Samuel Olusegun David , Chintua Enweremadu Christopher , Abdeljawad Thabet , Al-Mdallal Qasem M. , Afzal Asif
Published: February 2022

Natural gas processing, as one of the major energy sources, has become a focal point in boosting the energy value chain by processing high commercial value products such as natural gas liquids (NGL) and electricity generation. Natural gas processing has also amplified its usefulness to human well-being and global prosperity in different ways. However, the spate of gas flaring is a global phenomenon, despite advances in waste gas management technology. This research describes a unique integrated plant that recovers NGL and produces electricity via waste gas for the energy conversion process. Exergetic analysis has been offered to identify the causes of irreversibilities in the plant. Simulation models were built using the AspenOne HYSYS V10 and Aspen Plus V10 software to conceptualize the plant. The recovery of 60 kBD NGL and 2.55 kg mol/s of 97% lean methane gas (95% purity) as the residue was achieved from 320 MMSCFD of waste gas processing. The residue methane gas is combusted in a combustion chamber to recover hot gas in a heat recovery steam generator (HRSG) for steam generation and production of 646 MW of electricity. Analysis revealed that the heat exchangers collectively accounted for about 78% exergy destruction in the NGL recovery plant, while the 3 and 1.54%, respectively, of exergy is destroyed and lost in the demethanizer. The steam power plant showed similar irreversibilities with the boiler exchanger accounting for up to 88% exergy destruction. About 1.4% of exergy is lost as flue gas to the environment. At optimization, overall exergy efficiency reached 77.5 and 80.6% in the NGL recovery and steam power plant, respectively. Thus, this integrated plant model has not only demonstrated a marked improvement to similar models but is also a lucrative alternative to waste flare gas management. It is also proven to be a “flare-capture” alternative model for fossil fuels-related emission reduction and optimization tool for waste gas to energy.
Transformer Vibration Detection Based on YOLOv4 and Optical Flow in Background of High Proportion of Renewable Energy Access
Authors: Su Lei , Huang Hua , Qin Lunming , Zhao Wenbin
Published: February 2022

In recent years, large-scale renewable energy access to substations has brought overload, harmonic, short circuit and other problems, which has led to an increase in the failure rate and shortening the service life of important power equipment such as transformers. Transformer is one of the key equipment in power system, and its operation status has an important impact on the safe and stable operation of power grid. In order to realize the real-time state evaluation of transformer, a real-time vibration signal detection method based on video is proposed in this paper. Firstly, YOLOv4 is used to detect the transformer object, and then the pyramid Lucas-Kanade optical flow method and Otsu method are used to calculate the transformer vibration vector. Experimental results show that the transformer vibration vector can be calculated in real time and accurately by using the proposed algorithm, so as to realize the real-time reliable analysis of the transformer state.
A Global Assessment of Sustainable Development: Integrating Socioeconomic, Resource and Environmental Dimensions
Authors: Sun Jie , Jin Hui , Tsai Fu-Sheng , Jakovljevic Mihajlo
Published: February 2022

Sustainable development and its assessment have increasingly played a key background role in government policymaking across the world. Generally, sustainable development is defined as the coordination of economic, environmental, and social development in order to balance intra-generational welfare and maximize inter-generational overall welfare. Therefore, the purpose of our research is to assess national sustainable development from the perspective of integrating economic, environmental, and social dimensions, and then to better monitor the status of sustainable development. We first adopt and modify the National Sustainable Development Index, which has been proposed as a way to amend the Human Development Index, including 12 indicators (weighted by the Entropy Method) in economic, environmental, and social dimensions. After that, we assess the sustainable development status of 179 countries from 2010 to 2016. The result shows that there is no obvious trend of narrowing the gap in sustainable development levels among countries, or even an expanding trend in this period. We also make a comparison between the original NSDI and our modified NSDI and find that the modified NSDI not only retains the merits but also makes up for the shortcomings of the original one in acceptability, reliability, and continuity.
Dynamics of Dietary Mercury Determined by Mercury Speciation and Isotopic Composition in Dicentrarchus labrax
Authors: Pinzone Marianna , Cransveld Alice , De Boeck Gudrun , Shrivastava Jyotsna , Tessier Emmanuel , Bérail Sylvain , Schnitzler Joseph G. , Amouroux David , Das Krishna
Published: February 2022

Seafood has a great ecological and nutritional value for human and wildlife communities. However, accumulation of mercury (Hg) in fish is a concern to animal and human health. There is a crucial need to understand Hg speciation in marine organisms through controlled feeding experiments. This study represents a first assessment of the biological processes that may influence Hg bioaccumulation and dynamics in a marine predatory fish. We conducted a feeding experiment to investigate the dynamics of MeHg and iHg, as well as Hg isotopes in the liver and muscles of captive juvenile seabass (Dicentrarchus labrax). Three groups of juvenile seabass were fed in captivity during 3 weeks of acclimatization and 6 weeks of experiment. Each group was fed with pellets containing environmentally relevant MeHg concentrations (Control, 200 and 500 ng g−1 dw). We monitored the evolution of MeHg and iHg concentrations as well as Hg isotopic values in liver and muscle. We determined Hg dynamics with respect to the contamination level in the fish diet. Muscle δ202Hg and Δ199Hg turnover rates ranged between 33 and 14 days (Low diet) to 5 and 9 days (Mod diet). Liver δ202Hg and Δ199Hg turnover rates ranged between 3 and 7 days (Low diet) to 3 and 2 days (Mod diet), respectively. Hg species concentrations and δ202Hg varied over time between diet groups and tissues, showing the occurrence of internal mass-dependent fractionation (MDF). No significant intra-tissue and temporal Hg mass-independent fractionation (MIF) was observed. The results of our experiment are strongly in favor of the existence of MeHg demethylation in a coastal predatory fish exposed to low to moderate concentrations of environmental Hg. The decrease over time of δ202Hg in muscle of seabass from the most contaminated diet was accompanied by a temporal increase in iHg, pointing to possible Hg detoxification processes occurring in this tissue when dietary Hg exposure is high. The absence of Hg MDF and different turnover between muscle and liver in seabass exposed to 500 ng Hg g−1 confirmed that Hg speciation and bioaccumulation in juvenile fish are controlled by Hg levels and speciation in their diet.
Abundance and Characterization of Microplastics in Main Urban Ditches Across the Bahir Dar City, Ethiopia
Authors: Mhiret Gela Sahlu , Aragaw Tadele Assefa
Published: February 2022

Microplastics (MPs) pollution in water bodies, wastewater, and sewage is of concern due to their probable effects on the environment and human health. This study is a first-time attempt to evaluate MPs occurrence, abundance, characteristics, and polymeric types in sediment and agglomerated sewage water from several urban ditches in Bahir Dar, Ethiopia, in two class sizes (> 0.5 and < 0.5 mm). Out of the total of 239 MP particles, 61.09% were of <0.5 mm and this dominant fraction was transparent and consisted of fragmentary shapes. The mean abundances of <0.5 mm particles were 5 ± 1.00 items/50 g in sediment and 3.00 ± 1.00 items/ml in agglomerated sewage water. Similarly, the abundances of >0.5 mm fractions were 2.33 ± 0.58 items/50 g in sediment and 1.33 ± 0.58 items/50 ml in Agglomerated sewage water. Polyethylene (PE), Polypropylene (PP), polyethylene terephthalate (PET), Polystyrene (PS), polyamide (PA), and polyvinylchloride (PVC), were the most detected plastics. However, PET and PVC were not detected in the agglomerated sewage water samples.
Integrated Analysis of ceRNA Network to Reveal Potential Prognostic Biomarkers for Glioblastoma
Authors: Liu Ruifei , Gao Zhengzheng , Li Qiwei , Fu Qiang , Han Dongwei , Wang Jixi , Li Ji , Guo Ying , Shi Yuchen
Published: February 2022

Glioblastoma (GBM), originating in the brain, is a universally aggressive malignant tumor with a particularly poor prognosis. Therefore, insight into the critical role of underlying genetic mechanisms is essential to developing new therapeutic approaches. This study aims to identify potential markers with clinical and prognostic significance in GBM. To this end, increasing numbers of differentially expressed RNA have been identified used to construct competitive endogenous RNA networks for prognostic analysis via comparison and analysis of RNA expression levels of tumor and normal tissues in glioblastoma. This analysis demonstrated that the RNA expression patterns of normal and tumor samples were significantly different. Thus, the resulting differentially expressed RNAs were used to construct competitive endogenous RNA (competing endogenous RNA, ceRNA) networks. The functional enrichment indicated mRNAs in the network are critically involved in a variety of biological functions. Additionally, the prognostic analysis suggested 27 lncRNAs, including LOXL1-AS1, AL356414.1, etc., were significantly associated with patient survival. Given the prognostic significance of these 27 lncRNAs in GBM, we sought to classify the samples. Importantly, Kaplan-Meier analysis revealed that survival times varied significantly among the different categories. Overall, these results identify that the candidate lncRNAs are potential prognostic markers of GBM and its corresponding mRNAs may be a potential target for therapy.
RETRACTED: Mitochondrial-Associated Protein LRPPRC is Related With Poor Prognosis Potentially and Exerts as an Oncogene Via Maintaining Mitochondrial Function in Pancreatic Cancer
Authors: Wang Li , Luo Jun , Li Yuchen , Lu Yanrong , Zhang Yi , Tian Bole , Zhao Ziyi , Hu Qiong-ying
Published: February 2022

Background: The mitochondrial-associated protein leucine-rich pentatricopeptide repeat-containing (LRPPRC) exerts multiple functions involved in physiological processes, including mitochondrial gene translation, cell cycle progression, and tumorigenesis. Previously, LRPPRC was reported to regulate mitophagy by interacting with Bcl-2 and Beclin-1 and thus modifying the activation of PI3KCIII and autophagy. Considering that LRPPRC was found to be negatively associated with survival rate, we hypothesize that LRPPRC may be involved in pancreatic cancer progression via its regulation of autophagy.

Methods: Real-time quantitative polymerase chain reaction was performed to detect the expression of LRPPRC in 90 paired pancreatic cancer and adjacent tissues and five pancreatic cancer cell lines. Mitochondrial reactive oxidative species level and function were measured. Mitophagy was measured by performing to detect LC3 levels.

Results: By performing a real-time quantitative polymerase chain reaction, the association of LRPPRC with the prognosis of pancreatic cancer was established, and pancreatic cancer tissues had significantly higher LRPPRC expression than adjacent tissues. LRPPRC was negatively associated with the overall survival rate. LRPPRC was also upregulated in pancreatic cancer cell lines. Knockdown of LRPPRC promoted reactive oxidative species accumulation, decreased mitochondrial membrane potential, promoted autophagy/mitophagy, and induced mitochondrial dysfunction. Subsequently, knockdown of LRPPRC inhibited malignant behaviors in PANC-1 cells, including proliferation, migration, invasion, tumor formation, and chemoresistance to gemcitabine. Finally, by inhibiting autophagy/mitophagy using 3-MA, the inhibitory effect of LRPPRC knockdown on proliferation was reversed.

Conclusion: Taken together, our results indicate that LRPPRC may act as an oncogene via maintaining mitochondrial homeostasis and could be used as a predictive marker for patient prognosis in pancreatic cancer.
Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis
Authors: Liu Tingwei , Shen Jiacheng , He Qizhi , Xu Shaohua
Published: February 2022

Ovarian cancer (OC) is the most lethal gynecological malignancy, in which chemoresistance is a crucial factor leading to the poor prognosis. Recently, immunotherapy has brought new light for the treatment of solid tumors. Hence, as a kind of immunologically active cancer, it is reasonably necessary to explore the potential mechanism between immune characteristics and cisplatin resistance in OC. Our study focused on the important role of cisplatin resistance-related lncRNAs on mediating the OC tumor immune microenvironment (TIME) using an integrative analysis based on the Cancer Genome Atlas (TCGA) database. First, the cisplatin resistance-related differentially expressed lncRNAs (DELs) and mRNAs (DEMs) were preliminarily screened to construct a DEL–DEM co-expression network. Next, the protein–protein interaction (PPI) network and pivot analysis were performed to reveal the relevance of these lncRNAs with tumor immune response. Second, the novel lncRNA CTD-2288O8.1 was identified as a key gene for the OC cisplatin resistance formation by qRT-PCR and survival analysis. Gain- and loss-of-function assays (Cell Counting Kit-8 (CCK-8) assay, wound-healing scratch assay, transwell assay, and colony formation assay) further verified the activity of CTD-2288O8.1 in OC progression as well. Third, gene set enrichment analysis (GSEA) was applied along with the correlation analyses of CTD-2288O8.1 with ImmuneScore, tumor-infiltrating immune cells (TICs), and immune inhibitory checkpoint molecules, illustrating that CTD-2288O8.1 was strongly associated with the TIME and has the potential to predict the effect of OC immunotherapy. In addition, basic experiments demonstrated that the expression of CTD-2288O8.1 impacted the EGFR/AKT signal pathway activity of OC tumor cells. Of greater significance, it promoted the M2 polarization of macrophage, which is a type of the most important components of the TIME in solid tumor. Taking together, our study revealed cisplatin resistance-related lncRNAs closely linked with tumor immunity in OC, underscoring the potential mechanism of the TIME in conferring cisplatin resistance, which provided the research basis for further clinical treatment. CTD-2288O8.1 was identified to mediate cisplatin resistance and affect the response of immunotherapy, which could serve as a promising biomarker for guiding clinical treatment and improving prognosis in OC.
Teachers' Perceptions and Experiences of Menstrual Cycle Education and Support in UK Schools
Authors: Brown Natalie , Williams Rebekah , Bruinvels Georgie , Piasecki Jessica , Forrest Laura J.
Published: February 2022

The purpose of this study was 2-fold, to (1) explore current education provision in UK schools including barriers to menstrual cycle education and (2) assess the perceived support teachers received to deliver menstrual cycle education. Seven hundred eighty-nine teachers (91% female) from all stages of school education in England (48%), Scotland (24%), Wales (22%) and Northern Ireland (6%) completed an online survey. The survey captured information on menstrual education in schools, teacher's knowledge and confidence of the menstrual cycle, support provided to teachers, provision of menstrual products in school and perceived impact of the menstrual cycle on young people in school. Four hundred ninety-eight teachers reported lessons were provided on the menstrual cycle (63%), predominantly delivered within personal, social, health and economic or science subjects, with over half of the lessons focusing on the biology (56%) or provision of menstrual products (40%) rather than lived experiences (14%). Teachers perceived the menstrual cycle affected participation in PE (88%), pupil confidence (88%), school attendance (82%) and attitude and behavior (82%). Overall, 80% of teachers felt receiving training would be beneficial to improve menstrual education. The results highlight education is scientifically focused, with less education on management of symptoms or lived experiences. Teachers also perceive the menstrual cycle to influence multiple aspects of school attendance and personal performance. There is a need to address menstrual education provided in schools across the UK to help empower girls to manage their menstrual cycle, preventing a negative impact on health and school performance.
Mycobacterial PPE36 Modulates Host Inflammation by Promoting E3 Ligase Smurf1-Mediated MyD88 Degradation
Authors: Peng Zhangli , Yue Yan , Xiong Sidong
Published: February 2022

Mycobacterium tuberculosis (Mtb) PPE36, a cell-wall-associated protein, is highly specific and conserved for the Mtb complex group. Although PPE36 has been proven essential for iron utilization, little is known about it in regulating host immune responses. Here we exhibited that PPE36 was preferentially enriched in Mtb virulent strains and could efficiently inhibit host inflammatory responses and increase bacterial loads in infected macrophages and mice. In exploring the underlying mechanisms, we found that PPE36 could robustly inhibit the activation of inflammatory NF-κB and MAPK (Erk, p38, and Jnk) pathways by promoting E3 ligase Smurf1-mediated ubiquitination and proteasomal degradation of MyD88 protein. Our research revealed a previously unknown function of PPE36 on modulating host immune responses and provided some clues to the development of novel tuberculosis treatment strategies based on immune regulation.
Pembrolizumab Plus Chemotherapy Versus Chemotherapy Monotherapy as a First-Line Treatment in Elderly Patients (≥75 Years Old) With Non-Small-Cell Lung Cancer
Authors: Yang Zhengyu , Chen Ya , Wang Yanan , Hu Minjuan , Qian Fangfei , Zhang Yanwei , Zhang Bo , Zhang Wei , Han Baohui
Published: February 2022

Objective

Several trials have shown that pembrolizumab plus chemotherapy was more effective in patients with advanced non-small-cell lung cancer (NSCLC) than chemotherapy monotherapy. However, whether pembrolizumab plus chemotherapy is still a better choice for first-line treatment in elderly patients (≥75 years old) remain unknown. We retrospectively compared the efficacy and safety of these two treatments in elderly patients.

Patients and Methods

We collected data of 136 elderly patients with advanced NSCLC who were treated with pembrolizumab plus chemotherapy or chemotherapy monotherapy in our hospital from 2018 to 2020. We compared the progression-free survival (PFS) and overall survival (OS) of patients and analyzed which subgroups might benefit more significantly from pembrolizumab plus chemotherapy.

Results

In total population, pembrolizumab plus chemotherapy showed superior PFS and OS than chemotherapy monotherapy (PFS: 12.50 months vs. 5.30 months, P<0.001; OS: unreached vs. 21.27 months, P=0.037). Subgroup analysis showed patients with positive PD-L1 expression, stage IV, good performance score (ECOG-PS <2), fewer comorbidities (simplified comorbidity score <9) or female patients had demonstrated a more evident OS benefit in pembrolizumab plus chemotherapy. In terms of safety, the pembrolizumab plus chemotherapy group had higher treatment discontinuation (26% vs. 5%).

Conclusions

Elderly patients using pembrolizumab plus chemotherapy achieved longer PFS and OS, but were more likely to discontinue due to adverse effects, so disease stage, PD-L1 expression, ECOG-PS and comorbidities should be considered when selecting first-line treatment.
Tuft Cells and Their Role in Intestinal Diseases
Authors: Hendel Sebastian Kjærgaard , Kellermann Lauge , Hausmann Annika , Bindslev Niels , Jensen Kim Bak , Nielsen Ole Haagen
Published: February 2022

The interests in intestinal epithelial tuft cells, their basic physiology, involvement in immune responses and relevance for gut diseases, have increased dramatically over the last fifteen years. A key discovery in 2016 of their close connection to helminthic and protozoan infection has further spurred the exploration of these rare chemosensory epithelial cells. Although very sparse in number, tuft cells are now known as important sentinels in the gastrointestinal tract as they monitor intestinal content using succinate as well as sweet and bitter taste receptors. Upon stimulation, tuft cells secrete a broad palette of effector molecules, including interleukin-25, prostaglandin E2 and D2, cysteinyl leukotriene C4, acetylcholine, thymic stromal lymphopoietin, and β-endorphins, some of which with immunomodulatory functions. Tuft cells have proven indispensable in anti-helminthic and anti-protozoan immunity. Most studies on tuft cells are based on murine experiments using double cortin-like kinase 1 (DCLK1) as a marker, while human intestinal tuft cells can be identified by their expression of the cyclooxygenase-1 enzyme. So far, only few studies have examined tuft cells in humans and their relation to gut disease. Here, we present an updated view on intestinal epithelial tuft cells, their physiology, immunological hub function, and their involvement in human disease. We close with a discussion on how tuft cells may have potential therapeutic value in a clinical context.
The Unfolded Protein Response at the Tumor-Immune Interface
Authors: Zanetti Maurizio , Xian Su , Dosset Magalie , Carter Hannah
Published: February 2022

The tumor-immune interface has surged to primary relevance in an effort to understand the hurdles facing immune surveillance and cancer immunotherapy. Reports over the past decades have indicated a role for the unfolded protein response (UPR) in modulating not only tumor cell fitness and drug resistance, but also local immunity, with emphasis on the phenotype and altered function of immune cells such as myeloid cells and T cells. Emerging evidence also suggests that aneuploidy correlates with local immune dysregulation. Recently, we reported that the UPR serves as a link between aneuploidy and immune cell dysregulation in a cell nonautonomous way. These new findings add considerable complexity to the organization of the tumor microenvironment (TME) and the origin of its altered function. In this review, we summarize these data and also discuss the role of aneuploidy as a negative regulator of local immunity.
Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis
Authors: Yang Yapeng , Zheng Xiaojiao , Wang Yuqing , Tan Xiang , Zou Huicong , Feng Shuaifei , Zhang Hang , Zhang Zeyue , He Jinhui , Cui Bota , Zhang Xueying , Wu Zhifeng , Dong Miaomiao , Cheng Wei , Tao Shiyu , Wei Hong
Published: February 2022

In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including Alistipes putredinis, Akkermansia muciniphila, Bifidobacterium adolescentis, short-chain fatty acids (SCFAs)-producing bacterium Christensenella minuta, and secondary bile acids (SBAs)-producing bacterium Clostridium leptum. In the UC intervention group, the SCFA-producing bacterium Bacteroides stercoris, IBD-related bacterium Ruminococcus gnavus, Enterococcus faecalis, and the conditional pathogen Bacteroides caccae, were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.
Is It All About the Data? How Extruded Polystyrene Escaped Single-Use Plastic Directive Market Restrictions
Authors: Troya María Del Camino , Power Orla-Peach , Kopke Kathrin
Published: February 2022

The Single-Use Plastics Directive (EU) 72/2019/904 is the main legislation governing plastic pollution, inclusive of marine plastic pollution in the European Union (EU). The Directive has issued market restrictions on several single-use plastic products which contribute to marine plastic pollution, including foamed polystyrene products made of expanded polystyrene (EPS). However, extruded polystyrene (XPS) which is commonly used in the same single-use plastics products as EPS has been omitted from the market placement restrictions within the scope of the Directive. This has subsequently compromised the Single-Use Plastics Directive’s effectiveness for reducing marine plastic pollution and hinders the efforts of related EU instruments such as the Marine Strategy Framework Directive, Descriptor 10 toward achieving Good Environmental Status across the marine environment in the EU. This paper provides some background on EPS and XPS, and discusses plastic pollution policy making in the EU, while further addressing the role of quantitative data in the European Joint Research Centre’s Technical Report on Top Marine Beach Litter Items in the EU for the formulation of policy regulating foamed polystyrene derived marine plastic pollution. We also provide an overview of how the communication gaps in the polymer science nomenclature for polystyrene may have contributed to the development of misnomers for extruded and EPS, consequently compromising necessary data gathering efforts. Our perspective hopes to incite conversations on communication gaps between scientists and policy makers and emphasise the need for gathering quantitative disaggregated data on the foamed polystyrene market to inform European plastic pollution legislation adequately.
Autoimmune Encephalitis With Multiple Auto-Antibodies With Concomitant Human Herpesvirus-7 and Ovarian Teratoma: A Case Report
Authors: Yang Jianhua , Wu Pengcheng , Liu Xianghong , Xia Han , Lai Zhaohui
Published: February 2022

Infectious etiologies and tumors are common triggers of autoimmune encephalitis. We herein reported a rare case of autoimmune encephalitis with multiple autoantibodies in cerebrospinal fluid (CSF) and serum, with concomitant human herpesvirus 7 (HHV-7) infection and ovarian teratoma. A 36-year-old woman presented with mental and behavioral changes and gibberish for 13 days, followed by fever for 1 day. Her brain MRI indicated limbic encephalitis. Metagenomic next-generation sequencing (mNGS) of CSF revealed HHV-7. Antibody testing showed positive anti-N-methyl-D-aspartate receptor (NMDAR) and anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibodies in CSF and serum. Ovarian teratoma was considered after pelvic MRI, which was then pathologically confirmed after laparoscopic ovariectomy. Her conditions improved after laparoscopic surgery, intravenous steroids, immunoglobulin, and rituximab therapy. Our findings suggested that the combination of multiple therapies including antiviral, immunotherapy, and resection of tumors were appropriate and improved the prognosis, when HHV-7 infection and ovarian teratoma were concomitant with multiple anti-neuronal antibodies of autoimmune encephalitis.
Transcriptome and Gut Microbiota Profiling Revealed the Protective Effect of Tibetan Tea on Ulcerative Colitis in Mice
Authors: Wang Ning , Wu Tao , Du Di , Mei Jie , Luo Huibo , Liu Zishan , Saleemi Muhammad Kashif , Zhang Runhui , Chang Candace , Mehmood Muhammad Aamer , Zhu Hui
Published: February 2022

Traditionally, Ya’an Tibetan tea is routinely consumed by local people in the Tibet region. It is believed to possess promising anti-inflammatory benefits. This study was conducted to elucidate the protective impact of Tibetan tea extract (TTE) on dextran sodium sulfate (DSS)-induced colitis in mice. Mice were split into four groups: control (C) group, Tibetan tea (T) group, DSS-induced model (CD) group, and Tibetan tea + DSS (TD) group. The intake of TTE significantly reduced the clinical symptoms of ulcerative colitis (UC) by alleviating the impact of cellular damage and reducing glandular hypertrophy and the infiltration of inflammatory cells. UC led to a prominent shift of the microbial communities in the gut. Interestingly, the beneficial microbes, such as Lactobacillus reuteri, Bifidobacterium choerinum, and Lactobacillus intestinalis, were significantly increased in TTE-treated mice when compared to any other experimental group. The transcriptome analysis revealed that the positive effect of TTE on UC could be attributed to changes in the G alpha (i) signaling pathway and the innate immune system. The genes related to inflammation and immune system pathways were differentially expressed in the TTE-treated group. Moreover, the relative expression of genes linked to the inflammatory TLR4/MyD88/NF-κB signaling pathway was significantly downregulated toward the level of normal control samples in the TD group. Overall, this study revealed the modulatory effect by which TTE reversed the development and severity of chronic colon damage.
The Phylosymbiosis Pattern Between the Fig Wasps of the Same Genus and Their Associated Microbiota
Authors: Li Jiaxing , Wei Xianqin , Huang Dawei , Xiao Jinhua
Published: February 2022

Microbial communities can be critical for many metazoans, which can lead to the observation of phylosymbiosis with phylogenetically related species sharing similar microbial communities. Most of the previous studies on phylosymbiosis were conducted across the host families or genera. However, it is unclear whether the phylosymbiosis signal is still prevalent at lower taxonomic levels. In this study, 54 individuals from six species of the fig wasp genus Ceratosolen (Hymenoptera: Agaonidae) collected from nine natural populations and their associated microbiota were investigated. The fig wasp species were morphologically identified and further determined by mitochondrial CO1 gene fragments and nuclear ITS2 sequences, and the V4 region of 16S rRNA gene was sequenced to analyze the bacterial communities. The results suggest a significant positive correlation between host genetic characteristics and microbial diversity characteristics, indicating the phylosymbiosis signal between the phylogeny of insect hosts and the associated microbiota in the lower classification level within a genus. Moreover, we found that the endosymbiotic Wolbachia carried by fig wasps led to a decrease in bacterial diversity of host-associated microbial communities. This study contributes to our understanding of the role of host phylogeny, as well as the role of endosymbionts in shaping the host-associated microbial community.
Food-Grade Expression of Manganese Peroxidases in Recombinant Kluyveromyces lactis and Degradation of Aflatoxin B1 Using Fermentation Supernatants
Authors: Xia Yu , He Rui , Sun Ying , Zhou Hangyu , Gao Minjie , Hu Xiuyu , Cui Xiaobing , Cheng Qianqian , Wang Zhouping
Published: February 2022

Aflatoxins are naturally occurring high-toxic secondary metabolites, which cause worldwide environmental contaminations and wastes of food and feed resources and severely threaten human health. Thus, the highly efficient methods and technologies for detoxification of aflatoxins are urgently needed in a long term. In this work, we report the construction of recombinant Kluyveromyces lactis strains GG799(pKLAC1-Phsmnp), GG799(pKLAC1-Plomnp), GG799(pKLAC1-Phcmnp), and then the food-grade expression of the three manganese peroxidases in these strains, followed by the degradation of aflatoxin B1 (AFB1) using the fermentation supernatants. The expression of the manganese peroxidases was achieved in a food-grade manner since Kluyveromyces lactis is food-safe and suitable for application in food or feed industries. The inducible expression process of the optimal recombinant strain GG799(pKLAC1-Phcmnp) and the aflatoxin B1 degradation process were both optimized in detail. After optimization, the degradation ratio reached 75.71%, which was an increase of 49.86% compared to the unoptimized results. The degradation product was analyzed and determined to be AFB1-8,9-dihydrodiol. The recombinant strain GG799(pKLAC1-Phcmnp) supernatants degraded more than 90% of AFB1 in the peanut samples after twice treatments. The structural computational analysis for further mutagenesis of the enzyme PhcMnp was also conducted in this work. The food-grade recombinant yeast strain and the enzyme PhcMnp have potential to be applied in food or feed industries.
Biological Characterization of Yellow Fever Viruses Isolated From Non-human Primates in Brazil With Distinct Genomic Landscapes
Authors: Furtado Nathália Dias , Raphael Lidiane de Menezes , Ribeiro Ieda Pereira , de Mello Iasmim Silva , Fernandes Déberli Ruiz , Gómez Mariela Martínez , dos Santos Alexandre Araújo Cunha , Nogueira Mônica da Silva , de Castro Márcia Gonçalves , de Abreu Filipe Vieira Santos , Martins Lívia Carício , Vasconcelos Pedro Fernando da Costa , Lourenço-de-Oliveira Ricardo , Bonaldo Myrna Cristina
Published: February 2022

Since the beginning of the XXI Century, the yellow fever virus (YFV) has been cyclically spreading from the Amazon basin to Brazil’s South and Southeast regions, culminating in an unprecedented outbreak that started in 2016. In this work, we studied four YFV isolated from non-human primates obtained during outbreaks in the states of Rio Grande do Sul in 2008 (PR4408), Goiás (GO05), and Espírito Santo (ES-504) in 2017, and Rio de Janeiro (RJ 155) in 2019. These isolates have genomic differences mainly distributed in non-structural proteins. We compared the isolates’ rates of infection in mammal and mosquito cells and neurovirulence in adult mice. RJ 155 and PR4408 YFV isolates exhibited higher infectivity in mammalian cells and neurovirulence in mice. In mosquito Aag2 cells, GO05 and PR4408 displayed the lowest proliferation rates. These results suggest that RJ 155 and PR4408 YFV isolates carry some genomic markers that increase infectivity in mammal hosts. From this characterization, it is possible to contribute to discovering new molecular markers for the virulence of YFV.
Altered Dynamic Functional Connectivity in de novo Parkinson’s Disease Patients With Depression
Authors: Xu Jianxia , Yu Miao , Wang Hui , Li Yuqian , Li Lanting , Ren Jingru , Pan Chenxi , Liu Weiguo
Published: February 2022

Background

Depression is one of the most prevalent and disturbing non-motor symptoms in Parkinson’s disease (PD), with few dynamic functional connectivity (dFC) features measured in previous studies. Our aim was to investigate the alterations of the dynamics in de novo patients with PD with depression (dPD).

Methods

We performed dFC analysis on the data of resting-state functional MRI from 21 de novo dPD, 34 de novo patients with PD without depression (ndPD), and 43 healthy controls (HCs). Group independent component analysis, a sliding window approach, followed by k-means clustering were conducted to assess functional connectivity states (which represented highly structured connectivity patterns reoccurring over time) and temporal properties for comparison between groups. We further performed dynamic graph-theoretical analysis to examine the variability of topological metrics.

Results

Four distinct functional connectivity states were clustered via dFC analysis. Compared to patients with ndPD and HCs, patients with dPD showed increased fractional time and mean dwell time in state 2, characterized by default mode network (DMN)-dominated and cognitive executive network (CEN)-disconnected patterns. Besides, compared to HCs, patients with dPD and patients with ndPD both showed weaker dynamic connectivity within the sensorimotor network (SMN) in state 4, a regionally densely connected state. We additionally observed that patients with dPD presented less variability in the local efficiency of the network.

Conclusions

Our study demonstrated that altered network connection over time, mainly involving the DMN and CEN, with abnormal dynamic graph properties, may contribute to the presence of depression in patients with PD.
Hippocampal Malrotation Could Be Less Significant in Epilepsy Caused by Focal Cortical Dysplasia Type I and Type II
Authors: He Chenmin , Ye Lingqi , Chen Cong , Hu Lingli , Jin Bo , Ding Yao , Li Hong , Ding Meiping , Wang Shan , Wang Shuang
Published: February 2022

Objectives

Debates over the relationship between hippocampal malrotation (HIMAL) and epilepsy continue without consensus. This study explores the role of HIMAL in a cohort of epilepsy caused by focal cortical dysplasia (FCD).

Methods

In this study, 90 patients with epilepsy caused by FCD type I and type II and 48 healthy adults underwent a 3 Tesla MRI following a dedicated epilepsy protocol for the analysis of the prevalence and morphologic features of HIMAL. In addition, numerous clinical characteristics and hippocampal volumes were evaluated.

Results

The cohort included a total of 90 patients (32 were HIMAL, 58 were non-HIMAL). Among these patients, 32 (35.6%) had HIMAL (22 left, four right, and six bilateral), which did not differ from the 48 controls, where 16 (33.3%) had HIMAL (12 left, two right, and two bilateral). Neither the quantitative features of HIMAL (diameter ratio, dominant inferior temporal sulcus height ratio, medial distance ratio, dominant inferior temporal sulcus angle, and parahippocampal angle), nor the accompanying characteristics of HIMAL (vertical dominant inferior temporal sulcus, enlarged temporal horn, and a low position of ipsilateral fornix) showed differences between patients with FCD and controls. No statistical difference in the clinical characteristics between FCD patients with HIMAL and those without was found. Neither the side nor the existence of HIMAL was correlated with the lateralization and location of FCD. As to the hippocampal volume, there was no difference between FCD patients with HIMAL and those without.

Conclusion

Hippocampal malrotation is a common morphologic variant in healthy controls as well as in patients with epilepsy caused by FCD type I and type II. Hippocampal malrotation could be less significant in epilepsy caused by FCD type I and type II.
Erythrocyte Indices in Creutzfeldt–Jakob Disease Predict Survival Time
Authors: Kong Yu , Chen Zhongyun , Zhang Jing , Wu Liyong
Published: February 2022

Background

Creutzfeldt–Jakob disease (CJD) is a devastating neurodegenerative disease caused by propagation of abnormally folded prion proteins (PrPSc). Some fluid biomarkers have been reported to be associated with disease duration in CJD. Based on studies which have found that prion protein (PrPC) played a role in erythrocytic hematopoiesis, we evaluated the association between peripheral red blood cell indices and survival time in CJD.

Methods

We retrospectively collected data on peripheral red blood cell indices, including red blood cell (RBC) count, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW), from 125 CJD patients. Cox proportional hazard models were generated to determine whether red cell indices correlated with survival time of patients with CJD.

Results

Of the 125 included participants, 70 (56%) were male, and the mean age at diagnosis (SD) was 60.3 (9.5) years. Hemoglobin levels (hazard ratio 1.710, 95% CI 1.124–2.600, p = 0.012) and HCT (hazard ratio 1.689, 95% CI 1.112–2.565, p=0.014) were significantly associated with survival time after controlling for sex, age, and Barthel Index. Red blood cell count, MCV, MCH, MCHC, and RDW were not associated with survival time before or after adjusting for covariates.

Conclusions

Our study found that Hb and HCT were significantly associated with survival time in patients with CJD. These results may inform evaluation of the mechanisms of interaction between prion disease and hematopoiesis, and indicate that Hb and HCT may be potential prognostic biomarkers.
Flattened Structural Network Changes and Association of Hyperconnectivity With Symptom Severity in 2–7-Year-Old Children With Autism
Authors: Ouyang Minhui , Peng Yun , Sotardi Susan , Hu Di , Zhu Tianjia , Cheng Hua , Huang Hao
Published: February 2022

Understanding the brain differences present at the earliest possible diagnostic age for autism spectrum disorder (ASD) is crucial for delineating the underlying neuropathology of the disorder. However, knowledge of brain structural network changes in the early important developmental period between 2 and 7 years of age is limited in children with ASD. In this study, we aimed to fill the knowledge gap by characterizing age-related brain structural network changes in ASD from 2 to 7 years of age, and identify sensitive network-based imaging biomarkers that are significantly correlated with the symptom severity. Diffusion MRI was acquired in 30 children with ASD and 21 typically developmental (TD) children. With diffusion MRI and quantified clinical assessment, we conducted network-based analysis and correlation between graph-theory-based measurements and symptom severity. Significant age-by-group interaction was found in global network measures and nodal efficiencies during the developmental period of 2–7 years old. Compared with significant age-related growth of the structural network in TD, relatively flattened maturational trends were observed in ASD. Hyper-connectivity in the structural network with higher global efficiency, global network strength, and nodal efficiency were observed in children with ASD. Network edge strength in ASD also demonstrated hyper-connectivity in widespread anatomical connections, including those in default-mode, frontoparietal, and sensorimotor networks. Importantly, identified higher nodal efficiencies and higher network edge strengths were significantly correlated with symptom severity in ASD. Collectively, structural networks in ASD during this early developmental period of 2–7 years of age are characterized by hyper-connectivity and slower maturation, with aberrant hyper-connectivity significantly correlated with symptom severity. These aberrant network measures may serve as imaging biomarkers for ASD from 2 to 7 years of age.