bluuebunny/crossref_metadata_2025 huggingface dataset:
The Aversion Function of the Limbic Dopaminergic Neurons and Their Roles in Functional Neurological Disorders
Authors: He Zhengming , Jiang Yao , Gu Simeng , Wu Dandan , Qin Duo , Feng Guangkui , Ma Xianjun , Huang Jason H. , Wang Fushun
Published: September 2021

The Freudian theory of conversion suggested that the major symptoms of functional neurological disorders (FNDs) are due to internal conflicts at motivation, especially at the sex drive or libido. FND patients might behave properly at rewarding situations, but they do not know how to behave at aversive situations. Sex drive is the major source of dopamine (DA) release in the limbic area; however, the neural mechanism involved in FND is not clear. Dopaminergic (DAergic) neurons have been shown to play a key role in processing motivation-related information. Recently, DAergic neurons are found to be involved in reward-related prediction error, as well as the prediction of aversive information. Therefore, it is suggested that DA might change the rewarding reactions to aversive reactions at internal conflicts of FND. So DAergic neurons in the limbic areas might induce two major motivational functions: reward and aversion at internal conflicts. This article reviewed the recent advances on studies about DAergic neurons involved in aversive stimulus processing at internal conflicts and summarizes several neural pathways, including four limbic system brain regions, which are involved in the processing of aversion. Then the article discussed the vital function of these neural circuits in addictive behavior, depression treatment, and FNDs. In all, this review provided a prospect for future research on the aversion function of limbic system DA neurons and the therapy of FNDs.
Galectin-3 Enhances Vascular Endothelial Growth Factor-A Receptor 2 Activity in the Presence of Vascular Endothelial Growth Factor
Authors: Cano Issahy , Hu Zhengping , AbuSamra Dina B. , Saint-Geniez Magali , Ng Yin Shan Eric , Argüeso Pablo , D’Amore Patricia A.
Published: September 2021

Galectin-3 (Gal3) is a carbohydrate-binding protein reported to promote angiogenesis by influencing vascular endothelial growth factor-A receptor 2 (VEGFR2) signal transduction. Here we evaluated whether the ability of Gal3 to function as an angiogenic factor involved vascular endothelial growth factor (VEGF). To address this possibility we used human retinal microvascular endothelial cells (HRECs) to determine whether exogenous Gal3 requires VEGF to activate VEGFR2 signaling and if Gal3 is required for VEGF to activate VEGFR2. VEGFR2 phosphorylation and HREC migration assays, following either VEGF neutralization with ranibizumab or Gal3 silencing, revealed that VEGF endogenously produced by the HRECs was essential for the effect of exogenous Gal3 on VEGFR2 activation and cell migration, and that VEGF-induced VEGFR2 activation was not dependent on Gal3 in HRECs. Gal3 depletion led to no reduction in VEGF-induced cell function. Since Gal3 has been suggested to be a potential therapeutic target for VEGFR2-mediated angiogenesis, it is crucial to define the possible Gal3-mediated VEGFR2 signal transduction mechanism to aid the development of efficacious therapeutic strategies.
N6-Methyladenosine RNA Modification: An Emerging Immunotherapeutic Approach to Turning Up Cold Tumors
Authors: Zhan Lei , Zhang Junhui , Zhu Suding , Liu Xiaojing , Zhang Jing , Wang Wenyan , Fan Yijun , Sun Shiying , Wei Bing , Cao Yunxia
Published: September 2021

Immunotherapy is a novel clinical approach that has shown clinical efficacy in multiple cancers. However, only a fraction of patients respond well to immunotherapy. Immuno-oncological studies have identified the type of tumors that are sensitive to immunotherapy, the so-called hot tumors, while unresponsive tumors, known as “cold tumors,” have the potential to turn into hot ones. Therefore, the mechanisms underlying cold tumor formation must be elucidated, and efforts should be made to turn cold tumors into hot tumors. N6-methyladenosine (m6A) RNA modification affects the maturation and function of immune cells by controlling mRNA immunogenicity and innate immune components in the tumor microenvironment (TME), suggesting its predominant role in the development of tumors and its potential use as a target to improve cancer immunotherapy. In this review, we first describe the TME, cold and hot tumors, and m6A RNA modification. Then, we focus on the role of m6A RNA modification in cold tumor formation and regulation. Finally, we discuss the potential clinical implications and immunotherapeutic approaches of m6A RNA modification in cancer patients. In conclusion, m6A RNA modification is involved in cold tumor formation by regulating immunity, tumor-cell-intrinsic pathways, soluble inhibitory mediators in the TME, increasing metabolic competition, and affecting the tumor mutational burden. Furthermore, m6A RNA modification regulators may potentially be used as diagnostic and prognostic biomarkers for different types of cancer. In addition, targeting m6A RNA modification may sensitize cancers to immunotherapy, making it a promising immunotherapeutic approach for turning cold tumors into hot ones.
Spectral Data Analysis and Identification of Vancomycin Hydrochloride
Authors: Tian Ye , Chong Xiaomeng , Yao Shangchen , Xu Mingzhe
Published: September 2021

Objective: To establish a method for the determination of the chemical structure of vancomycin hydrochloride.

Methods: Nuclear magnetic resonance spectroscopy and mass spectrometry were conducted to analyze the chemical structure of vancomycin hydrochloride.

Results: In this study, the target compound (1) was identified as (Sα)-(3S, 6R, 7R, 22R, 23S, 26S, 36R, 38αR)-44-[[2-O-(3-amino-2, 3, 6-trideoxy-3-C-methyl-α-L-lyso-hexopyranosyl)-β-D-glucopyranosyl] oxy]-3-(carbamoylmethyl)-10, 19-dichloro-7, 22, 28, 30, 32-pentahydroxy-6-[[(2R)-4-methyl-2-(methylamino) pentanoyl] amino]-2, 5, 24, 38, 39-pentaoxo-2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 36, 37, 38, 38α-tetradecahydro-22H-8, 11: 18, 21-dietheno-23, 36-(iminomethano)-13, 16: 31, 35-dimetheno-1H, 13H-[1, 6, 9] oxadiazacyclohexadecino [4, 5-m] [10, 2, 16]-benzoxadiazacyclotetracosine-26-carboxylic acid hydrochloride.

Conclusion: The method used in this study is accurate and can be used for the production and structural elucidation of vancomycin hydrochloride.
Time-Lagged Prediction of Food Craving With Qualitative Distinct Predictor Types: An Application of BISCWIT
Authors: Kaiser Tim , Butter Björn , Arzt Samuel , Pannicke Björn , Reichenberger Julia , Ginzinger Simon , Blechert Jens
Published: September 2021

Food craving (FC) peaks are highly context-dependent and variable. Accurate prediction of FC might help preventing disadvantageous eating behavior. Here, we examine whether data from 2 weeks of ecological momentary assessment (EMA) questionnaires on stress and emotions (active EMA, aEMA) alongside temporal features and smartphone sensor data (passive EMA, pEMA) are able to predict FCs ~2.5 h into the future in N = 46 individuals. A logistic prediction approach with feature dimension reduction via Best Item Scale that is Cross-Validated, Weighted, Informative and Transparent (BISCWIT) was performed. While overall prediction accuracy was acceptable, passive sensing data alone was equally predictive to psychometric data. The frequency of which single predictors were considered for a model was rather balanced, indicating that aEMA and pEMA models were fully idiosyncratic.
Comparison of Nanomaterials for Enhanced Oil Recovery in Tight Sandstone Reservoir
Authors: Zhang Chenjun , Jin Xu , Tao Jiaping , Xiong Bo , Pan Zhijian , Meng Siwei , Ding Bin , Wang Ying , Liang Lihao
Published: September 2021

With dwindling conventional oil resources, the development of high-performance oil-displacing agents to exploit unconventional oil and gas resources has become a research focus, and new technical ideas have been proposed for petroleum engineering with the advancement of nanomaterials and technology. This study characterized the microscopic pore throat structure of the unconventional tight sandstone reservoir of Ordos Basin in China comprehensively by using high-resolution scanning electron microscopy, image panoramic mosaic technology, mineral quantitative scanning system, and 3D image of pore. A new nanofluid with diphenyl ether surfactants as shell and C10–C14 straight-chain hydrocarbon compounds as kernel was prepared according to the features of tight sandstone reservoirs. The basic physical properties of the nanofluid were evaluated and compared with those of three other generic oil-displacing agents to understand the oil-displacement effect and mechanism. Results show that this nanofluid remains relatively stable and dispersible with aging and its average particle size matches well with the pore throat size of the target reservoir, which increases the sweep volume effectively. Additionally, the change from oil-wet to water-wet can exert capillary imbibition. And the oil-water interfacial tension can be greatly reduced to the level of 10–2 mN/m because of nanofluid’s excellent interfacial activity, which improves the efficiency of oil washing in nano-scale pore throats. Finally, the core imbibition experiment further demonstrated the superiority of the nanofluid. Using the nanofluid in optimal concentration with cores of approximately 0.1 mD can achieve a recovery rate of 37.5%, which is higher than generic oil-displacing agents by up to 9%. This study demonstrates that the excellent performance of nanofluid in enhancing oil recovery and provides a reference for the development of unconventional reservoirs, which are difficult to function with generic agents.
High Pulse: Exploring the Exhibit Features of a Collaborative, Whole-Body Exhibition for Experiential Learning in Science Centers
Authors: Lykke Marianne , Skov Mette , Jantzen Christian
Published: September 2021

This research work explored how collaborative, whole-body exhibits affect science learning in informal out-of-school settings. Specifically, the study investigated how exhibit features guided visitors to engage actively in experiential exploration of the exhibition topics, and how these exhibit features guided visitors to make sense of the interaction and transform experiences into knowledge. The study took place at a science center in Denmark. The context was the PULSE exhibition consisting of eight individual exhibits that aimed at facilitating discussions on the importance of bodily activities for physical and social well-being. Together the exhibits formed the traditional parts of a family home and core family activities, for example, a kitchen for cooking. Each exhibit was built on experiencing through physical activity and revolved around one or several biological phenomena, for example, balance, coordination, and suppleness. All exhibits were designed for group interactions. The study explored the visitors’ experiences with the exhibition using data from walking interviews with 34 visitor groups comprising a total of 108 visitors. Each exhibit was composed of a set of exhibit features, and the study analyzed how these features supported the experiential learning. The findings showed that the whole-body activities and group collaborations formed the greatest motivation to participate in the exhibition and, thereby, explore the themes of the exhibition. As regard the visitors’ learning, most groups expressed the joy of physical movement, group work, and need of strategy planning to carry out the activities in their conversations, whereas only a few groups seemed to perceive and reflect on the biological phenomena presented. Due to the physically demanding activities and the required social collaboration, the visitors were not able to engage in in-depth explorations of the exhibition’s scientific themes. In some exhibits where scientific information was incorporated naturally in the activity through interactive videos, the visitors talked about the themes as a natural part of the activity. Altogether, the findings have been used to outline a set of design principles for collaborative whole-body exhibits.
A Novel Promising Endometrial Preparation Protocol for Frozen-Thawed Embryo Transfer: A Randomized Controlled Trial
Authors: Li Jian-Chun , Wang Yan-Hong , Peng li-Ying , Zhou Yun , Chao Shi-Bin
Published: September 2021

Background

In recent years frozen-thawed embryo transfer (FET) has played an increasingly important role in ART, but there is limited consensus on the most effective method of endometrial preparation (EP) for FET. Inspired by significantly higher implantation rate and clinical pregnancy rate of the depot GnRH-a protocol, we proposed a novel EP protocol named down-regulation ovulation-induction (DROI) aimed to improve pregnancy outcomes of FET.

Methods

This was a single-center, randomized controlled pilot trial. A total of 307 patients with freeze-all strategy scheduled for first FET were enrolled in the study. A total 261 embryos were transferred in DROI-FET group including 156 patients and 266 embryos were transferred in mNC-FET group including 151 patients. Reproductive outcomes were compared between the two groups.

Results

The basic characteristics of patients, and the average number, quality and stage of embryos transferred were comparable between the two groups. Our primary outcome, implantation rate(IR) in DROI-FET group, was significantly higher than that of the mNC-FET group (54.41% versus 35.71%, P<0.01). The clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in DROI-FET group was also higher than that in mNC-FET group (69.87% versus 50.33%, P<0.01; 64.10% versus 42.38%, P<0.01).

Conclusion(s)

Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.
Organic Matter Causes Chemical Pollutant Dissipation Along With Adsorption and Microbial Degradation
Authors: Harju A. Vilhelmiina , Närhi Ilkka , Mattsson Marja , Kerminen Kaisa , Kontro Merja H.
Published: September 2021

Views on the entry of organic pollutants into the organic matter (OM) decaying process are divergent, and in part poorly understood. To clarify these interactions, pesticide dissipation was monitored in organic and mineral soils not adapted to contaminants for 241 days; in groundwater sediment slurries adapted to pesticides for 399 days; and in their sterilized counterparts with and without peat (5%) or compost-peat-sand (CPS, 15%) mixture addition. The results showed that simazine, atrazine and terbuthylazine (not sediment slurries) were chemically dissipated in the organic soil, and peat or CPS-amended soils and sediment slurries, but not in the mineral soil or sediment slurries. Hexazinone was chemically dissipated best in the peat amended mineral soil and sediment slurries. In contrast, dichlobenil chemically dissipated in the mineral soil and sediment slurries. The dissipation product 2,6-dichlorobenzamide (BAM) concentrations were lowest in the mineral soil, while dissipation was generally poor regardless of plant-derived OM, only algal agar enhanced its chemical dissipation. Based on sterilized counterparts, only terbutryn appeared to be microbially degraded in the organic soil, i.e., chemical dissipation of pesticides would appear to be utmost important, and could be the first response in the natural cleansing capacity of the environment, during which microbial degradation evolves. Consistent with compound-specific dissipation in the mineral or organic environments, long-term concentrations of pentachloroaniline and hexachlorobenzene were lowest in the mineral-rich soils, while concentrations of dichlorodiphenyltrichloroethane (DTT) and metabolites were lowest in the organic soils of old market gardens. OM amendments changed pesticide dissipation in the mineral soil towards that observed in the organic soil; that is OM accelerated, slowed down or stopped dissipation.
Green Product Quality Supervision Strategy in Online Shopping With Consumer Evaluation and Complaint
Authors: He Hui , Zhang Siyi , Zhu Lilong
Published: September 2021

Green consumption is an important foundation for achieving stable and long-term economic development goals. With the rapid development of e-commerce and people’s widespread attention to sustainability, more and more consumers purchase green products online. Therefore, we consider consumer feedback mechanisms including evaluation and complaint and construct an evolutionary game model of green product quality supervision with the participation of governmental supervision department, third-party e-commerce platform, online seller and consumer, which analyzes the four parties’ evolutionary stable strategies. To verify the theoretical results, we conduct a numerical simulation by Matlab 2020b. Moreover, we study the conditions that make evolutionary stable strategy combination exist based on Lyapunov’s First Method. And we find that when consumer chooses complaint, (0, 0, 1) is likely to become an only evolutionary stable strategy combination. At this time, the online seller chooses to provide high-quality green product, third-party e-commerce platform chooses not to strengthen inspection, and governmental supervision department chooses to strictly supervise. Conversely, when the consumer chooses no complaint, (1, 0, 0) and (0, 0, 1) may become an evolutionary stable strategy combination. At this time, the online seller cannot be stable in providing high-quality green product. What’s more, governmental supervision department increases the penalty, which can incentivize a third-party e-commerce platform to strengthen inspection. Third-party e-commerce platform increases the reward and can promote online seller to provide high-quality green product. On the one hand, this paper enriches the theoretical basis of online shopping green product quality supervision. On the other hand, compared with existing literature, it extends the main body of the evolutionary game to four paries and broadens the application scope of the game model. In addition, it has put forward feasible suggestions for the government supervision department to strengthen the quality supervision, and provided decision-making support for the third-party e-commerce platform to assume the responsibility of quality inspection.
Radiative Impacts of Aerosols During COVID-19 Lockdown Period Over the Indian Region
Authors: Bhawar Rohini L. , Fadnavis Suvarna , Kumar Vinay , Rahul P. R. C. , Sinha Tushar , Lolli Simone
Published: September 2021

The COVID-19 lockdown restrictions influenced global atmospheric aerosols. We report aerosol variations over India using multiple remote sensing datasets [Moderate Resolution Imaging Spectroradiometer (MODIS), Ozone Monitoring Instrument (OMI), Cloud-Aerosol Lidar, and Infrared Pathfinder (CALIPSO)], and model reanalysis [Copernicus Atmosphere Monitoring Service (CAMS)] during the lockdown implemented during the COVID-19 pandemic outbreak period from March 25 to April 14, 2020. Our analysis shows that, during this period, MODIS and CALIPSO showed a 30–40% reduction in aerosol optical depth (AOD) over the Indo-Gangetic Plain (IGP) with respect to decadal climatology (2010–2019). The absorbing aerosol index and dust optical depth measurements also showed a notable reduction over the Indian region, highlighting less emission of anthropogenic dust and also a reduced dust transport from West Asia during the lockdown period. On the contrary, central India showed an ∼12% AOD enhancement. CALIPSO measurements revealed that this increase was due to transported biomass burning aerosols. Analysis of MODIS fire data product and CAMS fire fluxes (black carbon, SO2, organic carbon, and nitrates) showed intense fire activity all over India but densely clustered over central India. Thus, we show that the lockdown restrictions implemented at the government level have significantly improved the air quality over northern India but fires offset its effects over central India. The biomass-burning aerosols formed a layer near 2–4 km (AOD 0.08–0.1) that produced heating at 3–4 K/day and a consequent negative radiative forcing at the surface of ∼−65 W/m2 (±40 W/m2) over the central Indian region.
Intelligence Quotient Variability in Klinefelter Syndrome Is Associated With GTPBP6 Expression Under Regulation of X-Chromosome Inactivation Pattern
Authors: Simonetti Luciane , Ferreira Lucas G. A. , Vidi Angela Cristina , Souza Janaina Sena de , Kunii Ilda S. , Melaragno Maria Isabel , Mello Claudia Berlim de , Carvalheira Gianna , Dias da Silva Magnus R.
Published: September 2021

Klinefelter syndrome (KS) displays a broad dysmorphological, endocrinological, and neuropsychological clinical spectrum. We hypothesized that the neurocognitive dysfunction present in KS relies on an imbalance in X-chromosome gene expression. Thus, the X-chromosome inactivation (XCI) pattern and neurocognitive X-linked gene expression were tested and correlated with intelligence quotient (IQ) scores. We evaluated 11 KS patients by (a) IQ assessment, (b) analyzing the XCI patterns using both HUMARA and ZDHHC15 gene assays, and (c) blood RT-qPCR to investigate seven X-linked genes related to neurocognitive development (GTPBP6, EIF2S3, ITM2A, HUWE1, KDM5C, GDI1, and VAMP7) and XIST in comparison with 14 (male and female) controls. Considering IQ 80 as the standard minimum reference, we verified that the variability in IQ scores in KS patients seemed to be associated with the XCI pattern. Seven individuals in the KS group presented a random X-inactivation (RXI) and lower average IQ than the four individuals who presented a skewed X-inactivation (SXI) pattern. The evaluation of gene expression showed higher GTPBP6 expression in KS patients with RXI than in controls (p = 0.0059). Interestingly, the expression of GTPBP6 in KS patients with SXI did not differ from that observed in controls. Therefore, our data suggest for the first time that GTPBP6 expression is negatively associated with full-scale IQ under the regulation of the type of XCI pattern. The SXI pattern may regulate GTPBP6 expression, thereby dampening the impairment in cognitive performance and playing a role in intelligence variability in individuals with KS, which warrants further mechanistic investigations.
Investigation of the Basic Steps in the Chromosome Conformation Capture Procedure
Authors: Bylino Oleg V. , Ibragimov Airat N. , Pravednikova Anna E. , Shidlovskii Yulii V.
Published: September 2021

A constellation of chromosome conformation capture methods (С-methods) are an important tool for biochemical analysis of the spatial interactions between DNA regions that are separated in the primary sequence. All these methods are based on the long sequence of basic steps of treating cells, nuclei, chromatin, and finally DNA, thus representing a significant technical challenge. Here, we present an in-depth study of the basic steps in the chromatin conformation capture procedure (3С), which was performed using Drosophila Schneider 2 cells as a model. We investigated the steps of cell lysis, nuclei washing, nucleoplasm extraction, chromatin treatment with SDS/Triton X-100, restriction enzyme digestion, chromatin ligation, reversion of cross-links, DNA extraction, treatment of a 3C library with RNases, and purification of the 3C library. Several options were studied, and optimal conditions were found. Our work contributes to the understanding of the 3C basic steps and provides a useful guide to the 3C procedure.
Pegylated Liposomal Doxorubicin Versus Epirubicin as Adjuvant Therapy for Stage I–III Breast Cancer
Authors: Hu Wenxian , Lv Kezhen , Teng Rongyue , Chen Jida , Xu Chenpu , Jin Lidan , Chen Yongxia , Zhao Wenhe
Published: September 2021

Background: Conventional anthracyclines, like epirubicin, are cornerstone drugs for breast cancer treatment of all stages, but their cumulative toxicity could cause life-threatening side effects. Pegylated liposomal doxorubicin (PLD), an effective anti-breast cancer drug, has lower toxicity than conventional anthracyclines. This retrospective study compared the efficacy and toxicity profiles between PLD and epirubicin as adjuvant therapy for breast cancer.

Patients and Methods: A total of 1,471 patients diagnosed with stage I–III breast cancer between 2000 and 2018 were included in this study, among which 661 were treated with PLD and 810 with epirubicin, with 45.9 months as the median follow-up time. Anti-breast cancer efficacy was assessed with overall survival (OS) and disease-free survival (DFS), while cardiac toxicity was assessed with left ventricular ejection fraction (LVEF) and electrocardiogram (ECG).

Results: The Kaplan–Meier method and Cox proportional hazards model revealed that there was no statistical difference in OS or DFS between patients treated with PLD and epirubicin, regardless of cancer stages or molecular subtypes (all p-values > 0.05). In addition, patients had significantly better LEVF and ECG data after adjuvant therapy with PLD (both p-values < 0.05).

Conclusion: Based on the large sample size and the long follow-up time of this study, we conclude that PLD has a similar anti-breast cancer efficacy as epirubicin while inducing lower level of cardiac toxicity in Han Chinese. This study suggests that PLD-based adjuvant chemotherapy could be a better option than epirubicin for breast cancer patients especially with existing cardiac disease.
Subcortical Hypermetabolism Associated With Cortical Hypometabolism Is a Common Metabolic Pattern in Patients With Anti-Leucine-Rich Glioma-Inactivated 1 Antibody Encephalitis
Authors: Zhao Xiaobin , Zhao Shaokun , Chen Yaojing , Zhang Zhanjun , Li Xiaotong , Liu Xiao , Lv Ruijuan , Wang Qun , Ai Lin
Published: September 2021

Purpose

Brain 18F-fluorodeoxyglucose positron emission tomography (FDG PET) is a sensitive technique for assisting in the diagnosis of patients with anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis. However, the common pattern of this disorder assessed by FDG PET remains unknown. The present study aimed to explore the glucose metabolic patterns of this disorder based on PET voxel analysis.

Methods

This retrospective study enrolled 25 patients with anti-LGI1 encephalitis, who were admitted in Beijing Tiantan Hospital between September 2014 and July 2019. The glucose metabolic pattern was compared between the included patients and 44 age- and gender-matched healthy controls using Statistical Parametric Mapping. Then, the correlation between the metabolic pattern and scaled activities of daily living (ADLs) of the patients was assessed.

Results

The median time from symptom onset to PET scans was 9 w (range:2-53w). The groupwise analysis revealed that patients with anti-LGI1 encephalitis had left hippocampal hypermetabolism and hypometabolism in almost all neocortical regions. The individual-level results showed most patients presented a decreased metabolism in neocortical regions, as well as an increase in metabolism in the hippocampus and basal ganglia. Furthermore, the metabolic gradient between hippocampus and neocortical regions was positively associated with the ADLs (frontal lobe, r=0.529, P=0.008; parietal lobe, r=0.474, P=0.019; occipital lobe, r=0.413, P=0.045; temporal lobe, r=0.490, P=0.015), respectively. In addition, the patients with facio-brachial dystonic seizures (FBDS) presented bilateral putamen hypermetabolism, when compared to patients without FBDS and healthy controls.

Conclusion

Subcortical hypermetabolism associated with cortical hypometabolism presented with a common metabolic pattern in patients with anti-LGI1 encephalitis in the present study. The resolution of the metabolic gradient of the hippocampal hypermetabolism and neocortical hypometabolism may bring about improved clinical neurologic disability.
SARS-CoV-2 Coronavirus Spike Protein-Induced Apoptosis, Inflammatory, and Oxidative Stress Responses in THP-1-Like-Macrophages: Potential Role of Angiotensin-Converting Enzyme Inhibitor (Perindopril)
Authors: Barhoumi Tlili , Alghanem Bandar , Shaibah Hayat , Mansour Fatmah A. , Alamri Hassan S. , Akiel Maaged A. , Alroqi Fayhan , Boudjelal Mohammad
Published: September 2021

A purified spike (S) glycoprotein of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) coronavirus was used to study its effects on THP-1 macrophages, peripheral blood mononuclear cells (PBMCs), and HUVEC cells. The S protein mediates the entry of SARS-CoV-2 into cells through binding to the angiotensin-converting enzyme 2 (ACE2) receptors. We measured the viability, intracellular cytokine release, oxidative stress, proinflammatory markers, and THP-1-like macrophage polarization. We observed an increase in apoptosis, ROS generation, MCP-1, and intracellular calcium expression in the THP-1 macrophages. Stimulation with the S protein polarizes the THP-1 macrophages towards proinflammatory futures with an increase in the TNFα and MHC-II M1-like phenotype markers. Treating the cells with an ACE inhibitor, perindopril, at 100 µM reduced apoptosis, ROS, and MHC-II expression induced by S protein. We analyzed the sensitivity of the HUVEC cells after the exposure to a conditioned media (CM) of THP-1 macrophages stimulated with the S protein. The CM induced endothelial cell apoptosis and MCP-1 expression. Treatment with perindopril reduced these effects. However, the direct stimulation of the HUVEC cells with the S protein, slightly increased HIF1α and MCP-1 expression, which was significantly increased by the ACE inhibitor treatment. The S protein stimulation induced ROS generation and changed the mitogenic responses of the PBMCs through the upregulation of TNFα and interleukin (IL)-17 cytokine expression. These effects were reduced by the perindopril (100 µM) treatment. Proteomic analysis of the S protein stimulated THP-1 macrophages with or without perindopril (100 µM) exposed more than 400 differentially regulated proteins. Our results provide a mechanistic analysis suggesting that the blood and vascular components could be activated directly through S protein systemically present in the circulation and that the activation of the local renin angiotensin system may be partially involved in this process.

Graphical

Suggested pathways that might be involved at least in part in S protein inducing activation of inflammatory markers (red narrow) and angiotensin-converting enzyme inhibitor (ACEi) modulation of this process (green narrow).
m6A Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Pancreatic Cancer
Authors: Sun Mengyu , Xie Meng , Zhang Tongyue , Wang Yijun , Huang Wenjie , Xia Limin
Published: September 2021

Recent studies have shown that RNA N6-methyladenosine (m6A) modification plays an important part in tumorigenesis and immune-related biological processes. However, the comprehensive landscape of immune cell infiltration characteristics in the tumor microenvironment (TME) mediated by m6A methylation modification in pancreatic cancer has not yet been elucidated. Based on consensus clustering algorithm, we identified two m6A modification subtypes and then determined two m6A-related gene subtypes among 434 pancreatic cancer samples. The TME characteristics of the identified gene subtypes were highly consistent with the immune-hot phenotype and the immune-cold phenotype respectively. According to the m6A score extracted from the m6A-related signature genes, patients can be divided into high and low m6A score groups. The low score group displayed a better prognosis and relatively strong immune infiltration. Further analysis showed that low m6A score correlated with lower tumor mutation burden and PD-L1 expression, and indicated a better response to immunotherapy. In general, m6A methylation modification is closely related to the diversity and complexity of immune infiltration in TME. Evaluating the m6A modification pattern and immune infiltration characteristics of individual tumors can help deepen our understanding of the tumor microenvironment landscape and promote a more effective clinical practice of immunotherapy.
Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8+ T Cell Proliferation
Authors: Sierra Jessica M. , Secchiari Florencia , Nuñez Sol Y. , Iraolagoitia Ximena L. Raffo , Ziblat Andrea , Friedrich Adrián D. , Regge María V. , Santilli M. Cecilia , Torres Nicolás I. , Gantov Mariana , Trotta Aldana , Ameri Carlos , Vitagliano Gonzalo , Pita Hernando Ríos , Rico Luis , Rovegno Agustín , Richards Nicolás , Domaica Carolina I. , Zwirner Norberto W. , Fuertes Mercedes B.
Published: September 2021

Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.
Environmental and Geomorphological Effects on the Distribution of Deep-Sea Canyon and Seamount Communities in the Northwest Atlantic
Authors: Mello-Rafter Kristen , Sowers Derek , Malik Mashkoor , Watling Les , Mayer Larry A. , Dijkstra Jennifer A.
Published: September 2021

Deep sea canyons and seamounts are topographically complex features that are considered to be biological hotspots. Anthropogenic pressures related to climate change and human activities are placing the species that inhabit these features at risk. Though studies have examined species composition on seamounts and canyons, few have compared communities between them, and even fewer studies have examined how species’ abundances correlate with environmental conditions or geomorphology. Consequently, this study compares species composition, community structure, and environmental variables between Northwest Atlantic continental margin canyons and seamounts along the New England Seamount Chain. Geoforms were also related to the occurrence of phyla and biodiversity. Overall, there was a significant difference in species composition between canyons and seamounts with sponges, corals, sea urchins and seastars contributing heavily to observed differences. Environmental conditions of temperature and salinity and the seafloor property slope contributed significantly to communities observed on seamounts, while substrate, depth and salinity contributed significantly to canyon communities. Abundances were significantly higher in canyons, but taxonomic richness, evenness, and diversity were all greater on seamounts. In an era where climate change and human activity have the potential to alter environmental parameters in the deep sea, it is important to examine factors that influence the spatial distribution of deep-sea benthic communities.
The Broadband Nonlinear Optical Response in Graphene/MoS2/Ag Thin Films at Near Infrared
Authors: Sun Di , Fang Yu , Yan Xiaoyan , Shan Wen , Sun Wenjun , Meng Qingyu
Published: September 2021

Graphene/MoS2/Ag thin films were successfully prepared by the magnetron sputtering technique and liquid phase exfoliation. Structure, morphology, optical properties, and nonlinear optical characteristics of the graphene/MoS2/Ag and graphene/MoS2 thin films were studied by X-ray diffractometer, spectrophotometer, field-scanning electron microscope, and femtosecond (fs) Z-scan technique. The results of the fs Z-scan experiment indicate that the graphene/MoS2/Ag thin films exhibit reverse saturable absorption properties due to the free carrier absorption and two-photon absorption. More importantly, with the increase of DC magnetron sputtering power (from 5 to 15 W), the local surface plasmon resonance effect of the Ag thin films increases, which leads to the enhancement of nonlinear optical properties of the graphene/MoS2/Ag thin films. The nonlinear absorption coefficients of the graphene/MoS2/Ag thin films are increased from 1.14 × 10–10 to 1.8 × 10–10 m/W at 800 nm and from 4.79 × 10–11 to 6.79 × 10–11 m/W at 1,030 nm, and the nonlinear refraction index of the graphene/MoS2/Ag thin films is -4.37 × 10–17∼−4.18 × 10–16 m2/W under the excitation of 800 and 1,030 nm, respectively. Moreover, when the graphene/MoS2/Ag thin films were excited at 800 and 1,030 nm, respectively, the nonlinear figure of merit values of the graphene/MoS2/Ag thin films are increased from 1.23 to 2.91 and from 1.30 to 1.47, which are enough to support the application of the graphene/MoS2/Ag thin films in the field of all-optical switching applications.
A Generic Nomogram Predicting the Stage of Liver Fibrosis Based on Serum Biochemical Indicators Among Chronic Hepatitis B Patients
Authors: Xu Xueying , Wang Wusheng , Zhang Qimeng , Cai Weijie , Wu Mingcheng , Qin Tiantian , Liu Hongbo
Published: September 2021

Introduction: Liver fibrosis staging is of great importance for reducing unnecessary injuries and prompting treatment in chronic viral hepatitis B patients. Liver biopsy is not suitable to act a screening method although it is a gold standard because of various shortcomings. This study aimed to establish a predictive nomogram as a convenient tool to effectively identify potential patients with different stages of liver fibrosis for patients with chronic hepatitis B.

Methods: A nomogram for multinomial model was developed in a training set to calculate the probability for each stage of fibrosis and tested in a validation set. Fibrosis stages were subgrouped as followed: severe fibrosis/cirrhosis (F3–F4), moderate fibrosis (F2), and nil-mild fibrosis (F0–F1). The indicators were demographic characteristics and biochemical indicators of patients. Continuous indicators were divided into several groups according to the optimal candidate value generated by the decision tree.

Results: This study recruited 964 HBV patients undergoing percutaneous liver biopsy. The multinomial model with 10 indicators was transformed into the final nomogram. The calibration plot showed a good agreement between nomogram-predicted and observed probability of different fibrosis stages. Areas under the receiver operating characteristics (AUROCs) for severe fibrosis/cirrhosis were 0.809 for training set and 0.879 for validation set. For moderate fibrosis, the AUROCs were 0.75 and 0.781. For nil-mild fibrosis, the AUROCs were 0.792 and 0.843. All the results above showed great predictive performance in predicting the stage of fibrosis by our nomogram.

Conclusion: Our model demonstrated good discrimination and extensibility in internal and external validation. The proposed nomogram in this study resulted in great reliability and it can be widely used as a convenient and efficient way.
A Systems-Level Analysis of Total-Body PET Data Reveals Complex Skeletal Metabolism Networks in vivo
Authors: Suchacki Karla J. , Alcaide-Corral Carlos J. , Nimale Samah , Macaskill Mark G. , Stimson Roland H. , Farquharson Colin , Freeman Tom C. , Tavares Adriana A. S.
Published: September 2021

Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary. in vitro molecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactions in vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactions in vivo using total-body positron emission tomography (PET) network analysis of murine 18F-FDG scans, as a biomarker of glucose metabolism in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network, which could not be identified using single tissue simplistic PET standard uptake values analysis. The application of our approach could reveal new physiological and pathological tissue interactions beyond skeletal metabolism, due to PET radiotracers diversity and the advent of clinical total-body PET systems.
Metagenomics Reveals That Proper Placement After Long-Distance Transportation Significantly Affects Calf Nasopharyngeal Microbiota and Is Critical for the Prevention of Respiratory Diseases
Authors: Cui Yaocheng , Qi Jiancheng , Cai Dongjie , Fang Jing , Xie Yue , Guo Hongrui , Chen Shiyi , Ma Xiaoping , Gou Liping , Cui Hengmin , Geng Yi , Ye Gang , Zhong Zhijun , Ren Zhihua , Hu Yanchun , Wang Ya , Deng Junliang , Yu Shuming , Cao Suizhong , Zou Huawei , Wang Zhisheng , Zuo Zhicai
Published: September 2021

Transportation is an inevitable phase for the cattle industry, and its effect on the respiratory system of transported cattle remains controversial. To reveal cattle’s nasopharyngeal microbiota dynamics, we tracked a batch of beef calves purchased from an auction market, transported to a farm by vehicle within 3 days, and adaptively fed for 7 days. Before and after the transport and after the placement, a total of 18 nasopharyngeal mucosal samples were collected, and microbial profiles were obtained using a metagenomic shotgun sequencing approach. The diversity, composition, structure, and function of the microbiota were collected at each time point, and their difference was analyzed. The results showed that, before the transportation, there were a great abundance of potential bovine respiratory disease (BRD)-related pathogens, and the transportation did not significantly change their abundance. After the transportation, 7 days of placement significantly decreased the risk of BRD by decreasing the abundance of potential BRD-related pathogens even if the diversity was decreased. We also discussed the controversial results of transportation’s effect in previous works and the decrease in diversity induced by placement. Our work provided more accurate information about the effect of transportation and the followed placement on the calf nasopharyngeal microbial community, indicated the importance of adaptive placement after long-distance transport, and is helpful to prevent BRD induced by transportation stress.
Comparative Mitogenomic Analysis and the Evolution of Rhizoctonia solani Anastomosis Groups
Authors: Lin Runmao , Xia Yuan , Liu Yao , Zhang Danhua , Xiang Xing , Niu Xianyu , Jiang Linjia , Wang Xiaolin , Zheng Aiping
Published: September 2021

Mitochondria are the major energy source for cell functions. However, for the plant fungal pathogens, mitogenome variations and their roles during the host infection processes remain largely unknown. Rhizoctonia solani, an important soil-borne pathogen, forms different anastomosis groups (AGs) and adapts to a broad range of hosts in nature. Here, we reported three complete mitogenomes of AG1-IA RSIA1, AG1-IB RSIB1, and AG1-IC, and performed a comparative analysis with nine published Rhizoctonia mitogenomes (AG1-IA XN, AG1-IB 7/3/14, AG3, AG4, and five Rhizoctonia sp. mitogenomes). These mitogenomes encoded 15 typical proteins (cox1-3, cob, atp6, atp8-9, nad1-6, nad4L, and rps3) and several LAGLIDADG/GIY-YIG endonucleases with sizes ranging from 109,017 bp (Rhizoctonia sp. SM) to 235,849 bp (AG3). We found that their large sizes were mainly contributed by repeat sequences and genes encoding endonucleases. We identified the complete sequence of the rps3 gene in 10 Rhizoctonia mitogenomes, which contained 14 positively selected sites. Moreover, we inferred a robust maximum-likelihood phylogeny of 32 Basidiomycota mitogenomes, representing that seven R. solani and other five Rhizoctonia sp. lineages formed two parallel branches in Agaricomycotina. The comparative analysis showed that mitogenomes of Basidiomycota pathogens had high GC content and mitogenomes of R. solani had high repeat content. Compared to other strains, the AG1-IC strain had low substitution rates, which may affect its mitochondrial phylogenetic placement in the R. solani clade. Additionally, with the published RNA-seq data, we investigated gene expression patterns from different AGs during host infection stages. The expressed genes from AG1-IA (host: rice) and AG3 (host: potato) mainly formed four groups by k-mean partitioning analysis. However, conserved genes represented varied expression patterns, and only the patterns of rps3-nad2 and nad1-m3g18/mag28 (an LAGLIDADG endonuclease) were conserved in AG1-IA and AG3 as shown by the correlation coefficient analysis, suggesting regulation of gene repertoires adapting to infect varied hosts. The results of variations in mitogenome characteristics and the gene substitution rates and expression patterns may provide insights into the evolution of R. solani mitogenomes.
Whole Genome Sequence of Alternaria alternata, the Causal Agent of Black Spot of Kiwifruit
Authors: Huang Ke , Tang Jianming , Zou Yong , Sun Xiangcheng , Lan Jianbin , Wang Wei , Xu Panpan , Wu Xiangwei , Ma Rui , Wang Qi , Wang Zhenshuo , Liu Jia
Published: September 2021

Alternaria alternata is a pathogen in a wide range of agriculture crops and causes significant economic losses. A strain of A. alternata (Y784-BC03) was isolated and identified from “Hongyang” kiwifruit and demonstrated to cause black spot infections on fruits. The genome sequence of Y784-BC03 was obtained using Nanopore MinION technology. The assembled genome is composed of 33,869,130bp (32.30Mb) comprising 10 chromosomes and 11,954 genes. A total of 2,180 virulence factors were predicted to be present in the obtained genome sequence. The virulence factors comprised genes encoding secondary metabolites, including non-host-specific toxins, cell wall-degrading enzymes, and major transcriptional regulators. The predicted gene clusters encoding genes for the biosynthesis and export of secondary metabolites in the genome of Y784-BC03 were associated with non-host-specific toxins, including cercosporin, dothistromin, and versicolorin B. Major transcriptional regulators of different mycotoxin biosynthesis pathways were identified, including the transcriptional regulators, polyketide synthase, P450 monooxygenase, and major facilitator superfamily transporters.