bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection
Authors: Qin Wanhai , Scicluna Brendon P. , van der Poll Tom
Published: July 2021

Host cells undergo complex transcriptional reprogramming upon infection. Epigenetic changes play a key role in the immune response to bacteria, among which DNA modifications that include methylation have received much attention in recent years. The extent of DNA methylation is well known to regulate gene expression. Whilst historically DNA methylation was considered to be a stable epigenetic modification, accumulating evidence indicates that DNA methylation patterns can be altered rapidly upon exposure of cells to changing environments and pathogens. Furthermore, the action of proteins regulating DNA methylation, particularly DNA methyltransferases and ten-eleven translocation methylcytosine dioxygenases, may be modulated, at least in part, by bacteria. This review discusses the principles of DNA methylation, and recent insights about the regulation of host DNA methylation during bacterial infection.
RGC-32 Acts as a Hub to Regulate the Transcriptomic Changes Associated With Astrocyte Development and Reactive Astrocytosis
Authors: Tatomir Alexandru , Beltrand Austin , Nguyen Vinh , Courneya Jean-Paul , Boodhoo Dallas , Cudrici Cornelia , Muresanu Dafin F. , Rus Violeta , Badea Tudor C. , Rus Horea
Published: July 2021

Response Gene to Complement 32 (RGC-32) is an important mediator of the TGF-β signaling pathway, and an increasing amount of evidence implicates this protein in regulating astrocyte biology. We showed recently that spinal cord astrocytes in mice lacking RGC-32 display an immature phenotype reminiscent of progenitors and radial glia, with an overall elongated morphology, increased proliferative capacity, and increased expression of progenitor markers when compared to their wild-type (WT) counterparts that make them incapable of undergoing reactive changes during the acute phase of experimental autoimmune encephalomyelitis (EAE). Here, in order to decipher the molecular networks underlying RGC-32’s ability to regulate astrocytic maturation and reactivity, we performed next-generation sequencing of RNA from WT and RGC-32 knockout (KO) neonatal mouse brain astrocytes, either unstimulated or stimulated with the pleiotropic cytokine TGF-β. Pathway enrichment analysis showed that RGC-32 is critical for the TGF-β-induced up-regulation of transcripts encoding proteins involved in brain development and tissue remodeling, such as axonal guidance molecules, transcription factors, extracellular matrix (ECM)-related proteins, and proteoglycans. Our next-generation sequencing of RNA analysis also demonstrated that a lack of RGC-32 results in a significant induction of WD repeat and FYVE domain-containing protein 1 (Wdfy1) and stanniocalcin-1 (Stc1). Immunohistochemical analysis of spinal cords isolated from normal adult mice and mice with EAE at the peak of disease showed that RGC-32 is necessary for the in vivo expression of ephrin receptor type A7 in reactive astrocytes, and that the lack of RGC-32 results in a higher number of homeodomain-only protein homeobox (HOPX)+ and CD133+ radial glia cells. Collectively, these findings suggest that RGC-32 plays a major role in modulating the transcriptomic changes in astrocytes that ultimately lead to molecular programs involved in astrocytic differentiation and reactive changes during neuroinflammation.
Dodging the Host Interferon-Stimulated Gene Mediated Innate Immunity by HIV-1: A Brief Update on Intrinsic Mechanisms and Counter-Mechanisms
Authors: Chintala Kumaraswami , Mohareer Krishnaveni , Banerjee Sharmistha
Published: July 2021

Host restriction factors affect different phases of a viral life cycle, contributing to innate immunity as the first line of defense against viruses, including HIV-1. These restriction factors are constitutively expressed, but triggered upon infection by interferons. Both pre-integration and post-integration events of the HIV-1 life cycle appear to play distinct roles in the induction of interferon-stimulated genes (ISGs), many of which encode antiviral restriction factors. However, HIV-1 counteracts the mechanisms mediated by these restriction factors through its encoded components. Here, we review the recent findings of pathways that lead to the induction of ISGs, and the mechanisms employed by the restriction factors such as IFITMs, APOBEC3s, MX2, and ISG15 in preventing HIV-1 replication. We also reflect on the current understanding of the counter-mechanisms employed by HIV-1 to evade innate immune responses and overcome host restriction factors. Overall, this mini-review provides recent insights into the HIV-1-host cross talk bridging the understanding between intracellular immunity and research avenues in the field of therapeutic interventions against HIV-1.
GVHD Pathogenesis, Prevention and Treatment: Lessons From Humanized Mouse Transplant Models
Authors: Hess Nicholas J. , Brown Matthew E. , Capitini Christian M.
Published: July 2021

Graft-vs-host disease (GVHD) is the most common cause of non-relapse mortality following allogeneic hematopoietic stem cell transplantation (HSCT) despite advances in conditioning regimens, HLA genotyping and immune suppression. While murine studies have yielded important insights into the cellular responses of GVHD, differences between murine and human biology has hindered the translation of novel therapies into the clinic. Recently, the field has expanded the ability to investigate primary human T cell responses through the transplantation of human T cells into immunodeficient mice. These xenogeneic HSCT models benefit from the human T cell receptors, CD4 and CD8 proteins having cross-reactivity to murine MHC in addition to several cytokines and co-stimulatory proteins. This has allowed for the direct assessment of key factors in GVHD pathogenesis to be investigated prior to entering clinical trials. In this review, we will summarize the current state of clinical GVHD research and discuss how xenogeneic HSCT models will aid in advancing the current pipeline of novel GVHD prophylaxis therapies into the clinic.
Feeding of Aulacomya atra Under Different Organic Matter Sources (Autochthonous and Allochthonous) in a Chilean Patagonia Fjord Ecosystem
Authors: Montero Paulina , Coppari Martina , Betti Federico , Bavestrello Giorgio , Daneri Giovanni
Published: July 2021

Aulacomya atra is an active suspension feeder, spatially dominant in the shallow-water hard-bottom benthic communities of the Chilean Patagonia fjords. In this region, the vertical flux of autochthonous organic matter (OM) reaching the benthos is augmented by allochthonous OM both from a terrestrial origin and from intensive salmon farming. This mixed pool of OM represents a potential source of food for a variety of benthic consumers, but to date little is known about the degree of utilization of these materials by filter feeders organisms. In this context, feeding experiments on A. atra in Puyuhuapi Fjord, Chilean Patagonia, were conducted during summer and winter 2018–2019. These experiments were designed to determine ingestion rates (IR) of A. atra fed with autochthonous (bacterial and microplanktonic community) and allochthonous (salmon food pellet) OM. Additionally, samples of A. atra tissues and suspended particulate organic matter (SPOM) were taken from the study area for stable isotope analysis. Data from laboratory experiments indicated that A. atra can feed on both autochthonous and allochthonous OM, but higher IR were detected in individuals fed with salmon food pellets. Because the IR is sensitive to food particle density rather than specific type of food, diet preferences of A. atra in feeding experiments could not be determined. Stable isotope analyses indicate that A. atra in natural environment preferentially exploits food with an isotopic signal corresponding to autochthonous OM, highlighting the primary role of phytoplankton carbon in their diet. Extensive utilization of terrestrially derived OM is therefore unlikely, although utilization of OM derived from salmon farming is not precluded because of the overlap in isotopic signal between food pellets and marine plankton.
Management Models of the Manila Clam (Ruditapes philippinarum) Fisheries in Invaded European Coastal Systems
Authors: Coelho Pedro , Carvalho Frederico , Goulding Thomas , Chainho Paula , Guerreiro José
Published: July 2021

The Manila clam (Ruditapes philippinarum, Adam & Reeve 1850) is a non-indigenous species that was introduced in Europe (France) in the 1970s for commercial purposes, and reached Portugal in the 1980s. Currently, it occurs in several European coastal systems, from the Bay of Biscay to the north Mediterranean. In Portugal, it is present in estuarine systems and coastal lagoons from the north to south, such as Ria de Aveiro, Óbidos Lagoon and Sado estuary, but a sharp rise in the prevalence of this species in the largest Portuguese estuary, the Tagus, resulted in the exponential growth of the number of harvesters and, consequently, an increase in the illegal exploitation of this resource. At least 1700 harvesters were estimated in this system and an annual catch volume of between around 4,000 and 17,000 t which corresponds to an annual value around €10,000,000 to €23,000,000 of sales. There is a general failure to comply with current legislation, both in relation to harvesting and marketing, as well as constraints arising from spatial planning instruments in force on the estuary. The failure to comply with sanitary standards for the exploitation and trade of bivalve mollusks presents a risk to public health and a social-economic issue resulting from this activity. The goal of this study is to propose management models for this activity with the aim of contributing to create a legal framework in which sustainable harvesting can be achieved, in the different systems where exploitation occurs. In order to accomplish this goal, the current state play, legal framework, regulation for harvesting and trade and relevant spatial planning instruments in Portugal are analyzed. In order to ascertain an adequate national management strategy, a variety of case studies in France, Spain and Italy were studied. The outcome is a management model which includes a co-management strategy of concessions as well as a mixed regime with concession areas and free areas. The creation of specific regulations; implementation of a co-management model with the active participation of harvesters; science-based regulation of a closed season and maximum daily quotas and an improved surveillance of the activity are recommended.
Decommissioning Research Needs for Offshore Oil and Gas Infrastructure in Australia
Authors: Melbourne-Thomas Jess , Hayes Keith R. , Hobday Alistair J. , Little L. Richard , Strzelecki Joanna , Thomson Damian P. , van Putten Ingrid , Hook Sharon E.
Published: July 2021

When offshore oil and gas infrastructure is no longer needed, it is either removed, partially removed, left in place, or left in place but repurposed. These processes are collectively referred to as decommissioning. Australian legislation requires oil and gas companies to develop acceptable plans for the safe removal of all offshore infrastructure at the end of a project’s life. Over the next 50 years, the liability for this decommissioning in Australia is expected to exceed US$45 billion. Unlike countries such as Norway, the United Kingdom and the Netherlands, Australian decommissioning activities are in their infancy, with only three cases (to date) in Commonwealth waters where infrastructure has been left in place or partially removed as part of decommissioning. Differences between the Australian marine environment and that of other regions around the world where decommissioning-related research is better progressed include very low sedimentation rates, both tropical and temperate habitats, different species composition, low primary production, and frequent tropical cyclones, as well as unique sociodemographic and cultural characteristics. Accordingly, the outcomes of the decision support tools used in other regions to identify preferred decommissioning options may not be equally applicable in Australia. Here we describe research to support risk and impact assessment for offshore decommissioning in Australia, where full removal of infrastructure is the “base case” regulatory default, but other options including partial removal and/or repurposing might provide similar or better outcomes when environmental, social, economic and seafood safety aspects are considered. Based on our review we propose an integrated framework for research needs to meet legislative requirements for decommissioning and identify research gaps that need to be addressed to inform decision-making for decommissioning in the Australian context.
Recent Dermatological Treatments for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Japan
Authors: Hsieh Ming-Hsiu , Watanabe Tomoya , Aihara Michiko
Published: July 2021

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious conditions characterized by necrosis of the skin and mucus membranes, and are mainly caused by medication and infections. Although the exact pathomechanism of SJS/TEN remains unclear, keratinocyte death is thought to be triggered by immune reactions to these antigens. While there is no established therapy for SJS/TEN, corticosteroids and intravenous immunoglobulin (IVIG) have been utilized as immunomodulator. We previously conducted a study to evaluate the efficacy of IVIG therapy in Japanese patients with SJS/TEN. IVIG was administered at a dosage of 400 mg/kg/day for 5 consecutive days as an additional therapy with systemic steroids. Prompt amelioration was observed in seven of the eight patients. All patients survived without sequelae. Recently, we retrospectively analyzed 132 cases of SJS/TEN treated in our two hospitals. The mortality rates in the patients treated with methylprednisolone pulse were 0% (0/31) for SJS and 7.0% (3/43) for TEN, and 0% (0/10) in the TEN patients treated with methylprednisolone pulse in combination with IVIG. These results suggest that early treatment with high-dose steroids, including methylprednisolone pulse therapy, and IVIG together with corticosteroids are possible therapeutic options to improve the prognosis of SJS/TEN.
Changing Patterns of Salmonella enterica Serovar Rissen From Humans, Food Animals, and Animal-Derived Foods in China, 1995–2019
Authors: Elbediwi Mohammed , Shi Daiwei , Biswas Silpak , Xu Xuebin , Yue Min
Published: July 2021

Salmonellosis represents a growing threat to global public health. Salmonella enterica remains the leading cause of bacterial foodborne diseases in China. Salmonella enterica serovar Rissen (S. Rissen) has been recognized as one of the emerging serovars among humans in different countries worldwide. However, knowledge on the prevalence of S. Rissen in China is largely lacking. To address essential epidemiological information for S. Rissen in China, a total of 1,182 S. Rissen isolates recovered from samples across the food chain were collected from 16 provinces or province-level cities between 1995 and 2019. Risk factors due to the consumption of animal-derived food products were also analyzed. We found S. Rissen is widely distributed, especially in the Eastern and Southern parts of China, and there is an increasing frequency in recent years as evidenced by the greater number of isolates recovered in 2016, 2017, and 2018. Interestingly, the majority of S. Rissen isolates recovered in this study were from human samples (63.4%; 749/1182), remarkably, 58.4% (438/749) were from asymptomatic carriers. We obtained most of the S. Rissen isolates from humans from Guangxi (59.5%; 446/749) and Shanghai (29.5%; 221/749). Among 302 human diarrheal isolates (40.3%; 302/749), we found 44.6% (139/311) of S. Rissen in children with diarrhea (age below 10 years old). This is of clinical significance as diarrhea is one of the crucial causes of child mortality globally and our findings here highlighted the importance of Salmonella infections in Chinese children. Additionally, S. Rissen isolates were also found to be associated with pork and poultry products in China. This study projected the most updated national-wide study of S. Rissen isolates obtained from different sources in China over the past two decades. Continued surveillance is warranted to further monitor this emerging serovar in China and elsewhere over the world.
Exploring the Interactions Between Neurophysiology and Cognitive and Behavioral Changes Induced by a Non-pharmacological Treatment: A Network Approach
Authors: Rodríguez-González Víctor , Gómez Carlos , Hoshi Hideyuki , Shigihara Yoshihito , Hornero Roberto , Poza Jesús
Published: July 2021

Dementia due to Alzheimer’s disease (AD) is a neurological syndrome which has an increasing impact on society, provoking behavioral, cognitive, and functional impairments. AD lacks an effective pharmacological intervention; thereby, non-pharmacological treatments (NPTs) play an important role, as they have been proven to ameliorate AD symptoms. Nevertheless, results associated with NPTs are patient-dependent, and new tools are needed to predict their outcome and to improve their effectiveness. In the present study, 19 patients with AD underwent an NPT for 83.1 ± 38.9 days (mean ± standard deviation). The NPT was a personalized intervention with physical, cognitive, and memory stimulation. The magnetoencephalographic activity was recorded at the beginning and at the end of the NPT to evaluate the neurophysiological state of each patient. Additionally, the cognitive (assessed by means of the Mini-Mental State Examination, MMSE) and behavioral (assessed in terms of the Dementia Behavior Disturbance Scale, DBD-13) status were collected before and after the NPT. We analyzed the interactions between cognitive, behavioral, and neurophysiological data by generating diverse association networks, able to intuitively characterize the relationships between variables of a different nature. Our results suggest that the NPT remarkably changed the structure of the association network, reinforcing the interactions between the DBD-13 and the neurophysiological parameters. We also found that the changes in cognition and behavior are related to the changes in spectral-based neurophysiological parameters. Furthermore, our results support the idea that MEG-derived parameters can predict NPT outcome; specifically, a lesser degree of AD neurophysiological alterations (i.e., neural oscillatory slowing, decreased variety of spectral components, and increased neural signal regularity) predicts a better NPT prognosis. This study provides deeper insights into the relationships between neurophysiology and both, cognitive and behavioral status, proving the potential of network-based methodology as a tool to further understand the complex interactions elicited by NPTs.
Altering Perceived Context: Transportation Cues Influence Novelty-Induced Context Exploration
Authors: Nemchek Victoria , Agee Laura A. , Malone Cassidy A. , Raskin Marissa , Seese Sydney , Monfils Marie H.
Published: July 2021

Context is the milieu in which everything occurs. Many research studies consider context, or even explicitly manipulate it; yet it remains challenging to characterize. We know that a context surrounds and influences tasks; however, the boundaries of its influence are difficult to define. In behavioral science, context is often operationalized by the physical environment in which the experiment takes place, and the boundaries of the context are assumed to begin at the entrance to that of the room or apparatus. Experiences during transportation to the testing space have been shown to impact rodent behavior and memory, but transportation’s relationship with novelty and physical environment is not fully understood. The current study explored how familiar vs. novel cues, both within a physical environment and preceding it, impact the perception of a context. We manipulated context on three levels: physical testing environment, object cues within that environment, and transportation cues preceding entrance to the testing environment. We found that novel transportation cues can change rats’ perception of both familiar and novel contexts. The effects of transportation on perceived context may be affected by the length of the retention interval, testing environment, and behavioral range. These data suggest that context is a broad concept that includes cues across time and is sensitive to small differences in experience.
Sparse Granger Causality Analysis Model Based on Sensors Correlation for Emotion Recognition Classification in Electroencephalography
Authors: Chen Dongwei , Miao Rui , Deng Zhaoyong , Han Na , Deng Chunjian
Published: July 2021

In recent years, affective computing based on electroencephalogram (EEG) data has attracted increased attention. As a classic EEG feature extraction model, Granger causality analysis has been widely used in emotion classification models, which construct a brain network by calculating the causal relationships between EEG sensors and select the key EEG features. Traditional EEG Granger causality analysis uses the L2 norm to extract features from the data, and so the results are susceptible to EEG artifacts. Recently, several researchers have proposed Granger causality analysis models based on the least absolute shrinkage and selection operator (LASSO) and the L1/2 norm to solve this problem. However, the conventional sparse Granger causality analysis model assumes that the connections between each sensor have the same prior probability. This paper shows that if the correlation between the EEG data from each sensor can be added to the Granger causality network as prior knowledge, the EEG feature selection ability and emotional classification ability of the sparse Granger causality model can be enhanced. Based on this idea, we propose a new emotional computing model, named the sparse Granger causality analysis model based on sensor correlation (SC-SGA). SC-SGA integrates the correlation between sensors as prior knowledge into the Granger causality analysis based on the L1/2 norm framework for feature extraction, and uses L2 norm logistic regression as the emotional classification algorithm. We report the results of experiments using two real EEG emotion datasets. These results demonstrate that the emotion classification accuracy of the SC-SGA model is better than that of existing models by 2.46–21.81%.
Psychedelics for Brain Injury: A Mini-Review
Authors: Khan Mia , Carter Gregory T. , Aggarwal Sunil K. , Holland Julie
Published: July 2021

Objective: Stroke and traumatic brain injury (TBI) are among the leading causes of disability. Even after engaging in rehabilitation, nearly half of patients with severe TBI requiring hospitalization are left with major disability. Despite decades of investigation, pharmacologic treatment of brain injury is still a field in its infancy. Recent clinical trials have begun into the use of psychedelic therapeutics for treatment of brain injury. This brief review aims to summarize the current state of the science's relevance to neurorehabilitation, and may act as a resource for those seeking to understand the precedence for these ongoing clinical trials.

Methods: Narrative mini-review of studies published related to psychedelic therapeutics and brain injury.

Results: Recent in vitro, in vivo, and case report studies suggest psychedelic pharmacotherapies may influence the future of brain injury treatment through modulation of neuroinflammation, hippocampal neurogenesis, neuroplasticity, and brain complexity.

Conclusions: Historical data on the safety of some of these substances could serve in effect as phase 0 and phase I studies. Further phase II trials will illuminate how these drugs may treat brain injury, particularly TBI and reperfusion injury from stroke.
Multisensory Integration-Attention Trade-Off in Cochlear-Implanted Deaf Individuals
Authors: van de Rijt Luuk P. H. , van Opstal A. John , van Wanrooij Marc M.
Published: July 2021

The cochlear implant (CI) allows profoundly deaf individuals to partially recover hearing. Still, due to the coarse acoustic information provided by the implant, CI users have considerable difficulties in recognizing speech, especially in noisy environments. CI users therefore rely heavily on visual cues to augment speech recognition, more so than normal-hearing individuals. However, it is unknown how attention to one (focused) or both (divided) modalities plays a role in multisensory speech recognition. Here we show that unisensory speech listening and reading were negatively impacted in divided-attention tasks for CI users—but not for normal-hearing individuals. Our psychophysical experiments revealed that, as expected, listening thresholds were consistently better for the normal-hearing, while lipreading thresholds were largely similar for the two groups. Moreover, audiovisual speech recognition for normal-hearing individuals could be described well by probabilistic summation of auditory and visual speech recognition, while CI users were better integrators than expected from statistical facilitation alone. Our results suggest that this benefit in integration comes at a cost. Unisensory speech recognition is degraded for CI users when attention needs to be divided across modalities. We conjecture that CI users exhibit an integration-attention trade-off. They focus solely on a single modality during focused-attention tasks, but need to divide their limited attentional resources in situations with uncertainty about the upcoming stimulus modality. We argue that in order to determine the benefit of a CI for speech recognition, situational factors need to be discounted by presenting speech in realistic or complex audiovisual environments.
Updated Database and Trends of Declared Low- and No-Calorie Sweeteners From Foods and Beverages Marketed in Spain
Authors: Samaniego-Vaesken Mª de Lourdes , González-Fernández Beatriz , Partearroyo Teresa , Urrialde Rafael , Varela-Moreiras Gregorio
Published: July 2021

Background: The past few years have witnessed an increase in the availability of food products containing one or more low- and no-calorie sweeteners (LNCS) in the Spanish market, mostly due to the new massive reformulation plan. However, these are not included in food composition tables or databases, and, therefore, assessment of their intake among the population is complex. This study aims to update a database including commercialized foods and beverages.

Method: A systematic search of ingredients information from the different food and beverage categories was undertaken during 2019 by recording the availability and type of LNCS declared in the information of the product from labels and online shopping platforms of retailers from Spain to update a previous food composition database compiled in 2017.

Results: A total of 1,238 products were identified. The major groups were sugar and sweets (24%), non-alcoholic beverages (21%), cereals and grains (19%), and milk and dairy products (14%) accounting for >70% of total products. The mainly declared LNCS were sorbitol (19.5%), sucralose (19.5%), and acesulfame K (19.2%).

Conclusion: There is a wide variety of products that include LNCS as a main ingredient with higher availability than when compared with the results of database of 2017, consequently, it might be expected that LNCS are commonly consumed at present in the Spanish diet.
NMN Maintains Intestinal Homeostasis by Regulating the Gut Microbiota
Authors: Huang Pan , Jiang Anqi , Wang Xuxin , Zhou Yan , Tang Weihong , Ren Caifang , Qian Xin , Zhou Zhengrong , Gong Aihua
Published: July 2021

The aim of this study was to determine the effects of long-term Nicotinamide mononucleotide (NMN) treatment on modulating gut microbiota diversity and composition, as well as its association with intestinal barrier function. In this study, C57BL/6J mice were fed different concentrations of NMN, and their feces were collected for detection of 16S rDNA and non-targeted metabolites to explore the effects of NMN on intestinal microbiota and metabolites. The results revealed that NMN increased the abundance of butyric acid-producing bacteria (Ruminococcae_UCG-014 and Prevotellaceae_NK3B31_group) and other probiotics (Akkermansia muciniphila), while the abundance of several harmful bacteria (Bilophila and Oscillibacter) were decreased after NMN treatment. Meanwhile, the level of bile acid-related metabolites in feces from the G1 group (0.1 mg/ml) was significantly increased compared to the control group, including cholic acid, taurodeoxycholic acid, taurocholic acid, glycocholic acid, and tauro-β-muricholic acid. In addition, long-term NMN treatment affected the permeability of the intestinal mucosa. The number of goblet cells and mucus thickness increased, as well as expression of tight junction protein. These results demonstrate that NMN reduced intestinal mucosal permeability and exerts a protective effect on the intestinal tract. This study lays the foundation for exploring NMN's utility in clinical research.
A Critical Review on Phytochemical Profile and Biological Effects of Turnip (Brassica rapa L.)
Authors: Cao Qingsui , Wang Ge , Peng Ye
Published: July 2021

A growing number of medicinal and edible plants have attracted increasing attention due to their abundant constituents and biological activities including turnip. Turnip (Brassica rapa L.) is an herbaceous biennial plant belonging to Cruciferae Brassica. As one of the oldest cultivated vegetables widely consumed in Asia, the turnip has received significant attention in the studies of its bioactive components and biological function. Multiple bioactive components in turnip, such as glucosinolates, isothiocyanate, phenolic compounds, flavonoids, and organic acids, were identified. The bioactivity studies on turnip revealed its anticancer, antimicrobe, anti-hypoxia, anti-diabetes, anti-oxidation, and nephroprotective activity. The present review mainly summarized the previous studies on the chemical compositions of turnip and the bioactivities associated with turnip. Further studies on the extraction and purification of compounds from a turnip as well as its potential molecular mechanisms are highly needed to utilize turnip as a functional food plant in a better way.
A First-In-Class, Humanized Antibody Targeting Alternatively Spliced Tissue Factor: Preclinical Evaluation in an Orthotopic Model of Pancreatic Ductal Adenocarcinoma
Authors: Lewis Clayton S. , Karve Aniruddha , Matiash Kateryna , Stone Timothy , Li Jingxing , Wang Jordon K. , Versteeg Henri H. , Aronow Bruce J. , Ahmad Syed A. , Desai Pankaj B. , Bogdanov Vladimir Y.
Published: July 2021

In 2021, pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer deaths in the United States. This is largely due to a lack of symptoms and limited treatment options, which extend survival by only a few weeks. There is thus an urgent need to develop new therapies effective against PDAC. Previously, we have shown that the growth of PDAC cells is suppressed when they are co-implanted with RabMab1, a rabbit monoclonal antibody specific for human alternatively spliced tissue factor (asTF). Here, we report on humanization of RabMab1, evaluation of its binding characteristics, and assessment of its in vivo properties. hRabMab1 binds asTF with a KD in the picomolar range; suppresses the migration of high-grade Pt45.P1 cells in Boyden chamber assays; has a long half-life in circulation (~ 5 weeks); and significantly slows the growth of pre-formed orthotopic Pt45.P1 tumors in athymic nude mice when administered intravenously. Immunohistochemical analysis of tumor tissue demonstrates the suppression of i) PDAC cell proliferation, ii) macrophage infiltration, and iii) neovascularization, whereas RNAseq analysis of tumor tissue reveals the suppression of pathways that promote cell division and focal adhesion. This is the first proof-of-concept study whereby a novel biologic targeting asTF has been investigated as a systemically administered single agent, with encouraging results. Given that hRabMab1 has a favorable PK profile and is able to suppress the growth of human PDAC cells in vivo, it comprises a promising candidate for further clinical development.
Emerging Perspectives on Leukemia Inhibitory Factor and its Receptor in Cancer
Authors: Christianson Joe , Oxford Julia Thom , Jorcyk Cheryl L.
Published: July 2021

Tumorigenesis and metastasis have deep connections to inflammation and inflammatory cytokines, but the mechanisms underlying these relationships are poorly understood. Leukemia Inhibitory Factor (LIF) and its receptor (LIFR), part of the interleukin-6 (IL-6) cytokine family, make up one such ill-defined piece of the puzzle connecting inflammation to cancer. Although other members of the IL-6 family have been shown to be involved in the metastasis of multiple types of cancer, the role of LIF and LIFR has been challenging to determine. Described by others in the past as enigmatic and paradoxical, LIF and LIFR are expressed in a diverse array of cells in the body, and the narrative surrounding them in cancer-related processes has been vague, and at times even contradictory. Despite this, recent insights into their functional roles in cancer have highlighted interesting patterns that may allude to a broader understanding of LIF and LIFR within tumor growth and metastasis. This review will discuss in depth the signaling pathways activated by LIF and LIFR specifically in the context of cancer–the purpose being to summarize recent literature concerning the downstream effects of LIF/LIFR signaling in a variety of cancer-related circumstances in an effort to begin teasing out the intricate web of contradictions that have made this pair so challenging to define.
Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy
Authors: Li Yue , Zhao Long , Li Xiao-Feng
Published: July 2021

Hypoxia is an important characteristic of most solid malignancies, and is closely related to tumor prognosis and therapeutic resistance. Hypoxia is one of the most important factors associated with resistance to conventional radiotherapy and chemotherapy. Therapies targeting tumor hypoxia have attracted considerable attention. Hypoxia-activated prodrugs (HAPs) are bioreductive drugs that are selectively activated under hypoxic conditions and that can accurately target the hypoxic regions of solid tumors. Both single-agent and combined use with other drugs have shown promising antitumor effects. In this review, we discuss the mechanism of action and the current preclinical and clinical progress of several of the most widely used HAPs, summarize their existing problems and shortcomings, and discuss future research prospects.
Clinical Significance of Metastasis or Micrometastasis to the Lymph Node Along the Superior Mesenteric Vein in Gastric Carcinoma: A Retrospective Analysis
Authors: Xu Xing , Zheng Guoliang , Zhang Tao , Zhao Yan , Zheng Zhichao
Published: July 2021

Background

The validity of lymphadenectomy of the lymph node along the superior mesenteric vein (LN14v) in gastric cancer remains controversial. The study investigated the characteristics and prognosis of gastric cancer with metastasis or micrometastasis to LN14v.

Methods

A retrospective study of 626 patients undergoing radical gastrectomy in our center from January 2003 to December 2015 was analyzed. In total, 303 patients had lymphadenectomy of LN14v, and lymph node micrometastasis was evaluated by immunohistochemical staining for cytokeratin nodes CK8/18. A logistic regression model was applied to confirm the predictive factors of micrometastasis. Survival analysis was performed to evaluate the effect of micrometastasis or metastasis on prognosis.

Results

The metastatic rate of the LN14v lymph node was 15.8%, and the micrometastatic rate was 3.3%. Multivariate analysis showed site, Borrmann classification, postoperative lymph node metastasis (pN), and metastasis in LN6 and LN9 were predictive factors for LN14v micrometastasis or metastasis (P < 0.05). The 5-year survival rate in the positive group (LN14v micrometastasis or metastasis) was 12.4%. The prognosis of patients without LN14v lymph node micrometastasis was better than that of the positive group, whereas the difference between group of LN14v micrometastasis and LN14v metastasis was not obvious. In matched analysis, patients with stage III gastric cancer L/M area, pN2-3, and LN6(+) who underwent lymphadenectomy of LN14v had better survival than those without lymphadenectomy of LN14v.

Conclusion

Lymph node micrometastasis may provide accurate prognostic information for patients with gastric cancer. Moreover, lymphadenectomy of LN14v might improve the survival of patients with stage III gastric cancer of L/M area, pN2-3, and LN6(+).
Potential Role of SWI/SNF Complex Subunit Actin-Like Protein 6A in Cervical Cancer
Authors: Wang Qingying , Cao Zuozeng , Wei Yingze , Zhang Jiawen , Cheng Zhongping
Published: July 2021

SWI/SNF complex subunit Actin-like protein 6A (ACTL6A) has been regarded as an oncogene, regulating the proliferation, migration and invasion of cancer cells. However, the expression pattern and biological role of ACTL6A in cervical cancer have not been reported. In this study, the mRNA expression and protein level of ACTL6A in cervical cancer samples were determined by public database and immunohistochemical (IHC) analysis. The effects of ACTL6A on cervical cancer cells were investigated via MTT, colony-formation assay, tumor xenografts and flow cytometry. Gene set enrichment analysis (GSEA) was used to explore the potential mechanism of ACTL6A in regulating tumorigenesis of cervical cancer. The results revealed that ACTL6A was markedly upregulated in cervical cancer tissues. Silencing ACTL6A expression resulted in decreased cervical cancer cell proliferation, colony formation and tumorigenesis in vitro and in vivo. Furthermore, we demonstrated that knockdown of ACTL6A induced cell cycle arrest at G1 phase, ACTL6A-mediated proliferation and cell cycle progression were c-Myc dependent. Our study provides the role of ACTL6A in cervical oncogenesis and reveals a potential target for therapeutic intervention in this cancer type.
Cinaciguat Prevents Postnatal Closure of Ductus Arteriosus by Vasodilation and Anti-remodeling in Neonatal Rats
Authors: Hung Yu-Chi , Liu Yi-Ching , Wu Bin-Nan , Yeh Jwu-Lai , Hsu Jong-Hau
Published: July 2021

Closure of the ductus arteriosus (DA) involves vasoconstriction and vascular remodeling. Cinaciguat, a soluble guanylyl cyclase (sGC) activator, was reported with vasodilatory and anti-remodeling effects on pulmonary hypertensive vessels. However, its effects on DA are not understood. Therefore, we investigated whether cinaciguat regulated DA patency and examined its underlying mechanisms. In vivo, we found that cinaciguat (10 mg/kg, i.p. at birth) prevented DA closure at 2 h after birth with luminal patency and attenuated intimal thickening. These anti-remodeling effects were associated with enhanced expression of cyclic guanosine monophosphate (cGMP) in DA. Ex vivo, cinaciguat dilated oxygen-induced DA constriction dose-dependently. Such vasodilatory effect was blunted by KT-5823, a PKG inhibitor. In DA smooth muscle cells (DASMCs), we further showed that cinaciguat inhibited angiotensin II (Ang II)-induced proliferation and migration of DASMCs. In addition, cinaciguat inhibited Ang II-induced mitochondrial reactive oxygen species (ROS) production. Finally, Ang II-activated MAPKs and Akt were also inhibited by cinaciguat. In conclusion, cinaciguat prevents postnatal DA closure by vasodilation and anti-remodeling through the cGMP/PKG pathway. The mechanisms underlying anti-remodeling effects include anti-proliferation and anti-migration, with attenuation of mitochondrial ROS production, MAPKs, and Akt signaling. Thus, this study implicates that sGC activation may be a promising novel strategy to regulate DA patency.
Enhanced Age-Related Resistance to Tomato Yellow Leaf Curl Virus in Tomato Is Associated With Higher Basal Resistance
Authors: Zhang Jing-Ru , Liu Shu-Sheng , Pan Li-Long
Published: July 2021

Tomato yellow leaf curl virus (TYLCV) is one of the most notorious plant pathogens affecting the production of tomato worldwide. While the occurrence of age-related resistance (ARR) against TYLCV has been reported, the factors impacting its development remain unknown. We conducted a series of experiments with three tomato cultivars that vary in basal resistance to TYLCV to explore factors involved in the development of ARR. Our data indicate that ARR is more pronounced in tomato cultivars with higher basal resistance. Additionally, increased plant biomass in older plants does not contribute to ARR. Virus source plants with a younger age at initial inoculation facilitates virus acquisition by whiteflies. Finally, an analysis on plant hormones suggests that salicylic acid (SA) may play a major role in the development of ARR in tomato against TYLCV. These findings provide new insights into the developmental resistance in tomato against TYLCV as well as clues for the deployment of ARR in the management of diseases caused by TYLCV.
Investigating the Influence of Tacit Knowledge Transformation Approach on Students’ Learning Ability
Authors: Zheyu Liu , Weijin Cui , Jihui Zhou , Yuan Wang , Ghani Usman , Zhai Xuesong
Published: July 2021

Tacit knowledge is an essential foundation for developing students’ learning ability, especially in understanding and solving problems. However, the transforming of tacit knowledge confront a big challenge during the outbreak of Corona Virus Disease 2019 (COVID-19), because most teaching and learning activities were conducted in online context, which impair a face-to-face interaction. To explore the effect of tacit knowledge on students’ learning ability in the online learning environments, the current study based on SECI model (The Socialization, Externalization, Combination, and Internalization) proposed to design the tacit knowledge transformation teaching approach. To assess the effectiveness of this approach, 60 elementary school students were recruited in the quasi-experiment. The results of retention test and transfer test showed that the experimental group, using the tacit knowledge transformation teaching approach, has significant improvement on learning ability than the control group. The current research theoretically provide a teaching strategy on tactic knowledge, and practically helps teachers to organize instructional activities, thereby, advocating the appropriate use of social media.
Sequential Congruency Effects of Reverse Stroop Interference on Event-Related Potential Components for Go- and Nogo-Stimuli
Authors: Suzuki Kota
Published: July 2021

Sequential congruency effects are observed in interference tasks, in which reaction times (RTs) are shorter for congruent stimuli preceded by congruent (cC) than incongruent stimuli (iC), and RTs are longer for incongruent stimuli preceded by congruent (cI) than incongruent stimuli (iI). These effects are interpreted as resulting from incongruent stimuli triggering attentional control in the next trial, which reduces cognitive control. This study aimed to examine sequential congruency effects on event-related potential (ERP) components for Go- and Nogo-stimuli. We used the hybrid reverse Stroop Go/Nogo task. The stimuli were Kanji characters, “赤” (i.e., red) and “青” (i.e., blue) painted in congruent and incongruent colors. Participants responded to one of the two characters (i.e, the Go-stimulus) and stopped responding to the other character (i.e., the Nogo-stimulus). The results indicated that the Nogo-N1 was reduced by trials preceded by incongruent stimuli compared with congruent ones, suggesting that color processing was inhibited by attentional control; however, there was no reduction in the Go-N1. In addition, the Nogo-N2 amplitudes were larger for cI than iI and iC than cC. On the other hand, the Go-N2 was not modulated by sequential modulation effects, which was lower for incongruent stimuli than congruent stimuli. These results indicate that the Nogo-N2 is involved in cognitive control, whereas the Go-N2 is associated with selection processing. These findings suggest that the modulation of sequential congruency effects of N1 and N2 required the response inhibition task demand; however, Go-P3 and Nogo-P3 amplitudes were the largest for cI. Therefore, the time range of ERP components might be related to the susceptibility of an interaction effect between response inhibition task demand and sequential congruency effects.
Can a Good Break Shot Determine the Game Outcome in 9-Ball?
Authors: Pan Jing Wen , Komar John , Sng Shawn Bing Kai , Kong Pui Wah
Published: July 2021

This study aimed to quantify the break shot characteristics and identify their significance in predicting the game outcomes in 9-ball tournaments. The break shots of 275 frames (241 men’s, 34 women’s) of professional tournaments were analyzed from two aspects: (1) cue ball position, represented by the distance between the cue ball and the table center, and (2) ball distribution, indicated by the standard deviation of Voronoi cell areas determined from all remaining balls on the table. Spearman correlation and binary logistic regression were utilized to identify associations and to predict the frame outcomes, respectively. Results showed that the more balls falling into the pockets during the break, the more clustered the remaining balls (rs = 0.232, p < 0.001). The closer the cue ball ending toward the table center, the more balls potted in the visit immediately after the break (rs = −0.144, p = 0.027). Neither cue ball position nor ball distribution could predict table clearance or winning of a frame. In conclusion, pocketing more balls during the break is associated with more clustered balls remaining on the table. Parking the cue ball near the table center after the break can facilitate potting more balls immediately after.
Addressing Challenges in Formal Research on Moribund Heritage Languages: A Path Forward
Authors: D'Alessandro Roberta , Natvig David , Putnam Michael T.
Published: July 2021

The substantial uptick in research on heritage languages over the past three decades has enhanced our understanding of the development of bilingual grammars throughout the lifespan. This interest has been accompanied by a noticeable increase of experimental work, often combined with some degree of formal rigor. Exclusively and predominantly formal research on these languages—especially studies whose empirical focus centers on moribund heritage varieties—occasionally encounters criticism, due primarily to a lack of understanding of the methodology and objectives of this body of research as a whole. The purpose of this positional essay is to once again elucidate with clarity the motivation and importance of formal linguistic research on these languages, providing a fruitful path forward for continued work in this well-established field of linguistic inquiry.