bluuebunny/crossref_metadata_2025 huggingface dataset:
Studying the Contribution of Serotonin to Neurodevelopmental Disorders. Can This Fly?
Authors: Carvajal-Oliveros Angel , Campusano Jorge M.
Published: January 2021

Serotonin is a biogenic amine that acts as neurotransmitter in different brain regions and is involved in complex behaviors, such as aggression or mood regulation. Thus, this amine is found in defined circuits and activates specific receptors in different target regions. Serotonin actions depend on extracellular levels of this amine, which are regulated by its synthetic enzymes and the plasma membrane transporter, SERT. Serotonin acts also as a neurotrophic signal in ontogeny and in the mature brain, controlling cell proliferation, differentiation, neurogenesis, and neural plasticity. Interestingly, early alterations in serotonergic signaling have been linked to a diversity of neurodevelopmental disorders, including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), or mental illnesses like schizophrenia or depression. It has been proposed that given the complex and numerous actions of serotonin, animal models could better serve to study the complexity of serotonin actions, while providing insights on how hindering serotonergic signaling could contribute to brain disorders. In this mini-review, it will be examined what the general properties of serotonin acting as a neurotransmitter in animals are, and furthermore, whether it is possible thatDrosophilacould be used to study the contribution of this amine to neurodevelopmental and mental disorders.
Case Report: Novel Arylsulfatase A (ARSA) Gene Mutations in a Patient With Adult-Onset Metachromatic Leukodystrophy Misdiagnosed as Multiple Sclerosis
Authors: Xu Lulu , Zhong Meixiang , Wang Yajuan , Wang Zhihong , Song Jie , Zhao Jing , Yu Hongyun , Yang Zhencui , Yan Wenjing , Zheng Xueping
Published: January 2021

Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary disorder characterized by the accumulation of sulfatide in the central and peripheral nervous systems. Herein, we present the case of an adult patient with MLD who had mild cognitive and psychiatric dysfunctions and severe vision disturbance, who was initially misdiagnosed as multiple sclerosis. Through genetic screening, this patient was later identified to have a full deletion of exon 4 and the novel p.P220L mutation in the arylsulfatase A (ARSA) gene. These mutations are reported for the first time in MLD. These data will help to update the mutation profiles of patients with MLD.
The Scientific Contributions of Bernard Cohen (1929–2019)
Authors: Maruta Jun
Published: January 2021

Throughout Bernard Cohen's active career at Mount Sinai that lasted over a half century, he was involved in research on vestibular control of the oculomotor, body postural, and autonomic systems in animals and humans, contributing to our understanding of such maladies as motion sickness, mal de débarquement syndrome, and orthostatic syncope. This review is an attempt to trace and connect Cohen's varied research interests and his approaches to them. His influence was vast. His scientific contributions will continue to drive research directions for many years to come.
Case Report: The Coronavirus Disease 2019 (COVID-19) Pneumonia With Multiple Thromboembolism
Authors: Cao Tingting , Zhang Guqin , Xie Huabing , Pellegrini Emily , Li Jin , Chen Xiaoxing , Pan Huaqin
Published: January 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, in late December 2019 and has since spread rapidly around the world. Severe coronavirus disease 2019 (COVID-19) pneumonia patients have abnormal blood coagulation function, but their thromboembolism prevalence is still unknown. We reported a case of a 49-year-old man infected with COVID-19, presenting with fever, chest pain, limb weakness, myalgia, and dyspnea. The patient was diagnosed with severe COVID-19 pneumonia, pulmonary thromboembolism (PTE), deep vein thrombosis (DVT), and cerebral infarction. He received supportive and empirical treatment including anticoagulant treatment, anti-inflammatory treatment, oxygen supply, and inhalation therapy. The patient's symptoms, CT images, and laboratory results improved after treatment, and a throat swab was reported to be negative for SARS-CoV-2 virus by polymerase chain reaction (PCR) test. However, on day 51 of illness onset, CT reexamination demonstrated hemorrhagic infarction. Anticoagulant therapy was discontinued temporarily. After the patient tested negative for SARS-CoV-2 virus by PCR test six more times, he was discharged and remained in home quarantine. This case highlights the importance of clinician attentiveness to the appearance of multiple thromboembolism, especially in patients with severe pulmonary damage. It also emphasizes the diagnostic value of early CT imaging and the need for effective treatment once thrombotic events occur.
A Fiber Alginate Co-culture Platform for the Differentiation of mESC and Modeling of the Neural Tube
Authors: Fannon Orla M. , Bithell Angela , Whalley Benjamin J. , Delivopoulos Evangelos
Published: January 2021

Alginate hydrogels are a commonly used substrate for in vitro 3D cell culture. These naturally derived biomaterials are highly tunable, biocompatible, and can be designed to mimic the elastic modulus of the adult brain at 1% w/v solution. Recent studies show that the molecular weight of the alginate can affect cell viability and differentiation. The relationship between the molecular weight, viscosity and ratio of G:M monomers of alginate hydrogels is complex, and the balance between these factors must be carefully considered when deciding on a suitable alginate hydrogel for stem cell research. This study investigates the formation of embryoid bodies (EB) from mouse embryonic stem cells, using low molecular weight (LMW) and high molecular weight (HMW) alginates. The cells are differentiated using a retinoic acid-based protocol, and the resulting aggregates are sectioned and stained for the presence of stem cells and the three germ layers (endoderm, mesoderm, and ectoderm). The results highlight that aggregates within LMW and HMW alginate are true EBs, as demonstrated by positive staining for markers of the three germ layers. Using tubular alginate scaffolds, formed with an adapted gradient maker protocol, we also propose a novel 3D platform for the patterned differentiation of mESCs, based on gradients of retinoic acid produced in situ by lateral motor column (LMC) motor neurons. The end product of our platform will be of great interest as it can be further developed into a powerful model of neural tube development.
A Novel Brain–Computer Interface Virtual Environment for Neurofeedback During Functional MRI
Authors: Baqapuri Halim I. , Roes Linda D. , Zvyagintsev Mikhail , Ramadan Souad , Keller Micha , Roecher Erik , Zweerings Jana , Klasen Martin , Gur Ruben C. , Mathiak Klaus
Published: January 2021

Virtual environments (VEs), in the recent years, have become more prevalent in neuroscience. These VEs can offer great flexibility, replicability, and control over the presented stimuli in an immersive setting. With recent developments, it has become feasible to achieve higher-quality visuals and VEs at a reasonable investment. Our aim in this project was to develop and implement a novel real-time functional magnetic resonance imaging (rt-fMRI)–based neurofeedback (NF) training paradigm, taking into account new technological advances that allow us to integrate complex stimuli into a visually updated and engaging VE. We built upon and developed a first-person shooter in which the dynamic change of the VE was the feedback variable in the brain–computer interface (BCI). We designed a study to assess the feasibility of the BCI in creating an immersive VE for NF training. In a randomized single-blinded fMRI-based NF-training session, 24 participants were randomly allocated into one of two groups: active and reduced contingency NF. All participants completed three runs of the shooter-game VE lasting 10 min each. Brain activity in a supplementary motor area region of interest regulated the possible movement speed of the player’s avatar and thus increased the reward probability. The gaming performance revealed that the participants were able to actively engage in game tasks and improve across sessions. All 24 participants reported being able to successfully employ NF strategies during the training while performing in-game tasks with significantly higher perceived NF control ratings in the NF group. Spectral analysis showed significant differential effects on brain activity between the groups. Connectivity analysis revealed significant differences, showing a lowered connectivity in the NF group compared to the reduced contingency-NF group. The self-assessment manikin ratings showed an increase in arousal in both groups but failed significance. Arousal has been linked to presence, or feelings of immersion, supporting the VE’s objective. Long paradigms, such as NF in MRI settings, can lead to mental fatigue; therefore, VEs can help overcome such limitations. The rewarding achievements from gaming targets can lead to implicit learning of self-regulation and may broaden the scope of NF applications.
Multisensory Interactions in Head and Body Centered Perception of Verticality
Authors: De Winkel Ksander N. , Edel Ellen , Happee Riender , Bülthoff Heinrich H.
Published: January 2021

Percepts of verticality are thought to be constructed as a weighted average of multisensory inputs, but the observed weights differ considerably between studies. In the present study, we evaluate whether this can be explained by differences in how visual, somatosensory and proprioceptive cues contribute to representations of the Head In Space (HIS) and Body In Space (BIS). Participants (10) were standing on a force plate on top of a motion platform while wearing a visualization device that allowed us to artificially tilt their visual surroundings. They were presented with (in)congruent combinations of visual, platform, and head tilt, and performed Rod & Frame Test (RFT) and Subjective Postural Vertical (SPV) tasks. We also recorded postural responses to evaluate the relation between perception and balance. The perception data shows that body tilt, head tilt, and visual tilt affect the HIS and BIS in both experimental tasks. For the RFT task, visual tilt induced considerable biases (≈ 10° for 36° visual tilt) in the direction of the vertical expressed in the visual scene; for the SPV task, participants also adjusted platform tilt to correct for illusory body tilt induced by the visual stimuli, but effects were much smaller (≈ 0.25°). Likewise, postural data from the SPV task indicate participants slightly shifted their weight to counteract visual tilt (0.3° for 36° visual tilt). The data reveal a striking dissociation of visual effects between the two tasks. We find that the data can be explained well using a model where percepts of the HIS and BIS are constructed from direct signals from head and body sensors, respectively, and indirect signals based on body and head signals but corrected for perceived neck tilt. These findings show that perception of the HIS and BIS derive from the same sensory signals, but see profoundly different weighting factors. We conclude that observations of different weightings between studies likely result from querying of distinct latent constructs referenced to the body or head in space.
Heart Rate Variability Modulates Interoceptive Accuracy
Authors: Lischke Alexander , Pahnke Rike , Mau-Moeller Anett , Weippert Matthias
Published: January 2021

Our emotional experiences depend on our interoceptive ability to perceive and interpret changes in our autonomous nervous system. An inaccurate perception and interpretation of autonomic changes impairs our ability to understand and regulate our emotional reactions. Impairments in emotion understanding and emotion regulation increase our risk for mental disorders, indicating that interoceptive deficits play an important role in the etiology and pathogenesis of mental disorders. We, thus, need measures to identify those of us whose interoceptive deficits impair their emotion understanding and emotion regulation. Here, we used cardiac measures to investigate how our ability to engage prefrontal and (para-)limbic brain region regions affects our ability to perceive and interpret cardiac changes. We administered a heartbeat detection task to a sample of healthy individuals (n = 113) whose prefrontal-(para-) limbic engagement had been determined on basis of a heart rate variability recording. We found a positive association between heartbeat detection and heart rate variability, implying that individuals with higher heart rate variability were more accurate in heartbeat detection than individuals with lower heart rate variability. These findings suggest that our interoceptive accuracy depends on our prefrontal-(para-)limbic engagement during the perception and interpretation of cardiac changes. Our findings also show that cardiac measures may be useful to investigate the association between interoceptive accuracy and prefrontal-(para-)limbic engagement in a time- and cost-efficient manner.
Isoflurane-Induced Burst Suppression Is a Thalamus-Modulated, Focal-Onset Rhythm With Persistent Local Asynchrony and Variable Propagation Patterns in Rats
Authors: Ming Qianwen , Liou Jyun-You , Yang Fan , Li Jing , Chu Chaojia , Zhou Qingchen , Wu Dan , Xu Shujia , Luo Peijuan , Liang Jianmin , Li Dan , Pryor Kane O. , Lin Weihong , Schwartz Theodore H. , Ma Hongtao
Published: January 2021

Background: Inhalational anesthetic-induced burst suppression (BS) is classically considered a bilaterally synchronous rhythm. However, local asynchrony has been predicted in theoretical studies and reported in patients with pre-existing focal pathology.

Method: We used high-speed widefield calcium imaging to study the spatiotemporal dynamics of isoflurane-induced BS in rats.

Results: We found that isoflurane-induced BS is not a globally synchronous rhythm. In the neocortex, neural activity first emerged in a spatially shifting, variably localized focus. Subsequent propagation across the whole cortex was rapid, typically within <100 milliseconds, giving the superficial resemblance to global synchrony. Neural activity remained locally asynchronous during the bursts, forming complex recurrent propagating waves. Despite propagation variability, spatial sequences of burst propagation were largely preserved between the hemispheres, and neural activity was highly correlated between the homotopic areas. The critical role of the thalamus in cortical burst initiation was demonstrated by using unilateral thalamic tetrodotoxin injection.

Conclusion: The classical impression that anesthetics-induced BS is a state of global brain synchrony is inaccurate. Bursts are a series of shifting local cortical events facilitated by thalamic projection that unfold as rapid, bilaterally asynchronous propagating waves.
Efficacy and Safety of PD-1/PD-L1 Inhibitors Plus Chemotherapy Versus PD-1/PD-L1 Inhibitors in Advanced Non-Small Cell Lung Cancer: A Network Analysis of Randomized Controlled Trials
Authors: Li Xiang , Yan Shi , Yang Jichun , Wang Yaqi , Lv Chao , Li Shaolei , Zhao Jun , Yang Yue , Zhuo Minglei , Wu Nan
Published: January 2021

Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms “immunotherapy” and “chemotherapy”. 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77–0.92), PFS (HR 0.80, 0.75–0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20–5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%–49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.

Systematic Review Registration

PROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).
Downregulation of miR-423-5p Contributes to the Radioresistance in Colorectal Cancer Cells
Authors: Shang Yuanyuan , Wang Lingfei , Zhu Zhe , Gao Wei , Li Dan , Zhou Zhuqing , Chen Lin , Fu Chuan-gang
Published: January 2021

Resistance to radiotherapy is the main reason causing treatment failure in locally advanced rectal cancer. MicroRNAs (miRNAs) have been well demonstrated to regulate cancer development and progression. However, how miRNAs regulate radiotherapy resistance in colorectal cancer remains unknown. Herein, we established two human colorectal cancer cell lines resistant to radiotherapy, named HCT116-R and RKO-R, using the strategy of fractionated irradiation. The radioresistant phenotypical changes of the two cell lines were validated by cell viability assay, colony formation assay and apoptosis assay. The miRNA expression profilings of HCT116-R and RKO-R were determined using RNA-seq analyses, and further confirmed by quantitative real-time PCR. Multiple miRNAs, including miR-423-5p, miR-7-5p, miR-522-3p, miR-3184-3p, and miR-3529-3p, were identified with altered expression in both of the radiotherapy-resistant cells, compared to the parental cells. The downregulation of miR-423-5p was further validated in the rectal cancer tissues from radiotherapy-resistant patients. Silencing of miR-423-5p in parental HCT116 and RKO cells decreased the sensitivity to radiation treatment, and inhibited the radiation-induced apoptosis. In consistence, overexpression of miR-423-5p in HCT116-R and RKO-R cells partially rescued their sensitivity to radiotherapy, and promoted the radiation-induced apoptosis. Bcl-xL (Bcl-2-like protein 1) was predicted to be a potential target gene for miR-423-5p, and miR-423-5p/Bcl-xL axis could be a critical mediator of radiosensitivity in colorectal cancer cells. The current finding not only revealed a novel role of miR-423-5p in regulating the radiosensitivity in colorectal cancer, but also suggested miR-423-5p as a molecular candidate for combination therapy with radiation to treat colorectal cancer.
Increased Circulating of CD54highCD181low Neutrophils in Myelodysplastic Syndrome
Authors: Yang Liyan , Li Hongzhao , Liu Yumei , Xie Xinyan , Zhang Huiqin , Niu Haiyue , Shao Zonghong , Xing Limin , Wang Huaquan
Published: January 2021

Myelodysplastic syndromes (MDSs) are a group of heterogeneous hematopoietic stem/progenitor cells clonal diseases, characteristic features with myeloid dysplasia, leading to abnormality of neutrophils. Recent studied have showed that neutrophils act not only as professional killers, but also as regulators of innate and adaptive immune in infection and inflammatory condition. The CD54highCD181low neutrophils are a kind of reverse-transmigrated neutrophils characterized proinflammatory phenotype. We investigated the frequency and functional properties of circulating CD54highCD181low neutrophils in patients with untreated MDS. Frequency of CD54highCD181low neutrophils was significantly increased in MDS patients and related to the severity of the disease. Furthermore, CD54highCD181low neutrophils suppressed CD8+ T cells functions in vitro. CD54highCD181low neutrophils lead to upregulation of PD1 on CD8+ T cells. Higher CD54highCD181low neutrophils were related to poor prognosis and more infections. The frequency of CD54highCD181low neutrophils decreased in high risk MDS patients who had response after treatment with decitabine. Overall, we identified CD54highCD181low neutrophils expanded in MDS. The exact mechanisms of increased CD54highCD181low neutrophils and its effect on immune function remain to be elucidated.
Transcriptome Analysis of the Inhibitory Effect of Sennoside A on the Metastasis of Hepatocellular Carcinoma Cells
Authors: Le Jiamei , Fu Yi , Han Qiuqin , Ma Yujie , Ji Houlin , Wei Xindong , Chen Yifan , Sun Yongning , Gao Yueqiu , Wu Hailong
Published: January 2021

Sennoside A (SA) is a bioactive component of Rheum officinale Baill. with an activity of irritant laxative, which has been reported to possess therapeutic potential in various diseases or conditions including obesity, insulin resistance, liver steatosis, prostate cancer and pancreatic cancer progression. However, whether SA has therapeutic potential in hepatocellular carcinoma (HCC) treatment remains elusive. In this study, we treated two HCC cell lines, HepG2 and SMMC-7721 with SA and found that SA selectively inhibited the growth of HCC cells by proliferation assay. SA has a good inhibitory effect on proliferation of HepG2 cells in a concentration dependent manner, but there was no effect on SMMC-7721 cells. Then we conducted transwell assays and transcriptome analysis in HCC cells and examined the effects of SA on HCC in vivo. The results showed that SA significantly inhibited the migration and invasion of HCC. Comparison of RNA-seq transcriptome profiles from control groups and SA-treated groups identified 171 and 264 differentially expressed genes (DEGs) in HepG2 and SMMC-7721 cells respectively, in which includes 2 overlapping up-regulated DEGs and 12 overlapping down-regulated DEGs between HepG2 and SMMC-7721 cells. The qPCR were applied to investigate the transcriptional level of 9 overlapping down-regulated DEGs related to cancer metastasis, and the results were consistent with RNA-seq data. The dominate pathways including Wnt signaling pathway, TNF signaling pathway, VEGF signaling pathway, and NF-κB signaling pathway were strongly inhibited by SA, which are involved in regulating cancer metastasis. Finally, we confirmed that the downregulation of KRT7 and KRT81 could inhibit HCC metastasis. This study has provided new insight into the understanding of the inhibitory effects and potential targets of SA on the metastasis of HCC.
Efficacy and Safety of Daprodustat for Anemia Therapy in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis
Authors: Zheng Qiyan , Wang Yahui , Yang Huisheng , Sun Luying , Fu Xinwen , Wei Ruojun , Liu Yu Ning , Liu Wei Jing
Published: January 2021

Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients.

Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs).

Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, −0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, −0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group.

Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.
Research on Quality Markers of Guizhi Fuling Prescription for Endometriosis Treatment Based on Gray Correlation Analysis Strategy
Authors: Chen Jinpeng , Gai Xiaohong , Xu Xu , Liu Yi , Ren Tao , Liu Suxiang , Ma Ting , Tian Chengwang , Liu Changxiao
Published: January 2021

Guizhi Fuling prescription (GFP), a prestigious prescription of traditional Chinese medicine (TCM) recorded in “Jingui Yaolue,” was composed of five Chinese medicines, including Moutan Cortex, Paeoniae Radix Alba, Persicae Semen, Poria Cocos, and Cinnamomi Ramulus. It was used for the treatment of endometriosis, primary dysmenorrhea, and blood stasis for centuries. However, its Quality Markers of treating endometriosis have not been clearly elucidated. In this study, a rapid ultraperformance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS/MS) method was established for Quality Markers investigation on GFP, and a total of 50 potentially bioactive constituents including triterpenoids, paeoniflorin and its derivatives, phenolic acids, and other species were identified based on their retention time, fragmentation pattern, and accurately measured mass value. Furthermore, regularity of recipe composition and gray correlation analysis revealed that all of the characteristic peaks contributed to the treatment of endometriosis. The relative correlation degrees were greater than 0.6. Among them, peaks 1 and 10, which were most closely correlated to the endometriosis, were identified as amygdalin and cinnamic acid. Finally, all of the active ingredients were molecularly docked with proteins associated with endometriosis by Schrodinger method. Among them, amygdalin, cinnamic acid, paeonol, gallic acid, and paeoniflorin had the lower binding energies. It was proposed that these constituents could be directed at Quality Markers for GFP. Thus, the integrated approach describing for revealing Quality Markers of GFP could be expected to provide a method for quality evaluation.
Spatial Lipidomics Reveals Anticancer Mechanisms of Bufalin in Combination with Cinobufagin in Tumor-Bearing Mice
Authors: Zhang Jinghui , Hong Yanjun , Xie Peisi , Chen Yang , Jiang Lilong , Yang Zhiyi , Cao Guodong , Chen Zhongjian , Liu Xuesong , Chen Yong , Wu Yongjiang , Cai Zongwei
Published: January 2021

Bufalin (BFL) and cinobufagin (CBF) are the principal bioactive constituents of Chansu, a widely used traditional Chinese medicine (TCM). The synergistic effects of potential active components are responsible for the bioactivities of TCM. Our results showed that the cotreatment with BFL and CBF confers superior anticancer efficacy compared to monotreatment. To reveal the underlying mechanisms of their cotreatment, an integrated method composed of mass spectrometry-based lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging was used to delineate the responses of tumor-bearing mice treated with BFL and CBF individually or in combination. The cotreatment with BFL and CBF modulated the sphingolipid metabolism and glycerophospholipid metabolism, and subsequently led to mitochondria-driven apoptosis and systemic disruption of biomembranes in tumor cells. Furthermore, we found that the disturbed lipid markers were mainly located in the non-necrotic tumor areas, the essential parts for the formation of solid tumor framework. Together, our findings revealed what occurred in tumor in response to the treatment of BFL and CBF, from lipids to enzymes, and thus provide insights into the critical role of lipid reprogramming in the satisfactory anticancer effect of BFL in combination with CBF.
SGLT1 Inhibition Attenuates Apoptosis in Diabetic Cardiomyopathy via the JNK and p38 Pathway
Authors: Lin Na , Lin Hui , Yang Qi , Lu Wenqiang , Sun Zhenzhu , Sun Shimin , Meng Liping , Chi Jufang , Guo Hangyuan
Published: January 2021

Background: Recent studies have revealed that a novel selective sodium-glucose cotransporter 1 (SGLT1) inhibiton has shown beneficial effects in cardiovascular diseases. However, the question of whether SGLT1 inhibition influences diabetic cardiomyopathy (DCM) remains unanswered. In this study, we investigated the influence and underlying mechanism of SGLTI inhibition on DCM.

Methods: SGLT1 levels were measured in diabetic patients with similar conditions who visited our hospital from January to December 2019. Wistar male rats (n = 50) were divided into five groups: control, diabetes induced by streptozotocin infusion, and diabetes treated with 0.5, 1.0, or 1.5 mg/kg mizagliflozin via stomach gavage for 12 weeks. H9C2 cardiomyocytes were treated with mizagliflozin and then exposed to a high glucose concentration (30 mmol/L). TUNEL assays were performed, and bcl2, bax, p-p38, p-Erk, p-JNK and caspase-3 levels were measured. We used siRNA and an SGLT1 overexpression plasmid to detect the effects of SGLT1.

Results: SGLT1 levels were significantly elevated in DCM patients, and receiver operating characteristic (ROC) curve analysis identified SGLT1 as influencing DCM. The area under the curve (AUC) was 0.705 (p < 0.05), with 65.8% sensitivity, and 62.2% specificity. SGLT1 inhibition appeared to attenuate apoptosis in DCM via the JNK and p38 pathway.

Conclusion: SGLT1 can be used as a marker for the diagnosis of DCM, and SGLT1 inhibition can attenuate apoptosis, thereby suppressing DCM development via the JNK and p38 pathway.
Influence of Multiple Animal Scanning on Image Quality for the Sedecal SuperArgus2R Preclinical PET Scanner
Authors: Efthimiou Nikos , Wright John D. , Clayton Luke , Renard Isaline , Zagni Federico , Caribé Paulo R.R.V. , Archibald Stephen J. , Cawthorne Christopher J.
Published: January 2021

Background: Increased throughput in small animal preclinical studies using positron emission tomography leads to reduced costs and improved efficiency of experimental design, however the presence of multiple off-centre subjects, as opposed to a single centered one, may affect image quality in several ways.

Methods: We evaluated the count rate performance using a NEMA scatter phantom. A Monte Carlo simulation of the system was validated against this dataset and used to simulate the count rate performance for dual scatter phantoms. NEMA NU4 image quality phantoms were then scanned in the central and offset positions, as well as in the offset position next to a uniform activity phantom. Uniformity, recovery coefficients and spillover ratios were then compared, as were two time frames for acquisition.

Results: Count rate performance assessed with a single NEMA scatter phantom was in line with previous literature, with simulated data in good agreement. Simulation of dual scatter phantoms showed an increase in scatter fraction. For the NEMA Image Quality phantom, uniformity and Recovery coefficients were degraded in the offset, and dual phantom cases, while spillover ratios were increased, notably when the chamber was placed nearest the gantry. Image quality metrics were comparable between the 20- and 10 min timeframes.

Conclusion: Dual animal scanning results in some loss of image quality on the Sedecal Argus PET scanner; however, this degradation is within acceptable limits.
Lending Diversification and Interconnectedness of the Syndicated Loan Market
Authors: Oh Gabjin , Park A-young
Published: January 2021

We investigate the effects of syndicated loan network centrality on bank performance. Syndicated loan network centrality measures the similarity and influence of the other banks within a given banks network. The network centrality constructed by syndicated loans can allow banks to gather and transfer valuable information and can thus facilitate profit-making acquisition in loan investment decisions. We use a planar maximally filtered graph to construct an interbank network using syndicated loan portfolios at the industry level. We show that the syndicated loan portfolios of high-centrality banks exhibit a higher level of portfolio diversification than those of low-centrality banks. We also document that our composite centrality measure of the bank network showed statistical significance in terms of bank performance even after controlling for the financial variables of market size, loan allocation, total asset, and loan diversification. Our findings suggest that the performance of a bank in a syndicated loan hierarchy is related to its position in this hierarchy.
The Gustavus Gene Can Regulate the Fecundity of the Green Peach Aphid, Myzus persicae (Sulzer)
Authors: Gao Yang , Ren Ruifan , Peng Jing , Wang Dongwei , Shi Xiaobin , Zheng Limin , Zhang Zhuo , Zhu Chunhui , Liu Yong , Dai Liangying , Zhang Deyong
Published: January 2021

Myzus persicae (Sulzer), commonly known as the green peach aphid, is a notorious pest that causes substantial losses to a range of crops and can transmit several plant viruses, including potato virus Y (PVY). Chemical insecticides provide only partial control of this pest and their use is not environmentally sustainable. In recent years, many genes related to growth, development, and reproduction have been used as targets for pest control. These include Gustavus (Gus), a highly conserved gene that has been reported to play an essential part in the genesis of germline cells and, hence, in fecundity in the model insect Drosophila melanogaster. We hypothesized that the Gustavus (Gus) gene was a potential target that could be used to regulate the M. persicae population. In this study, we report the first investigation of an ortholog of Gus in M. persicae, designated MpGus, and describe its role in the fecundity of this insect. First, we identified the MpGus mRNA sequence in the M. persicae transcriptome database, verified its identity with reverse transcription-polymerase chain reaction (RT-PCR), and then evaluated the transcription levels of MpGus in M. persicae nymphs of different instars and tissues with real-time quantitative PCR (RT-qPCR). To investigate its role in regulating the fecundity of M. persicae, we used RNA interference (RNAi) to silence the expression of MpGus in adult insects; this resulted in a significant reduction in the number of embryos (50.6%, P < 0.01) and newborn nymphs (55.7%, P < 0.01) in the treated aphids compared with controls. Interestingly, MpGus was also significantly downregulated in aphids fed on tobacco plants that had been pre-infected with PVYN, concomitant with a significant reduction (34.1%, P < 0.01) in M. persicae fecundity. Collectively, these data highlight the important role of MpGus in regulating fecundity in M. persicae and indicate that MpGus is a promising RNAi target gene for control of this pest species.
Effect of Fragmented DNA From Plant Pathogens on the Protection Against Wilt and Root Rot of Capsicum annuum L. Plants
Authors: Serrano-Jamaica Luz Maria , Villordo-Pineda Emiliano , González-Chavira Mario Martín , Guevara-González Ramón Gerardo , Medina-Ramos Gabriela
Published: January 2021

Chili pepper (Capsicum annuumL.) production is affected by wilt and root rot, the most devastating disease caused by the pathogen complex of oomycetePhytophthora capsiciLeon and the fungiFusarium oxysporumSchlecht andRhizoctonia solaniKühn, infecting roots, stems, leaves, and fruits. Fungicides are currently inefficient against this disease and have a high environmental impact. The use of elicitors is a sustainable alternative for inducing resistance to wilting and root rot. DNA fragments of an organism’s own origin (conspecific or self-DNA) have shown the ability to inhibit growth and activate defense mechanisms in some plant species. In this investigation, the effect of the fragmented DNA mixture ofPhytophthora capsiciL.,Fusarium oxysporumS., andRhizoctonia solaniK. on the protection against wilt and root rot ofCapsicum annuumL. plants was evaluated. Changes in plant performance, phenolics, and flavonoids contents, as well as gene expression involved in the production of defense metabolites after the fragmented and unfragmented DNA mixture in three concentrations (20, 60, and 100 μg mL–1) in chili peppers, were studied. The results obtained showed a decrease in plant height in 60 and 100 μg mL–1concentrations in absence of pathogens. Moreover, the treatment with fragmented DNA 100 μg mL–1showed significant increase in the content of phenolic compounds and total flavonoids as well as gene expression associated to plant defense in comparison with control plants. Interestingly, foliar application of DNA fragments of the pathogen complex to a concentration of 100 μg mL–1caused a 40% decrease in the mortality of infected plants with the pathogens at 30 days post-inoculation compared with control plants inoculated with the pathogen complex but not sprayed with DNA fragments. These results suggested a perspective for application of fragmented DNA of these pathogens at the agricultural level in crop protection strategies to cope with wilt and root rot inCapsicum.
Bradyrhizobium as the Only Rhizobial Inhabitant of Mung Bean (Vigna radiata) Nodules in Tropical Soils: A Strategy Based on Microbiome for Improving Biological Nitrogen Fixation Using Bio-Products
Authors: Favero Vinício Oliosi , Carvalho Rita Hilário , Motta Victória Monteiro , Leite Ana Beatriz Carneiro , Coelho Marcia Reed Rodrigues , Xavier Gustavo Ribeiro , Rumjanek Norma Gouvêa , Urquiaga Segundo
Published: January 2021

The mung bean has a great potential under tropical conditions given its high content of grain protein. Additionally, its ability to benefit from biological nitrogen fixation (BNF) through association with native rhizobia inhabiting nodule microbiome provides most of the nitrogen independence on fertilizers. Soil microbial communities which are influenced by biogeographical factors and soil properties, represent a source of rhizobacteria capable of stimulating plant growth. The objective of this study is to support selection of beneficial bacteria that form positive interactions with mung bean plants cultivated in tropical soils, as part of a seed inoculation program for increasing grain yield based on the BNF and other mechanisms. Two mung bean genotypes (Camaleão and Esmeralda) were cultivated in 10 soil samples. Nodule microbiome was characterized by next-generation sequencing using Illumina MiSeq 16S rRNA. More than 99% of nodule sequences showed similarity with Bradyrhizobium genus, the only rhizobial present in nodules in our study. Higher bacterial diversity of soil samples collected in agribusiness areas (MW_MT-I, II or III) was associated with Esmeralda genotype, while an organic agroecosystem soil sample (SE_RJ-V) showed the highest bacterial diversity independent of genotype. Furthermore, OTUs close to Bradyrhizobium elkanii have dominated in all soil samples, except in the sample from the organic agroecosystem, where just B. japonicum was present. Bacterial community of mung bean nodules is mainly influenced by soil pH, K, Ca, and P. Besides a difference on nodule colonization by OTU sequences close to the Pseudomonas genus regarding the two genotypes was detected too. Although representing a small rate, around 0.1% of the total, Pseudomonas OTUs were only retrieved from nodules of Esmeralda genotype, suggesting a different trait regarding specificity between macro- and micro-symbionts. The microbiome analysis will guide the next steps in the development of an inoculant for mung bean aiming to promote plant growth and grain yield, composed either by an efficient Bradyrhizobium strain on its own or co-inoculated with a Pseudomonas strain. Considering the results achieved, the assessment of microbial ecology parameters is a potent coadjuvant capable to accelerate the inoculant development process and to improve the benefits to the crop by soil microorganisms.
Enhanced Production of Aromatic Amino Acids in Tobacco Plants Leads to Increased Phenylpropanoid Metabolites and Tolerance to Stresses
Authors: Oliva Moran , Guy Aviv , Galili Gad , Dor Evgenia , Schweitzer Ron , Amir Rachel , Hacham Yael
Published: January 2021

Aromatic amino acids (AAAs) synthesized in plants via the shikimate pathway can serve as precursors for a wide range of secondary metabolites that are important for plant defense. The goals of the current study were to test the effect of increased AAAs on primary and secondary metabolic profiles and to reveal whether these plants are more tolerant to abiotic stresses (oxidative, drought and salt) and to Phelipanche egyptiaca (Egyptian broomrape), an obligate parasitic plant. To this end, tobacco (Nicotiana tabacum) plants were transformed with a bacterial gene (AroG) encode to feedback-insensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase, the first enzyme of the shikimate pathway. Two sets of transgenic plants were obtained: the first had low expression of the AroG protein, a normal phenotype and minor metabolic changes; the second had high accumulation of the AroG protein with normal, or deleterious morphological changes having a dramatic shift in plant metabolism. Metabolic profiling analysis revealed that the leaves of the transgenic plants had increased levels of phenylalanine (up to 43-fold), tyrosine (up to 24-fold) and tryptophan (up to 10-fold) compared to control plants having an empty vector (EV) and wild type (WT) plants. The significant increase in phenylalanine was accompanied by higher levels of metabolites that belong to the phenylpropanoid pathway. AroG plants showed improved tolerance to salt stress but not to oxidative or drought stress. The most significant improved tolerance was to P. aegyptiaca. Unlike WT/EV plants that were heavily infected by the parasite, the transgenic AroG plants strongly inhibited P. aegyptiaca development, and only a few stems of the parasite appeared above the soil. This delayed development of P. aegyptiaca could be the result of higher accumulation of several phenylpropanoids in the transgenic AroG plants and in P. aegyptiaca, that apparently affected its growth. These findings indicate that high levels of AAAs and their related metabolites have the potential of controlling the development of parasitic plants.
Subcellular Journey of Rare Cold Inducible 2 Protein in Plant Under Stressful Condition
Authors: Kim Hyun-Sung , Park Won , Lee Hyeon-Sook , Shin Jung-Ho , Ahn Sung-Ju
Published: January 2021

Rare cold inducible 2 (RCI2) proteins are small hydrophobic membrane proteins in plants, and it has been widely reported that RCI2 expressions are dramatically induced by salt, cold, and drought stresses in many species. The RCI2 proteins have been shown to regulate plasma membrane (PM) potential and enhance abiotic stress tolerance when over-expressed in plants. RCI2 protein structures contain two transmembrane domains that are thought to be PM intrinsic proteins and have been observed at the PM and endomembranes. However, cellular trafficking of RCI2s are not fully understood. In this review, we discussed (i) general properties of RCI2s characterized in many species, (ii) the uses of RCI2s as a tracer in live cell imaging analyses and when they are fused to fluorescence proteins during investigations into vesicle trafficking, and (iii) RCI2 functionalities such as their involvement in rapid diffusion, endocytosis, and protein interactions. Consequently, the connection between physiological characteristics of RCI2s and traffic of RCI2s interacting membrane proteins might be helpful to understand role of RCI2s contributing abiotic stresses tolerance.
Application of Machine Learning Algorithms in Plant Breeding: Predicting Yield From Hyperspectral Reflectance in Soybean
Authors: Yoosefzadeh-Najafabadi Mohsen , Earl Hugh J. , Tulpan Dan , Sulik John , Eskandari Milad
Published: January 2021

Recent substantial advances in high-throughput field phenotyping have provided plant breeders with affordable and efficient tools for evaluating a large number of genotypes for important agronomic traits at early growth stages. Nevertheless, the implementation of large datasets generated by high-throughput phenotyping tools such as hyperspectral reflectance in cultivar development programs is still challenging due to the essential need for intensive knowledge in computational and statistical analyses. In this study, the robustness of three common machine learning (ML) algorithms, multilayer perceptron (MLP), support vector machine (SVM), and random forest (RF), were evaluated for predicting soybean (Glycine max) seed yield using hyperspectral reflectance. For this aim, the hyperspectral reflectance data for the whole spectra ranged from 395 to 1005 nm, which were collected at the R4 and R5 growth stages on 250 soybean genotypes grown in four environments. The recursive feature elimination (RFE) approach was performed to reduce the dimensionality of the hyperspectral reflectance data and select variables with the largest importance values. The results indicated that R5 is more informative stage for measuring hyperspectral reflectance to predict seed yields. The 395 nm reflectance band was also identified as the high ranked band in predicting the soybean seed yield. By considering either full or selected variables as the input variables, the ML algorithms were evaluated individually and combined-version using the ensemble–stacking (E–S) method to predict the soybean yield. The RF algorithm had the highest performance with a value of 84% yield classification accuracy among all the individual tested algorithms. Therefore, by selecting RF as the metaClassifier for E–S method, the prediction accuracy increased to 0.93, using all variables, and 0.87, using selected variables showing the success of using E–S as one of the ensemble techniques. This study demonstrated that soybean breeders could implement E–S algorithm using either the full or selected spectra reflectance to select the high-yielding soybean genotypes, among a large number of genotypes, at early growth stages.
Fictosexuality, Fictoromance, and Fictophilia: A Qualitative Study of Love and Desire for Fictional Characters
Authors: Karhulahti Veli-Matti , Välisalo Tanja
Published: January 2021

Fictosexuality, fictoromance, and fictophilia are terms that have recently become popular in online environments as indicators of strong and lasting feelings of love, infatuation, or desire for one or more fictional characters. This article explores the phenomenon by qualitative thematic analysis of 71 relevant online discussions. Five central themes emerge from the data: (1) fictophilic paradox, (2) fictophilic stigma, (3) fictophilic behaviors, (4) fictophilic asexuality, and (5) fictophilic supernormal stimuli. The findings are further discussed and ultimately compared to the long-term debates on human sexuality in relation to fictional characters in Japanese media psychology. Contexts for future conversation and research are suggested.