bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Storage Conditions on the Quality, Metabolites, and Biological Activity of Soursop (Annona muricata. L.) Kombucha
Authors: Tan Wee Ching , Muhialdin Belal J. , Meor Hussin Anis Shobirin
Published: December 2020

Kombucha is a slightly alcoholic beverage produced using sugared tea via fermentation using the symbiotic culture of bacteria and yeast (SCOBY). This study aimed to optimize the production of soursop kombucha and determine the effects of different storage conditions on the quality, metabolites, and biological activity. The response surface method (RSM) results demonstrated that the optimum production parameters were 300 ml soursop juice, 700 ml black tea, and 150 g sugar and 14 days fermentation at 28°C. The storage conditions showed significant (P < 0.05) effects on the antioxidant activity including the highest antioxidant activity for the sample stored for 14 days at 25°C in light and the highest total phenolic content (TPC) for the sample stored for 7 days at 4°C in the dark. No significant effects were observed on the antimicrobial activity of soursop kombucha toward Escherichia coli and Staphylococcus aureus. The microbial population was reduced from the average of 106 CFU/ml before the storage to 104 CFU/ml after the storage at 4 and 25°C in dark and light conditions. The metabolites profiling demonstrated significant decline for the sucrose, acetic acid, gluconic acid, and ethanol, while glucose was significantly increased. The storage conditions for 21 days at 25°C in the dark reduced 98% of ethanol content. The novel findings of this study revealed that prolonged storage conditions have high potential to improve the quality, metabolites content, biological activity, and the Halal status of soursop kombucha.
7,3′,4′-Trihydroxyisoflavone, a Metabolite of the Soy Isoflavone Daidzein, Suppresses α-Melanocyte-Stimulating Hormone-Induced Melanogenesis by Targeting Melanocortin 1 Receptor
Authors: Kim Ji Hye , Lee Jae-Eun , Kim Taewon , Yeom Myung Hun , Park Jun Seong , di Luccio Eric , Chen Hanyong , Dong Zigang , Lee Ki Won , Kang Nam Joo
Published: December 2020

7,3′,4′-Trihydroxyisoflavone (7,3′,4′-THIF) is a metabolite of daidzein which is a representative isoflavone found in soybean. Recent studies suggested that 7,3′,4′-THIF exerts a hypopigmentary effect in B16F10 cells, however, its underlying molecular mechanisms and specific target protein remain unknown. Here, we found that 7,3′,4′-THIF, but not daidzein, inhibited α-melanocyte-stimulating hormone (MSH)-induced intracellular and extracellular melanin production in B16F10 cells by directly targeting melanocortin 1 receptor (MC1R). Western blot data showed that 7,3′,4′-THIF inhibited α-MSH-induced tyrosinase, tyrosinase-related protein-1 (TYRP-1), and tyrosinase-related protein-2 (TYRP-2) expressions through the inhibition of Microphthalmia-associated transcription factor (MITF) expression and cAMP response element-binding (CREB) phosphorylation. 7,3′,4′-THIF also inhibited α-MSH-induced dephosphorylation of AKT and phosphorylation of p38 and cAMP-dependent protein kinase (PKA). cAMP and Pull-down assays indicated that 7,3′,4′-THIF strongly inhibited forskolin-induced intracellular cAMP production and bound MC1R directly by competing with α-MSH. Moreover, 7,3′,4′-THIF inhibited α-MSH-induced intracellular melanin production in human epidermal melanocytes (HEMs). Collectively, these results demonstrate that 7,3′,4′-THIF targets MC1R, resulting in the suppression of melanin production, suggesting a protective role for 7,3′,4′-THIF against melanogenesis.
Analyzing In Silico the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin
Authors: Pitard Irène , Monet Damien , Goossens Pierre L. , Blondel Arnaud , Malliavin Thérèse E.
Published: December 2020

Molecular dynamics (MD) simulations have been recorded on the complex between the edema factor (EF) of Bacilllus anthracis and calmodulin (CaM), starting from a structure with the orthosteric inhibitor adefovir bound in the EF catalytic site. The starting structure has been destabilized by alternately suppressing different co-factors, such as adefovir ligand or ions, revealing several long-distance correlations between the conformation of CaM, the geometry of the CaM/EF interface, the enzymatic site and the overall organization of the complex. An allosteric communication between CaM/EF interface and the EF catalytic site, highlighted by these correlations, was confirmed by several bioinformatics approaches from the literature. A network of hydrogen bonds and stacking interactions extending from the helix V of of CaM, and the residues of the switches A, B and C, and connecting to catalytic site residues, is a plausible candidate for the mediation of allosteric communication. The greatest variability in volume between the different MD conditions was also found for cavities present at the EF/CaM interface and in the EF catalytic site. The similarity between the predictions from literature and the volume variability might introduce the volume variability as new descriptor of allostery.
Effects of Early Changes in Blood Pressure During Intravenous Thrombolysis on the Prognosis of Acute Ischemic Stroke Patients
Authors: Wang Zhong-Xiu , Wang Chao , Zhang Peng , Qu Yang , Guo Zhen-Ni , Yang Yi
Published: December 2020

Background: Intravenous thrombolysis (IVT) therapy is currently one of the best medical treatments available for patients with acute ischemic stroke. Studies have shown that blood pressure (BP) changes in patients treated with IVT are significantly correlated with prognosis.

Objective: Our study aimed to determine the relationship between BP changes during recombinant tissue plasminogen activator (rt-PA) infusion and the 3-month prognosis evaluated using the modified Rankin Scale (mRS) and determine the factors influencing BP changes during rt-PA infusion.

Methods: Consecutive patients who were treated with IVT and admitted to our stroke center between May 2015 and October 2017 were analyzed retrospectively. Patients were divided into two groups according to their 3-month prognosis status: patients with mRS ≤ 2 were defined as “favorable outcome group” and those with mRS ≥ 3 as “unfavorable outcome group”. First, the factors affecting prognosis after thrombolysis were analyzed. Second, we analyzed the relationship between BP and the prognosis. BP was taken before and at regular intervals of 15 min during the rt-PA infusion (1 h). The average value of BP during thrombolysis was calculated and compared to the baseline BP. BP decrease was defined as the difference between the baseline BP and the average BP, provided it was greater than 0 mmHg. Third, univariate and multivariate analyses were performed to identify factors that may contribute to BP decrease.

Results: In total, 458 patients were included. Patients with a lower baseline National Institute of Health Stroke Scale (NIHSS) score (8.25 ± 5.57 vs. 13.51 ± 7.42, P < 0.001), a higher Alberta Stroke Program Early CT Score (ASPECTS; 8.65 ± 1.82 vs. 8.13 ± 2.00, P = 0.005), decreased BP during thrombolysis (69.4% vs. 59.8%, P = 0.037), and steady BP (SD < 10 mmHg) were more likely to have a favorable outcome (73.9% vs. 60.6%, P = 0.019). High baseline BP (OR > 1), hypertension history (OR < 1), and baseline ASPECTS (OR > 1) were independent factors of BP change during thrombolysis.

Conclusion: Patients with decreased or steady BP during thrombolysis were more likely to have a favorable outcome. Baseline ASPECTS, baseline NIHSS score, and hypertension history influenced BP changes during thrombolysis.
Mechanisms Underlying the Antidepressant Effect of Acupuncture via the CaMK Signaling Pathway
Authors: Bai Lu , Zhang Di , Cui Tao-Tao , Li Ji-Fei , Gao Yang-Yang , Wang Nan-Yi , Jia Peng-Li , Zhang Hui-yuan , Sun Zhong-Ren , Zou Wei , Wang Long
Published: December 2020

The CaMK pathway has been proven to play an important role in regulating cognitive function and emotional response. Acupuncture through the CaMK pathway improves depression-like behavior and the molecular mechanism related to its antidepressant remains to be explored. In this study, we aimed to determine whether the ability of acupuncture at Baihui (GV20) and Shenting (GV24) points to treat depression is related to the regulation of key proteins in the CaMK pathway. A rat model of depression was induced by chronic unpredicted mild stress (CUMS). Model rats in the electroacupuncture group were subjected to acupuncture at the Baihui (GV20) and Shenting (GV24) acupoints once a day for 20 min. Model rats in the fluoxetine group were gavaged with fluoxetine (1.8 mg/kg). Immunohistochemistry and Western blotting assays were used to evaluate immunoreactivity for and the protein expression levels of CaMKII, CaMKIV, and CaM. The results showed that electroacupuncture had a significant effect in rats with depression. Electroacupuncture and fluoxetine regulated the expression of key proteins in the CaMK signaling pathway, which is related to depression, in the hippocampi of rats. This indicates that acupuncture at Baihui (GV20) and Shenting (GV24) may alleviate depressive symptoms and reduce work- and life-related burdens and stress by regulating the CaMK signaling pathway.
Molecular and Functional Characterization of Neurogenin-2 Induced Human Sensory Neurons
Authors: Hulme Amy J. , McArthur Jeffrey R. , Maksour Simon , Miellet Sara , Ooi Lezanne , Adams David J. , Finol-Urdaneta Rocio K. , Dottori Mirella
Published: December 2020

Sensory perception is fundamental to everyday life, yet understanding of human sensory physiology at the molecular level is hindered due to constraints on tissue availability. Emerging strategies to study and characterize peripheral neuropathies in vitro involve the use of human pluripotent stem cells (hPSCs) differentiated into dorsal root ganglion (DRG) sensory neurons. However, neuronal functionality and maturity are limited and underexplored. A recent and promising approach for directing hPSC differentiation towards functionally mature neurons involves the exogenous expression of Neurogenin-2 (NGN2). The optimized protocol described here generates sensory neurons from hPSC-derived neural crest (NC) progenitors through virally induced NGN2 expression. NC cells were derived from hPSCs via a small molecule inhibitor approach and enriched for migrating NC cells (66% SOX10+ cells). At the protein and transcript level, the resulting NGN2 induced sensory neurons (NGN2iSNs) express sensory neuron markers such as BRN3A (82% BRN3A+ cells), ISLET1 (91% ISLET1+ cells), TRKA, TRKB, and TRKC. Importantly, NGN2iSNs repetitively fire action potentials (APs) supported by voltage-gated sodium, potassium, and calcium conductances. In-depth analysis of the molecular basis of NGN2iSN excitability revealed functional expression of ion channels associated with the excitability of primary afferent neurons, such as Nav1.7, Nav1.8, Kv1.2, Kv2.1, BK, Cav2.1, Cav2.2, Cav3.2, ASICs and HCN among other ion channels, for which we provide functional and transcriptional evidence. Our characterization of stem cell-derived sensory neurons sheds light on the molecular basis of human sensory physiology and highlights the suitability of using hPSC-derived sensory neurons for modeling human DRG development and their potential in the study of human peripheral neuropathies and drug therapies.
The Effects of Repetitive Transcranial Magnetic Stimulation on Anxiety in Patients With Moderate to Severe Traumatic Brain Injury: A Post-hoc Analysis of a Randomized Clinical Trial
Authors: Rodrigues Priscila Aparecida , Zaninotto Ana Luiza , Ventresca Hayden M. , Neville Iuri Santana , Hayashi Cintya Yukie , Brunoni Andre R. , de Paula Guirado Vinicius Monteiro , Teixeira Manoel Jacobsen , Paiva Wellingson Silva
Published: December 2020

Background: Traumatic brain injury (TBI) is one of the leading causes of neuropsychiatric disorders in young adults. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to improve psychiatric symptoms in other neurologic disorders, such as focal epilepsy, Parkinson's disease, and fibromyalgia. However, the efficacy of rTMS as a treatment for anxiety in persons with TBI has never been investigated. This exploratory post-hoc analyzes the effects of rTMS on anxiety, depression and executive function in participants with moderate to severe chronic TBI.

Methods: Thirty-six participants with moderate to severe TBI and anxiety symptoms were randomly assigned to an active or sham rTMS condition in a 1:1 ratio. A 10-session protocol was used with 10-Hz rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) for 20 min each session, a total of 2,000 pulses were applied at each daily session (40 stimuli/train, 50 trains). Anxiety symptoms; depression and executive function were analyzed at baseline, after the last rTMS session, and 90 days post intervention.

Results: Twenty-seven participants completed the entire protocol and were included in the post-hoc analysis. Statistical analysis showed no interaction of group and time (p > 0.05) on anxiety scores. Both groups improved depressive and executive functions over time, without time and group interaction (ps < 0.05). No adverse effects were reported in either intervention group.

Conclusion: rTMS did not improve anxiety symptoms following high frequency rTMS in persons with moderate to severe TBI.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02167971.
Training and Transfer of Cue Updating in Older Adults Is Limited: Evidence From Behavioral and Neuronal Data
Authors: Kray Jutta , Ferdinand Nicola K. , Stenger Katharina
Published: December 2020

Cognitive control processes, such as updating task-relevant information while switching between multiple tasks, are substantially impaired in older adults. However, it has also been shown that these cognitive control processes can be improved by training interventions, e.g., by training in task switching. Here, we applied an event-related potential (ERP) approach to identify whether a cognitive training improves task-preparatory processes such as updating of relevant task goals. To do so, we applied a pretest-training-posttest design with eight training sessions. Two groups of older adults were either trained in task switching (treatment group) or in performing single tasks (control group) and we compared their performance to a group of untrained younger adults. To foster cue updating in the treatment group, we applied a cue-based switching task in which the two task cues were randomly selected prior to target presentation so that participants had time to prepare for the upcoming task. In contrast, the control group also received task cues but those were redundant as only one task had to be performed. We also examined whether training in cue updating during task switching can be transferred to a similar cognitive control task measuring updating of context information, namely a modified version of the AX-Continuous Performance Task (AX-CPT). The results revealed training-specific improvements in task switching, that is, a larger improvement in blocks requiring switching in comparison to single tasks at the behavioral level. In addition, training specific-effects were also found at the neuronal level. Older adults trained in cue updating while switching showed a reduction in mixing costs in the cue-related P3, indicating an improvement in preparatory updating processes. Additionally, P3 topography changed with training from a very broad to a parietally focused scalp distribution similar to the one found in younger adults. However, we did not obtain training-specific improvements in context updating in the AX-CPT neither at the behavioral level nor at the neuronal level. Results are discussed in the context of the ongoing debate on whether transfer of cognitive training improvements is possible.
Aberrant Brain Network Integration and Segregation in Diabetic Peripheral Neuropathy Revealed by Structural Connectomics
Authors: Yang Fangxue , Qu Minli , Zhang Youming , Zhao Linmei , Xing Wu , Zhou Gaofeng , Tang Jingyi , Wu Jing , Zhang Yuanchao , Liao Weihua
Published: December 2020

Diabetic peripheral neuropathy (DPN) is one of the most common forms of peripheral neuropathy, and its incidence has been increasing. Mounting evidence has shown that patients with DPN have been associated with widespread alterations in the structure, function and connectivity of the brain, suggesting possible alterations in large-scale brain networks. Using structural covariance networks as well as advanced graph-theory-based computational approaches, we investigated the topological abnormalities of large-scale brain networks for a relatively large sample of patients with DPN (N = 67) compared to matched healthy controls (HCs; N = 88). Compared with HCs, the structural covariance networks of patients with DPN showed an increased characteristic path length, clustering coefficient, sigma, transitivity, and modularity, suggestive of inefficient global integration and increased local segregation. These findings may improve our understanding of the pathophysiological mechanisms underlying alterations in the central nervous system of patients with DPN from the perspective of large-scale structural brain networks.
Life-Stage Dependent Plasticity in the Auditory System of a Songbird Is Signal and Emitter-Specific
Authors: Adreani Nicolas M. , D’Amelio Pietro B. , Gahr Manfred , ter Maat Andries
Published: December 2020

Social animals flexibly use a variety of vocalizations to communicate in complex and dynamic environments. However, it remains unknown whether the auditory perception of different vocalizations changes according to the ecological context. By using miniature wireless devices to synchronously record vocal interactions and local neural activity in freely-behaving zebra finches in combination with playback experiments, we investigate whether the auditory processing of vocalizations changes across life-history stages. We show that during breeding, females (but not males) increase their estrogen levels and reply faster to their mates when interacting vocally. These changes are associated with an increase in the amplitude of the female’s neural auditory responses. Furthermore, the changes in auditory response are not general, but specific to a subset of functionally distinct vocalizations and dependent on the emitter’s identity. These results provide novel insights into auditory plasticity of communication systems, showing that the perception of specific signals can shift according to ecologically-determined physiological states.
The Effects of Intranasal Oxytocin on Neural and Behavioral Responses to Social Touch in the Form of Massage
Authors: Chen Yuanshu , Li Qin , Zhang Qianqian , Kou Juan , Zhang Yingying , Cui Han , Wernicke Jennifer , Montag Christian , Becker Benjamin , Kendrick Keith M. , Yao Shuxia
Published: December 2020

Manually-administered massage can potently increase endogenous oxytocin concentrations and neural activity in social cognition and reward regions and intranasal oxytocin can increase the pleasantness of social touch. In the present study, we investigated whether intranasal oxytocin modulates behavioral and neural responses to foot massage applied manually or by machine using a randomized placebo-controlled within-subject pharmaco-fMRI design. 46 male participants underwent blocks of massage of each type where they both received and imagined receiving the massage. Intranasal oxytocin significantly increased subjective pleasantness ratings of the manual but not the machine massage and neural responses in key regions involved in reward (orbitofrontal cortex, dorsal striatum and ventral tegmental area), social cognition (superior temporal sulcus and inferior parietal lobule), emotion and salience (amygdala and anterior cingulate and insula) and default mode networks (medial prefrontal cortex, parahippocampal gyrus, posterior cingulate, and precuneus) as well as a number of sensory and motor processing regions. Both neural and behavioral effects of oxytocin occurred independent of whether subjects thought the massage was applied by a male or female masseur. These findings support the importance of oxytocin for enhancing positive behavioral and neural responses to social touch in the form of manually administered massage and that a combination of intranasal oxytocin and massage may have therapeutic potential in autism.

Clinical Trials Registration

The Effects of Oxytocin on Social Touch; registration ID: NCT03278860; URL: https://clinicaltrials.gov/ct2/show/NCT03278860.
Repositioning of Immunomodulators: A Ray of Hope for Alzheimer’s Disease?
Authors: Munafò Antonio , Burgaletto Chiara , Di Benedetto Giulia , Di Mauro Marco , Di Mauro Rosaria , Bernardini Renato , Cantarella Giuseppina
Published: December 2020

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder characterized by cognitive decline and by the presence of amyloid β plaques and neurofibrillary tangles in the brain. Despite recent advances in understanding its pathophysiological mechanisms, to date, there are no disease-modifying therapeutic options, to slow or halt the evolution of neurodegenerative processes in AD. Current pharmacological treatments only transiently mitigate the severity of symptoms, with modest or null overall improvement. Emerging evidence supports the concept that AD is affected by the impaired ability of the immune system to restrain the brain’s pathology. Deep understanding of the relationship between the nervous and the immune system may provide a novel arena to develop effective and safe drugs for AD treatment. Considering the crucial role of inflammatory/immune pathways in AD, here we discuss the current status of the immuno-oncological, immunomodulatory and anti-TNF-α drugs which are being used in preclinical studies or in ongoing clinical trials by means of the drug-repositioning approach.
GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets
Authors: Hussein Nada H. , Amin Nada S. , El Tayebi Hend M.
Published: December 2020

With millions of cases diagnosed annually and high economic burden to cover expensive costs, cancer is one of the most difficult diseases to treat due to late diagnosis and severe adverse effects from conventional therapy. This creates an urgent need to find new targets for early diagnosis and therapy. Progress in research revealed the key steps of carcinogenesis. They are called cancer hallmarks. Zooming in, cancer hallmarks are characterized by ligands binding to their cognate receptor and so triggering signaling cascade within cell to make response for stimulus. Accordingly, understanding membrane topology is vital. In this review, we shall discuss one type of transmembrane proteins: Glycosylphosphatidylinositol-Anchored Proteins (GPI-APs), with specific emphasis on those involved in tumor cells by evading immune surveillance and future applications for diagnosis and immune targeted therapy.
Intratumoral and Peritumoral Radiomics of Contrast-Enhanced CT for Prediction of Disease-Free Survival and Chemotherapy Response in Stage II/III Gastric Cancer
Authors: Li Junmeng , Zhang Chao , Wei Jia , Zheng Peiming , Zhang Hui , Xie Yi , Bai Junwei , Zhu Zhonglin , Zhou Kangneng , Liang Xiaokun , Xie Yaoqin , Qin Tao
Published: December 2020

Background

We evaluated the ability of radiomics based on intratumoral and peritumoral regions on preoperative gastric cancer (GC) contrast-enhanced CT imaging to predict disease-free survival (DFS) and chemotherapy response in stage II/III GC.

Methods

This study enrolled of 739 consecutive stage II/III GC patients. Within the intratumoral and peritumoral regions of CT images, 584 total radiomic features were computed at the portal venous-phase. A radiomics signature (RS) was generated by using support vector machine (SVM) based methods. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier analysis were used to determine the association of the RS and clinicopathological variables with DFS. A radiomics nomogram combining the radiomics signature and clinicopathological findings was constructed for individualized DFS estimation.

Results

The radiomics signature consisted of 26 features and was significantly associated with DFS in both the training and validation sets (both P<0.0001). Multivariate analysis showed that the RS was an independent predictor of DFS. The signature had a higher predictive accuracy than TNM stage and single radiomics features and clinicopathological factors. Further analysis showed that stage II/III patients with high scores were more likely to benefit from adjuvant chemotherapy.

Conclusion

The newly developed radiomics signature was a powerful predictor of DFS in GC, and it may predict which patients with stage II and III GC benefit from chemotherapy.
MicroRNAs Regulate Metabolic Phenotypes During Multicellular Tumor Spheroids Progression
Authors: Muciño-Olmos Erick Andrés , Vázquez-Jiménez Aarón , López-Esparza Diana Elena , Maldonado Vilma , Valverde Mahara , Resendis-Antonio Osbaldo
Published: December 2020

During tumor progression, cancer cells rewire their metabolism to face their bioenergetic demands. In recent years, microRNAs (miRNAs) have emerged as regulatory elements that inhibit the translation and stability of crucial mRNAs, some of them causing direct metabolic alterations in cancer. In this study, we investigated the relationship between miRNAs and their targets mRNAs that control metabolism, and how this fine-tuned regulation is diversified depending on the tumor stage. To do so, we implemented a paired analysis of RNA-seq and small RNA-seq in a breast cancer cell line (MCF7). The cell line was cultured in multicellular tumor spheroid (MCTS) and monoculture conditions. For MCTS, we selected two-time points during their development to recapitulate a proliferative and quiescent stage and contrast their miRNA and mRNA expression patterns associated with metabolism. As a result, we identified a set of new direct putative regulatory interactions between miRNAs and metabolic mRNAs representative for proliferative and quiescent stages. Notably, our study allows us to suggest that miR-3143 regulates the carbon metabolism by targeting hexokinase-2. Also, we found that the overexpression of several miRNAs could directly overturn the expression of mRNAs that control glycerophospholipid and N-Glycan metabolism. While this set of miRNAs downregulates their expression in the quiescent stage, the same set is upregulated in proliferative stages. This last finding suggests an additional metabolic switch of the above mentioned metabolic pathways between the quiescent and proliferative stages. Our results contribute to a better understanding of how miRNAs modulate the metabolic landscape in breast cancer MCTS, which eventually will help to design new strategies to mitigate cancer phenotype.
Nomogram for Predicting Lymph Node Involvement in Triple-Negative Breast Cancer
Authors: Cui Xiang , Zhu Hao , Huang Jisheng
Published: December 2020

Background

Lymph node metastasis of triple-negative breast cancer (TNBC) is essential in treatment strategy formulation. This study aimed to build a nomogram that predicts lymph node metastasis in patients with TNBC.

Materials and Methods

A total of 28,966 TNBC patients diagnosed from 2010 to 2017 in the Surveillance, Epidemiology and End Results (SEER) database were enrolled, and randomized 1:1 into the training and validation sets, respectively. Univariate and multivariate logistic regression analysis were applied to identify the predictive factors, which composed the nomogram. The receiver operating characteristic curves showed the efficacy of the nomogram.

Result

Multivariate logistic regression analyses revealed that age, race, tumor size, tumor primary site, and pathological grade were independent predictive factors of lymph node status. Integrating these independent predictive factors, a nomogram was successfully developed for predicting lymph node status, and further validated in the validation set. The areas under the receiver operating characteristic curves of the nomogram in the training and validation sets were 0.684 and 0.689 respectively, showing a satisfactory performance.

Conclusion

We constructed a nomogram to predict the lymph node status in TNBC patients. After further validation in additional large cohorts, the nomogram developed here would do better in predicting, providing more information for staging and treatment, and enabling tailored treatment in TNBC patients.
Prenatal Use of Sildenafil in Fetal Growth Restriction and Its Effect on Neonatal Tissue Oxygenation—A Retrospective Analysis of Hemodynamic Data From Participants of the Dutch STRIDER Trial
Authors: Terstappen Fieke , Richter Anne E. , Lely A. Titia , Hoebeek Freek E. , Elvan-Taspinar Ayten , Bos Arend F. , Ganzevoort Wessel , Pels Anouk , Lemmers Petra M. , Kooi Elisabeth M. W.
Published: December 2020

Objective: Sildenafil is under investigation as a potential agent to improve uteroplacental perfusion in fetal growth restriction (FGR). However, the STRIDER RCT was halted after interim analysis due to futility and higher rates of persistent pulmonary hypertension and mortality in sildenafil-exposed neonates. This hypothesis-generating study within the Dutch STRIDER trial sought to understand what happened to these neonates by studying their regional tissue oxygen saturation (rSO2) within the first 72 h after birth.

Methods: Pregnant women with FGR received 25 mg placebo or sildenafil thrice daily within the Dutch STRIDER trial. We retrospectively analyzed the cerebral and renal rSO2 monitored with near-infrared spectroscopy (NIRS) in a subset of neonates admitted to two participating neonatal intensive care units, in which NIRS is part of standard care. Secondarily, blood pressure and heart rate were analyzed to aid interpretation. Differences in oxygenation levels and interaction with time (slope) between placebo- and sildenafil-exposed groups were tested using mixed effects analyses with multiple comparisons tests.

Results: Cerebral rSO2 levels were not different between treatment groups (79 vs. 77%; both n = 14) with comparable slopes. Sildenafil-exposed infants (n = 5) showed lower renal rSO2 than placebo-exposed infants (n = 6) during several time intervals on day one and two. At 69–72 h, however, the sildenafil group showed higher renal rSO2 than the placebo group. Initially, diastolic blood pressure was higher and heart rate lower in the sildenafil than the placebo group, which changed during day two.

Conclusions: Although limited by sample size, our data suggest that prenatal sildenafil alters renal but not cerebral oxygenation in FGR neonates during the first 72 post-natal hours. The observed changes in renal oxygenation could reflect a vasoconstrictive rebound from sildenafil. Similar changes observed in accompanying vital parameters support this hypothesis.
A Novel Strategy for Decoding and Validating the Combination Principles of Huanglian Jiedu Decoction From Multi-Scale Perspective
Authors: Wang Ke-Xin , Gao Yao , Gong Wen-Xia , Ye Xiao-Feng , Fan Liu-Yi , Wang Chun , Gao Xue-Fei , Gao Li , Du Guan-Hua , Qin Xue-Mei , Lu Ai-Ping , Guan Dao-Gang
Published: December 2020

Traditional Chinese medicine (TCM) formulas treat complex diseases through combined botanical drugs which follow specific compatibility rules to reduce toxicity and increase efficiency. “Jun, Chen, Zuo and Shi” is one of most used compatibility rules in the combination of botanical drugs. However, due to the deficiency of traditional research methods, the quantified theoretical basis of herbal compatibility including principles of “Jun, Chen, Zuo and Shi” are still unclear. Network pharmacology is a new strategy based on system biology and multi-disciplines, which can systematically and comprehensively observe the intervention of drugs on disease networks, and is especially suitable for the research of TCM in the treatment of complex diseases. In this study, we systematically decoded the “Jun, Chen, Zuo and Shi” rules of Huanglian Jiedu Decoction (HJD) in the treatment of diseases for the first time. This interpretation method considered three levels of data. The data in the first level mainly depicts the characteristics of each component in single botanical drug of HJD, include the physical and chemical properties of component, ADME properties and functional enrichment analysis of component targets. The second level data is the characterization of component-target-protein (C-T-P) network in the whole protein-protein interaction (PPI) network, mainly include the characterization of degree and key communities in C-T-P network. The third level data is the characterization of intervention propagation properties of HJD in the treatment of different complex diseases, mainly include target coverage of pathogenic genes and propagation coefficient of intervention effect between target proteins and pathogenic genes. Finally, our method was validated by metabolic data, which could be used to detect the components absorbed into blood. This research shows the scientific basis of “Jun-Chen-Zuo-Shi” from a multi-dimensional perspective, and provides a good methodological reference for the subsequent interpretation of key components and speculation mechanism of the formula.
Reduced Treatment Sensitivity of SARS-CoV-2 After Multigenerational Human-to-Human Transmission
Authors: Wang Qiang , Yang Tong , Wang Yang
Published: December 2020

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a rapidly spreading worldwide pandemic, seriously threatening global public health security. At present, there is still no vaccine or specific drug available for the virus. Therefore, epidemiological prevention and control is crucial to block further spread of the disease. In this present study, based on the public information of COVID-19 in Qingdao, Shandong Province, China, we analyzed the epidemiological characteristics and treatment effects of 60 confirmed cases. It was revealed that the hospital stay of patients were imported from Wuhan or infected by Wuhan patients was obviously shorter than that of those who were imported from other regions or infected by them. In addition, in Hubei-related patients, the earlier transmission generation, which refers to the imported patients (G0) and the first-generation infections (G1), was associated with reduced cure time. Therefore, we speculated that the treatment sensitivity of SARS-CoV-2 decreased within interpersonal transmission in the early stage of this epidemic.
Wideband Absorption at Low Microwave Frequencies Assisted by Magnetic Squeezing in Metamaterials
Authors: Wang Zhenxu , Wang Jiafu , Han Yajuan , Fan Ya , Fu Xinmin , Pang Yongqiang , Yan Mingbao , Li Yongfeng , Ma Hua , Xu Zhuo , Qu Shaobo
Published: December 2020

In this paper, the magnetic squeezing effect in metamaterials is explored and applied to achieve wideband absorption in low-frequency microwave bands. To this end, a metamaterial absorber (MA) is proposed, which consists of a square lattice of a split ring resonator (SRR) placed on top of a magnetic absorbing material (MAM) layer backed by a conducting ground. In the positive resonance region of SRRs, a strong magnetic squeezing effect occurs and more concentrated magnetic field lines are confined within SRRs. This results in significant magnetic field enhancement within the MAM layer, which provides a prerequisite for high-efficiency absorption enhancement at low frequencies. To verify this method, we fabricated a prototype using a 3.0 mm thick silicone MAM sheet. Both the simulation and experiment results show that with the assistance of magnetic squeezing in the SRR array, the absorption at lower frequencies is significantly enhanced and is above 90% in 1.25–2.31 GHz under normal incidence. Furthermore, the MA exhibits satisfactory stability for different polarization states and incident angles due to the square lattice of the SRR array. This design method may find potential applications in fields such as electromagnetic compatibility, wireless communication, and others.
Lipid-Lowering Effects of Lotus Leaf Alcoholic Extract on Serum, Hepatopancreas, and Muscle of Juvenile Grass Carp via Gene Expression
Authors: Yao Junpeng , Hu Pengcheng , Zhu Yanhong , Xu Yingyan , Tan Qingsong , Liang Xufang
Published: December 2020

Compared with wild grass carp (Ctenopharyngodon idellus), intensively cultured fish displayed disordered lipid metabolism, showing excess lipid deposition in the hepatopancreas and muscle. Lotus leaf prevents fat accumulation in humans and may have similar effects on fish. This study explored the regulatory mechanisms by which the dietary addition of an alcoholic extract of lotus leaf (AELL) reduced lipid deposition in the hepatopancreas and muscle of juvenile grass carp. The fish (average initial weight: 34.00 ± 0.40 g) were fed four experimental diets containing different AELL levels (0, 0.07, 0.14, and 0.21%) for 8 weeks. Serum components, lipid droplet size, triacylglycerol (TAG) content, enzymatic activities, and mRNA levels of genes related to lipid metabolism in the hepatopancreas and muscle were analyzed. The results show that dietary AELL supplementation significantly reduced the TAG content and lipid droplet area in the histological sections as well as the fatty acid synthase (FAS) activity in both the hepatopancreas and muscle but enhanced the activities of lipoprotein lipase (LPL) and carnitine palmitoyltransferase I (CPT1) in both tissues. In addition, dietary AELL supplementation decreased the mRNA expression of genes involved in fatty acid uptake (cd36, fatp1/fatp4/fatp6, fabp10/fabp11, acsl1/acsl4) and de novo lipid synthesis (pgd, g6pd, and fasn) as well as the transcription factors pparg and srebf1 in the hepatopancreas and muscle but increased the mRNA levels of genes relating to lipid catabolism (cpt1a, lipe, pnpla2, lpl), lipid transportation (apob), and the transcription factor ppara in both tissues. In conclusion, dietary AELL supplementation reduced lipid accumulation in the hepatopancreas and muscle by affecting the gene expression of proteins with known effects on lipid metabolism in juvenile grass carp.
Novel Mechanical Strain Characterization of Ventilated ex vivo Porcine and Murine Lung using Digital Image Correlation
Authors: Mariano Crystal A. , Sattari Samaneh , Maghsoudi-Ganjeh Mohammad , Tartibi Mehrzad , Lo David D. , Eskandari Mona
Published: December 2020

Respiratory illnesses, such as bronchitis, emphysema, asthma, and COVID-19, substantially remodel lung tissue, deteriorate function, and culminate in a compromised breathing ability. Yet, the structural mechanics of the lung is significantly understudied. Classical pressure-volume air or saline inflation studies of the lung have attempted to characterize the organ’s elasticity and compliance, measuring deviatory responses in diseased states; however, these investigations are exclusively limited to the bulk composite or global response of the entire lung and disregard local expansion and stretch phenomena within the lung lobes, overlooking potentially valuable physiological insights, as particularly related to mechanical ventilation. Here, we present a method to collect the first non-contact, full-field deformation measures ofex vivoporcine and murine lungs and interface with a pressure-volume ventilation system to investigate lung behavior in real time. We share preliminary observations of heterogeneous and anisotropic strain distributions of the parenchymal surface, associative pressure-volume-strain loading dependencies during continuous loading, and consider the influence of inflation rate and maximum volume. This study serves as a crucial basis for future works to comprehensively characterize the regional response of the lung across various species, link local strains to global lung mechanics, examine the effect of breathing frequencies and volumes, investigate deformation gradients and evolutionary behaviors during breathing, and contrast healthy and pathological states. Measurements collected in this framework ultimately aim to inform predictive computational models and enable the effective development of ventilators and early diagnostic strategies.
Impact of Ringer’s Solution Challenge Stress to Immunostimulatory Experiment, Insights From Japanese Flounder
Authors: Liu Jinxiang , Li Zan , Wang Yujue , Zhang Quanqi
Published: December 2020

Ringer’s or phosphate buffer saline (PBS) solution buffer usually was used as dilution butter in intraperitoneal injection. Stress could activate immune response, inflammatory response and glycogen metabolic process. The impact of solution buffer as a stressor to immune system was ignored in immunostimulatory experiment. In this report, we tested the hypothesis that the innate immune response and glycogen metabolic process were altered when it were challenged with Ringer’s in Japanese flounder (Paralichthys olivaceus). RNA-seq was performed after challenge with Ringer’s at 8 h and 48 h. The data revealed that the expression profiles of blood, gill, and kidney were significantly changed. Differentially expressed genes (DEGs) were identified, and energy metabolic and immune-related genes were up-regulated or down-regulated obviously. GO and KEGG analyses showed that DEGs were mainly enriched in innate immune terms and pathways. Weighted gene co-expression networks analysis (WGCNA) also indicated the highest association module with stress. A total of 16 genes were detected in the gray module, which were immune-related and metabolic-related genes. These results provided fundamental information on intraperitoneal injection with solution buffer. It offered useful clues to further explore the functional mechanism of stress and immunity.
Improving Image-Based Plant Disease Classification With Generative Adversarial Network Under Limited Training Set
Authors: Bi Luning , Hu Guiping
Published: December 2020

Traditionally, plant disease recognition has mainly been done visually by human. It is often biased, time-consuming, and laborious. Machine learning methods based on plant leave images have been proposed to improve the disease recognition process. Convolutional neural networks (CNNs) have been adopted and proven to be very effective. Despite the good classification accuracy achieved by CNNs, the issue of limited training data remains. In most cases, the training dataset is often small due to significant effort in data collection and annotation. In this case, CNN methods tend to have the overfitting problem. In this paper, Wasserstein generative adversarial network with gradient penalty (WGAN-GP) is combined with label smoothing regularization (LSR) to improve the prediction accuracy and address the overfitting problem under limited training data. Experiments show that the proposed WGAN-GP enhanced classification method can improve the overall classification accuracy of plant diseases by 24.4% as compared to 20.2% using classic data augmentation and 22% using synthetic samples without LSR.
Light-Mediated Signaling and Metabolic Changes Coordinate Stomatal Opening and Closure
Authors: Yang Juan , Li Chunlian , Kong Dexin , Guo Fangyan , Wei Hongbin
Published: December 2020

Stomata are valves on the leaf surface controlling carbon dioxide (CO2) influx for photosynthesis and water loss by transpiration. Thus, plants have to evolve elaborate mechanisms controlling stomatal aperture to allow efficient photosynthesis while avoid excessive water loss. Light is not only the energy source for photosynthesis but also an important signal regulating stomatal movement during dark-to-light transition. Our knowledge concerning blue and red light signaling and light-induced metabolite changes that contribute to stomatal opening are accumulating. This review summarizes recent advances on the signaling components that lie between the perception of blue/red light and activation of the PM H+-ATPases, and on the negative regulation of stomatal opening by red light-activated phyB signaling and ultraviolet (UV-B and UV-A) irradiation. Besides, light-regulated guard cell (GC)-specific metabolic levels, mesophyll-derived sucrose, and CO2 concentration within GCs also play dual roles in stomatal opening. Thus, light-induced stomatal opening is tightly accompanied by brake mechanisms, allowing plants to coordinate carbon gain and water loss. Knowledge on the mechanisms regulating the trade-off between stomatal opening and closure may have potential applications toward generating superior crops with improved water use efficiency (CO2 gain vs. water loss).
Dissection for Floral Micromorphology and Plastid Genome of Valuable Medicinal Borages Arnebia and Lithospermum (Boraginaceae)
Authors: Park Inkyu , Yang Sungyu , Song Jun-Ho , Moon Byeong Cheol
Published: December 2020

The generaArnebiaandLithospermum(Lithospermeae-Boraginaceae) comprise 25–30 and 50–60 species, respectively. Some of them are economically valuable, as their roots frequently contain a purple-red dye used in the cosmetic industry. Furthermore, dried roots ofArnebia euchroma,A. guttata, andLithospermum erythrorhizon, which have been designated Lithospermi Radix, are used as traditional Korean herbal medicine. This study is the first report on the floral micromorphology and complete chloroplast (cp) genome sequences ofA. guttata(includingA. tibetana),A. euchroma, andL. erythrorhizon. We reveal great diversity in floral epidermal cell patterns, gynoecium, and structure of trichomes. The cp genomes were 149,361–150,465 bp in length, with conserved quadripartite structures. In total, 112 genes were identified, including 78 protein-coding regions, 30 tRNA genes, and four rRNA genes. Gene order, content, and orientation were highly conserved and were consistent with the general structure of angiosperm cp genomes. Comparison of the four cp genomes revealed locally divergent regions, mainly within intergenic spacer regions (atpH-atpI,petN-psbM,rbcL-psaI,ycf4-cemA,ndhF-rpl32, andndhC-trnV-UAC). To facilitate species identification, we developed molecular markerspsaA-ycf3(PSY),trnI-CAU- ycf2(TCY), andndhC-trnV-UAC(NCTV) based on divergence hotspots. High-resolution phylogenetic analysis revealed clear clustering and a close relationship ofArnebiato itsLithospermumsister group, which was supported by strong bootstrap values and posterior probabilities. Overall, gynoecium characteristics and genetic distance of cp genomes suggest thatA. tibetana, might be recognized as an independent species rather than a synonym ofA. guttata. The present morphological and cp genomic results provide useful information for future studies, such as taxonomic, phylogenetic, and evolutionary analysis of Boraginaceae.