bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric Emptying Is Not Delayed and Does Not Correlate With Attenuated Postprandial Blood Flow Increase in Medicated Patients With Early Parkinson's Disease
Authors: Siebner Thomas Hartwig , Fuglsang Stefan , Madelung Christopher Fugl , Løkkegaard Annemette , Bendtsen Flemming , Hove Jens Dahlgaard , Damgaard Morten , Madsen Jan Lysgård , Siebner Hartwig Roman
Published: February 2022

Background

We have recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in 23 medicated patients with Parkinson's disease (PD) compared to 23 age- and sex-matched healthy controls.

Objective

To investigate in a sub-sample of the original cohort whether the observed blood flow response in SMA after oral food intake is related to a delay in gastric emptying.

Methods

We studied 15 patients with PD in an “ON-medication” state with a mean disease duration of 3.9 ± 2.2 years and 15 healthy age- and sex-matched individuals. Participants underwent dynamic gastric scintigraphy 0, 30, 60, 120, 180 and 240 minutes after the intake of a standardized radiolabeled test meal. Gastric emptying was compared between groups. 14 of the 15 PD patients and 12 of the 15 healthy control subjects had previously undergone serial postprandial PC-MRI measurements. In these individuals, we tested for a relationship between gastric emptying and postprandial blood flow response in the SMA.

Results

The dynamics of gastric emptying did not differ between groups (p= 0.68). There was substantial inter-subject variability of gastric emptying in PD patients and healthy participants. Only a single PD patient had delayed gastric emptying. In those participants who had undergone PC-MRI, postprandial increase in SMA blood flow was attenuated in PD compared to healthy controls as reported previously (p= 0.006). Gastric emptying did not correlate with the timing and amplitude of postprandial blood flow increase in SMA.

Conclusion

Our preliminary results, obtained in a small group of early-stage PD patients who continued their usual dopamine replacement therapy, suggest that variations in gastric emptying after solid meal intake is within the normal range in the majority of cases. There is also no evidence for a tight relationship between the attenuated postprandial blood flow response in the SMA and normal variations in gastric emptying.
What Neuroscientists Think, and Don’t Think, About Consciousness
Authors: Kitchener Peter D. , Hales Colin G.
Published: February 2022

The approach the majority of neuroscientists take to the question of how consciousness is generated, it is probably fair to say, is to ignore it. Although there are active research programs looking at correlates of consciousness, and explorations of informational properties of what might be relevant neural ensembles, the tacitly implied mechanism of consciousness in these approaches is that it somehow just happens. This reliance on a “magical emergence” of consciousness does not address the “objectively unreasonable” proposition that elements that have no attributes or properties that can be said to relate to consciousness somehow aggregate to produce it. Neuroscience has furnished evidence that neurons are fundamental to consciousness; at the fine and gross scale, aspects of our conscious experience depend on specific patterns of neural activity – in some way, the connectivity of neurons computes the features of our experience. So how do we get from knowing that some specific configurations of cells produce consciousness to understanding why this would be the case? Behind the voltages and currents electrophysiologists measure is a staggeringly complex system of electromagnetic fields – these are the fundamental physics of neurons and glia in the brain. The brain is entirely made of electromagnetism (EM) phenomena from the level of the atoms up. The EM field literally manifests the computations, or signaling, or information processing/activities performed by connected cellular ensembles that generate a 1st-person perspective. An investigation into the EM field at the cellular scale provides the possibility of identifying the outward signs of a mechanism in fundamental terms (physics), as opposed to merely describing the correlates of our mental abstractions of it.
Inhibitory Control and the Structural Parcelation of the Right Inferior Frontal Gyrus
Authors: Boen Rune , Raud Liisa , Huster Rene J.
Published: February 2022

The right inferior frontal gyrus (rIFG) has most strongly, although not exclusively, been associated with response inhibition, not least based on covariations of behavioral performance measures and local gray matter characteristics. However, the white matter microstructure of the rIFG as well as its connectivity has been less in focus, especially when it comes to the consideration of potential subdivisions within this area. The present study reconstructed the structural connections of the three main subregions of the rIFG (i.e., pars opercularis, pars triangularis, and pars orbitalis) using diffusion tensor imaging, and further assessed their associations with behavioral measures of inhibitory control. The results revealed a marked heterogeneity of the three subregions with respect to the pattern and extent of their connections, with the pars orbitalis showing the most widespread inter-regional connectivity, while the pars opercularis showed the lowest number of interconnected regions. When relating behavioral performance measures of a stop signal task to brain structure, the data indicated an association between the dorsal opercular connectivity and the go reaction time and the stopping accuracy.
Linking Signal Relevancy and Intensity in Predictive Tactile Suppression
Authors: Beyvers Marie C. , Fraser Lindsey E. , Fiehler Katja
Published: February 2022

Predictable somatosensory feedback leads to a reduction in tactile sensitivity. This phenomenon, called tactile suppression, relies on a mechanism that uses an efference copy of motor commands to help select relevant aspects of incoming sensory signals. We investigated whether tactile suppression is modulated by (a) the task-relevancy of the predicted consequences of movement and (b) the intensity of related somatosensory feedback signals. Participants reached to a target region in the air in front of a screen; visual or tactile feedback indicated the reach was successful. Furthermore, tactile feedback intensity (strong vs. weak) varied across two groups of participants. We measured tactile suppression by comparing detection thresholds for a probing vibration applied to the finger either early or late during reach and at rest. As expected, we found an overall decrease in late-reach suppression, as no touch was involved at the end of the reach. We observed an increase in the degree of tactile suppression when strong tactile feedback was given at the end of the reach, compared to when weak tactile feedback or visual feedback was given. Our results suggest that the extent of tactile suppression can be adapted to different demands of somatosensory processing. Downregulation of this mechanism is invoked only when the consequences of missing a weak movement sequence are severe for the task. The decisive factor for the presence of tactile suppression seems not to be the predicted action effect as such, but the need to detect and process anticipated feedback signals occurring during movement.
Effect of Anti-seizure Medications on Functional Anatomy of Language: A Perspective From Language Functional Magnetic Resonance Imaging
Authors: Xiao Fenglai , Caciagli Lorenzo , Wandschneider Britta , Joshi Bhavini , Vos Sjoerd B. , Hill Andrea , Galovic Marian , Long Lili , Sone Daichi , Trimmel Karin , Sander Josemir W. , Zhou Dong , Thompson Pamela J. , Baxendale Sallie , Duncan John S. , Koepp Matthias J.
Published: February 2022

Background

In epilepsy, cognitive difficulties are common, partly a consequence of anti-seizure medications (ASM), and cognitive side-effects are often considered to be more disabling than seizures and significantly affect quality of life. Functional MRI during verbal fluency tasks demonstrated impaired frontal activation patterns and failed default mode network deactivation in people taking ASM with unfavourable cognitive profiles. The cognitive effect of ASMs given at different dosages in monotherapy, or in different combinations, remains to be determined.

Methods

Here, we compared the effects of different drug loads on verbal fluency functional MRI (fMRI) in people (i) taking dual therapy of ASMs either considered to be associated with moderate (levetiracetam, lamotrigine, lacosamide, carbamazepine/oxcarbazepine, eslicarbazepine, valproic acid; n = 119, 56 females) or severe (topiramate, zonisamide) side-effects; n = 119, 56 females), (ii) taking moderate ASMs in either mono-, dual- or triple-therapy (60 subjects in each group), or (iii) taking different dosages of ASMs with moderate side-effect profiles (n = 180). “Drug load” was defined as a composite value of numbers and dosages of medications, normalised to account for the highest and lowest dose of each specific prescribed medication.

Results

In people taking “moderate” ASMs (n = 119), we observed higher verbal-fluency related to left inferior frontal gyrus and right inferior parietal fMRI activations than in people taking “severe” ASMs (n = 119). Irrespective of the specific ASM, people on monotherapy (n = 60), showed greater frontal activations than people taking two (n = 60), or three ASMs (n = 60). People on two ASMs showed less default mode (precuneus) deactivation than those on monotherapy. In people treated with “moderate” ASMs (n = 180), increased drug load correlated with reduced activation of language-related regions and the right piriform cortex.

Conclusion

Our study delineates the effects of polytherapy and high doses of ASMs when given in monotherapy on the functional anatomy of language. Irrespective of the cognitive profile of individual ASMs, each additional ASM results in additional alterations of cognitive activation patterns. Selection of ASMs with moderate cognitive side effects, and low doses of ASMs when given in polytherapy, could reduce the cognitive effect.
BMNet: A New Region-Based Metric Learning Method for Early Alzheimer’s Disease Identification With FDG-PET Images
Authors: Cui Wenju , Yan Caiying , Yan Zhuangzhi , Peng Yunsong , Leng Yilin , Liu Chenlu , Chen Shuangqing , Jiang Xi , Zheng Jian , Yang Xiaodong
Published: February 2022

18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) reveals altered brain metabolism in individuals with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Some biomarkers derived from FDG-PET by computer-aided-diagnosis (CAD) technologies have been proved that they can accurately diagnosis normal control (NC), MCI, and AD. However, existing FDG-PET-based researches are still insufficient for the identification of early MCI (EMCI) and late MCI (LMCI). Compared with methods based other modalities, current methods with FDG-PET are also inadequate in using the inter-region-based features for the diagnosis of early AD. Moreover, considering the variability in different individuals, some hard samples which are very similar with both two classes limit the classification performance. To tackle these problems, in this paper, we propose a novel bilinear pooling and metric learning network (BMNet), which can extract the inter-region representation features and distinguish hard samples by constructing the embedding space. To validate the proposed method, we collect 898 FDG-PET images from Alzheimer’s disease neuroimaging initiative (ADNI) including 263 normal control (NC) patients, 290 EMCI patients, 147 LMCI patients, and 198 AD patients. Following the common preprocessing steps, 90 features are extracted from each FDG-PET image according to the automatic anatomical landmark (AAL) template and then sent into the proposed network. Extensive fivefold cross-validation experiments are performed for multiple two-class classifications. Experiments show that most metrics are improved after adding the bilinear pooling module and metric losses to the Baseline model respectively. Specifically, in the classification task between EMCI and LMCI, the specificity improves 6.38% after adding the triple metric loss, and the negative predictive value (NPV) improves 3.45% after using the bilinear pooling module. In addition, the accuracy of classification between EMCI and LMCI achieves 79.64% using imbalanced FDG-PET images, which illustrates that the proposed method yields a state-of-the-art result of the classification accuracy between EMCI and LMCI based on PET images.
Early Fractional Amplitude of Low Frequency Fluctuation Can Predict the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation Treatment for Migraine Without Aura
Authors: Feng Menghan , Zhang Yue , Wen Zeying , Hou Xiaoyan , Ye Yongsong , Fu Chengwei , Luo Wenting , Liu Bo
Published: February 2022

Migraine is a common primary headache disorder. Transcutaneous auricular vagus nerve stimulation (taVNS) has been verified to be effective in patients with migraine without aura (MWoA). However, there are large interindividual differences in patients’ responses to taVNS. This study aimed to explore whether pretreatment fractional amplitude of low frequency fluctuation (fALFF) features could predict clinical outcomes in MWoA patients after 4-week taVNS. Sixty MWoA patients and sixty well-matched healthy controls (HCs) were recruited, and migraineurs received 4-week taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the significant differences of fALFF were detected between MWoA patients and HCs using two-sample t-test. A mask of these significant regions was generated and used for subsequent analysis. The abnormal fALFF in the mask was used to predict taVNS efficacy for MWoA using a support vector regression (SVR) model combining with feature select of weight based on the LIBSVM toolbox. We found that (1) compared with HCs, MWoA patients exhibited increased fALFF in the left thalamus, left inferior parietal gyrus (IPG), bilateral precentral gyrus (PreCG), right postcentral gyrus (PoCG), and bilateral supplementary motor areas (SMAs), but decreased in the bilateral precuneus and left superior frontal gyrus (SFG)/medial prefrontal cortex (mPFC); (2) after 4-week taVNS treatment, the fALFF values significantly decreased in these brain regions based on the pretreatment comparison. Importantly, the decreased fALFF in the bilateral precuneus was positively associated with the reduction in the attack times (r = 0.357, p = 0.005, Bonferroni correction, 0.05/5), whereas the reduced fALFF in the right PoCG was negatively associated with reduced visual analog scale (VAS) scores (r = −0.267, p = 0.039, uncorrected); (3) the SVR model exhibited a good performance for prediction (r = 0.411, p < 0.001),which suggests that these extracted fALFF features could be used as reliable biomarkers to predict the treatment response of taVNS for MWoA patients. This study demonstrated that the baseline fALFF features have good potential for predicting individualized treatment response of taVNS in MWoA patients, and those weight brain areas are mainly involved in the thalamocortical (TC) circuits, default mode network (DMN), and descending pain modulation system (DPMS). This will contribute to well understanding the mechanism of taVNS in treating MWoA patients and may help to screen ideal patients who respond well to taVNS treatment.
Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway
Authors: Du Hongjie , Zhou Xuanchen , Shi Lei , Xia Ming , Wang Yajie , Guo Na , Hu Houyang , Zhang Pan , Yang Huiming , Zhu Fangyuan , Teng Zhenxiao , Liu Chengcheng , Zhao Miaoqing
Published: February 2022

The molecular mechanisms that regulate the proliferation and differentiation of inner ear spiral ganglion cells (SGCs) remain largely unknown. Shikonin (a naphthoquinone pigment isolated from the traditional Chinese herbal medicine comfrey root) has anti-oxidation, anti-apoptosis and promoting proliferation and differentiation effects on neural progenitor cells. To study the protective effect of shikonin on auditory nerve damage, we isolated spiral ganglion neuron cells (SGNs) and spiral ganglion Schwann cells (SGSs) that provide nutrients in vitro and pretreated them with shikonin. We found that shikonin can reduce ouabain, a drug that can selectively destroy SGNs and induce auditory nerve damage, caused SGNs proliferation decreased, neurite outgrowth inhibition, cells apoptosis and mitochondrial depolarization. In addition, we found that shikonin can increase the expression of Nrf2 and its downstream molecules HO-1 and NQO1, thereby enhancing the antioxidant capacity of SGNs and SGSs, promoting cells proliferation, and inhibiting cells apoptosis by activating the Nrf2/antioxidant response elements (ARE) signal pathway. However, knockdown of Nrf2 rescued the protective effect of shikonin on SGNs and SGSs damage. In addition, we injected shikonin pretreatment into mouse that ouabain-induced hearing loss and found that shikonin pretreatment has a defensive effect on auditory nerve damage. In summary, the results of this study indicate that shikonin could attenuate the level of oxidative stress in SGNs and SGSs through the Nrf2-ARE signaling pathway activated, induce the proliferation and differentiation of SGNs, and thereby improve the neurological hearing damage in mice. Therefore, shikonin may be a candidate therapeutic drug for endogenous antioxidants that can be used to treat neurological deafness.
A Bibliometric Analysis of Research on Ketamine From 2001 to 2020
Authors: Miao Huihui , Yu Kang , Gao Danyang , Lin Xiaowan , Cao Ying , Liu Xiao , Qiao Hui , Li Tianzuo
Published: February 2022

Background

Ketamine is an intravenous anesthetic with analgesic effects that has a rapid onset and short duration of action. Many studies have been conducted on the use of ketamine; however, the quantity and quality of such studies have not been reported. Therefore, we aimed to conduct a bibliometric analysis of research on ketamine from 2001 to 2020.

Methods

We used the Web of Science database to get publications on ketamine from January 2001 to December 2020. Various bibliographic information was collected, including the number of publications, year of publication, country of origin, journal name, research hotspots, citation count, and author information.

Results

A total of 5,192 articles were included in the analysis. The United States published the highest number of papers on ketamine and the United States participated in publishing the most papers and disclosure funds. The types of articles in clinical trials were cited more frequently. Most articles on ketamine were published in the journal Anesthesia and Analgesia. Furthermore, the antidepressant effect of ketamine has been a research hotspot for the last 20 years.

Conclusion

This study provided a comprehensive analysis of research on ketamine and highlighted the growing interest in ketamine and its antidepressant effects.
CHAIMELEON Project: Creation of a Pan-European Repository of Health Imaging Data for the Development of AI-Powered Cancer Management Tools
Authors: Bonmatí Luis Martí , Miguel Ana , Suárez Amelia , Aznar Mario , Beregi Jean Paul , Fournier Laure , Neri Emanuele , Laghi Andrea , França Manuela , Sardanelli Francesco , Penzkofer Tobias , Lambin Phillipe , Blanquer Ignacio , Menzel Marion I. , Seymour Karine , Figueiras Sergio , Krischak Katharina , Martínez Ricard , Mirsky Yisroel , Yang Guang , Alberich-Bayarri Ángel
Published: February 2022

The CHAIMELEON project aims to set up a pan-European repository of health imaging data, tools and methodologies, with the ambition to set a standard and provide resources for future AI experimentation for cancer management. The project is a 4 year long, EU-funded project tackling some of the most ambitious research in the fields of biomedical imaging, artificial intelligence and cancer treatment, addressing the four types of cancer that currently have the highest prevalence worldwide: lung, breast, prostate and colorectal. To allow this, clinical partners and external collaborators will populate the repository with multimodality (MR, CT, PET/CT) imaging and related clinical data. Subsequently, AI developers will enable a multimodal analytical data engine facilitating the interpretation, extraction and exploitation of the information stored at the repository. The development and implementation of AI-powered pipelines will enable advancement towards automating data deidentification, curation, annotation, integrity securing and image harmonization. By the end of the project, the usability and performance of the repository as a tool fostering AI experimentation will be technically validated, including a validation subphase by world-class European AI developers, participating in Open Challenges to the AI Community. Upon successful validation of the repository, a set of selected AI tools will undergo early in-silico validation in observational clinical studies coordinated by leading experts in the partner hospitals. Tool performance will be assessed, including external independent validation on hallmark clinical decisions in response to some of the currently most important clinical end points in cancer. The project brings together a consortium of 18 European partners including hospitals, universities, R&D centers and private research companies, constituting an ecosystem of infrastructures, biobanks, AI/in-silico experimentation and cloud computing technologies in oncology.
Prospective Clinical Trial of the Oncologic Outcomes and Safety of Extraperitoneal Laparoscopic Extended Retroperitoneal Lymph Node Dissection at Time of Nephroureterectomy for Upper Tract Urothelial Carcinoma
Authors: Huang Jiwei , Qian Hongyang , Yuan Yichu , Cai Xingyun , Chen Yonghui , Zhang Jin , Kong Wen , Wu Xiaorong , Cao Ming , Huang Yiran , Chen Haige , Xue Wei
Published: February 2022

Purpose

To determine the safety and feasibility of extraperitoneal laparoscopic extended lymph node dissection (LND) at the time of extraperitoneal laparoscopic radical nephroureterectomy (RNU).

Materials and Methods

Between May 2018 and March 2019, 39 patients with upper tract urothelial carcinoma (UTUC) received extraperitoneal laparoscopic RNU and concomitant extraperitoneal laparoscopic extended LND. All patients were followed for at least 90 days. Perioperative and pathological data including nodal status and perioperative complications were collected.

Results

Among all 39 patients, 12 patients had pT1, 6 had pT2, 20 had pT3 disease, and 1 had T4 disease. The median (range) lymph node count was 10 (5–22), with 8 patients having pathologically proven lymph node metastasis. The median (range) operating time was 225 (165–430) min, and the median estimated blood loss was 200 (60–800) ml. The median postoperative hemoglobin loss was 1.6 (0–4.2) g/dl. The median (range) postoperative hospital stays were 6 (3–26) days. Overall, 7 patients experienced minor (Clavien Grade I–II) postoperative complications with five patients having Clavien Grade I complications and two patients having Clavien Grade II complications. No major complication (Clavien grade III–IV) occurred. With a median follow-up of 38 months, a total of 8 patients (20.5%) developed local or distant recurrence and no regional LNs where extended LND were performed had recurrence.

Conclusions

The present prospective study demonstrated that extraperitoneal laparoscopic extended LND during extraperitoneal laparoscopic RNU for UTUC is a feasible and safe procedure which provides minimal invasion, rapid recovery, and potentially lower risk of regional LN recurrence. Larger prospective clinical trials with survival endpoints are needed to further determine its potential therapeutic benefits.

Trial Registration

ClinicalTrials.gov identifier NCT 03544437 www.clinicaltrials.gov
A Multi-Parametric Radiomics Nomogram for Preoperative Prediction of Microvascular Invasion Status in Intrahepatic Cholangiocarcinoma
Authors: Qian Xianling , Lu Xin , Ma Xijuan , Zhang Ying , Zhou Changwu , Wang Fang , Shi Yibing , Zeng Mengsu
Published: February 2022

Background

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer with increasing incidence in the last decades. Microvascular invasion (MVI) is a poor prognostic factor for patients with ICC, which correlates early recurrence and poor prognosis, and it can affect the selection of personalized therapeutic regime.

Purpose

This study aimed to develop and validate a radiomics-based nomogram for predicting MVI in ICC patients preoperatively.

Methods

A total of 163 pathologically confirmed ICC patients (training cohort: n = 130; validation cohort: n = 33) with postoperative Ga-DTPA-enhanced MR examination were enrolled, and a time-independent test cohort (n = 24) was collected for external validation. Univariate and multivariate analyses were used to determine the independent predictors of MVI status, which were then incorporated into the MVI prediction nomogram. Least absolute shrinkage and selection operator logistic regression was performed to select optimal features and construct radiomics models. The prediction performances of models were assessed by receiver operating characteristic (ROC) curve analysis. The performance of the MVI prediction nomogram was evaluated by its calibration, discrimination, and clinical utility.

Results

Larger tumor size (p = 0.003) and intrahepatic duct dilatation (p = 0.002) are independent predictors of MVI. The final radiomics model shows desirable and stable prediction performance in the training cohort (AUC = 0.950), validation cohort (AUC = 0.883), and test cohort (AUC = 0.812). The MVI prediction nomogram incorporates tumor size, intrahepatic duct dilatation, and the final radiomics model and achieves excellent predictive efficacy in training cohort (AUC = 0.953), validation cohort (AUC = 0.861), and test cohort (AUC = 0.819), fitting well in calibration curves (p > 0.05). Decision curve and clinical impact curve further confirm the clinical usefulness of the nomogram.

Conclusion

The nomogram incorporating tumor size, intrahepatic duct dilatation, and the final radiomics model is a potential biomarker for preoperative prediction of the MVI status in ICC patients.
Meridianins Rescue Cognitive Deficits, Spine Density and Neuroinflammation in the 5xFAD Model of Alzheimer’s Disease
Authors: Rodríguez-Urgellés Ened , Sancho-Balsells Anna , Chen Wanqi , López-Molina Laura , Ballasch Ivan , Castillo Ignacio del , Avila Conxita , Alberch Jordi , Giralt Albert
Published: February 2022

Glycogen synthase kinase 3β (GSK3β) is a core protein, with a relevant role in many neurodegenerative disorders including Alzheimer’s disease. The enzyme has been largely studied as a potential therapeutic target for several neurological diseases. Unfortunately, preclinical and clinical studies with several GSK3β inhibitors have failed due to many reasons such as excessive toxicity or lack of effects in human subjects. We previously reported that meridianins are potent GSK3β inhibitors without altering neuronal viability. In the present work, we examine whether meridianins are capable to inhibit neural GSK3β in vivo and if such inhibition induces improvements in the 5xFAD mouse model of Alzheimer’s Disease. Direct administration of meridianins in the third ventricle of 5xFAD mice induced robust improvements of recognition memory and cognitive flexibility as well as a rescue of the synaptic loss and an amelioration of neuroinflammatory processes. In summary, our study points out meridianins as a potential compound to treat neurodegenerative disorders associated with an hyperactivation of GSK3β such as Alzheimer’s disease.
The Chemical and Pharmacological Properties of Mitragynine and Its Diastereomers: An Insight Review
Authors: Karunakaran Thiruventhan , Ngew Kok Zhuo , Zailan Ahmad Alif Danial , Mian Jong Vivien Yi , Abu Bakar Mohamad Hafizi
Published: February 2022

Mitragynine, is a naturally occurring indole alkaloid that can be isolated from the leaves of a psychoactive medicinal plant. Mitragyna speciosa, also known as kratom, is found to possess promising analgesic effects on mediating the opioid receptors such as µ (MOR), δ (DOR), and κ (KOR). This alkaloid has therapeutic potential for pain management as it has limited adverse effect compared to a classical opioid, morphine. Mitragynine is frequently regarded to behave like an opioid but possesses milder withdrawal symptoms. The use of this alkaloid as the source of an analgesic candidate has been proven through comprehensive preclinical and clinical studies. The present data have shown that mitragynine is able to bind to opioid receptors, particularly MOR, to exhibit the analgesic effect. Moreover, the chemical and pharmacological aspects of mitragynine and its diastereomers, speciogynine, speciociliatine, and mitraciliatine, are discussed. It is interesting to know how the difference in stereochemical configuration could lead to the difference in the bioactivity of the respective compounds. Hence, in this review, the updated pharmacological and toxicological properties of mitragynine and its diastereomers are discussed to render a comprehensive understanding of the pharmacological properties of mitragynine and its diastereomers based on their structure–activity relationship study.
Nursing Exposure to Bisphenols as a Cause of Male Idiopathic Infertility
Authors: Fenclová Tereza , Řimnáčová Hedvika , Chemek Marouane , Havránková Jiřina , Klein Pavel , Králíčková Milena , Nevoral Jan
Published: February 2022

Idiopathic infertility is a serious problem, which can be caused and explained by exposure to endocrine disruptors, such as bisphenols. In our study, we studied transactional exposure to bisphenol and its effects on newborn male mice throughout their reproductive life. Newborn male mice were exposed to bisphenol S and bisphenol F through maternal milk from post-natal day 0 to post-natal day 15 at concentrations of 0.1 ng.g/bw/day and 10 ng.g/bw/day, respectively. Although there were minimal differences between the control and experimental groups in testicular tissue quality and spermatozoa quality, we discovered an interesting influence on early embryonic development. Moderate doses of bisphenol negatively affected cleavage of the early embryo and subsequently, the blastocyst rate, as well as the number of blastomeres per blastocyst. In our study, we focused on correlations between particular stages from spermatogenesis to blastocyst development. We followed epigenetic changes such as dimethylation of histone H3 and phosphorylation of histone H2 from germ cells to blastocysts; we discovered the transfer of DNA double-strand breaks through the paternal pronucleus from spermatozoa to blastomeres in the blastocyst. We elucidated the impact of sperm DNA damage on early embryonic development, and our results indicate that idiopathic infertility in adulthood may have causes related to the perinatal period.
Beneficial Effect of Long-Term Administration of Supplement With Trapa Bispinosa Roxb. and Lutein on Retinal Neurovascular Coupling in Type 2 Diabetic Mice
Authors: Hanaguri Junya , Yokota Harumasa , Kushiyama Akifumi , Kushiyama Sakura , Watanabe Masahisa , Yamagami Satoru , Nagaoka Taiji
Published: February 2022

Purpose

We investigated the effect of long-term administration of supplement with trapa bispinosa roxb. extract (TBE) and lutein on the susceptibility of retinal blood flow regulation in type 2 diabetic mice.

Methods

Six-week-old db/db mice were randomly divided into the untreated group (n = 6) and the treated group received the supplement with TBE and lutein (n = 6). The longitudinal changes in retinal blood flow responses to systemic hyperoxia and a flicker stimulation were evaluated every 2 weeks in diabetes db/db mice from age 8 to 14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of glial fibrillary acid protein (GFAP) and vascular endothelial growth factor (VEGF) by immunofluorescence.

Results

The resting retinal blood flow was steady and comparable between two groups throughout the study. In db/db mice with supplement, both blood flow responses were restored from 8 to 14 weeks of age compared with diabetic mice treated with the placebo. Supplement prevented the activation of GFAP and decreased the expression of VEGF detected by immunofluorescence compared with the diabetic mice treated with placebo.

Conclusion

We found that the long-term administration of supplement with TBE and lutein improved the impaired regulation of retinal blood flow in response to systemic hyperoxia and flicker stimulation, suggesting that these supplements can prevent diabetic retinopathy by improving abnormal neurovascular coupling in type 2 diabetic mice.
Effects of Postprandial Lipemia Combined With Disturbed Blood Flow on the Flow-Mediated Dilation, Oxidative Stress, and Endothelial Microvesicles in Healthy Subjects
Authors: Araujo Gustavo S. M. , Silva Thiago O. C. , Guerra Grazia M. , Izaias João E. , Rocha Helena M. N. , Faria Diego , Rocha Natalia G. , Dalmazo Aline Lopes , Araujo Amanda , Marciano Consolim-Colombo Fernanda , de Angelis Katia , Irigoyen Maria C. C. , Sales Allan R. K.
Published: February 2022

Aims

Both postprandial lipemia (PPL) and disturbed blood flow (DBF) induce endothelial dysfunction. However, the interactive effect of these stimuli on endothelial function is currently unknown. In the present study, we tested whether PPL plus DBF causes a greater reduction in flow-mediated dilation (FMD) than PPL and if this response is associated with elevations in oxidative stress and endothelial microvesicles (EMVs).

Methods

Eighteen individuals (aged 28 ± 1yrs, 3 females, and BMI 24.43 ± 0.8kg/m2) randomly underwent two experimental sessions: PPL and PPL plus DBF. FMD and venous blood samples were obtained at baseline and 30, 70, and 110 min after stimulation. PPL was induced by fat overload via mozzarella pizza ingestion and DBF by forearm cuff inflation to 75 mm Hg per 30 min. Lipidic profile, oxidative stress (thiobarbituric acid reactive substances, TBARS; ferric reducing/antioxidant power, FRAP; hydrogen peroxide, H2O2) and EMVs were measured in blood samples.

Results

Hypertriglyceridemia was observed in both sessions. Retrograde shear rate and oscillatory index responses were significantly higher in the PPL plus DBF compared with PPL. PPL plus DBF evoked a greater reduction in FMD than did PPL and EMVs, NADPH oxidase, and H2O2 similarly increased in both sessions, but TBARS and FRAP did not change.

Conclusion

These data indicate that the association of PPL plus DBF additively impairs endothelium-dependent function in 110 min after stimulus in healthy individuals, despite a similar increase in oxidative stress and EMVs. Further studies are needed to understand the mechanisms associated with the induced-endothelial dysfunction by association of PPL and DBF.
The Molecular Brakes of Adipose Tissue Lipolysis
Authors: Li Yongguo , Li Zhen , Ngandiri Devi Anggraini , Llerins Perez Mireia , Wolf Alexander , Wang Yuanyuan
Published: February 2022

Adaptation to changes in energy availability is pivotal for the survival of animals. Adipose tissue, the body’s largest reservoir of energy and a major source of metabolic fuel, exerts a buffering function for fluctuations in nutrient availability. This functional plasticity ranges from energy storage in the form of triglycerides during periods of excess energy intake to energy mobilization via lipolysis in the form of free fatty acids for other organs during states of energy demands. The subtle balance between energy storage and mobilization is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance, type 2 diabetes and cancer cachexia. As a result, adipocyte lipolysis is tightly regulated by complex regulatory mechanisms involving lipases and hormonal and biochemical signals that have opposing effects. In thermogenic brown and brite adipocytes, lipolysis stimulation is the canonical way for the activation of non-shivering thermogenesis. Lipolysis proceeds in an orderly and delicately regulated manner, with stimulation through cell-surface receptors via neurotransmitters, hormones, and autocrine/paracrine factors that activate various intracellular signal transduction pathways and increase kinase activity. The subsequent phosphorylation of perilipins, lipases, and cofactors initiates the translocation of key lipases from the cytoplasm to lipid droplets and enables protein-protein interactions to assemble the lipolytic machinery on the scaffolding perilipins at the surface of lipid droplets. Although activation of lipolysis has been well studied, the feedback fine-tuning is less well appreciated. This review focuses on the molecular brakes of lipolysis and discusses some of the divergent fine-tuning strategies in the negative feedback regulation of lipolysis, including delicate negative feedback loops, intermediary lipid metabolites-mediated allosteric regulation and dynamic protein–protein interactions. As aberrant adipocyte lipolysis is involved in various metabolic diseases and releasing the brakes on lipolysis in thermogenic adipocytes may activate thermogenesis, targeting adipocyte lipolysis is thus of therapeutic interest.
Dietary Administration of L-Carnitine During the Fattening Period of Early Feed Restricted Lambs Modifies Ruminal Fermentation but Does Not Improve Feed Efficiency
Authors: Martín Alba , Giráldez F. Javier , Cremonesi Paola , Castiglioni Bianca , Biscarini Filippo , Ceciliani Fabrizio , Santos Nuria , Andrés Sonia
Published: February 2022

Early feed restriction of lambs may program animals to achieve reduced feed efficiency traits as a consequence of permanent mitochondrial dysfunction. The hypothesis at the background of the present study is that dietary administration of L-Carnitine (a compound that promotes the activation and transportation of fatty acids into the mitochondria) during the fattening period of early feed restricted lambs can: (a) improve the biochemical profile of early feed restricted lambs, (b) improve feed efficiency, (c) modulate the ruminal and intestinal microbiota, and (d) induce changes in the gastrointestinal mucosa, including the immune status. Twenty-two newborn male Merino lambs were raised under natural conditions but separated from the dams for 9 h daily to allow feed restriction during the suckling period. At weaning, lambs were assigned to a control group being fed ad libitum a complete pelleted diet during the fattening phase (CTRL, n = 11), whereas the second group (CARN, n = 11) received the same diet supplemented with 3 g of L-Carnitine/kg diet. The results revealed that even though L-Carnitine was absorbed, feed efficiency was not modified by dietary L-Carnitine during the fattening period (residual feed intake, p > 0.05), whereas ruminal fermentation was improved [total short-chain fatty acids (SCFAs), 113 vs. 154 mmol/l; p = 0.036]. Moreover, a trend toward increased concentration of butyrate in the ileal content (0.568 vs. 1.194 mmol/100 ml SCFA; p = 0.074) was observed. Other effects, such as reduced heart weight, lower levels of markers related to muscle metabolism or damage, improved renal function, and increased ureagenesis, were detected in the CARN group. Limited changes in the microbiota were also detected. These findings suggest that L-Carnitine may improve ruminal fermentation parameters and maintain both the balance of gut microbiota and the health of the animals. However, the improved ruminal fermentation and the consequent greater accumulation of intramuscular fat might have hidden the effects caused by the ability of dietary L-Carnitine to increase fatty acid oxidation at the mitochondrial level. This would explain the lack of effects of L-Carnitine supplementation on feed efficiency and points toward the need of testing lower doses, probably in the context of animals being fed in excess non-protein nitrogen.
A Closer Examination of the ‘Abundant-Center’ for Ectomycorrhizal Fungal Community Associated With Picea crassifolia in China
Authors: Wang Xiaobing , Han Qisheng
Published: February 2022

A long-standing hypothesis in biogeography predicts that a species’ abundance is highest at the center of its geographical range and decreases toward its edges. In this study, we test the abundant-center hypothesis of ectomycorrhizal (ECM) fungal communities associated with Picea crassifolia, an endemic species widely distributed in northwest China. We analyzed the taxonomic richness and the relative abundance of ECM fungi in four main distribution areas, from center to edges. In total, 234 species of ECM fungi were detected, and of these, 137 species were shared among all four sites. Inocybe, Sebacina, Tomentella, and Cortinarius were the dominant genera. ECM fungal richness and biodiversity were highest at the central and lower at peripheral sites. Our results indicated that ECM fungal species richness was consistent with the abundant-center hypothesis, while the relative abundances of individual fungal genera shifted inconsistently across the plant’s range.
A COMPASS for VESPUCCI: A FAIR Way to Explore the Grapevine Transcriptomic Landscape
Authors: Moretto Marco , Sonego Paolo , Pilati Stefania , Matus José Tomás , Costantini Laura , Malacarne Giulia , Engelen Kristof
Published: February 2022

Successfully integrating transcriptomic experiments is a challenging task with the ultimate goal of analyzing gene expression data in the broader context of all available measurements, all from a single point of access. In its second major release VESPUCCI, the integrated database of gene expression data for grapevine, has been updated to be FAIR-compliant, employing standards and created with open-source technologies. It includes all public grapevine gene expression experiments from both microarray and RNA-seq platforms. Transcriptomic data can be accessed in multiple ways through the newly developed COMPASS GraphQL interface, while the expression values are normalized using different methodologies to flexibly satisfy different analysis requirements. Sample annotations are manually curated and use standard formats and ontologies. The updated version of VESPUCCI provides easy querying and analyzing of integrated grapevine gene expression (meta)data and can be seamlessly embedded in any analysis workflow or tools. VESPUCCI is freely accessible and offers several ways of interaction, depending on the specific goals and purposes and/or user expertise; an overview can be found at https://vespucci.readthedocs.io/.
Comparative and Phylogenetic Analysis Based on the Chloroplast Genome of Coleanthus subtilis (Tratt.) Seidel, a Protected Rare Species of Monotypic Genus
Authors: Ren Jing , Tian Jing , Jiang Hui , Zhu Xin-Xin , Mutie Fredrick Munyao , Wanga Vincent Okelo , Ding Shi-Xiong , Yang Jia-Xin , Dong Xiang , Chen Ling-Ling , Cai Xiu-Zhen , Hu Guang-Wan
Published: February 2022

Coleanthus subtilis (Tratt.) Seidel (Poaceae) is an ephemeral grass from the monotypic genus Coleanthus Seidl, which grows on wet muddy areas such as fishponds or reservoirs. As a rare species with strict habitat requirements, it is protected at international and national levels. In this study, we sequenced its whole chloroplast genome for the first time using the next-generation sequencing (NGS) technology on the Illumina platform, and performed a comparative and phylogenetic analysis with the related species in Poaceae. The complete chloroplast genome of C. subtilis is 135,915 bp in length, with a quadripartite structure having two 21,529 bp inverted repeat regions (IRs) dividing the entire circular genome into a large single copy region (LSC) of 80,100 bp and a small single copy region (SSC) of 12,757 bp. The overall GC content is 38.3%, while the GC contents in LSC, SSC, and IR regions are 36.3%, 32.4%, and 43.9%, respectively. A total of 129 genes were annotated in the chloroplast genome, including 83 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The accD gene and the introns of both clpP and rpoC1 genes were missing. In addition, the ycf1, ycf2, ycf15, and ycf68 were pseudogenes. Although the chloroplast genome structure of C. subtilis was found to be conserved and stable in general, 26 SSRs and 13 highly variable loci were detected, these regions have the potential to be developed as important molecular markers for the subfamily Pooideae. Phylogenetic analysis with species in Poaceae indicated that Coleanthus and Phippsia were sister groups, and provided new insights into the relationship between Coleanthus, Zingeria, and Colpodium. This study presents the initial chloroplast genome report of C. subtilis, which provides an essential data reference for further research on its origin.
Four-Year and Five-Developing-Stage Dynamic QTL Mapping for Tiller Number in the Hybrid Population of Agropyron Gaertn.
Authors: Che Yonghe , He Yutong , Song Nan , Yang Yanping , Wei Lai , Yang Xinming , Zhang Yan , Zhang Jinpeng , Han Haiming , Li Xiuquan , Zhou Shenghui , Liu Weihua , Li Lihui
Published: February 2022

Tiller number (TN) is an important agronomic trait affecting gramineous crop yield. To understand the static and dynamic information of quantitative trait locus (QTLs) controlling TN of Agropyron Gaertn., both the unconditional and conditional quantitative trait loci (QTL) mapping of TN were conducted using a cross-pollinated (CP) hybrid population with a total of 113 plant lines from the cross between Agropyron cristatum (L.) Gaertn. Z1842 and Allium mongolicum Keng Z2098, based on the phenotypic data of TN at five developmental stages [i.e., recovering stage (RS), jointing stage (JS), heading stage (HS), flowering stage (FS), and maturity stage (MS)] in 4 years (i.e., 2017, 2018, 2020, and 2021) and the genetic map constructed of 1,023 single-nucleotide polymorphism (SNP) markers. Thirty-seven QTLs controlling TN were detected using two analysis methods in 4 years, which were distributed in six linkage groups. Each QTL explained 2.96–31.11% of the phenotypic variation, with a logarithum of odds (LOD) value of 2.51–13.95. Nine of these loci detected both unconditional and conditional QTLs. Twelve unconditional major QTLs and sixteen conditional major QTLs were detected. Three relatively major stable conditional QTLs, namely, cQTN1-3, cQTN1-5, and cQTN4-1, were expressed in 2020 and 2021. Meantime, two pairs of major QTLs cQTN1-5 and qTN1-4 and also cQTN2-4 and qTN2-3 were located at the same interval but in different years. Except for qTN2-2 and qTN3-5/cQTN3-5, other thirty-four QTLs were first detected in this study. This study provides a better interpretation of genetic factors that selectively control tiller at different developmental stages and a reference for molecular marker-assisted selection in the related plant improvement.